Original Contribution
Effect of preemptive and preventive acetaminophen on postoperative pain score: a randomized, double-blind trial of patients undergoing lower extremity surgery

https://doi.org/10.1016/j.jclinane.2012.09.004Get rights and content

Abstract

Study Objective

To compare postoperative pain scores and rescue analgesic use in patients who received acetaminophen preoperatively or during skin closure versus those who received a placebo.

Design

Randomized, double-blind clinical trial.

Setting

University-based, tertiary-care hospital.

Patients

75 adult, ASA physical status 1 and 2 undergoing lower extremity orthopedic surgery.

Interventions

Patients were randomized to three groups. The control group received 100 mL of intravenous (IV) normal saline as a placebo. The preventive acetaminophen group received 100 mL of IV normal saline plus 15 mg/kg of acetaminophen prior to skin closure. The preemptive acetaminophen group received 15 mg/kg of IV acetaminophen combined with 100 mL of normal saline half an hour preoperatively.

Measurements

Pain was scored with the verbal rating scale and assessed 5 minutes before spinal anesthesia, and 6, 12, 18, and 24 hours after surgery. Total rescue meperidine consumption by each patient during the first 24 hours after surgery was also recorded.

Main Results

Pain scores were lower in both preemptive and preventive acetaminophen groups at 6 hours after surgery than in the placebo group (P < 0.001). There were no differences in pain scores after 6 hours between the preemptive and preventive groups. Total analgesic consumption 24 hours after surgery was lowest in the preemptive acetaminophen group (P < 0.01). Average time to initial analgesic requirement was slightly longer in the preemptive and preventive acetaminophen groups than the control group (P < 0.01).

Conclusion

In patients undergoing lower extremity surgery with spinal anesthesia, both preventive and preemptive acetaminophen may enhance analgesia and decrease postoperative analgesic consumption.

Introduction

Although pain is a predictable part of the postoperative experience, inadequate management of pain is common and may have profound implications [1]. Preemptive analgesia involves the administration of an analgesic before a painful stimulus in order to prevent the altered processing of afferent input which amplifies postoperative pain; effective preemptive analgesia should prevent the establishment of central sensitization caused by incisional and inflammatory injuries [2]. Preventive analgesia is based on the assumption that the only way to prevent central sensitization is to completely block any pain and afferent signals from the surgical wound from the time of incision until final wound healing. This concept focuses on the intensity and duration of the analgesic intervention rather than on timing [3].

The issue of preemptive and preventive analgesia for postoperative pain relief has been the topic of many trials in which interventions, methodology, terminology, and definitions have varied, thereby creating much controversy about these concepts [2], [3]. These trials may be divided into studies that used nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, N-methyl-D-aspartate receptor agonists, acetaminophen-group drugs, peripheral local anesthesia, epidural analgesia, or a combination of treatments [3], [4]. Although several trials showed that various antinociceptive techniques applied preoperatively were more effective in reducing postoperative central sensitization phenomena than postoperative administration, reviews of clinical findings have been mostly negative [3], [4], [5], [6]. However, there is still a widespread belief among clinicians in the efficacy of preemptive analgesia [3]. It is believed that by applying an analgesic medicine or technique, pain will either subside or be prevented prior to the painful stimulus, thus preventing central sensitization and consequently decreasing the need for postoperative analgesia [6].

Acetaminophen is a nonopioid drug whose mechanism of action has remained elusive. It is believed to inhibit the synthesis of prostaglandin in the central nervous system, and it peripherally blocks pain impulse generation by blocking the activation of nociceptors. Theoretically, acetaminophen may act in the spinal cord to block mechanisms that would otherwise enhance central sensitization. Acetaminophen has a good safety profile and easily passes through the blood-brain barrier, reaches a high concentration in the cerebrospinal fluid, and has an antinociceptive effect, which assures its effectiveness as an analgesic [7], [8]. Only a few clinical trials have examined the effect of preemptive or preventive acetaminophen, and the results have been contradictory [9], [10], [11]. No clinical trials have examined the effect of preemptive or preventive acetaminophen on postoperative pain scores and rescue analgesic use in patients scheduled to receive spinal anesthesia for lower extremity orthopedic surgery.

The aim of this study, therefore, was to compare postoperative pain scores and rescue analgesic use in patients who received acetaminophen preemptively or preventively versus a placebo. We designed this double-blind, randomized, placebo-controlled trial to test the hypothesis that the preemptive and preventive administration of acetaminophen, as compared with a placebo, would reduce postoperative acute pain and the amount of analgesics used in the postoperative period in patients who undergo lower extremity surgery.

Section snippets

Patients and methods

The study was approved by the Isfahan University of Medical Sciences Ethics Committee (approval no. 389455, 2010) and patients gave written, informed consent. Between July 2010 and February 2011, 75 consecutive adult, ASA physical status 1 and 2 patients who were scheduled for orthopedic lower extremity surgery during spinal anesthesia were studied. Patients were excluded from the study if they had any contraindication to the spinal anesthesia, a history of opioid use in the last 48 hours, any

Results

A total of 86 consecutive patients were recruited. Six patients refused to participate, and 5 patients did not meet our study criteria. Thus, 75 patients were randomized: 25 in the control group, 25 in the preemptive acetaminophen group, and 25 in the preventive acetaminophen group (Fig. 1). The three treatment groups were generally well matched at baseline with regard to age, gender, duration of surgery, site of surgery, and VRS scores (Table 1). No differences were found between the groups in

Discussion

The aim of this randomized, double-blind, placebo-controlled trial was to assess the timing of acetaminophen use to improve postoperative pain control. Both preemptive and preventive acetaminophen reduced postoperative pain as well as total analgesic consumption in the first 24 hours, and slightly prolonged the average time to initial analgesic use, lending support to the concept that both preemptive and preventive acetaminophen lead to relatively good analgesia. The group that received

Acknowledgments

We thank K. Shashok (AuthorAID in the Eastern Mediterranean) for improving the use of English in the manuscript. All authors vouch for the veracity and completeness of the reported data, and all authors contributed to various aspects of the trial design, data gathering and analysis, and preparation of the manuscript.

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