The use of an early ACTH test to identify hypoadrenalism-related hypotension in low birth weight infants.

OBJECTIVE: To investigate if in preterm newborns, an early adrenocorticotropin hormone (ACTH) test can identify possible transient adrenal insufficiency (TAI), using significant hypotension as a clinical marker. STUDY DESIGN: We studied 40 premature newborns born 24 to 29 weeks gestational age (GA) before 8 h of life. Serum cortisol levels were obtained before and 40 min after administration of 1.0 mcg kg(-1) cosyntropin. Inotropes were used to treat hypotension based on clinical assessment following no response to fluid boluses. Functional echocardiogram was used to support the clinical diagnosis of hypotension. The accuracy of the ACTH test was evaluated using receiver operating characteristic (ROC) curve. RESULT: Study patients had mean GA of 26.6 weeks and birth weight of 876 g. In all, 30% required inotropes. The area under the ROC curve for the ACTH test was 87%. Using a cutoff of an increase in cortisol below 12% from baseline had 75% sensitivity and 93% specificity for detecting hypotension. This cutoff was associated with bronchopulmonary dysplasia (8/12 vs 7/28, 95% CI: 0.1 to 0.72), but not with other morbidities or death. CONCLUSION: An early ACTH test using the above cutoff has high specificity for detecting hypotension, and thus, can serve as a marker for potential TAI in preterm newborns. Future studies should focus on identifying those newborns for which steroid supplementation would be most beneficial.

Sonographic 'molar tooth' sign in the diagnosis of Joubert syndrome.

The characteristic imaging finding common to Joubert syndrome and related disorders is the 'molar tooth' sign. The prenatal diagnosis of Joubert syndrome using both ultrasound and fetal magnetic resonance imaging (MRI) in families with an affected child has been reported previously. We report two cases in which the molar tooth sign was identified by sonography at 26 + 4 weeks and at 20 + 6 weeks, respectively, prior to fetal MRI or genetic testing. In both cases the finding was subsequently confirmed on fetal MRI. As definitive prenatal genetic testing may not be conclusive in Joubert syndrome, the ability to identify the molar tooth sign sonographically before 24 weeks provides a valuable adjunct to prenatal diagnosis.

High-flow nasal cannulae in the management of apnea of prematurity: a comparison with conventional nasal continuous positive airway pressure.

Apnea of prematurity (AOP) is frequently managed with nasal continuous positive airway pressure (NCPAP). Nasal cannula (NC) are used at low flows (<0.5 L/min) to deliver supplemental oxygen to neonates. A number of centers use high-flow nasal cannula (HFNC) in the management of AOP without measuring the positive distending pressure (PDP) generated. Objective. To determine the NC flow required to generate PDP equal to that provided by NCPAP at 6 cm H(2)O and to assess the effectiveness of HFNC as compared NCPAP in the management of AOP. Method. Forty premature infants, gestation 28.7 +/- 0.4 weeks (mean +/- standard error of mean), postconceptual age at study 30.3 +/- 0.6 weeks, birth weight 1256 +/- 66 g, study weight 1260 +/- 63 g who were being managed with conventional NCPAP for at least 24 hours for clinically significant apnea of prematurity, were enrolled in a trial of ventilator-generated conventional NCPAP versus infant NC at flows of up to 2.5 L/min. End expiratory esophageal pressure was measured on NCPAP and on NC, and the gas flow on NC was adjusted to generate an end expiratory esophageal pressure equal to that measured on NCPAP. Two 6-hour periods were continuously recorded and the data were stored on computer. Results. The flow required to generate a comparable PDP with NC varied with the infant's weight and was represented by the equation: flow (L/min) = 0.92 + 0.68x, x = weight in kg, R = 0.72. There was no difference in the frequency and duration of apnea, bradycardia or desaturation per recording between the 2 systems. Conclusion. NC at flows of 1 to 2.5 L/min can deliver PDP in premature neonates. HFNC is as effective as NCPAP in the management of AOP.

The western Canadian experience with congenital diaphragmatic hernia: perinatal factors predictive of extracorporeal membrane oxygenation and death.

