The osmole gap is used routinely as a screening test for the presence of exogenous osmotically active substances, such as the toxic alcohols ethylene glycol and methanol, particularly when the ability to measure serum concentrations of the substances is not available. The objectives of this study were: 1) to measure the diagnostic accuracy of the osmole gap for screening for ethylene glycol and methanol exposure, and 2) to identify whether a recently proposed modification of the ethanol coefficient affects the diagnostic accuracy.
Electronic laboratory records from two tertiary-care hospitals were searched to identify all patients for whom a serum ethylene glycol and methanol measurement was ordered between January 1, 1996 and March 31, 2002. Cases were eligible for analysis if serum sodium, blood urea nitrogen, glucose, ethanol, ethylene glycol, methanol, and osmolality were measured simultaneously. Serum molarity was calculated using the Smithline and Gardner equation and ethanol coefficients of 1 and 1.25 mOsm/mM. The diagnostic accuracy of the osmole gap was evaluated for identifying patients with toxic alcohol levels above the recommended threshold for antidotal therapy and hemodialysis using receiver-operator characteristic curves, likelihood ratios, and positive and negative predictive values.
One hundred and thirty-one patients were included in the analysis, 20 of whom had ethylene glycol or methanol serum concentrations above the threshold for antidotal therapy. The use of an ethanol coefficient of 1.25 mOsm/mM yielded higher specificities and positive predictive values, without affecting sensitivity and negative predictive values. Employing an osmole gap threshold of 10 for the identification of patients requiring antidotal therapy resulted in a sensitivity of 0.9 and 0.85, and a specificity of 0.22 and 0. 5, with equations 1 and 2 respectively. The sensitivity increased to 1 for both equations for the identification of patients requiring dialysis.
In this sample, an osmole gap threshold of 10 has a sensitivity and negative predictive value of 1 for identifying patients for whom hemodialysis is recommended, independent of the ethanol coefficient applied. In patients potentially requiring antidotal therapy, applying an ethanol coefficient of 1.25 resulted in a higher specificity and positive predictive value without compromising the sensitivity.
A rapid headspace-gas chromatography (HS-GC) method was developed for the analysis of ethylene glycol and propylene glycol in plasma and serum specimens using 1,3-propanediol as the internal standard. The method employed a single-step derivitization using phenylboronic acid, was linear to 200 mg/dL and had a lower limit of quantitation of 1 mg/dL suitable for clinical analyses. The analytical method described allows for laboratories with HS-GC instrumentation to analyze ethanol, methanol, isopropanol, ethylene glycol, and propylene glycol on a single instrument with rapid switch-over from alcohols to glycols analysis. In addition to the novel HS-GC method, a retrospective analysis of patient specimens containing ethylene glycol and propylene glycol was also described. A total of 36 patients ingested ethylene glycol, including 3 patients who presented with two separate admissions for ethylene glycol toxicity. Laboratory studies on presentation to hospital for these patients showed both osmolal and anion gap in 13 patients, osmolal but not anion gap in 13 patients, anion but not osmolal gap in 8 patients, and 1 patient with neither an osmolal nor anion gap. Acidosis on arterial blood gas was present in 13 cases. Only one fatality was seen; this was a patient with initial serum ethylene glycol concentration of 1282 mg/dL who died on third day of hospitalization. Propylene glycol was common in patients being managed for toxic ingestions, and was often attributed to iatrogenic administration of propylene glycol-containing medications such as activated charcoal and intravenous lorazepam. In six patients, propylene glycol contributed to an abnormally high osmolal gap. The common presence of propylene glycol in hospitalized patients emphasizes the importance of being able to identify both ethylene glycol and propylene glycol by chromatographic methods.
Electronic supplementary material
The online version of this article (doi:10.1186/2193-1801-2-203) contains supplementary material, which is available to authorized users.
