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Biomedical subjects

W Banner

Publications and source records attributed to W Banner.

At least 19 recordsLinked to original sources
PubMed1995

Oral dimercaptosuccinic acid and ongoing exposure to lead: effects on heme synthesis and lead distribution in a rat model.

Lead (Pb) exposure and subsequent toxicity continues to be a significant problem in the United States. Treatment with meso-2,3-dimercaptosuccinic acid (DMSA) has been reported to be effective in reducing the body's Pb burden, with fewer adverse side effects than other chelating agents. The oral availability and relative safety of DMSA presents the controversial option of treating patients with Pb poisoning on an outpatient basis. Despite recommendations that children be removed from the Pb contaminated environment, some children will inevitably be exposed to environmental Pb while receiving oral DMSA therapy. The study hypothesized that oral DMSA chelation therapy is beneficial even when faced with continued dietary Pb. Sprague-Dawley rats were exposed to Pb in water for 35 days and then placed in various treatment groups, including groups administered oral DMSA with and without concurrent Pb exposure. The concentration of Pb in blood and critical organs and Pb diuresis were measured. The effect of Pb on heme synthesis was determined by assaying the urinary delta-aminolevulinic acid (delta-ALA), and blood zinc protoporphyrin (ZPP). DMSA reversed the hematological effects of Pb, decreased the blood, brain, bone, kidney, and liver Pb concentration, and produced a marked Pb diuresis, even when challenged with ongoing Pb exposure. In conclusion, even though DMSA treatment without exposure to Pb is optimal, oral DMSA could be beneficial even when challenged with ongoing Pb exposure.

Administration, Oral↗
PubMed1994

Medical toxicology.

Chest pain is a manifestation of cocaine toxicity, but whether it is of an ischemic origin is unclear. A reexamination of the role of acetylcysteine in treating acetaminophen overdose has led to substantial changes in the indications for its use.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1994

Age-related amrinone pharmacokinetics in a pediatric population.

OBJECTIVES: To measure the plasma concentrations of amrinone and N-acetyl-amrinone achieved using current pediatric dosing recommendations. To examine the pharmacokinetics of amrinone in an extended age range of pediatric patients. To examine any age-related differences in the relative contribution of hepatic metabolism vs. renal elimination of amrinone. DESIGN: Prospective study. SETTING: A pediatric intensive care unit in a tertiary care teaching hospital. PATIENTS: Thirty-one patients aged 4 days to 15 yrs who required a constant infusion of amrinone. INTERVENTIONS: Blood samples were obtained 15 mins after each 0.75 mg/kg loading dose, and every 6 hrs during a constant infusion of amrinone to measure plasma amrinone, N-acetyl-amrinone and N-glycolyl-amrinone concentrations by high-performance liquid chromatography. Blood samples to measure amrinone, N-acetyl-amrinone, and N-glycolyl-amrinone concentrations during elimination were also obtained at regular intervals after discontinuation of the infusion. Six-hour urine collections were obtained to measure amrinone renal clearance. MEASUREMENTS AND MAIN RESULTS: Plasma amrinone concentrations > or = 2 micrograms/mL were obtained in 13 of 14 patients after a 3-mg/kg loading dose. There was a six-fold variability in steady-state plasma amrinone concentrations in patients receiving the same ordered infusion rate. There was a significant (p = .001) difference between the ordered and measured amrinone infusion rates. Six (19.4%) of 31 patients had steady-state plasma amrinone concentrations of < or = 2 micrograms/mL. There was a large variability in the volume of distribution, clearance, and elimination half-life which did not appear to be age-related. Renal clearance of amrinone ranged between 0.4 and 2.18 mL/kg/min, and did not increase with age. There was no increase in the proportion of children with a high plasma steady-state N-acetyl-amrinone/amrinone ratio over time from 1 to 24 months of life. CONCLUSIONS: Administering a 3-mg/kg amrinone loading dose in four divided doses over 1 hr resulted in relatively rapid therapeutic plasma concentrations without excessively high concentrations and good clinical tolerance. The wide interindividual variation in clearance and volume of distribution resulted in a variable dose-concentration relationship; children receiving lower amrinone infusion rates may-have subtherapeutic plasma steady-state concentrations. There did not appear to be any age-related change in renal clearance or hepatic metabolism of amrinone in children aged 1 to 24 months.

Adolescent↗
PubMed1994

Advances in the critical care of poisoned paediatric patients.

