La frecuencia cardiaca en fetos con circular de cordón / Heart rate in fetuses with coiling of funis

Objetivo: Se determinaron los valores de la frecuencia cardiaca y la incidencia de dips tipos i y ii en los fetos con circular de cordón. Diseño del estudio La muestra la integraron 40 pacientes, se dividió en 2 grupos: Grupo 1: 20 pacientes embarazadas con diagnóstico de circular de cordón o grupo problema; Grupo 2: 20 pacientes con embarazo normal o grupo testigo. Se practicaron registros de frecuencia cardiaca fetal y contractilidad uterina durante 2 h. Para el análisis estadístico se utilizaron el programa SPSS® y las pruebas t de Student y Z. Resultados En el grupo problema la frecuencia cardiaca fetal (FCF) fue de 138 latidos por minuto (lat/min) y en el testigo de 135 lat/min. En el primer grupo, esta se incrementó 3 lat. Se calculó si la diferencia entre medias era o no significativa. Se utilizaron las pruebas de Z-score cuyo valor fue de 8,65 y p < 0,01: esta fue significativa. En los 2 grupos se calcularon los valores de la amplitud de las aceleraciones. Estas fueron semejantes: 24 lat. La diferencia entre medias no fue significativa. El análisis comparativo entre el peso y la talla de los recién nacidos en el grupo problema fue de 3.100 g y la talla de 50,72 cm. En el testigo fue de 2.960 g y 49,77 cm respectivamente. La diferencia entre medias no fue significativa. A los recién nacidos se les valoró con la prueba de Apgar. En el grupo problema, durante el primer minuto la calificación tuvo un rango de 7-9 y en el quinto de 8-9. En el grupo testigo las calificaciones fueron semejantes. Se cuantificaron los dips tipos i y ii . De los primeros dips se registraron 3 y de los segundos 2, uno con gran amplitud y duración. No se registraron dips tipo iii . En ninguno de los partos hubo presencia de meconio. Conclusiones En la circular de cordón floja: no hubo cambios significativos en la FCF. Circular de cordón apretada produjo: dips tipo ii de gran amplitud (AU)

Objective: To determine heart rate and the frequency of type i and ii dips in fetuses with coiling of funis. Study design: There were 40 patients in the sample, divided in two groups: group 1: consisted of 20 pregnant women with a diagnosis of coiling of funis; group ii consisted of 20 patients with a normal pregnancy. Fetal heart rate (HR) and uterine contractility were recorded for 2 hours. For the statistical analysis, the SPSS® package, Z-score and Student’s t-test were used. Results: Fetal HR was 138 beats/min in group 1 and 135 beats/min in group ii. The difference between medians (Z-score) was 8.65, which was significant (P<.01).Amplitude and accelerations were calculated in both groups, with similar results (24 beats).The difference in means was not significant. The mean weight and height were compared in the two groups. Mean weight was 3,100 g in group 1 and 2,960 in group 1, while mean height was 50.72 cm in group i and 49.77 in group 2.The difference in means was not significant. Apgar tests were performed in both groups. In group 1, Apgar scores ranged from 7-9 at1 minute and from 8-9 at 5 minutes. Values were similar in group 2.Type i dips gave a reading of 3, and type ii dips a reading of 2 (one with marked height and duration). No type iii dips were observed. No meconium was found in any of the deliveries. Conclusions: In pregnancies with loosely coiled funises, there were no significant changes in fetal HR. In pregnancies with tightly coiled funises, type ii dips with wide amplitude and marked duration were found (AU)

Angiotensin-II type 1 receptor (AT1R) and alpha-1D adrenoceptor form a heterodimer during pregnancy-induced hypertension.

