Remdesivir for Patients Hospitalized with COVID-19 Severe Pneumonia: A National Cohort Study (Remdeco-19).

BACKGROUND: Given the rapidly evolving pandemic of COVID-19 in 2020, authorities focused on the repurposing of available drugs to develop timely and cost-effective therapeutic strategies. Evidence suggested the potential utility of remdesivir in the framework of an early access program. REMDECO-19 is a multicenter national cohort study assessing the ability of remdesivir to improve the outcome of patients hospitalized with COVID-19. METHODS: We conducted a retrospective real-life study that included all patients from the early access program of remdesivir in France. The primary endpoint was the clinical course evolution of critically ill and hospitalized COVID-19 patients treated with remdesivir. Secondary endpoints were the SOFA score evolution within 29 days following the admission and mortality at 29 and 90 days. RESULTS: Eighty-five patients were enrolled in 22 sites from January to April 2020. The median WHO and SOFA scores were respectively reduced by two and six points between days 1 and 29. Improvement in the WHO-CPS and the SOFA score were observed in 83.5% and 79.3% of patients, respectively, from day 10. However, there was no effect of remdesivir on the 90-day survival based on the control cohort for hospitalized COVID-19 patients with invasive ventilation. CONCLUSIONS: SOFA score appeared to be an attractive approach to assess remdesivir efficacy and stratify its utilization or not in critically ill patients with COVID-19. This study brings a new clinical benchmark for therapeutic decision making and supports the use of remdesivir for some hospitalized COVID-19 patients.

Evaluation of pressure in water-filled endotracheal tube cuffs in intubated patients undergoing hyperbaric oxygen treatment.

INTRODUCTION: Inflating endotracheal tube cuffs using water instead of air before hyperbaric oxygen treatment (HBOT) is common. The objective of this study was to assess cuff pressure (Pcuff), when the cuff was inflated using water, in normobaric conditions and during HBOT. METHODS: This was a prospective, observational study taking place in hyperbaric centre and intensive care unit of the University Hospital of Lille. Every patient who required tracheal intubation and HBOT at 253.3 kPa (2.5 atmospheres absolute [atm abs]) was included. Pcuff was measured using a pressure transductor connected to the cuff inflating port. Measurements were performed at 'normobaria' (1 atm abs) and during HBOT at 2.5 atm abs. RESULTS: Thirty patients were included between February and April 2016. Recordings were analysable in 27 patients. Mean Pcuff at normobaria was 60.8 (SD 42) cmH2O. Nineteen (70%) of patients had an excessive Pcuff (higher than 30 cmH2O). Coefficient of variation was 69%. Mean Pcuff at 2.5 atm abs was 51.6 (40.7) cmH2O, significantly lower than at normobaria (P < 0.0001). Coefficient of variation was 79%. In only five (18%) patients was Pcuff < 20 cmH2O at 2.5 atm abs. CONCLUSIONS: In normobaric conditions, when the cuff was inflated using water and not specifically controlled Pcuff was not predictable. The cuff was typically over-inflated exceeding safe pressure. During HBOT Pcuff decreased slightly.

Time course of central venous-to-arterial carbon dioxide tension difference in septic shock patients receiving incremental doses of dobutamine.

PURPOSE: To assess the time course of the central venous-arterial carbon dioxide tension difference (∆PCO2)-as an index of the carbon dioxide production (VCO2)/cardiac index (CI) ratio-in stable septic shock patients receiving incremental doses of dobutamine. METHODS: Twenty-two hemodynamically stable septic shock patients with no signs of global tissue hypoxia, as testified by normal blood lactate levels, were prospectively included. A dobutamine infusion was administered at a dose of up to 15 µg/kg/min in increments of 5 µg/kg/min every 30 min. Complete hemodynamic and gas measurements were obtained at baseline, and at each dose of dobutamine. RESULTS: Dobutamine induced a significant dose-dependent increase of CI from 0 to 15 µg/kg/min (P < 0.001). Oxygen consumption (VO2) and VCO2 were progressively increased by dobutamine. These increases were more marked between 10 and 15 µg/kg/min (8.3 and 8.6 %, respectively) than between the lower doses. ∆PCO2 and oxygen extraction (EO2) significantly decreased between 0 (8.0 ± 2.0 mmHg and 43.8 ± 13.4 %, respectively) and 10 µg/kg/min of dobutamine (4.2 ± 1.6 mmHg and 28.9 ± 7.9 %, respectively), but remained unchanged from 10 to 15 µg/kg/min (5.4 ± 2.4 mmHg and 29.5 ± 8.2 %, respectively). The central venous oxygen saturation significantly (ScvO2) increased from 0 to 10 µg/kg/min and remained unchanged from 10 to 15 µg/kg/min. Time courses of ∆PCO2, ScvO2, and EO2 were linked therefore to the biphasic changes of VO2 and VCO2. CONCLUSION: ∆PCO2 is a good indicator of the change of VCO2 induced by dobutamine. Measurement of ∆PCO2, along with ScvO2 and EO2, may be presented as a useful tool to assess the adequacy of oxygen supply versus metabolic and oxygen demand.

