In 11 ventilator-dependent patients, we undertook a head-to-head comparison of patient-ventilator interaction during four ventilator modes: assist-control ventilation (ACV), intermittent mandatory ventilation (IMV), pressure support (PS), and a combination of IMV and PS. Progressive increases in IMV rate and PS level each decreased inspiratory pressure-time product (PTP) (p < 0.0001). These reductions in PTP were greater with PS than with IMV at lower but proportional levels of maximal assistance (p < 0.005). When PS 10 cm H2O was added to a given level of IMV, greater reductions in PTP were achieved not only during intervening (PS) breaths (p < 0.001), but also during mandatory (volume-assisted) breaths (p < 0.0005); this additional unloading during mandatory breaths was proportional to the decrease in respiratory drive (dP/dt) during intervening breaths (r = 0.67, p < 0.0001). Maximal unloading occurred with ACV, achieving more than a fivefold decrease in PTP compared with unassisted breathing. Decreases in PTP were confined to the post-trigger phase, and PTP of the post-trigger phase correlated with dP/dt (r = 0.78, p < 0.0001). Effort during the trigger phase remained constant despite marked changes in drive and intrinsic positive end-expiratory pressure (PEEPi). Ineffective triggering occurred with all modes, and wasted PTP increased with increasing levels of assistance as a result of the accompanying decrease in drive and increase in volume. Breaths preceding nontriggering efforts had shorter respiratory cycle times (p < 0.0005) and expiratory times (p < 0.0001) and higher PEEPi (p < 0.0001), indicating that neural-mechanical asynchrony resulted from inspiratory activity commencing prematurely before elastic recoil pressure had fallen to a level that could be overcome by a patient's muscular effort. Thus, increases in the level of ventilator assistance produced progressive decreases in inspiratory muscle effort and dyspnea,which were accompanied by increases in the rate of ineffective triggering.

Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P &lt; .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

Mortality amongst critically ill patients with SARS is high. It causes predominantly severe respiratory failure, with little other organ failure, and a high incidence of barotrauma amongst those requiring mechanical ventilation.