Secondary Logo

Journal Logo

Extravascular Lung Water and Pulmonary Vascular Permeability Index Measured at the End of Surgery Are Independent Predictors of Prolonged Mechanical Ventilation in Patients Undergoing Liver Transplantation

Garutti, Ignacio PhD, MD*; Sanz, Javier PhD*; Olmedilla, Luis PhD, MD*; Tranche, Itziar PhD*; Vilchez, Almudena PhD*; Fernandez-Quero, Lorenzo PhD; Bañares, Rafael PhD, MD; Perez-Peña, Jose María PhD, MD*

doi: 10.1213/ANE.0000000000000875
Critical Care, Trauma, and Resuscitation: Research Report

BACKGROUND: Pulmonary edema (PE) after orthotopic liver transplantation (OLT) may compromise the postoperative course and prolong the duration of mechanical ventilation (MV) and intensive care unit length of stay. Hemodynamic monitoring with transpulmonary thermodilution permits quantification of extravascular lung water index (ELWI) and calculation of the pulmonary vascular permeability index (PVPI), which is the ratio between the ELWI and the pulmonary blood volume. This ratio can discriminate between PE hydrostatic and nonhydrostatic PE. We investigated the relationship between ELWI and PVPI values, measured at the end of surgery, and prolonged MV (PMV) in patients after OLT.

METHODS: We retrospectively studied 93 consecutive patients who underwent OLT. We recorded preoperative data including spirometry, echocardiography, severity liver disease with the Model for End-Stage Liver Disease score, and the Child-Pugh classification scores. Intraoperatively, we performed hemodynamic measurements with transpulmonary thermodilution and pulmonary arterial catheters after the induction of anesthesia, 10 minutes before reperfusion, and at the end of surgery. Moreover, we recorded the length of surgery, the amount of IV volume infused, the results of blood coagulation analyses, and blood transfusion. Postoperatively, we recorded the duration of MV and intensive care unit length of stay, mortality, and graft function. Patients were then classified as requiring PMV (>48 hours after surgery) or not. Statistical analyses, preoperative and intraoperative variables between patients with and without PMV, were compared using Mann-Whitney U tests. Receiver-operating characteristic curves were used to evaluate the ability of preoperative and intraoperative variables to predict PMV.

RESULTS: Twelve patients required PMV after surgery. Patients who required PMV exhibited increased ELWI (11.6 ± 3 mL/kg vs 9.3 ± 2 mL/kg, P = 0.0099) and PVPI values (2.94 ± 1 vs 1.8 ± 0.6, P = 0.000015) at the end of surgery. The areas under the receiver-operating characteristic curve were 0.890 ± 0.04 for PVPI with a 99% confidence interval of 0.782 to 0.958 and 0.730 ± 0.08 for ELWI with a 99% confidence interval of 0.594 to 0.839. Using a cutoff of 2.3 for PVPI allowed a sensitivity = 91.7%, a specificity = 83.8, a positive predictive value = 45.8%, and a negative predictive value = 98.5% for predicting PMV. A cutoff of 12 for ELWI allowed a sensitivity of 50%, specificity of 85%, positive predictive value of 33.3%, and negative predictive value of 91.9% for PMV.

CONCLUSIONS: PVPI and ELWI values obtained at the end of OLT are useful for predicting the need for postoperative PMV.

From the *Department of Anesthesia, Hospital General Universitario Gregorio Marañon, Madrid, Spain; Department of Anesthesia and Reanimation, Hospital General Universitario Gregorio Marañon, Madrid, Spain; and Department of Hepatology, Hospital General Universitario Gregorio Marañon, Madrid, Spain.

Accepted for publication April 12, 2015.

Funding: None.

The authors declare no conflicts of interest.

This report was previously presented, in part, at the Euroanesthesia 2012, and accepted to American Society of Anesthesiologists meeting New Orleans 2014.

Reprints will not be available from the authors.

Address correspondence to Ignacio Garutti, PhD, MD, Department of Anesthesia, Hospital General Universitario Gregorio Marañon, St. Alcalde Sainz de Baranda, 53 Madrid 28009, Spain. Address e-mail to

Orthotopic liver transplantation (OLT) is considered a high-risk surgery because of a high incidence of cardiac and pulmonary complications.1,2 Patients requiring prolonged mechanical ventilation (PMV), defined as >48 hours, have worse graft function, longer intensive care unit (ICU) length of stay, and a higher mortality rate.3,4 Identifying patients at high risk for PMV may permit modifications of postoperative care unit (POCU) management and the implementation of early measures to mitigate the adverse consequences of PMV.

