Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Prescription costs wikipedia , lookup
Psychedelic therapy wikipedia , lookup
Adherence (medicine) wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Neuropharmacology wikipedia , lookup
Dextropropoxyphene wikipedia , lookup
Theralizumab wikipedia , lookup
Psychopharmacology wikipedia , lookup
Dydrogesterone wikipedia , lookup
Picture depicting Sir Humphrey Davy experimenting Nitrous oxide at the pneumatic institution SOURCES OF PAIN IN THE ICU • Recent Surgery • Pre-existing Disease • Monitoring Devices – ex. Central lines, Pulmonary Artery Catheters. • Endotracheal tubes • Drains , Urinary Catheters. • Nursing Care – Suctioning, Dressing Changes. • Immobilisation CONSEQUENCES OF PAIN • Sleep Deprivation • Agitation • Splinting • Stress Response – • Stimulation of Autonomic Nervous System and release of Humoral factors leads to tachycardia and hypertension and increased myocardial oxygen consumption – myocardial ischemia or Infarction. • Hypercoagulability – altered humoral response leading to increased levels of factor VIII , fibrinogen, platelet activity and inhibition of fibrinolysis. • Immunosuppression – with reduction in number & function of granulocytes & lymphocytes. • Catabolism • Psychological Disturbances – vivid nightmares, hallucinations and paranoid delusions. PAIN ASSESSMENT • Most Reliable and Valid Indicator for Pain assessment is patient’s response and self report. • Therefore patient should be awake if possible. • Intensity – • Verbal Rating Scores – patient self suggests intensity – no pain/mild/moderate/severe/very severe/worst possible pain. • Visual Analog Scales – depicting on a chart the intensity of pain. • Numeric Rating Scales – scaled from 1-10 depending on the intensity. BEHAVIOURAL PAIN SCALE DELIRIUM AND AGITATION Fluctuating Mental Status Inattention Disorganized Thinking Altered level of Consciousness 80 % of ICU patients have delirium – may or may not be accompanied by agitation GOAL OF SEDATION • Daily goal is – AROUSABLE AND COMFORTABLE SEDATION • This approach facilitates reductions in ICU LOS and the Duration of Mechanical Ventilation compared to traditional sedative strategies. • The optimal level of sedation for most patients is – one which offers comfort while allowing interaction with the environment. • Sedation need to be protocolized and titrated to the goal : Lighten Sedation to appropriate wakefulness daily. Effect of this strategy on the outcomes : 1-7 day reduction in length of sedation and MV needs 50% reduction in tracheostomies BENEFITS OF ADEQUATE SEDATION AND ANALGESIA • Facilitates Mechanical Ventilation • Creates Anxiolysis, Analgesia, Amnesia • Decreases Oxygen Consumption • Reduces Dyspnea • Prevents Patient self- injury • Induces Sleep • Creates patient unawareness • Improves long term psychiatric outcomes • Permits delivery of efficient care • Reduces Nursing stress while ensuring Nursing safety • Increases family acceptance of ICU care GUIDELINES - SCCM • Depth and Quality of sedation should be routinely assessed in all ICU patients. • RASS and SAS are most valid and reliable scales for assessing quality and depth of sedation in ICU patients. • Use objective measures of brain function to adjunctively monitor sedation in patients receiving neuromuscular blocking agents. • EEG monitoring to be used for Non-Convulsive Seizure activity in ICU patients at risk for seizures, or to titrate electro suppressive medication to achieve burst suppression in ICU patients with elevated intracranial pressures. • Target the lightest possible level of sedation and/or use daily sedative interruption. • Use sedation protocols and checklists to facilitate ICU sedation management. • Suggest using Analgesia first – sedation for