Anti-interleukin-6 antibodies attenuate inflammation in a rat meningitis model.

OBJECTIVES: Interleukin-6 (IL-6) is elevated in the cerebrospinal fluid (CSF) of humans and animals with bacterial meningitis. This study's hypothesis was that anti-IL-6 antibodies will attenuate meningeal inflammation in a rat model of bacterial meningitis. METHODS: 14 male Sprague-Dawley rats were inoculated intracisternally (IC) with 0.1 mL of heat-killed pneumococci. At one hour post-inoculation, the rats received intraperitoneal doses of either 1.0 mL phosphate-buffered saline (PBS treatment group, n = 7) or 70 microg anti-IL-6 antibodies in 1.0 mL PBS (anti-IL-6 antibody treatment group, n = 7). Nine rats (normal group, n = 9) had no inoculation, and four rats (surgical sham group, n = 4) had IC inoculations of saline. At six hours post-inoculation, all the animals had CSF removed via IC tap. The CSF protein and white blood cell (WBC) count measures were compared using a t-test. RESULTS: Mean CSF WBC for the anti-IL-6 treatment group was 2,458/microL, versus the PBS controls' mean of 9,697/microL (p = 0.007). Mean CSF protein for the anti-IL-6 group was 180 mg/dL, versus 296 mg/dL for the controls (p = 0.032). The surgical sham and normal animals had normal CSF WBC and protein values. CONCLUSIONS: In this rat meningitis model, systemic treatment with anti-IL-6 antibodies after the induction of meningitis suppressed both CSF WBC count and CSF protein level, two important indices of meningeal inflammation.

Potassium repletion fails to interfere with reduction of serum lithium by sodium polystyrene sulfonate in mice.

OBJECTIVES: Previous studies have shown that oral sodium polystyrene sulfonate (SPS) lowers serum lithium concentrations after acute and chronic toxic lithium exposures. Because hypokalemia may represent a deterrent to the clinical use of SPS for lithium intoxication, this study was designed to determine whether potassium (K+) repletion interferes with the effect of SPS on serum lithium. METHODS: 168 male, CD-1 mice were given lithium chloride (LiCl) (250 mg/kg) by gavage at time 0. Half of the mice were then given SPS (5 g/kg/dose) and half an equivalent volume of water by gavage at times 20 and 40 minutes. Half of each of these subgroups was then given potassium chloride (KCl) (3 mmol/kg) intraperitoneally and half an equivalent volume of normal saline. The animals were then sacrificed at one, two, four, and eight hours after lithium administration and the sera were analyzed for lithium and K+ by atomic absorption spectrophotometry. The groups were compared with analysis of variance. RESULTS: The SPS lowered both lithium and K+ concentrations (ps < or = 0.0001). The KCl treatment was associated with transiently increased K+ concentrations (p < 0.0001) and with mildly elevated lithium concentrations when compared with the results of the animals not treated with KCl (p = 0.0016). The KCl treatment-associated increase in lithium concentration occurred both in the animals treated with water and in those treated with SPS. CONCLUSIONS: Potassium repletion did not interfere with the ability of SPS to lower serum lithium concentration in animals experimentally poisoned with lithium.

Lithium has no direct effect on cardiac function in the isolated, perfused rat heart.

To determine if lithium exerts direct cardiac toxicity, using an isolated, perfused rat heart model, paced and unpaced beating rat hearts were perfused with Krebs-Henseleit bicarbonate solution and left ventricular pressures were measured via a balloon-tipped catheter positioned in the left ventricle via the mitral valve. Following a stabilization period, hearts were then perfused with Krebs-Henseleit bicarbonate solution containing 1, 10, and 100 mM ionized lithium chloride or lithium carbonate in an antecedent dose-response protocol and perfused for 10 min. at each dose. To control for the possibility of osmotic effects from the high dose of lithium, an additional group was studied in which hearts were perfused with Krebs-Henseleit bicarbonate solution for an initial stabilization period, then perfused for an additional 20 min. with Krebs-Henseleit bicarbonate solution alone, and finally with Krebs-Henseleit bicarbonate solution containing mannitol (200 mOsm/l) for 10 min. Lithium did not have any effect on left ventricular peak systolic pressure, left ventricular end diastolic pressure, heart rate or coronary haemodynamics at concentrations of 1 or 10 mM. At 100 mM LiCl and Li2CO3, left ventricular peak systolic pressure decreased transiently during the first minute of lithium infusion, but recovered significant function by 10 min. Heart rate decreased significantly by 10 min. of infusion. These effects were also seen in the osmotic controls and thus do not appear to be a direct effect of lithium. At the doses tested, lithium had no direct effect on cardiac function which could not be explained by an osmotic effect.

