Rex Bickers

Alterations in cerebral blood flow and oxygen consumption during prolonged hypocarbia.

ABSTRACT. The effect of prolonged (2 h) hypocarbia on cerebral blood flow, oxygen delivery, extraction, and consumption was studied in eight, 1- to 4-day-old piglets. Hyperventilation to PaCO2 < 20 mm Hg acutely (30 min) decreased cerebral blood flow and oxygen oconsumption. Cerebral oxygen consumption was subsequently restored via increases in cerebral blood flow and thus, cerebral oxygen delivery. Cerebral oxygen extraction rose from a normocarbic baseline of 50 to 75% with acute hypocarbia and was maintained at this level. The percent decrease in blood flow to the cerebrum was greater than that to other brain regions during hypocarbia.

Pharmacokinetics of netilmicin in premature infants.

SummaryThe pharmacokinetics of netilmicin were studied in 12 premature infants with proven or presumed sepsis during the first month of life. Eleven of 12 patients received netilmicin 2.5 mg/kg intravenously every 12 h while one 770-gram birth weight infant received 2.5 mg/kg every 18 h. Mean steady-state peak and trough concentrations were 8.9 µg/ml and 2.8 µg/ml, respectively. Of twelve patients, 11 had trough serum concentration above 2 µg/ml and four had trough serum concentrations above 3 µg/ml. Mean total body clearance of netilmicin was 0.84 ml/min/kg. The mean clearance of 0.72 ml/min/kg was substantially lower in patients with a mean postnatal age of 2.7 days than the clearance of 1.10 ml/min/kg in patients with a mean postnatal age of 23 days. The mean apparent volume of distribution was 0.63 l/kg; and the mean elimination half-life was 8.6 h. A three-fold interpatient variation in pharmacokinetic parameters was seen. These data suggest the need for careful monitoring of netilmicin serum concentration in premature infants.

Tobramycin kinetics in newborn infants

TOBRAMYCIN is commonly used in newborn infants with suspected or proved sepsis or meningitis. Little is known, however, about tobramycin pharmacokinetics in these patients. Kaplan et al? reported serum concentrations and elimination half-life of tobramyein in premature infants after intramuscular administration. Total body clearance and apparent volume of distribution of tobramycin have not been reported. We characterize tobramycin pharmacokinetics after intravenous administration in newborn infants during the first week of postnatal life.

Budd-Chiari syndrome in a premature infant receiving total parenteral nutrition

A premature infant who developed Budd-Chiari syndrome as a complication of total parenteral nutrition through an inferior vena cava catheter is presented. A novel approach to the treatment of this otherwise lethal condition is described. This very unusual complication in pediatric patients may be seen with increased frequency as more premature infants are treated with central vein total parenteral nutrition.

The Effect of Naloxone on the Hemodynamics of the Newborn Piglet with Septic Shock

ABSTRACT. Naloxone has been shown to reverse the hemodynamic sequelae of experimental septic shock in adult animal models. Its effectiveness in the newborn has not been studied. To further investigate the efficacy of naloxone, we instrumented 18 piglets for continuous measurement of mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, heart rate, left ventricular pressure, contractility, cardiac output, and O2. Oxygen consumption, systemic vascular resistance, and pulmonary vascular resistance were calculated. Following a stabilization period, group B β-hemolytic Streptococci were infused over 30 min. Following the infusion, naloxone (1 mg/kg) was given followed by a continuous infusion of 1 mg/kg/h in nine treatment animals. Nine control animals were given an equal volume of saline. Both groups developed significant increases in mean pulmonary arterial pressure followed by a return to baseline. Oxygen consumption, cardiac output, contractility and mean arterial pressure decreased in both groups. Treatment with naloxone was associated with a cessation in the fall in the mean arterial pressure and the contractility. The difference in mean arterial pressure and contractility between groups was significant. The naloxone group had significantly improved 5–h survival. We speculate that naloxone may reverse some of the hemodynamic sequelae and improve survival in newborns with septic shock.

Publication Trends in Pediatrics in the Field of Neonatology: A Review of its First Half Century ♦ 1932

In connection with the 50th anniversary of Pediatrics, we created a database to analyze the relative contributions in neonatology, and major subdisciplines. The database was created by direct data entry (1948-65), and downloading from PubMed (1966-97). There were 14,480 original articles; 37% (5308) were judged to be neonatal. The table below lists the percent of articles in 10 subdisciplines by decade. The predominance of N/M/E and H/J in the first two decades reflect an early focus on such problems as feeding, hypoglycemia, hypocalcemia and erythroblastosis. HSR was initially a major component, and has returned to the forefront in 1988-97. N/D/B and RESP have steadily risen to their current levels of interest. We have also used the database to identify landmark publications which helped to reduce infant and neonatal mortality rates over the past 50 years: exchange transfusion, infection control (1948-57), neutral thermal environment, regulation of metabolism, amniocentesis/fetal transfusion, (1958-67), antenatal steroids, NCPAP, apnea therapy (1968-77), surfactant, HFV, cryotherapy (1978-87), inhaled NO, erythropoietin and sleep position(1988-97).

