Asian Cardiovasc Thorac Ann 2003;11:328-331
© 2003 Asia Publishing EXchange Ltd
Lung Function After Deep Hypothermic Cardiopulmonary Bypass in Infants
Su Zhao Kang, MD,
Sun Yong, MD,
Yang Yan Min, MD,
Zhang Hai Bo, MD,
Xu Zhi Wei, MD
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center, Xinua Hospital, Shanghai Second Medical University, Shanghai, People’s Republic of China
For reprint information contact: Su Zhaokang, MD Tel: 86 21 5873 2020 Fax: 86 21 5839 3915 email: scmcmud{at}online.sh.cn Department of Cardiac Surgery, Shanghai Children’s Medical Center, Shanghai 200127, People’s Republic of China.
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ABSTRACT
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There is increasing concern about neurologic injury due to deep hypothermia with low flow during repair of complex congenital heart defects in neonates and infants. Twenty infants with ventricular septal defect and pulmonary hypertension were randomly assigned to cardiac repair under deep hypothermia with circulatory arrest or deep hypothermia with low flow. Measurements of static pulmonary compliance, airway resistance, and respiratory index were performed before institution of cardiopulmonary bypass and at 5 minutes and 2 hours after cessation of cardiopulmonary bypass. Both groups had significant pulmonary dysfunction in terms of static pulmonary compliance, airway resistance, and respiratory index. There was greater impairment of pulmonary compliance and respiratory index after deep hypothermia with low flow, and this group required longer intensive care unit stay.
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INTRODUCTION
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Although technical refinements of cardiopulmonary bypass (CPB) have progressively improved the results of cardiac surgery, postoperative pulmonary dysfunction remains a serious complication, particularly for neonates and infants with congenital heart disease and pulmonary hypertension.1 Postoperative pulmonary dysfunction may increase the duration of mechanical ventilation, intensive care unit stay, hospital stay, and cost. More importantly, it is a major cause of infant death after cardiac surgery.
Deep hypothermia with circulatory arrest (DHCA) and deep hypothermia with low flow (DHLF) are often used during the repair of complex congenital heart defects in neonates and infants. Traditionally, DHCA was used because it provides a quiet bloodless surgical field that permits accurate repair of complex cardiac defects. However, the incidence of central nervous system dysfunction after DHCA ranges from 4% to 25%.2 Recently, DHLF has become popular because of a decrease in brain injury noted with its use. Nevertheless, the use of DHLF may injure other organs including the pulmonary system. There have been only two studies, both performed in piglets, which examined the effects of DHLF versus DHCA on pulmonary function.3,4 This study was undertaken to compare the effects of DHLF and DHCA on pulmonary dynamics in infants.
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PATIENTS AND METHODS
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Twenty infants with ventricular septal defect and pulmonary hypertension were enrolled in the study. Pulmonary hypertension was defined as a pulmonary-to-systemic arterial systolic pressure ratio of greater than 0.5. The patients’ ages and weights were limited to less than 15 months and less than 10 kg, to make their perioperative demographics comparable. Their ages ranged from 4 to 15 months, and their weights ranged from 4.5 to 8.5 kg. Patients were randomly allocated to the DHCA (n = 10) or DHLF (n = 10) group preoperatively. The patient profile in each group is shown in Table 1
. The study was approved by the Ethics Committee of Xinhua Hospital, and informed consent was obtained from the parents of all patients.
