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Phoenix, AZ, United States

Curry S.C.,The Good | Padilla-Jones A.,Banner Research Institute | O'Connor A.D.,The Good | Ruha A.-M.,The Good | And 5 more authors.
Journal of Medical Toxicology | Year: 2015

Elevated concentrations of serum acetaminophen-protein adducts, measured as protein-derived acetaminophen-cysteine (APAP-CYS), have been used to support a diagnosis of APAP-induced liver injury when histories and APAP levels are unhelpful. Adducts have been reported to undergo first-order elimination, with a terminal half-life of about 1.6 days. We wondered whether renal failure would affect APAP-CYS elimination half-life and whether continuous venovenous hemodiafiltration (CVVHDF), commonly used in liver failure patients, would remove adducts to lower their serum concentrations. Terminal elimination half-lives of serum APAP-CYS were compared between subjects with and without renal failure in a prospective cohort study of 168 adults who had ingested excessive doses of APAP. APAP-CYS concentrations were measured in plasma ultrafiltrate during CVVHDF at times of elevated serum adduct concentrations. Paired samples of urine and serum APAP-CYS concentrations were examined to help understand the potential importance of urinary elimination of serum adducts. APAP-CYS elimination half-life was longer in 15 renal failure subjects than in 28 subjects with normal renal function (41.3 ± 2.2 h versus 26.8 ± 1.1 h [mean ± SEM], respectively, p < 0.001). CVVHDF failed to remove detectable amounts of APAP-CYS in any of the nine subjects studied. Sixty-eight percent of 557 urine samples from 168 subjects contained no detectable APAP-CYS, despite levels in serum up to 16.99 μM. Terminal elimination half-life of serum APAP-CYS was prolonged in patients with renal failure for reasons unrelated to renal urinary adduct elimination, and consideration of prolonged elimination needs to be considered if attempting back-extrapolation of adduct concentrations. CVVHDF did not remove detectable APAP-CYS, suggesting approximate APAP-protein adduct molecular weights ≥ 50,000 Da. The presence of urinary APAP-CYS in the minority of instances was most compatible with renal adduct production and protein shedding into urine rather than elimination of serum adducts. © 2014, American College of Medical Toxicology. Source

O'Connor A.D.,The Good | Padilla-Jones A.,Banner Research Institute | Gerkin R.D.,The Good | Levine M.,University of Southern California | Levine M.,Banner Good Samaritan Medical Center
Journal of Medical Toxicology | Year: 2015

Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK > 1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25–42) years with a range of 14–65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n = 55), synthetic cathinone (n = 19), cocaine (n = 9), and other sympathomimetic (n = 6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK > 10,000 IU/L) for each of the four groups was synthetic cathinone with 5/19 (26 %), methamphetamine with 2/55 (3.6 %), cocaine with 1/9 (11 %), and other with 0/6 (0 %). Median maximal CK (range) by groups was as follows: synthetic cathinone, 2638 (62–350,000+) IU/L; methamphetamine, 665 (61–50,233) IU/L; cocaine, 276 (87–25,614) IU/L; and other, 142 (51–816) IU/L. A statistically significant difference (p = 0.004) was found when comparing maximal CK among the four groups. Exposure to a synthetic cathinone compared with other sympathomimetics was associated with increased risk of developing rhabdomyolysis and severe rhabdomyolysis with odds ratios of 3.09 and 7.98, respectively. In this cohort of patients with sympathomimetic toxicity, 42 % developed rhabdomyolysis. Synthetic cathinones were associated with an increased risk of rhabdomyolysis and severe rhabdomyolysis compared with other stimulants. © 2014, American College of Medical Toxicology. Source

Levine M.,Banner Good Samaritan Medical Center | Levine M.,University of Southern California | Levine M.,University of Arizona | Pizon A.F.,University of Pittsburgh | And 3 more authors.
Journal of Medical Toxicology | Year: 2014

