Pilot study of cerebral and somatic autoregulation using NIRS in preterm neonates.

BACKGROUND: As neonates transition from a relatively hypoxic environment to extra-uterine life, arterial oxygen saturation dramatically increases. This transition occurs while most organs have not fully matured. The ability for immature tissue to adequately extract and utilize oxygen remains largely unknown. With the development of near-infrared spectroscopy (NIRS), measuring specific tissue oxygen saturation (StO2) noninvasively, clinicians can measure StO2 and determine if adequate tissue oxygenation is maintained. The objective of this study is to determine the relationships of NIRS brain and somatic autoregulation function to patients' severity of illness. METHODS: In this prospective cohort pilot study, after parental consent, neonates less than 34 weeks with arterial access, were enrolled. The FORE-SIGHT NIRS probe was placed on the forehead and abdominal wall for 24 hours. Continuous arterial blood pressure, SpO2 and cerebral and somatic NIRS were used to derive autoregulation function. RESULTS: Data was obtained from 17 neonates (0.540 to 2.37 kg, gestation 23.0 to 33.2 weeks). The autoregulation function categorizes pressure passive index (PPI) values as good, borderline, or poor. For normal autoregulation function, PPI values tend to be low and fairly constant for a range of MAP. The PPI borderline zone is a hypothetical range of PPI values where autoregulation function transitions from good to poor. CONCLUSION: Our results show most premature neonates, as long as they maintained normal BP and systemic circulation can autoregulate cerebral perfusion. When BP are above or below the normal MAP for age, the neonate is at risk for losing brain and somatic autoregulation.

Influence of central hemodynamics on VV ECMO oxygen delivery in neonatal animal model.

BACKGROUND: Recirculation of oxygenated blood in venovenous extracorporeal membrane oxygenation (VV ECMO) can decrease the oxygen delivery provided by the ECMO support. This study investigated the influence of central hemodynamics and catheter position on the amount of recirculation and oxygen delivery during VV ECMO. METHODS: Recirculation was measured in seven newborn lambs (mean weight 4.7 kg) during VV ECMO using the ELSA Monitor (Transonic Systems, Inc., Ithaca, NY) and using the central venous line (CVL) method. The ECMO pump was set at the prescribed flow of 110-120 mL/kg/min for a targeted oxygen delivery rate of 6cc/kg/min without recirculation. Hemodynamic status before and during ECMO was also measured by the COstatus Monitor (Transonic Systems, Inc.,Ithaca, NY). RESULTS: Lambs with a higher cardiac index (>160 ml/min/kg), had a tendency to have higher percent oxygen delivery (65-94%, at prescribed flow) while lambs with lower cardiac index (<150 ml/min/kg), tended to have lower percent oxygen delivery (39-62%, at prescribed flow). ELSA recirculation measurements had a squared correlation coefficient R2 = 0.8 with the CVL method. CONCLUSIONS: The ELSA monitor provides an easy to use, non-invasive method to measure recirculation in VV ECMO. The data suggests that cardiac function may play an important prognostic role in achieving effective VV ECMO support.

Monitoring mesenteric tissue oxygenation with near-infrared spectroscopy during packed red blood cell transfusion in preterm infants.

OBJECTIVE: To monitor altered mesenteric tissue oxygen saturation (StO2) before and after blood transfusion. METHODS: We placed a 4-wavelength NIRS sensor (FORE-SIGHT, CASMED, Branford, CT USA) on the right lower abdominal quadrant prior to transfusion and measured StO2 for up to 48 hours post transfusion. Pulse oximetry (SpO2) data was collected simultaneously, with fractional tissue oxygen extraction (FTOE) and the [SpO2-StO2] difference calculated to normalize for hypoxic episodes. All data was combined and averaged in 30 minute windows for events before, during, and post transfusion to determine long term trends and analyzed using Repeated Measures ANOVA. 24 infants were enrolled in this study with 36 hours of data collected for 23 subjects and 48 hours for 16 subjects. RESULTS: We found no significant differences in any of the parameters when compared pre and post transfusion values at 3, 6, 12, 24 and 36 hours post transfusion. For the 16 subjects monitored to 48 hours, there was a significant decrease in FTOE and near significant increase in StO2 and reciprocal decrease in [SpO2 - StO2] at 48 hours post transfusion. CONCLUSIONS: There are several plausible mechanisms that may explain the relationship between necrotizing enterocolitis and PRBC transfusion; however, mesenteric tissue oxygen saturation changes did not clearly show that ischemia or re-perfusion injury to be one of the potential mechanisms.

