Unveiling the Rare Presentation of Acetylsalicylate Overdose: Grand Round.

BACKGROUND: This case report highlights a rare occurrence of aspirin overdose presenting only as severe coagulopathy. CASE PRESENTATION: An 85-year-old woman was admitted to the hospital with multiple lumbar vertebral compression fractures causing severe back pain. The patient had self-medicated with excessive consumption of Bufferin A containing 330 mg of aspirin. On arrival, she showed no typical symptoms of salicylate toxicity, such as nausea, vomiting, hyperventilation, tinnitus, or hearing loss. However, blood work revealed a significant decrease in vitamin K-dependent coagulation factors leading to coagulopathy. The administration of 20-mg menatetrenone (vitamin K) resulted in rapid improvement in coagulation abnormalities. The patient's blood salicylate level was later determined to be 42.7 mg/dL. DISCUSSION: Acute salicylate poisoning is known to cause coagulopathy because of the inhibition of vitamin K-dependent coagulation factors. However, this case is unique because it demonstrates coagulopathy as the sole manifestation of aspirin toxicity without any other symptoms. CONCLUSIONS: This case highlights the importance of considering the possibility of aspirin toxicity in patients with coagulopathy, especially those who are regularly consuming aspirin.

Does the renal portal valve exist in a raptor species? A study aimed at further evaluating the mechanism of toxicity of diclofenac in vultures.

Diclofenac has been responsible for the deaths of millions of vultures on the Asian subcontinent. While the pathology of toxicity is well described, the mechanism of toxicity remains elusive. However, it was postulated that toxicity could be related to the unique avian renal vascular structure known as the renal portal valve and that that diclofenac altered valve functionality with subsequent renal ischaemia. While plausible, the valva renalis portalis has only been described in a small number of other bird species such as the chicken (Gallus domesticus), the domestic duck (Anas platyrhynchos domesticus) and ostrich (Struthio camelus) but not a raptor. The aim of this study was to evaluate the renal anatomy and related vasculature of the Cape griffon vulture (Gyps coprotheres) (CGV), a species sensitive to the toxic effects of diclofenac, using gross anatomy, histology and vascular casting. The vasculature of the vulture was found to be almost identical to that of the domestic chicken with the valva renalis portalis present in the v. iliaca externa between the v. renalis renalis cranialis and the v. renalis caudalus. The valve was ring-shaped with finger-like processes and histologically was composed of smooth muscle. The valve was also well vascularized and was associated with a nerve plexus. Based on the findings of this study, the proposed mechanism of toxicity is anatomically possible.

Severe poisoning with naproxen causing coagulopathy.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their most frequent side effects (digestive, renal and metabolic disorders) but are lesser known for other effects, such as coagulation disturbances. In this issue, we report the case of a 58-year-old woman who ingested 26 g of naproxen in a suicidal attempt and developed cardiovascular shock, hypocoagulability and thrombopenia. Her outcome was positive (extubation 3 days after admission [D3], correction of haemostatic disruptions on D5 and of thrombopenia on D6). Naproxen plasma concentration was at a toxic concentration of 1320 mg/L at 6 hours after drug ingestion. Only few cases of hypocoagulopathy are reported with the NSAIDs, and this is the first case that can be attributed to naproxen. A possible explanation of this phenomenon following naproxen ingestion is an inhibition of thromboxane A2, usually attributed to NSAIDs, combined with an inhibition of activation of downstream the cascade.

A retrospective observational study on patients intoxicated by drugs and other xenobiotics.

