Kathleen A. Woodin

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 childrens 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.

Influenza in children with cancer

We prospectively followed a group of unimmunized, immunosuppressed children with cancer to determine their relative risk of influenza and the severity of infection compared with those of siblings or matched community controls. The incidence of influenza infection was higher in children with cancer (23/73, 32%) than in control subjects (10/70, 14%, p =0.02). A preseason hemagglutination inhibition titer≥1:32, generally used as a marker of successful immunization in vaccine trials, was protective for all children in the control groups, but did not prevent influenza infection in 24% of the patients with cancer. Infection rates of patients and community controls with titers ≥1:32 differed significantly ( p =0.006). No significant differences were noted in duration of reported symptoms between groups, and clinical complications occurred too infrequently to analyze. However, 2 (11%) of 18 of the cancer patients with positive culture results were hospitalized during the illness and one patient developed a nosocomial infection. None of the control children was hospitalized. These findings suggest the need for further study of the immunologic response of immunosuppressed children to influenza infection and a clinical efficacy trial of the influenza vaccine in these patients.

Relevance of common tests of cerebrospinal fluid in screening for bacterial meningitis

This study tests the hypothesis that if cerebrospinal fluid (CSF) has a nucleated blood cell count (NucBC) of less than 6/mm3, CSF tests other than bacterial culture need not be performed to exclude the diagnosis of bacterial meningitis in patients not receiving antimicrobial agents. The results of tests performed on the first specimen of CSF obtained for a given hospital visit from children younger than 3 years of age, exclusive of newborn infants admitted to the hospital on their date of birth, were analyzed. Of 3356 CSF specimens evaluated, 122 were from patients with bacterial meningitis; 460 specimens were analyzed separately because the erythrocyte count was greater than 1000/mm3. A negative CSF screening test result was defined as a CSF NucBC less than 6/mm3. In facilitating the diagnosis of bacterial meningitis, this screening test had a sensitivity of 98.4%, a specificity of 75.2%, and a negative predictive value of 99.9%. The other CSF tests varied widely in screening effectiveness: a Gram-stained smear had a sensitivity of 53% and a specificity of 97%. Receiver operating characteristic curve analysis was used to assess the screening relevance of CSF tests. The CSF NucBC and CSF segmented NucBC performed indistinguishably and superiorly compared with the CSF protein or glucose concentration and the ratio of CSF glucose to serum glucose concentration. Logistic regression analysis showed that the NucBC alone is superior to any combination of the other CSF tests. In a prospective study of 215 children younger than 3 years of age undergoing a lumbar puncture in our emergency department, 85% had empiric criteria identifying them as appropriate for an abbreviated CSF evaluation. The CSF NucBC was less than 6/mm3 in 70% of the 181 patients who would have been eligible for an abbreviated CSF evaluation. These data suggest that a strategy for the sequential testing of CSF could be adopted that would exclude unnecessary determinations and thereby save time, effort, and health care dollars.

Maternal immunization to prevent infectious diseases in the neonate or infant

The approach of providing passive protection to young infants by immunizing pregnant women can bypass the problems of immunological immaturity in the neonate, avoid or delay active immunization of the infant in the first year of life, and prevent transmission of an infection from the mother to the neonate. Optimal vaccines for this approach should induce high immunoglobulin G antibody titers that quickly reach their maximum level after immunization and persist at protective levels for several years, thus providing passive protection in subsequent pregnancies. Specific applications of this approach include the worldwide practice of maternal immunization with tetanus toxoid vaccine and ongoing studies of maternal immunization to prevent Haemophilus influenzae type b, group B streptococcal, pneumococcal, meningococcal, and human immunodeficiency virus infection in the infant. Addressing the cultural, sociological, and legal aspects of maternal immunization will be required to ensure the success of this approach.

Fluid Management in Bacterial Meningitis (BM)

Elevated plasma arginine vasopressin concentrations [AVP] and cerebral edema occur in BM. Therefore fluid restriction has been recommended in early management. However dehydration may also increase [AVP] and fluid restriction may decrease cerebral perfusion. A randomized, prospective study is in progress to establish the relationship between initial hydrastatus and [AVP], and to determine the effect of rehydration or fluid restriction on subsequent [AVP]. Six children with BM have been studied to date (table). Hydration was estimated clinically and determined by bromide space. [AVP] was measured at presentation, 24 hours later, and at the end of antibiotic therapy. No patient developed hyponatremia, SIADH, or fluid overload.Results to date suggest that children with BM are often dehydrated at the time of presentation and that replacement fluid therapy results in the normalization of [AVP].