Validation of near infrared spectroscopy to measure abdominal somatic tissue oxygen saturation in neonates.

OBJECTIVE: In this study, we validated the use of the FORE-SIGHT® (CAS Medical Systems, Branford, CT USA) tissue oximeter monitor on abdominal tissue oxygenation in infants ≤4 kg using a stool-interference compensation algorithm. STUDY DESIGN: A total of 40 neonates with an umbilical venous catheter (UVC) were enrolled in this study. We measured abdominal tissue saturation (StO2) values using FORE-SIGHT, and compared to a Reference StO2 value derived from weighted co-oximetry values from the UVC and pulse oximeter measurements. RESULTS: There was a strong correlation between NIRS calculated StO2 measurements when compared with the reference StO2, with an overall bias (sd) of -0.77 (5.06)% and a concordance correlation coefficient (CCC) of 0.789. CONCLUSION: Data from this validation study suggest that the FORE-SIGHT monitor, which compensates for the optical properties of stools in neonates, can yield accurate measures of abdominal tissue oxygen saturation.

Evaluation of the new generation dual-lumen catheter for neonatal ECMO.

OBJECTIVES: The purpose of this study was to compare the newly designed dual-lumen venovenous catheter (VR13, OriGen Biomedical, Austin, TX) with the current dual-lumen catheter (VV12, OriGen Biomedical). METHODS: Five newborn lambs, 1 to 5 days old and weighing 4.2 ± 0.5 kg, were cannulated with the VV13 OriGen catheter and placed on extracorporeal membrane oxygenation (ECMO). ECMO flows were increased from 200 to 600 ml/min, with measurements taken after the changes. The experiment was then repeated using the VV12 catheter. RESULTS: Recirculation values were equal for both catheters. The pressure drop at the reinfusion port was equal for both catheters at 200 ml/min, increasing to 275 mmHg at 500 ml/min for the VR13 vs. 240 mmHg for the VV12 catheter. CONCLUSION: These findings indicate that the VR13 catheter resulted in levels of recirculation equal to the VV12. Based on resistance measurements, we do not recommend the use of this new catheter beyond 400 ml/min until minor design changes are made.

Neonatal cerebral oximetry monitoring during ECMO cannulation.

OBJECTIVE: Neonates were monitored with a cerebral oximeter before, during, and after cannulation for ECMO to determine the direct effects of ligation of the right internal jugular vein and right carotid artery on cerebral oxygenation. STUDY DESIGN: After obtaining informed consent, we used the FORE-SIGHT Cerebral Oximeter (CAS Medical Systems, Branford, CT, USA) to monitor neonates undergoing surgical preparation for veno-arterial (VA) or veno-venous (VV) extracorporeal membrane oxygenation (ECMO). RESULT: A total of 17 subjects were monitored pre-ECMO for at least 48 h after cannulation. Of the 17 subjects, 12 experienced low cerebral tissue oxygen saturation (SctO(2)) <60% during pre-ECMO surgery, with most exhibiting the lowest SctO(2) values between cannulation to the onset of ECMO. Two subjects received cardiopulmonary resuscitation (CPR) during surgery and experienced very low SctO(2) (5 and 36%). Pulse oximetry was found to be unreliable during CPR because of diminished pulsatile flow. SctO(2) increased above 60% after the onset of ECMO for all subjects and remained stable. CONCLUSION: Neonates are vulnerable to SctO(2) during the pre-ECMO surgical period.

Validation of a noninvasive neonatal optical cerebral oximeter in veno-venous ECMO patients with a cephalad catheter.