120 REAL-TIME SPECTRUM ANALYSIS OF BRACHIAL DOPPLER SIGNALS IN NEONATES WITH PATENT DUCTUS ARTERIOSUS (PDA)

We previously reported a correlation between brachial artery pulsatility index (continuous wave velocitometry) and left atrial enlargement (echocardiographic LA:Ao ratio) in neonates with PDA.To further define the limitations of neonatal Doppler ultrasound for PDA evaluation, we compared the pulsatility index (PI) obtained by continuous wave (CW) velocitometry with the index obtained from spectral analysis (SA) of the audio Doppler signal in ten patients with suspected PDA. Twenty-one brachial examinations were obtained.Linear regression of the PI values obtained by CW and SA revealed a highly linear correlation (r=0.89, p<0.001) but the regression line was not the line of identity. Additionally, the standard deviation of the residuals is greater than that expected for identical measurements. PI values by both methods resolved into two distinct groups, representing normal arterial flow and reverse flow secondary to left-to-right shunt.Although CW measurements were lower than SA measurements, there was no difference in sensitivity for identifying infants with significant PDA.We conclude that CW pulsatility index is a satisfactory predictor of PI obtained by the more precise SA technique. Lower CW values may be related to inherent limitations of the zero crossing detector used to produce the CW signal.

1728 SEROTONIN (5HT) PULMONARY VASCULAR RESPONSES IN THE NEWBORN PIG: VASOCONSTRICTION AND REFLEX VASODILATION ARE INDEPENDENT PROCESSES

We have previously reported two-receptor mediation of 5HT pulmonary vasoconstriction and differences in the dose–response curves of acutely instrumented animals versus awoke chronic preparations.To further characterize 5HT pulmonary vascular responses, we investigated 5HT action in 0–5 day old pigs (n=12). In each experiment, animals underwent instrumentation for measurement of aortic pressure (peripheral cannula), pulmonary artery (PA) pressure and PA flow (via thoracotomy). For dose–response curves, 5HT was infused as a series of rapid bolus doses, ranging from 1–100 mcg/kg. Pharmacologic mediation of the response was investigated by repeating 5HT infusions after treatment with ketanserin (a 5HT–2 blocker) or lidocaine (an endothelial uptake blocker).The PA pressure response to 5HT was qualitatively consistent, but its magnitude exhibited a wide range of variation. The PA tracing was always biphasic, consisting of a rapid increase (2–10 torr) in PA pressure over 30–40 seconds, followed by reflex vasodilation (1–4 torr below baseline), which was slower in onset (1–2 min) and in time to recovery (4–6 min). The active dose range and peak vasoconstriction response were inversely related to baseline pressure (partly a function of age). Ketanserin blocked vasoconstriction completely at doses of 0.03–0.30 mg/kg, but the “reflex” vasodilation was unaffected. Lidocaine produced no blockade of vasoconstriction, but ablated the vasodilation phase.We speculate that 5HT pulmonary vasoconstriction is a direct effect on vascular smooth muscle, while the accompanying reflex vasodilation represents release of a second mediator in response to endothelial 5HT uptake.

1409 BRAIN BLOOD FLOW ALTERATIONS DURING PROLONGED RESPIRATORY ALKALOSIS (RA)

Hypocarbic RA acutely reduces brain blood flow (BBF) by 40-50%, however, most evidence in adult subjects suggests BBF normalizes during prolonged hypocarbia. We investigated the time course of this change in hyperventilated (HV) newborn piglets. Cardiac output (C.O.) and BBF (n=8) were determined by the microsphere method and brain oxygen consumption (VO2) and extraction (EO2) measured from the sagittal vein. Following baseline (B) (PaCO2 35-40) determinations, RA (PaCO2 15-20) was induced by hyperventilation. Measurements were repeated at 30, 60 and 120 minutes. Similar timed measurements in control piglets (PaCO2 35-40) showed no significant variation over time. Acutely (30″), RA decreased BBF (40%), but this degree of vasoconstriction was not maintained. EO2 was maintained at a consistantly elevated level during RA. Thus, VO2 initially decreased but then returned to B. We speculate that RA induced a maximal increase in EO2, with the late increase in BBF representing a vascular escape phenomenon which serves to preserve VO2.

Selection of Indexing Terms by Authors: A Proposal for Abstracts Submitted to the 1985 Meetings of the APS-SPR-APA

Selection of Indexing Terms by Authors: A Proposal for Abstracts Submitted to the 1985 Meetings of the APS-SPR-APA