Acute renal injury following methanol poisoning: analysis of a case series

The objective of this paper is to document the prevalence of indicators of acute renal injury in a series of methanol-poisoned patients treated in an intensive care unit and to discuss the possible mechanisms. This is a retrospective analysis of the medical records of 25 consecutive patients admitted to the intensive care unit after severe intentional methanol poisoning. Acute renal impairment was defined as a serum creatinine concentration higher than 177 micro mol/L and/or a urinary output on admission and for the first 24 h below 0.5 ml/kg/h. Clinical pathological signs of acute renal injury were found in 15 patients. In comparison with the 10 other patients taken as control group, the patients who developed renal injury had a lower blood pH value on admission, a higher serum osmolality, and a higher peak formate concentration. Two factors contributing to renal injury could be identified: hemolysis and myoglobinuria. The role of osmotic changes (osmotic nephrosis) or of a direct cytotoxic effect of formic acid remains speculative. Analysis of proteinuria suggests that proximal tubular cells may be preferentially affected. Results of histopathological evaluation of the kidney on a limited sample size (n = 5) were inconclusive but suggestive of possible hydropic changes in the proximal tubule secondary to methanol toxicity. Acute renal injury may be associated with other signs of severity in methanol poisoning, but it is almost always reversible in survivors. Indicators of acute renal injury were identified. The pathophysiology of this acute renal injury is multifactorial and far more complex than shock-related tubular necrosis.     

Hyperamylasemia and acute pancreatitis following anticholinesterase poisoning

A prospective study was undertaken to find the incidence of hyperamylasemia and acute pancreatitis in patients with anticholinesterase poisoning. This was done by serial estimation of total serum amylase and pancreatic imaging by ultrasonography and confirmed, if necessary, by computerized tomography. Anticholinesterase poisoning was caused by either ingestion or accidental exposure to organophosphates or carbamates; it was diagnosed when patients presented with features of cholinergic crisis, depressed serum butyrylcholinesterase activity of >50% and showed improvement following administration of atropine alone or atropine and 2-PAM. All the patients admitted with anticholinesterase poisoning between July 2001 and June 2005 were prospectively studied for elevated serum amylase. The serum amylase levels were estimated daily up to 10 days in survivors and in nonsurvivors till they survived. Ultrasonography of the abdomen was carried out in all to find swelling of the pancreas. Computerized tomography was undertaken in those who had a swollen pancreas or whose serum amylase levels were elevated significantly (> or =800 S.U). Of the 86 patients enrolled, 79 were taken up for analysis as data were incomplete in 7. Of the 79 patients, serum amylase was found to be elevated that is, >200 S.U. in 37 patients (46.95%). In three patients it was 800 S.U. One of them showed swollen pancreas on ultrasonography, which was confirmed by computerized tomography. This patient had ingested propoxyfur. In the other two patients, evidence of acute pancreatitis was not observed (on autopsy in one who died and on imaging in the other who survived). They had ingested chlorpyrifos. There was no significant correlation between the nature of the compounds (organophosphate or carbamates), inhibition of serum BUChE at admission, duration and severity of cholinergic syndrome and increase and time course of increase in serum amylase. Except for fenthion, significant persistent increase in serum amylase was not observed with individual compounds. The other associated abnormalities were polymorphonuclear leukocytosis (TLC >11,000/cumm) in all 37 patients who had elevated amylase, hyperglycemia (6/37) and, elevated transaminases (6/37). Mild elevation of serum amylase is common in patients with anticholinesterase poisoning. However, acute pancreatitis is rare.     

Prognostic factors in methanol poisoning

The aim of this study was to assess the clinical and laboratory factors in methanol poisoned patients to determine the prognosis of their toxicity. This survey was done as a prospective cross-sectional study in methanol-poisoned patients in Loghman-Hakim hospital poison center during 9 months from October 1999-June 2000. During this time 25 methanol-poisoned patients were admitted. The mortality rate was 12 (48%). Amongst survivors, three (23%) of the patients developed blindness due to their poisoning and the other 10 (77%) fully recovered without any complication. The mortality rate in comatose patients was nine (90%) while in non-comatose patients it was three (20%) (P<0.001). There was a significant difference in mean pH in the first arterial blood gas of patients who subsequently died (6.82+/-0.03) and survivors (7.15+/-0.06) (P<0.001, M-W). The mean time interval between poisoning and ED presentation in deceased patients were (46+/-15.7) hours, in survived with sequelae were (16.7+/-6.7) and in survived without sequelae were (10.3+/-7.2) hours (P<0.002, K-W). We found no significant difference between the survivors versus the patients who died regarding methanol. Simultaneous presence of ethanol and opium affected the outcome of the treatment for methanol intoxication favourably and unfavourably, respectively. In our study, poor prognosis was associated with pH<7, coma on admission and >24 hours delay from intake to admission.     

