Ketorolac-based analgesia improves outcomes for living kidney donors

BACKGROUND: To reduce the morbidity of living kidney donors we introduced ketorolac-based analgesia for patients undergoing open donor nephrectomy in August 1999. There are no prior reports on the use of ketorolac for patients undergoing donor nephrectomy. METHODS: We conducted a retrospective review of all 198 consecutive patients who underwent open living donor nephrectomy between January 1998 and July 2000 at our institution. We compared patients who underwent surgery before and after introduction of ketorolac-based analgesia. RESULTS: The introduction of ketorolac-based analgesia resulted in a reduction in length of postoperative stay from 3.7+/-0.1 to 3.1+/-0.1 days (P<0.001). Patients who underwent surgery after ketorolac introduction required 58% less narcotics (P<0.001), recalled having less postoperative pain, and stopped taking pain medications sooner than patients before routine ketorolac use. Moreover, these patients drank 38% more liquids on the first postoperative day (P<0.001) and were able to resume a regular diet sooner than patients who were not managed with ketorolac. Patients who received ketorolac had a slightly lower creatinine clearance on the second postoperative day relative to patients who did not (66 vs. 72% of preoperative calculated creatinine clearance, P=0.05). However at a minimum of 3 months postoperatively, creatinine clearance did not differ between the two groups (70 vs. 73%, P=0.92). There were no differences in the rates of complications between the two groups. CONCLUSIONS: The use of ketorolac to control postoperative pain for patients undergoing open donor nephrectomy reduced morbidity and was not associated with any effect on long-term renal function or increased risk of complications. This is the first study to demonstrate the safety of using ketorolac at the time of donor nephrectomy.     

Prospective double-blind study of effect of ketorolac administration after laparoscopic urologic surgery

BACKGROUND AND PURPOSE: To decrease postoperative dependence on narcotics for analgesia, we have evaluated ketorolac as an adjunct to perioperative pain control in patients undergoing laparoscopic urologic surgery. PATIENTS AND METHODS: Sixty-five patients (34 male, 31 female) were randomized to receive either ketorolac tromethamine (15-30 mg IV q 6 h) or placebo prior to laparoscopic surgery. Patient-controlled analgesia in the form of morphine sulfate was provided. Operative factors such as the type of surgery, operative time, and estimated blood loss were recorded. Postoperative factors such as analog pain score (range 0-10), narcotic usage, and length of stay were evaluated. RESULTS: Fifty-five patients completed the study. The average pain score was 2.2 and 4.5 for the ketorolac and placebo groups, respectively (P < 0.005). The mean amounts of total morphine used were 39.2 mg (ketorolac) and 62.5 mg (placebo) (P = 0.077). The length of stay was not significantly different in the ketorolac (2.5 days) and placebo (2.6 days) groups (P = 0.74). Operative times (P = 0.21) and estimated blood loss (P = 0.60) were not significantly different in the two groups. Ketorolac did not adversely affect renal function; serum creatinine changes were not significantly different from those in the patients receiving placebo (P = 0.50). Laparoscopic pyeloplasty necessitated more narcotic analgesia than did other laparoscopic procedures (P = 0.05). CONCLUSION: Ketorolac decreases the subjective perception of pain after laparoscopic urologic surgery. It is suggested that ketorolac administration decreases the amount of narcotic usage as well. Time to resumption of oral intake and length of hospital stay were not influenced by use of ketorolac.     

Safety of ketorolac in neonates and infants after cardiac surgery

BACKGROUND: Ketorolac is an injectable nonsteroidal anti-inflammatory drug that is often used as a transitional short-term analgesic to treat moderate pain and to decrease opioid use. There is a paucity of literature documenting the safety of using ketorolac in neonates and infants after cardiac surgery. METHODS: A retrospective chart review was performed which identified all patients <6 months of age who received ketorolac after cardiac surgery. Patients' demographic, surgical, and dosing data were collected. A Student's t-test was used to identify significant differences in renal and hematologic laboratory values at baseline and at 48 h of treatment. RESULTS: A total of 53 children <6 months of age received at least one dose of ketorolac after cardiac surgery. Eleven of 53 children (21%) were <1 month of age. The blood urea nitrogen/serum creatinine (SCr) levels increased from baseline at 48 h of therapy in all infants, but stayed within normal limits. The largest increase in SCr level from baseline on any day of ketorolac therapy was 26 micromol x l(-1) (0.3 mg x dl(-1)) which occurred in two neonates. Four patients (three infants and one neonate) had minor episodes of bleeding while being treated with ketorolac. There were no clinically significant changes in hemoglobin, hematocrit or platelet count. None of these episodes caused hemodynamic instability nor required transfusion of blood products. CONCLUSIONS: Ketorolac was used safely in neonates and infants who have had cardiac surgery at our institution. Ketorolac was not associated with any adverse hematologic or renal effects. Prospective investigation is warranted to further assess the safety and effectiveness of ketorolac in this patient population.     

