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.

The use of albumin in clinical practice.

The use of albumin in the clinical setting continues to generate controversy. Periodic shortages and the high cost of albumin have compelled many hospitals to develop guidelines regarding albumin administration. Our purpose is to review the human studies involving albumin. Particular emphasis will be placed on comparative trials involving albumin and the less expensive crystalloid solutions. It is hoped that this review will assist the clinician in making judgements concerning the appropriate use of albumin.

A paradigm for consensus. The University Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions.

OBJECTIVE: To develop contemporary, comprehensive guidelines for the appropriate and efficient use of albumin, nonprotein colloid, and crystalloid solutions. DESIGN: A systematic, literature-based, consensus exercise employing a modified Delphi method. PARTICIPANTS: Thirty-one medical and allied health professionals from 26 University Hospital Consortium (Oak Brook, Ill) member institutions were initially chosen to participate. Participants were selected on the basis of their recognized research in the use of albumin, nonprotein colloid, and crystalloid solutions, and/or experience in the review of appropriateness of such use. A total of 24 participants completed the exercise. MAIN OUTCOME MEASURES: Group responses were statistically analyzed in an iterative consensus development process. Five separate questionnaire rounds were designed to establish criteria for the appropriate use of albumin, nonprotein colloid, and crystalloid solutions. RESULTS: Consensus guidelines were developed outlining the appropriate use of these products for 12 clinical indications, including hemorrhagic shock, nonhemorrhagic (maldistributive) shock, hepatic resection, thermal injury, cerebral ischemia, nutritional intervention, cardiac surgery, hyperbilirubinemia of the newborn, cirrhosis and paracentesis, nephrotic syndrome, organ transplantation, and plasmapheresis. CONCLUSIONS: The Delphi method, a systematic, literature-based consensus process, was shown to be useful in the development of complex clinical practice guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. It is anticipated that the guidelines will assist health care providers to develop local institutional policies and procedures for the appropriate and efficient use of albumin and albumin alternatives. Institutions reviewing and updating existing local guidelines may use the University Hospital Consortium guidelines as a model for comparison.

Albumin and nonprotein colloid solution use in US academic health centers.

BACKGROUND: Crystalloids, nonprotein colloids (NPCs), and albumin are used for many indications. The use of the least costly agent in situations where these products are clinically interchangeable can reduce health care costs. OBJECTIVES: To characterize the prescribing of albumin and NPC. To evaluate the appropriateness and cost implications of their use. METHODS: An observational study conducted in 15 academic health centers from April 11 through May 6, 1994, to assess the appropriateness of albumin and NPC use, based on "model" consensus-derived indication guidelines. RESULTS: A total of 969 case report forms were evaluated. Albumin and NPCs were administered in 83% and 17% of the cases, respectively. Albumin and NPCs were administered mostly in the intensive care (50%) or operating room (31%) settings. The most common prescribers of these products were surgeons (45%) and anesthesiologists (20%). In 87% of cases, albumin or NPC was administered to reach a defined end point (eg, to achieve a target physiological state or to resolve a pathophysiological condition). Only one albumin recipient experienced an adverse event; no adverse events were noted with NPC administration. Approximately $203,000 was spent on albumin and NPC therapy for the 969 cases; $49,702 (24%) was spent on appropriate administrations, $124,939 (62%) on inappropriate administrations, and $28,014 (14%) on unevaluated indications. CONCLUSIONS: Evaluated against model guidelines, most of the albumin and NPC use in the study was found to be inappropriate. The need for institutions to define and implement guidelines that focus on the cost-efficient use of these agents is recommended in an increasingly cost-conscious health care environment.

Steady-state interaction between amiodarone and phenytoin in normal subjects.

Amiodarone has been reported to increase phenytoin levels. This study was designed to evaluate the pharmacokinetic basis of this interaction at steady-state. Pharmacokinetic parameters for phenytoin were determined after 14 days of oral phenytoin, 2 to 4 mg/kg/day, before and after oral amiodarone, 200 mg daily for 6 weeks in 7 healthy male subjects. During amiodarone therapy, area under the serum concentration time curve for phenytoin was increased from 208 +/- 82.8 (mean +/- standard deviation) to 292 +/- 108 mg.hr/liter (p = 0.015). Both the maximum and 24-hour phenytoin concentrations were increased from 10.75 +/- 3.75 and 6.67 +/- 3.51 micrograms/ml to 14.26 +/- 3.97 (p = 0.016) and 10.27 +/- 4.67 micrograms/ml (p = 0.012), respectively, during concomitant amiodarone treatment. Amiodarone caused a decrease in the oral clearance of phenytoin from 1.29 +/- 0.30 to 0.93 +/- 0.25 liters/hr (p = 0.002). These results were due to a reduction in phenytoin metabolism by amiodarone as evidenced by a decrease in the urinary excretion of the principal metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, 149 +/- 39.7 to 99.3 +/- 40.0 mg (p = 0.041) and no change in the unbound fraction of the total phenytoin concentration expressed as a percentage, 10.3 +/- 2.7 versus 10.7 +/- 2.1% (p = 0.28) during coadministration of amiodarone. The alterations in phenytoin pharmacokinetics suggest that steady-state doses of phenytoin of 2 to 4 mg/kg/day should be reduced at least 25% when amiodarone is concurrently administered. All dosage reductions should be guided by clinical and therapeutic drug monitoring.

