Presentation on theme: "Sedation and analgesia in ICU Dr. B. Uma University College of Medical Sciences & GTB Hospital, Delhi."— Presentation transcript:
Sedation and analgesia in ICU Dr. B. Uma University College of Medical Sciences & GTB Hospital, Delhi
Sedation Sedation comes from the Latin word sedare. Sedare = to calm or to allay fear Conscious sedation: A minimally depressed level of consciousness induced by the administration of pharmacologic agents in which a patient retains the ability to independently and continuously maintain an open airway and a regular breathing pattern, and to respond appropriately and rationally to physical stimulation and verbal commands
Why is sedation necessary? To improve patient comfort Facilitate interventions To allay fear, anxiety and agitation Adequate sleep Avoid pain Facilitation of mechanical ventilation/airway management/ weaning Protection against myocardial ischemia Amnesia during neuromuscular blockade
Goals for sedation and analgesia To minimize physical discomfort or pain during procedures To minimize psychological disturbance To maximize the potential for amnesia To guard patient safety To control behavior
Complications from pain and anxiety Stimulation of the autonomic nervous system and release of humoral factors → increased heart rate, blood pressure, and myocardial oxygen consumption → myocardial ischemia or infarction Altered humoral response can lead to hypercoagulability as a result of increased level of factor VIII, fibrinogen, platelet activity, and inhibition of fibrinolysis
Complications (contd.) Stress hormones also produce insulin resistance, increased metabolic rate, and protein catabolism Immunosuppression with reduction in number and function of lymphocytes and granulocytes Psychological disturbances - memories of vivid nightmares, hallucinations, and paranoid delusions
Assessment of pain and anxiety Any scoring system should be simple, easily performed, noninvasive, and reproducible. Six levels of sedation are used: 1. Anxious and agitated 2. Cooperative, orientated, and tranquil 3. Responds to verbal commands only 4. Asleep but brisk response to loud auditory stimulus/light glabellar tap 5. Asleep but sluggish response to loud auditory stimulus/light glabellar tap 6. Asleep, no response
Commonly used sedation tools Glasgow coma scale (GCS) – assessment of level of consciousness 6 point Ramsay scale – most commonly used sedation scale Sedation Agitation Scale (SAS) Motor Activity Assessment scale (MAAS) Richmond Agitation–Sedation Scale
Glasgow coma scale
GCS modified by Cook and Palma
Richmond agitation sedation scale ScoreTermDescription +4CombativeViolent; immediate danger to staff +3Very agitatedPulls/ removes tubes, catheters; aggressive +2AgitatedFrequent non purposeful movement; patient ventilator asynchrony +1RestlessAnxious or apprehensive 0Alert and calm DrowsyNot fully alert but awakens for >10s, with eye contact, to voice -2Light sedationBriefly awakens (<10s), with eye contact, to voice -3Moderate sedationAny movement to voice but no eye contact -4Deep sedationNo response to voice but movement to physical stimulation -5UnarousableNo response to voice or physical stimulation
Ramsay sedation scale Awake 1 Anxious and/or agitated 2Cooperative, oriented, and tranquil 3 Responds to commands Asleep 4 Quiescent with brisk response to light glabellar tap or loud auditory stimulus 5Sluggish response to light glabellar tap or loud auditory stimulus 6 No response
Sedation agitation scale 1: Unarousable 2: Very sedated 3: Sedated 4: Calm and cooperative 5: Agitated 6: Very agitated 7: Dangerous agitation
Bispectral index A practical, processed EEG parameter that measures the direct effects of sedatives on the brain Provides objective information about a patient’s response to sedation Numerical scale correlates to sedation endpoints Optimizes sedation assessment and titration
BIS monitor BIS sensor
BIS range guidelines
Value of BIS in ICU Minimize consequences of over- and under-sedation Improve quality of sedation management Objective sedation assessment Optimize clinical and economic outcomes
Recommendation for Assessment of Sedation The use of a validated sedation assessment scale (SAS, MAAS, or Vancouver Interaction and Calmness Scale [VICS]) is recommended. (Grade of recommendation = B) The SCCM guidelines state: Objective measures of sedation, such as Bispectral Index, have not been completely evaluated and are not yet proven useful in the ICU. (Grade of recommendation = C)