INTRODUCTION: Cerebral Oximetry is an optical technique that allows for noninvasive and continuous monitoring of brain oxygenation by determining tissue oxygen saturation (SctO2). In conjunction with pulse oximetry, cerebral oximetry offers a promising method to estimate cerebral venous oxygen saturation (SvO2). OBJECTIVE: The aim of this study was to validate the cerebral oximetry measurements with the cerebral oxygen saturation measured from blood drawn in neonates on veno-venous ECMO with existing cephalad catheter with a prototype neonatal cerebral oximeter developed by CAS Medical Systems (Branford, CT, USA). STUDY DESIGN: After obtaining informed consent, neonates undergoing VV-ECMO with cephalad catheterization were monitored by the CAS cerebral oximeter. Cephalad blood samples were periodically obtained to validate the monitor's accuracy. RESULTS: Seventeen neonates were studied with 1718 h of cerebral oximetry data collected. Compared to the reference values, the bias+/-precision for cerebral oximetry SctO2 was 0.4+/-5.1% and derived SvO2 was 0.6+/-7.3%. CONCLUSION: We recommend the use of this noninvasive method as an alternative to blood draws for cerebral venous saturation measurements in neonates requiring extracorporeal life support.

Clinical use of new-generation pulse oximeters in the neonatal intensive care unit.

Continuous monitoring by pulse oximetry is a common practice for preterm and critically ill newborns. A new generation of motion-tolerant pulse oximeters have been designed for improved clinical performance with a substantial reduction in alarm frequency. However, little is known about the differences among these new-generation pulse oximeters in the neonatal intensive care unit (NICU). The purpose of this study is to assess the clinical performance of two new-generation pulse oximeters in the NICU. Two new-generation pulse oximeters were used simultaneously to monitor 36 patients in the NICU. The two devices studied were the Philips FAST and the Masimo SET. Patients were randomly assigned for their digit selection and data were collected only when waveforms were of good quality and/or the pulse oximeter's pulse rate (PR) correlated with the electrocardiogram heart rate (HR). The data for oxygen saturation measurements, number of true and false alarms, and number of dropouts as well as the duration of dropouts for each pulse oximeter were recorded by the primary investigator at 5-minute intervals for a period of 2 hours on each patient. Dropouts are instances when the pulse oximeter alarm sounds due to its inability to identify the arterial pulse and provide an oxygen saturation reading. The mean gestational age for the study group was 32 weeks (rang, 24 to 42 weeks). Repeated-measures analysis of variance indicated no difference between the two devices across all time measurements (p=0.357). In addition, paired t-tests for true alarms and false alarms were not significant, with p-values of 0.151 and 0.869, respectively. There was a difference in the number of data dropouts (p<0.001): the Philips device had a nearly six-fold increase in the number of dropouts (Philips 247 versus Masimo 38). The duration of dropouts was also significant; the Philips device had three times longer duration of dropouts. Physiologic monitoring in the critical care setting requires accurate data measurements. The two new-generation pulse oximeters, the Philips FAST and Masimo SET, are equally sensitive in their ability to identify true and false alarms. Masimo pulse oximeter with its signal extraction technology, however, provides more consistent and accurate reporting of SpO2 values as demonstrated by its markedly decreased incidence of data dropouts. The Masimo unit appears to be more resistant to the effects of motion artifact.

Use of furosemide and hearing loss in neonatal intensive care survivors.

Hearing loss is a significant morbidity in survivors of the neonatal intensive care unit (NICU). The overall prevalence of hearing loss in neonates is 0.93 per 1000 live births, whereas in neonates weighing less than 2000 g, it is as high as 15.5 per 1000 live births. The increased incidence of hearing loss in NICU graduates has been attributed to their underlying disease process as well as exposure to ototoxic drugs including furosemide. A retrospective chart review of all neonatal intensive care survivors was done to evaluate the potential effect of furosemide on hearing loss. From July 2000 to January 2002, there were 57 neonates who received and 207 neonates who did not receive furosemide. The incidence of abnormal hearing screen was 15.5% in the furosemide group and 15.9% in the nonfurosemide group ( p = 0.9). Although the incidence of hearing loss is significantly higher in NICU graduates in comparison with the general neonatal population, it does not seem to be directly related to the use of furosemide.

Feasibility of red blood cell transfusion through small bore central venous catheters used in neonates.

