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Biomedical subjects

V Bhatt-Mehta

Publications and source records attributed to V Bhatt-Mehta.

At least 19 recordsLinked to original sources
PubMed2001

Maternal and transplacental pharmacokinetics of cefazolin.

OBJECTIVE: To evaluate the intrapartum pharmacokinetics of cefazolin, including delivery to amniotic fluid (AF) and fetal compartments, and to ascertain that adequate cefazolin concentrations are attained to exceed the mean concentration inhibiting 90% (MIC(90)) of group B streptococcus strains. METHODS: Cefazolin (1 g) was administered intravenously at five separate time intervals (0.5, 1, 2, 4, and 6 hours) before elective cesarean at term to 26 women with intact membranes and with no significant infections or cardiovascular, liver, or renal disease. Samples of maternal blood, cord blood, and AF were obtained at the time of delivery. Exact collection times relative to cefazolin infusion were noted. Amniotic fluid contaminated with blood or meconium was excluded. Cefazolin concentration was measured by high-pressure liquid chromatography. RESULTS: All maternal and cord plasma cefazolin levels, except one, were above the MIC(90) for Streptococcus agalactiae (group B streptococcus). For AF, all cefazolin levels, except two, were above the MIC(90). CONCLUSIONS: Cefazolin concentrations greater than or equal to the MIC(90) for group B streptococcus were attained in nearly all maternal, fetal, and AF samples. This information, together with the knowledge that there is rare resistance of group B streptococcus to cefazolin, supports the use of cefazolin as a better alternative than clindamycin or erythromycin for group B streptococcus prophylaxis in patients with a nonanaphylactic penicillin allergy.

Adult↗
PubMed1999

Lack of vancomycin-associated nephrotoxicity in newborn infants: a case-control study.

OBJECTIVE: The purpose of this study was to compare the incidence of nephrotoxicity, defined as doubling of baseline serum creatinine concentration, in newborn infants with peak vancomycin serum concentrations </=40 microg/mL at steady state to infants with peak vancomycin serum concentrations >40 microg/mL. A secondary objective was to correlate concomitant disease states and potentially nephrotoxic drug therapy with rises in serum creatinine in vancomycin recipients. METHODS: Newborn infants with culture-proven Staphylococcus aureus or coagulase-negative staphylococcal septicemia who received vancomycin therapy for >3 days between 1985 and 1995 were identified from an existing database and a review of medical record. All 69 patients included in the study had serial serum creatinine determinations, including a baseline value within 48 hours of starting treatment with vancomycin, and serum vancomycin concentrations determined after at least three doses, with peak and trough concentrations determined 1 hour after a 60-minute infusion and 15 to 30 minutes before a dose, respectively. Infants with congenital renal or cardiac anomalies were excluded. Demographic characteristics, vancomycin dosing regimen, serum vancomycin concentrations and sample times, concomitant drug therapy, and disease states were recorded. Patients were divided into group A (peak vancomycin concentration </=40 microg/mL) and group B (peak vancomycin concentration >40 microg/mL). The change in serum creatinine concentration between the start and end of vancomycin therapy was determined. Nephrotoxicity was identified if serum creatinine doubled at any time from the start to the end of vancomycin therapy. Alternative definitions of nephrotoxicity (any rise in serum creatinine to >0.6 mg/dL or new abnormalities of urine sediment) were used in additional analyses. RESULTS: A total of 69 evaluable patients (gestational age, 28.9 +/- 3.0 weeks; birth weight, 1219 +/- 516 g) were identified, 61 in group A and 8 in group B. Six patients in group A underwent doubling of serum creatinine concentration during vancomycin therapy, whereas none in group B did so. Serum creatinine doubled to >0.6 mg/dL in only 3 infants (all in group A). Any increase in serum creatinine to >0.6 mg/dL was seen in 10 infants, 9 of whom were in group A. No confounding variable, including previous or concomitant underlying disease states associated with renal dysfunction or treatment with other potentially nephrotoxic agents, were associated with a significant rise in serum creatinine. CONCLUSION: Vancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations >40 microg/mL.

