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Subcutaneous Heparin Dose in Underweight Criticall ...
Subcutaneous Heparin Dose in Underweight Critically Ill Patients
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Hi, my name is Bernice, and I'm the Burn Surgical Critical Care Pharmacist at Bridgeport Hospital, and I'll be presenting on subcutaneous heparin dose in underweight critically ill patients. This is my study team listed below. And disclosure-wise, me and my team have no actual or potential conflict of interest in relations to this presentation. So for a quick background, venous thromboembolism, or VTE, is the third most common vascular disorder following coronary syndromes and stroke. Critically ill patients have varying risk factors for VTE, including their acute illness, chronic illness, pre-hospital diagnosis, as well as ICU-specific events. Some risk factors are, but not limited to, surgery, trauma, sepsis, stroke, malignancies, burns, as well as lines. VTE is associated with an increased morbidity and mortality in critically ill patients, so it is very important to try to prevent VTEs in these patients. Chest guidelines recommend initiating pharmacologic prophylaxis with anticoagulants in critically ill high-risk patients as soon as possible to reduce the incidence of VTE. But of course, with these patients, there may also be a potential risk of bleeding as well. So for the rationale, there is limited evidence regarding the optimal dose for VTE pharmacologic prophylaxis in critically ill underweight patients. In underweight patients, they may potentially have an altered volume of distribution, which may increase, or which may have a lower volume of distribution, which may increase their exposure to anticoagulants and may potentially increase their risk for bleeding. So in real world experience, it suggests that critically ill underweight patients who receive standard dose of VTE prophylaxis had a higher incidence of significant bleeding. Given the limited evidence, this study aimed to evaluate the outcomes of standard dose heparin, or SDH, compared to dose-reduced heparin, or DRH, in critically ill underweight patients. So for the study objectives and methods, we evaluated if critically ill underweight patients have worse outcomes if they receive standard dose heparin compared to dose-reduced heparin for VTE prophylaxis. This was a retrospective multi-center observational electronic medical record review, which we included patients from July 1st, 2018 to September 30th, 2021. For the study population, we included patients who were 18 years of age and older and were underweight, which we defined as a body mass index of 18 kilograms per meter squared or less, admitted to the ICU for at least 48 hours or longer to ensure that we encompassed critically ill patients, and those who received subcutaneous heparin for at least 48 hours and longer to ensure that they had a steady dose of or steady state of heparin in their system. We defined standard dose heparin as 15,000 units per day or greater and dose-reduced heparin of less than 15,000 units per day. Patients were excluded if they died within 48 hours of admission, received agents other than heparin for VTE prophylaxis, and if they had COVID at admission and or during hospital stay because, of course, we've seen patients with COVID that have potential abnormal coagulopathy, and we did not want that to be a confounding variable in this review. For the outcomes, the primary outcomes, we looked at the development of new-onset bleed on subcutaneous heparin, which we defined new-onset bleed as either a fatal bleed, decrease in hemoglobin by two grams per deciliter within 24 hours, and requiring one or more unit transfusions of packed red blood cells or radiographic evidence of bleeding into a critical organ. Secondary outcomes, we looked at the development of new VTE, which was determined on ultrasound or CT imaging, and patients had to be on subcutaneous heparin for at least 48 hours without any disruption of therapy. We also looked at ICU and hospital length of stay, as well as in-hospital mortality. So for the study population, we reviewed a total of 370 patients, of which we ended up excluding 52 patients, majority of which was because the ICU length of stay was less than 48 hours. 13 patients were excluded because they had a VTE prophylaxis of less than 48 hours. Two patients were excluded because they were on other VTE prophylaxis, and one patient was excluded due to COVID. Overall, we had a total of 255 patients included in our review, of which 175 patients was in the standard-dose heparin group and 80 patients in the dose-reduced heparin group. So for the baseline demographics, overall, there was no differences in age. However, for gender, there was a higher number of females in the standard-dose subcutaneous heparin group compared to the dose-reduced heparin group. For the race, overall, we had a majority of Caucasians in both groups. However, there was no differences between the two groups. For height and weight, there was a higher number in the standard-dose heparin group. However, looking at the BMI, there was no difference between the two, about 17 or 16 in both groups. For past medical histories, which included coagulopathies, metastatic cancer, history of stroke, as well as PE and DVT, we found that at baseline, there was no differences between the two groups. Continuing on the baseline demographics, the SOFA score was 5 in both groups. Hemoglobin, platelets, and neurologic injury at baseline were similar. We looked at medications continued on admission, specifically medications such as antiplatelets, anticoagulants, and chronic NSAID use because it may potentially increase their risk for bleeding. And we found at baseline, there was no differences. And what was interesting is there was more patients in the dose-reduced heparin group that had or received TPA. However, there were no differences in those who received reversal agents. For the types of ICUs, we did have a variety of different patients in the different ICUs. Most were in the medical ICU, followed by the surgical ICU, and then the neurosurgery ICU. For the outcomes, for the primary outcomes, the incidence of bleeding was higher in the standard-dose subcutaneous heparin group of 16 patients compared to one patient in the dose-reduced heparin group. We found a statistical significant difference of a p-value of 0.04. For the secondary