Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospitalization

Objectives

Acute organophosphate (OP) poisoning causing alteration in acid-base equilibrium was reported before. Hence, different acid-base statuses may present in patients with acute poisoning due to OP exposure. This study aims to determine the impact of acid-base interpretation in patients with acute OP poisoning before hospitalization in medical care units and to describe the pattern of mortality with different acid-base statuses.

Design and Patients

Over a 9-year retrospective study, from July 1996 to August 2005, a total of 82 consecutive patients with acute OP poisoning were admitted to the China Medical University Hospital (Taichung, Taiwan) within 24 hours after exposure to OP and were enrolled into this study.

Results

Patients with acute OP poisoning were divided into 4 groups: without acidosis, metabolic acidosis, respiratory acidosis, and mixed acidosis. Overall survival (Kaplan-Meier curves) among groups was statistically significant (P < .0001). The mortality rate of acute OP poisoned patients with metabolic acidosis was 25%, and 75% of those patients died of cardiovascular failure. The mortality rate of acute OP poisoning with respiratory acidosis was 50%, and 50% of those patients died of respiratory failure.

Conclusions

Acid-base interpretation can be effective in quick diagnosis and prediction of the outcome of patients with acute OP poisoning (without acidosis < metabolic acidosis < respiratory acidosis < mixed acidosis) before hospitalization. Major causes of death are different between the respiratory acidosis and metabolic acidosis groups of patients with acute OP poisoning.     

Acute human Glufosinate-containing herbicide poisoning

Abstract

Background. Glufosinate-containing herbicides are commonly used worldwide. Data on acute human glufosinate poisoning however remain scarce. Methods. We retrospectively reviewed the medical records of all glufosinate poisoned cases reported to the Taiwan National Poison Control Center and two medical centers in Taiwan from August 1993 through February 2010. Their demographic and clinical data were then analyzed to identify potential predictors of severe effects following acute glufosinate poisoning. Results. One hundred and thirty-one patients, including 115 oral and 16 non-oral exposures, were eligible for final analysis. Among patients with oral exposure, 25 were asymptomatic, while the others developed gastrointestinal, neurological, cardiovascular, and/or respiratory manifestations. Seven patients (6.1%) died following deliberate glufosinate ingestion. The median dose of glufosinate ingestion was 30.4 grams (interquartile range 18.5–45.6 grams) in the severe/fatal group compared to 6.8 grams (interquartile range 3.7–16.2 grams) in the non-severe group (p <0.001). Older age (≥61 years; adjusted OR 4.9, 95% CI 1.3–17.9) and larger amount of glufosinate ingestion (≥13.9 grams; adjusted OR 25.2, 95% CI 4.8–132.5) were positively associated with the development of severe toxicity, whereas ethanol consumption (adjusted OR 0.1, 95% CI <0.1–0.5) was inversely associated with the risk of severe toxicity. Conclusion. Although glufosinate is generally thought to be of low toxicity to humans, severe effects can occur and may be associated with older age, larger amount of ingestion and absence of concomitant ethanol consumption.     

Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia

Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish ventilatory failure and hypercapnia. On the other hand, it is known that acute metabolic acidosis can also negatively affect (respiratory) muscle function and, therefore, could lead to a deterioration of respiratory failure. Moreover, we reasoned that the impact of metabolic acidosis on respiratory muscle strength and respiratory muscle endurance could be more pronounced in COPD patients as compared to asthma patients and healthy subjects, due to already impaired respiratory muscle function. In this study, the effect of metabolic acidosis was studied on peripheral muscle strength, peripheral muscle endurance, airway resistance, and on arterial carbon dioxide tension (PaCO₂). Acute metabolic acidosis was induced by administration of ammonium chloride (NH₄Cl). The effect of metabolic acidosis was studied on inspiratory and expiratory muscle strength and on respiratory muscle endurance. Effects were studied in a randomized, placebo‐controlled cross‐over design in 15 healthy subjects (4 male; age 33·2 ± 11·5 years; FEV₁ 108·3 ± 16·2% predicted), 14 asthma patients (5 male; age 48·1 ± 16·1 years; FEV₁ 101·6 ± 15·3% predicted), and 15 moderate to severe COPD patients (9 male; age 62·8 ± 6·8 years; FEV₁ 50·0 ± 11·8% predicted). An acute metabolic acidemia of BE –3·1 mmol.L^?1 was induced. Acute metabolic acidemia did not significantly affect strength or endurance of respiratory and peripheral muscles, respectively. In all subjects airway resistance was significantly decreased after induction of metabolic acidemia (mean difference –0·1 kPa.sec.L^?1 [95%‐CI: ?0·1 –?0·02]. In COPD patients PaCO₂ was significantly lowered during metabolic acidemia (mean difference –1·73 mmHg [?3·0 –?0·08]. In healthy subjects and in asthma patients no such effect was found. Acute metabolic acidemia did not significantly decrease respiratory or peripheral muscle strength, respectively muscle endurance in nomal subjects, asthma, or COPD patients. Metabolic acidemia significantly decreased airway resistance in asthma and COPD patients, as well as in healthy subjects. Moreover, acute metabolic acidemia slightly improved blood gas values in COPD patients. The results suggest that stimulation of ventilation in respiratory failure, by induction of metabolic acidemia will not lead to deterioration of the respiratory failure.     

Treatment of ethylene glycol poisoning

Ingestion of ethylene glycol may be an important contributor in patients with metabolic acidosis of unknown cause and subsequent renal failure. Expeditious diagnosis and treatment will limit metabolic toxicity and decrease morbidity and mortality. Ethylene glycol poisoning should be suspected in an intoxicated patient with anion gap acidosis, hypocalcemia, urinary crystals, and nontoxic blood alcohol concentration. Fomepizole is a newer agent with a specific indication for the treatment of ethylene glycol poisoning. Metabolic acidosis is resolved within three hours of initiating therapy. Initiation of fomepizole therapy before the serum creatinine concentration rises can minimize renal impairment. Compared with traditional ethanol treatment, advantages of fomepizole include lack of depression of the central nervous system and hypoglycemia, and easier maintenance of effective plasma levels.     

Massive ethylene glycol poisoning without evidence of crystalluria: a case for early intervention

A case of severe ethylene glycol poisoning is presented, characterized by protracted delirium, coma, and delayed adult respiratory distress syndrome. This patient never demonstrated evidence of calcium oxalate crystalluria or renal insufficiency. Ethylene glycol intoxication should be considered in the patient who presents with an altered mental status, unexplained metabolic acidosis, and elevated anion and osmolal gaps with or without crystalluria. Early empiric ethanol therapy and consideration of dialysis are recommended for those patients with such a presentation without evidence of abnormal levels of ketones, lactate, salicylate, or ethanol. It is proposed that early ethanol therapy may prevent the formation of ethylene glycol metabolites to the extent that calcium oxalate crystalluria is not seen.     

Acute ethylene glycol poisoning

Ethylene glycol, a major constituent of antifreeze, is metabolized by alcohol dehydrogenase to glycoaldehyde, glycolate, glyoxylate, and oxalate. The metabolites of ethylene glycol cause severe metabolic acidosis and central nervous system, pulmonary, and renal damage. Ethanol competes with ethylene glycol as an alternate substrate of alcohol dehydrogenase. Two cases of ethylene glycol poisoning associated with serum concentrations of 59 and 150 mg/dl are reported. One patient was protected from the toxic effects of the metabolites because of concomitant ethanol ingestion. In patients with unexplained anion and osmol gaps, early diagnosis and therapy with ethanol and hemodialysis help prevent the toxic manifestations of ethylene glycol poisoning.     