OBJECTIVES: Many research studies conducted in various toxicology centers point to drugs as the most common cause of intoxication. Long-term observations make it possible to clarify the nature of these poisonings. The aim of this study was to examine the trends and reasons of intoxication in patients hospitalized over a 10-year observation period (2005-2015), as well as to compare the number of patients poisoned with nonsteroidal anti-inflammatory drugs (NSAIDs), mainly over-the-counter (OTC) drugs. MATERIAL AND METHODS: A retrospective observational study examined the medical documentation of patients hospitalized in the Department of Toxicology and Internal Diseases of the T. Marciniak Lower Silesian Specialist Hospital in Wroclaw in 2005-2015, including the analysis of the causes of intoxication as well as total poisoning-related death statistics. Quarterly and annual analyses of the numerical data, and comparisons of the frequency of poisonings were included. The patient population from the area of Lower Silesia, Poland, was examined. RESULTS: The number of hospitalized patients has increased, with attempted suicide being the leading cause of death. Male intoxication and mortality have been found to predominate. Drugs are the most common cause of poisoning, and among these the most common are sedatives and psychotropic drugs. Intoxication due to NSAIDs, especially OTC drugs, increased significantly in the observation period. In 2005 no fatal cases were reported as a result of NSAID intoxication, while in 2015 mortality significantly increased to 43%. CONCLUSIONS: The lack of a common trend in poisonings is observed but the number of hospitalized patients has increased, especially among young people, which is consistent with global trends. Drugs are the most common cause of mortality, and a significant increase in NSAID (mainly OTC) poisonings in particular indicates the growing prevalence of an uncontrolled use of these drugs. Int J Occup Med Environ Health. 2019;32(4):489-501.

Availability of drug at convenient stores is not associated with an increased incidence of their poisoning.

PURPOSE: In late 2012, South Korea revised the Pharmaceutical Affairs Act to make selected medications including acetaminophen, ibuprofen, and cold medications available in nonpharmacy outlets, including the 24-hour convenient stores (CVS). The objective of this study was to identify whether the characteristics and trend of self-poisonings associated with these medications were altered after the legislative change. METHODS: A retrospective study was performed using national data from the Emergency Department (ED)-based Injury In-depth Surveillance database. The patients diagnosed with poisoning were sorted from 2011 to 2016 and included in the study. As the Act was implemented from 2013, the demographic characteristics and clinical outcomes were compared before and after January 2013. A piecewise regression analysis was performed to determine the association between the monthly use of acetaminophen, medication for cold, and nonsteroidal anti-inflammatory drugs (NSAIDs) and the incidence of total poisonings before and after the January 2013. RESULTS: Among 1 536 277 patients included in the database, 17 523 patients diagnosed with poisoning were enrolled. After the legislative change, the etiology of poisoning did not change, although the frequency of hospitalization from ED was significantly increased. The monthly trend for poisoning due to acetaminophen, cold medications, and NSAIDs showed no significant slope change between before and after the legislative change. The proportional use of acetaminophen and cold medications was significantly decreased, while that of NSAIDs was unchanged before and after the legislative change. CONCLUSIONS: The change in the Pharmaceutical Affairs Act was not associated with any change in the monthly frequency of medication-related poisoning.

Death of captive-bred vultures caused by flunixin poisoning in Italy.

Among non steroidal anti-inflammatory drugs (NSAIDs) diclofenac is considered the main cause for the decline of vulture populations in the Indian subcontinent since the '90 s. Chemical analysis showed high levels of flunixin (31,350 µg/kg) in beef which three captive Gyps vultures fed on, later dying with severe visceral gout. Levels in dead vultures' organs and tissues ranged from 4 to 38.5 µg/kg. The typical lesions and the concentrations found in beef indicate flunixin as the cause of death. This is the first observational study which correlates the concentration of flunixin in the meat ingested with that found in tissues of vultures.

Use of therapeutic plasma exchange to treat nonsteroidal anti-inflammatory drug overdose in dogs.