OBJECTIVE: To determine whether packed red blood cell transfusions through small-bore central venous catheters used in critically ill neonates results in significant hemolysis. DESIGN: In vitro experimental study using a mock transfusion setup incorporating a syringe pump, prestorage leukoreduced fresher, and older CPDA-1 red blood cell units and pressure transducer simulating neonatal transfusion through 1.9-Fr NeoPICC central venous catheter. SETTING: Laboratory setting. SUBJECTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Spun hematocrit, plasma free hemoglobin (hemoglobin), lactate dehydrogenase, and potassium were analyzed pretransfusion, at various times during transfusion, and posttransfusion. Intraluminal pressures were measured using a TruWave Disposable Pressure Transducer. Using fresher (5-8 days old) and older (29-30 days old) CPDA-1 red blood cells, we compared 2 and 20 mL/hr flow rates. Statistical analysis was performed using repeated measures of analysis of variance to compare the differences in means between flow rates. Mean intraluminal pressures at the end of each experiment were significantly higher at 20 mL/hr flow rates (>360 mm Hg) in both fresher and older red blood cells than at 2 mL/hr (range, 61-70 mm Hg). Overall, potassium, lactate dehydrogenase, and plasma free hemoglobin concentrations were significantly higher for older red blood cells at either 2 or 20 mL/hr (p<.001). Both fresher and older red blood cells demonstrated higher potassium concentrations at 20 mL/hr (22.4%, p<.001;0.7%, p>.05, respectively); however, these increases were not clinically significant. Furthermore, lactate dehydrogenase, hematocrit, and plasma free hemoglobin differences seen at 2 and 20 mL/hr did not coincide with changes in potassium. CONCLUSIONS: No clinically significant hemolysis was evidenced with red blood cell transfusion through small-bore central venous catheters when using fresher or older CPDA-1 red blood cells at 2 or 20 mL/hr.

Continuous blood gas monitoring using an in-dwelling optode method: comparison to intermittent arterial blood gas sampling in ECMO patients.

INTRODUCTION: The ability to measure postmembrane arterial blood gases is essential in the management of critically ill neonates treated with extracorporeal membrane oxygenation (ECMO). A new technology using, the Paratrend 7 system (Diametrics Medical, High Wycombe,UK) allows for continuous measurement of pH, PCO(2) and PO(2), and calculates oxygen saturation, bicarbonate, and base excess. OBJECTIVE: To evaluate and compare the results of continuous blood gas measurement using the Paratrend 7 system with a standard system of blood gas analysis in our intensive care unit. DESIGN: Prospective, controlled, interventional study. SETTING: The neonatal intensive care unit of a tertiary referral center. PATIENTS: Neonates who required extracorporeal life support and were expected to have frequent postmembrane arterial blood sampling during the testing period. RESEARCH DESIGN AND METHOD: To enable Paratrend 7 sensor access to the ECMO circuit, the postmembrane access port extension set that is routinely used for blood drawn for blood gas analysis was used. The study began with the insertion of the Paratrend 7 sensor. Subjects remained on the study until the ECMO was discontinued and/or frequent blood gases were no longer needed. The blood gas results from the Paratrend 7 system were not used in clinical management of the patient. BLOOD GAS MEASUREMENT: During the study period, with each blood sample drawn for laboratory analysis, a printout from the Paratrend 7 monitor was recorded for comparison. RESULTS: A total of 242 pairs of blood gas samples were collected from 10 neonates. The mean bias/precision for pH was -0.02/0.04; for PO(2) 68.35/93.44 mm Hg; and for PCO(2) 1.75/4.23 mm Hg. The correlation (r value) between the sensor reading and the blood gases were 0.89 for pH, 0.96 for PO(2), and 0.73 for PCO(2) (Table 1). CONCLUSION: The blood gases compared in the two methods had a strong correlation for pH, PCO(2) and PO(2). Results of this study indicate that this technology provides an accurate means of monitoring continuous blood gas parameters in neonatal ECMO patients. Use of the Paratrend 7 should allow reduced health-care provider exposure to blood and decreased patient iatrogenic blood loss.

Continuous blood gas monitoring using an in-dwelling optode method: clinical evaluation of the Neotrend sensor using a luer stub adaptor to access the umbilical artery catheter.

