Successful treatment of methemoglobinemia and acute renal failure after indoxacarb poisoning

Context. We report a case of systemic toxicity induced by indoxacarb, an oxadiazine insecticide. Previous reports have suggested the occurrence of methemoglobinemia after indoxacarb ingestion, but no case of indoxacarb-induced systemic toxicity, such as acute renal failure, has been reported thus far. Case details. A 71-year-old woman presented with indoxacarb poisoning, resulting in methemoglobinemia and acute renal failure. The methemoglobinemia improved after methylene blue administration, but rapidly progressive acute renal failure occurred 7 h after admission. She was treated with continuous veno-venous hemofiltration and intravenous sodium bicarbonate and recovered successfully. Discussion. Ingestion of indoxacarb may produce not only methemoglobinemia, but also systemic toxicities like acute renal failure, which can be successfully treated with aggressive therapy such as continuous veno-venous hemofiltration. Physicians should be alert to acute renal failure as a possible complication of indoxacarb ingestion, and treat it accordingly.     

Case report: severe mercuric sulphate poisoning treated with 2,3-dimercaptopropane-1-sulphonate and haemodiafiltration

Introduction

Inorganic mercury poisoning is uncommon, but when it occurs it can result in severe, life-threatening features and acute renal failure. Previous reports on the use of extracorporeal procedures such as haemodialysis and haemoperfusion have shown no significant removal of mercury. We report here the successful use of the chelating agent 2,3-dimercaptopropane-1-sulphonate (DMPS), together with continuous veno-venous haemodiafiltration (CVVHDF), in a patient with severe inorganic mercury poisoning.

Case report

A 40-year-old man presented with haematemesis after ingestion of 1 g mercuric sulphate and rapidly deteriorated in the emergency department, requiring intubation and ventilation. His initial blood mercury was 15 580 μg/l. At 4.5 hours after ingestion he was started on DMPS. He rapidly developed acute renal failure and so he was started on CVVHDF for renal support and in an attempt to improve mercury clearance; CVVHDF was continued for 14 days.

Methods

Regular ultradialysate and pre- and post-filtrate blood samples were taken and in addition all ultradialysate generated was collected to determine its mercury content.

Results

The total amount of mercury in the ultrafiltrate was 127 mg (12.7% of the ingested dose). The sieving coefficient ranged from 0.13 at 30-hours to 0.02 at 210-hours after ingestion. He developed no neurological features and was discharged from hospital on day 50. Five months after discharge from hospital he remained asymptomatic, with normal creatinine clearance.

Discussion

We describe a patient with severe inorganic mercury poisoning in whom full recovery occurred with the early use of the chelating agent DMPS and CVVHDF. There was removal of a significant amount of mercury by CVVHDF.

Conclusion

We feel that CVVHDF should be considered in patients with inorganic mercury poisoning, particularly those who develop acute renal failure, together with meticulous supportive care and adequate doses of chelation therapy with DMPS.     

Electrophysiological correlates of respiratory failure in acute organophosphate poisoning: Evidence for differential roles of muscarinic and nicotinic stimulation

Background. Respiratory failure in acute organophosphate (OP) poisoning can occur early and also relatively late in the clinical course, and the pathophysiology of respiratory failure at these different phases may have important clinical implications. Objective. To compare the electrophysiological findings in patients with early and late respiratory failure following acute OP poisoning. Methods. A prospective observational case series of consenting symptomatic patients with acute OP poisoning were assessed with daily physical examinations and repetitive nerve stimulation (RNS) studies. RNS was done on right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. Outcomes such as need for ventilation and development of intermediate syndrome (IMS) were noted. Early respiratory failure was defined as occurring within 24 hours of ingestion. Results. Seventy-eight patients were recruited for the clinical and electrophysiological study and of those 59 (75.6%) patients had ingested chlorpyrifos. Seven patients developed respiratory failure within 24 hours of ingestion with overt muscarinic signs. They had no electrophysiological abnormalities at median and ulnar nerves before intubation. Three of them later developed “forme fruste” IMS. Five other patients developed late respiratory failure after 24 hours of ingestion, and all of them showed progressive RNS changes indicating severe IMS prior to intubation. Conclusion. The normal RNS in all patients developing early respiratory failure suggests that it is due to a central nervous system (CNS) and muscarinic effect. This emphasizes the need for early rapid atropinisation as a priority, combating the nicotinic effects being less urgent. This is in contrast with the late respiratory failure, which has been shown to be associated with neuromuscular dysfunction. Further studies are needed to quantify CNS and muscarinic dysfunction to assist in the development of better treatments for the severe and early OP poisoning.     