Wood's lamp utility in the identification of semen.

BACKGROUND: The accurate detection of semen is critical to forensic, medical, and legal personnel. The Wood's lamp (WL) emits ultraviolet light (UVL) and has been identified as useful in rape evaluations because it is purported to cause semen to fluoresce. This study was intended to determine if semen can be distinguished from other products by WL analysis. METHODS: Investigators reviewed the previous training and frequency of use of the WL by emergency medicine and pediatric emergency medicine physicians at 2 medical centers. The participants were asked to use a WL to distinguish between a semen sample (<6 hours old) and 13 commonly used products. Next, 29 semen samples were collected and evaluated under high-power microscopy and under UVL. RESULTS: A total of 41 physicians participated in the study (68% male). The number of years practicing in an emergency setting spanned from.3 to 25 years with a mean of 7. 1 years. A total of 51% of participants trained in emergency medicine, 23% in pediatrics and pediatric emergency medicine. A total of 22% reported formal training in the collection of forensic evidence. A total of 62% of the physicians believed they have identified semen in the past; one third felt they could differentiate semen from other products under UVL. None of the 41 physicians were able to differentiate semen from other products using a WL. Moreover, the semen samples used for the study did not fluoresce under WL analysis. None of the 29 semen samples fluoresced whether wet or dry. The medicaments most commonly mistaken for semen were A&D ointment (Cardinal Health, Inc, Dublin, OH), Surgilube (Division of Atlanta, Inc, Melville, NY), Barrier cream (Carrington Laboratories, Inc, Irving, TX), and bacitracin (Division of Atlanta, Inc, Melville, NY). CONCLUSIONS: Participating physicians were unable to distinguish between semen and other common products, using the WL. Although the WL has been purported to be a useful tool as a screening device for the detection of seminal stains, the investigators have found it to be unreliable. Semen, previously reported to fluoresce under WL analysis, does not appear to do so. The correct identification of semen may be complicated by the presence of previously existing ointments and creams, some of which may be iatrogenically introduced (ie, Surgilube).

Mothers with histories of domestic violence in a pediatric emergency department.

OBJECTIVE: To determine the prevalence of domestic violence against mothers in a pediatric emergency department and the relationship of their children to the abusers. DESIGN: Cross-sectional survey of a convenience sample of mothers seeking treatment for their children. SETTING: An urban pediatric emergency department. PARTICIPANTS: A total of 157 mothers with children <3 years of age. Women were excluded if older children or partners were present. RESULTS: A total of 52% of women reported histories of adult physical abuse, 21% reported adult sexual abuse, and 28% reported childhood sexual abuse. A total of 10% of women were in abusive relationships in the past year. Victims of adult physical abuse were more likely to report histories of adult sexual abuse (relative risk [RR]: 4.93) or childhood sexual abuse (RR: 3.13). Intimate partners perpetrated 67% of physical abuse and 55% of sexual abuse. Relatives perpetrated 66% of childhood sexual abuse. Women who revealed histories of childhood sexual abuse were more likely to report adult sexual abuse (RR: 4. 93). A total of 40% of the perpetrators of adult physical abuse, 73% of the perpetrators of past year physical abuse, and 10% of the perpetrators of adult sexual abuse had regular contact with their victims' children. Health care providers screened only 21% of the women for past violence. Victims of domestic violence were no more likely to have been screened than those without histories of physical or sexual abuse. CONCLUSIONS: Mothers of young patients in a pediatric emergency department are often victims of domestic violence. Perpetrators are often close relatives and thus place the victims' children at risk for abuse and for the psychological trauma of witnessing violence. Given the prevalence of domestic violence, families may benefit from routine violence screening and interventions in pediatric emergency departments.

