doi: 10.1161/CIRCULATIONAHA.107.750596
(Circulation. 2008;118:S171-S176.)
© 2008 American Heart Association, Inc.
Surgery for Congenital Heart Disease |
Factors Associated With Prolonged Recovery After the Fontan Operation
From the Department of Cardiology, Children’s Hospital Boston, and Department of Pediatrics (J.W.S., M.A.S., R.R.T.), Harvard Medical School, Boston, Mass; the Department of Cardiology, Children’s Hospital Boston, and Department of Anesthesia (P.C.L.), Harvard Medical School, Boston, Mass; and the Department of Cardiovascular Surgery, Children’s Hospital, Boston, and Department of Surgery (J.E.M., P.J.d.N., F.A.P., E.A.B.), Harvard Medical School, Boston, Mass.
Correspondence to Joshua W. Salvin, MD, MPH, Department of Cardiology, Cardiac ICU Office, Bader 600, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. E-mail joshua.salvin{at}cardio.chboston.org
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Abstract |
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Background— Mortality and major morbidity after the Fontan operation is low in the current era. However, factors contributing to prolonged postoperative recovery are not clearly understood.
Methods and Results— Data on all patients admitted to the cardiac intensive care unit (CICU) after a Fontan operation between June 2001 and December 2005 were retrospectively analyzed. We excluded all patients who died, required Fontan takedown, or required ECMO. The study cohort was further divided into a prolonged recovery group that included patients with >75%ile for duration of mechanical ventilation or pleural drainage, and a standard recovery group which included all other patients. A multivariable logistic regression model was used to compare demographic, anatomic, and physiological variables between the prolonged and standard recovery groups. There were 226 Fontan operations performed. Of the study population (n=218), the median age was 2.61 years (1.0 to 31.9 years) and weight was 12.45 kg (8.4 to 77.5 kg). The most common diagnosis was hypoplastic left heart syndrome (n=80, 36.7%). A systemic right atrioventricular valve was present in 139 (63.7%). The lateral tunnel fenestrated Fontan was the most common surgery (n=195, 89.4%). Within the study population, 81 (38%) patients meet criteria for prolonged recovery. Univariate risk factors for prolonged recovery included higher preoperative PVR (P=0.033), longer bypass times (P=0.009), higher postbypass lactate level (P=0.017), higher postoperative central venous (P<0.001) common atrial pressure (P=0.042), inotropic score (P<0.001), and need for greater volume resuscitation during the 24 postoperative hours (>75% for the entire group; P<0.001). In a multivariable model, need for greater volume resuscitation (OR 2.81, 95% CI 1.30, 6.05) was the only independent risk factor for prolonged outcome after the Fontan operation.
Conclusions— High volume expansion in the early postoperative period is an independent risk factor for prolonged recovery. The need for high volume expansion may represent the compound effects of multiple risk factors including preoperative hemodynamics and a marked systemic inflammatory response to surgery and cardiopulmonary bypass, which in turn may mediate prolonged recovery.
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Introduction |
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Advances in surgical technique and postoperative management have led to broader inclusion of patients for the Fontan operation. There has been consistent improvement in intermediate- and long-term survival, particularly in patients with hypoplastic left heart syndrome (HLHS).1–4 Short-term morbidity and mortality have also declined, and previous authors have described demographic, anatomic, and hemodynamic variables that contribute to early failure or death after a Fontan operation.5–7 Although still important, the need for postoperative Fontan takedown or mechanical support of the circulation with extracorporeal membrane oxygenation (ECMO) has become less frequent in the current era.8 It is therefore necessary to explore more subtle markers of prolonged Fontan recovery, including protracted mechanical ventilation and pleural drainage. The aim of this study was to identify demographic, preoperative hemodynamic, intra-, and postoperative variables that contribute to prolonged course after a Fontan operation.
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Methods |
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Statement of Responsibility
The authors had full access to and take full responsibility for the integrity of the data. All authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
Study Design
We performed a retrospective review of all patients who underwent Fontan operation between June 2001 and December 2005. The Institutional Review Board at Children’s Hospital Boston approved the review of patient records for this study. Demographic, anatomic, and pre-, intra-, and postoperative physiological data were collected. Patients who died after the Fontan operation, required a Fontan takedown, or ECMO in the immediate postoperative period were explored in a descriptive fashion only. As these end points are insensitive markers for perioperative outcome in the current surgical era, these patients were excluded from further analysis. The study population thus included all patients who survived to CICU discharge without the need for Fontan takedown or ECMO.