Recent improvements in paediatric intensive care may potentially improve outcome for severely poisoned children. The application of advanced techniques of critical care to the poisoned paediatric patient encompasses a wide variety of therapeutic and technical innovations that are primarily directed towards support of the cardiopulmonary system and removal of toxins. New extracorporeal removal techniques such as continuous arterio-venous haemofiltration have not substantively increased our ability to remove toxins except in rare instances. Exotic techniques such as extracorporeal membrane oxygenation remain in the background for use in rare instances only, with little clear data on the relative risks and benefits of applying them.

Chelation Therapy↗
PubMed1994

Effects of two dosing regimens of intravenous ranitidine on gastric pH in critically ill children.

BACKGROUND: Gastric bleeding in children is associated with critical illness, shock, and physical trauma. Histamine-2 receptor antagonist therapy is used prophylactically to treat gastric bleeding, but it is not known whether bolus dosing or continuous infusion dosing is more effective. OBJECTIVES: To compare the effects of continuous infusion intravenous ranitidine and intravenous bolus dosing of ranitidine on gastric pH in critically ill children and to look for correlation between illness severity scores and gastric pH. METHODS: Sixteen critically ill children were randomized into two groups. Children in group 1 received bolus dosing on day 1 and continuous infusion of ranitidine on day 2. Group 2 received the continuous infusion on day 1 and bolus dosing on day 2. Equivalent doses of ranitidine were based on weight. Continuous infusion regimen: ranitidine bolus of 0.15 mg/kg followed by continuous infusion at 0.15 mg/kg per hour for 12 hours. Bolus regimen: 1 mg/kg, two doses 6 hours apart. Pediatric risk of mortality scores were recorded upon admission to the study. RESULTS: There was no statistically significant difference between regimens. Both raised gastric pH values above 4.0 during the treatment phase. There was no correlation between illness severity scores and gastric pH values. CONCLUSIONS: Both bolus dosing and continuous infusion dosing of 4 mg/kg per day of intravenous ranitidine were effective at raising and maintaining gastric pH in critically ill children.

Adolescent↗
PubMed1993

Modes of death in the pediatric intensive care unit: withdrawal and limitation of supportive care.

OBJECTIVE: To determine the frequency of withdrawal or limitation of supportive care for children dying in a pediatric intensive care unit (ICU). DESIGN: Retrospective review of medical records. SETTING: Pediatric ICU in a tertiary care children's hospital. PATIENTS: All children dying in the pediatric ICU over a 54-month period (n = 300). INTERVENTIONS: Medical record review. MEASUREMENTS AND MAIN RESULTS: Data recorded for each patient included diagnosis, mode of death, and whether the child was brain dead. Each patient was assigned to one of the following mode of death categories: brain dead; active withdrawal of supportive care (meaning removal of the endotracheal tube); failed cardiopulmonary resuscitation; allowed to die without cardiopulmonary resuscitation (do-not-resuscitate status). A total of 300 patients were identified. Diagnoses included postoperative congenital heart disease (n = 56), head trauma (n = 38), near-miss sudden infant death syndrome (n = 28), pneumonia (n = 22), sepsis (n = 21), near-drowning (n = 21), various anoxic insults (n = 20), multiple trauma (n = 17), and patients with other diagnoses (n = 77). Mode of death was active discontinuation of support in 95 (32%) patients, do-not-resuscitate status in 78 (26%), brain death in 70 (23%), and failed cardiopulmonary resuscitation in 57 (19%). CONCLUSIONS: In a large, multidisciplinary pediatric ICU, the most common mode of death was active withdrawal of support. In addition, more than half (173/300, 58%) of children dying in the pediatric ICU underwent either active withdrawal or limitation (do-not-resuscitate status) of supportive care.

Brain Death↗
PubMed1992

Hemodynamic effects of dobutamine in an intact animal model.

BACKGROUND AND METHODS: Actions of dobutamine at the beta 1, beta 2, and alpha 1 adrenoreceptors were studied in anesthetized dogs. Six animals received dobutamine (at infusion rates of 0 to 160 micrograms/kg/min) with and without beta-adrenergic receptor blockade. Five animals received phenylephrine (0 to 16 micrograms/kg/min), with and without concurrent dobutamine (20 micrograms/kg/min); this procedure was repeated in five animals after beta-blockade. RESULTS: Dobutamine (10 to 160 micrograms/kg/min) increased heart rate (HR), cardiac output, and left ventricular change in pressure over time, and decreased systemic vascular resistance. beta-blockade prevented only dobutamine-induced changes in HR. Mean arterial pressure (MAP), unaffected by dobutamine alone, decreased with concurrent beta-blockade. Phenylephrine (1 to 16 micrograms/kg/min)-induced increases in MAP were unaffected by dobutamine; with beta-blockade, phenylephrine reduced MAP. Dobutamine prevented a phenylephrine-induced increase in systemic vascular resistance, an effect eliminated by beta-adrenergic receptor blockade. CONCLUSIONS: Dobutamine appeared to be an agonist at the beta 1- and beta 2-adrenoreceptors and at the myocardial alpha-adrenoreceptor. Dobutamine appeared to be an alpha-adrenergic receptor antagonist in the peripheral vasculature.

