High vs Low Dose Dexamethasone on Complications in the Immediate Postoperative Phase After Mastectomy

Study Overview
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Brief Summary
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The aim of this study is to investigate the effect of a single preoperative high-dose steroid injection on complications in the immediate postoperative phase after breast cancer surgery, with removal of the breast (mastectomy). Primary outcome is the proportion patients who require transfer to the post anaesthesia care unit (PACU) and the proportion that can be transferred directly to the ward. Secondary outcomes are organospecific complications in the postanesthesia phase, pain and nausea the first 5 days, seroma and wound infection the first 14 days and readmissions the first 30 days after surgery. The investigators hypothesize that the frequency of transfer to the PACU and organospecific complications will be lower among patients receiving high dose dexamethasone. The investigators hypothesize, that there will be no difference in wound infections, seroma or readmissions.

Detailed Description
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Post-surgery, patients are traditionally observed and treated in post-anesthesia care units (PACU) until they are discharged to the ward (or directly home) assessed by standardized international discharge criteria. The research project Why in PACU? (Rigshospitalet, Denmark), has since the beginning of 2016 systematically collected and analyzed procedure-related complications in the recovery phase. The complications include pain, nausea/vomiting, circulatory and respiratory problems, orthostatic intolerance and cognitive disorders. Common to all the above-mentioned post-operative problems are the possible links to the inflammatory response caused by the surgical trauma. Glucocorticoids can in this context be central for the reduction of acute postoperative organ dysfunctions, caused by the anti-inflammatory effect. In a number of different surgical procedures, single dose, pre-operative glucocorticoids have been shown to reduce post-operative nausea and vomiting (PONV), acute pain and need of opioids as well as accelerate the convalescence. Meta-analyses also showed that single-dose administration of glucocorticoids (methylprednisolone and dexamethasone) for surgical patients is safe as opposed to long-term treatment. Based on positive results in other procedure-specific studies, all mastectomy patients at Rigshospitalet, have received pre-operative high-dose steroids, in the form of 24 mg dexamethasone injection since mid-2015. This has resulted in a decrease in the proportion of patients who need observation in PACU from 30 % to 10 %. The reduction is primarily due to less pain, less sedation, and lower opioid administration. Whether this is also partly due to a systemic effect (Hawthorn effect) as a result of increased focus on the area cannot be excluded. Prior to creating clinical recommendations and standards, it is required that the results be tested in a randomized, controlled, clinical trial. The study is not placebo-controlled since the positive effects of dexamethasone 8 mg on PONV have been shown in numerous trials, and is already being administered to all patients at the clinic. It would therefore not be ethically correct to withdraw from this practise.

Official Title
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Effect of High vs Low Dose Intravenous Dexamethasone on Complications in the Immediate Postoperative Phase After Mastectomy- a Randomized, Double-blind, Controlled Trial

Conditions
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Steroid, Dexamethasone, Glucocorticoids, Mastectomy, Breast Cancer, Pain, Postoperative, Nausea and Vomiting, Postoperative, Systemic Inflammatory Response Syndrome, Postoperative Complications