Up to 47% of patients develop pulmonary edema (PE) after OLT, which compromises the postoperative course and prolongs the length of mechanical ventilation (MV) and ICU stay.5 Two kinds of PE occur after OLT: hydrostatic (PEh) associated with volume overload and nonhydrostatic that reflects failure of capillary permeability regulation or permeability PE (PEp). Alveolar–capillary membrane integrity is impaired in end-stage liver disease6 and can be aggravated by exaggerated inflammatory responses such as those during ischemia–reperfusion OLT.7 This increased permeability results in the accumulation of protein-rich fluids outside of the vascular space.

Hemodynamic monitoring with transpulmonary thermodilution (TPTD) is often used to calculate the amount of extravascular lung water (ELWI). High ELWI values reflect the presence of PE that can lengthen the duration of MV.8 In critically ill patients, an elevated ELWI is prognostically significant because it is related to decreased survival.9 In the perioperative period, however, the prognostic value of ELWI is less clear, and the use of ELWI in patients undergoing OLT is even less well understood. The ratio between the ELWI and pulmonary blood volume, known as the pulmonary vascular permeability index (PVPI), can be used to discriminate between the PEh and the PEp. Patients with PEp exhibit higher PVPI values than those with PEh.10 The PVPI index has also been recently proposed as an indicator of outcomes for ICU patients generally.11

We hypothesized that increased intraoperative PVPI or ELWI values during OLT correlated with postoperative outcomes, including PMV. The aim of our study was to investigate the relationship of PVPI and ELWI values measured at the end of surgery to PMV (defined as MV for >48 hours) after OLT.

Back to Top | Article Outline


This was a case-controlled, retrospective, clinical study performed in the liver transplant unit of our institution. The study was conducted according to the principles of the Declaration of Helsinki and was approved by the local ethics committee. This committee waived the requirement for written informed consent.

Back to Top | Article Outline

Patient Characteristics

From March 2011 to December 2013, 97 adult patients underwent OLT from deceased donors. Patients who required MV before surgery were excluded. Preoperative data collection included the severity of liver disease (assessed using the Child-Pugh classification and the Model for End-Stage Liver Disease scores) and the etiology of liver failure. The degree of portal hypertension was evaluated by measuring hepatic venous pressure gradients. All patients underwent preoperative spirometry and transthoracic echocardiography, including a bubble study, to assess for intracardiac shunt and the presence of hepatopulmonary syndrome. Immediately before surgery, complete blood count and basic coagulation and biochemistry studies were performed. The last chest radiograph taken before surgery was reviewed.

Anesthesia was induced with etomidate (0.2 mg/kg), fentanyl (2 μg/kg), and rocuronium (1 mg/kg) and maintained with inhaled sevoflurane (0.5%–1%) and continuous infusions of midazolam (5 mg/h) and remifentanil (0.2–0.4 μg/kg/min). Muscle relaxation was maintained with rocuronium boluses as required. MV was established with a tidal volume of 6 to 8 mL/kg, and the respiratory rate was set to maintain an end-tidal carbon dioxide of 35 to 40 mm Hg.

Heart rate, pulse oximetry, and the bispectral index were monitored throughout and captured for data analysis. All patients had a left radial arterial line; a right jugular vein introducer and pulmonary arterial catheter (PAC) were used to monitor the central blood temperature, pulmonary arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index (CIPAC), and mixed venous oxygen saturation. A 20-cm catheter was inserted into the right femoral vein and threaded into the abdominal compartment to obtain the inferior cava venous pressure. A thermosensitive catheter (5-Fr 20-cm PVPK2015L20-A; Pulsion Medical Systems, Munich, Germany) was inserted through the right femoral artery and connected to a PiCCO2 system for continuous monitoring of blood pressure, global end-diastolic volume index (GEDI), stroke volume variation (SVV), pulse pressure variation (PPV), cardiac index (CITPTD), ELWI, and PVPI. TPTD measurements were recorded at 3 time points during surgery: after the induction of anesthesia, 10 minutes before reperfusion, and at the end of surgery. At each point, a complete blood count, coagulation, blood gas analysis, thromboelastometry clot analysis (Pentapharm GMBH, Munich, Germany), and chemistries were performed to guide the proper management of both fluids and blood products and to correct metabolic abnormalities and coagulation. Crystalloids were administered at a rate of 5 mL/kg/h, and 250- to 500-mL boluses of hydroxyethyl starch 6% were administered when the mean arterial pressure (MAP) was <60 mm Hg and the pulmonary capillary wedge pressure was <15 mm Hg but not <10 mm Hg. We recorded intravascular fluids administered during the operating room stay. When necessary, vasoconstrictor boluses (ephedrine or phenylephrine) were used to achieve an MAP >60 mm Hg. If the MAP goal was not achieved with vasoconstrictor boluses, norepinephrine was begun at the discretion of the attending anesthesiologist to target an MAP = 60 mm Hg.

