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Intravenous Acetaminophen Use in Postoperative Pain Management

Anesthesia Progress – As the use of pain management through prescription opioids continues to be a highly debated topic as it relates to developing a substance use disorder, clinicians are looking for less addictive options. Oral acetaminophen use for pain management has been widely accepted as part of a standard medication therapy in postoperative patients; however, the use of intravenous acetaminophen has yet to be thoroughly explored.

To analyze the pharmacokinetic-pharmacodynamic properties of using IV acetaminophen as a postoperative pain medication, researchers from the Showa University School of Dentistry and the Showa University School of Pharmacy in Tokyo, Japan, recently published a randomized, single-blind, crossover design study in the current issue of Anesthesia Progress. This trial sought to examine the timing of administration of IV acetaminophen to reach peak effectiveness for pain management in postoperative patients.

A total of 15 patients, 7 male and 8 female, with an average age of approximately 29 years, were randomized into two groups receiving either IV acetaminophen or placebo (saline). Patients received 1000-mg IV acetaminophen or saline via infusion pump for 15 minutes; vital signs were monitored at 60, 120, and 240 minutes. Pain was measured using the PainVision PS-2100 device and evaluated before IV administration and then at 0, 30, 60, 90, 120, 180, 240, and 300 minutes after.

“The PK model was developed using a two-compartment model, and the PD model was developed using a linear model and an effect compartment model,” according to lead researcher Maho Shinoda, DDS, and colleagues. The PK-PD measurements were based on plasma concentration level from 5-mL blood sample collected before administration at 0, 15, 30, 45, 60, 90, 120, 180, 240, and 300 minutes.

Trial results show a significant difference in pain levels between 90 and 300 minutes in the IV acetaminophen group, indicating that the effective onset of pain relief occurred 90 minutes after administration. The plasma concentration peaked immediately after administration of IV acetaminophen, which suggests a “significant time lag, as high as 180 minutes, was confirmed between the peak plasma concentration and the peak analgesic effect,” writes Shinoda et al. The American Society of Anesthesiologists guidelines state that “ASA members agree and the consultants strongly agree that acetaminophen should be considered as part of a postoperative multimodal pain management regimen,” yet the use IV acetaminophen has not been thoroughly explored. This research shows that the pain-relieving effect of IV administration begins approximately 90 minutes after and up to 5 hours post acetaminophen infusion, indicating that under the proper time constraints IV acetaminophen can assist in proper pain management of postoperative patients. No adverse effects were experienced by any patients, confirming the efficacy of this therapeutic approach.

Study author, Takehiko Iijima, DDS, PhD, adds “acetaminophen has been recognized to become effective after a considerable interval. No one has made clear how long it takes. Thus, the optimal regimen for how to prescribe acetaminophen has not been determined. Our article has shown that more than two hours are required to achieve the peak of effect site concentration.”

Full text of the article, “Optimal Timing of Intravenous Acetaminophen Administration for Postoperative Analgesia,” Anesthesia Progress, Vol. 69, No. 2, 2022, is now available at


About Anesthesia Progress

Anesthesia Progress is the official publication of the American Dental Society of Anesthesiology (ADSA). The quarterly journal is dedicated to providing a better understanding of the advances being made in the science of pain and anxiety control in dentistry. The journal invites submissions of review articles, reports on clinical techniques, case reports, and conference summaries. To learn more about the ADSA, visit:

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Samantha Weinkauf

Allen Press, Inc.


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