Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study.

In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor requirements) occurred among a subset of the patients who achieved neutrophil recovery after initiation of IMV; 61.5% of these patients survived to discharge from the intensive care unit (ICU). Improved survival among patients who subsequently achieved neutrophil recovery on IMV was not limited to those with peri-engraftment respiratory distress syndrome. The presence of a respiratory pathogen did not affect the risk of death while on IMV but was associated with an increased length of IMV (p < 0.01). Among patients undergoing HCT who develop respiratory failure and require advanced therapeutic support, neutrophil recovery at time of IMV and/or presence of a respiratory pathogen should not be used as determining factors when counseling families about survival.

Correction to: Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Safety and pharmacokinetics of multiple-dose anidulafungin in infants and neonates.

Candida infections are common and often fatal in infants and neonates. Anidulafungin has excellent activity against Candida species, but the pharmacokinetics (PK) and safety of the drug in infants and neonates are unknown. The object of our study was to determine the PK and safety of anidulafungin in infants and neonates at risk for invasive candidiasis. Intravenous anidulafungin (1.5 mg/kg/day maintenance dose) was administered to 15 infants and neonates over 3 to 5 days. Plasma samples were collected after the first dose and again after the third to fifth doses. The pharmacokinetic parameters of the drug were determined by noncompartmental analysis. Safety was assessed using National Cancer Institute common toxicity criteria. The study showed that drug exposure levels were similar between neonates and infants; the median areas under the concentration-time curve (range) was 75 (30-109) µg·h/ml and 98 (55-278) µg·h/ml (P = 0.12) for neonates and infants, respectively. No drug-related serious adverse events were observed. The study results indicate that neonates and infants receiving 1.5 mg/kg/day have anidulafungin exposure levels similar to those in children receiving similar weight-based dosing and in adult patients receiving 100 mg/day.

Heliox improves gas exchange during high-frequency ventilation in a pediatric model of acute lung injury.

Because heliox has a lower density as compared with air, we postulated that heliox would improve gas exchange during high-frequency oscillatory ventilation (HFOV) in a model of acute lung injury. In a prospective, cross-over trial, we studied 11 piglets with acute lung injury created by saline lavage. With initial conditions of permissive hypercapnia (Pa(CO(2)) 55-80 mm Hg), each piglet underwent HFOV with a fixed mean airway pressure, pressure oscillation, and ventilatory frequency. The following gas mixtures were used: oxygen-enriched air (60% O(2)/40% N(2)) and heliox (60% O(2)/ 40% He and 40% O(2)/60% He). Compared with oxygen-enriched air, the 40% and 60% helium gas mixtures reduced Pa(CO(2)) by an average of 10.5 and 20.3 mm Hg, respectively. A modest improvement in oxygenation was seen with the 40% helium mixture. We conclude that heliox significantly improves carbon dioxide elimination and modestly improves oxygenation during HFOV in a model of acute lung injury. On the basis of test lung data and plethysmography measurements, we also conclude that heliox improves carbon dioxide elimination primarily through increased tidal volume delivery. Although heliox improved gas exchange during HFOV in our model, increased tidal volume delivery may limit clinical applicability.

Liquid lung ventilation reduces neutrophil sequestration in a neonatal swine model of cardiopulmonary bypass.

OBJECTIVE: Liquid lung ventilation has been demonstrated to improve cardiorespiratory function after cardiopulmonary bypass. We hypothesized that liquid lung ventilation (LLV) would decrease the pulmonary inflammatory response after cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized, experimental, controlled, nonblinded study. SETTING: Animal research laboratory at a university setting. SUBJECTS: A total of 24 neonatal piglets. INTERVENTIONS: After intubation with a cuffed endotracheal tube, swine were conventionally ventilated. After surgical cannulation, each piglet was placed on conventional nonpulsatile CPB and cooled to 18 degrees C (64.4 degrees F). Subsequently, the animals were exposed to 90 mins of low-flow CPB (35 mL/kg/min). Animals were rewarmed to 37 degrees C (98.6 degrees F), removed from CPB, and ventilated for 90 min. Ten animals received conventional gas ventilation only (control), seven received initiation of LLV before CPB (prevention), and seven received initiation of LLV during the rewarming phase of CPB (treatment). After the animals were killed, the lungs were removed en bloc. The left lobe was dissected and formalin-fixed at 20 cm H2O overnight, followed by paraffin embedding. Sections were taken from the paraffin-embedded lungs. Neutrophil accumulation and lung injury were assessed by histochemical staining with leukocyte esterase and morphometrics, respectively. One hundred microscopic images were digitized from each tissue sample for lung morphometrics, and neutrophil counts were obtained from every fifth image. MEASUREMENTS AND MAIN RESULTS: Lung tissue sections showed a significantly lower number of neutrophils per alveolar area in the prevention and treatment groups than in the control group (control 681 +/- 65, prevention 380 +/- 49, treatment 412 +/- 101 neutrophils per alveolar area [cells/mm2]; p <.05 for both prevention and treatment compared with control). There were no differences in lung injury as assessed with morphometrics or hemodynamic measurements between any of the three groups. CONCLUSIONS: The data suggest that LLV reduces the CPB-induced neutrophil sequestration in the pulmonary parenchyma independent of its effects on the circulatory physiology or evidence of early lung injury.

