Tissue plasminogen activator for the treatment of thromboembolism in infants and children

We report our experience with the use of tissue plasminogen activator to treat 12 infants and children with various thromboembolic states after conventional thrombolytic agents had failed. The dosage range was between 0.1 to 0.5 mg/kg per hour. Complete clot dissolution occurred in seven cases after 2 hours to 3 days of therapy. Partial clot dissolution and clinical improvement were noted in another four patients. Bleeding complications were noted in 6 of the 12 patients and included bruising, oozing from various venipuncture sites, and bleeding; these complications were controlled by clinically available means. In all cases with bleeding the dose rate was in the higher range (0.46 to 0.50 mg/kg per hour). In one patient, restlessness, agitation, and screaming were noted during administration of tissue plasminogen activator and when it was reinstituted. We conclude that tissue plasminogen activator is effective in inducing clot lysis in children. Because the effective dose appears to overlap with those causing bleeding, we recommend that a dose of 0.1 mg/kg per hour be started and increased gradually if clot dissolution does not occur, with close monitoring for bleeding.     

Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children.

OBJECTIVES: In this study, we tried to determine the safety and outcomes of thrombolysis with tissue plasminogen activator of intravascular thrombus. STUDY DESIGN: Eighty consecutive children were treated between 1985 and 1999 in a tertiary care setting in a retrospective case series. There were 65 arterial thrombi (56 after cardiac catheterization) and 15 venous thrombi treated with tPA at an average dose of tPA of 0.5 mg/kg/hour for a median duration of 6 hours. RESULTS: Clot resolution was complete in 65% of children, partial in 20%, and there was no effect in 15%. There were major complications in 40%, minor complications in 30%, and no complications in 30%. Two patients had cerebral ischemia secondary to hypotension because of profound bleeding, with intracranial hemorrhage in 2 additional patients. Clot resolution was not related to patient age or weight, dose, and duration of tPA therapy and fibrinogen levels. However, complications were more likely in patients who weighed less, had a longer duration of therapy, a greater decrease in fibrinogen levels, and who failed to have resolution of their clot. CONCLUSIONS: tPA therapy can be effective in the thrombolysis of intravascular thrombus in children, but is associated with a low margin of safety and an unknown risk-benefit ratio.     

Failure of thrombolytic therapy in four children with extensive thromboses.

In three children with central vein thromboses and a fourth with a pulmonary artery thrombosis, thrombolytic therapy failed to produce ultrasonographic evidence of clot lysis. Low-dose streptokinase (50 to 250 U/kg per hour) was infused directly into the clot in three children, followed by streptokinase and urokinase in systemic doses (streptokinase, 1000 to 1750 U/kg per hour; urokinase, 4400 to 5000 U/kg per hour). A fourth child treated sequentially with systemic doses of streptokinase, urokinase, and recombinant tissue-type plasminogen activator developed a significant retroperitoneal and intrapleural hemorrhage after 19 hours of recombinant tissue-type plasminogen activator infusion at a dose of 0.7 mg/kg per hour. All of the children survived. The most likely reason for treatment failure was that the clots (estimated to be between 2 and 3 weeks of age) were organized and thus resistant to lysis. Early diagnosis and prompt thrombolysis of significant lesions may contribute to the successful management of pediatric thrombosis. However, controlled studies are clearly needed to establish guidelines for the optimal use of thrombolytic agents in children.     

Increased enoxaparin dosing is required for obese children

Weight-based dosing for enoxaparin is recommended in the 2008 American College of Chest Physicians (ACCP) guidelines for venous thromboembolism (VTE) prophylaxis. Enoxaparin 0.5 mg/kg per dose administered subcutaneously every 12 hours is recommended for this indication in children. There is no established upper dosing limit of enoxaparin for prophylaxis in children, and the US Food and Drug Administration-approved enoxaparin dose for adults for VTE prophylaxis is 30 mg subcutaneously every 12 hours or 40 mg subcutaneously daily. Therefore, we assumed that the upper limit for children is 40 mg subcutaneously daily. We reviewed 3 cases of obese adolescent boys who required large doses of enoxaparin to achieve the ACCP-recommended anti-factor Xa range of 0.1 to 0.3 IU/mL for the prevention of VTE. All 3 patients required doses of enoxaparin that are higher than that recommended for adults for VTE prophylaxis: patient A (BMI: 105.9) required >0.28 mg/kg per dose, patient B (BMI: 95.7) required 0.15 mg/kg per dose, and patient C (BMI: 29.9) required 0.49 mg/kg per dose. The desired anti-factor Xa range was achieved when enoxaparin was administered every 12 hours in each patient with no reported episodes of VTE. One patient had minor bruising, but no other adverse events were noted. Because of the variability in dose requirements and unpredictability in patient responses demonstrated in our 3 adolescents, prospective studies are needed to provide definitive recommendations on dosing of enoxaparin for VTE prophylaxis in this subset of obese pediatric patients.     

