Pharmacokinetics of recombinant human erythropoietin in children with renal failure.

The single-dose pharmacokinetics of recombinant human erythropoietin (rHuEpo; 40 units/kg1) were investigated in children (9-16 years) with end-stage renal failure. After an intravenous (i.v.) dose, serum rHuEpo concentrations declined in a monoexponential manner with a mean half-life (t1/2) of 5.6 +/- 3 h (+/- SEM; n = 9). Serum clearance and the apparent volume of distribution were estimated to be 10.1 +/- 0.9 ml h-1 kg-1 and 79.5 +/- 5.0 ml kg-1 (n = 9) respectively. Subcutaneous (s.c.) delivery resulted in serum values that peaked at 10 h, and thereafter concentrations declined slowly with a t1/2 of 21.1 +/- 4.5 h (n = 9). Serum rHuEpo concentrations were maximal at 14 h after i.p. administration and the t1/2 was 9.5 +/- 1.0 h (n = 3). The mean fraction absorbed of SC rHuEpo was 0.40 whereas after i.p. administration this fraction was only 0.17. These results show that after both s.c. and i.p. delivery, disposition of the hormone is rate-limited by absorption, and bioavailability for these extravascular routes is poor. In addition, comparison of the results with those available for adults indicates that rHuEpo is better absorbed but more rapidly cleared in children.     

The pharmacokinetics of the intravenous formulation of fentanyl citrate administered orally in children undergoing general anesthesia

The bioavailability of oral transmucosal fentanyl citrate (OTFC) in children is similar to that of fentanyl solution administered orally to adults. We hypothesized that administering an oral fentanyl solution to children would result in similar fentanyl plasma concentrations and pharmacokinetic variables as administering comparable doses of OTFC. In this pilot study, 10 healthy children requiring postoperative analgesia were enrolled. Each received the undiluted IV fentanyl formulation orally (approximately 10-15 microg/kg; maximum, 400 microg). Venous blood samples were collected from 15 to 600 min after administration. Pharmacokinetic variables were determined using noncompartmental analysis and were compared with a previously studied population of children who received a similar dose of OTFC. Pharmacokinetic variables for the orally administered IV fentanyl formulation were as follows: time to reach peak concentration = 1.7 +/- 1.6 h, peak concentration = 1.83 +/- 1.19 ng/mL, half-life = 4.7 +/- 2.8 h, area under the plasma concentration time curve = 6.46 +/- 3.96 h . ng(-1) . mL(-1), apparent oral volume of distribution (V/F) = 17.5 +/- 7.2 L/kg, apparent oral clearance (CL/F) = 3.33 +/- 2.25 L . kg(-1) . h(-1). Although both OTFC and orally administered IV fentanyl resulted in similar pharmacokinetic variables and plasma concentrations for a given dose, there was marked interpatient variability, particularly in the early hours after oral administration of the IV formulation of fentanyl. This suggests that this method of administration be used with caution until further data are available.     

Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy

Osteoclastogenesis inhibitory factor (OCIF) is a novel secreted protein that inhibits osteoclastogenesis both in vitro and in vivo. In this study, we examined the effects of OCIF on serum calcium (Ca) concentrations in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. In normal mice, a single intraperitoneal injection of OCIF reduced serum Ca levels in a dose-dependent manner. Significant decrease in serum Ca (by 1.6 ± 0.3 mg/dL, n = 5) was observed 2 h after the injection of OCIF at 20 mg/kg and the hypocalcemic effect continued for up to 12 h. Serum phosphate (Pi) concentrations also decreased in response to OCIF. Urinary excretion of Ca, Pi, and creatinine did not change significantly after injection of OCIF or vehicle. In hypercalcemic, tumor-bearing nude mice, a single intraperitoneal injection of OCIF at 20 mg/kg resulted in a dramatic decrease in serum Ca (maximal decrease 2.8 ± 0.37 mg/dL, n = 11), which continued for up to 24 h. The results suggest that OCIF decreased serum Ca through its inhibitory effect on bone resorption. Furthermore, it is suggested that OCIF has therapeutic potential for the treatment of hypercalcemic conditions such as malignancy-associated hypercalcemia.     