S-nitrosothiol repletion by an inhaled gas regulates pulmonary function.

NO synthases are widely distributed in the lung and are extensively involved in the control of airway and vascular homeostasis. It is recognized, however, that the O(2)-rich environment of the lung may predispose NO toward toxicity. These Janus faces of NO are manifest in recent clinical trials with inhaled NO gas, which has shown therapeutic benefit in some patient populations but increased morbidity in others. In the airways and circulation of humans, most NO bioactivity is packaged in the form of S-nitrosothiols (SNOs), which are relatively resistant to toxic reactions with O(2)/O(2)(-). This finding has led to the proposition that channeling of NO into SNOs may provide a natural defense against lung toxicity. The means to selectively manipulate the SNO pool, however, has not been previously possible. Here we report on a gas, O-nitrosoethanol (ENO), which does not react with O(2) or release NO and which markedly increases the concentration of indigenous species of SNO within airway lining fluid. Inhalation of ENO provided immediate relief from hypoxic pulmonary vasoconstriction without affecting systemic hemodynamics. Further, in a porcine model of lung injury, there was no rebound in cardiopulmonary hemodynamics or fall in oxygenation on stopping the drug (as seen with NO gas), and additionally ENO protected against a decline in cardiac output. Our data suggest that SNOs within the lung serve in matching ventilation to perfusion, and can be manipulated for therapeutic gain. Thus, ENO may be of particular benefit to patients with pulmonary hypertension, hypoxemia, and/or right heart failure, and may offer a new therapeutic approach in disorders such as asthma and cystic fibrosis, where the airways may be depleted of SNOs.

Tidal volumes for ventilated infants should be determined with a pneumotachometer placed at the endotracheal tube.

Many ventilators measure expired tidal volume (VT) without compensation either for the compliance of the ventilator circuit or for variations in the circuit setup. We hypothesized that the exhaled VT measured with a conventional ventilator at the expiratory valve would differ significantly from the exhaled VT measured with a pneumotachometer placed at the endotracheal tube. To investigate this we studied 98 infants and children requiring conventional ventilation. We used linear regression analysis to compare the VT obtained with the pneumotachometer with the ventilator-measured volume. An additional comparison was made between the pneumotachometer volume and a calculated effective VT. For infant circuits (n = 70), our analysis revealed a poor correlation between the expiratory VT measured with the pneumotachometer and the ventilator-measured volume (r(2) = 0.54). Similarly, the expiratory VT measured with the pneumotachometer did not correlate with the calculated effective volume (r(2) = 0.58). For pediatric circuits (n = 28), there was improved correlation between the expiratory VT measured with the pneumotachometer and both the ventilator-measured volume and the calculated effective VT (r(2) = 0.84 and r(2) = 0.85, respectively). The data demonstrate a significant discrepancy between expiratory VT measured at a ventilator and that measured with a pneumotachometer placed at the endotracheal tube in infants. Correcting for the compliance of the ventilator circuit by calculating the effective VT did not alter this discrepancy. In conventionally ventilated infants, exhaled VT should be determined with a pneumotachometer placed at the airway.

Right ventricular injury in young swine: effects of catecholamines on right ventricular function and pulmonary vascular mechanics.