Pregnancy courses with low response to angiotensin II and adrenergic agonists. In preeclampsia, both effects are reverted. It is known that angiotensin II regulates adrenergic system. It is not known, however, the interaction between both systems receptors. Our aim was to study if AT(1)R and alpha1D adrenoceptor heterodimerize in preeclampsia. We used subrenal aorctic coarctation in pregnant rats. Aortic tissues were prepared for confocal imaging and coimmunoprecipitated for alpha1D and AT(1) receptors. We found that AT(1)R and alpha1D adrenoceptor heterodimerize in both, healthy and preeclamptic groups. In healthy pregnant rats, heterodimer is barely detected. In preeclamptic rats however, we found higher heterodimerization. These results suggest that AT(1)R and alpha1D -adrenoceptor may form heterodimers, and may play a role in preeclampsia.

Analysis of fentanyl and norfentanyl in human plasma by liquid chromatography-tandem mass spectrometry using electrospray ionization.

This report describes a sensitive and specific high-performance liquid chromatography (HPLC)-electrospray ionization-tandem mass spectrometry (MS-MS) method for the detection of subnanogram concentrations of fentanyl and its metabolite norfentanyl in human plasma. The assay was based on a liquid-liquid extraction of 0.5 mL of human plasma, with a lower limit of quantitation (LLOQ) of 0.05 ng/mL. Sample extracts were analyzed using a ThermoQuest TSQ MS-MS interfaced with a Hewlett-Packard series 1100 HPLC and a Phenomenex (30 x 2.00-mm, 5 microLuna C18(2)) column. The intra-assay precision and accuracy ranged from 2.1 to 12.5% for both analytes at concentrations of 0.1, 0.5, 1.0, and 10 ng/mL. The interassay accuracy and precision ranged from 7.34 to 10.95%.

Pharmacokinetics and pharmacodynamics of ranitidine in critically ill children.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of ranitidine in critically ill children and to design a dosage regimen that achieves a gastric pH > or =4. DESIGN: Prospective, open-label, pharmacokinetic-pharmacodynamic study. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENTS: Mechanically ventilated, critically ill children > or =10 kg who required intravenous ranitidine for stress ulcer prophylaxis. INTERVENTIONS: Ranitidine pharmacokinetics were determined after a single intravenous dose. Gastric pH was monitored hourly via nasogastric pH probe. After the last blood sample, patients received an intravenous bolus of ranitidine (0.5 mg/kg) followed by a continuous infusion (0.1 mg x kg(-1) x hr(-1)). The infusion was increased incrementally (0.05 mg x kg(-1) x hr(-1)) until reaching gastric pH > or =4 for > or =75% of a 24-hr period, after which steady-state plasma concentrations were measured. Plasma concentrations were analyzed by high-pressure liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Twenty-three children (ranging in age from 1.4 to 17.1 yrs) were studied. Pharmacokinetic variables included a clearance of 511.7 +/- 219.7 mL x kg(-1) x hr(-1), volume of distribution of 1.53 +/- 0.99 L/kg, and half-life of 3.01 +/- 1.35 hrs. After the single intravenous dose (1.52 +/- 0.47 mg/kg), gastric pH increased from 1.6 +/- 1.0 to 5.1 +/- 1.1 (p <.001), which was associated with a plasma concentration of 373 +/- 257 ng/mL. Based on the pharmacokinetic variables, the dose of intravenous ranitidine required to target 373 ng/mL as the average steady-state concentration is 1.5 mg/kg administered every 8 hrs. During the continuous infusion, the mean steady-state ranitidine concentration associated with gastric pH > or =4 was 287 +/- 133 ng/mL. This concentration may be achieved with an intravenous loading dose of 0.45 mg/kg followed by a continuous infusion of 0.15 mg x kg(-1) x hr(-1). CONCLUSIONS: The pharmacokinetics of ranitidine in critically ill children are variable. The description of ranitidine's pharmacokinetics and pharmacodynamics in this study may used to design an initial ranitidine dosage regimen that targets a gastric pH > or =4. Thereafter, gastric pH should be monitored and the dose of ranitidine adjusted accordingly.

Albuterol delivery in a neonatal ventilated lung model: Nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers.