INTRODUCTION: Arterial blood gases are essential in the management of critically ill neonates. A new technology using the Neotrend system (Diametrics Medical) allows for continuous measurement of pH, PaCO(2), and PaO(2), and calculates oxygen saturation, bicarbonate, and base excess. OBJECTIVE: To evaluate and compare the results of continuous blood gas measurement using the Neotrend system with a standard system of blood gas analysis in our intensive care unit. DESIGN: Prospective, controlled, interventional study. SETTING: The neonatal intensive care unit of a tertiary referral center. PATIENTS: Neonates with respiratory distress who required respiratory support and frequent arterial blood gas sampling and had a UAC. RESEARCH DESIGN AND METHOD: To enable Neotrend sensor access to an existing Argyle umbilical artery catheter (UAC) the catheter was cut at the 25-cm mark and connected to an 18-gauge blunt needle luer stub adaptor (Vygon 95440). The study began with the insertion of the Neotrend sensor. Subjects remained on the study until the UAC was discontinued and/or frequent blood gases were no longer needed. The blood gas results from the Neotrend system were not used in clinical management of the patient. BLOOD GAS MEASUREMENT: During the study period, with each blood sample drawn for laboratory analysis, a printout from the Neotrend monitor was recorded for comparison. RESULTS: A total of 217 pairs of blood gas samples were collected from seven neonates. The mean bias/precision for pH was 0.01/0.04; for PaO(2) 0.72/18.5 mm Hg; and for PaCO(2) 3.96/2.63 mm Hg. The correlation (r value) between the sensor reading and the blood gases were 0.85 for pH, 0.96 for PaO(2), and 0.92 for PaCO(2). CONCLUSION: The blood gases compared in the two methods had a strong correlation for pH, PaCO(2), PaO(2), and oxygen saturation. Although the bicarbonate and base excess values showed suboptimal statistical correlation, the difference was not clinically relevant. Results of this study indicate that this technology provides an accurate means of monitoring continuous blood gas parameters in neonatal patients. It also allows reduced healthcare provider exposure to blood and decreased patient iatrogenic blood loss.

Acute pyelonephritis: comparison of diagnosis with 99mTc-DMSA, SPECT, spiral CT, MR imaging, and power Doppler US in an experimental pig model.

PURPOSE: To compare the sensitivity and specificity of technetium-99m dimercaptosuccinic acid (DMSA) single photon emission computed tomography (SPECT), spiral computed tomography (CT), magnetic resonance (MR) imaging, and power Doppler ultrasonography (US) for the detection and localization of acute pyelonephritis by using histopathologic findings as the standard of reference. MATERIALS AND METHODS: Bilateral vesicoureteric reflux was surgically created in 35 piglets (70 kidneys). One week later, a liquid bacterial culture of Escherichia coli was injected into the bladder. Three days after induction of urinary infection, imaging studies were performed, and the kidneys were removed for histopathologic examination. SPECT images were obtained 2-3 hours after injection of 99mTc-DMSA. Transverse and coronal MR images were obtained with gadolinium-enhanced fast inversion recovery. Transverse CT images were obtained before and after injection of contrast agent. Power Doppler US was performed in longitudinal, transverse, and coronal planes. Each kidney was divided into three zones for correlation of findings. RESULTS: Histopathologic examination revealed pyelonephritis in 102 zones in 38 kidneys. Sensitivity and specificity for detecting pyelonephritis in the kidneys were 92.1% and 93.8% for SPECT, 89.5% and 87.5% for MR imaging, 86.8% and 87.5% for CT, and 74.3% and 56.7% for US. Sensitivity and specificity for detecting pyelonephritis in the zones were 94.1% and 95.4% for SPECT, 91.2% and 92.6% for MR imaging, 88.2% and 93.5% for CT, and 56.6% and 81.4% for US. The pairwise comparison of these modalities showed no statistically significant difference among them except for US. CONCLUSION: 99mTc-DMSA SPECT, spiral CT, and MR imaging appear to be equally sensitive and reliable for the detection of acute pyelonephritis; power Doppler US is significantly less accurate.

Cerebral blood flow and metabolism during and after prolonged hypercapnia in newborn lambs.

