2060 TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 95-A N U M B E R 22 N O V E M B E R 2 0, 2 0 13
E V I D E N C E -B A S E D O R T H O PA E D I C S
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Evidence-Based Orthopaedics
Gabapentin Did Not Reduce Morphine Consumption, Pain, or Opioid-Related Side Effects in Total Knee Arthroplasty Paul JE, Nantha-Aree M, Buckley N, Cheng J, Thabane L, Tidy A, DeBeer J, Winemaker M, Wismer D, Punthakee D, Avram V. Gabapentin Does Not Improve Multimodal Analgesia Outcomes for Total Knee Arthroplasty: A Randomized Controlled Trial. Can J Anaesth. 2013 May;60(5):423-31. Question: In patients having total knee arthroplasty, does gabapentin reduce morphine consumption, pain, and opioid-related side effects?
inability to use patient-controlled analgesia (PCA). All patients completed follow-up. Intervention: Patients were randomly allocated to preoperative and postoperative gabapentin (n 5 52) or placebo (n 5 49). 2 hours before surgery, patients received acetaminophen (1000 mg by mouth) and intravenous ketorolac (15 mg) plus oral administration of either gabapentin (600 mg) or placebo. During surgery, patients received standardized spinal anesthesia. Postoperatively, patients received PCA morphine for 3 days, acetaminophen (1000 mg by mouth), and ketorolac (15 mg) every 6 hours; subjects also received gabapentin (200 mg by mouth every 8 hours) or placebo for 2 days postoperatively.
Design: Randomized (allocation concealed), blinded (patients, health-care providers, and study personnel), placebo-controlled trial with 72-hour follow-up. Setting: A tertiary care hospital in Hamilton, Ontario, Canada. Patients: 101 patients (mean age 63 years, 63% women) who were receiving total knee arthroplasty. Exclusion criteria included revision or bilateral arthroplasty; history of renal or hepatic impairment; allergy or intolerance to nonsteroidal antiinflammatory drugs, acetaminophen, morphine, gabapentin, or spinal anesthesia; drug or alcohol abuse; chronic pain syndrome treated with opioids up to 30 mg of morphine equivalence; untreated obstructive sleep apnea; seizure disorder; breast-feeding; and
Main outcome measures: The primary outcome was cumulative morphine consumption at seventytwo hours after surgery. Secondary outcomes
Gabapentin vs. placebo before and after total knee arthroplasty* Outcomes at 72 hours
Gabapentin
Placebo
Difference (95% CI)
Cumulative morphine consumption (mg)
26.2 (229.1 to 16.8)
66.3
72.5
Pain score at rest
2.2
2.0
0.2
Pain score with passive movement
3.2
3.2
0.1
Pain score with weight-bearing
4.4
4.1
0.3
*Values are expressed as the mean. Pain score range: 0 (no pain) to 10 (worst possible pain). CI = confidence interval.
included pain (score range, 0 [no pain] to 10 [worst possible pain]) at rest and with passive movement and weight-bearing, opioid side effects (nausea, vomiting, and pruritus; none to severe), gabapentin side effects (dizziness or light-headedness and visual disturbances), knee range of motion, and hemodynamic and respiratory variables. Main results: Analysis was by intention to treat. The study had 80% power to detect a 50% reduction in morphine consumption in the gabapentin group. The gabapentin and placebo groups did not differ in cumulative morphine consumption at 72 hours (Table). The groups did not differ in pain scores at rest, with movement, or with weight-bearing (Table). The incidence of nausea, vomiting, pruritus, dizziness or light-headedness, or visual disturbances was similar in both groups. Knee range of motion at discharge did not differ between the gabapentin and placebo groups (97.2° vs. 105.1°, respectively, for flexion and 3.6° vs. 3.0°, respectively, for extension). Conclusion: In patients having total knee arthroplasty, the addition of gabapentin to the PCA protocol did not reduce morphine consumption, pain, or opioid-related side effects. Source of funding: No external funding. For correspondence: Dr. J.E. Paul, Hamilton Health Sciences, Department of Anesthesia, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada. E-mail address: [email protected]
Commentary Postoperative pain after total knee arthroplasty is a major problem. The study by Paul and colleagues is important with regard to improving postoperative pain management after total knee arthroplasty. This research has been performed in a very rigorous manner: randomized, controlled, and blinded. On the other hand, there are concerns regarding patent selection, as patients with chronic pain were not included. This subgroup of patients might have obtained greater benefit from gabapentin, considering its proven efficacy in chronic pain management. The primary outcome was morphine consumption, as a surrogate for the effect of gabapentin on pain control. Therefore, the direct effect of gabapentin on pain control is not
evaluated because its effect on postoperative pain and knee function is biased by differing morphine consumption between patients. The most important conclusion from a practical point of view is that the use of gabapentin in the first three days after total knee arthroplasty is not indicated. Eliminating this medication will be cost effective and will also avoid the additional risks associated with yet another medication for patients who are recovering from a recent total knee arthroplasty. Stefano Zaffagnini, MD Rizzoli Orthopaedic Institute, Bologna, Italy
Disclosure: The author received no payments or services, either directly or indirectly (i.e., via his institution), from a third party in support of any aspect of this work. Neither the author nor his institution has had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, the author has not had any other relationships, or engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.
