Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial.

BACKGROUND: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections. METHODS: DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts. CONCLUSION: We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

Incidence of Venous Thromboembolism Following Major Emergency Abdominal Surgery.

BACKGROUND: In a retrospective cohort study, we looked at the incidence and risk factors of developing in-hospital venous thromboembolism (VTE) after major emergency abdominal surgery and the risk factors for developing a venous thrombosis. METHODS: Data were extracted through medical records from all patients undergoing major emergency abdominal surgery at a Danish University Hospital from 2010 until 2016. The primary outcome was the incidence of venous thrombosis developed in the time from surgery until discharge from hospital. The secondary outcomes were 30-day mortality and postoperative complications. Multivariate logistic analyses were used for confounder control. RESULTS: In total, 1179 patients who underwent major emergency abdominal surgery during 2010-2016 were included. Thirteen patients developed a postoperative venous thromboembolism (1.1%) while hospitalized. Eight patients developed a pulmonary embolism all verified by CT scan and five patients developed a deep venous thrombosis verified by ultrasound scan. Patients diagnosed with a VTE were significantly longer in hospital with a length of stay of 34 versus 14 days, P < 0.001, and they suffered significantly more surgical complications (69.2% vs. 30.4%, P = 0.007). Thirty-day mortality was equal in patients with and without a venous thrombosis. In a multivariate analysis adjusting for gender, ASA group, BMI, type of surgery, dalteparin dose and treatment with anticoagulants, we found that a dalteparin dose ≥5000 IU was associated with the risk of postoperative surgical complications (odds ratio 1.55, 95% CI 1.11-2.16, P = 0.009). CONCLUSION: In this study, we found a low incidence of venous thrombosis among patients undergoing major emergency abdominal surgery, comparable to the incidence after elective surgery.