Ethylene Glycol Toxicity: The Role of Serum Glycolic Acid In Hemodialysis

Objective: To correlate serum glycolic acid levels with clinical severity and outcome in ethylene glycol poisoning and to determine if glycolic acid levels are predictive of renal failure and the need for hemodialysis. Methods: We measured serum ethylene glycol and glycolic acid levels by gas chromatography/mass spectrometry for 41 admissions (39 patients) for ethylene glycol ingestion and performed retrospective chart reviews. Results: Eight patients died, all of whom developed acute renal failure. Of the survivors, 15 also developed acute renal failure, whereas 18 did not. Of those with normal renal function, 8 had glycolic acid levels below detection limits (<0.13 mmol/L) despite ethylene glycol levels as high as 710 mg/dL; 7 of these patients coingested ethanol. Pertinent initial laboratory data for each group are as follows (mean; range): Deceased: pH 6.99 (6.82–7.22); bicarbonate, 4.8 mmol/L (2–9); anion gap, 28.6 mmol/L (24–40); glycolic acid, 23.5 mmol/L (13.8–38.0); ethylene glycol, 136.5 mg/dL (6–272). Survived/acute renal failure: pH 7.07 (6.75–7.32); bicarbonate, 5.6 mmol/L (1–12); anion gap, 28.7 mmol/L (18–41); glycolic acid, 20.2 mmol/L (10.0–30.0); ethylene glycol, 238.8 mg/dL (12–810). No acute renal failure with glycolic acid >1.0 mmol/L: pH 7.29 (7.12–7.46); bicarbonate, 14.7 mmol/L (4–23); anion gap, 16.5 mmol/L (10–26); glycolic acid, 6.8 mmol/L (2.6–17.0); ethylene glycol, 269.1 mg/dL (6–675). No acute renal failure with glycolic acid <1.0 mmol/L: pH 7.41 (7.38–7.47); bicarbonate, 23.4 mmol/L (17–25); anion gap, 11.8 mmol/L (8–18); glycolic acid, 0.1 mmol/L (0–0.66); ethylene glycol, 211 mg/dL (8–710). The mean time postingestion to admission generally correlated with severity as follows: deceased, ≥10.4 h; survived/acute renal failure, ≥9.9 h; no acute renal failure with glycolic acid >1.0 mmol/L, ≥6.2 h; no acute renal failure with glycolic acid <1.0 mmol/L, ≥3.7 h. Hematuria was more prevalent than oxaluria (86% and 41%, respectively), but neither was individually predictive of acute renal failure. Good correlations were found between glycolic acid levels and anion gap (r² = 0.7724), pH (r² = 0.7921), and bicarbonate (r² = 0.6579); poor correlations (r² <0.0023) occurred between ethylene glycol levels and glycolic acid, pH, anion gap, and bicarbonate. Measured ethylene glycol values were highly correlated with ethylene glycol values calculated from the osmolal gap (r² = 0.9339), but the latter overestimates the true value by about 7%, on average. An initial glycolic acid level ≥10 mmol/L predicts acute renal failure with a sensitivity of 100%, a specificity of 94.4%, and an efficiency of 97.6%. Ethylene glycol levels are not predictive of acute renal failure or central nervous system manifestations of toxicity. If only ethylene glycol values are available (measured or calculated), an initial anion gap >20 mmol/L is 95.6% sensitive and 94.4% specific for acute renal failure when ethylene glycol is present. Likewise, initial pH <7.30 is 100% sensitive and 88.5% specific for acute renal failure. Conclusion: We propose glycolic acid <8 mmol/L as a criterion for the initiation of hemodialysis in ethylene glycol ingestion. Patients with glycolic acid <8 mmol/L probably do not need dialysis, regardless of the ethylene glycol concentration, when metabolism of ethylene glycol is therapeutically inhibited. In the absence of glycolic acid values, an anion gap >20 mmol/L or pH <7.30 predicts acute renal failure.     

Author Index

In 1987 two lethal adult cases of accidental ethylene glycol poisoning were given spectacular attention in the Swedish mass media. This resulted in an epidemic of intentional ethylene glycol poisonings. In addition to six cases related to alcohol abuse, another 30 severe suicidal poisonings were reported to the Swedish Poison Information Centre in five months. The clinical course and outcome in these 36 severe cases are reviewed. The primary clinical manifestations were metabolic acidosis, CNS disturbances and kidney damage with circulatory failure in the most severe cases. Mortality was 17%. Fragmentation of the normal striation in heart cells was found in two of the fatal cases and severe brain damage in all fatal poisonings. The degree of acidosis but not the serum ethylene glycol level correlated with both kidney damage and outcome. Treatment included ethanol, correction of the metabolic acidosis and dialysis. Four patients with serum ethylene glycol concentrations of 10-20 mmol/L (620-1240?mg/L) but with no or minimal metabolic acidosis were treated with ethanol alone; none of these patients developed renal damage.     

