The effect of sodium benzoate, L-carnitine, and phenylacetate on valproate-induced hyperammonemia in Male Wistar rats.

INTRODUCTION: L-carnitine (LC) is commonly used in the treatment of valproate-induced hyperammonemia (VIHA). LC prevents the production of ammonia with no significant effect on renal ammonia excretion. This study was conducted to evaluate the effect of sodium benzoate (SB) and phenyl acetate (PA) on reducing VIHA. MATERIALS AND METHODS: Eight groups treated with Sodium Valproate (SV) at 300 mg/kg and 15 minutes later with normal saline, SB (144 mg/kg), PA (0.3 g/kg), LC (2.5 g/kg), SB (144 mg/kg) plus PA (0.3 g/kg), or SB (144 mg/kg) plus PA (0.3 g/kg) plus LC (2.5 g/kg), intraperitoneally. Other groups were exposed to normal saline, SB, LC or PA alone. Animal's motor function and serum ammonia, lactate, and sodium levels were assessed at 0.5, 1, and 1.5 hours after the SV injection. RESULTS: The results showed that LC reduced SV-induced hyperammonemia just at one and half-hour after treatment (P<0.001). PA, alone or in combination with other antidotes, reduced serum ammonia at all evaluated times (P<0.001). LC improved the impaired motor function of animals only at 1.5 hours, while PA, alone or in combination decreased the motor function scores at different times. However, SB administration alone did not change SV-induced hyperammonemia or motor function impairment. There was no significant difference in the level of serum aminotransferases, blood urea nitrogen, and creatinine between groups. CONCLUSION: These findings define that PA had a better therapeutic effect on valproate-induced hyperammonemia in comparison with SB. Co-administration of LC with PA ameliorated the elevated levels of ammonia and may relieve potential therapeutic application against acute SV intoxication.

Bioavailability of rectal acetaminophen in children following anorectal surgery.

BACKGROUND: Acetaminophen is widely used as an analgesic and antipyretic agent in pediatrics. Although bioavailability of rectal acetaminophen is unpredictable, rectal route is a usual and acceptable method of prescription. Major anorectal surgery may alter the normal structure of the surgical site, especially the vascular elements and the normal connections between port and systemic vessels. As a result the pharmacokinetics of rectal medications might also be altered. Based on this hypothesis, we decided to study acetaminophen plasma concentration among children who underwent these types of surgeries to determine the pharmacokinetic of absorption, plasma concentration, safety, and efficacy of rectal acetaminophen. MATERIALS AND METHODS: The study included 20 cases with previous history of pull-through procedure owing to Hirschsprung's disease (HD), 20 cases with imperforate anus (IA) reconstructive surgeries who were admitted for colostomy closure, and 20 otherwise healthy cases of inguinal herniotomy. Venus blood sampling was done 4, 8 and 12 hrs after a single loading dose of rectal acetaminophen (40 mg/kg), and plasma acetaminophen concentration was compared between groups. RESULTS: Mean serum acetaminophen levels of the HD group were significantly higher than those of the herniotomy group (36.3 ±â€¯6.79, 27.4 ±â€¯8.42, 16.8 ±â€¯7.62 versus 25.9 ±â€¯9.12, 16.7 ±â€¯6.74, 8.1 ±â€¯5.79 (µg/ml) at 4, 8 and 12 hrs after drug administration and P < 0.05). The IA group had higher concentrations of plasma acetaminophen compared to the herniotomy group; however, the p values were not statistically significant. (31.4 ±â€¯10.39, 21.5 ±â€¯9.12, 13.3 ±â€¯6.79 versus 25.9 ±â€¯9.12, 16.7 ±â€¯6.74, 8.1 ±â€¯5.79 (µg/ml) at 4, 8 and 12 hrs after drug administration). Serum concentrations of acetaminophen in IA and HD patients were above the therapeutic range four hours after administering the loading dose (31.4 ±â€¯10.39 and 36.3 ±â€¯6.79 versus 5-20 µg/ml). CONCLUSION: Bioavailability of rectal acetaminophen might get altered after major anorectal surgery in children. Rectal acetaminophen should be administered with special caution among infants with history of anorectal operations. Repeated dose of rectal acetaminophen may cause the drug blood concentration to reach toxic levels in these patients. TYPE OF STUDY: Prospective comparative study. LEVEL OF EVIDENCE: Level II.