Acute right ventricular (RV) injury is commonly encountered in infants and children after cardiac surgery. Empiric medical therapy for these patients results from a paucity of data on which to base medical management and the absence of animal models that allow rigorous laboratory testing. Specifically, exogenous catecholamines have unclear effects on the injured right ventricle and pulmonary vasculature in the young. Ten anesthetized piglets (9-12 kg) were instrumented with epicardial transducers, micromanometers, and a pulmonary artery flow probe. RV injury was induced with a cryoablation probe. Dopamine at 10 microg/kg/min, dobutamine at 10 microg/kg/min, and epinephrine (EP) at 0.1 microg/kg/min were infused in a random order. RV contractility was evaluated using preload recruitable stroke work. Diastolic function was described by the end-diastolic pressure-volume relation, peak negative derivative of the pressure waveform, and peak filling rate. In addition to routine hemodynamic measurements, Fourier transformation of the pressure and flow waveforms allowed calculation of input resistance, characteristic impedance, RV total hydraulic power, and transpulmonary vascular efficiency. Cryoablation led to a stable reproducible injury, decreased preload recruitable stroke work, and impaired diastolic function as measured by all three indices. Infusion of each catecholamine improved preload recruitable stroke work and peak negative derivative of the pressure waveform. Dobutamine and EP both decreased indices of pulmonary vascular impedance, whereas EP was the only inotrope that significantly improved transpulmonary vascular efficiency. Although all three inotropes improved systolic and diastolic RV function, only EP decreased input resistance, decreased pulmonary vascular resistance, and increased transpulmonary vascular efficiency.

Deadspace to tidal volume ratio predicts successful extubation in infants and children.

OBJECTIVE: Using a modification of the Bohr equation, single-breath carbon dioxide capnography is a noninvasive technology for calculating physiologic dead space (V(D)/V(T)). The objective of this study was to identify a minimal V(D)/V(T) value for predicting successful extubation from mechanical ventilation in pediatric patients. DESIGN: Prospective, blinded, clinical study. SETTING: Medical and surgical pediatric intensive care unit of a university hospital. PATIENTS: Intubated children ranging in age from 1 wk to 18 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-five patients were identified by the pediatric intensive care unit clinical team as meeting criteria for extubation. Thirty minutes before the planned extubation, each patient was begun on pressure support ventilation set to deliver an exhaled tidal volume of 6 mL/kg. After 20 mins on pressure support ventilation, an arterial blood gas was obtained, V(D)/V(T) was calculated, and the patient was extubated. Over the next 48 hrs, the clinical team managed the patient without knowledge of the preextubation V(D)/V(T) value. Of the 45 patients studied, 25 had V(D)/V(T) < or =0.50. Of these patients, 24 of 25 (96%) were successfully extubated without needing additional ventilatory support. In an intermediate group of patients with V(D)/V(T) between 0.50 and 0.65, six of ten patients (60%) successfully extubated from mechanical ventilation. However, only two of ten patients (20%) with a V(D)/V(T) > or =0.65 were successfully extubated. Logistic regression analysis revealed a significant association between lower V(D)/V(T) and successful extubation. CONCLUSIONS: A V(D)/V(T) < or =0.50 reliably predicts successful extubation, whereas a V(D)/V(T) >0.65 identifies patients at risk for respiratory failure following extubation. There appears to be an intermediate V(D)/V(T) range (0.51-0.65) that is less predictive of successful extubation. Routine V(D)/V(T) monitoring of pediatric patients may permit earlier extubation and reduce unexpected extubation failures.

Negative pressure ventilation via chest cuirass to decrease ventilator-associated complications in infants with acute respiratory failure: a case series.

Pulmonary and nonpulmonary complications of invasive positive pressure ventilation are well documented in the medical literature. Many of these complications may be minimized by the use of noninvasive ventilation. During various periods of medical history, negative pressure ventilation, a form of noninvasive ventilation, has been used successfully. We report the use of negative pressure ventilation with a chest cuirass to avoid or decrease the complications of invasive positive pressure ventilation in three critically ill infants at two institutions. In each of these cases, chest cuirass ventilation improved the patient's clinical condition and decreased the requirement for more invasive therapy. These cases illustrate the need for further clinical evaluation of the use of negative pressure ventilation utilizing a chest cuirass.

High-frequency oscillatory ventilation in pediatric respiratory failure: a multicenter experience.