OBJECTIVE: To study the effects of prolonged (6 hrs) hypercapnia on cerebral blood flow and cerebral metabolism in newborn lambs and to evaluate the effects on cerebral blood flow and cerebral metabolism on return to normocapnia after prolonged hypercapnia. DESIGN: Animal studies, using the newborn lamb, with comparison to control group. SUBJECTS: Newborn lambs of mixed breed, 1-7 days of age, were used for the study. Two groups of animals were studied: a hypercapnic group (n = 10) and a normocapnic control group (n = 5). SETTING: Work was conducted in the research laboratories at Children's National Medical Center, Washington, DC. INTERVENTIONS: Animals were anesthetized with pentobarbital, intubated, paralyzed, and mechanically ventilated. After baseline measurements were made, CO2 was blended into the ventilator gas until a PaCO2 of 75-80 torr (10-10.6 kPa) was obtained. Measurements were made 1 hr after the desired PaCO2 was achieved and after 6 hrs of hypercapnia. After 6 hrs of hypercapnia, the ventilator gas was returned to the baseline value, that is, normocapnia. Measurements were made 30, 60, and 90 mins after PaCO2 returned to baseline. MEASUREMENTS: Six measurements were made during the study. For each measurement, blood samples were drawn from the sagittal sinus and brachiocephalic artery catheters and were analyzed for pH, hemoglobin concentration, oxygen saturation, and blood gas values. Cerebral blood flow (CBF) was measured by using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period. MAIN RESULTS: Increasing PaCO2 from 37 +/- 3 torr to 78 +/- 6 torr (4.9 +/- 0.4 kPa to 10.3 +/- 0.8 kPa) for 1 hr increased CBF by 355%. After 6 hrs of PaCO2 at 78 +/- 3 torr (10.3 +/- 0.4 kPa), CBF remained 195% above baseline. At 30 mins of normocapnia, CBF had returned to baseline and remained at baseline until the conclusion of the study, a total of 90 mins of normocapnia. Cerebral oxygen consumption did not change during hypercapnia or with return to normocapnia. Oxygen transport increased 331% above baseline after 1 hr of hypercapnia and stayed 180% above baseline after 6 hrs of hypercapnia. Fractional oxygen extraction decreased by 55% at 1 hr of hypercapnia and stayed 39% below baseline at 6 hrs of hypercapnia. CONCLUSIONS: Healthy lambs seem to tolerate undergoing hypercapnia for 6 hrs with a return to normocapnia. The return to baseline of CBF and cerebral metabolism at normocapnia seen in our study with lambs may explain why prolonged hypercapnia appears to be well tolerated in mechanically ventilated patients. If these results can be extrapolated to human subjects, our study in lambs supports evidence that patients who have undergone permissive hypercapnia seem to be neurologically unaffected.

Citrobacter sepsis and severe newborn respiratory failure supported with extracorporeal membrane oxygenation.

An infant with fulminant Citrobacter sepsis and respiratory failure is presented. The severity of respiratory failure and the need for systemic heparinization on extracorporeal membrane oxygenation delayed the opportunity of initial lumbar puncture to rule out meningitis. The infant was successfully treated with extracorporeal membrane oxygenation and long-term antibiotics. Repeated cranial computed tomography scans remained negative for intracerebral abscesses, and the infant is within normal limits for growth, neurologic status, and developmental status.

A comparison of intratracheal pulmonary ventilation to conventional ventilation in a surfactant deficient animal model.