The aim of this study was to compare albuterol delivery in a neonatal ventilated lung model, using three delivery methods: 1) jet nebulizer; 2) chlorofluorocarbon-pressurized metered dose inhaler (CFC-MDI) actuated into an ACE(R) spacer; and 3) hydrofluoroalkane-pressurized MDI (HFA-MDI) actuated into an ACE(R) spacer. The bench model consisted of a mechanically ventilated infant test lung with ventilator settings to simulate a very low birth weight neonate with moderate lung disease. Albuterol solution (0.5%) was nebulized at the humidifier and temperature port, 125 cm and 30 cm from the Y-piece, respectively. Albuterol metered dose inhalers (MDIs) were actuated into an ACE(R) spacer that was tested in two positions: 1) inline between the endotracheal (ET) tube and the Y-piece; and 2) attached to the ET tube and administered by manual ventilation. Albuterol was collected on a filter at the distal end of the ET tube and was quantitatively analyzed by high performance liquid chromatography. Albuterol delivery by CFC-MDI (position 1, 4.8 +/- 1.0%, vs. position 2, 3.8 +/- 1.6%, P > 0.05) and HFA-MDI (position 1, 5.7 +/- 1.6%, vs. position 2, 5.5 +/- 2.4%, P > 0.05) were significantly greater than delivery by nebulization at 30 cm (0.16 +/- 0.07%) and 125 cm (0.15 +/- 0.03%) from the Y-piece (P < 0.001). A single actuation of albuterol MDI delivered the equivalent of nebulizing 2.5-3.7 mg of albuterol solution. We conclude that albuterol administered by MDI and ACE(R) spacer resulted in more efficient delivery than by nebulization in this mechanically ventilated neonatal lung model. There was no significant difference in drug delivery between CFC-MDI and HFA-MDI; nor did the placement of the spacer significantly affect drug delivery.

Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU.

STUDY OBJECTIVE: To determine if enterally administered methadone can facilitate fentanyl discontinuation and prevent withdrawal in children at high risk for opioid abstinence syndrome. DESIGN: Retrospective analysis. SETTING: Pediatric intensive care unit (PICU) in a tertiary care children's hospital. PATIENTS: Twenty-two children (aged 6.1 +/- 5.4 yrs) who received continuous fentanyl infusion for 9 days or longer. INTERVENTION: Guidelines for initiating enteral methadone, rapidly tapering and discontinuing fentanyl infusions, and tapering methadone were implemented in the PICU. Development of opioid abstinence syndrome was evaluated during fentanyl and methadone dosage reductions and for 72 hours thereafter. MEASUREMENTS AND MAIN RESULTS: Children received fentanyl by continuous infusion for 17.8 +/- 8.4 days. Peak fentanyl infusion rate was 5.9 +/- 3.8 microg/kg/hour, and the median cumulative dose was 1302 microg/kg (range 354-7535 microg/kg). Methadone 0.50 +/- 0.22 mg/kg/day was begun 1.6 +/- 1.9 days before tapering fentanyl. The fentanyl infusion rate on starting the taper was 5.0 +/- 3.6 microg/kg/hour. Fentanyl was tapered and discontinued in a median of 2.6 days (range 0-11.9 days). Twenty-one patients had no opioid abstinence syndrome during or after fentanyl taper. One patient experienced significant opioid withdrawal after fentanyl discontinuation, which resolved after reinstitution of fentanyl and increasing the dosage of methadone to 0.3 mg/kg every 6 hours. Overall, methadone was tapered and discontinued in 18.2 +/- 11.9 days without precipitating opioid abstinence syndrome. CONCLUSION: Enteral administration of methadone may expedite fentanyl discontinuation and reduce the risk of withdrawal in critically ill children at high risk for opioid abstinence syndrome.

The effect of midazolam premedication on discharge time in pediatric patients undergoing general anesthesia for dental restorations.

