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Ann Thorac Surg 2006;81:1460-1465
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Pulmonary Artery Hypertension: Is It Really a Contraindicating Factor for Early Extubation in Children After Cardiac Surgery?

Vladimiro L. Vida, MD * , Juan Leon-Wyss, MD, Milagros Rojas, MD, Ricardo Mack, MD, Joaquin Barnoya, MD, MPH, Aldo R. Castañeda, MD, PhD

Pediatric Cardiac Surgery Unit of Guatemala (UNICARP), Guatemala Ciudad, Guatemala

Accepted for publication November 28, 2005.

* Address correspondence to Dr Vida, Unidad de Cirugia Cardiovascular de Guatemala (UNICAR), 9 Avenida, 8-00, Zona 11, Guatemala Ciudad, Guatemala (Email: vladimirovida{at}interfree.it).


   Abstract
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BACKGROUND: One of the perceived major contraindications to early extubation after pediatric cardiac surgery is preoperative pulmonary arterial hypertension (PAH). The objective of this study is to present the results of early extubation (within 6 hours after open heart surgery) in children who had varying degrees of preoperative pulmonary arterial hypertension.

METHODS: We reviewed the charts of 100 consecutive children who underwent subaortic ventricular septal defect closure and also had preoperative PAH. Outcomes measured included early extubation rate, clinical status of patients, and hospital costs.

RESULTS: The median age at surgery was 2.5 years (range, 0.4 to 30). Sixty-five patients were extubated successfully in the operating room; 25 additional patients were extubated in the intensive care unit within 6 hours from surgery, increasing the early extubation rate from 65% to 90%. Postoperative complications were present in 12 patients; 10 of these patients required mechanical ventilation for more than 6 hours, and 1 of them died postoperatively in septic shock. Two patients required reintubation 25 and 26 hours, respectively, after initial extubation in the operating room, for causes unrelated to pulmonary hypertensive crises or ventilatory failure. The mean cost of procedures in patients who had successful early extubation was US $3,786.50 ± 302.45. Every additional day in the intensive care unit, in case of delayed extubation, increased the overall cost of the procedure by 10%.

CONCLUSIONS: Pulmonary artery hypertension does not seems to be a contraindicating factor to early extubation in patients who underwent ventricular septal defect closure, and may be considered a feasible way to decrese postoperative intensive care unit stay and hospital costs.


   Introduction
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The postoperative care of children who have undergone surgery for congenital heart disease (CHD) has significantly improved the outcome of pediatric cardiac surgery during the past several years [1]. Early weaning from mechanical ventilation and extubation 6 to 8 hours after pediatric cardiac surgery has been advocated since the 1980s [2]. However, relatively few articles have been published on this subject, and those few addressed mostly selected group of patients [1, 3–9].

One of the perceived major contraindication to early extubation is preoperative pulmonary arterial hypertension (PAH), defined as a mean pressure in the main pulmonary artery (MPAP) of more than 25 mm Hg at rest [3, 7–14]. However, the degree of preoperative PAH that could contraindicate early weaning from mechanical ventilation has not yet been clearly identified.

The objective of this study is to present the results of early extubation (within 6 hours after open heart surgery) in 100 consecutive Guatemalan children who underwent closure of a ventricular septal defect (VSD) and also had varying degrees of preoperative PAH.


   Material and Methods
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We reviewed the charts of 100 consecutive children who were referred to the Pediatric Cardiac Surgery Unit of Guatemala (UNICARP) for subaortic VSD closure and also had preoperative PAH. Inclusion criteria were the presence of unrestricted VSD and preoperative PAH. A cardiac catheterization was performed in 32 patients (32%) to gather more information about their pulmonary vascular reactivity to 100% inspired fraction of oxygen (FiO2). Selected for cardiac catheterization were patients older than 2 year of age or who had bidirectional shunts across the VSD, or both.

