Comparison of two low-molecular-weight heparin dosing regimens for patients undergoing laparoscopic bariatric surgery.

BACKGROUND: Venous thromboembolic events (VTE) are a morbidity and mortality concern for patients undergoing laparoscopic bariatric surgery. Although VTE prophylaxis is recommended in bariatric surgery, data with regard to monitoring and appropriate dosing of low-molecular-weight heparin are limited. Enoxaparin prophylactic doses ranging from 30 to 60 mg every 12 h have been used for this population. The authors hypothesized that higher prophylactic enoxaparin doses (60 mg) would yield more appropriate heparin antifactor Xa (anti-Xa) concentrations than the 40-mg dosage for bariatric surgery patients. METHODS: Patients undergoing laparoscopic bariatric surgery by two surgeons during a 5-month period at one institution received enoxaprin 40 or 60 mg every 12 h. Anti-Xa levels were obtained 4 h after the first and third doses. Therapeutic levels were defined as 0.18 to 0.44 U/ml. Paired and unpaired t-tests and chi-square tests were used for statistical analysis as appropriate. RESULTS: The first-dose mean anti-Xa concentration was 0.173 U/ml in the 40-mg group and 0.261 U/ml in the 60-mg group (p < 0.005), compared with the third-dose mean anti-Xa levels of 0.21 and 0.43 U/ml, respectively (p < 0.001). After the third dose of enoxaparin, the percentage of patients with anti-Xa concentrations who remained subtherapeutic showed a statistically significant difference: 44% in the 40-mg group versus 0% in the 60-mg group (p = 0.02). However, no supratherapeutic anti-Xa concentrations were observed in the 40-mg group, whereas 57% of the third-dose levels in the 60-mg group were supratheraputic. The highest anti-Xa level was 0.54 U/ml, but none of the patients with this level experienced bleeding events. CONCLUSIONS: Enoxaparin 60-mg every 12 h was superior to a dosage of 40 mg every 12 h in achieving therapeutic anti-Xa concentrations and avoiding subtherapeutic anti-Xa levels. However, the 60-mg group had a number of supratherapeutic levels. Future studies evaluating the relationship of anti-Xa concentrations and outcomes with larger numbers of morbidly obese patients are needed.

Vitamin K-independent warfarin resistance after concurrent administration of warfarin and continuous enteral nutrition.

STUDY OBJECTIVE: To assess the influence of withholding continuous enteral nutrition for 1 hour before and after warfarin administration compared with the coadministration of warfarin with continuous enteral nutrition on changes in international normalized ratios (INRs). DESIGN: Retrospective, crossover case series. SETTING: Intensive care units of a university-affiliated medical center. PATIENTS: Six adults who required nutritional support for at least the first 10 consecutive days of warfarin therapy; during that 10-day period, they had a period of at least 3 consecutive days during which the enteral feeding was withheld for 1 hour before and after warfarin administration, and had a period of at least 3 consecutive days when feedings were not withheld during warfarin administration. Patients with advanced liver disease and those who received therapies, during the observation period, that significantly alter warfarin metabolism were omitted from the study. MEASUREMENTS AND MAIN RESULTS: The change in INR during the 3-day observation period when feedings were withheld for 1 hour before and after warfarin administration was significantly different versus the change in INR during coadministration of warfarin with continuous feeding (mean +/- SD 0.74 +/- 0.66 vs -0.13 +/- 0.81, p < or = 0.05). This difference in INR response occurred despite the administration of similar dosages of warfarin (5.6 +/- 2.1 vs 5.7 +/- 2.1 mg/day, p>0.05). Also noted was a clinically irrelevant, but statistically significant, difference in vitamin K intake between treatment periods (77 +/- 36 mug/day when feedings were withheld vs 102 +/- 28 microg/day when feedings were not withheld, p < or = 0.05). CONCLUSION: Continuous enteral nutrition should be withheld for 1 hour before and after warfarin administration to prevent enteral nutrition-associated warfarin resistance.

Anti-Xa levels in bariatric surgery patients receiving prophylactic enoxaparin.

BACKGROUND: Limited data exist regarding efficacy and dosing of low-molecular-weight heparins, including enoxaparin, for morbidly obese patients. Prophylactic doses of 30 to 60 mg every 12 h have been described in bariatric surgery patients with appropriate anti-Xa levels reported between 0.18 and 0.6 units/mL. METHODS: Fifty-two laparoscopic gastric bypass or banding patients were enrolled. Patients were divided into two groups by the dose of enoxaparin that was given: Group 1--enoxaparin 30 mg every 12 hours--and Group 2--enoxaparin 40 mg every 12 h. Anti-Xa levels were obtained 4 h after the first and third doses. Levels between 0.18-0.44 units/mL were considered appropriate. RESULTS: There were 19 patients (74% female, mean body mass index [BMI] 48.4 kg/m2) in Group 1 and 33 patients (82% female, mean BMI 48.5 kg/m2) in Group 2. In Group 1, anti-Xa levels were 0.06 and 0.08 units/mL after the first and third doses, respectively. In Group 2, anti-Xa levels were 0.14 and 0.15 units/mL after first and third doses, respectively (p = NS). There was a statistically significant difference in anti-Xa levels between Group 1 first dose and Group 2 first dose (p < 0.05) and between Group 1 third dose and Group 2 third dose (p < 0.05). Percentage of appropriate anti-Xa levels at first dose differed 0% vs. 30.8% (Group 1 vs. Group 2; p = 0.01) and at third dose 9.1% vs. 41.7% (Group 1 vs. Group 2; p = 0.155). CONCLUSION: When prophylactic dose enoxaparin of 30 mg every 12 h was changed to 40 mg every 12 h in bariatric surgery patients, anti-Xa levels significantly increased with prophylactic dose enoxaparin in bariatric surgery patients. The percentage of appropriate levels also increased; however, more than half of the patients receiving 40 mg every 12 hours failed to reach therapeutic levels. No levels were supratherapeutic. Dosage of 40 mg every 12 h may not be sufficient for bariatric surgery patients.

Current strategies for managing the patient with sepsis.

Key elements of the current approach to treating sepsis are reviewed, and examples are given to illustrate the difficulty of designing and evaluating trials in sepsis. A patient with sepsis is likely to have symptoms characteristic of the systemic inflammatory response syndrome. Initially, ruling out noninfective causes, locating the site of infection, and obtaining cultures before beginning antimicrobial therapy are critical. Aggressive fluid resuscitation and hemodynamic support are used to restore tissue perfusion and normalize cellular metabolism. Vasopressor therapy with dopamine or norepinephrine is needed in patients unresponsive to fluid resuscitation. Dobutamine should be administered in patients whose cardiac output is inadequate despite optimization of fluids and pressors. Supportive care includes deep vein thrombosis prophylaxis, nutrition support, stress ulcer prophylaxis, and management of acute lung injury. Attempts to modify the sepsis response and improve the outcome in these patients have yielded limited benefits. Recent small studies have shown benefits with low-dose hydrocortisone in patients with refractory sepsis. One challenge in study design is that a therapy may target a subset of patients that cannot be identified at the outset. Management of patients with suspected or documented sepsis focuses on hemodynamic support, appropriate antimicrobial therapy, and other supportive care.