Journal Article Annotations
2018, 4th Quarter

Surgery, Trauma, and Critical Care Psychiatry

Annotations by O. Joseph (“Joe”) Bienvenu, MD, PhD
January 2019

Benzodiazepine use and neuropsychiatric outcomes in the ICU: a systematic review
Anxiety, depression and post traumatic stress disorder after critical illness: a UK-wide prospective cohort study

PUBLICATION #1 — Surgery, Trauma, and Critical Care Psychiatry

Benzodiazepine use and neuropsychiatric outcomes in the ICU: a systematic review

Kok L, Slooter AJ, Hillegers MH, van Dijk D, Veldhuijzen DS

Abstract: Crit Care Med 2018; 46(10):1673-1680

Objectives: A systematic assessment of the role of benzodiazepine use during ICU stay as a risk factor for neuropsychiatric outcomes during and after ICU admission.
Data Sources: PubMed/Medline, EMBASE, The Cochrane Library, CINAHL, and PsychINFO.

Study Selection: Databases were searched independently by two reviewers for studies in adult (former) ICU patients, reporting benzodiazepine use, and neuropsychiatric outcomes of delirium, posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction.

Data Extraction: Data were extracted using a piloted extraction form; methodological quality of eligible studies was assessed by applying the Quality Index checklist.

Data Synthesis: Forty-nine of 3,066 unique studies identified were included. Thirty-five studies reported on neuropsychiatric outcome during hospitalization, 12 after discharge, and two at both time points. Twenty-four studies identified benzodiazepine use as a risk factor for delirium, whereas seven studies on delirium or related outcomes did not; six studies reported mixed findings. Studies with high methodological quality generally found benzodiazepine use to be a risk factor for the development of delirium. Five studies reported an association between benzodiazepine use and symptoms of posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction after ICU admission; five studies reported mixed findings, and in four studies, no association was found. No association was found with methodological quality and sample size for these findings. Meta-analysis was not feasible due to major differences in study methods.

Conclusions: The majority of included studies indicated that benzodiazepine use in the ICU is associated with delirium, symptoms of posttraumatic stress disorder, anxiety, depression, and cognitive dysfunction. Future well-designed studies and randomized controlled trials are necessary to rule out confounding by indication.

On PubMed: Crit Care Med 2018; 46(10):1673-1680

Annotation

Type of study: Systematic review

The finding: Kok et al systematically investigated the effect of benzodiazepines on common in-ICU and post-ICU neuropsychiatric phenomena, including delirium, long-term cognitive impairment, anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms. By far, the most studied outcome was in-ICU delirium. Kok et al report that, in most of the studies that examined the issue, benzodiazepines appeared causally related to delirium. In addition, the more rigorous studies in the review tended to confirm this result. Fewer studies examined the long-term post-ICU outcomes cognitive impairment, anxiety, depression, and PTSD symptoms. Nevertheless, results suggested that higher doses of benzodiazepines were associated with worse long-term cognitive outcomes, as well as more anxiety, depression, and PTSD symptoms.

Strength and weaknesses: Strengths include the systematic searches of relevant databases, as well as evaluation of methodologic quality of included studies. A weakness of the literature reviewed is that most studies that evaluated longer-term (post-ICU) outcomes were not randomized.

Relevance: Clinicians should administer as little benzodiazepine or other GABA-enhancing sedative medication as possible, in order to preserve brain functioning, shorten the duration of mechanical ventilation, allow in-ICU physical rehabilitation, and allow patients to cognitively and emotionally process what is occurring within and around them more completely.

PUBLICATION #2 — Surgery, Trauma, and Critical Care Psychiatry

Anxiety, depression and post traumatic stress disorder after critical illness: a UK-wide prospective cohort study

Hatch R, Young D, Barber V, Griffiths J, Harrison DA, Watkinson P

Abstract: Crit Care 2018; 22(1):310

Background: Survivors of intensive care are known to be at increased risk of developing longer-term psychopathology issues. We present a large UK multicentre study assessing the anxiety, depression and post-traumatic stress disorder (PTSD) caseness in the first year following discharge from an intensive care unit (ICU).

Methods: Design: prospective multicentre follow-up study of survivors of ICU in the UK.

Setting: patients from 26 ICUs in the UK.

Inclusion Criteria: patients who had received at least 24 h of level 3 ICU care and were 16 years of age or older.

Interventions: postal follow up: Hospital Anxiety and Depression Score (HADS) and the Post-Traumatic Stress Disorder (PTSD) Check List-Civilian (PCL-C) at 3 and 12 months following discharge from ICU.

Main Outcome Measure: caseness of anxiety, depression and PTSD, 2-year survival.

Results: In total, 21,633 patients admitted to ICU were included in the study. Postal questionnaires were sent to 13,155 survivors; of these 38% (4943/13155) responded and 55% (2731/4943) of respondents passed thresholds for one or more condition at 3 or 12 months following discharge. Caseness prevalence was 46%, 40% and 22% for anxiety, depression and PTSD respectively; 18% (870/4943 patients) met the caseness threshold for all three psychological conditions. Patients with symptoms of depression were 47% more likely to die during the first 2 years after discharge from ICU than those without (HR 1.47, CI 1.19-1.80).

Conclusions: Over half of those who respond to postal questionnaire following treatment on ICU in the UK reported significant symptoms of anxiety, depression or PTSD. When symptoms of one psychological disorder are present, there is a 65% chance they will co-occur with symptoms of one of the other two disorders. Depression following critical illness is associated with an increased mortality risk in the first 2 years following discharge from ICU.

On PubMed: Crit Care 2018; 22(1):310

Annotation

Type of study: Prospective cohort study

The finding: In this UK-wide multicenter outcome study, almost 5,000 critical illness survivors returned postal questionnaires that included the Hospital Anxiety and Depression Scale and the Civilian version of the PTSD Checklist. Of these 46%, 40%, and 22% had clinically significant symptoms of anxiety, depression, and PTSD at 3 and/or 12 months after discharge. Patients with clinically significant depressive symptoms were 47% more likely to die during the first 2 years after ICU.

Strength and weaknesses: This was a very large study, involving 26 ICUs; however, only 38% of survivors returned the postal questionnaires, potentially limiting generalizability.

Relevance: This is the first study of critical illness survivors to assess the effect of psychiatric morbidity on survival. Clinically significant depressive symptoms after critical illness either add risk for death through poor self-care, etc., or are a marker of risk for death.