High-versus low-dose, frequently administered, nebulized albuterol in children with severe, acute asthma

Thirty-two 5- to 17-year-old children who had severe, acute asthma were randomly assigned to receive either high doses (0.15 mg/kg of body weight per dose) or low doses (0.05 mg/kg of body weight per dose) of nebulized albuterol every 20 minutes for six doses. Compared with the low-dose regimen, the high-dose regimen resulted in significantly greater improvement in forced expiratory volume in 1 second, forced vital capacity, and wheeze score and a lower hospitalization rate. The changes in heart rate, respiratory rate, blood pressure, white blood cell count, and serum potassium concentration did not differ significantly between the groups. The incidence of side effects, which included tremor, hyperactivity, and vomiting, was not significantly different in the two populations. Serum albuterol levels varied widely, but there was no correlation between the levels and the increase in heart rate or other side effects. high-dose, frequently administered, nebulized albuterol appears both safe and effective in treating severe, acute asthma in children.     

Ara-C syndrome during low-dose continuous infusion therapy

Four patients with acute nonlymphocytic leukemia developed one or more components of the "ara-C syndrome" including fever, peritonitis, pericarditis, and a maculopapular rash during therapy with continuous infusions of low-dose (20 mg/m2/d) cytosine arabinoside (ara-C). These complications, described with standard and high doses of ara-C, have not been previously noted with low-dose regimens.     

Low-dose insulin infusion in the treatment of diabetic ketoacidosis: bolus versus no bolus

The effects of an initial iv bolus of insulin upon plasma glucose, blood gases, and electrolytes were assessed in 19 children with 20 episodes of diabetic ketoacidosis treated by a continuous low-dose insulin infusion of 0.1 unit/kg/hour. An iv bolus of insulin administered prior to low-dose insulin infusion accelerated the decline of plasma glucose concentration during the first hour of treatment, but differences in decline of mean plasma glucose concentration were not apparent thereafter. The mean time required for attaining "normoglycemia" (250 mg/dl) was similar, whether or not the initial bolus of insulin was given, with a smooth and predictable correction of initial hyperglycemia in the majority of children. However, an accelerated response was more frequent in those patients with compensated metabolic acidosis, who received an initial iv bolus of insulin; those with more severe metabolic acidosis took longer to recover. The data suggest that an initial iv bolus of insulin may not be required nor desirable in the majority of children with diabetic ketoacidosis treated by a standard low-dose insulin infusion regimen.     

Risk of bleeding and inhibitor development after circumcision of previously untreated or minimally treated severe hemophilia a children

Background: Surgery and intensive factor VIII (FVIII) replacement may be risk factors for development of inhibitors. Objective: To evaluate time and rate of inhibitor development postcircumcision over 12-month period, and to assess bleeding of children with severe hemophilia A after low-dose FVIII replacement and local hemostasis. Patients and Methods: Sixty-one previously untreated patients (PUPs) or minimally treated patients (MTPs) with severe hemophilia A less than 36 months were enrolled; 25 underwent circumcision during the 18-month enrollment period, and 36 matched patients were not circumcised. All patients were treated on demand with plasma-derived FVIII, and all were inhibitor negative at the time of enrollment. Intron 22 inversion was analyzed. A potent hemostatic agent (gelatin sponge) was applied on the site of surgery, and then dressed with gauze. Two doses of FVIII concentrate (25?U/kg) were given, 1?hour before circumcision and 1?hour before removal of dressing. The inhibitor was determined every 8 exposure days (EDs). Results: None of the patients had bleeding or infection, except one who had minimal transient bleeding 8?days after surgery, and was treated easily by a single dose of FVIII (50?U/kg). After a median of 16 EDs, high-titer inhibitors developed in seven patients: three patients in the circumcised group (12%) in contrast to four patients (11.1%) in the noncircumcised group. Conclusion: Two doses factor concentrate and gelatin sponge application were generally enough to prevent bleeding after circumcision of severe hemophilia A. Circumcision and low-dose FVIII protocol were not an additional risk for development of high-titer inhibitor.     

