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Extravascular Lung Water and Tissue Perfusion Biomarkers After Lung Resection Surgery Under a Normovolemic Fluid Protocol
Extravascular Lung Water and Tissue Perfusion Biomarkers After Lung Resection Surgery Under a Normovolemic Fluid Protocol Sherif Assaad, MD,* Tassos Kyriakides, PhD, George Tellides, MD, PhD,† Anthony W. Kim, MD,† Melissa Perkal, MD,‡ and Albert Perrino, MD* Objective: The optimal fluid management for lung resection surgery remains undefined. Concern related to postoperative pulmonary edema has led to the practice of fluid restriction. This practice risks hypovolemia and tissue hypoperfusion. The authors examined the extravascular lung water accumulation and tissue perfusion biomarkers under protective lung ventilation and normovolemia. Design: A prospective observational study. Setting: A single-center study. Participants: Forty patients aged 18 years or older undergoing lung resection surgery. Intervention: Patients were maintained on protective lung ventilation and a normovolemic fluid protocol. Hemodynamic variables, including global end-diastolic volume index, cardiac index, and extravascular lung water index, together with tissue perfusion biomarkers, including serum creatinine, lactic acid, central venous oxygen saturation, and brain natriuretic peptide, were measured perioperatively. Parametric or nonparametric techniques were used
A
DVANCES IN ONCOLOGIC PRACTICE have led to a worldwide increase in lung cancer resections over the past decade. Notably, this growth is composed primarily of lesser lung resections compared with pneumonectomies.1–3 Despite an improvement in the early mortality rate, pulmonary complications remain the main cause of postoperative morbidity. These range from mild complications, such as atelectasis and pneumonia, to the more severe acute respiratory distress syndrome (ARDS). The risk of developing ARDS after lung resection varies according to the extent of resection, with pneumonectomy carrying the highest risk (3%10% compared with 2%-5% for lesser resections) and a mortality rate of 26%. It is the concern with postoperative ARDS that has led to the practice of restrictive perioperative fluid therapy.4–6 Of particular concern with restricting perioperative fluids is the potential for hypovolemia and impaired tissue perfusion, which may result in organ dysfunction and postoperative acute kidney injury (AKI). The risk of AKI after lung resection varies between 6% and 24%, with a mortality rate of 3% to 20%.7–9 The fluid practices in thoracic surgery lie in marked contrast to the practice of goal-directed fluid therapy, often with the target of maximizing stroke volume with fluid boluses, that has been adopted for many noncardiac surgeries to improve outcome.10 The recent adoption of protective lung ventilation (PLV) strategy was shown to decrease the incidence of ARDS in patients after lung resection surgery. Interestingly, this reduction was found to be independent of the amount of fluids administered.11 To find an optimal fluid regimen for thoracic surgery in the PLV era, it is first required to establish the safety of normovolemia in these patients. This study tested the hypothesis that, in conjunction with a PLV strategy, a perioperative fluid protocol targeting normovolemia does not result in an increase in the accumulation of extravascular lung water.
to assess changes of these parameters over 72 hours postoperatively. Measurements and Main Results: The global end-diastolic volume index was maintained; cardiac index was increased, without a significant change in extravascular lung water index. Acute kidney injury based on AKIN criteria occurred in 3 patients (7.5%), and in 1 patient (2.5 %) based on RIFLE criteria. Lactic acid and central venous oxygen saturation remained within normal limits, and brain natriuretic peptide showed an insignificant increase. Conclusion: In patients undergoing lesser lung resections, a fluid protocol targeting normovolemia together with protective lung ventilation did not increase extravascular lung water. These results suggest further study to identify the optimal fluid regimen to mitigate pulmonic and extrapulmonic complications after lung resection. Published by Elsevier Inc. KEY WORDS: lung resection, fluid therapy, extravascular lung water, acute kidney injury METHODS
A single-center, prospective, observational study was conducted from January 2011 through May 2013. After approval of the study protocol by the institutional review board, informed consent was obtained from patients at least 18 years of age and scheduled for lung resection surgery for lung mass. Exclusion criteria included patients with an ejection fraction o40%, serum creatinine 42 mg/dL, or those scheduled for pneumonectomy. Hemodynamic Monitoring All patients were monitored using standard American Society of Anesthesiologist basic monitoring (leads II and V5 ECG, noninvasive blood pressure, pulse oximetry, continuous capnography and respiratory gas analysis, temperature, and urine output monitoring). In addition, transpulmonary thermodilution (PiCCO monitor, Pulsion Medical Systems, Munich, Germany) was performed via arterial and central venous catheters to calculate extravascular lung water index (EVLWI) together with other hemodynamic variables, ie, global end-diastolic volume index (GEDI) and cardiac index (CI). The arterial catheter was inserted into the brachial artery on the dependent side using a 4F (16-cm) pulsiocath (Pulsion Medical Systems). The central venous catheter was inserted on the same surgical side. After induction of general
From the *Cardiothoracic Anesthesia Service, †Cardiac Surgery Service; and ‡Department of Surgery and Intensive Care, and VA Connecticut Healthcare System and Yale University School of Medicine, New Haven, CT. Address reprint requests to Sherif Assaad, MD, Department of Anesthesiology, VA Healthcare System, 950 Campbell Avenue, West Haven, CT 06516. E-mail: [email protected] Published by Elsevier Inc. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.12.020
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 4 (August), 2015: pp 977–983
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anesthesia and initiation of two-lung mechanical ventilation in the supine position, the transpulmonary thermodilution measurement was performed using injection of 15 mL of cold saline. Three measurements within 15% of each other were obtained and averaged. This average was used as the baseline reference measurement. For 3 postoperative days (POD), at 8-hour intervals, the PiCCO monitor was recalibrated and a set of measurements were obtained. The average value of the 3 measurements acquired each day was used for data analysis. Tissue Biomarkers Tissue biomarker profile included serum creatinine, lactic acid, central venous oxygen saturation (ScVO2), and brain natriuretic peptide (BNP). These markers were measured daily for 3 postoperative days. Serum creatinine changes were compared with the preoperative value. BNP was measured preoperatively and compared with its value on POD 3. AKI was defined according to the Acute Kidney Injury Network (AKIN) and RIFLE criteria.12,13 Anesthetic Management and Mechanical Ventilation The anesthetic technique included induction of general anesthesia with fentanyl, propofol, and muscle relaxant, and was maintained with o1 MAC inhalation agent in 100% FiO2 during the one-lung ventilation period and converted to 30% FiO2 after resuming two-lung ventilation. A thoracic epidural was offered to all patients scheduled for open thoracotomy unless there was a contraindication. The epidural catheter was bolused with 6-to-8 mL of bupivacaine, together with 0.5 mg of hydromorphone, and was maintained at a continuous infusion rate of 6-to-8 mL/hour during the surgery and through POD 3. Hypotension resulting from epidural anesthetic vasodilation was treated with vasoactive drugs rather than intravenous fluids. An alternative analgesic approach consisting of continuous extrapleural intercostal nerve block or patient-controlled analgesia with intravenous narcotics was offered to patients scheduled for video-assisted thoracoscopic surgery or those with failed or contraindication to receive epidural analgesia. A PLV strategy was implemented during the one-lung ventilation period and continued after resumption of the twolung ventilation. This consisted of pressure-control ventilation aiming to achieve a tidal volume (VT) of 4-to-6 mL/kg of predicted body weight (PBW), peak airway pressure o30 cmH2O, PEEP of 5 cmH2O and performance of a vital capacity maneuver (sustained airway pressure of 30-to-35 cmH20 for 10 seconds) every 30 minutes. The fluid administration protocol was as follows: (1) IV maintenance fluid at a rate of 1.5 mL/kg/hour of total body weight with balanced salt solution,14 (Normosol, Hospira, Lake Forest, IL); the maintenance fluids were continued in the postoperative period until patients were able to tolerate adequate oral intake; (2) repletion of fasting hours with an IV fluid bolus (maintenance fluid X fasting hours); (3) repletion of evaporative fluid losses in open thoracotomy at a rate of 1 mL/kg/hour with IV balanced salt solution (Normosol); and (4) intraoperative blood loss was replaced in a 1:1 ratio with IV hetastarch solution 6% in lactated electrolyte injection (Hextend 670/0.7 by Hospira, Lake forest, IL) or with packed red blood cell transfusion if hematocrit dropped below 25%.
