Todd Sarge

Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury

BACKGROUND Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention. METHODS We randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes. RESULTS The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided group than in the control group (95% confidence interval, 78.1 to 98.3; P=0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P=0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P=0.01 by repeated-measures analysis of variance). CONCLUSIONS As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

Esophageal and transpulmonary pressures in acute respiratory failure

Objective:Pressure inflating the lung during mechanical ventilation is the difference between pressure applied at the airway opening (Pao) and pleural pressure (Ppl). Depending on the chest walls contribution to respiratory mechanics, a given positive end-expiratory and/or end-inspiratory plateau pressure may be appropriate for one patient but inadequate or potentially injurious for another. Thus, failure to account for chest wall mechanics may affect results in clinical trials of mechanical ventilation strategies in acute respiratory distress syndrome. By measuring esophageal pressure (Pes), we sought to characterize influence of the chest wall on Ppl and transpulmonary pressure (PL) in patients with acute respiratory failure. Design:Prospective observational study. Setting:Medical and surgical intensive care units at Beth Israel Deaconess Medical Center. Patients:Seventy patients with acute respiratory failure. Interventions:Placement of esophageal balloon-catheters. Measurements and Main Results:Airway, esophageal, and gastric pressures recorded at end-exhalation and end-inflation Pes averaged 17.5 ± 5.7 cm H2O at end-expiration and 21.2 ± 7.7 cm H2O at end-inflation and were not significantly correlated with body mass index or chest wall elastance. Estimated PL was 1.5 ± 6.3 cm H2O at end-expiration, 21.4 ± 9.3 cm H2O at end-inflation, and 18.4 ± 10.2 cm H2O (n = 40) during an end-inspiratory hold (plateau). Although PL at end-expiration was significantly correlated with positive end-expiratory pressure (p < .0001), only 24% of the variance in PL was explained by Pao (R2 = .243), and 52% was due to variation in Pes. Conclusions:In patients in acute respiratory failure, elevated esophageal pressures suggest that chest wall mechanical properties often contribute substantially and unpredictably to total respiratory impedance, and therefore Pao may not adequately predict PL or lung distention. Systematic use of esophageal manometry has the potential to improve ventilator management in acute respiratory failure by providing more direct assessment of lung distending pressure.

Esophageal pressures in acute lung injury: do they represent artifact or useful information about transpulmonary pressure, chest wall mechanics, and lung stress?

Acute lung injury can be worsened by inappropriate mechanical ventilation, and numerous experimental studies suggest that ventilator-induced lung injury is increased by excessive lung inflation at end inspiration or inadequate lung inflation at end expiration. Lung inflation depends not only on airway pressures from the ventilator but, also, pleural pressure within the chest wall. Although esophageal pressure (Pes) measurements are often used to estimate pleural pressures in healthy subjects and patients, they are widely mistrusted and rarely used in critical illness. To assess the credibility of Pes as an estimate of pleural pressure in critically ill patients, we compared Pes measurements in 48 patients with acute lung injury with simultaneously measured gastric and bladder pressures (Pga and P(blad)). End-expiratory Pes, Pga, and P(blad) were high and varied widely among patients, averaging 18.6 +/- 4.7, 18.4 +/- 5.6, and 19.3 +/- 7.8 cmH(2)O, respectively (mean +/- SD). End-expiratory Pes was correlated with Pga (P = 0.0004) and P(blad) (P = 0.0104) and unrelated to chest wall compliance. Pes-Pga differences were consistent with expected gravitational pressure gradients and transdiaphragmatic pressures. Transpulmonary pressure (airway pressure - Pes) was -2.8 +/- 4.9 cmH(2)O at end exhalation and 8.3 +/- 6.2 cmH(2)O at end inflation, values consistent with effects of mediastinal weight, gravitational gradients in pleural pressure, and airway closure at end exhalation. Lung parenchymal stress measured directly as end-inspiratory transpulmonary pressure was much less than stress inferred from the plateau airway pressures and lung and chest wall compliances. We suggest that Pes can be used to estimate transpulmonary pressures that are consistent with known physiology and can provide meaningful information, otherwise unavailable, in critically ill patients.

Four cases of cardiopulmonary thromboembolism during liver transplantation without the use of antifibrinolytic drugs

Orthotopic liver transplantation (OLT) is one of the most demanding surgical procedures performed. Intraoperative bleeding can be substantial and related to both surgical and nonsurgical causes. A less common but previously reported phenomenon is intraoperative cardiopulmonary thromboembolism precipitating major patient morbidity and mortality. In this paper, we present four cases of intraoperative thromboembolism during OLT. These cases were performed without the concomitant use of antifibrinolytic drugs. We performed a review and analysis of previously reported cases of intraoperative thromboembolism during OLT. Possible causes of thromboembolism, clinical management, use of thromboelastography, and the role of antifibrinolytic drugs are discussed.