intubated and mechanically ventilated ICU patients. • Suggest using non-benzodiazepines (either Propofol or Dexmedetomidine) rather than Benzodiazepines (Midazolam or Lorazepam) in mechanically ventilated adult ICU patients. SCORING SYSTEM • Should be simple, easily performed, non invasive and easily reproducible. • Depth and Quality of Sedation should be routinely assessed in all ICU patients. • What is adequate sedation? RASS : 0-3 RAMSAY : 3 SAS : 3-4 RICHMOND AGITATION SEDATION SCALE RAMSAY SEDATION SCALE • Awake 1 Anxious and/or agitated 2 Cooperative , oriented and tranquil 3 Responds to commands • Asleep 4 Brisk response to light glabellar tap or loud auditory stimulus 5 Sluggish response to light glabellar tap or loud auditory stimulus 6 No response to light glabellar tap or loud auditory stimulus SEDATION AGITATION SCALE 1 2 3 4 5 6 7 Unarousable Very sedated Sedated Calm and Cooperative Agitated Very Agitated Dangerous Agitation MEASUREMENT OF BRAIN ACTIVITY • Objective measurement of brain function in patients receiving NMBA along with sedation. • Bispectral Index / EEG / Evoked potentials. BISPECTRAL INDEX • A practical, processed EEG parameter that measures the direct effects of sedatives on the brain • 3 components : Patient state Index Cerebral state Index Narcotrend Index BIS RANGE GUIDELINES ADVANTAGES OF BIS DISADVANTAGES OF BIS • Objective sedation assessment to patient’s • Prone to artefacts • Electromyography activity interferes with BIS response • Optimizes clinical and economic outcomes • Minimizes consequences of over and under sedation • Improves quality of sedation management • Numerical scale correlates to sedation endpoint. measures of sedation • Confounding factors influencing BIS scores Hypoglycaemia , Sleep , Temperature , Age, Drugs (Aminophylline, Epinephrine, Ketamine) • Increase variability of BIS in critically ill patients • Cannot be relied upon in circulatory arrest or hypothermia. EEG MONITORING • EEG monitoring to be used for Non-Convulsive Seizure activity in ICU patients at risk for seizures, or to titrate electro suppressive medication to achieve burst suppression in ICU patients with elevated intracranial pressures. • Target the lightest possible level of sedation and/or use daily sedative interruption. Daily interruption of sedation and analgesia : • Allow better assessment of patient’s sedative needs • Reduces drug bioaccumulation • Reduces incidence of post-traumatic stress disorder • Reduces complications of critical illness • More ventilator free days and earlier ICU and hospital discharge…but at the expense of a higher incidence of self- extubation. SEDATION THERAPY Use sedation protocols and checklists to facilitate ICU sedation management. Suggest using Analgesia first – sedation for intubated and mechanically ventilated ICU patients. NON PHARMACOLOGICAL THERAPY • Good Communication with regular reassurance from nursing staff • Environmental control such as humidity, lighting, temperature and noise • Explanation prior to procedures • Management of thirst, hunger, constipation and full bladder SEDATION AND ANALGESIA – PHARMACOLOGIC THERAPY The pharmacologic agent should possess the following qualities: • Both Sedative and Analgesic properties • Anxiolytic , Amnestic and Anticonvulsant properties • No prolonged effects on memory • Minimal Cardiovascular side effects • Controllable Respiratory side effects • Rapid onset/offset of action • No accumulation in renal/hepatic dysfunction • Inactive metabolites • Inexpensive • No interactions with other ICU drugs • No long term psychological effects SEDATION / ANALGESIA OPTIONS • Rule out reversible causes of discomfort and anxiety – Hypoxemia, Hypercarbia, toxic/drug side effects. • Assess comorbidities of the patient. • Keep in