Formate kinetics in methanol poisoning

OBJECTIVE: The objective is to describe the kinetics of formate, the main toxic metabolite of methanol, in a series of consecutive patients treated in the same intensive care unit for severe methanol poisoning. METHODS: The charts of the patients admitted between 1987 and 2001 were reviewed. Inclusion criteria were: a history of deliberate methanol ingestion, with a blood methanol concentration greater than 20 mg/dL (6.2 mmol/L) or a high anion gap metabolic acidosis. Indications for hemodialysis were: blood methanol concentration >50 mg/dL (15.8 mmol/L), metabolic acidosis (bicarbonate <15 mmol/L, arterial pH <7.30), visual toxicity. Antidotal therapy included ethanol administration in 22 cases, and fomepizole in three cases. Serial blood measurements were obtained for pH, bicarbonate, methanol and formate. Endogenous and hemodialysis elimination half-lives were calculated as t1/2 =0.693/Ke. Fick principle was applied for hemodialysis clearance calculation. RESULTS: The records of 25 methanol poisoned patients were analysed. Among them, 18 patients had sufficient data to allow accurate determinations of formate kinetics. Formate half-life elimination during hemodialysis was 1.80+/-0.78 h, which was statistically different from the values observed before or in the absence of dialysis (6.04+/-3.26 h, P =0.004). The mean hemodialysis formate clearance rate calculated in eight cases was 176+/-43 mL/min. A rebound in plasma formate concentration was observed in three patients after the discontinuation of hemodialysis. CONCLUSIONS: In accordance with previous isolated case reports and in contrast with a recent case series, our data document that hemodiaysis is effective in reducing formate elimination half-life. The impact on clinical outcome is still debatable.     

Formate kinetics in methanol poisoning

OBJECTIVE: We sought to describe the kinetics, dialysis clearance, and laboratory markers of formate (FA), the toxic metabolite of methanol (meOH). METHODS: Data were obtained from a prospective, multicenter study of fomepizole +/- dialysis for methanol poisoning. Inclusion criteria confirmed methanol exposure or suspicion of exposure plus either acidemia or abnormal osmolar gap. Dialysis indications were [meOH] > 50 mg/dL, pH < 7.1, refractory acidosis, or visual toxicity. Serial plasma formate, methanol, pH, and electrolyte measurements were made. Formate was determined by gas chromatography. Endogenous and dialysis elimination half-lives were calculated as t(1/2) = 0.693/Ke, with Ke (elimination constant) derived from the slope of log (FA) vs. time. Half-lives were compared with an unpaired Student's t-test. Dialysis clearance was calculated using the Fick Principle. Pearson correlation analysis compared initial formate with initial pH, serum bicarbonate, and anion gap. RESULTS: Eleven patients were treated in the study. Eight had detectable formate with mean [FA] of 15.1 mmol/L (range 0.5-34.8). Endogenous elimination half-life was 205 +/- 90 minutes. Elimination half-life during dialysis (n = 5) was 150 +/- 37 minutes, which was not different (t = 0.22; NS). The overall dialysis formate clearance rate was 223 +/- 25 mL/min. Correlation coefficients were: pH vs. formate r2 = 0.93; bicarbonate vs. formate r2 = 0.81; and anion gap vs. formate r2 = 0.76 (all p < 0.05). CONCLUSIONS: Although dialysis clears formate, it did not significantly enhance endogenous elimination in our series of patients. Low pH, low bicarbonate, and elevated anion gap correlate independently with formate presence.     

Homicidal methanol poisoning in a child

A case of homicidal poisoning of a 21-month-old child using methanol is presented. The child was found dead in his crib during a court-ordered visit to his father's home. He reportedly was experiencing "flu-like" symptoms the day before. Routine toxicology testing of specimens taken at autopsy revealed the presence of methanol in a concentration of 0.21%, 0.23%, 0.31%, 0.28%, and 0.26% (w/v or w/w) in heart blood, venous blood, urine, vitreous humor, and gastric contents, respectively. Formic acid concentrations were 1.0 and 6.4 g/L in heart blood and urine. No other drugs or chemicals were detected in comprehensive screening. Accidental ingestion of methanol was ruled out; however, the homicide investigation was complicated by the fact that up to seven adults at three different locations had been involved in the child's care. Minimal information in the literature on the time frame for the development of symptoms of methanol intoxication in a child of this age made predicting a likely time of ingestion difficult. Discussion of the investigation and the timeline for the poisoning that was eventually established are included.     