This study documents how congenital diaphragmatic hernia (CDH) is managed in level III neonatal intensive care units (NICUs) in western Canada and examines perinatal factors predictive of the need for extracorporeal membrane oxygenation (ECMO). Information was obtained retrospectively from all level III NICUs in western Canada about the management of infants with CDH between 1992 and 1996; 91 infants with isolated CDH were identified. A prenatal diagnosis was made in 42 cases (46%). Surfactant was used in 53%, high-frequency oscillation (HFO) in 29%, and nitric oxide (NO) in 27%. Of the 69 infants born in referral centers, 29 (42%) were referred for possible ECMO; 17 (59%) of those required ECMO, with 65% survival. The overall requirement for ECMO was 30%. Death or ECMO occurred in 40% of cases overall. Overall survival was 82%. Survival in those needing ECMO was 74%, and in those not needing ECMO 86%. Significant predictors of death or ECMO were: prenatal diagnosis (P < 0.05), maximum postductal arterial partial pressure of oxygen (PaO2) < 100 mmHg (P < 0.001), and an oxygenation index (OI) at 6 h > 15 (P < 0.001). In cases where there is a prenatal diagnosis of CDH the mother should deliver at an ECMO center. Alternatively, an OI of > 15 at 6 h and PaO2 < 100 mmHg should prompt referral to an ECMO center.

Neonatal pertussis requiring extracorporeal membrane oxygenation.

Despite widespread immunization against Bordetella pertussis, whooping cough remains potentially fatal in susceptible populations such as neonates. A case of neonatal pertussis with severe pulmonary hypertension (PH) requiring extracorporal membrane oxygenation (ECMO) is described. PH associated with pertussis severe enough to require ECMO is frequently irreversible and associated with a poor prognosis.

Quantification of recirculation by thermodilution during venovenous extracorporeal membrane oxygenation.

PURPOSE: The aim of this study was to determine whether recirculation could be quantified by a thermodilution technique during venovenous (VV) extracorporeal membrane oxygenation (ECMO) in a rabbit model. METHODS: Five New Zealand white rabbits, mean weight, 4.5 (range, 3.7 to 5.7) kg, were anesthetized, instrumented, cannulated with a double-lumen catheter, and placed on VV ECMO. Serial injections of ice-cold saline were performed at the arterial arm of the circuit, and the resultant temperature change at various pump flows was measured at the venous arm of the circuit using a thermistor-tipped catheter and a cardiac output computer. Results were compared with the respective 100% recirculation measured with all the circuit flow passing through the bridge. RESULTS: Using linear regression, recirculation percentage could be calculated as: 19 + 0.1 x pump flow (R2 = 0.81, P < .005). Recirculation correlated positively with pump flow. Variability between results at each flow was less than 10%. CONCLUSIONS: Recirculation can be quantified during VV ECMO by measuring the change in temperature in the venous arm using a cardiac output computer after injection of a known quantity of ice-cold saline in the arterial side of the circuit. The effect of interventions to reduce recirculation can be assessed conveniently and reliably.

Hypoplastic left heart syndrome: "to treat or not to treat".

OBJECTIVE: To review our experience in managing infants with hypoplastic left heart syndrome (HLHS) and to establish a consistent approach in counseling families based on our experience and on review of medical literature. METHODS: Infants were divided into three group periods based on significant changes in the approach to treatment. After a diagnosis of HLHS was made, a multidisciplinary team met the family to discuss different management options: compassionate care, active treatment by heart transplantation, or Norwood staged surgery. RESULTS: Parents of 58 infants (58%) opted for compassionate care, and 41 (42%) opted for active treatment. Seven infants underwent heart transplantation and all remain alive. A total of 27 infants underwent Norwood stage I, and 19 (70%) survived. There was a significant increase in parental choice for active treatment over the three time periods. CONCLUSION: These results indicate that HLHS can no longer be regarded as a uniformly fatal congenital anomaly. However, due to uncertainty about long-term outcome, discussion with parents should be open, and compassionate care should be presented as a management option until long-term data are available.

Diffuse neonatal haemangiomatosis.

A newborn girl with severe diffuse neonatal haemangiomatosis is described. She was treated with high dose systemic corticosteroids and high dose interferon-alpha-2a, but with fatal outcome. A review of the current literature is presented.