PURPOSE: The purpose of this study was to evaluate the effect of oral premedication with midazolam on recovery times of children undergoing dental restorations under general anesthesia. METHODS: The records of 106 children (1.2-11.3 years, ASA I or II) undergoing ambulatory dental restorations were randomly selected and retrospectively reviewed: 50 subjects received midazolam (M) 0.5 mg/kg orally approximately 30 minutes prior to their procedure and 56 control subjects received no premedication (C). General anesthesia consisted primarily of inhalational anesthesia. Time in the operating room (OR), post-anesthesia care unit (PACU) and same day surgery (SDS) were determined and compared between groups. RESULTS: Both groups were similar with respect to age and weight. There were no significant differences between groups in time spent in the OR, PACU or SDS (p>0.05). In a subset of children having shorter dental procedures (OR time < or =75 minutes, n=29), there remained no significant difference in discharge times between groups. CONCLUSIONS: Preoperative administration of oral midazolam does not delay discharge of children undergoing general anesthesia for dental rehabilitation.

The effect of confirmation calls on appointment-keeping behavior of patients in a children's hospital dental clinic.

PURPOSE: The objective of this prospective, randomized, controlled study was to evaluate whether confirmation calls made one or two working days before scheduled appointments reduce the percentage of broken appointments in a children's hospital dental clinic. METHODS: Patients were randomly assigned to three groups: 1) confirmation call made one working day before appointment, 2) confirmation call made two working days before appointment; and 3) control group (no confirmation call). Clinic staff made confirmation calls during normal office hours. Patient arrival was classified as 1) < or =15 minutes late; 2) > 15 minutes late; or 3) broken appointment. RESULTS: Three hundred and thirteen subjects were enrolled in the study: 77 subjects in group 1; 71 subjects in group 2; and 84 subjects in the control group. Eighty-one subjects (26%) could not be contacted by telephone. Overall, there was a 62% reduction in broken appointments among patients who received a confirmation call as compared to the control group. There was no significant difference between confirmation calls placed one or two working days prior to the appointment (P=0.51). Confirmation calls had no effect on punctuality. In comparing indigent care and private insurance, there was no significant difference in broken appointments. However, within the private insurance group, a confirmation call resulted in 93% of patients keeping their appointment as compared to 63% in the control group (P<0.001). No significant difference was noted in the indigent care group, with 79% of patients in the confirmation call group keeping their appointments as compared to 66% in the control group (P=. 093). CONCLUSIONS: Confirmation calls reduced the percentage of broken appointments in a pediatric dental clinic. There was no difference between calls placed one or two working days prior to the appointment. The greatest reduction in broken appointments was shown in the private insurance group.

Accumulation of CO(2) in reservoir devices during simulated neonatal mechanical ventilation.

Aerosolized albuterol is frequently administered to mechanically ventilated neonates by metered dose inhaler (MDI) and a reservoir device. These reservoirs are often placed between the Y-piece and endotracheal tube, thereby creating mechanical dead space and increasing the risk of rebreathing carbon dioxide (CO(2)). The objectives of this study were: 1) to quantify CO(2) accumulation in two commonly used reservoirs (ACE(R), Aerochamber(R)-MV) and a bidirectional nonreservoir actuator (Airlife(R) Minispacer) during mechanical ventilation of a neonatal lung model; and 2) to determine the effect of tidal volume (V(T)) on CO(2) accumulation. We hypothesized that the accumulation of CO(2) in these devices is clinically insignificant at the small tidal volumes used in mechanically ventilated premature neonates. The model was constructed to simulate CO(2) exhalation by a ventilated neonate and consisted of a neonatal ventilator circuit (rate = 40/min; peak inspiratory pressure (PIP) = 20 cm H(2)0) attached to a reservoir/actuator and neonatal test lung. The ventilator delivered inspiratory gas (room air) to the test lung, which was vented into the atmosphere by a small adjustable leak. Expiration was simulated by manually ventilating 7.1% CO(2) (partial pressure of CO(2) (PCO(2)) = 48 mm Hg) back through the model. Accumulation of CO(2) within the reservoir/actuator was measured using an end-tidal CO(2) monitor. Each 4-min experiment was conducted at three V(T) (7.5 mL, 15 mL, and 25 mL), and the median PCO(2) was calculated in 0.5-min increments. For V(T) = 7.5 mL, CO(2) accumulated slowly in the ACE(R) and Minispacer(R) and reached a maximum at 4.0 min (PCO(2) = 2.3 mm Hg and 7.3 mm Hg, respectively). In contrast, the Aerochamber(R)-MV rapidly reached a PCO(2) of 9.5-10.0 mm Hg by 1-1. 5 min. A similar trend occurred with V(T) = 15 mL; however, higher partial pressures (approximately 10-12 mm Hg) were achieved with all devices. At V(T) = 25 mL, PCO(2) rose rapidly with the ACE(R), Aerochamber(R)-MV, and Minispacer(R), reaching peaks of 17.2, 12.3, and 20.3 mm Hg, respectively (P < 0.05). In conclusion, accumulation of CO(2) in reservoir/actuator depends on V(T) as well as the chamber design and internal volume. Due to the short duration of use when administering drugs via MDI, accumulation of CO(2) in these devices is not likely to be clinically relevant for the majority of ventilated newborns.

