Bench-to-bedside review: Hypercapnic acidosis in lung injury - from 'permissive' to 'therapeutic'

Modern ventilation strategies for patients with acute lung injury and acute respiratory distress syndrome frequently result in hypercapnic acidosis (HCA), which is regarded as an acceptable side effect ('permissive hypercapnia'). Multiple experimental studies have demonstrated advantageous effects of HCA in several lung injury models. To date, however, human trials studying the effect of carbon dioxide per se on outcome in patients with lung injury have not been performed. While significant concerns regarding HCA remain, in particular the possible unfavorable effects on bacterial killing and the inhibition of pulmonary epithelial wound repair, the potential for HCA in attenuating lung injury is promising. The underlying mechanisms by which HCA exerts its protective effects are complex, but dampening of the inflammatory response seems to play a pivotal role. After briefly summarizing the physiological effects of HCA, a critical analysis of the available evidence on the potential beneficial effects of therapeutic HCA from in vitro, ex vivo and in vivo lung injury models and from human studies will be reviewed. In addition, the potential concerns in the clinical setting will be outlined

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems

Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not kn

In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems

Objectives: To evaluate in vitro drug recovery in cardiopulmonary bypass (CPB) systems used for pediatric cardiac surgery. Design: Observational in vitro study. Setting: Single-center university hospital. Participants: In vitro CPB systems used for pediatric cardiac surgery. Interventions: Three full neonatal, infant, and pediatric CPB systems were primed according to hospital protocol and kept running for 6 hours. Midazolam, propofol, sufentanil, and methylprednisolone were added to the venous side of the systems in doses commonly used for induction of general anesthesia. Blood samples were taken from the postoxygenator side of the circuit immediately after injection of the drugs and after 2, 5, 7, 10, 30, 60, 180, and 300 minutes. Measurements and Main Results: Linear mixed model analyses were performed to assess the relationship between log-transformed drug concentration (dependent variable) and type of CPB system and sample time point (independent variables). The mean percentage of drug recovery after 60 and 180 minutes compared with T1 was 41.7% (95% confidence interval [CI] 35.9-47.4) and 23.0% (95% CI 9.2-36.8) for sufentanil, 87.3% (95% CI 64.9-109.7) and 82.0% (95% CI 64.6-99.4) for midazolam, 41.3% (95% CI 15.5-67.2) and 25.0% (95% CI 4.7-45.3) for propofol, and 119.3% (95% CI 101.89-136.78) and 162.0% (95% CI 114.09-209.91) for methylprednisolone, respectively. Conclusions: The present in vitro experiment with neonatal, infant, and pediatric CPB systems shows a variable recovery of routinely used drugs with significant differences between drugs, but not between system categories (with the exception of propofol). The decreased recovery of mainly sufentanil and propofol could lead to suboptimal dosing of patients during cardiac surgery with CPB

A retrospective analysis of CO2 derived goal-directed perfusion variables under normothermic conditions: do we need to re-evaluate threshold values?

This study investigated if current predictive values for increased lactate formation: VCO2i > 60 ml min−1 m−2, respiratory quotient (RQ) > 0.90, and DO2/VCO2 < 5.0, are valid under normothermic conditions. CO2 derived parameters were analyzed in 91 patients undergoing normothermic CABG and related to increase of blood lactate concentrations during bypass. In this study population, 85 patients (93%) had a median VCO2i above 60 ml min−1 m−2 and 53 patients (58%) had a DO2/VCO2 ⩽ 5.0. Eighteen patients (20%) had a median RQ ⩾ 0.90, but RQ remained with a maximum value of 0.94 below the biological threshold of 1.0. Increase of lactate concentrations remained without clinical significance and showed weak correlations with VCO2i (rs = 0.277, p = 0.008) and RQ (rs = 0.346, p = 0.001). The cohort was separated for the different CO2 variables by their median value to compare increase in lactate concentration. Patients with a high VCO2i (⩾70 ml min−1 m−2) and a high RQ (⩾0.82) showed significant higher increase in lactate concentration compared to patients with VCO2i < 70 ml min−1 m−2 (p = 0.004), and a RQ < 0.82 (p = 0.012). Groups separated by a median DO2/VCO2 of 4.8 did not show a difference in increase of lactate concentration in blood. In summary, specific CO2 derived threshold values for the prediction of lactate formation, which have been reported in other studies, cannot be confirmed with our findings. However, a CO2 production ⩾70 ml min−1 m−2 and a RQ ⩾ 0.82 in this study population were correlated with increased lactate formation. Because CO2 production during bypass depends on patient temperature, a different cutoff value, that may take into account the influence of demographic variables, should be determined during normothermic CPB

The impact of critical illness on the expiratory muscles and the diaphragm assessed by ultrasound in mechanical ventilated children

Background: Critical illness has detrimental effects on the diaphragm, but the impact of critical illness on other major muscles of the respiratory pump has been largely neglected. This study aimed to determine the impact of critical illness on the most important muscles of the respiratory muscle pump, especially on the expiratory muscles in children during mechanical ventilation. In addition, the correlation between changes in thickness of the expiratory muscles and the diaphragm was assessed. Methods: This longitudinal observational cohort study performed at a tertiary pediatric intensive care unit included 34 mechanical ventilated children (> 1 month– 10%) in 44% of the children. Diaphragm and expiratory muscle thickness increased (> 10%) in 26% and 20% of the children, respectively. No correlation was found between contractile activity of the muscles and the development of atrophy. Furthermore, no correlation was found between changes in thickness of the diaphragm and the expiratory muscles (P = 0.537). Decrease in expiratory muscle thickness was significantly higher in patients failing extubation compared to successful extubation (− 34% vs − 4%, P = 0.014). Conclusions: Changes in diaphragm and expiratory muscles thickness develop rapidly after the initiation of mechanical ventilation. Changes in thickness of the diaphragm and expiratory muscles were not significantly correlated. These data provide a unique insight in the effects of critical illness on the respiratory muscle pump in children