Physicians' attitudes and perceptions of neuromuscular blocker infusions in ARDS

INTRODUCTION: With the COVID pandemic, and recently updated practice guidelines for neuromuscular infusion (NMBI) use during ARDS, the practices/perceptions of ICU physicians regarding NMBI use during ARDS may not be evidence-based. METHODS: We developed, tested, and electronicallyadministered a questionnaire (9 questions/70 subquestions) to medical and surgical ICU fellow and attending physicians at 3 geographically-diverse U.S. health systems (U Arizona, U Chicago, Mass General Brigham). The IRB-approved questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2 < 150) with critical hypoxemia where dyssynchrony causes were addressed and PEEP optimized. Weekly reminders were sent twice. RESULTS: Respondents [173/342(50.5%)] primarily worked as an attending 117(75%) in a medical ICU 94(60%) for 12±8 weeks/year. COVID+ ARDS patients were twice as likely to receive a NMBI (56±37 vs. 28±19%;p< 0.01). Respondents somewhat/strongly agreed a NMBI: should be reserved until after a trial of deep sedation 142 (82%) or proning 59 (34%), be dose-titrated based on trainof- four monitoring 107(62%);and effectively reduced dyssynchrony 149(86%), plateau pressure 106(62%) and barotrauma 102(60%). Few respondents [23(18%)] somewhat/strongly agreed a NMBI should be initiated at ARDS onset 20(12%) or administered at a fixed-dose 12(7%). Only 2/14 potential NMBI risks were frequently reported to be of high/very high concern: prolonged muscle weakness during steroids 135(79%) and paralysis awareness due to inadequate sedation 114(67%). Only absence of dyssynchrony 146(87%) was frequently reported to be a very/extremely important NMBI titration target. Train-of-four 78(46%) and BIS 39(23%) monitoring and plateau pressure 67(40%) or PaO2:FiO2 64(38%) evaluation were deemed less important. Absence of dysschrony 93(56%) and use ≥48 hours 87(53%) were preferred NMBI stopping criteria. For COVID+ patients, few felt reduced self-extubation and COVID aerosolization during reintubation 16(9%) or reduced ventilator adjustments 7(5%) were very/extremely important reasons for NMBI use. CONCLUSIONS: Most physicians agree NMBI infusions in ARDS should be reserved until after trials of deep sedation. Paralysis awareness and prolonged muscle weakness are the greatest NMBI use concerns. Unique considerations in COVID+ ARDS patients exist.

Mitigation of COVID-19 exposure during intubation of a patient with a difficult airway

Introduction: The Society of Critical Care Medicine (SCCM);endorse early intubation for COVID-19 patients with a FiO2 of greater > 0.40. Bag mask ventilation (BMV) is not recommended for fear of aerosol generated particles (AGP) exposure. Personnel protective equipment (PPE), N95 mask and eye protection is mandatory! Before intubation, the patient is administered high concentrations of oxygen to breathe, when the SpO2 increases to greater than > 97%, the advance airway providers (AAP) administers sedation. Once sedated, the AAP will perform a rapid sequence intubation (RSI) and place the patient on mechanical ventilator (MV).Case Review: A 41 year old male with a history for hypertension was admitted as a person under investigation (PUI) to a general nursing unit. Laboratory results confirmed that he was positive for COVID-19. He was on a 6 L/min nasal cannula = 0.44 with a SpO2 - 93 to 94% and abnormal breathing;28 to 30 breaths/min. His provider team called to have him intubated. He was administered higher oxygen concentrations to breathe via face mask, his SpO2 increased to 97 - 98%. Sedation was administered. Intubation with a Glide-Scope was attempted;after several failed attempts, SpO2 decreased to < 60%. BMV with a viral filter (VF) was implemented to mitigate provider and environmental exposure. The filter had an efficiency rating of 99.9% for filtering a virus and bacteria, which connected directly onto the resuscitation bag mask. He was successfully ventilated with a resuscitation bag and mask, SpO2 returned to 95-96%. He was successfully intubated;he was then transported to a COVID-19 cohort unit via ventilator with close suction and VF-heat moisture exchanger (HME). Conclusion: Our institutional review team reviewed this case and made modifications to intubate immediately order to consider risk to benefit for stable versus unstable and what actions should be taken into consideration;current location, need for additional staff, equipment and transporting the patient. Additional VF are now a part of standard operating procedure (SOP) for mechanical ventilation transport and available for BMV. Viral filters are important during unexpected airway crisis, especially for patient's diagnosed with COVID-19.