The first postoperative day (POD#0) was defined as the time period between transfer from the operating room to the CICU through 7:00 AM on the morning after surgery. Operative lactate was analyzed by the peak reported value during cardiopulmonary bypass. CICU lactate, alanine transaminase (ALT), aspartate aminotransferase (AST), and serum creatinine were analyzed using the peak value on POD#0. Arterial blood gas and hematocrit data were analyzed using CICU admission values. The admission central venous pressure (CVP) represents the mean Fontan pathway pressure as measured by internal jugular catheter pressure tracing, whereas the admission left atrial pressure (LAP) represents the mean common atrial pressure as measured by an intracardiac common atrial line pressure tracing. An inotropic score for POD#0 was calculated with a previously described formula: [dopamine + dobutamine + (milrinone*10) + (epinephrine*100)], using peak infusions rates measured in micrograms/kilogram/min.9,10 Peak mean airway pressure (Paw) was recorded in centimeters of water (cmH20).
Two fluid exposure cohorts, a low-volume and a high-volume resuscitation group, were created based on the 75%ile for volume resuscitation (ml/kg) administered on POD#0. Resuscitation fluid was retrospectively identified as any volume (colloid, crystalloid, or blood products) exceeding the standard maintenance fluids and medication infusion volumes for the first postoperative night. In our institutional practice, volume was given at the discretion of the attending cardiac intensivist or cardiovascular surgeon to maintain adequate circulatory parameters and was not standardized. Time of mechanical ventilation was measured in hours from admission to the CICU until first extubation of the trachea. A trial of extubation was performed when the patient exhibited stable Fontan hemodynamics, reasonable gas exchange and lung compliance, no evidence of surgical bleeding, and a level of consciousness appropriate for airway protection, as outlined in our Institutional Clinical Practice Guideline. Chest tube (CT) days are defined as the number of days until pleural drainage rate was less than 50 milliliters in 24 hours. As chest tube removal was often not complete during the CICU stay, this time is inclusive of both CICU and ward days. CICU length of stay (LOS) was measured starting at POD#0. Fontan takedown before CICU discharge was a dichotomous variable, as was the need extracorporeal membrane oxygenation (ECMO) or death.
A composite outcome variable incorporating time of mechanical ventilation and CT days was used to further categorize the study population into prolonged recovery and standard recovery groups. The prolonged recovery group included any patient exceeding the 75%ile for either ventilator hours or CT days. CICU LOS was not used in the composite outcome variable, as transfer from the CICU was not solely dependent on standardized medical practice.
Statistical Analysis
Demographics were described using median and range and subsequently compared using appropriate descriptive statistics. Chi square tests, and when appropriate, Fisher exact tests were used to test for differences in proportions between the outcome groups. Preoperative catheterization, bypass strategy, intraoperative, CICU laboratory, and CICU hemodynamic variables were compared between the two outcome groups using the Student t test or Mann–Whitney U test, as appropriate. Bivariate logistic analysis was performed to determine associations between pre-, intra-, and postoperative demographic, anatomic, and physiological variables and the prolonged recovery outcome group. A multivariable logistic regression model included all statistically significant predictors from bivariate analysis (P
0.05), along with factors shown clinically or in the literature to be associated with outcome. Additional univariate analysis was performed to determine associations between clinically relevant preoperative demographic, anatomic, and physiological variables and the high volume resuscitation group.
All statistical tests were 2-sided, and type I error was controlled at 0.05. Analyses were performed using SAS (version 9.1, SAS Institute) and SPSS (Version 15.0 for Windows, SPSS Inc).
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Results |
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Demographics
Two hundred twenty-six Fontan operations were performed between June 2001 and December 2005. The median age at the time of Fontan was 2.6 years (0.4 to 41.5 years), and the median weight was 12.5 kilograms (8.4 to 82 kilograms). The most common diagnosis was hypoplastic left heart syndrome (HLHS, n=81, 36.9%), and a systemic right-sided AV valve was present in 141 (62.7%). The most common pre-Fontan anatomy was a superior cavopulmonary anastomosis (n=195, 86.3%), and the preferred surgical technique (n=197, 87.2%) was the lateral tunnel fenestrated Fontan. Secondary surgical procedures included PA augmentation (n=19, 8.4%), systemic AV valve plasty (n=20, 8.8%), and arch reconstruction (n=2, 0.9%). All Fontan operations were performed on cardiopulmonary bypass (CPB), with a mean±SD total bypass time (TBT) of 107.9±46.9 minutes. Cross-clamping of the aorta (AXC) was performed in 151 (58.2%), with a mean±SD AXC time of 52.3±15.9 minutes. The median resuscitation volume on the first postoperative night was 61.3 mL/kg, with the 75%ile at 86.1 mL/kg. The majority (80.2%) of resuscitation volume was given in the form of 5% albumin, with the remainder as packed red blood cells (14.3%), or a combination of other blood products and crystalloid.