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Data Analysis Descriptive statistics were used to report the distribution of patients’ demographic and clinical characteristics. Data are presented as mean ⫾ SD (continuous variables) and percentages (categoric variables). Parametric (paired t test) or nonparametric (Wilcoxon signed-rank test) techniques were used as appropriate to assess changes (from baseline) of important clinical parameters (EVLWI, CI, and GEDI) and various tissue biomarkers in the perioperative period (serum creatinine and BNP). All analyses were performed using SAS 9.3, SAS Inc (SAS Institute Inc., Cary, NC). A post-hoc analysis was performed to assess the power to detect up to 20% increase in mean EVLWI15 over the 3 postoperative days compared with baseline. In addition, multivariable regression analysis was performed using the primary outcome of 3-day change in EVLWI compared with baseline. RESULTS
Forty-three patients consented for the study. Three patients were excluded (1 patient elected to have surgery in an outside facility and 2 patients were diagnosed with lymph node involvement after mediastinoscopy). The remaining 40 patients consisted of 3 females and 37 males, with a mean age of 67 years (54 to 83 years). All patients underwent either wedge resection or lobectomy except 1 patient who was scheduled for left upper lobectomy but proceeded to left pneumonectomy secondary to central invasion of the tumor. Hemodynamic data were incomplete for 1 patient on POD 1, 4 patients on POD 2, and 8 patients on POD 3 secondary to intensive care unit discharge and/or removal of their pulsiocath catheter. The patients’ perioperative characteristics are shown in Table 1. All patients were extubated at the end of surgery except 1 patient who developed hypercarbic respiratory acidosis and required 1 day of mechanical ventilatory support. Three patients were reintubated on POD 1 to 3 secondary to mucus plug causing lung collapse (1), or poor respiratory effort secondary to inadequate postoperative analgesia (2). Hemodynamic variables showed no significant increase in global end-diastolic volume index (Fig 1) and a marked increase in cardiac index (Fig 2). Extravascular lung water index showed no significant change over the 3 postoperative days, when compared with baseline values (Fig 3). In addition, no patient met the ARDS criteria as per the Berlin definition of acute respiratory distress syndrome. Post-hoc power analysis revealed that the study’s sample size (n ¼ 40) would allow for the detection of up to 20% increase in the 3-day mean EVLWI compared with baseline, with a power of 89.7% at an alpha-level of 0.05. Multivariable regression analysis was performed using the primary outcome of 3-day change in EVLWI compared with baseline as the dependent variable. Independent variables used included patient characteristics (eg, gender, alcohol use) and procedure characteristics (eg, mediastinoscopy before surgery, side of surgery, type of procedure [VATS/thoracotomy], part of lung resected [upper/middle/lower], and extent of resection [wedge resection/lobectomy]). None of these variables reached statistical significance at the 0.05 level. AKI based on AKIN criteria during POD 1 to 3 occurred in 3 patients (7.5%), all AKIN stage 1, with each patient showing
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3.5 ⫾ 0.8 2.5 ⫾ 0.7 79 ⫾ 19
The incidence of intraoperative hypotension episodes and the use of vasopressors were limited. Twelve out of the 40 patients required phenylephrine and/or ephedrine boluses, and no patient required continuous vasopressor infusion. In the AKI group, 1 of 3 patients developed intraoperative hypotension requiring phenylephrine (2 boluses, total 200 mg) compared with 11 of 37 patients in the non-AKI group (mean dose 387 ⫾ 271 mg). The changes in serum creatinine, lactic acid, ScVO2, and BNP for the group are displayed in Table 2. Serum creatinine showed slightly lower values in the postoperative period compared with baseline (p o 0.05), and lactic acid and ScVO2 remained within normal limits from day of surgery through postoperative day 3. BNP showed an insignificant rise on postoperative day 3 compared with baseline.
22 18
DISCUSSION
Table 1. Patient Characteristics American Society of Anesthesiologists (ASA) status
2 3 4 Alcohol use Yes No Mediastinoscopy before lung resection Yes No PFT: FVC (L) FEV1 (L) DLCO (%) Surgery side Right Left Surgery type Wedge Lobectomy Pneumonectomy Surgical approach VATS Open thoracotomy Pathology Positive Negative Analgesic approach Thoracic epidural Intercostal block PCA Surgical duration (min) One-lung ventilation duration (min) One-lung ventilation Tidal volume (mL/kg) Paw (cmH2O) PEEP (cmH2O) OR fluids Crystalloids (mL) Colloids (mL) PRBCs (units) EBL Number of patients receiving ephedrine Dose (mg) Number of patients receiving phenylephrine Dose (mg) Postoperative fluids Day of surgery (mL) POD 1 (mL) POD 2 (mL) POD 3 (mL) Average/day
1 31 8 24 16 12 28
10 29 1 20 20 32 8 26 11 3 366 ⫾ 89 223 ⫾ 88 4.5 ⫾ 0.2 20 ⫾ 4 5 ⫾ 1.2 ⫾ ⫾ ⫾ ⫾ 3 17.5 ⫾ 9 367 ⫾
2241 263 0.1 293
1557 2110 1166 1140 1528
⫾ ⫾ ⫾ ⫾ ⫾
488 286 0.5 273 8.3 262 686 1200 1078 1481 810
NOTE. Results are shown as mean ⫾ standard deviation. Abbreviations: PFT, Pulmonary Function Test; FVC, Forced Vital Capacity; FEV1, Forced Expiratory Volume in 1 Second; DLCO, Diffusion Capacity; VATS, Video Assisted Thoracic Surgery; PCA, Patient Controlled Analgesia; Paw, Peak Airway Pressure; PEEP, Positive End-Expiratory Pressure; OR, Operating Room; PRBC, Packed Red Blood Cells; POD, Postoperative Day.
full recovery of their serum creatinine to preoperative values within 24 hours. AKI based on RIFLE criteria occurred in 1 patient (2.5 %) on POD 3.
