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Pediatric Circulatory Shock Christa Jefferis Kirk, PharmD [email protected] Seattle Children’s Hospital Seattle, Washington Objectives • Understand the physiology behind circulation and shock • Gain a basic understanding of how shock initially develops and potential consequences • Recognize the various types of shock • Know the basic treatment of pediatric shock including fluid replacement and pharmacologic intervention • Briefly discuss PALS and how the pharmacists can help 1 Definition and Basic physiology What is it and how does it happen? What is circulatory shock? • “When systemic oxygen and nutrient supply become acutely inadequate to meet the metabolic demands of the body’s organ systems.” 2 Other ways to think about it… • Demand > Supply • “The O (2) won’t go where the blood don’t flow” • Oxygen delivery man Physiology of Blood Pressure Maintenance Myocardial Contractility Force applied Stroke Volume (volume of blood ejected from left ventricle) Preload Volume of blood in ventricle Cardiac Output Heart Rate Blood Pressure Systemic Vascular Resistance Afterload Resistance to contraction 3 Physiology Goal (maintain blood pressure) BP CO x SVR HR x SV Preload, Afterload, Contractility Four Essential Components of Oxygen and Nutrient Delivery • Fluid • preload • Pump • contractility • Vessels • create afterload with alteration in vascular tone • Flow • affected by structure and systemic vascular resistance 4 Classification and physiology of Shock How do we tell them apart? Types of Shock • Hypovolemic (fluid) • Hemorrhagic • Nonhemorrhagic • Cardiogenic (pump) • Distributive (vessels) • Septic (fluid/vessels/pump) • Obstructive (flow) 5 Classification of Shock Compensated • Blood flow is normal/increased but mal-distributed, vital organs perfused • Signs: elevated heart rate, “flash” or delayed capillary refill, fussy/irritable Uncompensated • Reduction in circulating volume due to compromised microvascular perfusion, diminished perfusion to vital organs • Signs: decreased heart rate, decreased capillary refill, altered mental status (lethargy, coma), hypotonia, hypotension Irreversible • Little or no perfusion vital organs • Irreparable damage • Signs: hemodynamics unresponsive to all treatment, death 6 Hypovolemic Shock • Decreased preload • Primary cause of shock in pediatrics worldwide (6-20 million deaths annually) Loss of volume: • Water loss • Blood loss • Internal/external Common Causes? • • • i.e. Not enough fluid for the pump Physiology of Hypovolemic Shock • Hemorrhage • Dehydration Low intravascular volume Decreased Stroke Volume • Decreased preload • Decreased ventricular filling • Decreased cardiac output • Increased heart rate Inadequate supply of O2 and nutrients to body 7 Cardiogenic Shock • • • • • Decreased contractility • Pump is not working effectively Underlying cardiac dysfunction Electrical – arrhythmia Mechanical • Cardiomyopathy • Metabolic acidosis • Anatomic malformations • Hypoxia Common causes: • congenital heart disease • recent cardiac surgery • recent viral illness • late septic shock Physiology of Cardiogenic Shock • Arrhythmia • Myocarditis • Congenital heart defect Decreased contractility and LV function Decreased stroke volume • Pump is defective • Decreased volume of blood ejected • Decreased cardiac output Inadequate supply of O2 and nutrients to body 8 Distributive Shock • • • • Decreased vascular tone – weak and/or leaky pipes Neurological damage leads to inhibition of sympathetic nerve system Anaphylaxis leads to compromised vessel integrity and capillary leak Causes: • • • • allergic reaction (bee stings, medication reactions) trauma infections (early sepsis) drug intoxication – which ones?? Physiology of Distributive Shock • *Anaphylaxis = antibody/antigen → vasoactive mediators • Neurogenic = decreased sympathetic response Venous and arterial dilation Decreased Stroke Volume • *Capillary leak • Decreased venous return • Decreased vascular resistance • *Peripheral edema • Decreased cardiac output • Hypotension Inadequate supply of O2 and nutrients to body 9 Obstructive Shock • Decreased stroke volume due to obstruction on or around the heart • • • Something