Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

How patient families are provided with information during intensive care: A survey of practices

International audienceMany critically ill patients are incapable of receiving information or expressing their own opinion on treatment decisions due to the severity of their disease, or because they are under sedation. French legislation requires that when a physician proposes further tests or treatment for a patient, this proposal should be accompanied by clear and honest information that is appropriate in view of the circumstances and the patient's state of health, and the physician must obtain the patient's consent before proceeding. However, this is often impossible in critical care. We evaluated whether provisions for surrogates are adequate in meeting information needs of patients and families in critical care.Survey of intensive care physicians by electronic questionnaire in December 2010 and January 2011 to evaluate actual practices. The questionnaire comprised 6 domains covering various aspects relating to the information of patients' relatives as regards diagnostic testing in critical care, when the patient was unable to be appropriately informed. We recorded responders' socio-demographic data (age, how long in practice, where they practised).Among 1279 physicians contacted, 139 (10.8%) from 98 critical care departments (France, Belgium, Switzerland) responded. A total of 66.2% said they believed it is possible to perform diagnostic tests without informing the patient's relatives. Invasive or high-risk tests, time available to provide information, and quality of prior relations with the patient's family were factors likely to prompt the physician to inform the family, while potentially serious implications for the relatives, and degree of relation of the family member to the patient were reported to make the physician more reluctant to inform relatives. Less than 6% considered routine procedures to require provision of information to relatives.Our results suggest that modalities for providing information to families and relatives, as defined by current French legislation, are not suitable to the context of critical care

What are the ethical dimensions in the profession of intensive care specialist?

International audienceTwo essential components of the profession of a medical doctor are the constant review of the patient's therapeutic project, and collaboration between healthcare professionals. The profession of intensive care unit (ICU) physician goes further in terms of responsibility, vis-à-vis the intensive treatments dispensed to the patients, and the physician's responsibilities towards the patient's family and the caregiving team, also bearing in mind that ICU care is costly in terms of human and financial resources. In this review, we address the profession of ICU physician from the perspective of the ethical questions that arise constantly, focusing on the timeframe of the reflection process. Firstly, admission to the ICU must be anticipated. The concept of advance care planning is a suitable tool for this, and in case of non-admission to the ICU, does not by any means constitute an abandonment of the patient, because palliative care can also be anticipated, with a view to avoiding suffering for the patient and their family. Next, during an ICU stay, while the technical aspects undoubtedly characterise the ICU best at the start of the patient's stay, the process of reflection rapidly becomes preponderant, and involves the analysis of often complex situations with a view to defining the level of therapeutic engagement and optimizing the care dispensed to the patient. Last, a further ethical issue concerns the decision to re-admit (or not) a patient to the ICU. This decision can be made, for example, in the framework of a systematic, formalised, structured, multidisciplinary meeting at the end of an ICU stay, using a similar procedure to that implemented for decisions relating to withholding or withdrawal of life-sustaining therapies. The profession of ICU physician is not simply a question of prolonging or sustaining life, but is also fraught with ethical questions about how best to employ their competences. In this regard, it is essential to foster interdisciplinary collaboration, and emphasise the need for ICU physicians to be involved in the development of therapeutic projects, particularly when the disease in question is likely to be complicated by acute situations that may require admission of the patient to the ICU

The concept of a surrogate is ill adapted to intensive care: Criteria for recognizing a reference person

IF 2.445International audiencePurpose: In the intensive care unit (ICU), caregivers may find it difficult to identify a suitable person in the patient's entourage to serve as a reference when there is no official surrogate.Methods: We developed a 12-item questionnaire to identify factors potentially important for caregivers when identifying a reference person. Each criterion was evaluated as regards its importance for the role of reference. Responses were on a scale of 0 (not important) to 10 (extremely important). We recorded respondent's age, job title, and number of years' ICU experience. The questionnaire was distributed to all health care professionals in 2 French ICUs.Results: Among 144 staff, 128 were contacted; 99 completed the questionnaire (77% response rate; 20 physicians [ 11 residents], 51 nurses, 28 nurse's aides). Items classed as most important attributes for a reference person were knowledge of patient's wishes and values, emotional attachment, adequate understanding of the clinical history, and designation as a surrogate before admission. There were no significant differences according to respondent's age, job title, or experience.Conclusion: Caregivers identify a reference person based on criteria such as knowledge of the patient's wishes, emotional bond with the patient, an adequate understanding of the clinical history, and designation as surrogate before admission. (C) 2015 Elsevier Inc. All rights reserved

Severe serotonin syndrome caused by an interaction between an antidepressant and a cough syrup

International audienc

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis

IF 79.258 (2017)International audienceBackgroundAcute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial.MethodsIn a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days.ResultsThe trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients).ConclusionsAmong patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590.

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

ObjectivesAmong patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p p p p p p p p = 0.007).ConclusionsAmong STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc