Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU  Dalhousie Critical Care Lecture Series
Objectives <ul><li>Participants should be able to: </li></ul><ul><li>Describe the SCCM guidelines for sedation, analgesia,...
Sources of Pain <ul><li>Recent surgery </li></ul><ul><li>Pre-existing Disease </li></ul><ul><li>Monitoring Devices e.g., c...
Consequences of Pain <ul><li>Sleep deprivation </li></ul><ul><li>Agitation </li></ul><ul><li>Stress response  </li></ul><u...
Pain Assessment <ul><li>The most reliable and valid indicator of pain is  the patient’s self report </li></ul><ul><li>Ther...
<ul><li>Patients receiving analgesia-first approaches consistently achieve comfort goals and less than half require supple...
Daily Goal is Arousable,  Comfortable Sedation <ul><li>Sedation needs to be protocolized and titrated to goal: </li></ul><...
Sedation Assessment <ul><li>Richmond Agitation Sedation Assessment Scale </li></ul><ul><ul><li>+4 Overtly Combative </li><...
Protocols and Assessment Tools <ul><li>SCCM practice guidelines can be used as a template for institution-specific protoco...
Sedating/Analgesia Options <ul><li>Rule out reversible causes of discomfort/anxiety such as hypoxemia, hypercarbia, and to...
Treatment Modalities <ul><li>Proper Positioning </li></ul><ul><li>Stabilization of Fractures </li></ul><ul><li>Cold/Heat A...
Overview of SCCM Algorithm 1 2 3 4 Jacobi J, Fraser GL, Coursin D, et al.  Crit Care Med. 2002;30:119-141.
Pain Assessment <ul><li>Sedated and unconscious patients are very difficult to assess for pain – either its presence or in...
Address Pain
Opiates <ul><li>Benefits </li></ul><ul><ul><li>Relieve pain or the sensibility to noxious stimuli </li></ul></ul><ul><ul><...
Opiate Analgesic Options: Fentanyl, Morphine, Hydromorphone * Offset prolonged after long-term use ** Active metabolite ac...
Fentanyl half life over time
Sample Analgesia Protocol Numeric Rating Scale
Address Sedation Yes
Sedation Options: Benzodiazepines (Midazolam and Lorazepam) <ul><li>Pharmacokinetics/dynamics </li></ul><ul><ul><li>Loraze...
Why Does Midazolam Change From a Short- to a Long-acting Benzodiazepine When Given for a Prolonged Period of Time? Hours D...
Context Specific Half-life Accumulation in a deep compartment is a function of fat solubility and may explain the long dur...
Sedation Options: Propofol <ul><li>Pharmacology: GABA agonist </li></ul><ul><li>Pharmacokinetics/dynamics: onset 1 - 2 min...
Propofol <ul><li>Carson SS, Kress JP, Rodgers JE, et al. A randomized trial of intermittent lorazepam versus propofol with...
Sample Sedation Protocol Sedation-agitation Scale Riker RR et al. Crit Care Med. 1999;27:1325.
Opiate and Benzodiazepine Withdrawal <ul><li>Frequency related to dose and duration </li></ul><ul><ul><li>32% if receiving...
Significance of ICU Delirium <ul><li>Seen in > 50% of ICU patients  </li></ul><ul><li>Three times higher risk of death by ...
Delirium <ul><li>Acute onset of mental status changes or a fluctuating course </li></ul><ul><li>& </li></ul><ul><li>2. Ina...
Risk Factors for Delirium <ul><li>Primary CNS Dx </li></ul><ul><li>Benzodiazepine use </li></ul><ul><li>Infection </li></u...
Diagnostic Tools: ICU <ul><li>Routine monitoring recommended by SCCM </li></ul><ul><ul><li>Only 6% of ICUs use Confusion A...
Delirium Screening Checklist <ul><li>No Patient Participation </li></ul><ul><ul><li>Delirium Screening Checklist </li></ul...
Treatment of Delirium <ul><li>Correct inciting factor, but as for pain…relief need not be delayed while identifying causat...
Haloperidol <ul><li>No prospective randomized controlled trials in ICU delirium  </li></ul><ul><li>> 700 published reports...
Atypical Antipsychotics: Quetiapine, Olanzapine, Risperidone, Ziprasidone <ul><li>Mechanism of action unknown </li></ul><u...
