Evaluation of very low-dose subcutaneous vitamin K during postoperative warfarin therapy.

STUDY OBJECTIVE: To determine the effect of very low-dose subcutaneous vitamin K (SCVK) compared with withholding warfarin for above-target international normalized ratio (INR) values after joint surgery. DESIGN: Historical controlled study. SETTING: University hospital. SUBJECTS: One hundred thirty-nine patients beginning warfarin after total joint surgery. INTERVENTION: For a high INR, warfarin was either withheld or SCVK 100, 300, or 400 microg was administered, depending on INR value. MEASUREMENTS AND MAIN RESULTS: The primary outcome was change in INR from the day of intervention (day 1) to the next day (day 2). Adjusting for day 1 INR, the mean day 2 INR was 2.10 (95% confidence interval [CI] 1.86-2.33) after SCVK, compared with 2.73 (95% CI 2.50-2.96) in controls. This corresponded to declines of -0.72 and -0.08, respectively (p=0.001). CONCLUSION: In orthopedic patients starting warfarin therapy, very low-dose SCVK was more effective than withholding warfarin in reducing high INRs. Investigations in other populations and assessment of the effect of low-dose SCVK on postoperative bleeding are indicated.

The association of vitamin K status with warfarin sensitivity at the onset of treatment.

We investigated the association of vitamin K status with warfarin sensitivity among 40 orthopaedic patients beginning perioperative algorithm-dosed warfarin. Baseline vitamin K status was assessed using plasma vitamin K-1 and vitamin K-1 2,3 epoxide concentrations, and a questionnaire-based estimation of usual vitamin K intake. Warfarin sensitivity was assessed as the increase in the International Normalized Ratio (INR) after two doses of 5 mg of warfarin and as the 4-d accumulation of under-gamma-carboxylated prothrombin (PIVKA-II), adjusted for warfarin dose requirement. Multivariate models were used to assess vitamin K variables as predictors of warfarin sensitivity. The mean INR increase was 0.53 U and the mean PIVKA-II increase was 771 ng/ml/mg warfarin. Demographic factors were not associated with warfarin response. For each 1 standard deviation (SD) lower value of plasma vitamin K-1, but not the other vitamin K variables, the INR rose 0.24 U (P < or = 0.01). A higher usual vitamin K intake and plasma vitamin K-1, and lower plasma vitamin K-1 2,3 epoxide, were all associated with a lower PIVKA-II increase over 4 d. Respective differences in PIVKA-II accumulation per SD increase of each variable were -165, -218 and 236 ng/ml/mg warfarin (all P < or = 0.05). We concluded that dietary and biochemical measures of vitamin K status were associated with early warfarin sensitivity.

Implementation of curriculum guidelines for pharmacology and pharmacotherapeutics in FNP graduate programs: a national survey.

Model Pharmacology and Pharmacotherapeutics Curriculum Guidelines were developed by the National Council of State Boards of Nursing and the National Organization of Nurse Practitioner Faculties and published in 1998. To date, no publication of evaluation of adoption or adherence to these guidelines is available. The purpose of this survey was to determine how family nurse practitioner programs incorporate the guidelines into their curriculum. A mailed self-report questionnaire to 193 schools yielded a 41% response rate. Eighty-five percent (n = 68) of the programs have not yet fully integrated the guidelines into their curriculum. Difficulties addressing the extensive content within a 3-credit course and the challenges of teaching students with varied clinical backgrounds and knowledge levels were frequently cited. Although further study of achievement of the guidelines is necessary, an increase in credit allocation, consideration of a conceptual approach to the topic, and use of varied teaching strategies may make achievement of the guidelines more realistic.

Anaphylactoid reaction to muromonab-CD3 in a pediatric renal transplant recipient.

Muromonab-CD3 (OKT3), a murine IgG2a antibody directed against the T3 (CD3) complex on mature lymphocytes, triggers adverse immune reactions. Anaphylactic reactions have occurred in patients exposed to OKT3 and are mediated by anti-OKT3 IgE antibodies. The reactions are not antibody mediated and can occur within seconds of administration of a mast cell secretogogue. A renal transplant recipient became hypotensive and hypoxic immediately after receiving her first dose of OKT3 and required advanced life support. Serum antibody tests were negative for anti-OKT3 IgG, IgE, and antimouse protein antibodies. To our knowledge, this is the first published report of a patient with an anaphylactoid reaction to the initial infusion of OKT3.

Elevated pancreatic enzymes after extended propofol therapy.

Propofol is a sedative hypnotic agent often administered for intensive care sedation. A 28-year-old man who suffered a severe head injury developed elevated pancreatic enzymes after receiving extended high-dosage propofol therapy. Amylase and lipase values gradually reduced toward normal after the drug was discontinued. Possible propofol-induced pancreatitis was reported with short-term but not with prolonged therapy. A definitive cause-and-effect relationship is unclear since head trauma also was reported to cause elevated pancreatic enzymes. Intensive care practitioners should be aware of this potential reaction.

Regional pharmacokinetics educational program.

