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J Thorac Cardiovasc Surg 2008;136:1207-1214
© 2008 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Carbon dioxide—a complex gas in a complex circulation: Its effects on systemic hemodynamics and oxygen transport, cerebral, and splanchnic circulation in neonates after the Norwood procedure

Jia Li, MD, PhD*, Gencheng Zhang, MD, PhD, Helen Holtby, MD, Bruno Bissonnette, MD, Golden Wang, MD, Andrew N. Redington, MD, Glen S. Van Arsdell, MD

The Heart Center, Hospital for Sick Children, Toronto, Ontario, Canada

Received for publication August 24, 2007; revisions received October 17, 2007; accepted for publication February 25, 2008.

* Reprint requests: Jia Li, MD, PhD, Division of Cardiology, The Heart Center, Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8. (Email: jia.li{at}yahoo.com).


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Objective: Carbon dioxide is suggested to increase oxygen delivery after the Norwood procedure. We sought to quantitatively define the effects of stepwise increases in arterial carbon dioxide tension on systemic oxygen transport and cerebral and splanchnic circulation after the Norwood procedure.

Methods: Seven sedated, paralyzed, and mechanically ventilated neonates were studied after the Norwood procedure. Arterial carbon dioxide tension increased from 40-50-60 mm Hg using inspired carbon dioxide. Each step was 30 minutes. Pulmonary and systemic blood flow, vascular resistance, and oxygen delivery were calculated with the measurement of oxygen consumption and blood gases and pressures from the aorta, superior vena cava, and pulmonary vein. Plasma epinephrine and norepinephrine were measured. Cerebral and splanchnic oxygen saturations were measured by near-infrared spectroscopy, and cerebral blood flow velocity was measured by transcranial Doppler.

Results: Stepwise increase in arterial carbon dioxide tension was associated with a decrease in systemic vascular resistance (P < .001) and an increase in systemic blood flow (P < .01) and oxygen delivery (P < .0001), but not with significant changes in total pulmonary vascular resistance and pulmonary blood flow. Cerebral oxygen saturation increased (P < .0001), and splanchnic oxygen saturation decreased (P < .01). Oxygen consumption decreased (P < .01), and epinephrine and norepinephrine increased (P < .01 and .05).

Conclusion: Moderate hypercapnia increases systemic blood flow because of its effect on systemic vascular resistance after the Norwood procedure. The increase in systemic blood flow is primarily a consequence of increased cerebral blood flow that compromises splanchnic circulation. The decrease in oxygen consumption improves oxygen transport, but the increase in catecholamines may be undesirable. Clinical use of carbon dioxide aiming to improve oxygen delivery should be with caution.

Abbreviations and Acronyms CO2 = carbon dioxide; CPB = cardiopulmonary bypass; DO2 = systemic oxygen delivery; NIRS = near-infrared spectroscopy; PaCO2 = arterial carbon dioxide tension; PaO 2 = arterial oxygen tension; PVR = pulmonary vascular resistance; Qp = pulmonary blood flow; Qs = systemic blood flow; ScO2 = cerebral oxygen saturation; SsO2 = splanchnic oxygen saturation; SVR = systemic vascular resistance; tPVR = total pulmonary vascular resistance; VO2 = systemic oxygen consumption


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
The important goal and challenge in the management of neonates after the Norwood procedure is to maintain adequate systemic blood flow (Qs) and oxygen delivery (DO2) to sustain tissue oxygenation. In these neonates, DO2 is reduced because of impaired myocardial function, and systemic oxygen consumption (VO2) is increased as a result of cardiopulmonary bypass (CPB) and secondary systemic inflammatory response.1Go The complex pathophysiology with univentricular and parallel circulation profoundly affects oxygen transport after the Norwood procedure and seriously limits the postoperative management. The lack of adequate animal models of single ventricle anatomy or physiology makes it difficult to study.2-4Go Clinical studies have been limited because of the use of indirect indicators of arterial and superior vena caval oxygen saturations as surrogates of DO2.5,6Go

Carbon dioxide (CO2) has been suggested to increase DO2 in neonates both before and after the Norwood procedure.2-6Go Consequently, it is a common practice to maintain a relatively high arterial CO2 tension (PaCO 2) mostly by hypoventilation. It is believed that the potent pulmonary vasoconstrictive effect of CO2 decreases pulmonary blood flow (Qp), and Qp:Qs thereby increases Qs. This may be incorrect. As we have recently reported, using directly measured systemic hemodynamics and oxygen transport, Qp has little impact on DO2 in the presence of mechanical limitation by the Blalock-Taussig shunt and relative fixed total pulmonary vascular resistance (tPVR) (inclusive of the resistance of the Blalock-Taussig shunt and pulmonary vascular bed), and DO2 is mostly determined by SVR.1Go Given the potent vasodilating effect of CO2 on systemic circulation,7Go particularly the cerebral vascular bed,8,9Go it was hypothesized that the increase in Qs and DO2 by CO2 may be the result of its effect on systemic circulation rather than the pulmonary vasculature, and that the increase in Qs may be the result of an increase in cerebral blood flow instead of splanchnic perfusion.

