Hypotonic versus isotonic maintenance intravenous fluid therapy in hospitalized children: a systematic review

A systematic review of studies comparing hypotonic versus isotonic intravenous maintenance fluids in hospitalized children was conducted to determine whether hypotonic solutions increase the risk of acute hyponatremia. Studies were identified from electronic databases and hand-searched reference lists. A total of 283 abstracts were reviewed, 55 full-text articles were retrieved, and 3 studies were included. All studies were observational and were overall inconclusive. All authors cautioned against the routine use of hypotonic maintenance fluids, but hypotonic fluid administration did not always explain the development of acute hyponatremia. Further evidence is required as to the appropriate maintenance solution for hospitalized children.     

Randomised trial of oral versus sequential intravenous/oral cephalosporins in children with pyelonephritis

The hypothesis was tested that oral antibiotic treatment in children with acute pyelonephritis and scintigraphy-documented lesions is equally as efficacious as sequential intravenous/oral therapy with respect to the incidence of renal scarring. A randomised multi-centre trial was conducted in 365 children aged 6 months to 16 years with bacterial growth in cultures from urine collected by catheter. The children were assigned to receive either oral ceftibuten (9 mg/kg once daily) for 14 days or intravenous ceftriaxone (50 mg/kg once daily) for 3 days followed by oral ceftibuten for 11 days. Only patients with lesions detected on acute-phase dimercaptosuccinic acid (DMSA) scintigraphy underwent follow-up scintigraphy. Efficacy was evaluated by the rate of renal scarring after 6 months on follow-up scintigraphy. Of 219 children with lesions on acute-phase scintigraphy, 152 completed the study; 80 (72 females, median age 2.2 years) were given ceftibuten and 72 (62 females, median age 1.6 years) were given ceftriaxone/ceftibuten. Patients in the intravenous/oral group had significantly higher C-reactive protein (CRP) concentrations at baseline and larger lesion(s) on acute-phase scintigraphy. Follow-up scintigraphy showed renal scarring in 21/80 children treated with ceftibuten and 33/72 with ceftriaxone/ceftibuten (p = 0.01). However, after adjustment for the confounding variables (CRP and size of acute-phase lesion), no significant difference was observed for renal scarring between the two groups (p = 0.2). Renal scarring correlated with the extent of the acute-phase lesion (r = 0.60, p < 0.0001) and the grade of vesico-ureteric reflux (r = 0.31, p = 0.03), and was more frequent in refluxing renal units (p = 0.04). The majority of patients, i.e. 44 in the oral group and 47 in the intravenous/oral group, were managed as out-patients. Side effects were not observed. From this study, we can conclude that once-daily oral ceftibuten for 14 days yielded comparable results to sequential ceftriaxone/ceftibuten treatment in children aged 6 months to 16 years with DMSA-documented acute pyelonephritis and it allowed out-patient management in the majority of these children.     

Home intravenous versus oral antibiotics following appendectomy for perforated appendicitis in children: a randomized controlled trial

Purpose

To compare the effect of home intravenous (IV) versus oral antibiotic therapy on complication rates and resource utilization following appendectomy for perforated appendicitis.

Methods

This was a randomized controlled trial of patients aged 4–17 with surgically treated perforated appendicitis from January 2011 to November 2013. Perforation was defined intraoperatively and divided into three grades: I—contained perforation, II—localized contamination to right gutter/pelvis, and III—diffuse contamination. Patients were randomized to complete a ten-day course of home antibiotic therapy with either IV ertapenem or oral amoxicillin–clavulanate. Thirty-day postoperative complication rates including abscess, readmission, wound infection, and charges were compared.

Results

Eighty-two patients were enrolled. Forty four (54%) were randomized to the IV group and 38 (46%) to the oral group. IV patients were older (12.3?±?3.6 versus 10.1?±?3.6, p?<?0.05) with higher BMI (20.9?±?5.8 versus 17.9?±?3.5, p?<?0.05). There were no differences in gender, comorbidities, or perforation grade (I—20.4% vs. 26.3%, II—36.4% vs. 34.2%, III—43.2% vs. 39.5%, all p?>?0.05). Comparing IV to oral, there was no difference in length of stay (4.4?±?1.5 versus 4.4?±?2.0 days, p?>?0.05), postoperative abscess rate (11.6% vs. 8.1%, p?>?0.05), or readmission rate (14.0% vs. 16.2%, p?>?0.05). Hospital and outpatient charges were higher in the IV group (p?<?0.0001).

Conclusion

Oral antibiotics had equivalent outcomes and incurred fewer charges than IV antibiotics following appendectomy for perforated appendicitis.

     

Cerebrospinal fluid pyrazinamide concentrations in children with tuberculous meningitis

Cerebrospinal fluid pyrazinamide concentrations were determined by high pressure liquid chromatography in 53 samples from 13 children who had tuberculous meningitis complicated by increased intracranial pressure. Peak concentrations of up to 50 micrograms/ml were achieved between 1 1/2 and 2 1/2 hours after pyrazinamide administration and in most cases a concentration of 20 micrograms/ml or more was achieved. We conclude that pyrazinamide easily gains entry into the cerebrospinal fluid of children with tuberculous meningitis and should be included in treatment regimens for that disease.     

Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy

We hypothesized that plasma arginine vasopressin (AVP) concentrations in children with meningitis are appropriate for the children's degree of hypovolemia, even though the concentrations were higher than expected for the serum osmolality. A randomized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours. Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours. Nineteen children, 2 months to 17 years of age, were studied; 13 had bacterial meningitis (12 with Haemophilus influenzae type b). Ten children (seven with bacterial meningitis) received a mean of 1.42 times the calculated maintenance fluid requirements, and nine (six with bacterial meningitis) were restricted to a mean of 0.65 times maintenance. Children in the maintenance group also received significantly more sodium (mean = 6.3 mEq/kg/24 hr) than children in the fluid-restricted group (mean = 2.0 mEq/kg/24 hr). The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun. The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction (p = 0.005), and the change in AVP concentration correlated with the amount of sodium given (p less than 0.02). This study supports the hypothesis that serum AVP concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney. Patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone.     

Types of fluid disorder in children with bacterial meningitis.

As part of a prospective study of children with bacterial meningitis we analyzed in 36 patients of our hospital the fluid balance on admission and during the first three days of treatment. On admission 10 of them (28%) had inappropriate antidiuretic hormone secretion SIADH, 10 (28%) hypo-osmolal and 10 (28%) iso-osmolal contraction. Six patients (17%) had no clear fluid disorder. The patients with SIADH had significantly lower mean serum NA+ (127 vs. 132 mEq/l, p less than 0.01) and higher mean urine Na+ (111 vs. 26 mEq/l, p less than 0.01) concentration as well as higher mean urinary Na+/K+ ratio (2.23 vs. 0.365, p less than 0.005) than the patients with hypo-osmolal contraction. They also tended to be younger and have a shorter history of fever. The patients with SIADH had a less strict fluid restriction than the patients with hypo-osmolal contraction, and their fluid balance normalized more slowly. Our findings support initial water restriction for all children with bacterial meningitis.     

Cerebrospinal fluid concentrations of ethionamide in children with tuberculous meningitis

Cerebrospinal fluid ethionamide concentrations were determined in 18 children (median age 26.5 months) with tuberculous meningitis complicated by raised intracranial pressure. Lumbar spinal fluid specimens were obtained before and after weekly hour-long monitoring of intracranial pressure. Thirty-five paired and four single specimens were evaluated. A dosage schedule of 15 mg/kg was used on 26 occasions, and a spinal fluid ethionamide concentration of 2.5 micrograms/ml, the in vitro minimal inhibitory concentration for Mycobacterium tuberculosis, was exceeded on only seven occasions (27%). A dosage of 20 mg/kg was administered on 13 occasions, and in only two instances (15%) was a concentration of 2.5 micrograms/ml not achieved. Ethionamide in a single daily dosage of 20 mg/kg should be considered for the initial treatment of tuberculous meningitis when the presence of isoniazid-resistant M. tuberculosis cannot be excluded.     

Differentiating acute bacterial meningitis from acute viral meningitis among children with cerebrospinal fluid pleocytosis: a multivariable regression model

BACKGROUND: Although accurate models for predicting acute bacterial meningitis exist, most have narrow application because of the specific variables selected for them. In this study, we estimate the accuracy of a simple new model with potentially broader applicability. METHODS: On the basis of previous reports, we created a reduced multivariable logistic regression model for predicting bacterial meningitis that relies on age (years) (AGE), cerebrospinal fluid (CSF), total protein (TP) and total neutrophil count (TNC) alone. Data were from children ages 1 month-18 years diagnosed with acute enteroviral or bacterial meningitis whose initial CSF revealed >7 white blood cells/mm. A fractional polynomial model was specified and validated internally by the bootstrap procedure. The area under the receiver operating characteristic curve (discrimination: criterion standard, >0.7), the Hosmer-Lemeshow deciles-of-risk statistic (calibration: criterion standard, P > 0.05) and sensitivity-specificity pairs at prespecified probability thresholds of the model were computed. RESULTS: We identified 60 children with bacterial meningitis and 82 with enteroviral meningitis. At an area under the receiver operating characteristic curve of 0.97, our model represented by the equation: log odds of bacterial meningitis = 0.343 - 0.003 TNC - 34.802 TP + 21.991 TP - 0.345 AGE, was highly accurate when differentiating between bacterial and enteroviral meningitis. The model fit the data well (Hosmer-Lemeshow statistic; P =[r] 0.53). At probability cutoffs between 0.1 and 0.4, the model had sensitivity values between 98 and 92% and specificity values between 62 and 94%. CONCLUSIONS: Among children with CSF pleocytosis, a prediction model based exclusively on age, CSF total protein and CSF neutrophils differentiates accurately between acute bacterial and viral meningitis.     

Anti-interleukin-8 auto-antibodies in cerebrospinal fluid of children with purulent meningitis

BACKGROUND: Cerebrospinal fluid (CSF) of patients with purulent meningitis contains a high concentration of interleukin (IL)-8. Recently, the presence of anti-IL-8 auto-antibodies was noted in blood and alveolar fluid. Therefore, measurement of the concentration of anti-IL-8 auto-antibodies was attempted in CSF of children with and without meningitis. METHODS AND RESULTS: We measured the concentration of anti-IL-8 auto-antibodies in CSF of children with purulent or aseptic meningitis and those without meningitis. The CSF obtained on admission showed a significantly higher concentration of anti-IL-8 IgG and IgM auto-antibodies in children with purulent meningitis, compared with those with aseptic meningitis or without meningitis. Among the three groups of children, the concentration of IL-8 was also significantly higher in CSF of children with purulent meningitis. CONCLUSION: Because the anti-IL-8 IgG auto-antibody binds to IL-8 and inhibits IL-8 interaction with specific receptors on neutrophils, the presence of anti-IL-8 auto-antibodies seems to provide a mechanism that limits the bioavailability of free IL-8 in CSF.