DREAMS

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DREAMS Trial Collaborators and West Midlands Research Committee. "Dexamethasone versus standard treatment for postoperative nausea and vomiting in gastrointestinal surgery: randomised controlled trial (DREAMS Trial)". BMJ. 2017. 357:1455.
PubMed

Clinical Question

Does preoperative dexamethasone reduce postoperative vomiting or provide other measurable benefits in surgical recovery compared to standard care?

Bottom Line

The addition of one dose of 8mg of IV dexamethasone at induction of anaesthesia significantly reduces the incidence of both postoperative nausea and vomiting at 24 hours and the need for antiemetics for up to 72 hours with no increase in adverse events.

Major Points

Postoperative nausea and vomiting (PONV) affects 30% of patients, making it the most common complications after surgery [1] [2]. PONV is often related to anaesthetic use, but for bowel surgery teh disruption, resection, and contamination promote postoperative ileus, which has a major effect on PONV. There is limited evidence about which types of surgery are a higher risk for PONV. A systematic review of the risk factors of PONV found that laproscopic surgery and increased operative time were independent risk factors for PONV [3]. There are numerous published studies about PONV after biliary or urological surgery, but very few about small or large bowel procedures. One of these studies demonstrated that even when using a new recovery protocol, 35% of patients undergoing colonic resection required antiemetics postoperatively [4]. Dexamethasone is a powerful corticosteroid, that has significant side effects with prolonged use, however a single dose is not associated with this risk [5]. It has been shown to effectively reduce PONV in low and intermediate risk surgeries [6].

In the DREAMS trial 1350 patients in 45 UK hospitals were recruited and randomly matched to an additional dexamethasone group or to a standard care group. A large study [7] found a reduction in PONV of 28%-37%, therefore the DREAMS trial used 24% as their non inferiority value. After analysis it was found that 25.5% of patients in the dexamethasone group experienced PONV compared to 33.0% in the standard care group (95% CI 5-22; P=0.003). Additional antiemetics were given to 39.3% of patients in the dexamethasone group and 51.9% in the standard care group (NNT 8, 5 to 11; P<0.001). There were no increase in complications from dexamethasone.

Based on these results the researchers of the DREAMS trial concluded that in patients who underwent large or small bowel surgery, a single dose of 8mg of IV dexamethasone (in addition to standard care) significantly reduced PONV in the first 24 hours after surgery and the need for antiemetics 72 hours after surgery. Dexamethasone was also found to be safe in these patients, with no increased risk in adverse events. This evidence strongly supports that patients undergoing bowel surgery would benefit from the use of dexamethasone at induction as an antiemetic agent.

Guidelines

No guidelines have been published that reflect the results of this trial.

Design

Detailed information on the design of this study can be found on the trial registration page. [8].

  • Pragmatic, blinded, multicenter, randomized controlled trial
  • N=1350
    • Dexamethasone (n=674)
    • No Dexamethasone (n=676)
  • Setting: 45 UK Hospitals
  • Enrollment: June 20 2011-January 31 2014
  • Follow Up Length: 1 month
  • Analysis: Intention-to-treat
  • Primary outcome: Reported vomiting within 24 hours reported by patient or clinician

Population

Inclusion Criteria

  • Patients undergoing laparoscopic and open colorectal resections for malignant or benign pathology
  • Age 18-90

Exclusion Criteria

  • Obstructed procedures
  • Pregnancy
  • Known adverse reaction to dexamethasone
  • Patients currently taking any form of steroid medication
  • Diabetic/hyperglycaemic patients
  • Active gastric ulceration
  • Wideangle glaucoma
  • Patients under the age of 18 or over age 90
  • Patients unable or unwilling to give informed consent

Baseline Characteristics

  • Dexamethasone
    • Mean age: 63.6
    • Female: 42.0%
    • Male: 58.0%
    • Non-smoker (n): 85.2%
    • Smoker: 14.8%
      • Mean Pack Years: 27.4
    • ASA Grade:
      • P1 (normal healthy patient): 23.3%
      • P2 (mild systemic disease): 59.6%
      • P3 (severe systemic disease): 16.8%
      • P4 (severe life threatening disease): 0.3%

Interventions

All patients underwent general anaesthesia and received a single dose of a routine antiemetic (other than dexamethasone) preoperatively as standard care determined by the attending anaesthetist. This was done prior to administration of the study intervention to ensure allocations were concealed until standard care was delivered.

  • Dexamethasone:
    • 8 mg IV dexamethasone before the start of surgery
    • Postoperative antiemetics administered at the request of the patient.
  • No Dexamethasone:
    • Nothing in addition to standard care.
    • Postoperative antiemetics administered at the request of the patient.

Outcomes

Comparisons are dexamethasone vs. no dexamethasone.