Acute isoniazid exposures and antidote availability.

BACKGROUND: Over the past 10 years the reported incidence of acute isoniazid (INH)-related poisonings has increased, with 507 cases reported in 1996. Parenteral pyridoxine is the antidote for INH-induced seizures, but 5-g aliquot recommended to treat an ingestion of unknown quantity of INH is not always readily available to emergency physicians. OBJECTIVE: To determine the hospital availability of pyridoxine. METHODS: One hundred thirty questionnaires were distributed nationwide to the pharmacies and emergency departments (ED) of hospitals containing pediatric emergency medicine (PEM) fellowships and/or emergency medicine (EM) residencies. Questions were posed regarding the availability, quantity, location, and deemed importance of pyridoxine at each institution. RESULTS: Responses were received from 81% of the hospitals with fellowships and 80% of the hospitals with residencies. Half of the former and one third of the latter reported not having the recommended 5-g aliquot available. Eighty percent of the hospitals with PEM programs and 71% with EM residencies with an adequate stock store it in the hospital's pharmacy, as opposed to in the ED. Thirty-four states were represented, 18 of which have experienced an increase in tuberculosis (TB) from 1993 to 1994; 6/18 (33%) of those did not have the pyridoxine available, and 7/18 (39%) did not deem it necessary. CONCLUSIONS: Our results imply that between one third and one half of the respondents would be ill-equipped to treat acute INH neurotoxicity. Establishing regional distribution centers may alleviate this deficiency, specifically in urban areas with a high incidence or a positive percent increase in TB.

Effect of amiloride on age-dependent cardiac dysfunction after ischemia/reperfusion in the isolated, perfused rat heart.

This study was intended to compare the cardiac consequences of ischemia/reperfusion and amiloride treatment in immature (2-3 wk), juvenile (4-6 wk), and adult (3-5 mo) rats using an isolated, perfused heart model. Male immature, juvenile, and adult rats were anticoagulated and anesthetized. Hearts were harvested and coronary arteries were perfused on a Langendorff apparatus via retrograde perfusion of the aorta at a constant coronary flow (initially determined by perfusing the heart at 50 mm Hg perfusion pressure) with oxygenated Krebs-Henseleit-Bicarbonate (KHB) solution. Left ventricular peak systolic (LVPSP) and end diastolic (LVEDP) pressures were measured via a balloon-tipped catheter placed in the left ventricle through the mitral valve. Following a 20-30 min stabilization period, hearts underwent 30 min of normothermic ischemia and were then reperfused with Krebs-Henseleit-Bicarbonate alone for 30 min, or Krebs-Henseleit-Bicarbonate containing 500 microM amiloride for 5 min followed by Krebs-Henseleit-Bicarbonate alone for 25 min (n = 6/age group). Left ventricular generated pressure was calculated (left ventricular peak systolic-left ventricular end diastolic) and used as a measure of ventricular function. All hearts demonstrated a decrease in generated pressure, respectively, from preischemic levels at 15 and 30 min of reperfusion, although this decrease was significantly less for the immature hearts. Ischemia/reperfusion injury was attenuated by amiloride in adult and juvenile hearts, whereas ischemia/reperfusion injury was worsened by amiloride in immature hearts. Although immature hearts were relatively resistant to ischemia/reperfusion injury compared with adult and juvenile hearts, the presence of amiloride during reperfusion resulted in more severe ventricular dysfunction in immature hearts. These data suggest a differential age-dependent mechanism of sarcolemmal ion exchange in response to ischemia/reperfusion.

Effect of metoclopramide dose on preventing emesis after oral administration of N-acetylcysteine for acetaminophen overdose.

