Randomized Clinical Trial of Intravenous Acetaminophen as an Analgesic Adjunct for Older Adults With Acute Severe Pain

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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.

Section: Discussionmentioning

confidence: 99%

Section: Interventionmentioning

confidence: 99%

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confidence: 99%

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

Bijur

Friedman

White

et al. 2020

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“…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.…”

Section: Discussionmentioning

confidence: 81%

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

Minotti

Mansella

Sieber

et al. 2022

Background: Pain is one of the main reasons to present to emergency departments (EDs). Opioids are indispensable for acute pain management but are associated with side effects, misuse, and dependence. The aim of this study was to test whether a single dose of intravenous (IV) acetaminophen (paracetamol) can reduce the use of morphine for pain relief and/or morphine-related adverse events (AEs).Methods: ED patients >18 years with acute pain (i.e., Numeric Rating Scale [NRS] > 4) were screened for eligibility. Patients with analgesia in the past 6 h, chronic pain, or clinical instability were excluded. Patients were randomized in a 1:1 ratio to receive either morphine 0.1 mg/kg and 1 g acetaminophen IV or morphine 0.1 mg/kg and placebo IV. The intervention was double-blinded. Additional morphine 0.05 mg/kg IV was administered every 15 minutes until pain relief (defined as NRS < 4) and whether the pain recurred. The primary outcome was the mean morphine dose for pain relief.Secondary outcomes were the total amount of morphine given, time to achieve pain relief, and AEs.Results: A total of 220 patients were randomized and 202 evaluated for the primary outcome. The mean morphine dose for pain relief was similar in both groups (acetaminophen 0.15 mg ± 0.07 mg/kg, placebo 0.16 ± 0.07 mg/kg). There were no differences in the total amount of morphine given (acetaminophen 0.19 ± 0.09 mg/kg, placebo 0.19 ± 0.1 mg/kg), the time to achieve pain relief (acetaminophen 30 min [95% CI 17-31 min], placebo 30 min [95% CI 30-35 min]), and the frequency of AEs (overall 27.4%). Time to pain recurrence did not differ significantly between the groups (hazard ratio 1.23 [0.76-1.98], p = 0.40). Conclusions:In ED patients, acetaminophen had no additional effect on pain control or morphine-sparing effect at the time of first morphine administration. Titrated morphine with the algorithm used was highly effective, with 80% of all patients reporting pain relief within 60 min of starting therapy.

“…Alternative and adjunctive therapies to opioids have been recently investigated; however, the study results have been mixed. Most of the studies illustrating significant pain control with IV acetaminophen have been done in populations with acute pain due to fractures, renal colic, or postoperative pain 14,16–18,22–26 . A recent study by Blok et al 20 comparing IV acetaminophen to morphine in adults with acute pain in the ED failed to demonstrate an opioid‐sparing effect but showed that a small number of patients used less opioids in the following 24 hours after discharge.…”

Section: Discussionmentioning

confidence: 99%

Does Intravenous Acetaminophen Reduce Opioid Requirement in Pediatric Emergency Department Patients With Acute Sickle Cell Crises?

Dhebaria

Sivitz

Tejani

2020

Objective We evaluated the ability of intravenous (IV) acetaminophen to reduce the amount of opioid medication administered in pediatric patients with sickle cell disease (SCD) having vasoocclusive crisis (VOC) in an emergency department (ED) setting. Methods This was a prospective, randomized, double‐blind placebo‐controlled trial at an academic urban pediatric ED. Participants included patients with SCD, aged 4 to 16 years, with VOC pain. All patients received a 0.1 mg/kg dose of IV morphine, 0.5 mg/kg ketorolac, or both. Patients were randomized to receive either 15 mg/kg IV acetaminophen or placebo. Patients were reassessed every 30 minutes to see whether additional opioid doses were indicated to a maximum of three doses. The total morphine given, pain scores, rates of admissions, 72‐hour return visits, and adverse events were assessed for each group. Results Of 71 subjects randomized, 35 patients in the acetaminophen group and 36 patients in the control group were analyzed. Baseline characteristics and initial pain scores were similar in both groups. The mean total amount of morphine given was 8.6 mg (95% confidence interval [CI] = 6.5 to 10.8) in the acetaminophen group and 8.0 mg (95% CI = 5.9 to 10.2) in the placebo group. The mean total cumulative morphine dosing was 0.2 mg/kg (95% CI = 0.1 to 0.2 mg/kg) in the acetaminophen group and 0.2 mg/kg (95% CI = 0.1 to 0.2 mg/kg) in the control group. The mean pain score at time of disposition was 5.5 (95% CI = 4.3 to 6.6) in the acetaminophen group and 5.2 (95% CI = 4.2 to 6.3) in the placebo group. There were no clinical or statistically significant differences between the rates of admission, 72‐hour return visits, or adverse events. Conclusion In this study, patients who received IV acetaminophen did not receive less morphine than patients in the placebo group. Disposition pain scores for the two groups were also equivalent. We conclude that IV acetaminophen, when used in addition to morphine for pediatric sickle cell VOC pain, does not provide an opioid‐sparing effect. Further searches for adjunctive nonaddictive pain medicines are indicated.