氨溴索预先给药对兔单肺通气时肺损伤的影响

目的 评价氨溴索预先给药对兔单肺通气时肺损伤的影响.方法 家兔67只随机分为4组,麻醉下气管插管,机械通气,A组(n=18)持续双肺通气4 h,B组(n=16)、C组(n=15)和D组(n=18)单肺通气2 h后恢复双肺通气2 h,C组和D组在单肺通气前分别静脉注射氨溴索5、15 mg/kg(生理盐水稀释至20 ml),B组给予等容量生理盐水.分别于麻醉前(基础状态)、单肺通气1、2 h、恢复双肺通气1、2 h时采集静脉血样,测定血清超氧化物歧化酶(SOD)活性、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和IL-8浓度,进行白细胞(WBC)计数和中性粒细胞计数,最后一次采集血样后,处死动物,取双侧肺组织,光镜下观察肺组织病理学.结果 与A组比较,B组、C组和D组SOD活性降低,TNF-α、IL-6、IL-8、WBC计数和中性粒细胞计数升高(P<0.05或0.01).与B组比较,C组和D组SOD活性升高,TNF-α、IL-6、IL-8、WBC计数和中性粒细胞计数降低(P<0.05或0.01).C组和D组间上述指标差异无统计学意义(P>0.05).A组双侧肺组织未见明显损伤;C组和D组非通气侧肺组织损伤轻于B组.结论 静脉注射氨溴索5、15 mg/kg可减轻单肺通气诱发兔肺损伤,其机制与抑制炎性反应及脂质过氧化反应有关.     

Bioartificial Liver Using Hepatocytes on Biosilon Microcamers: Treatment of Chemically Induced Acute Hepatic Failure in Rats

An artificial liver support procedure based on hemoperfusion via hepatocytes cultured on microcarriers is described. The efficiency of the system was assessed by the survival rate of rats treated with either lethal dosage of 7% CCl4 [30 ml/kg body weight (b.w.)] or D-galactosamine (2.5 g/kg b.w.). In CCl4-treated rats, hemoperfusion via empty microcarriers (n = 16) revealed no surviving animals, whereas the use of the bioartificial liver (n = 11) resulted in 80% (p less than 0.01) and 60% (p less than 0.05) survival 48 and 168 h after hepatotoxin, respectively. For the same time periods, the survival rate in D-galactosamine-intoxicated rats after hemoperfusion with hepatocytes (n = 20) was approximately 60% (p less than 0.05) and was only 5% in those of rats treated with empty microcarriers (n = 20). Sublethal dosage of 7% CCl4 (15 ml/kg b.w.) caused 25% mortality and prolonged (48 h) increase of activity of the liver enzymes and bilirubin levels in the serum of surviving animals. In these rats (n = 8) at the end of 3 h of hemoperfusion via hepatocytes, the bilirubin concentration decreased by 45% as compared with the control group (n = 6) treated with empty microcarriers. Moreover, by 48 h after intoxication, the use of the bioartificial liver resulted in more than a three-fold decrease in glutamate-oxaloacetate transaminase and a 10-fold decrease in glutamate-pyruvate transaminase serum activity as well as a fivefold decline in total and a ninefold decline in conjugated bilirubin levels as compared with the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Initial and Subsequent Dosing of Rectal Acetaminophen in Children: A 24-Hour Pharmacokinetic Study of New Dose Recommendations

Background: Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors' previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10-20 [mu]g/ml, without evidence of accumulation.

Methods: Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration.

Results: All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, the target range was maintained 60 +/- 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 [mu]g/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses.     

Diclofenac or acetaminophen for analgesia in paediatric tonsillectomy outpatients

BACKGROUND: In order to establish an effective drug regimen, we compared the analgesic efficacy of oral diclofenac and high-dose acetaminophen on pain after tonsillectomy. METHODS: In this randomised, double-blind study 48 children, 5 to 15 years of age, following tonsillectomy were assigned to receive either diclofenac 2-3 mg kg(-1) 24 h(-1) (n=24) or acetaminophen 90 mg kg(-1) 24 h(-1) (n=24) for the first three days after surgery. Postoperative pain was assessed by self-report each day before scheduled medication at 7 h, 12 h, 18 h and 23 h. RESULTS: The number of children rating severe pain was high in both the diclofenac group, 5-50%, and in the acetaminophen group, 12-58% during the three day study period. Pain scores in the diclofenac group were only significantly lower at 12 h on day 1-3 compared to pain scores in the acetaminophen group (P<0.05). None of the children in the diclofenac group experienced any episodes of nausea/vomiting compared to 9 children in the acetaminophen group on day 1. The incidences of nausea/vomiting increased with pain (P<0.05). None of the 48 children experienced any episodes of bleeding. CONCLUSIONS: This study indicates that diclofenac was no more effective than high-dose acetaminophen (90 mg vs. 60 mg kg(-1) 24 h(-1)) for analgesia, but resulted in a lower incidence of nausea and vomiting in patients following tonsillectomy.     

