Lactic acidosis in theophylline overdose

An 18-year-old man with theophylline overdose developed an increased anion gap metabolic acidosis. Serum lactate levels were markedly elevated. A direct correlation was found between the increasing theophylline level, clinical hyperadrenergic state, and the worsening acidosis. Early hemoperfusion reversed the acidosis, the elevated serum theophylline level, and the hyperadrenergic state. This case substantiates the role of lactate accumulation in the metabolic acidosis associated with isolated theophylline toxicity.     

Lactic acidosis following intentional overdose by inhalation of salmeterol and fluticasone

ABSTRACTIatrogenic bacterial meningitis (IBM) is a rare but serious complication of neuraxial procedures, such as spinal and epidural anesthesia or lumbar puncture. We report a case of a 46-year-old female who presented to the emergency department with bacterial meningitis after spinal anesthesia. We review the existing literature outlining the pathogenesis, vector hypothesis, diagnosis, treatment, and prevention as they relate to IBM. We highlight the role of the emergency physician in the rapid diagnosis of this disease, and underscore the need for sterile technique when performing lumbar punctures.     

Poor tolerance of oral activated charcoal with theophylline overdose

Vomiting is a common manifestation of theophylline toxicity and may limit the tolerance of orally administered activated charcoal (OAC). However, this potentially important interaction has received little attention. The records of 33 consecutive patients who presented to the emergency department with serum theophylline concentrations greater than 30 micrograms/ml and toxic symptoms and who were treated with OAC were reviewed. Seventeen (22%) of the 76 OAC doses were vomited. Six patients who had ingested theophylline as a single acute overdose vomited all 11 OAC doses administered, whereas 27 patients receiving chronic theophylline therapy vomited only six (11%) of 65 OAC doses. Vomited doses were associated with higher serum theophylline concentrations. Although theophylline-related vomiting preceded OAC intolerance in all acute toxicity patients, this condition was not predictive of OAC vomiting for chronic toxicity patients.     

Hyperlactataemia and metabolic acidosis following paracetamol overdose

Plasma lactate concentrations and acid-base status were determined in 53 patients poisoned with paracetamol. Eleven patients (Group 1) had plasma paracetamol concentrations below the standard treatment decision line; 19 cases (Group 2) presenting within 15 h of overdose had plasma paracetamol concentrations above the treatment line and received N-acetylcysteine. The remaining 23 patients (Group 3) arrived at hospital too late (more than 15 h after overdose) for treatment with N-acetylcysteine to be completely effective. Compensated metabolic acidosis was present on admission in 55 per cent of Group 1 and 42 per cent of Group 2 patients, and a further 21 per cent of cases in Group 2 had an uncompensated metabolic acidosis. Half the patients in Group 3 were acidotic: 22 per cent had a compensated and 26 per cent an uncompensated metabolic acidosis. On admission, the mean plasma lactate concentration was elevated in both Group 2 and Group 3 patients though not in Group 1 cases. Plasma lactate concentration then fell to normal in patients in Group 2 but became mildly elevated again in some cases at a time which coincided closely with the peak in serum aspartate aminotransferase activity. In patients presenting within 15 h of overdose there was a significant correlation between the elevation in plasma concentrations of lactate and paracetamol at admission. In patients presenting late (Group 3), plasma lactate remained elevated for longer than in Group 2 and acidosis and hyperlactataemia were prominent features in the four patients who died. This study demonstrates first that hyperlactataemia, with or without significant acid-base disturbance, is common following paracetamol overdose particularly in those who are severely poisoned. As uncompensated metabolic acidosis is found in 20 per cent of patients who present early and require protective therapy, it should be sought and corrected if it does not remit spontaneously. Second, half the patients presenting too late for effective treatment are acidotic and those with an uncompensated metabolic acidosis resistant to correction have a poor prognosis. Paracetamol poisoning should be considered in the differential diagnosis of metabolic acidosis of unknown aetiology.     

