The risk assessment profile score identifies trauma patients at risk for deep vein thrombosis.

BACKGROUND: The identification of trauma patients at risk for the development of deep venous thrombosis (DVT) at the time of admission remains difficult. The purpose of this study is to validate the risk assessment profile (RAP) score to stratify patients for DVT prophylaxis. METHODS: All patients admitted from November 1998 thru May 1999 were evaluated for enrollment. We prospectively assigned patients as low risk or high risk for DVT using the RAP score. High-risk patients received both pharmacologic and mechanical prophylaxis. Low-risk patients received none. Surveillance duplex Doppler scans were performed each week of hospitalization or if symptoms developed. Hospital charges for prophylaxis were used to determine the savings in the low-risk group. Statistical differences between the risk groups for each factor of the RAP and development of DVT were determined by the chi-squared test, with significance at a probability value of less than .05. RESULTS: There were 102 high-risk (64%) and 58 low-risk (36%) individuals studied. Eleven of the high-risk group (10.8%) experienced the development of DVT (asymptomatic, 64%). None of the low-risk group was diagnosed with DVT. Five of the 16 RAP factors were statistically significant for DVT. Eliminating prophylaxis and Doppler scans in low-risk patients resulted in a total savings of $18,908 in hospital charges. CONCLUSIONS: The RAP score correctly identified trauma patients at increased risk for the development of DVT. Despite prophylaxis, the high-risk group warrants surveillance scans. Withholding prophylaxis in low-risk patients can reduce hospital charges without risk.

Pharmacokinetic optimisation of the treatment of embolic disorders.

Management of thromboembolic disease involves administration of anticoagulants, thrombolytics or antiplatelet agents to lyse or prevent thrombus extension. Despite widespread use and decades of experience with some of these agents, much is unknown about the effects of dose and plasma concentration on patient response. Unfractionated heparin (UFH) improves outcome in many thromboembolic disorders when administered to a target activated partial thromboplastin time (aPTT) or plasma heparin concentration. UFH exhibits dose-dependency both with absorption from subcutaneous sites and elimination. Doses based on bodyweight or estimated blood volume attain therapeutic aPTTs faster than fixed or standard doses. Low molecular weight heparins (LMWHs) were developed to increase the anti-factor Xa:anti-factor IIa activities. Several different LMWHs are as effective as UFH in treating deep venous thrombosis. Evidence fails to support a relationship between anti-factor Xa activity and either thrombosis evolution or bleeding. No comparisons have been made between bodyweight-based and anti-factor Xa activity-based doses. The dose of orally administered warfarin is adjusted to achieve a target International Normalised Ratio (INR). Maintenance doses are estimated on the basis of the patient's INR during the first 3 days of therapy: the dose required to achieve an optimal INR decreases with age > 50 years. The thrombolytic agents are administered in standard doses to achieve rapid thrombolysis with minimal alteration in systemic haemostasis. Accelerated intravenous alteplase may result in the highest rate of coronary artery reperfusion. Nevertheless, standard doses of streptokinase, anisoylated plasminogen streptokinase complex and alteplase result in similar 1-month mortality rates. The minimal advantage seen with alteplase is offset by higher rates of stroke. Future trials will focus on administration strategies achieving rapid thrombolysis, while minimising the risk of serious bleeding. With the antiplatelet agents, unpredictability in the pharmacokinetic parameters of different products has confounded interpretation of published reports. Optimal aspirin (acetylsalicylic acid) administration would include administration of an initial dose of 160 to 325mg after an acute vascular event, followed by maintenance dosages of approximately 75 mg/day for prophylaxis or treatment. Ticlopidine does not exhibit a relationship between either plasma concentration or dose and adverse effects, while pharmacodynamic effects may be dose-, but not plasma concentration-, dependent. The correlation between the concentration of dipyridamole and some of its antiplatelet effects may be the strongest amongst all the antiplatelet agents. However, unfortunately all clinical trials used standard doses and the current consensus is that dipyridamole alone is not an effective antiplatelet agent.

The effect of thrombocytosis on serum potassium and phosphorus concentrations.

Thrombocytosis is a cause of falsely elevated serum potassium concentrations, and phosphorus concentrations may be similarly distorted. Because plasma concentrations are not affected, the difference between the serum and plasma concentrations detects spurious elevations. The authors, in this study, sought to determine the degree of correlation between thrombocytosis and false elevations in serum potassium and phosphorus concentrations. Ninety-one general, medical/surgical patients with elevated platelet counts were identified by laboratory reports. Subjects were stratified into blocks by platelet count. Samples were obtained simultaneously for serum and plasma potassium and phosphorus concentrations and complete blood counts. The serum minus plasma concentrations for potassium (Kdiff) and phosphorus (Pdiff) were calculated and analyzed against each other and the platelet count by linear regression. A control group of 20 subjects with normal platelet counts was used to verify laboratory results with literature values. The Kdiff and Pdiff values in the control group very closely approximated literature values of 0.4 mmol/L and 0.08 mmol/L, respectively. Platelet count was a moderate predictor of Kdiff, r2 = 0.55 (p = 0.00001). Kdiff exceeded the upper limit of control at a platelet count of approximately 600 x 10(9)/L. Platelet count also correlated with Pdiff, r2 = 0.31 (p = 0.00001). Additionally, Kdiff correlated with Pdiff, r2 = 0.39 (p = 0.00001). Thrombocytosis is associated with false elevations in measured serum potassium and phosphorus concentrations. Additionally, the magnitude of elevations in potassium and phosphorus concentrations appear to be related.