Adrenergic beta-Antagonists↗
PubMed1992

Influence of assay methods on serum concentrations of digoxin during FAB fragment treatment.

The treatment of digoxin intoxication has been revolutionized by digoxin specific antibody fragments (Fab). Serum digoxin concentrations may be inaccurate after this treatment. We report a case of digoxin intoxication where the results of serum concentration determinations were strikingly disparate depending on the assay used. To investigate this discrepancy we compared serum samples spiked with digoxin from 0-50 ng/mL in the presence of increasing concentrations of digoxin specific Fab-fragments. Samples were measured using the Abbott TDx assay with and without ultrafiltration of the sample and the Dade-Stratus radial partition assay. The TDx assay was statistically reduced by the Fab-fragments although the magnitude of the effect was small. The radial partition assay was dramatically affected by the addition of Fab-fragments. The predicted non-Fab bound concentration correlated highly with the measured concentration. When samples were ultrafiltered prior to TDx assay, the measured concentration was dramatically depressed but the regression of predicted non-Fab bound concentration versus observed had a significantly lower slope than for the radial partition assay. We hypothesize that this difference is due to serum protein binding in addition to Fab-fragment binding. We conclude that the radial partition assay gives the best approximation of digoxin concentration remaining unbound to Fab-fragments. Ultrafiltration followed by TDx assay gives an acceptable approximation.

Antigen-Antibody Reactions↗
PubMed1991

Efficacy of dopamine and norepinephrine for treatment of hemodynamic compromise in amitriptyline intoxication.

BACKGROUND AND METHODS: Dopamine and norepinephrine were evaluated for treatment of hemodynamic compromise in amitriptyline intoxication. Fifteen anesthetized dogs underwent hemodynamic monitoring and amitriptyline intoxication, and received three infusion rates of dopamine (5, 15, and 30 micrograms/kg.min) and three infusion rates of norepinephrine (0.25, 0.5, and 1.0 micrograms/kg.min), sequentially, with hemodynamic measurements at each dose. Data were analyzed using repeated-measures analysis of variance; p less than .05 was considered significant. RESULTS: Amitriptyline intoxication lowered cardiac output, peak left ventricular dP/dt, and mean arterial pressure (MAP). All doses of norepinephrine and the two higher doses of dopamine increased cardiac output, MAP, and peak left ventricular dP/dt during the intoxicated state. Both agents restored all variables to preintoxication values. Values obtained at the highest doses of the two drugs were not different for any variable. CONCLUSION: Dopamine and norepinephrine each appeared effective in reversing amitriptyline-induced hemodynamic alterations.

Amitriptyline↗
PubMed1991

Nonlinear dobutamine pharmacokinetics in a pediatric population.

OBJECTIVE: To evaluate a linear kinetic model for dobutamine clearance. DESIGN: A prospective evaluation of pediatric patients receiving continuous infusions of dobutamine at varying doses. SETTING: A pediatric critical care unit. PATIENTS: Twelve patients age 2 days to 9 yrs and weighing 2.7 to 33 kg who required vasopressor therapy. Infusion rates for dobutamine ranged from 2 to 15 micrograms/kg.min. MEASUREMENTS AND MAIN RESULTS: Serum concentrations varied from 6.4 to 347 ng/mL (21 to 1151 nmol/L). Concentration was found to increase with dose. However, the relationship of clearance to steady-state concentration had a negative slope. Values for clearance varied from 32 to 625 mL/kg.min. Multiple analysis of variance on age, weight, and co-infused dopamine showed that these factors did not influence the relationship of clearance to steady-state concentration. Analysis to show an underlying model failed to differentiate Michaelis-Menten from nonlinear binding or mixed models on the basis of these data. CONCLUSIONS: Dobutamine pharmacokinetics do not appear to follow a simple linear model. Based on the current data, neither age nor the added infusion of dopamine affects the clearance of dobutamine.

