Peri-mortem rigidity in a fatal case of severe salicylate poisoning.

INTRODUCTION: There has been a previous case report of peri-arrest muscle rigidity in the setting of severe salicylate poisoning (serum salicylate concentration 1,500 mg/L), described as paratonia or rapid rigor mortis. We present an image of rapid rigor mortis in another fatal salicylate poisoning. CASE SUMMARY: We report a 42-year-old male with severe salicylate poisoning (peak salicylate concentration 1,600 mg/L). During the peri-arrest period, the patient developed isotonic flexion of the upper and lower extremities, the clinical signs of rapid-occurring rigor mortis. Despite resuscitative efforts, the patient died. IMAGE: Our patient is exhibiting peri-arrest rigidity in the upper extremities. DISCUSSION: Peri-mortem rigidity is due to depletion of adenosine triphosphate. Severe salicylate poisoning causes uncoupling of oxidative phosphorylation which prevents the production of adenosine triphosphate, which is required to release myosin from actin to allow the muscle to relax. A limitation of our report is that we did not definitively exclude other uncouplers of oxidative phosphorylation, such as 2,4-dinitrophenol. However, the history of aspirin ingestion was provided by the patient and corroborated by his mother, and it was confirmed by measurement of his salicylate concentration. CONCLUSION: We hypothesize that in our patient, rapid-occurring rigor mortis likely resulted from depletion of adenosine triphosphate. This occurred as a result of uncoupling of oxidative phosphorylation in the mitochondria from severe salicylate poisoning, as adenosine triphosphate is required for muscle relaxation.

Pseudohyperchloremia and Negative Anion Gap - Think Salicylate!

BACKGROUND: Pseudohyperchloremia results in a very low or negative anion gap. Historically, the most common cause of this artifact was bromide poisoning. Bromide salts have been removed from most medications and bromism has become very uncommon. More recently, the introduction of chloride ion selective sensing electrodes (Cl-ISE) has generated a new cause of pseudohyperchloremia-salicylate poisoning. We describe 5 such patients and quantitate the error generated by this measurement artifact. METHODS: The magnitude of artifactual hyperchloremia generated by high salicylate levels was quantified in 5 patients by measuring chloride concentration with several Cl-ISEs from different manufacturers and with Cl-ISEs of different "ages," and comparing these results to measurements with a chloridometer (coulometric titration), which is free of the salicylate artifact. RESULTS: Cl-ISEs from different manufacturers generated a wide range of artifactual chloride concentration elevation. Furthermore, the same Cl-ISE generated increasingly severe pseudohyperchloremia as it was repeatedly reused over time and "aged." CONCLUSIONS: Salicylate interferes with measurement of the blood chloride concentration when a Cl-ISE is used. The severity of this artifact is related to the salicylate level, the specific Cl-ISE, and the "age" of the electrode. Toxic blood salicylate levels can generate marked pseudohyperchloremia, and consequently, an artifactual very small or negative anion gap. The large anion gap metabolic acidosis typical of salicylate poisoning is masked by this artifact. Salicylate has become the most common cause of pseudohyperchloremia, and physicians should immediately consider salicylate poisoning whenever the combination of hyperchloremia and a very small or negative anion gap is reported by the laboratory.

Routine Laboratory Screening for Acetaminophen and Salicylate Ingestion in Preadmission Psychiatric Patients Is Unnecessary.

STUDY OBJECTIVE: Screening preadmission psychiatric patients for acetaminophen or salicylate overdose is unnecessary in the absence of specific clinical concern for medication ingestion. METHODS: This was a multicenter retrospective cohort study of 3 Veteran's Administration emergency departments that medically evaluate patients prior to psychiatric admission. During the 10-year study period, these departments followed screening protocols that required the measurement of acetaminophen and salicylate levels on every patient prior to psychiatric admission. We examined all the acetaminophen and salicylate assays performed to see if any that were sent for screening led to a diagnosis of overdose and/or the administration of antidotal therapy. RESULTS: A total of 33,439 combined acetaminophen and salicylate assays were sent on 10,482 unique patients over approximately 17,000 patient encounters. An estimated 29,000 assays were sent for screening purposes only-87% (95% confidence interval [CI] 85% to 89%) of salicylate assays and 85% (95% CI 83% to 87%) of acetaminophen assays. We identified 43 patients with elevated acetaminophen levels and 11 with elevated salicylate levels. Among these patients, only 6 in total had their levels drawn for screening purposes only, with no history of suspected ingestion; in all but 1 patient, the levels were only slightly above the reference range. None of the patients with elevated levels identified by screening had clinical toxicity or received antidotal therapy. CONCLUSION: Over a 10-year period, 3 Veteran's Administration emergency departments performed psychiatric preadmission screening protocols with acetaminophen and salicylate assays approximately 17,000 times without diagnosing a single case of toxicity. Our results suggest that this practice is unnecessary and wasteful.