Helmet noninvasive ventilation versus high flow nasal cannula for COVID-19 related acute hypoxemic respiratory failure

RATIONALE: A high percentage of patients with Covid-19 associated acute hypoxemic respiratory failure (AHRF) receive invasive mechanical ventilation, which is associated with a high mortality. Noninvasive ventilation (NIV) offers an alternative to invasive mechanical ventilation, though its role in both de novo AHRF and pandemic viral pneumonia has been controversial. Our group has previously demonstrated that NIV delivered by helmet reduces endotracheal intubation rates and improves mortality in patients with acute respiratory distress syndrome when compared to facemask NIV in a randomized controlled clinical trial (1). Limited data are available on the comparative efficacy of noninvasive respiratory support strategies in patients with AHRF due to Covid-19. NIV by helmet interface offers a promising strategy for these patients and may avert the need for endotracheal intubation. METHODS: All patients with Covid-19 associated AHRF admitted to the intensive care unit and managed initially with noninvasive respiratory support between March 1 and July 31, 2020 were identified. Those who received helmet NIV were matched with patients who received HFNC (high flow nasal cannula) using propensity scores in a 1:1 ratio without replacement. Baseline characteristics and therapies that differed on univariable analysis were used for matching. After matching, univariable analysis was conducted comparing the HFNC and helmet NIV groups. RESULTS: 78 patients initially managed with HFNC and 31 patients managed with helmet NIV (excluding 7 patients who received helmet NIV after intubation) were identified. Matching resulted in similar groups according to baseline characteristics and therapies received. The primary composite outcome of intubation or inhospital mortality occurred in 20 (64.5%) patients in the helmet group and 20 (64.5%) patients in the control group (absolute difference, 0%;95% CI,-23.4% to 23.4%;p=1.00). In-hospital mortality in the helmet NIV group was similar to that of the HFNC control group (absolute difference-9.7%;95% CI,-34.4% to 15.0%;p=0.45). In patients treated with helmet NIV, gas exchange improved significantly following application with an increase in the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen from 72 to 141 (mean difference, 69;95% CI 26 to 112;p=0.003). CONCLUSIONS: While limited by the small sample size and observational nature, there was no significant difference observed in outcomes of patients with Covid-19 associated AHRF managed with helmet NIV compared to HFNC. After application of helmet NIV, a significant improvement in gas exchange was observed. REFERENCES: 1. Patel BK, et al. JAMA, 2016.

Long-term psychological and cognitive outcomes of patients with COVID-19

Rationale: Intensive care unit (ICU) survivorship has well documented physical disability1,2 psychological sequelae, and cognitive dysfunction3,4 all combined under the umbrella of Post-Intensive Care Syndrome (PICS). The COVID-19 pandemic is concerning for overwhelming health care resources in the short-term, but the longterm consequences of this large cohort of patients surviving critical illness remains ill-defined. It also remains unclear if the unique context of health care delivery such as lack of visitors and cohorting patients during the pandemic exacerbates the psychological and cognitive impairments of PICS. Methods: All patients admitted to the ICU with COVID-19 were eligible for enrollment in this prospective observational study. We performed a global assessment of cognitive function (using the Montreal Cognitive Assessment tool (T-MoCA)), posttraumatic stress disorder (using the Impact event scale (IES-Revised)), and depression/anxiety (using Hospital Anxiety and Depression scale (HADS)) in ICU survivors at 6 months after hospital discharge. Interviews were conducted via telephone or in-person when possible. Results: From April 10, 2020 thru November 17th, 2020 one hundred patients were enrolled upon hospital discharge. Eighty-two patients reached the 6-month milestone after hospital discharge and 22 (26.8%) of these patients required invasive mechanical ventilation. Of this eligible cohort, seven patients died, two were cognitively unable to complete the evaluations, four refused to participate, and thirteen were lost to follow-up. Fifty-six patients completed the evaluation with 74.7% follow-up (56/75 alive patients). Symptoms of probable post-traumatic stress disorder were reported in 2 patients (3.6%). Depression and Anxiety was reported in 5 patients (8.9%) respectively. Cognitive impairment was present in 47.3% of patients with a median T-MoCA score of 18 [15.5-19]. There was no difference in T-MoCA scores based on whether patients required invasive mechanical ventilation (IMV) (IMV 17 [15-20.5] vs not intubated 18 [16-19];p=0.89). Conclusions: Our preliminary long-term follow-up data suggest that symptoms of post-traumatic stress after COVID-19 infection are rare. In addition, less than 10% of patients reported anxiety and depression six months after hospital discharge. Interestingly, cognitive impairment as measured by T-MOCA was present in almost half of the patients. Further follow-up on the long term effects of COVID-19 related critical illness is warranted as we adapt during this pandemic.