A cost analysis of enterally administered lorazepam in the pediatric intensive care unit.

OBJECTIVE: To determine the cost savings of replacing intravenous midazolam with enterally administered lorazepam in mechanically ventilated children who require long-term continuous sedation. DESIGN: Retrospective review of patients treated according to a preestablished pediatric intensive care unit (ICU) sedation protocol. SETTING: Twenty-six-bed pediatric ICU in a tertiary care children's hospital. PATIENTS: The records of 30 mechanically ventilated children were analyzed. The median age was 1.5 yrs and the median weight was 8.0 kg. Patients required continuous sedation for a total of 16 days (median). INTERVENTIONS: According to our pediatric ICU sedation protocol, midazolam infusion was continued until the hourly midazolam requirement was stable for at least 24 hrs. Thereafter, patients with a nasojejunal tube who were likely to require a minimum of three additional days of continuous sedation were transitioned from intravenous midazolam to enterally administered lorazepam. The goal in transitioning therapy was to titrate the lorazepam dose and reduce midazolam administration while maintaining an unchanged level of sedation. MEASUREMENTS AND MAIN RESULTS: The rate of midazolam administration was significantly (p<.05) reduced beginning on day 1 of lorazepam treatment. Midazolam was successfully discontinued in 24 (80%) patients in 3 days (median), and adequate and appropriate sedation was maintained with lorazepam monotherapy. Six patients in whom midazolam could not be discontinued experienced a 52% reduction in the rate of midazolam administration as a result of adding lorazepam. Total projected midazolam utilization was defined as the sum of midazolam administration before initiating lorazepam and the projected midazolam requirement after initiating lorazepam. Projected midazolam cost was calculated as the product of total projected midazolam utilization and midazolam acquisition cost. Actual expenditures for both midazolam and lorazepam were subtracted from the projected midazolam cost to calculate the estimated cost savings. Overall, midazolam utilization (in milligrams) was reduced by 46.7+/-27.6% (median 52). Total projected midazolam cost for the 30 patients was $90,771. The actual cost of midazolam and lorazepam combined was $47,867, resulting in a cost savings of $42,904. CONCLUSIONS: Transitioning from intravenous midazolam to enterally administered lorazepam in critically ill children who require long-term sedation results in significant cost savings. The oral formulation of lorazepam was convenient to use, inexpensive, and effective in maintaining a continuous and appropriate level of sedation once midazolam was discontinued.

Gastric pH control in critically ill children receiving intravenous ranitidine.