思密达对百草枯中毒大鼠急性肺损伤的治疗

目的:通过观察思密达对百草枯中毒大鼠血浆百草枯浓度和肺组织病理改变,探讨思密达在治疗百草枯中毒大鼠急性肺损伤中的作用。方法:制备百草枯中毒模型,分别于10 min和30 min给予思密达进行干预治疗。测定各组大鼠2、6、24、48、72 h的血浆百草枯浓度,摘取左肺制备肺组织病理切片,光镜下观察肺组织的病理改变并进行肺损伤评分。结果:思密达10 min干预组血浆百草枯浓度明显低于模型组和30 min干预组;思密达干预组大鼠肺组织病理评分比模型组明显降低,且10 min干预组大鼠24、48、72 h肺损伤比30 min干预组明显减轻。结论:思密达可以通过降低大鼠血浆百草枯浓度而对中毒大鼠肺组织起到保护作用,且思密达的应用越早越好。     

急性口服甲醇中毒血甲醇浓度与代谢性酸中毒的关系

目的探讨急性口服甲醇中毒血甲醇浓度与代谢性酸中毒的关系及其对血液透析(HD)适应症的影响.方法观察53例急性口服甲醇中毒患者血液甲醇浓度(M)、血二氧化碳结合力(CO2CP)和阴离子间隙(AG),按是否行HD治疗分为HD治疗组(GHD)、非HD治疗组(GNHD);用气相色谱顶空进样法(GC)测定M;并按不同M水平进行分析.结果①两组间logM、CO2CP和AG均有显著差异;②M在0.5～7.8mmol/L时,两组间出现例数无显著性差异;③CO2CP＜15mmol/L的HD患者中,大部分(22例,85%)M＜15.6mmol/L,其中有18例(69%)M＜7.8mmol/L.结论在应用M＞15.6mmol/L作为HD适应征时,应充分考虑其与代谢性酸中毒的关系.     

Ultrastructural changes in rat liver treated with pralidoxime following acute organophosphate poisoning

We investigated the ultrastructural effects of methamidophos and the positive effects of 2-pralidoxime (2-PAM) on the liver. Male Wistar-albino rats were assigned to 4 groups and all were treated per os: Group 1 (n=10) received 30 mg/kg methamidophos; Group 2 (n=7) (serving as controls for Group 1) received physiologic NaCl; Group 3 (n=10) received 30 mg/kg methamidophos and was treated with 2-PAM and atropine when cholinergic symptoms were noted; and Group 4 (n=7) (serving as controls for Group 3) was treated with physiologic NaCl. Plasma cholinesterase was measured using radioimmunoassay. Liver tissues were prepared for electron microscopic studies. Methamidophos treatment of Group 1 led to serious changes in hepatocytes and organelles. These changes were not detected in Group 3. In Group 1, the chromatin content of some hepatocyte nuclei and cytoplasmic density increased; these cells also became vacuolar in appearance as a result of lysis in the mitochondrial matrices. In some cells, the lipid content constituted the majority of the cytoplasm. Furthermore, these cells were surrounded by glycogen accumulation. In some areas of the perisinusoidal zone, collagen fibers had increased to form bands. None of these changes were noted in Group 3. These findings suggest that acute organophosphate poisoning causes serious histopathological effects in rat liver, but that these changes are reversible with appropriate treatment strategies.     

急性肾损伤对百草枯中毒患者预后的影响

目的分析急性肾损伤对百草枯中毒患者预后的影响。方法急性百草枯中毒患者56例,分为急性肾损伤组及无急性肾损伤组,以住院期间死亡为观察终点,分析两者死亡数及病死率的差异。结果在56例中出现急性肾损伤的患者36例,死亡24例,占急性肾损伤患者66.67%。无急性肾损伤患者20例,死亡7例,占无急性肾损伤患者35%,二者有统计学意义(P<0.05)。结论急性肾损伤是导致百草枯中毒患者预后恶化的重要因素。     

An alleged poisoning with methanol and formaldehyde.

It was alleged that a defendant added an unspecified amount of undyed formalin solution, containing formaldehyde and methanol, to the victim's bottle of ice and drinking water. The medical report indicated that except for a slight elevation of total creatine kinase, all other chemistry profiles were within normal ranges. The elevation of creatine kinase suggested muscle injury and inflammation; however, the significance of this elevation was not clear. Toxicological evaluations were made by conducting risk assessments. Based upon the medical report and risk assessments, the following conclusions were made: The calculated exposure doses of methanol and formaldehyde were too low to cause appreciable adverse effects; however, formaldehyde may have irritated the gastrointestinal tract causing smooth muscle and mucosal inflammation. The doses of methanol and formaldehyde were too low to cause death. The exposure scenario (a single oral exposure to formaldehyde) would not likely increase the cancer risk in the victim. The risk assessments provided resulted in a reduction in charge from attempted murder to felony.     

