Evaluating Pain Outcomes of Ketorolac Administration in Children Undergoing Circumcision

Pain, Postoperative Clinical Trial

Official title:

A Pilot Study Evaluating Pain Outcomes of Ketorolac Administration in Children Undergoing Circumcision

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02973958
• Other study ID #: REB16-1876
• Status: Completed
• Phase: Phase 1
• Start date: February 1, 2017
• Est. completion date: June 28, 2018

Study information

• Verified date: June 2018
• Source: Alberta Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Circumcision is the most common surgical procedure performed by Pediatric Urologists. Ketorolac has been shown to have an efficacy similar to morphine in multi-modal analgesic regimens without the commonly associated adverse effects. This study aims to see if giving ketorolac during the operation will result in better pain control. We hypothesize that ketorolac will result in pain control similar to morphine with a lower incidence of side effects such as nausea and vomiting.

Description:

Prospective, randomized, single-blinded study will be conducted from January 2017- December 2017. A total of two groups will present. Patients with planned circumcision surgery will initially be identified by the surgeon. Patients will then be randomized into treatment (perioperative ketorolac) or control groups (no ketorolac).

A computer-generated randomized block design program will be used to allocate patients to either the treatment (ketorolac) or control (no ketorolac) group. All children will receive a 15 mg/kg oral dose of acetaminophen prior to surgery unless contraindicated. General anesthesia will be induced with sevoflurane via facemask. After establishing venous access, a laryngeal mask will be inserted, and anesthesia maintained with 1 minimum alveolar anesthetic concentration (MAC) of sevoflurane in oxygen/air 50/50 mixture. The DPNB nerve block will be performed by a pediatric urologist using a 23 GA needle inserted below the Buck fascia. Once the needle tip is positioned appropriately, and after a negative aspiration test, 0.2mL/kg (maximum 10mL) of 0.25% bupivacaine is injected in small aliquots, with intermittent aspiration throughout. In all patients, skin incision is performed at least 5 min after placement of the nerve block. At the beginning of the circumcision procedure once the patient is asleep, patients in the treatment group will receive a 0.5 mg/kg intravenous dose of ketorolac. Patients will be advised to take ibuprofen and acetaminophen post-operatively as needed.

Patients' demographic information, time needed to perform the block, time of block onset and duration of surgery will be recorded. The mean arterial pressure, heart rate and oxygen saturation, expired sevoflurane end tidal concentration and MAC will be systematically collected pre-operatively, intra-operatively and post-operatively in the recovery room. The primary outcome of post-operative pain will be evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The usage of these two scales will be performed as deemed appropriate by the research assistant. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. The FLACC score is a well-established postoperative pain measure using 5 items scored between 0-2, which has been validated in patients from 6 months up to 7 years of age (9.10). The Wong-Baker FACES pain scale that has been used post-operatively that allows patients to select a face that relates to their current feeling of pain (11). These faces are rated on a scale of 10. A FLACC or Wong-Baker FACES score will be recorded every 15 minutes for the first hour and every 30 minutes for up to 2 hours following discharge from the PACU into the day stay surgical unit. If the score is found to be >3 (moderate pain 4-6, severe pain 7-10), the patient will receive an intravenous morphine dose of 0.05mg/kg. An additional dose may be given 15 minutes following the initial dose of morphine if analgesia is inadequate (score >4). Postoperatively, the child will be monitored every 15 minutes during the first hour and every 30 minutes for the next 2 hours until discharge home. Discharge will be based on normal institutional criteria including level of awareness, hemodynamic stability and absence of pain, bleeding, nausea and vomiting. Prior to discharge, parents will be provided with any additional analgesics required at home and will be contacted 24 hours following their surgery to complete the parents' postoperative pain measure (PPPM) (12). The PPPM is a well-established post-operative pain assessment tool with high inter-rater reliability and construct validity, which has been designed specifically for use by parents in the post-operative care of their children. The measure includes 15 items scored between 0 and 1. The questionnaire will be completed over the telephone at a time corresponding to 24 hours post-surgical closure. Amount of pain and analgesia consumption data will then be collected by contacting the parents 24 hours post procedure.

As there are no previous studies analyzing the post-operative analgesic effects of ketorolac in pediatric patients undergoing circumcision this study will act as a pilot study. A total sample size of 30 patients will be used based on previous recommendations for pilot studies and accounting for 20% attrition. There will be 15 patients in both the ketorolac and no ketorolac groups.

The primary outcome variable will be the averaged FLACC or Wong-Baker FACES pain score during hospital stay (average of all pain scores taken every 15 minutes for the first hour and every 30 minutes thereafter until discharge). Normality (using the Shapiro-Wilk test) will be assessed for the primary outcome variable, as this will guide our choice of parametric or non-parametric statistical analysis (e.g. unpaired t-test or Mann-Whitney U test). We will also complete statistical analysis to assess differences in patient characteristics (e.g. weight, height, age) and pre-op pain scores between the two groups. As such, Shapiro-Wilk tests will be required to assess normality and guide test selection. With respect to within factor comparisons, repeated measures ANOVA analysis with post-hoc Bonferroni correction for multiple comparisons will be used to assess differences in pain scores within patients receiving the same treatment (e.g. to access whether significant differences in pain scores occurred in patients receiving ketorolac across the time points of pain score recording). An analogous within factor repeated measures ANOVA will thus be used to assess differences in pain scores at collected time points in patients that did not receive ketorolac. Significant differences in nominal data between the two groups will be assessed using Fisher's exact test or Pearson's chi-square test for association.

