Intentional use of carbapenem antibiotics for valproic acid toxicity: A case report.

WHAT IS KNOWN AND OBJECTIVE: The interaction between valproic acid (VPA) and carbapenem antibiotics is well described with previous reports suggesting a reduction in VPA half-life between 47% and 90%. As described in this case, this interaction might be beneficial in the setting of toxic VPA ingestion. CASE DESCRIPTION: An intubated, unresponsive patient arrived via emergency medical services after toxic VPA ingestion. Meropenem was prescribed for a suspected pneumonia and to take advantage of the VPA interaction. We observed a 56% decline in half-life with short-term meropenem dosing and an improvement in mental status shortly after administration. WHAT IS NEW AND CONCLUSION: Our findings suggest a potential role for short-term carbapenem therapy for VPA overdose.

Medication administration errors in adult patients in the ICU.

OBJECTIVE: To quantify the incidence and specify the types of medication administration errors from a list of error-prone medications and to determine if patient harm resulted from these errors. DESIGN: An observational evaluation. SETTING: Five intensive care units (ICUs) in the United States. PATIENTS AND PARTICIPANTS: Eight hundred fifty-one patients who were at least 18 years of age and admitted to surgical, medical or mixed ICUs during a 3 month period were included. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A list of error-prone medications was adapted from the literature and evaluated for medication errors and patient harm. Of 5,744 observations in 851 patients, 187 (3.3%) medication administration errors were detected. the therapeutic classes most commonly associated with errors were vasoactive drugs 61 (32.6%) and sedative/analgesics 48 (25.7%). The most common type of error was wrong infusion rate with 71 (40.1%) errors. Twenty-one errors did not reach the patient and 159 reached the patient but did not result in harm, increased monitoring or intervention. Five errors required increased patient monitoring and two required intervention. None of the errors resulted in patient death. CONCLUSIONS: This multicenter evaluation found fewer medication administration errors than the published literature, possibly due to the varying observational techniques and pharmacist involvement. Lorazepam and wrong infusion rates are associated with errors that occurred frequently, resulted in the greatest potential for harm and were common oversights in the system. These errors should be considered potential areas for betterment in the medication use process to improve patient safety.

Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery.

OBJECTIVE: To review the use of systemic hemostatic medications for reducing bleeding and transfusion requirements with cardiac surgery. DATA SOURCES: Articles were obtained through computerized searches involving MEDLINE (from 1966 to September 2000). Additionally, several textbooks containing information on the diagnosis and management of bleeding associated with cardiac surgery were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: Due to the large number of randomized investigations involving systemic hemostatic medications for reducing bleeding associated with cardiac surgery, the article selection process focused on recent randomized controlled trials, metaanalyses and pharmacoeconomic evaluations. DATA EXTRACTION: The primary outcomes extracted from the literature were blood loss and associated transfusion requirements, although other outcome measures such as mortality were extracted when available. DATA SYNTHESIS: Although the majority of investigations for reducing cardiac bleeding and transfusion requirements have involved aprotinin, evidence from recent meta-analyses and randomized trials indicates that the synthetic antifibrinolytic agents, aminocaproic acid and tranexamic acid, have similar clinical efficacy. Additionally, aminocaproic acid (and to a lesser extent tranexamic acid) is much less costly. More comparative information of hemostatic agents is needed retative to other outcomes (eg., reoperation rates, myocardial infarction, stroke). There is insufficient evidence to recommend the use of desmopressin for reducing bleeding and transfusion requirements in cardiac surgery, although certain subsets of patients may benefit from its use. CONCLUSIONS: Of the medications that have been used to reduce bleeding and transfusion requirements with cardiac surgery, the antifibrinolytic agents have the best evidence supporting their use. Aminocaproic acid is the least costly therapy based on medication costs and transfusion requirements.

Systemic hemostatic medications for reducing surgical blood loss.