Ethylene glycol; Glycols; Gas chromatography; Propylene glycol; Toxicology
This discussion will highlight the following 9 specific points that related to metabolic acidosis caused by various toxins. The current recommendation suggests that alcohol dehydrogenase inhibitor fomepizole is preferred to ethanol in treatment of methanol and ethylene glycol poisoning, but analysis of the enzyme kinetics indicates that ethanol is a better alternative. In the presence of a modest increase in serum osmolal gap (<30 mOsm/L), the starting dose of ethanol should be far less than the usual recommended dose. One can take advantage of the high vapor pressure of methanol in the treatment of methanol poisoning when hemodialysis is not readily available. Profuse sweating with increased water ingestion can be highly effective in reducing methanol levels. Impaired production of ammonia by the proximal tubule of the kidney plays a major role in the development of metabolic acidosis in pyroglutamic acidosis. Glycine, not oxalate, is the main final end product of ethylene glycol metabolism. Metabolism of ethylene glycol to oxalate, albeit important clinically, represents less than 1% of ethylene glycol disposal. Urine osmolal gap would be useful in the diagnosis of ethylene glycol poisoning, but not in methanol poisoning. Hemodialysis is important in the treatment of methanol poisoning and ethylene glycol poisoning with renal impairment, with or without fomepizole or ethanol treatment. Severe leucocytosis is a highly sensitive indicator of ethylene glycol poisoning. Uncoupling of oxidative phosphorylation by salicylate can explain most of the manifestations of salicylate poisoning.
metabolic acidosis; toxin; ethylene glycol; methanol; poisoning; urine osmolal gap
Objectives. The optimal antidote for the treatment of ethylene glycol or methanol intoxication is not known. The objective of this systematic review is to describe all available data on the use of ethanol and fomepizole for methanol and ethylene glycol intoxication. Data Source. A systematic search of MEDLINE and EMBASE was conducted.
Study Selection. Published studies involving the use of ethanol or fomepizole, or both, in adults who presented within 72 hours of toxic alcohol ingestion were included. Our search yielded a total of 145 studies for our analysis. There were no randomized controlled trials, and no head-to-head trials. Data Extraction. Variables were evaluated for all publications by one independent author using a standardized data collection form. Data Synthesis. 897 patients with toxic alcohol ingestion were identified. 720 (80.3%) were treated with ethanol (505 Me, 215 EG), 146 (16.3%) with fomepizole (81 Me, 65 EG), and 33 (3.7%) with both antidotes (18 Me, 15 EG). Mortality in patients treated with ethanol was 21.8% for Me and 18.1% for EG. In those administered fomepizole, mortality was 17.1% for Me and 4.1% for EG. Adverse events were uncommon. Conclusion. The data supporting the use of one antidote is inconclusive. Further investigation is warranted.
Methanol, ethylene glycol, and diethylene glycol intoxications can produce visual disturbances, neurological disturbances, acute renal failure, pulmonary dysfunction, cardiac dysfunction, metabolic acidosis, and death. Metabolic acidosis and an increased serum osmolality are important clues to their diagnosis. The former reflects the organic acids produced by metabolism of the parent alcohol, while the latter is due to accumulation of the offending alcohol. However, neither the clinical nor the laboratory findings are specific for toxic alcohol ingestions.
The definitive diagnosis of the alcohol intoxications is commonly based on detection of the alcohol or its metabolites in blood. Early diagnosis is important, because initiation of appropriate treatment can markedly lessen their morbidity and mortality.
At present detection of the parent alcohol in body fluids is inferred from its measurement in blood. This measurement is often performed by specialty laboratories using expensive equipment, and a long delay between obtaining the specimen and getting the results is not unusual. In this report, we describe liquid- based tests that detect methanol, ethylene glycol, diethylene glycol, and ethanol in saliva. The tests are sensitive and they have different specificity for each of the alcohols facilitating distinction among them. The relatively high sensitivity and specificity of the tests as a whole will facilitate the rapid diagnosis of each of these alcohol intoxications.
methanol; ethylene glycol; diethyelene glycol; alcohol dehydrogenase; alcohol oxidase; sodium periodate; potassium permanganate
Ethylene glycol is a widely used chemical that is capable of causing significant injury if ingested. Treatment for ethylene glycol poisoning typically includes basic supportive care, alcohol dehydrogenase inhibition, and hemodialysis. Recent data have suggested that hemodialysis may not be necessary for cases of ethylene glycol poisoning that can be treated with fomepizole as blocking therapy before acidosis or renal dysfunction develops.