mind the potential side effects of the drug chosen. • Target irreversible aetiologies of Pain and Agitation. PHARMACOKINETIC CONSIDERATIONS • Patient’s Fluid Volume Status • Capillary Leak (Changing volume of distribution) • Serum Protein Levels • Renal and Hepatic Function • Hepatic Blood Flow • Competition of combinations of drugs for carrier molecules, metabolic and excretory pathways. CHOICE OF ANALGESIA OPIOID ANALGESIA • Natural chemical derivative of opium • Act on opioid receptors (mu, kappa and sigma receptors) present in the central nervous system and other body systems • Effects – Analgesia, Sedation, Euphoria, Pupillary constriction, Respiratory depression, Bradycardia, Nausea, Vomiting, Constipation, Urinary retention, Pruritis & Physical Dependence • Most commonly used drugs for pain relief in the ICU • Given as intravenous bolus doses or infusions • No amnestic effects like Benzodiazepines CLASSIFICATION OF OPIOIDS OPIOIDS Morphine & its analogues Semisynthetic & synthetic agents Phenylpiperidine derivatives – pethidine, fentanyl Methadone Derivatives – Methadone, Dextropropoxy phene Benzomorphan derivatives – Pentazocine Thebaine DerivativesBuprenorphine Morphine Diamorphine Codeine (Hydrocodone) COMMONLY USED IV OPIOIDS FEATURES MORPHINE FENTANYL HYDROCODONE Onset of action 5-10 mins 1-2 mins 5-15 mins Bolus Dosing 2-4 mg every 1-2 hrs 0.35-0.5 mcg/kg every 0.5-1 hr 0.2-0.6 mg every 1-2 hrs Infusion Rate 2-30 mg/hr 0.7-10 mcg/kg/hr 0.5-3 mg /hr Lipid Solubility x 600x 0.2x Active Metabolites Yes No Yes Histamine Release Yes No No Dose Adjustment for Renal Failure Decrease by 50% None None SOME OTHER OPIOIDS • REMIFENTANYL Ultra short acting opioid given by continuous iv infusion 1.5mcg/kg loading dose f/b continuous infusion at 0.5-15 mcg/kg/hr Analgesic effects are lost within 10 mins of stopping the infusion Drug Metabolism is by non-specific esterases in the plasma – no dose adjustment in hepatic or renal failure Most advantageous in Traumatic Head Injury patients where frequent assessment of cerebral function is required Abrupt cessation can cause withdrawal – beneficial if combined with a longer acting opioid • An Agonist on K –receptors PENTAZOCINE a weak antagonist at mu and delta receptors • Used to relieve moderate pain analgesia by activating receptors in the spinal cord • Less euphoria compared to morphine • Can be administered orally or parenterally • Adverse Reactions – Dysphoria – higher doses can cause Hallucinations , Nightmares, Tachycardia , Hypotension and Dizziness Tolerance and dependence on repeated use • Combined with Phenergan to avoid side effects like nausea and vomiting and give a mild sedative effect • Oral tablets have Naloxone combination to prevent crushing and iv abuse TRAMADOL • Acts via the mu receptor • Also Inhibits uptake of Serotonin and Noradrenaline with presynaptic stimulation of serotonin release • Used for moderate to severe pain in the post-operative patient • Dose – 50-100 mg (i.v. , oral or i.m.) 4 - 6 hourly up to a maximum of 600 mg/day SIDE EFFECTS OF OPIOIDS Vasodilatation and Hypotension Respiratory Depression Depression of Gut Motility Confusion THE ABSTINENCE SYNDROME Withdrawal Symptoms that occur on sudden cessation/reduction of opioid medication. • Irritability • Tremors • Aggression • Fever • Diaphoresis • Piloerection • Pupillary Dilatation • Diarrhoea • Insomnia Treatment – Reinstitution of and then slow withdrawal of opioid or introduction of opioid in combination with a BZD NON OPIOID ANALGESIA – NSAIDS AND OTHERS Dosing KETOROLAC IBUPROFEN ACETAMINOPHEN 30 mg i.v. or i.m. every 6 hrs for up to 5 days 400-800 mg i.v. every 6 hrs 1 gram i.v. every 6 hrs Reduce dosing by 50 % for age>65yrs or body weight <50kg. Comment Daily dose should not exceed 4 