This observational study of lung resection surgery patients managed with a fluid protocol targeting normovolemia in conjunction with PLV showed that EVLWI does not increase postoperatively. The study protocol resulted in maintenance of cardiac preload as assessed by GEDI and an enhanced CI. This cardiovascular hemodynamic profile was associated with a favorable tissue perfusion biomarker profile as shown by normal serum lactic acid and central venous oxygen saturations. Serum creatinine for the group fell over the study period, although 3 patients met the stage-1 AKIN criteria postoperatively. In each case, AKI was short-lived, with full recovery of serum creatinine seen within 24 hours. Multiple risk factors have been associated with the development of ARDS after lung resection surgery, including major resections like pneumonectomy, large tidal volumes and high peak airway pressures during the one-lung ventilation period, and excessive perioperative fluid intake.4–6,16 The findings, that normovolemia does not result in increases in EVLWI, were consistent with the current understanding of ARDS after lung resection as primarily a disorder of capillary permeability rather than that of elevated hydrostatic pressure. Dull et al17 reported that a doubling of left atrial pressure is required to significantly increase the pulmonary capillary permeability coefficient. This is due to the adaptive properties of the pulmonary circulation, which mitigates increases in pulmonary capillary pressure in response to changes in intravascular volume.18 This response partly can explain the difference in the incidence of postoperative ARDS between pneumonectomy and lesser resections. With pneumonectomy, the entire right-heart output is directed to the opposite lung, which can overwhelm the adaptive mechanisms of the remaining pulmonary circulation, even under normovolemic conditions, resulting in a rise in pulmonary capillary pressure.19 Prior studies showing increased fluid administration to be associated with ARDS after lung resection studied mixed surgical groups, which included pneumonectomy as well as lesser resections. Thus, interpretation of the impact of fluid administration on lesser resections is complicated.5,6 Further, these studies were performed before adoption of the practice of PLV. Because of these limitations, the role of fluid load as a causative factor in lesser resection cases managed by PLV is ill-defined. The study results do not support a causative role for
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Fig 1. Postoperative changes in GEDI (mL/m2) compared with baseline preoperative value. Abbreviations: GEDI, global end-diastolic index; NS, not significant; Max, maximum; Avg, average; Min, minimum; STL, supine two-lung ventilation; POD, postoperative day.
fluids increasing EVLWI in patients managed with the target of normovolemia under PLV. There is strong evidence that ventilator-induced lung injury is a causative factor for after-lung-resection ARDS. Large tidal volumes traditionally used (8-10 mL/kg) can result in physical strain to the alveolar wall, resulting in upregulation of pulmonary cytokines and local inflammatory process of the lungs, causing increased permeability and systemic inflammatory response.20–22
This biotrauma presents as capillary leak and pulmonary edema. Accordingly, small tidal volumes (less than 8 mL/kg PBW) are now recommended for all patients at the initiation of mechanical ventilation.23,24 In thoracic surgery, Licker et al11 compared patients who received PLV with VT 5.3 mL/kg to those who received VT 7.1 mL/kg PBW and showed that the incidence of ARDS dropped from 3.7% to 0.9% despite no difference in the perioperative fluid intake between the 2 groups.
Fig 2. Postoperative changes in CI (L/min/m2) compared with baseline preoperative value. Abbreviations: CI, cardiac index; Max, maximum; Avg, average; Min, minimum; STL, supine two-lung ventilation; POD, postoperative day.
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Fig 3. Postoperative changes in EVLWI (mL/kg) compared with preoperative baseline value. Abbreviations: EVLWI, extravascular lung water index; NS, not significant; Max, maximum; Avg, average; Min, minimum; STL, supine two-lung ventilation; POD, postoperative day.
Recent findings have challenged the role of hydrostatic forces as described by the Starling principle and demonstrated non-Starling mechanisms related to glycocalyx integrity to account for the development of ventilator-induced lung-injury induced pulmonary edema.17 The present results provide further support to the move of the clinical management of lung resection patients from a focus of restrictive fluids to a new focus of restrictive ventilation and normovolemia. Acute kidney injury after lung resection surgery has been underappreciated for years. One of the reasons for this was the lack of a unified, sensitive definition for acute kidney injury. The Society of Thoracic Surgeons database reported an incidence of 1.4% for AKI after lung resection surgery. This low incidence is explained by their definition of AKI to patients requiring renal replacement therapy.25 In contrast, studies using more sensitive markers of renal injury have found AKI rates of 6% to 24%, with a mortality rate of 3% to 20%.7–9 In an effort to unify the diagnosis of AKI, in 2004 the Acute Dialysis Quality Initiative Group introduced a classification system of AKI called the RIFLE criteria (risk, injury, failure, loss, and end-stage renal disease).13 This was followed in 2007 with the Acute Kidney Injury Network (AKIN) classification
system.12 AKIN classification used a Z0.3 mg/dL increase or a 1.5- to 2-fold increase in serum creatinine as criteria for stage 1 AKI. The development of AKI as defined by either the AKIN or RIFLE classifications in cardiac and thoracic surgery was associated with lower long-term survival rates. When stratified according to the severity of AKI, advanced AKI stages were associated with progressively higher mortality rates.26,27 In thoracic surgery patients, Licker et al 9 reported an AKI incidence of 6.8% using the RIFLE criteria, with a significantly increased mortality rate of 19.8% compared with those without AKI. In their study, they identified the ASA class 3 and 4, the extent of surgical resection and the duration of surgery as independent risk factors for developing AKI. These findings were confirmed by Ishikawa et al,8 who reported an AKI incidence of 5.9% according to the AKIN classification. The mortality rate was nearly 4-fold higher in the AKI group although the study was not powered to show a statistically significant difference at the p ¼ 0.05 level. Golledge et al7 found similar results in a lung resection cohort with a renal impairment rate of 24%, and significantly increased mortality of 19% compared with the non-AKI patients. In the present high-risk study population of elderly, predominantly ASA class
Table 2. Postoperative Tissue Biomarkers
Serum creatinine* (mg/dL) Lactic acid (mg/dL) Central venous oxygen saturation (%) Brain natriuretic† peptide (pg/mL)
Baseline
Day of Surgery
POD 1
POD 2
POD 3
1.0 ⫾ 0.3
0.9 ⫾ 0.22 1.5 ⫾ 0.9 74 ⫾ 9
0.9 ⫾ 0.4 1.5 ⫾ 0.5 73 ⫾ 8
0.87 ⫾ 0.3 1.2 ⫾ 0.5 71 ⫾ 7
0.86 ⫾ 0.2 0.8 ⫾ 0.3 69 ⫾ 8 158 ⫾ 136
97 ⫾ 168
Abbreviation: POD, postoperative day. NOTE. Results are shown as mean ⫾ standard deviation. *The changes in serum creatinine from day of surgery through each postoperative day were significantly lower than baseline (p o 0.0001). †The change from baseline was not statistically significant.