Anti-Bacterial Agents↗
PubMed1996

Current guidelines for the treatment of acute pain in children.

Premature and full-term neonates, infants and children are capable of experiencing pain just like adults, and deserve aggressive treatment. Assessment of pain is difficult in the preverbal group. However, physiological and behavioural responses to noxious stimuli are well developed even in the fetus, and modifying these responses through treatment can affect outcome. Treatment options include systemic opioid and nonopioid analgesics as well as local anaesthetics, all of which are effective when chosen on the basis of the type and intensity of the pain. Dosage modification is necessary based on age and organ function. Nonopioid analgesics are useful supplements to reduce opioid analgesic dose and should be used when indicated. Drug dependence and withdrawal can be avoided by using the opioids appropriately and following logical weaning schedules after long term use of these agents. Use of needles for administering analgesia is still an intimidating part of the process for young children. The development of drugs having fewer adverse effects and noninvasive administration techniques will be important research priorities in the future.

Adult↗
PubMed1995

Stability of propofol with parenteral nutrient solutions during simulated Y-site injection.

The stability of propofol in three parenteral nutrient (PN) solutions was studied. Nine combinations of three PN solutions (with amino acid concentrations of 1.5, 2.5, and 5.0%) and three propofol concentrations (0.5, 2.0, and 3.0 mg/mL) were prepared in triplicate and stored at 22 degrees C under fluorescent light. Duplicate samples were visually inspected for color changes, precipitation, or gas formation, and the pH of the samples was determined. These samples were evaluated for propofol content by high-performance liquid chromatography at zero, one, three, and five hours. The stability of the vehicle for propofol injection (similar in composition to fat emulsion) was evaluated by visual inspection, pH determination, and particle-size measurements at zero, one, three, and five hours. The concentration of propofol in all of the propofol-PN combinations remained greater than 90% of the initial concentration except for the combination of propofol 0.5 mg/mL and the 1.5% amino acid PN solution, which contained only 72% of the initial propofol concentration five hours after the start of the study. Visual examination revealed no evidence of color change, precipitation, gas formation, creaming, or streaking in any of the propofol-PN solution combinations. No substantial changes in pH occurred. The particle size of the vehicle for propofol remained relatively constant throughout the study period. Propofol 2 and 3 mg/mL was stable for five hours during simulated Y-site injection with PN solutions containing 1.5, 2.5, and 5% amino acids. Propofol 0.5 mg/mL was stable during simulated Y-site injection with the same PN nutrition solutions for five hours, except for the solution containing 1.5% amino acid.

Chemistry, Pharmaceutical↗
PubMed1994

Randomized, blind trial of dopamine versus dobutamine for treatment of hypotension in preterm infants with respiratory distress syndrome.

To compare the efficacy of dopamine and dobutamine for the treatment of hypotension (mean arterial blood pressure, < or = 30 mm Hg) in preterm (< or = 34 weeks of gestation) infants with respiratory distress syndrome in the first 24 hours of life, we enrolled 63 hypotensive preterm infants in a randomized, blind trial. Inclusion criteria required an arterial catheter for measurement of mean arterial blood pressure, treatment with exogenous surfactant, and persistent hypotension after volume expansion with 20 ml/kg (packed erythrocytes if hematocrit < 0.40, 5% albumin if > or = 0.40). Intravenous study drug infusions were initiated at 5 micrograms/kg per minute and then increased in increments of 5 micrograms/kg per minute at 20-minute intervals until a mean arterial blood pressure > 30 mm Hg was attained and sustained for > or = 30 minutes (success) or a maximum rate of 20 micrograms/kg per minute was reached without resolution of hypotension (failure). The study groups at entry were comparable for birth weight, gestational age, postnatal age, gender, birth depression, hematocrit < 0.40, heart rate, oxygenation index, delivery route, maternal chorioamnionitis, and maternal magnesium or ritodrine therapy. No infants in the dopamine group had a treatment failure (0/31; 0%); (16%) of 32 infants failed to respond to dobutamine (p = 0.028). Success was attained at < or = 10 micrograms/kg per minute in 30 (97%) of 31 infants given dopamine and in 22 (69%) of 32 infants given dobutamine (p < 0.01). Among those treated successfully, the increase in mean arterial blood pressure was significantly higher in those given dopamine (mean, 11.3 vs 6.8 mm Hg; p = 0.003). We conclude that dopamine is more effective than dobutamine for the early treatment of hypotension in preterm infants with respiratory distress syndrome.