BACKGROUND: Therapeutic plasma exchange (TPE) may be an effective technique for treatment of accidental nonsteroidal anti-inflammatory drug (NSAID) overdose, but information regarding the use of this technique in veterinary medicine is currently limited. OBJECTIVES: To evaluate the overall outcome for dogs with NSAID overdose treated with TPE and to determine if any presenting factors can predict or influence overall outcome. Secondary objectives included investigating TPE complications as well as the utility of other adjunctive treatments. ANIMALS: Eleven client-owned dogs presented for NSAID overdose that received TPE. All patients also received additional supportive treatment including IV lipid infusion. METHODS: Retrospective review of medical records. RESULTS: Eleven cases were included in the study. Of these, the NSAID ingested was ibuprofen in 6 (54.5%), naproxen in 4 (36.4%), and deracoxib in 1 (9.1%). All dogs survived to discharge with 3 (27.3%) developing acute kidney injury during hospitalization. A larger initial dose of NSAID ingested was associated with a higher maximum serum creatinine concentration during hospitalization (P = .04) and larger change in serum creatinine concentration from baseline (P = .02). Six dogs (54.5%) developed complications associated with TPE. The use of other treatments did not affect the overall outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: We identified TPE as an effective treatment for NSAID overdose with good outcomes despite high doses of NSAID ingestion in dogs treated with a single TPE treatment. Complications were common but did not affect the final outcome. Therapeutic plasma exchange should be considered in patients presenting for high-dose NSAID ingestion.

Central nervous system toxicity due to mefenamic acid.

Mefenamic acid is a fenamate nonsteroidal anti-inflammatory (NSAI) drug, which is used for several years for pain management. However, it has been rarely reported that, mefenamic acid can induce central nervous system toxicity both in toxic doses and therapeutic usage. We report a case of a 27-year-old female who presented to the emergency department (ED) with altered mental status and vomiting. On admission to the ED, she was lethargic and disoriented. Her vital signs were normal and her physical examination was completely normal except dysarthric speech. The etiology of altered mental status was investigated with electrolyte levels, cranial computed tomography, cranial magnetic resonance imaging and EEG, however the results were normal. Her blood gas analysis revealed a deep metabolic acidosis with a pH of 7.14. Neither etiologic agent nor drug use history was provided at the presentation; she had only osteogenesis imperfecta since several years and she had been using various NSAI drugs. However, her relatives later stated that, she took mefenamic acid for her pains since two weeks. After her admission to intensive care unit, her neurologic state was improved gradually after plasmapheresis and she was discharged healthy. Although mefenamic acid has been considered as one of the safe NSAI drugs, its effects due to central nervous system toxicity should be cautiously handled.

Refractory Hypotension Caused by Prazosin Overdose Combined With Acetaminophen and Naproxen Toxicity: A Case Report and Review of the Literature.

BACKGROUND: Pediatric exposure to prazosin is unusual because it is most commonly indicated for the treatment of hypertension. Prazosin's increase in popularity as a treatment for posttraumatic stress disorder makes it important for emergency physicians to be aware of how to manage potential toxic ingestion because of prazosin overdose. CASE REPORT: A 16-year-old, 76-kg female presented after ingesting 110 mg of prazosin, 209.3 g of acetaminophen, and 55 g of naproxen. She was admitted to the pediatric intensive care unit for rapidly deteriorating hypotension (lowest blood pressure 47/19 mm Hg) refractory to aggressive fluid resuscitation and infusions of epinephrine and norepinephrine each at 0.5 mcg/kg/min. Stabilization of blood pressure was eventually achieved, and associated with use of a vasopressin infusion of 0.004 units/kg/min. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Because of the increasing exposure of children to prazosin, clinicians should be aware of the pharmacology behind alpha-1 antagonist overdose and consider treatment options, such as vasopressin, when hypotension is resistant to standard fluid and catecholamine therapy.

Treatment of carprofen overdose with therapeutic plasma exchange in a dog.

OBJECTIVE: To report the use of therapeutic plasma exchange (TPE) in a dog with carprofen toxicosis. SUMMARY: A 6-year-old female neutered Bichon Frise weighing 6.9 kg was examined after it had ingested 72 mg/kg carprofen. Mild dehydration without azotemia and with a urine specific gravity of 1.050 was noted at presentation. Treatment consisted of induction of emesis, symptomatic medical therapy, and TPE. The TPE achieved 1.5 plasma volume exchanges over 3 hours. Blood samples and effluent samples were collected every 30 minutes during TPE and additional blood samples were collected 11 and 35 hours after treatment. Carprofen concentrations in these samples were determined by high-pressure liquid chromatography. A 51% reduction in serum carprofen concentration was achieved following TPE. NEW OR UNIQUE INFORMATION PROVIDED: This report describes the successful reduction of plasma carprofen concentration in a dog using TPE. Although recent studies suggest that this particular dog may not have received a toxic dose, a 51% reduction of plasma carprofen concentration was achieved over 180 minutes, and TPE may be beneficial for treatment of dogs that have ingested higher doses.

