Inability to obtain deferred consent due to early death in emergency research: effect on validity of clinical trial results

PURPOSE: To illustrate the impact on the validity of trial results due to excluding patients from a randomized controlled trial for whom no deferred consent could be obtained after randomization because study procedures had already been finished. METHODS: The unadjusted and adjusted primary outcome measures of a recent randomized controlled multicentre study in the field of intensive care medicine were compared, including (n = 348) or excluding (n = 289) patients with missing deferred consent. RESULTS: Thirty-nine patients (11%) died early, before the patient or his/her proxy could be approached and consent be obtained. In another 20 patients (6%), it was not possible to inform proxies and ask consent within the period of study procedures. A significant treatment effect (p = 0.006) in the adjusted analysis became non-significant (p = 0.35) when the patients with missing deferred consent were excluded. CONCLUSIONS: Exclusion of patients without obtained deferred consent can reduce statistical power, introduce selection bias, make randomization asymmetrical, decrease external validity and thereby jeopardize study results. This may have implications for emergency research in various disciplines

Anticipation of distress after discontinuation of mechanical ventilation in the ICU at the end of life

Background: A considerable number of patients admitted to the intensive care unit (ICU) die following withdrawal of mechanical ventilation. After discontinuation of ventilation without proper preparation, excessive respiratory secretion is common, resulting in a 'death rattle'. Post-extubation stridor can give rise to the relatives' perception that the patient is choking and suffering. Existing protocols lack adequate anticipatory preparation to respond to all distressing symptoms. Methods: We analyzed existing treatment strategies in distressing symptoms after discontinuation of mechanical ventilation. Conclusion: The actual period of discontinuation of mechanical ventilation can be very short, but thoughtful anticipation of distressing symptoms takes time. There is an ethical responsibility to anticipate and treat (iatrogenic) symptoms such as pain, dyspnea-associated respiratory distress, anxiety, delirium, post-extubation stridor, and excessive broncho-pulmonary secretions. This makes withdrawal of mechanical ventilation in ICU patients a thoughtful process, taking palliative actions instead of fast terminal actions. We developed a flowchart covering all possible distressi