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  1. 1. Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU Giuditta Angelini, MD University of Wisconsin Madison, WI Gil Fraser, PharmD, FCCM Maine Medical Center Portland, ME Doug Coursin, MD, FCCM University of Wisconsin Madison, WI
  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><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 </li></ul>
  3. 3. What We Know About ICU Agitation/Discomfort <ul><li>Prevalence </li></ul><ul><ul><li>50% incidence in those with length of stay > 24 hours </li></ul></ul><ul><li>Primary causes: unrelieved pain, delirium, anxiety, sleep deprivation, etc. </li></ul><ul><li>Immediate sequelae: </li></ul><ul><ul><li>Patient-ventilator dyssynchrony </li></ul></ul><ul><ul><li>Increased oxygen consumption </li></ul></ul><ul><ul><li>Self (and health care provider) injury </li></ul></ul><ul><ul><li>Family anxiety </li></ul></ul><ul><li>Long-term sequelae: chronic anxiety disorders and post-traumatic stress disorder (PTSD) </li></ul>
  4. 4. Recall in the ICU <ul><li>Some degree of recall occurs in up to 70% of ICU patients. </li></ul><ul><ul><li>Anxiety, fear, pain, panic, agony, or nightmares reported in 90% of those who did have recall. </li></ul></ul><ul><li>Potentially cruel: </li></ul><ul><ul><li>Up to 36% recalled some aspect of paralysis. </li></ul></ul><ul><li>Associated with PTSD in ARDS? </li></ul><ul><ul><li>41% risk of recall of two or more traumatic experiences. </li></ul></ul><ul><li>Associated with PTSD in cardiac surgery </li></ul>
  5. 5. Appropriate Recall May be Important <ul><li>Factual memories (even unpleasant ones) help to put ICU experience into perspective </li></ul><ul><li>Delusional memories risk panic attacks and PTSD </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>
  6. 6. 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>
  7. 7. 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>
  8. 8. 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>
  9. 9. Overview of SCCM Algorithm 1 2 3 4 Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:119-141.
  10. 10. Address Pain
  11. 11. 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>
  12. 12. 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
  13. 13. Sample Analgesia Protocol Numeric Rating Scale
  14. 14. Address Sedation Yes
  15. 15. 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><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>
  16. 16. 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>
  17. 17. Sample Sedation Protocol Sedation-agitation Scale Riker RR et al. Crit Care Med. 1999;27:1325.
  18. 18. Sedation Options: Dexmedetomidine <ul><li>Alpha-2-adrenergic agonist like clonidine but with much less imidazole activity </li></ul><ul><li>Has been shown to decrease the need for other sedation in postoperative ICU patients </li></ul><ul><li>Potentially useful while decreasing other sedatives to prevent withdrawal </li></ul><ul><li>Benefits </li></ul><ul><ul><li>Does not cause respiratory depression </li></ul></ul><ul><ul><li>Short-acting </li></ul></ul><ul><ul><li>Produces sympatholysis which may be advantageous in certain patients such as postop cardiac surgery </li></ul></ul><ul><li>Risks </li></ul><ul><ul><li>No amnesia </li></ul></ul><ul><ul><li>Small number of patients reported distress upon recollection of ICU period despite good sedation scores due to excessive awareness </li></ul></ul><ul><ul><li>Bradycardia and hypotension can be excessive, necessitating drug cessation and other intervention </li></ul></ul>
  19. 19. 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>
  20. 20. 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>
  21. 21. 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
  22. 22. Risk Factors for Delirium <ul><li>Primary CNS Dx </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>
  23. 23. 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>
  24. 24. 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.
  25. 25. 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>
  26. 26. 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>
  27. 27. 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>
  28. 28. 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>
  29. 29. 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>
  30. 30. 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>
  31. 31. 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>
  32. 32. 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>
  33. 33. 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>
  34. 34. 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>
  35. 35. 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>
  36. 36. 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>Increased potential for baseline neurologic deficit and EEG interference in ICU patients </li></ul><ul><li>No randomized controlled studies to support reliable use in ICU. </li></ul><ul><li>Other neuromonitoring (awareness) modalities are likely to be developed. </li></ul><ul><li>Cessation of NMB as soon as safe in conjunction with other patient parameters should be a daily consideration. </li></ul>
  37. 37. 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>
  38. 38. Sample NMBA Protocol
  39. 39. References <ul><li>Jacobi J, et al. Crit Care Med . 2002;30:119-141. </li></ul><ul><li>Jones, et al. Crit Care Med . 2001;29:573-580. </li></ul><ul><li>Cammarano, et al. Crit Care Med . 1998;26:676. </li></ul><ul><li>Ely, et al. JAMA . 2004;292:168. </li></ul>
  40. 40. 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>
  41. 41. 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>
  42. 42. 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>
  43. 43. 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>
  44. 44. 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>
  45. 45. 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>