Dobutamine↗
PubMed1994

Neonatal adrenergic blockade following single dose maternal labetalol administration.

A single 30 mg intravenous dose of labetalol given 20 minutes prior to cesarean delivery at 35 weeks of gestation for severe pregnancy-induced hypertension was associated with symptoms of beta-adrenergic blockade (hypoglycemia, bradycardia, hypotension) in preterm twins. The infants were subsequently found to have therapeutic labetalol concentrations (180 and 150 ng/mL) in umbilical cord blood. The pharmacology of transplacental labetalol is reviewed and potential mechanisms for neonatal beta-adrenergic blockade are discussed.

Adult↗
PubMed1993

Stability of midazolam hydrochloride in extemporaneously prepared flavored gelatin.

The stability of midazolam hydrochloride in flavored gelatin was evaluated after storage at 4 degrees C for 14 days and at -20 degrees C for 28 days. A flavored liquid gelatin mixture was prepared and mixed with midazolam hydrochloride injection in final concentrations of midazolam 1 and 2 mg/mL. Gelatin cups containing 5 and 15 mg of midazolam were prepared by measuring appropriate volumes of the gelatin stock solutions and were stored in a refrigerator at 4 degrees C or in a freezer at -20 degrees C. Immediately after preparation and at 7 and 14 days, three refrigerated and three frozen gelatin samples of each midazolam concentration were visually inspected, tested for pH, and assayed for midazolam concentration by high-performance liquid chromatography. The frozen gelatin samples were also evaluated at 21 and 28 days; three whole and three partial gelatin samples were assayed for midazolam content to determine the uniformity of drug distribution within each sample. All samples maintained greater than 96% of the initial midazolam concentration throughout the study. There was no appreciable change in color, odor, or pH. The midazolam content of the gelatin in the cups was uniform. An extemporaneously compounded preparation of midazolam hydrochloride in flavored gelatin was stable when stored for 14 days at 4 degrees C and for 28 days at -20 degrees C. Distribution of midazolam hydrochloride in the gelatin was uniform.

Drug Stability↗
PubMed1993

Stability of midazolam hydrochloride in parenteral nutrient solutions.

The compatibility and stability of midazolam hydrochloride in three parenteral nutrient (PN) solutions and the stability of 15 amino acids in the presence of midazolam hydrochloride were studied. Six combinations of three PN solutions with amino acid concentrations of 1.5%, 2.5%, and 5% and two midazolam concentrations (0.1 and 0.5 mg/mL) were prepared in triplicate and stored at room temperature under normal fluorescent lighting. Duplicate samples were visually inspected for color change, precipitation, or gas formation and tested for pH. The samples were evaluated for midazolam and amino acid content by high-performance liquid chromatography at zero, one, three, and five hours. Midazolam and amino acid concentrations did not change significantly during the study. There was no evidence of color change, precipitation, or gas formation with any midazolam-PN solution combination when the combinations were examined visually and under a microscope, and no substantial changes in pH occurred. Midazolam 0.1 and 0.5 mg/mL (as the hydrochloride salt) was stable in the three PN solutions studied; in addition, the amino acids present in the 1.5%, 2.5%, and 5% amino acid PN solutions were stable when combined with midazolam at concentrations of 0.1 and 0.5 mg/mL.

