Scheduled intravenous ketorolac is safe and reduces narcotic use after robotic-assisted simple prostatectomy.

We sought to examine whether scheduled intravenous (IV) ketorolac decreased post-operative narcotic utilization and changed peri-operative outcomes (including complications) in patients undergoing robotic-assisted simple prostatectomy (RASP). An IRB-approved, retrospective chart review was performed of all patients undergoing RASP at a single institution from November 2017 to July 2019. Patient demographic, peri-operative, and post-operative data, including morphine equivalent use (MEU), were collected. Scheduled ketorolac use was implemented at the surgeon's discretion for up to 5 days post-operatively. The primary outcome was MEU in the post-operative stay. Two hundred seven men underwent RASP during the study period, of which 143 (69%) received scheduled ketorolac. No differences in patient demographics, prostate size, prior opioid utilization, or operative characteristics were identified between groups. Median MEU was significant less (5 vs 15, p < 0.001) in patients receiving scheduled ketorolac. Significantly more patients receiving scheduled ketorolac did not require the use of any narcotic during hospitalization (30% vs 11%, p = 0.005). On multivariable linear regression adjusted for age, BMI, prior opioid use, and length of stay, ketorolac use independently associated with decreased narcotic use (p = 0.003). No significant difference in transfusion rates were identified (3.5% vs. 1.6%, p = 0.44). Scheduled ketorolac is effective in reducing post-operative, in-hospital opioid utilization without increasing morbidity after RASP. Almost a third of patients on scheduled ketorolac did not require any opioids post-operatively.

Local ketorolac infiltration for postoperative pain in open trigger finger surgery: a randomized controlled trial.

BACKGROUND: Multimodal analgesia is crucial for effective postoperative pain management in minor hand surgeries, enhancing patient satisfaction. The use of local wound infiltration with Ketorolac as an adjuvant pain management strategy is proposed for open trigger finger release surgery. This study aims to compare pain scores and functional outcomes between local wound infiltration with Ketorolac and oral non-steroidal anti-inflammatory drugs. METHODS: This study is a double-blind, parallel design, randomized controlled trials. Sixty-nine patients underwent trigger finger surgery between December 2021 and October 2022 were randomized into one of three groups: oral Ibuprofen alone group, local Ketorolac alone group and local Ketorolac with oral Ibuprofen group. The assessment included postoperative numeric rating scale (NRS) pain score, Disabilities of the Arm, Shoulder, and Hand (DASH) score, grip strength, mobility of proximal interphalangeal (PIP) joint. and complications. RESULTS: NRS pain scores during movement of the operated fingers were significantly lower at 6 h in local Ketorolac alone group and local Ketorolac with oral Ibuprofen group compared to oral Ibuprofen alone group. However, there were no significant differences between the groups in postoperative DASH scores, grip strength, mobility of PIP joints, and complications. CONCLUSIONS: Local infiltration of Ketorolac as an adjunct in postoperative pain management has been shown to provide superior analgesia during finger movement within the initial 6 h following trigger finger surgery, in comparison to oral NSAIDs. CLINICAL TRIAL REGISTRATION: Thaiclinicaltrials.org identifier: TCTR20210825002. Registered 25/08/2021. https://www.thaiclinicaltrials.org/show/TCTR20210825002.

Efficacy of a Multimodal Surgical Site Injection for Postoperative Pain Control in Pediatric Patients With Cerebral Palsy Undergoing Hip Reconstruction: A Randomized Controlled Trial.

