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

Phase 4

Completed

• Conditions: Postoperative Complications; Dexamethasone; Pain, Postoperative; Mastectomy; Glucocorticoids; Nausea and Vomiting, Postoperative; Systemic Inflammatory Response Syndrome; Breast Cancer; Steroid
• Interventions: Drug: Dexamethasone

• Registration Number: NCT03125941
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-03-27
• Study First Submitted: 2017-03-28
• Study First Submitted QC: 2017-04-19
• Study First Posted: 2017-04-24
• Primary Completion: 2018-04-22
• Study Completion: 2018-04-22
• Results First Submitted: 2019-05-02
• Status Verified: 2019-11
• Results First Submitted QC: 2019-11-27
• Last Update Submitted: 2019-11-27
• Results First Posted: 2019-12-02
• Last Update Posted: 2019-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• planned unilateral mastectomy with or without axillary dissection or sentinel node in the study period
• informed signed consent

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexamethasone 8 mg	Dexamethasone	Dexamethasone 8 mg pre-operative
Dexamethasone 24 mg	Dexamethasone	Dexamethasone 24 mg pre-operative

Primary Outcome Measures

Name	Time	Method
Transfer to Post-anesthesia Care Unit (PACU)	Within 1 hour post-surgery	Number of patients meeting criteria for transfer to PACU post-surgery

Secondary Outcome Measures

Name	Time	Method
Discharge Score, Arrival at Ward	within 3 hours	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.
Post Operative Nausea and Vomiting (PONV).	days 0-4	Self-reported nausea, questionnaire, day 0-4. Number of participants reporting nausea and/or vomiting
Quality of Sleep	days 0-4	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
Discharge Score, Arrival at PACU	within 3 hours	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.
Total Length of Stay in PACU	12 hours	Length of stay in the post-anesthesia care unit (PACU), measured as hours and minutes, from start of procedure, to discharge from PACU
Discharge Score,(Modified Aldrete Discharge Score), Operating Room	At transfer from operating room, within 1 hour post-surgery	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.
Total Length of Stay in Hospital	24-48 hours	Length of stay in hospital, measured from start of procedure to discharge from hospital to home
Secondary Transfer	24-48 hours	Secondary transfer to PACU from ward, or to intensive care unit from PACU
Number of Participants With Complication	24 hours	complications requiring treatment until discharge
Pain, Numeric Rating Scale	days 0-4	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.
Number of Participants With Seroma, Requiring Treatment	14 days	Seroma, requiring treatment the first 14 days.
Readmission	30 days	Any readmission, days 0-30
Mental Status	days 0-4	Self-reported feelings of restlessness, sadness and fatigue (days 0-4). Questionnaire (anwers possible: yes or no. Numbers are patients answering yes)

Trial Locations

Locations (1)

Rigshospitalet; 🇩🇰 Copenhagen, Denmark