Sedation therapy 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 Variety for the patient e.g. radio
Pharmacologic therapy The sedative agent should possess the following qualities: Both sedative and analgesic properties 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
Benzodiazepines Anxiolytic, anticonvulsant, amnesic, hypnotic and provide some muscle relaxation Effects are mediated by depressing the excitability of the limbic system via reversible binding at GABA- benzodiazepine receptor complex Minimal cardiorespiratory depressant effect The common drugs in this class are diazepam, midazolam, and lorazepam
Benzodiazepines: Midazolam Water-soluble Short elimination half life (1-4 hrs) No long acting metabolites In ICU patients, midazolam's elimination half-life may be greatly prolonged and clinically important accumulation may occur Minimal dose: 1 to 2 mg bolus 0.5 to 10 mg/hr
Benzodiazepines: Diazepam Elimination half-life of 21 to 37 hours Major active metabolite, desmethyldiazepam, has a half-life of 48 to 96 hours In terms of cost, diazepam has a clear advantage, being one-tenth the price of midazolam. Minimal dose: 5 to 10mg bolus Infusions not recommended
Benzodiazepines : Lorazepam Lower lipid-solubility than midazolam Less hypotesnion Metabolised by liver to inactive metabolites Lower cost Loading dose: mg/kg Infusion dose: mg/kg/hr
Flumazenil Benzodiazepine antagonist Given in incremental doses of 0.2 to 0.5 mg upto 3 mg Onset – 2 min Duration- 30 to 60 min
Propofol The mode of action of propofol is via the GABA receptor Rapid onset of action; metabolized rapidly hepatically and extrahepatically Recovery within 10 minutes of discontinuation, can accumulate with prolonged use Ideally infused via a large or central vein Prolonged infusions –increase triglyceride and cholesterol levels A theoretical maximum recommended dose is 4 mg/kg/hour.
Propofol (contd.) Bolus dose – not recommended to 100μg/kg/hr Theoretical maximum dose- 4mg/kg/hr Cautious about propofol infusion syndrome
Propofol: adverse effects Hypotension Reliable, dose-related Decreased SVR and contractility (CO) Respiratory depression Apnea with bolus dosing Synergistic CV and respiratory depression with opioids Vehicle (soybean emulsion): Hypertriglyceridemia Venoirritation Infection
Propofol infusion syndrome Propofol infusion syndrome is an adverse drug event associated with high doses (>4 mg/kg per hour or >67 µg/kg per minute) and long-term (>48 hours) use of propofol. Clinical features: - Cardiomyopathy with acute cardiac failure. - Myopathy. - Metabolic acidosis, K + - Hepatomegaly. Inhibition of FFA entry into mitochondria failure of its metabolism.
Management Supportive treatments addressing the clinical manifestations The propofol infusion should be discontinued immediately Alternative sedative should be started Intravenous crystalloid and colloid replacement and vasopressor and/or inotropic support Cardiac pacing may be used for symptomatic bradycardia Hemodialysis or continuous renal replacement therapy to treat the acute renal failure
Ketamine Ketamine acts at the N-methyl-D-aspartate (NMDA) receptor In subanesthetic doses, sedative and analgesic Generally not used because of the increase in blood pressure, intracranial pressure (ICP), and pulse rate Bronchodilatory properties, sometimes has a role in severe asthma In the ICU conjunction with a narcotic Dose : 5 to 30 μg/kg/min
Others ETOMIDATE :For maintenance of hypnosis, target concentration of 300 to 500 ng/mL may be achieved by administration of a two- or three-stage infusion BARBITURATES: Barbiturates such as Pentothal have been used in the ICU, especially in the management of patients with head injuries and seizure disorders. They cause significant cardiovascular depression and accumulate during infusions, leading to prolonged recovery times.
Others (contd.) BUTYROPHENONES AND PHENOTHIAZINES An aggressive dosing regimen of haloperidol may be useful in a patient with delirium to promote calm, 2 to 10 mg IV every 10 to 15 minutes until the desired response is achieved VOLATILE AGENTS Isoflurane has been used in concentrations of up to 0.6% for longterm sedation, with minimal cardiorespiratory side effects and rapid awakening. Desflurane has been shown to be effective in sedation, with rapid offset of effects.