A 33-year-old man presented to the emergency department 1 hour after drinking approximately 1/2 gallon of ethylene glycol antifreeze and an unknown quantity of beer. On arrival he was mildly inebriated but otherwise displayed no other features of ethylene glycol poisoning. Fomepizole therapy was initiated and initial laboratory studies later revealed an osmol gap of 157 mOsm and an ethylene glycol concentration of 706 mg/dL. Nephrology and toxicology services were consulted. Over the next 3 days, fomepizole therapy was continued while the patient’s acid-base status and renal function were closely monitored. No evidence of acid-base abnormalities or renal impairment was ever observed and the patient was discharged to psychiatric care on the fourth hospital day.
This report describes the case of a patient who presented soon after a massive ingestion of ethylene glycol with very high serum concentrations. He was successfully treated using fomepizole and basic supportive care. Our patient developed neither renal insufficiency nor metabolic acidosis. His concomitant ethanol consumption, early presentation, and treatment likely contributed to his favorable outcome. This case report underscores the effectiveness of supportive care and fomepizole in the treatment of ethylene glycol poisoning.
ethylene glycol; ingestion; fomepizole; poisoning; hemodialysis
Poison center consultations for potential toxic alcohol poisonings are challenging because blood levels are typically not immediately available. The primary objective of this study was to determine whether readily obtainable laboratory values can be used to accurately and rapidly diagnose these poisonings. Over a 15-month period, patients with a history of toxic alcohol ingestion or a metabolic acidemia (pH ≤ 7.30 or serum bicarbonate ≤ 18 mEq/L) that prompted a poison center consultation were enrolled. A predictive logistic regression model was used to assess the combined ability of serum pH, calcium, osmolar gap, and anion gap levels to predict a final diagnosis of toxic alcohol poisoning. There were 102 subjects included in the analysis. A total of 44% (45/102) patients had a final diagnosis of ethylene glycol (EG) poisoning. Higher levels of calcium, osmolar gap, and anion gap were independently associated with statistically significant or marginally significant increases in the odds of a final diagnosis of EG poisoning. The c-index was estimated at 0.81, indicating that the model showed a reasonable ability to discriminate EG cases from others. The final model had a sensitivity and specificity of 78% and 89%, respectively, and positive and negative predictive values of 84% and 83% respectively. The combination of elevated calcium, osmolar gap, and anion gap is associated with a high likelihood of EG poisoning, but clinician gestalt is still essential for its diagnosis. Further refinement of the model is needed.
Toxic Alcohol; Ethylene Glycol; Poison Center
Fomepizole is used to treat and prevent toxicity from ethylene glycol poisoning. Treatment with fomepizole without hemodialysis in massive ethylene glycol ingestion has been rarely reported in the literature; however, published literature and practice guidelines recommend considering dialysis for ethylene glycol levels >50 mg/dL. We report a case of massive ethylene glycol ingestion resulting in the highest serum ethylene glycol concentration in a patient without ethanol co-ingestion who was treated with fomepizole and was not hemodialyzed. A 48-year-old male presented to the emergency department after reportedly ingesting >1liter of antifreeze in an attempt at self-harm. He denied concomitant ethanol consumption. His initial presenting serum ethylene glycol level was 700 mg/dL, with normal renal function, and a metabolic acidosis with a high anion gap. One hour after presentation, he was started on intravenous fomepizole. Treatment with fomepizole continued until the patient's plasma ethylene glycol concentration was 16 mg/dL. His metabolic acidosis quickly resolved, he had no adverse reactions to the treatment, and his renal function remained normal. Ultimately, he was discharged to a psychiatric unit without sequelae. Published literature and practice guidelines suggests considering hemodialysis initiation in patients with an ethylene glycol level >50 mg/dL. This recommendation is anecdotally, rather than evidence, based. With the potential risks inherent in hemodialysis, our case provides evidence that treatment with fomepizole without hemodialysis appears to be a viable alternative option in patients with even extremely high plasma ethylene glycol concentrations as long as their renal function is intact.
