Jonathan Hellmann

Blood-Brain Barrier Permeability to Lactic Acid in the Newborn Dog: Lactate as a Cerebral Metabolic Fuel

The arteriovenous difference (A-V) method was utilized to assess the permeability of the blood-brain barrier to lactic acid in paralyzed and artificially ventilated newborn dogs. A femoral artery and the sagittal sinus were cannulated to sample arterial and cerebral venous blood simultaneously for measurements of glucose and lactate during normoglycemia, normoglycemia and hyperlactatemia, insulin-induced hypoglycemia, or hypoglycemia and hyperlactatemia. During normoglycemia, arterial lactate concentrations remained less than 2 mmoles/liter for up to 2 h; mean A-Vlactate was essentially zero. Arterial lactate increased up to 8 mmoles/liter during intravenous infusion of neutralized 10 mM L-lactic acid. During hyperlactatemia, the A-Vlactate was directly proportional to the arterial concentration of the metabolite, a finding which is consistent with transport into brain either by simple diffusion or via a carrier with saturability greater than 8 mmoles/liter. During hypoglycemia (mean arterial glucose = 27 mg/dl), A-Vglucose was reduced by 71% with a significant increase in A-Vlactate at an arterial lactate level of 1.3 mmoles/liter. Hyperlactatemia combined with hypoglycemia resulted in A-Vlactate which was 2–3 fold greater than during normoglycemia at similar arterial lactate concentrations. Brain/blood lactate ratios declined by 83% during hypoglycemia compared with normogly-cemic ratios, indicating that, once in brain, lactic acid was actively consumed for oxidative processes. These experimental observations may have clinical relevance in newborn human infants when concentrations of lactate in blood often approach or even exceed those of glucose.Speculation: Lactic acid, which is elevated in blood immediately following birth, may enter the perinatal brain to supplement glucose as a metabolic fuel.

Trends in cause-specific mortality at a Canadian outborn NICU.

OBJECTIVE: To retrospectively review changes in the causes of death of infants dying in the NICU at Canadas largest outborn pediatric center. PATIENTS AND METHODS: All inpatient deaths at the Hospital for Sick Childrens NICU that occurred in the years 1997, 2002, and 2007 were retrospectively reviewed to identify the primary cause of death. Classification of the cause of death was based on a modified version of the Perinatal Society of Australia and New Zealands Neonatal Death Classification. RESULTS: The annual mortality rate remained relatively constant (average of 7.6 deaths per 100 admissions between 1988 and 2007). A total of 156 deaths were analyzed: 53 in 1997; 50 in 2002; and 53 in 2007. The chronological age at which premature infants died increased significantly over the 3 time periods (P = .01). The proportion of deaths attributable to extreme prematurity and intraventricular hemorrhage decreased over the study period, whereas the proportion of deaths attributed to gastrointestinal causes (specifically necrotizing enterocolitis and focal intestinal perforation) increased. The proportion of infants for whom there was a decision to limit care before death was stable at between 83% and 92%. CONCLUSIONS: A larger proportion of outborn premature infants admitted to the Hospital for Sick Childrens NICU seem to be surviving the early problems of prematurity only to succumb to late complications.

NEONATAL SEPSIS DUE TO GROUP G STREPTOCOCCI

Abstract. Appelbaum, P. C., Friedman, Z., Fairbrother, P. F., Hellmann, J. and Hallgren, E. J. (Departments of Pathology, Paediatrics, and Obstetrics and Gynaecology, Hershey Medical Center, Hershey, Pennsylvania, USA). Neonatal sepsis due to group G streptococci. Acta Paediatr Scand, 69: 559, 1980.—Two cases of neonatal septicaemia due to group G streptococci (Streptococcus canis) are described. In one patient, infection coexisted with transient neonatal hyperthyroidism, while, in the other, concomitant group G streptococcal septicaemia and endometritis in the mother was seen. Group G streptococci are rare causes of infection, especially in the paediatric age group. Bacteria were identified by serological and biochemical methods. Both neonates responded well to penicillin therapy, but the maternal infection required combination therapy with penicillin G, gentamicin, and chloramphenicol. The literature on systemic group G streptococcal infection is briefly reviewed. With increasing use of serotyping in the identification of β‐haemolytic streptococci, non‐group A organisms will probably be identified more frequently from neonatal and other infections.

Cerebral Oxidative Metabolism in Perinatal Post‐hemorrhagic Hydrocephalus

Survivors of perinatal intraventricular hemorrhage often develop a distinct clinical syndrome characterized by hydrocephalus and biochemical abnormalities in cerebrospinal fluid. The authors investigated six neonates with post‐hemorrhagic obstructive hydro‐cephalus in order to identify cerebral metabolic disturbances responsible for the hypo‐glycorrhachia observed in this disorder.