Feasibility of physical and occupational therapy in critically ill patients with COVID-19 infection

Rationale:Early mobilization and physical rehabilitation improve functional outcomes and are essential to high quality critical care. Despite its importance, it is common for rehabilitation to be deferred in the critically ill due to a variety of barriers, including infection with SARS-CoV-2. We present a single academic center's experience providing physical and occupational therapy to critically ill patients infected with SARS-CoV-2. Methods:All patients with Coronavirus Disease 2019 (COVID-19) associated illness admitted to the intensive care unit (ICU) from March 1st to July 31st, 2020 were identified in this retrospective chart review. Patients who received at least one therapy treatment session were included in the study. Results:Three-hundred and seventy-nine physical and occupational therapy sessions were conducted with 116 patients. The majority (85%) of patients were admitted to the ICU for hypoxemic respiratory failure. The median number of treatment sessions during ICU admission per patient was 2, (IQR: 1-4). The median time from ICU admission to first PT session was 4 days (IQR, 3-5). The median percentage of ICU days with physical and occupational therapy treatment was 33% (IQR, 21-50). The median session length was 25 minutes (IQR, 25-30min). Sitting was achieved in 353 sessions, (93%) standing was achieved in 261 sessions (69%), walking was achieved in 185 sessions (48%), and sitting in the bedside chair 118 times (31%).Patients with respiratory failure completed therapy sessions while receiving mechanical ventilation (21% of sessions), high flow nasal cannula (45% of sessions), non-invasive positive pressure ventilation by helmet and facemask (7% of sessions), and ECMO (12% of sessions). Patients requiring vasoactive medications (4%) and continuous renal replacement therapy (6%) were also treated by physical and occupational therapy. Delirium, determined by confusion assessment method (CAM-ICU), was frequently encountered by the physical and occupational therapy teams and was not an absolute barrier (32%) (Table 1). Discharge destinations included: home (n=57, 61%), acute rehabilitation units (n=16, 17%), long term acute care hospitals (n=9, 10%), sub-acute care centers (n=8, 8%), and skilled nursing facilities (n=4, 4%). No members of the therapy team were diagnosed with SARS-CoV-2 during the study period. Conclusions:This report demonstrates the feasibility of conducting physical and occupational therapy in COVID-19 specific ICUs. Providing therapy services appeared to be safe for patients and members of the therapy team, as adverse events were rare and no therapist was diagnosed with COVID-19.

Predictors of mortality in COVID 19 associated respiratory failure among predominantly African American patients

Rationale:Patients with COVID-19 frequently develop severe respiratory disease and may require invasive mechanical ventilation. A study of primarily white patients intubated for COVID-19 associated respiratory failure found predictors of 28-day mortality to be respiratory system compliance, age, tidal volume, arterial pH and heart rate. Little is known about the outcomes of minority populations with severe COVID-19 pneumonia. Therefore, we present an analysis of the predictors of mortality in a group of primarily African American patients with COVID-19 associated respiratory failure. Methods:All adult patients admitted to the University of Chicago COVID-19 intensive care unit receiving invasive mechanical ventilation between March 1st and June 31st, 2020 were identified. Patients were included in the study if they had at least one recorded measure of plateau airway pressure while receiving volume-controlled ventilation allowing determination of driving pressure and lung compliance. Univariable analysis was conducted comparing survivors with those who died in-hospital followed by construction of a multivariable logistic regression model predicting in-hospital mortality based on significant factors from univariable analysis, excluding colinear variables. Results:Eighty-five patients were included in this retrospective study. Patients were primarily African American (n=73, 86%). Among all study patients, median tidal volume was 6.0 cc/kg ideal body weight (IQR 5.8-6.2), PEEP was 8 cm H2O (IQR 5.0-10), and driving pressure was 14 cm H2O (IQR 11-16). Median respiratory system compliance was 27 ml/cm H2O (IQR 21-34). Salvage therapies for refractory hypoxemia in the cohort included prone positioning (27%), paralysis (27%), inhaled pulmonary vasodilators (19%), and extracorporeal membrane oxygenation (1%). In the multivariable logistic regression model, age (OR 1.077, 95% CI 1.031 to 1.125, p=0.001) and driving pressure (OR 1.174, 95% CI 1.009 to 1.366, p=0.038) were found to be independent predictors of mortality. Conclusions:In a predominantly African American patient population with COVID-19 pneumonia requiring invasive mechanical ventilation, higher driving pressure was predictive of overall mortality. These finding are consistent with the work of Botta et al (2020), who demonstrated reduced lung compliance was predictive of mortality among a largely white group of patients with severe COVID-19 pneumonia. While minority populations infected with COVID-19 have been found worse outcomes, early lung mechanics appear to be comparable to white patients. These findings support that higher driving pressures and low lung compliance are indicative of serious lung injury which may lead to death.

