Journal Article Annotations
2020, 4th Quarter

Critical Care

Annotations by O. Joseph Bienvenu, MD, PhD, Natalie O.Fedotova, MD, PhD, Jordan H. Rosen, MD
December, 2020

Is COVID-19 Associated With Posttraumatic Stress Disorder?
A Novel Approach to ICU Survivor Care: A Population Health Quality Improvement Project
Effect of Nonsedation on Cognitive Function in Survivors of Critical Illness
Analgesia and Sedation in patients with ARDS

PUBLICATION #1 — Critical Care

Is COVID-19 Associated With Posttraumatic Stress Disorder?

Mathilde Horn, Marielle Wathelet, Thomas Fovet, Ali Amad, Fanny Vuotto, Karine Faure, Thibault Astier, Hélène Noël, Margot Henry Stéphane Duhem, Guillaume Vaiva, Fabien D’Hondt

Abstract: J Clin Psychiatry. 2020 Dec 8;82(1):20m13641. doi: 10.4088/JCP.20m13641.

Objective:
To assess the prevalence of and risk factors for posttraumatic stress disorder (PTSD) in patients with COVID-19.

Methods:
We conducted a cohort study between March and May 2020 at the Lille University Hospital (France), including all patients with laboratory-confirmed COVID-19. Psychological distress symptoms were measured 3 weeks after onset of COVID-19 symptoms using the Impact of Event Scale-6 items (IES-6). The evaluation of PTSD symptoms using the PTSD Checklist for DSM-5 (PCL-5) took place 1 month later. Bivariate analyses were performed to analyze the relationship between PCL-5 scores and the demographic and health variables. The significant variables were then introduced into a multivariable linear regression analysis to establish their relative contributions to the severity of PTSD symptoms.

Results:
180 patients were included in this study, and 138 patients completed the 2 evaluations. Among the 180 patients, 70.4% patients required hospitalization, and 30.7% were admitted to the intensive care unit. The prevalence of PTSD was 6.5%, and the predictive factors of PTSD included psychological distress at the onset of the illness and a stay in an intensive care unit.

Conclusions:
The prevalence of PTSD in patients with COVID-19 is not as high as that reported among patients during previous epidemics. Initial psychological responses were predictive of a PTSD diagnosis, even though most patients showing acute psychological distress (33.5% of the sample) improved in the following weeks. PTSD symptoms also increased following a stay in an intensive care unit. Future studies should assess the long-term consequences of COVID-19 on patients’ mental health.

Annotation

The finding:
Interestingly, all of the patients with clinically significant PTSD symptoms at last follow-up had elevated IES-6 scores 3 weeks after infection. Perhaps not surprisingly, patients who required critical care had higher PTSD symptoms at follow-up. As expected, prior psychiatric morbidity and use of psychiatric medication prior to COVID-19 were associated with later PTSD symptoms; however, neither of these was a significant predictor in a multivariable model (i.e., early PTSD symptoms appeared to share variance with prior psychiatric history and use of psychiatric medication).

Strength and weaknesses:
The authors assessed all patients with confirmed COVID-19, regardless of need for hospitalization or intensive care. In addition, most of the eligible patients completed at least one assessment, and more than half completed both assessments. Though this was a monocentric study, the hospital serves a whole region with several cities.

Relevance:
C-L psychiatrists may be those most likely to meet COVID-affected patients, as inpatients or outpatients. Thus, it is helpful for us to be aware of the risk factors for persistent symptoms, including prior psychiatric morbidity, medication treatment, and, especially, early psychological distress and need for intensive care.

