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Biomedical subjects

Brian L Erstad

Publications and source records attributed to Brian L Erstad.

At least 19 recordsLinked to original sources
PubMed2006

Estimation of creatinine clearance in end-stage liver disease.

BACKGROUND: Estimation of renal function in patients with end-stage liver disease (ESLD) is complicated by several factors. OBJECTIVE: To develop a practical and relatively inexpensive method for estimating creatinine production and clearance in patients with ESLD. METHODS: Serum creatinine concentrations and urinary excretion of creatinine were measured in 27 patients with moderate-to-severe liver disease with the goal of developing equations to predict creatinine clearance from serum creatinine. Subjects were studied during an initial evaluation for a liver transplant program. Two 24 hour urine specimens were collected along with 3 serum samples over a 2 day evaluation period. Serum and urine creatinine concentrations were determined using both a modified Jaffé (autoanalyzer) method and an HPLC method. The data were analyzed using nonlinear mixed-effects modeling. RESULTS: Considering both statistical criteria and physiological conventions through allometric scaling theory, creatinine clearance (mL/min) in males can be estimated as (80/serum creatinine) x (actual body weight/70)0.75. For females, the same equation is valid, but the result is multiplied by 0.661. A simplified equation without the exponent is presented, along with equations that are appropriate when an HPLC assay is used for greater specificity. CONCLUSIONS: These equations offer potential for improved estimation of creatinine clearance in patients with liver impairment; however, they need further validation using an independent group of subjects.

Algorithms↗
PubMed2006

Medication errors and adverse drug events in an intensive care unit: direct observation approach for detection.

OBJECTIVE: To determine the incidence and preventability of medication errors and potential/actual adverse drug events. To evaluate system failures leading to error occurrence. DESIGN: Prospective, direct observation study. SETTING: Tertiary care academic medical center. PATIENTS: Patients in a medical/surgical intensive care unit. INTERVENTIONS: Observers would intervene only in the event that the medication error would cause substantial patient harm or discomfort. MEASUREMENTS AND MAIN RESULTS: The observers identified 185 incidents during a pilot period and four phases totaling 16.5 days (33 12-hr shifts). Two independent evaluators concluded that 13 of 35 (37%) actual adverse drug events were nonpreventable (i.e., not medication errors). An additional 40 of the remaining 172 medication errors were judged not to be clinically important. Of the 132 medication errors classified as clinically important, 110 (83%) led to potential adverse drug events and 22 (17%) led to actual, preventable adverse drug events. There was one error (i.e., resulting in a potential or actual, preventable adverse drug event) for every five doses of medication administered. The potential adverse drug events mostly occurred in the administration and dispensing stages of the medication use process (34% in each); all of the actual, preventable adverse drug events occurred in the prescribing (77%) and administration (23%) stages. Errors of omission accounted for the majority of potential and actual, preventable adverse drug events (23%), followed by errors due to wrong dose (20%), wrong drug (16%), wrong administration technique (15%), and drug-drug interaction (10%). CONCLUSIONS: Using a direct observation approach, we found a higher incidence of potential and actual, preventable adverse drug events and an increased ratio of potential to actual, preventable adverse drug events compared with studies that used chart reviews and solicited incident reporting. All of the potential adverse drug events and approximately two thirds of the actual adverse drug events were judged to be preventable. There was one preventable error for every five doses of medication administered; most errors were due to dose omission, wrong dose, wrong drug, wrong technique, or interactions.

Academic Medical Centers↗
PubMed2006

Pharmacologic management of constipation in the critically ill patient.

STUDY OBJECTIVE: To compare the effectiveness of common laxatives in producing a bowel movement in patients admitted to a medical intensive care unit (MICU). DESIGN: Retrospective medical record review. SETTING: MICU of an academic medical center. PATIENTS: Ninety-five patients admitted to the MICU from July 1-October 31, 2004. MEASUREMENTS AND MAIN RESULTS: Fifty patients satisfied the inclusion criteria. Patient-specific data such as age, weight, sex, length of MICU stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, dietary intake, opioid intake, laxative intake, and bowel movements were recorded during the first 96 hours of admission. Logistic regression analysis was used to compare patients who did and did not have a bowel movement. Of the 50 patients, 25 did not have a bowel movement during the first 96 hours of MICU admission. Patients given a stimulant laxative (senna, bisacodyl) and/or an osmotic laxative (lactulose, milk of magnesia) were more likely to have a bowel movement (odds ratio [OR] 26.6, 95% confidence interval [CI] 3.2-221, p=0.002). Opioid intake, expressed as logarithmic morphine equivalents, was negatively associated with occurrence of a bowel movement (OR 0.76, 95% CI 0.59-0.97, p=0.027). Disease severity, as determined by APACHE II score, was also negatively associated with a bowel movement (OR 0.84, 95% CI 0.7-0.99, p=0.04). CONCLUSION: Critically ill patients have a high frequency of constipation, and opioid therapy is a significant risk factor. Routine administration of stimulant or osmotic laxatives should be considered for this patient population.