Ethylene glycol; Fomepizole; Hemodialysis; Overdose
A case of propylene glycol poisoning is described in a 39 year old woman which resulted in her admission to hospital in status epilepticus. She had had a long-standing history of uncontrollable epilepsy. The diagnosis of propylene glycol poisoning resulted directly from the finding of a high plasma osmolal gap on admission. This finding would have been missed if later samples only had been analysed. Plasma osmolality and the osmolal gap should be considered first line investigations in patients presenting with metabolic acidosis and cerebral signs and symptoms. Since her discharge from hospital a year ago the patient has had no further seizures.
Ethylene glycol poisoning may pose diagnostic difficulties if the history of ingestion is not volunteered, or if the presentation is delayed. This is because the biochemical features of high anion-gap metabolic acidosis and an osmolar gap resolve within 24 to 72 hours as the ethylene glycol is metabolized to toxic metabolites. This case illustrates the less well-known clinical features of delayed ethylene glycol poisoning, including multiple cranial and peripheral neuropathies, and the clinical findings which may point towards this diagnosis in the absence of a history of ingestion.
A 53-year-old Afro-Caribbean man presented with vomiting, abdominal pain and oliguria, and was found to have acute renal failure requiring emergency hemofiltration, and raised inflammatory markers. Computed tomography imaging of the abdomen revealed the appearance of bilateral pyelonephritis, however he failed to improve with broad-spectrum antibiotics, and subsequently developed multiple cranial neuropathies and increasing obtundation, necessitating intubation and ventilation. Computed tomography of the brain showed no focal lesions, and a lumbar puncture revealed a raised cerebrospinal fluid opening pressure and cyto-albuminological dissociation. Nerve conduction studies revealed a sensorimotor radiculoneuropathy mimicking a Guillain-Barre type lesion with an atypical distribution. It was only about two weeks after presentation that the history of ethylene glycol ingestion one week before presentation was confirmed. He had a slow recovery on the intensive care unit, requiring renal replacement therapy for eight weeks, and complicated by acute respiratory distress syndrome, neuropathic pain and a slow neurological recovery requiring prolonged rehabilitation.
Although neuropathy as a result of ethylene glycol poisoning has been described in a few case reports, all of these were in the context of a known history of ingestion. As the diagnosis may well be obscured if the history of ingestion is not elucidated, it is important to be aware of this possibility especially if presentation is delayed.
A 69-year-old man presented to the emergency department after being found unconscious by his son. He had experienced headache the previous day but had been otherwise well. Investigations revealed a severe metabolic acidosis, raised lactate and acute kidney injury. The calculated anion and osmolar gap were both elevated at 37.7 and 39.3, respectively. Due to his reduced Glasgow coma score (GCS) he was intubated and a CT scan performed: only a small, mature pontine infarct was found of uncertain significance. Further questioning of the family revealed accidental ingestion of 150 ml of a ‘blue liquid’ 24 h earlier (later identified as car screenwash). With ethylene glycol (EG) poisoning suspected, he was given intravenous ethanol, fomepizole (a competitive inhibitor of alcohol dehydrogenase) and haemofiltration. Despite the delayed presentation, prompt recognition and treatment of EG poisoning led to a successful discharge in this case.