Accuracy of a first-order model for estimating initial heparin dosage.

The accuracy of a first-order pharmacokinetic model for determining initial heparin infusion rates was studied, and factors that could affect the accuracy of the method were investigated. Patients who received an i.v. infusion of heparin for at least 24 hours for treatment of deep-vein thrombosis, pulmonary embolism (PE), or myocardial infarction were identified by retrospective chart review. A therapeutic dosage of heparin was defined by an activated partial thromboplastin time of 45-75 seconds. Heparin dosages were calculated by using estimated blood volume as the heparin volume of distribution, a desired steady-state heparin concentration of 0.30 units/mL, and an elimination rate constant of 0.832 hr-1. The difference between the calculated dosage and the actual therapeutic dosage was calculated. The differences for various patient subgroups were compared, and the estimated dosages were regressed against the actual dosages to determine their predictive value. Data for 49 patients were analyzed. The mean +/- S.E. difference between the actual and calculated dosages was 29.2 +/- 37.1 units/hr. No significant differences were evident according to sex or indication for therapy. Smokers and nonsmokers differed, as did obese and lean patients. The equation appeared to be more accurate in nonsmokers than smokers. The addition of 200 units/hr to the calculated dosage for patients with PE resulted in minor improvement in the predictive capacity of the equation. Moderate agreement was observed between the actual and calculated heparin dosages in non-smokers of various body weights.

Sorbitol content of selected oral liquids.

OBJECTIVE: Excipients in pharmaceuticals usually are considered inert, and may be overlooked in the differential diagnosis of diarrhea. Sorbitol-containing medicinal liquids are capable of inducing osmotic diarrhea. We reviewed the oral liquids in our formulary to determine their sorbitol content and to evaluate the availability of this information. DESIGN: The oral liquids stocked by our hospital were determined through a computer search and manual inspection of the pharmacy storeroom. Three common sources of drug information were consulted to determine each product's sorbitol content: manufacturers' product information, American Hospital Formulary Service (AHFS) Drug Information 91, and Facts and Comparisons Drug Information. We then contacted each manufacturer by mail or telephone to verify the information. SETTING: The study was conducted at the University of Cincinnati Hospital, a tertiary-care, teaching hospital. RESULTS: A total of 129 products (98 chemical entities) were reviewed. Fifty-four (42 percent) of the products examined contained sorbitol. The frequency of sorbitol presence by liquid type was: solutions (33 percent), suspensions (43 percent), syrups (59 percent), elixirs (43 percent), concentrates (67 percent), drops (33 percent), tinctures (0 percent), and emulsions (0 percent). The percentage of listings indicating the presence of sorbitol was: manufacturer's product information (79 percent), Facts and Comparisons (52 percent), and AHFS Drug Information 91 (13 percent). Only three of the 54 products had the exact sorbitol content stated in any source.

Fat emulsion effects on prothrombin time in warfarin anticoagulated patients: an in vitro study.

The effect of lipid emulsions on prothrombin time in blood from anticoagulated patients was determined. Blood samples were obtained from 23 patients therapeutically anticoagulated with warfarin (prothrombin time 1.3-2.0 x control). Varying amounts of an intravenous lipid emulsion (Intra-lipid) were added to the blood to simulate concentrations seen in vivo with a constant lipid infusion. The prothrombin time was measured on the plasma from these samples and compared to the prothrombin time of the plasma samples without lipid. The mean decrease in prothrombin times were: 0.29 sec at 50 micrograms/ml, 0.23 sec at 100 micrograms/ml, and 0.29 sec at 200 micrograms/ml. All concentrations showed a statistically significant decrease (p less than 0.05) when compared to the control by the Scheffe test. Lipid emulsions appear to decrease the prothrombin times in anti-coagulated patients. The differences however, were small and not of clinical significance at the concentrations tested.

Warfarin resistance and enteral feedings.