is blocking the heart or the pipes around the heart Causes: • tamponade • tension pneumothorax • pulmonary embolism Must then treat the underlying problem with a procedure or medication in order to resolve Physiology of Obstructive Shock • Tamponade • Congenital heart disease • Pulmonary embolism Decreased contractility Decreased stroke volume • Reduced ventricular filling during diastole • Increased afterload • Decreased cardiac output • Increased heart rate Inadequate supply of O2 and nutrients to body 10 Stages of Septic Shock Early “warm” Late “cold” General idea Decreased peripheral vascular resistance; increased cardiac output Increased peripheral vascular resistance; decreased cardiac output Cardiac function Heart rate is elevated BP is normal Heart rate is elevated/diminished BP is lower Peripheral Perfusion Extremities are warm and with increased pulses “Flash” capillary refill Extremities are cold with decreased pulses Significantly prolonged capillary refill Brain Agitated, irritable Lethargic, unresponsive Kidneys Diminished urine output Little to no urine output End Organ Function: Physiology of Early Septic Shock • Infection releases cytokines, vasoactive mediators • Vessels and tissues harmed Peripheral vasodilation Decreased stroke volume • Increased edema and capillary leak • Increased heart rate and contractility • Decreased cardiac output • Increased heart rate Inadequate supply of O2 and nutrients to body 11 Physiology of Late Septic Shock • Increased heart rate • Endotoxins affect heart function • Heart unable to keep up with demand Decreased contractility and LV function Decreased stroke volume • Increased preload • Increased afterload • Heart begins to fail • Decreased heart rate • Bradycardia • Hypotension Multi-organ System Failure Identifying patients in shock 12 History and Physical Exam Eating/drinking Nausea/vomiting/diarrhea Trauma/injury Fever Edema/”tenting”/rash Liver – enlarged/normal/”down” Clinical Assessment • History • Heart rate/Blood pressure • Peripheral circulation • Capillary refill • Pulses • Extremity temperature • Respiratory status • End Organ Perfusion 13 History and Physical Exam Eating/drinking Nausea/vomiting/diarrhea Trauma/injury Fever Edema/”tenting”/rash Liver – enlarged/normal/”down” Cardiovascular • Heart Rate • Generally rate is elevated if: • ≥180 bpm for infants • ≥160 bpm for children greater than 1 year old • Blood Pressure • General rule of thumb for lower limit of systolic blood pressure: • SBP= 70 + (2 x age in years) • DBP is age related but usually between 50-80 14 Cardiovascular and Respiratory Rates Age Heart Rate (beats per min) Neonates (full term, <28 days) Infants (1-12 months) Children (1-7 years) 120-180 Systolic Blood Pressure (mmHg) 60-90 Mean Arterial Pressure (mmHg) 55 Respiratory Rate (breaths per min) 40-60 120-180 70-95 60 25-50 120-160 80-110 65 15-30 Children (7-18 years) 90-140 90-140 65 12-20 Hypotension • Ominous sign in pediatric patients (vs. adults) • Children are able to maintain normal cardiac output and blood pressure even after significant loss of volume by increasing heart rate and vascular tone (co=hr x sv). • Hypotension does not become evident until the body has worn out its own compensating responses. • Important to recognize and treat shock in a timely manner • BEFORE hypotension occurs 15 Peripheral Circulation • Skin Perfusion • Capillary Refill Time • normal is ≤2 seconds • Temperature • Color/mottling • Peripheral Pulses • Present or absent? • Strength: diminished, normal, bounding Respiratory • Respiratory Status Pulse Oximetry (oxygen saturation levels) Normal 95-100% Mild hypoxia 91-94% Moderate hypoxia 86-90% Severe hypoxia ≤85% • Rate and pattern • Work of breathing • Oxygenation: color of skin/lips, pulse oximetry 16 End Organ Perfusion • CNS Perfusion • • • • Mental status Response to pain Muscle tone Pupil size/response • Renal Perfusion • Urine output > 1mL/kg/hr Treatment We know what it is…now what do we do? 17 Treatment (simplified) PALS Replace fluid losses Correct electrolytes Blood products for blood loss Cultures/antibiotics (when appropriate) Unresponsive to fluids = vasopressors Steroids only if indicated ECLS Goal Directed Therapy • Recognize shock FAST • • Replete intravascular volume quickly • • Han, Carcillo, et al noted early recognition based on capillary refill and blood pressure (i.e. no labs needed) and treatment within the first hour reduced mortality by 40%. Carcillo et al revealed data that administration of fluids ≥ 60ml/kg within the first hour of presentation significantly reduced mortality in pediatric patients – some patients required up to 200ml/kg. Improve capillary refill time (CR ≤ 2 seconds) • Han et al demonstrated that each hour delayed in improving BP and CR created a 2-fold increase in odds ratio for mortality. Normal BP and HR for age • Han et al noted that aggressive, early treatment in the ED improved survival by 9-fold in neonatal and pediatric septic shock patients. 18 Pediatric Advanced Life Support • • • • • CAB – compressions, airway, breathing CPR Intubate – increases oxygen – less demand on the heart Establish venous access • Peripheral within 90 seconds • Intraosseous (tibia or sternum) • Central venous catheter Consider hypothermia Fluid Management • Crystalloid vs. Colloid • Crystalloid • normal saline or lactated ringer’s • first choice • Colloid • Dextran, albumin, blood products, hydroxyethyl starch • Large molecules that draw fluid into intravascular space • Good for volume concerns (heart patients) and thirdspacing 19 Vasoactive Medications Inotropes Phosphodiesterase inhibitors Dopamine Epinephrine Dobutamine Milrinone ↑ contractility ↑ heart rate ↓ SVR ↑ contractility ↑coronary perfusion Vasoconstrictors Epinephrine (>0.3mcg/kg/min) Norepinephrine Dopamine (>10mcg/kg/min) Vasopressin ↑ SVR ↑ contractility (except vasopressin) Improving Stroke Volume Increase preload Increase contractility (↑ heart rate) Increase SVR (↑ vasoconstriction) Reduce afterload • Volume • crystalloid or colloid • blood products • Vasoactive medications • lower dose dopamine or epinephrine • dobutamine • Good for distributive shock and “cold” shock • Vasoactive medications • higher dose dopamine and epinephrine • norepinephrine • Good for cardiogenic shock and “warm” shock • Vasodilators • Milrinone 20 Recognize Shock Initial Therapy Establish access Establish IV access Maintain airway Oxygenate Volume 10mL/kg (neonate) 20mL/kg (pediatric) Initially up to 60mL/kg Correct electrolyte abnormalities (glucose, calcium, potassium) Get cultures Start antibiotics (if indicated) Fluid Resistant Shock More volume (consider blood products) Treat underlying causes (tamponade, pneumothorax, etc) Secure airway (intubate) Dopamine (peripheral if necessary) Titrate up to 10mcg/kg/min Refractory Shock COLD SHOCK ADD low dose epinephrine via central line Consider milrinone WARM SHOCK ADD high dose epinephrine or norepinephrine via central line Steroids?? ECMO?? When to Add Steroids • Continued hypotension after extensive vasopressor administration • History of adrenal insufficiency • Patient has been on steroids • CNS abnormality • Purpura fulminans • Anaphylaxis 21 Extracorporeal Life Support (ECLS) • Provides a means of oxygenating the blood outside the body • Many studies have shown it increases survival rates and improves post-resuscitation outcomes Image from: www.nlm.nih.gov Case presentation What does the real thing look like? 22 History • LKS is a 2 year old little girl s/p tonsillectomy 2 days prior to admission. • She was sent home on post-op day 0 and was initially doing well. • Later that evening she became tired and fussy in addition to refusing to eat. She had a fever and vomited once. • The next morning she appeared lethargic and pale. Physical Exam • Clinical presentation • Lethargic, glossy eyes • Unresponsive to pain • Pale • Exam notable for: • • • • • • Cool, clammy extremities Capillary refill = 6 seconds HR=166 BP=78/34 Temp=39.8 Mom stated she had only required a few diaper changes in the last 12 hours. 