POINT: Whether Informed Consent Should Be Obtained for Apnea Testing in the Determination of Death by Neurologic Criteria? Yes

Abstract

Apnea testing (AT) should not be done in the first place; but if a physician insists on doing it anyway, informed consent should be obtained (online supplemental material can be found that provides detailed evidentiary support and full references). AT is integral to diagnostic protocols for “brain death” (BD), also called “death by neurologic criteria” (DNC).1Wijdicks E.F.M. Varelas P.N. Gronseth G.S. Greer D.M. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology. 2010; 74: 1911-1918Crossref PubMed Scopus (661) Google Scholar, 2Nakagawa T.A. Ashwal S. Mathur M. et al.Guidelines for the determination of brain death in infants and children: an update of the 1987 Task Force recommendations.Crit Care Med. 2011; 39: 2139-2155Crossref PubMed Scopus (84) Google Scholar, 3Greer D.M. Shemie S.D. Lewis A. et al.Determination of brain death/death by neurologic criteria: the World Brain Death Project.JAMA. 2020; 324: 1078-1097Crossref PubMed Scopus (102) Google Scholar It is precisely what renders these protocols ethically different from a standard neurologic examination. Certain confounding factors rarely are considered in practice.4Joffe A.R. Anton N.R. Duff J.P. The apnea test: rationale, confounders, and criticism.J Child Neurol. 2010; 25: 1435-1443Crossref Scopus (38) Google Scholar,5Joffe A.R. Hansen G. Tibballs J. The World Brain Death Project: the more you say it does not make it true.J Clin Ethics. 2021; 32: 97-108Google Scholar High cervical cord injury invalidates the clinical assessment of medullary respiratory drive. It is a common, potentially reversible, sequela of tonsillar herniation, yet it is hardly ever excluded. Central hypothyroidism and hypoadrenalism could further depress respiratory drive; they are common in BD but rarely excluded or corrected. The 2010 adult guidelines require Paco2 ≥ 60 mm Hg OR a 20-mm Hg increase over baseline1Wijdicks E.F.M. Varelas P.N. Gronseth G.S. Greer D.M. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology. 2010; 74: 1911-1918Crossref PubMed Scopus (661) Google Scholar; the 2011 pediatric guidelines require ≥ 60 mm Hg AND ≥ 20 mm Hg above baseline.2Nakagawa T.A. Ashwal S. Mathur M. et al.Guidelines for the determination of brain death in infants and children: an update of the 1987 Task Force recommendations.Crit Care Med. 2011; 39: 2139-2155Crossref PubMed Scopus (84) Google Scholar In many cases, the choice of conjunction occasions no practical consequence; however, in some cases, it literally could make the difference between life and death. Consider patient A with Paco2 of 63 mm Hg and an increase of 15 mm Hg and patient B with Paco2 of 56 mm Hg and an increase of 22 mm Hg. Under the adult guidelines, ATs for both patients are positive; under the pediatric guidelines, both are indeterminate. Proposals to specify these guidelines as the statutory “medical standard” for BD/DNC would carve this inconsistency into legal stone. The 60 mm Hg Paco2 threshold is based on expert consensus, not evidence. Published counterevidence is ignored: breathing resumption at Paco2 values of 112, 91, 77, 71, > 61, and > 60 mm Hg (Supplemental Table 1). For every published case, there must be many unpublished ones. A survey of “all pediatric critical care medicine fellowship directors in the United States and Canada” found that “10%…recall pediatric patients who took spontaneous breaths at Paco2 levels of > 60 torr.”6Brilli R.J. Bigos D. Apnea threshold and pediatric brain death [letter].Crit Care Med. 2000; 28: 1257Crossref Scopus (11) Google Scholar AT produces hypercarbia while avoiding hypoxemia by prehyperoxygenation and maintaining 100% oxygen flow. The theory is that hypercarbia is a much more potent medullary stimulus than hypoxia.3Greer D.M. Shemie S.D. Lewis A. et al.Determination of brain death/death by neurologic criteria: the World Brain Death Project.JAMA. 2020; 324: 1078-1097Crossref PubMed Scopus (102) Google Scholar(Suppl 4,p43) However, the isolated caudal medulla generates a gasping response to hypoxia.4Joffe A.R. Anton N.R. Duff J.P. The apnea test: rationale, confounders, and criticism.J Child Neurol. 2010; 25: 1435-1443Crossref Scopus (38) Google Scholar,5Joffe A.R. Hansen G. Tibballs J. The World Brain Death Project: the more you say it does not make it true.J Clin Ethics. 