A 3-year old male who sustained 2nd and 3rd degree burns that covered approximately 60% TBSA presented to a large adult and pediatric verified burn center. On hospital day (HD) 26 of his stay, Candida fungemia was identified by blood culture, delaying operative management until HD 47. On HD 47, after his first operative intervention, the patient developed a persistent metabolic and lactic acidosis. On HD 66, a search for a cause of his osmol gap of 56 mOsm/kg revealed a potential source-propylene glycol. Previous studies have implicated the propylene glycol emulsifier in the silver sulfadiazine that was being applied to his skin as a rare cause of lactic acidosis in severely burned patients. Within 24 hours of stopping the silver sulfadiazine therapy, his lactic acidosis and osmol gap resolved; within 72 hours his metabolic acidosis resolved. Silver sulfadiazine is commonly used adjunct therapy in the treatment of 2nd and 3rd degree burns and generally has few adverse reactions. The absorption of propylene glycol systemically can rarely occur when applied to extensive burns, presumably due to the disruption of the skin barrier; the half-life of PG is 10 hours and can be prolonged with renal disease because ~50% of the sulfadiazine is excreted in the urine unchanged. When propylene glycol is present systemically, it is metabolized to lactic acid in the liver, which can cause a lactic acidosis. Several commonly used drugs also use propylene glycol as an emulsifier, including IV preparations of lorazepam, pentobarbital, phenobarbital, and phenytoin. In all of these clinical scenarios, including severe burn patients that are being treated with silver sulfadiazine, both lactic acid and propylene glycol levels should be measured to monitor for this rare, potentially serious co-morbidity.
Burn; propylene glycol; silver sulfadiazine; metabolic acidosis; hyperosmolality
The incidence of methanol (CH3OH) intoxication differs enormously from country to country. Methanol intoxication is extremely rare in the Dutch population. Even a low dose can already be potentially lethal. Patients are conventionally treated with hemodialysis. Therefore we'd like to present a report of a foreign sailor in Rotterdam who accidentally caused himself severe methanol intoxication, with a maximum measured concentration of 4.4 g/L.
The patient presented with hemodynamic instability and severe metabolic acidosis with pH 6.69. The anion gap was 39 mmol/L and the osmol gap 73 mosmol/kg. Treatment with ethanol and continuous venovenous hemodiafiltration (CVVH-DF) was initiated. Despite the hemodynamic instability it is was possible to achieve rapid correction of pH and methanol concentration with CVVH-DF while maintaining a stable and therapeutic ethanol serum concentration. Despite hemodynamic and acid-base improvement, our patient developed massive cerebral edema leading to brain death. Permission for organ donation was unfortunately not ascertained.
We conclude that in a hemodynamic instable situation high methanol concentrations and methanol-induced derangements of homeostasis are safely and effectively treated with CVVH-DF and that severe cerebral edema is another possible cause of death rather than the classical bleeding in the putamen area.
Etomidate is a widely used intravenous induction agent that is especially useful for patients at risk for hypotension during anesthesia induction. Side effects limiting its use include adrenocortical suppression, acidosis, myoclonus, venous irritation, and phlebitis. The osmolality of etomidate prepared in propylene glycol appears to play a crucial role in causing phlebitis. The increased use of etomidate during the recent propofol shortage correlated with an increase in reported incidences of postoperative phlebitis and thrombophlebitis at Ochsner Clinic Foundation from October 2009 through April 2010. Several methods aim to prevent such occurrences, including pretreatment with lidocaine (and possibly esmolol), lower doses of etomidate, and injection into larger veins. The most compelling evidence suggests that using a lipid formulation of etomidate instead of the traditional propylene glycol preparation may dramatically decrease venous sequelae.
