Pharmacotherapy Considerations in Hospitalized Patients With COVID-19 Pneumonia

William Pruett, MD; Lee E. Morrow, MD, MSc, FCP, FCCP, FCCM, ATSF; Mark A. Malesker, PharmD, FCCP, FCCP, FCCM, FASHP, BCPS


US Pharmacist. 2020;45(44020):HS9-HS16. 

In This Article

Sedation, Analgesia, and Paralytics

No COVID-19–specific recommendations have been published regarding sedation to facilitate mechanical ventilation. Patients with COVID-19 pneumonia commonly need more prolonged ventilator support—2 weeks on average—and often require deeper sedation in order to tolerate the uncomfortable ARDS-like ventilator settings that are typically used. Although anecdotal, many experts suggest a sedation "ladder" that incorporates multiple medications used at lower doses.[1] These recommendations, which often include several agents (melatonin, diazepam, olanzapine, phenobarbital) that might be less commonly used in non–COVID-infected patients, are intended to avoid or minimize the impact of drug shortages.[1,2,6,8]

Although dexmedetomidine is the preferred sedative of some experts, given its favorable hemodynamic profile, others suggest that dexmedetomidine be reserved for weaning from ventilation.[8] Another strategy includes using clonidine as an adjunct to dexmedetomidine.[19] If deeper sedation is needed to facilitate vent synchrony, propofol is used. COVID-19 appears to potentiate the hypertriglyceridemia occurring with propofol, and triglycerides should be checked every 3 days; if the triglyceride level exceeds 500 mg/dL, an alternative sedative should be considered.[1] Reliance on benzodiazepines is discouraged, given the potential for development of physical dependence and subsequent risk of withdrawal. During shortages or to avoid benzodiazepine use, it has been suggested that phenobarbital be considered at doses similar to those used for status epilepticus. Atypical antipsychotics are also an option, with olanzapine preferred over its predecessors because it does not prolong the QT interval. If benzodiazepine use is necessary, these agents should be given only on an as-needed basis by IV push.

Appropriate analgesia facilitates ventilator synchrony, minimizes oxygen consumption, and can potentiate the sedating effects of several medications.[8] Opiates should be used judiciously, given their potential for dependence and withdrawal. Accordingly, scheduled acetaminophen should be considered for pain (and fever) in the absence of liver dysfunction. Fentanyl is generally the first-line opiate, followed by hydromorphone and morphine. All of these agents should be given as as-needed boluses, not as infusions. Ketamine has analgesic properties when properly dosed, and in times of shortage it can be administered as a continuous drip or as adjunctive boluses; its favorable hemodynamic profile is particularly appealing in patients with shock.[20] Given that ketamine is a weak inhibitor of interleukin-6, some have suggested that it might mitigate the cytokine storm seen in later phases of COVID-19 pneumonia. Potential limitations to the use of ketamine for sedation include drug-induced hypertension and/or tachycardia, agitation with higher doses, and the unreliability of bispectral-index (BIS) monitoring of the depth of sedation with this agent.[20]

The use of neuromuscular blocking agents (NMBAs) is controversial in patients with COVID-19 pneumonia, just as in most other critically ill patients. The Surviving Sepsis Campaign guidelines recommend that NMBAs be considered only after other options have been exhausted.[5] If a patient is dyssynchronous with the ventilator, has high ventilator pressures despite optimizing settings, and/or is not a candidate for prone ventilation, bolus doses of rocuronium or vecuronium may be given hourly as needed.[8] Patients requiring more than five doses of a NMBA per 24 hours should be transitioned to a continuous infusion of cisatracurium.[8] All patients receiving paralytics should be appropriately monitored for depth of paralysis (train of four) as well as for appropriate sedation and analgesia (BIS).