outcomes, looking at any new onset VTE, numerically, there was more in the standard-dose heparin group of four patients and one patient in the dose-reduced heparin group. However, there was no statistically significant difference. And there was no differences in hospital and ICU length of stay, as well as in-hospital mortality. For the therapy metric-wise, heparin dose was about 319 units per kick per day in the standard-dose heparin group, and about 221 units per kick per day in the dose-reduced heparin group. For the heparin duration, it was about eight days in both groups. I did provide a subgroup analysis specifically for the neurosurgery intensive care unit patients, given their increased risk for bleed and development of new VTEs. So overall, of the 255 patients that was included in the study, 45 patients were in the neurosurgical ICU, and of which 30 was in the standard-dose heparin group, and 15 was in the dose-reduced heparin group. The BMI was about 16 in both groups. And we looked at GCS for those with a TBI, modified Fisher score for those with subarachnoid hemorrhage, brain bleed size, which was determined by imaging, and INI-HSS score for those with stroke. And we found that at baseline, there was no differences between the two groups. SOFA score was, again, five in both groups, and no differences in hemoglobin, platelets, and medications continued on admission. Those who received TPA, there was two patients in the dose-reduced heparin group, compared to zero patients in the standard-dose group. However, we did not find a statistical significant difference. And there was no difference in those who received reversal agents. So for the outcomes in this cohort study, so the incidence of bleeding was seven in the standard-dose heparin group. So numerically, it was higher compared to the dose-reduced heparin group. We did not find a statistically significant difference with a p-value of 0.33. Looking at the ICU length of stay, it was about six days in the standard-dose heparin group, compared to eight days in the dose-reduced heparin group. So numerically, it was a little bit shorter in the standard-dose heparin group. However, looking at the hospital length of stay, it was a little bit longer in the standard-dose heparin group of about 19 days, compared to 14 days in the dose-reduced heparin group. But overall, there was no differences found statistically. As well, there's no differences in nuance of VTE and in-hospital mortality. So just going into a little bit more detail on the clinically relevant bleeding that we found, so overall, we had a total of 17 patients who had clinically relevant bleeding, of which 16 patients were in the standard-dose heparin group, and one patient in the dose-reduced heparin group. We had a total of four patients in the medical ICU with bleeds that was in the standard-dose heparin group, and the dosing was about 94 units per Kg per day, and the types of bleeds varied. Next, in the neural ICU, we had the most bleeds, with seven bleeds in the standard-dose heparin group, and one bleed in the dose-reduced heparin group. We had a variety of different types of bleeds, and only two bleeds from the transverse sinus. Dosing-wise was about 115 units per Kg in the standard-dose heparin group, and 123 units per Kg in the dose-reduced heparin group. In the surgical ICU, we had four patients with bleeds, two of which were GI bleeds. Dosing was about 104 units per Kg, and we had one patient in the cardiothoracic ICU due to acute blood loss anemia post-transplant, and the dosing was about 129 units per Kg. So for the limitations, this was a retrospective study design, so it does increase potential risk of confounding. We also did not report any home medications these patients were on, specifically medications that may increase their risk for bleeding, such as anticoagulants, antiplatelets, and our chronic NSAID use. However, we did encompass those that were continued on these medications in patients, and we found that at baseline, there was no differences between the two groups. We did have a relatively small sample size of 255 patients, which does make it difficult to detect differences in the outcomes as well as control for confounding variables. However, we did have a very diverse group of patients in a variety of different ICUs, which does make it or provide a more reasonable external validity for our results. Of course, since we only included patients who were critically ill, we cannot translate these results at this time for non-critically ill patients. Infection-wise, in underweight critically ill patients who received less than 15,000 units per day of heparin for VTE prophylaxis, there was a lower incidence of clinically relevant bleeding and no difference in new VTE, ICU and hospital length of stay, and in-hospital mortality compared to those who received 15,000 units per day or more. Findings suggest that dose-reduced heparin for VTE prophylaxis in critically ill patients with a BMI of 18 kilograms per meter square or less may be reasonable. But, of course, further prospective studies are needed to help support our results. Thank you, everyone, for listening, and I'll open up the floor for questions.
Video Summary
Bernice, a Burn Surgical Critical Care Pharmacist, presented a study on the subcutaneous heparin dose in underweight critically ill patients. The study aimed to compare the outcomes of standard dose heparin (SDH) and dose-reduced heparin (DRH) in these patients. The retrospective study included 255 patients and found that in patients who received less than 15,000 units per day of heparin, there was a lower incidence of bleeding and no difference in new VTE, ICU and hospital length of stay, and in-hospital mortality compared to those who received higher doses. The findings suggest that dose-reduced heparin may be reasonable for VTE prophylaxis in underweight critically ill patients.
Asset Subtitle
Pharmacology, 2023
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Type: star research | Star Research Presentations: Pharmacology II (SessionID 30016)
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Pharmacology
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Professional
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Anticoagulation
Year
2023
Keywords
subcutaneous heparin dose
underweight critically ill patients
dose-reduced heparin
retrospective study
VTE prophylaxis
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