Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) are first-line analgesics for emergency department (ED) patients with renal colic. Lower doses of intravenous (IV) ketorolac may provide similar pain relief to standard dosing in patients with acute pain. Patients with renal colic may be at increased risk of acute kidney injury; exposing them to lower doses of NSAIDs may put them at lower risk while providing equally effective analgesia. We conducted a pilot study to determine the feasibility of a randomized trial comparing the effectiveness and safety of low with standard ketorolac dosing in ED patients with suspected renal colic. The primary objective was to demonstrate the ability to achieve an enrolment target of 2 patients per week. Methods: We enrolled a convenience sample of adults presenting to an academic urban ED with unilateral flank pain suspected to be renal colic. We randomized patients to 10 mg (low dose, intervention) or 30 mg (standard dose, control). Participants, treating physicians and nurses, and researchers were blinded to treatment allocation. Our main feasibility outcome was the recruitment rate. Secondary outcomes were changes in pain scores (0-10) at 30 and 120 minutes post-ketorolac administration, vital signs, adverse events and ED length of stay. Results: We approached 82 patients, of whom 47 (57.3%) were eligible. Of these, 36 consented to participating and 30 were randomized. The proportion of screened patients who were enrolled was 36.6% (30/82). We completed enrolment over a 21-week period, with an average recruitment rate of 1.5 patients/week (range 0-4). The average baseline pain score for all participants was 6.9 (SD = 2.1). At 30 minutes post-ketorolac administration, the low dose group had a mean pain reduction of 2.0 points compared to a pain reduction of 1.7 in standard dose group (difference = 0.3, 90% CI: -0.7 to 1.4). Conclusion: These preliminary results support the possibility that low dose ketorolac may be efficacious in this patient population. We did not meet our target recruitment of 2 patients per week as this was primarily due to restricted recruitment hours. To successfully conduct a larger trial, we would need to expand both recruitment hours and the number of sites.

Background: Ketorolac has long been used to manage pain in the Emergency Department and has the advantage of being the only parenteral NSAID formulation. Despite multiple studies demonstrating an analgesic ceiling dose of 10mg for intravenous ketorolac, higher doses (30-60mg) are commonly ordered. Use of optimal doses of ketorolac (10mg) has the advantage of lower side effects and cost. Aim Statement: The aim of this project was to increase the usage of the optimal dose parenteral ketorolac (10mg) without increasing the use of additional, concomitant or rescue opioids (balancing measures). Measures & Design: This pre-/post-intervention comparison study (May 1, 2016 to April 30, 2018) included all patients ≥18 years of age that received parenteral ketorolac at one of 4 EDs in the Calgary zone. All data was captured via administrative data records. Stakeholders (ED leadership, analgesia committee, nursing and pharmacy) provided feedback and support for the project. Our multi-modal intervention included modifying all ED computerized order sets such that the default parenteral ketorolac dose was 10mg (post-intervention) from 30mg (pre-intervention), education (dissemination of evidence to support the changes to clinicians) and our pharmacy securing 10mg vials of ketorolac. At their discretion, physicians’ were still able to order other doses of ketorolac. Evaluation/Results: During the 2 year study period, 19290 patient records were identified where parenteral ketorolac was administered during the ED visit. Baseline characteristics were similar between the pre/post periods. Prior to the change in default dosing, 10.5% of orders were for ketorolac 10mg compared to 87% in the post-intervention period (p < 0.000). Statistical process charts support the above results and demonstrate that the changes have been sustained. There were no differences in patients receiving ketorolac as the only analgesic between the pre/post periods (42% vs 42%, p = 0.396), nor where there significant changes in concomitant opioid usage (46% vs 46%, p = 0.817), or rescue analgesia (11% vs 12%, p = 0.097). Discussion/Impact: In this large cohort, our multi-modal intervention, resulted in a significant increase in optimal ketorolac parenteral dosing without a significant change in additional opioid use. The results support the utility of computerized order set changes as the cornerstone of an effective and rapid knowledge translation strategy to align physician practice with best evidence.

We aimed to identify the risk factors for acute kidney injury in infants who have received ketorolac after a cardiac surgical procedure by identifying patients with a ≥50% increase in serum creatinine from baseline and matching them by age with three controls that had <50% increase in serum creatinine. Significant differences in primary surgical procedure, baseline serum creatinine, and concomitant aspirin use were noted. We conclude that the concomitant use of aspirin with ketorolac is associated with increased renal morbidity in young post-cardiac surgical infants.

