Eunice John

Pharmacokinetics of once-daily dosing of gentamicin in neonates☆☆☆

In a prospective, randomized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin, 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days. The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group, respectively, had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml (p < 0.05), 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml (p < 0.05), trough concentrations of 1.7 versus 1.7 micrograms/ml, elimination half-life of 8.8 versus 5.4 hours (p < 0.05), and volume of distribution at steady state of 0.67 versus 0.46 L/kg. No nephrotoxic effects were identified in any group. Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve. Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates.

Hypouricemia in Neonates with Syndrome of Inappropriate Secretion of Antidiuretic Hormone

ABSTRACT: A prospective study of serum levels of uric acid in 23 hyponatremic neonates was performed. Infants on diuretic medications or with renal failure were excluded. The infants were separated into two groups: group I consisted of 11 neonates with clinical evidence of syndrome of inappropriate secretion of antidiuretic hormone (SIADH), (mean ± SD serum sodium 127 ± 1.36 mEq/liter). Group II included 12 infants with hyponatremia (mean serum sodium 128 ± 1.10 mEq/liter) associated with decreased effective vascular volume manifest by a fractional sodium excretion <1%. The groups were similar for gestational and postnatal ages, birth weight, clinical conditions, and concurrent use of drugs. The serum urate concentation in neonates with SIADH was 2.46 ± 0.54 mg/dl; serum urate concentration in group II infants was 8.49 ± 2.45 mg/dL (p < 0.001). Water restriction in the group I infants with SIADH resulted in a rise in mean serum urate concentration (p < 0.001). Fractional excretion of urate was elevated during hyponatremia in the group I infants (to 78 ± 0.13%) and fell to 51 ± 0.08% after correction (p < 0.001). In group I infants, a direct correlation was found between fractional excretion of urate and sodium (r = 0.7667, p < 0.001). These results indicate that hypouricemia is common in infants with suspected SIADH and seems to be due to increased urate clearance secondary to volume expansion.

The use of bumetanide for oliguric acute renal failure in preterm infants

Objective: To determine the effects of bumetanide in preterm infants with oliguric acute renal failure (OARF). Study Design: Retrospective data review and multivariate analysis of urine output and serum creatinine, blood urea nitrogen, Na, K, Cl, and Ca levels before, during, and after bumetanide therapy in preterm infants with OARF whose conditions did not respond to furosemide therapy. Results: A total of 35 infants received bumetanide for OARF after an initial trial of furosemide. Their birth weight, gestational age at birth, and postconceptional age at OARF were 811 ± 326 g, 26 ± 2.75 wks, and 29.2 ± 2.7 wks, respectively. Twenty-nine of the 35 infants (83%) responded to bumetanide. Seventeen of the 35 infants subsequently died in the hospital due to multiorgan dysfunction. For the survivors (n = 18) and 11 of 17 of nonsurvivors, urine output increased from 0.6 ± 0.6 mL/kg/hr to 3.0 ± 2.1 mL/kg/hr during bumetanide therapy (p < .0005). Serum creatinine levels increased from 2.13 ± 0.83 mg/dL to 2.3 ± 0.92 mg/dL (p = .04) during bumetanide treatment, whereas blood urea nitrogen levels decreased after bumetanide therapy from 38 ± 19 mg/dL to 31.67 ± 21.6 mg/dL (p = .049). No significant changes were noted in serum sodium, chloride, or calcium concentration. Conclusions: Bumetanide therapy significantly increased urine output within 24–48 hrs, but its use was associated with a transient increase in serum creatinine level. Bumetanide can be used in preterm infants to reverse oliguria when therapy with furosemide fails. Prospective, randomized, controlled trials with long-term follow-up in preterm infants are necessary to establish the usefulness of bumetanide for OARF.

Effect of peritoneal dialysis on serum concentrations of three drugs commonly used in pediatric patients

The use of peritoneal dialysis in young infants bears the theoretical advantage that the relative size of their peritoneal surface area is twice that of adults. The movement of drugs across the peritoneum is affected by the physiochemical properties of the drug molecules and the pathophysiologic condition of the patient. It is observed that the peritoneal dialysis clearances of phenobarbital, amikacin and cefazolin in infants were 1.07-1.33, 0.54-0.86 and 0.40-1.02 ml/min, respectively. The dosage determination in the dialysis patients receiving these drugs is discussed.

THE EFFECT OF DOPAMINE ON RENAL FUNCTION IN NEWBORN PUPPIES

In adults, moderate doses of dopamine (D) (5 to 15 Ug/kg/min) increase renal blood flow; high doses (>20 μg/kg/min) decrease renal blood flow. Although many newborn infants with shock are treated with D, little is known about the effect of moderate dose of D in this age group. Thus we studied the renal effect of intravenous D before (C) during (E) and following (PE) the infusion of dopamine (10 μg/kg/min) in 1 wk old puppies (P). Renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (V) fractional sodium excretion (FENa) free water clearance and distribution of renal blood flow (RBD) were obtained before and during infusion of dopamine. The results are: M±SE, *P<.05 by paired t test.Outer cortical to inner cortical blood flow ratio decreased significantly during D infusion (P<.05). These studies demonstrate that D in moderate doses decreases RBF, GFR, and CH2O; increases FENa, and UV in puppies. These findings are similar to high output renal failure and should be interpreted with caution. Difference in renal response to moderate dose of D in adult and 1 week old may be a function of D receptors.