Neuromuscular Blockade (NMB) (Paralytics) in the Adult ICU <ul><li>Used most often acutely (single dose) to facilitate int...
Neuromuscular Blockade in the ICU <ul><li>Current use in ICU limited because of risk of prolonged weakness and other compl...
Neuromuscular Blocking Agents <ul><li>Two classes of NMBS: </li></ul><ul><ul><li>Depolarizers </li></ul></ul><ul><ul><ul><...
Quick Onset Muscle Relaxants for Intubation <ul><li>Patients with aspiration risk need rapid onset paralysis for intubatio...
Potential Contraindications of Succinylcholine <ul><li>Increases serum potassium by 0.5 to 1 meq/liter in all patients </l...
Neuromuscular Blocking Agents <ul><li>Nondepolarizing muscle relaxants </li></ul><ul><ul><li>Pancuronium, vecuronium, cisa...
Neuromuscular Blocking Agents <ul><li>Infusion doses </li></ul><ul><ul><li>Pancuronium 0.05 - 0.1 mg/kg/h </li></ul></ul><...
Monitoring NMBAs <ul><li>Goal - To prevent prolonged weakness associated with excessive NMBA administration </li></ul><ul>...
Monitoring Sedation During Paralysis <ul><li>Bispectral index is based on cumulative observation of a large number of clin...
Complications of Neuromuscular Blocking Agents <ul><li>Associated with inactivity: </li></ul><ul><ul><li>Muscle wasting, d...
Sample NMBA Protocol
Case Scenario #1 <ul><li>22-year-old male with isolated closed head injury who was intubated for GCS of 7 </li></ul><ul><l...
Case Scenario #1 - Answer <ul><li>Propofol will rapidly calm a patient who is displaying dangerous behavior without need f...
Case Scenario #2 <ul><li>54-year-old alcoholic who has been admitted for  Staph  sepsis </li></ul><ul><li>Intubated in the...
Case Scenario #2 - Answer <ul><li>This patient is oversedated.  Not only can a neurologic exam not be performed, but it wo...
Case Scenario #3 <ul><li>62-year-old, 65-kg woman with ARDS from aspiration pneumonia </li></ul><ul><li>Her ventilator set...
Case Scenario #3 - Answer <ul><li>This patient needs optimization of her sedatives, and potentially chemical paralysis to ...
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Sedation

  1. 1. Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU Dalhousie Critical Care Lecture Series
  2. 2. Objectives <ul><li>Participants should be able to: </li></ul><ul><li>Describe the SCCM guidelines for sedation, analgesia, and chemical paralysis </li></ul><ul><li>Describe the benefits of daily awakening/lightening and sedation titration programs </li></ul><ul><li>Devise a rational pharmacologic strategy based on treatment goals and comorbidities Participants should be able to: </li></ul>
  3. 3. Sources of Pain <ul><li>Recent surgery </li></ul><ul><li>Pre-existing Disease </li></ul><ul><li>Monitoring Devices e.g., central lines </li></ul><ul><li>Drains – urinary </li></ul><ul><li>ETT </li></ul><ul><li>Nursing care – suctioning/ dressing changes </li></ul><ul><li>Immobilisation </li></ul>
  4. 4. Consequences of Pain <ul><li>Sleep deprivation </li></ul><ul><li>Agitation </li></ul><ul><li>Stress response </li></ul><ul><ul><li>Tachycardia </li></ul></ul><ul><ul><li>Increased Myocardial Oxygen Consumption </li></ul></ul><ul><ul><li>Hypercoagulability </li></ul></ul><ul><ul><li>Immunosuppression </li></ul></ul><ul><ul><li>Catabolism </li></ul></ul><ul><li>Splinting </li></ul>
  5. 5. Pain Assessment <ul><li>The most reliable and valid indicator of pain is the patient’s self report </li></ul><ul><li>Therefore the patient should be awake if possible </li></ul><ul><li>Aggravating and Relieving factors </li></ul><ul><li>Intensity </li></ul><ul><ul><li>Verbal rating scores </li></ul></ul><ul><ul><li>Visual Analog Scales </li></ul></ul><ul><ul><li>Numeric Rating Scales </li></ul></ul>
  6. 6. <ul><li>Patients receiving analgesia-first approaches consistently achieve comfort goals and less than half require supplementation with propofol or a benzodiazepine. </li></ul><ul><li>This approach may facilitate reductions in ICU length of stay and the duration of mechanical ventilation compared to traditional sedative strategies </li></ul><ul><li>The optimal level of sedation for most patients is that which offers comfort while allowing for interaction with the environment. </li></ul>Daily Goal is Arousable, Comfortable Sedation Breen D, Karabinis A, Malbrain M, et al. Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients: a randomized trial. Crit Care 2005; 9:R200–R210. Kuhlen R, Putensen C. Remifentanil for analgesia-based in the intensive careunit. Crit Care 2004; 8:13–14.