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3 and 4 patients, undergoing more prolonged surgeries (mean duration of 366 ⫾ 89 min), the incidence of AKI was 7.5%. Most cases of renal impairment share an underlying common hypoperfusive pathogenesis.28 In a study of patients undergoing cardiac surgery, 80% of patients with postoperative renal damage evidenced a previous perioperative episode of hemodynamic instability.29 Fluids are a key component to support adequate perfusion. In certain patients, normovolemia might not be enough to achieve this, and the addition of inotropic drugs is required for hemodynamic optimization and oxygen delivery to the kidneys. A recent meta-analysis of highrisk surgical patients showed that perioperative hemodynamic optimization with adequate fluid loading and inotropic drugs in the perioperative period resulted in reduction in the incidence of AKI.30 In the current study, a normovolemic protocol was associated with an increase in CI even without the addition of inotropic support, resulting in normal tissue perfusion biomarkers. The calculation of extravascular lung water index using the transpulmonary thermodilution technique by the PiCCO monitor has been validated against the gold standard gravimetric method.31,32 Several investigators studied the prognostic value of EVLWI in critically ill patients and showed that elevated EVLWI was associated with a lower survival rate.33–35 It also was shown to be an early predictor of patients who are at risk
for developing ARDS.36 A 20% rise from baseline in EVLWI was associated with pulmonary complications in a group of esophageal resection patients.15 EVLWI also has been used as a marker for pulmonic injury to study the impact of protective lung ventilation.37 One of the potential limitations of the present study, other than the limited population, was the impact of lung resection on the single dye transpulmonary thermodilution calculation of the EVLWI. Naidu et al reported that the single dye approach could be used successfully to measure changes in EVLWI after lung resection.38 CONCLUSION
The use of a normovolemic fluid protocol in conjunction with protective lung ventilation did not increase lung water after lung resection surgery. These results suggest further examinations, including randomized controlled trials, to identify the optimal fluid regimen to mitigate pulmonic and extrapulmonic organ injury in patients undergoing lobectomy and wedge resections. ACKNOWLEDGMENT
The authors thank the surgical intensive care unit nurses at the West Haven VA hospital for their help in the study and also thank Ms. Cindy Mason for her help in data collection.
REFERENCES 1. Memtsoudis SG, Besculides MC, Zellos L, et al: Trends in lung surgery: United States 1988 to 2002. Chest 130:1462-1470, 2006 2. Riaz SP, Luchtenborg M, Coupland VH, et al: Trends in incidence of small cell lung cancer and all lung cancer. Lung Cancer 75: 280-284, 2012 3. Khakwani A, Rich AL, Powell HA, et al: Lung cancer survival in England: Trends in non-small-cell lung cancer survival over the duration of the National Lung Cancer Audit. Br J Cancer 109: 2058-2065, 2013 4. Parquin F, Marchal M, Mehiri S, et al: Post-pneumonectomy pulmonary edema: Analysis and risk factors. Eur J Cardiothorac Surg 10:929-932; discussion 933, 1996 5. Licker M, de Perrot M, Spiliopoulos A, et al: Risk factors for acute lung injury after thoracic surgery for lung cancer. Anesth Analg 97:1558-1565, 2003 6. Alam N, Park BJ, Wilton A, et al: Incidence and risk factors for lung injury after lung cancer resection. Ann Thorac Surg 84:10851091; discussion 1091, 2007 7. Golledge J, Goldstraw P: Renal impairment after thoracotomy: incidence, risk factors, and significance. Ann Thorac Surg 58:524-528, 1994 8. Ishikawa S, Griesdale DE, Lohser J: Acute kidney injury after lung resection surgery: Incidence and perioperative risk factors. Anesth Analg 114:1256-1262, 2012 9. Licker M, Cartier V, Robert J, et al: Risk factors of acute kidney injury according to RIFLE criteria after lung cancer surgery. Ann Thorac Surg 91:844-850, 2011 10. Noblett SE, Snowden CP, Shenton BK, et al: Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. Br J Surg 93: 1069-1076, 2006 11. Licker M, Diaper J, Villiger Y, et al: Impact of intraoperative lung-protective interventions in patients undergoing lung cancer surgery. Crit Care 13:R41, 2009
12. Mehta RL, Kellum JA, Shah SV, et al: Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31, 2007 13. Bellomo R, Ronco C, Kellum JA, et al: Acute renal failure— Definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204-R212, 2004 14. Evans RG, Naidu B: Does a conservative fluid management strategy in the perioperative management of lung resection patients reduce the risk of acute lung injury? Interact Cardiovasc Thorac Surg 15:498-504, 2012 15. Ueki H: Study on changes in extravascular lung water during early postoperative periods in thoracic esophageal cancer—with special emphasis on their relation to postoperative renal function [article in Japanese]. Nihon Kyobu Geka Gakkai Zasshi 38: 442-456, 1990 16. Blank RS, Hucklenbruch C, Gurka KK, et al: Intraoperative factors and the risk of respiratory complications after pneumonectomy. Ann Thorac Surg 92:1188-1194, 2011 17. Dull RO, Cluff M, Kingston J, et al: Lung heparan sulfates modulate K(fc) during increased vascular pressure: evidence for glycocalyx-mediated mechanotransduction. Am J Physiol Lung Cell Mol Physiol 302:L816-L828, 2012 18. West J: Respiratory Physiology: The Essentials (8th edition). Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins, 35-51, 2008 19. Waller DA, Keavey P, Woodfine L, et al: Pulmonary endothelial permeability changes after major lung resection. Ann Thorac Surg 61: 1435-1440, 1996 20. Hegeman MA, Hennus MP, Heijnen CJ, et al: Ventilator-induced endothelial activation and inflammation in the lung and distal organs. Crit Care 13:R182, 2009