Antagonism of antinociception produced by intrathecal clonidine by ketorolac in the rat: the role of the opioid system

The management of severe pain may require "balanced analgesia," involving the use of analgesics with different modes of action. Clonidine, an alpha(2)-adrenoreceptor agonist produces analgesia by itself as well as when given with morphine and local anesthetics. Ketorolac is indicated for the management of moderately severe acute pain and causes analgesia equivalent to morphine. This study was designed to investigate whether the addition of ketorolac promotes antinociception produced by intrathecal administration of clonidine in male Sprague-Dawley rats. Intrathecal injection of clonidine (1-30 microg) induced a dose-dependent increase in antinociception as measured by the tail flick (TF) and hot plate tests. Ketorolac alone (150-600 microg) increased the antinociception by 50%-60% only in the TF test. Ketorolac (10 microg) decreased clonidine (10 microg)-induced antinociception from 69.1% +/- 7.8% to 23.5% +/- 1. 6% (P < 0.05) in the TF test and 35.7% +/- 4.7% to 4.5% +/- 0.1% (P < 0.05) maximum possible effect in the hot plate test. Ketorolac also antagonized the effect of 30 microg of clonidine. The opioid receptor antagonist naloxone antagonized the antinociceptive effect of clonidine and ketorolac, indicating the involvement of the opioid system in the antinociception produced by clonidine or ketorolac. However, neither clonidine nor ketorolac (10(-8) to 10(-3) M) inhibited the binding of specific ligands to mu-, delta-, and kappa-opioid receptors, indicating a lack of direct interaction of clonidine and ketorolac with opioid receptors. These results suggest that intrathecal injection of ketorolac antagonizes the antinociception produced by clonidine.     

Drug choices for intravenous and spinal analgesia

Opioids remain at the center of most postoperative pain control therapies. The choice between full agonist opioids should be determined by the time for a given dose to produce its maximum effect (i.e., latency to peak effect), and the duration of action. There is little to choose between different opioids administered by patient-controlled analgesia. Parenterally-administered NSAIDs (e.g., ketorolac) contribute significantly to analgesia and reduce opioid requirements. Morphine may be the opioid of choice for epidural administration. The combination of epidural opioids and local anesthetics provides synergistic analgesia and appears to provide superior analgesia with activity. Several nonopioid receptor agonists are under investigation as neuraxial analgesics.     

Acute perioperative pain in neonates: An evidence-based review of neurophysiology and management

Current literature lacks systematic data on acute perioperative pain management in neonates and mainly focuses only on procedural pain management. In the current review, the neurophysiological basis of neonatal pain perception and the role of different analgesic drugs and techniques in perioperative pain management in neonates are systematically reviewed. Intravenous opioids such as morphine or fentanyl as either intermittent bolus or continuous infusion remain the most common modality for the treatment of perioperative pain. Paracetamol has a promising role in decreasing opioid requirement. However, routine use of ketorolac or other nonsteroidal anti-inflammatory drugs is not usually recommended. Epidural analgesia is safe in experienced hands and provides several benefits over systemic opioids such as early extubation and early return of bowel function.     

