A survey of anesthesiologists' and nurses' attitudes toward the implementation of an Anesthesia Information Management System on a labor and delivery floor.

BACKGROUND: An anesthesia information management system (AIMS) is most frequently used in the operating room, but not on labor and delivery (L&D). The purpose of this study is to describe the implementation of an AIMS on L&D and the attitudes of practitioners (anesthesiologists and nurses) toward the system. METHODS: The anesthesiology survey focused on satisfaction with the L&D AIMS, comparison of the L&D AIMS with a handwritten anesthesia record, and comparison of the L&D AIMS with the operating room AIMS. The nursing survey focused on nursing satisfaction with the L&D AIMS and comparison of the L&D AIMS with a handwritten anesthesia record. RESULTS: Most anesthesiologists (76%) were satisfied with the L&D AIMS and 73% would not want to revert back to the paper record. However, most anesthesiologists felt the operating room AIMS was either superior or equal to the L&D AIMS. Although few nurses (4%) preferred the anesthesiologists revert back to the handwritten record overall, the nurses were neutral in their assessment of the AIMS. Most of the criticism related to the location of the system; 56% believed it was not in a convenient location and 74% thought the AIMS equipment "got in their way". CONCLUSIONS: Overall, the anesthesiologists and nurses are satisfied with the L&D AIMS and would not want to switch back to a handwritten record. We conclude that AIMS should not be limited to the operating room setting and can successfully be used in L&D.

The use of a Bayesian forecasting model in the management of warfarin therapy after total hip arthroplasty.

This study was performed to compare the computer-based and physician-based management of warfarin therapy after total hip arthroplasty (THA). The computer-assisted and control groups of patients were placed on warfarin postoperatively and followed for a 1-month period. A significant difference (P<.05) was found between the mean number of days needed to reach therapeutic anticoagulation in the control group (4.7+/-3.0 days) and the experimental group (2.8+/-1.4 days) and the proportion of patients in each group who were discharged with a subtherapeutic international normalized ratio (INR) (INR <1.5). The computer-based management of warfarin therapy was more efficient than unaided physician-based management and therefore may lead to improved, cost-effective patient care by reducing length of hospital stay and complications attributable to nontherapeutic anticoagulation in THA patients.

Desmin 370 (Opocrin SpA/Alfa Wassermann).

Alfa Wassermann, in collaboration with Opocrin, is developing Desmin 370, an antithrombotic agent which is in phase III clinical trials for the treatment of deep vein thrombosis, and may have potential in the treatment of pulmonary embolism. The antithrombotic effect is attributed to the inhibition of thrombin generation, potentiation of heparin cofactor II activity, and local fibrinolytic effects. Opocrin is the product patent holder (EP-00221977 and US-04973580), while Alfa Wassermann is the developer and responsible for the clinical research.

Developing and testing a system to improve the quality of heparin anticoagulation in patients with acute cardiac syndromes.

We have taken a stepwise approach to improving the dosing of continuous intravenous heparin in patients with acute coronary syndromes. Our primary objective was to use computer modeling to develop a nomogram for managing heparin therapy and to put in place a continuous quality monitoring system to evaluate the nomogram's effectiveness. We prospectively collected data on 41 patients with unstable angina or myocardial infarction who were treated with heparin. Their response to heparin was computer modeled and the dose to achieve an activated partial thromboplastin time (aPTT) ratio of 2.0 was established. This dose was regressed against all demographic characteristics to establish predictors of heparin dose (phase I). The regression formula was used prospectively in 110 patients to initiate the infusion rate of heparin and a bolus dose to achieve an aPTT ratio of 2.5. Subsequent dosage adjustments were achieved by computer modeling the patient's aPTT response (phase II). A nomogram was developed that simulated the decisions achieved using computer-assisted methods. This was retrospectively tested and then prospectively tested in 50 patients using nursing staff (phase IV). The nomogram was then made generally available (phase IV) and has been tested in an additional 310 patients. Phase I: Of the original 41 patients, 32% of the aPTT ratios were in the therapeutic range, 36% were supratherapeutic, and 32% were subtherapeutic after the first 24 hours. Phases II and III resulted in 85% of the aPTT ratios between 1.5 and 2.5 at 24 hours. Phase 4 had similar results in 310 patients. The use of computer-assisted or a computer-generated nomogram to adjust heparin therapy results in better control of heparin therapy than using standard methods.