Near-infrared spectroscopy (NIRS) measures the equilibrium of oxyhemoglobin and deoxyhemoglobin in a mixture of veins, arteries, and capillaries in the underlying tissue and provides a noninvasive, continuous method to monitor regional tissue oxygenation.10Go NIRS has been extensively evaluated in the cerebral10Go and splanchnic11Go circulations of newborn infants and was adapted to continuously monitor cerebral oxygen saturation (ScO2) and splanchnic oxygen saturation (SsO2) in the present study.

This study aimed to quantitatively define the effects of a stepwise increase in PaCO 2 on the systemic hemodynamics, oxygen transport, and redistribution of systemic DO2 between cerebral and splanchnic circulations in neonates during the early postoperative period after the Norwood procedure.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusions
 References
 
Patients
This study was approved by the Research Ethics Board at the Hospital for Sick Children, Toronto, Canada. Written informed consent was obtained from the parents of 7 neonates (4 boys and 3 girls, age range 4–7 days) undergoing the classic Norwood procedure with Blalock-Taussig shunt between September of 2004 and October of 2006. The clinical characteristics of the patients are shown in Table 1 . Neonates undergoing the Norwood procedure with right ventricular to pulmonary arterial shunt or the Hybrid procedure with bilateral pulmonary artery bands and arterial duct stent during this period were excluded from the present study in the concern of their different characteristics in systemic hemodynamics and oxygen transport12Go and potential different responses to CO2.


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  		Table 1 Clinical data for the 7 patients
 
Intraoperative Procedures
All patients were intubated with cuffed endotracheal tubes (Microcuff-Heidelberg-Pediatric, Microcuff GmbH, Weinheim, Germany). A central venous line was inserted preoperatively through the internal jugular vein or the subclavian vein to the superior vena cava just above the atrium junction. A standard Norwood procedure with the 3.5-mm right modified Blalock-Taussig shunt was performed in all patients. Circulatory arrest was performed in 6 patients for 1 to 46 minutes and selected cerebral perfusion in 6 patients for 30 to 70 minutes at 30 to 35 mL/min/kg (Table 1). Phenoxybenzamine (0.25 mg/kg) was given in the heart-lung machine circuit after initiation of CPB. Before termination of CPB, milrinone (100 µg/kg) was given and dopamine (5 µg/kg/min) was initiated. A pulmonary venous line was inserted into the orifice of the right upper pulmonary vein.

Postoperative Management
The central temperature (esophageal) was maintained between 36°C and 37°C. Postoperative monitoring included arterial, superior vena caval, and pulmonary venous pressures, and heart rate. Sedation consisted of continuous intravenous infusion of morphine and intermittent injections of a muscle relaxant (pancuronium). Patients received time-cycled pressure control/pressure support ventilation. Hemoglobin was maintained between 14 and 16 mg/dL. Inotropic and vasoactive agents (dopamine, milrinone, and phenoxybenzamine) and volume infusions (5% albumin or blood) were administered according to our standard protocol.13Go

Methods of Measurements
Systemic oxygen consumption
VO2 was measured continuously using an AMIS2000 respiratory mass spectrometer (Innovision A/S, Odense, Denmark). This is a sensitive and accurate method for continuous gas analysis that allows simultaneous measurements of multiple gas fractions.1Go Inspired and end-tidal partial pressures of CO2 were continuously monitored using inlet sampling from the connection of the ventilator circuit to the endotracheal tube. This was used to estimate the rate of CO2 delivery into the inspired gas mixture.14Go The setup of the CO2 delivery and respiratory mass spectrometer with the ventilator circuit is described elsewhere.15Go

Calculations of hemodynamics and oxygen transport
Blood samples were taken from the arterial, superior vena caval, and pulmonary venous lines for the measurements of blood gases. Qp, Qs, SVR, tPVR, DO2, and oxygen extraction ratio (ERO2) were calculated using standard equations (Table 2 ).


