Extracorporeal membrane oxygenation versus invasive ventilation in patients with COVID-19 acute respiratory distress syndrome and pneumomediastinum: A cohort trial.

BACKGROUND: Patients with severe respiratory failure due to COVID-19 who are not under mechanical ventilation may develop severe hypoxemia when complicated with spontaneous pneumomediastinum (PM). These patients may be harmed by invasive ventilation. Alternatively, veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) may be applied. We report on the efficacy of V-V ECMO and invasive ventilation as initial advanced respiratory support in patients with COVID-19 and acute respiratory failure due to spontaneous PM. METHODS: This was a retrospective cohort study performed between March 2020 and January 2022. Enrolled patients had COVID-19 and acute respiratory failure due to spontaneous PM and were not invasively ventilated. Patients were treated in the intensive care unit (ICU) with invasive ventilation (invasive ventilation group) or V-V ECMO support (V-V ECMO group) as the main therapeutic option. The primary outcomes were mortality and ICU discharge at 90 days after ICU admission. RESULTS: Twenty-two patients were included in this study (invasive ventilation group: 13 [59%]; V-V ECMO group: 9 [41%]). The V-V ECMO strategy was significantly associated with lower mortality (hazard ratio [HR] 0.33 [95% CI 0.12-0.97], p = 0.04). Five (38%) patients in the V-V ECMO group were intubated and eight (89%) patients in the invasive ventilation group required V-V ECMO support within 30 days from ICU admission. Three (33%) patients in the V-V ECMO group were discharged from ICU within 90 days compared to one (8%) patient in the invasive ventilation group (HR 4.71 [95% CI 0.48-45.3], p = 0.18). CONCLUSIONS: Preliminary data suggest that V-V ECMO without invasive ventilation may improve survival in COVID-19-related acute respiratory failure due to spontaneous PM. The study's retrospective design and limited sample size underscore the necessity for additional investigation and warrant caution.

Evaluating the efficacy of a standardized 4 mL/kg fluid bolus technique in critically ill patients with elevated PvaCO2: secondary analysis of two prospective studies.

Background: Limiting the fluid bolus (FB) volume may attenuate side effects, including hemodilution and increased filling pressures, but it may also reduce hemodynamic responsiveness. The minimum volume to create hemodynamic effects is considered to be 4 mL/kg. In critically ill patients, the hemodynamic effects of FB with this volume have not been adequately investigated and compared to higher quantities. We hypothesized that a standardized FB approach using 4 mL/kg has comparable hemodynamic and metabolic effects to the common practice of physician-determined FB in critically ill patients. Methods: We conducted post hoc analysis of two trials in non-selected critically ill patients with central venous-to-arterial CO2 tension (PvaCO2) >6 mmHg and no acute bleeding. All patients received crystalloids either at a physician-determined volume and rate or at 4 mL/kg pump-administered at 1.2 L/h. Cardiac index (CI) was calculated with transthoracic echocardiogram, and arterial and venous blood gas samples were assessed before and after FB. Endpoints were changes in CI and oxygen delivery (DO2) >15%. Results: A total of 47 patients were eligible for the study, 15 of whom received physician-determined FB and 32 of whom received standardized FB. Patients in the physician-determined FB group received 16 (12-19) mL/kg at a fluid rate of 1.5 (1.5-1.9) L/h, compared to 4.1 (3.7-4.4) mL/kg at a fluid rate of 1.2 (1.2-1.2) L/h (p < 0.01) in the standardized FB group. The difference in CI elevations between the two groups was not statistically significant (8.8% [-0.1-19.9%] vs. 8.4% [0.3-23.2%], p = 0.76). Compared to physician-determined FB, the standardized FB technique had similar probabilities of increasing CI or DO2 by >15% (odds ratios: 1.3 [95% CI: 0.37-5.18], p = 0.66 and 1.83 [95% CI: 0.49-7.85], p = 0.38). Conclusion: A standardized FB protocol (4 mL/kg at 1.2 L/h) effectively reduced the volume of fluid administered to critically ill patients without compromising hemodynamic or metabolic effects.

Ammonia and nutritional therapy in the critically ill: when to worry, when to test and how to treat?

PURPOSE OF REVIEW: Hyperammonaemia is almost always develops in patients with severe liver failure and this remains the commonest cause of elevated ammonia concentrations in the ICU. Nonhepatic hyperammonaemia in ICU presents diagnostic and management challenges for treating clinicians. Nutritional and metabolic factors play an important role in the cause and management of these complex disorders. RECENT FINDINGS: Nonhepatic hyperammonaemia causes such as drugs, infection and inborn errors of metabolism may be unfamiliar to clinicians and risk being overlooked. Although cirrhotic patients may tolerate marked elevations in ammonia, other causes of acute severe hyperammonaemia may result in fatal cerebral oedema. Any coma of unclear cause should prompt urgent measurement of ammonia and severe elevations warrant immediate protective measures as well as treatments such as renal replacement therapy to avoid life-threatening neurological injury. SUMMARY: The current review explores important clinical considerations, the approach to testing and key treatment principles that may prevent progressive neurological damage and improve outcomes for patients with hyperammonaemia, especially from nonhepatic causes.

Existing and emerging therapies for the treatment of invasive candidiasis and candidemia.

INTRODUCTION: Invasive candidiasis or candidemia is a severe infection affecting more than 250,000 people worldwide every year. It is present in up to 16% of ICU patients. The prognosis of these infections is unfavorable, with global death estimated around 50,000 per year, which corresponds to up to 40% depending on patient severity and comorbidities. Therapeutic failure is not rare due to the emergence of multiresistant strains and of new species poorly responsive to current therapies like Candida auris. AREAS COVERED: We first review the positioning of antifungal drugs used to treat candidiasis, namely polyenes, azoles, echinocandins and pyrimidine analogues. We then discuss the progresses brought by new formulations, new derivatives within these classes, compounds acting on new targets or repurposed drugs in terms of pharmacokinetic profile, spectrum of activity, potency, safety or risk of drug-drug interactions. EXPERT OPINION: While new formulations (amphotericin B cochleate) improve oral bioavailability of the corresponding drugs, new azoles or echinocandins offer higher potency including against strains resistant to former generations of drugs. Repurposed drugs show synergism with current therapies in vitro. Results from ongoing and future clinical trials will be decisive to establish the interest for these drugs in our arsenal.