Evaluation of an enoxaparin dosing calculator using burn size and weigth. J Burn Care Res 2013

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Evaluation of an Enoxaparin Dosing Calculator Using Burn Size and Weight Iris Faraklas, RN, BSN, Maureen Ghanem, PharmD, Amalia Brown, BA, Amalia Cochran, MD, FACS

Previous research has shown that inadequate antifactor Xa levels (anti-Xa) occur in burn patients and may increase the risk of venous thromboembolic events (VTE). The objective of this retrospective review was to investigate the usefulness of an enoxaparin dosing algorithm using a previously published equation. With institutional review board approval, all acute burn patients at an American Burn Association–verified regional burn center who were treated with enoxaparin for VTE prophylaxis and had at least one anti-Xa from May 1, 2011 to December 15, 2012 were included. Patients with subprophylactic anti-Xa received increased enoxaparin dose per unit protocol with the goal of obtaining a prophylactic anti-Xa (0.2–0.4 U/ml). Sixty-four patients were included in our analysis. The regression equation was used in 33 patients for initial enoxaparin dosing (Eq) whereas 31 patients received traditionally recommended prophylaxis dosing (No-Eq). Groups were comparable in sex, age, weight, inhalation injury, and burn size. Initial enoxaparin dosing in Eq was significantly more likely to reach target than in No-Eq (73 vs 32%; P = .002). No episodes of hemorrhage, thrombocytopenia, or heparin sensitivity were documented in either group. Median final enoxaparin dose required to reach prophylactic level was 40 mg every 12 hours (range, 30–80 mg). Twenty-one No-Eq patients ultimately reached target, and 11 of these final doses were equivalent to or greater than the predicted equation. Ten patients never reached prophylactic anti-Xa before enoxaparin was discontinued (nine from No-Eq). Two patients, one from each group, developed VTE complications despite appropriate anti-Xa for prophylaxis. A strong correlation was shown between weight, burn size, and enoxaparin dose (r2 = .68; P < .001). Use of the enoxaparin dosing algorithm significantly increased the frequency of obtaining a target initial anti-Xa. There were no bleeding complications. Enoxaparin dosing correlates to burn size and weight, making a standard dose inappropriate because patient habitus and extent of burn injury are highly variable. This simple equation improves enoxaparin dosing for acute adult burn patients. (J Burn Care Res 2013;34:621–627)

Venous thromboembolic events (VTE) is an often silent complication in critically ill patients, which is strongly associated with poor outcomes.1 The American College of Chest Physicians recommends that all major trauma patients receive low–molecular-weight heparin (LMWH) or low-dose unfractionated heparin

From the Burn Trauma Intensive Care Unit, University of Utah Health Care, Salt Lake City. Presented at the 45th annual meeting of the American Burn Association, April 23–26, 2013, Palm Springs, CA. Address correspondence to Iris Faraklas, RN, BSN, University of Utah Health Care, 3B110 SOM, 30 North 1900 East, Salt Lake City, UT 84132. Copyright © 2013 by the American Burn Association 1559-047X/2013 DOI: 10.1097/BCR.0b013e3182a2a855

prophylaxis over no prophylaxis.2 In burn patients with additional risk factors (advanced age, morbid obesity, extensive or lower-extremity burns, other trauma, prolonged immobility, or femoral venous catheter), routine thomboprophylaxis is recommended.3 Among experts in burn research, estimates of the VTE incidence range from very low (0.4%4) to alarmingly high (23%5). A survey of 84 burn centers found that 76% provided routine VTE prophylaxis with widely varying regimens.6 Practice guidelines from the American Burn Association’s Committee on the Organization and Delivery of Burn Care indicate that although complications related to prophylaxis are unknown, prophylactic measures are warranted based on a suspicion that deep vein thrombosis incidence is greater than historically believed.7 621



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Our burn center adopted a thromboembolic prophylaxis protocol using enoxaparin, an LMWH. Our previous work showed that 30 mg of enoxaparin given every 12 hours (Q12Hrs) was subprophylactic for the vast majority of our burn patient population (76%).8 Using linear regression analysis, we identified that burn injury size (TBSA) and weight affected dose, generating the following equation for VTE prophylaxis: Enoxaparin dose in mg Q12Hrs = 22.8 + (3.3 × % TBSA/10) + (1.89 × (weight in kg)/10).8 The objective of the current study was to evaluate this equation by demonstrating that it enabled more patients to achieve prophylaxis with initial dosing.