At the time of surgery, general anesthesia was induced with fentanyl (5 mcg/kg intravenous [IV] dose) and sevofluorane (5%). A further dose of fentanyl (5 mcg/kg IV dose) in addition to sevofluorane (0.5% to 2%) was used for anesthesia maintenance. Cis-atracurium (0.1 mg/kg IV dose) was used for muscle relaxation. Ketorolac (1 mg/kg IV dose) was added for intraoperative pain control. Surgery was achieved through a midline sternotomy, using moderate hypothermia at 28°C, cardiopulmonary bypass (CPB), aortic cross-clamping, and cold crystalloid cardioplegic arrest. All VSDs were closed through the right atrium with an autologous pericardial patch, pretreated with glutaraldehide 6% for 15 minutes, using a continuous suture technique. To assess hemodynamic changes in the pulmonary vasculature, MPAP was measured in the operating room, before and after CPB and VSD closure, and was compared with invasive mean systemic arterial pressure (MSAP). Both measurements were taken simultaneously during mechanical ventilation at 50% inspired fraction of oxygen. According to preoperative MPAP/MSAP, patients were divided into three main groups: group 1 = MPAP 33% or less of MSAP; group 2 = MPAP between 33% and 66% of MSAP; and group 3 = MPAP 66% or more of MSAP.

Early extubation was defined as discontinuation from mechanical ventilation in the operating room or within 6 hours after surgery. The first 30 patients in this study, at the beginning of our experience with early weaning from mechanical ventilation, were if uncomplicated, evaluated for extubation in the intensive care unit (ICU) within 6 hours after surgery. Later on, patients were routinely extubated in the operating room if uncomplicated, if the postoperative MPAP/MSAP was less than 1, and if they had usual criteria for extubation, including adequate oxygenation in FiO2 of 40% or less, maintenance of pH 7.35 or greater, and partial pressure of carbon dioxide (pCO2) of 45 mm Hg or less on positive end-respiratory pressure less than 5 cm H2O, ventilator rate of more than 8 breaths per minute with pressure support less than 8 cm H2O, and if they had a consistent level of consciousness with adequate airway protective reflexes, and adequate air protective reflexes, and absence of accessory respiratory muscle recruitment.

Postoperative pain medications included morphine for the first 12 hours (0.1 mg/kg IV dose every 6 hours) and ketorolac (1 mg/kg dose IV every 8 hours). A pain scale, in addition to clinical data of patients, was used to monitor postoperative pain [15].

The early (less than 6 hours) and late (more than 6 hours) extubation groups were compared by patient's age, sex, nutritional status, presence of Down's syndrome, preoperative MPAP/MSPA, and CPB time, and also postextubation metabolic and respiratory parameters such as arterial pH, arterial oxygen pressure tension (PaO2)/FiO2, arterial carbon dioxide pressure tension (PaCO2), bicarbonate (HCO3), lactate, hematocrit, and central venous oxygen saturation in the superior vena cava (collected through the central venous line).

Actual hospital costs were calculated for patients who underwent VSD closure and early extubation. We considered only direct costs (patient care related) including (1) operating room (includes salaries of all personnel), (2) medications and material used during anesthesia and operation, (3) CPB equipment, (4) length of ICU and hospital stay, and (6) diagnostic tests (echocardiogram, electrocardiogram, chest radiograph). Results are presented as mean and standard deviation (median and range when data were not normally distributed). Differences between mean and proportions were assessed with analysis of variance if the variable was continuous or {chi}2 if dichotomous [16]. Fisher's exact test was used where sample size was small. Level of significance was set at less than 0.05.


   Results
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Median age at surgery was 2.5 years (range, 0.4 to 30). Twenty patients (20%) were younger than 12 months. Fifty-three patients were male (53%) and 47 (47%) were female. Down's syndrome was present in 19 patients (19%), and 67 patients (67%) evidenced chronic malnutrition. Thirty-seven patients (37%) had an associated CHD, including a single patent ductus arteriosus in 24 patients, a single ostium secundum atrial septal defect in 5 patients and combined patent ductus arteriosus and secundum atrial septal defect in the remaining 8 patients.

All patients underwent successful VSD closure. Additional surgical maneuvers included closure of a patent ductus arteriosus in 32 patients and closure of a secundum atrial septal defect in 13 patients (Table 1). Preoperative cardiac catheterization data are listed in Table 2.


