Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial.

PURPOSE: Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia. METHODS: In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score (< or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28. RESULTS: Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups. CONCLUSION: In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.

Macrophage Activation in COVID-19 Patients in Intensive Care Unit.

We report six cases of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, admitted to intensive care unit (ICU), for whom bone marrow aspirate revealed hemophagocytosis. We compared their clinical presentation and laboratory findings to those that can be encountered during a hemophagocytic lymphohistiocytosis. These observations might evoke a macrophage activation mechanism different from the one encountered in the hemophagocytic lymphohistiocytosis (HLH).

Characterization of pulmonary impairment associated with COVID-19 in patients requiring mechanical ventilation. / Caracterização do comprometimento pulmonar associado à COVID-19 em pacientes com necessidade de ventilação mecânica.

OBJECTIVE: To detect early respiratory and hemodynamic instability to characterize pulmonary impairment in patients with severe COVID-19. METHODS: We retrospectively analyzed data collected from COVID-19 patients suffering from acute respiratory failure requiring intubation and mechanical ventilation. We used transpulmonary thermodilution assessment with a PiCCO™ device. We collected demographic, respiratory, hemodynamic and echocardiographic data within the first 48 hours after admission. Descriptive statistics were used to summarize the data. RESULTS: Fifty-three patients with severe COVID-19 were admitted between March 22nd and April 7th. Twelve of them (22.6%) were monitored with a PiCCO™ device. Upon admission, the global-end diastolic volume indexed was normal (mean 738.8mL ± 209.2) and moderately increased at H48 (879mL ± 179), and the cardiac index was subnormal (2.84 ± 0.65). All patients showed extravascular lung water over 8mL/kg on admission (17.9 ± 8.9). We did not identify any argument for cardiogenic failure. CONCLUSION: In the case of severe COVID-19 pneumonia, hemodynamic and respiratory presentation is consistent with pulmonary edema without evidence of cardiogenic origin, favoring the diagnosis of acute respiratory distress syndrome.

OBJETIVO: Detectar precocemente a instabilidade respiratória e hemodinâmica para caracterizar o comprometimento pulmonar em pacientes com COVID-19 grave. MÉTODOS: Analisamos retrospectivamente os dados colhidos de pacientes com COVID-19 que apresentaram insuficiência respiratória aguda com necessidade de intubação e ventilação mecânica. Utilizamos a avaliação da termodiluição transpulmonar por meio do dispositivo PiCCO™. Foram coletados os dados demográficos, respiratórios, hemodinâmicos e ecocardiográficos dentro das primeiras 48 horas após a admissão. Para resumir os dados, utilizamos estatística descritiva. RESULTADOS: Entre 22 de março e 7 de abril de 2020, foram admitidos 23 pacientes com COVID-19 grave. Foram monitorados com o dispositivo PiCCO™ 12 (22,6%) deles. Quando da admissão, o volume diastólico final global indexado era normal (média de 738,8mL ± 209,2) e, na hora 48, encontrava-se moderadamente aumentado (879mL ± 179), enquanto o índice cardíaco se achava abaixo do normal (2,84 ± 0,65). Todos os pacientes revelaram a presença de água extravascular pulmonar acima de 8mL/kg na admissão (17,9 ± 8,9). Não identificamos qualquer evidência de origem cardiogênica. CONCLUSÃO: No caso de pneumonia grave por COVID-19, o quadro hemodinâmico e respiratório é compatível com edema pulmonar sem evidência de origem cardiogênica, o que favorece o diagnóstico de síndrome do desconforto respiratório agudo.