Alpha-2 Agonists N N H N Cl Clonidine CH 3 N N H Dexmedetomidine
2 Agonists Clonidine Selectivity: 2 : 1 250:1 Imidazole derivate 16:1 t 1/2 10 hrs Antihypertensive Dexmedetomidine Selectivity: 2 : :1 Imidazole derivate 31:1 t 1/2 2 hrs 94% protein bound Eliminated by liver/kidney Sedative Only available in IV form
Dexmedetomidine Pharmacology of dexmedetomidine alpha 2 agonist Molecular targets + neural substrates locus ceruleus natural sleep pathways Clinical paradigms for use of dextomed in anesthesia sedation + analgesia w/o respiratory depression attenuation of tachycardia smooth emergence + weaning from mechanical ventilation
Pharmacokinetics Rapid redistribution: 6 min Elimination half-life: 2 h Vd steady state: 118 L Clearance: 39 L/h Protein binding: 94% Metabolism: biotransformation in liver to inactive metabolites + excreted in urine No accumulation after infusions h Pharmacokinetics similar in young adults + elderly
Sedation Typical doses (target plasma levels ng/ml): 0.5 ug/kg load, 0.5 ug/kg/hr infusion 1.0 ug/kg load, 0.7 ug/kg/hr infusion Increase dose by bolus/infusion Load only - short procedures Patients with high sympathetic activity may need very high doses
Clonidine Clonidine is synergistic with opioids and acts at the spinal cord to inhibit nociceptive inputs, thus imparting analgesia It is contraindicated in hypovolemia and can cause hypotension, bradycardia, and dry mouth
The Art of Sedation Under sedation: Fighting the ventilator. V/Q mismatch. Accidental extubation. Catheter displacement. CV stress ischemia. Anxiety, awareness. Post-traumatic stress disorder. Over sedation: Tolerance, tachyphylaxis. Withdrawal syndrome. Delirium. Prolonged ventilation. CV depression. neuro testing. Sleep disturbance.
Analgesia in ICU Pain is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. Thus, perception of sensory events is a requirement, but actual tissue damage is not. Although a majority of ICU patients receive parenteral analgesics routinely, 50% of patients discharged from the ICU remember pain as their worst experience while in the ICU. This emphasizes the need for effective pain control in the ICU.
Indices of pain severity applicable in the critically ill Subjective Visual analogue scale Numeric rating scale Verbal descriptor scale Objective Vital signs measurements Behavioural responses
None mild moderate severe Verbal rating scale І─────────────────І No painWorst pain Visual analog scale
Recommendation for assessment of pain Use of the numeric rating scale(NRS) is recommended to assess pain. (Grade of recommendation = B) Patients who cannot communicate should be assessed through subjective observation of pain and physiological indicators and the change in these parameters following analgesic therapy. (Grade of recommendation =B)
Analgesics used in ICU Pain in the critically ill is best treated with a pure opioid agonist In a recent clinical guideline, the recommended choices have been narrowed to morphine, fentanyl, and hydromorphone. Other drugs with analgesic properties and variable use in critically ill patients are : meperidine (pethidine) tramadol nonsteroidal anti-inflammatory drugs (NSAIDs) mixed opioid agonist-antagonist agents ketamine, a sedative drug with analgesic qualities α2 agonists.