Perinatal Intraventricular Hemorrhage

Intraventricular hemorrhage (IVH) is at present one of the most commonly encountered acute perinatal insults to brain and is a major cause of death in low-birth-weight infants.12,30,67,89,90 IVH is associated clinically with respiratory distress in from 50 to 95% of cases and is the most common neuropathological finding in infants dying with this disorder.44 Improvement in the management of the complex of problems faced by the premature neonate has led to the survival of many infants who have sustained IVH. Recent statistics of longterm morbidity indicate an ultimately poor outcome with a high incidence of developmental retardation, hydrocephalus, cerebral palsy, and learning disability.16,35–38 If severe IVH is associated with intraparenchymal hemorrhage, then the mortality is 88% in preterm newborns less than 1000 g and is 36% in preterm neonates greater than 1000 g with most survivors severely afflicted.48a Therefore, accurate diagnosis of IVH, identification of prognostic factors, and management of posthemorrhagic complications have become of increasing importance in the neonatal intensive care unit population.

A Case of Severe Eosinophilia in a Preterm Infant

Eosinophilia of prematurity is commonly seen in premature infants as a result of many causes, although a sustained or progressive form is uncommon. Different pathophysiological hypotheses include decreased circulating adrenal steroids and foreign antigen exposure. We present here a case of prolonged extreme eosinophilia in a preterm infant complicated by thrombocytopenia. The patients eosinophil count reached 91.48 × 109/L and remitted with nonspecific treatment. A comprehensive clinical, laboratory, and radiologic assessment is usually required in the context of a hypereosinophilic preterm infant to recognize the triggering etiology. Nonspecific treatment was the modality of choice because of unclear etiology in our case. Preterm infants with blood eosinophilia might not need immunomodulatory treatment despite extremely high absolute eosinophil counts.

The Practice of Withdrawal of Life Sustaining Medical Technology (LSMT) in a Neonatal Intensive Care Unit (NICU)

The Practice of Withdrawal of Life Sustaining Medical Technology (LSMT) in a Neonatal Intensive Care Unit (NICU)

THE EFFECT OF INTRAVENTRICULAR HEMORRHAGE (IVH) ON REGIONAL CEREBRAL BLOOD FLOW (rCBF) IN NEWBORN DOGS

To further understand cerebral hemodynamics associated with IVH we measured rCBF in newborn dogs following infusion of blood into the lateral ventricle. The puppies were anesthetized, tracheostomized, paralyzed, ventilated and a cannula placed through the skull into the lateral ventricle. Cardiac and respiratory variations of the pressure tracing verified proper cannula position. Once stabilized, 3 cc/kg of autologous blood were infused through the ventricular cannula over 20 min at which time rCBF was determined by [14C]iodoantipyrine autoradiography. Control animals underwent the identical protocol except for the infusion of blood. Brain sectioning revealed the presence of blood throughout the ventricular system and subarachnoid space.The reason for the acute decrease in gray and white matter CBF is unclear but is probably related to increased intracranial pressure (ICP) and, in part, to the modest decrease in PaCO2. Nevertheless, this secondary cerebral ischemia following induced IVH may be relevant to the neurological morbidity seen in the human newborn.

CARDIOPULMONARY SUPPORT FOR NEONATAL MASSIVE PULMONARY HEMORRHAGE |[lpar]|MPH|[rpar]|

MPH is a condition associated with very high mortality. In 1981 in our Unit 7/8 neonates with MPH died. MPH was defined as hypoxemia(PaO2 40 in FiO2 .9)with fresh blood from the endotracheal tube & compatible chest X-ray features. Pathophysiologically MPH was considered as hemorrhagic pulmonary edema secondary to left ventricular dysfunction.1 We therefore attempted to improve left ventricular function by optimising ventilation (muscle relaxants, sedation, positive end expiratory pressure 8-10 cm H20, high mean airway pressure 18-25) & improving myocardial contraction(Dopamine 5-10mcg/kg/min ± Isuprel 0.1 - 0.3mcg/kg/min). 5 patients have been successfully managed with this protocol. Also, ventricular function was assessed in 2/5 patients with M-mode echocardiogram & showed improvement in left ventricular ejection fraction & resolution of paradoxical septal motion.We suggest that aggressive cardiopulmonary support including inotropes can alter the previous poor prognosis of MPH.1Cole: Pediatrics 512: 175-187, 1973.

1577 CEREBRAL METABOLIC RESPONSES TO ASPHYXIA AND RECOVERY IN NEWBORN DOGS

We used the arterio-venous (A-V) difference method to assess metabolic restoration of the brain following asphyxia in newborn dogs. Brain metabolites and energy reserves were analyzed (after in situ freezing) during and following the asphyxia produced by respiratory arrest for 8 min. pHa 6.9, paCO2 96, paO2 10.These findings indicate that during asphyxia anerobic metabolism exceeds glucose availability leading to depletion of ATP and P ∼ Cr. During reoxygenation the increased pyruvate at 10 min, positive A-Vlact and rebound in brain glucose indicate that lactate becomes the preferred substrate for oxidative processes during recovery.