Etomidate; phlebitis; propofol shortage; thrombophlebitis
Methanol ingestion is an uncommon form of poisoning that can cause severe metabolic disturbances and potentially fatal and often irreversible organ/tissue damage. The diagnosis is sometimes elusive and requires a high index of suspicion. Because extent and irreversibility of the damage caused by formic acid is time sensitive, methanol poisoning should be recognised promptly so that it can be treated. Metabolic acidosis associated with an increased anion gap and osmolar gap is an important laboratory finding but is not always present. A case of severe methanol poisoning is presented that demonstrates the unique challenges in the diagnosis and management, and the lack of readiness of the health care system for such cases. We highlight some of the diagnostic difficulties associated with treating a patient with a reduced level of consciousness and severe metabolic acidosis. We also review the pitfalls of using laboratory tests to rule out alcohol ingestion and discuss the definitive management of methanol poisoning.
HYPONATREMIA (SERUM SODIUM LEVEL LESS THAN 134 MMOL/L) is a common electrolyte disturbance. Its high prevalence and potential neurologic sequelae make a logical and rigorous differential diagnosis mandatory before any therapeutic intervention. A history of concurrent illness and medication use as well as the assessment of extracellular volume status on physical examination may provide useful clues as to the pathogenesis of hyponatremia. Measurement of the effective serum tonicity (serum osmolality less serum urea level) is the first step in the laboratory evaluation. In patients with normal or elevated effective serum osmolality (280 mOsm/kg or greater), pseudohyponatremia should be excluded. In the hypo-osmolar state (serum osmolality less than 280 mOsm/kg), urine osmolality is used to determine whether water excretion is normal or impaired. A urine osmolality value of less than 100 mOsm/kg indicates complete and appropriate suppression of antidiuretic hormone secretion. A urine sodium level less than 20 mmol/L is indicative of hypovolemia, whereas a level greater than 40 mmol/L is suggestive of the syndrome of inappropriate antidiuretic hormone secretion. Levels of hormones (thyroid-stimulating hormone and cortisol) and arterial blood gases should be determined in difficult cases of hyponatremia.
The relation between cerebrospinal fluid (CSF) and serum osmolality was studied in 16 patients with hyperosmolar hypernatraemic dehydration before treatment. After correcting shock and acidosis, 0-45% saline in 2-5 or 5% dextrose was infused in each patient over a 48- to 72-hour period. During rehydration, serum osmolality, electrolyte concentrations, urea nitrogen, and blood pH were measured sequentially. Five patients developed severe neurological abnormalities within 48 hours of addmission (convulsions 2, convulsions with hemiplegia 2, hemiplegia 1). Of these, 3 had residual defects on follow-up at least one year later. This group was indistinguishable from the 11 without significant neurological abnormality, both on clinical grounds before rehydration, and after analysis of admission and subsequent serum biochemical variables. A significant osmolar gap (greater than 4 mmol/kg H2O) between serum and CSF was found in 13 patients. Severe neurological disturbance only occurred when CSF osmolality exceeded that of serum by 7 or more mmol/kg H2O. Discriminant analysis of the paired osmolar data showed that D = -117+1-74 X(CSF osmolality) -1-41 X (serum osmolality), and that severe neurological abnormality was predicted when D was positive.
Methanol intoxication is a life-threatening condition. Hallmark of clinical presentations include severe wide anion gap metabolic acidosis with very high serum osmolar gap and visual complication.
We report a case of severe methanol intoxication with bilateral putaminal hemorrhage, an uncommon serious complication. A 56-year-old man presented with altered mental status. Fundus examination showed optic disc edema. Arterial Blood Gas (ABG) revealed severe anion gap metabolic acidosis with osmolal gap. Head computed tomography (CT) showed hypodense lesions in basal ganglia bilaterally. Hemodialysis and intravenous fomepizole were initiated. Serum methanol level was significantly elevated. Unfortunately, patient was lethargic 2 weeks after discharge. Repeated CT of head demonstrated new putaminal hemorrhages.
Bilateral putaminal hemorrhage is an uncommon but serious complication in methanol intoxication. Clinicians should have high index of suspicion for putaminal hemorrhage when patients with recent methanol intoxication present with altered mental status.