Bismuth Subsalicylate Coagulopathy in a Patient with Chronic Liver Disease.

Bismuth subsalicylate (BSS) is the active ingredient in over-the-counter antacid and antidiarrheal medications. Coagulopathy in the setting of acetylsalicylic acid toxicity is well documented but not in setting of bismuth subsalicylate overuse. We present a case report of coagulopathy from BSS poisoning in a patient with underlying cirrhosis. The patient's high prothrombin time suggests inhibition of vitamin K-dependent coagulation factors. The patient had decreased factor V activity, which is responsible for converting prothrombin to thrombin. Patients with cirrhosis often have hypoprothrombinemia which may be exacerbated by salicylate-induced coagulopathy. Given the widespread use of BSS products, physicians should recognize coagulopathy as a possible manifestation of toxicity especially in patients with underlying liver disease.

Managing Acute Salicylate Toxicity in the Emergency Department.

Salicylates are among the oldest and most widely used medication to date and are utilized for a variety of purposes including the management of fever, inflammation, pain, and cardiovascular prophylaxis. Reports from U.S. Poison Control Centers indicate that over 40,000 Americans are exposed to salicylate-containing substances annually, and although generally deemed safe, fatal intoxications can occur from a single ingestion. Although some ingestions are intentional, many are not, and are a result of the prevalence of salicylates in a wide array of prescription and over-the-counter substances. Because of the wide range of symptoms associated with toxic overdose, as well as the high rate of mortality and complications associated with these cases, the emergency nurse practitioner should have a systematic approach to diagnosing and treating these patients. This case narrative describes the clinical case of a 22-year-old man who presented to the emergency department after ingesting an unknown amount of a salicylate-containing medication. It demonstrates the difficulty associated with appropriately distinguishing between toxic ingestions, hallmark indicators that can assist in appropriate diagnoses, and key interventions that must be initiated in a timely manner to mitigate negative outcomes. This case also serves as the basis for a review of current practice guidelines, and provides the clinician with tools to ensure evidence-based interventions are not delayed, thus increasing the chance of recovery for this patient population.

Salicylate toxicity after undetectable serum salicylate concentration: a retrospective cohort study.

BACKGROUND: Salicylates are usually rapidly absorbed and quickly measurable in serum. An undetectable serum salicylate concentration ([ASA]) may occur early after ingestion and may be interpreted as evidence of non-exposure and not repeated. Although cases of delayed salicylate detection are reported rarely, the risk factors associated with this phenomenon are not known. RESEARCH QUESTION: What factors are associated with an early undetectable [ASA] in salicylate poisoning? METHODS: Records from a single regional poison center were searched from 2002 to 2016 for cases of salicylate toxicity treated with bicarbonate and [ASA] > 30 mg/dL. Cases were excluded if initial [ASA] was obtained >4 h after presentation. Case information, serial [ASA], and outcomes were recorded and compared between groups. RESULTS: A total of 313 records met all criteria with 11 initially undetectable [ASA] (3.5%) and 302 detectable [ASA] (96.5%). Time of first [ASA] occurred sooner in the undetectable [ASA] group (89 vs. 137 min, p = 0.011) while time to peak [ASA] was longer (640 vs. 321 min, p < .001). The longest interval between ingestion and undetectable [ASA] was 225 min. Peak [ASA] and reported mean ingested dose were similar in both groups (45 vs. 50 mg/dL, p = NS; 19.7 g vs. 32.9 g, p = NS). Coingestion of agents that delay gastric emptying were similar in both groups (18% [2/11] vs. 25% [76/302], p = NS, chi-square). Hemodialysis was performed in 9% (1/11) of undetectable [ASA] patients and 5.6% (17/302) of detectable [ASA] patients (p = NS, chi-square). A single death occurred in the entire cohort in a patient with an initially detectable [ASA]. DISCUSSION: In this series, a small but significant proportion (3.5%) of patients who developed [ASA] > 30 mg/dL had an initially undetectable [ASA]. Those with an undetectable [ASA] were measured earlier after ingestion with a longer time to peak [ASA]. However, neither coingestion of agents prolonging gastric emptying nor reported dose ingested was different between groups. Formulation was infrequently recorded but one undetectable [ASA] did ingest a non-enteric coated product. Limitations include the small number of patients with undetectable [ASA], use of single poison center data and partial data on co-ingestants and aspirin formulation. CONCLUSIONS: [ASA] may be undetectable early after an overdose and need for serial [ASA] in the evaluation of salicylate ingestion should be further explored. Additional research is needed to determine any causative factors and the optimal timing of [ASA] measurements.