We used IV bolus doses of furosemide when urine output was <0.5 mL/kg/h and the pulmonary capillary pressure (PCP) was >15 mm Hg. Dobutamine infusions were used when the PCP was >15 mm Hg and the CI <2 L/min/m2. Transfusion of packed red blood cells was performed to achieve hemoglobin values >8 g/dL. The administration of fibrinogen or platelets was performed based on the data provided by thromboelastography.

Intraoperative data collection also included donor liver warm and cold ischemia times, length of surgery, use of noradrenaline infusion, and the fluids and blood products that were administered intraoperatively.

An IV continuous tranexamic acid infusion (10 mg/kg/h) was begun after anesthetic induction and run until the completion of the hepatic artery anastomosis, except in cases with known prothrombotic states or preexisting thrombotic disease such as portal vein thrombosis. After reconstruction of the biliary tract, the indocyanine green plasma disappearance rate was measured with an LiMON monitor (Pulsion Medical Systems). The donor liver was preserved with the University of Wisconsin cold storage solution. The recipient hepatectomy and graft placement were performed according to the piggyback technique without venovenous bypass.

Back to Top | Article Outline

Postoperative Management

After surgery, all patients were transferred to the POCU where they had blood tests and chest radiographs. They were tracheally extubated in the POCU when they met the following criteria: awake and responding to verbal commands, a core body temperature of between 36°C and 37.5°C, a respiratory rate of <20 breaths/min, peripheral oxygen saturation >92% breathing spontaneously with inspiration fraction oxygen (FIO2) <0.5, and hemodynamically stable without the use of vasoactive drugs.

Patients then typically were discharged from the unit within 72 hours unless medically contraindicated. The PaO2/FIO2 ratio was calculated at admission and during the first 48 hours of the stay in the POCU.

The time to extubation, length of stay in the POCU, graft function, vasoactive drug and blood product requirements, and the need for reinterventions (intraabdominal acute bleeding, hepatic artery or portal vein thrombosis, transplantectomy, or retransplantation) during the stay in the POCU were also recorded. Early graft function in the first 72 hours was classified into 4 grades (I, II, III, and IV) based on the gamma-glutamyl transpeptidase international normalized ratio, bilirubin values, and level of consciousness.12

Back to Top | Article Outline

Statistical Analyses

The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 21.0 (IBM Corp., Armonk, NY). The R Project for Statistical Computing and the R open source software package pROC were used to compute the receiver-operating characteristic (ROC) curve and areas under the curve (AUC) for each parameter. Sample size determination was calculated a posteriori: with a sample size of 93 patients, 12 (12.9%) of them requiring PMV. The sample size determination can achieve a potency of 82% for detecting AUC-ROC ≥0.75. The normalities of the data distributions were tested using the Kolmogorov-Smirnov test of normality with Lilliefors correction. Multiple comparisons of means were performed. Mann-Whitney tests of continuous variables were used to compare patients who required PMV with those who did not. The results are expressed as the median and 25th to 75th percentile. Categorical variables were compared using the χ2 test or Fisher exact test. To evaluate the predictive values of the various preoperative and intraoperative variables that were collected, ROC curve analyses of the variables that were significantly different between the patients who required PMV and those who did not were performed. Confidence intervals were calculated for an exact binomial test with a confidence interval of 99%. We used the Youden index to select the best PVPI an ELWI cutoff values at the end of surgery for predicting PMV. Subsequently, the sensitivities, specificities, and positive and negative predictive values of these hemodynamic parameters in the prediction of PMV were calculated. A P value <0.01 was considered significant.

Back to Top | Article Outline


From March 2011 to December 2013, 97 consecutive patients undergoing liver transplantation were enrolled. Four patients were excluded because they had been on MV immediately before OLT (3 retransplants and 1 with fulminant hepatic failure). Twelve of the 93 patients (12.9%) required PMV. Demographic characteristics of the patients, severity of liver disease, and associated pathologies are presented in Table 1. Intraoperative factors, including length of surgery, warm and cold ischemia times, intraoperative fluid administration, and the need for continuous administration of vasoconstrictor drugs, during OLT were similar between the patients requiring PMV and those who did not (Table 2).

Table 1

Table 1

Table 2

Table 2

Hemodynamic and PaO2/FIO2 data recorded at each of the 3 time points studied are shown in Table 3. At baseline, no significant differences were found between groups in any of these values. At the end of the anhepatic phase, patients who required PMV exhibited ELWI and PVPI values that were higher than those of the patients who did not require this intervention. At the end of surgery, SVV, PPV, ELWI, and PVPI values were significantly higher in the PMV group (Table 3).