BACKGROUND: One in 4 children with cerebral palsy (CP) will undergo orthopaedic surgery during their childhood. Despite its ubiquity, postoperative pain control has been poorly studied in this patient population. Moreover, poor pain management has been associated with adverse surgical outcomes. Multimodal analgesic injections have been well studied in the adult population, demonstrating safety and efficacy in reducing postoperative pain and narcotic consumption, but this modality has not been studied in pediatric patients undergoing similarly complex procedures. The objective of this study was to evaluate the efficacy of a multimodal surgical site injection for postoperative pain control following operative management of hip dysplasia in patients with CP. METHODS: After obtaining IRB approval, a multicenter, randomized double-blind placebo control trial was completed. Patients below 18 years old with a diagnosis of CP who were scheduled for varus derotation osteotomy (VDRO) of the proximal femur were randomized to receive a surgical-site injection with either a combination of ropivacaine (3 mg/kg), epinephrine (0.5 mg), and ketorolac (0.5 mg/kg) (experimental group) or normal saline (control). All included patients had identical postoperative care, including immobilization, physical therapy, and standardized, multimodal postoperative pain control. Pain scores and narcotic consumption were recorded at regular intervals and compared between groups utilizing two-tailed t test or a nonparametric Mann-Whitney test for quantitative variables and a Fischer exact test for categorical variables. RESULTS: Thirty-four patients were included, evenly divided between study arms. There were no significant differences in demographic variables, gross motor function classification system (GMFCS), comorbidities, preoperative radiographic parameters, or concomitant surgeries between groups. Patients in the experimental group required significantly lower narcotic medications at all postoperative time points from PACU until hospital discharge compared with controls (0.41 ± 0.42 vs. 1.87 ± 2.05 total morphine mEQ/kg, P =0.01). Similarly, patients in the experimental group were found to have significantly lower pain scores throughout their hospital stays compared with controls (1.0 ± 0.6 vs. 2.4 ± 1.1 mean pain score, P <0.001). There were no significant differences in operative time, OR time, blood transfusion requirements or hospital length of stay between groups. There were no adverse medication reactions or injection site complications in either group. CONCLUSIONS: In patients with CP undergoing hip reconstruction, surgical-site injection with a multimodal analgesic combination improves pain control and reduces narcotic consumption in the early postoperative period with no observed adverse effects. SIGNIFICANCE: Local multimodal analgesic injections should be adopted as part of standard multimodal pain control in this patient population for all osseous surgeries. LEVEL OF EVIDENCE: Level I-therapeutic.

Early administration of ketorolac after cardiac surgery and postoperative complications: Analysis of the MIMIC-IV database.

Inflammation may contribute to postoperative cardiac complications and ketorolac, an anti-inflammatory agent inhibiting cyclooxygenase (COX), shows promise in enhancing cardiac graft patency by suppressing endothelial cell proliferation in animal studies. However, the safety of postoperative ketorolac use remains controversial. This study investigates the association between early ketorolac application and complications following cardiac surgery. Data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database fueled this retrospective cohort study. The primary outcome is a composite of mortality, pulmonary insufficiency, severe acute kidney injury (AKI), hemorrhage or hematoma, infection, cardiogenic shock, and cerebrovascular infarction postcardiac surgery. Propensity score matching (PSM; 1:1 match, caliper 0.2), multivariate logistic regression, interaction stratification analysis, pairwise algorithmic, and overlap weight model analyses were employed. Following inclusion and exclusion criteria, 7143 patients who underwent valvular surgery or coronary artery bypass grafting (CABG) were included. PSM created a balanced cohort of 3270 individuals (1635 in the ketorolac group). The matched cohort exhibited an 8.1% overall rate of postoperative complications, with a lower composite outcome rate in patients receiving ketorolac within 48 h of surgery compared with those without (PSM, OR 0.70 [95% CI, 0.54-0.90]). Consistent associations were observed in total cohort analyses, sensitivity, and subgroup analyses. Early ketorolac use within 48 h post-CABG or valvular procedures in adults is independently associated with a lower incidence of composite postoperative adverse events. Prospective trials are warranted to assess causality.

Intravenous Acetaminophen Versus Ketorolac for Prehospital Analgesia: A Retrospective Data Review.

BACKGROUND: Parenteral ketorolac and intravenous (IV) acetaminophen have been used for prehospital analgesia, yet limited data exist on their comparative effectiveness. STUDY OBJECTIVES: To evaluate the comparative effectiveness of IV acetaminophen and parenteral ketorolac for analgesia in the prehospital setting. METHODS: We conducted a retrospective cross-sectional evaluation of patients receiving IV acetaminophen or parenteral ketorolac for pain management in a large suburban EMS system between 1/1/2019 and 11/30/2021. The primary outcome was change in first to last pain score. Subgroup analysis was performed on patients with traumatic pain. We used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to estimate the treatment effect of acetaminophen versus ketorolac among all patients and the subgroup of those with traumatic pain. RESULTS: Of 2178 patients included, 856 (39.3%) received IV acetaminophen and 1322 (60.7%) received parenteral ketorolac. The unadjusted mean change in pain score was -1.9 (SD 2.4) for acetaminophen group and -2.4 (SD 2.4) for ketorolac. In the propensity score analyses, there was no statistically significant difference in pain score change for the acetaminophen group versus ketorolac among all patients (mean difference, IPTW: 0.11, 95% confidence interval [CI] -0.16, 0.37; PSM: 0.15, 95% CI -0.13, 0.43) and among those with traumatic pain (unadjusted: 0.18, 95% CI -0.35, 0.72; IPTW: 0.23, 95% CI -0.25, 0.71; PSM: -0.03, 95% CI -0.61, 0.54). CONCLUSIONS: We found no statistically significant difference in mean pain reduction of IV acetaminophen and parenteral ketorolac for management of acute pain.