Induction of anesthesia was achieved with intravenous administration of midazolam (0.2 mg•kg-1), fentanyl (20 µg•kg-1), and vecuronium bromide (0.1 mg•kg-1). After tracheal intubation, patients were mechanically ventilated to give a tidal volume of 15 mL per kg of body weight with an inspiratory mixture of 50% oxygen and 50% nitrous oxide, and a respiratory rate of 20–24 breaths per minute. General anesthesia was maintained with continuous intravenous infusion of fentanyl (10 µg•kg-1•h -1) and vecuronium bromide (70 mg•kg-1•h -1). A bolus of fentanyl (10 µg•kg-1) was also administered both at the time of skin incision and at the beginning of CPB. The CPB circuit consisted of a Sarns 8000 roller pump (Sarns, Inc., Ann Arbor, MI, USA) and a Baxter Oxim 06 Plus hollow-fiber oxygenator (Baxter Healthcare, Irvine, CA, USA). The circuit was primed with Ringer’s lactate solution, albumin, and packed red cells to maintain a hematocrit of 25% to 28%. The patients were placed on CPB (36°C) at 100 mL•kg-1•min -1, and cooled to 18°C (< 20 min). The cooling technique included core and surface cooling, using alpha-stat blood gas management in both groups. A flow rate of 25–50 mL•kg-1•min -1 was used during DHLF. Following cardiac repair, the patient was rewarmed to 35°C, weaned from CPB, and moved to the intensive care unit. Modified hemofiltration was used in all patients.
Measurements were performed before CPB (T0) and at 5 minutes (T1) and 2 hours (T2) after separation from CPB. At each time, Ppeak (peak airway pressure), Ppause (pause airway pressure), TV (tidal volume), and FiO2 (fraction of inspired oxygen) were measured by a Lung Mechanics Calculator 940 (Siemens-Elema AB, Solna, Sweden) and arterial blood gases were analyzed with an AVL OMNI modular system (AVL List GmbH, Graz, Austria). Respiratory index (RI) is a measure of the oxygenation function of lung, and an increase in RI reflects the presence of pulmonary shunting in a variety of conditions including atelectasis, pulmonary contusion, and pulmonary thromboembolism. We used RI as a marker of lung damage. The RI was calculated from arterial blood gas assay as follows:
where A-aDO2 is the alveolar-arterial oxygen difference:
Lung mechanics describe the pressures required to effect flow and volume. These include the pressure to effect flow through the major conducting airways, which is dependent on airway resistance (Raw), and the pressure to distend the lungs, which is dependent on static pulmonary compliance (Cstat). Raw is the energy (pressure) needed to move gas through the pulmonary conducting airways.
where F is the respiratory frequency, and insp. % is the inspiratory time of the respiratory cycle. Cstat is the change in lung volume for a given amount of applied pressure change. It reflects lung stiffness and expresses the volume of lung expanded per unit of transpulmonary pressure applied:
Clinical features including reduced Cstat, increased Raw and RI are physiologic responses to lung injury.
Statistical analysis was performed using Microsoft Excel. All results are expressed as mean ± standard deviation. Data were analyzed using Student’s paired t test to compare results within each group. The unpaired t test was used to compare results between groups. Differences were considered significant if p < 0.05.
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RESULTS
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There were no deaths in either group and there were no significant differences between the groups with respect to age, body weight, or the durations of aortic crossclamping, circulatory arrest or low-flow CPB (Table 1
). The CPB time of the DHLF group was significantly longer than that of the DHCA group (Table 1). Although there was no significant difference in postoperative mechanical ventilation time between the two groups, the postoperative intensive care unit stay of the DHLF group was significantly longer than that of the DHCA group (Table 1).
The value of Cstat at T0 was not significantly different between the two groups (Table 2), but it decreased significantly at T1 and T2 compared with T0 in both groups. There was no significant difference in Cstat between groups at T1, but it was significantly lower in the DHLF group compared with the DHCA group at T2 (Table 2 and Figure 1). Airway resistance was not significantly different between the two groups at any of the time periods assessed, but Raw increased significantly at T1 and T2 compared with T0 in both groups (Table 2 and Figure 2). Respiratory index was not significantly different between the two groups at T0, it increased at T1 and T2 compared with T0 in both groups, and RI in the DHLF group was significantly higher than in the DHCA group at T2 (Table 2 and Figure 3).
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Figure 1. Pulmonary static compliance (Cstat) before and after cardiopulmonary bypass (CPB) in deep hypothermia with circulatory arrest (DHCA) and deep hypothermia with low flow (DHLF) groups. T0 = before CPB, T1 = 5 minutes after CPB, T2 = 2 hours after CPB. *p < 0.01 vsT0, #p <0.01 vsT0.
