Results for “excellent” or “good” satisfaction were similar to those for “excellent” satisfaction with IV acetaminophen increasing “good to excellent” satisfaction with an odds ratio of 2.10 (95% CI 1.93–2.27, p < .001) in bivariate analysis. IV acetaminophen treatment remained significant in multivariable analysis (OR 2.54, 95% CI 2.33–2.75; p < .001), with opioid consumption, type of surgery, and last pain rating also significantly affecting incidence of “good to excellent” satisfaction. Interestingly, in contrast to results for “excellent” satisfaction, duration of anesthesia did not affect incidence of “excellent” or “good” satisfaction (p = .126).
Across the five studies, less total rescue medication (in morphine equivalents) was required in patients receiving 1 g of IV acetaminophen every 6 hr for 24 hr (mean 32.1 ± 30.0 mg) versus placebo (mean 38.7 ± 34.8 mg; p = .01). Additionally, last pain rating before measurement of patient satisfaction was similar in both IV acetaminophen and placebo groups (mean 1.39 ± 0.78 and mean 1.40 ± 0.77 on a scale of 0–3, respectively, p = .904).
In this pooled analysis of five randomized, placebo-controlled trials, a postoperative analgesic regimen including IV acetaminophen resulted in a statistically significant and clinically relevant improvement in patient satisfaction at 24 hr postsurgery compared to placebo. Specifically, patients receiving IV acetaminophen had more than double the incidence of “excellent” patient satisfaction ratings compared to those who received placebo. The impressive positive results of this analysis reconcile the varied results of the individual trials and suggest that the lack of statistical significance in individual trials may be due to differences in baseline incidences of “excellent” satisfaction in the populations studied or small sample sizes in the individual studies. To explore the methods through which IV acetaminophen increases patient satisfaction and gain further insight into other factors that may affect satisfaction, we performed multivariable analysis. We found that IV acetaminophen was the strongest modifiable factor for “excellent” patient satisfaction, independent of surgery type, the duration of anesthesia, postoperative opioid consumption, and last postsurgical pain rating, all of which significantly affected satisfaction. These results are similar with previous studies that have analyzed the various factors that influence global patient satisfaction (Jensen et al., 2004).
Patients receiving IV acetaminophen required less opioid rescue medication via the PCA pump than those who received placebo while maintaining similar pain control. Although we did not analyze whether IV acetaminophen's opioid-reducing effect led to a reduction in opioid-related side effects, such as nausea, vomiting, constipation, urinary retention, respiratory depression, and sedation (Benyamin et al., 2008), any such reduction could positively affect patient satisfaction. However, while we found that opioid consumption significantly affected patient satisfaction, based on the logistic regression results we can conclude that IV acetaminophen's effect on patient satisfaction was independent of the amount opioids consumed.
The principal strength of this pooled analysis is the common methodology found in these five randomized, placebo-controlled studies, allowing for a robust, patient-level evaluation of the impact of scheduled doses of IV acetaminophen in the first 24 hr for postoperative pain intensity on patient satisfaction. All included studies had comparable overall designs and similar primary and secondary endpoints. These study results do relate to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey and Value-Based Purchasing program. However, as the questions in our data were phrased slightly differently from the questions in the HCAHPS survey, the actual impact might differ.
A possible limitation of this analysis is that patients underwent different types of surgery, which may affect optimal analgesic regimen. However, while the type of surgery has a very strong effect on patient satisfaction, the significant increase in patient satisfaction with IV acetaminophen remains after type of surgery is accounted for in the multivariable analysis.
The authors wish to thank Donna Simcoe at Cadence Pharmaceuticals, Inc. for providing patient-level satisfaction data from the five clinical trials provided at the authors’ request. Furthermore, the authors thank Christine Pan (CPAN Statistical Consulting) for her preliminary statistical analyses, funded by Cadence Pharmaceuticals, Inc.
Benyamin R., Trescot A. M., Datta S., Buenaventura R., Adlaka R., Sehgal N., et al. Opioid complications and side effects. Pain Physician 2008;11(2 Suppl.):S105–S120.
Candiotti K., Singla N., Wininger S., Minkowitz H., Breitmeyer J. A randomized, double-blind, placebo-controlled, multi-center, parallel-group, multiple-dose study of the efficacy and safety of intravenous acetaminophen
over 48 hours for the treatment of postoperative pain after gynecologic surgery. Annual Regional Anesthesia Meeting 2008, Poster #13.
Collins S. L., Edwards J., Moore R. A., Smith L. A., McQuay H. J. Seeking a simple measure of analgesia for mega-trials: Is a single global assessment good enough? Pain 2001;91:189–194.
Fischer D., Stewart A. L., Bloch D. A., Lorig K., Laurent D., Holman H. Capturing the patient's view of change as a clinical outcome measure. Journal of the American Medical Association 1999;282:1157–1162.
Gimbel J., Royal M., Leclerc A., Smith H., Breitmeyer J. Efficacy and safety of IV acetaminophen in the treatment of pain following primary total hip arthroplasty: Results of a double-blind, randomized, placebo-controlled, multiple-dose 24 hour study. 24th Annual Meeting of the American Academy of Pain Medicine 2008.
