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Planning And Implementing Critical Care And Emergency Pharmaceuticals Jassin M. Jouria, MD Dr. Jassin M. Jouria is a medical doctor, professor of academic medicine, and medical author. He graduated from Ross University School of Medicine and has completed his clinical clerkship training in various teaching hospitals throughout New York, including King’s County Hospital Center and Brookdale Medical Center, among others. Dr. Jouria has passed all USMLE medical board exams, and has served as a test prep tutor and instructor for Kaplan. He has developed several medical courses and curricula for a variety of educational institutions. Dr. Jouria has also served on multiple levels in the academic field including faculty member and Department Chair. Dr. Jouria continues to serves as a Subject Matter Expert for several continuing education organizations covering multiple basic medical sciences. He has also developed several continuing medical education courses covering various topics in clinical medicine. Recently, Dr. Jouria has been contracted by the University of Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e-module training series for trauma patient management. Dr. Jouria is currently authoring an academic textbook on Human Anatomy & Physiology. Abstract Safe administration of medication in critical care and emergency settings is paramount to ensure optimal outcomes for patients. The most experienced medical and nursing clinicians are well aware of the fragility of critical care patients and the potential for the smallest mistake to result in serious consequences. Understanding the purpose, administration, monitoring, and potential consequences of pharmacological agents available to critical care and emergency department clinicians is necessary for them to make use of potentially life-saving treatments. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1 Policy Statement This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities. Continuing Education Credit Designation This educational activity is credited for 4 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Pharmacology content is 4 hours. Statement of Learning Need Critical care and emergency medicine is a relatively recent phenomenon in health care, and the role of pharmacists, physicians and certified nurses trained to work in critical care and emergency settings have expanded over recent years. As the intensive care units and emergency departments in hospital increasingly develop to include computerized equipment and software supporting unit-based services and highly trained interdisciplinary staff delivering care to patients diagnosed with critical conditions, so too does the highly important need of the right medication, dose and route to initially treat, stabilize and progress patients to a healthier state. Course Purpose To provide advanced learning in critical care and emergency pharmacology for clinicians working in hospital emergency and intensive care unit settings. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2 Target Audience Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion) Course Author & Planning Team Conflict of Interest Disclosures Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures Acknowledgement of Commercial Support There is no commercial support for this course. Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3 1. Within the ICU and critical care environment, metered-dose inhalers (MDIs) typically include medication formulations that have been created for MDIs, such as a. b. c. d. inhalable powder medications. any drug available in nebulized form. powder, liquid and water-soluble gel forms. bronchodilator medications and corticosteroids. 2. True or False: Pharmacokinetics in critical care patients are the only constant factors because drugs are absorbed, metabolized, and excreted based on the drug’s composition, not the current health status of the patient. a. True b. False 3. The following statement(s) is/are correct with respect to the use of inhaled medications in the critical care environment, such as ICU? a. Inhaled medications are rarely used in ICU. b. Inhaled medications are used except in patients who require mechanical ventilation. c. The method of administering inhaled drugs depends largely on the patient’s ability and health status. d. All of the above 4. _______________ is a muscarinic agonist that is used in an inhaled preparation form to test and diagnose asthma. a. b. c. d. Methacholine Budesonide Ipratropium bromide Albuterol 5. Which of the following inhaled medications specifically act on the beta-2 adrenergic receptors of the lungs to cause vasodilation of the bronchioles and to improve breathing? a. b. c. d. Ipratropium Heparin Methacholine Albuterol nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4 Introduction Administration of medication to any patient requires careful planning, keeping in mind the essential steps to ensuring that the correct medication is given to promote the best outcome. Health clinicians who give medication must follow the six rights of medication administration, including the right patient, medication, dose, route, time, and documentation. The steps of medication administration are even more significant in the critical care environment, where the clinician must often think and act quickly to respond to changes in the patient’s clinical status. Medication Administration In The ED And ICU Administering medication in the emergency department or the ICU adds another element of pressure. Within critical care, clinicians may need to administer medications quickly, without the luxury of time to check and recheck medications. Clinicians may need to recall formulas and calculate drug dosages quickly so that they may respond rapidly to a patient’s changing health status. There are often many interruptions during the course of care that could affect how medications are given. Because of the sometimes hectic and stressful pace of critical care, there is an increased risk of errors with medication administration. Because the patients being cared for in the ICU often have unstable conditions, administration of medications can lead to rapid changes. When drugs are administered inappropriately, there is a greater chance of harm to the patient, even if the incorrect action would be considered a minor error if it were made outside the ICU setting. Most patients in critical care are sicker overall when compared to their counterparts in other areas of the healthcare facility; they often have higher numbers of comorbidities present and they nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5 receive more medications. Critical care patients also undergo more treatments and procedures that can induce pain or anxiety and so they may have more prn medications to be given for comfort as well. Pharmacokinetics in critical a care patient may be altered because of the patient’s current health status; in other words, because critical illness can affect how drugs are absorbed, metabolized, and excreted, patients in the critical care environment are at higher risk of complications associated with drug administration when their bodies cannot process the drugs properly.45,68 There are various routes of drug administration used in critical care, however, clinicians who work in these environments may be more likely to administer drugs intravenously, orally, or as inhaled preparations. Inhaled Medication Inhaled medications are those drugs that are delivered to the lungs and that are taken into the body while breathing in. They may be commonly administered in the critical care environment, particularly in situations where patients have breathing difficulties due to chronic lung disease or bronchospasm, as well as among some patients who require mechanical ventilation. The method of administering inhaled drugs depends on the patient’s ability to take the medication, often as a result of the patient’s health status. An intubated patient must be given inhaled medications through part of the ventilator tubing. Alternatively, a patient who is not intubated can use other mechanisms for inhaling medications, but should be assessed for his or her ability to do so. This section covers the varied methods of inhalation medication.47-52 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6 For the patient who is not intubated, inhaled medications are administered through one of several devices that make it relatively easy to breathe in the medication and gain the effects of the drug. These devices typically include metered-dose inhalers, dry powder inhalers, or nebulizers. Metered-dose inhalers are some of the more common items used in the general public to administer prescription medications for asthma or COPD symptoms. Within the ICU and critical care environment, metered-dose inhalers (MDIs) may also be used; their use is restricted to those medication formulations that have been created for this specific mechanism of administration, and typically include bronchodilator medications and corticosteroids. The MDI consists of a canister, a propellant, and a metering valve, all of which are contained within a plastic holder that acts as an actuation device. The inhaler must be prepared prior to administration, so the clinician should shake the inhaler several times before use. When pressing on the actuator, the medication is ejected out through the mouthpiece, the amount of which is controlled by the metering valve. The patient who uses an inhaler must be able to briefly hold it in his mouth for administration, and needs to coordinate breathing with the drug’s administration. This involves breathing in at the same time the actuator is depressed so the drug can be inhaled. The patient must hold his breath for a few seconds after the drug is given. Some people have difficulties with coordinating the intake of medication with breathing in. When there is any confusion or difficulties with coordination and the inhaler is used incorrectly, the medication can be wasted and the patient will not receive an accurate dose, nor will he derive any benefits of the drug. When difficulties are encountered, a spacer may be added to the end of the inhaler to better ensure delivery of the drug. A spacer is typically nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7 made out of plastic and is a compartment in which one end connects to the mouthpiece of the inhaler, while the other end is placed in the patient’s mouth. After depressing the actuator, the medication enters the spacer, where it is held until the patient can breathe it in. With a spacer, the patient has a little more time to inhale the medicine if he cannot coordinate his breathing and the medication particles are not lost into the surrounding air. A dry powder inhaler uses the same type of mechanism for delivering medication to the patient, however with an MDI, the medicine is available in an aerosolized form, while a dry powder inhaler uses an inhalable powder. The dry powder inhaler also does not contain propellants that are found in the metered-dose mechanism. This type of inhaler is often used to manage lung conditions such as asthma or COPD, but the medications they contain are meant for long-term control, rather than for symptomatic use. Nebulizers are devices that transform medication that is in liquid form into fine mist particles that can be inhaled. There are typically many more inhaled medications that are available in nebulizer form than those that can be given by MDI. The medication to be given through a nebulizer is available as a prescription; the dose may already be contained within a prepackaged unit-dose vial of liquid that contains the exact amount, although sometimes the dose is measured from a larger container and added to the nebulizer. Once the machine is started, a small air compressor works to change the liquid particles into a mist. The nebulizer may have a mouthpiece in which the patient places one end into his mouth and inhales the mist and the medication. For some patients, a face mask, similar to those used for administering oxygen, can be utilized as well. A patient who takes inhalation medications through a nebulizer must be able to either hold the mouthpiece and breathe in the mist, or tolerate having a face mask on while the drug is nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 8 being given. This often requires that the person be sitting up and be conscious. The patient may also need to regulate his breathing so that it is slow and steady; a rapid breathing pace can affect how much of the drug actually makes it into the lungs. Inhaled medications can often work very quickly after they are administered; once the medication enters the lung, it is absorbed through the alveoli. Because the alveoli make up such a large area of lung tissue, absorption is often rapid and the drug is able to enter systemic circulation after passing across the alveolar membrane. Often, there are more difficulties with getting the medication into the lung for its absorption rather than the process of absorption itself. An exception to this is when the patient has chronic lung disease and the alveoli are damaged, which can significantly limit how much medication is able to be absorbed into circulation once it enters the lungs. Based on the equipment available for patients to take inhaled medications, there are many cases where some of the medication never even reaches the patient because it is expelled into the surrounding air. The mechanisms for providing inhaled medications must then be used correctly and the awake patient who receives the drugs may need to be educated about how to breathe and take the medication before giving the first dose. Intubated patients may also receive inhaled medications when the drug is administered through the ventilator tubing. Historically, research has shown that many patients who receive inhaled medications, either through nebulizer therapy or through pressurized MDIs, have often missed a majority of the medication because of the mechanisms of administration. Studies have shown that many patients, when given inhaled medication while on the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 9 ventilator, only receive a fraction of the drug while the rest of the medication is expelled into the surrounding air. However, changes in the structure of ventilators, as well as the systems for delivering inhaled medications have greatly improved the amount of medication that most ventilated patients are able to receive when given inhaled drugs. A study in the Journal of Aerosol Medicine and Pulmonary Drug Delivery shows that there are a number of methods of administering aerosolized medications to ventilated patients where the individual may receive up to 97.5 percent of the drug. The correct device to use when giving inhaled drugs is based on the type of medication being delivered, the understanding of the time it takes for the drug to take effect, and the type of ventilator in use. Pressurized MDIs can be used with ventilated patients to deliver inhaled medications. When giving an inhaled drug through this method, the inhaler is connected to a section of the ventilator circuit through an adaptor. The actuation of the drug must be synchronized to match the patient’s inspiration. When not synchronized to the time that the patient receives a breath from the ventilator, a significant amount of the medication can be lost. Use of a chamber spacer, similar to that used with a non-ventilated patient, is often successful in ensuring that the patient with a mechanical ventilator receives as much of the medication as possible. It is also more successful when the inhaler is placed on an area of the circuit that is closer to the endotracheal tube. Prior to actuating the device, the MDI must be shaken and primed. As with use of a MDI in a non-ventilated patient, a spacer may accompany this method of drug administration when a ventilator is used as well. Spacers, as discussed, are attachments connected to the inhaler that delay the time needed to disperse the drug. Metered-dose inhalers are very easy nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10 to use with the ventilator, however, not all drugs that are given as inhaled products are available through this device and must be given in nebulized form instead. Keep in mind that heat and humidity, which are often used in the ventilator circuit to prevent drying out of respiratory tissue and to improve mucous clearance, may affect the amount of drug that reaches the patient’s lungs when aerosolized medications are given. The heat and humidity may have an effect on the size of the aerosol particles, thus impacting their delivery to the lungs. However, it is often not possible or helpful to the patient to remove the humidifier in order to administer an inhaled medication. The practice of stopping the ventilator to disconnect the circuit to remove the heat and humidity may predispose the patient to other problems that can negate the positive effects of the inhaled drug. A drug that is given only once in a while through the ventilator may not warrant any change in heat and humidity, other drug preparations may need an alteration in the amount to be given with the dosage increased. There are also some mechanisms that may be used instead, particularly when the patient requires very frequent doses of inhaled medications and would benefit from administration through a dry ventilator circuit, such as with a moisture exchanger. The benefits and disadvantages associated with administering inhaled medication through the ventilator circuit to the intubated patient need to be realized with each situation and changes and adaptations made accordingly. The healthcare provider who administers inhaled medications to patients who require mechanical ventilation must then remember that there can be some effects of heat and humidity on the patient’s ability to receive the largest amount of the drug, and the drug’s effects on the patient’s clinical status should be monitored closely for signs of success. Since it is difficult to nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11 measure exactly how much of the aerosolized drug has actually reached the lung tissue, the caregiver must also continually assess and monitor for drug effects to determine therapeutic outcomes. Nebulizer therapy is another method of delivering inhaled medications to patients who use mechanical ventilation. The delivery of the drug and the amount of drug the patient actually receives is typically dependent on the type and rate of nebulizer used, the position where the nebulizer is placed on the ventilator circuit, and the type of spacer involved. Nebulizers used with mechanical ventilation are basically divided into three different types: jet, ultrasonic, and mesh nebulizers. Jet nebulizers are relatively easy to use and are one of the more inexpensive methods of inhaled medication administration in the ventilator-dependent population. Jet nebulizers work by breaking down the liquid into particles using compressed oxygen or air and a reservoir. The reservoir is used to manage the size of the particles if they are too large as they are transitioned from liquid. While easy to use, the jet nebulizer may alter the properties of the medication. Ultrasonic nebulizers work by creating ultrasonic vibrations that convert the medication solution into a mist that can be inhaled. The particles created may be slightly larger when compared to those with other types of nebulizers but the particle size is often consistent. As with some other kinds of nebulizers, ultrasonic nebulizers may leave some residual medication that the patient does not receive. This type of nebulizer is not used as often within the ICU because of its size and cost to use. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12 The mesh nebulizer converts liquid to particles for inhalation by moving the liquid through a fine mesh barrier. Mesh nebulizers have been shown to have a reduced drug residual with use, which means a greater amount of the inhaled drug reaches the patient. There is also less risk of contamination associated with their use because the reservoir is separate from the ventilator circuit. Mesh nebulizers are also quiet and they can be portable. Although many inhaled medications are given to treat respiratory conditions, there are also drugs available that can be given through the inhaled route but that are used for the treatment of other kinds of conditions. Clearly, bronchodilators are some of the more common drugs administered by inhalation; however, antibiotics, including tobramycin and azithromycin, can be administered in this method as well. Inhaled insulin (Afrezza®) is an inhalation powder that peaks within 12 to 15 minutes of administration and that may be beneficial for some patients with diabetes. Other examples of some agents administered via inhalation include nebulized heparin; corticosteroids, such as budesonide; and inhaled aerosolized prostaglandins. Muscarinic receptors are a type of acetylcholine receptor that can be found in the lung tissue. They are responsible for controlling and modifying smooth muscle tone, regulating mucus production, and managing lung inflammation. There are some drugs that act as muscarinic receptor agonists that may cause shortness of breath if they are inhaled. For example, methacholine is an inhaled preparation that is a muscarinic agonist that is used to test and diagnose asthma because it can cause shortness of breath and wheezing. The action of muscarinic receptors in the lungs may also be blocked by some kinds of medications that are administered as inhaled drugs. When stimulated, muscarinic receptors cause a decrease in heart rate, a decrease nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13 in cardiac contractility, and constriction of the bronchioles. A drug that is a parasympathetic blocker medication then blocks the action of these muscarinic receptors and therefore causes a reverse effect. Parasympathetic blocker medications are administered in different ways, but when used for their effects on the bronchioles, they may be given as inhaled preparations. An example of this is ipratropium bromide (Atrovent®), which is often used for the management of symptoms associated with chronic obstructive pulmonary disease. Ipratropium is given as an inhaled medication to block the muscarinic receptors and to cause bronchodilation, which increases airflow in the lungs and makes it easier for the patient to breathe. Ipratropium can also decrease the amount of mucus secretions in the patient’s lungs, which also promotes a clear airway and easier breathing. It may cause some negative side effects associated with the respiratory system. The most common side effects of ipratropium include respiratory tract infection, bronchitis, cough, sinusitis, and exacerbation of COPD symptoms. Other side effects may also include urinary tract infection, dyspepsia, and flu-like symptoms. Certain inhaled medications specifically act on the beta-2 adrenergic receptors of the lungs to cause vasodilation of the bronchioles and to improve breathing. Albuterol (Proventil®, Ventolin®) is an example of this type of medicine. Albuterol is a bronchodilator that is primarily used for the treatment of bronchospasm. It is administered as an inhaled medication, often through either a nebulizer or aerosol inhaler, where it quickly works in the lung tissue to stimulate the beta-2 receptors. Albuterol is often used as a rescue medication and it is the first choice of treatment of bronchospasm and has been shown through clinical trials to have a greater effect on smooth muscle relaxation in the bronchial tissue than isoproterenol, a sympathomimetic drug that also stimulates beta-2 receptors in the lungs, as nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 14 well as having longer-lasting effects and fewer cardiovascular effects than isoproterenol. Because of its effects on beta receptors, albuterol may cause some side effects, the most common include shakiness and tremor, and a fast pulse with a feeling of pounding heartbeat that may be irregularly paced. Albuterol may be successfully combined with other medications used for the treatment of bronchospasm. Combivent® is an inhaled medication that is a combination of albuterol and ipratropium, so this drug simultaneously stimulates beta-2 receptors and blocks muscarinic receptors to dilate the bronchioles, control wheezing, and decrease mucus secretions. While common and often available for use in the critical care setting, medications given through inhalers or nebulizers typically are used for their expected purposes and may be administered as part of ongoing treatment or in emergent, life-threatening situations. The American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology have given guidelines about selection of the most appropriate device and drug in different situations within the emergency department or the ICU. In short, the executive summary that was released determined that within the emergency department, including among cases of acute asthma and bronchospasm, the delivery of short-acting beta-2 agonist through an MDI or nebulizer is appropriate, based on the patient’s ability to accurately use these devices. The use of dry powder inhalers for these same conditions is not recommended at this point due to a lack of evidence regarding effectiveness. Additionally, the two medical associations have issued guidelines for the use of short-acting beta-2 agonists administered in the inpatient hospital setting, which state that the use of metered-dose inhalers and nebulizers, used with spacers when needed, are both appropriate for administration of these nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15 drugs. Among patients who are not using mechanical ventilation but who are severely dyspneic, the use of either intermittent or continuous nebulizers to administer medications is appropriate. Among patients who require mechanical ventilation, nebulizers and MDIs can be used to deliver beta-2 agonist medications, keeping in mind the technical factors that can affect delivery of these medications (for instance, the use of ventilator circuits, the presence of heat and humidity, the inspiratory rate of the patient) as well as the potential side effects caused by these drugs and their particular effects on the patient (including tachycardia and premature heart beats). Although there have been challenges with the administration of inhalation medications to patients in critical care, particularly among those who require mechanical ventilation, the therapeutic effects of these drugs are very important for the patients who need them for management of lung conditions and infections, as well as for treatment of some other symptoms of disease. As systems of administration continue to evolve, the ability to accurately administer these drugs and ensure that they are therapeutically effective will continue to improve. Intravenous Medication Intravenous administration of medications is one of the most common routes utilized in critical care. Many of these drugs act very quickly and produce rapid responses because they are administered directly into systemic circulation while bypassing the absorption stage. The rapid response of these drugs is often necessary for this population of patients because their health conditions may change rapidly and they may need the quick action and effects of IV medications to combat these changes. While the rapid effects of intravenous administration make these drugs preferable for use in critical care, they can also expose some patients to harm if they are not carefully nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 16 and appropriately administered and the patient continually monitored with their use. Administration of intravenous medication requires an IV catheter; this may be placed by emergency personnel prior to arrival at the healthcare center or it may be started upon arrival. Typically, a patient in critical care has at least one IV catheter in place or has a central venous catheter, which provides fluid and medication directly into the larger vessels of the circulatory system. The central catheter often has more than one port for administration of different types of fluids and medications that may or may not be compatible so that they can be given at the same time without having to wait or flush the lines in between doses. There are several different types of central venous catheters. Because of the size of these lines and their ability to reach directly into central circulation, they are often kept in place for several weeks or months at a time. They also require a physician or specially trained advanced practice nurse to place them. Intravenous medications may be administered through such types of central venous catheters as peripherally-inserted central catheter (PICC) lines, tunneled catheters, or implanted ports, as examples. In many healthcare centers, intravenous medications arrive in the emergency department or critical care unit prepackaged and ready for administration from the pharmacy, however, depending on the location and its policies, the bedside care providers often must combine and prepare IV formulas before giving them to patients. In emergency situations, such as when the patient needs advanced life support, the medications are available at the bedside, whether from the crash cart or in an easily accessible location so they can be given quickly. Intravenous medications are typically nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17 administered either as a bolus, which may be given IV push over a very short period, or as a short-term infusion that is given once and that is infused through a pump or is given as a piggyback to an infusion that is already in place. Intravenous medications may also be administered via continuous infusion. In this case, the fluid is prepared ahead of time in a syringe or bag; often, the dose of the drug must be mixed with a diluent such as dextrose water or normal saline. The infusion is administered over a period of hours, or if it is given continuously, it is connected to the IV pump and started for an indefinite period of time, depending on how the patient responds. For example, the clinician caring for an individual with low blood pressure may receive orders to start a dopamine infusion; the amount and rate is calculated based on the patient’s weight and blood pressure. The infusion may be set up to run continuously over a period of hours or days until it can eventually be discontinued when the patient’s blood pressure levels are stable. When a continuous infusion is in place for more than 24 hours, the IV tubing and the medication container often must be changed to decrease the risk of infection. In most cases, intravenous infusion medications that are given through an IV pump have the rate set and total volume computed and set by the pump, which often eliminates the need for calculation of flow rates and drip times. This provides a much safer method of medication administration and reduces the risk of medication errors. However, it is still important for any clinician who administers IV medications in critical care to have a basic understanding of how to calculate an appropriate flow rate, in case of emergency or in situations where a pump is not available.1,3,24,43 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 18 To calculate the IV flow rate, the nurse must know the drug concentration, which is the amount of the drug that is available within the given solution; and the medication dose, which is how much of the drug the patient should get over a specified period of time. This information is written in the orders from the provider. The concentration of the drug may vary slightly, depending on the type of medication. For example, dopamine may be delivered based on a calculation of micrograms/kilogram/minute, while some antibiotics are often calculated as milligrams/kilogram/hour, especially within pediatric populations. The nurse should be familiar with the basic units of common drugs that are given to be able to catch any errors of concentration if they occur. The dose of the drug should be available through the provider’s prescription and it should specify whether the drug should be given over a period of minutes or hours. At times, the flow rate may need to be calculated to determine the rate in which to set an infusion pump. Alternatively, the provider may also need to calculate drops (gtts) per minute when IV tubing is used without a pump and is controlled manually. It is extremely important to understand how to calculate infusion rates and to recognize the effects that the rate of infusion will have on a patient’s condition, particularly in the critical care setting, where administration of some intravenous medications can cause rapid and significant changes in the patient’s health. To calculate the rate of infusion when a pump is available and to infuse solution at a rate of mL/hour, the provider uses the formula: Amount of Solution (mL) = Total mL/hour Time in Hours nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 19 This type of calculation may be used more often with fluid administration, as opposed to medication doses. For example, a nurse receives an order for 1000 mL D5 ½ NS to be given over 8 hours. To calculate the infusion rate, the nurse would input the following: 1000 mL D5 ½ NS = 125 mL/hour 8 hours To calculate gtts per minute when the flow rate will be manually controlled, the following formula is used: Amount of Solution (mL or mL/hr) x gtt factor = Total gtt/minute Time in Minutes To utilize this formula, the clinician must first know the gtt factor, which is based on the infusion set used. The size of the drip set may range from a mini-drip set, which has a gtt factor of 60 gtts/mL, to a regular drip set, which has a rate of 10-20 gtts/mL. As an example, a nurse receives an order for Ancef, with the dose in a 50 mL solution, which must be given over 30 minutes. The gtt factor is 20 gtts/mL. The nurse uses the following calculation: 50 mL x 20 gtt = 33.3 gtts/minute 30 minutes These examples are just two samples of possible calculations that may be needed at the bedside of a critical care patient. Keep in mind that not all intravenous infusions will require formulaic calculations, though; in many cases, the drug is supplied with the information at hand and by connecting nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20 the drug to a pump, the clinician can administer IV drugs quickly and with relative ease. Regardless of whether IV drugs require infusion rate calculations, the caregiver giving the drugs is always responsible for ensuring that the patient is receiving the right drug at the correct rate. There are a great number of intravenous drugs that are administered in critical care. Some drugs are given continuously to maintain a patient’s state of health when he is relatively stable; examples may include IV antibiotics, diuretics, or opioid analgesics. Alternatively, some drugs are given intravenously and must be administered rapidly in life-threatening situations, including some vasopressors or antiarrhythmics. Depending on the patient’s current state of health, the nurse may administer many IV medications from various drug classes. Critical care is a specialty that requires a high degree of technical knowledge and the foresight to consider the most appropriate drugs based on the patient’s condition and to continuously monitor response to the drug. Intravenous medications, while fast-acting and effective, can also be very harmful to such a vulnerable population of patients if mistakes are made. Many patients in the ICU receive routine IV fluids, run at a continuous rate; these fluids may be coupled with other intravenous solutions as well, such as insulin or parenteral nutrition. When IV medications are ordered, they may also be given in a bolus or as an added continuous solution. The provider must then carefully check all medications for their rates of administration and the solutions in which they will be given for compatibility and to ensure that the patient is not getting too much. Fluid balance is an objective that can be disrupted when IV medications are given too quickly or too slowly, or if they are added unnecessarily to certain solutions. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21 Further, because patients often receive many intravenous medications in this setting, there is a greater potential for drug interactions, particularly when several drugs are given within short periods or when using the same IV line. Drug interactions occur when one drug changes the pharmacokinetics or pharmacodynamics of another drug and subsequently changes its expected effects. Drug interactions may cause antagonistic effects, in which one drug prevents the other from exerting its effects. With these types of drug interactions, the patient does not gain the benefits of at least one of the drugs given or its overall intensity of effects is reduced. This could occur accidentally, as when two drugs are administered at the same time and cause an antagonistic effect; however, there are times when this effect is desirable. An example is the administration of naloxone (Narcan™), which is an antidote to opioid drugs, and can be given to counteract the effects of these medications. Drug interactions may also cause synergistic effects, in which the drugs potentiate the effects of each other. When this occurs, the patient may experience greater effects of one or both drugs, results that can be positive or that can cause adverse effects. An example of a synergistic effect is the combination of opioids with an antihistamine that causes drowsiness. Opioids also can cause adverse effects of drowsiness and fatigue; giving these two kinds of drugs together can potentiate both adverse effects and could lead to significant changes in the patient’s condition, including stupor or loss of consciousness. Ideally, the clinician should be familiar with common drug interactions associated with certain intravenous medications before administration. While it is not possible to know all possible effects of all drugs, referencing potential interactions and spacing the timing of drug administration, when nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22 possible, can decrease the potential for these effects. This also includes familiarity with each drug’s time of onset, duration, and half-life, and what type of IV solution is compatible for administration. By utilizing reference guides, checking with other personnel, and using medical equipment appropriately, the clinician can safely administer intravenous medications that will be of great benefit to the patient. Oral Medication Oral medications are not as commonly administered in critical care when compared to intravenous drugs; many critically ill patients do not have the ability to swallow oral tablets or cannot tolerate ingestion and absorption of these drugs from the gastrointestinal tract. However, in the right circumstances, giving medications by mouth can be one of the easiest ways to administer drugs. There are some clinicians who believe that the oral route of administration is not as effective when compared to IV drugs. However, there are some medications that are only available through the oral route and that cannot be given any other way; drugs used to treat hyperlipidemia, such as atorvastatin, are some such examples. Further, if an orally administered drug is able to achieve the same tissue distribution as that of an intravenous drug, an oral medication is no less effective than the same kind of drug given via a different route. Although the route of oral administration requires an additional step of absorption to reach systemic circulation, the oral preparation is not necessarily less effective than other routes; instead, it may simply take longer to exert its effects.1,42,89 There are benefits as well as drawbacks to using oral medications in the emergency department or the ICU. For some patients who are able to swallow food and pills, oral medications are relatively simple to administer and require very little preparation. They can be given on a long-term basis nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 23 and often have fewer complications associated with their use, unlike some other routes of administration, such as problems with infection or fluid extravasation associated with the intravenous drug route. In terms of the different routes of medications available within healthcare, oral preparations are some of the most economical methods. A patient who receives enteral feedings through a nasogastric or gastrostomy tube can receive some types of oral medications if they are crushed and administered through the tubing. Alternatively, many patients in critical care do not have the option of taking oral medications, as the drugs they need are not available in oral form or they cannot take pills or tablets. Patients who are NPO (nothing by mouth) typically do not have the option to take oral medications. Some drugs, particularly those that are extended-release formulations, cannot be crushed and given through feeding tubes; if a patient is then unable to swallow the tablet by mouth, he would be unable to take the oral preparation of the drug. Oral medications also require an additional step in the process of pharmacokinetics in that they must be absorbed in the digestive tract before they can be distributed and metabolized by the body. Often, patients in critical care have health conditions that can affect drug absorption and can distort how the body is able to distribute an oral medication. An examination of the effects of drug administration on reducing medication errors in critical care, found in Clinical Pharmacology: Advances and Applications emphasized that a patient’s rapidly changing condition in critical care often means that taking an oral medication for the treatment of a deteriorating health condition will not work rapidly enough to produce the desired effects; instead, an individual whose health is deteriorating quickly often needs intravenous medications for rapid treatment. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 24 All of these factors must be taken into account when administering oral medications in critical care. Oral medications are available in different formulations, including those that are swallowed, such as with tablets or capsules. They may also be placed under the tongue (sublingual) or between the cheek and gums in the mouth (buccal) to be dissolved. When an individual is unable to swallow oral medications, the healthcare provider needs to make some accommodations to enable the patient to be able to successfully take his medication. This may mean crushing the medication, if appropriate, and mixing it in a substance that can easily be swallowed, such as applesauce. Not all oral medications can be crushed, so the exact order must be checked and verified before doing so. In some cases, requesting the medication in a slightly different form may be more appropriate. For instance, a patient may not be able to swallow an oral medication that is in tablet form, but he may be able to swallow the medicine if it is given as an oral syrup. The nurse often needs to assess the patient’s current state of health and self-care abilities before administering oral medications. Some patients are admitted to the hospital with pre-existing conditions and they have orders to continue to receive the same prescription drugs that they take at home. For instance, a patient who is admitted to the hospital for surgery and who normally takes lisinopril for hypertension at home may eventually start taking the same medication in the hospital once his condition has stabilized. Some people who are given intravenous medications while in the ICU may eventually be able to transition to taking oral medications, particularly if they will need to be discharged to home with a prescription. This transition is nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 25 not appropriate for all patients; those who are critically ill and who cannot tolerate oral medications should wait until they are in stable health before making the change, for obvious reasons. When possible, patients may be changed to oral medications for ease and cost of administration. The change may occur over time as the patient demonstrates the ability to take oral drugs. In light of the potential complications associated with oral drug administration in the ICU, caregivers must weigh decisions very carefully about when and if a patient is able to transition to oral medications. In all cases, oral medications must be labeled correctly and clearly; the healthcare clinician must always witness the patient as he takes the drug, rather than leaving the medication at the bedside for the patient to take on his own. Splitting tablets to administer one-half of a dose is a relatively common practice but it also increases the risk of errors. When dividing doses by splitting tablets, the provider should note whether the drug is safe for splitting, as noted on the packaging, and whether it is scored on the tablet. The nurse should use a pill splitter to divide the dose, which is the most accurate method of breaking the pill in half. Additionally, all oral drugs must be measured carefully, particularly if in liquid form; and if a drug is an extended-release formulation, it should be clearly noted prior to administration and never crushed to be given through a feeding tube. The administration of oral medications has its own benefits and challenges, similarly to other routes of medication administration. While oral medicines can be easy to dispense because they usually do not require mixing or changing the drug prior to administration, it is still important to thoroughly check every label and dose that comes from the pharmacy prior to giving the patient an oral drug. Consideration for the time that it takes for the drug to nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26 take effect must also be noted, as it will take longer to achieve therapeutic effectiveness for these kinds of drugs when compared to administering medications through other routes. Prescription Guidelines Within healthcare, all prescriptions, including their indications and details of drug administration, will come from a healthcare provider such as a physician, surgeon, or advanced practice nurse. The type of drug ordered is based on the patient’s clinical condition and diagnosis and the prescription is given with consideration for the drug’s effects, the time that it takes for drugs to exert their effects, the routes that the drug can be administered, and the overall goals for the patient’s outcomes. In some cases, drugs must be administered very rapidly in response to the patient’s condition. As a patient’s health status changes, drugs may be ordered in response to maintain a stable health state. Healthcare providers who prescribe drugs have guidance from the U.S. Food and Drug Administration, who provides indications for drug usage and appropriate doses and administration, in addition to information about adverse effects, use of certain drugs within special populations, and possible drug interactions.90 The guidelines for prescribing drugs vary depending on the circumstances under which the drug is administered and the patient’s health condition and potential response. Within critical care, the clinician may administer many different types of medications to control pain, calm or sedate the patient, or manage the person’s health condition, which sometimes is done during emergencies. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 27 Benzodiazepines Benzodiazepines have a number of uses in medicine, with the ultimate goal of causing relaxation, sedation, or a decrease in anxiety. Benzodiazepines typically act as sedative-hypnotics in the central nervous system in response to GABA receptors. Their use is primarily intended for anxiolysis, control of insomnia, or as muscle relaxants; they may also be combined with other drugs for their sedative effects during procedures. Benzodiazepines are often administered to patients in critical care because of the pain and distress that is often involved with care in these areas. Critically ill patients often undergo painful and frightening procedures and may be more likely to suffer from anxiety and pain as a result. Even the act of being turned and repositioned in bed has been described by some immobile patients as being extremely painful and difficult. Benzodiazepines combat much of the anxiety induced in these situations by promoting calm and reducing agitation and potential delirium associated with intensive care. This section highlights the usefulness of benzodiazepines in the ICU and emergency setting, as well as potential adverse effects clinicians should know.1,11,91-93 Some of the more commonly administered benzodiazepines include midazolam, lorazepam (Ativan®), and diazepam (Valium®). These three drugs all act as GABA receptor agonists. Midazolam hydrochloride is a shortacting benzodiazepine that may be administered IV or as an intramuscular injection. Because of its sedating effects, midazolam should only be used in cases where the patient can be monitored thoroughly for hemodynamic stability and for changes in level of consciousness. In addition to sedation, midazolam has been associated with respiratory depression and arrest in some patients. The drug achieves its sedating effects within three minutes nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 28 after being given intravenously; patients who receive the drug and who become sedated may have little or no memory of the events following the injection. One study that investigated midazolam administration during endoscopy showed that 71 percent of people in one center had no memory of the procedure after being given midazolam. Midazolam has a half-life of between 3 and 11 hours, and it is eliminated via hepatic metabolism. How much of it is actually distributed after administration can be affected by several factors, including female gender, advanced age, and obesity. Midazolam can be given as an initial bolus of 1 to 5 mg; as a continuous infusion, it can be administered at a rate of 1 to 5 mg/hour. Due to its effects on the central nervous system, administration of other medications that act as depressants may potentiate the effects of midazolam and should be avoided as much as possible. Midazolam may also be associated with an increased risk of delirium and tolerance when compared to some other sedative agents. Lorazepam also acts as a central nervous system depressant in that it causes sedation but does not necessarily impact the cardiovascular system. Lorazepam has been shown to be beneficial in reducing anxiety, promoting sedation, and controlling seizure activity. Within the critical care setting, it is most typically given IV or as an IM injection. Its half-life is approximately 8 to 15 hours and its onset of action is between 5 and 20 minutes, which is somewhat slower than some other kinds of benzodiazepines. Like midazolam, there may be an increased risk of delirium with use of lorazepam, and patients who have been given this drug should also be monitored for signs of excessive sedation. Lorazepam may be administered for the treatment of all kinds of seizures, including those due to status epilepticus. Note that when using lorazepam for this purpose, the patient nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 29 must be closely monitored because of potential complications of the seizures; lorazepam is just one drug that is used in seizure management in these cases and should not be considered the definitive treatment. Another GABA agonist benzodiazepine that may be used in critical care is diazepam. It is available as an oral preparation, but for critically ill patients, it is more commonly administered as an intravenous or intramuscular injection. Diazepam is used as a mild sedative to control anxiety and stress, particularly that which is associated with patient treatments or medical procedures while in the hospital. It may also be used to treat seizures and can control spasticity when neurological conditions such as cerebral palsy are present. Diazepam has a half-life of up to 120 hours, and it is metabolized by the liver. It is generally administered as a bolus dose and less often as continuous drip. As with other benzodiazepines, diazepam can cause such sedation that the patient may experience a change in level of consciousness, drowsiness, and amnesia of events. Its effects are potentiated with the administration of opioids or other sedatives that also act as central nervous system depressants. A typical dose of diazepam is 1 to 5 mg, depending on the patient’s condition. One contraindication that is common to most benzodiazepines is that these drugs should not be given to anyone with a history of glaucoma. Glaucoma is a condition in which there is increased pressure in the globe of the eye, which leads to a loss of vision. Most people with the condition have openangle glaucoma (90 percent), which develops slowly and causes increased pressure due to obstruction of drainage canals in the eye. Open-angle glaucoma leaves a wide angle between the iris and the cornea. In contrast, nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 30 narrow-angle glaucoma is less common but can cause a sudden rise in intraocular pressure from blocked drainage canals; in this type of glaucoma, there is a narrow angle left between the iris and the cornea. People who have narrow-angle glaucoma or untreated open-angle glaucoma should not be given benzodiazepines, as the drugs may increase intraocular pressure. The benzodiazepines cause pupil dilation when they exert their effects, which can increase pressure within the eye when the angle between the iris and cornea is very narrow. Despite the potential interactions that can occur with use of other drugs or when some chronic medical conditions are present, benzodiazepines can otherwise be safely administered to critically ill patients as long as they continue to be monitored for drug safety and effectiveness. Propofol Propofol (Diprivan®) is a sedative-hypnotic medication that is most commonly used to induce anesthesia during surgery; it is also used in critical care for sedation, such as in cases where mechanical ventilation is used or when a patient will be undergoing an anxiety-producing or painful bedside procedure. Propofol works as a GABA agonist to stimulate these specific receptors, which regulates anxiety and promotes muscle relaxation.1,25,33,44,95 The effects of propofol begin within approximately 40 seconds after it has been administered intravenously. It has a half-life of 1 to 3 minutes, which means that it may be administered either on a continuous basis throughout a procedure or additional doses must be given in order to maintain its effects. It is rapidly distributed and metabolized in the body, particularly when it is first given. With continued administration of bolus doses or with nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 31 ongoing continuous infusion, the rate of distribution slows slightly. When propofol is used only for a short time, such as during a relatively short surgical procedure, the patient may emerge from anesthesia very rapidly after the drug is discontinued. However, when propofol is used for longer periods, some studies have shown that it takes longer for propofol to clear the tissues, leading to longer times of emergence from anesthesia after its discontinuation. When giving propofol by repeat bolus injection, the provider should continually assess the patient’s hemodynamic and clinical status as a response to the previous injection before giving the next so that the dosage can be adjusted if necessary. When given for surgical induction, a typical dosing range in adults is 2 to 2.5 mg/kg, or about 40 mg given every 10 seconds. For continuous IV sedation in the intensive care unit, propofol may be given at a rate of 0.3 mg/kg/hr, increasing every 5 to 10 minutes by 0.3 mg/kg until reaching the desired amount of sedation. The actual rate and dose of propofol can vary based on the specific condition of the patient. Propofol can have a significant impact on the cardiovascular and respiratory systems. Patients who receive propofol can be at risk of decreased oxygen saturations, increased carbon dioxide levels, and hypotension, which may occur before an overall decrease in cardiac output. These effects are aggravated further when propofol is given with another drug that affects hemodynamics, such as with analgesic drugs. Propofol can cause respiratory depression and patients who are given the drug often require assisted ventilation, as its administration may lead to apnea. As previously discussed, moderate sedation involves the administration of sedatives during some procedures to keep patients comfortable. Propofol nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 32 may be used as part of moderate sedation to induce amnesia of the event and to reduce patient anxiety or movement during the procedure. Recall that with moderate sedation, the patient has a depressed level of consciousness. The American Society of Anesthesiologists recommends that even though propofol may be used for moderate sedation, any patient who receives propofol should be monitored as if he were receiving deep sedation. When deep sedation is used, such as during general surgery, the patient is monitored very closely and an anesthesiologist ensures the proper balance of anesthetic and sedative medications and provides intubation to assist the patient with breathing. Even though moderate sedation does not induce such effects, the use of propofol may increase the risk of apnea and loss of consciousness such that the provider should be able to respond as if the process were actually involving deep sedation. Any person who administers propofol should have the training to provide resuscitation for the patient who inadvertently enters a deeper state of sedation than originally intended. This includes an understanding of the purposes, proper dose, and potential complications associated with propofol, the ability to perform advanced cardiac life support procedures, if required; the ability to provide adequate airway management; and the understanding of early signs of possible complications of propofol, including bradycardia, hypoventilation, and decreased oxygen saturations. This includes the immediate availability of hemodynamic monitoring equipment, oxygen delivery equipment, and tools to provide an airway and ventilation. The healthcare provider who administers propofol must also have a thorough understanding of the appropriate elements for monitoring patient sedation and should be available immediately for assistance, if needed. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 33 Another element that must be considered with propofol administration is its lipophilic tendencies, in that it has the potential to accumulate in the adipose tissue of the patient, particularly when it is administered over a longer period of time. A drug is said to be lipophilic when it is capable of being dissolved in or absorbed into fatty tissues. When propofol is administered over time, if it is absorbed more into the patient’s adipose tissue, the drug may exert unstable effects that can make it dangerous to use; this is especially important when considering the longer term use of propofol in the morbidly obese patient who has a larger amount of adipose tissue. Even when the drug is discontinued, it may continue to exert effects over time to the detriment of the patient. In order to prevent this effect, the administration of propofol, particularly during surgery, should be controlled and kept to shorter periods and administration of other drugs that would exert the same effect but that do not accumulate in fat tissue should be considered instead. An example might be replacing propofol with another drug such as remifentanil or ketamine that are not necessarily stored in adipose tissue and that may exert more stable effects. Propofol infusion syndrome (PRIS) is a potentially life-threatening condition that can develop with propofol use. It occurs when a patient develops profound bradycardia that progresses to asystole in addition to one of four related conditions: metabolic acidosis, rhabdomyolysis, hyperlipidemia, or enlarged or fatty liver. According to an article by Loh, et al., in the journal Continuing Education in Anaesthesia, Critical Care & Pain, the occurrence of PRIS is not necessarily related to the dose or rate of propofol, but it may more commonly occur with continuous infusion, such as when providing ongoing sedation in the ICU. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 34 Patients who develop PRIS are more likely to have neurological injuries, to have simultaneous infusions of either corticosteroids or catecholamines, and may be younger in age. It may present as metabolic acidosis as a result of lactic acidosis and poor renal function. The patient often develops ECG changes suggestive of cardiac instability, including ST-segment elevations. Other cardiac arrhythmias may also be present. There are increased levels of lipids in the bloodstream as well as increased serum creatine kinase and myoglobin from skeletal muscle tissue breakdown. The management of PRIS involves continual monitoring of the patient’s condition, including laboratory levels of triglycerides, creatine kinase, and tests of kidney function, as well as cardiovascular changes noted with hemodynamic monitoring. The propofol should be discontinued as soon as PRIS is suspected and the drug replaced with another sedative agent.96 Unfortunately, PRIS can be very difficult to treat once it develops, which further supports the idea that propofol use must be done very carefully. Although the drug is very active and successful at inducing sedation and memory loss of potentially traumatic procedures, it is always used with caution. Butyrophenones Butyrophenones are a type of antipsychotic medication that may be administered for the management of various conditions, including acute psychosis or confusion. These drugs may also be referred to as neuroleptic medications or major tranquilizers. The two most common types of butyrophenones administered in critical care within the United States are haloperidol (Haldol®) and droperidol (Dridol®).1,11,97-101 There is greater potential for development of delirium within the intensive care environment; some sources state that delirium in this patient population can vary between 20 and 80 percent. The patient who develops nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 35 delirium typically exhibits a change in mental status, confusion, and memory loss that could cause agitation and aggression. The individual may have a depressed level of consciousness as well. Delirium is thought to develop in this population due to a variety of factors, including an alteration in oxygen levels to the brain, particularly following times of decreased oxygenation, the presence of infection or sepsis, severe pain from procedures or surgery, as a symptom of acute or chronic illness, or with concomitant administration of certain medications, including some analgesics and benzodiazepines. Unfortunately, despite the prevalence of delirium within critical care, the condition is often not recognized until the patient has suffered from its negative effects. Delirium is associated with an increased length of stay in the hospital, increased time needed for mechanical ventilation, and overall increased patient mortality. Butyrophenones may be given to patients who have developed delirium and who are suffering because they cannot think clearly, they have altered mental status, or they suffer from hallucinations. The administration of these kinds of antipsychotics can help patients overcome many of these symptoms and may be calming during this potentially frightening time. Additionally, some patients who are cared for in the ICU have dementia, which although different from ICU-related delirium, can still cause profound difficulties with thought control, memory, and problems with sleep. Dementia is permanent and develops slowly over time, as opposed to delirium, which can develop quickly with hospitalization. Some patients with dementia are at greater risk of developing delirium, as well. Haloperidol is a major antipsychotic often used for the management of schizophrenia. It exerts its effects by blocking dopamine receptors to relieve nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 36 hallucinations, confusion, and delusions. Historically, haloperidol has been a first choice of treatment of ICU delirium, however, it does carry an increased risk of adverse effects, some of which could be life-threatening. Some patients who have been given haloperidol have suffered from severe cardiac effects, including sudden death, QT prolongation, and torsades de pointes. Additionally, use of some antipsychotics such as haloperidol may lead to an increase in overall mortality among elderly patients with dementia-related psychosis. Studies regarding the use of haloperidol for management of delirium in ICU patients have been conflicting. A 2013 study in The Lancet looked at whether treatment with haloperidol would decrease the amount of time that critically ill patients would spend in delirium and found that administration of haloperidol did not necessarily decrease the length of delirium in studied patients. Alternatively, a 2014 review by Reade, et al., in The New England Journal of Medicine reported on studies that considered prophylactic haloperidol and determined that its administration prior to surgery reduced the severity and duration of delirium and that low-dose haloperidol decreased delirium during anesthesia induction. The research regarding the safety and effectiveness of haloperidol will continue and some experts advise to use other forms of antipsychotics for ICU delirium instead. Droperidol is another example of a butyrophenone medication. It is given as an injection and has been approved for the management of nausea and vomiting associated with surgery. It also has a marked tranquilizing effect and acts as a sedative, which can be calming to the anxious or distressed patient. A person who receives droperidol is more likely to feel relaxed and tranquil but does not necessarily experience a change in level of consciousness. Droperidol acts as an alpha-adrenergic antagonist and may nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 37 cause vasodilation, which can work against some of the effects of vasopressors. In a manner similar to haloperidol, droperidol can also cause negative cardiac effects, including QT prolongation and torsades de pointes, which could lead to sudden cardiac death. It should therefore never be given to a patient with a history of cardiac ECG abnormalities, particularly with QT abnormalities. It can be given intravenously or as an intramuscular injection; a typical single dose for an adult patient is 2.5 mg IV or 5 mg IM. Whether a person is exhibiting an altered mental status related to his medical condition or if he is suffering from acute psychosis, the administration of neuroleptic medications can be helpful in controlling symptoms. Although some of the safety factors associated with butyrophenones have been called into question, there are many cases where these types of drugs are appropriate and their use is warranted. As with administration of other kinds of medications in the critical care setting, continued monitoring for side effects and therapeutic outcomes when giving these drugs is essential to maintain patient safety and comfort. Opioids Opioid analgesics are commonly administered for pain control in the ICU as well as in the emergency department. Pain is frequently associated with the injuries and illnesses that require critical care; often, the pain is so intense that the affected patient requires rapid but ongoing relief. Opioid drugs are designed to manage the moderate to severe pain that often develops within this population. Many patients in these areas are also subjected to painful procedures that require opioid analgesia prior to start and after treatment is complete. There are any number of procedures that are painful for the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 38 patient, including wound care and dressing changes, placement of drains and tubes, suctioning of endotracheal tubes, or placement of central venous catheters. The American College of Critical Care Medicine recommends preemptive and prophylactic analgesia prior to painful procedures to alleviate pain in the ICU patient, including the administration of opioid analgesics.1,26,102 Opioid analgesics are the first-line drug of choice to treat non-neuropathic pain in critically ill adult patients. The type of opioid drug administered depends on the patient’s current medical condition. Since certain opioids may be metabolized and excreted in slightly different manners, one patient may tolerate the effects of a specific type of opioid, but another person in the same unit who is also experiencing pain may have a condition that would negatively affect the distribution or metabolism of the same drug. Additionally, drug doses of opioids are often prescribed with a range in mind, depending on the amount of pain the patient is experiencing and the extent of relief gained from the particular kind of drug. Within critical care, most opioids are given intravenously since this method eliminates the step of drug absorption and the drug is already given into systemic circulation. The patient can then achieve pain relief much more quickly than when given the drug through an oral or intramuscular route. Further, many patients in the ICU have altered gastrointestinal functioning: they may require enteral feedings through a nasogastric tube, they are NPO because of a treatment, or they may be so ill that they are unable to eat at all. In these cases, it is impractical to administer oral opioid analgesics and these patients would obviously require intravenous administration. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 39 As discussed, healthcare providers who care for patients in the critical care environment must be aware of any procedures that might induce pain as well as whether the patient is experiencing pain due to his overall condition. Frequent monitoring before, during, and after treatments is essential for providing pain control. Morphine is one of the most commonly administered opioid analgesics in critical care; it is frequently given for control of acute pain in the emergency department, as well as for pain due to procedures such as surgery or bedside treatments given in the ICU. It is classified as a Schedule II narcotic, and morphine has been shown to be effective in managing moderate to severe pain. It can be given safely with few side effects when monitored appropriately. Within critical care, morphine is almost always administered intravenously. For some patients who are conscious and alert, morphine delivery through patient-controlled analgesia (PCA) is a viable option for pain control over a period of hours or days of receiving care. When given intravenously, morphine has a rapid onset of action and it exerts its effects within approximately 20 minutes of administration. Its duration of action may last 4 to 5 hours. It is widely distributed and is metabolized by the liver. It has a half-life of approximately 2 to 4 hours in adults, but this amount is shorter in children. The actual dosing guidelines for morphine can vary widely; because morphine is also frequently given for control of pain associated with cancer, its chronic use may sometimes require very large doses for those patients. For non-cancer pain, adult patients may receive anywhere from 4 to 15 mg IV of morphine every 3 to 4 hours, based on pain intensity. For continuous infusion, morphine is often administered at a rate of 0.8 to 1 mg/hour, which may be given after an initial bolus dose. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 40 The most common side effects of morphine involve changes in central nervous system functioning; for a patient who is normally alert, this may mean an altered level of consciousness, dizziness, sedation, or even hallucinations. Morphine can also affect the nerve supply to the gastrointestinal tract, leading to constipation, nausea, and vomiting. Other side effects and complications of morphine include hypotension, bradycardia, blurred vision, and respiratory depression, which can be life threatening if not recognized quickly and promptly treated. Fentanyl is another kind of opioid analgesic commonly administered to patients in the emergency room and in the ICU for moderate or severe pain. Fentanyl may be administered through various routes, including intravenous, transdermal, and epidural methods, but it is often effectively administered as an intravenous preparation. As with morphine, fentanyl may be given through PCA for some patients. When given as an intravenous injection, it may be called by its brand name, Sublimaze®. Fentanyl has very powerful analgesic effects; it is said that a 0.1 mg dose of fentanyl is equivalent to 10 mg of morphine. Additionally, fentanyl does not produce histamine, which is a relatively common effect of some other opioid analgesics. Because of this, fentanyl is less likely to cause itching or hemodynamic instability. Fentanyl is also less likely to cause respiratory depression when compared to morphine, but because it is an opioid analgesic, it could lead to a slowed breathing rate. Patients who are given fentanyl may also experience bradycardia, dizziness, muscle stiffness, somnolence, and possible chest discomfort. In addition to morphine and fentanyl, there are various other kinds of opioid analgesics that may be used to successfully control patient pain in the ICU or nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 41 the emergency department. Most opioids, when titrated to effectiveness for each patient’s condition, are equally effective at controlling moderate to severe pain. Other examples of opioid analgesics that may be considered for use in critically ill patients include hydromorphone, methadone, and remifentanil hydrochloride (Ultiva®). Note that the administration of meperidine is not recommended in critically ill patients because of its risks of causing neurotoxicity. The administration of analgesic medications should not be limited to painproducing procedures. Although patients in the ICU commonly experience pain because of undergoing certain medical treatments, these patients also often experience pain at rest. All patients in critical care should be frequently assessed for pain while at rest in addition to pain associated with treatment measures. Based on the continual assessment and evaluation of pain, the appropriate dose of analgesia can be determined. Non-opioids Non-opioid analgesics are administered for treatment of mild-to-moderate pain and they may be given as adjuvants to opioids or other GABA analog drugs to decrease some of the adverse effects that may be associated with opioids. Non-opioid analgesics have slightly different mechanisms of action, depending on the drug used. Although they often can be used without a prescription, non-opioid analgesics may still cause adverse effects that can be significant. They can be administered orally as tablets or capsules, but within critical care, they are more likely to be given as intravenous preparations. Some of the more common non-opioid analgesics include acetaminophen, ibuprofen, and ketorolac.1,102 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 42 As discussed, acetaminophen is a mild pain reliever that has anti-pyretic qualities as well. Unlike NSAIDs, acetaminophen does not necessarily relieve inflammation. Its exact mechanism of action is not well understood. Historically, acetaminophen has only been given as an enteral or rectal dose, but in 2010, an intravenous preparation (Ofirmev®) was approved for use. Intravenous acetaminophen is given for moderate pain and is used as an adjunct to opioid medications. Its use may also decrease some of the need for larger amounts of opioids. The drug has a half-life of 2 hours and it exerts its effects within 5 to 10 minutes of administration. The appropriate dose of acetaminophen is 1000 mg, given every 4 to 6 hours, but not to exceed 4 g in 24 hours total. One of the more common types of NSAIDs, ibuprofen is a non-opioid analgesic that is useful for controlling mild-to-moderate pain and inflammation. As with acetaminophen, ibuprofen can be given as an adjunct to opioid analgesics to reduce opioid use and side effects. Ibuprofen has also been traditionally given as an oral preparation, but it is available in IV form as well. The FDA approved it for IV use in 2009. Ibuprofen is a non-selective COX inhibitor, which means that it inhibits both COX-1 and COX-2 enzymes that are responsible for creation of prostaglandins that contribute to pain. In addition to its control of pain and inflammation, ibuprofen may also act as a fever reducer. It can cause damage to the gastrointestinal tract, including development of ulcers and bleeding, and so should be used with caution in any patient with a history of gastrointestinal disease, as well as anyone with bleeding tendencies. Ibuprofen IV is administered as 400 to 800 mg every 6 hours and the dose is infused over a period of at least 30 minutes. A patient should not receive more than 3.2 g in 24 hours. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 43 Ketorolac (Toradol®) is also used for treatment of moderate pain. As with ibuprofen, ketorolac is an NSAID that also acts as a non-selective COX inhibitor to control pain and inflammation. It may be administered as an IV or intramuscular injection. Ketorolac has a half-life of up to 8 hours and a time of onset within 10 minutes of administration. It can be given as 30 to 60 mg once every 6 hours, and it should not be used for more than 5 days at a time. Because pain involves so many factors, the combination of non-opioid pain medications with opioid analgesics is often very effective in reducing pain in most patients and promoting comfort. Non-opioid analgesics, because they are less powerful than opioids, should not be used as the sole analgesic for pain control in patients, particularly those recovering from surgery or those undergoing painful medical procedures. However, when an individual is suffering from mild or moderate pain, non-opioid drugs may be used. Further, they are particularly helpful when interspersed with opioids on a rotating basis. For instance, a patient recovering from surgery may have severe pain and may be given an opioid analgesic, followed by a non-opioid analgesic shortly thereafter to maintain a state of comfort. Eventually, the person may be able to transition from intensive opioid use to non-opioids. Despite their lack of narcotic activity, non-opioid drugs are very valuable components when handling patient pain. Dopamine Dopamine hydrochloride is a vasopressor medication most commonly administered for the control of blood pressure and prevention of hypotension. A common brand name of dopamine is Intropin®.1,23 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 44 Dopamine is normally produced within the body as a neurotransmitter that works to improve cardiac function by increasing cardiac contractility and increasing heart rate and it improves blood flow to the tissues. Dopamine hydrochloride is a synthetic version of the neurotransmitter; it is formed from the amino acid L-DOPA and is a precursor to the neurotransmitter norepinephrine. Dopamine may be administered for any condition in which a patient has severe cardiac compromise; common situations may include severe injuries associated with trauma; heart failure or kidney failure, following cardiac surgery, or in cases of myocardial infarction. Dopamine is sometimes administered to newborn, premature infants with cardiac instability when a congenital heart defect is present. Dopamine is given as an intravenous injection via continuous infusion; it is typically not given as a bolus or intermittent infusion. It is available as a powder that must be diluted prior to use, however, in many facilities that have pharmacies that prepare IV medications, dopamine may be available to bedside clinicians already diluted and ready for administration. It has an approximate half-life of 2 minutes. Once given, dopamine acts as an agonist on dopaminergic receptors to exert its effects. It is metabolized by the liver and kidneys and is excreted in the urine. The amount of dopamine ordered varies slightly depending on the reasons for its administration. Typically, a dose ranges between 1 and 5 mcg/kg/minute, given by a continuous intravenous infusion, but the usual adult dose can be between 0.5 and 12 mcg/kg/minute, depending on severity of the patient’s condition. The amount may be titrated based on the patient’s response. A person who has continuous hemodynamic monitoring nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 45 may need dopamine titration based on his blood pressure values. The rate of dopamine administration can be increased or decreased as the blood pressure values fluctuate until he reaches a stable level. Because dopamine is given at a specific rate per kg per minute, the healthcare provider must first obtain an accurate patient weight and convert it to kilograms. The rate per kg per minute requires careful calculation for accurate therapeutic administration. As an example, a patient who weighs 220 lb. has an order for 8 mcg/kg/minute of dopamine. The drug is available as 800 mg in a 500 mL bag of D5W. This would be calculated as: 8 mcg x 99.8 kg (220 lb.) x 60 = 47.9 mg/hr 1000 47.9 mg x 500 mL = 29.9 mL/hr 800 mg This amount can then be recalculated as needed to increase or decrease the rate of the infusion, based on the patient’s response. Side effects of dopamine may be related to its effects on vasoconstriction and increased cardiac contractility, including tachycardia and palpitations, angina, atrial fibrillation, and ectopic heartbeats. Additionally, dopamine hydrochloride can cause side effects of nausea, vomiting, headache, anxiety, and dyspnea. A patient who has hypovolemia due to blood loss will require other measures of support to correct volume depletion before dopamine can be effective. In other words, with excess volume loss, dopamine’s effects of vasoconstriction will not correct blood pressure enough to prevent shock. The patient must nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46 first receive circulatory support through infusion of colloids or crystalloid solutions before being given dopamine. There are some cases where dopamine should not be given because of its interactions with other drugs or substances. Patients with pheochromocytoma, which is a tumor that develops on the adrenal gland, should not receive dopamine because the pheochromocytoma tumor secretes excess catecholamines, including epinephrine and norepinephrine. Dopamine is also a catecholamine, and the excess release of these substances could lead to organ damage. Additionally, dopamine has been shown to interact poorly when given to those who already take monoamine oxidase inhibitors (MAOIs), because of their effects on neurotransmitters in the brain. Consequently, any patient who already takes MAOIs should receive a reduced starting dose of dopamine, approximately 1/10th of a normal dose given. Because of its effects on the cardiovascular system, dopamine requires continuous hemodynamic monitoring throughout its use to determine fluctuations in patient blood pressure. The patient’s clinical status must also be monitored, as with use of any type of pressor. Since dopamine is typically given when a patient is already quite ill to begin with, routine monitoring and close supervision will most likely already be in place. Dobutamine Dobutamine (Dobutrex®) is primarily used in cases of decreased cardiac output and low blood pressure, particularly in states of cardiogenic shock. Dobutamine is an inotropic agent that is designed to improve heart muscle function. It stimulates the beta receptors of the heart to cause an increase in