Renal failure and hepatitis following ingestion of raw grass carp gallbladder: A case report

BACKGROUNDFish gallbladder has long been used as a folk remedy in Asian countries. Multiple organ damage after ingestion of fish gallbladder resulting in near mortality has been known to us. Here, we describe a case of acute renal failure (ARF) and hepatitis due to grass carp gallbladder poisoning and review the literature.CASE SUMMARYA previously healthy, 50-year-old woman was admitted to our hospital with a 2-d history of generalized abdominal pain and repeated vomiting following ingestion of two raw grass carp gallbladders in an attempt to alleviate her cough. She developed anuria on day 4 with markedly elevated serum creatinine, urea, bilirubin, alanine aminotransferase, and aspartate aminotransferase. Based on thorough evaluation of her history and prompt biochemical investigations, we diagnosed her with ARF and hepatitis secondary to fish gallbladder poisoning. Her renal biopsy revealed acute tubular necrosis, following which she underwent six sessions of conventional hemodialysis due to renal failure. Supportive treatment with gastric mucosal protectant and liver protectant was administered for targeted organ protection. The patient’s liver function gradually recovered, and serum creatinine was 164 mmol/L at discharge on day 24. Over a follow-up period of 2 wk, her renal function completely recovered.CONCLUSIONPhysicians should be mindful of toxic complications of raw grass carp gallbladder ingestion and we should promote awareness to reduce incidences of food poisoning.     

Delayed Neurologic Sequelae Resulting from Epidemic Diethylene Glycol Poisoning

Background. Diethylene glycol (DEG) is a well-known metabolic and renal toxin usually ingested accidentally as an ethanol substitute or as a contaminant in various medicinals. To date, most poisonings have occurred in third-world countries where early death from renal failure is very common. We report a series of seven patients presenting with epidemic DEG poisoning from a correctional facility with varying degrees of metabolic acidemia and acute renal impairment responding to emergent hemodialysis (HD). Significantly, three patients developed delayed neurologic toxicity which has not been well characterized in the past. Case Series. Seven male patients (age range 19–55) presented over a 36 h period following ingestion of varying quantities of DEG. Initially three patients, ingesting the largest quantities of DEG, presented more than 24 h postingestion with severe metabolic acidemia (pH range 6.8–7.1) and anuric acute renal failure requiring HD. All three remained dialysis-dependent and developed significant cranial neuropathies with bulbar palsy in the second week postingestion. One patient died with cerebral oedema and a progressive encephalopathy. Two further patients presented within 24 h of ingestion with normal renal function and a moderate metabolic acidemia (pH range 7.2–7.28) requiring HD. They remained well. Finally, two further patients presented with a history of trivial DEG ingestion and did not require any therapy. Neurologic signs in the two surviving initial presenters improved over 4–6 months although they remained dialysis-dependent. Conclusion. Unrecognized DEG poisoning may present with metabolic acidemia and anuric acute renal failure. Established renal impairment may predict subsequent delayed neurologic toxicity.     

Acute Endosulfan Poisoning with Cerebral Edema and Cardiac Failure

Background. Organochlorine insecticides are highly toxic compounds that are responsible for a number of severe intoxications worldwide with several deaths. Despite their widespread use in agriculture during the 1940s to 1960s and the well‐known signs and symptoms of intoxication, the clinical picture in case of poisoning varies. We report two cases of acute intentional endosulfan intoxication with cerebral edema and cardiac failure. Case Reports. Both cases developed life‐threatening signs like epileptic state, respiratory insufficiency and hemodynamic instability soon after ingestion. The survivor developed severe myocardial insufficiency and pulmonary edema documented by echocardiography and x‐ray of the chest. The deceased patient developed severe cerebral edema and multiorgan failure ten days after ingestion of Thiodan® 35. The peak serum concentration of endosulfan in the survivor was 0.12 mg/L approximately 23 hours after ingestion, whereas the peak blood concentration in the fatal case was 0.86 mg/L approximately 25 hours post‐ingestion. Post‐mortem endosulfan levels in different organs were determined. Conclusion. Endosulfan is a highly toxic organochlorine insecticide that produces well‐known neurological symptoms of tonic‐clonic convulsions, headache, dizziness and ataxia but also can cause gastrointestinal symptoms and metabolic disturbances. Life‐threatening cerebral edema and hemodynamic instability may occur. Treatment is symptomatic and supportive.     

