Sally Cai

Effect of inhaled hydrogen sulfide on metabolic responses in anesthetized, paralyzed, and mechanically ventilated piglets.

Objective: Induced hypometabolism may improve the balance between oxygen delivery and consumption and may help sustain tissue viability in critically ill patients with low cardiac output state. Inhaled hydrogen sulfide (H2S) has been shown to induce a suspended animation-like state in mice with a 90% decrease in oxygen consumption. We conducted a preclinical study to explore the potential effect of H2S on metabolic rate in large mammals. Design: Prospective study. Setting: Animal laboratory in a university hospital. Subjects: Eleven anesthetized, paralyzed, and mechanical ventilated piglets (5.8 ± 0.7 kg). Interventions: The right carotid artery and superior vena cava were cannulated for arterial pressure monitoring and blood gas sampling. Seven piglets were sequentially exposed to 20, 40, 60, and 80 ppm of H2S over a period of 6 hrs (each level for 1.5 hrs) (H2S group), and additionally four piglets were exposed to air over the same period (control group). Measurements and Main Results: Ambient temperature was fixed at 22°C throughout. Central body temperature, arterial pressure, and heart rate were continuously monitored. Oxygen consumption and carbon dioxide production were continuously measured using respiratory mass spectrometry. Cardiac output was calculated using the Fick principle. Central temperature and oxygen consumption significantly and linearly decreased over the H2S exposures (p < .0001 for both), the rates of which were significantly less compared with those in the control group (p < .01 for both). Mean arterial pressure increased significantly (p = .007), whereas heart rate (p = .14), cardiac output (p = .89), and lactate (p = .67) did not change significantly during H2S exposures in H2S group; all the variables decreased significantly in the control group (p < .01 for all), and p < .01 by comparison with H2S group except for lactate (p = .05). Conclusions: H2S does not appear to have hypometabolic effects in ambiently cooled large mammals and conversely appears to act as a hemodynamic and metabolic stimulant.

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

Objectives: To evaluate the clinical utility of near-infrared spectroscopic (NIRS) monitoring of cerebral (Sco2) and splanchnic (Sso2) oxygen saturations for estimation of systemic oxygen transport after the Norwood procedure. Methods: Sco2 and Sso2 were measured with NIRS cerebral and thoracolumbar probes (in humans). Respiratory mass spectrometry was used to measure systemic oxygen consumption (V̇o2). Arterial (Sao2), superior vena caval (Svo2) and pulmonary venous oxygen saturations were measured at 2 to 4 h intervals to derive pulmonary (Qp) and systemic blood flow (Qs), systemic oxygen delivery (Do2) and oxygen extraction ratio (ERo2). Mixed linear regression was used to test correlations. A study of 7 pigs after cardiopulmonary bypass (study 1) was followed by a study of 11 children after the Norwood procedure (study 2). Results:Study 1. Sco2 moderately correlated with Svo2, mean arterial pressure, Qs, Do2 and ERo2 (slope 0.30, 0.64. 2.30, 0.017 and −32.5, p < 0.0001) but not with Sao2, arterial oxygen pressure (Pao2), haemoglobin and V̇o2. Study 2. Sco2 correlated well with Svo2, Sao2, Pao2 and mean arterial pressure (slope 0.43, 0.61, 0.99 and 0.52, p < 0.0001) but not with haemoglobin (slope 0.24, p > 0.05). Sco2 correlated weakly with V̇o2 (slope −0.07, p  =  0.05) and moderately with Qs, Do2 and ERo2 (slope 3.2, 0.03, −33.2, p < 0.0001). Sso2 showed similar but weaker correlations. Conclusions: Sco2 and Sso2 may reflect the influence of haemodynamic variables and oxygen transport after the Norwood procedure. However, the interpretation of NIRS data, in terms of both absolute values and trends, is difficult to rely on clinically.