Excluded Patients
Patients who died (n=2, 0.9%), required Fontan takedown (n=2, 0.9%), or ECMO (n=7, 3.1%) were excluded from the study (n=8). Both deaths occurred in patients who were supported with ECMO in the early postoperative period. Both patients who underwent Fontan takedown survived, with one requiring early ECMO support (Figure).
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Study Population
There were 218 (96.5%) patients in the study cohort. Within this group, the median (interquartile range) duration of mechanical ventilation was 19.5 (13.5 to 27.25) hours, CT drainage was 64–9 days, and CICU LOS was 32–4 days. Two patients (0.9%) required repeat intubation. There were a total of 55 patients with >75%ile for ventilator days, and 39 patients with >75%ile for chest tube drainage. The study group was divided into prolonged recovery (n=81) and standard recovery (n=137) groups as defined in the methods section of this manuscript (Figure). Within the prolonged recovery group, 25 patients had only prolonged pleural drainage, 43 had only prolonged mechanical ventilation, and 13 had both prolonged pleural drainage and prolonged mechanical ventilation. Demographic and preoperative characteristics of the 2 outcome groups are shown in Table 1. Higher preoperative PVR (P=0.033) was the single preoperative characteristic associated with prolonged recovery in univariate analysis. Intraoperative differences between the two outcomes groups are shown in Table 2. Significant intraoperative characteristics of the prolonged recovery group included longer TBT (P=0.009) and higher postbypass lactate (P=0.017). Postoperative characteristics associated with prolonged recovery are shown in Table 3. These included higher AST (P=0.022), CVP (P<0.001), LAP (P=0.042), inotropic score (P<0.001), and high volume resuscitation (P<0.001). Bivariate associations and a multivariable model showing the association of demographic, pre-, intra-, and postoperative characteristics of the study population with prolonged recovery outcomes are shown in Table 4. The predictors included in the multivariable regression model were age, preoperative cath PVR, preoperative cath CVP, TBT, postoperative CVP, postoperative LAP, high volume resuscitation, and inotropic score. In this multivariable logistic regression model, high volume resuscitation (adjusted OR 2.81 95% CI [1.30, 6.05]) was the only significant risk factor, in the presence of the other variables, for prolonged CICU recovery.
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High Volume Resuscitation Exposure Group
There were 54 patients in the high volume resuscitation group. Patients in the high volume resuscitation group were significantly younger (P=0.006) and weighed less (P=0.001) than those in the low volume resuscitation group (Table 5). There was no significant difference in systemic AV valve, pre-Fontan anatomy, and surgical technique between the high and low volume groups. Preoperative catheterization data demonstrated significantly higher PVR in the high volume resuscitation group (P<0.001), with no significant difference in CVP or end-diastolic pressure. There was no significant difference in perfusion strategy or intraoperative variables including TBT, AXC time, or postbypass lactate. Although the admission CVP, TPG, and peak inotropic score was higher in the high volume group (P<0.001), there was no significant difference in the use of systemic vasodilators (milrinone or nipride), LAP, Paw, temporary pacing requirement, and fraction of resuscitation volume given as 5% albumin between the 2 volume resuscitation groups.
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Discussion |
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In this large retrospective study of patients predominantly undergoing the lateral tunnel fenestrated Fontan operation, we examined risk factors for prolonged recovery. A high volume requirement on the first postoperative night was the only independent risk factor on multivariable modeling associated with delayed recovery. Specific patient and procedural variables were not associated with prolonged recovery in this model.