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21. Gattinoni L, Pesenti A: The concept of "baby lung". Intensive Care Med 31:776-784, 2005 22. Gattinoni L, Protti A, Caironi P, et al: Ventilator-induced lung injury: the anatomical and physiological framework. Crit Care Med 38: S539-S548, 2010 23. Schultz MJ: Lung-protective mechanical ventilation with lower tidal volumes in patients not suffering from acute lung injury: A review of clinical studies. Med Sci Monit 14:RA22-RA26, 2008 24. Lellouche F, Dionne S, Simard S, et al: High tidal volumes in mechanically ventilated patients increase organ dysfunction after cardiac surgery. Anesthesiology 116:1072-1082, 2012 25. Boffa DJ, Allen MS, Grab JD, et al: Data from The Society of Thoracic Surgeons General Thoracic Surgery database: The surgical management of primary lung tumors. J Thorac Cardiovasc Surg 135: 247-254, 2008 26. Hansen MK, Gammelager H, Mikkelsen MM, et al: Postoperative acute kidney injury and five-year risk of death, myocardial infarction, and stroke among elective cardiac surgical patients: a cohort study. Crit Care 17:R292, 2013 27. Hobson CE, Yavas S, Segal MS, et al: Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 119:2444-2453, 2009 28. Tang IY, Murray PT: Prevention of perioperative acute renal failure: What works? Best Pract Res Clin Anaesthesiol 18:91-111, 2004 29. Mangano CM, Diamondstone LS, Ramsay JG, et al: Renal dysfunction after myocardial revascularization: Risk factors, adverse outcomes, and hospital resource utilization. The Multicenter Study of Perioperative Ischemia Research Group. Ann Intern Med 128:194-203, 1998
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30. Brienza N, Giglio MT, Marucci M, et al: Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study. Crit Care Med 37:2079-2090, 2009 31. Katzenelson R, Perel A, Berkenstadt H, et al: Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water. Crit Care Med 32:1550-1554, 2004 32. Kuzkov VV, Suborov EV, Kirov MY, et al: Extravascular lung water after pneumonectomy and one-lung ventilation in sheep. Crit Care Med 35:1550-1559, 2007 33. 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 27:420 e421-e428, 2012 34. Sakka SG, Klein M, Reinhart K, et al: Prognostic value of extravascular lung water in critically ill patients. Chest 122: 2080-2086, 2002 35. Yang CS, Qiu HB, Liu SQ, et al: The prognostic value of extravascular lung water index in critically ill septic shock patients [article in Chinese]. Zhonghua Nei Ke Za Zhi 45:192-195, 2006 36. LeTourneau JL, Pinney J, Phillips CR: Extravascular lung water predicts progression to acute lung injury in patients with increased risk*. Crit Care Med 40:847-854, 2012 37. Qutub H, El-Tahan MR, Mowafi HA, et al: Effect of tidal volume on extravascular lung water content during one-lung ventilation for video-assisted thoracoscopic surgery: A randomised, controlled trial. Eur J Anaesthesiol 31:466-473, 2014 38. Naidu BV, Dronavalli VB, Rajesh PB: Measuring lung water following major lung resection. Interact Cardiovasc Thorac Surg 8: 503-506, 2009
A
DVANCES IN ONCOLOGIC PRACTICE have led to a worldwide increase in lung cancer resections over the past decade. Notably, this growth is composed primarily of lesser lung resections compared with pneumonectomies.1–3 Despite an improvement in the early mortality rate, pulmonary complications remain the main cause of postoperative morbidity. These range from mild complications, such as atelectasis and pneumonia, to the more severe acute respiratory distress syndrome (ARDS). The risk of developing ARDS after lung resection varies according to the extent of resection, with pneumonectomy carrying the highest risk (3%10% compared with 2%-5% for lesser resections) and a mortality rate of 26%. It is the concern with postoperative ARDS that has led to the practice of restrictive perioperative fluid therapy.4–6 Of particular concern with restricting perioperative fluids is the potential for hypovolemia and impaired tissue perfusion, which may result in organ dysfunction and postoperative acute kidney injury (AKI). The risk of AKI after lung resection varies between 6% and 24%, with a mortality rate of 3% to 20%.7–9 The fluid practices in thoracic surgery lie in marked contrast to the practice of goal-directed fluid therapy, often with the target of maximizing stroke volume with fluid boluses, that has been adopted for many noncardiac surgeries to improve outcome.10 The recent adoption of protective lung ventilation (PLV) strategy was shown to decrease the incidence of ARDS in patients after lung resection surgery. Interestingly, this reduction was found to be independent of the amount of fluids administered.11 To find an optimal fluid regimen for thoracic surgery in the PLV era, it is first required to establish the safety of normovolemia in these patients. This study tested the hypothesis that, in conjunction with a PLV strategy, a perioperative fluid protocol targeting normovolemia does not result in an increase in the accumulation of extravascular lung water.
