Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination

Summary

Current standard of care prior to determination of brain death in subjects with suspected anoxic brain injury is to exclude complicating medical conditions that may confound clinical assessment (such as severe electrolyte, acid base, endocrine or circulatory disturbance), achieve normothermia and normal systolic blood pressure over 100 mmHg (with or without vasopressor use), exclude the presence of neuromuscular blocking agents (with the presence of a train of 4 twitches with maximal ulnar nerve stimulation) as well as to exclude the presence of CNS depressant drug effects. At the present time the latter is done by history, drug screen and allowing enough time for paralytic and sedative drugs to be metabolized and cleared from the body. Clearance is calculated by using 5 times the drug's half-life assuming normal hepatic and renal functions. Half-life can also be prolonged in subjects who have been treated with induced hypothermia. Literature search revealed articles with general guidelines and approaches to brain death, but none addressed pharmacological reversal of sedative drugs

Timeline

Start

2019-01-01

Primary completion

2021-07-20

Completion

2021-07-21

Publications

• Background Varelas PN, Lewis A. Modern Approach to Brain Death. Semin Neurol. 2016 Dec;36(6):625-630. doi: 10.1055/s-0036-1592317. Epub 2016 Dec 1.
• Background Wijdicks EF. Brain death guidelines explained. Semin Neurol. 2015 Apr;35(2):105-15. doi: 10.1055/s-0035-1547532. Epub 2015 Apr 3.
• Background Gardiner D, Shemie S, Manara A, Opdam H. International perspective on the diagnosis of death. Br J Anaesth. 2012 Jan;108 Suppl 1:i14-28. doi: 10.1093/bja/aer397.
• Background Wijdicks EF. Brain death worldwide: accepted fact but no global consensus in diagnostic criteria. Neurology. 2002 Jan 8;58(1):20-5. doi: 10.1212/wnl.58.1.20.
• Background Wijdicks EF. The diagnosis of brain death. N Engl J Med. 2001 Apr 19;344(16):1215-21. doi: 10.1056/NEJM200104193441606. No abstract available.
• Background Wijdicks EF. Determining brain death in adults [RETIRED]. Neurology. 1995 May;45(5):1003-11. doi: 10.1212/wnl.45.5.1003. No abstract available.
• Background Wahlster S, Wijdicks EF, Patel PV, Greer DM, Hemphill JC 3rd, Carone M, Mateen FJ. Brain death declaration: Practices and perceptions worldwide. Neurology. 2015 May 5;84(18):1870-9. doi: 10.1212/WNL.0000000000001540. Epub 2015 Apr 8.
• Background Wijdicks EF, Varelas PN, Gronseth GS, Greer DM; American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010 Jun 8;74(23):1911-8. doi: 10.1212/WNL.0b013e3181e242a8.
• Background Greer DM, Varelas PN, Haque S, Wijdicks EF. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology. 2008 Jan 22;70(4):284-9. doi: 10.1212/01.wnl.0000296278.59487.c2. Epub 2007 Dec 12.
• Background Shappell CN, Frank JI, Husari K, Sanchez M, Goldenberg F, Ardelt A. Practice variability in brain death determination: a call to action. Neurology. 2013 Dec 3;81(23):2009-14. doi: 10.1212/01.wnl.0000436938.70528.4a. Epub 2013 Nov 6.

Drugs

Indications