Intra-operative ketorolac 15 mg versus 30 mg for analgesia following cesarean delivery: a retrospective study

BackgroundKetorolac is a nonsteroidal anti-inflammatory drug used as part of multimodal analgesia in women undergoing cesarean delivery. The lowest effective dose of ketorolac that best optimizes analgesia without increasing side effects is unclear. We performed this retrospective study to compare the analgesic efficacy of 15 mg or 30 mg ketorolac administered intra-operatively to our obstetric population.MethodsWe included patients who underwent cesarean delivery under neuraxial anesthesia and received 15 mg or 30 mg of ketorolac intra-operatively. Our multimodal analgesic regimen is standardized and includes 150 µg spinal or 3 mg epidural morphine, 975 mg rectal acetaminophen, and 15–30 mg intravenous ketorolac within 15 min of surgery completion. The primary outcome was opioid use in the first 6 h after surgery. Secondary outcomes were opioid use at 24 and 48 h, opioid dose, pain scores, breastfeeding, postoperative serum creatinine and need for rescue anti-emetics.ResultsOne-thousand-three-hundred and forty-nine patients were analyzed (15 mg ketorolac n=999; 30 mg n=350). There was no difference between the two groups in patient demographics or intra-operative characteristics. There was no significant difference between groups for opioid use at 6 h after surgery (50.3% vs 52.0%, odds ratio [95% confidence interval] 1.13 [0.87 to 1.47]). There were also no significant differences between the groups for secondary outcomes.ConclusionsThere was no difference in opioid use between patients receiving either a 15 mg or a 30 mg dose of ketorolac given intra-operatively for postoperative analgesia following cesarean delivery.     

Ketorolac vs tramadol in the treatment of postoperative pain during maxillofacial surgery.

BACKGROUND: This study aims to assess the best postoperative analgesia during maxillofacial surgery by using small doses of ketorolac or tramadol or their association and evaluates the presence of adverse effects due to NSAID or opioid use. METHODS: After their informed consent, 51 patients ASA I and II undergoing major maxillofacial surgery, were randomised in three groups and the following protocol was used: group K received ketorolac (30 mg i.v.) at the time of skin closure and repeated after 8 hrs and 16 hrs from the end of the operation. Group T received tramadol (100 mg i.v.) in the same condition; and group KT received first tramadol (100 mg i.v.) during surgery and then ketorolac (30 mg) was given in the administrations that followed. Meperidine 50 mg was used in case of unsatisfactory analgesia. Pain was evaluated using pain intensity scores 2, 4, 6, 12 and 24 hours from the end of the operation. Data was analysed using Anova and c2 test. RESULTS: The groups were comparable with regard to age, weight, duration of surgery. Very good postoperative analgesia was recorded in three groups. There is no difference statistically between K, T and KT groups in the pain scores measured. Only a low number of patients required opioids administration to achieve adequate analgesia. The patients were considered to have achieved excellent analgesia in 64.8% in T group, in 41.2% of the K group and in 58.8% of the KT group. There were no cases of insufficient analgesia. We did not find a significant difference considering BP, HR, respiratory depression in the post-operative period. Vomiting was registered in 41.2% of this T group vs 11.2% of the K group and in 35.5% of the KT group. CONCLUSIONS: Ketorolac and Tramadol produced comparable, effective and low cost postoperative analgesia during maxillofacial surgery. There are only statistically significant differences considering side effects.     

Prospective randomized trial of ketorolac after congenital heart surgery

OBJECTIVE: Ketorolac is a potent nonsteroidal analgesic agent used to treat postoperative pain. It produces excellent analgesia without the sedating side effects of opioid analgesics. Routine use of ketorolac after cardiac surgery is limited by concerns of bleeding complications. The purpose of this study was to evaluate the risk of bleeding complications of ketorolac for treatment of pain after congenital heart surgery in infants and children. DESIGN: Prospective randomized, controlled trial. SETTING: Pediatric cardiac intensive care unit in tertiary teaching hospital. PARTICIPANTS: Seventy infants and children, median age 10 months (range 2.5-174), who underwent congenital heart surgery requiring cardiopulmonary bypass were randomized in the trial. INTERVENTION: Pain control was performed with ketorolac and opioid analgesics in one arm of the study and opioid analgesics alone in the other arm. OUTCOME MEASURES: The main outcome evaluated was bleeding complications measured by chest-tube drainage and wound and gastrointestinal bleeding. RESULTS: Thirty-five patients were randomized to each treatment arm. In the ketorolac group, the median chest-tube drainage was 13.3 (range 4-22) mL/kg/d, no patient had significant wound bleeding, and 1 (0.03%) patient had gastrointestinal bleeding. In the control group, the median chest-tube drainage was 16.5 (range 3-24) mL/kg/d, 1 (0.03%) patient had wound bleeding, and no patient had gastrointestinal bleeding. CONCLUSION: Ketorolac can be used to treat pain after congenital heart surgery without an increased risk of bleeding complications.     

