Joseph E Mazur

Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit

Objective:Intensive insulin therapy to normalize blood glucose may improve outcome in intensive care unit patients. We prospectively evaluated the implementation of an intensive insulin protocol in medical intensive care patients to identify and overcome obstacles that this complex therapy creates. Design:This prospective, quality assessment study was designed to establish a standard protocol for glucose control in critically ill patients. Setting:The study took place in the medical intensive care unit at the Medical University of South Carolina, a tertiary care center. Patients:Patients diagnosed with sepsis and two consecutive blood glucose measurements of >120 mg/dL were included in the study. Interventions:The protocol, targeting blood glucose of 80–120 mg/dL, was a multidisciplinary initiative involving extensive education of house staff before subject enrollment. Based on predefined criteria, patients were monitored daily for glycemic control, inclusion criteria, and protocol adherence. Protocol improvements were assessed at 6 and 12 months via nursing surveys. Measurements and Main Results:Seventy patients receiving insulin infusion for >8 hrs were included in data analysis, accounting for 4,920 glucose readings. Eighty-six hypoglycemic events were recorded, with the number of events decreasing from 7.6% to 0.3% by the final version of the protocol. Average duration on protocol was 6 days, and average time to target range was 5.4 hrs. Identifiable causes of hypoglycemia and survey results led to four protocol revisions by study completion. Conclusions:In comparison to studies suggesting that normoglycemia is an easily achievable goal, our protocol often recorded glucose values <80 mg/dL, although values <60 mg/dL were rare and usually due to protocol violations. In the interval before automated glucose-sensing insulin infusion devices become available for the intensive care unit, the current protocol is available to assist others in achieving target glucose levels shown to improve mortality rate in an intensive care unit population.

Intravenous Valproate in Status Epilepticus

OBJECTIVE: To evaluate the role of intravenous valproate sodium (IV VPA) in the treatment of status epilepticus (SE). DATA SOURCES: A literature search of the English language was performed (MEDLINE 1966–July 2000). Search terms included valproate, valproic acid, and status epilepticus. Bibliographies of articles chosen were reviewed to identify other possible sources. DATA SYNTHESIS: A review of the medical literature was conducted to evaluate the safety and efficacy of IV VPA in the treatment of SE. CONCLUSIONS: Experience with IV VPA in the treatment of SE is too limited to recommend its use as a first-line agent. IV VPA may represent a third- or fourth-line option in cases of SE when other agents are ineffective or contraindicated.

Efficacy of Short-Course, Low-Dose Corticosteroid Therapy for Acute Pulmonary Sarcoidosis Exacerbations

Background:Although corticosteroids are the drug of choice for acute exacerbations of pulmonary sarcoidosis, the dose and duration of therapy is not standardized. We reviewed the short-term treatment outcome (median duration = 21 days) of 36 patients with acute exacerbations of pulmonary sarcoidosis using low-dose corticosteroid therapy (20 mg or less of daily prednisone equivalent). To the best of our knowledge, this is the shortest period of time over which the treatment of pulmonary sarcoidosis with corticosteroids has been assessed. Methods:Patients were identified retrospectively from an institution-approved database. Patient symptoms and spirometry were obtained from chart review. Additional clinical data were obtained from chart and database review. Results:Follow-up visits occurred a median of 21 days after the date of the exacerbation (mean 25 ± 3 standard error of mean). The average prednisone dose was 19 mg ± 0.4 standard error of mean. Patients had significant improvement in spirometry on this low-dose treatment regimen by the time of their short-term follow-up (forced vital capacity percent predicted improved from 68 to 82 [P < 0.0001] and was not significantly different from baseline; forced expiratory volume in 1 second percent predicted improved from 57 to 72 [P < 0.0001] and was not significantly different from baseline). Pulmonary symptoms also improved. Conclusions:Treatment of acute exacerbations of pulmonary sarcoidosis with 20 mg prednisone for a median of 21 days improved spirometry back to baseline and improved clinical symptoms. These data suggest that this corticosteroid dose can be safely used initially, and an attempt at tapering can be considered within the first month.