  7. 7. Daily Goal is Arousable, Comfortable Sedation <ul><li>Sedation needs to be protocolized and titrated to goal: </li></ul><ul><ul><li>Lighten sedation to appropriate wakefulness daily. </li></ul></ul><ul><li>Effect of this strategy on outcomes: </li></ul><ul><ul><li>One- to seven-day reduction in length of sedation and mechanical ventilation needs </li></ul></ul><ul><ul><li>50% reduction in tracheostomies </li></ul></ul><ul><ul><li>Three-fold reduction in the need for diagnostic evaluation of CNS </li></ul></ul>
  8. 8. Sedation Assessment <ul><li>Richmond Agitation Sedation Assessment Scale </li></ul><ul><ul><li>+4 Overtly Combative </li></ul></ul><ul><ul><li>+3 Very Agitated </li></ul></ul><ul><ul><li>+2 Agitated </li></ul></ul><ul><ul><li>+1 Restless </li></ul></ul><ul><ul><li>0 </li></ul></ul><ul><ul><li>Alert and Calm </li></ul></ul><ul><ul><li>-1 Drowsy </li></ul></ul><ul><ul><li>-2 Light Sedation </li></ul></ul><ul><ul><li>-3 Moderate Sedation </li></ul></ul><ul><ul><li>-4 Deep Sedation </li></ul></ul><ul><ul><li>-5 Unarousable </li></ul></ul>Ely et al JAMA 2003;289:2983-2991
  9. 9. Protocols and Assessment Tools <ul><li>SCCM practice guidelines can be used as a template for institution-specific protocols. </li></ul><ul><li>Titration of sedatives and analgesics guided by assessment tools: </li></ul><ul><ul><li>Validated sedation assessment tools (Ramsay Sedation Scale [RSS], Sedation-Agitation Scale [SAS], Richmond Sedation-agitation Scale [RSAS], etc.) </li></ul></ul><ul><ul><ul><li>- No evidence that one is preferred over another </li></ul></ul></ul><ul><ul><li>Pain assessment tools - none validated in ICU (numeric rating scale [NRS], visual analogue scale [VAS], etc.) </li></ul></ul>
  10. 10. Sedating/Analgesia Options <ul><li>Rule out reversible causes of discomfort/anxiety such as hypoxemia, hypercarbia, and toxic/drug side effect. </li></ul><ul><li>Assess comorbidities and potential side effects of drugs chosen. </li></ul><ul><li>Target irreversible etiologies of pain and agitation. </li></ul>
  11. 11. Treatment Modalities <ul><li>Proper Positioning </li></ul><ul><li>Stabilization of Fractures </li></ul><ul><li>Cold/Heat Application </li></ul><ul><li>Pharmacology </li></ul><ul><ul><li>NSAIDS – coagulation effects/renal effects/GI effects </li></ul></ul><ul><ul><li>Regional – coagulation </li></ul></ul><ul><ul><li>Acetaminophen – liver toxicity </li></ul></ul><ul><ul><li>Opioids by default </li></ul></ul>
  12. 12. Overview of SCCM Algorithm 1 2 3 4 Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:119-141.
