Servo i

Eighteen pigs (weight 31.5 ± 2.12 Kg; range 29 to 36 Kg) were induced [18 (link)], intubated with the aforementioned ETTs and connected to a mechanical ventilator (SERVO-I, Maquet, Fairfield, NJ USA). Internal ETT cuff pressure was maintained at 28 cm H₂0 through a mechanical device [19 (link)]. Anesthesia was maintained with a continuous infusion of midazolam, 0.2 to 0.8 mg/Kg/h, and fentanyl 5 to 10 μg/Kg/h, in order to maintain cessation of spontaneous movements, following painful stimulation. Pigs were ventilated in volume-control, square-wave inspiratory flow, inspiratory fraction of oxygen of 40%, duty cycle of 0.25, tidal volume 8 mL/Kg, without positive end-expiratory pressure (PEEP), and respiratory rate adjusted to maintain Pa_CO2 within the physiologic range. Inspiratory gases were conditioned through a heated humidifier (Conchatherm III, Hudson RCI, Temecula, CA, USA). Throughout the study, 50 mg/Kg of ceftriaxone was administered every 12 hours to prevent pulmonary colonization by endogenous pathogens. Endotracheal suctioning was performed every 6 hours or when clinically indicated. Importantly, saline was never instilled into the airways throughout the suction procedure. Quality of mucus (normal or purulent) was recorded. Body temperature and white blood cells count were assessed every 12 hours.

After animal preparation, lungs were ventilated mechanically with Servo‐i (MAQUET) via PCV or PSV (flow triggering) during which a researcher (E.B.C.) adjusted the driving pressure to V_T ≈ 6 ml/kg (PEEP = 3 cmH₂O and FiO₂ = 0.4). As PCV inherently requires neuromuscular blockade, animals in this group were paralyzed by intravenous administration of pancuronium bromide (1 mg/kg; Cristália). Pilot studies were performed in the CF strategy group to estimate the minimal amount of Ringer's lactate (B. Braun) required to maintain normovolemia (evaluated using echocardiography) and MAP ≥70 mmHg for 1 h in experimental ALI. The mean cumulative fluids infused in both the CF‐PCV and CF‐PSV groups were multiplied by 4 for the cumulative amount of fluid for LF; thus, the infusion rate was adjusted for the LF‐PSV and LF‐PCV groups for 1 h (n = 6 per group). The pilot procedure did not hinder the randomization of the animals. The study design and temporal evolution are summarized in Figure 1. At T₆₀, heparin was injected (1000 U i.v.), and the animals were euthanized by an intravenous overdose of sodium thiopental (60 mg/kg; Cristália). The trachea was clamped at PEEP = 3 cmH₂O, and the lungs and kidneys were removed en bloc for histology and molecular biology analysis.

This was a prospective, observational study performed in a surgical ICU at a university hospital. The noninterventional study's objectives and data-collection procedures were approved by the Institutional Review Board (IRB) for human subjects at our hospital (N°20/2010 Commission d’Evaluation Ethique des Recherches Non Interventionnelles, Amiens University Hospital, Amiens, France). Informed consent was waived because the IRB considered the protocol to be part of usual care in clinical practice.
The main inclusion criteria were as follows: (a) patients undergoing TTE for hemodynamic assessment; (b) age older than 18 years; and (c) sedated and mechanically ventilated patients who were synchronized with the respirator (the Servo-i, Maquet, Germany). The main exclusion criteria were as follows: (a) patients with changes in hemodynamic status during the various measurement (changes in catecholamine doses, fluid expansion, and so on), and (b) poor visualization of the IVC by even the most experienced operator.

At enrollment in this study, all included patients were sedated and ventilated using the volume-controlled mode (Servo-I, Maquet, Solna, Sweden). The V_T was adjusted to 6–8 mL/kg predicted body weight (PBW), and other parameters were set according to the decision of the clinicians in charge. Patients also had a central venous catheter and a thermistor-tipped arterial catheter in the femoral artery connected to a transpulmonary thermodilution device (PiCCO, Philips Medizin System, Boeblingen, Germany). After a 5-min stabilization of ventilation (Baseline), the inspiratory effort was assessed by airway occlusion pressure (P_0.1) and end-expiratory occlusion. Then, a fluid challenge was performed with a 250 ml saline bolus infused within 10 min (Fig. 1). Patients were classified as fluid responders if an increase in CO greater than or equal to 10% followed fluid administration [12 (link)].Fig. 1

Study design

All patients fulfilled the diagnosis of acute circulatory failure (see above). We assessed FR in each patient to decide the fluid management strategy. During the study period, there was no modification in the doses of vasopressor or sedative agents and no other fluid infusion. This study was stopped in cases of (1) new cardiac arrhythmias, (2) a > 20 mmHg decline of MAP from baseline, or (3) oxygen saturation (SpO₂) < 90% for > 2 min.

All measurements were taken at baseline without phrenic nerve stimulation with the intact phrenic nerve and at the different stimulation levels still with the phrenic nerve being intact. Thereafter, the phrenic nerve was transected, and the same varying stimulation levels were applied. Diaphragmatic movement was recorded by fluoroscopy (Ziehm Vista, Ziehm, Nuremberg, Germany) and evaluated with a tangent drawn at the highest point of the right hemi-diaphragm. At this point, diaphragmatic movement was measured at a right angle in millimeters. Arterial blood gas analyses were conducted in a RapidPoint® 500 analyzer (Siemens Healthineers, Erlangen, Germany). Ventilation parameters were measured using Servo-i (Maquet, Rastatt, Germany), and baseline ventilation settings were an inspiratory pressure of 15 cmH₂O, a positive end-expiratory pressure of 5 cmH₂O, and a ventilation rate of 15/min.