OBJECTIVE: The use of high-frequency oscillatory ventilation (HFOV) has increased dramatically in the management of respiratory failure in pediatric patients. We surveyed ten pediatric centers that frequently use high-frequency oscillation to describe current clinical practice and to examine factors related to improved outcomes. DESIGN: Retrospective, observational questionnaire study. SETTING: Ten tertiary care pediatric intensive care units. PATIENTS: Two hundred ninety patients managed with HFOV between January 1997 and June 1998. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified according to presence or absence of preexisting lung disease, symptomatic respiratory syncytial virus infection, or presence of cyanotic heart disease or residual right-to-left intracardiac shunt. In addition, patients for whom HFOV acutely failed were analyzed separately. Those patients with preexisting lung disease were significantly smaller, had a significantly higher incidence of pulmonary infection as the triggering etiology, and had a significantly greater duration of conventional ventilation before institution of HFOV compared with patients without preexisting lung disease. Stepwise logistic regression was used to predict mortality and the occurrence of chronic lung disease in survivors. In patients without preexisting lung disease, the model predicted a 70% probability of death when the oxygenation index (OI) after 24 hrs was 28 in the immunocompromised patients and 64 in the patients without immunocompromise. In the immunocompromised patients, the model predicted a 90% probability of death when the OI after 24 hrs was 58. In survivors without preexisting lung disease, the model predicted a 70% probability of developing chronic lung disease when the OI at 24 hrs was 31 in the patients with sepsis syndrome and 50 in the patients without sepsis syndrome. In the patients with sepsis syndrome, the model predicted a 90% probability of developing chronic lung disease when the OI at 24 hrs was 45. CONCLUSIONS: Given the number of centers involved and the size of the database, we feel that our results broadly reflect current practice in the use of HFOV in pediatric patients. These results may help in deciding which patients are most likely to benefit from aggressive intervention by using extracorporeal techniques and may help identify high-risk populations appropriate for prospective study of innovative modes of supporting gas exchange (e.g., partial liquid breathing or intratracheal pulmonary ventilation).

Optimizing liquid ventilation as a lung protection strategy for neonatal cardiopulmonary bypass: full functional residual capacity dosing is more effective than half functional residual capacity dosing.

OBJECTIVE: To evaluate and compare the protective effects of two different perflubron doses on hemodynamics and lung function in a neonatal animal model of cardiopulmonary bypass-induced lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory of the Department of Surgery, Duke University Medical Center. SUBJECTS: Twenty-one neonatal swine. INTERVENTIONS: One-wk-old swine (2.2-3.2 kg) were randomized to receive cardiopulmonary bypass with full functional residual capacity perflubron (n = 7), cardiopulmonary bypass with half functional residual capacity perflubron (n = 7), or cardiopulmonary bypass alone (n = 7). This last group served as control animals, receiving cardiopulmonary bypass with conventional ventilation. Liquid lung ventilation animals received perflubron via the endotracheal tube at either full functional residual capacity (16-20 mL/kg) or half functional residual capacity (10 mL/kg) before the initiation of cardiopulmonary bypass. Each animal was placed on nonpulsatile cardiopulmonary bypass and cooled to a nasopharyngeal temperature of 18 degrees C (64.4 degrees F). Low-flow cardiopulmonary bypass (35 mL/kg/min) was instituted for 90 mins. The blood flow rate was then returned to 100 mL/kg/min. The animals were warmed to 36 degrees C (96.8 degrees F) and separated from cardiopulmonary bypass. Data were obtained at 30, 60, and 90 mins after separation from cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary bypass without liquid lung ventilation resulted in a significant decrease in cardiac output and oxygen delivery and a significant increase in pulmonary vascular resistance in the post-bypass period. Full functional residual capacity liquid lung ventilation administered before bypass resulted in no change in cardiac output and oxygen delivery after bypass. Full functional residual capacity liquid lung ventilation resulted in lower pulmonary vascular resistance after bypass compared with both control and half functional residual capacity liquid lung ventilation animals. CONCLUSIONS: These data suggest that liquid lung ventilation dosing at full functional residual capacity before bypass is more effective than half functional residual capacity in minimizing the lung injury associated with neonatal cardiopulmonary bypass. Full functional residual capacity dosing may optimize alveolar distention and lung volume, as well as improve oxygen delivery compared with half functional residual capacity dosing.

Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass.