  13. 13. Pain Assessment <ul><li>Sedated and unconscious patients are very difficult to assess for pain – either its presence or intensity </li></ul><ul><li>Over or Under-estimated with adverse consequences in either case </li></ul>
  14. 14. Address Pain
  15. 15. Opiates <ul><li>Benefits </li></ul><ul><ul><li>Relieve pain or the sensibility to noxious stimuli </li></ul></ul><ul><ul><li>Sedation trending toward a change in sensorium, especially with more lipid soluble forms including morphine and hydromorphone. </li></ul></ul><ul><li>Risks </li></ul><ul><ul><li>Respiratory depression </li></ul></ul><ul><ul><li>NO amnesia </li></ul></ul><ul><ul><li>Pruritus </li></ul></ul><ul><ul><li>Ileus </li></ul></ul><ul><ul><li>Urinary retention </li></ul></ul><ul><ul><li>Histamine release causing venodilation predominantly from morphine </li></ul></ul><ul><ul><li>Morphine metabolites which accumulate in renal failure can be analgesic and anti-analgesic. </li></ul></ul><ul><ul><li>Meperidine should be avoided due to neurotoxic metabolites which accumulate, especially in renal failure, but also produces more sensorium changes and less analgesia than other opioids. </li></ul></ul>
  16. 16. Opiate Analgesic Options: Fentanyl, Morphine, Hydromorphone * Offset prolonged after long-term use ** Active metabolite accumulation causes excessive narcosis 10 mg 1.5 mg 100 mcg Equivalent doses X Avoid in hemodynamic instability X Preload reduction X** Avoid in renal disease X* Rapid offset X Rapid onset Morphine Hydromorphone Fentanyl
  17. 17. Fentanyl half life over time
  18. 18. Sample Analgesia Protocol Numeric Rating Scale
  19. 19. Address Sedation Yes
  20. 20. Sedation Options: Benzodiazepines (Midazolam and Lorazepam) <ul><li>Pharmacokinetics/dynamics </li></ul><ul><ul><li>Lorazepam: onset 5 - 10 minutes, half-life 10 hours, glucuronidated </li></ul></ul><ul><ul><li>Midazolam: onset 1 - 2 minutes, half-life 3 hours, metabolized by cytochrome P450, active metabolite (1-OH) accumulates in renal disease </li></ul></ul><ul><li>Benefits </li></ul><ul><ul><li>Anxiolytic </li></ul></ul><ul><ul><li>Amnestic </li></ul></ul><ul><ul><li>Sedating </li></ul></ul><ul><li>Risks </li></ul><ul><ul><li>Delirium </li></ul></ul><ul><ul><ul><li>Pandharipande P, Ely EW. Sedative and analgesic medications: risk factors for delirium and sleep disturbances in the critically ill. Crit Care Clin 2006;22:313–327 </li></ul></ul></ul><ul><ul><li>NO analgesia </li></ul></ul><ul><ul><li>Excessive sedation: especially after long-term sustained use </li></ul></ul><ul><ul><li>Propylene glycol toxicity (parenteral lorazepam): significance uncertain </li></ul></ul><ul><ul><ul><li>- Evaluate when a patient has unexplained acidosis </li></ul></ul></ul><ul><ul><ul><li>- Particularly problematic in alcoholics (due to doses used) and renal failure </li></ul></ul></ul><ul><ul><li>Respiratory failure (especially with concurrent opiate use) </li></ul></ul><ul><ul><li>Withdrawal </li></ul></ul>
  21. 21. Why Does Midazolam Change From a Short- to a Long-acting Benzodiazepine When Given for a Prolonged Period of Time? Hours Duration of midazolam therapy Chest. 1993;103:55.
  22. 22. Context Specific Half-life Accumulation in a deep compartment is a function of fat solubility and may explain the long duration of action of midazolam after long-term use.
  23. 23. Sedation Options: Propofol <ul><li>Pharmacology: GABA agonist </li></ul><ul><li>Pharmacokinetics/dynamics: onset 1 - 2 minutes, terminal half-life 6 hours, duration 10 minutes, hepatic metabolism </li></ul><ul><li>Benefits </li></ul><ul><ul><li>Rapid onset and offset and easily titrated </li></ul></ul><ul><ul><li>Hypnotic and antiemetic </li></ul></ul><ul><ul><li>Can be used for intractable seizures and elevated intracranial pressure </li></ul></ul><ul><li>Risks </li></ul><ul><ul><li>Not reliably amnestic, especially at low doses </li></ul></ul><ul><ul><li>NO analgesia! </li></ul></ul><ul><ul><li>Hypotension </li></ul></ul><ul><ul><li>Hypertriglyceridemia; lipid source (1.1 kcal/ml) </li></ul></ul><ul><ul><li>Respiratory depression </li></ul></ul><ul><ul><li>Propofol Infusion Syndrome </li></ul></ul><ul><ul><ul><li>- Cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure </li></ul></ul></ul><ul><ul><ul><li>- Caution should be exercised at doses > 80 mcg/kg/min for more than 48 hours </li></ul></ul></ul><ul><ul><ul><li>- Particularly problematic when used simultaneously in patient receiving catecholamines and/or steroids </li></ul></ul></ul>
  24. 24. Propofol <ul><li>Carson SS, Kress JP, Rodgers JE, et al. A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med 2006; 34:1326–1332. </li></ul><ul><li>Propofol sedation vs lorazepam using the same sedation titration goals and daily sedation interruption </li></ul><ul><li>Mechanical ventilation duration was shorter with propofol than with lorazepam (5.8 vs. 8.4 days, P¼0.04) despite the use of identical </li></ul>
  25. 25. Sample Sedation Protocol Sedation-agitation Scale Riker RR et al. Crit Care Med. 1999;27:1325.
