Molecular mechanisms of muscular and non-muscular actions of neuromuscular blocking agents in critical illness.

Despite frequent use of neuromuscular blocking agents in critical illness, changes in neuromuscular transmission with critical illness are not well appreciated. Recent studies have provided greater insights into the molecular mechanisms for beneficial muscular effects and non-muscular anti-inflammatory properties of neuromuscular blocking agents. This review summarises the normal structure and function of the neuromuscular junction and its transformation to a 'denervation-like' state in critical illness, the underlying cause of aberrant neuromuscular blocking agent pharmacology. We also address the important favourable and adverse consequences and molecular bases for these consequences during neuromuscular blocking agent use in critical illness. This review, therefore, provides an enhanced understanding of clinical therapeutic effects and novel pathways for the salutary and aberrant effects of neuromuscular blocking agents when used during acquired pathologic states of critical illness.

A Prospective Observational Study on Short and Long-Term Outcomes of COVID-19 Patients with Acute Hypoxic Respiratory Failure Treated with High-Flow Nasal Cannula.

(1) The use of high-flow nasal cannula (HFNC) combined with frequent respiratory monitoring in patients with acute hypoxic respiratory failure due to COVID-19 has been shown to reduce intubation and mechanical ventilation. (2) This prospective, single-center, observational study included consecutive adult patients with COVID-19 pneumonia treated with a high-flow nasal cannula. Hemodynamic parameters, respiratory rate, inspiratory fraction of oxygen (FiO2), saturation of oxygen (SpO2), and the ratio of oxygen saturation to respiratory rate (ROX) were recorded prior to treatment initiation and every 2 h for 24 h. A 6-month follow-up questionnaire was also conducted. (3) Over the study period, 153 of 187 patients were eligible for HFNC. Of these patients, 80% required intubation and 37% of the intubated patients died in hospital. Male sex (OR = 4.65; 95% CI [1.28; 20.6], p = 0.03) and higher BMI (OR = 2.63; 95% CI [1.14; 6.76], p = 0.03) were associated with an increased risk for new limitations at 6-months after hospital discharge. (4) 20% of patients who received HFNC did not require intubation and were discharged alive from the hospital. Male sex and higher BMI were associated with poor long-term functional outcomes.

Reduced Effective Oxygen Delivery and Ventilation with a Surgical Facemask Placed under Compared to over an Oxygen Mask: A Comparative Study.

OBJECTIVES: Consensus guidelines for perioperative anesthesia management during the COVID-19 pandemic recommend that patients wear a facemask in addition to their oxygen mask or nasal cannulae following tracheal extubation, where this is practical. The effects on effective oxygen delivery and ventilation of a surgical facemask under compared to over an oxygen (O2) mask are unclear. DESIGN: Single-center, comparative pilot study. Setting. Endoscopy procedure room at a major academic hospital. SUBJECTS: Five healthy anesthesiologists. Interventions. Using a carbon dioxide (CO2) sampling line positioned at the lips, the fraction of inspired O2 (FiO2), fraction of expiratory O2 (FeO2), expiratory end-tidal CO2 (EtCO2), and respiratory rate (RR) were measured under the following conditions: (1) a surgical facemask only, (2) a surgical facemask under an O2 mask, (3) an O2 mask only, and (4) a surgical facemask over an O2 mask. Measurements and Main Results. The sampled fractional expired oxygen (FeO2) at the lips was significantly lower when the surgical facemask was under compared to when over the O2 mask (27.9± 1.68 vs. 49.9 ± 6.27, p = 0.001), while there was no significant difference in inspired oxygen (FiO2). The sampled expiratory EtCO2 was significantly higher when the surgical facemask was under the O2 mask compared to when over the O2 mask (28.3 ± 8.5 vs. 23.5 ± 7.6, p = 0.026). The RR was not significantly different when the surgical facemask was under compared to over the O2 mask. CONCLUSIONS: Effective oxygen delivery and ventilation was reduced (lower FeO2 and increased EtCO2) when a surgical facemask was placed under compared to over an O2 mask.

Severe COVID pneumonia and undetectable B cells after vaccination in patients previously treated with rituximab: a case series.