Critical timing of bladder embryogenesis in an adriamycin-exposed rat fetal model: a clue to the origin of the bladder

BACKGROUND/PURPOSE: Administration of Adriamycin (ADR) in utero to pregnant rats (vaginal plug, day 0) on gestational days (GD) 6 to 9 resulted in the offspring having a cluster of malformations, including absence of bladder in 100% of cases. This study aimed to determine the critical timing of the embryological window in bladder development in this animal model. METHODS: Timed-pregnant rats were divided randomly and injected intraperitoneally with ADR at 2 mg/kg on GD 6 to 9; GD 7 to 10; GD 8 to 11; GD 9 to 12; GD 6,8, and 9 (missing GD 7); and GD 6, 7, and 9 (missing GD 8). The control group received saline. Fetuses were harvested near term on GD 21 and dissected under a dissecting microscope and examined for gross anorectal and urogenital anomalies. RESULTS: Administration of ADR on GD 6 to 9 (n = 63); GD 7 to 10 (n = 42); and GD 6, 7, and 9 (n = 35) resulted in 100%, 83%, and 77% bladder agenesis respectively, in contrast with 53% and 26% on GD 8 to 11 (n = 36) and GD 6, 8, and 9 (n = 49), respectively. The control (n = 52) and the GD 9 to 12 (n = 27) groups all had normal bladder development. The proportion of other urogenital and anorectal anomalies mirror that of bladder agenesis. CONCLUSION: The results showed GD 7 to be the critical embryological timing in which bladder development can be affected by ADR, possibly by targeting the gene that is expressed in the embryonic bladder during this narrow time interval.     

Glycopeptide pharmacokinetics in current paediatric cardiac surgery practice.

OBJECTIVE: To examine the evolution of serum concentrations of prophylactic glycopeptides administered during state-of-the-art cardiopulmonary bypass (CPB) and vigorous haemodiafiltration in paediatric patients undergoing cardiac surgery. METHODS: We enrolled infants and children <3 years of age who, based on the preoperative microbiological screening, age and surgical complexity, were at high risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Antimicrobial prophylaxis with glycopeptides was administered to 22 patients, randomly assigned to vancomycin (VAN; n=11) versus teicoplanin (TEC; n=11). Fixed doses of each drug (15 mg/kg for VAN and 8 mg/kg for TEC) were administered immediately before the operation, at the time of priming of the extracorporeal circuit, upon admission to the intensive care unit and for 48 h thereafter, q. 8 h for VAN, and once daily for TEC. Vigorous haemodiafiltration was applied during and briefly after CPB. RESULTS: The second dose of drug added to the prime prevented a fall in serum drug concentrations at the onset of CPB in both groups. A 77% decrease in VAN, versus 53% in TEC concentrations, was observed after the conclusion of CPB. Serum concentrations of TEC>10 microg/ml were observed throughout the treatment period in 91% of patients, while 55% of patients assigned to VAN had serum concentrations consistently >5 microg/ml (p=0.08). Therapeutic serum concentrations were maintained throughout the intraoperative period, particularly with TEC, administered before the first surgical incision, followed by a supplemental bolus in the priming fluid of CPB. Postoperative surgical wound infections occurred in neither group. CONCLUSIONS: The prophylactic use of glycopeptides in paediatric patients at high risk of MRSA infection undergoing cardiac surgery was safe and effective. TEC might be the drug of choice, since stable, therapeutic serum concentrations were easily maintained throughout the treatment period.     

