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J Thorac Cardiovasc Surg 2000;119:525-533
© 2000 Mosby, Inc.
SURGERY FOR CONGENITAL HEART DISEASE |
From the Cardiothoracic Unit,a Great Ormond Street Hospital for Children NHS Trust, London; and the Departments of Cardiac Surgery,b Anaesthesia,c and Paediatrics,d Royal Brompton and Harefield NHS Trust, London, United Kingdom.
Supported by the British Heart Foundation.
Address for reprints: Professor Andrew N. Redington, Professor of Cardiology, Cardiothoracic Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond St, London WC1N 3JH (E-mail: reding{at}ibm.net ).
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Abstract |
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Introduction |
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1-3 that are related to central body temperature 1 and the systemic inflammatory response. 2 However, few data have assessed the changes that occur in systemic oxygen balance in the early hours after cardiopulmonary bypass in children. 4,5 Nonetheless, it is likely that these changes may differ from those that occur in adults for a number of reasons. First, resting VO 2 is greater in young children than in adults. 6 Second, deep hypothermia and circulatory arrest are commonly used during a pediatric cardiac operation, which may alter VO 2 and DO 2. Finally, the biochemical and hormonal responses to this stress have been reported to be greater after a cardiac operation in infants and children than in adults. 7,8 In the early postoperative period, an important goal of therapy is to achieve optimal tissue oxygenation at the lowest energy cost, particularly within the injured myocardium. Although the incidence of serious tissue hypoperfusion is now low, relative tissue hypoxia because of marginal tissue perfusion, which is often accompanied by lactate acidosis, remains relatively common in patients undergoing cardiopulmonary bypass. 3,9-11 The causes, implications, and optimal management of this imbalance between DO 2 and tissue demands are less well known, however. The aim of this study was to obtain a better understanding of VO 2, together with its determinants, early after pediatric cardiac operations. |
Methods |
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Cardiopulmonary bypass was performed under conditions of moderate to deep hypothermia with the lowest nasopharyngeal temperature between 15°C and 33°C (median, 27°C), nonpulsatile flow, and cold crystalloid cardioplegia. A flow on cardiopulmonary bypass ranging from 100 to 150 mL · min–1 · kg–1 was maintained, and the mean perfusion pressure was adjusted between 40 and 50 mm Hg by using isoflurane to vasodilate and metaraminol to vasoconstrict when required. Cardiopulmonary bypass was maintained for 24 to 157 minutes (median, 58 minutes), and aortic crossclamping was maintained for 13 to 90 minutes (median, 38 minutes). Patients were continued on bypass for between 6 and 64 minutes (median, 27 minutes) during rewarming until the central body temperature was restored to 36.9°C ± 0.4°C (mean ± SD) and hemodynamic stability was achieved. A pulmonary arterial line was inserted before the termination of bypass. Positive-pressure ventilation was recommenced after the discontinuation of bypass.
On return to the intensive care unit, the patients’ lungs were mechanically ventilated by using volume-cycled intermittent positive-pressure ventilation (Servo ventilator 900C; Siemens Medical Systems, Solna, Sweden). All received continuous intravenous infusions of vecuronium (74-256 µg · kg–1 · h–1), morphine (40 µg · kg–1 · h–1), and midazolam (150 µg · kg–1 · h–1) during the study period. The minute volume was adjusted to give an arterial carbon dioxide tension of 4 to 6 kPa. The inspiratory oxygen concentration was less than 60% in all patients. All patients were naturally rewarmed without any external heating, except for one young infant of 2 months who was nursed in a Babytherm bed (4200 Dräger; Draeger Medical Limited, Hemel Hemstead, United Kingdom) and a 15-year-old girl with a central-to-skin temperature gradient of 10°C who was covered with an external heating blanket. Dopamine, dobutamine, and glyceryl trinitrate were used according to each patient’s hemodynamic condition. After the study, patients were allowed to awaken when body temperature and circulation were stable. Patients were extubated on the basis of clinical judgment. All patients underwent echocardiography, which excluded residual intracardiac shunting.
Methods of measurements
Patient monitoring
All children had continuous invasive monitoring of systemic and pulmonary arterial and central venous pressures. Heart rate was continuously monitored, and the central body temperature (rectal) and peripheral temperature on the skin at the great toe were monitored with standard temperature probes (Hewlett Packard, Bracknell, United Kingdom).
