Pre-operative coagulopathy management of a neonate with complex congenital heart disease: a case study.

Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms. The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction. A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. On admission, he was in respiratory arrest suffering from profound acidemia. In addition, the child was hypothermic (30.1 degrees C), septic (Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation-DIC). The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) >106 s, platelet count 30,000 mm(3), fibrinogen 15 mg dL(-1) and antithrombin III (AT-III) 10%. Before cardiac surgery could be performed, the patient's DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml). In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33. Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32. Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy. The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day. The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital heart disease.

Increased survival in low birth weight neonates given prophylactic surfactant.

OBJECTIVE: To compare the effectiveness of a prophylactic surfactant treatment strategy (PRO) to the effectiveness of a rescue (RESC) surfactant treatment strategy in patients at high risk for developing hyaline membrane disease (HMD). STUDY DESIGN: We analyzed data from a retrospective cohort consisting of all patients admitted to the neonatal intensive care units at the centers participating in the recently completed Infasurf-Survanta Comparative Trial. To be in the cohort, a patient had to be admitted during the trial, be <48 hours of age on admission, have a gestational age of <30 weeks, have a birth weight of 501 to 1250 gm, and be free of congenital anomalies. Twelve centers participated in this study. They contributed 1097 patients of whom 381 were treated with a PRO strategy. RESULTS: Survival was significantly higher in the PRO-strategy patients (84% vs 72%, p < 0.05) as was survival without oxygen requirement at a postconceptional age of 36 weeks (60% vs 46%, p < 0.05). In addition, the patients with PRO had a lower prevalence of grade III and IV intraventricular hemorrhage (IVH, 9% vs 14%, p < 0.05). All analyses were controlled for birth weight and type of study center. CONCLUSION: These data support the conclusion that using a PRO treatment strategy results in improved survival in patients at risk for developing HMD. A PRO treatment strategy may also decrease the likelihood of developing a severe IVH.

Hematological abnormalities in neonatal patients treated with extracorporeal membrane oxygenation (ECMO).

The physical process of extracorporeal membrane oxygenation (ECMO) results in derangement of the hemostatic mechanism, which may lead to increased morbidity, secondary to the disease process. The purpose of this study was to evaluate the hematological status of neonates undergoing ECMO therapy, and to evaluate coagulation tests in predicting hemorrhagic risk. Following Institutional Review Board approval, 30 patients undergoing ECMO treatment were retrospectively entered into this study. Medical records were reviewed and indicators of hemostasis, transfusion, morbidity, and outcomes recorded. Assessment of coagulation was determined through serial analysis of platelet count, fibrinogen concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III, fibrin split products, D-dimers, plasma free hemoglobin, activated clotting time, ionized calcium, and thrombelastography (TEG). Median total transfusion requirements for all patients were 1.79 ml/kg/ECMO hr. Fifty-seven percent of the 30 patients were diagnosed as coagulopathic according to Extracorporeal Life Support Organization standards. Patients were separated into either a hemorrhagic group (HEM, > 2.0 ml/kg/ECMO hr, n = 13) or a nonhemorrhagic group (N-HEM, n = 17), with HEM patients requiring twice the transfusion volume of N-HEM (p < 0.0001). Hemorrhagic complications were reported in 53.8% of the HEM patients vs. 35.3% in the N-HEM group. HEM patients were transfused with significantly greater quantities of platelets on days 1, 3, 5, and 8 and packed red blood cells on day 7 when compared to N-HEM (p < 0.05). TEG determination showed significant differences between groups on days 3 and 6 (p < 0.005), and 8 (p < 0.05). Derangements in hemostasis resulting from ECMO are profound, with methods of assessing coagulation complicated by both the variability in patient condition and lack of specificity of laboratory tests. Interpretation of TEG data has shown to be a valuable supplement for managing this challenging patient population.

Comparison of Infasurf (calf lung surfactant extract) to Survanta (Beractant) in the treatment and prevention of respiratory distress syndrome.

OBJECTIVE: To compare the relative safety and efficacy of Infasurf (calf lung surfactant extract; ONY, Inc, Amherst, NY, IND #27169) versus Survanta (Beractant, Ross Laboratories, Columbus, OH) in reducing the acute severity of respiratory distress syndrome (RDS) when given at birth and to infants with established RDS. DESIGN: A prospective, randomized, double-blind, multicenter clinical trial. SETTING: Thirteen neonatal intensive care units participated in the treatment arm: seven of these concurrently participated in the prevention arm. PATIENTS: The treatment arm enrolled infants of

Plasma fentanyl levels in infants undergoing extracorporeal membrane oxygenation.

