SCCM Resource Library-03-Prophylactic Anticoagulation Dosing in Aneurysmal Subarachnoid Hemorrhage Patients Requiring an EVD

Video Transcription

My name is Chidozie Upabi. I'm a clinical pharmacist at Emory University Hospital, and today I will be talking to you about my research project titled, Prophylactic Anticoagulation  Dosing in Subarachnoid Hemorrhage Patients Requiring an EVD.  Myself, as well as the other investigators on this slide, have nothing to disclose. I will start this presentation by providing some background information on subarachnoid  hemorrhage. It is a type of stroke defined by bleeding into the subarachnoid space, in most instances secondary to a rupture of an aneurysm. There is a significant increase  in morbidity and mortality in this patient population, with the estimated mortality incidence described in the literature of up to 24%. Hydrocephalus occurs in up to 87% of these  patients and is characterized by an increase in cerebral spinal fluid, or CSF, and consequentially  intracranial pressure, or ICP. External ventricular drains, or EVDs, therefore become an important  part of therapy for these patients as they are used for the drainage of CSF and excess blood and to relieve and measure ICP. Patients with EVDs are at increased risk for hemorrhage  when the EVD catheters are manipulated, and these tract hemorrhages lead to a significant  worsening in functional and cognitive outcomes, since the tract usually runs through the frontal  lobe of the brain. These patients have an increased duration of hospital stay, coupled with extensive immobilization, leading to an increased risk in venous thromboembolism,  or VTE. The incidence of VTE in this patient population is up to 25% in the literature, and data currently only supports the use of subcutaneous, unfractionated heparin plus  mechanical prophylaxis for thromboeprophylaxis. There is limited data to validate the use  of low molecular weight heparin, such as anoxaparin, in these patients, and specifically there  is no data that describes its use in patients requiring an EVD. The concern is, even while on prophylactic anticoagulation dosing, patients with EVDs still have an increased risk of  secondary intracranial hemorrhage. Emory University Hospital, however, has been using anoxaparin  for VTE prophylaxis in this patient population for the last 15 years, due to its more predictable  bioavailability, as well as the increased incidence of heparin-induced thrombocytopenia, or HIT, in patients using heparin. This chart provides a visual of the dosing strategy that  is used. These patients are dosed 0.5 mg per kg, which will ultimately provide a dose of 20, 30, or 40 mg daily, and in certain instances 30 or 40 mg Q12, depending on how  much the patient weighs over 120 kg. In patients with impaired renal function, either chronically  or acutely, we will utilize unfractionated heparin, typically dosed 5,000 units Q8-Q12. Although the use of anti-TEN-A levels is not routinely recommended to be measured in  patients receiving anoxaparin prophylactically, this data has been collected in EUH neurosurgical  patients to measure the efficacy and safety of the treatment. This chart provides a visual of the protocol. We aim for an anti-TEN-A level goal of 0.1 to 0.3 units per ml collected  as close as possible to four hours after the first steady-state dose. Those adjustments  are made at increments of 10 mg up or down, depending on if the level is sub- or supra-therapeutic.  Having now gone through some background information, I would like to present the purpose of this  research, which is to examine the rate of ICH as well as VTE in subarachnoid hemorrhage  patients requiring an EVD who receive thromboprophylaxis. Transitioning into methods, this was an IRB-approved  retrospective chart review of subarachnoid hemorrhage patients admitted from 2012 to 2017 within Emory's Neurocritical Care Unit. The primary outcome was the incidence of ICH  following the initiation of prophylactic anoxaparin or unfractionated heparin after surgical treatment  and placement of an EVD. The secondary outcome focuses on the incidence of symptomatic VTE  following initiation of prophylactic anoxaparin or unfractionated heparin after surgical treatment  and placement of an EVD. ICH events were determined using computed tomography scans of the head,  and the occurrence of VTE was determined by venous duplex scans of the lower and upper extremities. Earlier, I specified symptomatic VTE, and the reason I gave that specification  is because these are not routinely performed, and only done so when patients are symptomatic for possible VTE. Patients included were 18 years of age and above, admitted from 2012  to 2017, and had been diagnosed with subarachnoid hemorrhage followed by securement. These patients  also had EVDs placed and received either prophylactic anoxaparin or unfractionated heparin. A total  of 868 patients met these criteria, with 627 being placed within an anoxaparin group denoted  as low molecular weight heparin on this slide and upcoming charts and graphs, and 114 within  the unfractionated heparin group. 127 patients did not receive any treatment. Listed within this table are baseline demographics of the patients within the cohort, with most of the  patients being women, which is typical of subarachnoid hemorrhage. Most of the patients were also black or white, with the average age of patients being about 55. Here are some  additional baseline characteristics, and as you can see, there was a high percentage of patients with hypertension, and many were smokers, both of which are predominant risk  factors for patients with subarachnoid hemorrhage. I also want to point out that only about 5%  of the patients had CKD, or end-stage renal disease, and this is one of the reasons that many of the patients included in this data collection were treated with anoxaparin, as  unfractionated heparin was reserved for patients with either chronic or acute renal impairment.  Now as we look at the primary outcome, starting first with the incidence of ICH, we see that from a simple comparison, there is a small difference in the percentages of ICH events  between the treatment groups, and that this difference is statistically significant. When  evaluating this data statistically, we can use logistic regression, considering the incidence  of ICH is a binary outcome, since we are evaluating whether the event occurs or not, and is also  dependent on other variables or covariates from the data collection. With the incidence of ICH as the outcome, we can control for other parameters or covariates, including  those listed on the baseline characteristics slide, such as patient demographics, BMI, risk factors for subarachnoid hemorrhage, and the surgical approach that was used for  the specific patient. By performing this logistic regression, and focusing on the treatment  with anoxaparin, while controlling for those other parameters, we see that the use of anoxaparin  was not associated with a higher risk of ICH when compared with unfractionated heparin. The odds ratio for anoxaparin treatment was about 1.48, with a 95% confidence interval  of 0.83 to 2.65. We must also take into consideration, though, that although the simple comparison  between the two treatments shown in the last slide was statistically significant, the patient population is not one that is allocated at random. The decision to give unfractionated  heparin versus anoxaparin is based primarily on renal impairment. It is important to examine the results, keeping this piece of information in mind.  For a secondary outcome, when we look at the incidence of VTE within these patients, and make a simple comparison, we see again that there is only a small difference among the  percentages of VTE occurrence between the groups with statistical significance similar to what was observed with ICH events. By once again performing an additional logistic  regression, but focusing this time on VTE as the outcome, and similarly controlling for the same parameters of covariates previously described, such as baseline demographics,  surgical approach used, and et cetera, we see that the treatment with anoxaparin was not associated with a higher risk of VTE when compared to unfractionated heparin. The odds  ratio for anoxaparin treatment was about 1.77, with a 95% confidence interval ranging from 0.69 to 4.54. Before I conclude, I want to briefly go over  the use of anti-TENA levels within these patients, since this is practice not commonly described  in the literature. As we can see, most of the patients, 83% to be exact, who received 0.5-microcig dosing fell within the goal range of 0.1 to 0.3. However, there were  no clinically significant differences, so this research did not show any particular advantage in measuring anti-TENA levels, but also keep in mind that this study was not  designed specifically to do so. In conclusion, anoxaparin and unfractionated heparin deliver similar risk and benefit, while anoxaparin is dosed once daily with  the ability to be titrated. There are also other benefits that anoxaparin has over unfractionated  heparin, such as having improved bioavailability and limiting the incidence of HIT, as mentioned  previously. The incidence of ICH as well as VTE is also similar to what we see in the literature. Taking all this into consideration, we can say that it appears that anoxaparin  can be a viable alternative to subcutaneous unfractionated heparin for VTE prophylaxis and subarachnoid hemorrhage patients requiring an EVD.  And with that, I would like to say thank you for your time and I hope that you have a blessed remainder to your day. Thank you.

