Month: May 2022

Naloxone Dosing

Indication: progressive obtundation suggestive of imminent respiratory failure in non-ventilated patients

1.) Spontaneous respirations present

  • dilute naloxone 0.4mg/1mL ampule with 9 mL normal saline (total volume 10mL) and administer naloxone 0.04 mg bolus injections titrate up every few minutes until respiratory rate >12

2.) Apneic

  • initial dose should be higher (0.2 to 1mg)

3.) Cardiac arrest

  • initial dose 2mg

Reference:

UpToDate. (2022). Retrieved 30 May 2022, from https://www.uptodate.com/contents/pain-control-in-the-critically-ill-adult-patient?search=pain%20control%20critically%20ill&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Haloperidol Dosing Regimen

NOTE: haloperidol is commonly administered IV, but this has not been approved by US FDA. (IV administration may increase risk of torsades de pointes and sudden cardiac death.)

DOSING REGIMEN:

  • haloperidol 2.5 to 5 mg IV bolus q6h PRN
  • Based on severity
    • mild agitation – 0.5 to 2 mg
    • moderate agitation – 2-5 mg
    • severe agitation – 10-20 mg
    • repeat dose as frequently as ever 15-30 mins in severe agitation until desired level of sedation is achieved
  • continuous infusion – start at 10mg/h then increase 5mg/hr every 30 minutes as needed until calm is achieved
  • once calm restored, start maintenance dose – give 25% of totalloading dose every 6 hours

Safe maximum daily dose unknown – case reports of doses as high as 945mg/day. Doses >200mg/day have been safely administered up to 15 consecutive days.

Reference:

UpToDate. (2022). Retrieved 30 May 2022, from https://www.uptodate.com/contents/sedative-analgesic-medications-in-critically-ill-adults-properties-dosage-regimens-and-adverse-effects?search=sedative%20analgesic&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Distinctive Trajectories of Neurocritical Illness

This is an interesting figure that depicts the different trajectories of functional decline or recovery among patients withneurocritical illnesses. Onset is usually sudden, with a precipitous decline from normal baselinefunction. Most patients do not progress to cardiovascular or brain death though, but rather, survive with some form of disability.

Reference:

Frontera, J., Curtis, J., Nelson, J., Campbell, M., Gabriel, M., & Mosenthal, A. et al. (2015). Integrating Palliative Care Into the Care of Neurocritically Ill Patients. Critical Care Medicine, 43(9), 1964-1977. doi: 10.1097/ccm.0000000000001131

DOACs for Cerebral Venous Thrombosis

2 Trials:

  • RE-SPECT CVT Trial
  • ACTION CVT Trial

RE-SPECT Cerebral Venous Thrombosis (CVT) Trial Design

Trial Design: Exploratory, prospective, randomized parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication. 9 countries. 120 patients randomized.

Results: 120 patients, 2 treatment groups (dabigatran 150mg BID vs dose-adjusted warfarin x 24 weeks)

  • No recurrent VTEs were observed.
  • One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group.
  • One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non–major bleeding event.
  • Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7).

Conclusion: Patients anticoagulated with dabigatran or warfarin had low risk of recurrent VTEs and risk of bleeding similar with both meds – dabigatran adn warfarin may be safe and effective for preventing VTEs in patients with CVT.

ACTION-CVT Trial

Trial Design: Multicenter international retrospective study (US, Europe, NZ). 845 patients met inclusion criteria.

Results: DOAC treatment was associated with

  • similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51–1.73]; P=0.84)
  • similar risk of death (aHR, 0.78 [95% CI, 0.22–2.76]; P=0.70),
  • rimilar rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48–1.73]; P=0.79)
  • lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15–0.82]; P=0.02)

Conclusion: Treatment with DOACs is associated with similar clinical and radiographic outcomes and favorable safety profile compared with warfarin.

Limitations: not blinded, retrospective design, large lost-to-follow-up, recurrent rates include de-novo and existing CVT, unclear INR levels, asymptomatic patients did not get imaging

Bottom-line: These studies appear to favor DOACs (lesser bleed, similar efficacy) but needs more data, better studies.

References:

Ferro, J., Coutinho, J., Dentali, F., Kobayashi, A., Alasheev, A., & Canhão, P. et al. (2019). Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis. JAMA Neurology, 76(12), 1457. doi: 10.1001/jamaneurol.2019.2764

Yaghi, S., Shu, L., Bakradze, E., Salehi Omran, S., Giles, J., & Amar, J. et al. (2022). Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study. Stroke, 53(3), 728-738. doi: 10.1161/strokeaha.121.037541