Parecoxib added to patient-controlled postoperative morphine analgesia may reduce delirium and nausea or vomiting in older adults having elective total hip or knee replacement
EBM Focus - Volume 12, Issue 28
- Postoperative delirium may be more likely with opioid-based analgesia. Adjunct parecoxib may reduce postoperative opioid use.
- In a recent trial, 620 adults (mean age 70 years) having total hip or knee replacement with patient-controlled postoperative morphine analgesia were randomized to adjunct parecoxib 40 mg IV twice daily for 3 days vs. adjunct saline.
- Adjunct parecoxib reduced incident delirium (in 6.1% vs. 11%, risk ratio 0.56, 95% CI 0.33-0.96) and incident nausea or vomiting (in 6.5% vs. 11%, risk ratio 0.59, 95% CI 0.35-0.99) over the first 5 postoperative days.
Postoperative delirium following orthopedic surgery is a potential complication which is associated with poor outcomes (Age Ageing 2011 May;40(3):312, Lancet 2014 Mar 8;383(9920):911) and may be more likely with opioid-based analgesia (Aging Clin Exp Res 2017 Apr;29(2):115). Adjunct cyclooxygenase-2 (COX-2) inhibitors such as celecoxib or parecoxib may reduce postoperative opioid use (J Arthroplasty 2013 Feb;28(2):207, Pain Ther 2017 Jun;6(1):61). To assess the effects of adjunct parecoxib on postoperative delirium, 620 adults (mean age 70 years, 74% women) having elective total hip or knee replacement with postoperative morphine analgesia were randomized to adjunct parecoxib sodium 40 mg IV vs. adjunct saline twice daily for 3 days following surgery. Patients were excluded for preoperative delirium, preoperative American Society of Anesthesiologists physical status ≥ IV, and contraindications for parecoxib such as New York Heart Association functional classification ≥ III and active peptic ulcers. Postoperative analgesia consisted of patient-controlled morphine 1 mg IV bolus with a 6-minute lockout plus a 0.5 mg/hour continuous IV infusion, and additional IV morphine if needed, for 3 days. Supplemental oral morphine was given as necessary after termination of the 3-day IV regimen. Intraoperative anesthesia and sedation consisted of combined spinal-epidural anesthesia plus propofol, midazolam, and/or fentanyl as deemed necessary. All patients also had prophylactic ondansetron at the end of surgery. The primary outcome was incident delirium, defined according to the Confusion Assessment Method as mental status change (acute onset or fluctuating course), inattention, and either disorganized thinking or altered consciousness.
Incident delirium within the first 5 postoperative days was observed in 6.1% of patients with adjunct parecoxib and 11% with adjunct saline (risk ratio [RR] 0.56, 95% CI 0.33-0.96, NNT 21). Patients taking parecoxib also had a lower risk of nausea or vomiting over the first 5 postoperative days (in 6.5% vs. 11%, RR 0.59, 95% CI 0.35-0.99, NNT 23), slightly lower median pain (1 vs. 2 on a 10-point scale, p < 0.001) and cumulative IV morphine consumption (53.2 vs. 58.6 mg, p < 0.001) at 3 days after surgery, and a non-significantly lower frequency of supplemental oral morphine use (in 5.8% vs. 8.4%). In addition, among 562 patients who had cognitive impairment assessments at baseline and at 5 days after surgery, impairment (defined as a ≥ 2 point reduction from baseline on the Mini-Mental State Examination) occurred in 9.7% vs. 19.4% (RR 0.5, 95% CI 0.34-0.77, NNT 11). There were no significant differences between groups in other postoperative adverse events, occurring in 11.6% vs. 12.3%, most commonly lower limb thrombosis (in 6.1% vs. 5.2%), cardiovascular complications (2.6% vs. 1.6%), and pulmonary complications (1.3% vs. 2.9%). Occurrence of gastrointestinal events such as bleeding was not reported.
This trial demonstrated that the addition of parecoxib 40 mg IV twice daily to postoperative patient-controlled IV morphine analgesia may reduce the risks of postoperative delirium and nausea or vomiting, and may have other benefits, in older patients having elective total knee or hip replacement. The 95% confidence intervals in the risk reductions included clinically unimportant reductions and the magnitudes of the effects in those and other outcomes were small. The authors speculate that the small effect sizes may be partly due to the use of combined spinal-epidural anesthesia rather than general anesthesia, the use of a continuous morphine infusion in addition to the patient-controlled boluses, and the exclusion of patients needing non-elective surgery or who were otherwise in poor preoperative condition. The rates of adverse gastrointestinal events, a possible risk with non-steroidal anti-inflammatory drugs (NSAIDs) in general, were not explicitly described. Finally, parecoxib itself is not FDA-approved in the United States (PubChem CID 119828), but is available elsewhere. This study suggests that adjunct parecoxib may reduce delirium and nausea or vomiting in patients having opioid-based analgesia following total hip or knee replacement, possibly due to reduced opioid consumption; additional research is necessary to assess efficacy of other adjunct analgesic medications.