Hemodynamic Characteristics of Neonates Following First Stage Palliation for Hypoplastic Left Heart Syndrome
Background It is widely held that the postoperative course of patients with hypoplastic left heart syndrome (HLHS) after stage 1 palliation is characterized by hemodynamic instability, which in part may be due to excessive pulmonary blood flow. Hence, avoidance of alkalosis and the use of minimally oxygen-enriched inspiratory gas are thought by many to be important, although there is little pertinent published data. This study was undertaken to characterize the postoperative course and to determine whether the Fio2 and blood pH are related to indices of hemodynamic stability in these infants.
Methods and Results The postoperative course of 25 consecutive infants undergoing first stage palliation for HLHS were retrospectively reviewed and the following data were obtained: arterial pressure, arterial blood gas measurements, the inotropic agents used, and multiple respiratory parameters. There was one operative death, and 2 patients died within 2 days, but 22 were extubated (mean, 5.2±4.1 days after surgery). Hospital mortality was 24%. Mean pH was ≥7.51 for the first 9 hours after surgery and was ≥7.45 for the entire period. The mean Fio2 was ≥50% for the first 18 hours. The Pao2 was appropriate (37±6 mm Hg at 1 hour after surgery, increasing to 45±5 mm Hg by hour 73). Only modest inotropic support was needed to maintain appropriate blood pressure.
Conclusions These data suggest that neither alkalosis nor relatively high inspired oxygen necessarily cause hemodynamic instability in these patients. To what extent these results are generalizable is unclear, but they suggest that there is nothing inherent with HLHS that mandates postoperative hemodynamic instability or unacceptable mortality.
Although little published data exists, it is widely held that the postoperative course of patients with hypoplastic left heart syndrome (HLHS) after stage 1 palliation is often characterized by hemodynamic instability and a substantial risk of patient death.1 While the basis for this tendency for instability is doubtless multifactorial, considerable emphasis has been placed on the potentially deleterious effect of excessive pulmonary blood flow,2 3 as this diminishes systemic perfusion, including coronary blood flow. Because alkalosis4 and possibly enriched inspired oxygen5 are pulmonary vasodilators, it might be expected that careful avoidance of alkalosis and the use of minimally oxygen-enriched inspiratory gas are important to a satisfactory outcome. While there is considerable theoretical and anecdotal data to support this approach, we are unaware of any published information that actually establishes the efficacy or necessity of this strategy.
The purpose of this retrospective review is twofold: first, to determine whether the Fio2 and blood pH in the early postoperative period are related to hemodynamic stability and outcome in infants with HLHS who have undergone stage 1 palliation and second, using the need for intravenous inotropic agents, variability and magnitude of systemic blood pressure, and duration of intubation as indices of postoperative hemodynamic stability, to characterize the postoperative course of these infants.
Between July 1993 and March 1994, 25 consecutive infants underwent stage 1 palliation for HLHS. All except 6 had aortic and/or mitral atresia, and all had severe hypoplasia of the left ventricle. None had undergone any previous surgery or balloon aortic valvuloplasty. The age at operation ranged from 2 to 16 days (mean, 7.3±4 days) except for 1 patient, who was 93 days old at operation. Weight ranged from 2.06 to 3.90 kg (mean, 3.28±0.46 kg). Three neonates initially presented in shock, but all were stable at the time of operation.
The method of repair was essentially as previously described.6 With the use of hypothermic circulatory arrest, the septum primum was excised, the main pulmonary artery trunk was divided, the aortic arch was augmented using an allograft patch, and a Goretex shunt was placed from the innominate artery to the pulmonary artery bifurcation. The determination of the appropriate shunt size can be difficult. In general, 3.5-mm shunts are used in patients weighing less than 3.5 kg, and 4.0-mm shunts are used in those weighing greater than 3.5 kg. Patients with restrictive atrial septa or those with pulmonary congestion from other causes may require relatively larger shunts. The shunts ranged in length from 13 to 17 mm. Sixteen infants had a 3.5-mm-diameter shunt (mean patient weight, 3.4±0.34 kg); 8 had a 4.0-mm-diameter shunt (mean patient weight, 3.2±0.53 kg), and 1 had a 5-mm-diameter shunt (patient weight, 3.6 kg). Three of these patients initially had a 3.5-mm-diameter shunt, which was subsequently replaced with a 4-mm-diameter shunt because of hypoxia either immediately after cardiopulmonary bypass or in the early postoperative period. The mean duration of cardiopulmonary bypass was 75±16 minutes, with a mean circulatory arrest time of 48±10 minutes.
All patients were initially paralyzed with pancuronium, 0.1 mg/kg as needed, and sedated with a continuous intravenous infusion of fentanyl, 5 μg/kg per hour. Fentanyl was used because it has been shown to suppress the hormonal stress response to cardiac surgery in neonates and to improve patient outcome.7 In addition, fentanyl may help to reduce lability in pulmonary vascular resistance in the postoperative period.8 After the initial 12 to 24 hours, most patients demonstrated hemodynamic stability; the pancuronium and fentanyl were discontinued, and a continuous infusion of morphine sulfate (10 to 30 μg/kg per hour) was begun. The initial ventilator settings (Siemens 900c ventilator; volume control mode) are given in Table 1⇓. Criteria for the discontinuation of mechanical ventilation included stable and appropriate hemodynamic parameters, substantial resolution of postoperative edema (weight within 5% of preoperative value), adequate respiratory effort, and the lack of contraindications.