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  		Table 2 Equations using oxygen consumption to calculate hemodynamics and oxygen transport parameters
 
Regional oxygenation
Measurements of cerebral and splanchnic oxygenation were made using NIRS to measure ScO2 and SsO2. The 2 NIRS probes (Somanetics INVOS 5100A, Troy, Mich) were placed in the midline on the forehead of the patient (ScO2) and slightly to the right of midline on the thoracic-lumbar flank (SsO2),16Go and recordings were made at 1-minute intervals.

Cerebral blood flow velocity
The flow velocity was measured with transcranial Doppler with a 2 MHz pulse-wave ultrasound transducer, which was fixed above the zygomatic arch (Medasonics Inc, Fremont, Calif) and interrogated the portion of middle cerebral artery near its junction with the anterior cerebral artery.9Go

Plasma norepinephrine and epinephrine
An arterial blood sample of 2 mL was withdrawn into an EDTA tube. The simultaneous determination of plasma norepinephrine and epinephrine was measured by high-performance liquid chromatography coupled with electrochemical detection.17Go

Study Protocol
The study protocol was instituted during the period of 48 to 72 hours after the Norwood procedure when a relatively cardiorespiratory steady state was achieved. Inspiratory O2 fraction was 0.21 to 0.25. The protocol consisted of 4 stages. At baseline, PaCO 2 was adjusted to 40 mm Hg by modifying minute ventilation. Subsequently, CO2 was delivered to the inspired gas mixture to reach PaCO 2 tensions of 50 and 60 mm Hg sequentially. Finally, additional CO2 was withdrawn and the measurements were repeated at a PaCO 2 of approximately 40 mm Hg. Each stage was for 30 minutes. At the end of each stage, blood gases (including arterial lactate), systemic hemodynamics and oxygen transport, ScO2 and SsO2, and cerebral arterial blood flow velocity were recorded, and arterial blood samples were taken for the measurements of plasma epinephrine and norepinephrine. Before the study, echocardiography was performed to ensure that the aortic arch and Blalock-Taussig shunt were unobstructed.

Statistics
The results are given as mean ± standard deviation. The data, collected at 4 levels of PaCO 2 (40, 50, and 60 mm Hg, and then 40 mm Hg), were analyzed by repeated-measures analysis of variance for quadratic effect. A quadratic effect was indicated by a statistically significant parameter estimate for the time sequence effect. The actual estimate for the inverted parabolas was negative, indicating a return toward baseline for the outcome. Pairwise comparison was performed between the data at different levels of CO2. The overall P value and adjusted P value for multiple comparisons were calculated using the Tukey-Kramer adjustment. We used the statistical software SAS version 8.2 (Cary, NC).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusions
 References
 
Patients
All 7 patients received an infusion of milrinone (0.66–0.99 µg/kg/min), and 3 of them received phenoxybenzamine (0.5–2.0 mg/kg/d) during the study period. Dopamine had been terminated within the first 36 hours in all patients. None of the patients received epinephrine or norepinephrine during the postoperative period. Patients were extubated 4 to 25 days (median 9 days) after the operation.

Changes During the Study Protocol
The stepwise increase in PaCO 2 from 40 ± 4 to 53 ± 5 to 61 ± 6 mm Hg led to a decrease in arterial pH from 7.39 ± 0.05 to 7.28 ± 0.07 to 7.23 ± 0.08 (P < .0001) (Table 3 ; Figure 1 ). This was not associated with any significant change in tPVR, Qp, SaO2, or pulmonary venous O2 saturation. The stepwise increase in PaCO 2 was associated with a significant decrease in SVR (P < .001) and Qp:Qs (P < .05), and a significant increase in arterial oxygen tension (PaO 2) (P < .0001), Qs (P < .01), and DO2 (P < .0001). A significant decrease in central body temperature (P < .05), VO2 (P < .01), ERO2 (P < .01), and lactate (P < .001) were observed. Norepinephrine (P < .05) and epinephrine (P < .01) significantly increased. Cerebral arterial blood flow peak velocity and ScO2, as well as superior vena caval O2 saturation, significantly increased (P < .0001 for all), whereas SsO2 significantly decreased (P < .01). These changes were significantly greater when PaCO 2 increased from 40 to 50 mm Hg compared with PaCO 2 from 50 to 60 mm Hg, including PaO 2 (P < .0001), VO2 (P < .05), lactate (P < .05), cerebral arterial blood flow peak velocity (P < .01), ScO2 (P < .0001), superior venous O2 saturation (P < .0001), and norepinephrine (P < .05). DO2 increased significantly at both stages of PaCO 2 (P < .05). The changes in the remaining variables (temperature, SVR, Qs, Qp:Qs, CO, ERO2) did not achieve statistical significance between either of the 2 sequential stages, despite the significant changes over the 3 levels of PaCO 2. There was a small although insignificant increase in heart rate and arterial blood pressure over the stepwise increase in PaCO 2. As PaCO 2 decreased from 60 ± 6 mm Hg to 44 ± 5 mm Hg with discontinuation of added CO2, these variables returned toward baseline.