Type of study (EBM guide):
Cohort study

PUBLICATION #2 — Critical Care

A Novel Approach to ICU Survivor Care: A Population Health Quality Improvement Project

Kenneth P Snell, Cynthia L Beiter, Erin L Hall, Anthony S Junod, Bradley J Wilson, Daniel K Lepone, Jeremy R McIntyre, Danielle Phelps Swartz, Andrea L Berger, H Lester Kirchner, Janet F Tomcavage, Karen A Korzick

Abstract: J Clin Psychiatry. 2020 Dec 8;82(1):20m13641. doi: 10.4088/JCP.20m13641.Crit Care Med. 2020 Dec;48(12):e1164-e1170. doi: 10.1097/CCM.0000000000004579.

Objectives:
Deliver a novel interdisciplinary care process for ICU survivor care and their primary family caregivers, and assess mortality, readmission rates, and economic impact compared with usual care.

Design:
Population health quality improvement comparative study with retrospective data analysis.

Setting:
A single tertiary care rural hospital with medical/surgical, neuroscience, trauma, and cardiac ICUs.

Patients:
ICU survivors.

Interventions:
Reorganization of existing post discharge health care delivery resources to form an ICU survivor clinic care process and compare this new process to post discharge usual care process.

Measurements and main results:
Demographic data, Acute Physiology and Chronic Health Evaluation IV scores, and Charlson Comorbidity Index scores were extracted from the electronic health record. Additional data was extracted from the care manager database. Economic data were extracted from the Geisinger Health Plan database and analyzed by a health economist. During 13-month period analyzed, patients in the ICU survivor care had reduced mortality compared with usual care, as determined by the Kaplan-Meier method (ICU survivor care 0.89 vs usual care 0.71; log-rank p = 0.0108) and risk-adjusted stabilized inverse probability of treatment weighting (hazard ratio, 0.157; 95% CI, 0.058-0.427). Readmission for ICU survivor care versus usual care: at 30 days (10.4% vs 26.3%; stabilized inverse probability of treatment weighting hazard ratio, 0.539; 95% CI, 0.224-1.297) and at 60 days (16.7% vs 34.7%; stabilized inverse probability of treatment weighting hazard ratio, 0.525; 95% CI, 0.240-1.145). Financial data analysis indicates estimated annual cost savings to Geisinger Health Plan ranges from $247,052 to $424,846 during the time period analyzed.

Conclusions:
Our ICU survivor care process results in decreased mortality and a net annual cost savings to the insurer compared with usual care processes. There was no statistically significant difference in readmission rates.

Annotation

The finding:
This was a serious quality improvement project, in which clinicians at Geisinger began engaging patients and their primary family care givers (FCGs) while the patients were still hospitalized. Multiple professionals provided comprehensive in-person assessments of all domains of the post-intensive care syndrome (psychological, cognitive, and physical) and simultaneously assessed FCG well-being. They provided continued support to the patient, FCG, and primary care provider until resolution of reversible conditions or acclimation of the patient and FCG to permanent conditions. The authors did this by creating an intensive care unit (ICU) survivor care clinic. The paper links to lots of thoughtful supplementary materials that could be useful to others wishing to create such a clinic. Compared with usual care, enrollment in the ICU survivor care clinic was associated with significantly decreased mortality and healthcare costs.

Strength and weaknesses:
There was a potential self-selection bias, as patients and FCGs were not randomized to the intervention or usual care. However, the authors deserve a lot of credit for developing a truly holistic follow-up care program for patients and FCGs – truly amazing.

Relevance:
C-L psychiatrists and other clinicians are becoming increasingly aware of the neuropsychiatric problems that commonly afflict critical illness survivors. Being a provider in a multidisciplinary follow-up clinic like this could be incredibly rewarding, and this paper provides lots of practical information to set one up for critical illness survivors and their FCGs.

Type of study (EBM guide):
Other (enter a free text description on the document)
Population health quality improvement comparative study with retrospective data analysis

PUBLICATION #3 — Critical Care

Effect of Nonsedation on Cognitive Function in Survivors of Critical Illness

Helene Korvenius Nedergaard, Hanne Irene Jensen, Mette Stylsvig, Hanne Tanghus Olsen, Serkan Korkmaz, Thomas Strøm, Palle Toft

Abstract: Crit Care Med. 2020 Dec;48(12):1790-1798. doi: 10.1097/CCM.0000000000004573.