An evaluation of the analgesic efficacy of intravenous regional anesthesia with lidocaine and ketorolac using a forearm versus upper arm tourniquet

Intravenous regional anesthesia (IVRA) using a forearm tourniquet may be a potentially safer technique compared with using an upper arm tourniquet. Ketorolac is a useful adjuvant to lidocaine for IVRA. In this study, we assessed the analgesic efficacy of administering IVRA lidocaine and ketorolac with either a forearm or upper arm tourniquet for outpatient hand surgery. Upper arm IVRA was established using 40 mL of a solution containing 200 mg of lidocaine and ketorolac 20 mg (0.5 mg/mL). Forearm IVRA was established using 20 mL of a solution containing 100 mg of lidocaine and ketorolac 10 mg (0.5 mg/mL). Onset and duration of sensory block as well as postoperative pain and analgesic use were recorded. The patients who received forearm IVRA had a significantly longer period during which they required no analgesics (701 +/- 133 min) compared with 624 +/- 80 min for the upper arm IVRA ketorolac patients (P = 0.032). Onset of sensory block was similar between the two groups; however, recovery of sensation was significantly longer in the Forearm IVRA (22 +/- 5 min) group compared with the Upper Arm IVRA (13 +/- 3 min) group (P < 0.05). There were no differences in postoperative analgesic use or pain scores between the two groups. We conclude that forearm IVRA with lidocaine and ketorolac provides safe and effective perioperative analgesia for patients undergoing ambulatory hand surgery. This technique results in a longer duration of sensory block and prolonged postoperative analgesia compared with upper arm IVRA while using one-half the doses of both lidocaine and ketorolac. IMPLICATIONS: Forearm tourniquet intravenous regional anesthesia (IVRA) with 50% less lidocaine and ketorolac provides for both a longer duration of sensory block and prolonged postoperative analgesia compared with upper arm IVRA.     

Effect of ketorolac on renal function after donor nephrectomy

Objectives. To evaluate the safety of ketorolac, a nonsteroidal anti-inflammatory drug, that is being used more frequently for postoperative analgesia, we performed a detailed analysis of healthy patients undergoing open donor nephrectomy.Methods. We conducted a retrospective review of 198 consecutive patients who underwent open living donor nephrectomy between January 1998 and July 2000. We compared patients who were and were not given ketorolac. Regression analysis was used to determine whether any significant interactions were present between ketorolac and donor age, sex, weight, estimated surgical blood loss, or operative time in terms of its effect on renal function. Creatinine clearance was calculated by the Gault-Cockcroft equation.Results. Among the 83 patients given ketorolac, the mean amount received was 200 mg (range 30 to 360, median 210). No differences were found in the preoperative creatinine clearance between patients who did (118 ± 29 mL/min) or did not (118 ± 27 mL/min, P = 0.89) receive ketorolac. Patients who received ketorolac had a slightly lower creatinine clearance on the second postoperative day relative to patients who did not receive ketorolac (66% versus 72% of preoperative calculated creatinine clearance, P = 0.05). However, at a minimum of 3 months postoperatively, the creatinine clearance did not differ between the two groups (70% versus 73%, P = 0.92). Among patients who received ketorolac, no significant association was found between the amount received and renal function at any point tested. In the regression analysis, no significant interactions were found between ketorolac and the clinical variables of age, sex, weight, estimated surgical blood loss, or operative time. Moreover, in an analysis of only the patients who received ketorolac, no significant interactions were found between the amount of ketorolac received and the clinical variables of age, sex, weight, estimated surgical blood loss, or operative time.Conclusions. Ketorolac use was not associated with any long-term impairment in renal function when used during the first 2 postoperative days in healthy patients undergoing open donor nephrectomy. Moreover, in the range administered, no subset of patients or maximal ketorolac dose was identified at which ketorolac use was not safe.     