The Esophageal Pressure-Guided Ventilation 2 (EPVent2) trial protocol: a multicentre, randomised clinical trial of mechanical ventilation guided by transpulmonary pressure

Introduction Optimal ventilator management for patients with acute respiratory distress syndrome (ARDS) remains uncertain. Lower tidal volume ventilation appears to be beneficial, but optimal management of positive end-expiratory pressure (PEEP) remains unclear. The Esophageal Pressure-Guided Ventilation 2 Trial (EPVent2) aims to examine the impact of mechanical ventilation directed at maintaining a positive transpulmonary pressure (PTP) in patients with moderate-to-severe ARDS. Methods and analysis EPVent2 is a multicentre, prospective, randomised, phase II clinical trial testing the hypothesis that the use of a PTP-guided ventilation strategy will lead to improvement in composite outcomes of mortality and time off the ventilator at 28 days as compared with a high-PEEP control. This study will enrol 200 study participants from 11 hospitals across North America. The trial will utilise a primary composite end point that incorporates death and days off the ventilator at 28 days to test the primary hypothesis that adjusting ventilator pressure to achieve positive PTP values will result in improved mortality and ventilator-free days. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approvals of the protocol as well as informed consent documents were also obtained from the Institutional Review Board of each participating institution prior to enrolling study participants at each respective site. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to PubMed Central in accordance with the National Institute of Health Public Access Policy. Trial registration number ClinicalTrials.gov under number NCT01681225.

Raising positive end-expiratory pressures in ARDS to achieve a positive transpulmonary pressure does not cause hemodynamic compromise

Intensive Care Med (2014) 40:126–128 DOI 10.1007/s00134-013-3127-1 Todd Sarge Stephen H. Loring Maayan Yitsak-Sade Atul Malhotra Victor Novack Daniel Talmor Raising positive end-expiratory pressures in ARDS to achieve a positive transpulmonary pressure does not cause hemodynamic compromise Received: 24 September 2013 Accepted: 27 September 2013 Published online: 15 October 2013 O Springer-Verlag Berlin Heidelberg and ESICM 2013 Dear Editor, High positive end-expiratory pressure (PEEP) is associated with improved survival in patients with moderate to severe acute respiratory distress syn- drome (ARDS) [1], but high PEEP has also been reported to cause right heart failure and hemodynamic com- promise [2]. In our previous trial of ventilator management in ARDS [3], setting PEEP to achieve a positive transpulmonary pressure estimated using esophageal manometry usually increased PEEP, often significantly, but also led to better blood oxygena- tion and respiratory compliance than the control PEEP. To determine whether such manipulations of PEEP degrade hemodynamic function, we LETTER performed a retrospective analysis of the 61 patients in the EPVent Trial, who were all ventilated to achieve a target range of arterial oxygenation after hemodynamic resuscitation by protocol [3]. Subjects in the inter- vention group had PEEP set to maintain oxygenation at a positive estimated transpulmonary pressure (P L = airway pressure - esophageal pressure), whereas those in the con- trol group had PEEP set according to a standard table based on oxygenation as in the ARDSNet low tidal volume trial [4]. Mean arterial pressure (MAP), heart rate, central venous pressure (CVP), vasopressor require- ments, fluid balance, and simplified organ failure assessment (SOFA) scores were analyzed for the 3 days following enrollment. The primary between-group comparison was MAP, and secondary comparisons were cardiovascular SOFA score, urine output, creatinine level, and length-of-stay fluid balance. Baseline characteristics and sever- ity of illness were similar between groups. PEEP and plateau pressures were markedly higher in the inter- vention group (initial PEEP averaged 18.7 vs 11.0 cmH 2 O and plateau pressure 31.4 vs 25.1 cmH 2 O in intervention and control groups, respectively) [3]. Nonetheless, hemodynamic vari- ables including MAP and cardiovascular SOFA score were similar between groups (Fig. 1). MAP improved slightly over the first 72 h in both groups (between-group P = 0.576), fluid balance was reduced toward zero in both groups (between-group P = 0.245), and urine output improved in both groups (between-group P = 0.701). The cardiovascular component of the SOFA score, fluid balance, creatinine levels, urine output, and MAP were compared between groups and tested by generalized estimating equations with adjustment for covariates. None was significantly affected by group assignment. Although limited by the small sample size, these results indicate that raising PEEP as part of a strategy to optimize transpulmonary pressure in adequately resuscitated patients does not result in detectable impairment in hemodynamics, organ function mea- sured by SOFA scores, fluid balance, or vasopressor requirement. With normal lungs, high alveolar pressures in the absence of adequate volume expansion may compress pulmonary vasculature and increase pulmonary vascular resistance (PVR), reducing cardiac output and impairing right heart function [5]. However, in ARDS, low lung volume and atelec- tasis may also increase PVR. Under these circumstances, raising PEEP could recruit collapsed lung and lower PVR. In this way, raising PEEP to prevent both lung collapse and overdistension may improve the hemodynamic function. We conclude that in patients with ARDS, individualizing PEEP to optimize transpulmonary pressures using esophageal manometry does not compromise hemodynamic function. We are currently studying the

345: BARRIERS TO PROVIDING QUALITY END OF LIFE CARE IN THE ICU RESULTS OF A MULTICENTER SURVEY

Crit Care Med 2015 • Volume 43 • Number 12 (Suppl.) quality and 3 of poor quality. The patients who had a PC consultation in the ICU, when compared to the ones who did not, showed a trend towards reduction in ICU and hospital LOS. This was statistically significant in the high quality studies. Mortality outcomes were similar in both patient groups. PC consultations also lead to a significant reduction in ICU and total hospital costs in 5 of the 8 eligible trials. Using weighted means, ICU costs were (control vs PC)

Targeting transpulmonary pressure to prevent ventilator induced lung injury

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Cytokine release following recruitment maneuvers.

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Intrathecal morphine reduces breakthrough pain during labour epidural analgesia

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