Sedation, Analgesia, and Paralysis in COVID-19 Patients in the Setting of Drug Shortages

Abstract

The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global pandemic. The 2019 coronavirus disease (COVID-19) presents with a spectrum of symptoms ranging from mild to critical illness requiring intensive care unit (ICU) admission. Acute respiratory distress syndrome is a major complication in patients with severe COVID-19 disease. Currently, there are no recognized pharmacological therapies for COVID-19. However, a large number of COVID-19 patients require respiratory support, with a high percentage requiring invasive ventilation. The rapid spread of the infection has led to a surge in the rate of hospitalizations and ICU admissions, which created a challenge to public health, research, and medical communities. The high demand for several therapies, including sedatives, analgesics, and paralytics, that are often utilized in the care of COVID-19 patients requiring mechanical ventilation, has created pressure on the supply chain resulting in shortages in these critical medications. This has led clinicians to develop conservation strategies and explore alternative therapies for sedation, analgesia, and paralysis in COVID-19 patients. Several of these alternative approaches have demonstrated acceptable levels of sedation, analgesia, and paralysis in different settings but they are not commonly used in the ICU. Additionally, they have unique pharmaceutical properties, limitations, and adverse effects. This narrative review summarizes the literature on alternative drug therapies for the management of sedation, analgesia, and paralysis in COVID-19 patients. Also, this document serves as a resource for clinicians in current and future respiratory illness pandemics in the setting of drug shortages.

Analgesia and sedation in patients with ARDS

“…Effective strategies target sedation minimization and reduce medication accumulation [2]. The use of shortacting drugs with no or minimal active metabolites (e.g., propofol, dexmedetomidine, fentanyl, sufentanil, remifentanil) may be associated with better outcomes [2], but they can be costly and their availability is limited in resource-constrained situations, such as the current COVID-19 pandemic [11].…”

“…However, trials informing these recommendations enrolled few ARDS patients; patients requiring paralytic therapy, extracorporeal membrane oxygenation (ECMO) or with shock were often excluded; light sedation care bundles (e.g., ABCDEF [42][43][44][45]), delirium prevention and protocolized weaning were rarely used; and multimodal analgesia/sedation approaches were restricted [2,10]. When individualizing analgesic/sedative therapy for adults with ARDS, pharmacologic differences among agents should be considered [11].…”

“…Dexmedetomidine, an alpha-2 agonist, does not cause immunosuppression nor reduce respiratory drive, has analgesic sparing properties, and unlike propofol or midazolam, may improve sleep and may be associated with a lower prevalence of delirium. A very deep level of sedation is not possible with dexmedetomidine alone [2,11,51]. When used as the primary sedative agent in a large RCT of a heterogeneous group of mechanically ventilated ICU patients, two-thirds of patients randomized to dexmedetomidine also received propofol and outcomes were similar between the two groups [8].…”

“…The manuscript was written by authors grouped by section, following their own search of literature and own experience, then homogenized by coordinators (GC, JPK), and reviewed and revised by all authors. The rationale for such review is particularly relevant during the ongoing coronavirus disease 2019 (COVID- 19) pandemic due to urgent concerns about analgesic, sedative, and paralytic shortages and surging admissions that overwhelm ICU bed capacity [9][10][11][12].…”

Dexmedetomidine in COVID-19: probing promises with prudence!

“…While the peak DEX-doses >0.8 µg/kg/hr and daily cumulative DEX-doses >12.9 µg/kg/day have been described to be associated with an elevated withdrawal incidence [7], lack of presentation of the contextual DEXdose administered in the COVID-19 patient featured in the Stockton and Kyle-Sidell case-report, captivates attention [1]. However, withdrawal can be prevented with the meticulous use of drug or mitigated with clonidine [5]. Nevertheless, delving into the current scenario of the riddling uncertainties in staging an ideal management plan against the novel intriguing viral enemy [10,11], I get reminded of the Bertrand Russell quote: When one admits that nothing is certain one must, I think, also add that some things are more nearly certain than others...…”