Monitoring of sedation in mechanically ventilated patients using remote technology.

PURPOSE OF REVIEW: Two years of coronavirus disease 2019 (COVID-19) pandemic highlighted that excessive sedation in the ICU leading to coma and other adverse outcomes remains pervasive. There is a need to improve monitoring and management of sedation in mechanically ventilated patients. Remote technologies that are based on automated analysis of electroencephalogram (EEG) could enhance standard care and alert clinicians real-time when severe EEG suppression or other abnormal brain states are detected. RECENT FINDINGS: High rates of drug-induced coma as well as delirium were found in several large cohorts of mechanically ventilated patients with COVID-19 pneumonia. In patients with acute respiratory distress syndrome, high doses of sedatives comparable to general anesthesia have been commonly administered without defined EEG endpoints. Continuous limited-channel EEG can reveal pathologic brain states such as burst suppression, that cannot be diagnosed by neurological examination alone. Recent studies documented that machine learning-based analysis of continuous EEG signal is feasible and that this approach can identify burst suppression as well as delirium with high specificity. SUMMARY: Preventing oversedation in the ICU remains a challenge. Continuous monitoring of EEG activity, automated EEG analysis, and generation of alerts to clinicians may reduce drug-induced coma and potentially improve patient outcomes.

An examination of sedation requirements and practices for mechanically ventilated critically ill patients with COVID-19.

PURPOSE: Preliminary reports suggest that critically ill patients with coronavirus disease 2019 (COVID-19) infection requiring mechanical ventilation may have markedly increased sedation needs compared with critically ill, mechanically ventilated patients without COVID-19. We conducted a study to examine sedative use for this patient population within multiple intensive care units (ICUs) of a large academic medical center. METHODS: A retrospective, single-center cohort study of sedation practices for critically ill patients with COVID-19 during the first 10 days of mechanical ventilation was conducted in 8 ICUs at Massachusetts General Hospital, Boston, MA. The study population was a sequential cohort of 86 critically ill, mechanically ventilated patients with COVID-19. Data characterizing the sedative medications, doses, drug combinations, and duration of administration were collected daily and compared to published recommendations for sedation of critically ill patients without COVID-19. The associations between drug doses, number of drugs administered, baseline patient characteristics, and inflammatory markers were investigated. RESULTS: Among the study cohort, propofol and hydromorphone were the most common initial drug combination, with these medications being used on a given day in up to 100% and 88% of patients, respectively. The doses of sedative and analgesic infusions increased for patients over the first 10 days, reaching or exceeding the upper limits of published dosage guidelines for propofol (48% of patients), dexmedetomidine (29%), midazolam (7.7%), ketamine (32%), and hydromorphone (38%). The number of sedative and analgesic agents simultaneously administered increased over time for each patient, with more than 50% of patients requiring 3 or more agents by day 2. Compared with patients requiring 3 or fewer agents, patients requiring more than 3 agents were of younger age, had an increased body mass index, had increased serum ferritin and lactate dehydrogenase concentrations, had a lower Pao2:Fio2 (ratio of arterial partial pressure of oxygen to fraction of inspired oxygen), and were more likely to receive neuromuscular blockade. CONCLUSION: Our study confirmed the clinical impression of elevated sedative use in critically ill, mechanically ventilated patients with COVID-19 relative to guideline-recommended sedation practices in other critically ill populations.

Standard Sedation and Sedation With Isoflurane in Mechanically Ventilated Patients With Coronavirus Disease 2019.

OBJECTIVES: To describe sedative and analgesic drug utilization in a cohort of critically ill patients with coronavirus disease 2019 and compare standard sedation with an alternative approach using inhaled isoflurane. DESIGN: This was a retrospective cohort study designed to compare doses of sedatives between ICU patients receiving standard IV sedation and patients receiving mixed sedation including inhaled isoflurane. Data were obtained from electronic medical records. SETTING: ICU at large academic medical center where mechanical ventilation was delivered with Draeger Apollo (Draeger Medical, Telford, PA) anesthesia machines. PATIENTS: Consecutive adult patients (≥ 18 yr) with confirmed coronavirus disease 2019 admitted to ICU between April 2, 2020, and May 4, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-five mechanically ventilated patients were included in the study, with a mean (sd) age of 59.4 (12.8) years. Twenty-three patients (65.7%) were men. Seventeen patients (48.6%) received standard IV sedation, whereas 18 (51.4%) also received isoflurane. The mean duration of mechanical ventilation (sd) was 23.3 (11.6) days in the standard sedation group and 23.8 (12.5) days in the isoflurane group. Mean (sd) duration of isoflurane exposure was 5.61 (2.99) days, representing 29.1% of total sedation time (sd, 20.4). Cumulative opioid exposure did not differ between the standard sedation and isoflurane sedation groups (mean morphine milligram equivalent 6668 [sd, 1,346] vs 6678 [sd, 2,000] mg). However, the initiation of isoflurane in patients was associated with decreased utilization of propofol (mean daily amount 3,656 [sd, 1,635] before vs 950 [sd, 1,804] mg during isoflurane) and hydromorphone (mean daily amount 48 [sd, 30] before vs 23 [sd, 27] mg). CONCLUSIONS: In the subjects that received isoflurane, its use was associated with significant decreases in propofol and hydromorphone infusions.

Hyperoxia and modulation of pulmonary vascular and immune responses in COVID-19.

Oxygen is the most commonly used therapy in hospitalized patients with COVID-19. In those patients who develop worsening pneumonia and acute respiratory distress syndrome (ARDS), high concentrations of oxygen may need to be administered for prolonged time periods, often together with mechanical ventilation. Hyperoxia, although lifesaving and essential for maintaining adequate oxygenation in the short term, may have adverse long-term consequences upon lung parenchymal structure and function. How hyperoxia per se impacts lung disease in COVID-19 has remained largely unexplored. Numbers of experimental studies have previously established that hyperoxia is associated with deleterious outcomes inclusive of perturbations in immunologic responses, abnormal metabolic function, and alterations in hemodynamics and alveolar barrier function. Such changes may ultimately progress into clinically evident lung injury and adverse remodeling and result in parenchymal fibrosis when exposure is prolonged. Given that significant exposure to hyperoxia in patients with severe COVID-19 may be unavoidable to preserve life, these sequelae of hyperoxia, superimposed on the cytopathic effects of SARS-CoV-2 virus, may well impact pathogenesis of COVID-19-induced ARDS.

SARS-CoV-2 viral load is associated with increased disease severity and mortality.

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.