Preemptive analgesic effects of ketorolac in ankle fracture surgery

BACKGROUND: Preemptive analgesia has been difficult to show in human experiments. If ketorolac has preemptive effects, then there may be an advantage to administering it at the beginning of surgery despite the potential for increased blood loss. METHODS: The authors performed a randomized, double-blind, controlled trial of 48 patients scheduled for ankle fracture surgery in a county trauma hospital. Anesthesia management was standardized and included adequate opioid analgesia (5 microg/kg fentanyl and 0.1 mg/kg morphine). Intravenous 30 mg ketorolac was administered to 23 patients before tourniquet inflation and to 25 patients after tourniquet inflation. Visual analog scale pain scores, morphine patient-controlled analgesia consumption, nausea-vomiting, and postoperative bleeding were measured. RESULTS: The 23 patients given ketorolac before tourniquet inflation had no increase in pain postoperatively compared with their preoperative baseline (P = 0.280). The 25 patients who received ketorolac minutes later after tourniquet inflation had significant increases in their postoperative pain compared with their preoperative baseline (P = 0.00116). This effect was short-lived, and by 6 h the pain score in this group was not significantly more than it was preoperatively. Intergroup comparison showed a lower visual analog scale score at 2 (P = 0.0203) and 4 h (P = 0.00549) in the preemptive group and lower nausea scores at hour 6 (P = 0.00704). There was no difference in patient-controlled analgesia consumption between groups. CONCLUSIONS: Intravenous 30 mg ketorolac appears to have preemptive analgesic effects in patients undergoing ankle fracture repair. Ketorolac administered before tourniquet inflation prevents postoperative pain being perceived as more intense than preoperative pain.     

Ketorolac use and risk of bleeding after appendectomy in children with perforated appendicitis

BackgroundKetorolac is an opioid sparing agent commonly used in children. However, ketorolac may be avoided in children with peritonitis owing to a possible increased risk of bleeding.MethodsA retrospective cohort study of healthy children 2–18 years who underwent appendectomy for perforated appendicitis was performed using the Pediatric Health Information System (2009–2019). Multivariable logistic regression was used to evaluate the association between perioperative ketorolac use and postoperative blood transfusions within 30 days of surgery, adjusting for patient and hospital level factors. An interaction between ketorolac and ibuprofen was evaluated to identify synergistic effects.ResultsOverall, 55,603 children with perforated appendicitis underwent appendectomy and 82.3% (N = 45,769) received ketorolac. Of those, 32% (N = 14,864) also received ibuprofen. Receipt of a blood transfusion was infrequent (N = 189, 0.3%). On multivariable logistic regression analysis, perioperative ketorolac administration was associated with decreased odds of a blood transfusion (OR 0.53, 95% CI: 0.35–0.79). However, children receiving ketorolac and ibuprofen were more likely to require a blood transfusion (OR 1.99, 95% CI: 1.42–2.79). In a subset of children receiving ketorolac, each additional day of ketorolac was associated with an increase odds of blood transfusion (OR 1.39, 95% CI: 1.30–1.49).ConclusionPerioperative ketorolac alone is not associated with an increased risk of significant bleeding in children undergoing appendectomy for perforated appendicitis. However, use of both ketorolac and ibuprofen during hospitalization was associated with increased risk of bleeding, although precise timing of administration of these medications was unable to be determined. Extended ketorolac use was also associated with increased risk of bleeding requiring blood transfusion.Level of evidenceLevel III.     