Analgesics, Opioid↗
PubMed2005

Improving predictive modeling in pediatric drug development: pharmacokinetics, pharmacodynamics, and mechanistic modeling.

A workshop was conducted on November 18-19, 2004, to address the issue of improving predictive models for drug delivery to developing humans. Although considerable progress has been made for adult humans, large gaps remain for predicting pharmacokinetic/pharmacodynamic (PK/PD) outcome in children because most adult models have not been tested during development. The goals of the meeting included a description of when, during development, infants/children become adult-like in handling drugs. The issue of incorporating the most recent advances into the predictive models was also addressed: both the use of imaging approaches and genomic information were considered. Disease state, as exemplified by obesity, was addressed as a modifier of drug pharmacokinetics and pharmacodynamics during development. Issues addressed in this workshop should be considered in the development of new predictive and mechanistic models of drug kinetics and dynamics in the developing human.

Adult↗
PubMed2005

Retrospective evaluation of inhaled prostaglandins in patients with acute respiratory distress syndrome.

STUDY OBJECTIVES: To determine whether use of inhaled alprostadil (PGE 1 ) or epoprostenol (PGI 2 ) significantly improved oxygenation in patients with acute respiratory distress syndrome (ARDS), and to determine whether differences between the two drugs exist with regard to oxygenation, duration of mechanical ventilation and hospitalization, adverse effects, and survival. DESIGN: Retrospective chart review. SETTING: A 360-bed tertiary care teaching facility with medical and surgical intensive care units. PATIENTS: Twenty-seven patients admitted to the hospital who received either PGI 2 or PGE 1 for a primary or secondary diagnosis of ARDS. MEASUREMENTS AND MAIN RESULTS: Seventeen patients received inhaled PGE 1 and 10 received inhaled PGI 2 . There were no significant changes in the ratio of arterial partial pressure of oxygen (PaO 2 ):fraction of inspired oxygen (FiO 2 ) and in the PaO 2 , from baseline to any time point that was analyzed during treatment, for patients receiving either PGE 1 (p=0.2120 and 0.3399, respectively) or PGI 2 (p=0.1655 and 0.0784, respectively). CONCLUSION: No statistically significant improvement in oxygenation was observed in patients receiving either PGE 1 or PGI 2 . In addition, no significant differences were found between the two prostaglandins for the variables studied. Until positive results from large, prospective studies are available, we recommend that these inhaled prostaglandins not be used to treat ARDS.

Administration, Inhalation↗
PubMed2005

Key articles and guidelines relative to intensive care unit pharmacology--2004.

Compilations of key articles and guidelines in a particular clinical practice area are useful not only to clinicians who practice in that area, but to all clinicians. We compiled pertinent articles and guidelines pertaining to drug therapy in the intensive care setting from the perspective of actively practicing critical care pharmacists. This document differs from the original 2002 version in that a broader assembly of intensive care practitioners was involved in the compilation.

Drug Therapy↗
PubMed2004

What is the evidence for using hemostatic agents in surgery?

The pharmacological methods used to achieve systemic hemostasis have generated much discussion due to concerns of serious adverse effects (e.g., thromboembolic complications) and costs of therapy in addition to efficacy considerations. There are a limited number of well-controlled trials involving pharmacological hemostasis for spine surgery. In the largest double-blinded randomized controlled trial to date involving spine surgery, there was a trend toward reduced homologous transfusion in patients receiving aprotinin, but the only statistically significant result ( p<0.001) was a reduction in autologous red cell donations. The findings of this trial are important, since the investigators used a number of restrictive transfusion strategies (e.g., autologous donation, low hematocrit trigger for transfusion, blood-salvaging procedures with the exception of no cell saver) that were not always employed in earlier trials involving hemostatic agents. Smaller studies involving antifibrinolytic agents other than aprotinin have demonstrated reductions in blood loss and transfusion requirements in patients undergoing spine surgery, although the results were not always statistically significant. A very large randomized trial would be required to address comparative medication- and transfusion-related adverse events; such a trial involving patients undergoing cardiac surgery is currently being performed. Additionally, cost-effectiveness analyses are needed to help define the role of these agents based on the data that is available.