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  		Table 3 Arterial blood gas, systemic, cerebral and splanchnic oxygen transport, and circulating norepinephrine and epinephrine during the staged increases of carbon dioxide in 7 neonates after the Norwood procedure
 

Figure 1
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  		Figure 1. Changes (mean ± standard deviation) in systemic hemodynamics and oxygen transport, including systemic vascular resistance, tPVR, Qp, Qs, VO2, DO2, ERO2, lactate, ScO2, SsO2, and plasma epinephrine and norepinephrine concentration during the stepwise increases in PaCO 2 from 40 to 50 to 60 mm Hg and after the termination of the additional inspired CO2 at PaCO 2 40 mm Hg. SVR, Systemic vascular resistance; tPVR, total pulmonary vascular resistance; ERO2, oxygen extraction ration; DO2, oxygen delivery; VO2, oxygen consumption; PaCO 2, arterial carbon dioxide tension; ScO2, cerebral oxygen saturation; SsO2, splanchnic oxygen saturation; Qp, pulmonary blood flow; Qs, systemic blood flow.

 
The levels of norepinephrine and epinephrine at baseline PaCO 2 (40 mm Hg) varied widely between patients (3.4–25.0 nmol/L for norepinephrine and 0.1–14.0 nmol/L for epinephrine). The levels of norepinephrine and epinephrine at each level of PaCO 2 were not correlated with VO2 or any of hemodynamics and oxygen transport variables (r2 < 0.20, P > .05 for all).


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusions
 References
 
This is the first quantitative assessment of the effects of moderate hypercapnia with respiratory acidosis on systemic hemodynamics, oxygen transport, cerebral, and splanchnic circulation in neonates early after the Norwood procedure. The present data demonstrate that a stepwise increase in PaCO 2 is not associated with significant changes in tPVR and Qp, whereas a significant decrease in SVR resulted in a significant increase in Qs and DO2. The increase in Qs occurred mainly as a consequence of increased cerebral blood flow, as indicated by increased ScO2 and cerebral arterial blood flow velocity, compromising splanchnic oxygenation, as indicated by a decreased SsO2. The decrease in VO2 further improved the balance of systemic oxygen transport as demonstrated by the significant decrease in ERO2 and arterial lactate. In paradox to the decrease in VO2, plasma norepinephrine and epinephrine increased. This is associated with a small increase in heart rate and arterial blood pressure.

Carbon Dioxide Effects: Pulmonary Versus Systemic Circulation
CO2 increases pulmonary vascular resistance (PVR) in biventricular circulation, and this has been generally used to explain the mechanisms for the increase in Qs and DO2 in the univentricular and parallel circulation as by decreasing Qp and Qp:Qs.2-5Go On the basis of this speculation, hypoxia and hypercapnia as potent pulmonary vasoconstrictors were advocated. Although hypoxia fails to improve DO2 and may even be deleterious,3,5Go induced hypercapnia mostly by hypoventilation remains a common practice aiming to improve DO2.5,6Go Although the present data support previous findings, they reveal that the increase in Qs and DO2 during hypercapnia is due to the direct effect on the systemic circulation rather than the pulmonary circulation. This is supported by little changes in tPVR and Qp. In other words, in the presence of mechanical limitation by the Blalock-Taussig shunt, the change in PVR per se plays a limited role to determine tPVR and Qp. We have recently demonstrated that tPVR has little impact on DO2, and that SVR is the most important determinant of Qs and DO2 in neonates after the Norwood procedure.1Go It should be remembered that CO2 is also a potent systemic vasodilator via its action on smooth muscle cells and endothelium of peripheral and cerebral arteries.7,8Go The decrease in SVR and the consequent increase in Qs and DO2 during hypercapnia are clearly demonstrated in the present data. Systemic afterload reduction with agents such as alpha-blockade phenoxybenzamine nitric oxide donor sodium nitroprusside or a phosphodiesterase III inhibitor milrinone has been increasingly used as a primary management strategy in these patients both before and after the Norwood procedure, with improved postoperative outcomes.13,18-20Go Therefore, in the concept of optimization of DO2 in the Norwood or single-ventricle physiology, emphasis should shift from PVR and Qp, even beyond Qp:Qs, directly to SVR and Qs.