Transient non-cardiogenic pulmonary edema following massive ingestion of ethylene glycol butyl ether

A case of acute poisoning with ethylene glycol butyl ether (EGBE) is reported in a chronic alcohol abuser. On admission the 53-year-old patient was comatose with metabolic acidosis, shock, and noncardiogenic pulmonary edema confirmed by haemodynamic study. Following supportive treatment and haemodialysis the outcome was favorable. The relationship between respiratory failure and EGBE is examined.     

Acetazolamide Causes Worsening Acidosis in Uncompensated COPD Exacerbations: Increased Awareness Needed for Patient Safety

BackgroundAcetazolamide has been studied extensively in post-hypercapnic alkalosis as a tool to facilitate ventilator weaning in chronic obstructive pulmonary disease (COPD). It has also been utilized to facilitate respiratory drive in nonmechanically ventilated patients with COPD. Although this is generally a forgiving intervention, providers must carefully select patients for this medication, as it can cause severe acidosis and deterioration of clinical status in severe COPD cases. The present report describes two cases of patients who developed worsening acidosis and hypercapnia after receiving acetazolamide in acute respiratory failure.Case ReportCase 1 was a 72-year-old obese male with COPD who was dependent on supplemental oxygen and presented to the emergency department (ED) with acute on chronic hypercapnic respiratory failure. He was given a one-time dose of acetazolamide in the ED for “respiratory failure made worse by severe metabolic alkalosis.” His arterial blood gas (ABG) worsened overnight, accompanied by decreased mental status: pH 7.32, paCO₂ 82 mm Hg, paO₂ 50 mm Hg, HCO₃ 41.7 mmol/L, FiO₂ 32% to pH 7.21, paCO₂ 91.7 mm Hg, paO₂ 59 mm Hg, HCO₃ 36.6 mmol/L, and FiO₂ 32%. Case 2 was a 62-year-old male with COPD who was dependent on supplemental oxygen and presented to the ED with acute on chronic hypercapnic respiratory failure. He was given acetazolamide in the ED with similar results: ABG on presentation pH 7.37, paCO₂ 79.3 mm Hg, paO₂ 77.6 mm Hg, HCO₃ 45.5 mmol/L, and FiO₂ 32%. The next morning, ABG was pH 7.29, paCO₂ 79 mm Hg, paO₂ 77 mm Hg, HCO₃ 45.5 mmol/L, and FiO₂ 32%.Why Should an Emergency Physician Be Aware of This?Acetazolamide given early in the uncompensated setting can worsen acidosis and potentiate clinical deterioration.     

The role of calcium oxalate crystal deposition in cerebral vessels during ethylene glycol poisoning

Ethylene glycol (EG) poisoning can lead to serious morbidity or death, which occurs following conversion of ethylene glycol to toxic metabolites. These metabolites affect multiple organ/systems leading to metabolic acidosis, cardiopulmonary depression, acute renal failure and central nervous system deficits. Treatment consists of correcting metabolic acidosis with bicarbonate administration, dialysis to remove toxic metabolites and administration of fomepizole or ethanol to prevent conversion of EG to toxic intermediates. Occasionally in the literature, fatal cases of EG poisoning have been described in which calcium oxalate crystal deposition has occurred in the walls of CNS vessels, sometimes with associated neuropathy. We describe a case of fatal EG poisoning in which the development of rapid cerebral edema was documented by CT scan and was accompanied by definitive evidence of birefringent crystals within walls of CNS blood vessels, with associated inflammation and edema. This case and others in the literature suggest that cerebral edema, and perhaps injury to other organs, could result from oxalate crystal deposition in small blood vessels in the brain and other organs.     

Acute salicylate poisoning: risk factors for severe outcome

Context: Salicylate poisoning remains a significant public health threat with more than 20,000 exposures reported annually in the United States.

Objective: We aimed to establish early predictors of severe in-hospital outcomes in Emergency Department patients presenting with acute salicylate poisoning.

