Congenital diaphragmatic hernia in Minnesota. Impact of antenatal diagnosis on survival.

OBJECTIVE: We characterized the natural history and true mortality of congenital diaphragmatic hernia (CDH) in newborn patients by identifying all infants born with this condition in a fixed geographic region over a 2-year period. We examined this population to determine the frequency of intrauterine diagnosis, the outcome of prenatally diagnosed infants, and the impact of deaths in infants with an unsuspected diagnosis (the "hidden mortality") on the overall outcome of this condition. DESIGN: This was a retrospective population survey of all infants born with CDH in Minnesota between June 1988 and June 1990. SETTING: All Minnesota birth and death records were reviewed to identify patients with the diagnosis of CDH. A separate survey of all level 3 intensive care nurseries was conducted and the record of each identified patient was reviewed. Extracorporeal membrane oxygenation was available throughout the study period. MAIN OUTCOME MEASURE: Survival to hospital discharge and short-term morbidity were examined for each patient. RESULTS: Survival was 60% (29/48). Eleven of 19 deaths occurred in patients born prematurely and/or with coexisting major anomalies. Eight percent (4/48) of patients died within the first hour of life prior to diagnosis (hidden mortality). Intrauterine diagnosis of CDH was made in 15 patients. Survival was 60% (9/15) in infants whose conditions were diagnosed in utero, a rate identical to that for infants whose conditions were diagnosed in the postnatal period (61% [20/33]). There was no relationship between age at fetal diagnosis and mortality. CONCLUSIONS: The hidden mortality of CDH was low. Almost half of the total mortality for CDH was associated with coexisting, additional anomalies. Patients who were not offered extracorporeal membrane oxygenation owing to prematurity, other major anomalies, or birth at a center that did not offer extracorporeal membrane oxygenation accounted for 84% (16/19) of deaths. These data will be useful for determining the impact of new therapeutic strategies on the mortality of CDH.

Activated clotting time tests with heparinase in the management of pediatric patients on cardiopulmonary bypass.

Routine ACT tests cannot distinguish between prolonged blood clotting due to heparin effect or acquired abnormalities of the coagulation system after a loading dose of heparin. The purpose of this study was to examine an ACT test that inactivates heparin with Heparinase allowing for ACT assessment with and without heparin effect (HR-ACT with/without Heparinase, HemoTec, Inc.). The HR-ACT values were compared with the standard OR procedure that employed the Hemochron ACT. Twenty pediatric patients undergoing cardiopulmonary bypass for repair of cardiac defects were examined. All comparative ACT values were obtained from the same blood sample. Five sampling times were examined: 1) A baseline ACT was obtained before heparin had been administered; 2) A pre bypass ACT after a single heparin dose; 3) On bypass; 4) A post protamine ACT at the conclusion of surgery; and 5) In the Intensive Care Unit (PICU), 1 hour post protamine. The HemoTec HR-ACT with Heparinase and HR-ACT tests differentiated clotting time results that reflected coagulation status without the heparin effect. It identified those patients on bypass who were less than 5 kg, with prolonged ACTs that were due in part to hemodilution despite efforts at hemoconcentration.

Predictive performance of three methods of activated clotting time measurement in neonatal ECMO patients.

Previously reported activated clotting time (ACT) data in adults demonstrated higher values with the HemoTec LRACT (HT) and TriMed ACTivator (TM) techniques than with the Hemochron System P214/215 (HC) technique throughout a range of heparin concentrations. This study sought to determine if a difference exists in ACT values of neonatal patients receiving ECMO. ACTs were performed in nine neonatal ECMO patients using the HC, HT, and TM techniques. Techniques were compared for positive or negative direction of any prediction difference (bias), and the typical value of a difference (precision). Simultaneous, duplicate, morning, and afternoon ACT comparisons were obtained using all three techniques. Forty-six comparisons of HC values in the 180-240 sec range were analyzed. All techniques produced results different from the same sample. The HT and TM techniques were upwardly biased by 51 and 148 sec, respectively, when evaluated against HC. HT was negatively biased by 123 sec when evaluated against TM. Because ACT values vary among techniques, ACT target ranges should be technique specific. Future references to ACT data should identify the equipment and procedures employed.

Comparison of pressure-volume-flow relationships in centrifugal and roller pump extracorporeal membrane oxygenation systems for neonates.

Theoretical advantages and risks exist for the use of both the centrifugal and roller pump systems in neonatal extracorporeal membrane oxygenation (ECMO). The authors studied the pressure-volume-flow relationships in clinically configured ECMO systems using these two pumps and a simulated patient to characterize differences in the circuit mechanics of the two systems, and thereby improve the design of subsequent clinical comparative trials of the pumps themselves. The relationship between flow and pressure generated across the pump was identical for the two systems. Within the range of clinically used flows, there was a direct relationship between pump revolution and flow with the roller pump, and between pump revolution and pressure generated for the centrifugal pump. Flow was limited in both systems by restrictions on negative pressure generating capacity. In the roller pump circuit, the venous reservoir (bladder box) assembly interrupted flow when negative pressure exceeded -20 mmHg; in the centrifugal pump system, forward flow stopped when negative pressure exceeded -100 mmHg. Volume had no detectable effect on the patient-pump inlet pressure gradient until critically low volumes were reached. At that point, removal of a few milliliters of volume led to large increases in the pressure gradient. The authors conclude that differences in pressure-volume-flow relationships between roller and centrifugal pump ECMO systems are due to the presence of the bladder box in the roller pump circuit. The advantages and disadvantages of the greater negative pressure in the centrifugal pump system require further study.