grams. NSAID Has anti-inflammatory and antipyretic effects. NSAID Actions are similar to ketorolac. No anti-inflammatory effects which is a major disadvantage n critically ill patients.. Serious complications are uncommon when treatment is limited to less than 5 days. Serious complications are uncommon when used for short term pain relief. Since it is not a NSAID , the side effect profile for this group is safe except for hepatotoxicity in high doses. Side effects of NSAIDS – Renal Dysfunction, GI Bleeding, Increased bleeding tendency due to platelet inhibition. NEUROPATHIC PAIN • Pain attributed to Diabetic Neuropathy and other Chronic illnesses causing nerve root pain • Recommended Drugs : Gabapentin – 600 mg every 8 hrs ( MOA: acts on postsynaptic voltage gated calcium channels – inhibition of calcium influx & decrease in presynaptic excitatory neurotransmitter release) Carbamazepine – 100 mg every 6 hrs Pregabalin – same mechanism of action as gabapentin but higher efficacy and faster onset of action. CHOICE OF SEDATIVES BENZODIAZEPINES • Anxiolytic, Anticonvulsant, Amnesic, Hypnotic and provides some muscle relaxation. • Effects are mediated by depressing the excitability of the limbic system via reversible binding at GABA receptor complex • Minimal Cardiorespiratory depressant effect • Common Drugs in this class are Diazepam, Midazolam and Lorazepam • Patient related factors that affect BZD response – Age, Concurrent pathology, Prior alcohol use, Concurrent therapy with other sedative use • Higher Volume of Distribution and slower clearance in the elderly MIDAZOLAM LORAZEPAM DIAZEPAM LOADING DOSE 0.01-0.05 mg/kg 0.02-0.04 mg /kg 0.05-0.2 mg/kg MAINTENANCE DOSE 0.02-0.1 mg/kg/hr 0.01-0.1 mg/kg/hr Rarely used ONSET 1-5 mins 5-20 mins 2-5 mins DURATION 2-4 hrs 2-6 hrs 3-11 hrs CARDIAC EFFECTS Minimal Minimal Present RESPIRATORY EFFECTS Important Depressant Effect Important Depressant Effect Important Depressant Effect ANALGESIA None None None AMNESIA Potent None None ACTIVE METABOLITES Yes No Yes SIDE EFFECTS Low BP Low BP/ Propylene glycol toxicity & nephrotoxicity Low BP, Phlebitis PROPOFOL • The mode of action of Propofol is via the GABA receptor • Rapid onset of action – 1-2 mins • Metabolised rapidly hepatically and extrahepatically • Recovery is within 10 mins of discontinuation, can accumulate with prolonged use • Ideally to be infused via a large or a central vein • Prolonged infusions – increase Triglyceride and Cholesterol levels • Theoretical maximum dose is 4 mg/kg/hr • Bolus Dose – not recommended • Infusions at 25 to 100 mcg/kg/hr • Caution : PRIS – Propofol Related Infusion Syndrome PROPOFOL – ADVERSE EFFECTS • Hypotension Dose related Decreased SVR and Contractility (Cardiac output) • Respiratory Depression Apnea can occur with Bolus Dosing • Synergistic Cardiovascular and Respiratory Depression with Opioids • Vehicle (Soybean Emulsion) Hypertriglyceridemia Phlebitis Infection PROPOFOL RELATED INFUSION SYNDROME • Adverse drug event associated with high doses(>4 mg/kg/hr or >67mcg/kg/min) and long term use for >48 hrs • Clinical Features Cardiomyopathy with acute cardiac failure Bradycardia Myopathy with or without Rhabdomyolysis Severe Metabolic Acidosis Hyperkalemia Renal Failure Hepatic Dysfunction • Inhibition of Free Fatty Acid entry into the mitochondria due to mitochondrial respiratory chain inhibition by propool results in failure of fat metabolism. • MANAGEMENT Supportive treatments addressing the clinical manifestations The propofol infusion should be discontinued immediately Alternative Sedative agent should be started Intravenous Crystalloid and colloid replacement and vasopressor or inotropic support Cardiac pacing for symptomatic bradycardia Hemodialysis or continuous renal replacement therapy