Aprotinin↗
PubMed2004

Stress ulcer prophylaxis in the postoperative period.

PURPOSE: The implications of recent studies for guidelines that pertain to stress ulcer prophylaxis in the postoperative period are discussed. SUMMARY: The therapeutic guidelines on stress ulcer prophylaxis published by the American Society of Health-System Pharmacists (ASHP) provided clinicians with recommendations regarding appropriate candidates for stress ulcer prophylaxis and selection of a pharmacologic agent. Since these guidelines were published in 1999, additional research has been completed to resolve some of the controversial issues surrounding stress ulcer prophylaxis. The frequency of stress-induced bleeding in recent investigations continues to be highly variable, depending on the definition used to describe bleeding. In general, investigations that evaluate overt bleeding or bleeding without hemodynamic changes or blood transfusion report higher frequencies of bleeding than those that evaluate clinically important bleeding. Similar to that reported in the initial ASHP guidelines, the frequency of clinically important bleeding in recent investigations is low. In addition, the majority of recently published prospective studies and a meta-analysis have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents. As a result, some experts have suggested that advances in critical care are more influential in the development of stress-induced bleeding than the use of pharmacologic agents. Recently published investigations support the effectiveness of institution-specific guidelines to help clinicians identify appropriate candidates for stress ulcer prophylaxis. The selection of an optimal pharmacologic agent for stress ulcer prophylaxis continues to be debated. The majority of recent studies have involved the administration of proton-pump inhibitors (PPIs). In general, these studies have demonstrated that PPIs are at least as effective as histamine H2-receptor antagonists at increasing gastric pH, but adequately powered studies investigating the endpoint of clinically important bleeding are needed. Similar to the initial ASHP guidelines, the development of institution-specific guidelines is recommended to identify the most appropriate pharmacologic treatment. CONCLUSION: The frequency of clinically important bleeding reported in recent studies is low. The majority of recently published prospective studies and meta-analyses found little significant reduction in bleeding with pharmacologic prophylaxis.

Anti-Ulcer Agents↗
PubMed2004

Use of epoetin alfa in critically ill patients.

OBJECTIVE: To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia. DATA SOURCES: A MEDLINE search (1966-July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials. DATA SYNTHESIS: Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective. CONCLUSIONS: Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.

Anemia↗
PubMed2004

Medication errors involving continuously infused medications in a surgical intensive care unit.

OBJECTIVE: To document the incidence of medication errors related to medications administered by continuous infusion. DESIGN: Observational study. SETTING: Sixteen-bed surgical intensive care unit. MEASUREMENTS AND MAIN RESULTS: All continuous infusions in the surgical intensive care unit were evaluated at least once daily for correct flow-sheet charting, concentration, infusion rate, and dose administered, as well as patients' heights and weights (actual, ideal, and "dry"). Collected information was examined to determine the error rate, types of errors occurring, and weight used for dose calculation. Variations inpatient weight measures were compared. Seventy-one patients with 202 total infusions were observed. Errors involving continuously infused medications in our surgical intensive care unit occurred at a rate of 105.9 per 1,000 patient days. For nonweight-based infusions, 94% of doses were delivered correctly. Slightly >10% of the doses administered for weight-based infusions (dose based on dry body weight) were incorrect. Significant differences were found between the weight measurements recorded, but this did not translate into statistically significant differences in the apparent calculated doses delivered. CONCLUSIONS: Medications delivered by continuous infusion, particularly those that are weight based, can contribute to medication errors in the intensive care unit. A large proportion (87.6%) of doses for weight-based infusions was calculated based on estimated or unreliable admission weights. There were no severe consequences resulting from the errors observed in this 1 month investigation; however, depending on the pharmacokinetic characteristics of the drug being administered, there is a potential to deliver artificially low or high doses resulting in subtherapeutic or adverse effects.

Female↗
PubMed2004

Cost-effectiveness of proton pump inhibitor therapy for acute peptic ulcer-related bleeding.

