Evaluating Pain Outcomes of Ketorolac Administration in Children Undergoing Circumcision

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pain, Postoperative, Phimosis, Paraphimosis, Balanitis

Intervention / Treatment
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* Drug: Bupivacaine
* Drug: Sevoflurane
* Drug: Acetaminophen
* Drug: Ibuprofen
* Drug: Ketorolac


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No ketorolac<br>15 mg/kg oral dose of acetaminophen is administered prior to surgery. 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 is done 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. Patients will be advised to take ibuprofen and acetaminophen post-operatively as needed. | Drug: Bupivacaine<br>* See active comparator description<br>* Other names: Marcaine;Drug: Sevoflurane<br>* See active comparator description<br>* Other names: Sojourn;Drug: Acetaminophen<br>* See active comparator description<br>* Other names: Tylenol;Drug: Ibuprofen<br>* See active comparator description<br>* Other names: Advil;|
| Experimental: Peri-operative ketorolac<br>Exactly same as the no ketorolac group except at the beginning of the circumcision, once the patient is asleep, patients in the perioperative ketorolac group will also receive a 0.5 mg/kg intravenous dose of ketorolac. | Drug: Bupivacaine<br>* See active comparator description<br>* Other names: Marcaine;Drug: Sevoflurane<br>* See active comparator description<br>* Other names: Sojourn;Drug: Acetaminophen<br>* See active comparator description<br>* Other names: Tylenol;Drug: Ibuprofen<br>* See active comparator description<br>* Other names: Advil;Drug: Ketorolac<br>* See experimental arm description<br>* Other names: Toradol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total ibuprofen consumption | Evaluated and compiled through anesthesia notes, post-operative nursing care notes and parental telephone follow-up | 24 hours post-operatively | 
| Total acetaminophen consumption | Evaluated and compiled through anesthesia notes, post-operative nursing care notes and parental telephone follow-up | 24 hours post-operatively | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Penis, Pain, Ketorolac, Circumcision