Safety of ketorolac in the pediatric population after ureteroneocystostomy

PURPOSE: Ketorolac has been used to provide effective postoperative analgesia in children and decreases hospitalization for pediatric patients undergoing ureteroneocystostomy. However, it can cause severe side effects, including increased bleeding and renal insufficiency, which can be devastating in a child. Little has been reported on the safety of ketorolac by evaluating creatinine, hematocrit and complications. MATERIALS AND METHODS: An institutional retrospective review was performed during an 18-month period in which 118 patients underwent ureteroneocystostomy. One group containing 50 patients received caudal anesthetic preoperatively and narcotic analgesics postoperatively, while another 68 received caudal anesthetic preoperatively and ketorolac postoperatively. Patient ages, type of procedure, preoperative and postoperative creatinine and hematocrit, and complications were noted in each cohort. RESULTS: Average patient age of the control analgesic and ketorolac groups was 5.3 years (range 1 to 17) and 5.5 (1 to 12), respectively. There was no statistical difference between postoperative creatinine (0.68 and 0.65 mg./dl.) and hematocrit (33% and 34%) between the groups. One patient in each group had increased creatinine postoperatively. Minor complications, for example ileus and bladder spasms, were equivalent in both groups. No patient receiving ketorolac had any allergic or hypersensitivity reaction to the medication, and no major complications were reported. CONCLUSIONS: Ketorolac given after ureteroneocystostomy did not cause a significant decrease in hematocrit, increase in creatinine or overall complications. Because of the safety of ketorolac in our series, and ability to decrease hospital stay and narcotic requirements in children as reported previously, it is used as standard postoperative protocol after ureteroneocystostomy at our institution.     

The effect of ketorolac and sevoflurane anesthesia on renal glomerular and tubular function.

We assessed the renal effects of the combination of ketorolac and sevoflurane anesthesia by using sensitive and specific markers of renal proximal and distal tubular and glomerular function. Thirty women (ASA physical status I and II) undergoing breast surgery received either ketorolac 30 mg IM or saline at premedication, at the end, and 6 h after anesthesia maintained with sevoflurane. Peak levels of serum fluoride at 2 h after the end of anesthesia were 30.1 micromol/L (21.0-50.0 micromol/L) in the Ketorolac group and 33.3 micromol/L (13.0-38.0 micromol/L) in the Control group (mean and range, not significant). Urine alpha1-microglobulin indexed to urine creatinine was increased from 2 h after the start of anesthesia until the first postoperative day in the Ketorolac group (peak level, 0.8 +/- 0.4 mg/mmol; upper limit of normal, 0.7 mg/mmol) but did not change in the Control group. Urine glutathione-S-transferase (GST)-alpha indexed to urine creatinine (GST-alpha/creatinine) and GST-pi/creatinine were increased 2 h after anesthesia and returned to baseline values thereafter in both groups. There were no changes in serum cystatin C and urine kallikrein or urine output per hour between groups. The perioperative administration of ketorolac to healthy, well hydrated patients anesthetized with sevoflurane did not produce renal glomerular or tubular dysfunction. IMPLICATIONS: Ketorolac 90 mg IM, given in divided doses over approximately 10 h to patients anesthetized with sevoflurane with a fresh gas flow rate of 4-6 L/min, did not result in clinically significant changes in renal glomerular or tubular function.     

Perioperative management of the child on long-term opioids

The strategies used to manage children exposed to long-term opioids are extrapolated from adult literature. Opioid consumption during the perioperative period is more than three times that observed in patients not taking chronic opioids. A sparing use of opioids in the perioperative period results in both poor pain management and withdrawal phenomena. The child's pre-existing opioid requirement should be maintained, and acute pain associated with operative procedures should be managed with additional analgesia. This usually comprises short-acting opioids, regional or local anesthesia, and adjuvant therapies. Long-acting opioids, transdermal opioid patches, and implantable pumps can be used to maintain the regular opioid requirement. Intravenous infusion, nurse controlled analgesia, patient-controlled analgesia, or oral formulations are invaluable for supplemental requirements postoperatively. Effective management requires more than simply increasing opioid dose during this time. Collaboration of the child, family, and all teams involved is necessary. While chronic pain or palliative care teams and other staff experienced with the care of children suffering chronic pain may have helpful input, many pediatric hospitals do not have chronic pain teams, and many patients receiving long-term opioids are not palliative. Acute pain services are appropriate to deal with those on long-term opioids in the perioperative setting and do so successfully in many centers. Staff caring for such children in the perioperative period should be aware of the challenges these children face and be educated before surgery about strategies for postoperative management and discharge planning.     