The effect of heparin on three whole blood activated clotting tests and thrombin time.

Whole blood activated clotting time (ACT) can be determined by many different methods that use a variety of clotting cascade activators and end-points. This study compared the results of three whole blood ACT instruments at equivalent concentrations of heparin. Whole blood (9.8 ml) from 10 healthy adult volunteers without coagulation abnormalities was added to 0.2 ml of heparin solution producing heparin concentrations of 0, 0.1, 0.2, 0.4, 0.6, 0.8, and 1.0 U/ml. Coagulation status was determined in duplicate with the Hemochron 400 System (HC), the HemoTec Automated Coagulation Timer (HT), and the TriMed ACTivator (TM). Thrombin times or dilutions (TT) were also determined for each sample. Baseline values did not differ (p greater than 0.05); however, the HT and TM ACT values were significantly longer (p less than 0.05) than the HC ACT values at predicted heparin concentrations greater than 0.2 U/ml. Results from the HT and TM instruments were not significantly different. The HT and TM instruments both provided a greater ACT range over the heparin concentrations tested. Of the tests studied to monitor heparin therapy, mean scaled TTs showed the best correlation with predicted heparin concentrations.

Comparison of six ECMO selection criteria and analysis of factors influencing their accuracy.

This study compared six extracorporeal membrane oxygenation (ECMO) selection criteria in 42 neonates and analyzed factors influencing the accuracy of outcome predictions. The sensitivity of the criteria in identifying fatal cases varied from 0.44 to 0.94 and the specificity of predictions of survival ranged from 0.42 to 0.69. The criterion having the highest sensitivity had the lowest specificity and conversely the criterion with the lowest sensitivity had the highest specificity. Overall accuracy of the criteria, as measured by the total number of correct outcome predictions, differed little among the criteria (23/42 to 27/42 correct predictions). Three factors influenced predictive accuracy: 1) a primary diagnosis of congenital diaphragmatic hernia (CDH) was associated with a greater mortality (P less than 0.001) and a significantly higher positive predictive value (PPV) for all criteria (P = 0.0009-0.012) than that seen in patients with other primary diagnoses; 2) calculating the alveolar-arterial oxygen gradient using an assumed, rather than measured barometric pressure, or estimating oxygenation index using a calculated, rather than a measured, mean airway pressure, increased false positive mortality predictions in non-CDH patients; and 3) requiring a peak inspiratory pressure (PIP) of at least 50 cm H2O in the definition of maximal medical management, rather than a PIP of 20-49 cm H2O, significantly increased the PPV for three of four criteria examined (P = 0.02-0.04). Awareness of these factors may facilitate the identification of neonates who need ECMO to survive.

Procedural variables which affect activated clotting time test results during extracorporeal membrane oxygenation therapy.

Hemorrhage secondary to heparin therapy is one of the most serious risks of extracorporeal membrane oxygenation (ECMO). This study determined those variables which affect the precision of activated clotting time (ACT) measurements used to monitor heparin therapy. Heparin therapy of eight neonatal lambs was monitored during ECMO with two Hemochron 400 machines to determine the effects of intermachine variability, test volume, speed and direction of agitation, and interpersonnel variability on ACT values. Test volume (0.25 vs. 0.4 ml) and agitation speed (2 shakes/sec vs. one shake/sec) resulted in significantly different ACT values (p less than .05). The mean matched ACT values determined from different agitation directions (vertical vs. horizontal) or the use of a stepper pipette to measure test volume vs. visual estimation of test volume were not significantly different. Variability in ACT test results is significantly increased by variations in test volume or agitation (speed and direction), intermachine variability, and by interpersonnel technique. These variables should be considered when devising protocols for ACT monitoring and management of heparin therapy.

Extracorporeal membrane oxygenation: radiographic appearance of the neonatal chest.

The chest radiographs of 26 newborns treated with extracorporeal membrane oxygenation (ECMO) for intractable respiratory failure were reviewed. The typical radiographic appearance of the lungs in these patients is that of diffuse pulmonary opacification with variable volume loss. Air bronchograms and patchy basilar atelectasis are also common findings. Generally, decreasing ECMO requirements were reflected in improving chest radiographs with radiographic improvement lagging behind clinical improvement. Of 167 chest radiographs available for evaluation, 105 (62.8%) reflected changes in ECMO flow rates. Radiographs in patients with individual diagnoses of hyaline membrane disease, meconium aspiration syndrome and sepsis showed the best correlation with clinical improvement (95 [69%] of 137 radiographs). Those obtained in patients with congenital diaphragmatic hernia and persistent pulmonary hypertension of the newborn alone showed the poorest correlation (10 [30%] of 30 of radiographs). Neither the absolute degree of radiographic abnormality nor degree of radiographic improvement correlated well with ECMO requirements. Initial radiographs were useful in confirming the position of bypass cannulae and respiratory tubes. Routine daily examinations did not reveal unexpected abnormalities. However, radiographs taken during periods of increased ECMO requirements due to patent ductus arteriosus or volume overload showed worsening lung opacification.