Clinical trial NCT03280043: Risk of Hematoma After Ketorolac Use in Reduction Mammoplasty.
Official title: Does Ketorolac Increase the Risk of Hematoma After Reduction Mammoplasty? A Case-control Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Reduction
Reduction Mammoplasty
Hematoma
Hemorrhage
Keywords: Breast reduction
Reduction mammoplasty
Hematoma
Hemorrhage
Ketorolac
Toradol
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2017-09-12
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Medical coders will identify all possible cases of hematoma by searching the key words "hemorrhage," "hematoma," and "plastic surgery". Hematomas post reduction mammoplasty will be manually retrieved and reviewed. Control patients will be randomly pulled from the database of uncomplicated reduction mammoplasties.

Brief summary: The investigators hope to answer the question, "does ketorolac increase the risk of hematoma after reduction mammoplasty?" using a case-control study. All patients who developed a hematoma post reduction mammoplasty (cases) at our institution, and match these with women who had an uncomplicated reduction mammoplasty (controls), and then compare frequency of ketorolac exposure between these two groups as the primary outcome. If ketorolac increases the risk of hematoma, one should expect cases to have been exposed to ketorolac more frequently than controls. Based on previously existing literature, the investigators hypothesize that cases and controls will not differ in their ketorolac exposure, that is, ketorolac does not increase the risk of hematoma.

Detailed description: The electronic health record databases of St. Joseph's Healthcare Hamilton and Hamilton Health Sciences will be searched, using the coding system, for all cases of reduction mammoplasty with post--operative hematoma as a complication. Only hematomas which required return to the operating room for evacuation will be included (i.e. those treated with observation or needle aspiration will be excluded).

Cases are defined as patients suffering a hematoma post reduction mammoplasty will be identified through hospital coding, and matched with controls based on the following criteria: age, body mass index (BMI), pre-existing hypertension, and institution. Controls are defined as patients who had uncomplicated reduction mammoplasty, and will be randomly pulled through retrospective chart review within the same databases, in the same time period (±5 years).

All patient data will be de--identified, and all devices containing patient information will remain on hospital grounds, and be encrypted according to our hospital protocols. The following data will be extracted from patient charts: age, date of surgery, body mass index, surgeon, anesthetist, volume of breast tissue removed per breast, comorbidities, platelet count, coagulation profile, ketorolac and opioid use including dose, timing, frequency, duration, and route of administration of both, time to discharge including length of stay if overnight, comorbidities (including smoking status), American Society of Anesthesiology score, and post--operative usage of drains.

Matching of cases and controls will be performed by the primary investigator (JB), and at the time of matching, the only visible patient information will be the de-identified patient identification (ID) and the four matching variables (ketorolac exposure was not visible).

The frequency of ketorolac exposure between cases and controls will then be reviewed, and the odds ratio (OR) of exposure to ketorolac, with 95% confidence intervals will be calculated. A two by two table will be generated from our data. Since the incidence of hematoma formation after reduction mammoplasty is very low, the odds ratio will closely approximate the relative risk. To evaluate the statistical significance of the ORs, a level of significance of 0.05 will be used. Independent samples t-test will be used to compare continuous demographic data, and Chi-square analysis will be used for ordinal or categorical data between cases and controls.

Sample size was calculated using the POWER program, described by Dupont and Plummer in 1990. A sample size of 25 cases matched with 25 controls (total n = 50) was required from the following data:

* p0 = 0.32 (approximate rate of ketorolac exposure amongst breast reduction patients from previous literature from Cawthorn et al.)
* α = 0.05 (chance of type I error)
* P = 0.8 (power)
* m = 1 (matching ratio1:1)
* Ψ = 3.6 (estimated risk ratio of developing hematoma post breast reduction if exposed to ketorolac, Cawthorn et al.)
* Φ = 0.2 (measurable difference)

Eligibility criteria: Inclusion Criteria:

Cases:

- Patients who developed hematoma post-reduction mammoplasty requiring repeat surgery

Controls:

- Uncomplicated bilateral reduction mammoplasty

Exclusion Criteria:

* Hematoma patients treated with observation or needle aspiration
* Concomitant surgeries in addition to the reduction mammoplasty
* Allergy/sensitivity to non-steroidal anti-inflammatory drugs
* Unilateral reduction mammoplasty
* Male reduction mammoplasty
* Documented bleeding disorders

Primary outcomes:
measure: Ketorolac exposure.
timeFrame: Sept 2015 - Aug 2017.
Secondary outcomes:
measure: Year of reduction mammoplasty.
timeFrame: Sept 2015 - Aug 2017.
measure: Age of patients in each group will be calculated.
timeFrame: Sept 2015 - Aug 2017.
measure: Body mass index compared between cases and controls.
timeFrame: Sept 2015 - Aug 2017.
measure: Volume of breast tissue resected during surgery (in grams) for each patient.
timeFrame: Sept 2015 - Aug 2017.
measure: Pre-operative platelet count.
timeFrame: Sept 2015 - Aug 2017.
measure: Smoking status.
timeFrame: Sept 2015 - Aug 2017.
measure: American society of anesthesiologist (ASA) score.
timeFrame: Sept 2015 - Aug 2017.
measure: Specific breast side of hematoma occurrence (left versus right).
timeFrame: Sept 2015 - Aug 2017.
measure: Post-operative opioid consumption.
timeFrame: Sept 2015 - Aug 2017.
measure: Surgeon's description of bleeding encountered during hematoma take-back.
timeFrame: Sept 2015 - Aug 2017.
measure: Ketorolac dose.
timeFrame: Sept 2015 - Aug 2017.
measure: Ketorolac route given.
timeFrame: Sept 2015 - Aug 2017.
measure: Timing of ketorolac dose.
timeFrame: Sept 2015 - Aug 2017.
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
Study officials:
affiliation: McMaster University
name: Achilleas Thoma, MD, MSc, BSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cawthorn TR, Phelan R, Davidson JS, Turner KE. Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty. Can J Anaesth. 2012 May;59(5):466-72. doi: 10.1007/s12630-012-9682-z. Epub 2012 Mar 21.