Effect of weight, sex, age, clinical diagnosis, and thromboplastin reagent on steady-state intravenous heparin requirements.

BACKGROUND: There is a significant direct relationship between steady-state intravenous heparin dose requirements and total body weight. Less is known about whether sex, age, clinical diagnosis, and the thromboplastin used to measure the activated partial thromboplastin time (aPTT) affect heparin dose requirements. METHODS: Four cohorts of patients treated with intravenous heparin were gathered from 3 hospitals: 2 cohorts with deep vein thrombosis (DVT) and 2 cohorts with coronary artery disease (CAD). For each clinical diagnosis, half the patients were monitored using one aPTT reagent and the remainder were monitored using a second reagent. Heparin doses and aPTT measurements were recorded, and the dose necessary to achieve an aPTT ratio of 2.0 was calculated using a computer software program. RESULTS: We analyzed the records of 340 patients: 165 with DVT and 175 with CAD. Using analysis of variance, there was a significant difference in the steady-state heparin requirements among patients with DVT compared with patients with CAD (P < .001). For each clinical diagnosis, the use of a different thromboplastin reagent did not affect heparin dose requirements (P > .42). Linear regression modeling disclosed that the steady-state heparin dose for patients with DVT was a function of weight plus an effect modifier involving weight and age, whereas for patients with CAD there was only a weak relationship with weight. CONCLUSIONS: Steady-state heparin dose requirements were significantly different in patients with DVT compared with patients with CAD, suggesting that different dosing nomograms are needed for each condition. For patients with DVT, the accuracy of the initial heparin dose estimate may be improved by considering the patient's age and weight.

Changes in plasma warfarin levels and variations in steady-state prothrombin times.

OBJECTIVE: To determine the relative contribution of changes in the plasma warfarin level to variation in the serial steady-state prothrombin times. METHODS: This was a prospective observational cohort study performed at two outpatient anticoagulation clinics. Serial prothrombin times and paired plasma total warfarin levels were determined in a convenience sample of otherwise healthy patients who required long-term oral anticoagulation therapy with warfarin. RESULTS: Serial measurements were obtained from 129 patients, 60 of whom provided three or more serial samples. Analysis of covariance showed a highly significant (p = 0.0001) relationship between the anticoagulant effect and the logarithm of the warfarin concentration (R2 = 0.75), with 15.3% of the total variance attributable to the effect of warfarin and 31.1% attributable to individual variation in sensitivity to warfarin. In an analysis of the subjects who had three or more serial measurements, the mean weighted correlation coefficient for the relationship between the logarithm of the warfarin concentration and the anticoagulant response varied widely, from strongly negative to strongly positive, and as the range of observed prothrombin times increased, stronger positive correlation was observed. CONCLUSIONS: In this cohort, the plasma warfarin level was a strong predictor of observed changes in serial prothrombin time measurements. However, the correlation between clotting times and warfarin levels varied widely among subjects, particularly when the range of observed prothrombin times was moderate. This suggests that in these subjects, other factors, such as measurement error or pharmacodynamic changes, played a major role.

Computer-assisted dosing of heparin. Management with a pharmacy-based anticoagulation service.

BACKGROUND: Expert consultation by means of established practice guidelines has been shown to lead to improved accuracy of inpatient anticoagulation therapy, with a reduction in the frequency of hemorrhagic complications. We evaluated a different strategy to improve the accuracy of in-hospital anticoagulation: pharmacy-based, computer-assisted dosing of intravenous heparin therapy. METHODS: Patients treated with computer-assisted dosing of heparin (N = 131) were compared with a randomly selected historical cohort (N = 57) in whom heparin therapy was managed by the primary physician. All patients treated by the pharmacy team received a bolus of heparin, 70 U/kg of ideal body weight, except for patients with pulmonary embolism, who received 100 U/kg of ideal body weight. A computer-generated infusion dose was selected (generally 13 to 16 U/kg per hour). The target was an activated partial thromboplastin time (APTT) ratio of 1.8 times the patient's baseline APTT, with a therapeutic range of 1.5 to 2.5 times baseline. Computer-assisted dosage recommendations were generated after each APTT measurement. RESULTS: In the historical control group, 62% of the patients achieved a therapeutic APTT during the first 24 hours; 17% failed to reach a therapeutic level by 48 hours. The median time to reach a therapeutic APTT was 15 hours. Of all 696 APTTs in this group, 42% were below, 43% in, and 15% above the therapeutic range. In the computer-assisted group, 90% achieved a therapeutic APTT within 24 hours (P < .001); 97% had a therapeutic APTT by 48 hours (P < .01). The median time to achieve a therapeutic APTT was 7 hours (P < .001). Of all 880 APTTs in this group, 17% were below, 75% in, and 8% above the therapeutic range (P < .001). CONCLUSIONS: Pharmacy-based, computer-assisted dosing of heparin is feasible and results in faster and more accurate anticoagulant dosing.