OBJECTIVE: To determine whether the dose of ranitidine recommended in commonly used pediatric drug dosage handbooks (2 to 4 mg/kg/day i.v.) results in successful gastric pH control (pH of >4) in critically ill children. DESIGN: Prospective sample. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENTS: Fifty consecutive patients who received >24 hrs of scheduled intermittent intravenous ranitidine for stress ulcer prophylaxis were enrolled in the study. Patients with renal or hepatic dysfunction and those who received enteral nutrition through the nasogastric tube were excluded from enrollment. INTERVENTION: Gastric pH was determined at the end of the ranitidine dosing interval, 1 hr after the dose, and at the midpoint between doses. All pH measurements were made from a sample of nasogastric aspirate, using pH sensitive paper. Gastric pH control with ranitidine was considered unsuccessful (poorly controlled) if the pH was <4 for any of the three measurements. MEASUREMENTS AND MAIN RESULTS: Forty-five patients (median age 36 mos; range 2 wks to 264 mos) were included in the analysis. Eighty-two percent of the patients were mechanically ventilated, 16% were pharmacologically paralyzed, 18% required vasoactive infusions, 36% were nourished via transpyloric feeding tubes, and 7% received total parenteral nutrition. Gastric pH was poorly controlled in 36% of patients. Among these patients, the pH at the end of the dosing interval was significantly lower than the pH measured at 1 hr or at the midpoint between doses (p < .05). Seventy-one percent of patients who received <3 mg/kg/day of ranitidine had poor gastric pH control as compared with 19% who received a minimum of 3 mg/kg/day (p< .05). Poor control of gastric pH was not associated with feeding, intubation status, presence of pharmacologic paralysis, use of vasoactive infusions, or age (p > .05). CONCLUSIONS: The minimum ranitidine dose recommended in commonly used pediatric drug references resulted in unsuccessful gastric pH control in a high percentage of pediatric intensive care unit patients. Critically ill children with normal renal and hepatic function should be treated with a minimum 3 mg/kg/day of intravenous ranitidine and the dose should be titrated to a gastric pH of > or =4.

Albuterol in acute bronchiolitis--continued therapy despite poor response?

To determine whether clinicians continue to treat acute bronchiolitis with nebulized albuterol despite lack of clinical improvement after such treatment, we reviewed the medical records of 90 randomly selected infants and children with the primary diagnosis of that disorder who were treated in this 232-bed tertiary care children's hospital. Clinical improvement and no clinical improvement were defined as improvement and lack of improvement, respectively, in air movement, wheezing, retractions, oxygen saturation, work of breathing, and respiratory rate after administration of nebulized albuterol. Response to nebulized albuterol was determined from explicit written documentation in the medical records. Of 68 children who received nebulized albuterol in the emergency department, 52% had written documentation indicating no clinical improvement; however, 94% had admission orders to continue the therapy. Within 12 hours after admission, 61% were again noted to have no clinical improvement with nebulized albuterol. Eighty-seven percent of nonresponders continued to receive albuterol throughout hospitalization, and 54% continued to receive it after discharge. Continuing therapy despite lack of response resulted in unnecessary medical expenses.

Evaluation of intranasal midazolam in children undergoing esophagogastroduodenoscopy.

BACKGROUND: Intravenous midazolam and opioids are used to produce conscious sedation in children undergoing esophagogastroduodenoscopy (EGD). However, children may experience significant fear and anxiety before receiving these medications, especially during separation from parents and during venipuncture. Intranasal administration of midazolam represents a noninvasive method of sedating children before anxiety-producing events. The objective of this study was to determine whether premedication with intranasal midazolam reduces stress and anxiety of separation from parents and of undergoing venipuncture, while maintaining adequate sedation during EGD. METHODS: This was a prospective, randomized, double-blind study in 40 children, aged 2 to 12 years, who were undergoing EGD. Patients in group I were premedicated with intranasal placebo (0.9% NaCl) followed 10 minutes later by intravenous midazolam (0.05 mg/kg) and intravenous meperidine (1 mg/ kg). Patients in group II were premedicated with intranasal midazolam (0.2 mg/kg) followed by intravenous placebo (0.9% NaCl) and intravenous meperidine (1 mg/kg). Anxiolysis and sedation were scored by a blinded observer, who identified minor and major negative behaviors during four observation periods: intranasal drug administration, separation from parents, venipuncture, and EGD. RESULTS: Premedication with intranasal midazolam significantly reduced negative behaviors during separation from parents (p < 0.05); however, no difference between regimens was noted during venipuncture or EGD. Negative behaviors appeared to increase during administration of intranasal midazolam or placebo. CONCLUSIONS: Premedication with intranasal midazolam is effective in reducing negative behaviors during separation from parents, while it maintains sedation during the endoscopic procedure. The benefits of intranasal administration may be negated, however, by irritation, and discomfort caused by intranasal drug delivery.