Intravenous Ethanol for the Treatment of Alcohol Withdrawal Syndrome in Critically Ill Patients

Critically ill patients with alcoholism are at greater risk of morbidity and mortality from alcohol withdrawal syndrome than are patients without alcoholism. Benzodiazepines are considered the drugs of choice for the prevention and treatment of alcohol withdrawal syndrome, but some studies have suggested that intravenous ethanol may be as effective as those agents, as well as being less sedating. We evaluated the evidence regarding the use of intravenous ethanol for the prevention and treatment of alcohol withdrawal syndrome in critically ill patients in order to determine its role in this patient population. Because of the paucity of well‐designed clinical trials, and because of intravenous ethanols questionable efficacy, inconsistent pharmacokinetic profile, and relatively narrow therapeutic index, routine use of this drug is not recommended in critically ill patients who have alcohol withdrawal syndrome or are at risk for it.

Fatality related to a 30-g venlafaxine overdose.

A 30‐g venlafaxine overdose resulted in death for a 39‐year‐old woman whose 43‐day clinical course was highlighted by refractory hypotension and the resulting complications of bowel ischemia and perforation. Her venlafaxine and O‐desmethylvenlafaxine levels, analyzed by high‐performance liquid chromatography one day after ingestion, were 21.82 mg/L (therapeutic range 0.1–0.5 mg/L) and 3.33 mg/L (0.2–0.4 mg/L), respectively. These levels remained elevated for over 7 days. Postulated explanations for these extended elevated levels were saturation of drug metabolism, decreased drug metabolism, and existence of a genetic polymorphism. Our patients venlafaxine overdose produced a wide variety of clinical challenges, to include seizures, tachycardia, decreased level of consciousness, refractory hypotension, and bowel dysmotility. In addition, this case augments the growing body of literature that suggests that venlafaxine may be fatal in overdose situations.

Clinical Usefulness of Recombinant Activated Factor VII in Patients with Liver Failure Undergoing Invasive Procedures

Objective: To evaluate the use of recombinant activated factor VII (rFVIIa) in patients with liver failure undergoing invasive procedures. Methods: An OVID/MEDUNE and PubMed search (1997-June 2011) was performed to identify literature on the use of rFVIIa to reduce bleeding risk in patients with liver failure undergoing invasive procedures. Study Selection and Data Extraction: English-language data evaluating the efficacy of rFVIIa to reverse coagulopathies prior to invasive procedures in patients with liver disease were included. Data Synthesis: Following administration of rFVIIa, prothrombin time (PT) and international normalized ratio (INR) response is within 30 minutes. Doses ranging from 20 to 120 μg/kg have been studied, with a reduction in PT seen in a dose-dependent manner. One study in patients with no bleeding administered 5, 20, and 80 μg/kg sequentially during a 24-day period. All doses provided reversal of prolonged PT within 10 minutes, and the duration was dose-dependent. In a study of 15 patients with fulminant liver failure, requiring intracranial pressure monitor placement, a rFVIIa dose of 40 μg/kg was compared to fresh frozen plasma. In patients who received rFVIIa, the PT and INR normalized, compared to none of the patients in the fresh frozen plasma group. Conclusions: Retrospective and prospective data demonstrate that rFVIIa effectively reverses elevated PT and INR, reducing the risk of bleeding and safely facilitating invasive procedures. Based on available data, a dose of 20-40 μg/kg 30 minutes prior to an invasive procedure should be considered in patients with acute or chronic liver failure at risk for bleeding complications. A major limitation of rFVIIa use is the high cost of therapy. A prospective, randomized trial could help determine the appropriate dose of rFVIIa, timing of dose in relationship to procedure, and usefulness of subsequent doses.

Terlipressin in Hepatorenal Syndrome

Objective: To compare the pharmacology, dosing, and adverse reactions of vasopressin and terlipressin for the treatment of hepatorenal syndrome (HRS) and assess the efficacy of the investigational drug terlipressin for HRS. Data Sources: Articles evaluating prospective studies for vasopressin and terlipressin were discussed after being identified through PubMed (1966-November 2010), International Pharmaceutical Abstracts (1970-November 2010), and EMBASE (1985-November 2010) with combinations of the following terms: vasopressin, terlipressin, and hepatorenal syndrome. In addition, reference citations from publications identified were reviewed. Thirteen studies were identified for terlipressin, along with 4 meta-analyses and 1 case report. For vasopressin, 2 studies were identified. Study Selection and Data Extraction: Prospective clinical studies directly comparing terlipressin and vasopressin were evaluated, as well as prospective clinical studies and meta-analyses for terlipressin in HRS. Data Synthesis: NO randomized, placebo-controlled trials using vasopressin for the treatment of type I HRS have been published, and 4 randomized studies Involving 197 patients provide the most current outcome data for use of terlipressin in HRS. Terlipressin differs significantly from vasopressin with regard to its pharmacology, dosing, and adverse drug reaction profile. There is a paucity of data on vasopressin for HRS. Conclusions: NO definitive recommendations can be made for the use of terlipressin for this indication until further, well-conducted studies are performed.