  26. 26. Opiate and Benzodiazepine Withdrawal <ul><li>Frequency related to dose and duration </li></ul><ul><ul><li>32% if receiving high doses for longer than a week </li></ul></ul><ul><li>Onset depends on the half-lives of the parent drug and its active metabolites </li></ul><ul><li>Clinical signs and symptoms are common among agents </li></ul><ul><ul><li>CNS activation: seizures, hallucinations, </li></ul></ul><ul><ul><li>GI disturbances: nausea, vomiting, diarrhea </li></ul></ul><ul><ul><li>Sympathetic hyperactivity: tachycardia, hypertension, tachypnea, sweating, fever </li></ul></ul><ul><li>No prospectively evaluated weaning protocols available </li></ul><ul><ul><li>10 - 20% daily decrease in dose </li></ul></ul><ul><ul><li>20 - 40% initial decrease in dose with additional daily reductions of 10 - 20% </li></ul></ul><ul><li>Consider conversion to longer acting agent or transdermal delivery form </li></ul>
  27. 27. Significance of ICU Delirium <ul><li>Seen in > 50% of ICU patients </li></ul><ul><li>Three times higher risk of death by six months </li></ul><ul><li>Five fewer ventilator free days (days alive and off vent.), adjusted P = 0.03 </li></ul><ul><li>Four times greater frequency of medical device removal </li></ul><ul><li>Nine times higher incidence of cognitive impairment at hospital discharge </li></ul>
  28. 28. Delirium <ul><li>Acute onset of mental status changes or a fluctuating course </li></ul><ul><li>& </li></ul><ul><li>2. Inattention </li></ul><ul><li>& </li></ul>or Courtesy of W Ely, MD 3. Disorganized Thinking 4. Altered level of consciousness
  29. 29. Risk Factors for Delirium <ul><li>Primary CNS Dx </li></ul><ul><li>Benzodiazepine use </li></ul><ul><li>Infection </li></ul><ul><li>Metabolic derangement </li></ul><ul><li>Pain </li></ul><ul><li>Sleep deprivation </li></ul><ul><li>Age </li></ul><ul><li>Substances including tobacco (withdrawal as well as direct effect) </li></ul>
  30. 30. Diagnostic Tools: ICU <ul><li>Routine monitoring recommended by SCCM </li></ul><ul><ul><li>Only 6% of ICUs use Confusion Assessment Method (CAM-ICU) or Delirium Screening Checklist (DSC) </li></ul></ul><ul><li>Requires Patient Participation </li></ul><ul><ul><li>Cognitive Test for Delirium </li></ul></ul><ul><ul><li>Abbreviated Cognitive Test for Delirium </li></ul></ul><ul><ul><li>CAM-ICU </li></ul></ul><ul><ul><li>Ely. JAMA. 2001;286: 2703-2710. </li></ul></ul>
  31. 31. Delirium Screening Checklist <ul><li>No Patient Participation </li></ul><ul><ul><li>Delirium Screening Checklist </li></ul></ul>Bergeron. Intensive Care Med. 2001;27:859.
