Kurt Kleinschmidt

Intravenous fat emulsion therapy for intentional sustained-release verapamil overdose

We report the first case of sustained-release verapamil toxicity treated with Intralipid fat emulsion (IFE). Toxicity was confirmed by elevated serial serum verapamil and metabolite, norverapamil, levels. Most previously reported cases of IFE therapy involve local anaesthetic toxicity and cardiac arrest. Our patient was in shock despite standard therapy. No adverse events were noted and the patient fully recovered.

State of the Art Review: Intravenous Fat Emulsions: Current Applications, Safety Profile, and Clinical Implications

Objective To review the current state of the science regarding intravenous fat emulsions (IVFEs), with an emphasis on their safety profile. Data sources Articles were identified via a search of the MEDLINE database, including publications from 1979 to December 2009, using a search string that included the terms parenteral nutrition, lipid emulsion, fat emulsion, IVFE, safety, adverse effect, neonate intralipid, and terms describing a range of specific adverse events (AEs) such as pancreatitis. Study selection and data extraction We selected articles that allowed us to compare the results of clinical trials involving delivery of medications via IVFEs with the historical use and effects of IVFEs in parenteral nutrition, with an emphasis on AEs. We focused on 2 drugs in current use that are administered intravenously in lipid emulsions: propofol and clevidipine. Data synthesis Clearance of the fat particles in IVFEs is mediated by the enzyme lipoprotein lipase. AEs are more likely if the rate or duration of IVFE administration exceeds the enzymes clearance capacity. AEs are also more likely after administration of a 10% IVFE formulation than a 20% formulation, because the higher concentration of free phospholipid in the 10% formulation interferes with lipoprotein lipase activity. AEs can be reduced by administering IVFEs at a dosage ≤2.5 g/kg/day and at a rate ≤0.11 g/kg/h. The anesthetic agent propofol, which is formulated in a 10% IVFE, has been used clinically for 25 years. Typical AEs associated with propofol use include infection, high plasma triglyceride concentrations, and pancreatitis. Recent clinical trials involving clevidipine, which is formulated in a 20% IVFE, have demonstrated a low rate of lipid-related AEs. Conclusions The results of this review demonstrate that IVFEs are well tolerated when administered in accordance with guideline recommendations.

Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation

Synthetic cannabinoids have been popular recreational drugs of abuse for their psychoactive properties. Five of the many synthetic cannabinoids have been recently banned in the United States because of their unknown and potentially harmful adverse effects. Little is known about these substances. They are thought to have natural cannabinoid-like effects but have different chemical structures. Adverse effects related to synthetic cannabinoids are not well known. We provide clinical effects and patient outcome following K9 use. In addition, we briefly review synthetic cannabinoids. We present a 17-year-old adolescent boy with chest pain, tachycardia, and then bradycardia associated with smoking K9. Two synthetic cannabinoids, JWH-018 and JWH-073, were confirmed on laboratory analysis. In addition to the limited current data, we demonstrate harmful adverse effects related to toxicity of 2 synthetic cannabinoids. Further studies are needed.

Synthetic cannabinoid and marijuana exposures reported to poison centers

Synthetic cannabinoids have recently gained popularity as a recreational drug because they are believed to result in a marijuana-like high. This investigation compared synthetic cannabinoids and marijuana exposures reported to a large statewide poison center system. Synthetic cannabinoid and marijuana exposures reported to Texas poison centers during 2010 were identified. The distribution of exposures to the two agents with respect to various demographic and clinical factors were compared by calculating the rate ratio (RR) of the synthetic cannabinoid and marijuana percentages for each subgroup and 95% confidence interval (CI). The proportion of synthetic cannabinoid and marijuana exposures, respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38–2.61), 74.9% and 65.7% in male (RR 1.14, 95% CI 0.87–1.51), 40.2% and 56.6% age ≤19 years (RR 0.71, 95% CI 0.52–0.98), 79.2% and 58.6% occurring at a residence (RR 1.35, 95% CI 1.02–1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28–1.00), and 59.3% and 41.4% with serious medical outcomes (RR 1.43, 95% CI 1.03–2.05). Compared to marijuana, synthetic cannabinoid exposures were more likely to be used through inhalation, to involve adults, to be used at a residence, and to result in serious outcomes.

