Shelby L. Corman

Use of Lipid Emulsion to Reverse Local Anesthetic–Induced Toxicity

Objective: To evaluate the use of lipid emulsion for reversal of local anesthetic–induced toxicity. Data Sources: Literature was accessed through PubMed and OVID (1966–May 2007) using the search terms lipid emulsion and local anesthetic. Reference lists were consulted to identify additional publications. Study Selection and Data Extraction: All articles published in English were evaluated for inclusion. Publications describing the use of lipid emulsion for reversal of local anesthetic in either humans or animals were included. Data Synthesis: It has been suggested that lipid emulsion (Intralipid) may reverse local anesthetic toxicity by extracting lipophilic local anesthetics from aqueous plasma or tissues or by counteracting local anesthetic inhibition of myocardial fatty acid oxygenation. Studies in rats and dogs have shown that lipid emulsion is effective in resuscitating animals who are asystolic after the administration of intravenous bupivacaine. Three case reports support the use of lipid emulsion to reverse systemic toxicity, including seizures, electrocardiogram abnormalities, and cardiac arrest, resulting from the administration of levobupivacaine, ropivacaine, bupivacaine, or mepivacaine. The regimens used in these cases consisted of bolus doses of 1,2–2 mL/kg followed by continuous infusions of 0.25–0.5 mL/kg/min. All of the patients recovered fully with no neurologic sequelae. Conclusions: Literature describing animal studies and human case reports suggests that lipid emulsion is effective in the reversal of local anesthetic toxicity. The potential risks of administering the relatively high doses of this agent are uncertain, and the optimal dose has not been established. In light of these uncertainties, it is appropriate to administer lipid emulsion only after advanced cardiac life support has failed and prior to cardiopulmonary bypass

Influence of medications and diagnoses on fall risk in psychiatric inpatients

PURPOSE The influence of medications and diagnoses on fall risk in psychiatric inpatients was evaluated. METHODS In this retrospective case-control study, psychiatric inpatients age 18 years or older with a documented fall that was reported served as study cases. These patients were matched to control patients from the same hospital (1:1) by admission year, sex, and age. Psychiatric diagnoses evaluated included major depressive disorder, schizophrenia or schizoaffective disorder, bipolar disorder, Alzheimers disease and dementia, anxiety or neurosis, delirium, personality disorder, and obsessive-compulsive disorder. Medications assessed as independent variables were conventional antipsychotics, atypical antipsychotics, selective serotonin-reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, monoamine oxidase inhibitors, lithium, anticonvulsants, benzodiazepines, nonbenzodiazepine sleep aids, Alzheimers disease medications, antihistamines, antiarrhythmics, antihypertensives, benign prostatic hyperplasia medications, oral hypoglycemic agents, histamine H(2)-receptor blockers, laxatives and stool softeners, muscle relaxants, nonsteroidal antiinflammatory drugs, opioids, Parkinsons disease medications, and overactive bladder medications. Univariate logistic regression models were developed for each risk factor to determine its impact on fall risk. RESULTS A total of 774 patient cases were matched with controls. Most falls occurred on the second day of hospitalization. Medications associated with a higher risk of falls were alpha-blockers, nonbenzodiazepine sleep aids, benzodiazepines, H(2)-blockers, lithium, antipsychotics, atypical antidepressants, anticonvulsants, and laxatives and stool softeners. Patients with a diagnosis of dementia and Alzheimers disease also had an increased risk of falling. CONCLUSION Alpha-blockers, nonbenzodiazepine sleep aids, benzodiazepines, H(2)-blockers, lithium, atypical antipsychotics, atypical antidepressants, anticonvulsants and mood stabilizers, conventional anti-psychotics, laxatives and stool softeners, and dementia and Alzheimers disease were significant predictors of inpatient falls in a psychiatric population.