Jahr J. S., Filocamo P., Singh S. Intravenous acetaminophen
: A review of pharmacoeconomic science for perioperative use. American Journal of Therapeutics 2013;20:189–199.
Jensen M. P., Mendoza T., Hanna D. B., Chen C., Cleeland C. S. The analgesic effects that underlie patient satisfaction
with treatment. Pain 2004;110:480–487.
McNicol E. D., Tzortzopoulou A., Cepeda M. S., Francia M. B., Farhat T., Schumann R. Single-dose intravenous paracetamol or propacetamol for prevention or treatment of postoperative pain: A systematic review and meta-analysis. British Journal of Anaesthesia 2011;106:764–775.
Minkowitz H., Royal M., Leclerc A., Kenney B., Breitmeyer J. Efficacy and safety of IV acetaminophen in the treatment of pain following vaginal hysterectomy: Results of a double-blind, randomized, placebo-controlled, multiple-dose, 24 hour study. 24th Annual Meeting of the American Academy of Pain Medicine 2008.
National Association of Public Hospitals and Health Systems (NAPH). HCAHPS survey: Patients’ perspective of care. 2008. Online material, Retrieved February 27, 2013, from http://www.naph.org
Pettersson P. H., Jakobsson J., Owall A. Intravenous acetaminophen
reduced the use of opioids compared with oral administration after coronary artery bypass grafting. Journal of Cardiothoracic and Vascular Anesthesia 2005;19:306–309.
Sinatra R. S., Jahr J. S., Reynolds L. W., Viscusi E. R., Groudine S. B., Payen-Champenois C. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen
injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology 2005;102:822–831.
Singla N. K., Parulan C., Samson R., Hutchinson J., Bushnell R., Beja E. G., et al. Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen. Pain Practice 2012;12:523–532.
Stahmer S. A., Shofer F. S., Marino A., Shepherd S., Abbuhl S. Do quantitative changes in pain intensity correlate with pain relief and satisfaction? Academic Emergency Medicine 1998;5:851–857.
Tzortzopoulou A., McNicol E. D., Cepeda M. S., Francia M. B., Farhat T., Schumann R. Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain. Cochrane Database of Systematic Reviews 2011;5:CD007126.
Wininger S. J., Miller H., Minkowitz H. S., Royal M. A., Ang R. Y., Breitmeyer J. B., et al.. A randomized, double-blind, placebo-controlled, multi-center, repeat-dose study of two intravenous acetaminophen
dosing regimens for the treatment of pain after abdominal laparoscopic surgery. Clinical Therapeutics 2010;32:2348–2369.
Wu C. L., Naqibuddin M., Fleisher L. A. Measurement of patient satisfaction
as an outcome of regional anesthesia and analgesia: A systematic review. Regional Anesthesia and Pain Medicine 2001;26:196–208.
Conflict of Interest
Christian Apfel, MD, PhD, was a former Associate Professor of the Department of Anesthesia and Perioperative Clinical Research Care and the Department of Biostatistics and Epidemiology at University of California, San Francisco and a former employee of Cadence Pharmaceuticals, Inc. Dr. Apfel is currently an Adjunct Associate Professor, Department of Epidemiology & Biostatistics, University of California, San Francisco and a consultant for Cadence Pharmaceuticals, Inc. Kimberly Souza performed this research when she was a member of the Department of Anesthesia & Perioperative Care, University of California, San Francisco. Ms. Souza is now a student at Stanford School of Medicine, Stanford, CA. Ms. Dalal was a former Clinical Research Assistant with the Department of Anesthesiology, but is now a first-year resident with the Department of Internal Medicine at The Ohio State University Wexner Medical Center.
Christian C. Apfel, MD, PhD, is an Adjunct Associate Professor at the Department of Epidemiology & Biostatistics, University of California, San Francisco. Dr. Apfel is focused on clinical research on a wide range of outcomes, including but not limited to postoperative nausea, vomiting, pain, and tumor response and survival in cancer research, etc. In collaboration with other colleagues he performs evidence-based quantitative systematic reviews, epidemiological research, and controlled clinical single- and multicenter investigator-initiated or registration trials.
Kimberly Souza, BS, is an MD Candidate, Stanford School of Medicine, Stanford, CA. Ms. Souza performed this research when she was a member of the Department of Anesthesia & Perioperative Care, University of California, San Francisco.
Juan Portillo, MD, is a Postdoctoral Researcher in the Department of Anesthesiology at The Ohio State University Wexner Medical Center. Dr. Portillo has research experience with sponsored and principal investigator initiated research trials, as well as with oral and poster presentations at scientific research meetings.
Poorvi Dalal, DO, is a first-year resident with the Department of Internal Medicine at The Ohio State University Wexner Medical Center. Dr. Dalal performed this research when she was a Clinical Research Assistant with the Department of Anesthesiology at The Ohio State University Wexner Medical Center.
Sergio D. Bergese, MD, is Associate Professor of the Department of Anesthesiology and Neurological Surgery, The Ohio State University Wexner Medical Center. Dr. Bergese's areas of interest are in postoperative pain, postoperative nausea and vomiting, postoperative delirium, and patient monitoring devices.