咪哒唑仑与地西泮治疗小儿急性惊厥的对照研究

目的：比较咪哒唑仑（MDL）与地西泮（DZP）治疗小儿急性惊厥的疗效,探讨小儿急性惊厥安全、高效的治疗方法。方法：将120例急性惊厥患儿随机分为MDL组(60例)和DZP组(60例),分别予MDL（0.3~0.5 mg/kg）和DZP(0.5~1 mg/kg)治疗,对出现惊厥反复或呈惊厥持续状态患儿,前组给予MDL维持（每小时1~8 mg/kg）,后组给予DZP维持（每小时0.5~1 mg/kg）或联合苯巴比妥钠治疗,比较两种方法疗效。结果：全部患儿于10 min内惊厥得到基本控制,MDL组与DZP组平均控制时间差异无统计学意义。MDL组与DZP组分别有5例及13例患儿10 min后出现惊厥反复或呈惊厥持续状态。维持治疗后平均控制时间分别为40±32 min和69±24 min,差异有统计学意义 (P<0．05)。两组中无一例出现与MDL及DZP相关的副反应。结论：MDL用于治疗小儿急性惊厥安全、高效,对于惊厥反复或呈惊厥持续状态患儿,疗效优于DZP。［中国当代儿科杂志,2010,12（7）：530-532］     

Development of an optimal lidocaine infusion strategy for neonatal seizures

Introduction Lidocaine is an effective drug for the treatment of neonatal convulsions not responding to traditional anticonvulsant therapy. However, one of the side-effects is a risk of cardiac arrhythmias. The aim of this study was to develop an optimal dosing strategy with minimal risk of cardiac arrhythmias.Materials and methods As a first step, we studied 20 neonates during routine treatment of neonatal seizures with lidocaine. All were given a loading dose of 2 mg/kg in 10 min, followed by the continuous infusion of 6 mg/kg per hour for 12 h, 4 mg/kg per hour for 12 h and finally 2 mg/kg per hour for 12 h. Effectiveness, cardiac toxicity and lidocaine plasma concentrations were then determined.Results No cardiac arrhythmias were observed, and lidocaine was effective in 76% of the treatments. In most of the treatments (13 out of 20) maximal lidocaine plasma concentrations were >9 mg/L. Plasma levels >9 mg/L have been related to cardiac toxicity when used as an anti-arrhythmic drug in adults. It was of interest that all preterm infants showed high lidocaine plasma levels. Secondly, we developed the optimal dosing regimen, which was defined as an infusion regimen at which maximal lidocaine plasma concentrations are <9 mg/L. Simulations with the developed pharmacokinetic model indicated a reduction in the infusion duration of lidocaine at 6 mg/kg per hour from 12 to 6 h. Thirdly, the new lidocaine dosing regimen was evaluated. Fifteen neonates (16 treatments) were studied. No cardiac arrhythmias were observed, and lidocaine was effective in 78% of the treatments. In most of the treatments (11 out of 16) maximal lidocaine plasma concentrations were <9 mg/L. Again preterm infants showed relatively high lidocaine plasma levels.Conclusion A new lidocaine dosing schedule was developed. This new regimen should have a lower risk of cardiac arrhythmias and appears to be as effective in term infants. For preterm infants the optimal regimen needs to be determined.     

