Randomized, double-blinded, placebo-controlled trial comparing two multimodal opioid-minimizing pain management regimens following transsphenoidal surgery

Abstract

OBJECTIVE Pain control is an important clinical consideration and quality-of-care metric. No studies have examined postoperative pain control following transsphenoidal surgery for pituitary lesions. The study goals were to 1) report postoperative pain scores following transsphenoidal surgery, 2) determine if multimodal opioid-minimizing pain regimens yielded satisfactory postoperative pain control, and 3) determine if intravenous (IV) ibuprofen improved postoperative pain scores and reduced opioid use compared with placebo. METHODS This study was a single-center, randomized, double-blinded, placebo-controlled intervention trial involving adult patients with planned transsphenoidal surgery for pituitary tumors randomized into 2 groups. Group 1 patients were treated with scheduled IV ibuprofen, scheduled oral acetaminophen, and rescue opioids. Group 2 patients were treated with IV placebo, scheduled oral acetaminophen, and rescue opioids. The primary end point was patient pain scores (visual analog scale [VAS], rated 0-10) for 48 hours after surgery. The secondary end point was opioid use as estimated by oral morphine equivalents (OMEs). RESULTS Of 136 patients screened, 62 were enrolled (28 in Group 1, 34 in Group 2). The study was terminated early because the primary and secondary end points were reached. Baseline characteristics between groups were well matched except for age (Group 1, 59.3 ± 14.4 years; Group 2, 49.8 ± 16.2 years; p = 0.02). Mean VAS pain scores were significantly different, with a 43% reduction in Group 1 (1.7 ± 2.2) compared with Group 2 (3.0 ± 2.8; p < 0.0001). Opioid use was significantly different, with a 58% reduction in Group 1 (26.3 ± 28.7 mg OME) compared with Group 2 (62.5 ± 63.8 mg OME; p < 0.0001). CONCLUSIONS Multimodal opioid-minimizing pain-management protocols resulted in acceptable pain control following transsphenoidal surgery. IV ibuprofen resulted in significantly improved pain scores and significantly decreased opioid use compared with placebo. Postoperative multimodal pain management, including a nonsteroidal antiinflammatory medication, should be considered after surgery to improve patient comfort and to limit opioid use. Clinical trial registration no.: NCT02351700 (clinicaltrials.gov) ■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: randomized, controlled trial; evidence: Class III.

Narrative Summary of Recently Published Literature on Intravenous Ibuprofen

“…Of the 9 studies analyzed, 4 (Singla et al, 13 Shepherd et al, 25 Viswanath et al, 26 and Uribe et al 27 ) investigated the efficacy of IVIB using pain scores and postoperative opioid use. IVIB was reproducibly more effective in reducing postoperative pain and the quantity of opioids used than were placebo, IV acetaminophen, an analgesic regimen with placebo, oral acetaminophen, and IV ketorolac in patients undergoing orthopedic, trans-sphenoidal, third molar, and arthroscopic knee surgery, respectively.…”

“…Shepherd et al 25 measured postoperative pain; quantified the efficacy of multimodal, opioidminimizing pain management relative to the adequacy of postoperative pain control, and quantified postoperative pain and opioid use for comparisons between IVIB and IV placebo (saline). They randomized 62 adult patients undergoing transsphenoidal surgery for pituitary tumors to receive oral acetaminophen plus either IVIB or IV placebo, with rescue opioids given as needed in both groups.…”

Efficacy and Safety of an Intravenous Acetaminophen/Ibuprofen Fixed-dose Combination After Bunionectomy: a Randomized, Double-blind, Factorial, Placebo-controlled Trial

“…7 Another small single-center, double-blinded study found that the addition of intravenous ibuprofen 800 mg to oral acetaminophen 1000 mg in patients undergoing transsphenoidal surgery reduced pain scores and opioid consumption over a 48-hour period. 8 Multimodal analgesia with intravenous acetaminophen and other nonsteroidal anti-inflammatory drugs (ketoprofen, diclofenac, and parecoxib) is supported by a number of studies. 17e19 The safety profile of the FDC was broadly comparable to either active agent alone.…”

“…There is limited evidence regarding the effect of combining ibuprofen and acetaminophen when one or both drugs are administered parenterally; published reports suggest that co-treatment affords superior pain relief. 7,8 To simplify multimodal analgesia and extend the therapeutic advantages of existing fixed-dose combination tablets to patients in whom parenteral administration is clinically justified, a fixed-dose combination containing ibuprofen 300 mg + acetaminophen 1000 mg in 100-mL solution for infusion has been developed (henceforth FDC). It has previously been shown that when given together by this route, there is no pharmacokinetic interaction between the 2 active ingredients.…”

Opioid-Sparing Multimodal Analgesia After Selective Dorsal Rhizotomy

“…through a single-level laminectomy. [17][18][19][20][21][22] Postoperatively, patients were either in the postanesthesia care unit until admitted to the PICU or directly admitted to the PICU. Starting on POD 1, patients were on the hospitalist service.…”