Colchicine poisoning: the dark side of an ancient drug

Introduction. Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome. Methods. We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included “colchicine” and “poisoning” or “overdose” or “toxicity” or “intoxication.” Toxicokinetics. Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. Therapeutic and toxic doses. The usual adult oral doses for FMF is 1.2–2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5–0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7–26 mg. Drug interactions. CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy. Mechanisms of toxicity. Colchicine's toxicity is an extension of its mechanism of action – binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi-organ dysfunction and failure. Reproductive toxicology and lactation. Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation. Clinical features. Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10–24 h after ingestion – gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion – multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness. Diagnosis. History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia). Management. Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available. Conclusion. Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.     

Clinical features and outcome of patients with amatoxin-containing mushroom poisoning

Objective.?We aimed to determine clinical and laboratory findings that were different between those patients who died and those who survived and to look for factors associated with the mortality in amatoxin-containing mushroom poisoning. Methods.?The mushroom poisoning patients who were admitted to our clinic between 1996 and 2009 were retrospectively evaluated. The diagnosis was based on a history of mushroom ingestion, clinical picture and the presence of serum alpha-amanitin. Patients were divided into two groups as the survival group and the fatality group. Clinical and laboratory findings were compared between the two groups. Relation between variables and clinical outcome was analyzed. Results.?A total of 144 amatoxin poisoning patients were included in this study. Patients who died were more likely to have demonstrated low mean arterial pressure, encephalopathy, mucosal hemorrhage, oliguria–anuria, hypoglycemia, and thrombocytopenia during the hospitalization. Low sodium values and high urea, AST, ALT, total bilirubin, LDH, prothrombin time, international normalized ratio, and activated partial thromboplastin time values were associated with increased likelihood of mortality. Nineteen patients developed acute renal failure. Fourteen patients developed acute hepatic failure. All the 14 patients who died developed acute hepatic failure. The mortality rate was 9.7%. Conclusions.?The factors associated with mortality determined in this retrospective study may be helpful for clinical outcome assessment and monitoring of patients with amatoxin-containing mushroom poisoning.     

Oliguric and non-oliguric acute renal failure in malaria in west zone of rajasthan,India-A comparative study

ObjectiveTo report a comparative clinical and histopathological study on oliguric and non-oliguric acute renal failure (ARF) in malaria.Method311 consecutive cases of malaria out of which 74 (23.79%) had ARF as per WHO criteria were conducted. Mean age was 32.58 (range 15–60 years) and male: female was 2:1.ResultMost of the cases developed ARF within 10 d of onset. 18 cases (11 falciparum, 2 mixed, 5 vivax) presented with oliguric and 56 (41 falciparum, 6 mixed, 9 vivax) with non-oliguric renal failure. Associated major manifestations were jaundice (75.68%), cerebral malaria (41.89%), bleeding manifestations (32.43%), severe anemia (27.03%), hypotension (25.68%), multi-organ failure (18.92%), severe thrombocytopenia (12.16%), and ARDS (8.11%). Kidney biopsy (n=20) showed acute tubular necrosis (n=7), Mesangioproliferative glomerulonephritis (n=4) or both (n=9). Hemodialysis was done in 8 cases of oliguric renal failure out of which 4 survived (average no. of session 2.9).ConclusionMost of the cases recovered within 3 weeks. Total mortality was 28.38% (n=21) and mortality was more in oliguric renal failure (72.22%) as compare to non-oliguric renal failure (14.29%).     