Basal ganglion hemorrhage; Metabolic acidosis; Methanol intoxication; Putaminal hemorrhage
A patient presented with severe acidosis and a point-of-care lactate measurement of 42 mmol/L. Mesenteric ischemia was suspected, with a potential need for laparotomy; however, plasma lactate measurements were below 4 mmol/L. Ethylene glycol ingestion was subsequently diagnosed. We therefore wished to determine why discrepancies in lactate measurements occur and whether this “lactate gap” could be clinically useful.
We phlebotomized blood, added various concentrations of metabolites of ethylene glycol, and tested the resulting samples with the 5 most common lactate analyzers.
With the Radiometer 700 point-of-care analyzer, glycolate addition resulted in an artifactual, massive lactate elevation, even at low glycolate concentrations. Another major ethylene glycol metabolite, glyoxylate (but not oxalate or formate), caused similar elevations. The i-STAT and Bayer point-of-care analyzers and the Beckman and Vitros laboratory analyzers reported minimal lactate elevations. Lactate gap was determined by comparing the Radiometer result with the corresponding result from any of the other analyzers.
We demonstrated how inappropriate laparotomy or delayed therapy might occur if clinicians are unaware of this phenomenon or have access to only a single analyzer. We also showed that lactate gap can be exploited to expedite treatment, diagnose late ethylene-glycol ingestion and terminate dialysis. By comparing lactate results from the iSTAT or Bayer devices with that from the Radiometer, ethylene-glycol ingestion can be diagnosed at the point of care. This can expedite diagnosis and treatment by hours, compared with waiting for laboratory results for plasma ethylene glycol.
Methanol poisoning is a relatively rare but potentially serious medical emergency. Toxicity results when methanol is successively oxidized to the active metabolites formaldehyde and formic acid. We report a case of a 23-year-old male, a high daily alcohol consumer, who attended the local primary health care centre complaining of sudden visual loss. A presumed diagnosis of methanol intoxication was suggested based on the patient’s visual impairment and the history of alcohol ingestion. Specific therapy was initiated before a definitive diagnosis. Gas chromatographic determination of methanol levels confirmed the initial diagnostic suspicion. In this case, prompt recognition of methanol intoxication and treatment conditioned a favorable clinical outcome. Given that timely diagnosis and antidote administration are crucial issues in terms of prognosis, we underline the necessity for physicians to be alert for entities provoked by rare environmental factors.
methanol intoxication; visual loss; diagnosis; management
Of 61 cases of ibuprofen overdosage reported consecutively to the Rocky Mountain Poison and Drug Center from September 1985 through April 1986, 16 were excluded because of incomplete follow-up or concurrent medication ingestion. A toxic reaction developed in 7 (16%) of the remaining 45 patients. Nausea, vomiting, abdominal cramps, mild central nervous system depression, coma, tachycardia, apnea, metabolic acidosis with or without respiratory alkalosis, hematemesis, and oliguric renal failure were noted. Two of six adults had a toxic reaction, and one died. Among pediatric patients, 5/39 (13%) had a toxic reaction. Of patients whose ibuprofen ingestion was less than 104 mg per kg, none became ill. All patients in whom the time of ingestion was known (six of seven) and who had a toxic reaction did so within four hours of ingestion. An ibuprofen overdose, although usually benign, can occasionally produce serious toxicity.
The plant species reported here are traditionally used in Northern Peru for a wide range of illnesses. Most remedies are prepared as ethanol or aqueous extracts and then ingested. The aim of this study was to evaluate the potential toxicity of these extracts.
Materials and methods
The toxicity of ethanolic and water extracts of 341 plant species was determined using a Brine-Shrimp assay.
Overall 24% of the species in water extract and 76% of the species in alcoholic extract showed elevated toxicity levels to brine-shrimp. Although in most cases multiple extracts of the same species showed very similar toxicity values, in some cases the toxicity of different extracts of the same species varied from non-toxic to highly toxic.