Perioperative pharmacokinetics of ibuprofen enantiomers after rectal administration

BACKGROUND: Ibuprofen is a nonsteroidal anti-inflammatory drug which has both peripheral and central analgesic effects. Ibuprofen has been shown to be an effective antipyretic and postoperative analgesic drug both in adults and children with few side effects. Pharmacokinetics of rectal ibuprofen has not been studied, although suppositories are frequently used for perioperative pain control in children. METHODS: There were four study groups: full-term infants aged 1-7 weeks (n = 9), infants aged 8-25 weeks (n = 8), and infants aged 26-52 weeks (n = 7). Adult patients were 20-40 years old (n = 7). Ibuprofen suppository 20 mg.kg(-1) was administered after induction of anesthesia. Blood samples were collected from 20 min to 10 h after dosing and pharmacokinetic analysis of ibuprofen enantiomers were done. RESULTS: Both ibuprofen enantiomers were detectable in blood in 20 min. Total ibuprofen plasma concentrations >10 mg.l(-1) were seen from 40 min to 8 h. Values for T(max) of ibuprofen enantiomers and total ibuprofen were higher in the adult group than any of the infant groups (P < 0.05). In addition, values for physiological (standardized) t(1/2) of (R)-(-)- and (S)-(+)-ibuprofen were higher in infants aged 1-7 weeks than the adults (P < 0.05). None of the other pharmacokinetic variables, C(max), AUC, chronological t(1/2) or AUC ratio differed between the groups. CONCLUSIONS: A single dose of ibuprofen suppository 20 mg.kg(-1) after induction of anesthesia guarantees analgesic plasma concentrations during the early postoperative period. Except for the delayed absorption of ibuprofen in adults and higher physiological t(1/2) in infants aged 1-7 weeks, no major pharmacokinetic differences were observed between study groups.     

Initial and subsequent dosing of rectal acetaminophen in children: a 24-hour pharmacokinetic study of new dose recommendations

BACKGROUND: Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors' previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10-20 microg/ml, without evidence of accumulation. METHODS: Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration. RESULTS: All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, the target range was maintained 60 +/- 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 microg/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses. CONCLUSIONS: A rectal acetaminophen loading dose of 40 mg/kg followed by 20-mg/kg doses every 6 h results in serum concentrations centered at the target range of 10-20 microg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.     

Continuous fluid resuscitation and splenectomy for treatment of uncontrolled hemorrhagic shock after massive splenic injury

BACKGROUND: Using a standardized massive splenic injury (MSI) model of uncontrolled hemorrhagic shock, we studied the effect of continuous fluid resuscitation and splenectomy on the hemodynamic response and survival in rats. METHODS: The animals were randomized into seven groups: group 1 (n = 8), sham-operated; group 2 (n = 8), MSI untreated; group 3 (n = 8), MSI treated with 7.5 mL/kg/h of 7.5% NaCl (hypertonic saline [HTS]) for 1 hour; group 4 (n = 8), MSI treated with 7.5 mL/kg/h hydroxyethyl starch (HES-7.5) for 1 hour; group 5 (n = 8) MSI treated with 35 mL/kg/h Ringer's lactate (RL) solution (RL-35) for 1 hour; group 6 (n = 8) MSI treated with 70 mL/kg/h RL for 1 hour (RL-70); and group 7 (n = 8), MSI treated with 105 mL/kg/h RL for 1 hour (RL-105). In all MSI groups, splenectomy was performed 45 minutes after injury. RESULTS: MSI in untreated group 2 resulted in a fall of mean arterial pressure from 105.9 +/- 10.7 mm Hg to 27.0 +/- 6.7 mm Hg (p < 0.001) in 60 minutes. Mean survival time after splenectomy in this group was 160.7 +/- 29.7 minutes, and total blood loss was 34.8 +/- 4.7% of blood volume. Continuous HTS infusion with splenectomy in group 3 was followed by a total blood loss of 38.7 +/- 4.4% and mean survival time was 176.5 +/- 23.2 minutes. HES-7.5 infusion and splenectomy was followed by a total blood loss of 39.6 +/- 2.5% and survival time was 171.6 +/- 19.5 minutes. Continuous infusion of increasing volumes of RL in groups 5, 6, and 7 was followed by increase in blood loss to 29.0 +/- 4.1%, 50.2 +/- 3.1% (p < 0.001), and 62.7 +/- 7.1% (p < 0.002) of total blood volume, respectively. Mean survival time in groups 5, 6, and 7 was 233.5 +/- 6.5 minutes (p < 0.04), 207.6 +/- 17.0 minutes (p < 0.05), and 158 +/- 26 minutes, respectively. CONCLUSION: Continuous infusion of large-volume RL and splenectomy after massive splenic injury resulted in a significant increase in intra-abdominal bleeding and shortened survival time compared with small-volume RL infusion.     