OBJECTIVE: To determine the effect of the metoclopramide dose on the prevention of vomiting of N-acetylcysteine in acetaminophen overdose. METHODS: Patients with acetaminophen ingestions receiving metoclopramide prior to emergency department administration of N-acetylcysteine were included. Emergency Department and poison center records were reviewed for administration of metoclopramide pre-N-acetylcysteine and incidence of subsequent vomiting. The treatment group was defined as patients receiving high-dose metoclopramide (20-50 mg intravenously) prior to the loading dose of N-acetylcysteine. Controls were patients receiving standard-dose (< 20 mg intravenously) metoclopramide prior to loading dose of N-acetylcysteine. Outcome was vomiting within 60 minutes of N-acetylcysteine administration. RESULTS: Twelve of 19 patients (63%) receiving standard-dose metoclopramide vomited N-acetylcysteine. Only 5 of 23 patients (22%) receiving high-dose metoclopramide vomited N-acetylcysteine (crude odds ratio: 6.2; 95% CI [1.3-30.3]). After controlling for confounding in the logistic regression model, the effect of high-dose metoclopramide in preventing vomiting of N-acetylcysteine remained significant (adjusted odds ratio: 17.0; 95% CI [2.6-110.0]). CONCLUSION: This study supports the efficacy of high-dose metoclopramide to prevent emesis after the oral loading dose of N-acetylcysteine.

Use of sodium polystyrene sulfonate for reduction of plasma lithium concentrations after chronic lithium dosing in mice.

OBJECTIVES: Previous studies have shown that oral sodium polystyrene sulfonate lowers plasma lithium concentrations after acutely administered oral doses of lithium chloride. However, a significant proportion of lithium overdose cases resulting in morbidity and mortality are those in which exposure to lithium is chronic. This study was designed to determine whether multiple oral doses of sodium polystyrene sulfonate are effective in reducing plasma lithium concentrations after chronic dosing. DESIGN: Placebo-controlled animal study. INTERVENTIONS: One hundred thirty mice were given 75 mM lithium chloride in their drinking water for a period of 14 days. At the end of that period, half of the animals were given orogastric sodium polystyrene sulfonate at 5 g/kg/dose 0, 60, 120, 180, and 360 minutes after the cessation of lithium chloride; the remaining half received orogastric water at equivalent times. Subgroups of each group were sacrificed at 90, 150, 330, 480, 1440, and 2880 minutes after lithium chloride cessation and plasma analyzed for lithium content. Lithium concentrations were compared by analysis of variance and single degree of freedom contrasts. Significance was set at an alpha level of 0.05. RESULTS: Lithium concentration was lower overall in the animals treated with sodium polystyrene sulfonate (p < .0001) and specifically at 150, 330, and 480 minutes after lithium chloride cessation (p < .05). CONCLUSIONS: Repetitive oral doses of sodium polystyrene sulfonate effectively lowered plasma lithium concentrations. Further study may ultimately define a role for the use of sodium polystyrene sulfonate in the treatment of patients with chronic lithium toxicity.

Frozen oral hydration as an alternative to conventional enteral fluids.

BACKGROUND: Oral hydration therapy is effective in dehydration, but is often bypassed or may fail. OBJECTIVE: To compare the tolerance (amount accepted minus amount vomited) of a frozen solution (FS) (Revital-ICE, PTS Labs, Deerfield, Ill) with the conventional glucose electrolyte solution (CS). DESIGN: Prospective, controlled crossover trial. SETTING: Pediatric emergency department. PARTICIPANTS: A convenience sample of 91 children with enteritis, 6 months to 13 years of age, with mild or moderate dehydration. INTERVENTION: Children were offered either FS or CS. Each group was offered 10 mL/kg of either product during a 90-minute trial period, in 3 equal aliquots, and was monitored for the quantities consumed and vomited. Complete treatment failures (absolute refusal) were crossed over to the alternate product and intake was recorded. MAIN OUTCOME MEASURES: Tolerance of the full 10 mL/kg of the original product offered and, for treatment failures, the percentage who tolerated the alternate product. RESULTS: Of the patients who initially received FS, 23 (55%) tolerated the full amount offered, compared with 5 (11%) in the CS group (P < .001). Of the 57% who completely refused CS, after crossover, 20% tolerated the full amount of FS and 33% tolerated between 5 and 9 mL/kg of FS and were discharged from the hospital. The original treatment failures for FS (12%) were crossed over to CS; none tolerated more than 5 mL/kg CONCLUSIONS: Children with mild or moderate dehydration are more likely to tolerate FS than CS. Conventional solution failures crossed over to FS had a greater tolerance rate than the reverse.

