Randomized Clinical Trial of Intravenous (IV) Acetaminophen as an Adjunct to IV Hydromorphone for Acute Severe Pain in Emergency Department Patients

Abstract

Background A fundamental challenge for emergency department (ED) clinicians is to relieve severe, acute pain while simultaneously avoiding adverse events associated with opioid analgesics. Because there is evidence that intravenous (IV) acetaminophen is an effective adjuvant analgesic in postoperative settings, we examined whether it also has a role in the ED. Methods This was a two‐arm, double‐blind randomized clinical trial. All patients received 1 mg of IV hydromorphone. Patients were then randomized to receive 1 g of IV acetaminophen or placebo. The primary outcome was the between‐group difference in change in pain from baseline (before treatment) to 60 minutes after administration of study drugs, measured on an 11‐point numeric rating scale (NRS). Results Of 828 patients screened, 162 were enrolled and 159 had the primary outcome. Patients allocated to acetaminophen + hydromorphone had a mean decline in pain from baseline to 60 minutes of 6.2 NRS units; those receiving placebo + hydromorphone had a mean decline of 5.4, a difference of 0.8 NRS units (95% confidence interval [CI] = −0.01 to 1.8). Two patients in each group received additional analgesics in the first 60 minutes of the study. At 120 minutes the NRS pain difference was 0.6 (95% CI = –0.4 to 1.6). A total of 26.9% of patients who received acetaminophen wanted more analgesia versus 37.7% of those given placebo (difference = –10.8%, 95% CI = −24.3% to 4.4%). The incidence of adverse effects was similar in both groups. Conclusions The addition of 1 g of IV acetaminophen to 1 mg of IV hydromorphone provided neither clinically meaningful nor statistically superior analgesia than hydromorphone alone.

Intravenous acetaminophen does not reduce morphine use for pain relief in emergency department patients: A multicenter, randomized, double‐blind, placebo‐controlled trial

“…The main findings of this study were excellent pain control using a titrated and individualized morphine analgesia in the majority of ED patients with moderate to severe pain and the absence of a difference between additional acetaminophen or placebo. These results are similar to those of previous studies that showed a lack of superiority of combining hydromorphone with acetaminophen 22,23 or combining various opioids with acetaminophen. 13 However, these studies did not take advantage of titrated and individualized opioid therapy, while an older study using the hydromorphone 1 + 1 mg titration approach showed favorable results, but 42% of all patients only needed a single dose, reflecting the inclusion of patients with less severe pain.…”

“…Overall, it remains unclear why acetaminophen seems to have an opioid‐sparing effect in postoperative use but not in patients presenting to the ED with moderate to severe acute pain. However, given the data on fixed‐dose opioids 13,22,23 or titrated and individualized morphine in this study (not providing evidence of differences in efficacy or side effects), it seems unlikely that acetaminophen would have an effect in ED patients. Furthermore, in ED patients with moderate to severe acute pain, initial analgesia with acetaminophen alone may delay administration of opioids and consecutive pain relief and should therefore not be considered standard treatment.…”

“…According to a Cochrane review, the amount of opioids needed could be reduced to up to 25% when acetaminophen was added for pain control—with a similar rate of unwanted side effects 12 . However, it seems unlikely that such side effects can be massively reduced in an emergency cohort that often suffers from nausea and vomiting at presentation and before initiation of therapy 23 . Furthermore, it is debatable whether these most frequent side effects are dose‐dependent, as they can occur even at very low doses 27 …”

“…12 However, it seems unlikely that such side effects can be massively reduced in an emergency cohort that often suffers from nausea and vomiting at presentation and before initiation of therapy. 23 Furthermore, it is debatable whether these most frequent side effects are dose-dependent, as they can occur even at very low doses. 27 Overall, it remains unclear why acetaminophen seems to have an opioid-sparing effect in postoperative use but not in patients presenting to the ED with moderate to severe acute pain.…”

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

“…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.…”