A prospective randomized comparison of the accuracy of computer-assisted versus GUSTO nomogram--directed heparin therapy.

Failure to adequately anticoagulate the blood of patients receiving recombinant tissue plasminogen activator (TPA) leads to greater rates of rethrombosis. In a multicentered, randomized trial in 51 patients we compared the ability to achieve and maintain therapeutic anticoagulation by use of computer-assisted heparin therapy or the GUSTO (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) heparin nomogram guidelines in patients with myocardial infarction treated with recombinant TPA. Heparin therapy was initiated with either computer-generated starting doses or GUSTO guideline starting doses. Activated partial thromboplastin times were measured every 6 to 8 hours for the first 24 hours. The therapeutic range used in this trial was 1.5 to 2.5 times the patient's baseline activated partial thromboplastin time (APTT). Ninety-four percent of the APTT ratios in the computer group were equal to or greater than 1.5 in the first 24 hours compared with 78% in the GUSTO group (p < 0.009). No significant difference in bleeding was found (7.7% for GUSTO; 4.2% for computer). Incremental time-dependent changes in heparin dose were found (day 1, 1110 +/- 243 units/hr, APTT ratio = 2.5 +/- 1.4; day 3, 1380 +/- 374 units/hr, APTT ratio, 1.9 +/- 0.4). Computer-assisted heparin therapy TPA results in superior anticoagulation accuracy compared with the GUSTO guidelines. In addition, the pharmacodynamic response to heparin changes in the 2 to 3 days after administration of TPA, leading to greater heparin requirements.

Treatment of proximal deep-vein thrombosis using subcutaneously administered calcium heparin: comparison with intravenous sodium heparin.

In a prospective, randomized clinical trial we compared the efficacy of subcutaneously (SC) administered (every 8 h) calcium heparin to intravenous (IV) sodium heparin in the treatment of proximal deep-vein thrombosis (DVT). A secondary objective was to give enough heparin to achieve a therapeutic anticoagulant effect by the end of the first 24 h. Five of 36 patients (14%) in the SC heparin group failed to achieve a therapeutic anticoagulant effect by the end of the first 24 h compared to 2 of 23 patients (9%) in the IV group (p = NS; 95% CI for true difference = -11.7% to 22.1%). Two of 31 patients (6.5%) in the SC group had venographic evidence of clot propagation compared to 1 of 19 patients (5.3%) in the IV group (p = NS; 95% CI for true difference = -12.4% to 14.8%). The rate of major hemorrhagic complications was similar in each group (approximately 15%). We conclude: (1) using a large initial dose of SC heparin, a therapeutic anticoagulant effect can be readily achieved within 24 h, and (2) combining the results of this trial with previous studies, the efficacy of SC administered calcium appears to be comparable to IV sodium heparin.

Predicting pharmacodynamic response to tissue plasminogen activator: a preliminary report.

All thrombolytic agents have produced significant variation in clinical response (patency, reocclusion, bleeding) when administered in recommended doses in patients with myocardial infarction. We have evaluated the in vitro clot lysis response in 19 normal subjects and the pharmacodynamic response to tissue plasminogen activator (TPA) in 9 patients with myocardial infarction using a new, fresh, whole blood clot lysis system. Further, we have developed a Bayesian forecasting system for predicting response to TPA. Sensitivity to TPA (slope of the concentration/log response curve) varied significantly in patients with myocardial infarction (mean, 1.05 +/- 1.1). The mean clearance, volume of distribution, and half life were 55 +/- 13 L/h, 41 +/- 47 L, and 0.41 +/- 0.46 h. Using from zero to three clot lysis feedback times, the mean percentage mean absolute error varied from 65 to 16.4%. A relationship between mean clot lysis time and clinical reperfusion was established. Thus, a system for quantitating and predicting response to TPA was developed and successfully tested. Future extensive clinical trials will be necessary to evaluate fully the use of this system in clinical practice.