Oxygen consumption
VO 2 was measured continuously by using on-line respiratory mass spectrometry according to our previously described method. 12 This is a highly sensitive and accurate method for continuous gas analysis that allows simultaneous measurements of multiple gas fractions within a mixture. An Amis 2000 quadrupole mass spectrometer (Innovision A/S, Odense, Denmark) was adapted for use in patients ventilated with the Servo ventilator 900C. VO 2 was measured by using the mixed expirate inert gas (argon) dilution method. 13 This requires analysis of inspired and expired gases, together with the collection of all expired gas. Before the study, the cuff of the endotracheal tube was inflated to prevent leak. The pressure within the cuff was measured with a manometer, and in all cases, to prevent hypoperfusion of the airway mucosa, pressure was maintained below arterial diastolic pressure. We performed a 2-point calibration of the mass spectrometer, exposing the distal inlet both to a 4-gas calibration mixture (nitrogen, oxygen, carbon dioxide, and argon) and to zero gas (closed inlet). This calibration was repeated at 30-minute intervals throughout the study period. The calibration of tracer gas flow (argon) was achieved by using a designated flowmeter (CT Platon, Basingstoke, United Kingdom; accuracy, ±1.25%). Ambient humidity, temperature, and atmospheric pressure were recorded from an electronic barometer (BA-888; Oregon Scientific, Portland, Ore).
DO 2, oxygen extraction, and lactate levels
Measurements were made for the first 4 hours after return to the intensive care unit. Arterial and mixed venous blood samples were taken at approximately 30-minute intervals from the peripheral arterial and pulmonary arterial catheters. Sampling was avoided if a change in ventilatory or hemodynamic support was made within 15 minutes. Blood samples were analyzed for oxygen, carbon dioxide, and lactate levels by using a blood analyzer (Rapidlab 865; Chiron Diagnostics, Halstead, United Kingdom). Cardiac output (CO) was then calculated by using the direct Fick method, according to the following equation:
CO = VO 2/(CaO 2 – CvO 2),
where CaO 2 and CvO 2 indicate arterial and mixed venous oxygen contents, respectively.
DO 2 and the oxygen extraction ratio (ERO 2) were then calculated by using the following equations:
DO 2 = CO x CaO 2
and
ERO 2 = VO 2/DO 2.
Statistical analysis
Data are expressed as means ± SD. Comparisons were carried out by using the unpaired 2-tailed t test. Correlation between 2 data sets was assessed by using the correlation coefficient. The change of the data over the study period was analyzed with single-factor analysis of variance.
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Results |
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The arterial blood lactate level measured on arrival was 1.8 ± 0.8 mmol/L, with levels of less than 2.0 mmol/L in 11 patients, 2.0 to 3.0 mmol/L in 8 patients, and 3.8 mmol/L in 1 patient. There were no significant differences between the patients with blood lactate levels of less than 2 mmol/L and those with blood lactate levels of 2 to 3 mmol/L with respect to age, baseline VO 2, DO 2, central temperature (Table II), or the interval between the time of termination of bypass and the time of sampling (109.4 ± 27.6 minutes for the group with normal lactate levels and 104.3 ± 17.6 minutes for the group with high lactate levels). However, patients with initial lactate levels of less than 2 mmol/L tended to have had shorter cardiopulmonary bypass and aortic crossclamp times and a deeper level of hypothermia during the operation (Table III), although differences did not achieve statistical significance.
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). Comparing between patients, the peak increase in VO 2 during the study period was significantly correlated with the peak increase in central temperature (r = 0.73, P = .001) but not with the peak increase in peripheral temperature (r = 0.34, P = .14; Fig 2). There was also a close temporal relationship between the peak of VO 2 and the highest recorded central temperature. As a result, for every increase in central temperature of 1°C, VO 2 increased by 11.3% ± 8.0%.
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). Oxygen extraction was more variable but tended to decrease slightly over time (P = .1, Fig 1). The peak increase in VO 2 was significantly correlated with the peak increase in DO 2 (r = 0.64, P = .002). There was a variable change in oxygen extraction at the time of peak VO 2 compared with the baseline values (r = 0.001, P = 1.0; Fig 2).
