Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread use of hydroxychloroquine and azithromycin despite the lack of conclusive evidence for their safety and efficacy. We evaluated the association between treatment with hydroxychloroquine and/or azithromycin and hospital mortality as the primary outcome. We compared the hospital mortality of patients treated with hydroxychloroquine alone, azithromycin alone, or their combination to the mortality of patients who received neither drug. A logistic multivariate model with overlap weight propensity score was used for estimation of odds ratios (ORs) with 95% confidence intervals (95% CIs). One thousand four hundred and three patients with SARS-CoV-2 infection were admitted to the hospital. At the time of the analysis, the outcome was available for 1376 (98%) of them. Five hundred and eighty-seven patients (42%) received azithromycin and 377 patients (27%) received hydroxychloroquine, alone or in combination. In-hospital mortality was 26%. After the adjusted analysis, azithromycin alone was associated with lower mortality (OR 0.60, 95% CI 0.42-0.85) compared to no treatment. Hydroxychloroquine alone (OR 0.76, 95% CI 0.53-1.08) and the combination of azithromycin and hydroxychloroquine (OR 1.13, 95% CI 0.77-1.69) were not associated with hospital mortality. In this cohort of patients, azithromycin alone was associated with lower hospital mortality but hydroxychloroquine was not associated with increased or reduced mortality. While we await randomized clinical trials, these data support the use of azithromycin in novel coronavirus disease 2019 (COVID-19) and can contribute to better understanding of its role in further meta-analyses.

Cardiac index and oxygen delivery during low and high tidal volume ventilation strategies in patients with acute respiratory distress syndrome: a crossover randomized clinical trial.

INTRODUCTION: The beneficial effect of low tidal volume (TV) ventilation strategy on mortality in patients with acute respiratory distress syndrome (ARDS) has been attributed to the protective effect on ventilator-induced lung injury, and yet its effect on cardiovascular function might also play an important role. The aim of this study was to assess whether low TV ventilation improves cardiac output and oxygen delivery compared with high TV ventilation strategy in patients with ARDS. METHODS: In this crossover randomized clinical trial 16 ARDS patients were recruited in an intensive care unit at a university-affiliated hospital. Each patient was ventilated for 30 min with low (6 mL/kg) and 30 min with high (12 mL/kg) TV. The two experimental periods, applied in random order and with allocation concealment, were separated by 30 min of basal ventilation. Minute ventilation was constantly maintained by appropriate respiratory rate changes. RESULTS: Compared with high TV ventilation, low TV ventilation showed decreased pH (7.37 vs. 7.41, P = 0.001) and increased PaCO2 (49 vs. 43 mmHg; P = 0.002). Cardiac index and oxygen delivery index were increased with low compared with high TV ventilation (3.9 vs. 3.5 L.min⁻¹.m⁻², P = 0.012, and 521 vs. 463 mL.min⁻¹.m⁻², P = 0.002, respectively), while oxygen extraction ratio decreased (0.36 vs. 0.44, P = 0.027). In four patients oxygen extraction ratio was >0.5 during high TV but not during low TV strategy. The magnitude of the change in cardiac index was positively associated with PaCO2 variation (P = 0.004), while it was unrelated to the magnitude of changes in TV and airway pressure. The decrease of cardiac index was predicted by PaCO2 reduction, with and area under ROC curve of 0.72. CONCLUSIONS: Our findings suggest that a low TV ventilation strategy increases cardiac index and oxygen delivery, thus supporting the hypothesis that the beneficial effect of low TV ventilation in patients with ARDS could be partially explained by hemodynamic improvement. In other words, low tidal volume ventilation could be protective also for the cardiovascular system and not only for the lung. The slight increase of PaCO2 during low TV ventilation seems to predict the increase of cardiac index. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00713713.

Prediction of arterial pressure increase after fluid challenge.

BACKGROUND: Mean arterial pressure above 65 mmHg is recommended for critically ill hypotensive patients whereas they do not benefit from supranormal cardiac output values. In this study we investigated if the increase of mean arterial pressure after volume expansion could be predicted by cardiovascular and renal variables. This is a relevant topic because unnecessary positive fluid balance increases mortality, organ dysfunction and Intensive Care Unit length of stay. METHODS: Thirty-six hypotensive patients (mean arterial pressure < 65 mmH) received a fluid challenge with hydroxyethyl starch. Patients were excluded if they had active bleeding and/or required changes in vasoactive agents infusion rate in the previous 30 minutes. Responders were defined by the increase of mean arterial pressure value to over 65 mmHg or by more than 20% with respect to the value recorded before fluid challenge. Measurements were performed before and at one hour after the end of fluid challenge. RESULTS: Twenty-two patients (61%) increased arterial pressure after volume expansion. Baseline heart rate, arterial pressure, central venous pressure, central venous saturation, central venous to arterial PCO2 difference, lactate, urinary output, fractional excretion of sodium and urinary sodium/potassium ratio were similar between responder and non-responder. Only 7 out of 36 patients had valuable dynamic indices and then we excluded them from analysis. When the variables were tested as predictors of responders, they showed values of areas under the ROC curve ranging between 0.502 and 0.604. Logistic regression did not reveal any association between variables and responder definition. CONCLUSIONS: Fluid challenge did not improve arterial pressure in about one third of hypotensive critically ill patients. Cardiovascular and renal variables did not enable us to predict the individual response to volume administration. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00721604.

Remifentanil improves breathing pattern and reduces inspiratory workload in tachypneic patients.

BACKGROUND: Properly titrated opiates decrease respiratory rate but do not affect tidal volume or induce respiratory acidosis. OBJECTIVE: To determine whether remifentanil improves breathing pattern or reduces inspiratory effort in patients with acute respiratory failure and tachypnea or rapid shallow breathing. METHODS: We studied 14 patients who developed tachypnea and/or rapid shallow breathing if the pressure support level was reduced. During pressure support ventilation, each patient received 30-min infusions, separated by 30 min, of remifentanil and placebo. Measurements were obtained before commencing and before stopping each infusion, and after 3 min of unassisted breathing. The main outcomes were rapid shallow breathing index and change in pressure-time product. RESULTS: Remifentanil did not significantly affect tidal volume. During pressure support ventilation, remifentanil infusion reduced respiratory rate, pressure-time product, and cardiovascular double product (heart rate × systolic arterial pressure) without modifying the sedation score. Mean P(aCO(2)) showed a small and clinically negligible increase during remifentanil, but P(aCO(2)) increased more in the hypercapnic patients than in the normocapnic patients. Remifentanil reduced the rapid shallow breathing index after 3 min of unassisted breathing. CONCLUSIONS: Remifentanil improved respiratory pattern and decreased inspiratory muscles effort in patients with tachypnea or rapid shallow breathing, but did not affect oxygenation or sedation. Though the acid-base balance did not show clinically relevant changes on average, we cannot exclude the possibility that remifentanil might prolong weaning in hypercapnic patients. (Clinical-Trials.gov registration NCT00665119.)