Primary Outcomes

Postoperative vomiting within 24 hours of surgery
25.5% vs. 33.2% (RR 0.77; 95% CI 0.65-0.92; P=0.003)

Secondary Outcomes

Postoperative vomiting within 25-72 hours of surgery
33.7% vs. 37.6% (RR 0.90; 95% CI 0.78-1.03 P=0.14)
Postoperative vomiting within 73-120 hours of surgery
22.6% vs. 22.2% (RR 1.02; 95% CI 0.83-1.24; P=0.87)
Patient reported clinically important PONV within 24 hours of surgery
8.6% vs. 12.7% (RR 0.68; 95% CI 0.49-0.94; P=0.02)
Patient reported clinically important PONV within 72 hours of surgery
16.7% vs. 15.7% (RR 1.06; 95% CI 0.82-1.38; P=0.64)
Patient reported clinically important PONV within 120 hours of surgery
15.8% vs. 16.5% (RR 1.00; 95% CI 0.74-1.35; P=0.90)
On demand antiemetic use in the first 24 hours after surgery
39.3% vs. 51.9% (RR 0.76; 95% CI 0.67-0.85; P<0.001)
On demand antiemetic use in the first 25-72 hours after surgery
52.4% vs. 62.9% (RR 0.83; 95% CI 0.76-0.91; P<0.001)
On demand antiemetic use in the first 73-120 hours after surgery
40.9% vs. 42.4% (RR 0.97; 95% CI 0.86-1.10; P=0.65)
Return to diet and fluids within 24 hours of surgery
62.3% vs. 53.1% (RR 1.17; 95% CI 1.07-1.29; P<0.001)
Return to diet and fluids within 72 hours of surgery
80.9% vs. 79.2% (RR 0.96; 95% CI 0.96-1.07; P=0.68)
Return to diet and fluids within 120 hours of surgery
83.4% vs. 83.0% (RR 1.00; 95% CI 0.95-1.06; P=0.86)
Health related quality of life (measured by EQ5D) at discharge or 120 hours
0.54 vs. 0.52 (95% CI −0.02- 0.52; P=0.41)
Health related quality of life (measured by EQ5D) at 30 days
0.74 vs. 0.75 (95% CI −0.03- 0.02; P=0.69)
Fatigue (measured by FACIT-F) at discharge or 120 hours
103.0 vs. 102.0 (95% CI -2.3-4.4; P=0.54)
Fatigue (measured by FACIT-F) at 30 days
121.4 vs. 120.4 (95% CI -2.1-4.2; P=0.50)
Length of hospitalization (median number of days)
6 (IQR 4-9) vs. 6 (IQR 4-10) (hazard ratio 1.02; 95% CI 0.90-1.14; P=0.79)

Subgroup Analysis

There was no evidence that the reduction in vomiting within 24 hours with dexamethasone differed in planned subgroup analyses according to:

  • Type of surgery (P=0.91)
  • Whether the patient was assigned to an enhanced recovery pathway (P=0.51)
  • Smoking (P=0.68)
  • ASA grade (P=0.79)
  • Postoperative pain relief (P=0.39)
  • Sex (P=0.78)

Adverse Events

Patient death (all-cause)
1.9% vs. 2.5% (RR 0.77; 95% CI 0.38-1.57; P=0.47)
Infection within 30 days of surgery (all-cause)
10.2% vs. 9.9% (RR 1.03; 95% CI 0.75-1.42; P=0.84)
Superficial wound infection within 30 days of surgery
6.4% vs 6.1% (RR 1.05; 95% CI 0.70-1.59; P=0.81)
Urinary tract infection within 30 days of surgery
1.6% vs. 1.2% (RR 1.38; 95% CI 0.56-3.41; P=0.48)
Respiratory tract infection within 30 days of surgery
1.0% vs. 2.2% (RR 0.47; 95% CI 0.19-1.14; P=0.09)
Anastomotic leaks within 30 days of surgery
1.6% vs. 3.1% (RR 0.53; 95% CI 0.26-1.08; P=0.08)
Intraabdominal abscesses
0.3% vs. 0.1% (RR 2.01; 95% CI 0.18-22.1; P=0.62)

Criticisms

The authors identified the following limitations of the DREAMS trial:

  • No use of a placebo.
  • In 14% of participants anaesthetists administered more than one standard antiemetic.
  • detailed analysis of patient reported outcomes beyond 24 hours were restricted to patients who were not discharged home.
  • The optimal dose of dexamethasone required has yet to be established.

Funding

The DREAMS trial was supported by:

  • Birmingham Surgical Trials Consortium (development and delivery)
  • Royal College of Surgeons and Rosetrees Clinical Research Initiative (development and delivery)
  • Birmingham ECMC (local support for the pilot)

Further Reading

  1. Gan TJ & Postoperative nausea and vomiting--can it be eliminated?. JAMA 2002. 287:1233-6.
  2. Cohen MM et al. The postoperative interview: assessing risk factors for nausea and vomiting. Anesth. Analg. 1994. 78:7-16.
  3. Apfel CC et al. Evidence-based analysis of risk factors for postoperative nausea and vomiting. Br J Anaesth 2012. 109:742-53.
  4. Ehrlich A et al. Evaluation of a fast-track protocol for patients undergoing colorectal surgery. Scand J Surg 2014. 103:182-188.
  5. Sauerland S et al. Risks and benefits of preoperative high dose methylprednisolone in surgical patients: a systematic review. Drug Saf 2000. 23:449-61.
  6. Apfel CC et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N. Engl. J. Med. 2004. 350:2441-51.
  7. Apfel CC et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N. Engl. J. Med. 2004. 350:2441-51.
  8. Magill, Laura. "Dexamethasone Reduces Emesis After Major gastrointestinal Surgery (DREAMS trial)", ISRCT Registry, Birmingham, 26 June 2012. Retrieved on 11 February 2018