Critical Care

Journal Article Annotations
2024, 3rd Quarter

Critical Care

Annotations by Natalie Fedotova, MD, PhD
October, 2024

  1. Resilience after severe critical illness: a prospective, multicentre, observational study (RESIREA).
  2. Quetiapine Versus Haloperidol in the Management of Hyperactive Delirium: Randomized Controlled Trial.

PUBLICATION #1 — Critical Care

Resilience after severe critical illness: a prospective, multicentre, observational study (RESIREA).
Alice Mathieu, Jean Reignier, Amélie Le Gouge, Gaetan Plantefeve, Jean-Paul Mira, Laurent Argaud, Pierre Asfar, Julio Badie, Nicolae-Vlad Botoc, Hoang-Nam Bui, Delphine Chatellier, Louis Chauvelot, Christophe Cracco, Michael Darmon, Agathe Delbove, Jérôme Devaquet, Louis-Marie Dumont, Olivier Gontier, Samuel Groyer, Yannick Hourmant, Samir Jaber, Fabien Lambiotte, Benjamin Madeux, Julien Maizel, Olivier Martinet, Virginie Maxime, Emmanuelle Mercier, Mai-Anh Nay, Saad Nseir, Gael Piton, Jean-Pierre Quenot, Anne Renault, Jean-Philippe Rigaud, Francis Schneider, Michel Sirodot, Bertrand Souweine, Fabienne Tamion, Didier Thévenin, Nathalie Thieulot-Rolin, Francois Tinturier, Patrice Tirot 50 , Isabelle Vinatier, Christophe Vinsonneau, Jean-Baptiste Lascarrou, Alexandra Laurent, NUTRIREA-3 Trial Investigators; Clinical Research In Intensive Care and Sepsis (CRICS-TRIGGERSEP) Group.

Annotation

The finding:
In this prospective, observational study across 41 French ICUs, with phone interviews conducted by psychologists several months post discharge, higher psychological resilience was associated with lower PTSD burden and higher health-related quality of life.  Resilience, in turn, was independently associated with stronger social supports and less threatening perception of illness but not with baseline patient characteristics or variables related to the acute illness.  

Strength and weaknesses:
This is a large, prospective, multi-center study, employing trained psychologists –  blind to medical data –  for post-discharge phone interviews.  As this study was conducted in parallel with NUTRIREA-3 (a trial evaluating the impact of low-calorie, low-protein feeding in adults receiving invasive mechanical ventilation and vasopressor support for shock), the participants were a somewhat homogenous sample who survived severe critical illness – this is a potential qualification of generalizability but the severity of illness may be a strength as well.  Methodologically, due to logistical issues, some patients were interviewed only once and others twice (at 3 months and 12 months post discharge); the authors subsequently argued that, when available, resilience and PTSD data did not change over this period of time and it was reasonable to use the latest data for each patient.  About 31% of eligible patients could not be interviewed; however, they did not differ substantially from the included patients in terms of baseline characteristics.  Finally, this is an observational study which does not allow for conclusions regarding causation. There are also no data on pre-illness levels of resilience or PTSD.

Relevance: 
With a number of caveats, this study suggests that introducing interventions targeting perceptions of illness and social supports may strengthen resilience, subsequently decreasing PTSD burden and increasing health-related quality of life for survivors of critical illness.  It underscores the crucial role of mental health professionals during ICU admissions as well as in post-ICU follow-up visits to promote recovery.


PUBLICATION #2 — Critical Care

Quetiapine Versus Haloperidol in the Management of Hyperactive Delirium: Randomized Controlled Trial.
Tamer Zakhary, Islam Ahmed, Ibrahim Luttfi, Mina Montasser.

Annotation 

The finding:
In this single-center randomized controlled trial (RCT) involving ICU patients with hyperactive delirium, subjects were randomized to receive either low-dose oral/nasogastric quetiapine (25-50 mg/day) or low-dose oral/nasogastric haloperidol (1-2 mg/day) to manage agitation. The results indicated that quetiapine was effective in reducing the length of ICU stay and increasing the number of sleeping hours per night. However, there were no significant differences between the two groups in terms of response rate, the necessity for mechanical ventilation, overall hospital length of stay, or mortality rates. While both groups reported QTc prolongation (quetiapine n=3, haloperidol n=1), only patients in the haloperidol group reported EPS (n = 4).

Strength and weaknesses:  
The authors pursued a randomized, double-blind design, focusing on patients with hyperactive delirium only.  On the other hand, the trial did not include a placebo arm, the data were collected from a single medical center, and the trial was likely underpowered for some of the outcomes given sample size (n = 100).  The selection criteria were narrow and likely excluded some of the more severely ill and agitated patients (e.g., unable to accept oral or nasogastric medication, acute renal injury, hepatic failure, substance-induced delirium, previous use of antipsychotics, etc.).   The antipsychotic doses were imprecise (presented as a range), potentially not equivalent, and administered only once per day, at different times, with no uptitration plan.   It is not clear which symptoms were considered to be “agitation,” and based on the dosage and frequency, the overall agitation was likely not severe. Finally, it is not specified how the administration of antipsychotics impacted the use of other sedating or rescue medications, such as benzodiazepines.

Relevance: 
Given the limitations described above, it is difficult to make sweeping conclusions. However, this trial is a randomized head-to-head comparison of two widely used antipsychotics in critically ill patients with a specific motoric subtype of delirium.  For agitated, critically ill patients with hyperactive delirium, whose medical status and level of agitation allow for oral or nasogastric administration, quetiapine may be helpful with lower risk of EPS and other potential benefits, such as sleep support.  It is unclear whether reported decrease in ICU length of stay was secondary to improvement in the day-night cycle or other unreported variables (e.g., theoretical decrease in the use of deliriogenic agents).  Overall, this study is unlikely to change how CL psychiatrists approach agitation or delirium management, but we may see even more interest in the use of quetiapine in critical care settings.