The initial choice of inotropic agent used and the rate of infusion were determined in the operating room. An infusion of dopamine at 5 μg/kg per minute was routinely initiated just before discontinuing cardiopulmonary bypass. Dopamine was chosen because it provides β-adrenergic support of the myocardium and is more effective in maintaining systemic blood pressure than dobutamine and amrinone. Dobutamine was occasionally used, particularly in those patients with evidence of decreased peripheral perfusion despite an adequate systemic arterial blood pressure. Subsequent manipulations in inotrope infusion were made to obtain adequate blood pressure (systolic blood pressure >65 mm Hg), tissue perfusion, and urine output. The only other medications routinely used in the first 72 hours after operation were prophylactic antibiotics, midazolam or lorazepam, and diuretics. The volume of colloid-containing solutions infused was based on the hemodynamic status of the patient; central venous pressure generally was 5 to 10 mm Hg.
From a retrospective chart review, the following data were obtained: systemic arterial blood pressure, hematocrit, arterial blood gas measurements, Fio2, delivered tidal volume, respiratory rate, mean airway pressure, and the type and amount of inotropic agents infused. These values were recorded for the following times: the first hour after surgery, then every 4 hours×2, then every 8 hours until 73 hours after surgery. In some cases, the relevant parameter may not have been obtained at the exact time specified; in these cases, the temporally closest value was used. The number of days after surgery to extubation and the number of days in the intensive care unit after operation also were determined. Finally, the three highest Pao2 measurements after extubation (usually with an Fio2 <0.4) were recorded.
Data are presented as mean±SD. Pearson’s product-moment correlations were computed in two ways, first for each follow-up time and then accumulating all available data for each subject across all follow-up times.
Summary of Patient Outcome
Table 2⇓ summarizes the outcome of the 25 patients reviewed. All except 1 survived operation, and 22 of the 24 were extubated. One patient, who had been stable and doing well, died during manipulation of a central venous line 24 hours after surgery. A second patient died 32 hours after surgery for unknown reasons after having been in a low-output state since operation. Time to extubation ranged from 2 to 20 days after operation (mean, 5.2±4.1 days). There were three deaths after extubation but before hospital discharge, two of which occurred in patients no longer in the intensive care unit. These deaths were all sudden, unexplained, and in patients who appeared to be doing well. The total hospital mortality in this group of patients was therefore 24%. The mean stay in the intensive care unit was 7.4±4.9 days (range, 4 to 23 days).
Mechanical Ventilator Support
Table 1⇑ details the ventilatory support given to these patients over the course of the first 73 hours. As might be expected, minute ventilation and mean airway pressure declined as the time progressed and the patients were able to provide more spontaneous ventilation. The initial Fio2 was high, remaining above 50% until 17 hours after surgery, and did not approach 21% until ≈73 hours after surgery.
Arterial Blood Gases and Blood Pressure
There was considerable variability in arterial pH and Paco2 (Fig 1⇓), but on average, these patients were significantly alkalotic throughout the first 73 postoperative hours, in part as a result of hyperventilation (Fig 2⇓). There was no obvious link between alkalosis and poor outcome. In fact, one of the two patients who died before extubation had arterial pH values less than most of the survivors. Further evidence that alkalosis did not harm systemic perfusion is provided by the finding that blood pressure was not significantly correlated with pH at most of the follow-up times (eg, correlation averaged over the times for BP and pH was 0.054). The correlation between systolic blood pressures and pH accumulating all follow-up times for all subjects was 0.007. However there is evidence that blood pressure and arterial Po2 have a trend toward a positive correlation, eg, the correlation averaged over times for systolic blood pressure and arterial Po2 was 0.20, and the correlation between systolic blood pressure and arterial Po2 accumulating all follow-up times for all subjects was 0.26. Despite alkalosis, the arterial Po2 was generally appropriate and showed an upward trend as the pH decreased (Figs 2, 3). The arterial Po2 tended to be negatively correlated with pH, eg, the correlation between arterial Po2 and pH averaged over the follow-up times was −.20 and the correlation accumulating all follow-up times for each subject was −.27.
Inotropic Support and Systemic Blood Pressure
All patients were initially treated with inotropic agents (18 with dopamine, 3 with dobutamine, and 3 with both). Epinephrine (doses of 0.02, 0.08, and 0.35 μg/kg per minute) was subsequently added in 3 patients and amrinone (5 μg/kg per minute) in 1 patient. The average initial mean combined dose of dopamine and dobutamine was only 7.8 μg/kg per minute, and it fell to 5.5 μg/kg per minute by 73 hours after surgery. Forty-one percent of surviving patients were no longer receiving inotropic agents by the 73rd postoperative hour (Fig 4⇓). The use of modest inotropic support did not preclude hemodynamic stability: Mean systolic and diastolic blood pressures varied relatively little during the first 73 hours after operation (Fig 5⇓) and were well within an acceptable range for patients of this age.
The hematocrit varied very little in the postoperative period. Mean hematocrit ranged from 50% (postoperative hour 3) to 53% (73 hours after operation).
This retrospective review suggests the following:
(1) Relatively high Fio2 with significant alkalosis in the postoperative period neither precludes a successful outcome nor is necessarily attended by systemic hypotension or the need for a high level of pressor support in infants after first stage palliation for HLHS. Virtually all of our patients were alkalotic, many of them significantly so, for the first 73 hours after surgery (Fig 2⇑), yet only modest inotropic support was sufficient for adequate blood pressure (Figs 4⇑ and 5⇑). These infants were also well enough to be successfully extubated relatively soon after operation. Neither of the two deaths in mechanically ventilated patients could be reasonably ascribed to alkalosis.
If one stipulates that excessive pulmonary blood flow per force results in hemodynamic instability (and poor outcome), there are at least two possible explanations for the apparent lack of deleterious effects of high Fio2 and alkalosis: (a) High Fio2 and alkalosis have relatively little effect on pulmonary vascular resistance in this setting. While alveolar hypoxia is unequivocally a powerful pulmonary vasoconstrictor,9 it is less clear that alveolar hyperoxia causes pulmonary vascular resistance to fall below baseline, and in fact some data suggest that it does not.10 Similarly, while alkalosis clearly appears to dilate the constricted pulmonary circulation,4 if baseline resistance is low its effect may be minimal. While possible, these explanations run counter to considerable experience that suggests that hyperventilation in infants with unrestrictive aortopulmonary communications (eg, patent ductus arteriosus) can cause excessive pulmonary blood flow and systemic hypotension. (b) The major restriction to pulmonary blood flow in our patients occurs within the innominate to pulmonary artery shunt, and pulmonary vascular resistance is therefore relatively unimportant in determining pulmonary blood flow. While the fact that the Pao2 in these patients ultimately increased to 46 mm Hg after extubation (saturation ≈80%) suggests that the shunts were not excessively restrictive, it is possible that they effectively limited pulmonary blood flow. We favor this explanation for the apparent lack of effect of alkalosis on Pao2 and hemodynamic stability (but see also further discussion regarding mechanical ventilation, below), although the available data do not allow a definite interpretation.
(2) The postoperative course of a patient with HLHS after stage 1 palliation need not be characterized by hemodynamic instability, at least as judged by the need for pressor support, lability of blood pressure, and the duration of mechanical ventilation needed after surgery. This fact is consistent with our general impression that these patients require comparatively few adjustments in medical support after surgery and are relatively easy to manage. That this should be the case is perhaps not surprising, since the factors that determine the postoperative hemodynamic characteristics of these patients doubtless include many that are distinct from the technique of postoperative medical management: The preoperative condition and age of the patient, the duration of cardiopulmonary bypass and circulatory arrest, the efficacy of myocardial protection, and freedom from residual cardiac lesions (eg, aortic obstruction) are all important. Our data suggesting a lack of linkage between alkalosis and significant pulmonary overcirculation also suggest that the effective size of the innominate to pulmonary artery shunt may be of considerable significance.
Another possibly significant factor is the precise nature of mechanical ventilation used. Our patients received relatively high tidal volumes (22.5 mL/kg) throughout the early postoperative period and initially had relatively high mean airway pressures (8.1 cm/H2O). The generous inflation volume and pressure may have increased pulmonary vascular resistance through one or more mechanisms11 12 and hence limited what might have otherwise been excessive pulmonary blood flow. The relatively high hematocrit, which was maintained throughout the postoperative period, also may have increased pulmonary vascular resistance.13
The data presented here leave many questions unanswered regarding the physiology of these patients and what constitutes optimal postoperative management. In addition, our experience may not be readily applicable to other institutions where various aspects of the preoperative, intraoperative, and postoperative management of these patients may differ from ours. Nevertheless, this experience suggests that there is nothing inherent in the anatomy or physiology of babies with HLHS that ineluctably leads to postoperative hemodynamic instability or unacceptable early mortality.
Presented in part at the 67th Annual Meeting of the American Heart Association, Dallas, Tex, November 15, 1994.
- Copyright © 1995 by American Heart Association
Murdison KA, Baffa JM, Farrell PE Jr, Chang AC, Barber G, Norwood WI, Murphy JD. Hypoplastic left heart syndrome: outcome after initial reconstruction and before modified Fontan procedure. Circulation. 1990;82(suppl IV):IV-199-IV-207.
Fishman AP. Respiratory gases in the regulation of the pulmonary circulation. Physiol Rev. 1961;41:214-280.
Fuhrman BP, Smith-Wright DL, Venkataraman S, Howland DF. Pulmonary vascular resistance after cessation of positive end-expiratory pressure. J Appl Physiol. 1989;66:660-668.