Overall, the mean arterial blood lactate level decreased to 1.5 ± 0.7 mmol/L (P = .001, Fig 1). Among those with lactate levels of 2.0 to 3.0 mmol/L on arrival, 3 had persistently high levels (2-3 mmol/L) during the first 2 hours, but in each it had fallen below 2 mmol/L by the end of the study period. In those with elevated lactate levels at 2 hours, VO 2, DO 2, and oxygen extraction levels in this subgroup at this time were similar to those with lactate levels of less than 2 mmol/L (Table II).
The patient with the highest lactate level at the beginning of the study had a peak level of 6.5 mmol/L at 90 minutes and was the only patient with a significant elevated level at the end of the study (3.9 mmol/L). In this 15-year-old patient, VO 2 increased progressively by 25.5% from 106.1 mL · min–1 · m–2 on arrival. DO 2 was initially low (241.3 mL · min–1 · m–2), and there was a large central-to-skin temperature difference (9.6°C). During the study, DO 2 increased by 91.7%, and oxygen extraction decreased by 34.1% (from 0.44 to 0.29). Although she required substantial inotropic and vasodilator support in the early postoperative period, she was successfully extubated at 10 hours after arrival in the intensive care unit.
In the 11 patients with normal lactate levels, inotropic support was used in 8 patients, with dopamine (3-6 µg · kg–1 · min–1) in 7 patients and with dobutamine (3 µg · kg–1 · min–1) in the other. In the 9 patients with a lactate level of more than 2.0 mmol/L, dopamine (2-10 µg · kg–1 · min–1) was used in 4 patients, and dobutamine (6 µg · kg–1 · min–1) was used in 2.
Age and VO 2
To correct for the potential confounding effects of temperature, the VO 2 measured when the core temperature was closest to 37°C (36.5°C-38.0°C; any time during the 4-hour period) was taken to analyze its relationship with age (Fig 3). In patients older than 3 months, a close negative correlation was found between age and VO 2 (r = –0.76). However, the 2 patients aged less than 3 months had a significantly lower VO 2 (104.4 and 107.1 mL · min–1 · m–2, respectively) compared with the rest of the group.
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Discussion |
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Our study confirms that there is a wide variability of VO 2 in children after cardiac operations, although over all our average values of VO 2 were lower than those previously reported in sedated children in the early postoperative period. 4 This may be related to the effects of paralysis in our children, all of whom were heavily sedated and paralyzed with a vecuronium infusion during the study to obviate the confounding effects of movement, agitation, and pain on VO 2 and to allow a more precise analysis of its determinants.
The determinants of VO 2
Age
It is widely known that VO 2 expressed as a function of body surface area is greater in younger than in older awake children. 6 This relationship has also been reported in sedated children with congenital heart malformations during cardiac catheterization 14 and in anesthetized children before a cardiac operation. 4 This relationship seems to be less obvious in studies in children younger than 3 months 14 and some infants, 4 in whom VO 2 may be significantly lower than expected. A similar trend was seen in our patients after cardiac bypass operations, with an inverse relationship between age and VO 2 for those over 3 months when measured at normothermia.
Body temperature and cardiopulmonary bypass with hypothermia
In early experimental studies performed with adult volunteers, an increase of 1°C in body temperature was shown to increase VO 2 by 13%. 15 A relationship between body temperature and the increase in VO 2 has also been demonstrated in adults and children after cardiac bypass operations. 1,4 Our data reinforces these previous observations, with an approximate 11% rise in VO 2 per degree of central temperature. Furthermore, there was a close temporal relationship between the peak of VO 2 and the highest recorded central temperature. Because no external heat supply was used in all but 2 patients, our results demonstrate the relationship of VO 2 and central body temperature under natural rewarming conditions after hypothermic cardiopulmonary bypass.
The increase in central body temperature may be attributed to 2 factors: normal homeostatic rewarming and fever induced by the inflammatory response after hypothermic cardiopulmonary bypass. Although central temperature is returned to normal by active rewarming at the end of cardiopulmonary bypass, muscle and subcutaneous fat remain hypothermic, and therefore only 65% of the heat loss is returned to the patient by active rewarming. 16 In our patients central body temperature was 36.8°C at termination of bypass and was 36.6°C (mean) on arrival in the intensive care unit. Subsequently, the time taken to reach a central body temperature of 38°C varied from 1 to 4 hours. The increase in VO 2 during this time presumably reflects the need to generate heat and the catabolic effects of fever and inflammation. Attempts to reduce this increase in VO 2 during rewarming from hypothermic cardiopulmonary bypass have been made. Extended active rewarming during bypass failed to reduce the increase in VO 2 postoperatively in one study, 17 but in other studies provision of an external heat supply was reported to reduce the oxygen uptake in adults during the rewarming period. 18,19 Our study also showed no correlation between active rewarming time or the temperature at the end of bypass with the increase of VO 2, and because only 2 patients were treated with an external heat supply, no comment regarding the use of external heating in children can be made.
