Intravenous Acetaminophen and Hydromorphone: The Bad and the Ugly of Emergency Department Pain Management

The Editor: We read with great interest the study by Bijur et al.1 that evaluated the analgesic efficacy of intravenous (IV) acetaminophen as an adjunct to IV hydromorphone for the treatment of severe, acute pain in the emergency department (ED). The study found that there was no significant difference in analgesia when 1 g of IV acetaminophen was added to 1 mg of IV hydromorphone. While we are in complete agreement with the authors about the utilization of combinations of analgesics from different therapeutic classes, we were surprised by the study of these two specific drugs. Intravenous acetaminophen is a nontitratable and weak analgesic that does not result in opioid sparing or reduce opioid-related adverse effects. Additionally, it does not provide analgesic superiority over the oral and rectal routes beyond the initial 15 minutes after administration. Furthermore, a prohibitive acquisition cost would preclude most EDs from utilizing this medication routinely for pain control.2 The addition of a single dose of this weak analgesic to an extremely potent opioid is unlikely to affect the analgesic efficacy of the latter and can be misinterpreted to bolster support for this opioid. The authors acknowledge that reducing opioid use and exploring nonopioid modalities are important in curbing opioid-related consequences. However, the choice of opioid is also important, as individual opioids have different abuse liability and adverse effect profiles. IV hydromorphone's high lipophilicity allows it to cross the blood brain barrier rapidly, resulting in euphoria and reinforcing effects. As such, hydromorphone has a higher potential for addiction and abuse than other opioids such as morphine. Previous research has demonstrated that oral and parenteral hydromorphone produced significantly more euphoria and reinforcement than morphine in individuals with a history of opioid dependence. These findings have also been replicated in individuals without a history of opioid use disorder. Additionally, hydromorphone has had a 438% increase in nonmedical use from 2004 to 2011 and a significant increase in street value compared to less abuse-liable opioids.3 Hydromorphone is used as a heroin substitute in "heroin" vending machines in Vancouver, Canada.4 In addition to increased recreational use potential, parenteral hydromorphone causes significantly higher rates of excessive sedation, hypoxia, respiratory depression, and the need for naloxone administration compared with other opioids. Many of the adverse events have been attributed to excessive hydromorphone dosing.3 At this time, we do not know how the acute parenteral administration of hydromorphone contributes to subsequent opioid use or addiction, but there are indicators that hydromorphone is more dangerous than other opioids. Hydromorphone should not be the first-line opioid used in the ED. While we do advocate for continued research examining combinations of opioid and nonopioid therapies for both efficacy and harm from opioid analgesics, we hope that future studies will focus on studying less abuse-liable but equianalgesic opioids as part of opioid stewardship efforts in cost-conscious manner.

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