Comparison of the Profiles of Postoperative Systemic Hemodynamics and Oxygen Transport in Neonates After the Hybrid or the Norwood Procedure A Pilot Study

Background— After the Norwood procedure, early postoperative neonatal physiology is characterized by hemodynamic instability and imbalance of oxygen transport that is commonly attributed to surgical myocardial injury and a systemic inflammatory response to cardiopulmonary bypass (CPB). Because the Hybrid procedure (arterial duct stenting and bilateral pulmonary artery banding) avoids CPB, cardioplegic arrest, and circulatory arrest, we hypothesized that the Hybrid procedure is associated with superior postoperative hemodynamics and oxygen transport. Methods and Results— Oxygen consumption (VO2) was continuously measured using respiratory mass spectrometry for 72 hours after Hybrid (n=6) and Norwood (n=13) procedures. Arterial, superior vena cava, and pulmonary venous blood gases and pressures were measured at 2- to 4-hour intervals to calculate systemic and pulmonary blood flows (Qs, Qp), and systemic vascular resistance (SVR), total pulmonary vascular resistance including pulmonary arterial band or B-T shunt (tPVR), cardiac output (CO), oxygen delivery (DO2), and oxygen extraction ratio (ERO2). Rate-pressure product was calculated as heart rate×systolic arterial pressure. When compared with the Norwood procedure, the early postoperative Hybrid patients had lower CO, higher SVR, and higher Qp:Qs ratios. In addition, the DO2 and VO2 were both lower in the Hybrids with higher ERO2 and lactate levels. This early postoperative pattern reversed after 48 hours. Conclusions— Although Hybrid procedure avoids CPB and cardioplegic arrest, the early hemodynamic profile is not superior to the Norwood in terms of cardiac output and control of pulmonary blood flow. These data strongly suggest that a “hands off” approach to postoperative care in Hybrid patients may not be appropriate in patients with preoperative diminished myocardial function; and in such patients a Norwood-derived management strategy (afterload reduction and inotropic support) should be considered.

The influence of systemic hemodynamics and oxygen transport on cerebral oxygen saturation in neonates after the Norwood procedure.

OBJECTIVES Ischemic brain injury is an important morbidity in neonates after the Norwood procedure. Its relationship to systemic hemodynamic oxygen transport is poorly understood. METHODS Sixteen neonates undergoing the Norwood procedure were studied. Continuous cerebral oxygen saturation was measured by near-infrared spectroscopy. Continuous oxygen consumption was measured by respiratory mass spectrometry. Pulmonary and systemic blood flow, systemic vascular resistance, oxygen delivery, and oxygen extraction ratio were derived with measurements of arterial, and superior vena cava and pulmonary venous gases and pressures at 2- to 4-hour intervals during the first 72 hours in the intensive care unit. RESULTS Mean cerebral oxygen saturation was 66% +/- 12% before the operation, reduced to 51% +/- 13% on arrival in the intensive care unit, and remained low during the first 8 hours; it increased to 56% +/- 9% at 72 hours, still significantly lower than the preoperative level (P < .05). Postoperatively, cerebral oxygen saturation was closely and positively correlated with systemic arterial pressure, arterial oxygen saturation, and arterial oxygen tension and negatively with oxygen extraction ratio (P < .0001 for all). Cerebral oxygen saturation was moderately and positively correlated with systemic blood flow and oxygen delivery (P < .0001 for both). It was weakly and positively correlated with pulmonary blood flow (P = .001) and hemoglobin (P = .02) and negatively correlated with systemic vascular resistance (P = .003). It was not correlated with oxygen consumption (P > .05). CONCLUSIONS Cerebral oxygen saturation decreased significantly in neonates during the early postoperative period after the Norwood procedure and was significantly influenced by systemic hemodynamic and metabolic events. As such, hemodynamic interventions to modify systemic oxygen transport may provide further opportunities to reduce the risk of cerebral ischemia and improve neurodevelopmental outcomes.

