Intravenous (IV) acetaminophen has been demonstrated to be safe and effective, but because of its comparatively high cost, it is prescribed far less to patients after spine surgery than oral (PO) formulations.* During a Best Paper session at the North American Spine Society Annual Meeting, researchers reported that IV acetaminophen may be a better value for use in circumferential lumbar spine surgery due to the reduction in indirect costs and avoidance of potential opioid dependence.

The study, titled “Single-Center, Randomized Controlled Trial of Intravenous Versus Oral Acetaminophen Administration in Perioperative Care of Circumferential Lumbar Fusion: A Comparative Effectiveness Study,” was presented by Christina Dowe, BS, clinical research coordinator at Hospital for Special Surgery in New York. The prospective trial included patients aged 18 to 80 years who had failed conservative management for more than 12 months and subsequently underwent circumferential lumbar fusion surgery. Patients were excluded if they had already undergone lumbar surgery at the index level(s), were diagnosed with osteoporosis, had dysphagia prohibiting PO administration, or had a history of substance abuse. Outcome measures were opioid equivalence, length of hospital stay (LOS), visual analog scale (VAS) measurements, and Oswestry Disability Index (ODI) scores.

Patients were randomized to receive IV or PO acetaminophen. Preoperatively, patients completed a baseline analgesic regimen questionnaire; completed surveys, including VAS, Short Form-12, and ODI; and were administered their first acetaminophen dose within three hours of the first surgical incision. Postoperatively, patients received seven subsequent doses of their assigned acetaminophen, with access to supplemental analgesics if needed. Analgesic usage and VAS scores were monitored until discharge. Surveys were completed at six-week and six-month follow-up.

Postoperatively, the daily morphine equivalence taken by the IV acetaminophen group was 66 percent less than the oral acetaminophen group (P < 0.05), with significant differences also observed between the one- and two-level fusion cohorts. The difference in average LOS between groups was not statistically significant.

A substantial difference

“Although not all opioid addictions begin with a prescription, we were pleased to find that the group assigned to the IV acetaminophen regimen took significantly less opioid medication and had shorter hospital stays than the group assigned to oral acetaminophen,” Ms. Dowe said. “Despite the large cost discrepancy between the two formulations, by significantly reducing opioid usage—and its costs due to associated side effects such as potential addiction—that cost difference becomes far less dramatic and far less significant.” She said the researchers were most surprised by “how substantial the difference in patient opioid usage was between both groups.”

In conjunction with an overall reduction in opioid usage, patient surveys indicated better improvement of pain management with the use of IV acetaminophen following circumferential lumbar spine surgery, Ms. Dowe noted. “Despite the large discrepancy between the two formulations in cost-to-perceived-benefit ratio, by significantly reducing the opioid usage and, therefore, its costs due to associated side effects, that discrepancy becomes far less dramatic. Our findings suggest that IV acetaminophen is a safe and effective alternative to current opioid-based postoperative analgesic regimens, with a promising answer to the national public health emergency plaguing communities across the United States.”

*The IV version was approved by the Food and Drug Administration in 2010; a 1 gm vial averages $35, not objectively exorbitant relative to the price of some drugs but approximately 35 times the plain cost of the PO version.

Study coauthors, along with Ms. Dowe, are Antonio T. Brecevich, MD; Samuel Grinberg, BA; Tucker C. Callanan, BS; Frank P. Cammisa, MD; Andrew A. Sama, MD; Alexander P. Hughes, MD; Matthew E. Cunningham, MD, PhD; Darren R. Lebl, MD; Federico P. Girardi, MD; Russel C. Huang, MD; Celeste Abjornson, PhD; and Chad M. Craig, MD, FACP (principal investigator), all of Hospital for Special Surgery in New York.

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

Exploring opioids at NASS

Several other studies presented at the North American Spine Society (NASS) Annual Meeting addressed pain control and opioid consumption.

In a study examining the effect of the use of liposomal bupivacaine on narcotic consumption in adult deformity surgery, 159 consecutive adults undergoing elective spinal fusion (mean age, 54.2 years) for scoliosis or kyphosis by a single surgeon received either peri-incisional injections of combined liposomal and standard bupivacaine or standard bupivacaine only. Michael S. Chang, MD, of Sonoran Spine Center in Tempe, Ariz., reported that patients receiving liposomal bupivacaine consumed 18 percent less morphine milligram equivalent (MME) units compared to the control group (259 mg versus 316 mg, respectively) over the course of hospitalization. The liposomal group also transitioned off intravenous (IV) narcotics significantly earlier, with 52.6 percent less IV use by postoperative day three compared to the control arm (12.0 mg versus 25.4 mg, respectively; P = 0.03). However, the reduction in narcotic use did not significantly impact length of stay (LOS), as the protocol requirement of return of bowel movements before discharge was a limiting factor. There were also no significant differences in complication rates overall and specifically in ileus and superficial wound infection. In addition, no differences in functional outcome scores were observed at six weeks postoperatively.

Another study, which examined the implementation of a standardized multimodal analgesia protocol for posterior lumbar fusion, found that the protocol led to a reduction in pain scores, opioid consumption, opioid-related adverse events (AEs), and LOS after posterior lumbar fusion. Corey Walker, MD, of Barrow Neurological Institute in Phoenix, reported that the study, which involved 115 pre– and 126 post–protocol-implementation patients, found that average patient-reported pain scores significantly improved in the first 24 hours postoperatively (5.8 versus 4.6, respectively; P < 0.001) and 24 to 72 hours postoperatively (4.9 versus 4.0, respectively; P < 0.001) following use of the pain protocol. Likewise, maximum pain scores during those periods and time to achieving appropriate pain control were also significantly improved (P < 0.05). Opioid consumption significantly decreased during the first 72 hours (128 MME versus 97 MME, respectively; P < 0.001). Patients in the post–protocol-implementation cohort had a significantly decreased LOS (4.7 days versus 3.9 days, respectively; P < 0.001). Regarding opioid-related AEs, there was a reduction in the incidence of constipation (58 percent versus 44 percent, respectively; P < 0.001).

A study on the impact of surgical invasiveness and patient factors on long-term opioid use in adult spinal deformity (ASD) surgery found that increasing surgical invasiveness affected perioperative but not long-term opioid use and that “long-term opioid use seems to be related to patient-specific factors such as frailty, mental health, and, most importantly, preoperative opioid use.” Brian J. Neuman, MD, of Johns Hopkins University, reported that in the 517 study patients who completed two-year follow-up, increasing surgical invasiveness was not associated with increased long-term opioid use (P > 0.05) but that patients with an ASD-Surgical Invasiveness Index (SR) of 120–160 and > 160 had higher odds of short-term use irrespective of baseline use. Subgroup analysis showed that only in the ASD-SR > 160 group, frail patients, and patients with a mental component summary score of the Short Form-36 Health Survey < 50 at baseline were more likely to have long-term use. Age and sex had no influence on postoperative narcotic use. The most consistent risk factor for long-term opioid use was opioid use at baseline. “Interestingly, preoperative opioid use was associated with the highest odds ratio for long-term use in the lowest invasiveness group,” Dr. Neuman said.