Recommendations for Thromboprophylaxis in Hospitalized COVID Patients

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Hospitalized COVID AC Recs.May2020

Reference:

Northwell Health COVID19 and Guidance on Management of Antithrombotic Therapy; Dr. Alex C. Spyropoulos System Director – Anticoagulation and Clinical Thrombosis Services; Graphic Editor: Dr. Rachel-Maria Brown, Director – Inpatient Cardiac Services

SCCM Guidelines on COVID-19 Management – summarized

SCCM released a guideline on the management of COVID-19.  For those pressed for time, I’ve condensed the guidelines into a 13-page Q&A format.  The questions are formulated by me based on the guideline content and the answers are lifted from the SCCM guidelines, some of which I have reformatted from passive to active voice for easier reading.  Please reference the original guideline text, or message me if there are any errors.

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(download PDF file here)

REFERENCE:

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Waleed Alhazzani, Morten Hylander Møller, Yaseen M. Arabi , Mark Loeb, Michelle Ng Gong, Eddy Fan, Simon Oczkowski, Mitchell M. Levy, Lennie Derde, Amy Dzierba, Bin Du, Michael Aboodi, Hannah Wunsch, Maurizio Cecconi, Younsuck Koh, Daniel S. Chertow, Kathryn Maitland, Fayez Alshamsi, Emilie Belley-Cote, Massimiliano Greco, Matthew Laundy, Jill S. Morgan, Jozef Kesecioglu , Allison McGeer, Leonard Mermel, Manoj J. Mammen, Paul E. Alexander, Amy Arrington, John Centofanti, Giuseppe Citerio, Bandar Baw, Ziad A. Memish, Naomi Hammond, Frederick G. Hayden, Laura Evans, Andrew Rhodes

Enhanced Recover After Surgery (ERAS) for Neuro-oncologic Surgeries

Enhanced Recovery After Surgery (ERAS) was originally conceptualized to decrease morbidity after colorectal surgery and has since been expanded to encompass other abdominopelvic surgeries.  A review article from Journal of Clinical Neuroscience (2015) applied the ERAS concept to elective craniotomies for tumor resections to facilitate hospital discharge for cancer patients, expedite subsequent chemoradiothrapy and improve patient outcome.

The guidelines proposed include:

  1. Pre-operative
    1. Patients should routinely be counselled on what to expect from surgery. (Low, Strong)
    2. Patients should abstain from alcohol and smoking 1 month prior to surgery (Mod, Strong)
    3. Patients should be given enteral nutrition preoperatively. (Mod, Strong)
    4. Patients may benefit from immunonutrition perioperatively. (Mod, Weak)
    5. Patient should be encouraged to load with carbohydrates perioperatively.*  (Low, Strong)

*Perioperative oral CHO loading up to 2 hours prior to surgery has been shown to attenuate insulin resistance and improve subjective feelings of hunger, thirst, and post-operative fatigue compared with fasting.  As CHO beverages are a clear liquid, perioperative CHO loading should be encouraged.

  1. Intra-operative 
    1. Surgeon should minimize scalp shaving. (Mod, Weak)
    2. Cefazolin should be given within 1 hour prior to skin incision.  For patients with MRSA, vancomycin should be initiated 1 hour prior to skin incision. (High, Strong)
    3. Surgeon should utilize scalp in filtration and scalp blocks for craniotomies. (Mod, Strong)
    4. There is no evidence that short-acting anesthetics are superior to longer acting anesthetics, nor TIVA to pure inhalational anesthetics.
    5.  Minimally invasive surgery may improve patient recovery and satisfaction. (Very low, Weak)
  2. Post-operative
    1. Gabapentin / pregabalin / tramadol have side effect profiles that are unfavorable for craniotomy. (Low, Weak)
    2. Low evidence for efficacy of intravenous acetaminophen, but side effect profile is favorable.  (Mod, Strong)
    3. There may be a role for limited dosing of COX-2 inhibitors and flupirtine pending further research.  (Low, Weak)
    4. Routine serotonin receptor antagonists and dexamethasone is recommended for PONV.  (High, Strong)
    5. Aprepitant should be reserved for patients at high risk of PONV due to higher cost and limited effectiveness.  TEAS (transcutaneous electrical acupoint stimulation) requires further study.  (Low, Weak)
    6. Scopolamine and promethazine side effect profiles make them undesirable as first-line nausea meds.  (Low, Weak)
    7. Avoid hypothermia.  (High, Strong)
    8. Remove Foley on posteroperative day 1 or as early as feasible.  (Mod, Strong)
    9. Post-operative TPN not needed except for patients in prolonged comatose state.  (Mod, Strong)
    10. Encourage early mobilization.  (High, Strong)
  3. Others:
    1. Patients should use graduated compression stockings and intermittent pneumatic compression to prevent VTE.  Routine use of anticoagulants is not recommended. (High, Strong)
    2. Audit measure routinely.  (Mod, Strong)

