Severe hyperammonemia from intense skeletal muscle activity: A rare case report and literature review.

RATIONALE: Adult hyperammonemia is most often the result of hepatic dysfunction. Hyperammonemia in the setting of normal hepatic function is a much less common phenomenon and has usually been associated with medications and certain disease states. Here, we present an unusual case of severe hyperammonemia caused physiologically by intense muscle activity in a patient lacking any evidence of liver disease. PATIENT CONCERNS: A 36-year-old woman was brought to the emergency department for a suicide attempt after being found covered in Lysol and Clorox germicidal bleach. She was noted to be in a state of violent psychosis with extreme agitation and had to be sedated and intubated for airway protection. DIAGNOSIS AND INTERVENTIONS: Initial labs revealed hyperammonemia, lactic acidosis, and anion gap metabolic acidosis. Aminotransferases, bilirubin, and creatine kinase (CK) were normal. Renal function, prothrombin time, activated partial thromboplastin time, and international normalized ratio were also unremarkable and remained so at 24 hours. Ethyl alcohol, acetaminophen, salicylate, and valproic acid were all undetectable in blood. She received 2 doses of lactulose overnight, with a subsequent bowel movement. Next day, her mentation, serum ammonia level, and lactic acid level were back to normal, and she was extubated. Aminotransferases and CK levels were elevated but improved with supportive care. A detailed history and relevant biochemical investigations were unremarkable for any other etiology of hyperammonemia including the common inborn errors of metabolism (IEM). The combination of clinical findings of extreme skeletal muscle activity along with hyperammonemia and lactic acidosis, and subsequently rhabdomyolysis in the setting of unremarkable history and otherwise normal hepatic function strongly suggest the myokinetic origin of hyperammonemia in the patient. OUTCOME: The patient recovered well with supportive care and was discharged on day 5. LESSONS: This unique case illustrates the important role of skeletal muscle in the human metabolism of ammonia. In our discussion, we also elucidate the underlying pathophysiology, with the objective of improving clinician understanding of various differential diagnoses.

[About a cresol intoxication]. / A propos d'une intoxication aux crésols.

Cresols are phenol derivatives commonly used as surface disinfectants. Ingestion may cause local mucocutaneous damage and extensive systemic toxicity : central nervous, cardiovascular, hematological, hepatic, renal and pulmonary. We describe the case of a 33-year-old woman who swallowed, without suicidal intent, 50 to 70 cm3 of a 50% cresol solution. Coma occurred within 5 minutes of ingestion, she presented a bradypnea with desaturation, and the SMUR team performed on-site an orotracheal intubation. On arrival at the hospital, the patient had typical caustic lesions around her mouth. Immediate management consisted of ventilatory support, instillation of activated charcoal by nasogastric tube, empirical intravenous methylene blue and effective vascular filling. Within one hour of admission, she developed hypotension, ventricular arrhythmias, and acute renal failure. Toxic hepatitis occurred within 24 hours. The 24-hour gastroscopy showed erosive esophagitis and erythematous gastropathy and duodenopathy. No urine or blood dosage can be performed. The patient left the hospital on the fifth day and her liver function normalized after one month. The treatment of phenol poisoning consists primarily of rapid decontamination and the support of vital functions. Diagnostic assays are not available routinely and anamnesis, as well as some semiological cardinal points, is essential.