Theophylline overdose: acute single ingestion versus chronic repeated overmedication

Currently available guidelines for managing theophylline intoxication do not distinguish between acute single ingestion and chronic repeated overmedication and do not reliably predict which patients should undergo hemoperfusion. Although hemoperfusion is widely recommended when serum concentrations exceed 40-60 mg/l, many patients with acute overdose tolerate much higher levels without serious toxicity. Because manifestations of toxicity might be dependent on the chronicity of the overdose, the authors retrospectively compared the clinical features of 15 patients with chronic repeated overmedication with those of 27 patients suffering acute single overdose. Patients suffering chronic repeated overmedication developed seizures (7/15) and serious arrhythmias (4/15) with serum levels of 28-70 mg/l. By contrast, only one of 19 patients suffering acute single overdose with peak levels less than 100 mg/l had seizures, and only two of 19 with levels less than 100 mg/l had serious arrhythmias. However, of the eight single-overdose patients with levels over 100 mg/l, seven had seizures and three had serious arrhythmias. Single-overdose patients were easily recognized by the presence of hypotension, hypokalemia, and low serum bicarbonate, features not present in chronic-type patients. Thus, while patients with theophylline overdose caused by chronic repeated overmedication frequently develop seizures and arrhythmias with serum levels of 40-70 mg/l, those with acute single ingestion are highly unlikely to suffer serious complications unless serum levels exceed 100 mg/l. Management of the intoxication, especially selection of patients for hemoperfusion, should be based on whether the overdose is caused by an acute single ingestion or chronic repeated overmedication.     

Fever-induced changes in theophylline pharmacokinetics in rats

Summary— Our aim was to document possible alterations of theophylline pharmacokinetics in rats during fever. Two groups (group A = normothermic controls, group B = fever-induced animals) of Wistar AF IOPS male rats were injected at 19 30 h either with 2 g/kg of brewer's yeast subcutaneously (20% w/v) or with the equivalent volume of saline. Twelve hours later at 07 30 h the two groups received a single 12 mg/kg/IP dose of theophylline. Blood samples were obtained by retro-orbital sinus puncture 0, 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours after administration. A third group of 10 male IOPS rats (group C) were used under the same experimental conditions in order to determine the influence of brewer's yeast-induced fever on biological parameters. C_max, T_max, C_max/T_max, T 1/2, Cl, Vd and AUC were determined according to a one-compartment open model. Our results confirm the fever-induced decrease in total plasma proteins and albumin but do not demonstrate any significant change in theophylline pharmacokinetic parameters.     

Guanfacine overdose resulting in initial hypertension and subsequent delayed,persistent orthostatic hypotension

Introduction. Guanfacine is an α₂-adrenoreceptor agonist used for the treatment of attention-deficit hyperactivity disorder and tic disorders. Few reports exist regarding overdose with guanfacine.?Case Report. A 16-year-old female with Tourette's syndrome presented with diaphoresis, dry mouth, and hypertension 8 h after ingesting 25 mg of guanfacine. These symptoms improved and her blood pressure (BP) normalized over 2 h. Thirty hours following ingestion, she experienced near syncope and returned to the emergency department. She was noted to have orthostatic hypotension and a prolonged QTc interval of 593 ms on electrocardiogram. With only fluid support, she was asymptomatic by 60 h postingestion and her QTc interval had improved to 511 ms.?Discussion. This experience suggests a much delayed onset of symptoms may occur and that the QTc interval may be prolonged, necessitating a longer period of monitoring in a patient presenting with an overdose.     

Caffeine fatalities – Do sales restrictions prevent intentional intoxications?

Objective. Caffeine is widely available in beverages and in different over-the-counter products, including tablets containing 100 mg caffeine. Because intentional fatal intoxications with caffeine occur, the maximum quantity of caffeine tablets that can be bought over the counter in a single purchase was restricted from 250 to 30 in Sweden in the year 2004. The objective of this article was to study the effect of this decision on the number of fatal caffeine intoxications. Method. In Sweden 95% of all cases undergoing forensic autopsy are screened for a number of drugs including caffeine. All cases during January 1993–September 2009 with a caffeine concentration above 80 μg/g blood were recorded. Results. During the study period toxicological investigations were performed in 83,580 forensic autopsies. Caffeine contributed to the fatal outcome in 20 cases (0.02%). Thirteen (65%) of these fatalities occurred before the introduction of the sales restriction. However, no fatal intoxications where caffeine contributed to the cause of death was recorded between May 2007 and September 2009. Conclusion. Overdoses of tablets containing caffeine can be fatal, suicides as well as accidents occur. Restricting the maximum quantity of caffeine tablets available over the counter seemed to be effective in preventing suicides because of caffeine although some time elapsed until the effect was noted. Further monitoring is required to ensure that the observed lower caffeine mortality is a sustained effect.     