Methods: This was a secondary data analysis of adult salicylate overdoses from a prospective cohort study of acute drug overdoses at two urban university teaching hospitals from 2009 to 2013. Patients were included based on confirmed salicylate ingestion and enrolled consecutively. Demographics, clinical parameters, treatment and disposition were collected from the medical record. Severe outcome was defined as a composite occurrence of acidemia (pH <7.3 or bicarbonate <16?mEq/L), hemodialysis, and/or death.

Results: Out of 1997 overdoses screened, 48 patients met inclusion/exclusion criteria. Patient characteristics were 43.8% male, median age 32 (range 18–87), mean initial salicylate concentration 28.1?mg/dL (SD 26.6), and 20.8% classified as severe outcome. Univariate analysis indicated that age, respiratory rate, lactate, coma, and the presence of co-ingestions were significantly associated with severe outcome, while initial salicylate concentration alone had no association. However, when adjusted for salicylate concentration, only age (OR 1.13; 95% CI 1.02–1.26) and respiratory rate (OR 1.29; 95% CI 1.02–1.63) were independent predictors. Additionally, lactate showed excellent test characteristics to predict severe outcome, with an optimal cutpoint of 2.25?mmol/L (78% sensitivity, 67% specificity).

Conclusions: In adult Emergency Department patients with acute salicylate poisoning, independent predictors of severe outcome were older age and increased respiratory rate, as well as initial serum lactate, while initial salicylate concentration alone was not predictive.     

早期血气分析对急性有机磷农药中毒患者预后的预测

目的 探讨急性有机磷农药中毒(AOPP)患者的酸碱平衡与死亡率的关系.方法 回顾性研究我院2000-01～2006-01在急诊科就诊并收入住院的78例连续的、中毒时间在24 h内的AOPP患者,依据第一次动脉血气结果 判断是否存在酸中毒及酸中毒类型,并对各类型的死亡率进行比较.结果 AOPP患者分为无酸中毒组、代谢性酸中毒组、呼吸性酸中毒组和混合型酸中毒组,组间死亡率比较差异有统计学意义(P＜0.01).有代谢性酸中毒的AOPP患者死亡率为22.5%,其中71.4%死于心力衰竭;有呼吸性酸中毒的AOPP患者死亡率为42.9%,其中66.7%死于呼吸衰竭.结论 酸碱度能有效预测AOPP患者的死亡率, 代谢性酸中毒组的死亡原因与呼吸性酸中毒组不同.     

Acute Poisoning with a Herbicide Containing Imazapyr (Arsenal): A Report of Six Cases

Background: Acute pesticide poisoning is a major cause of morbidity and mortality in Taiwan and herbicides are most frequently implicated. Imazapyr [2-(4-isopropyl-4-methyl-5-oxo-2 imidazoline-2-yl)nicotinic acid] is a new herbicide, recently registered in Taiwan under the tradename “Arsenal” (Imazapyr 23.1%, Cyanamid Taiwan Corporation, Taipei). Imazapyr is also marketed as Assault, Chopper, Contain, and Pivot. To the best of our knowledge, there is no information in the literature concerning acute toxicity in humans after ingestion of herbicides containing this compound. Method: Six cases of acute poisoning with Arsenal occurred during the period 1993–1997 in a single hospital. Emergency room records and medical charts were reviewed. Results: Of 6 cases, 5 were suicide attempts and 1 was an act of violence inflicted on a child. Three of the 6 patients (50%) presented with severe symptoms, including impairment of consciousness and respiratory distress requiring intubation. Other presentations included metabolic acidosis (2), hypotension (2), leukocytosis (3), fever (2), mild elevation of hepatic transaminase and creatinine (2), unconjugated hyperbilirubinemia (2), oral ulceration (2), pharyngolaryngitis (2), and chemical burns of the cornea (1). All cases had copious vomiting after ingestion of Arsenal. No mortality occurred. Conclusion: According to our observations, it appeared the toxic syndrome that results from a large quantity (> 100 mL) of Arsenal herbicide ingestion consists of hypotension, pulmonary dysfunction, oral mucosal and gastrointestinal irritation, and transient liver and renal dysfunction. However, the existence of a dose-response relationship, with increasing amounts of ingestion resulting in more severe symptoms, needs further observation and studies that include a larger series.     