Objectives:
Critical illness can cause severe cognitive impairments. The objective of this trial was to assess the effect of nonsedation versus sedation with a daily wake-up call during mechanical ventilation on cognitive function in adult survivors of critical illness.

Design:
Single-center substudy of the multicenter, randomized Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Mechanical Ventilation trial. Three months after ICU-discharge participants were tested for cognitive function by a neuropsychologist.

Setting:
Mixed 14-bed ICU in teaching hospital.

Patients:
A total of 205 critically ill, orally intubated, and mechanically ventilated adults.

Interventions:
Patients were randomized within the first 24 hours from intubation to either nonsedation with sufficient analgesia or light sedation with a daily wake-up call during mechanical ventilation.

Measurements and main results:
A total of 118 patients survived to follow-up and 89 participated (75%). The participating survivors in the two groups did not differ regarding baseline data or premorbid cognitive impairments. Sedated patients had received more sedatives, whereas doses of morphine and antipsychotics were equal. The primary outcome was that no significant difference was found in the number of patients with mild/moderate cognitive impairments (six nonsedated patients vs four sedated patients) or severe cognitive impairments (16 nonsedated patients vs 17 sedated patients; p = 0.71). Secondary outcomes were cognitive test scores, and no differences were found between the scores in nonsedated and sedated patients. Hypothetical worst case scenarios where all patients, who had not participated in follow-up assessment, were assumed to have severe cognitive impairments were analyzed, but still no difference between the groups was found. We found more patients with delirium in the sedated group (96% vs 69% of patients; p = 0.002) and increased duration of delirium in sedated patients (median 5 vs 1 d; p < 0.001). Delirium subtypes were equally distributed between the groups, with hypoactive delirium most frequent (61%), followed by mixed delirium (39%).

Conclusions:
Nonsedation did not affect cognitive function 3 months after ICU-discharge.

Annotation

The finding:
The authors examined a subgroup of 205 critically-ill, mechanically ventilated patients from a single center mixed ICU (part of multi-center NONSEDA trial), who were randomized within the first 24 hours to receive sedation with a daily wake-up call (propofol x 48 hours, then midazolam, with a target RASS of -2 to -3; with morphine PRN) or nonsedation (morphine PRN only). In case of delirium (assessed via CAM-ICU), nonpharmacological interventions followed by haloperidol were utilized. The primary outcome was the number of patients experiencing cognitive impairment as assessed at 3 months post-ICU discharge. In this single-center substudy, nonsedation during mechanical ventilation in the ICU did not impact cognitive function at 3 months post-ICU discharge. In the nonsedation group, however, occurrence of delirium was less frequent and the duration of delirium was shorter. The nonsedation group received fewer sedatives (propofol and midazolam) but did not require more morphine or haloperidol.

Strength and weaknesses:
The strengths of this study include randomization and increased external validity, as patients with pre-existing cognitive impairment were not excluded. At the same time, several characteristics of the study design favored the null hypothesis. First, the sedation was light: the difference in RASS scores between the sedation and nonsedation groups was only approximately 1 and the target of -2 to -3 was only achieved in the sedation group during the first day. Second, although delirium – a risk factor for cognitive deficits – was less frequent in the nonsedation group, it still occurred in almost 70% of the sample. Finally, this study was likely underpowered (e.g., there are non-significant trends toward fewer days of mechanical ventilation and shorter length of hospital stay in the nonsedation group), and the sample did not allow for a more nuanced subgroup analysis. Thus, this study sheds some light on nonsedation as a general strategy but does not speak to the potential interaction with pre-existing patient characteristics, where nonsedation may be of particular benefit to the most vulnerable individuals. A larger sample size to detect the potentially diluted effect or perform subgroup analyses are necessary to answer this question.

