Journal Article Annotations
2021, 1st Quarter

Critical Care

Annotations by O. Joseph Bienvenu, MD, PhD, Natalie O.Fedotova, MD, PhD, Jordan H. Rosen, MD
March, 2021

Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis
Motoric Subtypes of Delirium and Long-Term Functional and Mental Health Outcomes in Adults After Critical Illness
Intensive Care Unit-Specific Virtual Reality for Psychological Recovery After ICU Treatment for COVID-19; A Brief Case Report

PUBLICATION #1 — Critical Care

Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis

Christopher G Hughes, Patrick T Mailloux, John W Devlin, Joshua T Swan, Robert D Sanders, Antonio Anzueto, James C Jackson, Aimee S Hoskins, Brenda T Pun, Onur M Orun, Rameela Raman, Joanna L Stollings, Amy L Kiehl, Matthew S Duprey, Lan N Bui, Hollis R O’Neal Jr, Allison Snyder, Michael A Gropper, Kalpalatha K Guntupalli, Gregg J Stashenko, Mayur B Patel, Nathan E Brummel, Timothy D Girard, Robert S Dittus, Gordon R Bernard, E Wesley Ely, Pratik P Pandharipande, MENDS2 Study Investigators

Abstract: N Engl J Med. 2021 Feb 2. doi: 10.1056/NEJMoa2024922. Online ahead of print.

Background:
Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.

Methods:
In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.

Results:
Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses – 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.

Conclusions:
Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).

Annotation

The finding:
There was no difference found in days alive without delirium or coma, ventilator free days, death, or cognitive outcomes between the use of dexmedetomidine and propofol when targeting light sedation.

Strength and weaknesses:
This is a large, multi-center, double-blinded randomized controlled trial with well-designed methods and well-matched groups. Strict adherence to light sedation protocols was maintained. There was an episode of unmasking of 14% of patients, and there was some cross-contamination of sedative use in the two groups, though this was less common than in similar previous trials.

Relevance:
Previous trials have shown the clear benefit of light sedation over deep sedation, with dexmedetomidine and/or analgesia-based sedation primarily being used in the former and propofol and benzodiazepines being used in the latter. This well-run trial utilizing propofol strictly for light sedation is an important addition to the critical care literature that shows that similarly positive outcomes of light-sedation for mental status, time spend on the ventilator, and cognitive outcomes can be achieved with propofol. Psychiatrists who consult in intensive care settings often augment light sedation such as dexmedetomidine with psychiatric medications; it may be reasonable to also consider light sedation with propofol aided with psychiatric medication augmentation as well.

Type of study:
Randomized controlled trial

PUBLICATION #2 — Critical Care

Motoric Subtypes of Delirium and Long-Term Functional and Mental Health Outcomes in Adults After Critical Illness

Kimberly F Rengel, Christina J Hayhurst, James C Jackson, Christina S Boncyk, Mayur B Patel, Nathan E Brummel, Yaping Shi, Matthew S Shotwell, E Wesley Ely, Pratik P Pandharipande, Christopher G HughesKaren A Korzick

Abstract: Crit Care Med. 2021 Feb 23. doi: 10.1097/CCM.0000000000004920. Online ahead of print.

Objectives:
Adult ICU survivors that experience delirium are at high risk for developing new functional disabilities and mental health disorders. We sought to determine if individual motoric subtypes of delirium are associated with worse disability, depression, and/or post-traumatic stress disorder in ICU survivors.

Design:
Secondary analysis of a prospective multicenter cohort study.

Setting:
Academic, community, and Veteran Affairs hospitals.

Patients:
Adult ICU survivors of respiratory failure and/or shock.

Interventions:
We assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation and Sedation Scale daily during hospitalization. We classified delirium as hypoactive (Richmond Agitation and Sedation Scale ≤ 0) or hyperactive (Richmond Agitation and Sedation Scale > 0). At 3- and 12-month postdischarge, we assessed for dependence in activities of daily living and instrumental activities of daily living, symptoms of depression, and symptoms of post-traumatic stress disorder. Adjusting for baseline and inhospital covariates, multivariable regression examined the association of exposure to delirium motoric subtype and long-term outcomes.

Measurements and main results:
In our cohort of 556 adults with a median age of 62 years, hypoactive delirium was more common than hyperactive (68.9% vs 16.8%). Dependence on the activities of daily living was present in 37% at 3 months and 31% at 12 months, whereas dependence on instrumental activities of daily living was present in 63% at 3 months and 56% at 12 months. At both time points, depression and post-traumatic stress disorder rates were constant at 36% and 5%, respectively. Each additional day of hypoactive delirium was associated with higher instrumental activities of daily living dependence at 3 months only (0.24 points [95% CI, 0.07-0.41; p = 0.006]). There were no associations between the motoric delirium subtype and activities of daily living dependence, depression, or post-traumatic stress disorder.

