Early diagnosis of brain death in patients treated with central nervous system depressant drugs

Transplantation. 2000 Jul 15;70(1):131-5.


Background: Among the main causes for the relatively small number of organ donors, the delay in the diagnosis of brain death plays a major role. Administration of drugs causing central nervous system (CNS) depression prevents diagnosis of brain death by clinical and electroencephalographic criteria until serum clearance of the drug has occurred. Confirming brain death by demonstrating persistent intracranial circulatory arrest might decrease the length of the diagnostic process. We have carried out a prospective study to investigate whether 99 mTc-hexamethyl propylenamino oxime (99mTc-HMPAO) brain scintigraphy and/or transcranial Doppler ultrasound can speed up the diagnosis of brain death in patients treated with CNS depressant drugs.

Methods: All 138 consecutive patients with severe brain lesion that progressed to brain death in our center between January 1994 and December 1996 were controlled. Of them, 36 patients aged 1 to 65 years old (mean=25.6+/-18.3 years) who met clinical and EEG criteria for the diagnosis of brain death, except for the presence of significant serum levels of barbiturates (n=34), opiates (n=8), and benzodiazepines (n=3) were distributed in three groups according to the confirmatory test used; group 1: waiting for the metabolic clearance of CNS depressant drugs, or by demonstrating intracranial circulatory arrest with 99mTc-HMPAO (group 2) or transcranial Doppler (group 3). The delay in diagnosing brain death by the three methods was analyzed.

Results: The mean interval between the presumptive and the definitive diagnosis of brain death was 34.4+/-32.2 hr in group 1, 17.7+/-18.3 hr in group 2, and 5.0+/-4.6 hr in group 3 (P=0.004). The between-groups analysis showed that 99mTc-HMPAO and transcranial Doppler decreased the delay in diagnosing brain death with respect to waiting for drug clearance by 49% (P=0.16) and 85% (P<0.001), respectively. Moreover, transcranial Doppler decreased this time by 72% with respect to 99mTc-HMPAO (P<0.01).

Conclusions: Transcranial Doppler ultrasound and 99mTc-HMPAO brain scintigraphy can significantly reduce the time taken to confirm brain death in patients with significant serum levels of CNS depressant drugs. In this setting, transcranial Doppler is superior to 99mTc-HMPAO in reducing the waiting time for a firm diagnosis of brain death.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain / diagnostic imaging
  • Brain Death / diagnosis*
  • Central Nervous System Depressants / pharmacokinetics
  • Central Nervous System Depressants / pharmacology*
  • Child
  • Child, Preschool
  • Echoencephalography*
  • Female
  • Humans
  • Infant
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Prospective Studies
  • Radionuclide Imaging
  • Technetium Tc 99m Exametazime*
  • Ultrasonography, Doppler*


  • Central Nervous System Depressants
  • Technetium Tc 99m Exametazime