Oral dexmedetomidine attenuates hemodynamic responses during emergence from general anesthesia in chronically instrumented dogs.

This investigation evaluated the hemodynamic effects of orally administered dexmedetomidine in chronically instrumented dogs in the conscious state, during enflurane anesthesia, and after emergence. Four experimental groups (n = 9 each) were completed. In groups 1 and 2, dexmedetomidine (10 or 20 micrograms/kg, respectively) was administered orally, and hemodynamics, arterial blood gas tensions, and plasma norepinephrine concentrations were monitored for 6 h. Animals in groups 3 and 4 were given dexmedetomidine (20 micrograms/kg) or placebo orally, and hemodynamics, arterial blood gas tensions, and plasma norepinephrine concentrations were measured 1 h later with animals in the conscious state, after 30 min of enflurane anesthesia (1.0 MAC), and 2 and 7 min after extubation. Oral administration of dexmedetomidine resulted in sedation with significant decreases in heart rate (76 +/- 4 to 49 +/- 4 beats per min), rate-pressure product (11,500 +/- 650 to 6,100 +/- 600 mmHg. beats per min), cardiac output (2.2 +/- 0.2 to 1.2 +/- 0.4 l/min), and plasma norepinephrine concentrations (290 +/- 50 to 135 pg/ml). Peak effects occurred within 30 min and lasted approximately 3 h. No reduction in coronary blood flow velocity, decrease in regional contractile function, or respiratory depression was observed. Administration of dexmedetomidine before enflurane anesthesia also was associated with a reduction in heart rate and rate-pressure product, and dexmedetomidine prevented the increase in heart rate (146 +/- 9 vs. 60 +/- 7 beats per min) and arterial pressure (117 +/- 7 vs. 98 +/- 7 mmHg) during emergence from anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytokines in childhood hemolytic uremic syndrome and thrombotic thrombocytopenic purpura

Serum and urine cytokines were analyzed in children with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Interleukin-6 (IL-6) was elevated in the serum of 33 of 35 children with HUS (94%) and in 2 of 2 children with recurrent TTP. Serum IL-6 was higher in children with HUS who developed anuria, extrarenal manifestations during the acute phase of illness and/or chronic renal sequelae. Tumor necrosis factor- (TNF-) was detected in the serum of 7 patients with HUS (20%) and 1 patient with TTP. IL-6 and TNF- were elevated in the urine of 4 of 4 children with HUS and 2 of 2 children with TTP. Urinary levels were higher than serum levels, suggesting local production of cytokines in the urinary tract. Sequential serum and urine samples showed that IL-6 levels varied with disease activity. IL-6 and TNF- were not detected in the serum (n=25) and urine (n=15) of healthy children. We conclude that IL-6 in urine may be used to monitor disease activity in HUS and TTP.     

C-Reactive protein-determined injury severity: length of stay predictor in surgical infants

Background/Purpose

Serum C-reactive protein (CRP) levels reflect the severity of the metabolic response to injury in critically ill children. During this period, caloric overfeeding can increase complications and delay recovery. The authors hypothesized that by avoiding excessive caloric delivery, the effect of injury severity would be the major factor determining clinical outcome.

Methods

Twenty-eight surgical infants who had indirect calorimetry measurements while in the Neonatal Intensive Care Unit between August 2000 and January 2002 were studied. Serum CRP concentrations, mean energy expenditure (MEE), respiratory quotient (RQ), length of hospital stay (LOS), and caloric intake (I) at the time of indirect calorimetry were recorded. Data were analyzed using the Pearson product-moment correlation.

Results

Peak serum CRP was significantly correlated to LOS in all patients (r = 0.79, P < .0001). When net caloric balance (I-MEE) did not exceed 5 kcal/kg/d (n = 9), peak serum CRP was correlated positively with RQ (r = 0.66, P = .05). When I-MEE exceeded 5 kcal/kg/d (n = 19), the positive correlation of serum CRP with RQ was diminished (r = 0.23, P = .33).

Conclusions

CRP-measured injury severity is a major determinant of clinical outcome in surgical infants. In addition, overfeeding causes additional RQ elevation.     