INTRODUCTION: The risk of developing severe COVID-19 illness despite completing vaccination for patients who have previously received immunosuppressive therapy is unclear. CASE PRESENTATION: We present three patients who received rituximab for treatment of autoimmune disorders who subsequently developed severe COVID-19 pneumonia post-vaccination requiring intensive care unit admission and found to have undetectable B cells. DISCUSSION: While there have been concerns about the effectiveness of COVID-19 vaccines in this patient cohort, this is the first case series to report development of severe COVID-19 illness after completing vaccination in those who previously received rituximab. Guidelines for the optimal timing of COVID-19 vaccination in relation to immunosuppressive therapy have been recently published, albeit after many patients in this subpopulation have already been vaccinated. CONCLUSION: This case series brings attention to the limited humoral response to vaccines in patients treated with rituximab, highlights existing guidelines and their limitations, and raises future considerations about the potential benefits to testing vaccine responsiveness.

Teleguidance Technology for Endotracheal Intubation: A Scoping Review.

OBJECTIVES: Teleguidance facilitated intubation has recently reemerged during the coronavirus disease 2019 pandemic as a strategy to provide expert airway management guidance and consultation to practitioners in settings where such expertise is not readily available onsite or in-person. We conducted a scoping review to provide a synthesis of the available literature on teleguidance facilitated intubation. Specifically, we aimed to evaluate the feasibility, safety, and efficacy of teleguidance facilitated intubation given existing technology. DATA SOURCES: A librarian-assisted search was performed using three primary electronic medical databases from January 2000 to November 2020. STUDY SELECTION: Articles that reported outcomes focused on implementing or evaluating the performance of teleguidance facilitated intubation were included. DATA EXTRACTION: Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. DATA SYNTHESIS: Of 255 citations identified, 17 met eligibility criteria. Studies included prospective investigations and proof of technology reports. These studies were performed in clinical and simulation environments. Five of the prospective investigations that examined time to intubation and intubation success rates. Multiple different commercially available and noncommercial teleconference software systems were used in these studies. CONCLUSIONS: There is a limited body of literature evaluating the feasibility, safety, and efficacy of teleguidance facilitated intubation. Based on the studies available that examined a variety of technologies within simulation and clinical environments, teleguidance facilitated intubation appears to be feasible, safe, and efficacious. Given the exponential growth in the use of telemedicine technology during the coronavirus disease 2019 pandemic and the evidence supporting teleguidance facilitated intubation, there is a need to critically evaluate the most effective mechanisms to integrate and optimize these technologies across diverse practice settings.

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).

Rapid Expansion of the Airway Response Team to Meet the Needs of the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic has brought unprecedented numbers of patients with acute respiratory distress to medical centers. Hospital systems require rapid adaptation to respond to the increased demand for airway management while ensuring high quality patient care and provider safety. There is limited literature detailing successful system-level approaches to adapt to the surge of COVID-19 patients requiring airway management. METHODS: A deliberate system-level approach was used to expand a preexisting airway response service. Through a needs analysis (taking into account both existing resources and anticipated demands), we established priorities and solutions for the airway management challenges encountered during the pandemic. RESULTS: During our COVID-19 surge (March 10, 2020, through May 26, 2020), there were 619 airway consults, and the COVID airway response team (CART) performed 341 intubations. Despite a 4-fold increase in intubations during the surge, there was no increase in cardiac arrests or surgical airways and no documented COVID-19 infections among the CART. CONCLUSIONS: Our system-level approach successfully met the sudden escalation in demand in airway management incurred by the COVID-19 surge. The approach that addressed staffing needs prioritized provider protection and enhanced quality and safety monitoring may be adaptable to other institutions.

Nuts and bolts of COVID-19 associated coagulopathy: the essentials for management and treatment.

INTRODUCTION: COVID-19-associated coagulopathy (CAC) is a well-recognized hematologic complication among patients with severe COVID-19 disease, where macro- and micro-thrombosis can lead to multiorgan injury and failure. Major societal guidelines that have published on the management of CAC are based on consensus of expert opinion, with the current evidence available. As a result of limited studies, there are many clinical scenarios that are yet to be addressed, with expert opinion varying on a number of important clinical issues regarding CAC management. METHODS: In this review, we utilize current societal guidelines to provide a framework for practitioners in managing their patients with CAC. We have also provided three clinical scenarios that implement important principles of anticoagulation in patients with COVID-19. CONCLUSION: Overall, decisions should be made on acase by cases basis and based on the providers understanding of each patient's medical history, clinical course and perceived risk.