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  		Table 1. Demographic/Hemodynamic Data and Outcome of Patients With VSD According to Time of Postoperative Mechanical Ventilation
 

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  		Table 2. Preoperative Cardiac Catheterization Data (n = 32 Patients) According to Time of Postoperative Mechanical Ventilation
 
Sixty five patients (65%) were extubated successfully in the operating room. Twenty-five additional patients were extubated in the ICU within 6 hours from surgery, increasing the early extubation rate from 65% to 90% (Table 1). Postoperative MPAP decreased significantly in all patients if compared with preoperative MPAP (Tables 1, 2, and 3).Go There was no significant difference of postoperative MPAP between patients who were extubated early and patients requiring prolonged mechanical ventilation. However, note that 39 of 90 patients (43.3%) who were extubated early presented postoperative PAH, 11 of 38 patients (28.9%) in group 2 and 28 of 44 patients (63.6%) in group 3. No patients in group 1 presented with postoperative PAH (Tables 1, 2, and 3). Intravenous milrinone (0.5 µg · kg-1 · min-1) was added as standard practice in all 39 patients who presented postoperative PAH for 48 hours. The degree of PAH did not increase the incidence of postoperative complications nor the length of ICU and hospital stay among the various groups of patients who were extubated early (Table 3). Regarding postextubation metabolic and respiratory parameters, the arterial pH, PCO2, HCO3, and hematocrit were significantly lower in patients who were extubated early, as shown in Table 1. Thirty-one of 90 patients (34%) who were extubated early presented mild-to-moderate transient respiratory acidosis; none of them required specific treatment or interventions. No significant different of arterial pH, PaO2/FiO2, PCO2, HCO3, hematocrit, lactate, and central venous oxygen saturation existed among the three groups of patients with PAH.


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  		Table 3. Hemodynamic and Outcome Data of Patients With VSD Who Were Extubated Early According to the Degree of Preoperative Pulmonary Arterial Hypertension
 
Immediate postoperative complications were present in 12 patients (12%). Ten of these patients required mechanical ventilation for more than 6 hours. Five of them were extubated successfully within 24 hours after surgery, whereas the remaining 5 patients required a mean time of 126 ± 94.2 hours of mechanical ventilation (Table 4). One patient died postoperatively (1%) in septic shock that proved unresponsive to aggressive medical management (Table 4). Two patients (2%) required reintubation 25 and 26 hours, respectively, after initial extubation in the operating room. The first patient had a generalized tonic-clonic seizure event of 30 seconds, with a Glasgow coma scale score of 8 after the event. After treatment with phenylhydantoin, he was successfully extubated after 43 hours. The second patient had a systemic inflammatory response syndrome, which began 24 hours after surgery. This patient required endotracheal reintubation, high doses of catecholamines for 48 hours; his hemodynamics improved, and he was successfully extubated after 73 hours. At the time of discharge, all 99 surviving patients eventually were in stable clinical conditions.


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  		Table 4. Patients Who Required Mechanical Ventilation for More Than 6 Hours
 
Other Preoperative Variables and Outcome
Patients who were extubated early had a lower incidence of postoperative complications (p < 0.0001) and required a shorter time of ICU (p = 0.0001) and hospital stay (p < 0.04) (Table 1).

Patients with Down's syndrome presented with a significantly higher preoperative MPAP (54 ± 12.06 mm Hg versus 48.25 ± 11.19 mm Hg; p = 0.05), higher incidence of postoperative complications (p = 0.03), and required a longer period of mechanical ventilation (p = 0.008) when compared with patients without Down's syndrome (Table 1).

Patients who were extubated early (p < 0.0001) had a significantly shorter CPB time. Shorter time of CPB was also associated with a lower incidence of postoperative complications (p < 0.0001) and hospital mortality (p = 0.001; Table 3).

Age of patients less than 1 year proved not to be a risk factor for early extubation in this study.

Cost Evaluation
The mean cost for procedure in patients who underwent VSD closure and successful early extubation was US $3,786.50 ± 302.45. There were no significant differences in costs between patients extubated in the operating room and patients extubated within 6 hours after surgery in the ICU (US $3,6875.40 ± 298.34 versus US $3,799.50 ± 305.34). Every additional day in the ICU, in case of delayed extubation, increased the overall cost of the procedure by 10%.


   Comment
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Postoperative intensive care of children with CHD has placed, in recent years, much emphasis on earlier weaning from mechanical ventilation [1, 6]. Early extubation of children undergoing pediatric cardiac surgery had been proposed in 1980 [2] as a safe alternative to prolonged mechanical ventilation, even for patients with complex CHD. This approach is supposed to simplify the postoperative management, eliminate some of the complications related to postoperative care [17–19], shorten ICU and hospital stay, and therefore reduce costs [17]. Despite these supposed advantages, early extubation is still not a common practice [3].