Intervention / Treatment
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* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: planned unilateral mastectomy with or without axillary dissection or sentinel node in the study period informed signed consent Exclusion Criteria: Chronic/ongoing use of glucocorticoids (except inhalation therapy) ongoing use of immunosuppressive therapy insulin dependent diabetes pregnancy/breastfeeding allergies toward study medication, or medication in a standard treatment contralateral surgery (lumpectomy/mastectomy) at time of mastectomy surgery cannot be performed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexamethasone 8 mg<br>Dexamethasone 8 mg pre-operative | Drug: Dexamethasone<br>* pre-operative intravenous administration<br>|
| Active Comparator: Dexamethasone 24 mg<br>Dexamethasone 24 mg pre-operative | Drug: Dexamethasone<br>* pre-operative intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfer to Post-anesthesia Care Unit (PACU) | Number of patients meeting criteria for transfer to PACU post-surgery | Within 1 hour post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Discharge Score,(Modified Aldrete Discharge Score), Operating Room | Danish Society of Anesthesiology and Intensive Care Medicine (DASAIM) discharge score.Construct: The score consists of six modalities (subscores): Sedation,Oxygen saturation,blood pressure,heart rate,pain (at rest)and nausea.Each modality has a score between 0 and 3,and patients are considered dischargeable to the ward when the score sum of all criteria (total score) is 4 or less and no single score is above 1. All values (subscores) are considered best at 0 and worst at 3. Sedation: 0 fully awake, 1, sleeping aroused by verbal stimuli, 2 sleeping aroused by physical stimuli, 3 sleeping cannot be aroused. Oxygen saturation (%):0 ≥94, 1 90-93, 2 85-89, 3 <85. Blood pressure, systolic (mmHg): 0 100-220, 1 90-99. 2 80-89 or >220, 3<80. Heart rate; pr. min: 0 50-100, 1 101-120, 2 40-49 or 121-130, 3 <40 or >130. Pain (at rest) (Numeric rating scale 0-10): 0 0, 1 0-2, 2 3-6, 3 ≥ 7 Nausea (patient evaluation and nurse observation): 0 none, 1 light, 2 moderate, 3 severe or vomiting. | At transfer from operating room, within 1 hour post-surgery | 
| Discharge Score, Arrival at PACU | DASAIM score (Danish Society of Anesthesiology and Intensive Care Medicine). The score consists of six modalities: Sedation, Oxygen saturation, blood pressure, heart rate, pain (at rest) and nausea. Each modality has a score between 0 and 3, and patients are considered dischargeable to the ward when the score sum of all criteria is four or less and no single score is above one. Sedation: 0 fully awake, 1, sleeping aroused by verbal stimuli, 2 sleeping, aroused by physical stimuli, 3 sleeping, cannot be aroused. Oxygen saturation (%): 0 ≥ 94, 1 90-93, 2 85-89, 3 <85. Blood pressure, systolic (mmHg): 0 100-220, 1 90-99. 2 80-89 or >220, 3<80. Heart rate; pr. min: 0 50-100, 1 101-120, 2 40-49 or 121-130, 3 <40 or >130. Pain (at rest) (Numeric rating scale 0-10): 0 0, 1 0-2, 2 3-6, 3 ≥ 7 Nausea (patient evaluation and nurse observation): 0 none, 1 light, 2 moderate, 3 severe or vomiting. | within 3 hours | 
| Discharge Score, Arrival at Ward | DASAIM score (Danish Society of Anesthesiology and Intensive Care Medicine). The score consists of six modalities: Sedation, Oxygen saturation, blood pressure, heart rate, pain (at rest) and nausea. Each modality has a score between 0 and 3, and patients are considered dischargeable to the ward when the score sum of all criteria is four or less and no single score is above one. Sedation: 0 fully awake, 1, sleeping aroused by verbal stimuli, 2 sleeping, aroused by physical stimuli, 3 sleeping, cannot be aroused. Oxygen saturation (%): 0 ≥ 94, 1 90-93, 2 85-89, 3 <85. Blood pressure, systolic (mmHg): 0 100-220, 1 90-99. 2 80-89 or >220, 3<80. Heart rate; pr. min: 0 50-100, 1 101-120, 2 40-49 or 121-130, 3 <40 or >130. Pain (at rest) (Numeric rating scale 0-10): 0 0, 1 0-2, 2 3-6, 3 ≥ 7 Nausea (patient evaluation and nurse observation): 0 none, 1 light, 2 moderate, 3 severe or vomiting. | within 3 hours | 
| Number of Participants With Complication | complications requiring treatment until discharge | 24 hours | 
| Total Length of Stay in PACU | Length of stay in the post-anesthesia care unit (PACU), measured as hours and minutes, from start of procedure, to discharge from PACU | 12 hours | 
| Total Length of Stay in Hospital | Length of stay in hospital, measured from start of procedure to discharge from hospital to home | 24-48 hours | 
| Secondary Transfer | Secondary transfer to PACU from ward, or to intensive care unit from PACU | 24-48 hours | 
| Pain, Numeric Rating Scale | Self-reported pain (worst and average (average through that day), days 0-4) on a numeric rating scale (NRS) 0-10. 0 is no pain, 10 is worst pain imaginable.. Questionnaire. | days 0-4 | 
| Post Operative Nausea and Vomiting (PONV). | Self-reported nausea, questionnaire, day 0-4. Number of participants reporting nausea and/or vomiting | days 0-4 | 
| Quality of Sleep | Self-reported quality of sleep (days 0-4). Questionnaire. Dichotomized to Good sleep or sleep problems, numbers reported are number of patients with sleep problems | days 0-4 | 
| Mental Status | Self-reported feelings of restlessness, sadness and fatigue (days 0-4). Questionnaire (anwers possible: yes or no. Numbers are patients answering yes) | days 0-4 | 
| Number of Participants With Seroma, Requiring Treatment | Seroma, requiring treatment the first 14 days. | 14 days | 
| Readmission | Any readmission, days 0-30 | 30 days |