Opioids :Morphine Plasma levels do not correlate with clinical effect. Low lipid solubility causes slow equilibration across BBB. Metabolized in the liver by conjugation. Morphine-6- glucuronide active metabolite with sedative action. The analgesic dose is highly variable, and may be delivered as an intermittent boluses or as a continuous infusion. Minimal cardiovascular side effects Relatively contraindicated in asthma and renal failure
Fentanyl Fentanyl : synthetic opioid derived from meperidine (pethidine) Short-acting opioid with rapid onset After prolonged infusion the duration of action approaches that of morphine Does not accumulate in renal failure It does not cause histamine release and is suitable for analgesia in the hemodynamically unstable patient
Alfentanyl Alfentanil is a synthetic opioid Onset of action about five times faster than fentanyl, due to the small volume of distribution Less lipid soluble The duration of action is about one-third that of fentanyl Alfentanil has minimal cardiovascular effects
Remifentanil Remifentanil, an ultra-short-acting opioid metabolized by nonspecific tissue esterases Rapid onset of action Does not accumulate after infusions even in organ dysfunction. Selective mu-receptor agonist. Potency similar to fentanyl. Terminal half-life < 10 min. Rapid blood-brain equilibrium. Can cause significant bradycardia
MorphineHydromorphoneFentanyl Loading dose5-10 mg1-1.5 mg μg Onset10-20 min5-15 min1-2 min Duration2-3.5 hrs2-3 hrs30-60 min Infusion rate1-5 mg/hr mg/hr μg/hr Active metabolitesYes No Histamine releaseYesNo Cost / 24hrs5mg/hr: $ mg/hr: $ μg/hr: $ 5.50
Epidural analgesia OpioidsConcentration Morphine μg/ml Fentanyl2- 5 μg/ml Adverse effects of epidural analgesia are more common with morphine than fentanyl. Epidural morphine can produce respiratory depression, and the onset can be delayed up to 12 hours. The incidence of respiratory depression is equivalent with epidural and intravenous morphine. More frequent side effects of epidural analgesia include pruritis, nausea, and urinary retention.
Unwanted side-effects of opioids Respiratory depression Confusion Vasodilation Gut motility depression Opioids
Other opioid agonists Tramadol Synthetic 4-phenyl-piperidine analog of codeine Stimulates the µ-receptor 1/5th to 1/10th as potent as morphine Analgesic doses of tramadol may produce less respiratory depression and have minimal effects on gastrointestinal motor function
Naloxone Opioid antagonist Used to restore spontaneous ventilation in patients who breathe inadequately after opioid overdose Onset of action is 1 -2 min Duration of effect is min Dosage – 0.4 to 0.8mg Side effects: tachycardia, hypertension, pulmonary edema
Non steroidal anti inflammatory drugs There is only one NSAID approved for use in the United States: ketorolac. Nonspecific inhibitor of cyclooxygenase with strong analgesic activity and moderate anti inflammatory activity Metabolized in the liver and excreted by the kidneys Dose: 30 mg IV or 60 mg IM, f/b 30 mg IM or IV every 6 hours (maximum of 120 mg/day) for up to 5 days
iv paracetamol The time course of action is quick with iv paracetamol as it reaches peak concentration as soon as infusion is complete (about 15 minutes). According to the product information, the analgesic effect starts within 5 minutes, peaks at 1 hour and lasts 4 to 6 hours.
Clinical practice guidelines for sedation and analgesia from the Society of Critical Care Medicine and American College of Critical Care Medicine Pain
Pain An assessment of pain and the response to therapy should be regularly assessed using an appropriate pain scale. Therapeutic plans and goals should be developed for all patients. Recommended intravenous opioids are fentanyl for acute distress, fentanyl or hydromorphone for patients with hemodynamic instability or renal insufficiency, and morphine and hydromorphone for longer-term therapy. Scheduled doses or continuous infusions are preferred over intermittent boluses. Nonsteroidal anti-inflammatory drugs and acetaminophen can be useful adjuncts, but beware of renal insufficiency or gastrointestinal bleeding.
Sedation Treatment of pain and other reversible causes should be conducted before sedating an agitated patient. A treatment plan/goal should be established for each patient; therapy should be assessed with a sedation scale. Midazolam or diazepam is useful for the acutely agitated patient. Propofol is preferred when rapid awakening is crucial; triglyceride levels should be monitored for >2 d of continuous infusions. Lorazepam is recommended for longer infusions. Doses should be tapered daily to assess underlying mental status, and sedation protocols can be helpful and beneficial.
Guidelines for sedation and analgesia in ICU
References Gabrielli A, Layon A, Joseph, et al. Anesthesia in the ICU. Civetta, Taylor, & Kirby's: Critical Care, 4th Edition; Lippincott Williams & Wilkins:2009 Marino, PL. Analgesia and Sedation. ICU Book, 3rd Edition; Lippincott Williams & Wilkins:2007 Miller RD. Critical care protocols. Miller’s Anaesthesia. 7 th edition:2010