One of the perceived major reasons for failure of early extubation after surgery for CHD is the presence of preoperative PAH [7, 8, 11, 12, 20, 21]. Many institutions advocate continued ventilation, high-dose narcotic sedation, and often paralysis during the initial postoperative recovery of patients with CHD and pulmonary arterial hypertension. This is done to minimize the stress response to operation [5, 22–25] and prevent pulmonary hypertensive crisis, which has been reported to be the major cause of morbidity and mortality after cardiac surgery [13]. On the other hand, the positive intrapulmonary pressure caused by prolonged mechanical ventilation can increase pulmonary vascular resistance [26], and particularly suctioning through the endotracheal tube has been shown to trigger pulmonary hypertensive crisis in patients with preoperative PAH [24, 26].

According to this study, the presence and the degree of preoperative PAH did not exclude a successful early extubation. Ninety of 100 children with preoperative PAH and who underwent closure of a VSD were safely extubated within 6 hours after surgery. Thirty-nine of these patients had postoperative PAH and were treated postoperatively with intravenous milrinone (0.5 µg · kg-1 · min-1). Unfortunately in Guatemala, specific medications such as like inhaled nitric oxide and intravenous sildenafil for handling or stabilizing pulmonary artery hypertension are not currently available.

As regards the mild-to-moderate respiratory acidosis in 34% of patients who were extubated early, it was transient, and all patients had a uneventful postoperative course. Furthermore, postextubation respiratory and metabolic parameters seem to be unrelated to the degree of preoperative PAH.

Ten patients who were not extubated early had postoperative complications, which were linked to increased pulmonary vascular reactivity in only 1 patient. One patient died 5 days after surgery in septic shock; his death was unrelated to early extubation. Two patients (2%) required reintubation after 25 and 26 hours, respectively, after early extubation in the operating room. In neither of the 2 patients was the cause of reintubation associated with pulmonary hypertensive crisis.

To achieve early extubation, the anesthesia technique was modified. Total narcotic use was limited to 10 µg/kg dose of fentanyl administered during the operation, along with anesthesia maintenance with sevofluorane titrated to the patient's response. This provided adequate anesthesia during the procedure, allowing early postoperative recovery and early extubation in the operating room. As reported, the dose of pain medication we used seems to provide adequate postoperative pain relief.

Regarding other preoperative variables, patients who underwent early extubation after surgery had a shorter CPB time (46.02 ± 13.04 versus 71.7 ± 3.75 minutes). Longer CPB time (71.7 ± 3.75 versus 46.02 ± 13.04 minutes, p < 0.0001) in this study was associated with delayed extubation (longer than 6 hours) as well as a higher incidence of postoperative complications and mortality. It is also likely that a relatively longer period of CPB proportionally increased pulmonary vascular resistance, and has a significant effect on postoperative recovery in infants after cardiac operations [14].

In agreement with other reports from the literature [8, 12, 14], the success rate of early extubation in patients who had Down's syndrome was lower if compared with patients who did not have Down's syndrome (73.6% versus 93.8%; p = 0.02). However, regarding the 5 patients with Down's syndrome who required prolonged intubation (more than 6 hours), 3 of them were extubated successfully (patients 3, 5, 10; Tables 1 through 4) within 24 hours. Actually our policy is to extubate patients with VSD, PAH, and Down's syndrome in the operating room, if uncomplicated, in good hemodynamic conditions, with adequate respiratory parameters, and with MPAP/MSAP of less than 1.

In Guatemala, the cost advantages of early extubation were related mainly to reduction of postoperative ICU and hospital stay [17, 18], which allowed savings of as much as 10% per day. Costs were the same between patients who were extubated in the operating room and those who were extubated within 6 hours in the ICU.

Our study has several limitations. The small sample size and number of events included (only 2 reintubations) give our study a small power to detect a difference. A larger number of reintubations would be needed for a conclusive regression analysis. In conclusion, PAH does not seem to be a contraindicating factor to early extubation in patients who have undergone VSD closure, and may be considered a feasible way to decrease postoperative ICU stay and hospital costs.


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