Age Factors↗
PubMed1991

Skin necrosis complicating intraosseous infusion.

Bone marrow infusion is currently recommended as a useful technique for rapidly obtaining vascular access in critically ill children. Minor complications occur frequently, but serious complications of this technique are uncommon. We describe two patients with local skin necrosis complicating intraosseous infusion. To minimize the complications of this technique, we recommend placement verification before fluid infusion, careful monitoring for infiltration, and prompt removal after venous access is obtained.

Bone Marrow↗
PubMed1990

Failure of CAVH to remove digoxin-Fab complex in piglets.

Digoxin toxicity may be associated with renal failure and an inability to excrete the digoxin-Fab (antibody fragment) complex used in detoxification. We are unaware of any previous reports regarding the removal of digoxin-Fab fragment complex by continuous arteriovenous hemofiltration. Continuous arteriovenous hemofiltration allows ultrafiltration of molecules less than 50,000 daltons. Because the digoxin-Fab fragment complex has a molecular weight of 45 - 50,000 daltons, we evaluated the efficiency of continuous arteriovenous hemofiltration in removing the digoxin-Fab fragment complex. Three piglets were given 100 mcg/kg digoxin IM, in divided doses. Animals were anesthetized and continuous arteriovenous hemofiltration was begun using a Diafilter 10 cartridge. A mean ultrafiltration rate of 3.6 +/- 0.4 ml/min was obtained. The system equilibrated for 30 minutes and initial serum and ultrafiltrate digoxin levels were obtained. Mean serum values were total 6.20 +/- 1.74 ng/ml and free 3.72 +/- 0.88 ng/ml. Digibind 40 mg IV was given and then samples of serum and ultrafiltrate were obtained at 30, 60 and 90 minutes for digoxin levels. Mean values were as follows: 30 min serum total 54.23 +/- 26.13 ng/ml and free 0.08 +/- 0.08 ng/ml; 60 min serum total 61.24 +/- 27.31 ng/ml and free 0.07 +/- 0.04 ng/ml; and 90 min serum total 67.63 +/- 26.78 ng/ml and free 0.10 +/- 0.10 ng/ml. Ultrafiltrate levels throughout the experiment were negligible (less than or equal to 0.04 ng/ml). Continuous arteriovenous hemofiltration appears to be ineffective in removing the digoxin-Fab fragment complex.

Animals↗
PubMed1989

Hemodynamic effects of experimental iron poisoning.

The hemodynamic effects of severe iron poisoning were studied in five mongrel dogs. Anesthetized animals were instrumented with arterial, venous, and pulmonary artery thermodilution catheters. Iron intoxication was induced by orogastric administration of ferrous sulfate (600 mg/kg elemental iron). Pulmonary artery wedge pressure values were maintained near preintoxication values by saline infusion, and sodium bicarbonate (1.5 mEq/kg/dose) was given for pH less than 7.25. Hourly hemodynamic measurements were obtained for five hours. Cardiac output, mean arterial pressure, pH, and heart rate decreased significantly (P less than .05), whereas systemic vascular resistance, left ventricular stroke work, and oxygen consumption did not change. All animals developed metabolic acidosis despite saline (3.6 +/- 0.9 L, mean +/- SD) and bicarbonate administration (4.2 +/- 0.8 mEq/kg). These findings suggest that decreased cardiac output was partially due to decreased heart rate but not to decreased preload or abnormal left ventricular afterload. Alkali therapy and maintenance of oxygen consumption did not prevent development of metabolic acidosis.

Acidosis↗
PubMed1989

Continuous arteriovenous hemofiltration in experimental iron intoxication.

This study evaluated continuous arteriovenous hemofiltration (CAVH) as a method for removing the iron-deferoxamine complex in experimental iron intoxication. Five anesthetized dogs were instrumented for hemodynamic monitoring and then given 600 mg/kg of elemental iron as ferrous sulfate. After a 3-h absorption period, CAVH was begun from the femoral artery to femoral vein. Deferoxamine was infused into the arterial lines of the CAVH cartridge at increasing doses. We found a dose-dependent increase in the ultrafiltrate excretion of iron. However, most of the deferoxamine was excreted unbound. The efficiency of complex formation was greater at lower BP and ultrafiltrate formation rate, suggesting that inadequate mixing of deferoxamine with blood may occur when arterial administration is used. Iron excretion in the urine over the same time period was not significantly greater than that removed by CAVH. We conclude that CAVH can remove iron using deferoxamine as a chelating agent.

Animals↗