Significant correlation of comprehensive Aristotle score with total cardiac output during the early postoperative period after the Norwood procedure

BACKGROUND The comprehensive Aristotle score has been proposed as an individualized measure of the complexity of a given surgical procedure and has been reported to significantly correlate with postoperative morbidity and mortality after the Norwood procedure. An important factor leading to postoperative morbidity and mortality is low cardiac output. We studied the correlation between the comprehensive Aristotle score and cardiac output (CO) in infants after the Norwood procedure. METHODS AND RESULTS Respiratory mass spectrometry was used to continuously measure systemic oxygen consumption (VO(2)) in 22 infants for 72 hours postoperatively. Arterial, superior vena caval and pulmonary venous blood gases were measured at 2 to 4 hour intervals to calculate CO. The comprehensive Aristotle score was collected. Hospital mortality was 4.5%. The comprehensive Aristotle score ranged from 14.5 to 23.5 and negatively correlated with CO (P = 0.027). Among the patient-adjusted factors, myocardial dysfunction (n = 10), mechanical ventilation to treat cardiorespiratory failure (n = 9) and atrioventricular valve regurgitation (n = 4) (P = 0.01) negatively correlated with CO (P = 0.06 to 0.07). Aortic atresia (n = 9) was associated with a lower CO (P = 0.01) for the first 24 hours which linearly increased overtime (P = 0.0001). No correlation was found between CO and other factors (P > 0.3 for all). CONCLUSIONS Comprehensive Aristotle score significantly negatively correlates with CO after the Norwood procedure. A preoperative estimation of the comprehensive Aristotle score, particularly in association with myocardial dysfunction, mechanical ventilation to treat cardiorespiratory failure, atrioventricular valve regurgitation and aortic atresia may help to anticipate a high postoperative morbidity with low cardiac output syndrome.

Hyperglycaemia is negatively associated with systemic and cerebral oxygen transport in neonates after the Norwood procedure

OBJECTIVE Hyperglycaemia has been identified as a risk factor for adverse outcomes in critically ill patients, including those who have undergone cardiopulmonary bypass. Tight glucose control with insulin therapy has been shown to improve outcomes, but is not common practice for children following cardiopulmonary bypass. We examined the relationship between blood glucose level and systemic and cerebral oxygen transport in a uniform group of neonates after the Norwood procedure. METHODS Systemic oxygen consumption was measured using respiratory mass spectrometry in 17 neonates for 72 hours postoperatively. Cardiac output, systemic and total pulmonary vascular resistances - including the Blalock-Taussig shunt, systemic oxygen delivery and oxygen extraction ratio, as well as arterial lactate and glucose, were measured at 2- to 4-hour intervals. Cerebral oxygen saturation was measured by near-infrared spectroscopy. RESULTS Blood glucose levels ranged from 2.8 to 24.6 millimoles per litre. Elevated glucose level showed a significant negative correlation with cardiac output (p = 0.02) and cerebral oxygen saturation (p = 0.03), and a positive correlation with oxygen extraction ratio (p = 0.03). It tended to correlate positively with systemic vascular resistance (p = 0.09) and negatively with oxygen delivery (p = 0.09), but did not correlate with oxygen consumption (p = 0.13). CONCLUSIONS Hyperglycaemia is negatively associated with systemic haemodynamics, oxygen transport, and cerebral oxygenation status in neonates after the Norwood procedure. Further study is warranted to examine tight glucose control with insulin therapy on postoperative systemic and cerebral oxygen transport and functional outcomes in neonates after cardiopulmonary bypass.