Video Summary

In this research project titled "Prophylactic Anticoagulation Dosing in Subarachnoid Hemorrhage Patients Requiring an EVD", the researcher examined the use of anoxaparin and unfractionated heparin for thromboprophylaxis in subarachnoid hemorrhage patients who required an external ventricular drain (EVD). The study found that the incidence of intracranial hemorrhage (ICH) and venous thromboembolism (VTE) were similar between the two groups. Anoxaparin was found to be a viable alternative to unfractionated heparin for VTE prophylaxis in these patients, as it has improved bioavailability and a lower risk of heparin-induced thrombocytopenia. Ultimately, the study suggests that anoxaparin can be safely used in subarachnoid hemorrhage patients requiring an EVD.

Asset Subtitle

Neuroscience, Pharmacology, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Chidozie I. Ukpabi

Introduction/Hypothesis: Aneurysmal subarachnoid hemorrhage (aSAH) is commonly managed in neurocritical care units and is a significant cause of disability and mortality. Unfractionated heparin (UFH) is recommended to prevent venous thromboembolism (VTE) in this population following definitive aneurysm management. There is limited data validating the use of low molecular weight heparin (LMWH) in this population especially in patients requiring an external ventricular drain (EVD). Even while on prophylactic anticoagulation doses, patients with aSAH with EVDs have an increased risk of secondary intracranial hemorrhage (ICH). This study examined the rate of VTE and ICH retrospectively in aSAH patients in order to identify the safest and most effective anticoagulation dosing strategy.

Methods: Following IRB approval, all aSAH patients admitted to Emory University Hospital from 2012 - 2017 were screened. Patients with an EVD were analyzed for their VTE prophylactic regimen (LMWH â‰¤0.5mg/kg/day or UFH 5000 units q8 - 12h), VTE events based on ICD coding, and new ICH events based on imaging.

Results: Out of 1,351 patients screened, 862 required an EVD. 547 patients received prophylactic LMWH and 173 received UFH. VTE events occurred in 8.4% of patients receiving LMWH and 8.7% in those receiving UFH (p=0.9), while ICH occurred in 6.8% and 1.7% respectively (p<0.01). There was no difference in the dosing between the groups who developed VTE and those who did not. Using the prophylactic weight-based regimen, patients >70 kg had a statistically significant higher rate of VTE. In a regression analysis aiming at steady state anti-Xa levels between 0.1 - 0.3 units/mL, the risk of VTE is <9.6% and the risk of hemorrhage is <6.8% although this correlation did not achieve statistical significance.

Conclusions: This retrospective analysis of aSAH patients who required an EVD allows for an estimation of the efficacy and safety of a weight based VTE prophylactic regimen. LMWH demonstrated similar efficacy to UFH yet was associated with higher rates of EVD-related hemorrhage. Since patients weighing over 70 kg tend to develop VTE more frequently, using anti Xa levels could aid in adjusting the dose used while stratifying risk and benefit. Further prospective trials are required to optimize the care for this high-risk patient population.

Meta Tag

Content Type Presentation

Knowledge Area Neuroscience

Knowledge Area Pharmacology

Knowledge Level Advanced

Membership Level Select

Tag Subarachnoid Hemorrhage

Tag Anticoagulation

Year 2021

Keywords

Prophylactic Anticoagulation Dosing

Subarachnoid Hemorrhage Patients

Anoxaparin

Unfractionated Heparin

Thromboprophylaxis

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