Traditional preparation methods take different toxicity levels in aqueous and ethanol extracts into account when choosing the appropriate solvent for the preparation of a remedy.
Medicinal Plants; Ethnobotany; Brine Shrimp; Artemia salina; Toxicity; Northern Peru
An unresponsive 30-year-old female with a history of anxiety and chronic alcohol abuse presented to an emergency department with altered mental status and a severe metabolic acidosis. The patient was intubated for airway protection, and she empirically received folic acid, bicarbonate, and 5% ethanol continuous infusion for suspected ingestion of toxic alcohol. Following transfer to our institution, the patient was minimally responsive to noxious stimuli. She received fomepizole at dosing corrected for hemodialysis (HD), and bicarbonate via multiple boluses and continuous infusion. The ethanol drip was stopped. The nephrology service had been alerted to this patient’s arrival and condition; hemodialysis via a standard heparinized circuit was initiated immediately after her arrival, which produced a marked improvement in the patient’s acid-base status. Her serum methanol concentration subsequently returned at > 200 mg/dL.
After 12 hours and 2 sessions of hemodialysis, the patient remained unresponsive despite minimal sedation. Anisocoria was noted on exam. Computed tomography of the brain demonstrated a large hematoma in the left basal ganglia that extended into the left frontal and parietal white matter accompanied by intraventricular extension, midline shift, loss of grey-white differentiation throughout, suggesting tonsillar herniation (Figure 1). Forty-eight hours after presentation, radionuclide imaging of the brain revealed no intracranial blood flow; heart, lungs, liver, kidneys, and pancreas were subsequently harvested for transplantation.
Methanol; dialysis; heparin; hemorrhage
Hyponatremia occurring as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome is a common complication in patients with subarachnoid hemorrhage (SAH). The efficacy and safety of urea as treatment for SIADH-induced hyponatremia has not been reported in this population.
This is a retrospective analysis of all patients admitted to our department for nontraumatic SAH between January 2003 and December 2008 (n = 368). All patients with SIADH-induced hyponatremia (plasma sodium < 135 mEq/L, urine sodium > 20 mEq/L, and osmolality > 200 mOsm/kg; absence of overt dehydration or hypovolemia; no peripheral edema or renal failure; no history of adrenal or thyroid disease) routinely received urea per os when hyponatremia was associated with clinical deterioration or remained less than 130 mEq/L despite saline solution administration.
Forty-two patients developed SIADH and were treated with urea. Urea was started after a median of 7 (IQR, 5–10) days and given orally at doses of 15–30 g tid or qid for a median of 5 (IQR, 3–7) days. The median plasma sodium increase over the first day of treatment was 3 (IQR, 1–6) mEq/L. Hyponatremia was corrected in all patients, with median times to Na+ >130 and >135 mEq/L of 1 (IQR, 1–2) and 3 (IQR, 2–4) days, respectively. Urea was well tolerated, and no adverse effects were reported.
Oral urea is an effective and well-tolerated treatment for SIADH-induced hyponatremia in SAH patients.
Hyponatremia; SIADH; Sodium; Subarachnoid hemorrhage; Urea
This article reports the time course and clinical features of acute ethanol poisoning in an elderly man who had previously abstained from alcohol. Several hours after ingestion, severe hypotension and hypothermia developed, and the consciousness level was reduced. Supportive measures were sufficient to allow the patient's blood pressure and temperature to recover by 24 h post ingestion. The clinical manifestations of ethanol toxicity are often confounded by coexistent drug ingestion and variable periods of unconsciousness before arrival at hospital. This case highlights that hypotension and hypothermia may be explained on the basis of severe ethanol poisoning alone, in the absence of any other contributing factors. Clinical features of poisoning may be delayed by several hours and, therefore, patients presenting at the hospital should be considered for observation for at least 4 h after consumption of potentially toxic quantities. More severe toxicity should be anticipated in patients who normally abstain from alcohol.