Greater prognostic value of peak VO2 after exercise training program completion in heart failure patients.

BACKGROUND: Exercise capacity, best reflected by peak exercise oxygen consumption (peak VO(2)), is a powerful prognostic factor in patients with chronic heart failure (CHF). However, the optimal time to assess exercise capacity for prognosis remains unclear and whether an exercise training program (ETP) to improve exercise capacity alters the prognostic value of cardiopulmonary exercise (CPX) testing variables in CHF is unknown. METHODS AND RESULTS: CHF patients who underwent an ETP in two cardiac rehabilitation centers between 2004 and 2009 were prospectively included, and CPX testing was performed before and after ETP completion. We included 285 consecutive patients who underwent an ETP (19.4 ± 8.7 training sessions in 4 to 10 weeks), including segmental gymnastics and cycling sessions. During follow-up (12 months), 14 patients died, 6 underwent cardiac transplantation and 15 were hospitalized for acute heart failure. Univariate analysis and receiver operating characteristic (ROC) curve analysis showed that CPX variables, especially peak oxygen consumption and circulatory power (product of peak VO(2) × peak systolic blood pressure) before and after ETP completion predicted prognosis. However, CPX data obtained after ETP completion had the best prognostic value (area under the ROC curve = 0.79 ± 0.03 for peak VO(2) after ETP completion vs 0.64 ± 0.04 before ETP completion, p < 0.0001). The results did not change even when considering only deaths. CONCLUSION: In patients with stable CHF who can exercise, the prognostic value of CPX data seems greater after versus before completion of a hospital-based ETP. Therefore, CPX capacity for prognostic purposes should at best be assessed after cardiac rehabilitation.

The repeatability of Stewart's parameters and anion gap in a cohort of critically ill adult patients.

PURPOSE: To examine the repeatability of Stewart's parameters and anion gap in a cohort of critically ill patients and to determine the smallest detectable changes in individual patients. METHODS: A total of 161 patients were included prospectively. They underwent two subsequent blood samplings within 10 min of each other and samples were analyzed using the same central laboratory analyzer. Measured and calculated parameters from the two samples were compared. The repeatability was expressed as the smallest detectable difference (SDD), coefficient of variation (CV) and intraclass correlation coefficient (ICC). RESULTS: The mean differences ± SD (mEq/L) for the repeated measurements were 0.1 ± 0.76, 0.12 ± 0.68, -0.02 ± 1.02, and -0.08 ± 1.05 for the apparent strong ion difference (SID(app)), effective strong ion difference (SID(eff)), strong ion gap (SIG), and albumin-corrected anion gap (AG(corr)), respectively. The SDDs (mEq/L) for SID(app), SID(eff), SIG, and AG(corr), were ±1.49, ±1.33, ±2, and ±2.06, respectively. The CVs (%) for these variables were 1.4, 1.45, 13.3, and 4.15, respectively. The ICCs for all these variables were high, largely above 0.75. CONCLUSIONS: The repeatability of all these calculated variables was good. In repeated measurements, a change in value of these parameters exceeding 1.96√2 CV (%), the least significant change (LSC) or the SDD should be regarded as significant. Use of SDD is preferable to CV and LSC (%) because of its independence from the levels of variables and its expression in absolute units. Expressed as SDD, a SIG change value, e.g., of at least ±2 mEq/L should be significant.