Amino Acids↗
PubMed1992

Gentamicin pharmacokinetics in term neonates receiving extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) may affect the pharmacokinetics of certain drugs. The objectives of this study were to determine (1) the pharmacokinetics of gentamicin in neonates on ECMO and compare them to reported values for a similar patient population not on ECMO, (2) if the pharmacokinetics of gentamicin differ between venous-venous and venous-arterial bypass, and (3) if the pharmacokinetics of gentamicin are affected by oxygenator surface area (0.6 m2 vs 0.8 m2 oxygenators). The medical records of 29 term neonates who received gentamicin while on ECMO were reviewed. Data collected included gentamicin dosage, peak and trough serum concentrations determined at steady state, duration of treatment, time on ECMO, daily weights, and pertinent laboratory values. An initial dosage of gentamicin 2.5 mg/kg every 18 hours is suggested for term neonates on ECMO. Dosage adjustments should be based on gentamicin serum concentrations, and modifications may also be required after ECMO.

Bacterial Infections↗
PubMed1991

Dopamine pharmacokinetics in critically ill newborn infants.

Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5-20 micrograms.kg-1.min-1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013-0.3 microgram/ml. Total body clearance averaged 115 ml.kg-1.min-1. The apparent volume of distribution and elimination half life averaged 1.8 l.kg-1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.

Birth Weight↗
PubMed1991

Management of acute pain in children.

The pathophysiology, assessment, and pharmacologic management of acute pain in infants and children are reviewed, and the mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, and dosages of opioid analgesics, nonopioid analgesics, and local anesthetics used for regional blocks are discussed. The pathophysiology of pain and the physiologic rationale for treatment of pain are similar in children and adults. Severe pain can be controlled by i.v. or epidural administration of opioid analgesics. Neonates are more susceptible to the depressant effects of opioids, and opioid analgesia must be administered with caution in infants who are not receiving mechanical ventilation because of the associated risk of respiratory depression. Patient-controlled analgesia is a useful technique in older children. Acetaminophen and NSAIDs are useful for relieving milder pain of noninflammatory and inflammatory origin, respectively. Epidural or intrathecal administration of local anesthetics provides regional analgesia with minimal physiologic alterations. Topical application of local anesthetics is effective for many minor procedures. A variety of pain management techniques are available for the management of acute pain in pediatric patients. The development of drugs having fewer adverse effects and noninvasive administration techniques will be important research priorities in the coming years.

Acute Disease↗
PubMed1990

Stability of dopamine hydrochloride injection in the presence of dobutamine hydrochloride, tolazoline hydrochloride, and theophylline injections.

Dopamine hydrochloride is widely used to increase blood pressure, cardiac output, and peripheral perfusion in critically ill newborn infants and children with shock and congestive heart failure. These patients often require numerous other intravenous drugs such as dobutamine, tolazoline, and theophylline concurrently, but have limited venous access. As a result, two or more of these drugs may be administered through the same intravenous site. The objective of our study was to determine the physical compatibility and chemical stability of dopamine with dobutamine, tolazoline, and theophylline using simulated conditions encountered in the neonatal intensive care unit. Dopamine, dobutamine, tolazoline, and theophylline were studied at concentrations of 120 mg/100 mL, 120 mg/100 mL, 400 mg/100 mL, and 400 mg/500 mL, respectively, in 5% dextrose injection. The flow rate of dopamine was 0.3 mL/h while all combination drugs were run at 1 mL/h. Aliquots were collected at hourly intervals for 5 hours. A simultaneous static experiment was also performed by mixing dopamine with each combination drug in a ratio of 1:3 and allowing these to stand at room temperature. Samples were obtained at 0.5-hour intervals for 3 hours. Each aliquot was inspected visually for any change in color and clarity and analyzed in triplicate for dopamine content using high performance liquid chromatographic technique with electrochemical detection. Linear regression analysis was performed on the mean values of dopamine concentrations to assess its degradation. Dopamine was found to be physically and chemically stable with dobutamine, tolazoline, and theophylline. Thus, dopamine can be infused concurrently with any of these drugs in 5% dextrose injected at frequently used concentrations in newborn infants.