Synthetic Cannabinoid Exposures Reported to Texas Poison Centers

ABSTRACT Synthetic cannabinoid abuse is increasing in the United States. Synthetic cannabinoid exposures reported to Texas poison centers in 2010 were identified, and the distribution of exposures by selected factors was determined. There were 464 total cases. The number of exposures increased each month during January-July, then remained relatively constant for the next 5 months. The patients were 73.9% male and 57.3% were 20 years or older. Moderate or major effects or potentially toxic outcome occurred in 59.9% of the exposures. The most frequently reported clinical effects were tachycardia (37.3%), agitation (18.5%), drowsiness (18.5%), vomiting (15.7%), hallucinations (10.8%), and nausea (9.9%).

Practice patterns, outcomes, and end-organ dysfunction for patients with acute severe hypertension: The Studying the Treatment of Acute hyperTension (STAT) Registry

BACKGROUND Limited data are available on the care of patients with acute severe hypertension requiring hospitalization. We characterized contemporary practice patterns and outcomes for this population. METHODS STAT is a 25-institution, US registry of consecutive patients with acute severe hypertension (>180 mm Hg systolic and/or >110 mm Hg diastolic; >140 and/or >90 for subarachnoid hemorrhage) treated with intravenous therapy in a critical care setting. RESULTS One thousand five hundred eighty-eight patients were enrolled (January 2007 to April 2008). Median age was 58 years (interquartile range 49-70 years), 779 (49%) were women, and 892 (56%) were African American; 27% (n = 425) had a prior admission for acute hypertension and 486 (31%) had chronic kidney disease. Median qualifying blood pressure (BP) was 200 (186, 220) systolic and 110 (93, 123) mm Hg diastolic. Initial intravenous antihypertensive therapies used to control BP varied, with 1,009 (64%) patients requiring multiple drugs. Median time to achieve a systolic BP <160 mm Hg (<140 mm Hg for subarachnoid hemorrhage) was 4.0 (0.8, 12) hours; 893 (60%) had reelevation to >180 (>140 for subarachnoid hemorrhage) after initial control; and 63 (4.0%) developed iatrogenic hypotension. Hospital mortality was 6.9% (n = 109) with an aggregate 90-day mortality rate of 11% (174/1,588); 59% (n = 943) had acute/worsening end-organ dysfunction during hospitalization. The 90-day readmission rate was 37% (523/1,415), of which one quarter (132/523) was due to recurrent acute severe hypertension. CONCLUSION This study highlights heterogeneity in care, BP control, and outcomes of patients hospitalized with acute severe hypertension.

Clinical practices, complications, and mortality in neurological patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension registry.

Objective:To determine the demographic and clinical features, hospital complications, and predictors of 90-day mortality in neurologic patients with acute severe hypertension. Design:Studying the Treatment of Acute hyperTension (STAT) was a multicenter (n = 25) observational registry of adult critical care patients with severe hypertension treated with intravenous therapy. Setting:Emergency department or intensive care unit. Patients:A qualifying blood pressure measurement >180 mm Hg systolic or >110 mm Hg diastolic (>140/90 mm Hg for subarachnoid hemorrhage) was required for inclusion in the STAT registry. Patients with a primary neurologic admission diagnosis were included in the present analysis. Interventions:All patients were treated with at least one parenteral (bolus or continuous infusion) antihypertensive agent. Measurements and Main Results:Of 1,566 patients included in the STAT registry, 432 (28%) had a primary neurologic diagnosis. The most common diagnoses were subarachnoid hemorrhage (38%), intracerebral hemorrhage (31%), and acute ischemic stroke (18%). The most common initial drug was labetalol (48%), followed by nicardipine (15%), hydralazine (15%), and sodium nitroprusside (13%). Mortality at 90 days was substantially higher in neurologic than in non-neurologic patients (24% vs. 6%, p < .0001). Median initial blood pressure was 183/95 mm Hg and did not differ between survivors and nonsurvivors. In a multivariable analysis, neurologic patients who died experienced lower minimal blood pressure values (median 103/45 vs. 118/55 mm Hg, p < .0001) and were less likely to experience recurrent hypertension requiring intravenous treatment (29% vs. 51%, p = .0001) than those who survived. Mortality was also associated with an increased frequency of neurologic deterioration (32% vs. 10%, p < .0001). Conclusion:Neurologic emergencies account for approximately 30% of hospitalized patients with severe acute hypertension, and the majority of those who die. Mortality in hypertensive neurologic patients is associated with lower minimum blood pressure values, less rebound hypertension, and a higher frequency of neurologic deterioration. Excessive blood pressure reduction may contribute to poor outcome after severe brain injury.