OBJECTIVE: To review randomized trials involving the use of systemic hemostatic medications for reducing surgical blood loss. DATA SOURCES: Articles were obtained through searches of MEDLINE (1966-September 2000). The bibliographies of retrieved publications were reviewed for additional references. STUDY SELECTION: All randomized studies and pharmacoeconomic evaluations that involved medications used for systemic hemostasis in the perioperative period were included. DATA EXTRACTION: Randomized studies involving conjugated estrogens, aminocaproic acid, tranexamic acid, desmopressin, and aprotinin for systemic hemostasis were extracted. Studies of proton-pump inhibitors for upper gastrointestinal bleeding and octreotide for variceal bleeding were excluded, as were trials involving the use of any hemostatic agent for cardiovascular surgery. The primary outcome under review was a reduction in bleeding as defined by reduced transfusion requirements. DATA SYNTHESIS: There is limited efficacy and toxicity information concerning the use of conjugated estrogens for reducing surgery-related bleeding. Similarly, there are a limited number of randomized studies involving aminocaproic acid and tranexamic acid, and with the exception of tranexamic acid for reducing transfusion requirements with knee surgery, the study results are either conflicting or negative. For desmopressin, evidence from a substantial number of randomized trials documents its lack of efficacy. Aprotinin has reduced bleeding and transfusion requirements in a number of randomized studies involving patients undergoing orthopedic surgery, but cost-effectiveness studies are needed to better define its therapeutic role. Trials of aprotinin during hepatic surgery have yielded conflicting results. CONCLUSIONS: Most hemostatic medications used for reducing surgery-related bleeding have limited or contradictory evidence of efficacy.

Proton-pump inhibitors for acute peptic ulcer bleeding.

OBJECTIVE: To review the use of proton-pump inhibitors for acute peptic ulcer bleeding. DATA SOURCES: Articles were obtained through computerized searches of MEDLINE (1966-September 2000). Additionally, several textbooks containing information on the diagnosis and management of acute peptic ulcer bleeding were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: All randomized studies and pharmacoeconomic evaluations that used proton-pump inhibitor therapy for acute peptic ulcer bleeding were included. Randomized controlled trials and meta-analyses involving other therapies for treating peptic ulcer bleeding were also reviewed for possible inclusion. DATA EXTRACTION: The primary outcomes extracted from the literature were persistent or recurrent bleeding, transfusion requirements, need for endoscopic intervention or surgery, length of stay, and mortality. DATA SYNTHESIS: Data from double-blind, placebo-controlled trials involving more than 1000 patients demonstrate that short-term, high-dose omeprazole therapy is effective for reducing bleeding and transfusion requirements in patients with acute peptic ulcer bleeding. The patients most likely to benefit from this therapy are hospitalized patients at high risk for rebleeding and patients in whom endoscopic evaluation must be delayed or is unavailable. CONCLUSIONS: Omeprazole (and likely other proton-pump inhibitors) is useful in reducing bleeding and transfusion requirements in patients with acute peptic ulcer bleeding, although better delineation of appropriate candidates is needed.

Octreotide for acute variceal bleeding.

OBJECTIVE: To review the use o f octreotide for acute variceal bleeding. DATA SOURCES: Articles were obtained through computerized searches involving MEDLINE (from 1997 to October 2000). Additionally, several textbooks containing information on the diagnosis and management of acute variceal bleeding were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: All randomized studies and pharmacoeconomic evaluations that used octreotide therapy for acute variceal bleeding were considered. Randomized controlled trials and meta-analyses involving other therapies for treating variceal bleeding were also reviewed for possible inclusion. DATA EXTRACTION: The primary outcomes extracted from the literature were persistent or recurrent bleeding, need for endoscopic intervention or balloon tamponade, and mortality. DATA SYNTHESIS: Although both endoscopic therapies and medications are used to control bleeding and rebleeding episodes, the endoscopic approach has the additional goal of obliterating the varix. Since rebleeding episodes are common as long as the varix is present, endoscopic and medication therapies cannot be considered interchangeable based on bleeding control alone. However, octreotide by continuous intravenous infusion has demonstrated effectiveness in reducing blood loss and transfusion requirements as both an initial intervention (until definitive sclerotherapy can be performed) or as adjunctive therapy to endoscopic measures. Octreotide can be started quickly, has a relatively rapid onset of action, and does not require someone with endoscopy training to initiate. Additionally, octreotide is relatively free of significant adverse effects. CONCLUSIONS: While additional investigations are needed, particularly in the area of pharmacoeconomics, there is substantial evidence that octreotide is an efficacious therapy with relatively few adverse effects when used in the management of acute variceal bleeding.

Comparison of preoperative skin preparation products.