Treatment of convulsive status epilepticus with propofol: case report.

INTRODUCTION: Convulsive status epilepticus (CSE) refractory to treatment with benzodiazepines, phenobarbital, and phenytoin presents a challenge to pediatric emergency and critical care specialists. Prompt seizure control may prevent mortality and morbidity. CASE: A nine-month-old girl with hereditary fructose intolerance had prolonged, refractory CSE. Her seizures promptly stopped after administration of propofol (3 mg/kg bolus followed by infusion of 100 micrograms/kg/min). This dose resulted in electroencephalographic burst suppression. She required endotracheal intubation, invasive hemodynamic monitoring, and pressor support. DISCUSSION: This is the first pediatric case of prolonged, refractory CSE treated with propofol. The adult experience is reviewed. Propofol should be used only in a setting where definitive airway control and hemodynamic support is possible.

Pharmacokinetics of dexamethasone in premature neonates.

OBJECTIVE: Dexamethasone is frequently used in premature neonates with bronchopulmonary dysplasia, however little is known about its disposition in this population. METHODS: We evaluated the pharmacokinetics of dexamethasone in 9 premature neonates with a mean gestational age of 27.3 weeks and a postnatal age of 21.8 days. RESULTS: There was a strong relationship between clearance (4.96 ml.min-1.kg-1) and gestational age ( r = 0.884). Pharmacokinetic parameters were grouped based on a gestational age of less than 27 weeks (Group I) and greater than 27 weeks (Group II). Mean clearance in group I and group II was 1.69 and 7,57 ml.min-1.kg-1, respectively. Mean distribution volume in group I and II was 1.26 and 2.19 l.kg-1, respectively. No significant relationships were noted between the disposition of dexamethasone and ventilator requirements or adverse effects. CONCLUSION: The pharmacokinetics of dexamethasone in premature neonates was related to gestational age.

Stability of diluted dexamethasone sodium phosphate injection at two temperatures.

OBJECTIVE: Premature neonates with bronchopulmonary dysplasia frequently are treated with intravenous dexamethasone for their chronic lung disease. The injection volumes of the commercially available products often are too small to measure accurately. The objective of this study was to evaluate the stability over 28 days of dexamethasone sodium phosphate injection 4 mg/mL diluted with bacteriostatic NaCl 0.9% to 1 mg/mL. DESIGN: Ten vials of dexamethasone 1 mg/mL were prepared from dexamethasone sodium phosphate injection, USP 4 mg/mL and bacteriostatic NaCl 0.9% injection. Five vials were stored at 4 degrees C and five at 22 degrees C. Dexamethasone was measured on days 0, 1, 3, 7, 14, 21, and 28 by an accurate, reproducible, and stability-indicating HPLC method. Samples were also inspected visually for precipitation or discoloration on each study day. RESULTS: The samples retained at least 97.7 percent of the original concentration of dexamethasone sodium phosphate when stored at either 4 or 22 degrees C for 28 days. No discoloration or precipitation was observed. CONCLUSIONS: Dexamethasone sodium phosphate injection 1 mg/mL in bacteriostatic NaCl 0.9% was stable for 28 days at 4 and 22 degrees C.