Intravenous ibuprofen versus ketorolac for perioperative pain control in open abdominal hysterectomy: a randomized controlled trial.

BACKGROUND: We aimed to compare the analgesic effects of intravenous ibuprofen to ketorolac after open abdominal hysterectomy. METHODS: This randomized double-blinded controlled trial included adult women scheduled for elective open abdominal hysterectomy. Participants were randomized to receive either 30 mg ketorolac (n = 50) or 800 mg ibuprofen (n = 50) preoperatively, then every 8 h postoperatively for 24 h. All participants received paracetamol 1 gm/6 h. Rescue analgesic was given if the visual analogue scale (VAS) for pain assessment was > 3. The primary outcome was the mean postoperative dynamic VAS during the first 24 h. Secondary outcomes were static VAS, intraoperative fentanyl consumption, postoperative morphine consumption, time to independent movement, and patient's satisfaction. RESULTS: Forty-six patients in the ibuprofen group and fifty patients in the ketorolac group were analyzed. The 24-h dynamic and static VAS were similar in the two groups. The median (quartiles) dynamic VAS was 1.1 (0.9, 1.9) in the ibuprofen group versus 1.0 (0.7, 1.3) in the ketorolac group, P-value = 0.116; and the median (quartiles) static VAS was 0.9 (0.6, 1.3) in the ibuprofen group versus 0.7 (0.4, 1.1) in the ketorolac group, P-value = 0.113. The intra- and postoperative analgesic requirements were also similar in the two groups. However, patient satisfaction was slightly higher in the ketorolac group than that in the ibuprofen group (median [quartiles]: 6 [5, 7] versus 5 [4, 7], respectively), P-value: 0.009. CONCLUSION: The two drugs, intravenous ibuprofen and ketorolac produced similar analgesic profile in patients undergoing open abdominal hysterectomy receiving multimodal analgesic regimen. NCT05610384, Date of registration: 09/11/2022 CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05610384. https://clinicaltrials.gov/ct2/show/NCT05610384.

Opioid-Sparing Nonsteroid Anti-inflammatory Drugs Protocol in Patients Undergoing Intramedullary Nailing of Tibial Shaft Fractures: A Randomized Control Trial.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics commonly used in fracture management. Although previously associated with delayed fracture healing, multiple studies have demonstrated their safety, with minimal risks of fracture healing. Given the current opioid crisis in the United States, alternate pain control modalities are essential to reduce opioid consumption. This study aims to determine whether the combination of oral acetaminophen and intravenous ketorolac is a viable alternative to opioid-based pain management in closed tibial shaft fractures treated with intramedullary nailing. METHODS: We conducted a randomized controlled trial evaluating postoperative pain control and opioid consumption in patients with closed tibial shaft fractures who underwent intramedullary nailing. Patients were randomized into an NSAID-based pain control group (52 patients) and an opioid-based pain control group (44 patients). Visual analog scale (VAS) scores and morphine milligram equivalents (MMEs) were evaluated at 12-hour postoperative intervals during the first 48 hours after surgery. Nonunion and delayed healing rates were recorded for both groups. RESULTS: A statistically significant decrease in MMEs was noted at every measured interval (12, 24, 36, and 48 hours) in the NSAID group compared with the opioid group ( P -value 0.001, 0.001, 0.040, 0.024, respectively). No significant change in visual analog scale scores was observed at 12, 36, and 48 hours between both groups ( P -value 0.215, 0.12, and 0.083, respectively). A significant decrease in VAS scores was observed at the 24-hour interval in the NSAID group compared with the opioid group ( P -value 0.041). No significant differences in union rates were observed between groups ( P -value 0.820). DISCUSSION: Using an NSAID-based postoperative pain protocol led to a decrease in opioid consumption without affecting pain scores or union rates. Owing to the minimal risk of short-term NSAID use, their role in the perioperative management of tibia shaft fractures is justified, especially when they reduce opioid consumption markedly. LEVEL OF EVIDENCE: Therapeutic Level I.

Systemic absorption and gastrointestinal adverse effects from topical ketorolac and diclofenac ophthalmic solutions in healthy dogs.