In addition, hypercapnia produced a significant increase in PaO 2, with no significant change in SaO2 in the present study. This apparent contradiction is likely explained by the fact that increased PaCO 2 and acidosis cause a rightward shift in the oxyhemoglobin dissociation curve (Bohr effect), and for any given systemic saturation, PaO 2 is higher. The increase in PaO 2 may also contribute, to some extent, to the increase in DO2. Indeed, judicious use of higher inspired oxygen fraction has been suggested to improve DO2 in patients undergoing the Norwood procedure.21,22Go Bradley and colleagues21Go recently showed an improved DO2 (using indirect indicator of oxygen excess factor) by high inspired oxygen fraction, even with its potent pulmonary vasodilating effect. This further emphasizes the limited contribution of PVR to DO2 in the Norwood circulation.

Carbon Dioxide Effects: Upper Body Versus Lower Body Blood Flow
All the previous clinical studies have used superior vena caval oxygen saturation as a surrogate of DO2. This could not be completely avoided in the present study; the superior vena caval blood gas was also used as an estimate of the mixed venous oxygen content to calculate SVR and Qs. The derived SVR, Qs, and DO2 in the present study primarily reflect the cerebral vascular bed and may be different from the lower body.23Go This difference is most likely to be greater in the induced increases in PaCO 2, because CO2 is a potent cerebral vasodilator in normal subjects,8Go as well as in patients after CPB.9,24Go As a result, the present data, as those in previous clinical studies, may have overestimated the overall changes in SVR, Qs, and DO2 in response to CO2. In animal studies, this limitation was overcome with direct measurement of aortic flow (Qs) using an ultrasonic flow probe placed at the ascending aorta.2-4Go The percentage of increase in Qs was considerably less when compared with that in our patients (15% vs 57%) for the similar range of PaCO 2 changes.2Go Therefore, caution is needed when interpreting the increase in Qs and DO2 by CO2 in clinical practice as the overall DO2 to the whole body. As further shown in the present data, the increase in Qs at PaCO 2 from 40 to 60 mm Hg was associated with an increase in ScO2 and a decrease in SsO2, although to a lesser degree (12% ± 4% vs –8% ± 7%). It seems that the increase in Qs is primarily the consequence of a significant increase in cerebral blood flow at a certain cost of splanchnic perfusion. This is not entirely surprising, considering that the systemic vasodilating effect of CO2 occurs predominately in the brain and to some extent in the heart and nonrespiratory skeletal muscles, whereas little occurs in splanchnic organs.25,26Go Although ischemic brain injury is a major noncardiac morbidity in patients after the Norwood operation,27,28Go the increase in cerebral blood flow may be beneficial for brain function; the tradeoff of flow distribution with splanchnic perfusion may be undesirable in these patients. It has been shown that splanchnic organs may be at a higher risk of ischemia because of the lower critical oxygen extraction compared with the other organs;29Go inadequate splanchnic organ perfusion may be associated with adverse post-CPB outcomes.30Go It has been reported that gastrointestinal complications are common and related to mortality in patients after the Norwood procedure.31Go Therefore, it may be unwise to concentrate on maximizing DO2, ignoring regional and tissue perfusion. Further studies are warranted with direct measurements of both superior and inferior vena caval oxygen saturations in addition to NIRS monitoring to provide a clearer picture of CO2 effects on systemic and cerebral and splanchnic DO2.

Carbon Dioxide Effects: Decreased Systemic Oxygen Consumption Versus Increased Circulating Catecholamines
A significant decrease in VO2 was observed during hypercapnia in neonates after the Norwood procedure. This was accompanied with a significant decrease in central body temperature. This is the second time that this phenomenon has been observed in an intact organism, including animals and humans. The first report was in infants after bidirectional cavopulmonary anastomosis.14Go Hypercapnic acidosis exerts dual and opposite effects on metabolism and cardiovascular function.14Go Acidosis (respiratory or metabolic) directly depresses and alkalosis stimulates cellular metabolism in isolated cells and organ.32Go In intact organisms, acidosis stimulates a significant release of epinephrine and norepinephrine from sympathetic nerve endings and adrenal glands,33,34Go thus indirectly stimulating metabolism and cardiovascular function. The opposing effects may be essential to maintain metabolic and circulatory homeostasis. It has been shown that myocardia,35Go cerebral,8Go and systemic VO2 36,37Go remain unchanged or slightly increased in subjects with normal biventricular circulation. The mechanisms for the unique decrease in VO2 were speculated in our previous report,14Go as either reduced metabolic response to or decreased release of catecholamines in the unique circulations. In the present study, plasma epinephrine and norepinephrine were measured. The data showed that the baseline levels of epinephrine and norepinephrine at PaCO 2 of 40 mm Hg were markedly higher in our patients compared with healthy humans33Go and infants pre-CPB.38Go Although it has been well documented that hypothermic CPB for complete correction of congenital heart defects may induce significant increases in circulating epinephrine and norepinephrine, the levels largely return to preoperative baseline at 24 hours.38Go It is likely that the present group of neonates remained hemodynamically and metabolically stressed longer. It is somewhat surprising the altitude of increases in epinephrine and norepinephrine in our patients is comparable to that in healthy persons over the similar range of PaCO 2 increase.33Go If the release of catecholamines is not the case, the decreased response might be attributable to the deceased VO2 in our patients during hypercapnic acidosis. CPB may decrease the metabolic response to catecholamines.39Go The mechanism for the paradoxic changes in VO2 and circulating catecholamines remains unclear, and the clinical implication of the increased circulating catecholamines on cardiovascular function is uncertain. A small increase in heart rate and systemic arterial blood pressure was observed that is consistent with previous findings.33,36Go Any increase in cardiovascular work load might be undesirable in these post-Norwood neonates with marginal reserve of cardiovascular function. In addition, {alpha}-adrenergic receptor stimulation in the splanchnic vascular bed by epinephrine and norepinephrine may reduce the regional blood flow.40Go This might be partly attributable to the decrease in SsO2.