to assess changes of these parameters over 72 hours postoperatively. Measurements and Main Results: The global end-diastolic volume index was maintained; cardiac index was increased, without a significant change in extravascular lung water index. Acute kidney injury based on AKIN criteria occurred in 3 patients (7.5%), and in 1 patient (2.5 %) based on RIFLE criteria. Lactic acid and central venous oxygen saturation remained within normal limits, and brain natriuretic peptide showed an insignificant increase. Conclusion: In patients undergoing lesser lung resections, a fluid protocol targeting normovolemia together with protective lung ventilation did not increase extravascular lung water. These results suggest further study to identify the optimal fluid regimen to mitigate pulmonic and extrapulmonic complications after lung resection. Published by Elsevier Inc. KEY WORDS: lung resection, fluid therapy, extravascular lung water, acute kidney injury METHODS
A single-center, prospective, observational study was conducted from January 2011 through May 2013. After approval of the study protocol by the institutional review board, informed consent was obtained from patients at least 18 years of age and scheduled for lung resection surgery for lung mass. Exclusion criteria included patients with an ejection fraction o40%, serum creatinine 42 mg/dL, or those scheduled for pneumonectomy. Hemodynamic Monitoring All patients were monitored using standard American Society of Anesthesiologist basic monitoring (leads II and V5 ECG, noninvasive blood pressure, pulse oximetry, continuous capnography and respiratory gas analysis, temperature, and urine output monitoring). In addition, transpulmonary thermodilution (PiCCO monitor, Pulsion Medical Systems, Munich, Germany) was performed via arterial and central venous catheters to calculate extravascular lung water index (EVLWI) together with other hemodynamic variables, ie, global end-diastolic volume index (GEDI) and cardiac index (CI). The arterial catheter was inserted into the brachial artery on the dependent side using a 4F (16-cm) pulsiocath (Pulsion Medical Systems). The central venous catheter was inserted on the same surgical side. After induction of general
From the *Cardiothoracic Anesthesia Service, †Cardiac Surgery Service; and ‡Department of Surgery and Intensive Care, and VA Connecticut Healthcare System and Yale University School of Medicine, New Haven, CT. Address reprint requests to Sherif Assaad, MD, Department of Anesthesiology, VA Healthcare System, 950 Campbell Avenue, West Haven, CT 06516. E-mail: [email protected] Published by Elsevier Inc. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.12.020
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 4 (August), 2015: pp 977–983
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anesthesia and initiation of two-lung mechanical ventilation in the supine position, the transpulmonary thermodilution measurement was performed using injection of 15 mL of cold saline. Three measurements within 15% of each other were obtained and averaged. This average was used as the baseline reference measurement. For 3 postoperative days (POD), at 8-hour intervals, the PiCCO monitor was recalibrated and a set of measurements were obtained. The average value of the 3 measurements acquired each day was used for data analysis. Tissue Biomarkers Tissue biomarker profile included serum creatinine, lactic acid, central venous oxygen saturation (ScVO2), and brain natriuretic peptide (BNP). These markers were measured daily for 3 postoperative days. Serum creatinine changes were compared with the preoperative value. BNP was measured preoperatively and compared with its value on POD 3. AKI was defined according to the Acute Kidney Injury Network (AKIN) and RIFLE criteria.12,13 Anesthetic Management and Mechanical Ventilation The anesthetic technique included induction of general anesthesia with fentanyl, propofol, and muscle relaxant, and was maintained with o1 MAC inhalation agent in 100% FiO2 during the one-lung ventilation period and converted to 30% FiO2 after resuming two-lung ventilation. A thoracic epidural was offered to all patients scheduled for open thoracotomy unless there was a contraindication. The epidural catheter was bolused with 6-to-8 mL of bupivacaine, together with 0.5 mg of hydromorphone, and was maintained at a continuous infusion rate of 6-to-8 mL/hour during the surgery and through POD 3. Hypotension resulting from epidural anesthetic vasodilation was treated with vasoactive drugs rather than intravenous fluids. An alternative analgesic approach consisting of continuous extrapleural intercostal nerve block or patient-controlled analgesia with intravenous narcotics was offered to patients scheduled for video-assisted thoracoscopic surgery or those with failed or contraindication to receive epidural analgesia. A PLV strategy was implemented during the one-lung ventilation period and continued after resumption of the twolung ventilation. This consisted of pressure-control ventilation aiming to achieve a tidal volume (VT) of 4-to-6 mL/kg of predicted body weight (PBW), peak airway pressure o30 cmH2O, PEEP of 5 cmH2O and performance of a vital capacity maneuver (sustained airway pressure of 30-to-35 cmH20 for 10 seconds) every 30 minutes. The fluid administration protocol was as follows: (1) IV maintenance fluid at a rate of 1.5 mL/kg/hour of total body weight with balanced salt solution,14 (Normosol, Hospira, Lake Forest, IL); the maintenance fluids were continued in the postoperative period until patients were able to tolerate adequate oral intake; (2) repletion of fasting hours with an IV fluid bolus (maintenance fluid X fasting hours); (3) repletion of evaporative fluid losses in open thoracotomy at a rate of 1 mL/kg/hour with IV balanced salt solution (Normosol); and (4) intraoperative blood loss was replaced in a 1:1 ratio with IV hetastarch solution 6% in lactated electrolyte injection (Hextend 670/0.7 by Hospira, Lake forest, IL) or with packed red blood cell transfusion if hematocrit dropped below 25%.
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Data Analysis Descriptive statistics were used to report the distribution of patients’ demographic and clinical characteristics. Data are presented as mean ⫾ SD (continuous variables) and percentages (categoric variables). Parametric (paired t test) or nonparametric (Wilcoxon signed-rank test) techniques were used as appropriate to assess changes (from baseline) of important clinical parameters (EVLWI, CI, and GEDI) and various tissue biomarkers in the perioperative period (serum creatinine and BNP). All analyses were performed using SAS 9.3, SAS Inc (SAS Institute Inc., Cary, NC). A post-hoc analysis was performed to assess the power to detect up to 20% increase in mean EVLWI15 over the 3 postoperative days compared with baseline. In addition, multivariable regression analysis was performed using the primary outcome of 3-day change in EVLWI compared with baseline. RESULTS
Forty-three patients consented for the study. Three patients were excluded (1 patient elected to have surgery in an outside facility and 2 patients were diagnosed with lymph node involvement after mediastinoscopy). The remaining 40 patients consisted of 3 females and 37 males, with a mean age of 67 years (54 to 83 years). All patients underwent either wedge resection or lobectomy except 1 patient who was scheduled for left upper lobectomy but proceeded to left pneumonectomy secondary to central invasion of the tumor. Hemodynamic data were incomplete for 1 patient on POD 1, 4 patients on POD 2, and 8 patients on POD 3 secondary to intensive care unit discharge and/or removal of their pulsiocath catheter. The patients’ perioperative characteristics are shown in Table 1. All patients were extubated at the end of surgery except 1 patient who developed hypercarbic respiratory acidosis and required 1 day of mechanical ventilatory support. Three patients were reintubated on POD 1 to 3 secondary to mucus plug causing lung collapse (1), or poor respiratory effort secondary to inadequate postoperative analgesia (2). Hemodynamic variables showed no significant increase in global end-diastolic volume index (Fig 1) and a marked increase in cardiac index (Fig 2). Extravascular lung water index showed no significant change over the 3 postoperative days, when compared with baseline values (Fig 3). In addition, no patient met the ARDS criteria as per the Berlin definition of acute respiratory distress syndrome. Post-hoc power analysis revealed that the study’s sample size (n ¼ 40) would allow for the detection of up to 20% increase in the 3-day mean EVLWI compared with baseline, with a power of 89.7% at an alpha-level of 0.05. Multivariable regression analysis was performed using the primary outcome of 3-day change in EVLWI compared with baseline as the dependent variable. Independent variables used included patient characteristics (eg, gender, alcohol use) and procedure characteristics (eg, mediastinoscopy before surgery, side of surgery, type of procedure [VATS/thoracotomy], part of lung resected [upper/middle/lower], and extent of resection [wedge resection/lobectomy]). None of these variables reached statistical significance at the 0.05 level. AKI based on AKIN criteria during POD 1 to 3 occurred in 3 patients (7.5%), all AKIN stage 1, with each patient showing
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3.5 ⫾ 0.8 2.5 ⫾ 0.7 79 ⫾ 19
The incidence of intraoperative hypotension episodes and the use of vasopressors were limited. Twelve out of the 40 patients required phenylephrine and/or ephedrine boluses, and no patient required continuous vasopressor infusion. In the AKI group, 1 of 3 patients developed intraoperative hypotension requiring phenylephrine (2 boluses, total 200 mg) compared with 11 of 37 patients in the non-AKI group (mean dose 387 ⫾ 271 mg). The changes in serum creatinine, lactic acid, ScVO2, and BNP for the group are displayed in Table 2. Serum creatinine showed slightly lower values in the postoperative period compared with baseline (p o 0.05), and lactic acid and ScVO2 remained within normal limits from day of surgery through postoperative day 3. BNP showed an insignificant rise on postoperative day 3 compared with baseline.