OBJECTIVE: To investigate systemic absorption and gastrointestinal (GI) adverse effects of topical ketorolac 0.5% and diclofenac 0.1% ophthalmic solutions. ANIMALS: 11 healthy purpose-bred Beagles. METHODS: Dogs were randomly assigned to receive either ketorolac (n = 6) or diclofenac (5), 1 drop in both eyes 4 times daily for 28 days. Upper GI endoscopy was performed on days 0 and 29 with mucosal lesion scores (0 to 7) assigned to each region evaluated. Plasma samples were collected on days 14, 21, and 28 for measurement of diclofenac and ketorolac using high-performance liquid chromatography-mass spectrometry. RESULTS: GI erosions and/or ulcers developed in all ketorolac-treated dogs and 1 of 5 diclofenac-treated dogs. Post-treatment mucosal lesion score for the antrum was higher in the ketorolac group than in the diclofenac group (P = .006) but not significantly different for any other region. Post-treatment antral mucosal lesion scores were significantly related to plasma ketorolac concentrations (P < .001). Ketorolac and diclofenac were detected in the plasma at all time points (median ketorolac day 14, 191 ng/mL; day 21, 173.5 ng/mL; and day 28, 179.5 ng/mL; and median diclofenac day 14, 21.1 ng/mL; day 21, 20.6 ng/mL; day 28, 27.5 ng/mL). Vomiting and decreased appetite events were observed uncommonly and were not significantly different between treatment groups. CLINICAL RELEVANCE: GI ulceration and erosion developed after ophthalmic administration of ketorolac and diclofenac, with higher plasma concentrations and more severe GI lesions associated with ketorolac. Clients should be alerted to this potential risk with ophthalmic use and informed to watch for systemic clinical signs that would warrant veterinary reevaluation.

Does Scheduled Low-Dose Short-Term NSAID (Ketorolac) Modulate Cytokine Levels After Orthopaedic Polytrauma? A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVES: To determine whether scheduled low-dose, short-term ketorolac modulates cytokine concentrations in orthopaedic polytrauma patients. DESIGN: Secondary analysis of a double-blinded, randomized controlled trial. SETTING: Single Level I trauma center from August 2018 to October 2022. PATIENT SELECTION CRITERIA: Orthopaedic polytrauma patients between 18 and 75 years with a New Injury Severity Score greater than 9 were enrolled. Participants were randomized to receive 15 mg of intravenous ketorolac every 6 hours for up to 5 inpatient days or 2 mL of intravenous saline similarly. OUTCOME MEASURES AND COMPARISONS: Daily concentrations of prostaglandin E2 and interleukin (IL)-1a, IL-1b, IL-6, and IL-10. Clinical outcomes included hospital and intensive care unit length of stay, pulmonary complications, and acute kidney injury. RESULTS: Seventy orthopaedic polytrauma patients were enrolled, with 35 participants randomized to the ketorolac group and 35 to the placebo group. The overall IL-10 trend over time was significantly different in the ketorolac group ( P = 0.043). IL-6 was 65.8% higher at enrollment compared to day 3 ( P < 0.001) when aggregated over both groups. There was no significant treatment effect for prostaglandin E2, IL-1a, or IL-1b ( P > 0.05). There were no significant differences in clinical outcomes between groups ( P > 0.05). CONCLUSIONS: Scheduled low-dose, short-term, intravenous ketorolac was associated with significantly different mean trends in IL-10 concentration in orthopaedic polytrauma patients with no significant differences in prostaglandin E2, IL-1a, IL-1b, or IL-6 levels between groups. The treatment did not have an impact on clinical outcomes of hospital or intensive care unit length of stay, pulmonary complications, or acute kidney injury. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

COMPARISON OF THE EFFECTS OF EIGHT DIFFERENT TOPICAL NONSTEROIDAL ANTI-INFLAMMATORY DRUGS ON REDUCING INTRAVITREAL INJECTION-INDUCED PAIN.

PURPOSE: To compare topical nonsteroidal anti-inflammatory drug (NSAID) efficacy on intravitreal injection-induced pain reduction and determine the most efficient topical NSAID. METHODS: This randomized-controlled study included 662 eyes of 662 patients. Based on the types of NSAID administered before intravitreal injection, eight subgroups were formed. In the control group, a sterile saline solution was applied instead of NSAIDs. The visual analog scale was used to assess pain scores after intravitreal injection. The visual analog scale scores were noted immediately and 6 hours following injection (sixth hour). RESULTS: Nepafenac 0.3%, nepafenac 0.1%, and bromfenac 0.09% had the lowest scores, immediately after and after 6 hours, with no significant differences. Diclofenac and ketorolac had higher visual analog scale scores than the first trio but lower scores than the control group. Flurbiprofen, pranoprofen, and indomethacin did not significantly affect immediate pain; however, at the sixth hour, the visual analog scale scores were significantly reduced. CONCLUSION: Nepafenac 0.3%, nepafenac 0.1%, and bromfenac 0.09% were the most effective NSAIDs for pain reduction. Although some NSAIDs did not have a significant effect on immediate pain, they all provided significant benefits at the sixth hour.