Implementation of a collaborative drug therapy management service for inpatients receiving direct thrombin inhibitors

PURPOSE The development and implementation of a collaborative drug therapy management (CDTM) service for inpatients receiving direct thrombin inhibitors (DTIs) are described. SUMMARY A pharmacist-driven DTI protocol was established to help establish guidelines for the use and monitoring of DTIs to ensure the effective and safe administration of these high-risk medications. The CDTM service and DTI dosing protocol, including order form development, were completed over a two-year period. The DTI order form consisted of five main sections: practice points pertaining to the clinical diagnosis of heparin-induced thrombocytopenia (HIT), initiation of DTIs, nurse- and pharmacist-driven instructions for the monitoring of DTI therapy, information to safely transition a patient from a DTI to warfarin, and a scoring system for determining the probability of HIT. A CDTM service for the inpatient setting was developed to improve patient outcomes and reduce medication errors related to the monitoring and adjusting of DTI dosages. To implement this service, three major areas were addressed: the credentialing of pharmacists, the ordering process, and required documentation. Challenges encountered during protocol development were eliminating the use of lepirudin, developing a comprehensive order form for two DTIs, obtaining approval of the DTI dosing protocol by the medical executive committee, and developing and implementing a comprehensive nursing education program for the new order form and protocol. CONCLUSION A dosing protocol for DTIs was developed to improve the use of these high-risk medications within an institution. The protocol provided physicians with the option of deferring DTI dosing to a pharmacist with appropriate credentials.

High-Dose Sedation and Analgesia During Extracorporeal Membrane Oxygenation: A Focus on the Adjunctive Use of Ketamine

ABSTRACT Use of ketamine in patients requiring extracorporeal membrane oxygenation (ECMO) has rarely been reported, and the optimal dosing strategy remains unclear. A patient admitted with hypoxic respiratory failure required ECMO in addition to continuous infusion of low-dose ketamine following titration of opioid and sedative medications to high doses. After initiation of ketamine, infusion rates of opioids and/or sedatives were maintained or decreased. Recorded Richmond Agitation-Sedation Scale (RASS) scores were −4 to −5 and documented pain scores were 0. No adverse effects were reported while receiving low-dose ketamine. This case illustrates that use of low-dose ketamine infusion may be a useful adjunctive agent in patients receiving ECMO and high-dose opioid and sedative medications.

The Use of Activated Recombinant Factor VII in a Patient with Fulminant Hepatic Failure Requiring Placement of an Intracranial Pressure Monitor

Objective: To evaluate the use of recombinant activated factor VII (rFVIIa) in a patient with fulminant hepatic failure (FHF) requiring placement of an intracranial pressure monitor. Case Summary: A 21-year-old female with no significant medical history was admitted to an outside hospital with elevated results of liver function tests. Subsequently, the patient was diagnosed with autoimmune hepatitis. Systemic corticosteroids were started, but her condition continued to decompensate. She was transferred to our tertiary care facility 5 days after initial presentation. The liver function test results remained elevated (eg, total bilirubin 27 mg/dL), and international normalized ratio (INR) was 3.57. The medical team decided to place an intracranial pressure monitor, with the neurosurgery teams goal being an INR less than 1.5 before placement of the monitor. After multiple units of fresh frozen plasma (FFP) failed to lower the patients INR, rFVIIa 40 μg/kg was administered. A rapid decrease of the INR allowed the neurosurgery team to perform the procedure without complications. Discussion: The use of rFVIIa allowed for decrease of this patients INR after multiple units of FFP had failed to correct it. The utility of INR as a marker of coagulopathy in fulminant hepatic failure has been debated, but it is currently used as the standard laboratory test prior to invasive procedures, as in the case presented here. Conclusions: The use of rFVIta for rapid decrease of INR in a patient with FHF prior to an invasive procedure was safe and efficacious. When considering the use of rFVIIa, clinicians should be aware of the risk of thrombosis. In our experience, and in the limited literature on the matter, rFVIIa 40 μg/kg appears to be an appropriate dose for decrease of the INR. Further studies are needed to confirm this finding.