  32. 32. Treatment of Delirium <ul><li>Correct inciting factor, but as for pain…relief need not be delayed while identifying causative factor </li></ul><ul><li>Control symptoms? </li></ul><ul><ul><li>No evidence that treatment reduces duration and severity of symptoms </li></ul></ul><ul><ul><li>Typical and atypical antipsychotic agents </li></ul></ul><ul><ul><li>Sedatives? </li></ul></ul><ul><ul><ul><li>Particularly in combination with antipsychotic and for drug/alcohol withdrawal delirium </li></ul></ul></ul><ul><li>No treatment FDA approved </li></ul>
  33. 33. Haloperidol <ul><li>No prospective randomized controlled trials in ICU delirium </li></ul><ul><li>> 700 published reports involving > 2,000 patients </li></ul><ul><li>The good: </li></ul><ul><ul><li>Hemodynamic neutrality </li></ul></ul><ul><ul><li>No effect on respiratory drive </li></ul></ul><ul><li>The bad: </li></ul><ul><ul><li>QTc prolongation and torsades de pointes </li></ul></ul><ul><ul><li>Neuoroleptic malignant syndrome - only three cases with IV haloperidol </li></ul></ul><ul><ul><li>Extrapyramidal side effects - less common with IV than oral haloperidol </li></ul></ul>
  34. 34. Atypical Antipsychotics: Quetiapine, Olanzapine, Risperidone, Ziprasidone <ul><li>Mechanism of action unknown </li></ul><ul><li>Less movement disorders than haloperidol </li></ul><ul><li>Enhanced effects on both positive (agitation) and negative (quiet) symptoms </li></ul><ul><li>Efficacy = haloperidol? </li></ul><ul><ul><li>One prospective randomized study showing equal efficacy of olanzapine to haldol with less EPS </li></ul></ul><ul><li>Issues </li></ul><ul><ul><li>Lack of available IV formulation </li></ul></ul><ul><ul><li>Troublesome reports of CVAs, hyperglycemia, NMS </li></ul></ul><ul><ul><li>Titratability hampered </li></ul></ul><ul><ul><ul><li>- QTc prolongation with ziprasidone IM </li></ul></ul></ul><ul><ul><ul><li>- Hypotension with olanzapine IM </li></ul></ul></ul>
  35. 35. Neuromuscular Blockade (NMB) (Paralytics) in the Adult ICU <ul><li>Used most often acutely (single dose) to facilitate intubation or selected procedures </li></ul><ul><li>Issues </li></ul><ul><ul><li>NO ANALGESIC or SEDATIVE properties </li></ul></ul><ul><ul><li>Concurrent sedation with amnestic effect is paramount analgesic as needed </li></ul></ul><ul><ul><li>Never use without the ability to establish and/or maintain a definitive airway with ventilation </li></ul></ul><ul><ul><li>If administering for prolonged period (> 6 - 12 hours), use an objective monitor to assess degree of paralysis. </li></ul></ul>
  36. 36. Neuromuscular Blockade in the ICU <ul><li>Current use in ICU limited because of risk of prolonged weakness and other complications </li></ul><ul><ul><li>Maximize sedative/analgesic infusions as much as possible prior to adding neuromuscular blockade </li></ul></ul><ul><li>Indications </li></ul><ul><ul><li>Facilitate mechanical ventilation, especially with abdominal compartment syndrome, high airway pressures, and dyssynchrony </li></ul></ul><ul><ul><li>Assist in control of elevated intracranial pressures </li></ul></ul><ul><ul><li>Reduce oxygen consumption </li></ul></ul><ul><ul><li>Prevent muscle spasm in neuroleptic malignant syndrome, tetanus, etc. </li></ul></ul><ul><ul><li>Protect surgical wounds or medical device placement </li></ul></ul>
  37. 37. Neuromuscular Blocking Agents <ul><li>Two classes of NMBS: </li></ul><ul><ul><li>Depolarizers </li></ul></ul><ul><ul><ul><li>- Succhinylcholine is the only drug in this class </li></ul></ul></ul><ul><ul><ul><li>- Prolonged binding to acetylcholine receptor to produce depolarization (fasciculations) and subsequent desensitization so that the motor endplate cannot respond to further stimulation right away </li></ul></ul></ul><ul><ul><li>Nondepolarizers </li></ul></ul><ul><ul><ul><li>- Blocks acetylcholine from postsynaptic receptor competitively </li></ul></ul></ul><ul><ul><ul><li>- Benzylisoquinoliniums </li></ul></ul></ul><ul><ul><ul><ul><li>Curare, atracurium, cisatracurium, mivacurium, doxacuronium </li></ul></ul></ul></ul><ul><ul><ul><li>- Aminosteroids </li></ul></ul></ul><ul><ul><ul><ul><li>Pancuronium, vecuronium, rococuronium </li></ul></ul></ul></ul>