heart rate and cardiac contractility. Dobutamine actually has an affinity for nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 47 both beta-1 and beta-2 receptors; when stimulating the beta-1 receptors, it acts as an inotrope and when stimulating beta-2 receptors, it can promote mild vasodilation. The drug is meant to only be used as a short-term preparation.1,23,23,103 A standard dose of dobutamine ranges from 2.5 to 10 mcg/kg/minute; as with dopamine, dobutamine is almost always given as a continuous intravenous infusion and not as an intermittent bolus. Once administered, its onset of action is within two minutes, leading to a fairly rapid response. It may be titrated based on patient response and by parameters ordered by the physician. For example, a patient’s dose of dobutamine may be increased as needed every 15 to 20 minutes by 2 mcg/kg/minute based on the receiving patient’s blood pressure response. In cases of decreased cardiac function because of shock, the patient may exhibit poor perfusion and decreased oxygenation because of poor cardiac output, which can greatly increase overall mortality. Administration of dobutamine for treatment of shock can increase blood flow through increased cardiac output and can promote tissue oxygenation. It has a halflife of 2 minutes. As with dopamine, dobutamine given in the presence of hypovolemia cannot be expected to correct low volume. When cardiac arrhythmias, including atrial fibrillation, are present, the patient requires an antiarrhythmic agent such as digoxin prior to receiving dobutamine; the arrhythmia should be treated first to prevent a deleterious response. Dobutamine causes side effects related to its effects on the cardiovascular system, including angina, ectopic heartbeats, an increase in atrioventricular nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 48 conduction, and tachycardia. It may also lead to an increase or decrease in blood pressure. Other adverse effects often seen with dobutamine include nausea, vomiting, paresthesia, dyspnea, and leg cramps.24 Although dobutamine causes initial vasodilation, some patients may experience such an increase in heart rate that systolic blood pressure levels may also greatly increase, requiring a dose reduction. The routine and continuous monitoring of patient hemodynamic status is essential with administration of dobutamine to prevent complications of cardiac arrhythmias, tachycardia, and hypertension. Isoproterenol Isoproterenol (Isuprel®) is an inotropic sympathomimetic drug used for the management of certain cardiovascular conditions, including myocardial infarction, hypotension leading to shock, heart failure, and certain cardiac arrhythmias. Isoproterenol works by stimulating the beta-1 receptors in the heart and the beta-2 adrenergic receptors found in the lungs and in the arteries of the skeletal muscles.1,34,35,38,113 Stimulation of the beta-1 receptors causes an increase in cardiac contractility, thereby improving the heart rate and the strength of the heart’s contractions. Beta-2 receptor stimulation dilates the size of the bronchioles, which improves respiratory rate by increasing air flow. The arteries of the skeletal muscles are also dilated, which increases blood flow to the muscles. Isoproterenol has an almost immediate onset of action when it is administered intravenously. It has a half-life of 2.5 to 5 minutes and its effects can last almost 15 minutes. Because of this, isoproterenol may need to be given as a repeat bolus dose or as a continuous infusion, depending on nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 49 the reasons for its use. It is rapidly distributed through the bloodstream following administration, metabolized at various locations in the body but primarily in the liver, and excreted through the urine. Side effects associated with isoproterenol include tachycardia, palpitations, diaphoresis, cardiac arrhythmias, tremor, and pulmonary edema. The increase in cardiac contractility leads to an increase in oxygen consumption and the patient may experience angina. Additionally, some people experience increased feelings of anxiety, restlessness, nervousness, headache, and dizziness. Within critical care, isoproterenol is primarily used in cases of cardiovascular compromise to support the patient’s hemodynamic system and improve blood flow. This is often during emergency cases or very critical situations in which the patient is suffering from a life-threatening condition. According to the manufacturer’s guidelines, isoproterenol is indicated in cases where shock or pacing is either not necessary or is not yet available, such as in cases of heart block, bradycardia, myocardial infarction and cardiac arrest; and for cases of bronchospasm that can develop during surgery and with mechanical ventilation. Because isoproterenol has significant effects on the cardiovascular system, it is also used in off-label methods with some success. Isoproterenol has effectively been used in some cases where other cardiac medications have not been successful in increasing cardiac contractility, in episodes of ventricular arrhythmias, or in patients receiving treatment for overdose of beta-blocker medications. Formerly, isoproterenol was administered as part of the algorithm of advanced cardiac life support (ACLS), but it is no longer considered to be a first-line treatment. Instead, isoproterenol should only be nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 50 administered after atropine, dopamine, and epinephrine if pacing is not available. It is never given to pediatric patients as part of advance life support procedures for cardiac arrest; it is only given for episodes of bronchospasm associated with status asthmaticus in this population. Isoproterenol is almost always administered as a continuous infusion and very rarely as a bolus dose, except in certain cases of off-label use, such as with rare, inherited conditions that cause cardiac arrhythmias. Even in these cases, isoproterenol is administered with a bolus dose followed by infusion. For most adults, the usual dose range is 0.1 to 1.5 mcg/kg/minute. Any patient that receives isoproterenol should be closely monitored for side effects of vasodilation, including the effects of hypotension. Isoproterenol has been implicated as possibly being responsible for the development of life-threatening cardiac arrhythmias, which further supports its need for frequent monitoring with use and discontinuation as soon as feasibly possible. A case study in The Journal of Innovations in Cardiac Rhythm Management discussed a situation where a female patient was admitted for treatment of narrow-complex tachycardia. She underwent electrophysiology studies to determine the source of the tachyarrhythmia and received an infusion of isoproterenol during the procedure, which lasted approximately 90 minutes. Following electrophysiology, she developed severe hypotension that progressed into pulseless electrical arrest and which required CPR. The healthcare team was able to resuscitate the patient and her initial hemodynamic studies showed damage consistent with stressinduced cardiomyopathy, a condition in which the left ventricle becomes enlarged, yet there is not evidence of an obstruction in the coronary arteries. The condition is sometimes called “broken heart syndrome.” The patient recovered from the cardiomyopathy after several weeks, but the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 51 case study authors postulated that the condition developed because of the infusion of isoproterenol. Their theory is that the isoproterenol caused the cardiomyopathy because of its potential for cardiac arrhythmias and that a prolonged infusion in this case led to the release of more catecholamines that contributed to the left ventricular damage. Further studies are needed to determine whether isoproterenol infusions can have this direct effect; additionally, the case study itself remained a hypothesis of the negative effects of isoproterenol, rather than a clinically proven causative factor in the cardiomyopathy. Due to its effects on the cardiovascular system, in particular the vasodilation of the blood vessels, isoproterenol should not be administered with other drugs with vasodilatory effects, such as dopamine. Because cardiac arrhythmia is one of the major side effects associated with isoproterenol, the patient who receives this drug should be placed on hemodynamic monitoring during administration, including continuous ECG, blood pressure, and heart rate monitoring, with care observation and assessment for any changes in cardiac rhythms. Phosphodiesterase Inhibitors Phosphodiesterase (PDE) inhibitors are drugs that work by blocking the effects of phosphodiesterase, an enzyme that contributes to various functions within the body. The PDE inhibitors are classified into different groups that range from PDE1 to PDE12. The PDE3 and PDE5 inhibitors are the most commonly administered drugs within critical care. PDE3 inhibitors are given to strengthen the intensity of cardiac contractions by decreasing preload and afterload, thereby increasing cardiac output. They are most often used for heart failure, particularly in cases that are otherwise unresponsive to other treatments.1,104-106 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 52 The drugs are thought to work by increasing the movement and storage of calcium in the cardiac cells. One of the more commonly administered PDE inhibitors that may be used in critical care is milrinone. Cilostazol, another PDE3 inhibitor, may be administered for some patients who suffer from intermittent claudication as a result of peripheral artery disease. Milrinone is an inotropic agent in that it strengthens the heart muscle; it also acts as a vasodilator to improve blood flow. Cyclic adenosine monophosphate (cAMP) is a signaling molecule, called a second messenger, that triggers physiological cell changes and that plays a role in metabolism and regulation of hormones. Milrinone acts as a selective inhibitor for cAMP phosphodiesterase enzymes in the heart and the smooth muscles of the blood vessels. This action impacts the movement of calcium into the cell and increases the force of the cardiac contraction. Milrinone can also increase left ventricular pressure and cause a vasodilatory effect. Milrinone is administered by IV infusion; it may take effect within 15 minutes of administration. For patients with heart failure, milrinone leads to decreased vascular resistance, decreased capillary wedge pressure, and slightly increased heart rate. The administration may then increase urine output in this population and if a patient with heart failure also has a prescribed diuretic, the dose may need to be adjusted. Milrinone has also been shown to improve symptoms of pulmonary hypertension in patients with heart failure. An article in the Annals of the American Thoracic Society stated that milrinone is often a first choice of medication among patients in this population. Although milrinone acts as an inotropic agent, it has less effect on the cardiac conduction system and will not increase cardiac output so much as to affect pulmonary artery pressures. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 53 The PDE5 inhibitors are most commonly known for their effects on circulation for the treatment of erectile dysfunction; an example of one of these drugs is sildenafil (Viagra®). However, they may also be implemented for treatment of some patients with pulmonary hypertension, which occurs as an increase in pulmonary artery pressure that leads to increased vascular resistance and ultimately, heart failure. Pulmonary hypertension can cause a decrease in PDE5, also known as cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5, as well as a decrease in the production of nitric oxide, which acts as a vasodilator. PDE5 is produced in the lungs and breaks down cGMP, which is normally responsible for keeping the blood vessels dilated. Inhibition of PDE5 then produces an opposite effect and allows vasodilation. The effects of sildenafil can be used to increase blood flow to correct erectile dysfunction, but the same effects improve vasodilation in the pulmonary vasculature to manage pulmonary hypertension. When administered for the latter purpose, it is marketed under the brand name Revatio®. Revatio may be given as an oral medication or as an IV injection. When administered intravenously, the dose is 2.5 to 10 mg three times per day, given every 4 to 6 hours. The drug has a half-life of approximately 4 hours. Patients who have been given Revatio have been shown to achieve a significant reduction in pulmonary artery pressures after administration. There are different types of pulmonary hypertension that are classified by the World Health Organization, so research into the effectiveness of different PDE inhibitors is an ongoing process. The continued use of both PDE3 and PDE5 inhibitors may provide prospective treatment for other forms of cardiac disease and hypertensive states in critical care patients in the future. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 54 Epinephrine Epinephrine is a natural substance in the body that has several actions, including that of a hormone and a neurotransmitter. Epinephrine is normally created from norepinephrine within a specific area of the kidneys. It works by increasing blood flow to the tissues and improving cardiac output.1,41,85-88 When given as a medication, epinephrine binds to alpha-1 adrenergic receptors found in the blood vessels. This binding effect causes vasoconstriction, which improves blood pressure and can relieve hypotension. A patient with such hypotension as to affect blood flow and oxygen to the critical organs may respond to epinephrine administration, thus restoring adequate blood flow. Binding of epinephrine to the alpha-1 adrenergic receptors also improves cardiac output, further increasing circulation of oxygenated blood. The increased cardiac output is manifested as an increase in cardiac contractility (an improvement in the force of the heart’s contractions), as well as an increase in heart rate and improved conduction of the heart’s electrical system through the atrioventricular node, which stimulates the heart to contract. Epinephrine is also a beta-1 and beta-2 receptor agonist in that it stimulates the beta receptors in the heart, which also promotes cardiac contractility. It stimulates the beta-2 receptors in the lungs and in the skeletal muscles, which increases blood flow to these sites, thereby improving breathing mechanisms and skeletal muscle movement. Epinephrine is one of the main drugs given during ACLS; it is particularly effective for the treatment of situations in which the patient has suffered cardiac arrest. During an emergency, epinephrine can be administered in 1 of 3 ways: intravenously, through an endotracheal tube, or through the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 55 intraosseous method. The doses are slightly different, depending on the route of administration. When given as a rapid push intravenously or into the bone through the intraosseous method, the dose is administered as 0.1 mg of a 1:10,000 solution, given every 3 to 5 minutes, as needed. Endotracheal administration is also given as a bolus dose; during ACLS, epinephrine can be administered directly into the endotracheal tube when ventilation is stopped momentarily to instill the medication directly. In this method, the epinephrine is absorbed through the lungs. The dose to administer when the drug is given through the endotracheal route is 2 to 2.5 mg epinephrine, diluted in 10 mL of normal saline. Epinephrine is sometimes referred to as adrenaline, and it is associated with the fight-or-flight mechanism. During times of acute stress, the sympathetic nervous system is stimulated and body processes speed up, including heart rate and muscle tone, as a result of the release of stress hormones, including epinephrine. This natural occurrence increases the heart rate and blood pressure normally in response to fear. Epinephrine then has a similar effect when it is administered as a medication. At low doses, epinephrine causes increased output; greater doses of epinephrine result in increased MAP due to greater levels of vasoconstriction. Of note, when a patient has suffered ischemia due to myocardial infarction, epinephrine should be used with caution. The increase in blood flow and cardiac contractility produced by the drug can raise blood pressure but also increase demand for oxygenated blood for the heart. This may actually cause the opposite of the intended effect by worsening ischemia. Epinephrine can be used for the treatment of septic shock and is considered the second choice of drug to administer, following norepinephrine. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 56 Additionally, epinephrine may be added to norepinephrine in some cases that otherwise show poor response to initial treatment. Some studies have shown that addition of epinephrine after initial norepinephrine dosing resulted in improved hemodynamic parameters because the epinephrine is thought to augment the effects of norepinephrine through is inotropic and vasoconstrictive actions. The decision of whether to add epinephrine after initial dosing with norepinephrine in cases of septic shock should be based on the patient’s clinical response. The patient’s clinical status will often be the first indicator of whether epinephrine administration has been successful in improving cardiac output and blood pressure. Typically, epinephrine is administered in situations where the patient is already receiving continuous hemodynamic monitoring, which will reflect sometimes even minor fluctuations in MAP and central venous pressure. The patient’s response is a useful indicator to guide administration of epinephrine, whether by hemodynamic changes following continuous infusion or by rapid bolus to stimulate the heart after arrest. Norepinephrine Norepinephrine is a naturally-occurring neurotransmitter in the body that affects the sympathetic adrenergic nerves. It is synthesized and released from the nerves following a combination of steps involving the release of the amino acid tyrosine, which is converted to DOPA and then to dopamine, which acts as a precursor and facilitates release of norepinephrine.1,37-40,86 Following release, much of the norepinephrine is eventually taken back up into the nervous system; however, some is also released into capillary circulation. Larger amounts of sympathetic stimulation lead to an increase in nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 57 norepinephrine release into circulation, which causes vasoconstriction and supports cardiac contractility. When administered in the clinical care setting, norepinephrine may be called by its brand name of Levophed™. It acts as an alpha-adrenergic receptor agonist to cause vasoconstriction, thereby increasing blood pressure and relieving some hypotension. Note that alpha-adrenergic receptors are not located within the skeletal muscles, as the beta receptors are. This is because when the alpha receptors are stimulated, they constrict, which is good for central blood pressure, but vasoconstriction within the muscle tissue is not necessarily helpful in the relief of hypotension and the skeletal muscles need to keep these arteries dilated in order to receive as much blood flow as possible. Norepinephrine also acts on the beta-adrenergic receptors of the heart to dilate the coronary arteries, resulting in more blood flow to the heart and improving its ability to contract. Norepinephrine is primarily used for the management of significant hypotension caused by certain disease states. It may also be administered in cases of cardiac arrest that result in life-threatening hypotension. Norepinephrine is always administered by intravenous injection, preferably into a central line rather than a peripheral IV. Due to its vasoconstrictive effects, norepinephrine has the potential to cause side effects associated with hypoxia from a lack of blood flow to certain tissues. While vasoconstriction can improve blood pressure, it can also increase the risk of obstruction within circulation, possibly leading to tissue ischemia. Other side effects that have been noted with norepinephrine include bradycardia, cardiac arrhythmias, anxiety, headache, and respiratory difficulties. When norepinephrine is administered as continuous infusion, the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 58 patient should also receive concomitant fluid and electrolyte therapy to support circulation and blood pressure maintenance. This recommendation also prevents the significant drop in blood pressure that could occur when norepinephrine is discontinued. The typical rate of administration of norepinephrine for adult patients is between 0.01 and 0.2 mcg/kg/minute. If possible, when first administering norepinephrine for correction of hypotension, the infusion rate should start out slowly and the patient should be monitored closely for the effects of the drug. The blood pressure level, once increased to a low-minimum systolic