Intravenous administration improved analgesia but did not lower opioid use

Acetaminophen given to children and adolescents after major spine surgery provided improved pain relief and appears to be safe and effective, according to a Finnish study presented at the 2011 annual meeting of the Scoliosis Research Society. However, the use of ace-taminophen did not reduce the use of oxycodone.

The randomized, placebo-controlled, double-blind study was conducted by Arja Hiller, MD, PhD, and associates at the Helsinki and Turku Children’s Hospitals; Ilkka Helenius, MD, PhD, presented the results.

NSAIDs have been used as adjuvants to opioids, but long-term use has shown that they can interfere with fracture healing, bone-tendon healing, and new bone formation.Thus, recommended practice has been to avoid their use in surgery for scoliosis and other pediatric conditions, despite the low risk of nonunion in these patients.

Acetaminophen, does not have the adverse effects of NSAIDs and has been found to achieve an opioid-sparing effect after orthopaedic surgery in adults. About 10 years ago, an intravenous (IV) form was developed. The form used in this study (Perfalgan, Bristol-Meyers Squibb Pharmaceuticals, Uxbridge, UK) delivers 10 mg of paracetamol/mL and is not approved for use in the United States.

The study involved 36 patients from 10 to 18 years of age who underwent surgery for adolescent idiopathic scoliosis or spondylolisthesis. All operations were performed by a single orthopaedic spine surgeon. Patients were excluded if they had severe, concomitant disease (ie, neuromuscular scoliosis, neurodegenerative disease), kidney or liver dysfunction, or if they had taken acetaminophen during the previous 3 days.

Pain medications
Patients were randomized to two groups of 18 children each at surgical closure. The acetaminophen group received IV acetaminophen (30 mg/kg) for 15 minutes with a maximum dose of 1.5 g. The placebo group received the same volume (3 mL/kg) of 0.9 percent intravenous saline. Subsequent doses of IV acetaminophen and placebo were administered 8 hours and 16 hours after the first dose.

Postoperative pain was assessed by one blinded investigator using the behavioral Objective Pain Scale (OPS), an observer assessment based on facial expression, vocalization, movement or rigidity of the limbs and body, response to handling and irritability, and measured cardiorespiratory variables. In OPS scoring, severe pain begins at 6, which researchers used as the signal for administration of additional pain medication (oxycodone 0.1 mg/kg IV).

Thirty-four patients completed the 24-hour study period per the dosage protocol. In the recovery room, the time from the end of anesthesia to removal of the tracheal tube was slightly shorter in the acetaminophen group than in the placebo group—19 minutes versus 27 minutes. No differences in OPS were found between the groups after removal of the tracheal tube. Time to first oxycodone dose with patient control from the end of anesthesia was 28 minutes shorter in the placebo group than in the acetaminophen group.

In the postoperative ward, 6 patients in the acetaminophen group and 13 patients in the placebo group had a visual analog scale pain score of 6 or higher (P < 0.05). Pain of this magnitude did not last as long in the aceta-minophen group as it did in the placebo group (20 hours versus 45 hours) (Fig. 1). Furthermore, fewer patients in the acetaminophen group needed additional analgesics (8 of 17 versus 16 of 18, P < 0.05).

No statistically significant differences in oxycodone consumption were found between the two groups during the 24-hour follow-up (1.3 mg/kg for the acetaminophen group; 1.4 mg/kg for the placebo group). The acetaminophen concentrations were not at toxic levels.

Although acetaminophen did provide enhanced pain relief, it did not reduce oxycodone consumption. The authors hypothesized that activation of peripheral pain pathways and release of chemical mediators might be more important than activation of central pain pathways after orthopaedic surgery. For this reason, acetaminophen alone may not diminish opioid consumption.

Dr. Helenius’ coauthors of “Acetaminophen improves analgesia but does not reduce opioid requirement after major spine surgery in children and adolescents” are Arja Hiller, MD, PhD; Elisa Nurmi, MD; Pertti J. Neuvonen, MD, PhD; Maija Kaukonen, MD, PhD; Tuula Hartikainen, RN; Reijo Korpela MD; Tomi Taivainen, MD, PhD; and Olli Meretoja, MD, PhD.

Disclosure information: Dr. Helenius—Baxter Finland, Synthes, Pediatric Research Foundation, Medtronic. The other authors reported no conflicts.

Terry Stanton is senior science writer for AAOS Now. He can be reached at tstanton@aaos.org

Bottom Line

• Acetaminophen has advantages over NSAIDs for pain relief and bone healing, and use of acetaminophen has demonstrated an opioid-sparing effect in adults undergoing surgery.
• This randomized, placebo-controlled trial in children undergoing spine surgery took place in Finland and used a form of IV acetaminophen not approved for use in the United States.
• IV acetaminophen provided better analgesia than placebo, but did not reduce consumption of oxycodone.
• Blood concentrations of acetaminophen in the patients did not reach toxic levels.