 

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Sample Neurosurgery-ERAS Guideline given to patients from Penn medicine: ERAS Neurosurgery

Reference:

Hagan, K., Bhavsar, S., Raza, S., Arnold, B., Arunkumar, R., Dang, A., Gottumukkala, V., Popat, K., Pratt, G., Rahlfs, T. and Cata, J. (2016). Enhanced recovery after surgery for oncological craniotomies. Journal of Clinical Neuroscience, 24, pp.10-16.

 

Guidelines for DVT Prophylaxis in Neurocritical Care (from NCS)

DVT Chemoprophylaxis Guideline Recommendations (summary) from the Neurocritical Care Society (published in 2016).

 

ISCHEMIC STROKE

  1. We recommend initiating VTE pharmacoprophylaxis as soon as is feasible in all patients with acute ischemic stroke. (Strong recommendation and high-quality evidence)
  2. In patients with acute ischemic stroke and restricted mobility, we recommend prophylactic-dose LMWH over prophylactic-dose UFH in combination with IPC. (Strong recommendation and high-quality evidence)
  3. Due to insufficient evidence, the panel could not issue a recommendation regarding the use of CS for VTE prophylaxis although their use does not appear to be harmful.
  4. In stroke patients undergoing hemicraniotomy or endovascular procedures, we suggest the use of UFH, LMWH, and/or IPC for VTE prophylaxis in the immediate postsurgical or endovascular epoch except when patients have received rTPA, in which case prophylaxis should be delayed 24 h. (Weak recommendation and low-quality evidence)

INTRACRANIAL HEMORRHAGE

  1. We recommend the use of IPC and/or GCS for VTE prophylaxis over no prophylaxis beginning at the time of hospital admission. (Strong recommendation and high-quality evidence)

  2. We suggest using prophylactic doses of subcutaneous UFH or LMWH to prevent VTE in patients with stable hematomas and no ongoing coagulopathy beginning within 48 h of hospital admission. (Weak recommendation and low-quality evidence)

  3. We suggest continuing mechanical VTE prophylaxis with IPCs in patients started on pharmacologic prophylaxis. (Weak recommendation low-quality evidence)

     

ANEURYSMAL SUBARACHNOID HEMORRHAGE

  1. We recommend VTE prophylaxis with UFH in all patients with aSAH (Strong recommendation and high-quality evidence) except in those with unsecured ruptured aneurysms expected to undergo surgery. (Strong recommendation and low-quality evidence)

  2. We recommend initiating IPCs as VTE prophylaxis as soon as patients with aSAH are admitted to the hospital. (Strong recommendation and moderate-quality evidence)

  3. We recommend VTE prophylaxis with UFH at least 24 h after an aneurysm has been secured by surgical approach or by coiling. (Strong recommendation and moderate-quality evidence)

TRAUMATIC BRAIN INJURY

  1. We recommend initiating IPC for VTE prophylaxis within 24 h of presentation of TBI or within 24 h after completion of craniotomy as supported by evidence in ischemic stroke and postoperative craniotomy. (Weak recommendation and low-quality evidence)
  2. We recommend initiating LMWH or UFH for VTE prophylaxis within 24–48 h of presentation in patients with TBI and ICH, or 24 h after craniotomy. (Weak recommendation and low-quality evidence).
  3. We recommend using mechanical devices such as IPC for VTE prophylaxis in patients with TBI, based on data from other Neurological injuries such as ischemic stroke. (Weak recommendation and low-quality evidence).

BRAIN TUMOR

We recommend VTE prophylaxis with either LMWH or UFH upon hospitalization for patients with brain tumors who are at low risk for major bleeding and who lack signs of hemorrhagic conversion. (Strong recommendation and moderate-quality evidence).