A 29-year analysis of acute peak salicylate concentrations in fatalities reported to United States poison centers.

BACKGROUND/OBJECTIVES: The threshold salicylate concentration commonly recommended to initiate extracorporeal elimination, in the absence of significant end-organ toxicity, is 100 mg/dL. Unfortunately, the grade of evidence to support this decision is low. Our primary aim is to describe highest reported salicylate concentrations in patients who died from acute salicylate ingestions. Our secondary aim is to determine if age or coingestants varied with highest reported salicylate concentration. METHODS: We analyzed acute salicylate fatalities reported to the National Poison Data System (NPDS) between 1 January 1986 and 31 December 2014. Included were patients who died during the index hospitalization and for which acute salicylate toxicity was the primary cause of death. We used descriptive statistics with standard deviations (SD) or 95% confidence intervals (CI) where appropriate. We created a general linear model that evaluated the association of age and coingestions with salicylate concentrations. We divided the patients into age quartiles to assess a possible interaction between age and salicylate concentration. RESULTS: We identified 602 acute salicylate fatalities that fit inclusion criteria. The mean peak reported fatal salicylate concentration across all age groups was 99.19 mg/dL (± 50.2 mg/dL). The median peak fatal salicylate concentration was 97.0 mg/dL. The oldest quartile had a lower mean concentration (age >57 years; 90.4 mg/dL) than the youngest quartile (age <30 years; 111.6 mg/dL, mean difference 21.2 mg/dL, 95%CI 6.1-36.3). Fatalities with a coingestant had a lower mean concentration of 91.5 mg/dL compared to 104.8 mg/dL among those ingesting salicylates alone (mean difference 13.4 mg/dL, 95%CI 21.4-5.3). Increasing age and the presence of any coingestions were negatively associated with fatal concentrations (estimates; 95%CI 0.41; 0.61-0.021 and -14.43; 22.45-6.42, respectively). When opioids were a coingestant, mean concentration was 72.8 (mean difference 32.1 95%CI 23.1-41.1). CONCLUSIONS: Using the current recommended hemodialysis threshold of 100 mg/dL, more than half of the patients would be deprived of this critical life-saving therapy. Additionally, increasing age and ingestion of other substances, especially opioids, are associated with lower peak fatal salicylate concentrations. A prospective, randomized controlled trial considering salicylate concentrations and other clinical factors may provide further guidance for hemodialysis.

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.

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.

Comparison of High-Fidelity Medical Simulation to Short-Answer Written Examination in the Assessment of Emergency Medicine Residents in Medical Toxicology.

We compared high-fidelity medical simulation to short-answer written examination in the assessment of emergency medicine residents (EMR) on a month-long medical toxicology rotation. Knowledge-based assessment tools using cases of an aspirin overdose and a tricyclic antidepressant overdose were used to assess all consecutive rotating EMR (n=53). Assessment by simulation had similar accuracy and precision but higher satisfaction rates when compared to written examination. Incorporating simulation into the ABEM certifying examination warrants further study.

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.