Sedation, Pain, Agitation & Paralysis

Rationale:

COVID patients requiring mechanical ventilation have an initial goal of moderate to deep sedation (RASS -3 to -5) to minimize risk of self-extubation. Furthermore, a subset of these patients suffer severe hypoxemia and require muscle paralytics to facilitate adequate oxygenation. Also of note, Stanford’s stock of medications will be dynamic and continuously changing and thus, prescribing patterns will need to be equally dynamic and work within the limits of drug availability.


Sedation:

  1. For non-intubated patients requiring sedation for agitation or delirium, utilize dexmedetomidine infusion initially (0.2-0.7mcg/kg/hr) with the goal to wean off within 48 hours, utilizing alpha-2 modulation with guanfacine and dopaminergic modulation with haloperidol. Refer to COVID-19 Delirium Guidelines for guidance and details.

  2. For intubated patients, goal RASS -3 to -5 for moderate to severe ARDS. While weaning ventilator towards extubation, lighten RASS goal to 0 to -1.

  3. General principles:

        1. Propofol can be used for sedation. Start 5mcg/kg/min and titrate by 5-10mcg/kg/min. Consider that due to the depth and duration of sedation needed, patients may be at higher risk for severe hypertriglyceridemia or sedation-related hypotension.

              • Obtain baseline triglycerides, recheck within 24 hours and again every 72 hours.

              • Monitor for signs of propofol infusion syndrome (PRIS), which is rare but may be fatal. Triglyceridemia is not a good indicator for PRIS and rather, unexplained hyperkalemia with EKG changes, rhabdomyolysis, and a metabolic acidosis due to otherwise unexplained lactatemia with an elevated creatine kinase are the earliest signs for PRIS [1].

              • If patients require more than 40 mcg/kg/min, consider supplementing sedation with other agents like enteric benzos or antipsychotics to avoid long-term, high doses of propofol.

              • Recommend early nutrition consult to review lipid calories and total caloric needs.

        2. For patients requiring a continuous benzodiazepine infusion:

              • consider supplementing 50% of their 24-hour requirement with scheduled enteric lorazepam (Ativan) or diazepam (Valium).

              • If the patient lacks enteric access, consider scheduled IV doses of longer acting intravenous agents, such as lorazepam or diazepam, so as to better conserve medications.

              • Monitor for signs of propylene glycol toxicity (lactic acidosis, SIRS physiology, worsening AKI) in patients on prolonged moderate doses of lorazepam (Ativan).

              • For patients with higher continuous infusion requirements, consider the addition of a ketamine infusion (10-20mg per hour) or dexmedetomidine (starting 0.2 to 0.3mcg/kg/hour, titrate up to 1.2mcg/kg/hr, monitoring for bradycardia and/or hypotension).

        3. If a patient’s primary problem is delirium, please reference the COVID-19 Delirium Guidelines section.

        4. If a provider has comfort with its use and titration, a low-dose ketamine infusion can be used as an adjunct for pain and sedation, particularly for patients with bronchospasm. Providers should monitor for ketamine-related increases in bronchorrhea and/or Qtc prolongation.

        5. To wean:

              • First, prioritize weaning off any continuous infusions.

              • Decrease all PRN or scheduled sedative doses by 20-50% and hold scheduled doses for a RASS of -2 or less.

              • Each subsequent day, give the previous 24hr total sedative requirement in divided doses, holding the dose for a RASS of -2 or less. Repeat this strategy every 24 hours to target RASS 0 to -1.

              • For benzodiazepine withdrawal syndrome (increased sympathetic tone, GI disturbances, restlessness precluding the ability to wean off the continuous benzodiazepine infusion), can again consider subanesthetic infusion of ketamine: (10-20mg per hour) or dexmedetomidine infusion (0.2-0.7mcg/kg/hr). Use cautiously in those with high secretion burden given risk of bronchorrhea and monitor for QT prolongation.

Analgesia:

  1. Opioids are the primary drug class-of-choice, especially hydromorphone or fentanyl. If these agents are in short supply, consider morphine infusion (caution in renal impairment) as primary analgesic.

  2. General principles:

        • In a hospital surge of COVID patients, many intravenous opioid analgesics may be in short supply. For patients on a continuous opiate infusion, supplement 50% of their 24-hour requirement with scheduled enteric oxycodone or morphine immediate release (MS-IR; avoid in renal impairment). Up-titrate daily as able to minimize infusion requirement.

        • Methadone (PO or IV) is not recommended as first-line and should be used with caution given complexity of dosing, titration, risk of QTc prolongation and equianalgesic conversions.

        • For patients lacking enteric access, can consider scheduled doses of IV hydromorphone or morphine as an adjunct or in place of continuous opiate infusions.

        • Consider multimodal pain management including scheduled gabapentin or acetaminophen, either enteric or IV formulations [2].

  3. To wean, mimic step 3 under the Sedation section above.


Paralytics:

  1. Vecuronium infusion should be first-line choice for most patients. Please note, desacetyl-vecuronium is a liver metabolite that has 80% of the potency of the primary agent, and is renally cleared.

  2. Cisatracurium may be in shortage so reserve only for patients with significant renal or hepatic impairment.

References:

  1. Hemphill S et al. Propofol infusion syndrome: a structured literature review and analysis of published case reports. Br J Anaesth 2019; 122:448-59.
  2. Devlin JW, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825.
  3. Waleed Alhazzani, et al. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019. Critical Care Medicine: March 27, 2020. Surviving Sepsis Campaign: Guidelines on the Management of... : Read Online: Critical Care Medicine | Society of Critical Care Medicine.

Pain, Agitation, Delirium, & Paralysis protocol (printer version)

Updated 5/29/2020