Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.

PURPOSE: Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its' optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock. METHODS: In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days. RESULTS: Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration. CONCLUSION: In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871 , June 25, 2020, retrospectively registered.

Lung ultrasound response to awake prone positioning predicts the need for intubation in patients with COVID-19 induced acute hypoxemic respiratory failure: an observational study.

BACKGROUND: Awake prone positioning (APP) reduces the intubation rate in COVID-19 patients treated by high-flow nasal cannula (HFNC). However, the lung aeration response to APP has not been addressed. We aimed to explore the lung aeration response to APP by lung ultrasound (LUS). METHODS: This two-center, prospective, observational study enrolled patients with COVID-19-induced acute hypoxemic respiratory failure treated by HFNC and APP. LUS score was recorded 5-10 min before, 1 h after APP, and 5-10 min after supine in the first APP session within the first three days. The primary outcome was LUS score changes in the first three days. Secondary outcomes included changes in SpO2/FiO2 ratio, respiratory rate and ROX index (SpO2/FiO2/respiratory rate) related to APP, and the rate of treatment success (patients who avoided intubation). RESULTS: Seventy-one patients were enrolled. LUS score decreased from 20 (interquartile range [IQR] 19-24) to 19 (18-21) (p < 0.001) after the first APP session, and to 19 (18-21) (p < 0.001) after three days. Compared to patients with treatment failure (n = 20, 28%), LUS score reduction after the first three days in patients with treatment success (n = 51) was greater (- 2.6 [95% confidence intervals - 3.1 to - 2.0] vs 0 [- 1.2 to 1.2], p = 0.001). A decrease in dorsal LUS score > 1 after the first APP session was associated with decreased risk for intubation (Relative risk 0.25 [0.09-0.69]). APP daily duration was correlated with LUS score reduction in patients with treatment success, especially in dorsal lung zones (r = - 0.76; p < 0.001). CONCLUSIONS: In patients with acute hypoxemic respiratory failure due to COVID-19 and treated by HFNC, APP reduced LUS score. The reduction in dorsal LUS scores after APP was associated with treatment success. The longer duration on APP was correlated with greater lung aeration. Trial registration This study was prospectively registered on clinicaltrials.gov on April 22, 2021. Identification number NCT04855162 .