Table 3

Table 3

Postoperative graft function grade was different between PMV and non-PMV groups. Eight patients (66%) in the PMV group versus 11 (13%) in the non-PMV group showed an III or IV graft function grade (P = 0.00020 and odds ratio 13.1 with 99% confidence interval, 2.2–77.9). Three, 2, and 3 patients of the PMV group who showed early graft dysfunction were retransplanted, died, or recovered, respectively.

Box plots of the ELWI and PVPI values at the end of surgery for each of the groups of patients are also shown (Fig. 1).

Figure 1

Figure 1

Analyses of the ROC curves of factors significantly associated with PMV were performed. The AUC-ROC curves are shown in Table 4.

Table 4

Table 4

At the end of surgery, we selected PVPI and ELWI cutoff values that exhibited the best sensitivity and specificity for predicting PMV. The best PVPI cutoff was 2.3, and the best ELWI cutoff was 12 mL/kg. Sensitivity, specificity, positive predictive value, and negative predictive value of different cutoff PVPI and ELWI values at the end of surgery are shown in Table 5.

Table 5

Table 5

Table 6

Table 6

We subsequently analyzed the postoperative course of patients according to ELWIs ≥ or <12 mL/kg and PVPI ≥ or <2.3 at the end of surgery (Table 6). ELWI ≥12 predicted longer hospital stays. In addition, patients with PVPI ≥2.3 required longer durations of MV, had more retransplantations, and required more surgeries within the first week compared with the patients with PVPIs <2.3 at the end of the surgery.

Back to Top | Article Outline


The injection of a cold indicator into the central venous circulation and detection of dilution curve in the aorta through a femoral artery catheter allows for the assessment of the amount of extravascular lung water and provides information about the integrity of pulmonary capillary permeability. In our study, we have observed that PVPI values measured by TPTD before the end of surgery predicted the need for MV in the first 2 postoperative days after OLT. ELWI, although less predictive, was also useful for this purpose. PMV after surgery is traditionally regarded as a postoperative pulmonary complication13 but may reflect damage to organs (poor graft function), brain (impaired consciousness), heart (hemodynamic instability and heart failure), and the presence of immediate surgical complications. Several preoperative and intraoperative factors that prolong the length of MV after OLT have been described, including preoperative respiratory status, severity and cause of liver disease, and excessive fluid and/or blood administration.14–19 We found no relationship between these preoperative and intraoperative variables and the incidence of serious postoperative complications. However, these risk factors may still have affected the time to tracheal extubation because PMV was defined as a need for MV for >48 hours.

Until now, the feasibility of using intraoperative hemodynamic variables to predict the need for PMV had not been extensively evaluated. We observed that intraoperative hemodynamic parameters provided by TPTD at the end of OLT were strongly correlated with the need for PMV than factors associated with the clinical condition of the patient preoperatively.20

The patients who required PMV exhibited lower GEDIs and higher SVVs and PPVs at the end of the intervention. These findings suggest that the intravascular volumes of these patients were lower than those of the other patients and/or that the patients on PMV required greater volumes than they received during surgery. However, we followed a traditional goal-directed hemodynamic therapy based on MAP, CI, and PCP values, and these values were similar between the 2 groups. In view of the results of our study, we have changed our hemodynamic monitoring practices and no longer use PAC to measure mixed saturation venous mixed oxygen during OLT; we use TDTP measured with a central venous catheter to continuously monitor central saturation venous mixed oxygen.

The coexistence of data suggesting the presence of PE (high ELWI) with data that informs us of the existence of hypovolemia (GEDI <650 mL/m2) in PMV group patients may seem paradoxical. We cannot ignore the possibility that underresuscitation led to the sequelae of hypoperfusion. However, PMV group patients showed a similar CI, SVV, and GEDI before reperfusion than non-PMV patients, and we could already see at this time that ELWI and PVPI values were higher in the PMV group. Thus, it seems that patients on PMV would have received larger amount of fluids than the non-PMV patients if we had used SVV, PPV, or GEDI to titrate fluid therapy.