Les crésols sont des dérivés de phénol communément utilisés comme désinfectants de surfaces. Leur ingestion peut causer des dommages cutanéomuqueux locaux ainsi qu'une toxicité systémique étendue : nerveuse centrale, cardiovasculaire, hématologique, hépatique, rénale et pulmonaire. Nous décrivons le cas d'une femme de 33 ans ayant ingéré sans intention suicidaire, 50 à 70 cm3 d'une solution crésolique à 50 %. Le coma est survenu dans les 5 min suivant l'ingestion, elle présentait une bradypnée avec désaturation et l'équipe de SMUR a procédé à l'intubation orotrachéale sur place. A l'arrivée à l'hôpital, la patiente présentait des lésions caustiques typiques sur le pourtour de la bouche. La prise en charge immédiate a consisté en une assistance ventilatoire, instillation de charbon activé par sonde nasogastrique, bleu de méthylène empirique intraveineux et remplissage vasculaire efficace. Dans l'heure suivant son admission, elle a présenté une hypotension artérielle, des troubles de rythme ventriculaire et une insuffisance rénale aiguë. Une hépatite toxique s'est révélée dans les 24 h suivantes. La gastroscopie à 24 h mettra en évidence une oesophagite érosive et une gastropathie et duodénopathie érythémateuses. Aucun dosage urinaire ou sanguin n'a pu être pratiqué. La patiente quittera l'hôpital au cinquième jour et sa fonction hépatique se normalisera après un mois. Le traitement de l'intoxication aux phénols consiste avant tout en une décontamination rapide ainsi qu'en le support des fonctions vitales. Les dosages diagnostiques ne sont pas disponibles en routine et l'anamnèse, ainsi que quelques points sémiologiques cardinaux, sont primordiaux.

Autopsy report for chemical burns from cresol solution.

Cresol, which is used as a disinfectant and insecticide, has erosive effects on epidermal and epithelial tissues in the body. Oral exposure causes gastrointestinal corrosive injuries as a direct chemical burn. We report herein a case of suicidal poisoning by ingestion of cresol solution. An octogenarian man with depression was found dead approximately 14 h after exposure to less than 500 mL of saponated cresol solution. Macroscopically, corrosive lesions such as red-to-brown-colored epithelium and edematous thickening of walls were seen in the skin, mouth, oral cavity, esophagus, and stomach. Histopathologically, coagulative necrosis and vascular dilatation were detected from mucosal to muscular layers in the esophagus, stomach, and duodenum. Congestive edema of the lungs, edematous changes in the brain, and proximal tubular necrosis of the kidneys were seen, suggesting acute circulatory disturbance due to shock. This human case offers valuable information on the direct irritation and shock induced by systemic exposure to corrosive substances.

A case of black urine and dark skin - cresol poisoning.

INTRODUCTION: Cresol is a phenol derivative used as a disinfectant worldwide. Acute cresol poisoning is potentially fatal as it may cause multiple organ failure. We present a case of acute cresol intoxication in a male patient to illustrate the effects of cresol poisoning. CASE: A 42-year-old male presented with black urine, painless brownish dermal burns, and a strong carbolic acid odor. The patient was immediately resuscitated with adequate oxygenation and aggressive fluid resuscitation. He was subsequently admitted to the intensive care unit, where his treatment course was complicated by pneumonia, gastrointestinal bleeding, hepatic dysfunction, and acute renal failure. After receiving supportive intensive care, the patient recovered and was discharged with no sequelae. CONCLUSION: The distinctive clinical features of this case may be useful in diagnosis, because laboratory analytical methods for cresols are not routinely available at most hospitals.

Identification of estrogenic/anti-estrogenic compounds in diesel exhaust particulate extract.

Diesel exhaust particulate extract (DEPE) was obtained from diesel exhaust particulates with Soxhlet extraction using dichloromethane. After separating DEPE into 11 fractions by liquid-liquid extraction, the neutral fraction (N) showed anti-estrogenic activity and the weak acid (phenol) fraction (WA(P)) showed estrogenic and anti-estrogenic activities by a yeast two-hybrid assay system expressing human estrogen receptor alpha. Both fractions were thoroughly fractionated by silica gel column chromatography and reversed-phase HPLC. In the WA(P) fraction, 3-methyl-4-nitrophenol and 2,6-dimethyl-4-nitrophenol were identified by LC-MS/MS as estrogenic compounds. This is the first study to identify 2,6-dimethyl-4-nitrophenol in DEPE and the first study to show that it is an estrogenic compound. In the N fraction, 1-hydroxypyrene was also identified by LC-MS/MS as an anti-estrogenic compound.

A fatal case of saponated cresol ingestion.