  38. 38. Quick Onset Muscle Relaxants for Intubation <ul><li>Patients with aspiration risk need rapid onset paralysis for intubation. </li></ul><ul><li>Not usually used for continuous maintenance infusions </li></ul><ul><li>Rocuronium </li></ul><ul><ul><li>Nondepolarizer with about an hour duration and 10% renal elimination </li></ul></ul><ul><ul><li>Dose is 1.2 mg/kg to have intubating conditions in 45 seconds </li></ul></ul><ul><li>Succinylcholine </li></ul><ul><ul><li>Depolarizer with a usual duration of 10 minutes </li></ul></ul><ul><ul><li>All or none train of four after administration due to desensitization (can be prolonged in patients with abnormal plasma cholinesterase) </li></ul></ul><ul><ul><li>Dose is 1 - 2 mg/kg to have intubating conditions in 30 seconds </li></ul></ul>
  39. 39. Potential Contraindications of Succinylcholine <ul><li>Increases serum potassium by 0.5 to 1 meq/liter in all patients </li></ul><ul><li>Can cause bradycardia, anaphylaxis, and muscle pain </li></ul><ul><li>Potentially increases intragastric, intraocular, and intracranial pressure </li></ul><ul><li>Severely elevates potassium due to proliferation of extrajunctional receptors in patients with denervation injury, stroke, trauma, or burns of more than 24 hours </li></ul>
  40. 40. Neuromuscular Blocking Agents <ul><li>Nondepolarizing muscle relaxants </li></ul><ul><ul><li>Pancuronium, vecuronium, cisatracurium </li></ul></ul><ul><ul><li>All rapid onset (2 - 3 minutes) </li></ul></ul><ul><ul><li>Differ in duration (pancuronium 1 - 2 hours, vecuronium 0.5 hours, cisatracurium 0.5 hours) </li></ul></ul><ul><ul><li>Differ in route of elimination (pancuronium = renal/liver, vecuronium = renal/bile, cisatracurium = Hoffman degradation) </li></ul></ul>
  41. 41. Neuromuscular Blocking Agents <ul><li>Infusion doses </li></ul><ul><ul><li>Pancuronium 0.05 - 0.1 mg/kg/h </li></ul></ul><ul><ul><li>Vecuronium 0.05 - 0.1 mg/kg/h </li></ul></ul><ul><ul><li>Cisatracurium 0.03 - 0.6 mg/kg/h </li></ul></ul><ul><li>Other distinguishing features </li></ul><ul><ul><li>Pancuronium causes tachycardia </li></ul></ul><ul><ul><li>Vecuronium has neutral effects on hemodynamics but has several renally excreted active metabolites </li></ul></ul><ul><ul><li>Elimination of cisatracurium is not affected by organ dysfunction, but it is expensive </li></ul></ul>
  42. 42. Monitoring NMBAs <ul><li>Goal - To prevent prolonged weakness associated with excessive NMBA administration </li></ul><ul><li>Methods: </li></ul><ul><ul><li>Perform NMBA dose reduction or cessation once daily if possible </li></ul></ul><ul><ul><li>Clinical evaluation: Assess skeletal muscle movement and respiratory effort </li></ul></ul><ul><ul><li>Peripheral nerve stimulation </li></ul></ul><ul><ul><ul><li>- Train of four response consists of four stimulae of 2 Hz, 0.2 msec in duration, and 500 msec apart. </li></ul></ul></ul><ul><ul><ul><li>- Comparison of T4 (4 th twitch) and T1 with a fade in strength means that 75% of receptors are blocked. </li></ul></ul></ul><ul><ul><ul><li>- Only T1 or T1 and 2 is used for goal in ICU and indicates up to 90% of receptors are blocked. </li></ul></ul></ul>
  43. 43. Monitoring Sedation During Paralysis <ul><li>Bispectral index is based on cumulative observation of a large number of clinical cases correlating clinical signs with EEG signals. </li></ul><ul><li>While used to titrate appropriate sedation (and amnesia) in anesthetized patients to the least amount required, not proven to achieve this goal. </li></ul><ul><li>Studies in anesthetized patients </li></ul><ul><ul><li>40–60 for deep surgical anesthesia </li></ul></ul><ul><ul><li>70–90 for light anesthesia </li></ul></ul><ul><li>No randomized controlled studies to support reliable use in ICU. </li></ul><ul><li>Cessation of NMB as soon as safe in conjunction with other patient parameters should be a daily consideration. </li></ul>