Functional and quality of life outcomes of critically ill covid-19 survivors at hospital discharge and six months

RATIONALE: Survivors of critical illness are at risk for long-term physical disability and poor quality of life. Changes in health care delivery, such as visitor restrictions and limited availability of therapy services coupled with economic hardship due to the COVID-19 pandemic may exacerbate these long-term consequences. Methods: Patients with respiratory failure requiring advanced respiratory support (endotracheal tube, noninvasive ventilation, or high-flow nasal cannula) and/or shock admitted to the intensive care unit (ICU) with COVID-19 were eligible for enrollment in this prospective observational study. We assessed quality of life (using short form-36 [SF-36]), work status, and independence in activities of daily living (ADLs) in survivors at hospital discharge and 6 months. Quality of life scores were compared to US population norms. An SF-36 score ≥50 is the population norm for both physical and mental scores;scores <45 define significant physical or mental health impairment. Patients underwent assessment for ICU-acquired weakness (ICU-AW) and functional impairment (using Functional Status Score for the ICU (FSS-ICU)) by physical and occupational therapists upon hospital discharge. An FSS-ICU score ≥28 is associated with discharge to home. Analysis of changes over time for the quality of life assessment were performed using paired t-test and tests of proportions. Results: 100 patients were enrolled from April to November 2020. On hospital discharge, 39% of patients had ICU-AW. The median FSS-ICU score on discharge was 24 [20-29], consistent with functional impairment. Fifty-six patients completed the 6-month evaluation with 74.7% follow-up (56/75 alive patients). Mental health impairment was reported by 33% of patients on hospital discharge and declined to 13% at 6 months (p=0.007). Physical health impairment was reported by 70% at discharge and persisted in 46% of patients at 6 months (p=0.007). Patients were independent in ADLs at both hospital admission and 6 months post discharge (90 vs 91%). Only 56% of patients who had been working prior to hospitalization had returned to work at 6 months. Conclusions: Impairments in quality of life and neuromuscular weakness were present at hospital discharge in a significant number of ICU survivors of COVID-19. Similar to the trajectory described in survivors of acute respiratory distress syndrome, despite relatively normal mental health quality of life, persistent physical health impairment was noted in almost half of the survivors at 6 months. Further investigation of the long-term effects of COVID-19 related critical illness and its distinction from post-ICU syndromes from non-COVID-19 critical illness is warranted.

Psychological and cognitive outcomes of critically ill covid-19 patients at hospital discharge

RationaleThe novel coronavirus, COVID-19, can cause critical illness in up to 5% of infected patients. Although the sequelae of surviving critical illness are known, limited data exist regarding the psychological and cognitive outcomes specifically in survivors of COVID-19. Given the social isolation, scarcity of multidisciplinary staff, and socio-economic impact of the pandemic, understanding the cognitive and psychological impact of surviving critical illness due to COVID-19 is of utmost importance. MethodsA prospective observational cohort study at an academic medical center enrolled critically ill patients with confirmed COVID-19 infection. Upon hospital discharge, cognitive and psychological sequelae were measured using the following validated assessments: Montreal Cognitive Assessment (MoCA), Impact of Event Score (IES), and the Hospital Anxiety and Depression scale (HADS). Cognitive impairment was defined as a MoCA score <26. Probable post-traumatic stress disorder (PTSD) was defined as an IES score >32. Significant symptoms of anxiety and depression were defined as a HADS subscale score of ≥8. ResultsFrom April 10, 2020 through November 17, 2020, 100 adult critically ill patients were enrolled, of which 27 were invasively mechanically ventilated. Eighty-nine patients underwent cognitive and psychological evaluation upon hospital discharge. Of the 11 patients who did not complete the evaluation, 2 died prior to discharge, 4 had significant cognitive impairment, 2 were discharged prior to survey completion, and 3 refused. Cognitive impairment was present in 93% of patients (n=83) with a median MoCA score of 17 [13-22]. Patients with cognitive impairment tended to be older (62 years old [53-71] vs 50 [41-58];p=0.17). Ten patients (11%) had probable PTSD with a median IES score of 4 [0-17] in the overall cohort. Seventeen patients (19%) reported significant depressive symptoms and twenty patients (22%) noted significant symptoms of anxiety. ConclusionPrior coronavirus outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) were associated with anxiety, depression, impaired memory and confusion occurring in approximately one-third of patients at hospital discharge. In contrast, cognitive impairment in ICU survivors of COVID-19 infection was nearly universal on hospital discharge. This impairment is not completely explained by coexistent psychiatric symptoms of anxiety or depression, which were present in only one-fifth of the ICU survivors.

Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial.

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.