Effect of patient-controlled analgesia on development of postoperative nausea and vomiting in patients undergoing microvascular decompression: a prospective randomized controlled trial.

OBJECTIVE: Postoperative nausea and vomiting (PONV) occurs frequently after microvascular decompression (MVD). Fentanyl, an opioid, is strongly related to the development of PONV, and ketorolac, a nonsteroidal anti-inflammatory drug, has been approved for postoperative pain management. However, how ketorolac-based patient-controlled analgesia (PCA) causes PONV or how its efficacy differs from that of fentanyl-based PCA after MVD is unclear. In this study, the authors compared ketorolac-based with fentanyl-based PCA in terms of the incidence and severity of PONV and analgesia after MVD. METHODS: This prospective, double-blind, single-center, randomized controlled trial conducted from December 2021 to February 2023 included patients with MVD who were randomly allocated to the ketorolac- or fentanyl-based PCA group postoperatively. The incidence (primary outcome) and severity of PONV and rescue antiemetic requirements were determined during the first 48 hours postoperatively. Additionally, postoperative pain scores, rescue analgesic requirement, PCA usage, and satisfaction scores were assessed during the study period. PONV severity and postoperative pain scores were assessed using an 11-point numeric rating scale (0 = none, 10 = extremely). Satisfaction scores for PONV and pain were determined (0 = very dissatisfied, 10 = very satisfied). Categorical variables were analyzed using the chi-square or Fisher's exact test. Continuous variables were analyzed using the Student t-test or Mann-Whitney U-test based on normal distribution. RESULTS: Of 185 screened patients, 91 were excluded based on predetermined exclusion criteria; 87 patients (43 in the ketorolac group and 44 in the fentanyl group) were analyzed and showed no significant differences in demographic data between groups. PONV incidence (48.8% vs 79.5%, p = 0.003) and severity (p = 0.004) were lower in the ketorolac-based PCA group than in the fentanyl-based PCA group. In the ketorolac group, there was a significant reduction in rescue antiemetic requirements compared with the fentanyl group (p = 0.049). The number of discontinuations was lower in the ketorolac-based PCA group than in the fentanyl-based PCA group (p = 0.001), whereas no significant differences in postoperative pain were found between the two groups. CONCLUSIONS: In patients with MVD, ketorolac-based PCA resulted in a decrease in PONV incidence and severity compared with fentanyl-based PCA, with analgesic effects similar to those of fentanyl-based PCA. This study provides clinical evidence that ketorolac-based PCA may be a valid alternative to fentanyl-based PCA in postoperative care.

Neurotrophic Keratopathy after wide retinal endolaser and postoperative Ketorolac eye drops: A case series.

PURPOSE: We report a series of 5 cases, happened in a period of 5 months, who developed neurotrophic keratopathy (NK) following pars plana vitrectomy (PPV) and retinal endolaser for rhegmatogenous retinal detachment (RRD). In our several decennary experience of surgical center predominantly based on vitreoretinal surgery, we had rare cases of postoperative NK. These recent cases of post-surgical NK happened contextually to our change of postoperative non-steroidal anti-inflammatory drugs (NSAIDs) drops, based on Ketorolac Tromethamine 0.5% eye drops. CASES PRESENTATION: Five patients with a mean age of 61 ± 7.3 years were treated with one or more PPV with intraoperative peripheral endolaser for RRD. Nobody had previous herpetic keratitis, systemic disease like diabetes mellitus or other predisposing factors for NK. In the postoperative period, all patients received Ketorolac Tromethamine 0.5% eye drops for a mean period of 54 ± 25 days. During follow-up visits they developed NK and they were successfully treated with suspension of Ketorolac eye drops, application of therapeutic contact lens or amniotic membrane patch and topical lubricant therapy. CONCLUSIONS: Postoperative Ketorolac eye drops, in patients who underwent PPV with endolaser, may reduce the corneal sensitivity, predispose to epithelial disruption and NK development. Studies are needed to explore the effect of NSAIDs on corneal sensitivity reduction in patient who will undergo PPV and extensive endolaser.

Ketorolac in neonates and infants following congenital heart surgery: a retrospective review.