level (~90 to 100 mmHg) can then be maintained with the current rate of norepinephrine to avoid organ and tissue ischemia. When vasopressors are needed to sustain adequate blood pressure in the critical care setting, early administration of norepinephrine is preferable to delaying administration and has been shown to reduce overall mortality in ICU patients. A study by Bai, et al., in the journal Critical Care showed that timing of vasopressor administration matters more than the actual kind of vasopressor given and that a greater delay in administration of norepinephrine for treatment of hypotension associated with septic shock was related to a significantly increased risk of death. The study showed that in cases of septic shock that were under review, for every one-hour delay that norepinephrine was initiated, there was an increase in mortality rate by 5.3 percent. Each case may vary slightly in which vasopressors are needed and the actual time of the drug is given. As discussed, there are some cases in which fluid resuscitation is needed to correct hypovolemia before pressors such as norepinephrine can be given; alternatively, sometimes excess fluid volume is unnecessary to correct hypotension and would actually be detrimental to the patient’s condition. When this occurs, the delay of nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 59 administering norepinephrine has been shown to be harmful for some patients. In cases of septic shock, norepinephrine is considered the first choice of vasopressor to use for correction of arterial blood pressure. Researchers arrived at this conclusion after extensive testing and analyses of research results. Although dopamine can also be used as a vasoconstrictor, norepinephrine works more rapidly than dopamine; it also produces a stronger response that is more consistent in its effects. Further studies are needed to consider the success of norepinephrine in comparison to other types of vasopressor medications. Phenylephrine The drug phenylephrine is given to counteract the effects of hypotension, particularly among patients undergoing anesthesia or those with septic shock. Phenylephrine is an alpha-1 agonist, so it binds to these receptors in the vascular smooth muscles to cause vasoconstriction.1,58,84-86,89 Prior to administering phenylephrine, the clinician should ensure that the patient’s blood volume levels have been corrected, as the drug may not be effective when hypovolemia is present. Further, metabolic acidosis may also impact the effectiveness of phenylephrine, so patient monitoring with arterial blood gases and for symptoms of respiratory compromise should be considered and corrected prior to administration. Phenylephrine may be given as a bolus dose or continuous infusion, depending on the conditions in which it is administered. It is more likely to be given as a bolus in cases where a patient has hypotension due to surgical anesthesia. When administering a bolus, a typical initial dose is 50 to 250 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 60 mcg, with the patient being constantly monitored for blood pressure effects. Following an initial bolus, an ongoing infusion of phenylephrine may be needed, depending on patient response. Phenylephrine may be administered as part of treatment for septic shock, however it is not considered a first choice when compared to norepinephrine. The Surviving Sepsis Campaign states that in cases of septic shock, phenylephrine should only be used when norepinephrine could cause cardiac arrhythmias, where the patient has consistently low blood pressure but not decreased cardiac output, or as another resort when the patient has not responded to other treatments. When given for treatment of shock, phenylephrine should only be administered as continuous infusion and not as a bolus dose. A dose of 0.5 to 6 mcg/kg/min may be given on a continuous basis and titrated according to blood pressure response. Note that doses greater than 6 mcg/kg/min are not necessarily associated with higher levels of blood pressure. In a manner similar to some other types of vasopressors, phenylephrine can cause some negative effects associated with the cardiovascular system. It may worsen cases of angina, if present, because it can affect the vasoconstriction of the coronary vessels. Additionally, patients who have suffered spinal cord injuries or have neurogenic shock should not be given phenylephrine because it could cause reflex bradycardia. Finally, the use of phenylephrine, when combined with other pressor drugs that cause vasoconstriction, can have serious adverse effects, including ischemia. Any patient who experiences bradycardia or symptoms of ischemia when being monitored after phenylephrine administration should have the drug discontinued and may need treatment with an alpha-adrenergic agonist to counteract the effects. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 61 Ephedrine Ephedrine is a drug that is derived from plants of the Ephedra genus; it is used as a treatment for hypotension and for bronchodilation. Ephedrine acts as an alpha- and beta-adrenergic receptor to stimulate heart contractions and promote smooth muscle cell relaxation to improve breathing rates when an individual is suffering from wheezing or asthma-associated conditions.1,109 Some patients, when recovering from anesthesia, may experience hypotension, particularly following spinal anesthesia. Ephedrine may be administered in these cases to counteract the hypotension and to raise blood pressure. It is thought that the increase in blood pressure comes primarily from increased cardiac output of ephedrine and less from peripheral vasoconstriction. Ephedrine is known as an adrenergic activator in that it has the added effect of releasing norepinephrine from storage, which can be beneficial in the circulatory system. The release of norepinephrine in turn affects the adrenergic receptors to exert further effects, which is an indirect activity of ephedrine. Ephedrine is less commonly used as an ongoing infusion in the ICU when compared to its use during surgery for treatment of anesthesia-induced hypotension. The drug may also be administered prophylactically during surgery to reduce the risk of low blood pressure, but the exact dose still needs clarification. A study in the Journal of Anaesthesiology Clinical Pharmacology found that administration of high-dose ephedrine (0.15 mg/kg) during surgery with general anesthesia can have a significant effect in preventing hypotension associated with anesthesia induction. The study compared high-dose ephedrine with low dose preparations (0.07 mg/kg) and nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 62 placebo, and the participants with the least decline in mean arterial pressures were those who received high-dose ephedrine. The induction agents in the study were propofol and remifentanil, however, other drugs given with anesthesia administration can also cause hypotension that may need further treatment with ephedrine. Intravenous ephedrine has a half-life of up to 6 hours and duration of action of 3 hours. It can take effect within 2 minutes of administration. Intravenous administration of ephedrine for acute hypotension may be given as a bolus dose or as continuous infusion. A bolus dose of ephedrine can be given as 200 to 300 mcg IV over 1 minute, and repeated in 15 minutes for effect. This bolus can also be followed by continuous infusion at a rate of 5 to 20 mcg/minute. When given for treatment of bronchospasm associated with asthma, ephedrine may be given as an inhaled preparation. A dose of inhaled ephedrine is given as 100 to 200 mcg (1 to 2 puffs) through metered-dose inhaler, every 4 hours, or 5 mg diluted in 10 mL of sodium chloride every 4 to 6 hours when given through a nebulizer. Note that ephedrine is not necessarily a first choice of treatment for bronchospasm; while useful in releasing constricted bronchioles, there are other agents that may be more therapeutic in these cases. Ephedrine has the potential to produce positive outcomes in patients with unstable blood pressure, although it may not be used as commonly as some other vasopressors. However, because it exerts both direct and indirect adrenergic activity, ephedrine can be considered as a treatment used in the same methods as some catecholamine drugs, including norepinephrine and epinephrine. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 63 Vasopressin Vasopressin is a hormone that can be added to some of the more powerful vasopressors used to control blood pressure (epinephrine, norepinephrine). The addition of vasopressin may further support vasoconstriction to resolve hypotension.1,85-87,106,109 As noted, vasopressin acts on V receptors, found throughout the blood vessels, kidneys, liver, and the brain, to regulate vasoconstriction, body temperature, and urine output. Vasopressin can control some intravascular volume by exerting antidiuretic effects to maintain fluid in the body instead of allowing it to be excreted as urine. Vasopressin does not necessarily increase blood pressure levels when administered to healthy adults, but when given to those who are already suffering from hypotension as a result of disease states, it can produce significant changes in blood pressure. It is indicated for the treatment of hemorrhage, such as in cases of bleeding esophageal varices, to reduce the overall rate of blood loss. During cases of septic shock, vasopressin may be added along with norepinephrine to assist with raising blood pressure levels if the patient is otherwise unresponsive to other pressor therapy. Historically, vasopressin was administered as part of ACLS protocol for treatment of cardiac arrest, but it was removed from the algorithm in 2015. Vasopressin has a half-life of up to 20 minutes, so it is often given as continuous IV infusion to exert its effects. For cases of septic shock, vasopressin is administered at a rate of 0.01 to 0.04 units/hour.108 This infusion rate increases SVR while maintaining normal blood flow in other vital areas, including the brain, lungs, and kidneys. Vasopressin may cause some adverse effects related to blood flow due to vasoconstriction; however, nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 64 side effects are not as common when the drug is given in smaller doses. One of the more common effects is myocardial ischemia, which can occur if vasopressin causes significant constriction of the coronary blood vessels, thereby reducing blood flow to the heart. Vasopressin analogs are drugs that are similar to antidiuretic hormone in that they exert many of the same effects, but they do not have the same chemical structures. One of the more commonly administered vasopressin analogs is terlipressin, which may have some advantages over vasopressin itself. Terlipressin is a type of synthetic vasopressin analog that can be used for management of low blood pressure in cases where there is acute blood loss, such as with treatment of bleeding esophageal varices. In situations such as septic shock when the first drug of choice, norepinephrine is unsuccessful, terlipressin may be administered instead. In studies among animal models studying treatment of hemorrhagic shock, administration of terlipressin has been shown to be beneficial when given during the early stages. A review in the journal BioMed Research International showed that in some cases of hemorrhagic shock, vasopressin was more effective than other types of vasopressors. Note that vasopressin or terlipressin are not indicated for use as the sole pressor for support in cases of shock, including septic shock. A patient who experiences hypotension as a result of shock or bleeding can benefit from administration of vasopressin. While the drug is often not a strong enough vasopressor to be used entirely alone in very critical situations, it is a useful adjunctive medication that can support other pressors in targeting low blood pressure. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 65 Nitroglycerin Nitroglycerin (Nitrostat®, NitroMist®) is a nitrate medication primarily used for the treatment of chest pain associated with angina, as well as for some patients experiencing myocardial infarction, to some people with heart failure or those suffering severe hypertension, and for patients following certain types of cardiac surgery.1,53,55,56,98 Nitroglycerin was discovered for its use as a medication over 150 years ago and is commonly employed as a first-line treatment for patients experiencing cardiac ischemia. The drug is a nitrate that releases the chemical compound nitric oxide. In turn, the nitric oxide activates guanylate cyclase, a type of enzyme that promotes formation of guanosine 3'5' monophosphate in the smooth muscles. The smooth muscles of the blood vessels are regulated by myosin light chains; these chains play a significant role in the contraction of the blood vessels to control vasodilation and vasoconstriction. As a result of the creation of guanosine 3’5’ monophosphate, the myosin light chains are altered through dephosphorylation, leading to relaxation of the muscle cells and consequent vasodilation. Angina develops when the coronary blood vessels that supply blood to the heart become blocked and blood flow is reduced. Most often, this obstruction occurs as a result of coronary artery disease. This feeling is often temporary and can be alleviated by taking a drug such as nitroglycerin to increase the size of the coronary blood vessels and to improve blood flow. An individual who experiences angina may have one of two forms: stable or unstable angina. Stable angina describes the feelings of discomfort that occur after activity or exercise. Increased activity results in increased oxygen demands and blood supply to the heart, but if the coronary blood vessels are occluded, angina can develop. Unstable angina occurs when the individual nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 66 experiences chest pain in the absence of increased activity or movement; the discomfort occurs even when there is not a particular increased demand for oxygenated blood to the heart. Nitroglycerin has been shown to improve discomfort associated with both stable and unstable angina. For many people who have been diagnosed with coronary artery disease and who experience angina, a typical dose as prescribed may be taken at the onset of chest pain. For example, someone who has stable angina and has developed chest pain may administer 1 or 2 sublingual sprays of nitroglycerin to alleviate the pain. If the chest pain remains unresolved after self-administration of nitroglycerin, the person may go to the emergency department for further help. Nitroglycerin is available in a variety of forms and routes for administration. The most appropriate route to use depends on the patient’s current condition and his ability to take the medication. Nitroglycerin can be administered sublingually to be dissolved, as a sublingual spray into the mouth, as an oral tablet or capsule (available as regular and extended-release formulations); as a transdermal patch, typically applied to the chest or back; in ointment form, in which the medication is smoothed onto the skin, and as an intravenous dose. Sublingual tablets of nitroglycerin are available as compressed tablets that can dissolve under the tongue. The sublingual route of administration is most commonly used for management of angina, whether in the emergency department or when the patient is at home and prior to arrival for care. The sublingual form is available in three different strengths: 0.3 mg, 0.4 mg, and 0.6 mg. For the patient who is complaining of angina, one sublingual tablet may be given every five minutes until angina is controlled, however, nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 67 administration of more than three tablets in 15 minutes requires further medical care. Sublingual nitroglycerin is primarily metabolized by the liver, and metabolism is the primary route of drug elimination. It has a half-life of approximately 2 to 3 minutes, and the effects remain for up to 25 minutes after administration. A myocardial infarction is a clinically serious situation, even if it may present with similar symptoms as angina. Unstable angina itself may progress to myocardial infarction; the two conditions are sometimes confused upon the patient’s initial presentation for care. Myocardial infarction also often develops as a result of coronary artery disease, but rather than causing a temporary blockage in the coronary arteries, portions of the heart tissue die from lack of oxygen. The cell injury causes a rise in cardiac enzymes that can be identified upon laboratory testing. The heart’s function, particularly the left ventricle, eventually becomes strained. Ejection fraction decreases, leading to electrical conduction abnormalities that are noted on ECG, particularly as ST-T segment changes. Eventually, the patient experiences heart failure and a shock state that includes inadequate perfusion to vital organs. In the inpatient setting, nitroglycerin is also administered to patients who are experiencing myocardial ischemia. It may also be implemented following open-heart surgery, including during the post-op period after coronary artery bypass grafting (CABG) to maintain blood flow and vasodilation, and because the risk of coronary artery spasm during this period is elevated. Because of its effects on the blood vessels, nitroglycerin reduces the strain on the heart by decreasing preload to decrease overall oxygen demand. When the veins dilate from the action of the drug, there is a slight increase nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 68 in blood pooling in the peripheral tissues and consequent decrease in venous blood return to the heart, which causes the decreased preload. In addition to a decrease in preload, nitroglycerin reduces afterload through a decrease in arterial venous pressure with dilation of the arteries. Additionally, dilation of the coronary vessels improves oxygen supply to the heart, so the effects of nitroglycerin are actually two-fold: it has the ability to balance the supply-demand relationship between oxygen and nutrients in the heart when ischemia occurs. Nitroglycerin is also used for the treatment of severe hypertension, as its vasodilatory effects increase the size of blood vessels and cause a reduction in blood pressure levels. The effects on the venous circulation lead to a reduction in central venous pressure when levels are high and left ventricular cardiac output is improved because of decreased systemic vascular resistance. Because of its effects, nitroglycerin should not be administered with some other drugs that can cause synergistic outcomes. For example, use of nitroglycerin with a patient who has a prescription for sildenafil for pulmonary hypertension can cause a rapid drop in blood pressure and should be avoided. Although nitroglycerin is used for severe hypertension, it should also not be given to any patient who is experiencing hypertensive encephalopathy because it can cause an increase in intracranial pressure. Long-term use of nitroglycerin may cause deleterious effects for the patient, particularly in response to some vasoconstricting drugs. Ferreira, et al., in the Circulation Journal state that prolonged use of nitroglycerin can lead to changes in the heart muscle cells that may lead to an increase in infarct size when myocardial infarction is present. Additionally, repeated and ongoing nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 69 doses of nitroglycerin may result in pharmacological resistance and a decreased effect. This nitrate tolerance that develops with consistent use of nitroglycerin causes a loss of the therapeutic effects on the cardiovascular system, requiring higher doses each time to achieve the same outcomes. To avoid nitrate tolerance that may develop with this drug, the patient may need to have breaks from the drug, known as nitrate-free intervals for several hours per day. When administering nitroglycerin as an intravenous infusion, the dose must be diluted first within a dextrose solution or in normal saline. An initial adult starting dose of IV nitroglycerin is approximately 5 mcg/minute as an infusion, increasing the dose as needed every 3 to 5 minutes by 5 mcg/minute each time, until a maximum dose of 20 mcg/minute. The provider may continue to increase the dose incrementally to achieve desired effects, but this process should be considered on a case-by-case basis. The patient should be continuously monitored through drug administration for the presence of adverse effects as well as signs of drug effectiveness and hemodynamic stability. Nitroglycerin should always be administered with caution, with the patient carefully monitored throughout the time of dosing to determine if any ill effects have developed. Additionally, nitroglycerin may cause headache, and symptoms of low blood pressure, including dizziness, weakness, palpitations, pallor, and diaphoresis. The dose of nitroglycerin can cause very rapid and powerful effects in the patient, leading to relief of angina and improved circulation, but also a risk of hypotension and further ischemia. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 70 Nitroprusside Sodium nitroprusside (Nitropress®) is a potent vasodilator that increases the size of the arteries and veins after administration. It is most commonly administered for patients in hypertensive crisis.1,57,58, Nitroprusside induces a drop in blood pressure by its effects on oxyhemoglobin; when combined, nitroprusside splits to form methemoglobin while simultaneously releasing nitric oxide. This reduces intracellular calcium in the smooth muscle cells and contributes to vasodilation. Although sodium nitroprusside can have significant effects on circulation, its impact on cardiac output is less consistent when compared to nitroglycerin. As with nitroglycerin, a small amount of pooling of blood in the peripheral tissues can decrease pressure on the heart and may lead to a decrease in venous return to the heart as well as decreased blood pressure. Nitroprusside is given by continuous IV infusion and not as a bolus injection. The usual rate of infusion for adults is approximately 0.5 – 4 mcg/kg/minute. The dose should start at a slower rate, increasing as the patient tolerates and depending on clinical response. Nitroprusside takes effect within a few seconds after administration. It has an approximate halflife of 2 to 3 minutes, which requires continuous infusion for ongoing effects. All patients who receive sodium nitroprusside should be monitored continuously for side effects, effects of the drug, and to maintain hemodynamic stability, particularly for blood pressure. Because of its effects on blood pressure, nitroprusside can cause significant hypotension, which can be corrected by stopping the infusion. The patient may suffer such severely low blood pressure that vital organs suffer from a lack of perfusion. Prolonged infusion of the drug can also exacerbate nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 71 myocardial ischemia when the vasodilatory effects increase the oxygen requirements of the heart. The coronary vessels benefit from the effects of nitroprusside, however, other areas may divert blood to support the cardiac cells but can then become depleted and develop ischemia. Prolonged administration of nitroprusside is also associated with cyanide toxicity and elevated methemoglobin levels. When nitroprusside combines with oxyhemoglobin and releases nitric oxide, it also releases free cyanide. In small amounts, this may have negligible effects, however, there is potential for toxicity when the infusion rate of the nitroprusside is faster than the rate of cyanide excretion. A patient who has developed cyanide toxicity may exhibit confusion and tachypnea; laboratory evaluations typically manifest as metabolic acidosis and the venous blood sample may appear bright red. If symptoms of cyanide toxicity develop, the nitroprusside solution should be discontinued and the patient should be given sodium thiosulfate, as well as 100 percent oxygen. An alternative drug with similar effects may need to be employed; other drugs such as labetalol, nicardipine (Cardene®), and fenoldopam (Corlopam®) all have similar antihypertensive effects as sodium nitroprusside but without the risk of cyanide toxicity. Additionally, nitroprusside administration may increase the risk of methemoglobinemia, although this effect is often only associated with high levels of drug administration. Nitroprusside forms methemoglobin when it combines with carboxyhemoglobin after administration. Elevated levels of methemoglobin can then lead to methemoglobinemia, in which the patient experiences cyanosis and shortness of breath because the hemoglobin is unable to bind to oxygen in the bloodstream. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 72 Nitroprusside affects all areas of the circulatory system to promote healthy blood pressure levels because it is non-selective. It contributes to increased circulation in the brain by dilating the cerebral blood vessels. It should therefore be used with extreme caution among patients at risk of increased intracranial pressure, as the effects of nitroprusside can contribute to such an increase in cerebral blood flow as to worsen elevated intracranial pressure. Most people who receive nitroprusside in the hospital are already on continuous hemodynamic monitoring and may have continuous arterial pressure monitoring, which is beneficial for ongoing evaluation of blood pressure and patient response to the drug. Overall, the use of nitroprusside requires a distinct balance of administering enough of the drug to counteract hypertension and avoid severe consequences of hypertensive crisis, while eluding such a drop in blood pressure as to cause other adverse effects. Labetalol Labetalol is a beta-blocker medication that is primarily used for the treatment of severe hypertension. It is an adrenergic receptor antagonist that blocks the actions of alpha-1 as well as beta-adrenergic receptors. The drug is selective for alpha-1 receptors but is non-selective for beta receptors. Its effects on these receptors lead to a decrease in atrioventricular condition and sinoatrial discharge, a decrease in the force of heart muscle contractions, decreased systemic vascular resistance, and vasodilation.1,59,110 Labetalol’s effects on peripheral vascular resistance, as well as an increase in cardiac output occur with mixed effects and are not always consistent in all patients. Labetalol may be administered as an oral tablet; a prescription for the drug is sometimes given to patients with hypertension to control blood pressure and to maintain normal levels when it is taken at home. When nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 73 given orally, labetalol has the same effect on the cardiovascular system as when it is given intravenously, but the effects of oral dosing take longer because of the added step of drug absorption after administration. Oral labetalol may be started for hospitalized patients after adequate blood pressure levels have been achieved with IV infusion. Once ready to start oral labetalol, the initial dose is 200 mg, which can be repeated in 6 to 12 hours, depending on patient response. Labetalol is typically administered as an IV infusion for hospitalized patients; it may be given as an IV injection or as continuous dose. Individual injections are given slowly over the course of 2 minutes, with repeat doses given after 10 minutes, depending on the patient’s blood pressure response. Continuous infusion must be given with the dose diluted in solution and the dose and rate titrated according to the patient’s blood pressure response. The patient who receives labetalol should be on continuous hemodynamic monitoring to assess blood pressure levels. The most common side effect associated with labetalol is orthostatic hypotension. As the side effects are worsened when the patient is not lying down, anyone who receives labetalol and who develops hypotension should be kept supine or assisted to lie in the supine position. When starting an infusion of labetalol, the patient should be lying down to prevent the risk of orthostatic hypotension and to decrease the effects of low blood pressure if it should develop. Additionally, labetalol should not be given to patients who already have a history of hypotension or cardiogenic shock, those with bradycardia, heart failure, or greater than first-degree heart block. Other side effects of labetalol include dizziness, lightheadedness, fatigue, and headache. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 74 Labetalol may also be used in patients who have increased intracranial pressure associated with a brain injury. Acute intracranial hypertension describes a state in which intracranial pressure (ICP) is sustained above 20 mmHg. The condition may develop as a result of massive stroke, intracerebral hemorrhage, or traumatic brain injury, and it typically requires intensive and critical patient care. One element of managing intracranial hypertension is to optimize cerebral perfusion pressures. Administration of labetalol is one method of lowering ICP. A review by Ragland, et al., in the Journal of Neurocritical Care recommended that administration of a shortacting blood pressure lowering agent such as labetalol could decrease the patient’s MAP, which may then cause a reduction in the ICP. Despite the negative effects associated with high blood pressure, too rapid of vasodilation could occur with drug administration, causing hypotension. As result, blood pressure levels must be continuously monitored with labetalol use, not only during the infusion, but also for time afterward until the drug has cleared the body to ensure that the patient remains in a stable clinical state. Summary The safe administration of medications to critically ill patients is part of the overall goals of care for this population. Effective drug administration involves using critical thinking skills to determine the most appropriate drug for the situation based on knowledge of its therapeutic effects, and being able to respond to changes in the patient’s clinical status after the drug has been given. This specific population of patients is particularly vulnerable to changes in medication dosages and to mistakes that could happen with improper medication administration. Identifying the most appropriate methods of administration, as well as possible complications of medications nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 75 in the critical care and emergency settings is essential for providing effective care. Because the patients being cared for in the ICU and ED often have unstable conditions, administration of medications can lead to rapid changes. When drugs are administered inappropriately, there is a greater chance of harm to the patient, even if the incorrect action would be considered a minor error if it were made outside the ICU and ED setting. Most patients in critical care are sicker overall when compared to their counterparts in other areas of the healthcare facility; they often have higher numbers of comorbidities present and they receive more medications. Critical care patients also undergo more treatments and procedures that can induce pain or anxiety and so they may have more medications given as needed for comfort as well. Ideally, the clinician should be familiar with the common drugs used to treat critical care patients, including common drug interactions. Being familiar with a drug’s time of onset, duration, and half-life will help to support clinical decision-making during a patient’s course of care. By utilizing reference guides, checking with other personnel, and using medical equipment appropriately, the clinician can safely administer medications and achieve benefit the patient. Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation. Completing the study questions is optional and is NOT a course requirement. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 76 1. Within the ICU and critical care environment, metered-dose inhalers (MDIs) typically include medication formulations that have been created for MDIs, such as a. b. c. d. inhalable powder medications. any drug available in nebulized form. powder, liquid and water-soluble gel forms. bronchodilator medications and corticosteroids. 2. True or False: Pharmacokinetics in critical care patients are the only constant factors because drugs are absorbed, metabolized, and excreted based on the drug’s composition, not the current health status of the patient. a. True b. False 3. The following statement(s) is/are correct with respect to the use of inhaled medications in the critical care environment, such as ICU? a. Inhaled medications are rarely used in ICU. b. Inhaled medications are used except in patients who require mechanical ventilation. c. The method of administering inhaled drugs depends largely on the patient’s ability and health status. d. All of the above 4. _______________ is a muscarinic agonist that is used in an inhaled preparation form to test and diagnose asthma. a. b. c. d. Methacholine Budesonide Ipratropium bromide Albuterol 5. Which of the following inhaled medications specifically act on the beta-2 adrenergic receptors of the lungs to cause vasodilation of the bronchioles and to improve breathing? a. b. c. d. Ipratropium Heparin Methacholine Albuterol nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 77 6. True or False: Intubated patients may also receive inhaled medications when the drug is administered through the ventilator tubing. a. True b. False 7. Muscarinic receptors are a type of acetylcholine receptor that can be found in the a. b. c. d. lung tissue. neuromuscular junction. skeletal muscles. liver. 8. When stimulated, muscarinic receptors cause a. b. c. d. an increase in heart rate. vasodilation. constriction of the bronchioles. All of the above 9. ______________ is given as an inhaled medication to block the muscarinic receptors and to cause bronchodilation, which increases airflow in the lungs and makes it easier for the patient to breathe. a. b. c. d. Methacholine Albuterol Ipratropium Isoproterenol 10. Clinical trials have shown that ____________, a beta-2 receptors stimulator, has a greater effect on smooth muscle relaxation in the bronchial tissue than isoproterenol with fewer cardiovascular effects than isoproterenol. a. b. c. d. azithromycin tobramycin methacholine albuterol nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 78 11. The most common side effects of ipratropium include a. b. c. d. vasodilation. bronchodilation. an increase in heart rate. exacerbation of COPD symptoms. 12. The American College of Chest Physicians’ and the American College of Asthma, Allergy, and Immunology’s guidelines for delivery of short-acting beta-2 agonist through an MDI or nebulizer in cases of acute asthma and bronchospasm include: a. use of an MDI is not recommended. b. delivery through an MDI or nebulizer is appropriate, based on the patient’s ability to accurately use these devices. c. use of dry powder inhalers is recommended over MDI or nebulizer. d. the use of dry powder inhalers is recommended based on the patient’s ability to use this device. 13. Nebulizers known as ________________ work by breaking down the liquid into particles using compressed oxygen or air and a reservoir. a. b. c. d. Jet nebulizers Bronchodilators Mesh nebulizers Ultrasonic nebulizers 14. True or False: According to the American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology, patients who are not using mechanical ventilation but who are severely dyspneic, should not use intermittent or continuous nebulizers to administer medications. a. True b. False 15. Which type of nebulizer is not used as often within the ICU because of its size and cost to use? a. b. c. d. Jet nebulizers Dilator nebulizers Mesh nebulizers Ultrasonic nebulizers nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 79 16. There is also less risk of contamination associated with the use of ______________ nebulizers because the reservoir is separate from the ventilator circuit. a. b. c. d. jet dilator mesh ultrasonic 17. True or False: Bronchodilators are some of the more common drugs administered by inhalation; however, antibiotics, including tobramycin and azithromycin, can be administered in this method as well. a. True b. False 18. Intravenous administration of medications act very quickly and produce rapid responses because they are administered directly into systemic circulation while a. b. c. d. eliminating the risk of infection from administering drugs. bypassing the distribution stage. bypassing the absorption stage. bypassing the blood-brain barrier system. 19. Part of the calculation for the IV flow rate includes the ______________________, which is the amount of the drug that is available within the given solution. a. b. c. d. drug concentration medication dose calculate drops (gtts) per minute time-spacing of drug administration 20. When a continuous infusion is in place for more than 24 hours, the IV tubing and the medication container often must be changed a. b. c. d. to to to to adjust the rate of administration. decrease the drug concentration. catch any errors of drug concentration. decrease the risk of infection. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 80 21. True or False: The nurse should be familiar with the basic units of common drugs that are given to be able to catch any errors of concentration if they occur. a. True b. False 22. A nurse receives an order for 1000 mL D5 ½ NS to be given over 8 hours. To calculate the infusion rate when a pump will be used, the nurse would ______________________ to obtain the mL/hour. a. b. c. d. divide 8 hours by 1000 mL D5 ½ NS need to know drops (gtts) per minute multiply 60 minutes times 8 divide 1000 mL D5 ½ NS by 8 hours 23. The size of the drip set may range from a mini-drip set to a regular drip set. A mini-drip set has a gtt factor (drops per minute) of a. b. c. d. 10-20 gtts/mL. 15 gtts/mL. 60 gtts/mL. 25 gtts/mL. 24. A nurse receives an order for Ancef, with the dose in a 50 mL solution, which must be given over 30 minutes. The gtt factor is 20 gtts/mL. The nurse uses the following calculation: a. b. c. d. (20 gtt ÷ 50 mL) x 30 minutes = 12 gtts/minute. (50 mL ÷ 20 gtt) x 30 minutes = 75 gtts/minute. 20 gtt x 30 minutes ÷ 50 mL = 12 gtts/minute. 50 mL x 20 gtt ÷ 30 minutes = 33.3 gtts/minute. 25. True or False: Before administration of certain intravenous medications, the clinician should be familiar with all possible effects of all drugs. a. True b. False nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 81 26. Oral medications are not as commonly administered in critical care environments when compared to intravenous drugs because a. oral medications are never the easiest way to administer drugs. b. many critically ill patients do not have the ability to swallow oral tablets. c. oral administration is not effective in ICU settings. d. oral administration requires drug distribution, whereas IV does not. 27. _________________ typically act as sedative-hypnotics in the central nervous system in response to GABA receptors. a. b. c. d. Butyrophenones Haloperidol Benzodiazepines Droperidol 28. Benzodiazepines are often administered to patients in critical care to control a. b. c. d. confusion. hallucinations. pain and distress. symptoms from glaucoma. 29. Lorazepam is a benzodiazepine that has been shown a. b. c. d. to be beneficial in controlling seizure activity. to impact the cardiovascular system regularly. to be beneficial with a reduced risk of delirium. All of the above 30. True or False: Splitting tablets to administer one-half of a dose is a relatively common practice but it also increases the risk of errors. a. True b. False nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 82 31. Which of the following benzodiazepines, used in critical care, has a half-life of up to 120 hours? a. b. c. d. Lorazepam Propofol Midazolam Diazepam 32. ____________ is a sedative-hypnotic medication that is most commonly used to induce anesthesia during surgery. a. b. c. d. Diazepam Propofol Midazolam Lorazepam 33. ____________________ are a type of antipsychotic medication that may be administered for the management of various conditions, including acute psychosis or confusion. a. b. c. d. Benzodiazepines Neuroleptic medications Opioid analgesics Butyrophenones 34. When propofol is administered intravenously a. b. c. d. its effects begin within approximately 40 seconds. it has a half-life of 4 hours. it cannot be used for long procedures. it is best used together with analgesic drugs. 35. True or False: Historically, haloperidol has been a first choice of treatment of ICU delirium, however, it does carry an increased risk of adverse effects, some of which could be life-threatening. a. True b. False nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 83 36. _________________ are the first-line drug of choice to treat non-neuropathic pain in critically ill adult patients. a. b. c. d. Neuroleptic medications Butyrophenones Opioid analgesics Benzodiazepines 37. Which of the following opioid analgesics is not recommended in critically ill patients because of its risks of causing neurotoxicity? a. b. c. d. Methadone Meperidine Hydromorphone Remifentanil hydrochloride 38. ______________________ is a vasopressor medication most commonly administered for the control of blood pressure and prevention of hypotension. a. b. c. d. Meperidine Ibuprofen Ketorolac Dopamine hydrochloride 39. Another element that must be considered with ____________ administration is its lipophilic tendencies, in that it has the potential to accumulate in the adipose tissue of the patient. a. b. c. d. meperidine ibuprofen propofol ketorolac 40. ________________is a beta-blocker medication that is primarily used for the treatment of severe hypertension. a. b. c. d. Dobutamine Labetalol Ketorolac Isoproterenol nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 84 CORRECT ANSWERS: 1. Within the ICU and critical care environment, metered-dose inhalers (MDIs) typically include medication formulations that have been created for MDIs, such as d. bronchodilator medications and corticosteroids. “Within the ICU and critical care environment, metered-dose inhalers (MDIs) may also be used; their use is restricted to those medication formulations that have been created for this specific mechanism of administration, and typically include bronchodilator medications and corticosteroids…. Metered-dose inhalers are very easy to use with the ventilator, however, not all drugs that are given as inhaled products are available through this device and must be given in nebulized form instead.” 