Plasma levels of fentanyl were analyzed in 12 infants undergoing extracorporeal membrane oxygenation who received a fentanyl bolus (5 to 10 micrograms/kg) followed by infusion at 1 to 6.3 micrograms/kg/hr. Fentanyl levels, averaging 11 samples/infant, were measured by radioimmunoassay (mean 19.7 +/- 35.7 ng/ml; n = 140). Eight of the infants, all with a primary diagnosis other than congenital diaphragmatic hernia, survived with relatively short (< 7 days) courses on extracorporeal membrane oxygenation; this group of infants did not develop tolerance to fentanyl and could be maintained on infusion rates of < 5 micrograms/kg/hr throughout. The four infants with congenital diaphragmatic hernia had longer extracorporeal membrane oxygenation runs and three did not survive; their plasma fentanyl levels were consistently higher and while the infusion rates were higher early on extracorporeal membrane oxygenation, they did not exceed 7 micrograms/kg/hr and actually decreased after 5 days on extracorporeal membrane oxygenation. Five infants (42%) received lorazepam in addition to fentanyl for at least one sampling time. The fentanyl infusion dose and plasma level were higher in the congenital diaphragmatic hernia nonsurvivors who did not receive lorazepam (p < 0.001). A decrease in fentanyl clearance correlated with renal dysfunction (p < 0.01). A bolus of fentanyl followed by infusion of relatively low doses (1 to 5 micrograms/kg/hr) provides adequate analgesia for infants on extracorporeal membrane oxygenation, particularly when it is supplemented with intravenous lorazepam whenever needed to control infant movement.

Plasma beta-endorphin in neonates: effect of prematurity, gender, and respiratory status.

A consecutive cohort of 87 infants (46 infants less than 37 weeks gestational age and 41 term infants greater than or equal to 37 weeks gestation) admitted to the Neonatal Intensive Care Unit (NICU) and a convenience cohort of 27 term well babies at the University of Nebraska Medical Center (Omaha, NE) were evaluated for plasma beta-endorphin (beta E) levels during the first 4 h after birth. Demographic data, maternal history, and respiratory status at the time of sampling as well as development of documented apneic episodes during the initial hospitalization were analyzed for all infants. All NICU infants had higher plasma beta E levels than the control infants. Premature infants had significantly higher neonatal plasma beta E levels than term infants in either the control or NICU groups, but the response was gender specific; premature males had higher plasma beta E than premature females (P = 0.008). Perinatal stress, including respiratory problems, was associated with the increase in plasma beta E, but prematurity and being male were significantly predictors of an elevated plasma beta E level. Immaturity in respiratory control, as evaluated by the development of documented apneic episodes during the infant's initial hospitalization, did not correlate with an elevated perinatal plasma beta E level.

Prostaglandin F1 alpha levels during and after neonatal extracorporeal membrane oxygenation.

Infants receiving extracorporeal membrane oxygenation therapy undergo long-term cardiopulmonary bypass, are systemically heparinized, and frequently receive platelet transfusions. Prostacyclin is a powerful inhibitor of platelet aggregation as well as a potent vasodilator. The levels of its stable metabolite prostaglandin F1 alpha increase significantly in children undergoing cardiopulmonary bypass during heart operations but decrease to preoperative levels after bypass. To determine the effect of long-term bypass on prostacyclin levels, multiple plasma samples were analyzed in 10 human neonates both during extracorporeal membrane oxygenation therapy and within 24 hours after extracorporeal membrane oxygenation. Prostaglandin F1 alpha, the stable metabolite of prostacyclin, was quantitated by radioimmunoassay in picograms per milliliter. Prostaglandin F1 alpha levels were elevated while the patients received extracorporeal membrane oxygenation therapy but decreased with duration of extracorporeal membrane oxygenation. In most infants, prostaglandin F1 alpha levels rose again during weaning from extracorporeal membrane oxygenation and remained elevated for 24 hours after extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation course influenced circulating prostaglandin F1 alpha levels. Fluctuating prostaglandin F1 alpha levels are of clinical significance in the management of vasomotor tone and platelet function, common problems in the care and the prevention of hemorrhage in these critically ill infants.

Ventilatory changes in convalescent infants positioned in car seats.