Treatment of ibuprofen intoxication in a dog via therapeutic plasma exchange.

OBJECTIVE: To describe the treatment of ibuprofen intoxication with therapeutic plasma exchange in a dog (TPE). SUMMARY: A 13-year-old male neutered mixed breed dog presented after ingesting approximately 200 mg/kg of ibuprofen. Treatment consisted of supportive medical therapy with IV fluids, gastrointestinal protectants, antiemetics and prostaglandin analogs, and TPE. A cycle of TPE was performed over 180 minutes, achieving 1.5 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Ibuprofen concentrations were determined in the samples by high-pressure liquid chromatography. Post TPE, the dog was continued on supportive medical therapy and was discharged 96 hours after the overdose. NEW OR UNIQUE INFORMATION: This report describes the use of TPE as an adjunct for ibuprofen intoxication. An 85% reduction in plasma ibuprofen concentration occurred and recovery from a potentially lethal ingestion of ibuprofen was achieved with TPE and supportive care. TPE should be considered when presented with acute ibuprofen intoxication due to the rapid and efficacious nature of therapy.

Treatment of meloxicam overdose in a dog via therapeutic plasma exchange.

OBJECTIVE: To describe the treatment of a meloxicam overdose in a dog with therapeutic plasma exchange (TPE). CASE SUMMARY: A 6-month-old female Bulldog, presented for routine laparoscopic ovariectomy. Postoperatively the dog received an accidental overdose of meloxicam (1 mg/kg IV [intravenously]). The patient was treated with supportive medical therapy and TPE over 210 minutes achieving 1.2 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Meloxicam concentrations were determined in the samples by high pressure liquid chromatography. Post TPE, the dog continued to receive supportive medical therapy and was discharged 48 hours after the overdose. The dog remained asymptomatic for meloxicam intoxication. Follow-up rechecks at 1 and 6 weeks were unremarkable with no further treatment required. NEW OR UNIQUE INFORMATION: This report describes the successful use of TPE adjunctively following an acute meloxicam overdose. An 82% reduction of plasma meloxicam concentration was achieved over 210 minutes. Twenty-four hours after therapy, a 47% sustained reduction of plasma meloxicam was measured after redistribution of drug between body compartments.

The association of hemodialysis and survival in intubated salicylate-poisoned patients.

INTRODUCTION: Salicylate poisonings are common due to their multiple uses and wide availability. The variation of presenting symptoms contributes to inconsistent treatments in the emergency department. Patients with severe salicylate overdose require a high minute ventilation. Early in the course of an overdose, a patient will require hyperventilation. If they become too fatigued to compensate, mechanical ventilation may be needed. It can be impossible to recreate such a high minute ventilation with mechanical ventilation. This places patients at a high risk for decompensation and death. Hemodialysis is an effective elimination technique for salicylate overdose and should be considered early. METHODS: All salicylate cases reported to the Illinois Poison Center were reviewed from 2003-2014. All intubated patients with a salicylate level >50mg/dl were included for analysis. Survival was compared to measured serum salicylate level and the administration of hemodialysis. RESULTS: 56 Cases were identified with an overall survival rate of 73.2% in patients with a serum salicylate level >50mg/dl. When patients did not receive hemodialysis, a peak salicylate level >50mg/dl had a 56% survival rate and 0% survival when the level was >80mg/dl. In the patients who received hemodialysis, a peak salicylate level >50mg/dl had a 83.9% survival rate and 83.3% survival when the level was >80mg/dl. CONCLUSION: Survival was decreased in these patients if hemodialysis was not performed. Mortality increases with the measured serum salicylate level. Timely hemodialysis for intubated salicylate overdose patients decreases mortality.

Delayed Salicylate Toxicity in a 17-Year-Old Girl With Initially Undetectable Salicylate Concentration 3.9 Hours After Ingestion.

