Comparison of heparin dosing based on actual body weight in non-obese, obese and morbidly obese critically ill patients

Abstract

Background:Obesity is endemic in the United States and obese patients are at increased risk of thromboembolism but little data are available for dosing unfractionated heparin (UFH). We evaluated the relationship between obesity and UFH efficacy during critical illness by examining UFH infusions in non-obese, obese, and morbidly obese critically ill patients.Materials and Methods:Retrospective review of UFH infusions in non-obese, obese, and morbidly obese critically ill patients. Heparin was initiated without a bolus at 16 units/kg/h or 12 units/kg/h in obese and morbidly obese patients. Demographics, UFH dosage/therapy duration, laboratory values, and bleeding events were reviewed for patients receiving UFH for >24 h. Steady state (SS) was defined as the dosage that resulted in three consecutive activated partial thromboplastin times (aPTT) within target range.Results:Sixty-two patients were analyzed including 21 non-obese (mean body mass index (BMI) 24.2 ± 2.3); 21 obese (BMI 34.1 ± 3.1); and 20 morbidly obese (mean BMI 55.3 ± 13.7). Patients had otherwise similar demographics. Although 92% had at least one therapeutic aPTT, only 55% of patients reached SS. Six patients developed minor bleeding, but no major hemorrhagic complications. The dosing of heparin based on actual body weight (units/kg/h) and time to first therapeutic aPTT was similar between groups, but dose was statistically higher at steady state in the non-obese (16.3 ± 5.3 non-obese, 11.6 ± 5.5 obese and 11.1 ± 1.2 obese, P = 0.01) with similar times to steady state.Conclusions:Dosing of UFH in morbidly obese and obese critically ill patients based on actual body weight and a reduced initial dose was associated with similar time to first therapeutic aPTT and steady state.

Higher Maximum Doses and Infusion Rates Compared with Standard Unfractionated Heparin Therapy Are Associated with Adequate Anticoagulation without Increased Bleeding in Both Obese and Nonobese Patients with Cardiovascular Indications

“…Weight‐based dosing regimens used to determine the initial bolus and continuous infusion of UFH are widely implemented and have become the standard of practice for administration. Several studies suggest that use of a weight‐based UFH nomogram, compared with a fixed dosing regimen, significantly lowers the risk of recurrent thromboembolism in patients with NSTEMI/UA . Current guideline recommendations for a dosing strategy using a maximum bolus dose and infusion rate preceded the current obesity epidemic in the United States.…”

“…Previous studies compared UFH dosing in nonobese patients with obese and morbidly obese patients receiving UFH infusions. One group found that the mean time to achieve therapeutic aPTT values was similar among these three groups, ranging from 16.8–20.8 hours from the start of infusion . Another study also noted significant delay in time to achieve therapeutic anticoagulation in nonobese patients (21.3 and 29.9 hrs for morbidly obese and nonobese patients, respectively) .…”

“…Optimizing UFH dosing is challenging in obese patients due to their physiologic changes and altered pharmacokinetics . The efficacy of UFH depends on volume of distribution and total blood volume . Obese patients have higher plasma volume due to an increase in vasculature required to perfuse the adipose tissue, although adipose tissue contains less vasculature proportional to muscle and other tissue .…”

“…Calculation of an estimated blood volume in the obese population has been attempted, but the utility of this calculation for UFH dosing is limited, in part due to the individual differences in adipose tissue vasculature between patients not accounted for in the equation . Obesity may also contribute to changes in protein binding and drug clearance, although the implications of these changes on UFH remain unclear …”

“…4 The efficacy of UFH depends on volume of distribution and total blood volume. 5 Obese patients have higher plasma volume due to an increase in vasculature required to perfuse the adipose tissue, although adipose tissue contains less vasculature proportional to muscle and other tissue. 6 Because the volume of distribution of UFH is approximately the same as the blood volume, obese patients consequently have a higher volume of distribution and may require increased doses of UFH.…”