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.

Effects of coadministration of propafenone on the pharmacokinetics of digoxin in healthy volunteer subjects.

Previous reports have suggested an interaction between propafenone and digoxin. We investigated the pharmacokinetics of IV digoxin when given alone (Phase I), after pretreatment with propafenone 150 mg every 8 hours for seven days (Phase II), and after propafenone 300 mg every 8 hours for 7 days (Phase III). The total body clearance of digoxin during Phase I was 2.45 ml/min/kg and was 2.17 ml/min/kg during Phase II (NS) and decreased to 1.92 ml/min/kg during Phase III (P less than 0.05). The renal clearance and half-life of digoxin were not significantly altered by propafenone. There was a trend towards a decrease in the volume of distribution of digoxin from 9.43 L/kg in Phase I, to 9.33 L/kg in Phase II, and 8.02 L/kg in Phase III. Similarly there was a trend towards a decreased nonrenal clearance of digoxin from 1.21 ml/min/kg during Phase I to 1.01 ml/min/kg during Phase II and to 0.75 ml/min/kg during Phase III. The changes in volume of distribution and nonrenal clearance parallel each other resulting in no change in the elimination half-life of digoxin. It is postulated that the mechanism of this interaction is due to decreases in the volume of distribution and nonrenal elimination of digoxin by propafenone. The degree of this interaction was related to the dose of propafenone. The magnitude of this interaction may be greater in patients and, thus, may require a reduction in the digoxin dose.

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.

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.

Viral infectivity of albumin and plasma protein fraction.

Original research, reviews, and case reports discussing viral infectivity of blood- and plasma-derived products were reviewed to determine the potential viral infectivity of human serum albumin (HSA) and plasma protein fraction (PPF). Data concerning viral infectivity viral screening and inactivation procedures, and viral outbreaks associated with blood and plasma products were extracted and evaluated for pertinence to HSA and PPF. The starting material used for fractionation, the manufacturing process, postmanufacturing handling, and immunocompetence of HSA or PPF recipients were assessed to determine risk of symptomatic viral disease after transfusion. Both HSA and PPF are manufactured with pasteurization procedures that have led to an excellent viral safety record based on 50 years of clinical use. One outbreak of hepatitis B was associated with PPF as a result of an unreliable manufacturing process that has been corrected. The pasteurization process is effective in eradicating known viral pathogens when good manufacturing practices are followed. Continued surveillance of such products is warranted for viruses not included in routine screening procedures and for those that are resistant to current inactivation methods.

Subcapsular hematoma after laparoscopic cholecystectomy, associated with ketorolac administration.

Ketorolac is the first injectable nonsteroidal antiinflammatory drug used as an analgesic in the perioperative period. Its adverse effect profile is different from that of the opioid analgesics; in particular, in its lack of respiratory depressive actions. However, ketorolac has risks associated with its perioperative administration, including episodes of substantial gastrointestinal bleeding. A patient undergoing elective laparoscopic cholecystectomy developed a subcapsular hepatic hematoma shortly after receiving a dose of injectable ketorolac. No evidence of parenchymal injury was found on laparoscopy, which argues against iatrogenic trauma. Clinicians should be aware that ketorolac may cause or aggravate bleeding, and it should be used with caution in perioperative patients.

Toxic shock-like syndrome.

Invasive group A streptococcal infection has important diagnostic and therapeutic implications in patients with necrotizing fasciitis. We cared for a man with the full-blown syndrome in whom many features of toxic shock syndrome were present, including profound hypotension and renal failure. The diagnostic similarities of toxic shock syndrome and the toxic shock-like syndrome caused by group A Streptococcus could have led to inappropriate treatment. Successful therapy in our patient included high doses initially of broad-spectrum antibiotics, repeated operative debridement of the lower leg (the affected limb), and ultimately, reconstructive surgery consisting primarily of split-thickness skin grafts. The reemergence of invasive streptococcal infections may relate to changes either in virulence factors of the causative streptococcus or in exotoxins elaborated by this microorganism. A causative relationship between an exotoxin produced by group A Streptococcus and the toxic shock-like syndrome has not yet been established.