Relevance:
This study adds to the previous findings on the safety and non-inferiority of light sedation compared to nonsedation, suggesting that it does not affect cognitive function at 3 months. It shows that nonsedation leads to less delirium but does not translate into a difference in cognitive status at this time interval. In addition, nonsedation as a strategy does not increase morphine or haloperidol use. Psychiatrists may be particularly helpful in recommending and monitoring antipsychotic dosing in nonsedation protocols. On the other hand, this substudy may be underpowered and its results interpreted in that context.

Type of study (EBM guide):
Other (enter a free text description on the document) Substudy of an RCT

PUBLICATION #4 — Critical Care

Analgesia and Sedation in patients with ARDS

Gerald Chanques, Jean-Michel Constantin, John W Devlin, E Wesley Ely, Gilles L Fraser, Céline Gélinas, Timothy D Girard, Claude Guérin, Matthieu Jabaudon, Samir Jaber, Sangeeta Mehta, Thomas Langer, Michael J Murray, Pratik Pandharipande, Bhakti Patel, Jean-François Payen, Kathleen Puntillo, Bram Rochwerg, Yahya Shehabi, Thomas Strøm, Hanne Tanghus Olsen, John P Kress

Abstract: Intensive Care Med. 2020 Dec;46(12):2342-2356. doi: 10.1007/s00134-020-06307-9. Epub 2020 Nov 10.

Acute Respiratory Distress Syndrome (ARDS) is one of the most demanding conditions in an Intensive Care Unit (ICU). Management of analgesia and sedation in ARDS is particularly challenging. An expert panel was convened to produce a “state-of-the-art” article to support clinicians in the optimal management of analgesia/sedation in mechanically ventilated adults with ARDS, including those with COVID-19. Current ICU analgesia/sedation guidelines promote analgesia first and minimization of sedation, wakefulness, delirium prevention and early rehabilitation to facilitate ventilator and ICU liberation. However, these strategies cannot always be applied to patients with ARDS who sometimes require deep sedation and/or paralysis. Patients with severe ARDS may be under-represented in analgesia/sedation studies and currently recommended strategies may not be feasible. With lightened sedation, distress-related symptoms (e.g., pain and discomfort, anxiety, dyspnea) and patient-ventilator asynchrony should be systematically assessed and managed through interprofessional collaboration, prioritizing analgesia and anxiolysis. Adaptation of ventilator settings (e.g., use of a pressure-set mode, spontaneous breathing, sensitive inspiratory trigger) should be systematically considered before additional medications are administered. Managing the mechanical ventilator is of paramount importance to avoid the unnecessary use of deep sedation and/or paralysis. Therefore, applying an “ABCDEF-R” bundle (R = Respiratory-drive-control) may be beneficial in ARDS patients. Further studies are needed, especially regarding the use and long-term effects of fast-offset drugs (e.g., remifentanil, volatile anesthetics) and the electrophysiological assessment of analgesia/sedation (e.g., electroencephalogram devices, heart-rate variability, and video pupillometry). This review is particularly relevant during the COVID-19 pandemic given drug shortages and limited ICU-bed capacity.

Annotation

The finding:
This is an expert-driven narrative review designed to support clinicians in their management of sedation and analgesia in ARDS patients due to urgent concerns about analgesic, sedative and paralytic shortages during the coronavirus pandemic.

Strength and weaknesses:
This was a reviewed written by collaborators on the PADIS guidelines for analgesia and sedation in critical illness. This was not a trial with data.

Relevance:
Psychiatrists are often consulted to help manage delirium in the setting of critical illness, especially during the COVID-19 pandemic. Understanding the current expert opinions, guidelines and rationale behind sedation and analgesia management gives psychiatrists seeing patients in ICUs a larger ability to engage in conversations around lightening sedation through adjunctive medications such as antipsychotics, alpha-agonists, or opioid-sparing analgesics.

Type of study:
Expert review