Evaluation of a standardized protocol using lepirudin or argatroban for heparin-induced thrombocytopenia.

STUDY OBJECTIVE: To evaluate the effectiveness of our institutions heparin-induced thrombocytopenia (HIT) protocol in achieving a therapeutic activated partial thromboplastin time (aPTT) and to evaluate patient outcomes related to bleeding and thrombotic events before and after protocol implementation. DESIGN: Retrospective, single-center, pre- and post- assessment of a protocol previously approved at our institution. SETTING: 400-bed community hospital serving surrounding rural populations with emphasis in cardiothoracic surgery. PATIENTS: Retrospective chart review based on drug charge data identified 29 patients that received either argatroban or lepirudin for greater than 24 hours. Nineteen patients received either argatroban or lepirudin prior to HIT-protocol implementation, while the remaining ten received either drug after the HIT protocol was implemented. INTERVENTION: Implementation of HIT protocol occurred in March 2009. Patients were divided into pre-protocol and post-protocol groups. RESULTS: Primary outcome was to evaluate the number of therapeutic, subtherapeutic, and supratherapeutic aPTTs between two groups. In the pre-protocol group, aPTTs were therapeutic, subtherapeutic, and supratherapeutic 48.5% (164/338), 14.2% (48/338), and 37.2% (126/338) of the time, respectively. Meanwhile aPTTs in the post-protocol group were therapeutic, subtherapeutic, and supratherapeutic 46.6% (89/191), 22% (42/191), and 31.4% (60/191) of the time, respectively. The number of subtherapeutic aPTTs was statistically higher in the post-protocol group compared to the pre-protocol group. Secondary endpoints included the number of bleeding events and number of thrombotic events. None of the secondary endpoints reached statistical significance. Time to therapeutic aPTT was also evaluated: in the pre-protocol group median time (range) was 15 hours (2-108.6) compared to 8.1 hours (2.3-94.2) in the post-protocol group. CONCLUSIONS: Adoption and implementation of HIT protocol at our institution resulted in significantly more subtherapeutic aPTTs as compared to time prior to protocol. Although not statistically significant, the time required to obtain therapeutic aPTT was reduced by almost 50% after protocol implementation, which could be of clinical importance. Larger studies are needed to continue to assess if standardized protocols are effective in treatment of HIT.

Continuous versus intermittent infusion of prophylactic cefoxitin after colorectal surgery: a pilot study.

STUDY OBJECTIVE: To compare 30-day postoperative surgical site infections (SSIs) and rates of antibiotic discontinuation within 24 hours after surgery in patients receiving continuous-infusion versus intermittent-infusion cefoxitin for postoperative antibiotic prophylaxis. DESIGN: Retrospective, cohort-matched pilot study. SETTING: Tertiary-care medical center. PATIENTS: One hundred sixteen adults undergoing colorectal surgery between August 1, 2004, and February 28, 2007. INTERVENTION: Cefoxitin prophylaxis was administered as a continuous infusion in 58 patients and as an intermittent infusion in 58 patients (controls). The controls received weight-based doses of cefoxitin (1 g if < or = 80 kg or 2 g if > 80 kg) every 8 hours for three doses, starting 3 hours after surgery and completed within 24 hours. The continuous-infusion group were given weight-based doses of cefoxitin (3 g if < or = 80 kg, 6 g if > 80 kg), started immediately after surgery and infused over 20 hours. MEASUREMENTS AND MAIN RESULTS: Patients and controls were matched according to colorectal procedure and risk index category. They were stratified by medium risk (50 patients) and low risk (66 patients) for the end point of 30-day postoperative SSI. For the 25 medium-risk patients who received the continuous infusion, a 50% relative reduction in the 30-day postoperative SSI rate was observed with continuous versus intermittent infusion (4% vs 8%, p=0.55). For the 66 low-risk patients, 30-day postoperative SSI rates were equal (3%) with both intermittent and continuous infusions. Risk stratification was not performed for the proportion of patients who discontinued antibiotic prophylaxis within 24 hours after surgery. All patients receiving the continuous infusion met this end point compared with 47 (83.9%) of the 56 controls (p=0.0015) included in the analysis. CONCLUSION: Compared with intermittent infusion, continuous infusion of cefoxitin for postoperative prophylaxis resulted in a nonsignificant reduction in 30-day postoperative SSI rates in medium-risk patients undergoing colorectal surgery. Continuous infusion also resulted in reliable discontinuation of postoperative prophylaxis within 24 hours.

Cefazolin tolerance does not predict ceftriaxone hypersensitivity: unique side chains precipitate anaphylaxis.

A 48-year-old woman with a questionable history of an unspecified ceftriaxone allergy was treated with cefazolin for surgical antibiotic prophylaxis. After she tolerated cefazolin therapy for 4 days, the medical staff concluded that her allergy history was inaccurate, and she was treated with intravenous ceftriaxone for suspected nosocomial pneumonia. Approximately 10 minutes after the start of the infusion, the patient experienced anaphylaxis. Initial symptoms of oral angioedema and laryngopharyngeal constriction progressed to dyspnea, tachypnea, hypotension, and tachycardia, all of which quickly resolved after immediate treatment with hydrocortisone, diphenhydramine, and epinephrine. Skin testing with cefazolin, cefepime, and ceftriaxone revealed that the likely allergic determinant mediating the patient's hypersensitivity reaction was the unique ceftriaxone R2 side chain and not the beta-lactam ring, which initially was suspected by the physician. Immunoglobulin E-mediated hypersensitivity reactions to cephalosporins may occur due to antibody complexes with the beta-lactam ring or various cephalosporin side chains. Misconceptions regarding the nature of cephalosporin allergies complicate antibiotic selection for patients with questionable allergy histories and may lead to inappropriate drug reexposure and anaphylaxis. Detailed understanding of the antigenic determinants that mediate hypersensitivity reactions is essential for clinicians to avoid type 1 reactions in patients with a suspected allergy to cephalosporins.

Drotrecogin alfa (activated) approved for treatment of severe sepsis.

Drotrecogin alfa (activated) is a recombinant form of human activated protein C that has been shown to reduce mortality in severely septic patients with a high risk of death. Given the complexity of the inclusion and exclusion criteria, the stability and unique duration of infusion, and the cost of treatment, therapy with this agent should be carefully considered to ensure its appropriate use.