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.

Falsely decreased total serum calcium concentration associated with iron dextran injection.

We cared for a patient in whom iron dextran administration interfered with the determination of total serum calcium concentration. An unexpected elevation in serum phosphorus concentration also occurred after the iron dextran infusion. A MEDLINE search from 1966 to present was conducted, and the manufacturer of the iron dextran was contacted for information related to these findings. Several drugs and diseases were found that may decrease serum calcium and increase phosphorus concentrations. We found one anecdotal citation of iron dextran interfering with serum calcium concentrations, but no reports of interference with serum phosphorus concentrations. Doses of iron dextran in excess of 250 mg may cause a false decrease in total calcium concentration more than 4 hours after the infusion is completed. A false increase in serum phosphorus concentrations after the infusion requires further investigation.

Patients' perceptions of increased pharmacy contact.

This prospective, randomized study was conducted to determine if increased patient contact between pharmacists and patients would result in greater patient awareness and satisfaction with their hospital stay and particularly with pharmacists and pharmacy services. Eligible patients were randomized to receive either the usual pharmacy care with minimum contact with the pharmacist, or expanded services based on increased contact with the pharmacist. A questionnaire was used to determine patient awareness and satisfaction. Statistically significant differences were found between the groups on awareness and satisfaction with pharmacy services scales as well as total scores. Total patient scores were highly reliable, with an alpha coefficient of 0.87. In addition, comments by patients in the group with increased contact were overwhelmingly positive, in contrast to those receiving usual care. Patients desire and appreciate greater contact with pharmacists.

Albumin and prealbumin concentrations in patients receiving postoperative parenteral nutrition.

This prospective, nonrandomized study was conducted to compare the increases in albumin and prealbumin concentrations in postoperative patients given adequate nutrition support. All surgery patients at least 18 years of age and who required parenteral nutrition were included. Of 86 patients evaluated, 16 met all criteria for study entry. Blood for albumin concentrations was drawn within 48 hours of beginning parenteral nutrition and then weekly. Blood for prealbumin concentrations was drawn within 48 hours of beginning parenteral nutrition and then twice weekly. Albumin concentrations increased from 2.00 +/- 0.35 to 2.21 +/- 0.42 g/dl (NS). Prealbumin concentrations increased from 11.97 +/- 6.31 to 17.29 +/- 8.93 mg/dl (p = 0.017). All but one prealbumin concentration was in the normal range for our laboratory when parenteral nutrition was discontinued. None of the albumin concentrations were ever in the normal range. The prealbumin concentration is a better indicator than albumin of nutrition status in the postoperative patient. Since prealbumin concentrations typically rise into the normal range within a week after adequate caloric supplementation, clinicians may avoid unnecessary increases in protein-calorie intake and laboratory testing of nutrition status by using this measurement.

Management of alcohol withdrawal.

The diagnosis, evaluation and assessment, supportive care, and pharmacologic treatment of acute alcohol withdrawal are reviewed. Patients in alcohol withdrawal have decreased or stopped their heavy, prolonged ingestion of alcohol and have subsequently begun to have at least two of the following symptoms: autonomic hyperactivity, tremor, nausea or vomiting, hallucinations, psychomotor agitation, anxiety, and grand mal seizures. Evaluation of the patient at risk for alcohol withdrawal should include a complete history and physical examination; laboratory tests are often indicated. The patient's progress should be assessed before, during, and after therapy, preferably with a validated instrument. After the initial evaluation and assessment but before the administration of dextrose-containing solutions, a 100-mg dose of thiamine hydrochloride should be given by i.m. or i.v. injection. Routine supplementation with calcium, magnesium, and phosphate is questionable. The need for fluid and electrolyte administration varies depending on losses. Most patients in alcohol withdrawal can be managed with supportive care alone, but for more severe or complicated withdrawal, pharmacologic therapy may be necessary. Benzodiazepines, especially diazepam and chlordiazepoxide, are the drugs of choice. Barbiturates, beta-blockers, and antipsychotics are generally not recommended as first-line therapy. Several drugs in other classes, including carbamazepine and clonidine, have been shown to be about as effective as benzodiazepines in a few studies, but the studies were small, the patients were usually in mild withdrawal, and validated instruments for assessing withdrawal were often not used. Some agents, such as beta-blockers, may play a role as adjuncts to, not replacements for, benzodiazepine therapy. For patients in alcohol withdrawal who do not respond to supportive care, benzodiazepines are the treatment of choice.