Study Limitations
The order of exposure to the different CO2 tensions was not randomized. However, it is unlikely that the findings were due merely to the sequence of changes because the final CO2 level of 40 mm Hg demonstrated a reversal of changes noted with each previous sequential increase in CO2 tension.

The changes were monitored for 30 minutes at each level of PaCO 2, and therefore we could not address the effects of prolonged or severe hypercapnia. The use of superior vena caval blood as an estimation of the mixed venous gas for the calculations of SVR, Qs, and DO2 may be a limitation and was discussed above.

NIRS was used to estimate cerebral and splanchnic oxygenation in our study. As mentioned above, NIRS measures oxygen saturation in the mixture of arteries, capillaries, and veins in a small part of underlining tissue and thus may not precisely reflect the overall balance of cerebral or splanchnic oxygen transport or precisely measure the regional blood flow or DO2. Nonetheless, in the patients who were sedated and paralyzed, VO2 was minimized. The change in regional oxygen saturation as measured by NIRS may largely reflect the changes in regional blood flow and DO2 (ie, in the brain and splanchnic organs) in our current study.


   Conclusions
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
References
 
CO2 exerts complex effects on systemic and regional oxygen transport in neonates after the Norwood procedure. Moderate hypercapnia with acidosis increases Qs and DO2 via the direct systemic vasodilatation effect, rather than the effect on pulmonary vasoconstriction as previously proposed. The increase in Qs and DO2 is primarily the consequence of increase cerebral blood flow, with an undesirable tradeoff of splanchnic oxygenation. In addition, CO2 decreases VO2, contributing to the balance of systemic oxygen transport. The implication of the increase in circulating catecholamines remains uncertain. Clinical use of CO2 aiming to improve DO2 in patients with univentricular and parallel circulation should be with caution. Our data ask further understanding of oxygen transport, not only at the systemic level but also at the regional and tissue level, when designing any intervention aiming to improve oxygen status in critically ill patients after CPB.


   Footnotes
 
This study was supported by the Heart and Stroke Foundation of Canada (J.L., A.N.R and G.S.V).