Acid-base disturbances in acute poisoning and their association with survival

PurposeThe purpose was to investigate the association between acid-base disturbances and mortality in acute poisoning.Materials and methodsWe performed a retrospective cross-sectional exploratory study on all acutely poisoned patients older than 12 years who had been admitted to the main tertiary toxicology hospital in Tehran between March and August 2010.ResultsOf a total of 1167 patients (median age = 25 years, 50.9% male), 98 died (74.5% male). Psychotropic medications were the most common cause of poisoning (36.5%), whereas narcotics and psychodysleptics were the most common cause of death (23.5%). Mixed respiratory alkalosis and metabolic acidosis with normal pH were the most common acid-base status (333, 28.5%). However, patients with primary metabolic acidosis and respiratory compensation had significantly higher mortality (31 cases, 18.8%). Logistic regression analysis identified age (odds ratio [OR], 1.051; 95% confidence interval [CI], 1.031-1.070; P < .001), intensive care unit admission (OR, 12.405; 95% CI, 7.178-21.440; P < .001), consciousness level (OR, 1.752; 95% CI, 1.301-2.359; P < .001), hospitalization period (OR, 1.1361; 95% CI, 1.079-1.195; P < .001), severe metabolic acidosis (OR, 6.016; 95% CI, 1.647-21.968; P = .007), and primary respiratory alkalosis (OR, 5.579; 95% CI, 1.353-23.001; P = .017) as death predictors during hospitalization (P < .001).ConclusionOn-arrival acid-base status predicts survival and can be used in prognostication of the poisoned patients.     

What can clinicians learn from therapeutic studies about the treatment of acute oral methotrexate poisoning?

Context: Methotrexate (MTX) is an anti-folate drug that has been utilized in both malignant and chronic inflammatory conditions. Doctors are often concerned with a potential adverse outcome when managing patients with acute oral MTX poisoning given its potential for serious adverse reactions at therapeutic doses. However, there is surprisingly little data from acute poisoning cases and more data from the therapeutic use of high-dose MTX.

Objectives: To review pharmacokinetic and pharmacological properties of MTX and systematically review series of acute MTX poisonings and therapeutic studies on high-dose MTX that provide pharmacokinetic or clinical data.

Methods: An Embase (1974–October 2016) and Medline (1946–October 2016) search was performed by combining “MTX” and “overdose/poison” or “MTX” and “toxicity” or “MTX” and “high-dose MTX” or “MTX” and “bioavailability” or “pharmacokinetics”; 25, 135, 109 and 365 articles were found, respectively, after duplicates were removed. There were 15 papers that provided clinical data on acute ingestion and toxicity that occurred with low-dose administration. Eighteen papers were on high-dose MTX (>1?g per m² body surface area) used as a single chemotherapy agent which provided pharmacokinetic or clinical data on MTX toxicity. Thirty papers were reviewed to determine the toxic dose, pharmacokinetics, risk factors, clinical symptoms and management of acute MTX toxicity. Given the limited acute poisoning data, a retrospective audit was performed through the consultant records of the New South Wales Poisons Information Centre from April 2004 to July 2015 to examine the clinical syndrome and toxicity of acute oral MTX poisoning.

Pharmacokinetics: Reduced MTX bioavailability is a result of saturable absorption. Although maximal bioavailable absorption occurs at a dose of ～15?mg?m^?2, splitting the dose increases bioavailability. MTX clearance is proportional to renal function.

Acute toxicity: Oncologists prescribe doses up to 12?g?m^?2 of MTX. Patients treated with an intravenous dose of MTX?<1g?m^?2 do not require folinic acid rescue. MTX toxicity correlates better with duration and extent of exposure than peak serum concentration.

Acute oral poisoning: Acute oral MTX poisoning in 177 patients did not report any severe toxicity. In the New South Wales Poisons Information Centre audit data (2004–2015), 51 cases of acute MTX poisoning were reported, of which 15 were accidental paediatric ingestions. The median reported paediatric ingestion was 50?mg (IQR: 10–100; range: 10–150) with a median age of 2 years (IQR: 2–2; range: 1–4). Of the 36 patients with acute deliberate MTX poisoning, median age and dose were 47 years (IQR: 31–62; range: 10–85) and 325?mg (IQR: 85–500; range: 40–1000), respectively. Of the 19 patients who had serum MTX concentrations measured, all were significantly below the concentrations used in oncology and the folinic acid rescue nomogram line and no patient reported adverse sequelae.