22 18
DISCUSSION
Table 1. Patient Characteristics American Society of Anesthesiologists (ASA) status
2 3 4 Alcohol use Yes No Mediastinoscopy before lung resection Yes No PFT: FVC (L) FEV1 (L) DLCO (%) Surgery side Right Left Surgery type Wedge Lobectomy Pneumonectomy Surgical approach VATS Open thoracotomy Pathology Positive Negative Analgesic approach Thoracic epidural Intercostal block PCA Surgical duration (min) One-lung ventilation duration (min) One-lung ventilation Tidal volume (mL/kg) Paw (cmH2O) PEEP (cmH2O) OR fluids Crystalloids (mL) Colloids (mL) PRBCs (units) EBL Number of patients receiving ephedrine Dose (mg) Number of patients receiving phenylephrine Dose (mg) Postoperative fluids Day of surgery (mL) POD 1 (mL) POD 2 (mL) POD 3 (mL) Average/day
1 31 8 24 16 12 28
10 29 1 20 20 32 8 26 11 3 366 ⫾ 89 223 ⫾ 88 4.5 ⫾ 0.2 20 ⫾ 4 5 ⫾ 1.2 ⫾ ⫾ ⫾ ⫾ 3 17.5 ⫾ 9 367 ⫾
2241 263 0.1 293
1557 2110 1166 1140 1528
⫾ ⫾ ⫾ ⫾ ⫾
488 286 0.5 273 8.3 262 686 1200 1078 1481 810
NOTE. Results are shown as mean ⫾ standard deviation. Abbreviations: PFT, Pulmonary Function Test; FVC, Forced Vital Capacity; FEV1, Forced Expiratory Volume in 1 Second; DLCO, Diffusion Capacity; VATS, Video Assisted Thoracic Surgery; PCA, Patient Controlled Analgesia; Paw, Peak Airway Pressure; PEEP, Positive End-Expiratory Pressure; OR, Operating Room; PRBC, Packed Red Blood Cells; POD, Postoperative Day.
full recovery of their serum creatinine to preoperative values within 24 hours. AKI based on RIFLE criteria occurred in 1 patient (2.5 %) on POD 3.
This observational study of lung resection surgery patients managed with a fluid protocol targeting normovolemia in conjunction with PLV showed that EVLWI does not increase postoperatively. The study protocol resulted in maintenance of cardiac preload as assessed by GEDI and an enhanced CI. This cardiovascular hemodynamic profile was associated with a favorable tissue perfusion biomarker profile as shown by normal serum lactic acid and central venous oxygen saturations. Serum creatinine for the group fell over the study period, although 3 patients met the stage-1 AKIN criteria postoperatively. In each case, AKI was short-lived, with full recovery of serum creatinine seen within 24 hours. Multiple risk factors have been associated with the development of ARDS after lung resection surgery, including major resections like pneumonectomy, large tidal volumes and high peak airway pressures during the one-lung ventilation period, and excessive perioperative fluid intake.4–6,16 The findings, that normovolemia does not result in increases in EVLWI, were consistent with the current understanding of ARDS after lung resection as primarily a disorder of capillary permeability rather than that of elevated hydrostatic pressure. Dull et al17 reported that a doubling of left atrial pressure is required to significantly increase the pulmonary capillary permeability coefficient. This is due to the adaptive properties of the pulmonary circulation, which mitigates increases in pulmonary capillary pressure in response to changes in intravascular volume.18 This response partly can explain the difference in the incidence of postoperative ARDS between pneumonectomy and lesser resections. With pneumonectomy, the entire right-heart output is directed to the opposite lung, which can overwhelm the adaptive mechanisms of the remaining pulmonary circulation, even under normovolemic conditions, resulting in a rise in pulmonary capillary pressure.19 Prior studies showing increased fluid administration to be associated with ARDS after lung resection studied mixed surgical groups, which included pneumonectomy as well as lesser resections. Thus, interpretation of the impact of fluid administration on lesser resections is complicated.5,6 Further, these studies were performed before adoption of the practice of PLV. Because of these limitations, the role of fluid load as a causative factor in lesser resection cases managed by PLV is ill-defined. The study results do not support a causative role for
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Fig 1. Postoperative changes in GEDI (mL/m2) compared with baseline preoperative value. Abbreviations: GEDI, global end-diastolic index; NS, not significant; Max, maximum; Avg, average; Min, minimum; STL, supine two-lung ventilation; POD, postoperative day.
fluids increasing EVLWI in patients managed with the target of normovolemia under PLV. There is strong evidence that ventilator-induced lung injury is a causative factor for after-lung-resection ARDS. Large tidal volumes traditionally used (8-10 mL/kg) can result in physical strain to the alveolar wall, resulting in upregulation of pulmonary cytokines and local inflammatory process of the lungs, causing increased permeability and systemic inflammatory response.20–22
This biotrauma presents as capillary leak and pulmonary edema. Accordingly, small tidal volumes (less than 8 mL/kg PBW) are now recommended for all patients at the initiation of mechanical ventilation.23,24 In thoracic surgery, Licker et al11 compared patients who received PLV with VT 5.3 mL/kg to those who received VT 7.1 mL/kg PBW and showed that the incidence of ARDS dropped from 3.7% to 0.9% despite no difference in the perioperative fluid intake between the 2 groups.
Fig 2. Postoperative changes in CI (L/min/m2) compared with baseline preoperative value. Abbreviations: CI, cardiac index; Max, maximum; Avg, average; Min, minimum; STL, supine two-lung ventilation; POD, postoperative day.
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Fig 3. Postoperative changes in EVLWI (mL/kg) compared with preoperative baseline value. Abbreviations: EVLWI, extravascular lung water index; NS, not significant; Max, maximum; Avg, average; Min, minimum; STL, supine two-lung ventilation; POD, postoperative day.