Factors and methodology in achieving ideal delivery temperatures for intravenous and lavage fluid in hypothermia.

A study was undertaken to determine the relationship between temperature and delivery rate of warmed intravenous fluid using standard intravenous infusion equipment and tubing. One-liter bags of 0.9% NaCl were warmed to 60 degrees C and run through standard microdrip tubing for 1 hour at rates of 1,000, 800, 600, and 400 mL/h. Thermistor probes were placed into the bag and into the tubing at 0, 100, 180, 230, and 280 cm from the intravenous bag. Separate fluid bags were also warmed to 39.3 degrees and 75 degrees C, and the fluid was run through the same apparatus at 1,000 mL/h and 200 mL/h, respectively. Temperatures were recorded at each site at the start of the infusion and every 10 minutes thereafter for 1 hour, Subsequently, 60-mL syringes of fluid warmed to 39.5 degrees C were eluted through 50 cm tubing over 10 minutes at 300 mL/h and 360 mL/h. Mean delivery temperature over each 10-minute infusion was determined. Fluid preheated to 39.3 degrees C approached room temperature at delivery even at a flow rate of 1,000 mL/h and tubing lengths as short as 100 cm. Fluid preheated to 60 degrees C was delivered at near 37 degrees C using tubing lengths as long as 280 cm when eluted at 1,000 mL/h. Fluid preheated to 39 degrees C in 60-mL syringes and eluted through 50 cm of tubing over a period of 10 minutes at 300 mL/h or 360 mL/h was delivered near a mean temperature of 37 degrees C. These results show that warmed fluid can be delivered through standard intravenous tubing at or near 37 degrees C if the fluid is preheated to 60 degrees C and eluted through long tubing (280 cm) at high flow rates (1,000 mL/h). Alternatively, fluid warmed to 37 degrees C to 42 degrees C can be delivered at or near 37 degrees C via intermittent bolus through short tubing (50 cm) either by hand or syringe pump. The latter approach would be particularly beneficial in the pediatric population, in whom it is not advisable to administer fluid at flow rates as high as 1,000 mL/h.

Enhancement of lithium elimination by multiple-dose sodium polystyrene sulfonate.

OBJECTIVE: To determine whether multiple doses of sodium polystyrene sulfonate (SPS) enhance the elimination of IV-administered lithium (Li). METHODS: The study was a placebo-controlled, investigator-unblinded, murine trial of multiple doses of SPS on serum Li concentrations. Seventy-five male CD-1 mice were given IV pretreatment with LiCl (125 mg/ kg) followed by gavage treatments with SPS (5 g/kg/dose) 20, 40, 90, 150, and 210 minutes after LiCl (experimental group) or deionized water at equivalent times (control group). Subgroups of each treatment group were sacrificed at 1, 2, 4, and 6 hours after LiCl administration and blood was collected for Li analysis. RESULTS: Statistical analyses indicated that the SPS group had lower serum Li concentrations overall than did the control animals. This difference was apparent at the 2-, 4-, and 6-hour time points. CONCLUSION: In this murine model, repetitive doses of orogastric SPS enhanced the elimination of parenterally administered Li.

Sodium polystyrene sulfonate treatment for lithium toxicity: effects on serum potassium concentrations.

OBJECTIVE: To examine the effects of sodium polystyrene sulfonate (SPS) on serum potassium (K) concentrations in mice pretreated with parenteral lithium (Li). METHODS: A placebo-controlled murine model trial of SPS therapy following IV Li was performed. Sixty male CD-1 mice weighing 18-22 g were administered either IV LiCl (125 mg/kg) or a control solution (normal saline). Half of the mice in each of these groups were then given orogastric water 20, 40, 90, 150, and 210 minutes after LiCl or normal saline; the other half received SPS (5 g/kg/dose) at equivalent times. Subgroups of each of these four groups were sacrificed at one, two, and six hours after pretreatment and the serum was analyzed for K concentration. Serum K concentrations for the various groups were compared with analysis of variance and Newman-Keuls tests for the comparison of multiple means. RESULTS: A statistically significant reduction of serum K concentrations occurred in the animals that received SPS treatment following either IV saline or LiCl solutions. The degree of K reduction that resulted from the combination of LiCl and SPS treatment (35% reduction at six hours, compared with the placebo-treated controls) was larger than that which resulted from either IV Li with oral water (15% reduction) or IV saline with oral SPS (20% reduction). CONCLUSIONS: These findings suggest that development of hypokalemia may represent a potential limitation in the use of SPS in the treatment for Li toxicity.