Low-molecular-weight heparin in thrombotic disease in children and adolescents

PURPOSE: The use of unfractionated heparin (UFH) in children is problematic. In adults, subcutaneous low-molecular-weight heparin (LMWH) is as effective as UFH in the treatment of thrombosis. Because pediatric data are limited, the authors studied the use of enoxaparin in children. PATIENTS AND METHODS: Nineteen children (ages 18 days to 19 years; median age, 40 months) with indications for thrombosis treatment or prophylaxis were studied. Six patients (median age, 33 months), treated on a protocol that included pharmacokinetic studies, initially received enoxaparin 1 mg/kg subcutaneously every 12 hours; doses then were adjusted until target plasma levels of 0.5 to 1.2 anti-Xa U/mL were achieved. The records of 13 additional patients treated with enoxaparin off study were reviewed. RESULTS: In the first six patients, enoxaparin pharmacokinetics was found to be similar to that in adults; once targeted levels were achieved, these remained stable. Among all 19 subjects, 14 had treatment of active thrombosis and 5 underwent thrombosis prophylaxis. For treatment of thrombosis, enoxaparin 1 mg/kg initially was administered subcutaneously every 12 hours. Target anti-Xa levels were achieved with 0.55 to 1.5 mg/kg every 12 hours (mean, 0.98 mg/kg; median, 1.0 mg/kg) in 1 to 7 days (median, 1 day). All patients in the treatment group had clinical improvement within 2 to 5 days, and 12 had follow-up radiological studies that confirmed this. For prophylaxis, enoxaparin was given at 1 mg/kg subcutaneously every 24 hours. No new thrombi were clinically evident in this group. There was no major bleeding with enoxaparin; one patient had transient mild mucosal oozing. CONCLUSION: In this limited population, enoxaparin seems to be a safe, effective, and convenient alternative to UFH in children and adolescents. The adult therapeutic target range of 0.5 to 1.2 anti-Xa U/mL is readily achievable with a starting dose of 1 mg/kg every 12 hours in most children. Initial close monitoring with plasma anti-Xa activity should be done and doses adjusted to achieve target range, particularly in neonates. In the population of this study, enoxaparin seems as effective as UFH in the period immediately thrombotic episode. These results should be confirmed in the ongoing randomized trial comparing LMWH with UFH in children.     

Oliguria and tolazoline pharmacokinetics in the newborn

Tolazoline treatment of neonates has been reported since 1965. Dosages increased from pulse doses of 1 to 2 mg/kg to continuous infusions of 10 mg/kg X h before neonatal plasma tolazoline concentrations were measured. We developed a microassay for tolazoline and determined neonatal distribution volume, 1.61 +/- 0.21 L/kg, and disposition rate constant (beta), 0.0027 +/- 0.005 min-1 (mean +/- SEM). Half-life (gamma) ranged from 1.47 to 41.25 (median = 4.43) hours and correlated inversely with urine output (x); y (h) = -0.46 + 7.63/x (mL/kg X h), r = .61, P less than .05. The highest plasma tolazoline concentration in a neonate was 20.3 mg/L. Lethal tolazoline concentrations in lambs ranged from 21.8 to 56.8 mg/L. Initial tolazoline concentrations during infusions and after 1- to 2-mg/kg pulse doses ranged from 0.35 to 2.3 mg/L and PaO2 increased greater than or equal to 15 mm Hg in 64% of 14 treatments. The average neonatal pharmacokinetics predict that each 1 mg of tolazoline HCl per kilogram pulse dose will increase the plasma concentration of tolazoline base by 0.5 mg/L. The plasma concentration should remain constant with infusion dose increments of 0.16 mg of tolazoline HCl per kilogram per hour for every 1.0-mg/kg loading dose. Tolazoline dose requirements for specific patients will vary, especially with renal dysfunction. Reduced tolazoline doses were used to treat two patients, concentrations remained constant, and PaO2 was maintained. Tolazoline doses derived from neonatal kinetics are less than current infusion doses and may avoid high concentrations.     

Successful thrombolysis by prolonged low-dose alteplase in catheter-directed infusion

Catheter-directed thrombolysis is a sophisticated method in the treatment of thromboembolism with maximum effect on the thrombus and minimal systemic effect. The consequences are enhanced local thrombolysis and a reduction in general bleeding tendency, compared with systemic thrombolysis. At our institution, two children had successful thrombolysis by prolonged continuous catheter-directed low-dose alteplase. The first patient, a boy with Fontan physiology, was successfully treated for a massive pulmonary thromboembolism by catheter-directed very low-dose alteplase for five days. The second patient, who suffered from relapsing nephrotic syndrome, achieved satisfactory thrombolysis of an arterial leg thrombosis after four days of continuous catheter-directed low-dose alteplase.

Conclusion: Although catheter-directed thrombolysis seems to be a valuable method in thrombolytic therapy, there is a lack of evidence-based recommendations concerning dosage, effect of bolus, simultaneous anticoagulation and duration of treatment for children.     