2. True or False: Pharmacokinetics in critical care patients are the only constant factors because drugs are absorbed, metabolized, and excreted based on the drug’s composition, not the current health status of the patient. b. False “Pharmacokinetics in a critical care patient may be altered because of the patient’s current health status; in other words, because critical illness can affect how drugs are absorbed, metabolized, and excreted, patients in the critical care environment are at higher risk of complications associated with drug administration when their bodies cannot process the drugs properly.” 3. The following statement(s) is/are correct with respect to the use of inhaled medications in the critical care environment, such as ICU? c. The method of administering inhaled drugs depends largely on the patient’s ability and health status. “Inhaled medications are those drugs that are delivered to the lungs and that are taken into the body while breathing in. They may be commonly administered in the critical care environment, particularly in situations where patients have breathing difficulties due to chronic lung disease or bronchospasm, as well as among some patients who nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 85 require mechanical ventilation. The method of administering inhaled drugs depends on the patient’s ability to take the medication, often as a result of the patient’s health status.” 4. _______________ is a muscarinic agonist that is used in an inhaled preparation form to test and diagnose asthma. a. Methacholine “… methacholine is an inhaled preparation that is a muscarinic agonist that is used to test and diagnose asthma because it can cause shortness of breath and wheezing.” 5. Which of the following inhaled medications specifically act on the beta-2 adrenergic receptors of the lungs to cause vasodilation of the bronchioles and to improve breathing? d. Albuterol “Certain inhaled medications specifically act on the beta-2 adrenergic receptors of the lungs to cause vasodilation of the bronchioles and to improve breathing. Albuterol (Proventil®, Ventolin®) is an example of this type of medicine.” 6. True or False: Intubated patients may also receive inhaled medications when the drug is administered through the ventilator tubing. a. True “Intubated patients may also receive inhaled medications when the drug is administered through the ventilator tubing.” 7. Muscarinic receptors are a type of acetylcholine receptor that can be found in the a. lung tissue. “Muscarinic receptors are a type of acetylcholine receptor that can be found in the lung tissue. They are responsible for controlling and modifying smooth muscle tone, regulating mucus production, and managing lung inflammation.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 86 8. When stimulated, muscarinic receptors cause c. constriction of the bronchioles. “When stimulated, muscarinic receptors cause a decrease in heart rate, a decrease in cardiac contractility, and constriction of the bronchioles.” 9. ______________ is given as an inhaled medication to block the muscarinic receptors and to cause bronchodilation, which increases airflow in the lungs and makes it easier for the patient to breathe. c. Ipratropium “Ipratropium is given as an inhaled medication to block the muscarinic receptors and to cause bronchodilation, which increases airflow in the lungs and makes it easier for the patient to breathe. Ipratropium can also decrease the amount of mucus secretions in the patient’s lungs, which also promotes a clear airway and easier breathing.” 10. Clinical trials have shown that ____________, a beta-2 receptors stimulator, has a greater effect on smooth muscle relaxation in the bronchial tissue than isoproterenol with fewer cardiovascular effects than isoproterenol. d. albuterol “Albuterol is often used as a rescue medication and it is the first choice of treatment of bronchospasm and has been shown through clinical trials to have a greater effect on smooth muscle relaxation in the bronchial tissue than isoproterenol, a sympathomimetic drug that also stimulates beta-2 receptors in the lungs, as well as having longer-lasting effects and fewer cardiovascular effects than isoproterenol.” 11. The most common side effects of ipratropium include d. exacerbation of COPD symptoms. “Ipratropium can also decrease the amount of mucus secretions in the patient’s lungs, which also promotes a clear airway and easier breathing. It may cause some negative side effects associated with nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 87 the respiratory system. The most common side effects of ipratropium include respiratory tract infection, bronchitis, cough, sinusitis, and exacerbation of COPD symptoms. Other side effects may also include urinary tract infection, dyspepsia, and flu-like symptoms.” 12. The American College of Chest Physicians’ and the American College of Asthma, Allergy, and Immunology’s guidelines for delivery of short-acting beta-2 agonist through an MDI or nebulizer in cases of acute asthma and bronchospasm include: b. delivery through an MDI or nebulizer is appropriate, based on the patient’s ability to accurately use these devices. “The American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology have given guidelines about selection of the most appropriate device and drug in different situations within the emergency department or the ICU. In short, the executive summary that was released determined that within the emergency department, including among cases of acute asthma and bronchospasm, the delivery of short-acting beta-2 agonist through an MDI or nebulizer is appropriate, based on the patient’s ability to accurately use these devices. The use of dry powder inhalers for these same conditions is not recommended at this point due to a lack of evidence regarding effectiveness.” 13. Nebulizers known as ________________ work by breaking down the liquid into particles using compressed oxygen or air and a reservoir. a. Jet nebulizers “Jet nebulizers are relatively easy to use and are one of the more inexpensive methods of inhaled medication administration in the ventilator-dependent population. Jet nebulizers work by breaking down the liquid into particles using compressed oxygen or air and a reservoir…. Ultrasonic nebulizers work by creating ultrasonic vibrations that convert the medication solution into a mist that can be inhaled…. The mesh nebulizer converts liquid to particles for inhalation by moving the liquid through a fine mesh barrier.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 88 14. True or False: According to the American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology, patients who are not using mechanical ventilation but who are severely dyspneic, should not use intermittent or continuous nebulizers to administer medications. b. False “Additionally, the two medical associations have issued guidelines for the use of short-acting beta-2 agonists administered in the inpatient hospital setting, which state that the use of metered-dose inhalers and nebulizers, used with spacers when needed, are both appropriate for administration of these drugs. Among patients who are not using mechanical ventilation but who are severely dyspneic, the use of either intermittent or continuous nebulizers to administer medications is appropriate.” 15. Which type of nebulizer is not used as often within the ICU because of its size and cost to use? d. Ultrasonic nebulizers “… ultrasonic nebulizers may leave some residual medication that the patient does not receive. This type of nebulizer is not used as often within the ICU because of its size and cost to use.” 16. There is also less risk of contamination associated with the use of ______________ nebulizers because the reservoir is separate from the ventilator circuit. c. mesh “Mesh nebulizers have been shown to have a reduced drug residual with use, which means a greater amount of the inhaled drug reaches the patient. There is also less risk of contamination associated with their use because the reservoir is separate from the ventilator circuit.” 17. True or False: Bronchodilators are some of the more common drugs administered by inhalation; however, antibiotics, including tobramycin and azithromycin, can be administered in this method as well. a. True nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 89 “Clearly, bronchodilators are some of the more common drugs administered by inhalation; however, antibiotics, including tobramycin and azithromycin, can be administered in this method as well.” 18. Intravenous administration of medications act very quickly and produce rapid responses because they are administered directly into systemic circulation while c. bypassing the absorption stage. “Intravenous administration of medications is one of the most common routes utilized in critical care. Many of these drugs act very quickly and produce rapid responses because they are administered directly into systemic circulation while bypassing the absorption stage.” 19. Part of the calculation for the IV flow rate includes the ______________________, which is the amount of the drug that is available within the given solution. a. drug concentration 20. When a continuous infusion is in place for more than 24 hours, the IV tubing and the medication container often must be changed d. to decrease the risk of infection. “When a continuous infusion is in place for more than 24 hours, the IV tubing and the medication container often must be changed to decrease the risk of infection.” 21. True or False: The nurse should be familiar with the basic units of common drugs that are given to be able to catch any errors of concentration if they occur. a. True “The nurse should be familiar with the basic units of common drugs that are given to be able to catch any errors of concentration if they occur. The dose of the drug should be available through the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 90 provider’s prescription and it should specify whether the drug should be given over a period of minutes or hours.” 22. A nurse receives an order for 1000 mL D5 ½ NS to be given over 8 hours. To calculate the infusion rate when a pump will be used, the nurse would ______________________ to obtain the mL/hour. d. divide 1000 mL D5 ½ NS by 8 hours “… a nurse receives an order for 1000 mL D5 ½ NS to be given over 8 hours. To calculate the infusion rate, the nurse would input the following: 1000 mL D5 ½ NS = 125 mL/hour 8 hours” 23. The size of the drip set may range from a mini-drip set to a regular drip set. A mini-drip set has a gtt factor (drops per minute) of c. 60 gtts/mL. “The size of the drip set may range from a mini-drip set, which has a gtt factor of 60 gtts/mL, to a regular drip set, which has a rate of 1020 gtts/mL.” 24. A nurse receives an order for Ancef, with the dose in a 50 mL solution, which must be given over 30 minutes. The gtt factor is 20 gtts/mL. The nurse uses the following calculation: d. 50 mL x 20 gtt ÷ 30 minutes = 33.3 gtts/minute. “… a nurse receives an order for Ancef, with the dose in a 50 mL solution, which must be given over 30 minutes. The gtt factor is 20 gtts/mL. The nurse uses the following calculation: 50 mL x 20 gtt = 33.3 gtts/minute 30 minutes” nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 91 25. True or False: Before administration of certain intravenous medications, the clinician should be familiar with all possible effects of all drugs. b. False “Ideally, the clinician should be familiar with common drug interactions associated with certain intravenous medications before administration. While it is not possible to know all possible effects of all drugs, referencing potential interactions and spacing the timing of drug administration, when possible, can decrease the potential for these effects. This also includes familiarity with each drug’s time of onset, duration, and half-life, and what type of IV solution is compatible for administration. By utilizing reference guides, checking with other personnel, and using medical equipment appropriately, the clinician can safely administer intravenous medications that will be of great benefit to the patient.” 26. Oral medications are not as commonly administered in critical care environments when compared to intravenous drugs because b. many critically ill patients do not have the ability to swallow oral tablets. “Oral medications are not as commonly administered in critical care when compared to intravenous drugs; many critically ill patients do not have the ability to swallow oral tablets or cannot tolerate ingestion and absorption of these drugs from the gastrointestinal tract. However, in the right circumstances, giving medications by mouth can be one of the easiest ways to administer drugs. There are some clinicians who believe that the oral route of administration is not as effective when compared to IV drugs. However, there are some medications that are only available through the oral route and that cannot be given any other way; drugs used to treat hyperlipidemia, such as atorvastatin, are some such examples. Further, if an orally administered drug is able to achieve the same tissue distribution as that of an intravenous drug, an oral medication is no less effective than the same kind of drug given via a different route. Although the route of oral administration requires an additional step of absorption to reach systemic circulation, the oral preparation is not necessarily less effective than other routes; instead, it may simply take longer to exert its effects.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 92 27. _________________ typically act as sedative-hypnotics in the central nervous system in response to GABA receptors. c. Benzodiazepines “Benzodiazepines typically act as sedative-hypnotics in the central nervous system in response to GABA receptors.” 28. Benzodiazepines are often administered to patients in critical care to control c. pain and distress. “Benzodiazepines are often administered to patients in critical care because of the pain and distress that is often involved with care in these areas. Critically ill patients often undergo painful and frightening procedures and may be more likely to suffer from anxiety and pain as a result…. One contraindication that is common to most benzodiazepines is that these drugs should not be given to anyone with a history of glaucoma. People who have narrow-angle glaucoma or untreated open-angle glaucoma should not be given benzodiazepines, as the drugs may increase intraocular pressure.” 29. Lorazepam is a benzodiazepine that has been shown a. to be beneficial in controlling seizure activity. “Lorazepam also acts as a central nervous system depressant in that it causes sedation but does not necessarily impact the cardiovascular system. Lorazepam has been shown to be beneficial in reducing anxiety, promoting sedation, and controlling seizure activity…. Like midazolam, there may be an increased risk of delirium with use of lorazepam, and patients who have been given this drug should also be monitored for signs of excessive sedation.” 30. True or False: Splitting tablets to administer one-half of a dose is a relatively common practice but it also increases the risk of errors. a. True “Splitting tablets to administer one-half of a dose is a relatively common practice but it also increases the risk of errors. When dividing doses by splitting tablets, the provider should note whether nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 93 the drug is safe for splitting, as noted on the packaging, and whether it is scored on the tablet. The nurse should use a pill splitter to divide the dose, which is the most accurate method of breaking the pill in half.” 31. Which of the following benzodiazepines, used in critical care, has a half-life of up to 120 hours? d. Diazepam “Another GABA agonist benzodiazepine that may be used in critical care is diazepam has a half-life of up to 120 hours.” 32. ____________ is a sedative-hypnotic medication that is most commonly used to induce anesthesia during surgery. b. Propofol “Propofol (Diprivan®) is a sedative-hypnotic medication that is most commonly used to induce anesthesia during surgery;…” 33. ____________________ are a type of antipsychotic medication that may be administered for the management of various conditions, including acute psychosis or confusion. d. Butyrophenones “Butyrophenones are a type of antipsychotic medication that may be administered for the management of various conditions, including acute psychosis or confusion.” 34. When propofol is administered intravenously a. its effects begin within approximately 40 seconds. “The effects of propofol begin within approximately 40 seconds after it has been administered intravenously. It has a half-life of 1 to 3 minutes, which means that it may be administered either on a continuous basis throughout a procedure or additional doses must be given in order to maintain its effects…. Propofol can have a significant impact on the cardiovascular and respiratory systems. Patients who receive propofol can be at risk of decreased oxygen saturations, increased carbon dioxide levels, and hypotension, which may occur before an overall decrease in cardiac output. These effects nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 94 are aggravated further when propofol is given with another drug that affects hemodynamics, such as with analgesic drugs.” 35. True or False: Historically, haloperidol has been a first choice of treatment of ICU delirium, however, it does carry an increased risk of adverse effects, some of which could be life-threatening. a. True “Historically, haloperidol has been a first choice of treatment of ICU delirium, however, it does carry an increased risk of adverse effects, some of which could be life-threatening.” 36. _________________ are the first-line drug of choice to treat non-neuropathic pain in critically ill adult patients. c. Opioid analgesics “Opioid analgesics are the first-line drug of choice to treat nonneuropathic pain in critically ill adult patients.” 37. Which of the following opioid analgesics is not recommended in critically ill patients because of its risks of causing neurotoxicity? b. Meperidine “Other examples of opioid analgesics that may be considered for use in critically ill patients include hydromorphone, methadone, and remifentanil hydrochloride (Ultiva®). Note that the administration of meperidine is not recommended in critically ill patients because of its risks of causing neurotoxicity.” 38. ______________________ is a vasopressor medication most commonly administered for the control of blood pressure and prevention of hypotension. d. Dopamine hydrochloride “Dopamine hydrochloride is a vasopressor medication most commonly administered for the control of blood pressure and prevention of hypotension.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 95 39. Another element that must be considered with ____________ administration is its lipophilic tendencies, in that it has the potential to accumulate in the adipose tissue of the patient. c. propofol “Another element that must be considered with propofol administration is its lipophilic tendencies, in that it has the potential to accumulate in the adipose tissue of the patient, particularly when it is administered over a longer period of time.” 40. ________________is a beta-blocker medication that is primarily used for the treatment of severe hypertension. b. Labetalol “Labetalol is a beta-blocker medication that is primarily used for the treatment of severe hypertension. It is an adrenergic receptor antagonist that blocks the actions of alpha-1 as well as betaadrenergic receptors.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 96 References The References below include published works and in-text citations of published works that are intended as helpful material for your further reading. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Physician’s Desk Reference (2017). Retrieved online at http://www.pdr.net/browse-by-drug-name. Le, J. (2016). Overview of pharmacokinetics. Retrieved from http://www.merckmanuals.com/professional/clinicalpharmacology/pharmacokinetics/overview-of-pharmacokinetics Marini, J., Wheeler, A. (2010). Critical care medicine: the essentials. Philadelphia, PA: Lippincott Williams & Wilkins UNC Eshelman School of Pharmacy. (2017). Intramuscular. Retrieved from http://pharmlabs.unc.edu/labs/parenterals/intramuscular.htm Spruill, W., Wade, W., DiPiro, J., Blouin, R., Pruemer, J. (2014). 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