Impact of Nonsteroidal Antiinflammatory Drugs on the Cardioprotective Effects of Aspirin

OBJECTIVE: To examine the evidence of a pharmacodynamic interaction between aspirin and nonsteroidal antiinflammatory drugs (NSAIDs); specifically, to determine whether a deleterious relationship exists with respect to the cardioprotective effects of aspirin. DATA SOURCES: Primary articles were identified by a MEDLINE search (1966—May 2004). Search terms included aspirin, nonsteroidal antiinflammatory drug, drug interaction, mortality, myocardial infarction, and stroke. STUDY SELECTION AND DATA EXTRACTION: All prospective and retrospective studies conducted in human subjects and investigating the potential interaction between aspirin and NSAIDs were included. DATA SYNTHESIS: Several controlled pharmacodynamic studies indicate that the sustained inhibition of cyclooxygenase activity by aspirin is blunted in the presence of some NSAIDs. While these data are fairly consistent, they are limited in that they rely on surrogate markers and not clinical outcomes. Observational studies have shown conflicting results regarding the effect of combination NSAID and aspirin therapy on mortality risk and incidence of myocardial infarction. CONCLUSIONS: Pharmacodynamic data indicating an interaction between aspirin and NSAIDs have not translated to a consistent clinical effect in observational studies. In the absence of a randomized, controlled, clinical outcomes study, there is insufficient evidence to dictate a change in therapy.

Eltrombopag: A Novel Oral Thrombopoietin Receptor Agonist

Objective: To review the pharmacology and pharmacokinetics and evaluate the safety and efficacy of eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura (ITP) and thrombocytopenia associated with hepatitis C virus (HCV) cirrhosis. Data Sources: A Cochrane Controlled Trial Register, clinicaltrials.gov, EMBASE, and MEDLINE search was performed (January 1966–March 2010) using the key terms eltrombopag and SB-497115-GR. Searches were limited to published English-language studies in humans and a reference review of the pertinent literature was conducted. Study Selection and Data Extraction: Published pharmacokinetic data and safety and efficacy trials, case reports, and case series on the use of eltrombopag were selected for inclusion. Data Synthesis: Eltrombopag is a novel second-generation thrombopoietin receptor agonist that was approved by the Food and Drug Administration for the treatment of chronic ITP in patients who had an insufficient response to corticosteroids, intravenous immune globulin, or splenectomy. Eltrombopag has been shown to be superior to placebo in increasing platelet counts, with more patients achieving counts >50 × 103/μL. One study has also shown eltrombopag to be effective in the treatment of thrombocytopenia associated with HCV cirrhosis. Eltrombopag has a boxed warning related to risk of hepatotoxicity, with criteria for discontinuation in patients with elevated liver enzyme levels or clinical signs of liver damage. As such, close monitoring of laboratory parameters is required, and patients must be registered with the PROMACTA CARES program. Conclusions: Eltrombopag is effective in increasing platelet counts in patients with chronic ITP and in patients with HCV cirrhosis. In the treatment of ITP, eltrombopag has been studied only for short durations and is more expensive than first-line oral corticosteroids; therefore, it should be considered a second-tine agent. More studies are needed to identify a place in therapy for eltrombopag in the treatment of thrombocytopenia associated with HCV cirrhosis.

Effect of long-term tacrolimus immunosuppression on renal function in liver transplant recipients

Study Objectives. To describe changes in renal function occurring after long‐term treatment with tacrolimus in clinically stable liver transplant recipients, and to identify risk factors for a clinically significant decline in renal function in these patients.

Low-Dose Granisetron for Postoperative Nausea and Vomiting Prophylaxis

OBJECTIVE To evaluate the use of low-dose granisetron in postoperative nausea and vomiting prophylaxis. DATA SOURCES Clinical trials available through PubMed and OVID (1966—July 2003), as well as information supplied by the drug manufacturer, were accessed. DATA SYNTHESIS Safety concerns associated with droperidol and limited availability of other agents have created a need to restructure prophylaxis guidelines for postoperative nausea and vomiting. It has recently been proposed that granisetron may be effective at a dose that is one-tenth of the Food and Drug Administration—approved dose. Conflicting evidence for this regimen is evaluated. CONCLUSIONS Based on the scarcity of supporting data, this regimen is not recommended for prophylaxis in patients at risk for postoperative nausea and vomiting.

Early risk factors for persistent anemia after kidney transplantation.

Study Objective. To identify predictors of persistent posttransplant anemia that appear within the first week after kidney transplantation in order to determine the high‐risk patients who might receive the most benefit from erythropoiesis‐stimulating agents.