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 

  1. Li J, Zhang G, Holtby HM, McCrindle BW, Cai S, Humpl T, et al. Profiles of hemodynamics and oxygen transport derived using continuous measured oxygen consumption following the Norwood procedure. J Thorac Cardiovasc Surg 2007;133:441-448.[Abstract/Free Full Text]
  2. Mora GA, Pizarro C, Jacobs ML, Norwood WI. Experimental model of single ventricle. Influence of carbon dioxide on pulmonary vascular dynamics. Circulation 1994;90:II43-II46.[Medline]
  3. Reddy VM, Liddicoat JR, Fineman JR, McElhinney DB, Klein JR, Hanley FL. Fetal model of single ventricle physiology: hemodynamic effects of oxygen, nitric oxide, carbon dioxide, and hypoxia in the early postnatal period. J Thorac Cardiovasc Surg 1996;112:437-449.[Abstract/Free Full Text]
  4. Riordan CJ, Randsbeck F, Storey JH, Montgomery WD, Santamore WP, Austin III EH. Effects of oxygen, positive end-expiratory pressure, and carbon dioxide on oxygen delivery in an animal model of the univentricular heart. J Thorac Cardiovasc Surg 1996;112:644-654.[Abstract/Free Full Text]
  5. Bradley SM, Simsic JM, Atz AM. Hemodynamic effects of inspired carbon dioxide after the Norwood procedure. Ann Thorac Surg 2001;72:2088-2093.[Abstract/Free Full Text]
  6. Tabbutt S, Ramamoorthy C, Montenegro LM, Durning SM, Kurth CD, Steven JM, et al. Impact of inspired gas mixtures on preoperative infants with hypoplastic left heart syndrome during controlled ventilation. Circulation 2001;104:I159-I164.
  7. Fukuda S, Matsumoto M, Nishimura N, Fujiwara N, Shimoji K, Takeshita H, et al. Endothelial modulation of norepinephrine-induced constriction of rat aorta at normal and high C02 tensions. Am J Physiol 1990;258:H1049-H1054.[Medline]
  8. Kety SS, Schmidt CF. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young man. J Clin Invest 1948;27:484-492.[Medline]
  9. Hoskote A, Li J, Hickey C, Erickson S, Van Arsdell G, Stephens D, et al. The effects of carbon dioxide on oxygenation, systemic, cerebral and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis. J Am Coll Cardiol 2004;6(44):1501-1509.
  10. Wyatt JS, Cope M, Delpy DT, Wray S, Reynolds EO. Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry. Lancet 1986;2:1063-1066.[Medline]
  11. Petros AJ, Heys R, Tasker RC, Fortune PM, Roberts I, Kiely E. Near infrared spectroscopy can detect changes in splanchnic oxygen delivery in neonates during apnoeic episodes. Eur J Pediatr 1999;158:173-174.[Medline]
  12. Li J, Zhang G, Benson L, Holtby H, Cai S, Humpl T, et al. Comparison of the profiles of postoperative systemic hemodynamics and oxygen transport in neonates after the hybrid or the Norwood procedure: a pilot study. Circulation 2007;116(11 Suppl):I179-I187.
  13. De Oliveira NC, Van Arsdell GS. Practical use of alpha blockade strategy in the management of hypoplastic left heart syndrome following stage one palliation with a Blalock-Taussig shunt. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2004;7:11-15.[Medline]
  14. Li J, Hoskote A, Hickey C, Van Arsdell G, Redington A, Adatia I. Hypercapnia improves systemic oxygenation and decreases oxygen consumption and blood lactate levels in children after bidirectional cavopulmonary shunt operation. Crit Care Med 2005;33:984-989.[Medline]
  15. Li J, Redington AN. Unique technique for assessing the effects of CO2 on oxygen transport variables. J Intensive Care Med 2006;13:169-175.
  16. Li J, Van Arsdell GS, Zhang G, Cai S, Humpl T, Caldarone CA, et al. Assessment of the relationship between cerebral and splanchnic oxygen saturations measured by near-infrared spectroscopy and direct measurements of systemic haemodynamic variables and oxygen transport after the Norwood procedure. Heart 2006;92:1678-1685.[Abstract/Free Full Text]
  17. Musso NR, Vergassola C, Pende A, Lotti G. Reversed-phase HPLC separation of plasma norepinephrine, epinephrine, and dopamine, with three-electrode coulometric detection. Clin Chem 1989;35:1975-1977.[Abstract/Free Full Text]
  18. Stieh J, Fischer G, Scheewe J, Uebing A, Dutschke P, Jung O, et al. Impact of preoperative treatment strategies on the early perioperative outcome in neonates with hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 2006;131:1122-1129.[Abstract/Free Full Text]
  19. De Oliveira NC, Ashburn DA, Khalid F, Burkhart HM, Adatia IT, Holtby HM, et al. Prevention of early sudden circulatory collapse after the Norwood operation. Circulation 2004;110:II133-II138.
  20. Tweddell JS, Hoffman GM, Fedderly RT, Berger S, Thomas Jr. JP, Ghanayem NS, et al. Phenoxybenzamine improves systemic oxygen delivery after the Norwood procedure. Ann Thorac Surg 1999;67:161-167.[Abstract/Free Full Text]