Recent findings have challenged the role of hydrostatic forces as described by the Starling principle and demonstrated non-Starling mechanisms related to glycocalyx integrity to account for the development of ventilator-induced lung-injury induced pulmonary edema.17 The present results provide further support to the move of the clinical management of lung resection patients from a focus of restrictive fluids to a new focus of restrictive ventilation and normovolemia. Acute kidney injury after lung resection surgery has been underappreciated for years. One of the reasons for this was the lack of a unified, sensitive definition for acute kidney injury. The Society of Thoracic Surgeons database reported an incidence of 1.4% for AKI after lung resection surgery. This low incidence is explained by their definition of AKI to patients requiring renal replacement therapy.25 In contrast, studies using more sensitive markers of renal injury have found AKI rates of 6% to 24%, with a mortality rate of 3% to 20%.7–9 In an effort to unify the diagnosis of AKI, in 2004 the Acute Dialysis Quality Initiative Group introduced a classification system of AKI called the RIFLE criteria (risk, injury, failure, loss, and end-stage renal disease).13 This was followed in 2007 with the Acute Kidney Injury Network (AKIN) classification
system.12 AKIN classification used a Z0.3 mg/dL increase or a 1.5- to 2-fold increase in serum creatinine as criteria for stage 1 AKI. The development of AKI as defined by either the AKIN or RIFLE classifications in cardiac and thoracic surgery was associated with lower long-term survival rates. When stratified according to the severity of AKI, advanced AKI stages were associated with progressively higher mortality rates.26,27 In thoracic surgery patients, Licker et al 9 reported an AKI incidence of 6.8% using the RIFLE criteria, with a significantly increased mortality rate of 19.8% compared with those without AKI. In their study, they identified the ASA class 3 and 4, the extent of surgical resection and the duration of surgery as independent risk factors for developing AKI. These findings were confirmed by Ishikawa et al,8 who reported an AKI incidence of 5.9% according to the AKIN classification. The mortality rate was nearly 4-fold higher in the AKI group although the study was not powered to show a statistically significant difference at the p ¼ 0.05 level. Golledge et al7 found similar results in a lung resection cohort with a renal impairment rate of 24%, and significantly increased mortality of 19% compared with the non-AKI patients. In the present high-risk study population of elderly, predominantly ASA class
Table 2. Postoperative Tissue Biomarkers
Serum creatinine* (mg/dL) Lactic acid (mg/dL) Central venous oxygen saturation (%) Brain natriuretic† peptide (pg/mL)
Baseline
Day of Surgery
POD 1
POD 2
POD 3
1.0 ⫾ 0.3
0.9 ⫾ 0.22 1.5 ⫾ 0.9 74 ⫾ 9
0.9 ⫾ 0.4 1.5 ⫾ 0.5 73 ⫾ 8
0.87 ⫾ 0.3 1.2 ⫾ 0.5 71 ⫾ 7
0.86 ⫾ 0.2 0.8 ⫾ 0.3 69 ⫾ 8 158 ⫾ 136
97 ⫾ 168
Abbreviation: POD, postoperative day. NOTE. Results are shown as mean ⫾ standard deviation. *The changes in serum creatinine from day of surgery through each postoperative day were significantly lower than baseline (p o 0.0001). †The change from baseline was not statistically significant.
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3 and 4 patients, undergoing more prolonged surgeries (mean duration of 366 ⫾ 89 min), the incidence of AKI was 7.5%. Most cases of renal impairment share an underlying common hypoperfusive pathogenesis.28 In a study of patients undergoing cardiac surgery, 80% of patients with postoperative renal damage evidenced a previous perioperative episode of hemodynamic instability.29 Fluids are a key component to support adequate perfusion. In certain patients, normovolemia might not be enough to achieve this, and the addition of inotropic drugs is required for hemodynamic optimization and oxygen delivery to the kidneys. A recent meta-analysis of highrisk surgical patients showed that perioperative hemodynamic optimization with adequate fluid loading and inotropic drugs in the perioperative period resulted in reduction in the incidence of AKI.30 In the current study, a normovolemic protocol was associated with an increase in CI even without the addition of inotropic support, resulting in normal tissue perfusion biomarkers. The calculation of extravascular lung water index using the transpulmonary thermodilution technique by the PiCCO monitor has been validated against the gold standard gravimetric method.31,32 Several investigators studied the prognostic value of EVLWI in critically ill patients and showed that elevated EVLWI was associated with a lower survival rate.33–35 It also was shown to be an early predictor of patients who are at risk
for developing ARDS.36 A 20% rise from baseline in EVLWI was associated with pulmonary complications in a group of esophageal resection patients.15 EVLWI also has been used as a marker for pulmonic injury to study the impact of protective lung ventilation.37 One of the potential limitations of the present study, other than the limited population, was the impact of lung resection on the single dye transpulmonary thermodilution calculation of the EVLWI. Naidu et al reported that the single dye approach could be used successfully to measure changes in EVLWI after lung resection.38 CONCLUSION
The use of a normovolemic fluid protocol in conjunction with protective lung ventilation did not increase lung water after lung resection surgery. These results suggest further examinations, including randomized controlled trials, to identify the optimal fluid regimen to mitigate pulmonic and extrapulmonic organ injury in patients undergoing lobectomy and wedge resections. ACKNOWLEDGMENT
The authors thank the surgical intensive care unit nurses at the West Haven VA hospital for their help in the study and also thank Ms. Cindy Mason for her help in data collection.
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30. Brienza N, Giglio MT, Marucci M, et al: Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study. Crit Care Med 37:2079-2090, 2009 31. Katzenelson R, Perel A, Berkenstadt H, et al: Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water. Crit Care Med 32:1550-1554, 2004 32. Kuzkov VV, Suborov EV, Kirov MY, et al: Extravascular lung water after pneumonectomy and one-lung ventilation in sheep. Crit Care Med 35:1550-1559, 2007 33. 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 27:420 e421-e428, 2012 34. Sakka SG, Klein M, Reinhart K, et al: Prognostic value of extravascular lung water in critically ill patients. Chest 122: 2080-2086, 2002 35. Yang CS, Qiu HB, Liu SQ, et al: The prognostic value of extravascular lung water index in critically ill septic shock patients [article in Chinese]. Zhonghua Nei Ke Za Zhi 45:192-195, 2006 36. LeTourneau JL, Pinney J, Phillips CR: Extravascular lung water predicts progression to acute lung injury in patients with increased risk*. Crit Care Med 40:847-854, 2012 37. Qutub H, El-Tahan MR, Mowafi HA, et al: Effect of tidal volume on extravascular lung water content during one-lung ventilation for video-assisted thoracoscopic surgery: A randomised, controlled trial. Eur J Anaesthesiol 31:466-473, 2014 38. Naidu BV, Dronavalli VB, Rajesh PB: Measuring lung water following major lung resection. Interact Cardiovasc Thorac Surg 8: 503-506, 2009