We compared application, drying, and removal times as well as user satisfaction of four preoperative skin preparation products. All products were applied to 25 subjects, allowed to dry, and removed. Operating room personnel who applied the products were asked to complete a user-satisfaction survey. Application and drying times were longest with the povidone iodine paint and scrub product (p<0.05). That product had the highest rating for overall user satisfaction. Cost-minimization analysis revealed that although alcohol-containing products had lower overall costs, savings may not outweigh associated safety risks.

Population pharmacokinetics of aminoglycosides in critically ill trauma patients on once-daily regimens.

BACKGROUND: Once-daily dosing regimens of aminoglycosides are routinely used in critically ill trauma patients. However, the pharmacokinetic parameters are variable in these patients. The purpose of this study was to evaluate the pharmacokinetics of aminoglycosides in critically ill trauma patients receiving once-daily dosing regimens. METHODS: At least two aminoglycoside concentrations were measured in each patient. Population pharmacokinetic parameters were estimated on the basis of a one-compartment structural model and the program nonlinear mixed effects modeling. RESULTS: Fifty-three aminoglycoside concentrations from 19 patients were analyzed. The aminoglycoside clearance was 5.47 L/h. The mean volume of distribution was 22.2 L (0.3 L/kg). The mean half-life was 2.9 hours. Serum-aminoglycoside concentrations were undetectable for longer than 12 hours in 4 of 19 patients. Weight, age, or serum creatinine did not significantly explain the variability. CONCLUSION: There is marked variability in aminoglycoside pharmacokinetic parameters in critically ill trauma patients. This may lead to prolonged drug-free intervals. Individualized dosing of critically ill trauma patients on the basis of at least two serum-aminoglycoside concentrations seems indicated when using once-daily dosing regimens.

Enteral nutrition support in acute pancreatitis.

OBJECTIVE: To review the controversies surrounding the use of nutritional interventions, particularly enteral support, in patients with acute pancreatitis. DATA SOURCES: Articles were obtained through a MEDLINE search (1966-June 1999). Additionally, several textbooks containing information on the diagnosis and management of acute pancreatitis were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: All original investigations in humans pertaining to the use of enteral nutritional support in acute pancreatitis were reviewed for inclusion. Studies that investigated parenteral nutrition in acute pancreatitis were also reviewed, with preference given to controlled comparisons with enteral regimens or no nutritional support. DATA EXTRACTION: The primary outcomes extracted from the literature were time to oral feeding tolerance, complications (e.g., infection) associated with nutritional support, and length of stay. DATA SYNTHESIS: The duration of pancreatitis and time to oral feedings is similar whether patients receive enteral (i.e., jejunal tube feedings) or parenteral nutrition. Additionally, complications, length of stay, and costs are either similar or decreased with enteral versus parenteral nutrition. CONCLUSIONS: Current evidence suggests that the enteral rather than parenteral route should be used to provide nutrition to patients with acute pancreatitis. Parenteral nutrition should be reserved for patients in whom nasojejunal feeding is not possible.

Treatment of hypertension in the perioperative patient.

OBJECTIVE: To review studies and drug therapy relating to the treatment of hypertension in perioperative patients. DATA SOURCES: Articles were selected from a MEDLINE search (1966-August 1998), and several textbooks on hypertension and surgery were reviewed. In addition, bibliographies of all articles and textbook chapters were studied for articles not found in the computerized searches. STUDY SELECTION: Clinical studies involving hypertension in the perioperative setting were included. The initial search was limited to studies conducted in humans and published in English. DATA EXTRACTION: Information regarding drug therapy was reviewed and guidelines were constructed for managing surgical patients with acute blood pressure elevations. DATA SYNTHESIS: Although nitroprusside and nitroglycerin, with their short onset of action and duration of effect, are indicated for hypertensive emergencies, a variety of agents are available for hypertensive urgencies. An algorithm that can be used as a template for the development of intrainstitutional guidelines is provided. CONCLUSIONS: Due to the scarcity of comparative trials, decisions involving agents for the treatment of perioperative hypertension must often be made based on combined efficacy, toxicity, cost, and convenience considerations.

A prospective study of pain control in the emergency department.