INTRODUCTION: Pain management is essential in the immediate post-surgical period. We sought to describe the ketorolac dose regimen in neonates and infants following cardiac surgery. Secondary outcomes included renal dysfunction, bleeding, and pain management. METHODS: We performed a single-centre retrospective cohort study of neonates and infants (aged < 12 months) who received ketorolac following cardiac surgery, from November 2020 through November 2021 (inclusive). Ketorolac was administered at 0.5 mg/kg every 6 hours. Safety was defined by absence of a clinically significant decline in renal function (i.e., increase in serum creatinine [SCr] by ≥ 0.3 mg/dL from baseline within 48 hours and/or urine output ≤ 0.5 mL/kg/hour for 6 hours) and absence of clinically significant bleeding defined as major by International Society on Thrombosis and Hemostasis paediatric criteria or Severe/Fatal Bleeding Events by Nellis et al. Efficacy measures included pain scores and opioid utilisation. RESULTS: Fifty-five patients met eligibility criteria. The median (range) dose and duration of ketorolac administration was 0.5 mg/kg/dose for 48 (6-90) hours. Among all patients, there was not a statistically significant difference observed in median SCr within 48 hours of baseline (p > .9). There were no major or severe bleeding events. The median (range) opioid requirements (morphine intravenous equivalents per kg per day) at 48 hours post-ketorolac initiation was 0.1 (0-0.8) mg/kg/day. CONCLUSIONS: If validated prospectively, these findings suggest that a ketorolac regimen 0.5 mg/kg/dose every 6 hours in neonates and infants post-cardiac surgery may be safe with regard to renal function and bleeding risk, and effective regarding opioid-sparing capacity.

Comparison of Preemptive Effect of Intravenous Ketorolac Versus Nalbuphine on Postoperative Shivering and Pain in Patients Undergoing Surgery Under Spinal Anesthesia: A Prospective, Randomized, Double-Blind Study.

BACKGROUND: Postoperative pain and postanesthesia shivering are the two common problems in patients undergoing surgery under spinal anesthesia (SA). The present study aimed to compare the preemptive prescription of the single dose of intravenous (IV) ketorolac versus nalbuphine on postoperative shivering and pain in patients undergoing surgery under SA. METHODS: Present study was a prospective, randomized double-blind study, conducted on patients of either gender, with American Society of Anesthesiologists physical status class I or II, aged 21-60 years, posted for elective lower abdominal surgeries under SA. Patients were randomized by computer-generated random numbers into two groups of 50 patients each: group N (received 0.2 mg/kg nalbuphine IV) and group K (received 0.5 mg/kg ketorolac IV). RESULTS: The incidence of postoperative shivering was 22 % and 36 % in groups N and K respectively and the difference was statistically significant. The first request for analgesia (minutes) was later in group N (295.17 ± 54.62) than in group K (223.80 ± 15.34) and the difference was statistically significant. Increased total analgesic consumption was noted more in group K (131.34 ± 43.27) than in group N (79.23 ± 21.34), and the difference was statistically significant (P < 0.0001). The incidence of side effects was comparable among both groups. CONCLUSION: Preemptive nalbuphine had less incidence of postoperative shivering, delayed first request for analgesia, and less total analgesic consumption than ketorolac in patients undergoing surgery under SA.

The Effect of Perianal Tramadol Infiltration on Postoperative Pain Following Hemorrhoidectomy.

INTRODUCTION: The present study was attempted to evaluate the effect of perianal infiltration of tramadol on postoperative pain in patients undergoing hemorrhoidectomy. METHOD: This double-blind clinical trial study was carried out on 90 patients with grade 3 and 4 hemorrhoids undergoing hemorrhoidectomy. Patients were randomly assigned into 3 groups of control or bupivacaine or tramadol. Before the surgery, perianal infiltration of .25% bupivacaine or tramadol or normal saline was prescribed to each group, respectively. Data on pain severity (based on the visual analog scale (VAS), the duration of surgery, sedation score, pain at the first defecation, first request time for additional analgesia, nausea and vomiting, and analgesic intakes) were evaluated and analyzed. RESULTS: Duration of surgery was almost similar in all 3 groups (P = .974). The results showed a significant difference in pain score between 3 groups (P ≤.05) at all times after the surgery. In addition, the means of sedation scores (P = .03), pain score at the first defecation (P = .001), the time to first analgesic request (P = .001), and ketorolac administration times (P = .01) were significantly different between 3 groups. Finally, no complication was reported regarding postoperative nausea and vomiting. CONCLUSION: Given the notable efficacy of tramadol in reducing pain after hemorrhoidectomy and its minor side effects, this medication is suggested as an effective topical anesthetic to decrease pain after hemorrhoidectomy.

Randomised trial of IV metoclopramide vs IV ketorolac in treatment of acute primary headaches.

