Objectives To determine whether preoperative dexamethasone reduces postoperative vomiting in patients undergoing elective bowel surgery and whether it is associated with other measurable benefits during recovery from surgery, including quicker return to oral diet and reduced length of stay. Design Pragmatic two arm parallel group randomised trial with blinded postoperative care and outcome assessment. Setting 45 UK hospitals. Participants 1350 patients aged 18 or over undergoing elective open or laparoscopic bowel surgery for malignant or benign pathology. Interventions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia compared with standard care. Main outcome measures Primary outcome: reported vomiting within 24 hours reported by patient or clinician. Secondary outcomes: vomiting with 72 and 120 hours reported by patient or clinician; use of antiemetics and postoperative nausea and vomiting at 24, 72, and 120 hours rated by patient; fatigue and quality of life at 120 hours or discharge and at 30 days; time to return to fluid and food intake; length of hospital stay; adverse events. Results 1350 participants were recruited and randomly allocated to additional dexamethasone (n=674) or standard care (n=676) at induction of anaesthesia. Vomiting within 24 hours of surgery occurred in 172 (25.5%) participants in the dexamethasone arm and 223 (33.0%) allocated standard care (number needed to treat (NNT) 13, 95% confidence interval 5 to 22; P=0.003). Additional postoperative antiemetics were given (on demand) to 265 (39.3%) participants allocated dexamethasone and 351 (51.9%) allocated standard care (NNT 8, 5 to 11; P<0.001). Reduction in on demand antiemetics remained up to 72 hours. There was no increase in complications. Conclusions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia significantly reduces both the incidence of postoperative nausea and vomiting at 24 hours and the need for rescue antiemetics for up to 72 hours in patients undergoing large and small bowel surgery, with no increase in adverse events. Trial registration EudraCT (2010-022894-32) and ISRCTN (ISRCTN21973627).
In 228 ambulatory patients receiving treatment with warfarin, there was a progressive decline in the dose required to produce an equivalent degree of anticoagulant control with increasing age from the third decade onwards. However, the relationship between age and dose was significant only in patients receiving warfarin after episodes of venous thromboembolism or because of coronary artery disease. Patient weight was also related to warfarin requirements, although it was less important a determinant than age.
1 The relationship between warfarin dose, total and free plasma warfarin concentration, and anticoagulant effect was examined at several steady-state levels in fifteen patients during withdrawal of warfarin therapy. 2 Total plasma clearance was significantly correlated with the free fraction in plasma (r=0.955). 3 There was an age related decline in the dose of warfarin, and in the total and free plasma warfarin concentrations required to produce the same anticoagulant effect. However, neither total nor free plasma warfarin clearances varied with age. 4 Individual patients' log concentration-effect relationships were linear above a prothrombin ratio of 1.2 and there was a significant correlation (r= -0.586) between the slope and the free fraction of warfarin in plasma. It is suggested that plasma protein binding may reflect the interaction between warfarin and its effector site in the hepatocyte.
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