Although nonopiate analgesics may be particularly useful in the immediate postoperative period after major surgery, their use has been associated with haemodynamic adverse effects during postoperative pain treatment and in critically ill patients in intensive care. The effect of a single intravenous dose of metamizol (dipyrone) 2g, ketorolac 30mg and propacetamol 1g on haemodynamic variables and pain control in the immediate postoperative period after heart surgery is compared. Seventy-two patients undergoing elective coronary and/or heart valve surgery, were included in a cohort study of 1-years duration (1998). After weaning from mechanical ventilation and extubation, haemodynamic variables and a 4-point verbal rating pain scale were asseseed at base-line and 60 min after the administration of a single doses of metamizol, ketorolac or propacetamol. The Student's t-test for paired samples was used to compare changes produced by the study medications. A significant, but small, decrease in radial artery blood pressure was observed in all treatment groups which had little clinical relevance; no vasodilator effects were observed and ventricular function showed only minor changes: propacetamol decreased cardiac index by 10% and a 15% decrease in right ventricular work was also observed. Metamizol and ketorolac produced a 10% decrease in the left ventricular work index. Pain scores showed a statistically significant decrease in all treatment groups. The analgesic effects of metamizol, ketorolac and propacetamol were not associated with a clinically significant impairment in haemodynamic function when administered to haemodynamically stable patients.

One hundred and thirty-seven patients were studied to assess whether the timing of a dose of ketorolac affected cumulative morphine requirements during the first 12 post-operative hours. Pain, sedation and nausea scores, respiratory rate and degree of operative blood loss were also recorded. Thirty-six patients (group A) were given placebo injections pre- and intra-operatively. Thirty-one patients (group B) received placebo pre-operatively and ketorolac 30 mg intra-operatively. Thirty-six patients (group C) received ketorolac 10 mg pre-operatively and ketorolac 20 mg intra-operatively and thirty-four patients (group D) were given ketorolac 30 mg pre-operatively and placebo intra-operatively. Post-operative analgesia was with intravenous (i.v.) morphine administered using a patient controlled analgesia (PCA) device. Analysis of variance revealed a significant difference in morphine consumption at 1, 2, 4, 8 and 12 h post-operatively (P < 0.05) between group A (no ketorolac) and groups B, C and D (ketorolac). However, there were no significant differences between groups B, C and D during the study period. Thus, the timing of ketorolac administration made no difference to overall morphine consumption. Pain, nausea, sedation and respiratory rate scores were similar in all four groups. There was a significantly greater blood loss in patients receiving ketorolac (groups B, C and D) compared with those receiving placebo alone (group A).

Two cases of bradycardia following the intra-operative use of ketorolac given intravenously (i.v.) to children are reported. We examine why this may not have been previously reported and make recommendations regarding its use.

Sixty patients presenting for in-patient gynaecological laparoscopic surgery were randomly allocated to receive either diclofenac 75 mg (n = 20), ketorolac 30 mg (n = 20) or piroxicam 20 mg (n = 20) as an intramuscular (i.m.) injection immediately after induction of anaesthesia. Post-operative Visual Analogue Scores at rest, over the first 24 h after surgery, using a 10 cm scale, ranged from 3.2–0.5 in the diclofenac group, 2.7–0.85 in the ketorolac group and 2.8–0.5 in the piroxicam group. The scores did not differ significantly between the three groups (P > 0.05). Mean time (SD) to first analgesia was 27 (94) min in the piroxicam group, 16 (30) min in the diclofenac group and 62 (120) min in the piroxicam group. Six out of 20 patients in the diclofenac group required further analgesia compared with nine out of 20 in the other two drug groups, this was not significant. There were no reports of increased bleeding, bronchoconstriction, bleeding from the upper gastrointestinal tract, renal impairment or pain from the intramuscular (i.m.) injection site in any of the groups. The administration of a non-steroidal anti-inflammatory drug to patients presenting for laparoscopic surgery reduces post-operative pain and analgesic requirements, and piroxicam 20 mg provides a suitable alternative to 75 mg diclofenac and 20 mg ketorolac.