A postoperative fever or temperature overshoot (>38°C) was seen in 15 of 20 children. Fever is one of the signs of the systemic inflammatory response induced by cardiopulmonary bypass. 20,21 It has been reported that this inflammatory response may help to explain the 50% variability of VO 2. 2 It follows, but remains to be demonstrated, that strategies that reduce systemic inflammatory response 22 should reduce the increase in VO 2. A more pragmatic approach may be to actively reduce the central temperature. Moat and associates 23 induced moderate hypothermia (32°C-33°C) in children with refractory low cardiac output states after a cardiac operation to reduce systemic, as well as myocardial, oxygen consumption. VO 2 was not measured in this study, but end-organ function appeared to improve with this strategy. Clearly, however, a more formal assessment of the relationship between cardiac output, VO 2, and central temperature is required before this can be recommended as routine therapy.
Relationship between VO 2, DO 2, and oxygen extraction
The increase in VO 2 was accompanied with an increase in DO 2, although with variable changes in oxygen extraction. This finding is in agreement with that of one study 9 but different from findings in some other studies, 1,4,10 which found that the increase in VO 2 depends mostly on the capacity of tissue oxygen extraction, whereas the relation with cardiac output is relatively weak because of impaired cardiac function after a cardiac operation. This may be because our group of children had a relatively stable cardiac function preoperatively. However, the close relationship between VO 2 and DO 2 as such should not be interpreted as the so-called VO 2 and DO 2 dependency phenomenon. To demonstrate this phenomenon in individual patients would first require independent measurement of VO 2 and DO 2 and would secondly require repeated determinations of VO 2 during imposed acute changes in DO 2 over a limited period of time. These were not done in the present study.
Arterial blood lactate and oxygen balance
Blood lactate levels are commonly measured to assess the adequacy of tissue perfusion and the balance between oxygen supply and demand in patients after cardiac bypass operations. Mild hyperlactatemia is relatively common after cardiopulmonary bypass, typically with a range of 2 to 4 mmol/L, 3,9-11 although higher levels (>5.0 mmol/L) have been reported. 24-26 Only one of our patients fell into this category. This patient had a low DO 2 (241.3 mL · min–1 · m–2), a large central-to-skin temperature gradient, and clinical evidence of a low cardiac output early after an operation. The lactate level fell as the DO 2 increased in response to inotropic and vasodilator support and surface rewarming. It is also likely that this lactate acidosis was associated with a defect of tissue oxygen extraction because despite a 91.7% increase in DO 2, VO 2 increased by only 25.5%, and the lactate level remained significantly elevated at the end of the study period. The lactate acidosis in this case should not be confused with the so-called type B lactate acidosis 24 described in other postoperative studies.
The pathophysiology of the more modest hyperlactatemia seen frequently after cardiac operations remains uncertain. A relationship between plasma lactate level and both cardiac output 27 and outcome 25,26 has been suggested, but at the levels measured in our studies, this was not the case. There was a tendency for the duration of cardiopulmonary bypass, aortic crossclamp time, and the depth of intraoperative hypothermia to be greater in the patients with lactate levels of greater than 2.0 mmol/L on arrival, which is in keeping with the findings of others, 24 but the difference was statistically insignificant in our study. If absolute cardiac index is not important, then its distribution may be a factor. The gastrointestinal tract is suggested to be the major source of lactate around the time of cardiopulmonary bypass, 28 and splanchnic ischemia has been found to persist during the first few postoperative hours from studies on the basis of gastric tonometry. 29,30 What is clear, however, is that a modestly elevated blood lactate level does not predict more important failure of global DO 2 and cannot be used either as an index of cardiac output or expected outcome.
Limitations of our study
Our study was performed in relatively stable and older children. No neonates with circulatory arrest with hypothermia were included. In addition, because our values for systemic oxygen delivery were derived from the measured oxygen consumption, the potential for mathematical coupling limits our ability to analyze the relationship between these parameters regarding the phenomenon of delivery-dependency of oxygen consumption.
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Acknowledgments |
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