Fluid delivery from infusion-pump syringes.

Fluid-delivery rates of five small-volume infusion-pump syringes were compared. The study consisted of a comparison of the infusion-pump syringes in their respective infusion pumps (1) set for continuous delivery at 1 mL/hr, (2) set for continuous delivery at 3 mL/hr, and (3) set to deliver 1-mL bolus volumes during continuous delivery at 4 mL/hr. The Life-care prefilled 30-mL syringe (Abbott), the DBL 30-mL syringe no. 770205 (DBL Inc.), and the Pump-Jet 30-mL syringe no. 1931 (International Medication Systems) were tested in the Lifecare PCA Plus II infusion pump no. 4100 (Abbott). The 30-mL Pump-Jet syringe no. 1911 (International Medication Systems) and the DBL 30-mL syringe no. 709700 (DBL Inc.) were tested in the Stratofuse PCA infusion pump (Baxter). The infusion pumps were set to deliver fluid continuously at 1 mL/hr for 30 hours, and the solutions were collected separately and weighed. The procedure was repeated with the infusion rate set at 3 mL/hr for 10 hours. For the third part of the study, each syringe was tested to deliver 1-mL boluses with 0, 5, 15, and 25 mL removed from the syringe. The solutions were collected and weighed before and after each bolus was delivered. The volume of solution collected was calculated by using the specific gravity of the solution. The syringes delivered significantly different volumes during the first hour of infusion at both the 1- and 3-mL/hr rates. Differences also existed across time for most of the syringes. Bolus volumes varied greatly after infusion of 0 or 5 mL of fluid but were acceptable for the remainder of the infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Recognition and treatment of ethanol abuse in trauma patients.

OBJECTIVE: To evaluate physicians' recognition of possible ethanol-related complications in trauma patients, and to compare benzodiazepine requirements in patients with positive and negative blood-ethanol concentrations. DESIGN: Retrospective investigation. SETTING: University medical center (level I trauma center). PATIENTS: One hundred thirty-one trauma patients more than 18 years of age who were admitted for at least 24 hours. OUTCOME MEASURES: (1) Physicians' recognition of ethanol (EtOH) as a potential factor complicating patient recovery in trauma patients admitted with positive blood-EtOH concentrations. (2) The amount of benzodiazepines administered to trauma patients with positive EtOH-blood concentrations compared to trauma patients with no detectable EtOH in their blood. RESULTS: The presence of EtOH in the blood or the potential for EtOH withdrawal was mentioned in the progress notes of approximately one fourth of the patients with positive blood-EtOH concentrations. Thiamine was administered in 8.2% of patients with EtOH-related injuries. Benzodiazepine requirements were significantly higher in patients with positive versus negative blood-EtOH concentrations. CONCLUSIONS: Prompt recognition and charting of suspected ethanol abuse is recommended, in conjunction with prompt administration of thiamine. It should be anticipated that patients with positive blood-ethanol concentrations will require higher doses of benzodiazepines compared to trauma patients without ethanol-related injuries.

Albumin audit results and guidelines for use. University Medical Center, Tucson, Arizona.

OBJECTIVE: To identify patients receiving albumin, develop guidelines for albumin use, and examine distribution and billing procedures. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: All patients received albumin in a four-week period. Patients were identified concurrently using intensive care unit surveys and the pharmacy computer system, and retrospectively using billing statements. Data were analyzed from 73 of 79 patients (92.4 percent); 6 (7.6 percent) had no record of albumin being ordered or administered. Pediatric patient data were used only in the financial calculations. DATA COLLECTION: Demographics and albumin dosages were recorded for all patients. Prescribing service and indications for use were recorded in adults. Albumin administered was compared with the amount billed to each patient. MAIN RESULTS: Sixty adult patients aged 14-91 y (median 62) received 1-69 units (median 4 units [1 unit = 12.5 g albumin]) and 470 total units. Surgical services prescribed albumin in 73 percent and medical services in 27 percent of the patients. Common indications for albumin included volume expansion (65 percent), as intraoperative fluid (13 percent), and to increase urine output (10 percent). The pharmacy computer system identified 63 percent of the patients. Of these, 13 percent were not billed for albumin they received. Examinations of patient billing statements found that up to $17,740 a year (15 percent) of albumin administered is not billed. The floor-stock distribution system used in the intensive care units contributed to most errors. CONCLUSIONS: Recommendations addressing the problems identified in this audit were made to the pharmacy, medical, nursing, and billing departments. Guidelines for albumin use were formulated and approved by the hospital's pharmacy and therapeutics committee.