Choosing the right drug
The keys to success for sedation of ICU patients are choosing the right drug at the right dose for the right duration and the right mode of delivery, and applying them to the right population. However, as noted in a recent study, the pandemic poses unique challenges to clinicians in how they care for critically ill COVID-19 patients who require sedation (Anesth Analg. 2020 Apr 22. doi: 10.1213/ANE.0000000000004887). The use of provisional work areas “has escalated because of the amount of patients we’ve had to care for over the past nine months,” Dr. Greenberg said. “We’ve used alternate providers who are not necessarily familiar with the sedation and analgesic protocols and how to use these specific medications. Drug shortages have been on the rise, so there’s a need to understand alternative agents that can be used.”
COVID-19 patients face the potential risk for an increase in drug-drug interactions and side effects due to the polypharmacy that is often required to provide adequate sedation during mechanical ventilation. He noted that these patients may have “unusually high” analgesia and sedation requirements, particularly when they’re mechanically ventilated. A hypothesis as to why patients with COVID-19 require so much sedation and analgesia is that they often have a high respiratory drive and ventilator dyssynchrony, which requires increased neuromuscular blockade. “They also have an intense inflammatory response, which may be linked to tolerance of specific opioids and other medications,” Dr. Greenberg said. “Many ventilated COVID-19 patients are of younger age and previously in good health, and therefore, have an excellent metabolism. Health care providers are concerned about self-extubation. This prompts bedside providers to administer more sedatives to prevent this unwanted complication. There may also be a reduction of drip modifications by health care workers because of the potential risk of contracting COVID-19 when going into the room multiple times and for long periods of time” (Anesth Analg. 2020;131[1]:e34-e35).
According to a sedation resource on the SCCM website, about 5% of COVID-19 patients require mechanical ventilation. “There has been a massive shortage of the usual drugs that we use,” Dr. Greenberg said. “The demand for sedatives has increased by approximately 91%, while the demand for analgesics has increased by 79%, and neuromuscular blocker demand has increased by 105%.”
A retrospective study of 24 COVID-19 patients who required ventilation in the ICU found that the median daily dose of benzodiazepines was significantly higher, compared with the median daily dose used in the OSCILLATE trial (a median of 270 mg vs. 199 mg, respectively; Anesth Analg. 2020;131[4]e198-e200. doi: 10.1213/ane.0000000000005131). In addition, their median daily dose of opioid was approximately three times higher, compared with patients in the OSCILLATE trial (a median of 775 mg vs. 289 mg). Other agents used included propofol (84%), dexmedetomidine (53%), and ketamine (11%).
“A potential strategy for COVID-19 ICU patient sedation should be analgesia first, as indicated in the 2018 PADIS guidelines,” Dr. Greenberg advised. “We should also apply nonpharmacologic measures to reduce delirium. In nonintubated patients, we should use light to moderate sedation, targeting a RASS of –2 to +1, using hydromorphone or fentanyl boluses for analgesia and midazolam boluses or dexmedetomidine for sedation,.”
For intubated patients, he continued, target a RASS of –3 to –4, or –4 to –5 in those who require neuromuscular blockade. “Use propofol first then intermittent boluses of benzodiazepines,” said Dr. Greenberg, editor-in-chief of the Anesthesia Patient Safety Foundation newsletter. “For heavy sedation, use midazolam and supplement with ketamine and other analgesics and sedatives such as barbiturates, methadone, and even inhalation anesthetics in some cases.”
For analgesia in intubated patients, use fentanyl boluses then infusion. “Patients can easily become tachyphylactic to fentanyl, and it has a long context-sensitive half time,” he said. “Hydromorphone may be least affected by organ dysfunction.”
Dr. Greenberg concluded his presentation by stating that more studies are required “to delineate the best analgesia/sedation strategies and monitoring modalities for COVID-19 ICU patients.”
In commenting on the presentation, Mangala Narasimhan, DO, FCCP, senior vice president and director of critical care services at Northwell Health, said that the recommendations regarding sedation highlight a struggle that ICU providers have been dealing with during the COVID-19 epidemic.
Dr. Mangala Narasimhan
“There have been unique challenges with COVID-19 and intubated patients. We have seen severe ventilator dyssynchrony and prolonged duration of mechanical ventilation. I think we can all agree that these patients have extremely high metabolic rates, have required high levels of sedation, have an increased need for neuromuscular blockade, and have high levels of delirium for extended periods of time. The recommendations provided here are reasonable. Strategies to prevent delirium should be employed, pain management should be prioritized, analgesics can help reduce the need for opioids. Alternatives to sedation are useful in this patient population and are well tolerated. Drug shortages have provided additional challenges to these strategies and have required us to think about the use of alternative agents. The recommendations echo the experience we have had with large numbers of intubated COVID-19 patients.”
Dr. Greenberg disclosed that he receives a stipend from the Anesthesia Patient Safety Foundation for serving as editor-in-chief of the foundation’s newsletter.