Thrombolytic therapy using a low dose of tissue plasminogen activator in children

ObjectiveTo analyse the efficacy and side effects of low doses of tissue plasminogen activator for the treatment of acute arterial and/or venous thrombosis in children.Patients and methodsProspective observational clinical study. 18 children between 1 months and 11 years treated with low doses (0.01-0.06 mg/kg/h) of continuous intravenous thrombolytic therapy with t-PA were studied.ResultsA total of 94% of patients improved with low doses t-PA (72% complete resolution of the thrombosis and 22% partial resolution). One patient suffered a severe haemorrhage secondary to t-Pa and had to stop the treatment. The incidence of severe side effects was low (5%)ConclusionsThrombolytic therapy with low doses of t-PA (0.01-0.05 mg/kg/h) is effective in a high percentage of children with acute arterial and/or venous thrombosis and produces a relatively low frequency of side effects.     

The pharmacokinetics and safety of micafungin, a novel echinocandin, in premature infants

BACKGROUND:: Candidal fungal infection rates in neonates are increasing and are a significant cause of mortality, especially in low birth weight infants. Micafungin is an echinocandin that works by inhibiting 1,3-beta-D-glucan synthase, an enzyme responsible for fungal cell wall synthesis. The objective of this study was to determine the safety and pharmacokinetics of micafungin in premature infants. METHODS:: This was a phase I, single-dose, multicenter, open-label, sequential-dose trial of intravenous micafungin investigating 3 doses (0.75 mg/kg, 1.5 mg/kg and 3.0 mg/kg) in 18 premature infants weighing >1000 g (n = 6 in each dosage group). A further 5 infants (500-1000 g) were enrolled in the 0.75 mg/kg dosage group only. RESULTS:: The mean +/- standard deviation gestational age in the >1000 g dosage group was 26.4 +/- 2.4 weeks and, on entry, patients had one or more of a variety of underlying conditions, including sepsis, pneumonia and other infections caused by Candida or other species. Micafungin pharmacokinetics in preterm infants appears linear. However, premature infants >1000 g on average displayed a shorter half-life (8 hours) and a more rapid rate of clearance (approximately 39 mL/h per kg) compared with published data in older children and adults. All doses of micafungin were well tolerated and no serious drug-related adverse events were observed. CONCLUSIONS:: Single doses of micafungin, ranging up to 3.0 mg/kg, appear well tolerated in premature infants weighing >1000 g. The drug's elimination half-life and total plasma clearance in preterm infants appear dissimilar to published values for these parameters in older children and adults. The reason(s) for this apparent difference remain to be investigated.     

Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease

We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant differences between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (² = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD.     

Suppression of gastric acid secretion by intravenous administration of famotidine in children

This study was designed to establish appropriate dosing requirements for intravenous use of famotidine, a new H2-receptor antagonist, in pediatric patients. Eighteen children, 2 to 69 months of age (mean +/- SD: 31 +/- 23 months), were treated with intravenously administered famotidine to prevent bleeding of the upper gastrointestinal tract. Continuous intragastric pH monitoring was carried out to ascertain the effectiveness of various intravenous doses. An initial dose of 0.4 mg/kg was given and repeated only after the intragastric pH had dropped to less than 4.0 for 2 hours. Increased doses were given (0.8, 1.2, and 1.6 mg/kg) if the previous dose did not raise the intragastric pH to greater than 4.0 for greater than or equal to 6 hours. Sixteen patients achieved an intragastric pH greater than or equal to 4.0 for greater than or equal to 6 hours, 13 with a dose of 0.4 mg/kg, and three with a dose of 0.8 mg/kg. The mean duration of continuous pH greater than 4.0 per dose was 9.0 +/- 7.5 hours. Ten patients received two or more intravenous doses of famotidine; the mean duration of pH greater than 4.0 after the second dose was less than that after the first (14.9 +/- 8.0 hours vs 6.9 +/- 3.2 hours, p less than 0.01). We conclude that intravenous famotidine therapy raises gastric pH to greater than 4.0 for approximately 9 hours in most children. Prolonged intravenous use of famotidine rapidly leads to a decreased duration of efficacy, necessitating intragastric pH monitoring to assess the effectiveness of treatment.     