Successful chelation therapy in a case of neonatal iron overload following intravascular intrauterine transfusion.

OBJECTIVE: We report a newborn infant who was successfully treated with chelation therapy having developed severe liver disease secondary to iron overload following multiple intrauterine, intravascular transfusions (IVTs). STUDY DESIGN: Case report with review of the literature. RESULTS: An infant was born at 33 weeks' gestation having received multiple IVTs for severe rhesus hemolytic disease. At birth there was severe anemia with hydrops and ascites. Severe liver disease was present with portal hypertension, coagulopathy and abnormal liver enzymes. A liver biopsy showed histologic features consistent with iron overload. The serum ferritin was in excess of 4000 micrograms/l. A 7-week course of deferoxamine resulted in a marked reduction in ferritin levels and significant improvement in liver function. CONCLUSION: The possibility of neonatal iron overload following multiple IVTs should be borne in mind. Successful chelation therapy is possible in such cases.

A case of pseudocholinesterase deficiency in the neonate.

A case of inherited pseudocholinesterase deficiency, which presents in the new-born period, has not been reported previously in the literature. This case highlights the importance of obtaining a complete anesthetic family history in all neonatal surgical conditions.

Congenital orbital teratoma.

A case of congenital orbital teratoma is described in which there was no organized eye only microscopic evidence of ocular tissues within the disorganized teratoma. A baby boy presented at birth with a 10-x-8-cm mass extruding from the left orbit. Magnetic resonance imaging (MRI) showed a mixed cystic-solid orbital mass containing areas of calcification and deforming the bony orbit around its margins. There was no organized eye and no intracranial extension. The eye was removed with reconstruction of the eyelids. Histopathology showed representation from all three germ cell layers consistent with a teratoma. There was no organized eye, but some disorganized ocular structures within the teratoma. Follow-up has been uneventful. Neonatologists and pediatricians should be aware of the possible diagnoses in a newborn presenting with an orbital mass, so that early definitive surgery can be performed with preservation of the globe where possible.

Myeloid colony-stimulating factors: use in the newborn.

Bacterial and fungal sepsis are major causes of morbidity and mortality in the newborn. Multiple factors contribute to this increased susceptibility to infection, including quantitative and qualitative neutrophil defects, with a reduction in neutrophil number and function. Neutropenia in the newborn may occur in association with sepsis and has a poor prognosis. In addition to antibiotic therapy and supportive care, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used to reduce morbidity and mortality. Granulocyte CSF is the physiological regulator of neutrophil production and function. Administration of G-CSF results in increased neutrophil production and counts and improved neutrophil function. Several studies of animal and human newborns having neutropenia or suspected sepsis investigated the use of G-CSF and GM-CSF to elevate neutrophil counts and reduce morbidity and mortality in this population. Results of small clinical trials using G-CSF and GM-CSF in very low-birth-weight infants having neutropenia show increased neutrophil counts and a reduced incidence of sepsis during the neonatal period. Despite these promising early results, further studies of the safety and efficacy of G-CSF and GM-CSF administration in neonates are required before their routine use can be recommended as either prophylaxis or treatment for neonatal sepsis.

The Edmonton experience with venovenous extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Despite the proven effectiveness of venovenous extracorporeal membrane oxygenation (VV ECMO) in the treatment of neonates with severe respiratory failure, this technique is not widely used. The purpose of this study was to assess the authors' policy of preferred use of VV ECMO with a cephalad catheter and to compare the results with those of the Extracorporeal Life Support Organization (ELSO) Registry. METHODS: Charts of neonatal ECMO candidates were reviewed retrospectively. Data were collected for gestational age, birth weight, and diagnosis. Severity of illness was assessed by oxygenation index, lactate levels, and inotropic requirements before cannulation. Patients were divided into three groups: venovenous (VV), venoarterial (VA), and VV to VA ECMO. A cephalad catheter was inserted in the distal part of the jugular vein. RESULTS: Sixty-five neonates were supported with ECMO. Cannulation with a double lumen venovenous (VVDL) catheter was attempted in 63 neonates and successfully accomplished in 57. A survival rate of 86% was observed in neonates initially placed on VV ECMO. Five neonates initially placed on VV ECMO underwent conversion to VA ECMO. CONCLUSIONS: This study showed that the authors' preferred policy of VV ECMO did not result in an increase in mortality rate based on a comparison with ELSO data. VV ECMO with a cephalad catheter provides adequate support for unstable neonates with respiratory failure.