J Bone Joint Surg Am. 2013;95:2060
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http://dx.doi.org/10.2106/JBJS.9522.ebo401
E V I D E N C E -B A S E D O R T H O PA E D I C S
d
d
d
Evidence-Based Orthopaedics
Gabapentin Did Not Reduce Morphine Consumption, Pain, or Opioid-Related Side Effects in Total Knee Arthroplasty Paul JE, Nantha-Aree M, Buckley N, Cheng J, Thabane L, Tidy A, DeBeer J, Winemaker M, Wismer D, Punthakee D, Avram V. Gabapentin Does Not Improve Multimodal Analgesia Outcomes for Total Knee Arthroplasty: A Randomized Controlled Trial. Can J Anaesth. 2013 May;60(5):423-31. Question: In patients having total knee arthroplasty, does gabapentin reduce morphine consumption, pain, and opioid-related side effects?
inability to use patient-controlled analgesia (PCA). All patients completed follow-up. Intervention: Patients were randomly allocated to preoperative and postoperative gabapentin (n 5 52) or placebo (n 5 49). 2 hours before surgery, patients received acetaminophen (1000 mg by mouth) and intravenous ketorolac (15 mg) plus oral administration of either gabapentin (600 mg) or placebo. During surgery, patients received standardized spinal anesthesia. Postoperatively, patients received PCA morphine for 3 days, acetaminophen (1000 mg by mouth), and ketorolac (15 mg) every 6 hours; subjects also received gabapentin (200 mg by mouth every 8 hours) or placebo for 2 days postoperatively.
Design: Randomized (allocation concealed), blinded (patients, health-care providers, and study personnel), placebo-controlled trial with 72-hour follow-up. Setting: A tertiary care hospital in Hamilton, Ontario, Canada. Patients: 101 patients (mean age 63 years, 63% women) who were receiving total knee arthroplasty. Exclusion criteria included revision or bilateral arthroplasty; history of renal or hepatic impairment; allergy or intolerance to nonsteroidal antiinflammatory drugs, acetaminophen, morphine, gabapentin, or spinal anesthesia; drug or alcohol abuse; chronic pain syndrome treated with opioids up to 30 mg of morphine equivalence; untreated obstructive sleep apnea; seizure disorder; breast-feeding; and
Main outcome measures: The primary outcome was cumulative morphine consumption at seventytwo hours after surgery. Secondary outcomes
Gabapentin vs. placebo before and after total knee arthroplasty* Outcomes at 72 hours
Gabapentin
Placebo
Difference (95% CI)
Cumulative morphine consumption (mg)
26.2 (229.1 to 16.8)
66.3
72.5
Pain score at rest
2.2
2.0
0.2
Pain score with passive movement
3.2
3.2
0.1
Pain score with weight-bearing
4.4
4.1
0.3
*Values are expressed as the mean. Pain score range: 0 (no pain) to 10 (worst possible pain). CI = confidence interval.
included pain (score range, 0 [no pain] to 10 [worst possible pain]) at rest and with passive movement and weight-bearing, opioid side effects (nausea, vomiting, and pruritus; none to severe), gabapentin side effects (dizziness or light-headedness and visual disturbances), knee range of motion, and hemodynamic and respiratory variables. Main results: Analysis was by intention to treat. The study had 80% power to detect a 50% reduction in morphine consumption in the gabapentin group. The gabapentin and placebo groups did not differ in cumulative morphine consumption at 72 hours (Table). The groups did not differ in pain scores at rest, with movement, or with weight-bearing (Table). The incidence of nausea, vomiting, pruritus, dizziness or light-headedness, or visual disturbances was similar in both groups. Knee range of motion at discharge did not differ between the gabapentin and placebo groups (97.2° vs. 105.1°, respectively, for flexion and 3.6° vs. 3.0°, respectively, for extension). Conclusion: In patients having total knee arthroplasty, the addition of gabapentin to the PCA protocol did not reduce morphine consumption, pain, or opioid-related side effects. Source of funding: No external funding. For correspondence: Dr. J.E. Paul, Hamilton Health Sciences, Department of Anesthesia, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada. E-mail address: [email protected]
Commentary Postoperative pain after total knee arthroplasty is a major problem. The study by Paul and colleagues is important with regard to improving postoperative pain management after total knee arthroplasty. This research has been performed in a very rigorous manner: randomized, controlled, and blinded. On the other hand, there are concerns regarding patent selection, as patients with chronic pain were not included. This subgroup of patients might have obtained greater benefit from gabapentin, considering its proven efficacy in chronic pain management. The primary outcome was morphine consumption, as a surrogate for the effect of gabapentin on pain control. Therefore, the direct effect of gabapentin on pain control is not
evaluated because its effect on postoperative pain and knee function is biased by differing morphine consumption between patients. The most important conclusion from a practical point of view is that the use of gabapentin in the first three days after total knee arthroplasty is not indicated. Eliminating this medication will be cost effective and will also avoid the additional risks associated with yet another medication for patients who are recovering from a recent total knee arthroplasty. Stefano Zaffagnini, MD Rizzoli Orthopaedic Institute, Bologna, Italy
Disclosure: The author received no payments or services, either directly or indirectly (i.e., via his institution), from a third party in support of any aspect of this work. Neither the author nor his institution has had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, the author has not had any other relationships, or engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.
J Bone Joint Surg Am. 2013;95:2060
d
http://dx.doi.org/10.2106/JBJS.9522.ebo401