Outpatient management of warfarin therapy: comparison of computer-predicted dosage adjustment to skilled professional care.

In a prospective, randomized clinical trial, we compared the accuracy of warfarin dosage-adjustments predictions using a computer program to the skill of an experienced anticoagulation nurse-specialist. The computer program predicts the steady state warfarin dose by applying Bayesian forecasting techniques to a mathematical model of the dynamic pharmacologic response to warfarin. Fifty patients who were receiving chronic warfarin therapy and who required a dosage adjustment because their prothrombin time was greater than or equal to 2 s away from their target prothrombin time were enrolled. The baseline characteristics of each group were similar, including the mean of the absolute value of the differences between initial prothrombin times and corresponding target prothrombin times. After a new a new warfarin dose was predicted, the prothrombin time was measured at least 7 days after dosage adjustment. Overall, the results in each group were comparable. There was no significant difference between groups and the mean of the absolute value of the differences between final prothrombin times and target prothrombin times, nor was there a difference in the proportion of patients who had a final prothrombin time within 2 s of the target prothrombin time. We conclude that the accuracy of warfarin dosage adjustments made using computer modeling is comparable to the skill of an anticoagulation nurse-specialist.

Predicting the daily prothrombin time response to warfarin.

Our objective was to evaluate the effectiveness of a computer program to predict daily prothrombin time (PT) response to warfarin therapy using prospectively collected data. The program's predictive performance (precision) and accuracy (bias) were evaluated using fraction mean absolute error and fraction mean error, respectively. We analyzed data from 40 patients using from zero to nine PT feedbacks. The fraction mean absolute error varied from 0.058 to 0.13. The program utilized a pharmacokinetic/pharmacodynamic Bayesian forecasting system to predict prothrombin response.

A novel whole blood capillary technic for measuring the prothrombin time.

The prothrombin time (PT) is frequently performed to monitor anticoagulant therapy. Although relatively simple to perform, it requires venipuncture and laboratory resources for sample handling and analysis. A recently developed capillary whole blood device that uses fingerstick samples was evaluated. Paired capillary whole blood and reference plasma PTs were performed in 858 samples from 732 subjects. The PT for normal volunteers (n = 193) was 11.8 +/- 0.9 seconds with the use of the new instrument and 12.1 +/- 0.5 seconds with the use of the reference method. In samples from 539 patients receiving anticoagulants, the correlation coefficient between the two methods was 0.96. Venous whole blood without anticoagulant and capillary whole blood gave equivalent results, which suggests that the fingersticks do not effect the quality of the specimen. Variation in hematocrit between 23.4% (0.34) and 53.8% (0.538) did not alter the performance of the instrument. The new instrument is easy to use and may allow testing by nonlaboratory personnel and patients. It obviates the need for venipuncture, provides immediate results, and appears to be comparable in accuracy to current reference methods.

Effect of using warfarin plasma concentrations in Bayesian forecasting of prothrombin-time response.

The predictive performance of a Bayesian computer program using prothrombin-time (PT) response data with and without warfarin plasma concentrations to forecast patients' PTs at the time of hospital discharge was evaluated. A log-linear pharmacokinetic-pharmacodynamic model was used to describe and predict warfarin dose response in patients recently started on warfarin sodium. Individual patients' pharmacodynamic variables relating warfarin concentration to clotting-factor synthesis were obtained by Bayesian nonlinear regression analysis. Pharmacokinetic values for warfarin clearance and volume of distribution were either calculated using nonlinear regression from measured plasma warfarin concentrations or estimated based on literature-derived population regression equations. Percent mean absolute prediction error (precision) and prediction error (bias) for PT predictions were compared among and between analysis methods that used only literature data to estimate PT response and methods that used zero to five PTs with or without warfarin plasma concentrations. Eleven women and eight men completed the study. Predictions after four days of warfarin therapy using PT measurements beginning after either the first or third warfarin dose were clinically useful regardless of whether warfarin concentrations were used in the predictions. Predictions using fewer than four PT measurements were imprecise and biased. The Bayesian method in this study provided good predictions of PTs immediately before hospital discharge based on warfarin dosing and PT response after either four or five days of therapy. The use of warfarin plasma concentrations in the pharmacokinetic-pharmacodynamic model used here appears unwarranted.