Because premature infants have been shown to be at risk for hypoxia and bradycardia when positioned in standard car seats, this study was done to confirm this finding in a larger sample, to investigate convalescent term infants in the neonatal intensive care unit for respiratory compromise in car seats, and to determine the physiologic mechanism or mechanisms responsible. Extensive multichannel polygraph recordings were obtained and pulmonary function tests were performed on 50 convalescent infants from the neonatal intensive care unit before, during, and after placement in a Cosco-Peterson First Ride car seat. Mean total dynamic compliance, total pulmonary resistance, and work of breathing improved in the car seat. Thirty percent of premature infants experienced hypoxia, bradycardia, or both in a car seat; in this group, tidal volume was lower (p = 0.02). In 11 of 16 infants with abnormal findings, oxygen desaturation was temporally related to episodes of short and mixed apnea. No term convalescent infant experienced respiratory difficulty in a car seat regardless of primary diagnosis. We conclude that premature infants may have respiratory compromise of a multifactorial nature when in car seats. Further development of car seats is necessary if such respiratory problems are to be avoided.

Theophylline treatment in the neonate with apnea: effect on growth hormone, thyroid hormone and TRH induced TSH secretion.

Caffeine has been shown to markedly alter growth hormone (GH), thyroid stimulating hormone (TSH), and thyroid hormones in animal studies. Similar studies in the human are lacking. To determine the effect of theophylline treatment on endocrine function in neonates with apnea, 10 infants were studied prospectively pretreatment, immediately following therapeutic blood levels of theophylline, at 2, 4, and 6 weeks thereafter and finally 2 weeks after discontinuation of theophylline. T4, free T4, T3, GH, and basal and stimulated TSH were measured at each study period. Results show no significant difference consequent to theophylline therapy on basal thyroid or GH secretion and thyrotropin-releasing hormone (TRH) induced TSH response at any study interval. We conclude there is no evidence to suspect abnormality occurring in growth, thyroid function and GH secretion in neonates receiving theophylline for breathing disorders.

Outcome of cardiopulmonary resuscitation in the neonatal intensive care unit.

This retrospective review of 83 infants undergoing CPR in the neonatal ICU of a teaching hospital found that 12 (14%) patients were discharged from the hospital and seven (8%) were alive at least 1 yr after discharge. Of these seven, five appeared neurologically intact. From another perspective, 41% (12/29) of the patients who survived at least 24 h after CPR were discharged alive. Factors significantly (p less than .05) associated with poor outcome included sepsis, oliguria 24 h before and/or after arrest, prematurity, and intraventricular hemorrhage. Variables significantly (p less than .05) related to good outcome were the need for intubation during resuscitation and the diagnosis of major congenital anomalies. Intraventricular hemorrhage was the single most powerful variable in the regression analysis. Outcome statistics from this study were strikingly similar to currently available adult data.

Risk of hypoventilation in premature infants in car seats.

We examined 30 newborn infants for respiratory compromise before, during, and after placement in a recommended car seat restraining device. Twelve infants were premature with a history of apnea, eight were premature without known apnea, and 10 were born at term. Both premature groups had significant decreases in oxygen saturation while in the car seat (P less than 0.01) and more frequent desaturation episodes less than 80% (P less than 0.001). Premature infants with a history of apnea had more bradycardia events (P less than 0.05). No normal term infant had any of these problems. In addition, oxygen saturation trended downward from baseline for all premature infants during the recovery interval (P = 0.07). We conclude that currently available car seats may place premature infants at risk for significant hypoxia and ventilatory compromise.

Penicillin-intermediate pneumococci in a children's hospital.

During the three-year period from 1981 to 1984, all clinical isolates of Streptococcus pneumoniae were screened for resistance to penicillin in the clinical bacteriology laboratory at The Children's Hospital of Alabama, Birmingham. Twenty-eight of 828 isolates were presumed resistant by disk diffusion testing with 1-microgram oxacillin disks (zone diameter, less than 20 mm). Seventeen of the 28 (61%) were found to be intermediately sensitive to penicillin by a conventional agar dilution method. Penicillin-intermediate strains had a minimal inhibitory concentration of 0.125 to 0.5 mg/L; no penicillin-resistant (minimal inhibitory concentration, greater than 1 mg/L) strains were encountered. The prevalence of penicillin-intermediate strains was thus 17 of 828 isolates, or 2.1%. These strains were also examined for susceptibility to ampicillin, vancomycin, cefotaxime, and chloramphenicol. We present the clinical features of 17 patients with disease due to penicillin-intermediate pneumococci.