We believe that the effects of ischemia/reperfusion (I/R) liver injury on lungs could explain the higher ELWI and PVPI observed in our PMV group. In a previous study, our group showed that intraoperative plasma disappearance rate values predict early graft dysfunction after OLT.21 In this new study, lower intraoperative plasma disappearance rate values seen in the PMV group suggest that intraoperative graft function could be impaired to some degree. Lung is the organ most sensitive to I/R liver injury. Liver injury can result in damage to the alveolar–capillary membrane because of the accumulation of neutrophils, macrophages, and platelet aggregates and perivascular edema and subsequent fluid and protein transudation into the extravascular space that results in the formation of PE.22,23 Three main mechanisms have been proposed to explain lung injury related with liver I/R: (1) During the anhepatic phase, there is an increase in endotoxin concentrations entering the circulation from intestinal bacterial flora and resulting in alveolar neutrophil activation and subsequent alveolocapillary membrane injury. Liu et al.24 have demonstrated that interruptions in hepatic blood flow of >60 to 90 minutes resulted in an increased alveolar–capillary membrane leak and increased capillary permeability. (2) Release of cytokines from the liver graft to the bloodstream after reperfusion triggers the production of cytokines in the lung, which interact with pulmonary capillaries favoring the formation of PE.25 (3) Oxidative stress has been implicated in lung injury after liver reperfusion. The release of reactive oxygen species from hepatic endothelium and neutrophils triggers the inflammatory response in the lungs through the activation of transcription factors and gene expression of proinflammatory mediators.26 Chan et al.,27 in an experimental in vivo study, noted an excessive release in reactive oxygen species with an increase in lung water and vascular permeability.

Current evidence supports the use of ELWI as a measure of PE and a tool for evaluating factors affecting the clinical course of patients such as reduced gas exchange, increased requirement for MV, prolonged stay in the POCU, and mortality.8,28 Because of the high incidences of PE that have been described in some studies,5,29 monitoring ELWI might be particularly useful for patients undergoing OLT.

The PVPI is defined as the ratio between the ELWI and pulmonary blood volume. High PVPI values suggest ELWI with a low pulmonary blood volume, possibly because of alterations in pulmonary capillary permeability.9 van der Heijden and Groeneveld30 observed that PVPI values are related to abnormalities in capillary permeability, as assessed by radionuclide gallium-labeled transferrin, among nonseptic patients admitted to the ICU (for causes including noncardiothoracic surgery, trauma, and acute hemorrhage). These authors also found that altered pulmonary capillary permeability is not related to fluid overload or colloid osmotic or hydrostatic pressures. In the present study, we observed high PVPI values at the end of the surgery suggestive of incipient PEp. Such values are an ominous sign in the immediate postoperative OLT period. Aduen et al.29 found that patients with PEs on chest radiography and PCPs <18 mm Hg have worse outcomes than those with PEs that are accompanied by PCPs >18 mm Hg (29% vs 0% mortality, respectively). Snowden et al.5 also noted that the presence of pulmonary infiltrate is suggestive of PE in patients undergoing OLT not only because of hydrostatic causes. They also noted that patients with PEs unrelated to fluid overload have a worse prognosis. Our findings corroborate the notion outlined in the studies cited that capillary permeability damage and increased permeability are associated with a poor postoperative course among patients undergoing OLT. We speculate that injuries to pulmonary capillary permeability because of ischemia/reperfusion (as evaluated by high PVPI values) are accompanied by increases in systemic capillary permeability. In our study, we administered similar amounts of fluids to the 2 groups; however, the patients on PMV exhibited lower GEDI values than the non-PMV patients.

We observed that ELWIs ≥12 mL/kg predicted the need for PMV. However, our analyses revealed that PVPI was a stronger independent predictor of PMV. Little information is available regarding the best PVPI cutoff for application in clinical practice. Monnet et al.31 used a PVPI cutoff of 3 to improve the prognoses of patients who were admitted to ICUs. Recently, Kushimoto et al.10 proposed that using PVPI values >2.6 to 2.8 for the diagnosis of adult respiratory distress syndrome in ICU patients would provide a sensitivity and specificity of 90% and 95%, respectively. In our patients, the PVPI cutoff that best predicted PMV was 2.3. These values would likely have been higher if we had performed the measurements during the early stay in the POCU. Furthermore, this PVPI cutoff was also useful for predicting other postoperative variables (i.e., retransplantation surgery in the first week and the lengths of ICU and hospital stays). We believe that further studies are clearly needed to identify the most appropriate values for the detection of pulmonary vascular permeability abnormalities that affect postoperative prognoses and the clinical management recommendations that should be provided when such situations are encountered.

Patients with postoperative PEh after OLT usually respond well to postoperative fluid restriction. However, the course of PEp is primarily related to postoperative hepatic graft function,15 perhaps because the dysfunctioning liver graft cannot metabolize the many systemic proinflammatory substances released during I/R. Also, a nonfunctioning necrotic liver graft (toxic liver syndrome) could release toxic substances that damage lung alveolocapillary membrane.