The effects of dextrose infusion and head position on neurologic outcome after complete cerebral ischemia in primates: examination of a model

The hypothesis that iv dextrose infusion prior to--and head position during--cerebral ischemia would influence the severity and pattern of neurologic injury was tested in primates. Fifteen pigtail monkeys weighing 3.3 +/- 0.2 kg (mean +/- SE) were subjected to 17 min complete cerebral ischemia followed by 24 h intensive care treatment and neurologic assessment for an additional 72 h. Monkeys were given 50 ml iv infusions of either dextrose 5% in 0.45% saline solution (n = 8) or lactated Ringer's solution (n = 7) during the preparatory period. This volume corresponds to approximately 1 1/70 kg individual. These same monkeys were placed in either the lateral (n = 3), prone (n = 5), or supine (n = 7) position during the ischemic period. Two monkeys failed to meet preestablished protocol criteria and were excluded from data analysis. Blood glucose immediately preischemia in the dextrose-treated group (181 +/- 19 mg X dl-1) was not significantly greater than in the group given lactated Ringer's solution (140 +/- 6 mg X dl-1; P = 0.07). Dextrose infusion resulted in significantly greater cerebral injury at 96 h postischemia when comparing both neurologic (P less than 0.05) and histopathology (P less than 0.05) scores. Specifically, dextrose administration resulted in the greatest injury to the insular cortex, thalamus, Purkinje cells, and substantia nigra. Although blood glucose was less than 250 mg X dl-1 in all monkeys at the time of complete cerebral ischemia, there was a high correlation between blood glucose rank and neurologic function rank (rs = 0.76; P less than 0.005). The authors were unable to note any effect of head position on the distribution of histopathologic lesions. Prior to removing the brain for histopathologic studies, four monkeys were given repeat infusions of 50 ml dextrose 5% in 0.45% saline solution over 11 +/- 1 min. These infusions produced increases in blood glucose from 56.7 +/- 7.6 to 244 +/- 24.9 mg X dl-1 (P less than 0.01) and increases in brain glucose from 1.64 +/- 0.22 to 5.11 +/- 0.48 mumol X g-1 (P less than 0.01).     

Serum S100B concentrations are increased after closed head injury in children: a preliminary study

Traumatic brain injury (TBI) is a leading cause of death and disability in children. The current gold standards for diagnosis of TBI after closed head injury (CHI) have limitations, particularly in cases of inflicted injury. S100B is a protein that is specific to astrocytes. Serum S100B concentrations are increased in adults after CHI; there are no studies of serum S100B after CHI in children. The goal of this study was to measure the serum concentrations of S100B in children inflicted and noninflicted mild, moderate, and severe CHI. CHI severity was defined by initial Glasgow Coma Scale score. Forty-five children aged 0-13 years with mild (n = 27), moderate (n = 6), and severe (n = 12) CHI were enrolled prospectively. Blood was obtained as soon as possible after injury (range: 0.5-15.25 h) and every 12 h for up to 5 days when vascular access was available. Single control samples were obtained from 16 children aged 0-11 years with isolated long-bone fractures. Twenty-two patients (49%), including both patients with inflicted CHI, had an abnormal initial serum S100B concentration where an abnormal concentration was defined as greater than mean control concentration plus two standard deviations. S100B was detectable more than 12 h after injury only in patients with severe CHI. We conclude that serum S100B is increased in almost half of children after mild, moderate, and severe inflicted and noninflicted CHI. The increase is transient, lasting less than 12 h after injury, except in children with severe injury. Future research will focus on the possibility of using serum S100B as a screening test for inflicted CHI.     

Effect of intraoperative fluid management on outcome after intraabdominal surgery