An independent group of experts not directly involved in the conduct of this study will be assembled by open invitation to participate. This board will periodically review and evaluate the accumulated study data for participant safety, study conduct and progress, and, when appropriate, efficacy. Furthermore, they will make recommendations concerning the continuation, modification, or termination of the trial. The board will meet before the start of the trial to discuss the protocol, definition of a quorum, and guidelines for monitoring the study. Thereafter, the board will convene as often as necessary, but at least once annually.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 28, 2018
• Est. primary completion date: June 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• All children admitted for circumcision at the Alberta Children's Hospital

Exclusion Criteria:

• History of allergic reactions to local anesthetics or ketorolac

• Bleeding diatheses

• Coagulopathy

• Infection at the injection site.

Related Conditions & MeSH terms

• Balanitis
• Pain, Postoperative
• Paraphimosis
• Phimosis

Intervention

Drug:
• Bupivacaine
See active comparator description
• Sevoflurane
See active comparator description
• Acetaminophen
See active comparator description
• Ibuprofen
See active comparator description
• Ketorolac
See experimental arm description

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
Alberta Children's Hospital

Country where clinical trial is conducted

Canada, 

References & Publications (12)

Adler R, Ottaway MS, Gould S. Circumcision: we have heard from the experts; now let's hear from the parents. Pediatrics. 2001 Feb;107(2):E20. — View Citation

Allan CY, Jacqueline PA, Shubhda JH. Caudal epidural block versus other methods of postoperative pain relief for circumcision in boys. Cochrane Database Syst Rev. 2003;(2):CD003005. Review. Update in: Cochrane Database Syst Rev. 2008;(4):CD003005. — View Citation

American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012 Feb;116(2):248-73. doi: 10.1097/ALN.0b013e31823c1030. — View Citation

Brady-Fryer B, Wiebe N, Lander JA. Pain relief for neonatal circumcision. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004217. Review. — View Citation

Chambers CT, Finley GA, McGrath PJ, Walsh TM. The parents' postoperative pain measure: replication and extension to 2-6-year-old children. Pain. 2003 Oct;105(3):437-43. — View Citation

Chambers CT, Hardial J, Craig KD, Court C, Montgomery C. Faces scales for the measurement of postoperative pain intensity in children following minor surgery. Clin J Pain. 2005 May-Jun;21(3):277-85. — View Citation

De Oliveira GS Jr, Agarwal D, Benzon HT. Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. Anesth Analg. 2012 Feb;114(2):424-33. doi: 10.1213/ANE.0b013e3182334d68. Epub 2011 Sep 29. Review. — View Citation

Gunter JB, Varughese AM, Harrington JF, Wittkugel EP, Patankar SS, Matar MM, Lowe EE, Myer CM 3rd, Willging JP. Recovery and complications after tonsillectomy in children: a comparison of ketorolac and morphine. Anesth Analg. 1995 Dec;81(6):1136-41. — View Citation

Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics 4.4: 287-291, 2005

Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997 May-Jun;23(3):293-7. — View Citation

Sutters KA, Levine JD, Dibble S, Savedra M, Miaskowski C. Analgesic efficacy and safety of single-dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy. Pain. 1995 Apr;61(1):145-53. — View Citation

von Baeyer CL, Spagrud LJ. Systematic review of observational (behavioral) measures of pain for children and adolescents aged 3 to 18 years. Pain. 2007 Jan;127(1-2):140-50. Epub 2006 Sep 25. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	Immediately following the procedure
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	15 minutes post-operatively
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	30 minutes post-operatively
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	45 minutes post-operatively
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	60 minutes post-operatively
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	90 minutes post-operatively
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	120 minutes post-operatively
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	150 minutes post-operatively
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	180 minutes post-operatively
Primary	Post-operative pain	Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique through telephone follow-up with parental input. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain	24 hours post-operatively
Secondary	Total ibuprofen consumption	Evaluated and compiled through anesthesia notes, post-operative nursing care notes and parental telephone follow-up	24 hours post-operatively
Secondary	Total acetaminophen consumption	Evaluated and compiled through anesthesia notes, post-operative nursing care notes and parental telephone follow-up	24 hours post-operatively
Secondary	Incidence of bleeding requiring medical attention	Bleeding events will be compiled through post-anesthetic care unit, surgical short stay unit, clinic and emergency department notes	Up to 2 weeks

External Links

•   Ketorolac compound summary. Pubchem Substance Website. National Center for Biotechnology, US National Library of Medicine