Author: Bruce Buckley
The danger that there won’t be enough medications to facilitate mechanical ventilation in COVID-19 patients is sharply rising just as coronavirus infections surge in hotspots around the nation, according to a new Vizient analysis of 13 critical sedatives, opioids and paralytic drugs.
“What we’re seeing right now is an unprecedented demand for these medications, and we’re not at an apex yet from what our data are showing,” said Dan Kistner, PharmD, the group vice president of pharmacy solutions at Vizient Inc. “My biggest fear is that in a few weeks down the road, we’re going to see pictures on the news of ventilators in a closet that can’t be used because we don’t have the drugs.”
Erin Fox, PharmD, BCPS, the senior director of Drug Information and Support Services at the University of Utah Health, in Salt Lake City, said, “Hospitals are facing two to 10 times their normal ventilated population. This means that you need two to 10 times the amount of medications. That is not so easy in these days of allocations and limits placed on the amounts of controlled substances you can order.”
Vizient normally tracks about 200 acute and chronic “workhorse medications” used in hospitals, Dr. Kistner said. “About 69 drugs have our special attention because of the unusually high demand we’re seeing across the country,” he said. For this analysis, Vizient focused on 13 of the hardest hit—each often administered to facilitate mechanical ventilation and patient comfort throughout the course of therapy.
The study used purchase order data from Vizient’s hospital and health-system members to calculate customer demand and fill rate trends for the 13 agents in March. They were divided into three groups: Six in the first group were sedatives or anesthetics; opioid analgesics made up the second group; the third consisted of four neuromuscular blocking agents.
In the sedative/anesthetic group—which included propofol, dexmedetomidine and lorazepam—the end-of-March fill rate was down to as low as 48% just as demand was increasing by 91%. For the three opioids in the second group—hydromorphone, fentanyl and morphine—March demand rose 79% while the fill rate decreased to as low as 71%. The trend was the worst for the four neuromuscular blockers: Demand was up by 105% as the fill rate declined to as low as 37%.
In all three groups, Dr. Kistner pointed out, the green line on the chart denoting the raw fill rate continued to decline throughout March. “You can’t wait till it gets to 50%,” he said in an earlier interview. “You have to act now, because it takes weeks to bring new sterile infusion products to market.” Vizient later updated the data to show that the fill rate had already fallen below 50% for two of the groups.
John W. Devlin, PharmD, a professor of pharmacy at Northeastern University, in Boston, and the chair of the Society of Critical Care Medicine’s 2018 “Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU,” said the shortages of sedatives, opioids and neuromuscular blocking agents are only likely to worsen as new COVID-19 cases surge across the country.
“In the Boston area, we are seeing an ever-increasing prevalence of COVID-19-associated acute respiratory distress syndrome (ARDS),” he said. “The complex ventilator settings and proning required to treat the severe hypoxemia found in these ARDS patients sometimes requires deep sedation to reduce oxygen consumption, high-dose opioids to reduce respiratory drive, and paralysis with neuromuscular blockers to reduce airway pressure and optimize ventilator compliance.”
Dr. Devlin recalled the critical propofol shortage that occurred during the 2009-2010 H1N1 pandemic, which caused problems but was obviated by the increased use of benzodiazepines like midazolam. The current situation is far more difficult, he said, because the shortages “are really across the board.”
In the face of these shortages, Dr. Devlin highlighted potential strategies to reduce the daily use of IV sedatives, IV opioids and neuromuscular blockers in mechanically ventilated patients with COVID-19. He said ICU clinicians are striving to minimize their time at the bedside and thus likely to keep COVID-19 patients more deeply sedated than usual. But he noted that not all COVID-19 patients require deep sedation throughout the course of mechanical ventilation.
“The ICU team should evaluate sedation goals at least daily,” he advised, “and continuously infused sedation should be interrupted or decreased in patients who are excessively sedated.”
Dr. Devlin further suggested that acute episodes of agitation or pain can generally be treated by IV boluses of opioids and/or sedatives; increases in the infusion are not always needed. Ventilator dyssynchrony should generally be managed with ventilator adjustments before administering more sedation, he said.
He added: “The recent ROSE-PETAL RCT [randomized controlled trial] demonstrated that the routine administration of continuous IV neuromuscular therapy does not improve outcomes in patients with ARDS; neuromuscular blockers should generally be administered on an intermittent ‘as-needed’ IV push basis.” (N Engl J Med 2019;380:1997-2008).
For patients with functional nasogastric or enteral access, Dr. Devlin said clinicians should consider administering oral opioids, such as oxycodone or methadone, and/or sedatives such as lorazepam, to reduce continuous IV infusions. In the absence of first-line sedatives, he added, clinicians can consider using other classes of medications known to have sedating properties, including phenobarbital, valproic acid, haloperidol, quetiapine or ketamine.
Lastly, he said, the administration of nonopioid analgesics in a multimodal approach that’s often used in postsurgical patients—for example, acetaminophen, lidocaine and ketamine—may help reduce opioid requirements in COVID-19 patients requiring mechanical ventilation in the ICU.