RENAL RESPONSE TO TOLAZOLINE IN NORMAL AND HYPOXEMIC NEWBORN PUPPIES

The present study was designed to investigate the effect of tolazoline (T), hypoxia (H), and tolazoline and hypoxia (TH) on renal functions. Each animal served as its own control. Hypoxia was induced by administering 5% O2 and 95% N2O for 45 minutes. Following a bolus injection of tolazoline (2mg/kg), a continuous infusion was given (2mg/kg/hr). Blood pressure (BP), renal blood flow (RBF), glomerular filteration rate (GFR), fractional excretion of sodium (FEna), and urine volume (UV) were measured by conventional methods. The change in PaO2 were similar in H and TH groups. In T, there were no changes in BP, RBF, GFR, FEna, and UV during control and experimental periods. In H, at the onset of the experiment, BP increased from a mean value of 50±10mmHg to 65±20mmHg, then remained at 50±10mmHg. In TH, following the administration of tolazoline, BP decreased from 49±5mmHg to 29±2 mmHg and remained low thereafter. A greater than 40% decrease in GFR was observed in H and 60% in TH group. RBF decreased 1.5 fold (P < .05) in H while 4 fold in TH (P <.05). FEna and UV however, increased 17 and 6 fold in H (P < .05) while the increase was 21 (P < .05) and 2.4 fold in TH. These results suggest: 1. Tolazoline does not have an adverse effect on BP and renal functions. 2. Hypoxia produces decrease in GFR and RBF. 3. Tolazoline in the presence of hypoxia produces more severe changes in renal functions.

Total Body Cooling Versus Selective Head Cooling: Brain and Systemic Organ Temperature Dynamics during Hypotherma and Re-Warming in Piglets

Total Body Cooling Versus Selective Head Cooling: Brain and Systemic Organ Temperature Dynamics during Hypotherma and Re-Warming in Piglets

Effect of tolazoline on renal function in newborn puppies.

Tolazoline is used in pulmonary hypertension and hypoperfusion syndrome during the neonatal period. Some of the side effects of tolazoline are hypotension, bleeding disorders and renal dysfunction. The present study was designed to investigate the effect of hypoxia and tolazoline on renal function in newborn puppies. The data in normal animals administered tolazoline alone did not reveal any statistically significant changes in blood pressure or in renal function. In the hypoxia group changes in renal function were noticed in spite of normal blood pressure. When tolazoline was administered to the hypoxic animals, a marked decrease in blood pressure resulted. Indeed, changes in renal function were more profound in the hypoxic animals receiving tolazoline than in hypoxic animals not receiving tolazoline, even though some of the renal functional values did not reach statistical significance.

1048 FEVER IN A HEMODIALYSIS PATIENT

Prolonged unexplained fever is a continuing problem in chronic renal failure patients on hemodialysis (HD) and poses a diagnostic problem. These patients have an increase in susceptibility to various infections, caused by usual pathogens, as well as by opportunistic organisms.We report a 10-year-old patient with chronic renal failure on HD, who developed prolonged unexplained fever secondary to pseudomembranous colitis associated with clostridium difficile toxin in the stools. She was admitted for HD and treated with tobramycin and cefazolin for fever, pneumonia and atelectasis of left lung for 3 weeks. Fever recurred 3 weeks after antibiotic therapy (AT) and persisted for 6 more weeks. She also developed bloody diarrhea 4 weeks after AT. Blood, stool, urine and sputum cultures for virus, fungus, and bacteria were negative. Stool, however, was positive for clostridium difficile toxin (CDT) (>1:1000). She became afebrile 2 days after oral vancomycin therapy (VT). Diarrhea and fever recurred when VT was discontinued but normalized after restarting VT therapy. Clostridium difficile infection should be considered in prolonged unexplained fever in HD patients.

1552 COMPARISON OF TWO ANIMAL MODELS IN ARTIFICIAL SURFACTANT THERAPY FOR HYALINE MEMBRANE DISEASE (HMD)

Preterm baboon (B) and lambs (L) have been used as models for different surfactant studies. Varying responses have been recorded. We studied and compared the responses of these models to S-TA therapy. Animals delivered prematurely (B:76% and L:83% term) by C-section were used. All had HMD. S-TA 100 mg/kg was instilled into trachea at 2 hrs. of age. Controls received no S-TA. Sequential a/APO2 data are shown. Treated B had sustained improvement in a/APO2 up to 16 hrs. and mean airway pressure dropped from 14.5±1.1 to 10.2±0.5 cmH2O p<.001. In lambs improvement in a/APO2 was significant but transient lasting only 2-3 hrs, with deterioration by 4-5 hrs. Pressure vol. curves at autopsy showed significantly larger hysteresis in treated baboons than lambs. Two other treated baboons could be maintained alive for 36 hrs. We conclude: 1) Differences in response to S-TA therapy may be species related, 2) Baboon HMD model may be better for studies of long term effects of surfactant therapy than the lambs.