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Figure 2. Airway resistance (Raw) before and after cardiopulmonary bypass (CPB) in deep hypothermia with circulatory arrest (DHCA) and deep hypothermia with low flow (DHLF) groups. T0 = before CPB, T1 = 5 minutes after CPB, T2 = 2 hours after CPB. *p < 0.01 vs T0.
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Figure 3. . Respiratory index (RI) before and after cardiopulmonary bypass (CPB) in the deep hypothermia with circulatory arrest (DHCA) group and the deep hypothermia with low flow (DHLF) group. T0 = before CPB, T1 = 5 minutes after CPB, T2 = 2 hours after CPB. *p < 0.01 vs T0.  p < 0.01 vs DHCA.
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DISCUSSION
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The development and use of DHCA and DHLF were milestones in the history of cardiac surgery, making possible the repair of complex heart defects in neonates and infants, with reduced operative morbidity and mortality. Traditionally, DHCA has been preferred because of its simplicity, allowing the removal of cannulae during repair of heart defects. The use of DHLF rather than DHCA to prevent central nervous system morbidity is currently increasing, but despite the improved neurologic outcome, DHLF may cause dysfunction of other organs.5 Studies by Skaryak and colleagues3 and Yang and colleagues 4 on pulmonary function changes after DHLF and DHCA both indicated that DHLF produced greater pulmonary dysfunction than DHCA. The results of this study in infants and neonates with ventricular septal defect and pulmonary hypertension suggest that DHLF produced more lung injury than DHCA, in agreement with the previous findings in animal studies.
Undeniably, CPB can cause pulmonary dysfunction. On the molecular and cellular level, the exact mechanisms leading to pulmonary dysfunction after CPB are not yet fully clarified. A systemic inflammatory response that results from contact of blood components with the nonphysiologic surface of the bypass circuit, and ischemia-reperfusion injury are thought to be the main reasons for pulmonary dysfunction after CPB.6 Exposure of blood to artificial surfaces results in the activation of coagulation, fibrinolysis, and platelets. Neutrophils and the complement system are activated soon afterward, releasing inflammatory mediators that induce tissue injury and cause organ dysfunction.7–9 During total CPB, the lung is perfused solely by the bronchial arterial system, with the risk of ischemic injury. Ischemia may also initiate an inflammatory response because exposure of endothelial cells to hypoxia leads to a decrease in endothelial ATP levels and induction of interleukin, followed by increased expression of intercellular adhesion molecules.10 Endothelial cells then express surface antigens that are targets for activated neutrophils which adhere to the endothelium on reperfusion and produce cytotoxic enzymes.11 Pulmonary endothelial damage after CPB could result in further abnormalities of pulmonary compliance, pulmonary edema and increased alveolar-arterial O2 gradients.12,13
If ischemia was the primary mechanism of pulmonary injury in CPB, one would expect equal or greater pulmonary dysfunction in the DHCA group compared to the DHLF group. In this study, the duration of CPB in the DHLF group was significantly longer than that of the DHCA group, and we hypothesize that the increased exposure to foreign material in the bypass circuit may have led to more complement- and neutrophil-mediated injury of the neonatal pulmonary endothelium so as to produce greater pulmonary dysfunction in the DHLF infants. Currently, there is a trend in congenital heart surgery for earlier repair and the use of DHLF in place of DHCA, but postoperative pulmonary dysfunction remains an unresolved issue in these infants. This study suggests that when DHLF is used to prevent central nervous system injury, the increased risk of pulmonary dysfunction must be fully anticipated, and measures to prevent further pulmonary dysfunction should be taken. Alternating DHCA and DHLF during CPB, thereby limiting the duration of each, may be a way to minimize both brain and lung injury.
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ACKNOWLEDGMENTS
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We are grateful to Dr. Daniel E Torphy, former Associate Professor and Chief of General Pediatrics at the Medical College of Wisconsin, USA, for his help with the manuscript.
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ABSTRACT
INTRODUCTION