BACKGROUND: The debate over the correct perioperative fluid management is unresolved. METHODS: The impact of two intraoperative fluid regimes on postoperative outcome was prospectively evaluated in 152 patients with an American Society of Anesthesiologists physical status of I-III who were undergoing elective intraabdominal surgery. Patients were randomly assigned to receive intraoperatively either liberal (liberal protocol group [LPG], n = 75; bolus of 10 ml/kg followed by 12 ml x kg(-1) x h(-1)) or restrictive (restrictive protocol group [RPG], n = 77; 4 ml x kg(-1) x h(-1)) amounts of lactated Ringer's solution. The primary endpoint was the number of patients who died or experienced complications. The secondary endpoints included time to initial passage of flatus and feces, duration of hospital stay, and changes in body weight, hematocrit, and albumin serum concentration in the first 3 postoperative days. RESULTS: The number of patients with complications was lower in the RPG (P = 0.046). Patients in the LPG passed flatus and feces significantly later (flatus, median [range]: 4 [3-7] days in the LPG vs. 3 [2-7] days in the RPG; P < 0.001; feces: 6 [4-9] days in the LPG vs. 4 [3-9] days in the RPG; P < 0.001), and their postoperative hospital stay was significantly longer (9 [7-24] days in the LPG vs. 8 [6-21] days in the RPG; P = 0.01). Significantly larger increases in body weight were observed in the LPG compared with the RPG (P < 0.01). In the first 3 postoperative days, hematocrit and albumin concentrations were significantly higher in the RPG compared with the LPG. CONCLUSIONS: In patients undergoing elective intraabdominal surgery, intraoperative use of restrictive fluid management may be advantageous because it reduces postoperative morbidity and shortens hospital stay.     

Effect of oral liquids and ranitidine on gastric fluid volume and pH in children undergoing outpatient surgery

Eighty-eight children (mean age 5.6 yr, range 1-14 yr) about to undergo elective outpatient surgery were randomly assigned to four groups. All children were given phenolsulfonphthalein (PSP) orally 2-3 h before the scheduled time of surgery as a marker dye to assess gastric emptying. Immediately after receiving PSP they were given: group A--liquids, up to 5 ml/kg + placebo (glucose water 0.2 ml/kg); group B--liquids, up to 5 ml/kg + ranitidine 2 mg/kg in glucose water 0.2 ml/kg; group C--placebo only; group D--ranitidine only. Gastric contents were aspirated after induction of anesthesia. Mean volume (range) in ml/kg of aspirated gastric fluid in each group was: group A--0.34 (0-1.0); group B--0.17 (0.07); group C--0.25 (0-1.1); group D--0.16 (0-0.6). The pH mean (range) value was: group A--1.83 (0.9-3.6); group B--4.76 (2.0-7.7); group C--2.10 (1.2-4.1); group D--3.97 (1.3-7.3). PSP could not be detected in the gastric samples from children in whom the ingestion-sampling interval was more than 2.25 h. In comparison with prolonged starvation, administration of oral liquids without ranitidine 2-3 h preoperatively did not produce a significant increase in mean volume of gastric aspirate, and there was no increase in the number of patients with gastric aspirate greater than 0.4 ml/kg. Administration of ranitidine with or without fluids resulted in a decrease in both volume and acidity of gastric contents.     

Continuous fascia iliaca compartment block in children: a prospective evaluation of plasma bupivacaine concentrations, pain scores, and side effects

We sought to determine the plasma concentrations of bupivacaine and its main metabolite after continuous fascia iliaca compartment (FIC) block in children. Twenty children (9.9 +/- 4 yr, 38 +/- 19 kg) received a continuous FIC block for either postoperative analgesia (n = 16) or femoral shaft fracture (n = 4). A bolus dose of 0.25% bupivacaine (1.56 +/- 0.3 mg/kg) with epinephrine was followed by a continuous administration of 0.1% bupivacaine (0.135 +/- 0.03 mg. kg(-)(1). h(-)(1)) for 48 h. Plasma bupivacaine levels were determined at 24 h and 48 h by using gas liquid chromatography. Heart rate, arterial blood pressure, respiratory rate, side effects, and pain scores were recorded at 4-h intervals during 48 h. No significant differences were found between mean plasma bupivacaine levels at 24 h (0.71 +/- 0.4 microg/mL) and at 48 h (0.84 +/- 0.4 microg/mL) (P = 0.33). FIC block provided adequate analgesia in most cases. No severe adverse effects were noted. We conclude that the bupivacaine plasma concentrations during continuous FIC block in children are within the safety margins. FIC block is well tolerated, and provides satisfactory pain relief in most cases. IMPLICATIONS: In this study, we have shown that, in children, continuous fascia iliaca compartment block, a technique providing neural blockade of the thigh and the anterior part of the knee, was associated with safe plasma bupivacaine concentrations, was well tolerated, and provided satisfactory pain scores in most cases.