OBJECTIVE: To compare intratracheal pulmonary ventilation (ITPV) with conventional ventilation in a rabbit model of surfactant deficiency. DESIGN: A prospective randomized animal study. SETTING: The Children's National Medical Center Research Animal Facility in Washington, DC. SUBJECTS: Adult male New Zealand white rabbits (n = 20), weighing 1.4-4.2 kg. INTERVENTIONS: After anesthesia and catheter placement, rabbits were tracheotomized, paralyzed, and placed on the conventional ventilator. We determined pulmonary functions at baseline. We washed surfactant out of the lungs by using serial bronchoalveolar lavages. Pulmonary function studies were determined after completion of the bronchoalveolar lavages and were used as an indication of severity of lung injury. Animals were randomized into two groups: We placed ten animals on ITPV, using the ITPV reverse thruster catheter designed by Kolobow and a prototype ITPV ventilator designed at Children's National Medical Center; we placed ten animals on conventional ventilation using the Sechrist iv-100 ventilator. Arterial blood gases were drawn every 15 mins, and the ventilator settings were adjusted to the minimal level that would maintain arterial blood gases in the following ranges: pH 7.35-7.45, PaCO2 30-40 torr (3.995.33 kPa), PaO2 50-70 torr (6.66-9.33 kPa). Animals were ventilated with the randomized ventilation techniques for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Peak inspiratory pressure, mean airway pressure, and positive end-expiratory pressure were measured at the distal end of the endotracheal tube. We recorded these variables plus respiratory rate at baseline and every 30 mins for a total of 4 hrs of ventilation. Lung compliance did not differ between groups at the postlavage study period (ITPV, 0.56+/-0.13 mL/cm H2O/kg; conventional 0.49+/-0.15 mL/cm H2O/kg). At the end of the 4 hr study period, peak inspiratory pressure (ITPV, 26.2+/-4.6 cm H2O; conventional, 32.4+/-5.04 cm H2O, p = .007) and positive end-expiratory pressure (ITPV, 3.9+/-1.96 cm H2O; conventional, 6.3+/-1.42 cm H2O, p = .005) were lower in the ITPV ventilation group. Peak inspiratory pressure was significantly lower in the ITPV group by 2 hrs into the study. CONCLUSION: In this model of surfactant deficiency lung injury, ventilation and oxygenation were achieved at significantly lower ventilator settings using ITPV compared with conventional ventilation. Long-term studies are needed to determine whether this reduction in ventilation is maintained, and if so, if lung injury is reduced.

Neurodevelopmental outcome in ECMO vs near-miss ECMO patients at 5 years of age.

The objective of this study was to compare the outcome of children at 5 years of age who were treated with extracorporeal membrane oxygenation (ECMO) and those who were critically ill but did not meet ECMO criteria, identified as near-miss ECMO. In one of the longest studies of its kind, we compared the neurodevelopmental outcome of 76 5-year-old ECMO-treated children with 20 5-year-old near-miss ECMO patients with similar primary diagnoses. The two groups were compared for demographic data, level of ventilatory support, and degree of hyperventilation. The comprehensive assessment protocol included an assessment of intelligence (IQ), attainment of preacademic and early academic skills, and parents' report of adaptive behavior. Both groups had similar demographic data and primary diagnosis. The near-miss ECMO patients required increased ventilatory support but not significantly more than the ECMO patients. The cognitive outcome was similar in both groups with mean estimated Full-Scale IQ in the normal range for near-miss and ECMO groups (89 and 97, respectively). Rates of severe mental handicap (FSIQ < 70) (near-miss = 11%, ECMO = 12%) and risk for school failure (near-miss = 38%, ECMO = 37%) were also similar. More parents of near-miss ECMO patients reported immature adaptive skills than did parents of ECMO patients, although the numbers were small in each group. Rates of parent-reported child behavior problems were similar in both groups. ECMO and near-miss ECMO patients have similar cognitive and adaptive outcomes at 5 years of age. A significant number in each group are at risk of school failure and should be closely followed up.

The current status of neonatal extracorporeal membrane oxygenation.

Marked changes have occurred in the practice of neonatal extracorporeal membrane oxygenation (ECMO) since the first survivor in 1975. Coagulation management has been markedly refined, new catheters allow ECMO to be done either in a venoarterial or venovenous (VV) mode, depending on cardiac function in the infant. A new design of the VV catheter will allow this technique to be used in more infants in the future. New therapies for respiratory failure have changed the complexion of the population being treated with ECMO. The 34 to 36 week gestation infant with respiratory distress syndrome and/or pulmonary hypertension rarely needs ECMO therapy due to the effectiveness of surfactant and high frequency oscillation. Present day survival for infants treated with ECMO for many diagnostic categories ranges between 90% to 100%. The effects of new interventions must be evaluated with regard to their effect on morbidity when being considered prior to ECMO. Neuro-developmental outcome is encouraging, but does indicate that ECMO and the near-miss ECMO patients need to be followed closely into school age. The number of patients being treated per ECMO center has dropped significantly over the last 10 years from 18 to 9. This brings forward the question about regional needs for ECMO Centers and how to assure that centers have enough patients to maintain their clinical competencies. The challenge for the future is where to place ECMO as a therapy. Should it remain a rescue therapy? Or should there now be a trial comparing ECMO to conventional therapies, with morbidity and cost of care as the outcome variables?

