Harvey SE, Elbourne D, Ashcroft J, et al: Informed consent in clinical trials in critical care: Experience from the PAC-Man Study

Intensive Care National Audit & Research Centre ICNARC, Londinium, England, United Kingdom
Intensive Care Medicine (Impact Factor: 7.21). 01/2007; 32(12):2020-5. DOI: 10.1007/s00134-006-0358-4
Source: PubMed


To identify the proportion of critically ill patients able to consent to participation in a randomised controlled trial (RCT) and to assess to what extent patient consent and relative assent processes could be conducted according to ethics committee permission.
Descriptive study nested in an RCT.
Fifty-six UK intensive care units participating in the PAC-Man trial.
First 500 patients consecutively enrolled into PAC-Man.
The outcome measures were patient consent and/or relative assent. Of the 498 patients included, 13 (2.6%) provided consent before randomisation. Of the remaining 485 patients, relative assent was obtained for 394 patients (81.2%), and refused post-randomisation for 3 patients (0.6%). No relatives were available for 15 patients (3.1%), and it was unclear from documentation whether relative assent had been obtained for 73 patients (15.1%). Of the 482 patients who did not provide consent prior to randomisation, 188 (39%) survived. Of these, 175 (93.1%) gave retrospective informed consent, six (3.2%) refused, and seven (3.7%) did not regain mental competency.
A very small proportion of patients were able to give consent before randomisation. Due to the high in-hospital mortality (60.6%), only around one third of the remaining patients could provide consent retrospectively. This study demonstrates difficulties experienced in obtaining consent from critically ill patients to participate in medical research and raises important issues about the ethical basis of the consent process in critical care.

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    • "In this previous validation study a 1 point rise in the mean SOFA score was associated with a significant mortality increase (mean SOFA 2.1 to 3.0 = 20%, 3.1 to 4.0 = 36.1% and 4.1 to 5.0 = 73.1% mortality; odds ratio 3.06, 95% CI 2.36 to 3.97). We will recruit an additional 3% (16 patients) to account for potential loss to follow-up and withdrawal of consent, as seen in previous UK ICU trials [37], giving a total of 516 patients with 258 in each arm (Figure 1). "
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    ABSTRACT: Background Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients. Methods/Design This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μ or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom. Discussion This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action. Trial registration Current controlled trials ISRCTN12776039 (19 September 2013)
    Trials 06/2014; 15(1):199. DOI:10.1186/1745-6215-15-199 · 1.73 Impact Factor
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    ABSTRACT: The resident internal medicine called from the Emergency Department (ED). “Can you please come and see my patient, I think he is becoming septic and needs admission to the intensive care”. In the ED we found a confused older patient with an oxygen mask who was clearly dyspnoeic, the urinary catheter was filled with a dark brown fluid, the collecting bag was empty. The resident reported that he admitted the patient 4 hours earlier as he suspected pneumonia. On admission the patient was hypoxic but this clearly improved with the supplemental oxygen. The resident was still waiting for all the laboratory results and the chest X-ray. However, now that the patient had developed hypotension he thought the patient was clearly at risk and intensive care admission was required. When we asked why he had not called us earlier, he replied that he intended to admit the patient to the general ward as he was haemodynamically stable and oxygenation had improved on supplemental oxygen so intensive care admission was not required. When reviewing the blood sample that was drawn 30 min following presentation, besides hypoxaemia, an increased lactate level of 4.6 mmol/l was present. The resident pointed out that hyperlactataemia in sepsis is not related to tissue hypoxia but rather is a marker of increased aerobic metabolism. Therefore he thought there was no need to react to this hyperlactataemia. In this case presentation the presence of hyperlactataemia did not result in treatment consequences. When having read this thesis the reader should be able to indicate whether the resident was right or wrong in this decision. The general aim of this thesis is to evaluate the clinical value of blood lactate monitoring by assessing various aspects of lactate monitoring, including aetiology, the prognostic value and the impact on clinical outcome when incorporating lactate measurement in a treatment algorithm at the bedside. As the process of obtaining informed consent for participation in research is challenging in intensive care patients due to the emergency nature of critical illness, the secondary aim of this thesis is to evaluate consent procedures in emergency critical care research.
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    ABSTRACT: Without Abstract
    Intensive Care Medicine 12/2006; 32(11):1689-90. DOI:10.1007/s00134-006-0386-0 · 7.21 Impact Factor
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