OBJECTIVES: Increasing evidence has suggested the benefits of dexmedetomidine in patients with sepsis. Dexmedetomidine may increase vasopressor sensitivity, which may be of interest in the setting of refractory septic shock. The α2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS) pilot study aimed to evaluate the effect of dexmedetomidine on the vasopressor response in patients with refractory septic shock. DESIGN: This study was a multicenter, randomized, placebo-controlled, double-blind pilot trial. SETTING: The study was conducted in 5 ICUs in France. PATIENTS: Inclusion criteria were septic shock (Sepsis-3 definition) and norepinephrine requirement greater than or equal to 0.25 µg/kg/min (0.5 µg/kg/min of norepinephrine tartrate) with persistent circulatory failure (defined by lactate > 2 mmol/L, oliguria, or skin mottling) and invasive mechanical ventilation. INTERVENTIONS: The arterial pressure response to phenylephrine was measured before starting the treatment (0 hr), at 6 hours (primary outcome), and 12 hours. In the treatment arm, dexmedetomidine was given at a fixed dose of 1 µg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Inclusions were stopped early because of higher mortality in the dexmedetomidine arm. Thirty-two patients of the 36 planned were included. Response to phenylephrine at 6 hours was lower in the dexmedetomidine group than in the placebo group (1.26 ± 0.23 vs. 1.45 ± 0.26; p = 0.048), although this difference was also observed at baseline (p = 0.029). There were no significant differences between the groups in terms of cumulative norepinephrine dose, lactatemia, Sequential Organ Failure Assessment score, fluid balance, ventilation-free days, or occurrence of bradycardia. Mortality on day 3 was higher in the dexmedetomidine group than in the placebo group, with a difference that diminished and was no longer significant on 30 and 90 days. CONCLUSIONS: Patients in the dexmedetomidine arm had a significantly lower response to phenylephrine at all study times including baseline, which might have contributed to higher early mortality in the dexmedetomidine arm and preclude to conclude on dexmedetomidine efficacy in refractory septic shock. However, heart rate was not decreased in the dexmedetomidine arm.

Postextubation respiratory failure (PRF) frequently complicates weaning from mechanical ventilation and may increase morbidity/mortality. Noninvasive ventilation (NIV) alternating with high-flow nasal oxygen (HFNO) may prevent PRF. Ventilated patients without chronic obstructive pulmonary disease (COPD) and at high-risk of PRF defined as a lung ultrasound score (LUS) ≥ 14 assessed during the spontaneous breathing trial, were included in a French-Chinese randomised controlled trial. PRF was defined by 2 among the following signs: SpO2 < 90%; Respiratory rate > 30 /min; hypercapnia; haemodynamic and/or neurological disturbances of respiratory origin. In the intervention group, prophylactic NIV alternating with HFNO was administered for 48 h following extubation. In the control group, conventional oxygen was used. Clinicians were informed on the LUS in the intervention group, those in the control group remained blind. The primary outcome was the incidence of PRF 48 h after extubation. Secondary outcomes were incidence of PRF and reintubation at day 7, number of ventilator-free days at day 28, length of ICU stay and mortality at day 28 and 90. Two hundred and forty patients were randomised and 227 analysed (intervention group = 128 and control group = 99). PRF at H48 was reduced in the intervention group compared to the control group: relative risk 0.52 (0.31 to 0.88), p = 0.01. The benefit persisted at day 7: relative risk 0.62 (0.44 to 0.96), p = 0.02. Weaning failure imposing reconnection to mechanical ventilation was not reduced. In patients who developed PRF and were treated by rescue NIV, reintubation was avoided in 44% of control patients and in 12% of intervention patients (p = 0.008). Other secondary outcomes were not different between groups. From a resource utilisation standpoint, prophylactic NIV alternating with HFNO was more demanding and costly than conventional oxygen with rescue NIV to achieve same clinical outcome. Compared to conventional oxygenation, prophylactic NIV alternating with HFNO significantly reduced postextubation respiratory failure but failed to reduce reintubation rate and mortality in patients without COPD at high risk of extubation failure. Prophylactic NIV alternating with HFNO was as efficient as recue NIV to treat postextubation respiratory failure.

Background: Elevated plasma levels of glucagon-like peptide-1 (GLP-1) have been associated with poor clinical outcome in patients with sepsis. This study investigated the association between GLP-1 levels, and survival at 90 days in a large cohort of critically ill patients. Methods: All patients aged ≥ 18 years admitted to the intensive care unit (ICU) in a large university hospital, and receiving ≥1 life support therapy for organ failure were eligible for inclusion. Plasma samples were taken within 24h of ICU admission. We measured GLP-1 using a commercial ELISA kit. Cumulative probability of death at 90 days (D90) was plotted using the Kaplan-Meier method by quartiles of GLP-1. The effect of GLP-1 quartile on D90 survival was analyzed using a Cox proportional hazards model. Results: A total of 507 patients had GLP-1 dosage; mean age 64.5 ± 14.5 years; 179 (35.3%) women. GLP-1 levels ranged from 0.03 to 129.2 (median 7.3[IQR:3.3;19.1]). Higher mean age, SOFA, SAPS II, and LPS 3HM were found in patients with higher GLP-1 quartile by univariate analysis. Overall, 229 patients (45.2%) died within 90 days. The cumulative probability of death was significantly associated with GLP-1 quartile (p log rank<0.0001). After adjustment for age, SOFA, renal replacement therapy and vasopressor treatment, a significantly increased risk was observed only for patients with the highest quartile of GLP-1 (adjusted hazard ratio 1.65 [1.06; 2.56] for 4^th vs 1^st quartile of GLP-1). Conclusion: After adjusting for demographic and clinical characteristics, only the highest quartile of GLP-1 remained independently associated with an increased risk of death at 90 days after admission to ICU.

Postintensive care syndrome (PICS) encompasses physical, psychological, and cognitive sequelae following an intensive care unit (ICU) stay, with repercussi

The emergence of the new SARS-CoV-2 in December 2019 caused a worldwide pandemic of the resultant disease, COVID-19. There was a massive surge in admissions to intensive care units (ICU), notably of patients with hypoxaemic acute respiratory failure. In these patients, optimal oxygen therapy was crucial. In this article, we discuss tracheal intubation to provide mechanical ventilation in patients with hypoxaemic acute respiratory failure due to SARS-CoV-2. We first describe the pathophysiology of respiratory anomalies leading to acute respiratory distress syndrome (ARDS) due to infection with SARS-CoV-2, and then briefly review management, focusing particularly on the ventilation strategy. Overall, the ventilatory management of ARDS due to SARS-CoV-2 infection is largely the same as that applied in ARDS from other causes, and lung-protective ventilation is recommended. The difference lies in the initial clinical presentation, with profound hypoxaemia often observed concomitantly with near-normal pulmonary compliance.