INTRODUCTION: Headache is one of the most common neurological conditions among emergency department visits (ED), although the best therapy has not been identified yet. Therefore, in the current study, we aimed to compare the pain-relieving effect of metoclopramide and ketorolac in acute primary headaches patients. METHODS: This double-blind, randomised clinical trial was conducted at Golestan Hospital, Ahvaz, Iran. This research involved all adult patients with acute primary (migraine or tension-type) headaches presented to the ED. Pain intensity was assessed with 0 to 10 verbal Numeric Rating Scales (NRS). The subjects were randomised into 10 mg intravenous (IV) metoclopramide or 30 mg IV ketorolac groups. Pain score and drug adverse reactions were compared between the two groups at baseline, 15, 30, and 60 min after baseline. RESULTS: 108 patients completed this trial and were equally divided into two groups (mean age of 34 ± 8.54 years; 57.4% female). Before treatment, the mean pain score was 6.9 and 6.8 in metoclopramide and ketorolac groups, respectively (p > 0.05). Metoclopramide failed to provide more improvement in pain score at 30 min (p = 0.55) and 60 min (p = 0.15) from baseline. There were no serious adverse events in this study. Only five patients required rescue medication which four of them were in ketorolac group. CONCLUSION: We were unable to reject the null hypothesis that there would be no difference in pain outcomes between metoclopramide and ketorolac.

Comparing two doses of intramuscular ketorolac for treatment of acute musculoskeletal pain in a military emergency department.

STUDY OBJECTIVE: The goal of the study was to assess a low-dose versus a high-dose of intramuscular (IM) ketorolac for non-inferiority in adults with acute MSK pain in an emergency department (ED). METHODS: This was a single-blinded, randomized controlled, non-inferiority trial of adults presenting to an ED with a chief complaint of acute MSK pain. Patients were randomized to either a 15 mg or a 60 mg IM ketorolac dose. The primary outcome was the mean difference of change in pain from baseline to 60-min between the two groups as reported on a 100-mm (mm) visual analog scale (VAS). Secondary outcomes included the mean difference of change in VAS scores at 30-min and the incidence of reported adverse effects associated with the administration of ketorolac. RESULTS: One hundred ten patients were randomized with 55 in each group. The mean difference in pain between groups at 60-min (0.2 mm [95% CI -8.5-8.7]; p = .98) and 30 min (-1.7 mm [95% CI -8.5-5.1; p = .63) was less than the predetermined non-inferiority margin of 13 mm. There were no major adverse effects reported. Minor adverse effects were more frequent in the 60 mg group (n = 9; 16.4% vs. n = 1; 1.8%; p = .016) with burning at the injection site being the most commonly reported. CONCLUSIONS: A 15 mg dose of IM ketorolac was found to be non-inferior to a 60 mg dose for acute MSK pain in adults presenting to the ED. Discontinuing the practice of ordering 60 mg doses of IM ketorolac in place of a lower dose for acute MSK pain should be considered.

The Analgesic Benefits of Ketorolac to Local Anesthetic Wound Infiltration Is Statistically Significant But Clinically Unimportant: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Even though ketorolac-infiltration is said to provide superior postoperative analgesic benefits in different surgical procedures, its safety and efficacy remain to be validated because of the lack of high-quality evidence. We aimed to summarize the efficacy and safety of ketorolac-infiltration based on published randomized-controlled trials (RCTs). Approach: This work followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, assessing the methodological quality of systematic reviews and the Cochrane Collaboration recommendations. We searched for RCTs evaluating the efficacy of ketorolac-infiltration in adults in the PubMed, Web of Science, Embase, Cochrane Library, Chinese databases, and Google Scholar. The two co-primary outcomes of this meta-analysis were rescue analgesic consumption in the 24-h postoperative period and rest pain scores. Results: Twelve trials (761 patients) were analyzed. Ketorolac-infiltration provided a clinically unimportant benefit in morphine consumption (mean difference, -2.81 mg; 95% confidence interval [CI], -5.11 to -0.50; p = 0.02; moderate-quality evidence). Low-to-moderate quality evidence supported a brief (2-6 h), clinically subtle, but statistically consistent effect of surgical site ketorolac-infiltration in reducing wound pain at rest. High-quality evidence supported shorter hospital stays for surgical patients receiving local ketorolac-infiltration when compared to controls (mean difference, -0.12 days; 95% CI, -0.17 to -0.08; p < 0.00001). Further, ketorolac-infiltration does not improve any opioid-related side effects. Innovation: Ketorolac-infiltration provides statistically significant but clinically unimportant benefits for improving postoperative wound pain. Conclusion: Overall, despite the fact that current moderate-to-high quality of evidence does not support routine using of ketorolac as an adjuvant to local anesthetic for wound infiltration, these findings underscore the importance of optimizing agents and sustained delivery parameters in postoperative local anesthetic practice. Clinical Trials.gov ID: CRD42021229095.

