Materials and methods

Study design and setting

This prospective, single-center, randomized controlled trial was conducted in the Department of Accident and Emergency, Pakistan Ordnance Factories (POF) Hospital, Wah Cantt, Pakistan, over a six-month period from July 14, 2022, to December 31, 2022. The study was designed to compare the analgesic efficacy and short-term safety of IV lidocaine with IV ketorolac in adult patients presenting with suspected renal colic.

Ethical considerations

Ethical approval was obtained from the Institutional Ethical Review Committee of POF Hospital, Wah Cantt, prior to commencement of the study (Institutional Review Board (IRB) No. 4119/4/HOD ER/Hosp). Written informed consent was obtained from all participants before enrolment in accordance with institutional ethical requirements and the principles of the Declaration of Helsinki.

Participants

Adult patients presenting to the ED with clinically suspected renal colic were screened for eligibility. Patients aged between 18 and 65 years presenting with acute unilateral flank pain suggestive of renal colic and a Visual Analogue Scale (VAS) pain score of ≥7 were eligible for inclusion. Patients were excluded if they had a known allergy or hypersensitivity to lidocaine or ketorolac, hemodynamic instability, significant cardiovascular disease (including ischemic heart disease, previous myocardial infarction, atrial fibrillation, advanced heart block, Wolff-Parkinson-White syndrome, prolonged QT interval, or symptomatic bradycardia), chronic liver disease, chronic kidney disease, seizure disorder, inflammatory bowel disease, active gastrointestinal bleeding, hepatitis, altered mental status, pregnancy or breastfeeding, severe uncontrolled hypertension (blood pressure > 180/120 mmHg), or previous enrolment in the study.

Sample size

The sample size was determined prospectively during the study protocol development and IRB application. The calculation was performed using the WHO Sample Size Calculator based on an estimated population proportion of 15% for stone disease, as reported by Rizvi et al. [20], with an absolute precision of 8% and a 95% confidence level (α = 0.05). This yielded a required sample size of 90 participants. Accordingly, 90 patients were enrolled and randomized equally between the two treatment groups (45 participants per group).

Randomization, allocation concealment, and blinding

Eligible participants were enrolled consecutively and randomly allocated in a 1:1 ratio to receive either IV lidocaine or IV ketorolac using the lottery method. Allocation concealment was achieved using sequentially numbered, opaque, sealed envelopes prepared by the principal investigator before patient enrolment. Following written informed consent, the next sequential envelope was opened to determine treatment allocation. This was an open-label study; therefore, neither the participants nor the treating clinicians were blinded to the allocated intervention because of the differences in drug preparation and administration. Outcome assessment was performed according to the predefined study protocol.

Interventions

Participants allocated to the lidocaine group received IV lidocaine at a dose of 1.5 mg/kg diluted in 100 mL of 0.9% normal saline and administered over 15 minutes. This dosing regimen was selected based on the randomized controlled trial by Soleimanpour et al. [9], which demonstrated that IV lidocaine at this dose was effective and well tolerated for the management of acute renal colic. Participants allocated to the ketorolac group received a single 30 mg dose of IV ketorolac administered as a slow IV bolus. All patients were monitored throughout drug administration. Participants with persistent severe pain 30 minutes after treatment received rescue analgesia with IV nalbuphine (0.1 mg/kg) according to departmental protocol and remained under observation for a further 90 minutes to monitor for adverse events.

Outcome measures

The primary outcome was successful pain relief, defined as a reduction of at least three points on the VAS from baseline, assessed 30 minutes after administration of the study medication. Secondary outcomes included the occurrence of adverse drug reactions and the requirement for rescue analgesia during the observation period.

Statistical analysis

Statistical analysis was performed using IBM SPSS Statistics version 23.0 (IBM Corp., Armonk, NY, USA). Continuous variables were summarized as mean ± standard deviation (SD), whereas categorical variables were presented as frequencies and percentages. Baseline demographic characteristics were compared descriptively between the treatment groups.

The primary outcome (successful pain relief) and categorical secondary outcomes (rescue analgesia requirement and adverse events) were compared using the Pearson Chi-squared test. Fisher's exact test was used when expected cell counts were small. Effect estimates are presented as absolute risk difference, relative risk, 95% confidence intervals (CIs), and Phi coefficient as the measure of effect size for Chi-squared analyses.

All statistical tests were two-sided, and a p-value < 0.05 was considered statistically significant. Outcome data were complete for all randomized participants. Therefore, an intention-to-treat analysis was performed, with all randomized participants analyzed in the groups to which they were originally allocated.