Repetition of intentional drug overdose: a population-based study

Context: Intentional overdose is a leading method of self-harm and suicide, and repeat attempts strongly predict eventual death by suicide.

Objectives: To determine the risk of recurrence after a first intentional overdose. Secondary objectives included characterization of the temporal course and potential predictors of repeat overdose, a strong risk factor for death from suicide.

Methods: Design: Population-based cohort study.

Setting: Ontario, Canada, from 1 April 2002 to 31 March 2013.

Participants: All Ontario residents presenting to an emergency department after a first intentional overdose.

Main outcome measures: The incidence and timing of recurrent overdose.

Results: We followed 81,675 patients discharged from hospital after a first intentional overdose. Overall, 13,903 (17.0%) returned with a repeat overdose after a median interval of 288 (inter-quartile range: 62 to 834) days. Of these, 4493 (5.5%) had multiple repeat episodes. Factors associated with repeat self-poisoning included psychiatric care in the preceding year (adjusted hazard ratio [aHR] 1.55; 95% confidence interval [CI] 1.50 to 1.61), alcohol dependence (aHR 1.41; 95% CI 1.35 to 1.46) and documented depression (aHR 1.39; 95% CI 1.34 to 1.44). Female sex, rural residence, lower socioeconomic status, ingestion of psychoactive drugs and younger age were also weakly associated with repeat overdose.

Discussion: Hospital presentation for repetition of intentional overdose is common, with recurrent episodes often far removed from the first. While several factors predict overdose repetition, none is particularly strong.

Conclusion: Secondary prevention initiatives should be implemented for all individuals who present to the emergency department and survive intentional overdose.     

Metabolic acidosis and coma following a severe acetaminophen overdose

OBJECTIVE: To report a case of metabolic acidosis and coma in a severe acetaminophen overdose. CASE SUMMARY: A 29-year-old white woman was admitted to the emergency department with a diminished level of consciousness and metabolic acidosis. The toxicology screen revealed a serum acetaminophen concentration of 1072 microg/mL, and she was consequently treated with intravenous acetylcysteine. Despite the elevated concentration, the patient did not manifest signs of hepatotoxicity. DISCUSSION: Metabolic acidosis and coma are rare manifestations in acetaminophen overdoses. In published case reports, severe acetaminophen ingestion independently causes metabolic acidosis and coma in the absence of hepatotoxicity. The mechanism by which metabolic acidosis occurs is not clearly defined. Studies conducted on animals demonstrated that in severe overdoses, acetaminophen may cause lactic acidosis by inhibiting mitochondrial respiration. The mechanism by which acetaminophen can cause coma is still unknown. CONCLUSIONS: Severe acetaminophen overdoses can independently cause metabolic acidosis and coma in the absence of hepatotoxicity.     

An unusual case of hyperglycemia, abdominal pain, and increased anion gap acidosis

In this case report we try to illustrate the importance of correct diagnostic reasoning and the misleading features of point-of-care testing. This case illustrates that even though hyperglycemia, ketonuria, a raised anion gap metabolic acidosis, and acute abdominal pain almost inevitably warrant a diagnosis of diabetic ketoacidosis, other possibilities still exist and need to be excluded. In that light, we emphasize the clinical and therapeutic importance of determining serum lactate and urinary ketones in the differential diagnosis of a raised anion gap metabolic acidosis.     

When acetaminophen use becomes toxic. Treating acute accidental and intentional overdose

Whether accidental or intentional, acetaminophen poisoning is not uncommon; in fact, it is the most common drug-induced cause of liver failure. When hepatic glutathione is depleted, the toxic metabolite NAPQI fails to be conjugated and causes hepatic injury. At risk are chronic alcoholics, binge drinkers, patients taking medications that induce the P-450 isoenzyme system, and those with concomitant liver disease. The four phases that make up the clinical course of acetaminophen poisoning distinguish signs, symptoms, and laboratory values according to severity. In diagnosing acetaminophen toxicity, adequate history taking and serial measurements of acetaminophen level are essential. Treatment is rooted in three goals: decreasing the absorption of acetaminophen using activated charcoal, replacing hepatic glutathione using acetylcysteine, and supportive care in the case of hepatic failure. The prognosis depends on the amount ingested and the time of presentation after ingestion.     