Prenatal ultrasound diagnosis of seizures.

We present a case of fetal diagnosed by ultrasound. Clinical aspects of this patient and the differential diagnosis of early neonatal seizures are discussed. A diagnosis of fetal seizures confirmed by ultrasonography is a rare event. Review of the literature shows only four cases of documented fetal seizures. This report describes a case of fetal seizures diagnosed in utero, its management, and the neonatal outcome. We also discuss the differential diagnosis.

Cardiopulmonary effects of tumor necrosis factor-alpha in the piglet: influence of cyclooxygenase inhibition.

Tumor necrosis factor-alpha (TNF) is believed to play an important role in mediating many of the pathophysiologic changes accompanying bacterial sepsis. In order to characterize the cardiopulmonary responses to TNF in a young animal model and to determine to what extent these changes were secondary to cyclooxygenase byproducts, three groups of mechanically ventilated piglets received an infusion of either TNF, indomethacin followed by TNF (Indo+TNF) or neither (control). Compared to controls at 120 min, TNF resulted in the following changes beginning 30-60 min after the infusion began: mean pulmonary artery pressure (Ppa) increased from 1.7 +/- 0.3 to 4.4 +/- 0.7 kPa (13 +/- 2 to 33 +/- 5 mm Hg) (p < 0.001); cardiac output (CO) fell from 0.28 +/- 0.05 to 0.20 +/- 0.07 liters/kg/min (p < 0.01); mean arterial blood pressure (Psa) decreased from 9.5 +/- 1.2 to 7.9 +/- 1.9 kPa (71 +/- 9 to 59 +/- 14 mm Hg) as did pH from 7.49 +/- 0.04 to 7.13 +/- 0.17 (p < 0.001). Dynamic lung compliance (Cdyn) also decreased; however, pulmonary resistance (RI) remained unchanged. Thromboxane B2 (TxB2) rose in all animals at 60 min coincident with Psa elevation and was significantly blocked by Indo (p < 0.03). In the Indo+TNF group the early TNF-induced rise in Psa was blunted compared to the TNF group [2.9 +/- 1.2 vs. 3.6 +/- 0.8 kPa (22 +/- 3 vs. 27 +/- 6 mm Hg; p < 0.04)] as were the late decreases in pH and Psa (p < 0.04). There were no significant changes in Cdyn secondary to Indo. Although delayed, the hemodynamic changes observed with TNF infusion are similar to those reported for piglets receiving group B streptococci; however, in contrast to the latter the early changes secondary to TNF are only mildly effected by indomethacin. The significant improvement in the late occurring hypotension and acidosis suggests that TNF may act in part via the cyclooxygenase pathway as a mediator of the late hypotension associated with sepsis.

Hemodynamic effects of continuous negative extrathoracic pressure and continuous positive airway pressure in piglets with normal lungs.

The hemodynamic effects produced by continuous positive airway pressure (CPAP) and continuous negative extrathoracic pressure (CNEP) of 4 and 8 cm H2O were compared in 8 normal, spontaneously breathing piglets. Arterial blood gases and hemodynamic measurements were obtained before and during CPAP and CNEP of 4 and 8 cm H2O. CPAP 8 cm H2O and CNEP 8 cm H2O produced significant increases (p less than 0.01) in PaO2 from baselines 76 +/- 3 to 85 +/- 3 and 77 +/- 4 to 85 +/- 3 mm Hg, respectively. No significant changes occurred in PaCO2 or cardiac index, except during CPAP 8 cm H2O [38 +/- 1 to 44 +/- 2 mm Hg (p less than 0.05) and 376 +/- 30 to 330 +/- 30 ml/kg/min (p less than 0.05), respectively]. During CPAP of 4 cm H2O, significant increases occurred in mean right atrial pressure (Pra) (2.1 +/- 0.3 to 3.3 +/- 0.4 mm Hg; p less than 0.01), left ventricular end-diastolic pressure (LVEDP) (2.8 +/- 0.4 to 3.7 +/- 0.3 mm Hg; p less than 0.01), and mean pulmonary artery pressure (Ppa) (12.9 +/- 0.8 to 15.1 +/- 0.8 mm Hg; p less than 0.01). CPAP of 8 cm H2O produced marked increases in Pra (2.1 +/- 0.2 to 4.9 +/- 0.7 mm Hg; p less than 0.01), LVEDP (2.7 +/- 0.5 to 4.5 +/- 0.4 mm Hg; p less than 0.01) and Ppa (12.8 +/- 0.8 to 17.7 +/- 0.6 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of alpha adrenergic blockade on brain blood flow and ventilation during hypoxia in newborn piglets.