Management of acute oral poisoning: Due to the low bioavailability of MTX, treatment is not necessary for single ingestions. Oral folinic acid may be used to lower the bioavailability further with large ingestions?>1?g?m^?2. Oral followed by intravenous folinic acid may be used in patients with staggered ingestion?>36?h or patients with acute overdose and renal impairment (eGFR <45?mL/min/1.73?m²).

Conclusions: As a consequence of saturable absorption MTXs bioavailability is so low that neither accidental paediatric MTX ingestion nor acute deliberate MTX overdose causes toxicity. An acute oral overdose will not provide a bioavailable dose even close to 1?g?m^?2 of parenteral MTX. Hence, no treatment is required in acute ingestion unless the patient has renal failure or staggered ingestion. There is also no need to monitor MTX concentrations in acute oral MTX poisoning.     

Assessment of glufosinate-containing herbicide exposure: A multi-center retrospective study

BackgroundExposure to glufosinate ammonium, an herbicide used worldwide, can cause CNS and respiratory toxicities. This study aimed to analyze acute human glufosinate ammonium poisoning.Materials and methodsThis multicenter retrospective cohort study involved five medical institutes affiliated with the Chang Gung Memorial Hospital system. Patients with glufosinate ammonium exposure visiting the emergency department (ED) between January 2008 and December 2020 were included.ResultsIn total, 95 patients were enrolled. Compared to exposure via the non-oral route, patients exposed orally (n = 61) had lower GCS scores, higher mortality rates, and longer hospital lengths of stay (P-value: <0.001, 0.002, and < 0.001, respectively). In the subgroup analysis among oral exposure patients, the survival group had a lower amount of estimated glufosinate ingestion than the non-survival group (10.5 [3.4–27] vs. 40.5 [27–47.3] g, P-value: 0.022), lower rate of substance co-exposure (9 [19.6%] vs. 10 [66.7%] P-value: 0.001), and lower rate of paraquat co-exposure (0 [0%] vs. 7 [46.7%] P < 0.001) compared with the mortality group. In the orally-exposed and non-paraquat co-exposure patients (n = 54), age > 70 years and GCS score < 9 at triage presented a high sensitivity (100.00%, 95% CI: 63.06–100.00%) and medium specificity (58.70%, 95% CI: 43.23–73.00%) in predicting mortality.ConclusionOld age, change in consciousness, and paraquat co-exposure were associated with higher mortality in human glufosinate poisoning. Age > 70 years and GCS score < 9 at triage could be predictors of mortality in patients with acute oral glufosinate poisoning.     

4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man

Abstract

4-Methylpyrazole (4 MP) is a strong inhibitor of alcohol dehydrogenase. Its use in acute ethylene glycol (EG) or methanol intoxication has been suggested in experimental studies about its efficacy and safety. We report three cases of accidental intoxication with ethylene glycol in man treated orally with 20?mg/kg/day of 4 MP. The treatment was maintained until plasma EG concentrations became unmeasurable. The patients were admitted early during the course of the poisoning. Their neurological status was good. A slight metabolic acidosis observed in two cases was easily corrected and did not recur. Renal function remained normal in all cases. No patient underwent hemodialysis. On admission plasma EG concentrations were 24.2 mmol/1, 13 mmol/l and 9.7 mmol/1 respectively. Plasma EG half-lives were 14.5, 11.5 and 14.75 hours respectively. Plasma oxalate concentrations and the rate of urine oxalate elimination, determined in two patients, were high on admission but quickly returned to normal. Concerning possible side effects of 4 MP, a skin rash was observed in one patient and a possible eosinophilía in the others. These three cases suggest that 4 MP may decrease the metabolic consequences of EG poisoning in man and may be of therapeutic value when administered early during the course of the intoxication before coma, seizures and organic renal failure have occurred.