We report the case of a 17-year-old girl with a 126-mg/kg nonenteric coated aspirin ingestion with nontoxic salicylate concentrations at 1.5 and 3.9 hours postingestion, who developed tinnitus and vomiting an estimated 8 hours postingestion, and who was subsequently found to have a toxic salicylate concentration at 22.7 hours postingestion. This case, as well as previous cases of delayed aspirin therapy, may prompt providers to consider educating patients and their care providers regarding the need to return for further testing if symptoms, such as vomiting or tinnitus, develop after an aspirin ingestion.

Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service.

AIMS: Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti-inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared rates of CNS toxicity after overdose between mefenamic acid, ibuprofen, diclofenac and naproxen, as reported in telephone enquiries to the UK National Poisons Information Service (NPIS). METHODS: NPIS telephone enquiries related to the four NSAIDs, received between January 2007 and December 2013, were analysed, comparing the frequency of reported CNS toxicity (convulsions, altered conscious level, agitation or aggression, confusion or disorientation) using multivariable logistic regression. RESULTS: Of 22 937 patient-specific telephone enquiries, 10 398 did not involve co-ingestion of other substances (mefenamic acid 461, ibuprofen 8090, diclofenac 1300, naproxen 547). Patients taking mefenamic acid were younger and more commonly female than those using other NSAIDs. Those ingesting mefenamic acid were more likely to experience CNS toxicity than those ingesting the other NSAIDs combined [adjusted odds ratio (OR) 7.77, 95% confidence interval (CI) 5.68, 10.62], especially convulsions (adjusted OR 81.5, 95% CI 27.8, 238.8). Predictors of CNS toxicity included reported dose and age, but not gender. CONCLUSIONS: Mefenamic acid overdose is associated with a much larger and dose-related risk of CNS toxicity, especially convulsions, compared with overdose of other NSAIDs. The benefit-risk profile of mefenamic acid should now be re-evaluated in light of effective and less toxic alternatives.

Drug Toxicities of Common Analgesic Medications in the Emergency Department.

About 75% of patients present to the emergency department with a complaint of pain. There are multiple prescribed and over-the-counter medications that are available for the treatment of pain. Acetaminophen, opioids, and aspirin are commonly used agents that are available as single agents or in combination with other medications. However, all of these agents are susceptible to toxic overdose, which requires prompt recognition through clinical and laboratory assessment modalities and initiation of therapy to reduce the risk of morbidity and mortality.

Analysis of Gastric Lavage Reported to a Statewide Poison Control System.

BACKGROUND: As decontamination trends have evolved, gastric lavage (GL) has become a rare procedure. The current information regarding use, outcomes, and complications of GL could help refine indications for this invasive procedure. OBJECTIVES: We sought to determine case type, location, and complications of GL cases reported to a statewide poison control system. METHODS: This is a retrospective review of the California Poison Control System (CPCS) records from 2009 to 2012. Specific substances ingested, results and complications of GL, referring hospital ZIP codes, and outcomes were examined. RESULTS: Nine hundred twenty-three patients who underwent GL were included in the final analysis, ranging in age from 9 months to 88 years. There were 381 single and 540 multiple substance ingestions, with pill fragment return in 27%. Five hundred thirty-six GLs were performed with CPCS recommendation, while 387 were performed without. Complications were reported for 20 cases. There were 5 deaths, all after multiple ingestions. Among survivors, 37% were released from the emergency department, 13% were admitted to hospital wards, and 48% were admitted to intensive care units. The most commonly ingested substances were nontricyclic antidepressant psychotropics (n = 313), benzodiazepines (n = 233), acetaminophen (n = 191), nonsteroidal anti-inflammatory drugs (n = 107), diphenhydramine (n = 70), tricyclic antidepressants (n = 45), aspirin (n = 45), lithium (n = 36), and antifreeze (n = 10). The geographic distribution was clustered near regions of high population density, with a few exceptions. CONCLUSIONS: Toxic agents for which GL was performed reflected a broad spectrum of potential hazards, some of which are not life-threatening or have effective treatments. Continuing emergency physician and poison center staff education is required to assist in patient selection.