METHODS Patient Review With institutional review board approval, all patients admitted to our regional American Burn Association–verified burn center from May 1, 2011 through December 15, 2012 with acute burn injuries who were more than 14 years of age were screened. Patients who received enoxaparin prophylaxis and had one or more anti-Xa level for monitoring were included in this study.

Data Collection Demographic and injury data collected included age, sex, weight, height, body mass index (BMI), burn size expressed as percent TBSA, full-thickness burn injury, inhalation injury, outcome, and hospital length of stay. Treatment data collected included antifactor Xa level (anti-Xa) and enoxaparin doses. Patients were followed up until hospital discharge for the development of any adverse effects associated with enoxaparin; examples of adverse effects included unexpected bleeding, need for massive transfusions, hematoma-associated graft loss requiring surgical intervention, thrombocytopenia, or heparin-associated allergy.

Treatment Protocol Acute burn patients admitted to the burn center and anticipated to be nonambulatory for greater than 48 hours were placed on an enoxaparin dosing regimen for prophylaxis. Exclusion criteria included any contraindication to the use of enoxaparin, including intracranial bleeding or hemorrhagic stroke (within 48 hours), suspected or proven hematoma, creatinine clearance 1.6 mg/dl, epidural anesthesia, and head injury or neurotrauma. Patients were placed into a treatment group either using the regression equation (Eq) or not using the regression equation (No-Eq). Patient treatment was nonrandomized and was dependent on attending physician and pharmacist selection at the time VTE prophylaxis was initiated. No-Eq Group. The initial prophylactic enoxaparin dose was 30 mg given by subcutaneous injection Q12Hrs for nonobese adults or 0.5 mg/kg by subcutaneous injection Q12Hrs for obese adults who had BMI > 30 kg/m2 or weight >150 kg.9 Eq Group. The initial prophylactic enoxaparin dose was calculated using the following equation (mg): 22.8 + (3.3 × % TBSA/10) + (1.89 × (weight in kg)/10).8 This calculated dose was given by subcutaneous injection Q12Hrs. Peak anti-Xa was obtained from a national reference laboratory (ARUP, www.aruplab.com) between 3 and 5 hours after the third enoxaparin dose, consistent with timing of the peak steady state level of enoxaparin. These levels cost approximately $80 each, with results available within 2 hours. Regardless of treatment group, doses of enoxaparin were titrated up or down by 20% to achieve the recommended anti-Xa of 0.2 to 0.4 U/ml.10 VTE prophylaxis was discontinued when the patient was able to ambulate at least three times daily or at the discretion of the attending physician. Duplex ultrasounds were not routinely completed for surveillance, but were instead obtained based on clinical suspicion.

Statistical Analysis Statistical analysis was performed using Stata version 12.1 (Statacorp, College Station, TX). For comparison of patient demographics, Pearson χ2 or Fisher’s exact test was used for categorical variables; Wilcoxon’s rank-sum was used for continuous variables. Pearson correlation was used to measure the strength of association between demographic variables and enoxaparin dose at target anti-Xa. Linear regression analyses were performed to confirm injury characteristics that most influenced final adjusted enoxaparin dose. All reported P values are from a two-sided comparison.

RESULTS One hundred seventeen acute burn patients were admitted for more than 48 hours and received at least one dose of enoxaparin during this review period (Figure 1). Fifty-three patients were excluded

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Figure 1.  Patient flow diagram. Q12Hrs, Every 12 hours; Eq, regression equation; No-Eq, not using the regression equation.

from this review because enoxaparin was discontinued before a correctly drawn anti-Xa. The remaining 64 patients who received enoxaparin with at least one correctly obtained anti-Xa were included in the analysis. The majority of patients were older, overweight males with moderate burn injury (Table 1). There were no significant demographic or injury characteristic differences between the Eq and No-Eq groups. The median time until enoxaparin was first started was 1 day (range, 0–9 days) postadmission, and there was no significant difference between either group (1 vs 1 day; P = .606). Patient distribution is shown in Figure 1. In the Eq group, initial enoxaparin prophylactic dose was calculated using the regression formula for 33 patients. In the No-Eq group there were 31 patients, 19 were given 30 mg Q12Hrs. The remaining 12 were obese patients who received 0.5 mg/kg Q12Hrs:

nine patients received 40 mg Q12Hrs, two patients received 50 mg Q12Hrs, and one patient received 80 mg Q12Hrs. In Figure 2, each group was identified by percentage of patients reaching target at a specific dose. There were two obese patients in the No-Eq group who received 50 mg Q12Hrs but were below target. Eq patients were significantly more likely to reach anti-Xa target initially than No-Eq (73 vs 32%; P = .002; Table 2). One Eq patient had an initial level above target (0.48 U/ml). Enoxaparin doses were subsequently changed, as indicated in “Methods.” Eq patients were significantly more likely to achieve target anti-Xa level before enoxaparin was discontinued than No-Eq patients (3 vs 29%; P = .006). The median final dose was significantly higher in the Eq than the No-Eq group (50 vs. 40 mg Q12Hrs; P = .022). Twenty-one patients in the No-Eq