The presence of increased ELWI and/or PVPI values after graft reperfusion might alert the physicians that specific management strategies may be required for such patients during the neohepatic phase and in the early postoperative period after liver transplantation (although no studies have specifically evaluated the management of patients who present with elevated ELWI and/or PVPI values after OLT). In the absence of clear evidence, it may still be reasonable to pay close attention to the management of MV and intravascular volume-known challenges of postoperative liver transplant management.

First, high PVPI or ELWI values may prompt the application of protective measures during MV. Some evidence supports the early application of lung-protective ventilation. In an experimental study, Ota et al.32 reported that protective ventilation (Tidal Volume [TV] 6 mL/kg) can decrease lung inflammation after liver I/R. These authors observed that animals with high TVs after liver I/R exhibited increased pulmonary and perivascular edema, whereas animals that undergo protective ventilation did not. Knowing when to apply full lung-protective modes may be particularly important in patients undergoing OLT as the use of positive end-expiratory pressure (PEEP) may decrease hepatic blood flow, possibly by decreasing the cardiac output.33,34 However, 2 clinical studies evaluating the effects of PEEP on liver graft function did not observe any deleterious effects on systemic hemodynamic or liver graft function at PEEP levels 10 or even 15 cm H2O.35,36 Moreover, because increased ELWI may be associated with pleural effusions, early detection and drainage may be useful for facilitating MV.2

Second, intravascular volume management can affect the development and resolution of ELWI, whether caused by hydrostatic PE or changes in vascular permeability.37 Earlier studies have reported improvements in the resolution of PE and shorter MV duration and ICU length of stay in patients with high ELWI values managed with volume restriction.38 The 2006 ARDSnet trial comparing restrictive and liberal fluid management in acute respiratory distress syndrome also found improvements in lung function and shorter MV durations with a restrictive strategy.39 Furthermore, patients with end-stage liver disease are frequently hypoproteinemic, and the use of albumin with furosemide has been proposed to treat PE during the perioperative period.40 Such restrictive fluid strategies can be started after graft reperfusion when patients show elevated ELWI and/or PVPI values.

Third, several specific measures can be recommended for patients undergoing liver transplant who demonstrate elevated ELWI or PVPI values. Earlier imaging tests to detect the possible causes of liver reperfusion injury (e.g., portal and/or arterial thrombosis and primary malfunction) may be recommended for these patients. There is no conclusive evidence concerning the management of early graft dysfunction. When an initial poor function is detected, the use of continuous perfusion of prostaglandin I, or inhaled nitric oxide, has been proposed.41 In cases in which a primary nonfunction is established, the effectiveness of molecular adsorbent recirculating system to remove albumin-bound liver toxins from a patient’s blood has been shown.42 In patients at high risk for developing PMV after OLT, we increase pulmonary infection surveillance and change the standard antibiotic prophylaxis (trimethoprim/cotrimoxazole, teicoplanin, and ciprofloxacin) to another, broader, prophylaxis (trimethoprim/cotrimoxazole, meropenem, and anidulafungin). If a pulmonary infection is suspected, we added linezolid considering the possibility of a methicillin-resistant Staphylococcus aureus infection, and we decrease, or even withdraw, immunosuppression while evaluating the entire clinical picture.

Back to Top | Article Outline


Our results must be interpreted with caution because of the observational and noninterventional nature of this study. We did not use PVPI and ELWI values to manage patient hemodynamics. Such observational results reflect the predictive ability of these values because we did not try to correct them when they were altered.

We conclude that both PVPI and ELWI values obtained at the end of liver transplant surgery may predict the need for postoperative PMV. The nonhydrostatic type of PE, as identified by the PVPI at the end of surgery, likely resulted from alveolar–capillary membrane damage related to intraoperative liver I/R injury, and such PEs are associated with poor postoperative courses.

Back to Top | Article Outline


Name: Ignacio Garutti, PhD, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Ignacio Garutti has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Javier Sanz, PhD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Javier Sanz has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Luis Olmedilla, PhD, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Luis Olmedilla has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Itziar Tranche, PhD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Itziar Tranche has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Almudena Vilchez, PhD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Almudena Vilchez has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Lorenzo Fernandez-Quero, PhD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Lorenzo Fernandez-Quero has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Rafael Bañares, PhD, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Rafael Bañares has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Jose María Perez-Peña, PhD, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Jose María Perez-Peña has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

This manuscript was handled by: Avery Tung, MD.