  21. Bradley SM, Atz AM, Simsic JM. Redefining the impact of oxygen and hyperventilation after the Norwood procedure. J Thorac Cardiovasc Surg 2004;127:473-480.[Abstract/Free Full Text]
  22. Taeed R, Schwartz SM, Pearl JM, Raake JL, Beekman III RH, Manning PB, et al. Unrecognized pulmonary venous desaturation early after Norwood palliation confounds Qp:Qs assessment and compromises oxygen delivery. Circulation 2001;103:2699-2704.[Abstract/Free Full Text]
  23. Scheinman MM, Brown MA, Rapaport E. Critical assessment of use of central venous oxygen saturation as a mirror of mixed venous oxygen in severely ill cardiac patients. Circulation 1969;40:165-172.[Abstract/Free Full Text]
  24. Cheng W, Hartmann JF, Cameron DE, Griffiths EM, Kirsch JR, Traystman RJ. Cerebral blood flow during cardiopulmonary bypass: influence of temperature and pH management strategy. Ann Thorac Surg 1995;59:880-886.[Abstract/Free Full Text]
  25. Kiefer P, Nunes S, Kosonen P, Takala J. Effect of an acute increase in PCO2 on splanchnic perfusion and metabolism. Intensive Care Med 2001;27:775-778.[Medline]
  26. Davidson D, Stalcup SA, Mellins RB. Systemic hemodynamics affecting cardiac output during hypocapnic and hypercapnic hypoxia. J Appl Physiol 1986;60:1230-1236.[Abstract/Free Full Text]
  27. Dent CL, Spaeth JP, Jones BV, Schwartz SM, Glauser TA, Hallinan B, et al. Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion. J Thorac Cardiovasc Surg 2006;131:190-197.[Abstract/Free Full Text]
  28. Hoffman GM, Mussatto KA, Brosig CL, Ghanayem NS, Musa N, Fedderly RT, et al. Systemic venous oxygen saturation after the Norwood procedure and childhood neurodevelopmental outcome. J Thorac Cardiovasc Surg 2005;130:1094-1100.[Abstract/Free Full Text]
  29. Nelson DP, King CE, Dodd SL, Schumacker PT, Cain SM. Systemic and intestinal limits of 02 extraction in the dog. J Appl Physiol 1987;63:387-394.[Abstract/Free Full Text]
  30. Perez A, Schnitzler EJ, Minces PG. The value of gastric intramucosal pH in the postoperative period of cardiac surgery in pediatric patients. Crit Care Med 2000;28:1585-1589.[Medline]
  31. Jeffries HE, Wells WJ, Starnes VA, Wetzel RC, Moromisato DY. Gastrointestinal morbidity after Norwood palliation for hypoplastic left heart syndrome. Ann Thorac Surg 2006;81:982-987.[Abstract/Free Full Text]
  32. Canzanelli A, Greenblatt M, Rogers GA, Rapport D. The effect of pH changes on the in-vitro 02 consumption of tissues. Am J Physiol 1939;127:290-295.[Free Full Text]
  33. Sechzer PH, Egbert LD, Linde HW, Cooper DY, Dripps RD, Price HL. Effect of carbon dioxide inhalation on arterial pressure, ECG and plasma catecholamines and 17-OH corticosteroids in normal man. J Appl Physiol 1960;15:454-458.[Abstract/Free Full Text]
  34. Low JM, Gin T, Lee TW, Fung K. Effect of respiratory acidosis and alkalosis on plasma catecholamine concentrations in anaesthetized man. Clin Sci (Lond) 1993;84:69-72.[Medline]
  35. Rasmussen JP, Dauchot PJ, DePalma RG, Sorensen B, Regula G, Anton AH, et al. Cardiac function and hypercarbia. Arch Surg 1978;113:1196-1200.[Abstract/Free Full Text]
  36. Nahas GG, Ligou JC, Mehlman B. Effects of pH changes on 02 uptake and plasma catecholamine levels in the dog. Am J Physiol 1960;198:60-66.[Abstract/Free Full Text]
  37. Thorens JB, Jolliet P, Ritz M, Chevrolet JC. Effects of rapid permissive hypercapnia on hemodynamics, gas exchange, and oxygen transport and consumption during mechanical ventilation for the acute respiratory distress syndrome. Intensive Care Med 1996;22:182-191.[Medline]
  38. Gruber EM, Laussen PC, Casta A, Zimmerman AA, Zurakowski D, Reid R, et al. Stress response in infants undergoing cardiac surgery: a randomized study of fentanyl bolus, fentanyl infusion, and fentanyl-midazolam infusion. Anesth Analg 2001;92:88-90.
  39. Smiley RM, Vulliemoz Y. Cardiac surgery causes desensitization of the beta-adrenergic receptor system of human lymphocytes. Anesth Analg 1992;74:212-218.[Free Full Text]
  40. Duranteau J, Sitbon P, Teboul JL, Vicaut E, Anguel N, Richard C, et al. Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med 1999;27:893-900.[Medline]



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G. Zhang, H. Holtby, S. Cai, O. Al Radi, and J. Li
Aortic atresia is associated with an inferior systemic, cerebral, and splanchnic oxygen-transport status in neonates after the Norwood procedure
Eur J Cardiothorac Surg, March 1, 2011; 39(3): e13 - e21.
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