普罗帕酮急性中毒致心律失常和呼吸衰竭1例

1例21岁女性因家庭争吵试图自杀而自行吞服普罗帕酮50片(50mg/片).2h后出现头晕、乏力入院.血液毒物分析示普罗帕酮浓度为0.023 mg/L.心电图提示窦性心律,完全右束支传导阻滞.给予洗胃、导泻、补液以及肾上腺素,同时行血液滤过及血浆置换治疗.入院后4h患者出现Ⅰ型呼吸衰竭,立即给予经口气管插管,机械通气辅助呼吸.入院第2天行血浆置换治疗2h(置换血浆共2000 ml),其后血液普罗帕酮浓度为0.002 mg/L,遂停止血液净化治疗.第3天心电图检查恢复正常,呼吸机脱机,改予鼻导管吸氧,患者病情平稳.第7天患者痊愈出院.     

Magnetic resonance imaging of the rat brain following acute carbon monoxide poisoning.

Magnetic resonance (MR) may be used for repeatedly and non-invasively imaging the brain. Until now, no studies have used this approach to study the effects of carbon monoxide (CO) poisoning in a defined animal model. Conscious, Levine-prepared female rats (unilateral carotid artery and jugular vein occlusion) were exposed to 2400 ppm CO for 90 min, with or without the infusion of 50% glucose solution; CO-stimulated increases in blood glucose and lactate occurred in both groups, while blood pressure and body temperature fell. One to four hours following termination of CO exposure, increased cortical pixel intensity, cortical surface area and brain midline shift were observed on the operated side of the brain in some rats of both groups (i.e. responders = R), providing evidence of edema. At sacrifice, 5 h following termination of CO exposure, gross water content was increased on the left side in the corresponding cortical slices in R rats, providing another measure of edema. Significant positive correlations were found between left to right pixel intensity difference and water content difference, and between the extent of midline shift and water content difference. The elevations of blood glucose and lactate concentrations, and the magnitudes of CO-induced hypothermia and hypotension were similar to those in past studies, but appeared to exert no effect on the severity of cortical edema in terms of differences in pixel intensity, surface area, midline shift or gross tissue water content. Thus, the observed differences between the R rats is not explained by the available data.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of methanol and isopropanol poisoning with intravenous fomepizole

CASE REPORT: We report a case of mixed methanol and isopropanol poisoning in a patient who refused dialysis but agreed to treatment with intravenous fomepizole. The patient was asymptomatic on arrival, with initial blood methanol and isopropanol concentrations of 146 mg/dL and 39 mg/dL, respectively. Blood ethanol was undetectable. The patient was treated with fomepizole twice daily intravenously until blood methanol was undetectable. No side effects of therapy, other than transient eosinophilia, were observed. The evolution was uneventful and no metabolites of either alcohol were detected at any time during the hospitalization. The decay of plasma methanol and isopropanol under fomepizole treatment were well described by first-order kinetics. The plasma elimination half-lives of methanol and isopropanol were 47.6 hours and 27.7 hours, respectively. Fomepizole appears to have been effective in blocking the toxic metabolism of both methanol and isopropanol and was associated with a favorable outcome.     

Increased serum formate in the diagnosis of methanol poisoning

Early diagnosis is essential for successful treatment in methanol poisoning. Methanol detection by gas chromatography is not available in most hospitals. Methanol increases the osmolal gap in serum and its metabolite formate increases the anion gap. The sensitivity of these indirect diagnostic methods is not good at low concentrations of methanol or formate. We therefore studied the usefulness of formate measurement in diagnosing methanol poisoning. In 15 patients poisoned with methanol, serum formate was measured enzymatically on a Cobas Mira analyzer using formate dehydrogenase and nicotinamid adenine dinucleotid. Day-to-day coefficient of variation was 5%, and the upper reference limit was 2 mg/dL (0.4 mmol/L). Methanol was detected in all 15 patients of whom 14 had elevated serum formate concentrations. Anion gap was increased in 11 of 11, and osmolal gap in 11 patients of 15 examined. Metabolic acidosis was present in 12 of 15 patients, but pH was below 7.30 in only 9 of them. Four patients with no symptoms had formate concentrations in the range 2-38 mg/dL (0.5-8.3 mmol/L), indicating that increased serum formate was a sensitive indicator of methanol poisoning. Our results proved formate analyzes to be a simple, sensitive, and specific way of diagnosing methanol poisoning. Confounders are patients admitted early, or concomitant ethanol ingestion, and therefore no acidosis. This problem may, however, be omitted by repeated formate analysis in patients developing metabolic acidosis.