Table 1. Patient demographics*

No. males (%) Age (yrs) Height (cm) Weight (kg) BMI (kg/m2) % TBSA % Full thickness Inhalation injury (%)

Total (n = 64)

No-Eq (n = 31)

Eq (n = 33)

P Value**

47 (74%) 46 (33–61) 173 (165–180) 84 (73–103) 29.1 (24.2–33.0) 17 (8–25) 4 (0–9) 10 (16%)

20 (65%) 45 (28–61) 174 (164–180) 83 (72–104) 28.8 (24.2–33.6) 15 (9–21) 3.5 (0–8) 4 (13%)

27 (82%) 47 (37–60) 172 (166–182) 84 (75–100) 29.2 (24.5–31.9) 19 (8–27) 4 (0–15) 6 (18%)

.117 .498 .989 .762 .897 .122 .801 .734

BMI, body mass index; Eq, regression equation; No-Eq, not using the regression equation. *Median (interquartile range) unless otherwise noted. **Chi-square or Fisher’s exact test for dichotomous variables and Wilcoxon’s rank-sum for continuous variables.



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Figure 2.  Percentage of patients who achieve target anti-Xa levels with initial enoxaparin dose. There were no patients in the regression equation (Eq) group that initially received 30 or 80 mg every 12 hours (Q12Hrs), and correspondingly there were no patients in the not using the regression equation (No-Eq) group that received 60 or 70 mg Q12Hrs.

ultimately reached target and 52% (11) of these patients’ final dose were equivalent to or greater than the dose calculated by regression equation. Five patients’ anti-Xa was above target; four of these patients were in the Eq group. Each of these patients’ final and previous anti-Xa with corresponding enoxaparin doses are included in Table 3. Two older males with major thermal injury developed VTE despite adequate prophylactic anti-Xa levels; one patient was in each group. The patient in the No-Eq group who developed a VTE in his left atrium had a major burn injury with several

medical comorbidities including obesity and atrial fibrillation. His VTE was discovered more than 2 months postadmission, and his anti-Xa was at target (0.29 U/ml). The patient in the Eq group was morbidly obese (>35 BMI) and required aggressive sedation for severe alcohol withdrawal. He complained of left upper-arm pain with tenderness, and duplex ultrasound confirmed VTE 16 days postadmission. His anti-Xa was at target (0.32 U/ml), however, he had a peripherally inserted central catheter in his left arm. Both patients successfully reached therapeutic anticoagulation without incident.

Table 2. Results* Total (n = 64) % of patients with initial anti-Xa below target (n) % of patients with final anti-Xa below target (n) % of patients with initial anti-Xa at target (n) % of patients with final anti-Xa at target (n) Final enoxaparin dose (range) at target anti-Xa % Mortality (n) Length of stay (days)

45% (29) 16% (10) 53% (34) 77% (49) 40 (30–80) 10 % (6) 18 (13–29)

No-Eq (n = 31) 68% (21) 29% (9) 32% (10) 68% (21) 40 (30–80) 3% (1) 18 (13–26)

Eq, regression equation; No-Eq, not using the regression equation. *Median (interquartile range) unless otherwise noted, anti-Xa target: 0.2–0.4 U/ml. **Chi-square or Fisher’s exact test for dichotomous variables and Wilcoxon’s rank-sum for continuous variables.

Eq (n = 33)

P Value**

24% (8) 3% (1) 73% (24) 85% (28) 50 (40–80) 16% (5) 18 (14–33)

.002 .006 .002 .006 .022 .196 .536

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Table 3. Patients with above target (>0.4 U/ml) anti-Xa levels Patient

Above Anti-Xa (U/ml)

Corresponding Enoxaparin*

Prior Anti-Xa (U/ml)

Prior Enoxaparin*

Days Since Prior Anti-Xa

Length of Stay (days)

0.48 0.48 0.49 0.59 0.49

50 60 50 60 70

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