23 Goal: Recognize Shock FAST • Do you think this patient is in shock? • Why or why not? • If yes, what type of shock do you suspect? Goal: Replete Intravascular Volume QUICKLY • INITIAL THERAPY • Maintain airway, provide oxygen if necessary • Establish access • Unable to get a peripheral IV – what is the next step? • What would be the first medication you would recommend? • Based on her elevated temp and appearance what other medication(s) might be appropriate? • Obtain labs • Intubate 24 Labs • Finally you get some access and the following labs are ordered and reported to you: • HCT = 24% (normal = 35-45%) • Hgb=8.2 (normal = 11.5-14.5) • WBC=25.8 (normal = 6.0-15.5) • CRP=16.3 (normal < 0.8) • Abnormal coagulation labs (elevated INR) • pH=7.20; base deficit = -5 • Glucose=45 (normal=80-120) Goal: Address Potential Causes • INITIAL THERAPY • Heart rate improves to the 150’s – periphery remains cool • Team would like to give more fluid, based on the labs what fluid would you recommend? • How much of this fluid would you recommend? • What other labs would we want to correct? 25 Goal: Improve Capillary Refill Time and Maintain Normal Blood Pressure • TREAT RESISTANT SHOCK • After our initial therapy, BP drops from 100/52 to 53/17, what can we add? • After starting and titrating this medication, periphery remains cool and BP is only 75/35 – what would you add now? • If patient doesn’t respond after titration of infusions, what are other options? Pharmacist to the rescue Why should I know this…and how can I help? 26 Harness the Power of Pharmacy “By day, Bob Benton is a seemingly normal — and incredibly brilliant — pharmacist who runs his own small drug store. However, whenever evil or danger appears, he becomes the costumed crime-fighter known as the Black Terror. Thanks to “formic ethers” he invented, he has gained heightened strength, speed, agility, and endurance. But even more than that, he has the power of pharmacy.” From: www.politedissent.com “In this story, Ben Benton and his assistant Tim were attending an estate auction when a group of thugs “forcibly” persuaded an elderly antique buff from bidding on a certain old chair. The chair had been used to hide some priceless jewelry, which the gang stole, fought off the Black Terror, and then escaped.” 27 Role of the Pharmacist • Medication preparation/verification • Drug information • Record information - history/background of patient • Recognize signs and symptoms of adverse drug reactions • Toxicology resource • Act as a liaison for pharmacy services or products unvailable in the code cart or the code team. Why Pharmacists are Great! • Studies are emerging in adult and pediatric medicine that show that pharmacist participation in code/trauma situations is key to decreasing morbidity and mortality • More studies are needed but that means that more pharmacists must be more involved! 28 Questions? References • • • • • • • Yager P and Noviski N. Shock. Pediatrics in Review. 2010;31: 311-319 Brierly J, Carcillo JA, Choong K et al. Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock: 2007 Update from the American College of Critical Care Medicine. Critical Care Medicine 2009;37(2): 666-688. McKiernan C, Lieberman S. Circulatory Shock in Children: An Overview. Pediatrics in Review 2005 Dec;26(12): 451-460. Altermann D, Daley B, Kennedy, A, et. al. “Considerations in Pediatric Trauma.” 31 Aug. 2006. eMedicine. 25 Jan. 2007. <www.emedicine.com/med/topic3223.htm> Kelly S, Hays D, O’Brien T, et. al. (2005): Pharmacists Enhancing Patient Safety During Trauma Resucitations. ASHP Midyear, Las Vegas, Nevada. Carcillo JA, Davis AL, Zaritsky A. Role of Early Fluid Resuscitation in Pediatric Septic Shock. JAMA 1991; 266(9): 1242-5. Carcillo JA, Han, K, Lin J, and Orr R. Goal Directed Management of Pediatric Shock in the Emergency Department. Clin Ped Emer Med 2007; 8: 165-175. 29 References • • • • Han YY, Carcillo JA, Dragotta MA, et. al. Early Reversal of PediatricNeonatal Septic Shock by Community Physicians is Associated with Improved Outcomes. Pediatrics 2003; 112: 793-9. Rivers E, Nguyen B, Havstad, et. al. Early Goal Directed Therapy in the Treatment of Severe Sepsis and septic shock. N Engl J Med 2001; 346: 1368-77. Vernon DD, Furnival RA, Hansen KW et al. Effect of a pediatric trauma team response team on emergency department treatment time and mortality of pediatric trauma victims. Pediatrics 1999;103(1):20-4. Klabunde, Richard. “Cardiovascular Physiology.” Cardiovascular Physiology Concepts. 01 Jan 2007. Lippincott Williams 05 Feb. 2007. www.cvphysiology.com 30