(UNLOCKED) The Real-World Boards: Question #31
Wait, this brain death protocol we've been using is from 2021
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A 33-year-old man experienced a cardiac arrest after an opioid overdose. He is obese (BMI 45) but has no known medical history. He was resuscitated but experienced anoxic encephalopathy. Four days later, he is unresponsive to pain and has absent brainstem reflexes. Sodium is 148 mmol/L, BUN is 48 mg/dL (2x ULN), creatinine is 2.1 mg/dL (2x ULN), serum bicarbonate is 29 meq/L (=ULN), pH is 7.44, pCO2 40 mmHg, paO2 120 mmHg. Fentanyl infusion was discontinued 48 hours ago. Mean arterial pressure is 68 mmHg and pulse 108/min.
After preoxygenation with FIO2 1.0 for ten minutes, an apnea test is performed by changing the ventilator settings to CPAP mode (pressure support 8 cm H2O) with 100% FIO2. Mean arterial pressure is maintained between 65 and 70 mmHg throughout, on low-dose norepinephrine.
There are no respiratory efforts observed. After five minutes, arterial blood gas shows pH 7.31 and pCO2 of 61 mmHg (a 21 mmHg increase).
The organ procurement organization representative has been nearly omnipresent in the ICU, and makes a sad face, but you (an amateur poker player) notice her pupils dilate.
Death by neurologic criteria (brain death) was a new medical-legal concept created in the 1960s in response to two new simultaneous societal phenomena: neurologically devastated patients could be physiologically maintained on ventilators for prolonged periods, and emerging organ transplantation programs (and their growing lists of desperate patients) faced a scarcity of viable organs. The new construct allowed for the legal and ethical removal of organs from physiologically “alive” persons who, upon meeting stringent objective criteria, would henceforth be designated as neurologically and therefore legally “dead”.
After various medical, sociopolitical, and legal controversies regarding DNC arose in the early 21st century, the American Academy of Neurology, other U.S. societies, and the World Brain Death Project embarked on a project to shore up the concept of brain death, standardize its diagnosis, and bolster public trust.
The effort ran into challenges, many of which derive from the variability of human physiology, the persistence of edge cases, and the limitations of relatively crude bedside tests to infallibly guarantee “the irreversible cessation of all functions of the entire brain, including the brainstem” (the legal standard) in every patient with the necessary 100% sensitivity and specificity.
The AAN, SCCM, and pediatric societies nonetheless produced an updated guideline in 2023 that addressed many of the controversies and borderline cases of brain death.
Let’s examine how these complicate just two of the criteria for BD/DNC declaration, as applied to the case in the above board question.
Correction of Confounders
Confounding factors for encephalopathy must be corrected before declaring DNC/brain death. But most critically ill patients present with or develop confounding factors for encephalopathy. Which abnormalities are considered non-barriers to the determination of brain death, and how abnormal can they be? This is often the most vexing challenge in making the diagnosis of brain death with the required certainty.
The AAN guideline specifies some of these conditions, which include:
Hypotension: Systolic blood pressure must be ≥100 mmHg, and mean arterial pressure ≥75 mm Hg (with vasopressor use if needed). Patients with chronic high or low blood pressure should have their BP maintained near that mark.
Hypothermia: At least 24 hours is required after rewarming to 36°C before a BD/DNC evaluation, if core body temperature has been ≤35.5°C. Yet brain death has been demonstrated to be reversible more than 24 hours after normothermia has been restored.
Sedation: The evaluation should be delayed by at least 5 half-lives (e.g., fentanyl: <7 hours), while also factoring in liver or renal dysfunction, body mass index, age, and slowed metabolism from hypothermia. For example, in the elderly, fentanyl’s half-life is estimated to be five times as long as a young person’s. This could imply waiting longer than a week before brain death evaluation.
Metabolic/lab abnormalities: the panel specifies numerous lab values to be corrected before BD/DNC evaluation: sodium should be 130-160; glucose 70-300; pH 7.3 - 7.5; BUN <75; etc.
This list is not exhaustive, though it is exhausting: see the documents for even more caveats and cautions.
Apnea Testing
A complete guide to apnea testing can be found here. Some important points from the 2023 guideline include:
Patients may remain on the ventilator circuit in CPAP mode during apnea testing; the traditional method of instilling oxygen through a nasal cannula positioned above the carina is optional.
Although “8 to 10 minutes” is advised, an apnea test can be stopped earlier if the criteria of pCO2 ≥60 mmHg and ≥20 mmHg increase over baseline and pH <7.30 are met (e.g., on serial ABGs).
The pre-test ABG should be collected after preoxygenation (not before, as in the stem).
The apnea test must be aborted if at any point systolic BP falls below 100 mmHg, or MAP <75 mm Hg (with or without vasopressors).
For patients with baseline hypercarbia, the pCO2 increase must be ≥20 mmHg above their “known chronic elevated premorbid baseline level” (if there is a single known level!), with pH< 7.30.
For those with suspected baseline hypercarbia (like the patient in the stem), they must meet the usual criteria of pCO2 ≥60 mmHg and ≥20 mmHg increase over baseline and pH <7.30, and undergo ancillary testing (EEG, 4-vessel cerebral angiogram, radionuclide perfusion scintigraphy, or transcranial doppler ultrasonography).
EEG, CT angiogram, and MR angiogram should not be used as ancillary tests, as they have not been validated for this purpose, according to the panel.
As we reviewed here, though, when considering the level of certainty required, the guideline-approved brain death tests have not been well-validated, either:
Like many aspects of medicine, the concept of brain death seemed simple in an earlier era. Over decades, an evolving understanding has revealed cracks in the façade of its objective certainty, and of our ability to achieve perfection in its identification.
While most cases of death by neurologic criteria are clear-cut, clinicians should maintain extreme caution, a high vigilance for edge cases, and a stubborn resistance to pressure from financially conflicted actors, to avoid becoming implicated in near-catastrophic situations like this one.
Reflect to earn CME with Learner+
Sample reflection: I reviewed and reflected on the evolving understanding of death by neurological criteria (brain death), its increasingly complex definition and diagnosis, and the medical and legal implications for clinical practice.
References
Greer DM, Kirschen MP, Lewis A, et al. Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline: Report of the AAN Guidelines Subcommittee, AAP, CNS, and SCCM. Neurology. 2023;101(24). doi:https://doi.org/10.1212/WNL.0000000000207740
Lewis A, Kirschen MP, Greer D. The 2023 AAN/AAP/CNS/SCCM Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Practice Guideline: A Comparison With the 2010 and 2011 Guidelines. Neurology: Clinical Practice. 2023;13(6). doi:https://doi.org/10.1212/CPJ.0000000000200189
Crazy to see so much variation in responses to such a straight forward case. It really points to the lack of clarity or the perceived (in my opinion, overblown) concern of medicolegal risk that has neutered physicians. The only issue I see is the MAP <75 (which I forgot) but which could easily be remedied with some more NE and would absolutely not change the result. In my experience in the US, brain death is almost universally determined by a radiologist, contrary to all societal and state guidance.