The most common complaint in the emergency department is pain. The management of acute pain, however, has not been well studied. This prospective study was designed to assess pain intensity and relief along with satisfaction in the emergency department. Adult patients with a primary complaint of acute pain were asked to complete a two-part questionnaire administered by a research assistant. The first part was completed on arrival and the second part on discharge from the emergency department. The respondents were not permitted to see the first part of the questionnaire while completing the second. The questionnaire used an unmarked, horizontal 10-cm visual analog scale along with short answer questions to measure pain, relief, and satisfaction. Choice of drug therapy was decided by the physician according to usual treatment methods. Fifty-seven people presented with the chief complaint of pain. Of those, 30 (53%) were treated with medications. The mean level of pain on admission for treated patients was 6.64 compared with a mean level of pain on discharge of 4.02 (P =.0001). Untreated patients had a mean admission visual analog scale score of 4.19. Compared with treated patients, this difference was statistically significant (P =.001). A mean visual analog scale score of 5.43, representing the mean amount of pain relief, was reported among treated patients. Treated patients also reported a visual analog scale score of 6.46 in overall satisfaction with pain management. The results of this study indicate that there is a significant and clinical difference in levels of pain and satisfaction between admission and discharge in these patients in the emergency department.

Pharmacoeconomic comparison of an albumin-furosemide complex versus sequential therapy for renal insufficiency.

The purpose of this economic analysis was to develop an economic model using intra-institutional cost data for acute, oliguric renal insufficiency treated with either an albumin-furosemide complex or albumin followed by furosemide (sequential therapy). The perspective of this study was from the standpoint of the institution (University Medical Center, a teaching hospital). The decision tree and sensitivity analyses demonstrated that the albumin-furosemide complex would be more effective and less costly than sequential therapy for a range of outcome probabilities. Using effectiveness assumptions from published literature, the complex could avoid dialysis in 27% of patients compared with 8% of patients receiving sequential therapy. The complex would also be less costly ($7778 vs $8748). In terms of cost-effectiveness, the complex is $28,807 per averted dialysis compared with $109,350 for sequential therapy.

Lack of hematologic effects of recent ethanol ingestion by trauma patients.

A retrospective investigation was conducted to determine if acute ethanol (EtOH) ingestion before injury leads to hematologic impairment as noted by coagulation and transfusion parameters. Patients older than 18 years of age were grouped according to the presence or absence of detectable EtOH concentrations in the blood, with further subdivision based on an Injury Severity Score of 8 or less or 9 or more. The following direct and indirect indicators of hematologic function were studied: volume of resuscitation fluids administered (including blood products), prothrombin time, partial thromboplastin time, and hematocrit. Of the 304 patients who were evaluated, 152 had detectable EtOH concentrations and 136 had undetectable EtOH concentrations; 16 patients had not been tested for blood EtOH concentrations and were excluded from the analysis. There were no significant differences between groups with regard to blood or fluid requirements or coagulation parameters. Detectable blood EtOH concentrations in trauma patients are not associated with significant changes in transfusion requirements or coagulation parameters compared to patients without detectable EtOH concentrations.

Venous thromboembolism in multiple trauma patients.

Thromboembolic complications are frequent in patients with multiple trauma. The efficacy of unfractionated heparin for venous thrombosis prophylaxis has not been established. Based on limited prospective data, low-molecular-weight heparin appears to be more effective than unfractionated heparin and at least as effective as compression devices for preventing thromboembolic complications in these patients. Vena cava filters should be considered in high-risk patients who cannot receive anticoagulant therapy, but long-term filter use without concomitant anticoagulant therapy is associated with a substantial risk of recurrent thromboembolism.

Impacting cost and appropriateness of stress ulcer prophylaxis at a university medical center.