Back to Top | Article Outline


1. Plotkin JS, Scott VL, Pinna A, Dobsch BP, De Wolf AM, Kang Y. Morbidity and mortality in patients with coronary artery disease undergoing orthotopic liver transplantation. Liver Transpl Surg. 1996;2:426–30
2. Levesque E, Hoti E, Azoulay D, Honore I, Guignard B, Vibert E, Ichai P, Antoun F, Saliba F, Samuel D. Pulmonary complications after elective liver transplantation—incidence, risk factors, and outcome. Transplantation. 2012;94:532–8
3. Mandell MS, Campsen J, Zimmerman M, Biancofiore G, Tsou MY. The clinical value of early extubation. Curr Opin Organ Transplant. 2009;14:297–302
4. Neelakanta G, Sopher M, Chan S, Pregler J, Steadman R, Braunfeld M, Csete M. Early tracheal extubation after liver transplantation. J Cardiothorac Vasc Anesth. 1997;11:165–7
5. Snowden CP, Hughes T, Rose J, Roberts DR. Pulmonary edema in patients after liver transplantation. Liver Transpl. 2000;6:466–70
6. Schraufnagel DE, Malik R, Goel V, Ohara N, Chang SW. Lung capillary changes in hepatic cirrhosis in rats. Am J Physiol. 1997;272:L139–47
7. Chang SW, Ohara N. Increased pulmonary vascular permeability in rats with biliary cirrhosis: role of thromboxane A2. Am J Physiol. 1993;264:L245–52
8. Katzenelson R, Perel A, Berkenstadt H, Preisman S, Kogan S, Sternik L, Segal E. Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water. Crit Care Med. 2004;32:1550–4
9. Brown LM, Liu KD, Matthay MA. Measurement of extravascular lung water using the single indicator method in patients: research and potential clinical value. Am J Physiol Lung Cell Mol Physiol. 2009;297:L547–58
10. Kushimoto S, Taira Y, Kitazawa Y, Okuchi K, Sakamoto T, Ishikura H, Endo T, Yamanouchi S, Tagami T, Yamaguchi J, Yoshikawa K, Sugita M, Kase Y, Kanemura T, Takahashi H, Kuroki Y, Izumino H, Rinka H, Seo R, Takatori M, Kaneko T, Nakamura T, Irahara T, Saito N, Watanabe APiCCO Pulmonary Edema Study Group. PiCCO Pulmonary Edema Study Group. . The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome. Crit Care. 2012;16:R232
11. Jozwiak M, Silva S, Persichini R, Anguel N, Osman D, Richard C, Teboul JL, Monnet X. Extravascular lung water is an independent prognostic factor in patients with acute respiratory distress syndrome. Crit Care Med. 2013;41:472–80
12. Clavien PA, Camargo CA Jr, Croxford R, Langer B, Levy GA, Greig PD. Definition and classification of negative outcomes in solid organ transplantation. Application in liver transplantation. Ann Surg. 1994;220:109–20
13. Arozullah AM, Daley J, Henderson WG, Khuri SF. Multifactorial risk index for predicting postoperative respiratory failure in men after major noncardiac surgery. The National Veterans Administration Surgical Quality Improvement Program. Ann Surg. 2000;232:242–53
14. Glanemann M, Langrehr JM, Müller AR, Platz KP, Guckelberger O, Stange B, Neumann U, Raakow R, Keck H, Settmacher U, Bechstein WO, Neuhaus P. Incidence and risk factors of prolonged mechanical ventilation and causes of reintubation after liver transplantation. Transplant Proc. 1998;30:1874–5
15. Faenza S, Ravaglia MS, Cimatti M, Dante A, Spedicato S, Labate AM. Analysis of the causal factors of prolonged mechanical ventilation after orthotopic liver transplant. Transplant Proc. 2006;38:1131–4
16. Kleine M, Vondran FW, Johanning K, Timrott K, Bektas H, Lehner F, Klempnauer J, Schrem H. Respiratory risk score for the prediction of 3-month mortality and prolonged ventilation after liver transplantation. Liver Transpl. 2013;19:862–71
17. Feltracco P, Carollo C, Barbieri S, Pettenuzzo T, Ori C. Early respiratory complications after liver transplantation. World J Gastroenterol. 2013;19:9271–81
18. Jiang GQ, Peng MH, Yang DH. Effect of perioperative fluid therapy on early phase prognosis after liver transplantation. Hepatobiliary Pancreat Dis Int. 2008;7:367–72
19. Yost CS, Matthay MA, Gropper MA. Etiology of acute pulmonary edema during liver transplantation: a series of cases with analysis of the edema fluid. Chest. 2001;119:219–23
20. Smetana GW, Lawrence VA, Cornell JEAmerican College of Physicians. American College of Physicians. . Preoperative pulmonary risk stratification for noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Intern Med. 2006;144:581–95