BACKGROUND: Pulmonary hypertension and lung injury secondary to cardiopulmonary bypass (CPB) are probably caused by a combination of ischemia and inflammation. This study was undertaken to investigate the potential ischemic effects of cessation of pulmonary arterial flow during CPB on pulmonary injury. METHODS: Twenty neonatal piglets (2.5 to 3.1 kg) were randomly assigned to two groups. Group A (n = 10) underwent 90 minutes of CPB at full flow (100 mL x kg(-1) x min(-1)) and clamping of the main pulmonary artery (PA). Group B (n = 10) underwent 90 minutes of partial CPB (66 mL x kg(-1) x min(-1)) with continued mechanical ventilation and without clamping of the PA. All hearts were instrumented with micromanometers and a PA ultrasonic flow probe. Endothelial function was assessed by measuring endothelial-dependent relaxation (measured by change in pulmonary vascular resistance after PA infusion of acetylcholine) and endothelial-independent relaxation (measured by change in pulmonary vascular resistance after ventilator infusion of nitric oxide and PA infusion of sodium nitroprusside). RESULTS: All groups exhibited signs of pulmonary injury after CPB as evidenced by significantly increased pulmonary vascular resistance, increased alveolar-arterial O2 gradients, and decreased pulmonary compliance (p<0.05); however, pulmonary injury was significantly worse in group A (p<0.05). CONCLUSIONS: This study suggests that although exposure to CPB alone is enough to cause pulmonary injury, cessation of PA flow during CPB contributes significantly to this pulmonary dysfunction.

Increasing tidal volumes and pulmonary overdistention adversely affect pulmonary vascular mechanics and cardiac output in a pediatric swine model.

OBJECTIVES: In a pediatric swine model, the effects of increasing tidal volumes and the subsequent development of pulmonary overdistention on cardiopulmonary interactions were studied. The objective was to test the hypothesis that increasing tidal volumes adversely affect pulmonary vascular mechanics and cardiac output. An additional goal was to determine whether the effects of pulmonary overdistention are dependent on delivered tidal volume and/or positive end-expiratory pressure (PEEP, end-expiratory lung volume). DESIGN: Prospective, randomized, controlled laboratory trial. SETTING: University research laboratory. SUBJECTS: Eleven 4- to 6-wk-old swine, weighing 8 to 12 kg. INTERVENTIONS: Piglets with normal lungs were anesthetized, intubated, and paralyzed. After median sternotomy, pressure transducers were placed in the right ventricle, pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the pulmonary artery. MEASUREMENTS AND MAIN RESULTS: The swine were ventilated and data were collected with delivered tidal volumes of 10, 15, 20, and 25 mL/kg and PEEP settings of 5 and 10 cm H2O in a random order. Pulmonary overdistention was defined as a decrease in dynamic compliance of > or =20% when compared with a compliance measured at a baseline tidal volume of 10 mL/kg. At this baseline tidal volume, airway pressure-volume curves did not demonstrate pulmonary overdistention. Tidal volumes and airway pressures were measured by a pneumotachometer and the Pediatric Pulmonary Function Workstation. Inspiratory time (0.75 sec), FIO2 (0.3), and minute ventilation were held constant. We evaluated the pulmonary vascular and cardiac effects of the various tidal volume and PEEP settings by measuring pulmonary vascular resistance, pulmonary characteristic impedance, and cardiac output. When compared with a tidal volume of 10 mL/kg, a tidal volume of 20 mL/kg resulted in a significant decrease in dynamic compliance from 10.5 +/- 0.9 to 8.4 +/- 0.6 mL/cm H2O (p = .02) at a constant PEEP of 5 cm H2O. The decrease in dynamic compliance of 20% indicated the presence of pulmonary overdistention by definition. As the tidal volume was increased from 10 to 20 mL/kg, pulmonary vascular resistance (1351 +/- 94 vs. 2266 +/- 233 dyne x sec/cm5; p = .004) and characteristic impedance (167 +/- 12 vs. 219 +/- 22 dyne x sec/cm5; p = .02) significantly increased, while cardiac output significantly decreased (951 +/- 61 vs. 708 +/- 48 mL/min; p = .001). Each of these effects of pulmonary overdistention were further magnified when the tidal volume was increased to 25 mL/kg. The tidal volume-induced alterations in pulmonary vascular mechanics, characteristic impedance, and cardiac output occurred to a greater degree when the PEEP was increased to 10 cm H2O. Pulmonary vascular resistance and characteristic impedance were significantly increased and cardiac output significantly decreased for all tidal volumes studied at a PEEP of 10 cm H2O as compared with 5 cm H2O. CONCLUSIONS: Increasing tidal volumes, increasing PEEP levels, and the development of pulmonary overdistention had detrimental effects on the cardiovascular system by increasing pulmonary vascular resistance and characteristic impedance while significantly decreasing cardiac output. Delivered tidal volumes of >15 mL/kg should be utilized cautiously. Careful monitoring of respiratory mechanics and cardiac function, especially in neonatal and pediatric patients, is warranted.

