Impact of Timing of Tocilizumab Use in Hospitalized Patients With SARS-CoV-2 Infection.

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to be a global challenge due to the lack of definitive treatment strategies. We sought to determine the efficacy of early administration of anti-interleukin 6 therapy in reducing hospital mortality and progression to mechanical ventilation. METHODS: This was a retrospective chart review of 11,512 patients infected with SARS-CoV-2 who were admitted to a New York health system from March to May 2020. Tocilizumab was administered to subjects at the nasal cannula level of oxygen support to maintain an oxygen saturation of >88%. The Charlson comorbidity index was used as an objective assessment of the burden of comorbidities to predict 10-year mortality. The primary outcome of interest was hospital mortality. Secondary outcomes were progression to mechanical ventilation; the prevalence of venous thromboembolism and renal failure; and the change in C-reactive protein, D-dimer, and ferritin levels after tocilizumab administration. Propensity score matching by using a 1:2 protocol was used to match the tocilizumab and non-tocilizumab groups to minimize selection bias. The groups were matched on baseline demographic characteristics, including age, sex, and body mass index; Charlson comorbidity index score; laboratory markers, including ferritin, D-dimer, lactate dehydrogenase, and C-reactive protein values; and the maximum oxygen requirement at the time of tocilizumab administration. Mortality outcomes were evaluated based on the level of oxygen requirement and the day of hospitalization at the time of tocilizumab administration. RESULTS: The overall hospital mortality was significantly reduced in the tocilizumab group when tocilizumab was administered at the nasal cannula level (10.4% vs 22.0%; P = .002). In subjects who received tocilizumab at the nasal cannula level, the progression to mechanical ventilation was reduced versus subjects who were initially on higher levels of oxygen support (6.3% vs 18.7%; P < .001). There was no improvement in mortality when tocilizumab was given at the time of requiring non-rebreather, high-flow nasal cannula, noninvasive ventilator, or invasive ventilator. CONCLUSIONS: Early use of anti-interleukin 6 therapy may be associated with improved hospital mortality and reduction in progression to more severe coronavirus disease 2019.

High-Flow, Noninvasive Ventilation and Awake (Nonintubation) Proning in Patients With Coronavirus Disease 2019 With Respiratory Failure.

The coronavirus disease 2019 pandemic will be remembered for the rapidity with which it spread, the morbidity and mortality associated with it, and the paucity of evidence-based management guidelines. One of the major concerns of hospitals was to limit spread of infection to health-care workers. Because the virus is spread mainly by respiratory droplets and aerosolized particles, procedures that may potentially disperse viral particles, the so-called "aerosol-generating procedures" were avoided whenever possible. Included in this category were noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and awake (nonintubated) proning. Accordingly, at many health-care facilities, patients who had increasing oxygen requirements were emergently intubated and mechanically ventilated to avoid exposure to aerosol-generating procedures. With experience, physicians realized that mortality of invasively ventilated patients was high and it was not easy to extubate many of these patients. This raised the concern that HFNC and NIV were being underutilized to avoid intubation and to facilitate extubation. In this article, we attempt to separate fact from fiction and perception from reality pertaining to the aerosol dispersion with NIV, HFNC, and awake proning. We describe precautions that hospitals and health-care providers must take to mitigate risks with these devices. Finally, we take a practical approach in describing how we use the three techniques, including the common indications, contraindications, and practical aspects of application.

Update in Management of Severe Hypoxemic Respiratory Failure.

Mortality related to severe-moderate and severe ARDS remains high. We searched the literature to update this topic. We defined severe hypoxemic respiratory failure as Pao2/Fio2 < 150 mm Hg (ie, severe-moderate and severe ARDS). For these patients, we support setting the ventilator to a tidal volume of 4 to 8 mL/kg predicted body weight (PBW), with plateau pressure (Pplat) ≤ 30 cm H2O, and initial positive end-expiratory pressure (PEEP) of 10 to 12 cm H2O. To promote alveolar recruitment, we propose increasing PEEP in increments of 2 to 3 cm provided that Pplat remains ≤ 30 cm H2O and driving pressure does not increase. A fluid-restricted strategy is recommended, and nonrespiratory causes of hypoxemia should be considered. For patients who remain hypoxemic after PEEP optimization, neuromuscular blockade and prone positioning should be considered. Profound refractory hypoxemia (Pao2/Fio2 < 80 mm Hg) after PEEP titration is an indication to consider extracorporeal life support. This may necessitate early transfer to a center with expertise in these techniques. Inhaled vasodilators and nontraditional ventilator modes may improve oxygenation, but evidence for improved outcomes is weak.

Clinical significance of increased lipase levels on admission to the ICU.

STUDY OBJECTIVES: To examine the incidence, risk factors, and sequelae associated with asymptomatic hyperlipasemia in the ICU. SETTING: Medical and surgical ICUs. PATIENTS: Two hundred forty-five adult critically ill patients admitted to an ICU for > 72 h with a diagnosis other than pancreatitis were studied prospectively. MEASUREMENTS: Serum amylase and lipase were measured on ICU admission and every third day until normalized. Clinical parameters including the incidence of ileus, the ability to tolerate enteral feeds, and the results of radiologic studies were also recorded. RESULTS: Hyperlipasemia was present in 40% of patients (peak, 1,183 +/- 175 U/L; range, 209 to 8,620 U/L) [mean +/- SEM]. Increased multiple-organ dysfunction scores, hypotension, anemia, mechanical ventilation (MV), bacteremia, elevated liver function test results, and elevated creatinine and triglyceride levels were all associated with increased lipase levels. In multivariate analysis, hypotension, anemia, elevated serum bilirubin, and MV were independently associated with higher lipase levels. Although mortality was not different, ICU length of stay and the duration of MV were significantly greater in patients with increased lipase levels (p < 0.05). Fifty patients underwent imaging studies. Pancreatitis was confirmed in 11 patients. The mean peak lipase value was significantly increased in patients with a positive study finding as compared to those with negative findings: 2,231 +/- 715 U/L and 900 +/- 234 U/L, respectively (p < 0.01). Enteral feedings, when initiated, were tolerated in 94% of patients with increased lipase levels and 97% of patients with normal lipase levels. CONCLUSIONS: Elevated serum lipase levels are frequently encountered in critically ill patients. In the majority of these patients, enteral feedings are well tolerated and there are minimal clinical sequelae. Extremely high lipase levels may be associated with radiologic evidence of pancreatitis. Hypoperfusion and inflammatory processes associated with multiple-organ failure appear to be contribute to these increases.