Effect of delayed treatment with sodium polystyrene sulfonate on serum lithium concentrations in mice.

OBJECTIVES: To determine the efficacy of sodium polystyrene sulfonate (SPS) in lowering serum lithium (Li) concentrations. Specifically, to determine the effects of both different doses of SPS and different times to treatment with SPS on serum Li levels. METHODS: The study was a controlled, single-dose murine trial of SPS on serum Li levels. Male CD-1 mice (n = 525) were given orogastric LiCl and then divided into three main treatment groups: group SPS received a single orogastric administration of SPS in a dose of 5 gm/kg body weight at either 0, 15, 30, 45, or 90 minutes after LiCl; group half-SPS received a single orogastric administration of SPS in a dose of 2.5 gm/kg body weight at times equivalent to those of group SPS; and the control group received orogastric deionized water in a volume equivalent to that of group SPS at 0, 15, 30, 45, or 90 minutes after LiCl. Subgroups of seven to ten mice in each of the four treatment groups were sacrificed at one, two, four, and eight hours after administration of LiCl, and their blood was analyzed for Li concentration. RESULTS: 1) Single doses of SPS significantly lowered serum Li concentrations; 2) this effect was dose-related; 3) the delays in administration of SPS used in this study did not significantly reduce its ability to lower serum Li concentrations; and 4) even when administered after peak serum Li concentrations had been achieved, a single dose of SPS was effective in lowering serum Li levels. CONCLUSIONS: SPS may be efficacious in the treatment for Li toxicity under certain circumstances, even when there is delay to treatment. Additional study is warranted to further characterize the ability of SPS to alter Li kinetics.

Use of infrared thermometry to measure lavage and intravenous fluid temperature.

A study was conducted to determine the accuracy of tympanic thermometers for measuring the temperature of warmed fluids in fluid bags and in tubing at the delivery site (ie, beside the intravenous [IV] catheter). One-liter 0.9% saline bags were warmed in a microwave oven. A thermocouple electronic temperature probe was then used to measure the reference temperature. The probe was inserted into each bag and bathed in the fluid. Temperature changes were recorded simultaneously over a 20-minute period using the probe and a First Temp Tympanic Thermometer (Intelligent Medical Systems, Inc, Carlsbad, CA). The warmed fluid was then allowed to run through microdrip IV tubing. Temperature of the effluent was measured in the tubing using the tympanic thermometer externally and the probe internally at the same point. The two measures were compared using linear regression and Student's t tests. Overall, the correlation between the two probes was r = 0.99 for both the fluid bags and the IV tubing. The overall mean differences were small, 0.7 degrees C and 1.2 degrees C for the bags and tubing, respectively, but they were statistically different (P > .05). Data were analyzed in three temperature ranges: < 36 degrees C, 36 degrees C to 41 degrees C, and 41 degrees C. Again, small differences were found on the order of 1 degree C. It was concluded that infrared thermometry is an accurate method for measuring the initial and delivery temperature of warmed fluids. Although tympanic thermometer measurements were statistically different from reference readings in certain temperature ranges, these differences were small and not clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Child with idiopathic ventricular tachycardia of prolonged duration.

Ventricular tachycardia is a dangerous dysrhythmia most commonly encountered in adult patients with heart disease. It is uncommon for a previously healthy child to present to the emergency department with hemodynamically stable ventricular tachycardia. The diagnosis and management of this dysrhythmia may pose a significant challenge to the emergency physician. We present the case of a previously healthy child with a structurally normal heart who had ventricular tachycardia for a prolonged period. Common causes of childhood tachycardia and options for treatment of stable and unstable patients are discussed.