We describe here a case of suicidal poisoning by saponated cresol ingestion. A 41 year-old male was found unconsciousness in a park in the early morning, and an empty bottle of saponated cresol was found beside him. His death was confirmed approximately 2 hours later, despite attempts at resuscitation and intensive care. The autopsy revealed severe morphological damage of the upper gastrointestinal tract and congestion of the lung. We also observed by histopathological examination severe lung edema and severe erosion of the esophagus and stomach. Toxicological analysis also identified a high concentration of cresol isomer in the blood and gastric contents. The cause of death was given as cresol poisoning, based on the results of the autopsy and toxicological examination.

Determination of phenol and o-cresol by GC/MS in a fatal poisoning case.

A fatality due to the ingestion of solution containing phenol and o-cresol is described. The pathological findings were typical of acute substantial poisoning. Blood, urine and stomach content were obtained during post mortem examinations. Phenol and o-cresol were identified using GC/MS. The extractions from autopsy materials were obtained as follows: by gel permeation with cyclohexane/dichloromethane from stomach content, by solid phase extraction (SPE) from urine and by deproteinization with acetonitrile from blood. The phenol and o-cresol concentrations in the samples were found, respectively, as follows: 115.0 and 5.0 microg/g in the stomach contents, 58.3 and 1.9 microg/ml in the blood, 3.3 and 20.5 microg/ml in the urine. Distributions of phenol in fatal poisonings have been reported, but, usually, colorimetry was used as the analytical method and it cannot exclude the interference of other phenolic compounds.

Hepatocellular injury with hyperaminotransferasemia after cresol ingestion.

A 42-year-old man attempted suicide by ingesting about 150 mL of a saponated cresol solution containing about 50% cresol. His serum aminotransferase concentrations were elevated, and a coagulopathy was present at the time of admission, 15 hours after ingestion. The hyperaminotransferasemia and coagulopathy worsened on the second day, but resolved thereafter with supportive therapy. Histologic examination of a biopsy specimen obtained on the 14th day demonstrated focal dropout of hepatocytes (which were replaced by reticulin and collagen fibers), ballooning or hydropic degeneration of hepatocytes, and rapid regeneration with small hepatocytes in the periportal zones as well as in the centrilobular zones. A rapid onset of illness with periportal hepatocellular injury is inconsistent with damage due to a hepatotoxic metabolite of p-cresol produced by cytochrome P450, which has been suggested by studies in vitro. A direct transient noxious effect mediated via the portal or arterial circulation may be involved in hepatic injury after cresol ingestion.

Effects of chlorine and its cresylate byproducts on brain and lung performance.

Chlorine and potassium cresylate spilled from a train wreck forced evacuation of nearly 1000 people in and near the town of Alberton, Montana, in 1996. Because respiratory and other symptoms persisted in this population, neurobehavioral and pulmonary functions were evaluated in a cohort of exposed vs. unexposed individuals. Ninety-seven subjects were tested 7 wk after exposure. Three years later, 36 of the original subjects were retested, along with 21 new patients exposed in the same incident. These 57 were compared with 22 unexposed individuals. Twenty-six neurobehavioral functions were tested, and spirometry was performed on each subject. At 7 wk postexposure, patients showed significant differences in 5 neurobehavioral functions (i.e., balance, simple reaction time, abnormal visual quadrants, vocabulary, and information), compared with the unexposed individuals recruited in 1999. Patients' Profile of Mood States scores and frequencies of 35 symptoms were also elevated, compared with the unexposed group. At 3 yr postexposure, patients exhibited differences in 7 additional neurobehavioral functions (i.e., choice reaction time, balance with eyes open, color errors, visual fields, Culture Fair, and verbal recall). Respiratory symptoms were increased, but pulmonary functions did not change. Exposure to chlorine and potassium cresylate produced neurobehavioral impairments that have been observed to increase across 3 yr. Spills in heavily populated areas could injure thousands, overwhelming medical facilities.

An autopsy case of poisoning by massive absorption of cresol a short time before death.