Effect of nitric oxide and high-frequency oscillatory ventilation in meconium aspiration syndrome.

OBJECTIVE: To test the hypothesis that inhaled nitric oxide, when combined with high-frequency oscillatory ventilation, is an effective therapeutic agent in meconium aspiration syndrome. DESIGN: Prospective, interventional study. SETTING: The animal research laboratory at The Children's National Medical Center. SUBJECTS: Five newborn piglets, 1-2 wks old, weighing 3.6 +/- 0.2 kg. INTERVENTION: Animals were anesthetized, paralyzed, intubated, and ventilated. Catheters were placed in the femoral vein and artery and the pulmonary artery. After 1 hr of recovery, 10 mL/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated with a SensorMedics oscillator to maintain arterial blood gases in a normal range (pH, 7.35-7.45; Paco2, 40-45 mm Hg [5.3-6.0 kPa]; Pao2, 70-90 mm Hg [9.3-12.0 kPa]). Ventilator settings were increased as needed until maximum settings as follows: Fio2, 1.00; proximal oscillatory pressure amplitude, 36 cm H2O; mean airway pressure, 25 cm H2O; frequency, 10 Hz. After a short period of stabilization, inhaled nitric oxide was administered. Concentrations of 40, 20, and 10 ppm were given and measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. To assure that there was no additive effect of inhaled nitric oxide, each dose was given for 20 mins followed by a 15-min normalization period at 0 ppm. MEASUREMENTS AND MAIN RESULTS: Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. Arterial saturation and partial pressure of arterial oxygen (Pao2) were significantly lower after meconium aspiration when compared with baseline. Administration of inhaled nitric oxide improved oxygenation without a significant decrease in pulmonary artery pressure. CONCLUSION: In this model of meconium aspiration syndrome, short-term exposure to inhaled nitric oxide when combined with high-frequency oscillatory ventilation improved oxygenation secondary to better distribution of inhaled nitric oxide. The increase in oxygenation may be secondary to improved ventilation perfusion mismatch, as the primary etiology of hypoxia in this model may be a combination of parenchymal lung disease and pulmonary hypertension.

Use of nitric oxide in meconium aspiration syndrome: lack of response.

PURPOSE: To test the hypothesis that inhaled nitric oxide (INO) may not be an effective therapeutic agent in meconium aspiration syndrome (MAS). DESIGN: Prospective, interventional study. SETTING: The animal research laboratory at The Children's National Medical Center. SUBJECTS: Seven newborn pigs, 2-7 days old, weighing 2.8 +/- 0.17 kg were used for the study. MATERIALS AND METHODS: Animals were anaesthetized, paralysed, intubated and ventilated. Catheters were placed in the jugular vein, carotid artery, and pulmonary artery. After 1 h of recovery 10 ml/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated to maintain ABGs in a normal range, i.e. pH = 7.35-7.45, PaCO2 = 40-45, and PaO2 = 70-90 torr. Ventilator settings were increased as needed until maximum settings of: FiO2 = 1.00, PIP = 40, IMV = 60. After 2 h of conventional ventilation or demonstration of significant lung disease by failure to maintain desired blood gases on maximum ventilator settings, INO was administered for 20 min in concentrations of 10, 20 and 40 ppm. To ensure that there was no additive effect of INO, a 15-min normalization period at 0 ppm was allowed between each dose of INO. Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to INO and after its discontinuation. RESULTS: Arterial saturation (SaO2) and PaO2 were significantly lower ([81 +/- 18] and [54 +/- 14], respectively) and PAP was significantly higher [24 +/- 3] after MAS when compared with baseline. Administration of INO did not improve oxygenation nor decrease PAP at any of the study doses. CONCLUSION: In this model of MAS, short-term exposure to INO did not decrease PAP nor improve oxygenation. It may be postulated that poor distribution of INO caused by the obstructive nature of this disease may be responsible for the lack of response in this disease state, or that the primary etiology for hypoxia is parenchymal lung disease and not pulmonary hypertension.