OBJECTIVE: The purpose of this investigation was to perform a cost-effectiveness analysis of adjunctive oral and intravenous proton pump inhibitor (PPI) therapies for patients with acute peptic ulcer-related bleeding of sufficient severity to warrant hospitalization. DESIGN: Cost-effectiveness investigation. Four clinical scenarios were considered: scenario 1, diagnostic endoscopy with oral PPI therapy; scenario 2, diagnostic and therapeutic endoscopy with high-dose intravenous PPI therapy; scenario 3, diagnostic and therapeutic endoscopy available with oral PPI therapy; and scenario 4, diagnostic and therapeutic endoscopy (no PPI). Effectiveness was evaluated in terms of episodes of bleeding averted and quality-adjusted life years. SETTING: University teaching hospital in the United States. PATIENTS: Hospitalized patients with acute peptic ulcer bleeding. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Therapeutic endoscopy with high-dose intravenous PPI therapy (scenario 2) was the most cost-effective approach in terms of bleeding episode averted (8,490 vs. 10,201 US dollars for scenario 1, 8,756 US dollars for scenario 3, and 12,459 US dollars for scenario 4) and per quality-adjusted life year (4,810 vs. 5,533 US dollars for scenario 1, 4,946 US dollars for scenario 3, and 5,876 US dollars for scenario 4). The high-dose intravenous PPI scenario was the dominant approach as evidenced by both superior effectiveness and lower costs over the range of probability and cost variables used in the sensitivity analysis. However, the dominance would be lost if the purchase cost of the intravenous PPI was substantially higher than the baseline cost assumed in this investigation (61 US dollars per 3-day course of therapy). CONCLUSION: High-dose intravenous PPI therapy in conjunction with therapeutic endoscopy is the most cost-effective approach for the management of hospitalized patients with acute peptic ulcer bleeding.

Acute Disease↗
PubMed2004

Prescribing and self-administration of morphine in Hispanic and non Hispanic Caucasian patients treated with patient-controlled analgesia.

The purpose of this study was to determine whether differences in either prescribing or self-administration of morphine exist between Hispanic and White (Caucasian) post-operative patients treated with patient-controlled analgesia (PCA). A review of the medical records of 30 Hispanic and 30 White patients who received postoperative PCA was conducted. Both prescribed and self-administered morphine were analyzed using a two-sided, two-sample Student's t-test. No differences in the amount of morphine prescribed (11.23 +/- 3.22 mg/hr in Hispanic patients, 11.05 +/- 4.28 mg/hr in White patients; p = 0.8503) or self-administered (2.58 +/- 2.02 mg/hr in Hispanic patients, 3.32 +/- 3.00 mg/hr in White patients; p = 0.2711) were discovered. This study identified no statistically significant difference in either opioid prescribing or self-administration between Hispanic and White post-operative patients.

Analgesia, Patient-Controlled↗
PubMed2003

Dosing of medications in morbidly obese patients in the intensive care unit setting.

OBJECTIVE: To derive recommendations for the dosing of commonly used medications in the morbidly obese patient in the ICU. DATA SOURCES: Articles were obtained through computerized searches involving MEDLINE. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: All studies involving the pharmacokinetics or pharmacodynamics of medications in obese subjects or patients. DATA EXTRACTION: The emphasis was on studies involving morbidly obese patients but, in the absence of such data, investigations involving lesser forms of obesity were extracted. DATA SYNTHESIS: There is a paucity of data upon which to make recommendations for dosing commonly used medications in the morbidly obese patient in the ICU, although recommendations were provided based on the available information. CONCLUSIONS: There is clearly a need for more investigations involving dosing regimens of medications in the morbidly obese population. Until such studies are available, the clinician must try to derive the best dosing regimens for medications based on the limited pharmacokinetic data available for some agents and clinical judgement.

Analgesics, Opioid↗
PubMed2003

The cost of enhanced acid suppression.

Peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), and upper gastrointestinal bleeding are conditions that can make large demands on health care resources. Acid suppression is common therapy for these conditions. The economic implications of managing Helicobacter pylori-related PUD, GERD, and upper gastrointestinal bleeds were considered by several investigators. Economic analyses of drug regimens for PUD show that eradication is more cost effective than H2-receptor antagonist (H2RA) maintenance therapy. Although various eradication regimens have been compared, the results depend on a number of assumptions that preclude general conclusions regarding cost-effectiveness. Economic analyses related to GERD are hindered by the often chronic, relapsing nature of the disease, particularly once therapy is discontinued. Therefore, as with PUD, results of the economic analyses depend largely on initial assumptions relative to the model employed. With regard to upper gastrointestinal bleeding, proton pump inhibitors (PPIs) are potent acid suppressors that may help prevent rebleeding that was managed endoscopically. Further clinical and economic investigations of PPIs for stress ulcer prophylaxis are necessary. Cost-effectiveness studies comparing PPIs and H2RAs should focus on overall costs of managing these conditions and include economic benefits of preventing complications, and not on drug-acquisition costs alone.

Anti-Ulcer Agents↗