Plant toxins and acute medicinal plant poisoning in children: A systematic literature review.

BACKGROUND: For many years, medicinal plants and herbal therapy have been widely used in different societies for the treatment of various diseases. Besides their therapeutic potency, some of the medicinal plants have strong toxicity in human, especially in children and elderly. Despite common beliefs that natural products are safe, there have been few reports on their toxicities. MATERIALS AND METHODS: In the present study, we aimed to systematically review the literature wherein acute plant poisoning and herbal intoxication have been reported in pediatric patients. After literature search and selection of the appropriate documents, the desired data were extracted and described qualitatively. RESULTS: A total of 127 articles with overall 1453 intoxicated cases were collected. The results of this study showed that some medicinal plants can cause acute poisoning and complications such as hepatic and renal failure in children. CONCLUSION: The findings of this survey showed that acute plant poisoning can be life?threatening in children, and since a single?ingested dose of toxic plants can cause acute poisoning, parents should be aware of these toxic effects and compare the side effects of self?medication with its potential benefits.

A Study of the Importance of Clonus Symptoms in Patients with Tramadol Poisoning.

OBJECTIVES: Clinical studies to reduce the side effects of tramadol, such as seizure, are necessary. Owing to the high prevalence of tramadol consumption and subsequent complications that result from seizures, the aim of the present study was to find a relationship between clonus and prediction of seizure outcome in patients with tramadol overdose. This can be used to determine the need for essential actions if a significant indicator of preventive medical measures is observed. METHODS: In this case-control study, three groups of patients poisoned with tramadol and with marked ankle clonus were evaluated. A sample size of 50 patients per group was calculated using the Cohen first method. The data were analyzed using SPSS16 software. RESULTS: All patients with ankle clonus were evaluated. Seizures occurred most commonly in patients aged 21-25 years or younger. The patients who received the preventive medication of magnesium sulfate were seizure-free for 72 h after admission. CONCLUSION: It is recommended that, for all patients referred with tramadol poisoning who have symptoms of ankle clonus, the administration of magnesium sulfate should be considered in addition to medication for the prevention of seizures and arrhythmias.

Frequency of Electrocardiographic Abnormalities in Tramadol Poisoned Patients; a Brief Report.

INTRODUCTION: Previous studies have raised the probably of cardiac manifestation in tramadol poisoning. However, conclusive information on electrocardiographic (ECG) abnormalities of tramadol overdose remains to be explained. Therefore, the present study aimed to evaluate the epidemiology of ECG abnormalities in tramadol poisoned patients. METHODS: In a prospective cross-sectional study, all patients with tramadol poisoning, who were admitted to the emergency department of Loghman Hospital during 2012 - 2013, were evaluated. Patients' baseline characteristics and ECG findings including axis, rate, rhythm, PR interval, QRS duration, QTc interval, evidence of Brugada pattern, and evidence of blocks were recorded. Obtained Data were descriptively analyzed using SPSS 21.0 statistical software. RESULTS: 1402 patients with the mean age of 24 ± 6 years were studied (71.1% male). Sinus tachycardia was detected in 463 (33%) patients, sinus bradycardia in one patient (0.07%), right axis deviation in 340 (24.2), QRS widening in 91 (6.5%), long QTc interval in 259 (18.4%), dominant S wave in either I or aVL lead in 395 (28.1%), and right bundle branch block in 73 (5.2%). Increased PR interval was not detected in any cases. The evidence of Brugada pattern was observed in 2 (0.14%) patients (100% male), both symptomatized with seizure. All abnormalities had same sex distribution. CONCLUSION: Based on the results of the present study, the most common types of ECG changes were sinus tachycardia, a deep S wave in leads I and aVL, right axis deviation, and long QTc interval, respectively. Brugada pattern and sinus bradycardia were rarely presented.