Warfarin, a vitamin K antagonist, is widely used for the prophylaxis and treatment of thromboembolic disease. While guidelines exist for management of a supratherapeutic international normalized ratio following therapeutic warfarin use, these guidelines are not designed for management of the acute warfarin overdose. There is a paucity of literature describing the latter. The primary objective of this manuscript is to characterize the coagulopathy and describe the bleeding events that occur after a warfarin overdose. A secondary goal is to describe the amount of vitamin K administered to patients presenting with warfarin overdoses. A retrospective chart review of patients admitted with an acute warfarin overdose at two tertiary care medical centers in the USA was conducted. Clinical characteristics were abstracted, and bleeding categories (major, minor, trivial) were defined a priori. Twenty-three patients were admitted during the time period; males accounted for 15/23 (62.5 %) subjects. The median (interquartile range (IQR)) age was 43 (32-48.5) years. Seventeen subjects received vitamin K, with a median (IQR) dose of 15 (10-50) mg. The maximal total amount of vitamin K administered to a single patient during the index hospitalization was 110 mg. Three bleeding events occurred; one classified as major, and two as minor. All patients made a full recovery. In this case series of acute warfarin overdose, nearly all patients developed a coagulopathy, and nearly three-quarters of patients received vitamin K. Bleeding events occurred in a minority of patients. © 2014 American College of Medical Toxicology. Source

Levine M.,University of Southern California | Levine M.,University of Arizona | Ruha A.-M.,University of Arizona | Padilla-Jones A.,Banner Research Institute | And 2 more authors.
Academic Emergency Medicine | Year: 2014

Objectives Rattlesnake envenomations commonly produce coagulopathy and thrombocytopenia, yet clinically significant bleeding is uncommon. It is unknown if patients who use antiplatelet or anticoagulant medications prior to envenomation are at increased risk for bleeding after envenomation. Methods This was a retrospective cohort study of patients age 14 years and older who were admitted to a single academic medical center for rattlesnake envenomation. Patients who reported use of antiplatelet or anticoagulant medications prior to envenomation were compared to patients not on those medications. Severity and timing of bleeding was compared between groups, as was a composite endpoint of major bleeding at any time, shock, readmission, or death. Results A total of 319 patients met inclusion criteria; 31 (9.7%) were documented to be taking antiplatelet or anticoagulant medications including aspirin, clopidogrel, and/or warfarin. Seventeen of the 319 patients developed bleeding associated with envenomation (major = 9; minor = 4; trivial = 4), with major bleeding occurring in five patients on antiplatelet or anticoagulant medications versus four patients not on antiplatelet or anticoagulant medications (p < 0.001). Seven of the 17 presented with early bleeding. This early bleeding occurred in three of 31 (9.7%) patients on antiplatelet or anticoagulant medications and four of 288 (1.4%) patients not on antiplatelet or anticoagulant medications (relative risk [RR] = 6.9; 95% confidence interval [CI] = 1.6 to 29.4; p = 0.022). Clinical outcome data were available for 300 of the 319 (94%) subjects following discharge. Late bleeding (bleeding after discharge from the index hospitalization) occurred in nine subjects, one of whom also had early bleeding (major = 2, minor = 3, trivial = 4). Three of these nine subjects with late bleeding were on antiplatelet or anticoagulant medications, compared with six not on antiplatelet or anticoagulant medications (p = 0.042). Both cases of late major bleeding occurred in patients on antiplatelet or anticoagulant medications. Therefore, among patients with follow-up data available, the overall rate of bleeding (early and late) was seven of 28 (25%) in patients taking antiplatelet or anticoagulant medications and 10 of 273 (3.7%) in patients not taking antiplatelet or anticoagulant medications (p < 0.001). The use of antiplatelet or anticoagulant medications was also associated with an increased risk of reaching the composite endpoint of major bleeding, shock, readmission, or death (6 of 31, or 19.4% vs. 14 of 288, or 4.9%; RR = 3.98; 95% CI = 1.65 to 9.62; p = 0.008). Conclusions The risk of developing bleeding following rattlesnake envenomation is increased in patients who use antiplatelet or anticoagulant medications. This risk is greatest early after envenomation during the index hospitalization. However, risk of late, major bleeding appears also to be greatest in patients on antiplatelet or anticoagulant medications. Extra vigilance should be taken in patients on antiplatelet or anticoagulant medications and a careful risk/benefit analysis should be undertaken before continuing these medications in the weeks following the envenomation. © 2014 by the Society for Academic Emergency Medicine. Source

