key: cord-256639-4e0irb6d
authors: Jean-Michel, Vanessa; Caulier, Thomas; Delannoy, Pierre-Yves; Meybeck, Agnes; Georges, Hugues
title: Thiopental as substitute therapy for critically ill patients with COVID-19 requiring mechanical ventilation and prolonged sedation
date: 2020-09-06
journal: Med Intensiva
DOI: 10.1016/j.medin.2020.07.013
sha: 
doc_id: 256639
cord_uid: 4e0irb6d

nan

El uso de tiopental como alternativa para pacientes críticos con COVID-19 que requieren ventilación mecánica y sedación prolongada . The Food and Drug Administration recently issued a midazolam shortage and reported a more than 50% consumption increase for other common sedative drugs such as propofol due to high demand for patients with COVID-19 [3] .

Thiopental is commonly used in refractory status epilepticus as burst suppression therapy or in traumatic brain injury to limit increase in cranial pressure [4, 5] . For these patients, barbiturate therapy induce deep coma with bispectral index score lower than 20 and, as a result, prolonged MV [4] . To our knowledge no study has reported use of thiopental in critically ill patients besides acute neurological conditions. We retrospectively analyzed our experience with thiopental in our intensive care unit (ICU) Thiopental was progressively reduced by half every 12 hours according to clinical status and was delivered overall during 4.8 ± 1.8 days. Just before thiopental initiation, mean doses of midazolam and propofol were respectively 16 ± 7.6 and 120 ± 76.6 mg/h. Midazolam and propofol were completely stopped one hour after the thiopental loading dose in all patients.

Only one patient needed initiation of small doses of norepinephrine. Cisatracurium could be stopped 1.3 ± 1.2 days following thiopental initiation. Mean level of bispectral index monitoring during thiopental infusion was between 40 and 50. Dexmedetomedine, commonly used in our unit during sedative drugs withdrawal, was administered to 6 patients. A Richmond Agitation Sedation Scale (RASS) score at 0 was obtained 3.8 ± 1.1 days following thiopental cessation.

Five of seven patients survived the ICU stay. All surviving patients were discharged from the ICU with a Glasgow score ≥14 [5] .

More severely ill patients with COVID-19 require deep sedation with combination of multiple agents during 2-3 weeks. The recommended drug strategy to maintain a RASS score of -4 or -5 is the combination of midazolam with an opiate and propofol. [6] . However, prolonged and high requirements of sedatives and opioids can lead to drug tolerance, accumulation, withdrawal and/or propofol syndrome. Government agencies and medical organizations have reported major shortage of benzodiazepines and propofol during the COVID-19 pandemic and providing sedation with less commonly used agents as barbiturates has been suggested [1].

Major side effects of thiopental are essentially hypotension and prolonged ICU stay. In our unit, we have used thiopental in patients presenting with severe ventilator asynchrony despite delivery of usual recommended doses of sedatives, opioids and NMBA [7] . Low dose of Page 3 of 4 J o u r n a l P r e -p r o o f vasopressor was started in only one patient and norepinephrine was decreased in three patients 24 hours following thiopental initiation. BIS monitoring was used to determine adequate dosage of thiopental. Low BIS level (< 40 ) has been associated with long term mortality ( ≥ 1 year) [8] . In our study, a level ranged from 40 to 50 prevented deep sedation and large accumulation of barbiturates. Midazolam and propofol could be totally discontinued allowing a significant sparing of these drugs and extubation time was similar between the two groups.

Dexmedetomedine was used in the two groups of patients during withdrawal of sedative drugs to prevent occurrence of delirium as recommended by a recent guideline [6] . Another drug option for sedation of critically ill patients with COVID-19 could be inhaled volatile anaesthetics [9, 10] . Some studies have reported that inhaled agents such as isoflurane and sevoflurane shorten awakening and extubation times in mechanically ventilated patients compared to benzodiazepines or propofol. Another benefit of volatile anaesthetics could be pulmonary anti-inflammatory effects and dose-dependent bronchodilatation. However most of these studies included patients with a mean sedation duration less than 4 days and the potential effects of volatile anaesthetics in mechanically ventilated COVID-19 patients remains to be studied.

Thiopental seems to be an acceptable substitute to sedative drugs in this period of high midazolam and propofol demand for ICU patients with COVID-19. When barbiturate therapy can be discontinued, awakening occurs relatively quickly if bispectral index scores were kept between 40 and 50. 

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