2021; 32: 97-108Google Scholar Not only is its integrity not tested, but the hyperoxygenation even suppresses it. Untested hypoxic drive was plausibly behind the breathing after withdrawal of support in some reports of false-positive diagnosis of BD/DNC. Key to BD/DNC is irreversibility. Supplemental Table 2 lists six reports of resumed breathing after positive AT, surely the tip of an iceberg of unreported cases. The incidence of potential for return of breathing after positive AT is unknowable, because virtually all patients with positive test results have support withdrawn or organs removed. The AT literature documents the following serious complications: tension pneumothorax, pneumomediastinum, pneumoperitoneum, interstitial emphysema, subcutaneous emphysema, severe hypoxemia, severe acidosis, severe hypotension, pulmonary hypertension, bradycardia, cardiac arrhythmia, myocardial infarction, and cardiac arrest. With methodologic refinements, the incidence of such complications has decreased markedly; nevertheless, most have been reported even after 2010 by authors who were following the guidelines, so the current risk is clearly not zero. Another serious risk has received little attention: causing further brain damage and even precipitating BD.4Joffe A.R. Anton N.R. Duff J.P. The apnea test: rationale, confounders, and criticism.J Child Neurol. 2010; 25: 1435-1443Crossref Scopus (38) Google Scholar,5Joffe A.R. Hansen G. Tibballs J. The World Brain Death Project: the more you say it does not make it true.J Clin Ethics. 2021; 32: 97-108Google Scholar,7Coimbra C.G. Implications of ischemic penumbra for the diagnosis of brain death.Braz J Med Biol Res. 1999; 32: 1479-1487Crossref PubMed Scopus (63) Google Scholar, 8Tibballs J. It is time to abandon apneic-oxygenation testing for brain death.Arch Organ Transplant. 2020; 5: 006-0010Google Scholar, 9D.A. Shewmon. Statement in support of revising the Uniform Determination of Death Act and in opposition to a proposed revision [published online ahead of print May 14, 2021]. J Med Philos. https://doi.org/10.1093/jmp/jhab014Google Scholar Management guidelines for patients who are brain-injured warn that hypercarbia and acidosis (and with hypoxic-ischemic cause, possibly also hyperoxia) can exacerbate brain damage. Therefore, basic principles of neurointensive care include maintaining normocarbia, neutral pH, and normoxia. What these “best practices” uniformly emphasize to avoid is precisely what AT is designed to bring about. Management guidelines also enjoin avoiding hypotension, which is a common occurrence during AT. Deviation from these neuroprotective measures for only 10 to 15 minutes (typical duration of AT) could be all it takes to further damage a brain under high intracranial pressure with tenuous blood flow. Just a slight decrease in BP, which is insufficient to consider a hemodynamic complication, or a hypercarbia-induced slight increase in intracranial pressure could reduce blood flow critically to areas of the brain that are not already infarcted, possibly even precipitating intracranial circulatory arrest.7Coimbra C.G. Implications of ischemic penumbra for the diagnosis of brain death.Braz J Med Biol Res. 1999; 32: 1479-1487Crossref PubMed Scopus (63) Google Scholar The few promoters of AT who have acknowledged this risk dismiss it as merely “theoretically possible.”3Greer D.M. Shemie S.D. Lewis A. et al.Determination of brain death/death by neurologic criteria: the World Brain Death Project.JAMA. 2020; 324: 1078-1097Crossref PubMed Scopus (102) Google Scholar(Suppl 4,p46) Their arguments and my rebuttals are detailed in the Supplemental Material. Evidence from both intracranial monitoring and EEG during AT suggests that AT indeed decreases cerebral perfusion in some patients.10Schwarz G. Litscher G. Pfurtscheller G. Schalk H.V. Rumpl E. Fuchs G. Brain death: timing of apnea testing in primary brain stem lesion.Intensive Care Med. 1992; 18: 315-316Crossref Scopus (6) Google Scholar,11Roth C. Deinsberger W. Kleffmann J. Ferbert A. Intracranial pressure and cerebral perfusion pressure during apnoea testing for the diagnosis of brain death: an observational study.Eur J Neurol. 2015; 22: 1208-1214Crossref PubMed Scopus (24) Google Scholar Before conducting a procedure with plausible grounds for concern over a risk of exacerbating brain damage, the burden of proof lies with those claiming safety, not with those expressing concern. One cannot help wondering whether a patient like Jahi McMath, who was subjected to AT three times, might have experienced greater functional recovery had no AT been done.12Shewmon D.A. Salamon N. The extraordinary case of Jahi McMath.Perspect Biol Med. 2021; 64: 457-478Crossref Scopus (3) Google Scholar The same goes for other extraordinary cases with return of some brain function after a false-positive diagnosis of BD/DNC. That the ICU team already has given up on the patient by the time they decide to embark on a BD/DNC evaluation is reflected in the attitude toward serious systemic complications. In the AT literature, whenever a serious complication is bemoaned, the stated reason for regret is always and only that transplantable organs were lost. The irony is that the ATs that caused such organ wastage were unnecessary to begin with, which brings us to the next point. The DNC guidelines are like the two-faced Roman god Janus regarding the role of AT. On the one hand, it is “mandatory,” “essential,” and “indispensable”; on the other, if it cannot be performed, DNC can be diagnosed anyway by including an otherwise optional ancillary test.1Wijdicks E.F.M. Varelas P.N. Gronseth G.S. Greer D.M. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology. 2010; 74: 1911-1918Crossref PubMed Scopus (661) Google Scholar,2Nakagawa T.A. Ashwal S. Mathur M. et al.Guidelines for the determination of brain death in infants and children: an update of the 1987 Task Force recommendations.Crit Care Med. 2011; 39: 2139-2155Crossref PubMed Scopus (84) Google Scholar In one large study, BD/DNC was diagnosed in 10% without AT.13Wijdicks E.F.M. Rabinstein A.A. Manno E.M. Atkinson J.D. Pronouncing brain death. Contemporary practice and safety of the apnea test.Neurology. 2008; 71: 1240-1244Crossref Scopus (96) Google Scholar A few years ago, I asked a coauthor of the 2010 adult guidelines: “If BD can be diagnosed without AT and with supposedly equal certainty by including a risk-free ancillary test, why should AT be mandatory, given its non-zero risk?” The question seemed to surprise him, and he had no ready answer. Given all the aforementioned considerations, the question of informed consent seems almost absurd. Consent is required for such benign and beneficial procedures as skin biopsy. Imagine a surgeon proposing a new procedure for approval by the hospital’s medical staff: “This fantastic new procedure offers no benefit to the patient, does not accomplish its purpose, risks serious harm including brain damage and death, and is unnecessary. Oh, by the way, I wish to forego informed consent and to be authorized to perform it over the patient’s or proxy’s objection.” Need any more be said? The issue of informed consent for AT first arises not in the ICU but in the Department of Motor Vehicles and not with proxies but with potential future patients, while they still have the capacity to consent; however, the opportunity is withheld systematically.14Nair-Collins M. The public’s right to accurate and transparent information about brain death and organ transplantation.Hastings Cent Rep. 2018; 48: S43-S45Crossref Scopus (6) Google Scholar Instead of relevant information, they are given propaganda that appeals to altruism. Essentially, no nonmedical person who checks the organ donor box understands that they are implicitly agreeing to AT. The reason that informed consent for AT is so vigorously opposed by those invested in the current BD/DNC guidelines is that they realize that hardly anyone, once truly informed, would ever consent to it. Other contributions: The author thanks Drs Ari Joffe and Doyen Nguyen for their helpful feedback. This essay builds upon Truog’s and Tasker’s 2017 “Counterpoint” on the same topic (Chest 2017;152(4):702-4) and upon many of the Open Peer Commentaries in the June 2020 issue of the American Journal of Bioethics. Additional information: The e-Tables are available online under “Supplementary Data.” Download .docx (.45 MB) Help with docx files e-Online Data Rebuttal From Dr ShewmonCHESTVol. 161Issue 5PreviewMy esteemed colleague conflates apnea testing with diagnosis of death by neurologic criteria (DNC).1 The topic under discussion is whether consent is required for apnea testing, not for diagnosis of DNC. Full-Text PDF Rebuttal From Dr PopeCHESTVol. 161Issue 5PreviewShewmon1 completely avoids addressing the question of whether informed consent should be obtained for apnea testing in the determination of death by neurologic criteria. For Shewmon, this question is moot and “almost absurd” because he argues that we should never use apnea testing. He contends that it is unreliable, unsafe, and completely replaceable with ancillary testing. The question of consent arises only for those tests that we plan to administer. Because Shewmon contends that apnea testing should never be administered, he further contends that the question of consent never arises. Full-Text PDF COUNTERPOINT: Whether Informed Consent Should Be Obtained for Apnea Testing in the Determination of Death by Neurologic Criteria? NoCHESTVol. 161Issue 5PreviewFor 4 decades, in almost every US jurisdiction, the determination of death has been governed by the Uniform Determination of Death Act (UDDA).1 But since 2015, this law has come under increasing scrutiny in legislatures, courts, and scholarly literature.2 Most significantly, in July 2021, the Uniform Law Commission appointed a Drafting Committee to revise the UDDA. One of four charter questions for this Committee is whether to amend the UDDA to better clarify whether clinicians must obtain consent before testing for death by neurologic criteria, commonly referred to as “brain death/death by neurologic criteria” (BD/DNC). Full-Text PDF