Although early mortality rates after Fontan operation have been reported between 1% and 27%, there has been a decline in early mortality in the current surgical era. Many contemporary series now report rates as low as 1% to 7%.4–7,11–14 An elevated preoperative pulmonary artery pressure remains the most consistent risk factor for early death.4,5,11,12 Important procedural modifications, including the use of a fenestration and modified ultrafiltration, are also associated with declining mortality rates.5,7,15,16 Fontan failure requiring takedown or need for mechanical support with ECMO is also rare in the current surgical era.4,8,17 Risk factors for early failure as described by Gentles et al include preoperative mean pulmonary artery pressure, younger age, heterotaxy syndrome, right-sided tricuspid valve as the only systemic AVV, pulmonary artery distortion, nonfenestration, and longer bypass time. Other authors have described common AV valve anatomic variants,4,5 right ventricular morphology,18 younger age, high postoperative right atrial pressure, longer bypass and aortic cross clamp times, and preoperative palliation to be risk factors for Fontan failure.7,12 Risk of prolonged pleural drainage have been described in patients with lower preoperative oxygen saturation, higher preoperative pulmonary artery pressures, longer bypass times, diastolic dysfunction, and postoperative infections.5,6,19–21 Although, we found similar associations in our univariate analysis, these factors did not contribute prolonged recovery in our multivariable model.
Complications and prolonged CICU course after cardiac surgery are associated with higher risk of hospital acquired nosocomial infection,22 higher resource utilization, and poorer longer-term neurological outcomes.23,24 Defining factors associated with prolonged recovery may therefore be essential to improve long-term outcomes. Reasons contributing to high volume resuscitation as an independent risk factor for prolonged recovery remain unclear. In the first 24 hours after a Fontan operation, volume expansion with colloid or crystalloid is necessary to maintain adequate preload and cardiac output. Systemic inflammatory response to surgery and cardiopulmonary bypass may contribute to endothelial injury and capillary leak, although we have no available data to indicate patients with Fontan physiology are more at risk in this regard. Fontan baffle pressure and CVP need to be increased in select patients to maintain an elevated transpulmonary gradient associated with factors such as increased pulmonary vascular resistance, a pulmonary vascular bed with diminished cross-sectional area, or important serial stenoses. Elevation of ventricular end-diastolic pressure from impaired myocardial function may further elevate Fontan baffle pressure and potentially lead to a prolonged pleural drainage and mechanical ventilation. In univariate analysis, patients who required high volume were younger, weighed less, had higher preoperative pulmonary vascular resistance, higher CICU CVP, higher CICU TPG, and required more inotropic support on the first post operative night than patients in the low volume group. Although speculative, the need for high volume resuscitation in the early postoperative period may represent the compound effects of multiple risk factors including preoperative hemodynamics and a marked systemic inflammatory response to surgery and cardiopulmonary bypass, which in turn may mediate prolonged recovery. Furthermore, whether need for volume expansion is driven by variability in physician practice and experience cannot be excluded.
There are several limitations to this study. First, the study is a retrospective review of echocardiographic, catheterization, perfusion, and CICU databases and is therefore subject to physician practice variation with regard to administration of fluid, use of inotropic agents, and parameters for extubation and pleural tube discontinuation. It is likely, however, that this variability was spread randomly across the cohort, thus having minimal impact on the final analysis. Finally, postoperative laboratory data such as transaminases and lactate were measured consistently only since 2005 and were thus excluded from multivariable modeling.
Further study is warranted to explore the approach to postoperative fluid management. Volume, mainly in the form of colloid, is currently given to combat hypotension related to a preload dependent Fontan circulation. The etiology of this hypotension is often multifactorial, and may include factors such as relative hypovolemia, ventricular dysfunction, tachyarrhythmia, and altered flow across pulmonary vascular bed associated with mechanical ventilation. Although we should continue to routinely augment ventricular function with inotropes, aggressively treat tachyarrythmias, and use a low mean airway pressure ventilation strategy, a standardized and conservative approach to volume expansion aimed at optimization oxygen delivery may shorten duration of recovery. Recent data suggest that there is no survival advantage and possibly some detriment to the use of colloid for volume expansion.25,26 As cardiac surgical patients were not specifically explored, upcoming trials are planned to evaluate of the use of crystalloid in the postoperative cardiac surgical patient. Future research should also be directed at identification of inflammatory mediators that may place a subset of Fontan patients at risk for a profound systemic inflammatory response, high volume resuscitation, and prolonged recovery.
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Acknowledgments |
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Sources of Funding
This manuscript was supported by the Rochelle E. Rose CICU Clinical Research Fund.
Disclosures
None.
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Footnotes |
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Presented at the American Heart Association Scientific Sessions, November 4–7, 2007, Orlando, Fla.
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References |
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