to treat acute renal failure KETAMINE • Acts at the N-Methyl-D-Aspartate (NMDA) receptor • Prevents Nitric Oxide Synthase release • In sub anaesthetic doses it acts as a sedative and analgesic • Increases Blood pressure, Intracranial pressure and Heart rate • Bronchodilator properties, sometimes used in severe asthma • In the ICU used in conjunction with a narcotic (opioid or BZD) • Dose : 5-30 mcg/kg/min • ETOMIDATE OTHERS Can produce hypnosis with concentrations of 300-500 ng/ml • BARBITURATES Pentothal and Thiopentone have been used in the ICU in management of patients with head injuries and raised intracranial pressures & in treatment of refractory status epilepticus. They cause severe cardiovascular depression and accumulate during infusions leading to prolonged recovery times • VOLATILE AGENTS Isoflurane used in concentrations of up to 0.6% for long term sedation with minimal cardiorespiratory side effects and rapid awakening Desflurane is an effective sedative with rapid onset of effects • BUTYROPHENONES AND PHENOTHIAZINES HALOPERIDOL – Useful in patients with delirium to calm them Dopamine receptor antagonist Can be given oral, intramuscular and intravenous Intravenous route is the most preferable – improved absorption, no pain during injection, less patient anxiety and less EPS Bolus dosing – 0.5 mg in elderly to maximum of 10 mg in severe agitation 30 min interval between the doses to gauge effect of previous dose Combination with BZD can be used for rapid sedation – lowers total dose and hence less S/E (like EPS) Side Effects – EPS, Seizures, Neuroleptic Malignant Seizures, Tardive Dyskinesia, Hypotension, QT prolongation (main S/E) QUETIAPINE - treatment of delirium in patients of Parkinson’s Disease and Lewy Body Dementia ALPHA 2 AGONISTS •CLONIDINE Synergistic with opioids and acts the spinal cord to inhibit nociceptive inputs, thus imparts analgesia Contraindicated in hypovolemia and causes hypotension, bradycardia and dry mouth Selectivity : alpha 2 : alpha 1 – 250:1 T ½ is 10 hrs Is sometimes used as an antihypertensive •DEXMEDETOMIDINE Causes Anxiolysis, Amnesia, Analgesia Sedation occurs without respiratory depression Is also a sympatholytic Molecular targets & Neural substrates : Locus ceruleus and natural sleep pathways Smooth emergence & weaning from mechanical ventilation Selectivity : alpha 2 : alpha 1 – 1620:1 94% protein bound Eliminated by liver and kidney Onset is 5-10 mins , Rapid Redistribution is 6 min & T ½ is 2 hrs Only available in iv form Dosing – 1 mcg/kg loading dose over 10 mins f/b 0.2-0.7 mcg/kg/hr infusion Even after 12-24 hrs of infusion no risk of accumulation REGIONAL ANALGESIA TECHNIQUES • Nerve blocks for Thoracic and Abdominal wall – Intercostal Nerve Block , Paravertebral Block , Interpleural Analgesia and Transversus Abdominis Plexus Block • Peripheral Nerve blocks for upper and lower extremities • Epidural analgesia – Long acting drugs – Ropivicaine and Bupivicaine • Better side effect profile with excellent patient tolerance but minimally used in ICU • Most useful in chronic pain syndromes – prevention and treatment. THE ART OF SEDATION • Under Sedation Fighting the ventilator V/Q mismatch Accidental Extubation Catheter Displacement Cardiovascular stress & Ischemia Anxiety , Awareness about procedures Post – traumatic stress disorder • Over Sedation Tolerance, tachyphylaxis Withdrawal Syndrome Delirium Prolonged Ventilation Cardiovascular Depression Sleep Disturbance Inability to test neurological function TITRATION OF SEDATIVE MEDICATIONS • Identify the target symptom or behaviour • Assess the severity • Agree on the appropriate symptom level for that patient at that time • Realize that changes will occur • Titrate the drug level to the achieve desired effect THANK YOU