Nutritional support via enteral feeding tubes may interfere with the response to medications by a number of mechanisms. A 31-year-old, white man was admitted after sustaining a gunshot wound to the chest and mandible. Subsequently, the patient developed pulmonary emboli documented by angiography. Attempts at anticoagulation with oral warfarin were unsuccessful while the patient was receiving 50-100 ml/hr of Osmolite through an Entriflex feeding tube and intermittent oral Ensure Plus supplements. Discontinuation of the Osmolite resulted in a prompt prolongation of the prothrombin time. The Ensure Plus was continued and adequate prothrombin times were achieved on 7.5 to 10 mg of warfarin daily. The total amount of vitamin K received from the enteral feedings ranged from 50 to 115 micrograms/day, which is less than the normal daily intake of 300 to 500 micrograms. Previous reports of warfarin resistance implicated older enteral feeding products with a much higher vitamin K content. Difficulty with anticoagulation may still be experienced with the newer formulations. It is unknown whether the vitamin K content or malabsorption of warfarin is the mechanism of resistance.

Microbiology of adult cellulitis.

Needle aspiration of cellulitis sites is commonly advocated to assist in the identification of causative organisms. Twenty-five nondiabetic, adult patients with a clinical diagnosis of cellulitis had site aspirations and blood cultures obtained before antibiotic therapy was initiated. Site cultures were positive in 6 of 25 patients. Blood cultures were positive in 4 of 25 patients. All organisms except one (Enterobacter agglomerans) were staphylococci or streptococci. The gram-negative bacilli were not believed to be a pathogen based on the patient's prompt response to nafcillin. In adult patients who do not have complications, the use of needle aspiration was not supported. Empiric treatment of cellulitis aimed at gram-positive cocci appears to be sufficient.

Warfarin resistance associated with intravenous lipid administration.

Intravenous lipids have been shown to have varying effects on coagulation parameters. A patient with short bowel syndrome and recurrent thrombotic episodes who required both intravenous lipids and anticoagulation is described. A constant infusion of a soybean oil emulsion (Intralipid) in his parenteral nutrient solution was demonstrated to interfere with the anticoagulant effect of warfarin. Termination of the infusion and rechallenge with warfarin resulted in prolongation of his prothrombin time to the therapeutic range. Reinstitution of a lipid-free parenteral nutrition regimen has allowed for successful continuation of warfarin therapy.

Warfarin therapy. The effect of heparin on prothrombin times.

Sharp decreases in the prothrombin time after discontinuing heparin have been reported in patients undergoing oral anticoagulant therapy. Twenty-five patients receiving continuous intravenously administered heparin and orally or intravenously administered warfarin were studied. All patients had prothrombin times greater than 1.40 times control, and activated partial thromboplastin times 1.5 to three times control before discontinuing heparin therapy. Prothrombin times on the heparin infusion and four to six hours after it was discontinued were compared. The mean change in the prothrombin time was -1.60 s with a range of +0.8 to -5.5 s. Eight (32%) of 25 patients had a decrease of greater than 2 s. The decrease in prothrombin time correlated poorly with heparin dose or activated partial thromboplastin time in patients taking heparin. Since the change in prothrombin time is unpredictable, a repeated prothrombin time is recommended after stopping heparin therapy prior to discharging a patient.

Automated administration of intermittent intravenous doses.

The cost difference of administering cimetidine 300 mg via intravenous piggyback (IVPB) every six hours by a conventional separate container system versus using an automated intermittent i.v. administration system was evaluated. The study was conducted in two phases. Phase 1 documented the amount of drug waste with the two systems, and phase 2 examined the practical use of the IVAC Multi Dose System. Nurses who administered the medication using the multiple-dose system completed a questionnaire on its operation. A materials cost analysis was performed to compare the two methods. The two systems were found to have approximately equivalent amounts of drug waste over the 30-day evaluation period of phase 1. The mean percentage of doses wasted was 12.2% with the conventional single-dose minibag method and 12.7% with the automated multiple-dose method. The multiple-dose system had a lower cost per dose of cimetidine ($2.25 versus $3.47). These savings appear to outweigh the cost of the additional equipment necessary for the automated system. The majority of nurses preferred the multiple-dose system. Potential problems encountered in accurately delivering doses with the multiple-dose automated system were identified, and possible solutions are suggested. The use of an automated multiple-dose i.v. administration system can potentially decrease the materials cost portion of drug administration. The total impact on hospital costs needs to be evaluated, and other comparisons with alternative administration systems need to be performed.

Warfarin absorption after massive small bowel resection.

Small bowel resection is often accompanied by malabsorption and nutritional deficiencies. Malabsorption of drugs may also occur; however, few reports have been published. We treated five patients with oral warfarin for thrombotic problems after substantial small bowel resection. All five had a documented hypoprothrombinemic response to the warfarin (patient prothrombin time: control greater than 1.5). Maintenance warfarin doses were up to 10 mg/day. Oral warfarin appears to be well absorbed after removal of the majority of the jejunum and ileum. This may indicate a proximal site of warfarin absorption.