The relationship between plasma concentrations of ionized calcium and magnesium with cardiac energetics and systemic oxygen transport in neonates after the Norwood procedure

OBJECTIVE We sought to determine the relationship between plasma calcium and magnesium concentrations with postoperative systemic hemodynamics and oxygen transport in neonates after the Norwood procedure. METHODS Postoperative systemic oxygen consumption was continuously measured using respiratory mass spectrometry for 72 hours in 17 neonates. Arterial, superior vena caval and pulmonary venous blood gases and pressures, plasma calcium, and lactate levels were measured at 2- to 4-hour intervals to calculate cardiac output, rate pressure product, cardiac power output, systemic oxygen delivery, and oxygen extraction ratio. Plasma magnesium levels were measured at 2- to 8-hour intervals. RESULTS Plasma calcium levels decreased in the first 8 hours from 1.08±0.13 mmol/L to 0.98±0.08 mmol/L, followed by an increase to 1.10±0.26 mmol/L at 72 hours (P<.0001). Mg2þ change was significantly related to time after logarithmic transformation, rapidly decreasing from 1.62±0.25 mg/L to 0.90±0.15 mg/L in the first 40 hours and further decreasing slowly thereafter to 0.64±0.13 mg/L at 72 hours (P<.0001). Plasma magnesium levels had a significant positive correlation with cardiac output (P=.008) and cardiac power output (P=.01), and a negative correlation with heart rate (P=.05). Plasma magnesium levels correlated positively with systemic oxygen delivery and negatively with systemic oxygen consumption (P=.08 for both), resulting in significant negative correlations with oxygen extraction ratio (P=.04) and lactate levels (P=.05). For a given cardiac power output, plasma magnesium showed a significantly negative correlation with rate pressure product (P=.01). Plasma calcium levels showed the opposite trend, which was statistically insignificant except for lactate (P=.007). CONCLUSIONS Plasma magnesium may exert favorable effects on myocardial energetics and systemic oxygen transport in neonates after the Norwood procedure, whereas plasma calcium may be harmful. Maintaining a relatively high level of plasma magnesium and a low level of plasma calcium may improve myocardial work efficiency and the balance of systemic and myocardial oxygen transport.

Aortic atresia is associated with an inferior systemic, cerebral, and splanchnic oxygen-transport status in neonates after the Norwood procedure §

OBJECTIVE Aortic atresia (AA) is a risk factor for mortality after the Norwood procedure. The mechanisms remain unknown. We compared the profiles of systemic, cerebral, and splanchnic oxygen transport in neonates with hypoplastic left-heart syndrome with AA or aortic stenosis (AS) after the Norwood procedure. METHODS Systemic oxygen consumption (VO(2)) was measured using respiratory mass spectrometry for 72 h in 17 neonates (nine in the AA group, eight in the AS group). Cardiac output (CO), systemic vascular resistance (SVR), oxygen delivery (DO(2)), and oxygen extraction ratio (ERO(2)) were calculated combining with blood gases and pressures at 2-4-h intervals. Cerebral (ScO(2)) and splanchnic (SsO(2)) oxygen saturations were measured by near-infrared spectroscopy. The doses of dopamine, milrinone, phenoxybenzamine, and vasopressin were recorded. Preoperative echocardiographic left-ventricular morphology and ejection fraction ratio were measured. RESULTS Compared with the AS group, the AA group had lower CO (p = 0.03), higher SVR (p = 0.002), lower DO(2) (p = 0.07), VO(2) (p = 0.003), and ScO(2) (p = 0.07) during the first 40 h. SsO(2) was insignificantly lower. Despite a similar ERO(2), the AA group had higher lactate (p = 0.01). The AA group received higher doses of milrinone (p < 0.0001), vasopressin (p = 0.005), and phenoxybenzamine (p = 0.02), and lower higher doses of dopamine (p = 0.07). Vasopressin adversely correlated with systemic oxygen-transport variables and SsO(2) (p < 0.05). The AA group had thicker left-ventricular posterior wall (p = 0.05) that was negatively correlated with CO (p = 0.02). CONCLUSIONS AA is associated with an inferior status of systemic, cerebral, and splanchnic oxygen transport after the Norwood procedure. Aggressive use of vasopressin may worsen systemic oxygen transport and decrease splanchnic perfusion.

