Larry E. Fleischmann

Management of hyponatremic seizures in children with hypertonic saline: a safe and effective strategy.

ObjectiveTo study efficacy and safety of hypertonic saline administration in the management of hyponatremic seizures. DesignRetrospective, observational, cross-sectional study with factorial design. SettingIn-patient population in a university hospital. PatientsAll children admitted with serum sodium concentrations <125 mmol/L. Sixty-nine episodes of severe hyponatremia in 60 children were reviewed. Forty-one of these children presented with seizures. InterventionsTwenty-five of 41 seizure patients received an iv bolus of 4 to 6 mL/kg body weight of 3% saline. Twenty-eight patients were treated with a benzodiazepine and/or phenobarbital with or without the subsequent administration of hypertonic saline. Measurements and Main ResultsThirteen treatment failures and ten instances of apnea occurred among the 28 patients treated with benzodiazepine/phenobarbital. Administration of hypertonic saline resulted in resolution of seizures and apnea in all cases. Those patients receiving 3% saline had a higher serum sodium increase rate from 0 to 4 hrs than the remaining patients (3.1 ± 1.3 vs. 1.7 ± 1.2 mmol/L-hr, p < .01). None developed subsequent neurologic deterioration or clinical manifestations of osmotic demyelination syndrome. ConclusionTreatment of hyponatremic seizures with routine anticonvulsants may be ineffective and is associated with a considerable incidence of apnea. A rapid increase in the serum sodium concentration by 3 to 5 mmol/L with the use of hypertonic saline is safe and efficacious in managing acute symptomatic hyponatremia. (Crit Care Med 1991;19:758)

Mercury Poisoning in Children The Value of N-Acetyl-D,L-Penicillamine in a Combined Therapeutic Approach

* Department of Pediatrics, Wayne State University School of Medicine, Poison Control Center, Children’s Hospital of Michigan. ** Department of Pediatrics, Wayne State University School of Medicine, Renal Service, Children’s Hospital of Michigan. Correspondence to Regine Aronow, M.D., 3901 Beaubien Boulevard, Detroit, Mich. 48201. * N-acetyl-D,L-Penicillamine was obtained from The Aldrich Chemical Company, Milwaukee, Wis. MERCURY POISONING, acute and chronic, still occurs in children despite centuries of knowledge concerning its toxic effects. Mercurial compounds as used in industry, medicine, agriculture, and the home afford opportunity for exposure. Corrective treatment has relied on ending the exposure while administering metal-binding agents to hasten the excretion of the mercury. The three cases reported here exemplify differing types of exposure to mercury, and differing approaches to therapy. However, with the informed consent of their respective parents, all the patients received oral N-aeetylTJ,L-Penicillamine* as a chelating agent.

Natriuresis-Induced Protection in Acute Myohemoglobinuric Renal Failure without Renal Cortical Renin Content Depletion in the Rat

The interrelationships of renal cortical renin content RCRC, sodium chloride excreting and the severity of renal failure were studied in the glycerol-induced acute myohemoglobinuric renal failure model in the rat. Protocols were designed to increase sodium chloride excretion without necessarily resulting in RCRC depletion. Our data fail to demonstrate a relationship between RCRC and severity of renal failure, but they demonstrate an excellent inverse correlation between the sodium chloride excretion of the animals in the 24 h prior to glycerol administration and the severity of resulitng renal failure. The protection of long-term saline-drinking animals should properly be ascribed to the associated natriuresis which develops much before RCRC depletion during the time course of saline drinking. The exact mechanism by which natriuresis exerts its protective effect needs further elucidation, but our data argue against a major role for RCRC in the pathogenesis of acute experimental renal failure.

Renal cortical and renal medullary necrosis in the first 3 months of life

Renal cortical necrosis, renal medullary necrosis, and combined renal cortical-medullary necrosis result from renal ischemia without vascular occlusion. Renal hypoperfusion and ischemic injury in infants have been ascribed to massive blood loss, hemolytic disease, septicemia, and severe hypoxemia. In a postmortem study we identified 82 cases among 1,638 autopsies during the 20 years between 1970 and 1989 in infants 3 months old or less at the time of death. The frequency of renal necrosis in autopsy cases increased significantly during the last 6 years of the study. The distribution of the renal lesion was cortical in 28, medullary in 23, and combined in 31. Forty infants carried diagnoses of congenital heart disease, 17 of asphysial shock, 9 of sepsis, 3 of infectious myocarditis, 9 of major malformations, 4 of anemic shock, 1 of vascular malformation, and 1 of gastroenteritis and dehydration. A significantly higher proportion of babies with congenital heart disease had cortical involvement. Comparison of clinical characteristics revealed a significantly higher frequency of prematurity, respiratory distress syndrome, bleeding diathesis, and possibly sepsis in the children with congenital heart disease, suggesting that these factors are important in the pathogenesis of the renal lesion. Fourteen infants underwent cardiac catheterization; there was no demonstrable association between the renal lesions and the use of radiographic contrast medium. We conclude that severe congenital heart disease itself is a risk factor for life-threatening renal cortical and medullary necrosis.

HgCl2-induced acute renal failure in the developing rat.