百草枯中毒致肺损害与急性肾功能衰竭治疗探讨

目的:观察百草枯中毒致肺损害和肾功能的变化,以探讨其抢救和治疗措施。方法:回顾性分析我院48例百草枯中毒并发肺损害和急性肾功能衰竭(ARF)患者的临床表现、X线胸片、血气分析和肾功能。结果:服毒后3天开始出现肺损害,7天达到高峰;肾功能衰竭和肺损害先后发生,严重者表现出急性呼吸窘迫综合征(ARDS)和ARF,死亡率达64.6%。所有患者均给予糖皮质激素治疗。ARDS病例接受对症治疗,部分使用呼吸机行机械通气治疗,效果不明显。肾功能损害者要接受对症治疗,个别行血液灌洗治疗,肾功能有所改善。结论:百草枯中毒致肺损害和肾损害的发生时间早、进展快、易引起ARDS和ARF,死亡率高,患者宜早期治疗。     

Immune-complex glomerulonephritis associated with Staphylococcus aureus infection of a totally implantable venous device

We report a previously unrecognized complication of totally implanted subcutaneous ports. A patient with a totally implantable central venous device developed a septic syndrome. Blood and injection-reservoir cultures grew Staphylococcus aureus. There was no evidence of endocarditis. The port was removed but acute oliguric renal failure developed. A percutaneous renal biopsy showed acute diffuse proliferative glomerulonephritis. There was no extracapillary crescent. On immunofluorescence study, capillary wall granular deposits stained brightly for IgG and C3. These findings were thought to be consistent with infection-associated immune-complex glomerulonephritis.     

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.     

Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score

Objectives: To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. Design: Prospective, multicenter, observational cohort analysis. Setting: Forty ICUs in 16 countries. Patients: All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. Measurements and results: Of the patients, 348 (24.7 %) developed ARF, as diagnosed by a serum creatinine of 300 μmol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p < 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8 % vs 14.0 %, p < 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95 %: 1.23–2.06], p < 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. Conclusion: In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients. Received: 9 August 1999/Final revision received: 24 January 2000/Accepted: 6 April 2000     

Multiple organ failure after an overdose of less than 0.4 mg/kg of colchicine: role of coingestants and drugs during intensive care management

Introduction. Although the ingestion of a dose of colchicine lower than 0.5 mg/kg is usually complicated by a mortality rate less than 5%, severe complications may be associated with drug–drug interactions in case of overdose combining other drugs.?Case report. A 33-year-old previously healthy woman was admitted after a drug overdose combining colchicine, atorvastatin, ibuprofen, diclofenac, and furosemide. The amount of colchicine ingested was exactly 20 mg, corresponding to 0.33 mg/kg. Despite this relatively low dose, she presented the clinical course that is usually seen with much larger colchicine ingestions. She developed acute renal and liver failure, acute lung injury, pancytopenia with sepsis, rhabdomyolysis, hypertriglyceridemia, and ultimately died on Day 14 from hyperammonemic encephalopathy, refractory hypoxemia, and cardiac arrhythmias.?Discussion. Serious drug–drug interactions may have complicated colchicine poisoning. In particular, atorvastatin, an inhibitor of P-glycoprotein and cytochrome P450 3A4, was likely responsible for an increased severity of rhabdomyolysis. In addition, propofol used for sedation during mechanical ventilation may have induced symptoms consistent with “propofol infusion syndrome,” with further muscular injury and hypertriglyceridemia. The mechanism of death was unusual and similar to Reye's syndrome.     

Outcome in post-traumatic acute renal failure when continuous renal replacement therapy is applied early vs. late

