The effect of ketorolac on posterior minimally invasive transforaminal lumbar interbody fusion: an interim analysis from a randomized, double-blinded, placebo-controlled trial.

BACKGROUND CONTEXT: Postoperative pain control following posterior lumbar fusion continues to be challenging and often requires high doses of opioids for pain relief. The use of ketorolac in spinal fusion is limited due to the risk of pseudarthrosis. However, recent literature suggests it may not affect fusion rates with short-term use and low doses. PURPOSE: We sought to demonstrate noninferiority regarding fusion rates in patients who received ketorolac after undergoing minimally invasive (MIS) posterior lumbar interbody fusion. Additionally, we sought to demonstrate ketorolac's opioid-sparing effect on analgesia in the immediate postoperative period. STUDY DESIGN/SETTING: This is a prospective, randomized, double-blinded, placebo-controlled trial. We are reporting our interim analysis. PATIENT SAMPLE: Adults with degenerative spinal conditions eligible to undergo a one to three-level MIS transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Six-month and 1-year radiographic fusion as determined by Suk criteria, postoperative opioid consumption as measured by intravenous milligram morphine equivalent, length of stay, and drug-related complications. Self-reported and functional measures include validated visual analog scale, short-form 12, and Oswestry Disability Index. METHODS: A double-blinded, randomized placebo-controlled, noninferiority trial of patients undergoing 1- to 3-level MIS TLIF was performed with bone morphogenetic protein (BMP). Patients were randomized to receive a 48-hour scheduled treatment of either intravenous ketorolac (15 mg every 6 hours) or saline in addition to a standardized pain regimen. The primary outcome was fusion. Secondary outcomes included 48-hour and total postoperative opioid use demonstrated as milligram morphine equivalence, pain scores, length of stay (LOS), and quality-of-life outcomes. Univariate analyses were performed. The present study provides results from a planned interim analysis. RESULTS: Two hundred and forty-six patients were analyzed per protocol. Patient characteristics were comparable between the groups. There was no significant difference in 1-year fusion rates between the two treatments (p=.53). The difference in proportion of solid fusion between the ketorolac and placebo groups did not reach inferiority (p=.072, 95% confidence interval, -.07 to .21). There was a significant reduction in total/48-hour mean opioid consumption (p<.001) and LOS (p=.001) for the ketorolac group while demonstrating equivalent mean pain scores in 48 hours postoperative (p=.20). There was no significant difference in rates of perioperative complications. CONCLUSIONS: Short-term use of low-dose ketorolac in patients who have undergone MIS TLIF with BMP demonstrated noninferior fusion rates. Ketorolac safely demonstrated a significant reduction in postoperative opioid use and LOS while maintaining equivalent postoperative pain control.

Efficacy and safety of cilostazol-nimodipine combined therapy on delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a prospective, randomised, double-blinded, placebo-controlled trial protocol.

INTRODUCTION: Delayed cerebral ischaemia (DCI) due to cerebral vasospasm (cVS) remains the foremost contributor to morbidity and mortality following aneurysmal subarachnoid haemorrhage (aSAH). Past efforts in preventing and treating DCI have failed to make any significant progress. To date, our most effective treatment involves the use of nimodipine, a calcium channel blocker. Recent studies have suggested that cilostazol, a platelet aggregation inhibitor, may prevent cVS. Thus far, no study has evaluated the effect of cilostazol plus nimodipine on the rate of DCI following aSAH. METHODS AND ANALYSIS: This is a multicentre, double-blinded, randomised, placebo-controlled superiority trial investigating the effect of cilostazol on DCI. Data concerning rates of DCI, symptomatic and radiographic vasospasm, length of intensive care unit stay, and long-term functional and quality-of-life (QoL) outcomes will be recorded. All data will be collected with the aim of demonstrating that the use of cilostazol plus nimodipine will safely decrease the incidence of DCI, and decrease the rates of both radiographic and symptomatic vasospasm with subsequent improvement in long-term functional and QoL outcomes when compared with nimodipine alone. ETHICS AND DISSEMINATION: Ethical approval was obtained from all participating hospitals by the Ascension Providence Hospital Institutional Review Board. The results of this study will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04148105.

The effect of ketorolac on posterior thoracolumbar spinal fusions: a prospective double-blinded randomised placebo-controlled trial protocol.

INTRODUCTION: Ketorolac has been shown to provide quality postoperative pain control and decrease opioid requirement with minimal side effects following spinal surgery. However, the literature addressing its use in spinal fusions is highly variable in both its effectiveness and complications, such as pseudarthrosis. Recent literature postulates that ketorolac may not affect fusion rates and large randomised controlled trials are needed to demonstrate ketorolac as a safe and effective adjuvant treatment to opioids for postoperative pain control. METHODS AND ANALYSIS: This is a multihospital, prospective, double-blinded, randomised placebo-controlled trial. Data concerning fusion rates, postoperative opioid use, pain scores, length of stay will be recorded with the aim of demonstrating that the use of ketorolac does not decrease thoracolumbar spinal fusion rates while identifying possible adverse events related to short-term minimal effective dose compared with placebo. Additionally, this investigation aims to demonstrate a decrease in postoperative opioid use demonstrated by a decrease in morphine equivalence while showing equivalent postoperative pain control and decrease the average length of stay. ETHICS AND DISSEMINATION: Ethical approval was obtained at all participating hospitals by the institutional review board. The results of this study will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03278691.

Oral dextromethorphan reduces perioperative analgesic administration in children undergoing tympanomastoid surgery.

OBJECTIVE: To determine whether oral dextromethorphan (1 mg/kg) given one hour prior to surgery decreases opioid administration in the perioperative period in children undergoing tympanomastoid surgery. METHODS: This was a prospective randomized double-blinded and placebo-controlled study in which 20 male and 18 female children (age 11.5 +/- 3.5 years) were enrolled. Nineteen children received dextromethorphan (DM), while the other 19 received placebos. Postoperative pain was assessed using a visual analogue scale and a pain score of > or =5 was treated with intravenous morphine sulfate. Patients were discharged home on oral oxycodone. RESULTS: The total doses of fentanyl administered during surgery were higher in the placebo group compared to the DM group (4.1 +/- 2 vs 2.6 +/- 1.4 microg/kg, P = 0.02) and the total doses of intravenous morphine administered in the postoperative period were also higher in the placebo group compared to the DM group (150 +/- 80 vs 73 +/- 56 microg/kg, P = 0.004). The placebo group had a higher pain score at the time of admission to the Day Surgery Unit (DSU) and a higher maximum pain score, compared to the DM group, during their combined stay in the Post-Anesthesia Care Unit and DSU (7.3 +/- 1.5 vs 3.1 +/- 2.6, P = 0.001). CONCLUSIONS: Premedication with DM reduces the need for opioid administration in the perioperative period in children undergoing tympanomastoid surgery. EBM RATING: A.