SPINAL CORD INJURY

  1. We recommend initiating VTE prophylaxis as early as possible, within 72 h of injury. (Strong recommendation and high-quality evidence)
  2. We recommend against using mechanical measures alone for VTE prophylaxis. (Weak recommendation and low-quality evidence)
  3. We recommend LMWH or adjusted dose UFH for VTE prophylaxis as soon as bleeding is controlled. (Strong recommendation and moderate-quality evidence)
  4. If VTE prophylaxis with LMWH or UFH is not possible, we suggest mechanical prophylaxis with IPC. (Weak recommendation and low-quality evidence)

NEUROMUSCULAR DISEASE

  1. We recommend using prophylactic doses of UFH (bid or tid) LMWH, or fondaparinux as the preferred method of VTE prophylaxis. (Strong recommendation and moderate-quality evidence)
  2. We recommend using IPC for VTE prophylaxis for patients in whom the bleeding risk is deemed too high for pharmacologic prophylaxis. (Strong recommendation and moderate-quality evidence)
  3. We suggest combining pharmacologic and mechanical VTE prophylaxis (with IPC) in patients with neuromuscular disease. (Weak recommendation and low-quality evidence)
  4. We suggest using GCS only for VTE prophylaxis in patients in whom neither pharmacologic prophylaxis nor IPC use is possible. (Weak recommendation and low-quality evidence)
  5. We suggest continuing VTE prophylaxis for an extended period of time, at a minimum for the duration of the acute hospitalization, or until the ability to ambulate returns. (Weak recommendation and very low-quality evidence)

SPINE SURGERY

  1. Ambulatory back surgery with unique positioning strategies such as prone or kneeling has been associated with zero rates of VTE, and we suggest considering the use of IPC only for VTE prophylaxis in this surgical population. (Weak recommendation and low-quality evidence)
  2. In standard elective spine surgery, we recommend using ambulation with mechanical VTE prophylaxis (GCS or IPC) alone, or combined with LMWH. In patients with increased risk for VTE, we recommend combined therapy with ambulation, GCS or IPC, and LMWH. (Strong recommendation and moderate-quality evidence).
  3. Because of the increased risk of bleeding, we recommend using UFH only as an alternative to other methods of VTE prophylaxis. (Strong recommendation and moderate-quality evidence)

COMPLICATED SPINAL SURGERY

  1. We recommend using IPC with LMWH or UFH. (Strong recommendation and moderate-quality evidence)
  2. We recommend against the routine use of IVC filters in the setting of severe spinal cord injury or complicated spine surgery. (Weak recommendation and low-quality evidence)
  3. We suggest considering a removable prophylactic IVC filter as a temporary measure only in patients with PE and DVT or those with DVT at risk for PE who cannot be anticoagulated. (Weak recommendation and low-quality evidence)

ELECTIVE CRANIOTOMY

  1. We recommend using IPC with either LMWH or UFH within 24 h after craniotomy. (Strong recommendation and moderate-quality evidence)
  2. We recommend the use of IPC with LMWH or UFH within 24 h after standard craniotomy in the setting of glioma resection. (Strong recommendation and moderate-quality evidence)

ELECTIVE INTRACRANIAL / INTRA-ARTERIAL PROCEDURES

  1. We suggest the use of CS and IPC until the patient is ambulatory. (Weak recommendation and low-quality evidence)
  2. We suggest immediate prophylactic anticoagulation with LWMH or UFH. (Weak recommendation and low-quality evidence)

INTRACRANIAL ENDOVASCULAR PROCEDURES

  1. We recommend initiating pharmacoprophylaxis with UFH and/or mechanical VTE prophylaxis with IPC or CS in patients with hemiparesis from stroke or other neurological injury within 24 h if activated prothrombin time is measured. (Weak recommendation and low-quality evidence) If during the procedure rTPA or other thrombolytics are used, then extra caution is advised, and delay of initiation of chemoprophylaxis only for at least 24 h after the procedure should be considered. (Weak recommendation and low-quality evidence)
  2. Patients undergoing elective procedures may not require LMWH or UFH, but may benefit from early ambulation, and/or mechanical prophylaxis with IPC or CS. (Weak recommendation- very low-quality evidence)

 

Reference:

Nyquist, P., Bautista, C., Jichici, D., Burns, J., Chhangani, S., DeFilippis, M., Goldenberg, F., Kim, K., Liu-DeRyke, X., Mack, W. and Meyer, K. (2015). Prophylaxis of Venous Thrombosis in Neurocritical Care Patients: An Evidence-Based Guideline: A Statement for Healthcare Professionals from the Neurocritical Care Society. Neurocritical Care, 24(1), pp.47-60.