Individualized Multimodal Physiologic Approach to Mechanical Ventilation in Patients With Obesity and Severe Acute Respiratory Distress Syndrome Reduced Venovenous Extracorporeal Membrane Oxygenation Utilization.

OBJECTIVE: To investigate whether individualized optimization of mechanical ventilation through the implementation of a lung rescue team could reduce the need for venovenous extracorporeal membrane oxygenation in patients with obesity and acute respiratory distress syndrome and decrease ICU and hospital length of stay and mortality. DESIGN: Single-center, retrospective study at the Massachusetts General Hospital from June 2015 to June 2019. PATIENTS: All patients with obesity and acute respiratory distress syndrome who were referred for venovenous extracorporeal membrane oxygenation evaluation due to hypoxemic respiratory failure. INTERVENTION: Evaluation and individualized optimization of mechanical ventilation by the lung rescue team before the decision to proceed with venovenous extracorporeal membrane oxygenation. The control group was those patients managed according to hospital standard of care without lung rescue team evaluation. MEASUREMENT AND MAIN RESULTS: All 20 patients (100%) allocated in the control group received venovenous extracorporeal membrane oxygenation, whereas 10 of 13 patients (77%) evaluated by the lung rescue team did not receive venovenous extracorporeal membrane oxygenation. Patients who underwent lung rescue team evaluation had a shorter duration of mechanical ventilation (p = 0.03) and shorter ICU length of stay (p = 0.03). There were no differences between groups in in-hospital, 30-day, or 1-year mortality. CONCLUSIONS: In this hypothesis-generating study, individualized optimization of mechanical ventilation of patients with acute respiratory distress syndrome and obesity by a lung rescue team was associated with a decrease in the utilization of venovenous extracorporeal membrane oxygenation, duration of mechanical ventilation, and ICU length of stay. Mortality was not modified by the lung rescue team intervention.

Efficiency of Prolonged Prone Positioning for Mechanically Ventilated Patients Infected with COVID-19.

Hypoxemia of the acute respiratory distress syndrome can be reduced by turning patients prone. Prone positioning (PP) is labor intensive, risks unplanned tracheal extubation, and can result in facial tissue injury. We retrospectively examined prolonged, repeated, and early versus later PP for 20 patients with COVID-19 respiratory failure. Blood gases and ventilator settings were collected before PP, at 1, 7, 12, 24, 32, and 39 h after PP, and 7 h after completion of PP. Analysis of variance was used for comparisons with baseline values at supine positions before turning prone. PP for >39 h maintained PaO2/FiO2 (P/F) ratios when turned supine; the P/F decrease at 7 h was not significant from the initial values when turned supine. Patients turned prone a second time, when again turned supine at 7 h, had significant decreased P/F. When PP started for an initial P/F ≤ 150 versus P/F > 150, the P/F increased throughout the PP and upon return to supine. Our results show that a single turn prone for >39 h is efficacious and saves the burden of multiple prone turns, and there is no significant advantage to initiating PP when P/F > 150 compared to P/F ≤ 150.

An examination of gastrointestinal absorption using the acetaminophen absorption test in critically ill patients with COVID-19: A retrospective cohort study.