Summary: The present investigation was undertaken to find the differences, if any, in the pattern of nephrotoxic acute renal failure (HgCl2,4.7 mg/kg body weight SC), in the developing rat and its relationship to the renin angiotensin system. No differences in renal cortical renin content were found between 2, 4, and 8 week olds, but plasma renin concentration was highest at 2 weeks and declined with age. Plasma renin was significantly increased in all groups 6 hr after HgCl2 injection, and the percentage of increase was highest in the 4 week olds. Despite these differences in initial plasma renin and in changes in plasma renin after HgCl2, the pattern of acute renal failure (as assessed by changes in blood urea nitrogen) was similar in the three groups for the first three days. Subsequently, the 4 and 8 week olds exhibited recovery (blood urea nitrogen began to decline), wheras blood urea nitrogen continued to increase to the fifth day in the 2 week olds. The mortality was highest in this group. No simple correlation was observed between basal renal renin, plasma renin, the increase in plasma renin following HgCl2 injection, and the pattern or severity of acute renal failure.Speculation: The delayed recovery of renal function in younger rats may be due to a limitation in their ability to eliminate nephrotoxin imposed by immaturity of both glomerular and tubular function.

Developmental Aspects of Peritoneal Dialysis Kinetics

The past few years have seen an increased use of peritoneal dialysis to treat acute and chronic renal failure in neonates and infants. Successful peritoneal dialysis depends upon an understanding of the mechanisms involved in peritoneal transport and the degree to which dialysis kinetics differ in the young. To be considered is an overview of the principles involved in peritoneal dialysis, the manner in which they are altered during the development process, and the available data defining transport across the peritoneal membrane in the young experimental animal and child.

Glycerol-Induced Myohemoglobinuric Acute Renal Failure in the Pregnant Rat

These studies examined the effects of the volume expansion and the enhanced activity of the renin-angiotensin system during pregnancy on the severity of glycerol-induced myoglobinuric acute renal failure (ARF) in the rat. Renal cortical renin content (RCRC) and plasma renin concentration (PRC) were measured during the first, second, and third weeks of pregnancy. There were no significant changes in RCRC during pregnancy, but PRC was significantly elevated by the third week (22 +/- 2 vs. 12 +/- 2 ng angiotensin I/ml/k, p less than 0.001), despite plasma volume expansion as assessed by changes in the hemotocrit (37.7 +/- 0.5 vs. 46.4 +/- 0.6%, p less than 0.001). Despite the elevated PRC, a significant reduction in the severity of ARF was seen during the third week of pregnancy, as assessed by both blood urea nitrogen and inulin clearance measurements. When a sustained natriuresis was superimposed earlier in pregnancy by saline drinking, significantly more protection against ARF was seen, but with less plasma volume expansion. These results suggest that the mechanism by which saline drinking confers protection may be independent of the degree of volume expansion but may be dependent upon the associated sustained natriuresis.

The Role of Sodium in Childhood Hypertension

Even though controversial, much data supports a relationship between sodium and blood pressure regulation. Despite such support, the precise role of the sodium ion in the hypertensive process remains elusive and many are not able to demonstrate positive correlations (1). Also, rela-tively few studies of this relationship in pediatric populations exist. To be considered here are mechanisms by which sodium and blood pressure may be related, the impact of altering sodium balance on blood pressure in normotensive and hypertensive adults and children, genetic influences on sodium homeostasis, and the treatment, control and prevention of hypertension by means of reducing one’s sodium load. Not considered here are studies demonstrating a role in the hypertensive process for calcium, (2), magnesium, (3), and chloride (4). This article focuses on the view that sodium plays an important role in primary hypertension.

1051 LACK OF A ROLE FOR RENAL RENIN (RCRC) IN DETERMINING SUSCEPTIBILITY TO MYOGLOBINURIC RENAL FAILURE (ARF) IN THE ABSENCE OF CHANGES IN Na INTAKE

We have investigated the role of changes in RCRC (independent of Na intake) in determining susceptibility to ARF. RCRC was altered in either direction from control (Grp A - normal Na intake) in S.D. rats by 1% NaCl drinking + S.Q. DOCA for 4 wks (Grp B) or by a low Na diet for 6 wks (Grp C). For the next 5 days the animals were continued on the previous Na intake (Grp B1 & C1),normal Na intake (Grp B2 & C2), or 1% NaCl (Grp C3). On the 5th day the 24 hour urinary Na, C1 and Osm excretions were determined and random members from each group were sacrificed for RCRC determination. ARF was induced in the rest by injection of 10 mg/kg of 50% glycerol. Tail vein BUNs were done; results are shown (mean ± SEM). The number of animals in parenthesis.

SODIUM EXCRETION (U Na V) AND RENAL CORTICAL RENIN CONXTENT (RCRC) IN ACUTE EXPERIMENTAL RENAL FAILURE (ARF)

We investigated the interrelationships of RCRC, UNaV and protection from ARF. Six groups of 225-300 Gm female Sprague Dowley rats received H2O (GR.A) or 1% Saline (S) to drink. Gr. B & C received S for 3d, D & E, S for 7d, F, S for 6 wks. C & E received deoxycorticosterone 2.5 mg IM for 3 & 7d respectively. UNaV was measured for the 24 hr. proceeding the experiment. Approximately ½ of each group was sacrificed. Kidneys were analyzed for RCRC. The other ½ received 10 ml/kg of 50% glycerol IM. Results are expressed as mean ± SEM.The inverse correlation of UNaV and BUN (r -0.9, p < 0.001) is consistent with a feedback hypothesis of regulation of GFR in ARF but, contrary to current concepts, the lack of correlation of RCRC and severity of ARF argues against a local role for the renin anglotensin system in it. Protection from ARF occurs long before RCRC depletion during the course of saline drinking.