Liquid ventilation improves pulmonary function and cardiac output in a neonatal swine model of cardiopulmonary bypass.

OBJECTIVE: Neonatal and infant cardiopulmonary bypass results in multiorgan system dysfunction. Organ protective strategies have traditionally been directed at the myocardium and brain while neglecting the sometimes severe injury to the lungs. We hypothesized that liquid ventilation would improve pulmonary function and cardiac output in neonates after cardiopulmonary bypass. METHODS: Twenty neonatal swine were randomized to receive cardiopulmonary bypass with or without liquid ventilation. In the liquid-ventilated group, a single dose of perflubron was administered before bypass. The control group was conventionally ventilated. Each animal was placed on nonpulsatile, hypothermic bypass. Low-flow cardiopulmonary bypass was performed for 60 minutes. The flow rate was returned to 125 ml/kg per minute, and after warming to 37 degrees C, the animals were removed from bypass. Hemodynamic and ventilatory data were obtained after bypass to assess the effects of liquid ventilation. RESULTS: Without liquid ventilation, cardiopulmonary bypass resulted in a significant decrease in cardiac output, oxygen delivery, and static pulmonary compliance compared with prebypass values. Input pulmonary resistance and characteristic impedance increased in these control animals. At 30, 60, and 90 minutes after bypass, the animals receiving liquid ventilation showed significantly increased cardiac output and static compliance and significantly decreased input pulmonary resistance and characteristic impedance compared with control animals not receiving liquid ventilation. CONCLUSIONS: Liquid ventilation improved pulmonary function after neonatal cardiopulmonary bypass while increasing cardiac output. The morbidity associated with cardiopulmonary bypass may be significantly reduced if the adverse pulmonary sequelae of bypass can be diminished. Liquid ventilation may become an important technique to protect the lungs from the deleterious effects of cardiopulmonary bypass.

Serum lactates correlate with mortality after operations for complex congenital heart disease.

BACKGROUND: The objective of this study was to determine whether serum lactate levels predict mortality in children less than 1 year of age who have undergone cardiopulmonary bypass and operations for complex congenital heart disease. METHODS: The initial lactate, maximum lactate, and lactate levels at 4 to 6 hours after operation were analyzed for each of 48 children less than 12 months of age who underwent cardiopulmonary bypass. RESULTS: Data were analyzed for the 6 patients who died and the 42 patients who survived. For the patients who died, the initial postoperative serum lactate, maximum lactate, and 4- to 6-hour lactate levels were significantly higher than those in the patients who survived. All patients with an initial lactate less than 7 mmol/L, a maximum lactate less than 9 mmol/L, or a 4- to 6-hour lactate level less than 4 mmol/L survived to hospital discharge. CONCLUSIONS: Serum lactate levels may be a useful predictor of mortality in children less than 1 year of age who have undergone cardiopulmonary bypass. An elevation in serum lactate level after a complex operation for congenital heart disease should be taken as a serious indicator of potential mortality.

Inhaled nitric oxide, right ventricular efficiency, and pulmonary vascular mechanics: selective vasodilation of small pulmonary vessels during hypoxic pulmonary vasoconstriction.

OBJECTIVE: In the setting of acute pulmonary artery hypertension, techniques to reduce right ventricular energy requirements may ameliorate cardiac failure and reduce morbidity and mortality. Inhaled nitric oxide, a selective pulmonary vasodilator, may be effective in the treatment of pulmonary artery hypertension, but its effects on cardiopulmonary interactions are poorly understood. METHODS: We therefore developed a model of hypoxic pulmonary vasoconstriction that mimics the clinical syndrome of acute pulmonary hypertension. Inhaled nitric oxide was administered in concentrations of 20, 40, and 80 ppm. RESULTS: During hypoxic pulmonary vasoconstriction, the administration of nitric oxide resulted in a significant improvement in pulmonary vascular mechanics and a reduction in right ventricular afterload. These improvements were a result of selective vasodilation of small pulmonary vessels and more efficient blood flow through the pulmonary vascular bed (improved transpulmonary vascular efficiency). The right ventricular total power output diminished during the inhalation of nitric oxide, indicating a reduction in right ventricular energy requirements. The net result of nitric oxide administration was an increase in right ventricular efficiency. CONCLUSION: These data suggest that nitric oxide may be beneficial to the failing right ventricle by improving pulmonary vascular mechanics and right ventricular efficiency.