Objective: To determine whether the timing of initiation of continuous renal replacement therapy (CRRT) affects outcome in patients with post-traumatic acute renal failure (ARF). Design: The medical records of patients treated with CRRT for post-traumatic ARF were retrospectively reviewed. Chi-square testing was used to test frequencies between groups, and Student's t -test was used to compare means. Setting: A Level I trauma center. Patients: 100 Adult trauma patients treated with CRRT for ARF from 1989 to 1997. Patients were characterized as “early” or “late” starters, based upon whether the blood urea nitrogen (BUN) was less than or greater than 60 mg/dl, prior to CRRT initiation. Results: The mean BUN of the early and late starters was 42.6 and 94.5 mg/dl, respectively (p < 0.0001). CRRT was initiated earlier in the hospital course of early starters compared to late starters (hospital day 10.5 vs 19.4, p < 0.0001). Creatinine clearance prior to CRRT did not differ statistically between the two groups. No significant difference was found between early and late starters with respect to Injury Severity Score, admission Glasgow Coma Scale, presence of shock at admission, age, gender distribution, or trauma type. Admission laboratory values including BUN, serum creatinine, lactate, and bilirubin as well as fluid and blood requirements in the first 24 h were statistically the same for the two groups, suggesting a similar risk of developing renal failure. Survival rate was significantly increased among early starters compared to late starters (39.0 vs 20.0 %, respectively, p = 0.041). Conclusions: This retrospective review indicates that an earlier initiation of CRRT, based on pre-CRRT BUN, may improve the rate of survival of trauma patients who develop ARF. Received: 23 October 1998 Final revision received: 12 May 1999 Accepted: 20 May 1999     

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 the severity of organophosphate (fenitrothion) poisoning based on its serum concentration and clinical parameters

Background. Fenitrothion (MEP) is the most frequent cause of organophosphate pesticides (OP) poisoning in Japan, but clinical parameters to predict its severity remain uncertain. Method. We evaluated 26 cases (12 males and 14 females) of MEP poisoning brought to our critical care center. Regarding acute lung injury (ALI) as a hallmark complication leading to poor recovery, we divided patients into two groups: cases without ALI (Grp1, n = 14), and cases who developed ALI (Grp2, n = 12) at various points after the poisoning. Serial changes in clinical parameters and laboratory test results were compared between them. Results. The median MEP concentrations on arrival (min～max) for Grp1 and Grp2 were 2.3 (0.5–5.1) and 4.6 (1.1–14.0) μg/ml, respectively. Serum pseudo-cholinesterase (PChE) levels on arrival were 21(< 10–59) U/L in Grp1 and < 10 in Grp2. Based on individual patient kinetics, we estimated MEP concentration at 2 and 24 hours after ingestion, and determined cutoff values for differentiating the two groups for each time point as 4.0 μg/ml and 0.5 μg/ml, respectively. By logistic regression analysis, two groups were distinguished with accuracy of 92.3% based on their time of arrival after ingestion and initial MEP concentration. Clinical parameters associated with ALI were days with miosis, days with PChE below 100 U/L, and days requiring administration of atropine. Conclusion. The severity of MEP poisoning is closely associated with both time to presentation after ingestion and initial MEP concentration. Serial monitoring of MEP concentrations in the first 24 hours is also useful in predicting the clinical course.     

Pancreatic Injury Following Acute Methanol Poisoning

Background: Methanol ingestion is a cause of potentially life-threatening poisoning with numerous systemic manifestations. Clinicians may overlook the possibility of acute pancreatitis in this setting. The objective of this paper is to document the incidence of this complication in a series of 22 patients and to discuss the respective role of methanol and ethanol in its pathogenesis. Case Report: A 54-year-old woman developed acute necrotizing pancreatitis following acute methanol poisoning. She was treated by hemodialysis, ethanol infusion, and folinic acid, but, despite maximal supportive therapy, she died from multiple organ failure 54 hours after the ingestion. Case Series: In a series of 22 consecutive patients admitted with a diagnosis of acute methanol poisoning, we found evidence of pancreatic damage in 11 patients. The abnormalities were present from admission and before ethanol therapy in 7 cases and developed after ethanol therapy in 4 cases. Seven patients had a history of chronic ethanol abuse, but no patient had previously suffered from acute or chronic pancreatitis. Three patients presented moderate-to-severe acute pancreatitis according to clinical and radiological criteria and required aggressive supportive therapy including peritoneal dialysis. One patient died from the direct consequences of acute necrotizing pancreatitis and 2 fully recovered from this event. Three patients evolved to brain death; autopsy revealed hemorrhagic lesions in the pancreas in only 1 case. Conclusions: Clinical, biological, and radiographic signs of acute pancreatic injury may be more common than previously realized. Acute methanol poisoning appears to produce pancreatic injury, although antidotal treatment with ethanol or prior chronic ethanol abuse may be contributing factors. Because ethanol treatment may complicate the pancreatic injury, fomepizole (4-methylpyrazole) may be the preferable antidote in acute methanol poisoning.