Conclusions:
Longer duration of hypoactive delirium, but not hyperactive, was associated with a minimal increase in early instrumental activities of daily living dependence scores in adult survivors of critical illness. Motoric delirium subtype was neither associated with early or late activities of daily living functional dependence or mental health outcomes, nor late instrumental activities of daily living functional dependence.

Annotation

The finding:
The authors performed a post-hoc analysis on 556 adult ICU patients from the BRAIN-ICU and MIND-ICU prospective cohort studies. During hospitalization, patients were monitored for development and duration of delirium (via the CAM-ICU), classified as hypoactive or hyperactive based on their RASS scores (≤0 and >0, respectively). Patients who presented with both psychomotor subtypes on the same day (during different assessments) qualified as having an additional day of each type of delirium. The primary analysis focused on the association of the number of days with hypoactive and hyperactive delirium with functional dependence (ADLs and IADLs), depression, and PTSD, evaluated at 3 and 12 months post-discharge. Hypoactive delirium was more prevalent and persistent in terms of duration. Each additional day of hypoactive, but not hyperactive, delirium was associated with a small increase in IADL dependence at 3 months only; it was not associated with outcomes at 12 months. There was no association between the duration of either type of delirium and ADL dependence, depression, or PTSD at 3 or 12 months.

Strength and weaknesses:
This study focused on data gathered via a prospective cohort investigation across multiple settings and includes several covariates in its models. Following previous literature, delirious patients with a RASS of 0 were classified as hypoactive, which does not allow for a separate analysis of patients with normal arousal who have been shown to have worse outcomes in prior work. The low prevalence of hyperactive delirium brings up questions about decreased power, and the dropout rate is concerning for survivor bias ((1040 evaluated in hospital, 781 progressed to follow-up phase, 556 were evaluated at 3 months, and 474 were evaluated at 12 months).

Relevance:
The association between the duration of hypoactive delirium and functional dependence at 3 months builds on previous work highlighting the deleterious effects of this particular psychomotor subtype, possibly due to limited engagement in activities such as early mobilization and PT. CL psychiatrists are often in the best position to diagnose this condition, which is simultaneously underrecognized and more prevalent. The lack of association between delirium duration, regardless of type, and outcomes at 12 months is surprising but should interpreted with caution in light of substantial dropout and classification of patients with normal arousal level in the hypoactive group. The innovative approach used to classify patients who exhibited hypoactive and hyperactive features on the same day highlights the challenge in separating psychomotor subtypes.

Type of study (EBM guide):
secondary analysis of a prospective cohort study

PUBLICATION #3 — Critical Care

Intensive Care Unit-Specific Virtual Reality for Psychological Recovery After ICU Treatment for COVID-19; A Brief Case Report

Johan H Vlake, Jasper van Bommel, Merel E Hellemons, Evert-Jan Wils, Diederik Gommers, Michel E van Genderen

Abstract: Front Med (Lausanne). 2021 Feb 5;7:629086. doi: 10.3389/fmed.2020.629086. eCollection 2020.

A substantial number of ICU survivors are expected due to the SARS-CoV-2 outbreak, who are at risk for psychological impairments, such as post-traumatic stress disorder (PTSD), anxiety, and depression. We designed a COVID-19 intensive care unit-specific virtual reality (ICU-VR) intervention and tested it on one of our COVID-19 patients. The impact of event scale-revised and the hospital anxiety and depression scale showed that this patient suffered from PTSD, anxiety, and depression on the day of the intervention. One week after receiving ICU-VR, levels of PTSD, anxiety and depression had normalized, and stayed normalized until 6 months after discharge. In conclusion, innovative technologies, such as VR, have the potential to improve psychological rehabilitation, and should therefore be considered by clinicians for the treatment of ICU-related psychological sequelae after COVID-19.

Annotation

The finding:
This is the first report from a series of studies these Dutch investigators are conducting into virtual reality interventions to improve psychiatric outcomes after critical illness (in patients and family members). The patient described had a very positive outcome with this novel intervention.

Strength and weaknesses:
This is a case report – not randomized, uses a single patient, so on. However, the authors share a lot of information regarding the development of their intervention. If this approach is shown useful in randomized trials, it is easy to imagine proliferation of similar interventions after critical illness, especially among those at high risk of poor outcomes (e.g., with early emotional distress post-ICU).

Relevance:
Virtual reality is another tool that may allow patients and family members to process what occurred during the critical illness and intensive care. This tool could have a major public health impact and improve long-term mental health outcomes.

Type of study (EBM guide):
Case series or report