 

Anticoagulation in Patients with Brain Metastases

Treatment:

  • Anticoagulate in patients with brain tumors and VTE except if risk of ICH is high: i.e.
    • melanoma mets
    • renal cell carcinoma mets
    • choriocarcinoma mets
    • thyroid carcinoma mets
  • treat x 3-6 months; long term if malignant gliomas
  • LMWH recommended versus warfarin
  • If risk of ICH high:
    • IVC filter if significant residual brain mets
    • if mets already removed / treated effectively and medical condition too unstable – anticoagulate

DVT Prophylaxis:

  • do not anticoagulate except in post-operative period
  • use SCDs with post-op LMWH or UFH 12-24 hours after surgery
  • cotninue prophylaxis until ambulation resumed

 

REFERENCE:

Uptodate. “Anticoagulant and antiplatelet therapy in patients with brain tumors.” Accessed 08/12/2016.

Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007; 25:5490.

 

DDAVP

DESMOPRESSIN:

  • vasopressin analogue
    • does not have vasoconstriction / antidiuretic effects of vasopressin
  • DDAVP = deamino-arginine vasopressin

 

Mechanism of Action:

  • Increases cAMP in renal tubular cells –> increases water permeability –> decreased urine volume
  • Increases plasma vWF, F8 and t-PA –> shortened aPTT and bleeding time

 

DOSAGE:

1. Uremic bleeding (off-label): 0.4 mcg/kg IV over 10 minutes

  • corrects bleeding time in 75% of patients with renal failure
  • renal failure with significant bleeding: 1 dose given empirically; 2nd dose 8-12h later
  • recommended dose: 0.3 ug/kg IV, SQ or 30 ug/Kg intranasally
  • effect lasts 6-8h, repeated dosing leads to tachyphylaxis; responsiveness restored if drug withheld x 3-4d

2. Prevention of surgical bleeding in uremia (off-label): 0.3 mcg/kg IV over 30 minutes

3. Diabetes insipidus:

  • IV, SubQ: 2 to 4 mcg daily (0.5-1 mL) in 2 DD or 1/10 of maintenance intranasal dose
  • Oral: 0.05 mg BID, titrate total daily dose to adequate antidiuresis (0.1 to 1.2 mg in 2-3 DD)
  • Intranasal (100 mcg/mL nasal solution): 10-40 mcg OD (0.1 to 0.4 mL) or in 2-3 DD

4. Hemophilia A and von Willebrand disease (type 1):

  • IV: 0.3 mcg/kg by slow infusion; may repeat dose if needed; if used preoperatively, administer 30 minutes before procedure
  • Intranasal (using high concentration spray [1.5 mg/mL] [eg, Stimate]): <50 kg: 150 mcg (1 spray in a single nostril); ≥50 kg: 300 mcg (1 spray each nostril); repeat use is determined by the patient’s clinical condition and laboratory work. If using preoperatively, administer 2 hours before surgery.

 

5. Reversal of Aspirin in ICH:  0.4 ug/Kg x 1 dose (max dose 20 ug) 

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DDAVP (From NCS Guidelines)

  1. Mechanism of Action (reversal of aspirin)
    1. vasopressin analog, little vasopressor activity
    2. increases endothelial release of large factor VII: vWF multimers
    3. may increase platelet membrane glycoprotein expression, promoting platelet adhesion to endothelium
  2. Data
    1. shown to reduce bleeding time, normalize hemostasis in uremic patients undergoing surgery; improved platelet function in uremic patients exposed to aspirin
    2. improved platelet function demonstrated in healthy populations on ASA / COX-1 inhibitors or ADPr inhibitors.
    3. shown to significantly reduce blood loss and improve thrombus formation in cardiac surgery patients exposed to ASA pre-op
  3. Reported side-effects:
    1. facial flushing, peripheral edema, hypervolemia, increased UO, hyponatremia;
    2. rare reports of cerebrovascular thrombosis

“Because of the low risk of serious side effects, the relatively low cost, and the suggestion of benefit in the aforementioned studies, we suggest consideration of a single dose of DDAVP (0.4 mcg/kg) in intracranial hemorrhage patients exposed to antiplatelet agents. In patients deemed appropriate (e.g., those undergoing a neurosurgical procedure), DDAVP can be used in addition to platelet transfusion.” NSC Guidelines

 

References

Marino, Paul L, and Kenneth M Sutin. The ICU Book. Philadelphia: Lippincott Williams & Wilkins, 2007. Print.

Uptodate.

Frontera, J., Lewin, J., Rabinstein, A., Aisiku, I., Alexandrov, A., & Cook, A. et al. (2016). Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage. Critical Care Medicine44(12), 2251-2257. doi: 10.1097/ccm.0000000000002057