The influence of cardiovascular changes on ventilation has been demonstrated in adult animals and humans (Jones, French, Weissman & Wasserman, 1981; Wasserman, Whipp & Castagna 1974). It has been suggested that neonatal hypoxic ventilatory depression may be related to some of the hemodynamic changes that occur during hypoxia (Brown & Lawson, 1988; Darnall, 1985; Suguihara, Bancalari, Bancalari, Hehre & Gerhardt, 1986). To test the possible relationship between the cardiovascular and ventilatory response to hypoxia in the newborn, eleven sedated spontaneously breathing piglets (age: 5.9 +/- 1.6 days; weight: 1795 +/- 317 g; SD) were studied before and after alpha adrenergic blockade with phenoxybenzamine. Minute ventilation (VE) was measured with a pneumotachograph, cardiac output (CO) by thermodilution and total and regional brain blood flow (BBF) with radiolabeled microspheres. Measurements were performed while the animals were breathing room air and after 10 min of hypoxia induced by breathing 10% O2. Hypoxia was again induced one hour after infusion of phenoxybenzamine (6 mg/kg over 30 min). After 10 min of hypoxia, in the absence of phenoxybenzamine, the animals responded with marked increases in VE (P less than 0.001), CO (P less than 0.001), BBF, and brain stem blood flow (BSBF) (P less than 0.02). However, the normal hemodynamic response to hypoxia was eliminated after alpha adrenergic blockade. There were significant decreases in systemic arterial blood pressure, CO, and BBF during hypoxia after phenoxybenzamine infusion; nevertheless, VE increased significantly (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of conventional and high frequency oscillatory ventilation in normal and septic piglets.

The cardiovascular effects of high frequency oscillation (HFO) and conventional ventilation (CMV) were evaluated in 10 piglets prior to and during an infusion of group B streptococci (GBS). Animals were randomized to begin ventilation with either HFO or CMV. Arterial blood gases, cardiac output (CO), and pulmonary artery (Ppa), pulmonary wedge (Ppw) and arterial blood pressures were measured. These values were recorded at a mean airway pressure (MAP) of 2 cm H2O for both modes of ventilation after which a continuous infusion of GBS (4 X 10(7) CFU/kg/min) was begun. MAP was increased in both ventilators in the following sequence: 4, 8 and 12 cm H2O. Prior to GBS infusion, HFO was associated with small but significant changes in hemodynamic parameters when compared to CMV for the following: Ppa (15 +/- 4 vs. 13 +/- 4.0 mm Hg; p less than 0.03), Ppw (3 +/- 1 vs. 2 +/- 1 mm Hg; p less than 0.02), and CO (0.24 +/- 0.08 vs. 0.25 +/- 0.09 l/min/kg; p less than 0.05). Similar statistically significant increases in Ppa (p less than 0.005) and Ppw (p less than 0.0001), and decrease in CO (p less than 0.007) were present during GBS infusion when animals were ventilated with HFO, irrespective of the MAP used. Our results suggest that the use of HFO in both normal piglets and those receiving an infusion of GBS results in mild but consistent impairment in cardiovascular function compared to CMV. In summary, these data demonstrate that HFO has no beneficial effect compared to CMV at similar MAP in the management of the septic piglet model and may in fact further compromise the animal's hemodynamic status.