Effective methimazole dose for childhood Graves' disease and use of free triiodothyronine combined with concurrent thyroid-stimulating hormone level to identify mild hyperthyroidism and delayed pituitary recovery

Appropriate methimazole dosing for initial treatment of childhood Graves' disease is uncertain. A retrospective chart review was performed on 5 to 17 year-old children treated for Graves' disease. Patients were divided into two groups depending on initial methimazole dosing: low-dose and high-dose regimens using <0.5 mg/kg/day and >0.5 mg/kg/day, respectively. The low-dose regimen was effective in 5/12 (42%) of patients and the high-dose regimen was effective in 27/33 (82%) of patients (p = 0.016). There was also a statistically significant dose/time interaction for levels of free thyroxine (T4) (p = 0.025). During treatment, 63.3% of diagnosable samples showed unambiguous hyperthyroidism or triiodothyronine (T3) toxicosis, 16.7% elevated free T3 with normal free T4 and T3 levels, indicating borderline hyperthyroidism, and 20% showed thyroid-stimulating hormone (TSH) suppression with normal or low levels of free T4 and free T3, indicating delayed recovery of pituitary TSH secretion. Free T3 levels combined with concurrent TSH levels permit differentiation of mild hyperthyroidism from delayed pituitary recovery.     

Extended-interval gentamicin administration in malnourished children

Malnourished children have several physiologic abnormalities that can affect drug distribution and elimination. The aim of this study was to determine the efficacy, safety and pharmacokinetics of a once-daily dose of gentamicin compared with conventional thrice-daily dosing in malnourished children. To our knowledge, it has not been investigated in this population so far. A total of 310 malnourished children of either gender aged 6 months to 5 years with diarrhea and pneumonia were randomized to receive intramuscular gentamicin 5 mg/kg/day once-daily (OD) (n=148) or the same total daily amount given in three divided doses (TD) (n=162) in addition to ceftriaxone 75 mg/kg/day. After 48 h at steady state, gentamicin pharmacokinetics was assessed by fluorescence polarization immunoassay in a subgroup of 59 children and 43 children in the OD and TD groups, respectively. The groups were equivalent in baseline demographic, clinical and laboratory characteristics. Good and partial clinical responses occurred in 64 per cent vs. 54 per cent and 25 per cent vs. 27 per cent in the OD and the TD children, respectively (p=NS for both comparisons). Five patients in each treatment group died. Renal toxicity defined by change in serum creatinine was not observed in any patient from either group. In the OD group, mean+/-SD serum gentamicin concentrations at 1 (peak), 3, 5, 8, 23, and 24 (trough value) hours after the dose were 11.7+/-4.1, 4.4+/-1.2, 2.08+/-0.9, 1.01+/-0.6, 0.31+/-0.09 and 0.29+/-0.07 mg/l respectively. In the TD group, mean +/-SD serum gentamicin concentration at 1 hour (peak) was 4.7+/-1.8 mg/l and the trough concentration was 0.48+/-0.21 mg/l. In OD group, the gentamicin trough concentration was significantly lower (p<0.001) and the peak concentration was significantly higher (p<0.001) compared to TD group. The results of this study indicate that once-daily gentamicin is effective and safe in malnourished children. Widespread implementation of once-daily dosing in malnourished children is appropriate and will reduce number of intramuscular injections and hospital costs.     

Successful clot lysis using low dose of streptokinase in 22 neonates with aortic thromboses

OBJECTIVE: To determine whether intravenous infusion of low dose of streptokinase was effective in lysing umbilical arterial catheter (UAC)-associated aortic thrombi. METHOD: A prospective cohort study of 31 consecutive newborn infants with UAC-associated aortic thrombi which were detected by abdominal ultrasonography after removal of UAC. Twenty-two infants were treated with intravenous infusion of low dose (1000 U/h) streptokinase, while nine others were not treated due to various contra-indications. Thrombolysis occurred after a mean interval of 2.2 days (standard deviation (SD) = 1.8) in the treated infants. In the untreated infants, spontaneous thrombolysis occurred significantly later, after a mean interval of 16.9 days (SD = 14.7) (95% confidence intervals of difference between mean intervals - 26.0, - 3.4; P = 0.02). Only one treated infant developed mild bleeding directly attributed to streptokinase therapy. CONCLUSION: Low dose streptokinase infusion was effective and safe in thrombolysing UAC-associated aortic thrombi.