OBJECTIVE: To determine the appropriateness and medication cost of stress ulcer prophylaxis before and after a targeted educational intervention. DESIGN: In the preintervention cohort (phase 1), 264 patients were evaluated over 2 months, using stress ulcer prophylaxis guidelines developed by a comprehensive literature search. Targeted educational programs were subsequently used to inform trauma housestaff on appropriate usage of stress ulcer prophylaxis medications with emphasis on using sucralfate. The postintervention cohort (phase 2) involved concurrent evaluation of 279 patients. Length of inappropriate stress ulcer prophylaxis (i.e., did not meet approved guidelines) between phases was compared using a Student's t-test for independent samples (alpha = .05). SETTING: A 365-bed university medical center. PATIENTS: Patients admitted to any of the intensive care units and all patients who were placed on histamine-2-antagonists or sucralfate for stress ulcer prophylaxis. INTERVENTIONS: Educational intervention regarding appropriate stress ulcer prophylaxis directed at the trauma service. MEASUREMENTS AND MAIN RESULTS: Patient demographics in the two phases were similar and there was no difference in the number of patient risk factors for stress-induced bleeding. The mean length of inappropriate stress ulcer prophylaxis was 5.78 +/- 4.36 days in phase 1 and 4.66 +/- 3.10 days in phase 2 (p < .05). Eighty-nine patients in phase 1 received inappropriate stress ulcer prophylaxis for a drug cost of $2,272.00 (mean $25.53 +/- 25.52) compared with 90 patients in phase 2 with a drug cost of $1,417.00 (mean $15.75 +/- 13.06). Three patients in each phase had clinically important bleeding (hemodynamic compromise or transfusion); all were receiving ranitidine. The mean total cost (fixed and variable) of hospitalization was $69,288.00 and $74,709.00 for the three patients who bled in each phase compared with $19,850.00 and $15,812.00 for all patients admitted to the intensive care unit in phases 1 and 2, respectively. The mean length of hospital stay was 30.00 days and 29.33 days for the three patients who bled in each phase compared with 11.54 days and 10.27 days for all patients admitted to the intensive care unit in phases 1 and 2, respectively. CONCLUSIONS: Cost savings are associated with more appropriate stress ulcer prophylaxis. Clinically important bleeding is uncommon but results in prolonged hospital stays and increased costs.

Site-specific pharmacokinetics and pharmacodynamics of intramuscular meperidine in elderly postoperative patients.

OBJECTIVE: To examine and compare the pharmacokinetics and pharmacodynamics of meperidine when administered intramuscularly at gluteal and deltoid sites in elderly postoperative patients. DESIGN: Prospective, randomized investigation. SETTING: Tertiary care university teaching hospital. PATIENTS: Fourteen patients 60 years of age or older who were undergoing general surgery. INTERVENTION: A single dose of meperidine 0.75 mg/kg given intramuscularly at either a deltoid or gluteal site. MAIN OUTCOME MEASURES: Pharmacokinetic (based on concentration-time curves) and pharmacodynamic (i.e., pain scales, need for additional pain medication) comparisons were made, based on site of meperidine injection. RESULTS: No statistically significant differences were found in the maximum plasma concentration, volume of distribution, or clearance of meperidine by site of injection. Substantial interpatient variability in pharmacokinetic parameters was noted for both sites (range of maximum concentrations: 191-500 ng/mL gluteal, 166-374 ng/mL deltoid). Although pain scores were similar for the two groups, four of the patients in the group given gluteal injection required additional breakthrough pain management within 4 hours of meperidine injection compared with one patient in the group given deltoid injection. CONCLUSIONS: There is no obvious relationship between meperidine pharmacokinetic and pharmacodynamic parameters, regardless of intramuscular injection site. Breakthrough pain is common when patients are given intramuscular injections postoperatively, particularly when the gluteal route is used. When meperidine is used for analgesia in elderly postoperative patients, consideration should be given to more rapid and predictable routes (e.g., intravenous injection) of meperidine administration.

Prescribing of analgesics in trauma patients.

OBJECTIVE: To evaluate whether initial orders of pain medications by physicians for trauma patients were in accordance with published guidelines. DESIGN: Concurrent, nonrandomized investigation conducted over 4 months. MATERIALS AND METHODS: All adult trauma patients admitted to the intensive care unit within 12 hours of injury who stayed for at least 1 hour were eligible for study admission. Patients with injuries prohibiting accurate pain assessment (e.g., Glasgow Coma Score < 8, spinal cord injury) were excluded. Initial orders for pain medications were compared to published guidelines; correlations between dose and patient demographics were studied. RESULTS: Of the 30 patients enrolled in the study, 83% were prescribed appropriate pain control regimens. The average dose of morphine administered during each of the 8-hour dosing intervals was approximately 12 mg. No relationship was found between patient age, sex, Glasgow Coma Score, and morphine dose; however, there was a positive correlation found between Injury Severity Score and dose. CONCLUSIONS: The majority of patients in this investigation were initially prescribed appropriate doses and intervals for pain management.