Two cases of intoxication with new synthetic opioid, U-47700

Abstract Background: Novel substances often referred to as “designer drugs” have emerged as drugs of abuse, and recognition of these is difficult as routine blood and urine screening tests do not detect these agents. U-47700 is a synthetic selective μ-opioid agonist that can be bought online for as little as

Hypertensive heart failure: patient characteristics, treatment, and outcomes

40 per gram. We report two patients presenting after insufflation of U-47700, with subsequent confirmation of this substance in urine samples. Case details: A 26-year-old man and 24-year-old woman insufflated a substance they believed to be “synthetic cocaine.” The man was found down with cyanosis and agonal respirations. He was intubated and taken to hospital where he recovered well with supportive care. The woman presented with anxiety, tremors and drowsiness and was admitted for observation. Urine samples from both patients were analyzed using GC/MS/MS and LC/QToF, and U-47700 was isolated in both cases. No other opioids were detected. Discussion: These cases are concerning because U-47700 is a relatively new agent that is easy to obtain over the internet and has the potential to cause significant morbidity and mortality.

PHARMACOLOGY OF LOW MOLECULAR WEIGHT HARPARINS

BACKGROUND Acute heart failure (AHF) is a common, poorly characterized manifestation of hypertensive emergency. We sought to describe characteristics, treatment, and outcomes of patients with severe hypertension complicated by AHF. METHODS AND RESULTS The observational retrospective Studying the Treatment of Acute hypertension (STAT) registry records data on emergency department and hospitalized patients receiving intravenous therapy for blood pressure (BP) greater than 180/110 mm Hg in 25 US hospitals. A subset of patients with HF was defined as pulmonary edema on chest x-ray (CXR) or an elevated B-type natriuretic peptide level (BNP > 500 or NTproBNP > 900 pg/mL) in patients with creatinine level 2.5 mg/dL or less. Remaining STAT patients, after excluding those with a primary neurologic diagnosis, constitute the non-HF cohort. An adverse composite outcome was defined as mechanical ventilation, intensive care unit (ICU) admission, hospital length of stay more than 1 week, or death within 30 days. Of 1199 patients, 302 (25.2%) had AHF. Acute HF patients and non-AHF patients were similar in age, sex, and overall mortality, but AHF patients were more commonly African American, with a history of HF, diabetes or chronic obstructive pulmonary disease, and prior hypertension admissions. Heart failure patients had higher creatinine and natriuretic peptide levels but lower ejection fraction. They were more likely admitted to the ICU; receive electrocardiograms, bilevel positive airway pressure ventilation, and CXRs; and be readmitted within 90 days. Finally, BP decreases lower than 120 mm Hg within 12 hours were associated with an increased rate of the composite adverse outcome. CONCLUSIONS Acute HF as a manifestation of hypertensive emergency is common, more likely in African Americans, and requires more clinical resources than patients with non-HF-related severe hypertension. Accurate BP control is critical, as declines less than 120 mm Hg were associated with increased adverse event rates.