Hypoxia-inducible factor (HIF1α) gene expression in human shock states.

INTRODUCTION: Hypoxia-inducible factor-1 (HIF1) controls the expression of genes involved in the cellular response to hypoxia. No information is available on its expression in critically ill patients. Thus, we designed the first clinical study in order to evaluate the role of HIF1α as a prognosis marker in patients with shock. METHODS: 50 consecutive adult patients with shock and 11 healthy volunteers were prospectively included. RNA was extracted from whole blood samples and expression of HIF1α was assessed over the first 4 hours of shock. The primary objective was to assess HIF1α as a prognostic marker in shock. Secondary objectives were to evaluate the role of HIF1α as a diagnostic and follow-up marker. Patient survival was evaluated at day 28. RESULTS: The causes of shock were sepsis (78%), hemorrhage (18%), and cardiac dysfunction (4%). The HIF1α expression was significantly higher in the shock patients than in the healthy volunteers (121 [72-168] vs. 48 [38-54] normalized copies, p < 0.01), whatever the measured isoforms. It was similar in non-survivors and survivors (108 [range 84-183] vs. 121 [range 72-185] normalized copies, p = 0.92), and did not significantly change within the study period. CONCLUSIONS: The present study is the first to demonstrate the increased expression of HIF1α in patients with shock. Further studies are needed to clarify the potential association with outcome. Our findings reinforce the value of monitoring plasma lactate levels to guide the treatment of shock.

Effect of open-lung vs conventional perioperative ventilation strategies on postoperative pulmonary complications after on-pump cardiac surgery: the PROVECS randomized clinical trial.

PURPOSE: To evaluate whether a perioperative open-lung ventilation strategy prevents postoperative pulmonary complications after elective on-pump cardiac surgery. METHODS: In a pragmatic, randomized, multicenter, controlled trial, we assigned patients planned for on-pump cardiac surgery to either a conventional ventilation strategy with no ventilation during cardiopulmonary bypass (CPB) and lower perioperative positive end-expiratory pressure (PEEP) levels (2 cm H2O) or an open-lung ventilation strategy that included maintaining ventilation during CPB along with perioperative recruitment maneuvers and higher PEEP levels (8 cm H2O). All study patients were ventilated with low-tidal volumes before and after CPB (6 to 8 ml/kg of predicted body weight). The primary end point was a composite of pulmonary complications occurring within the first 7 postoperative days. RESULTS: Among 493 randomized patients, 488 completed the study (mean age, 65.7 years; 360 (73.7%) men; 230 (47.1%) underwent isolated valve surgery). Postoperative pulmonary complications occurred in 133 of 243 patients (54.7%) assigned to open-lung ventilation and in 145 of 245 patients (59.2%) assigned to conventional ventilation (p = 0.32). Open-lung ventilation did not significantly reduce the use of high-flow nasal oxygenotherapy (8.6% vs 9.4%; p = 0.77), non-invasive ventilation (13.2% vs 15.5%; p = 0.46) or new invasive mechanical ventilation (0.8% vs 2.4%, p = 0.28). Mean alive ICU-free days at postoperative day 7 was 4.4 ± 1.3 days in the open-lung group vs 4.3 ± 1.3 days in the conventional group (mean difference, 0.1 ± 0.1 day, p = 0.51). Extra-pulmonary complications and adverse events did not significantly differ between groups. CONCLUSIONS: A perioperative open-lung ventilation including ventilation during CPB does not reduce the incidence of postoperative pulmonary complications as compared with usual care. This finding does not support the use of such a strategy in patients undergoing on-pump cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02866578. https://clinicaltrials.gov/ct2/show/NCT02866578.

Closed loop ventilation mode in Intensive Care Unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes.

BACKGROUND: There is an equipoise regarding closed-loop ventilation modes and the ability to reduce workload for providers. On one hand some settings are managed by the ventilator but on another hand the automatic mode introduces new settings for the user. METHODS: This randomized controlled trial compared the number of manual ventilator setting changes between a full closed loop ventilation and oxygenation mode (INTELLiVENT-ASV®) and conventional ventilation modes (volume assist control and pressure support) in Intensive Care Unit (ICU) patients. The secondary endpoints were to compare the number of arterial blood gas analysis, the sedation dose and the user acceptance. Sixty subjects with an expected duration of mechanical ventilation of at least 48 hours were randomized to be ventilated using INTELLiVENT-ASV® or conventional modes with a protocolized weaning. All manual ventilator setting changes were recorded continuously from inclusion to successful extubation or death. Arterial blood gases were performed upon decision of the clinician in charge. User acceptance score was assessed for nurses and physicians once daily using a Likert Scale. RESULTS: The number of manual ventilator setting changes per 24 h-period per subject was lower in INTELLiVENT-ASV® as compared to conventional ventilation group (5 [4-7] versus 10 [7-17]) manuals settings per subject per day [P<0.001]). The number of arterial blood gas analysis and the sedation doses were not significantly different between the groups. Nurses and physicians reported that INTELLiVENT-ASV® was significantly easier to use as compared to conventional ventilation (P<0.001 for nurses and P<0.01 for physicians). CONCLUSIONS: For mechanically ventilated ICU patients, INTELLiVENT-ASV® significantly reduces the number of manual ventilator setting changes with the same number of arterial blood gas analysis and sedation dose, and is easier to use for the caregivers as compared to conventional ventilation modes.