A 65-year-old male patient who was hospitalized with schizophrenia died about 15 min later after ingestion of a large volume of saponated cresol solution in a mental hospital. Fatal levels of free p- and m-cresol in the heart blood were detected at 458.8 and 957.3 microg/ml, respectively, which far exceeded the fatal levels determined previously. The levels in the heart muscle, liver and spleen tissues were also extremely high, and there was 250 ml of cresol-odor-emitting fluid in the stomach. The levels of glucuronic-acid-conjugated p- and m-cresols in the heart blood were 38.2 and 85.6 microg/ml, respectively. Although the high levels of cresols in the heart blood may be due to diffusion from the stomach contents, it is surmised that the essential levels of free and conjugated forms in blood were at least 99 and 240 microg/ml, respectively, considering the results of postmortem examinations and some case reports. It was concluded that about 340 microg/ml of the total cresols was absorbed in a very short period following oral ingestion of saponated cresol solution in this case.

Suspected cresol poisoning in cattle presented for slaughter.

Cresol poisoning was suspected in agroup of cattle presented for slaughter at a federaly inspected plant in Illinois. Four cattle died shortly after being unloaded at the slaughter facility, while another animal died after being returned to the feedlot of origin in Iowa. The clinical signs in the affected cattle were lethargy, depression, ataxia, leg weakness, sternal recumbency, dehydration, and severe bloating. Metacresol (3-methyl phenol), commonly found in disinfectants used to clean and sanitize farm equipment and barns, was detected in rumen content from 4 necropsied animals ranging from 25.3 to 52.6 ppm. The exact source of exposure was not identified, but was probably accidental on the farm of origin or on the trailers used for animal transit to the slaughter plant.

Acute respiratory distress syndrome following cutaneous exposure to Lysol: a case report.

Lysol (mixed cresols) is a brand of popular detergent commonly used to disinfect toilets and floors in Taiwan. We report a patient with acute respiratory failure immediately following chemical burns caused by skin contact with Lysol solution. On admission, chest radiography showed bilateral diffuse pulmonary infiltrates and an arterial blood gas analysis disclosed hypoxemia refractory to a high concentration of oxygen by inhalation. Under the impression of acute respiratory distress syndrome, our patient was admitted to the intensive care unit for respiratory care. Poor clinical improvement was noted, despite aggressive respiratory therapy. High-dose steroid therapy (hydrocortisone 30 mg/kg/day) was administered from the seventh day after mechanical ventilation began and the ratio of arterial partial pressure of oxygen to fractional concentration of oxygen in inspired gas improved thereafter. The amount of steroid was gradually tapered to the maintenance dose and the patient was successfully weaned from the ventilator after a 93-day course of mechanical ventilation.

Concentrated cresol intoxication.

Cresol, a commonly used disinfectant, may cause gastrointestinal corrosive injury, central nervous system and cardiovascular disturbances, and renal and hepatic injury following intoxication. We report a case of acute severe cresol poisoning after a suicide attempt with ingestion of a cresol-soap solution used as a toilet disinfectant. A 44-y-old male was found unconscious after ingesting 300 ml of 50% cresol-soap solution. Endotracheal intubation, gastric lavage and activated charcoal were given immediately which reversed his conscious. He had dermal burns, esophageal and gastric erosion, pneumonia, mixed metabolic acidosis and respiratory aklalosis, renal and liver function impairment, leucocytosis and dark urine. Acute renal failure and hemolysis developed, but he recovered after hemodialysis and intensive supportive care. Urine levels of p-cresol, m-cresol, o-cresol and phenol were respectively 2083, 2059, 125 and 68 mg/g creatinine at 7 h post-ingestion. Though the amount cresol claimed ingested by the patient (150 g) far exceeded the reported lethal dose (30-60 g), and multiple complications developed after massive ingestion, this patient recovered. The renal, pulmonary and hematological effects in this patient might have resulted from the direct toxicity of cresol and its metabolites.

Marked increases of aminotransferase levels after cresol ingestion.

A 26-year-old woman developed marked increases in levels of aminotransferases about 24 hours after ingestion of 70 mL of 50% cresol. Responding to supportive measures, the patient recovered without any significant complications. Cresol and/or its metabolite may have caused transient hepato-cellular injury in this patient. In cresol poisoning, hepato-cellular injury can manifest even after a 24-hour asymptomatic period.