  44. 44. Complications of Neuromuscular Blocking Agents <ul><li>Associated with inactivity: </li></ul><ul><ul><li>Muscle wasting, deconditioning, decubitus ulcers, corneal drying </li></ul></ul><ul><li>Associated with inability to assess patient: </li></ul><ul><ul><li>Recall, unrelieved pain, acute neurologic event, anxiety </li></ul></ul><ul><li>Associated with loss of respiratory function: </li></ul><ul><ul><li>Asphyxiation from ventilator malfunction or accidental extubation, atelectasis, pneumonia </li></ul></ul><ul><li>Other: </li></ul><ul><ul><li>Prolonged paralysis or acute NMBA related myopathy </li></ul></ul><ul><ul><ul><li>- Related to decreased membrane excitability or even muscle necrosis </li></ul></ul></ul><ul><ul><ul><li>- Risk can be compounded by concurrent use of steroids. </li></ul></ul></ul>
  45. 45. Sample NMBA Protocol
  46. 46. Case Scenario #1 <ul><li>22-year-old male with isolated closed head injury who was intubated for GCS of 7 </li></ul><ul><li>He received 5 mg of morphine, 40 mg of etomidate, and 100 mg of succinylcholine for his intubation. </li></ul><ul><li>He is covered in blood spurting from an arterial catheter that was just removed, and he appears to be reaching for his endotracheal tube. </li></ul><ul><li>What sedative would you use and why? </li></ul><ul><li>What are the particular advantages in this situation? </li></ul><ul><li>How could you avoid the disadvantages of this drug? </li></ul>
  47. 47. Case Scenario #1 - Answer <ul><li>Propofol will rapidly calm a patient who is displaying dangerous behavior without need for paralysis. </li></ul><ul><li>Titratable and can be weaned quickly to allow for neurologic exam </li></ul><ul><li>Can treat seizures and elevated ICP which may be present in a head trauma with GCS of eight or less </li></ul><ul><li>Minimizing dose and duration will avoid side effects. </li></ul>
  48. 48. Case Scenario #2 <ul><li>54-year-old alcoholic who has been admitted for Staph sepsis </li></ul><ul><li>Intubated in the ICU for seven days and is currently on midazolam at 10 mg/hour </li></ul><ul><li>His nurse was told in report that he was a “madman” on the evening shift. </li></ul><ul><li>Currently, he opens his eyes occasionally to voice but does not follow commands nor does he move his extremities to deep painful stimulation. </li></ul><ul><li>Is this appropriate sedation? </li></ul><ul><li>What would you like to do? </li></ul><ul><li>How would you institute your plan of action? </li></ul>
  49. 49. Case Scenario #2 - Answer <ul><li>This patient is oversedated. Not only can a neurologic exam not be performed, but it would be unlikely to be able to perform a wakeup test within one 24-hour period. </li></ul><ul><li>Given the need to examine the patient, midazolam should be stopped immediately. </li></ul><ul><li>Rescue sedatives including midazolam should be available if agitation develops. </li></ul><ul><li>Flumazenil should be avoided. </li></ul>
  50. 50. Case Scenario #3 <ul><li>62-year-old, 65-kg woman with ARDS from aspiration pneumonia </li></ul><ul><li>Her ventilator settings are PRVC 400, RR 18, PEEP 8, and FIO 2 100%. She is dyssynchronous with the ventilator and her plateau pressure is 37 mm Hg. </li></ul><ul><li>She is on propofol at 50 mcg/kg/min, which has been ongoing since admit four days ago. </li></ul><ul><li>She is also on norepinephrine 0.1 mcg/kg/min and she was just started on steroids. </li></ul><ul><li>What do you want to do next? </li></ul><ul><li>Do you want to continue the propofol? </li></ul><ul><li>Why or why not? </li></ul><ul><li>What two iatrogenic problems is she likely at risk for? </li></ul>
  51. 51. Case Scenario #3 - Answer <ul><li>This patient needs optimization of her sedatives, and potentially chemical paralysis to avoid complications of ventilator dyssynchrony and high airway pressures. </li></ul><ul><li>If you continue to use propofol, higher doses are required and the patient is already on norepinephrine. In addition, if paralysis is used, you do not have reliable amnesia. </li></ul><ul><li>She is at risk for propofol infusion syndrome and critical illness polyneuropathy. </li></ul>
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