An educational program for hospital pharmacists in and near Vermont is described and its impact on departmental clinical practice evaluated. Pharmacists were instructed by practitioners from a single institution in basic pharmacokinetics, practice guidelines for aminoglycoside therapy, and use of a computer program for aminoglycoside dosage determination. Participants completed a multiple-choice precourse test, a similar postcourse test, and a third test six months after class completion. Test scores were compared with those from a control group of pharmacists. Pharmacy directors from study group hospitals completed questionnaires measuring aminoglycoside clinical services before and six months after the program. Compared with the control group, participants scored higher on the postcourse tests. Results from the questionnaire indicate that the program affected clinical practice in almost all participating pharmacy departments. A consistent pharmacokinetic strategy for reviewing aminoglycoside dosages and evaluating serum aminoglycoside concentrations is now practiced in most Vermont hospitals. An educational program originating in one hospital can expand pharmacists' knowledge and influence departmental clinical practice throughout a region.

Multidisciplinary protocol for determining aminoglycoside dosage.

A protocol for determining optimal dosages of aminoglycosides early in therapy is described, and the effectiveness of the protocol is evaluated. The protocol was developed jointly by physicians and pharmacists at a 550-bed hospital to ensure that surgical patients prescribed aminoglycosides were quickly and consistently put on a safe and effective course of therapy. Physicians select an aminoglycoside and calculate a loading dose and initial maintenance dosage by using a nomogram printed on an antimicrobial order form. Nurses are trained to administer and document aminoglycoside doses accurately and to draw blood samples at the correct times. Pharmacists order serum aminoglycoside concentration assays, analyze the results, and recommend changes in dosage when necessary. To evaluate the effectiveness of the dosing protocol, the records of surgical patients treated before and after the protocol was in place were reviewed. Compared with the control group, a higher percentage of patients treated under the protocol were receiving therapeutic, nontoxic dosages of aminoglycosides within 48 hours of the start of therapy. In addition, fewer serum drug concentration tests were ordered per patient under the protocol, and the percentage of concentration determinations useful for analysis was higher. The mean duration of aminoglycoside therapy was identical before and after the protocol was instituted, and nephrotoxic reactions tended to be less common among the protocol patients. An aminoglycoside dosing protocol requiring the cooperation of pharmacists, nurses, and physicians provides a consistent, safe, and effective means of managing aminoglycoside therapy for the hospitalized patient.

Documenting pharmacists' interventions on a hospital's mainframe computer system.

The development and implementation of a code that enables pharmacists to document their clinical interventions in the hospital's computerized patient records is described. To allow data to be entered in patient records from terminals throughout the hospital that are linked to the mainframe computer, a code was developed to summarize each pharmacist recommendation. The coded information is added to the computer entry for the specific drug requiring intervention. A computer program was developed inhouse for generating daily reports of the pharmacist interventions. During an initial 25-day study period, 300 interventions were documented; house staff physicians accepted the pharmacists' recommendations in 257 (85.7%) of these interventions. An additional 17 (6%) of the interventions resulted from physicians' requests for pharmacists' recommendations. In addition to review of all pharmacist clinical interventions, this system allows review of a specific target drug to determine compliance with institutional drug-use guidelines. Through use of the computer program developed at this hospital, information that documents pharmacists' clinical services can be entered directly into patients' records on the hospital's mainframe computer system and retrieved as useful reports.

A practical approach enabling staff pharmacists to prospectively review and dose aminoglycoside therapy.

A simple and effective approach for staff pharmacists to prospectively review and dose aminoglycoside therapy is presented. A departmental policy was established requiring pharmacists to review each adult aminoglycoside order for appropriateness by means of a written audit form. Specific patient data and the aminoglycoside dose is obtained from an antibiotic order form and the patient's creatinine clearance is estimated using a modified Cockcoft and Gault equation. Proper initial dosage regimens are assessed by use of a modified Sarubbi and Hull nomogram or an in-house developed pharmacokinetic software program. The results demonstrate pharmacists were required to intervene in 26.8% of adult aminoglycoside orders. To determine if the percentage of pharmacist intervention changed over time, the results were compared to a sample period selected almost two years later. The percentage of pharmacists intervention was almost identical (25.3%). In both groups, over 90% of the pharmacists's dosing recommendations were accepted by the physician. The outcome of pharmacist's reviews were analyzed during the first study period. In courses of therapy with dosages recommended by pharmacists, therapeutic, non-toxic concentrations of gentamicin and tobramycin (peak 5-10 micrograms/ml, trough less than 2 micrograms/ml) comprised 47/54 (87%) of the interpretable levels. Patients judged by the pharmacist to have an appropriate dose during the initial review had 85/119 (71.4%) of interpretable serum levels in the therapeutic, non-toxic range. Without benefit of a formalized pharmacokinetic service, this program enables all staff pharmacists to perform a review of aminoglycoside therapy which ensures an appropriate initial dosage regimen. The completed aminoglycoside initial audit form serves as a communication tool as well as documentation for the department's quality assurance program.