The additive antinociceptive interaction between WIN 55,212-2, a cannabinoid agonist, and ketorolac

Combinations of nonsteroidal antiinflammatory drugs (NSAIDs) and opioids are widespread in the management of pain, allowing better analgesia with reduced side effects. Cannabinoids are promising analgesic drugs that have pharmacological properties similar to those of opioids. However, the beneficial effects of cannabinoids for pain treatment are counterbalanced by their psychotomimetic side effects. We designed the present study to evaluate the antinociceptive interaction between cannabinoids and NSAIDs in mice, using the acetic acid-induced writhing test and tail-flick test. Interactions were analyzed using isobolographic analysis. WIN 55,212-2, a cannabinoid agonist, and the NSAID ketorolac, either alone or in combination, produced dose-dependent antinociception in the writhing test. Isobolographic analysis showed additive interactions between WIN 55,212-2 and ketorolac when they were coadministered systemically. Ketorolac is inactive in the radiant heat tail-flick test in which WIN 55,212-2 was active. Ketorolac did not influence WIN 55,212-2-induced antinociception in the tail-flick test. This study demonstrated an additive antinociceptive interaction between WIN 55,212-2 and ketorolac in an inflammatory visceral pain model. The combination of cannabinoids and NSAIDs may have utility in the pharmacotherapy of pain.     

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

BACKGROUND CONTEXTPostoperative 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.PURPOSEWe 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/SETTINGThis is a prospective, randomized, double-blinded, placebo-controlled trial. We are reporting our interim analysis.PATIENT SAMPLEAdults with degenerative spinal conditions eligible to undergo a one to three-level MIS transforaminal lumbar interbody fusion (TLIF).OUTCOME MEASURESSix-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.METHODSA 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.RESULTSTwo 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.CONCLUSIONSShort-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.     

Use of intravenous ketorolac in the neonate and premature babies

BACKGROUND: Ketorolac is a powerful nonsteroidal anti-inflammatory drug widely used for pain control in children and adults. The aim of this study was to evaluate its safety and analgesic efficacy in the neonate. METHODS: Ketorolac was used in a group of 18 spontaneously breathing neonates presenting with chronic lung disease, for the control of postsurgical pain and pain from invasive procedures. Pain scores (Neonatal Infant Pain Scale) were assessed before and after i.v. administration of 1 mg.kg(-1) of ketorolac. RESULTS: Total pain control was achieved in 94.4% of the neonates. None of the neonates had haematological, renal or hepatic changes prior to treatment, and these complications did not occur after treatment. No neonate had systemic haemorrhage or bleeding from injection and blood withdrawal sites. CONCLUSIONS: Ketorolac could represent an efficacious analgesic alternative to opioids, particularly in neonates. It would avoid the side-effects associated with opioid analgesics, especially respiratory depression.     

Ketorolac or fentanyl to supplement local anesthesia?

Study Objective: To evaluate the usefulness of ketorolac in the treatment of intraoperative pain refractory to the administration of local anesthetic alone.

Design: Intraoperative acute-pain treatment model consisting of awake, nonsedated patients who randomly received either an opioid or a study drug in a double-blind fashion.

Setting: University medical center.

Patients: Eighty patients who underwent breast biopsy, lumpectomy, or central venous catheter placement.

Interventions: Patients received either ketorolac 1 mg/kg intravenously (IV) up to a total dose of 60 mg or fentanyl 3 μg/kg IV up to a total dose of 250 μg to supplement the local anesthetic.

Measurements and Main Results: Verbal pain evaluation and the visual analog scale (VAS) were used for perioperative measurement of pain. Heart rate (HR), blood pressure, and respiratory rate (RR) were recorded before and after analgesic drug injections at 10-minute intervals, both intraoperatively and while the patient was in the postanesthesia care unit (PACU). Speed of recovery was quantified by p-deletion and digit substitution tests on admission to the PACU and at 30-minute intervals until discharge. The frequency of nausea, vomiting, and pruritus were recorded. There were no differences between the groups in perioperative verbal pain evaluation, VAS scores, HR, systolic blood pressure, diastolic blood pressure, or RR. Patients who received ketorolac exhibited a significantly lower frequency of intraoperative and postoperative medication administration intraoperatively, than those who received fentanyl. No additional pain medication was required by patients in the PACU in either group.

Conclusions: Ketorolac is a useful alternative to fentanyl for the treatment of intraoperative pain refractory to the administration of local anesthetic alone during monitored anesthesia care. A decided advantage of ketorolac over fentanyl is the absence of nausea and vomiting in the intraoperative and postoperative periods.