Clinical Hemodynamic Parameters Do Not Accurately Reflect Systemic Oxygen Transport in Neonates after the Norwood Procedure

OBJECTIVES Clinical hemodynamic parameters (heart rate, systolic arterial pressure [SAP], and arterial and venous oxygen saturation saturations [SaO2 and SvO2 ]) are commonly used to guide management to optimize oxygen transport after the Norwood procedure. The adequacy of this practice has not been demonstrated. We examined the correlations between these clinical parameters and direct measurements of oxygen transport in these patients. METHODS Oxygen consumption (VO2 ) was measured using respiratory mass spectrometry for 72 hours in 17 neonates after the Norwood procedure. Arterial, superior vena caval, and pulmonary venous blood gases and pressures were measured at intervals of 2-4 hours to calculate cardiac output (CO), systemic and pulmonary blood flows (Qs , Qp), systemic vascular resistance (SVR), total pulmonary vascular resistance including the Blalock-Taussig shunt (tPVR), oxygen delivery (DO2), and extraction ratio (ERO2 ). Heart rate and SAP were also recorded. RESULTS Heart rate was positively correlated with VO2 (P = .004) and ERO2 (P = .005). SAP was positively correlated with CO (P = .006), VO2 (P = .02), ERO2 (P = .01), and SVR (P = .08). SaO2 was negatively correlated with tPVR, Qs, and DO2 but positively with Qp and SVR (P < .05 for all). SvO2 was positively correlated with CO, Qs , and DO2 (P < .0001 for all) and negatively correlated with SVR, VO2, and ERO2 (P < .05 for all). CONCLUSIONS Routine clinical hemodynamic parameters do not accurately reflect oxygen transport after the Norwood procedure, except for SvO2, which does not differentiate between VO2 and DO2. Higher heart rate and SAP are correlated with a worse balance of oxygen transport. The results of clinical hemodynamic monitoring should be interpreted with caution. Direct measurements of oxygen transport parameters are important in the care of neonates after the Norwood procedure.

The Optimal Timing of Stage 2 Palliation for Hypoplastic Left Heart Syndrome: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set

Background: In infants requiring 3-stage single-ventricle palliation for hypoplastic left heart syndrome, attrition after the Norwood procedure remains significant. The effect of the timing of stage 2 palliation (S2P), a physician-modifiable factor, on long-term survival is not well understood. We hypothesized that an optimal interval between the Norwood and S2P that both minimizes pre-S2P attrition and maximizes post-S2P survival exists and is associated with individual patient characteristics. Methods: The National Institutes of Health/National Heart, Lung, and Blood Institute Pediatric Heart Network Single Ventricle Reconstruction Trial public data set was used. Transplant-free survival (TFS) was modeled from (1) Norwood to S2P and (2) S2P to 3 years by using parametric hazard analysis. Factors associated with death or heart transplantation were determined for each interval. To account for staged procedures, risk-adjusted, 3-year, post-Norwood TFS (the probability of TFS at 3 years given survival to S2P) was calculated using parametric conditional survival analysis. TFS from the Norwood to S2P was first predicted. TFS after S2P to 3 years was then predicted and adjusted for attrition before S2P by multiplying by the estimate of TFS to S2P. The optimal timing of S2P was determined by generating nomograms of risk-adjusted, 3-year, post-Norwood, TFS versus the interval from the Norwood to S2P. Results: Of 547 included patients, 399 survived to S2P (73%). Of the survivors to S2P, 349 (87%) survived to 3-year follow-up. The median interval from the Norwood to S2P was 5.1 (interquartile range, 4.1–6.0) months. The risk-adjusted, 3-year, TFS was 68±7%. A Norwood-S2P interval of 3 to 6 months was associated with greatest 3-year TFS overall and in patients with few risk factors. In patients with multiple risk factors, TFS was severely compromised, regardless of the timing of S2P and most severely when S2P was performed early. No difference in the optimal timing of S2P existed when stratified by shunt type. Conclusions: In infants with few risk factors, progressing to S2P at 3 to 6 months after the Norwood procedure was associated with maximal TFS. Early S2P did not rescue patients with greater risk factor burdens. Instead, referral for heart transplantation may offer their best chance at long-term survival. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.