OBJECTIVE: Gastrointestinal (GI) dysfunction is prevalent in critically ill patients with coronavirus disease 2019 (COVID-19). The acetaminophen absorption test (AAT) has been previously described as a direct method for assessment of GI function. Our study determines whether the AAT can be used to assess GI function in critically ill COVID-19 patients, compared with traditional measures of GI function. DESIGN: Retrospective observational study of critically ill patients with COVID-19. SETTING: Three intensive care units at a tertiary care academic medical center. PATIENTS: Twenty critically ill patients with COVID-19. INTERVENTIONS: The results of AAT and traditional measures for assessing GI function were collected and compared. MEASUREMENTS AND MAIN RESULTS: Among the study cohort, 55% (11 of 20) of patients had evidence of malabsorption by AAT. Interestingly, all patients with evidence of malabsorption by AAT had clinical evidence of bowel function, as indicated by stool output and low gastric residuals during the prior 24 h. When comparing patients with a detectable acetaminophen level (positive AAT) with those who had undetectable acetaminophen levels (negative AAT), radiologic evidence of ileus was less frequent (20 vs 88%; P = .03), tolerated tube-feed rates were higher (40 vs 10 ml/h; P =.01), and there was a trend toward lower gastric residual volumes (45 vs 830 ml; P =.11). CONCLUSION: Malabsorption can occur in critically ill patients with COVID-19 despite commonly used clinical indicators of tube-feeding tolerance. The AAT provides a simple, rapid, and cost-effective mechanism by which enteral function can be efficiently assessed in COVID-19 patients.

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.

Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness.

BACKGROUND: Right ventricular (RV) dysfunction is common and associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19). In non-COVID-19 acute respiratory distress syndrome, RV dysfunction develops due to pulmonary hypoxic vasoconstriction, inflammation, and alveolar overdistension or atelectasis. Although similar pathogenic mechanisms may induce RV dysfunction in COVID-19, other COVID-19-specific pathology, such as pulmonary endothelialitis, thrombosis, or myocarditis, may also affect RV function. We quantified RV dysfunction by echocardiographic strain analysis and investigated its correlation with disease severity, ventilatory parameters, biomarkers, and imaging findings in critically ill COVID-19 patients. METHODS: We determined RV free wall longitudinal strain (FWLS) in 32 patients receiving mechanical ventilation for COVID-19-associated respiratory failure. Demographics, comorbid conditions, ventilatory parameters, medications, and laboratory findings were extracted from the medical record. Chest imaging was assessed to determine the severity of lung disease and the presence of pulmonary embolism. RESULTS: Abnormal FWLS was present in 66% of mechanically ventilated COVID-19 patients and was associated with higher lung compliance (39.6 vs 29.4 mL/cmH2O, P = 0.016), lower airway plateau pressures (21 vs 24 cmH2O, P = 0.043), lower tidal volume ventilation (5.74 vs 6.17 cc/kg, P = 0.031), and reduced left ventricular function. FWLS correlated negatively with age (r = -0.414, P = 0.018) and with serum troponin (r = 0.402, P = 0.034). Patients with abnormal RV strain did not exhibit decreased oxygenation or increased disease severity based on inflammatory markers, vasopressor requirements, or chest imaging findings. CONCLUSIONS: RV dysfunction is common among critically ill COVID-19 patients and is not related to abnormal lung mechanics or ventilatory pressures. Instead, patients with abnormal FWLS had more favorable lung compliance. RV dysfunction may be secondary to diffuse intravascular micro- and macro-thrombosis or direct myocardial damage. TRIAL REGISTRATION: National Institutes of Health #NCT04306393. Registered 10 March 2020, https://clinicaltrials.gov/ct2/show/NCT04306393.

Biplane Imaging Using Portable Ultrasound Devices for Vascular Access.

The use of ultrasound guidance for the placement of difficult IVs, arterial lines, and central venous access has become the standard of care. While imaging quality has improved over the last two decades, the lack of affordability, availability, and training have been major limitations in its routine clinical use. We detail the first reported use of biplane imaging using a portable ultrasound probe for difficult vascular access to increase first past success, efficiency, safety, and sterility during the coronavirus disease 2019 (COVID-19) pandemic.

Comparison of published guidelines for management of coagulopathy and thrombosis in critically ill patients with COVID 19: implications for clinical practice and future investigations.

Critically ill patients with COVID-19 are at increased risk for thrombotic complications which has led to an intense debate surrounding their anticoagulation management. In the absence of data from randomized controlled clinical trials, a number of consensus guidelines and recommendations have been published to facilitate clinical decision-making on this issue. However, substantive differences exist between these guidelines which can be difficult for clinicians. This review briefly summarizes the major societal guidelines and compares their similarities and differences. A common theme in all of the recommendations is to take an individualized approach to patient management and a call for prospective randomized clinical trials to address important anticoagulation issues in this population.