Levine M.,Banner Good Samaritan Medical Center | Levine M.,University of Arizona | Levine M.,University of Southern California | Curry S.C.,Banner Good Samaritan Medical Center | And 5 more authors.
Annals of Emergency Medicine | Year: 2013

Study objective: Verapamil or diltiazem overdose can cause severe morbidity and death, and there exist limited human data describing management and outcome of a large number of such patients. This article describes the management and outcome of patients with nondihydropyridine calcium-channel blocker overdose, with an emphasis on vasopressor dosing, at a single center. Methods: This study is a retrospective chart review of patients older than 14 years and admitted to the inpatient toxicology service of a single tertiary care medical center for treatment of verapamil or diltiazem overdose from 1987 through 2012, and who had the presence of either drug confirmed by urine drug screening. Patients were identified by review of patient encounter logs. Data abstracted from medical records included demographics, laboratory results, drugs used to support blood pressure, complications, and outcomes. A second group included patients with a reported calcium channel blocker ingestion but for whom results of the urine drug testing were no longer available. In an effort to assess selection bias, this group was included to determine whether patients who were excluded from the primary group only because of unavailability of urine drug screen results had different outcomes. Results: During the study period, 48 patients met inclusion criteria. The median age was 45 years, with a range of 15 to 76 years, and 52% were male patients. Verapamil accounted for 24 of 48 (50%) ingestions. Vasopressors were administered to 33 of 48 (69%) patients. Maximal vasopressor infusion doses were epinephrine 150 μg/minute, dopamine 100 μg/kg per minute, dobutamine 245 μg/kg per minute, isoproterenol 60 μg/minute, phenylephrine 250 μg/minute, and norepinephrine 100 μg/minute. The use of multiple vasopressors was common. Hyperinsulinemic euglycemia was used in 3 patients who also received multiple vasopressors. Eight probable or possible ischemic complications were noted in 5 of 48 (10%) patients. Gastrointestinal bleeding occurred in 3 of 48 (6%) patients; a brain magnetic resonance imaging in 1 patient suggested mild ischemia, without clinical evidence of infarction; 1 patient had ischemic bowel; and 3 patients developed renal failure from acute tubular necrosis, which resolved in each case. Six of the 8 ischemic complications were evident before use of vasopressor therapy. Three patients sustained inhospital cardiac arrest before admission and were successfully resuscitated. Each of these arrests occurred before instituting vasopressor infusions. One patient experienced a late cardiac arrest from primary respiratory arrest from administration of sedatives, and multiple organ system failure followed resuscitation, with death occurring during manipulation of a pulmonary artery catheter. The remaining 47 patients recovered. There were 12 patients in the group of additional poisoned patients for whom results of urine drug screening were unavailable. Four patients were treated with vasopressors, 2 experienced acute tubular necrosis that was present before vasopressor use, and all recovered. Conclusion: In our series of patients admitted with verapamil or diltiazem overdose, hypotension was common and managed with the use of multiple vasopressors and without hyperinsulinemic euglycemia in all but 3 cases. Despite high doses of vasopressors, ischemic complications were the exception and were usually present before use of vasopressors. Death occurred in a single patient whose death was not attributed directly to calcium-channel blocker toxicity. Vasopressor use after verapamil or diltiazem overdose was associated with good clinical outcomes without permanent sequelae. © 2013 American College of Emergency Physicians. Source

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