Single-dose intravenous ketorolac for acute postoperative pain in adults.

BACKGROUND: Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous ketorolac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 20 April 2020. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: Randomized double-blind trials that compared a single postoperative dose of intravenous ketorolac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period. Our secondary outcomes were time to and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related or opioid-related AEs. For subgroup analysis, we planned to analyze different doses of parenteral ketorolac separately and to analyze results based on the type of surgery performed. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 12 studies, involving 1905 participants undergoing various surgeries (pelvic/abdominal, dental, and orthopedic), with 17 to 83 participants receiving intravenous ketorolac in each study. Mean study population ages ranged from 22.5 years to 67.4 years. Most studies administered a dose of ketorolac of 30 mg; one study assessed 15 mg, and another administered 60 mg. Most studies had an unclear risk of bias for some domains, particularly allocation concealment and blinding, and a high risk of bias due to small sample size. The overall certainty of evidence for each outcome ranged from very low to moderate. Reasons for downgrading certainty included serious study limitations, inconsistency and imprecision. Ketorolac versus placebo Very low-certainty evidence from eight studies (658 participants) suggests that ketorolac results in a large increase in the number of participants achieving at least 50% pain relief over four hours compared to placebo, but the evidence is very uncertain (risk ratio (RR) 2.81, 95% confidence interval (CI) 1.80 to 4.37). The number needed to treat for one additional participant to benefit (NNTB) was 2.4 (95% CI 1.8 to 3.7). Low-certainty evidence from 10 studies (914 participants) demonstrates that ketorolac may result in a large increase in the number of participants achieving at least 50% pain relief over six hours compared to placebo (RR 3.26, 95% CI 1.93 to 5.51). The NNTB was 2.5 (95% CI 1.9 to 3.7). Among secondary outcomes, for time to rescue medication, moderate-certainty evidence comparing intravenous ketorolac versus placebo demonstrated a mean median of 271 minutes for ketorolac versus 104 minutes for placebo (6 studies, 633 participants). For the number of participants using rescue medication, very low-certainty evidence from five studies (417 participants) compared ketorolac with placebo. The RR was 0.60 (95% CI 0.36 to 1.00), that is, it did not demonstrate a difference between groups. Ketorolac probably results in a slight increase in total adverse event rates compared with placebo (74% versus 65%; 8 studies, 810 participants; RR 1.09, 95% CI 1.00 to 1.19; number needed to treat for an additional harmful event (NNTH) 16.7, 95% CI 8.3 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from eight studies (703 participants) did not demonstrate a difference in rates between ketorolac and placebo (RR 0.62, 95% CI 0.13 to 3.03). Ketorolac versus NSAIDs  Ketorolac was compared to parecoxib in four studies and diclofenac in two studies. For our primary outcome, over both four and six hours there was no evidence of a difference between intravenous ketorolac and another NSAID (low-certainty and moderate-certainty evidence, respectively). Over four hours, four studies (337 participants) produced an RR of 1.04 (95% CI 0.89 to 1.21) and over six hours, six studies (603 participants) produced an RR of 1.06 (95% CI 0.95 to 1.19). For time to rescue medication, low-certainty evidence from four studies (427 participants) suggested that participants receiving ketorolac waited an extra 35 minutes (mean median 331 minutes versus 296 minutes). For the number of participants using rescue medication, very low-certainty evidence from three studies (260 participants) compared ketorolac with another NSAID. The RR was 0.90 (95% CI 0.58 to 1.40), that is, there may be little or no difference between groups.   Ketorolac probably results in a slight increase in total adverse event rates compared with another NSAID (76% versus 68%, 5 studies, 516 participants; RR 1.11, 95% CI 1.00 to 1.23; NNTH 12.5, 95% CI 6.7 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from five studies (530 participants) did not demonstrate a difference in rates between ketorolac and another NSAID (RR 3.18, 95% CI 0.13 to 76.99). Only one of the five studies reported a single serious AE. AUTHORS' CONCLUSIONS: The amount and certainty of evidence for the use of intravenous ketorolac as a treatment for postoperative pain varies across efficacy and safety outcomes and amongst comparators, from very low to moderate. The available evidence indicates that postoperative intravenous ketorolac administration may offer substantial pain relief for most patients, but further research may impact this estimate. Adverse events appear to occur at a slightly higher rate in comparison to placebo and to other NSAIDs. Insufficient information is available to assess whether intravenous ketorolac has a different rate of gastrointestinal or surgical-site bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was a lack of studies in cardiovascular surgeries and in elderly populations who may be at increased risk for adverse events.