21. Olmedilla L, Pérez-Peña JM, Ripoll C, Garutti I, de Diego R, Salcedo M, Jiménez C, Bañares R. Early noninvasive measurement of the indocyanine green plasma disappearance rate accurately predicts early graft dysfunction and mortality after deceased donor liver transplantation. Liver Transpl. 2009;15:1247–53
22. Colletti LM, Kunkel SL, Walz A, Burdick MD, Kunkel RG, Wilke CA, Strieter RM. Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein. J Clin Invest. 1995;95:134–41
23. Hato S, Urakami A, Yamano T, Uemura T, Ota T, Hirai R, Shimizu N. Attenuation of liver and lung injury after hepatic ischemia and reperfusion by a cytokine-suppressive agent, FR167653. Eur Surg Res. 2001;33:202–9
24. Liu DL, Jeppsson B, Hakansson CH, Odselius R. Multiple-system organ damage resulting from prolonged hepatic inflow interruption. Arch Surg. 1996;131:442–7
25. Nastos C, Kalimeris K, Papoutsidakis N, Tasoulis MK, Lykoudis PM, Theodoraki K, Nastou D, Smyrniotis V, Arkadopoulos N. Global consequences of liver ischemia/reperfusion injury. Oxid Med Cell Longev. 2014;2014:906965
26. Rahman I, Gilmour PS, Jimenez LA, MacNee W. Oxidative stress and TNF-alpha induce histone acetylation and NF-kappaB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation. Mol Cell Biochem. 2002;234–235:239–48
27. Chan KC, Lin CJ, Lee PH, Chen CF, Lai YL, Sun WZ, Cheng YJ. Propofol attenuates the decrease of dynamic compliance and water content in the lung by decreasing oxidative radicals released from the reperfused liver. Anesth Analg. 2008;107:1284–9
28. Zhang Z, Lu B, Ni H. Prognostic value of extravascular lung water index in critically ill patients: a systematic review of the literature. J Crit Care. 2012;27:420.e1–8
29. Aduen JF, Stapelfeld WH. Clinical relevance of time of onset, duration, and type of pulmonary edema after liver transplantation. Liver Transpl. 2003;9:764–71
30. van der Heijden M, Groeneveld AB. Extravascular lung water to blood volume ratios as measures of pulmonary capillary permeability in nonseptic critically ill patients. J Crit Care. 2010;25:16–22
31. Monnet X, Anguel N, Osman D, Hamzaoui O, Richard C, Teboul JL. Assessing pulmonary permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary edema from ALI/ARDS. Intensive Care Med. 2007;33:448–53
32. Ota S, Nakamura K, Yazawa T, Kawaguchi Y, Baba Y, Kitaoka R, Morimura N, Goto T, Yamada Y, Kurahashi K. High tidal volume ventilation induces lung injury after hepatic ischemia-reperfusion. Am J Physiol Lung Cell Mol Physiol. 2007;292:L625–31
33. Matuschak GM, Pinsky MR, Rogers RM. Effects of positive end-expiratory pressure on hepatic blood flow and performance. J Appl Physiol (1985). 1987;62:1377–83
34. Kiefer P, Nunes S, Kosonen P, Takala J. Effect of positive end-expiratory pressure on splanchnic perfusion in acute lung injury. Intensive Care Med. 2000;26:376–83
35. Krenn CG, Krafft P, Schaefer B, Pokorny H, Schneider B, Pinsky MR, Steltzer H. Effects of positive end-expiratory pressure on hemodynamics and indocyanine green kinetics in patients after orthotopic liver transplantation. Crit Care Med. 2000;28:1760–5
36. Saner FH, Olde Damink SW, Pavlaković G, Sotiropoulos GC, Radtke A, Treckmann J, Beckebaum S, Cicinnati V, Paul A. How far can we go with positive end-expiratory pressure (PEEP) in liver transplant patients? J Clin Anesth. 2010;22:104–9
37. Mitchell JP, Schuller D, Calandrino FS, Schuster DP. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis. 1992;145:990–8
38. Eisenberg PR, Hansbrough JR, Anderson D, Schuster DP. A prospective study of lung water measurements during patient management in an intensive care unit. Am Rev Respir Dis. 1987;136:662–8
39. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin ALNational Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. . Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564–75
40. American Thoracic Society. . Evidence-based colloid use in the critically ill: American Thoracic Society consensus statement. Am J Respir Crit Care Med. 2004;170:1247–59
41. Chen XB, Xu MQ. Primary graft dysfunction after liver transplantation. Hepatobiliary Pancreat Dis Int. 2014;13:125–37
42. Novelli G, Annesini MC, Morabito V, Cinti P, Pugliese F, Novelli S, Piemonte V, Turchetti L, Rossi M, Berloco PB. Cytokine level modifications: molecular adsorbent recirculating system versus standard medical therapy. Transplant Proc. 2009;41:1243–8
© 2015 International Anesthesia Research Society