Dobutamine↗
PubMed1989

Dopamine and dobutamine in pediatric therapy.

Dopamine hydrochloride is widely used to increase blood pressure, cardiac output, urine output, and peripheral perfusion in neonates, infants, and older children with shock and cardiac failure. Its pharmacologic effects are dose dependent, and at low, intermediate, and high dosages include dilation of renal, mesenteric, and cerebral vasculature; inotropic response in the myocardium; and increases in peripheral and renal vascular resistance, respectively. The inotropic response is diminished in neonates compared with older children and adults due to maturational differences in norepinephrine stores. The clearance of dopamine varies widely in the pediatric population, depending on age. Its elimination half-life is approximately 2 minutes in full-term neonates and older children, and may be as long as 4-5 minutes in preterm infants. Due to immaturity of the autonomic nervous system, the drug may produce some adverse respiratory responses at high dose in neonates, the most common being tachycardia and cardiac arrhythmias. Dobutamine resembles dopamine chemically and is an analog of isoproterenol. It is relatively cardioselective at dosages used in clinical practice, with its main action being on beta 1-adrenergic receptors. Unlike dopamine, it does not have any effect on specific dopaminergic receptors. Dobutamine is used to increase cardiac output in infants and children with circulatory failure. Its elimination half-life is about 2 minutes in adults and older children. No information is available about its pharmacokinetics in neonates and infants. Adverse effects such as an increase in heart rate usually occur at high dosages.

Child↗
PubMedDate not supplied

Accuracy and reliability of dosing equations to individualize theophylline treatment of apnea of prematurity.

Apnea of prematurity is associated with high morbidity and mortality. Treatment generally includes supplemental oxygen and theophylline or caffeine. The half-life of theophylline is prolonged in newborns because of their immature cytochrome P-450 system, and there is considerable variation in the drug's metabolism in infants. We compared the accuracy, precision, and reliability of two equations that use postnatal age (PNA) to determine a maintenance dosage of theophylline with a standard maintenance dosage (SMD) that produced a steady-state serum theophylline concentration (STC) of 8 micrograms/ml for apnea of prematurity in 46 infants less than 34 weeks' gestational age (GA) and less than 36 weeks' postconceptional age (PCA). The two equations were mg/kg/day = [(0.2 x PNA in wks) + 5], and mg/kg/day = [(0.3 x PNA in wks) + 8]. Their reliability to predict the SMD was determined by correlation analysis. The precision and accuracy with which they predicted SMD were determined and analyzed by chi 2. The SMD did not correlate with the maintenance dosages calculated by equations 1 and 2 (r = 0.296 and 0.296, p > 0.05 in both cases). Multiple linear regression of SMD versus GA, PNA, and PCA was not significant (r = 0.33, p = 0.32). After stratifying data based on GA and performing correlation analysis of SMD versus PNA, a weak but significant correlation (r = 0.42, p = 0.517) was found for infants with GA between 31 and 34 weeks. Poor correlation was found between SMD versus PNA for infants 27-30 weeks' GA. Two new equations of the best fit line were generated using the same data.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMedDate not supplied

Fetal exposure to lisinopril: neonatal manifestations and management.

The use of angiotensin-converting enzyme (ACE) inhibitors in pregnancy has been associated with neonatal morbidity and mortality. The mechanism of renal dysfunction likely is related to fetal hypotension and prolonged decreased glomerular filtration. Six of 14 previously published cases of neonatal renal failure after maternal ACE inhibitor therapy resulted in death. Eight infants survived after peritoneal dialysis, some with residual renal impairment. Serum lisinopril levels and ACE activity in our patient indicate that during the anuric state the drug has an extremely prolonged half-life, and that it is removed by peritoneal dialysis. In view of this prolonged half-life and the drug's continued suppression of ACE activity and renal function, we recommend institution of early dialysis in infants with renal failure after maternal therapy with lisinopril.

Adolescent↗