Mirtazapine overdose is unlikely to cause major toxicity

Objective. There is limited information on mirtazapine overdose, but cases of severe effects (seizures, serotonin toxicity and coma) have been reported. We aimed to investigate the clinical effects and complications of mirtazapine overdose. Methods. This was an observational case series of mirtazapine overdoses (> 120 mg) identified from admissions to a toxicology unit between January 1987 and August 2013. Demographic information, details of ingestion, clinical effects, ECG parameters (HR, QT and QRS), and length of stay were extracted from a clinical database. Results. From 267 mirtazapine overdoses, there were 89 single-agent mirtazapine ingestions and 178 cases where mirtazapine was taken with at least one other drug. The median age of the 89 single-agent mirtazapine ingestions was 36 years [interquartile range (IQR): 26–49 years; Range: 15–81 years]; 45 were female (51%). The median ingested dose was 420 mg (IQR: 270–750 mg; Range: 150–1350 mg) and 41 patients (46%) had a Glasgow coma score (GCS) < 15, but the minimum GCS was 10. There were no seizures, serotonin toxicity or delirium. Tachycardia occurred in 29 patients (33%) and hypertension in 32 patients (36%). The median QRS was 80 ms (Range: 80–120 ms) and there were no cases with QT prolongation. There were no arrhythmias and no deaths. The median length of stay was 14 h (IQR: 8.8–18.2 h; Range:2.2–75 h). No single-agent mirtazapine patient was admitted to intensive care. The 178 patients taking co-ingestants had more severe toxicity depending on the co-ingested drug. Conclusion. Mirtazapine appears to be relatively benign in overdose, associated with tachycardia, mild hypertension and mild CNS depression not requiring intervention.     

Intravenous fat emulsion to reverse haemodynamic instability from intentional amitriptyline overdose

We report the first case of amitriptyline toxicity treated with intravenous fat emulsion (IFE). Toxicity was manifested as vasopressor-refractory haemodynamic instability despite standard therapy. Our patient recovered with no adverse effects noted.     

Use of continuous veno-venous haemodiafiltration therapy in dabigatran overdose

Context. Dabigatran etexilate is one of the newer oral anticoagulants and a direct thrombin inhibitor. Concerns regarding dabigatran's use include its lack of validated laboratory markers for measuring its anticoagulation effect, the impact of renal impairment on its clearance, and the lack of effective strategies for reversal of anticoagulation. Hemodialysis has been utilized to reverse the anticoagulant effects of dabigatran in therapeutic doses. However, hemodialysis may not be feasible in hemodynamically unstable patients. There is little data on clearance rates of dabigatran by continuous renal replacement therapies. Case details. A 66-year-old male presented following a poly-pharmacy overdose of 9 g of dabigatran in combination with metoprolol, amlodipine, olmesartan, and moxonidine. Eleven hours post overdose extracorporeal elimination was implemented as the patient developed worsening coagulopathy with an elevated international normalized ratio of 11 IU, an activated partial thromboplastin time of 115 s, and had renal impairment with a creatinine of 158 μmol/L. As the patient was hemodynamically unstable, continuous veno-venous hemodiafiltration was preferred over intermittent hemodialysis. Renal replacement therapy was performed for 32 h in total and the patient made a full recovery with no hemorrhagic complications or end organ injury. This patient developed a peak serum dabigatran level of 1560 ng/ml, 11 h postoverdose. Clearance of dabigatran via continuous veno-venous hemodiafiltration was calculated, using both the recovery and A-V pair methods, with a mean clearance of 58.1 and 31.9 ml/h, respectively, and a calculated mean extraction ratio of 0.2. Conclusion. There are few case reports and little experience when dabigatran is taken in overdose. This is a case report of a large dabigatran overdose presenting data on the extraction ratio and clearance of dabigatran using continuous veno-venous hemodiafiltration.