Withdrawal of Life-Sustaining Therapies and Brain Death in the Intensive Care Unit

ABSTRACT

The majority of patients who die in intensive care units (ICUs), do so as a result of the withdrawal of life-sustaining treatments or as a result of brain death. With the increasing shortage of transplantable organs, there is growing interest in both these patient populations and their potential for organ donation after cardiac death (DCD) or death by neurological criteria. Therefore, it is imperative for neurologists and neurosurgeons to be familiar with both processes when consulted to evaluate these very sick patients in the ICU. The medicolegal and ethical considerations, the factors that lead to the decision for withdrawal (with special attention to prognostication of the major neurological diseases encountered in an ICU), the process of withdrawal of life-sustaining treatment itself, and the DCD process will be examined. The medicolegal aspects of brain death will also be examined, with particular focus on the process and the various pitfalls and misconceptions.

KEYWORDS

Withdrawal of life support - brain death - intensive care unit - neurological - death by cardiac death

REFERENCES

• 1 Angus D C, Barnato A E, Linde-Zwirble W T et al.. Use of intensive care at the end of life in the United States: an epidemiologic study.  Crit Care Med. 2004;  32 638-643
• 2 Gordo F, Nunez A, Calvo E, Algora A. Intrahospital mortality after discharge from the ICU (hidden mortality) in patients who required mechanical ventilation.  Med Clin (Barc). 2003;  121 241-244
• 3 Wallis C B, Davies H T, Shearer A J. Why do patients die on general wards after discharge from intensive care units?.  Anaesthesia. 1997;  52 9-14
• 4 Cook D, Rocker G, Marshall J et al.. Withdrawal of mechanical ventilation in anticipation of death in the intensive care unit.  N Engl J Med. 2003;  349 1123-1132
• 5 Hall R I, Rocker G M. End-of-life care in the ICU: treatments provided when life support was or was not withdrawn.  Chest. 2000;  118 1424-1430
• 6 Keenan S P, Busche K D, Chen L M, McCarthy L, Inman K J, Sibbald W J. A retrospective review of a large cohort of patients undergoing the process of withholding or withdrawal of life support.  Crit Care Med. 1997;  25 1324-1331
• 7 Prendergast T J, Luce J M. Increasing incidence of withholding and withdrawal of life support from the critically ill.  Am J Respir Crit Care Med. 1997;  155 15-20
• 8 Lawrence A, Havill J H. An audit of deaths occurring in hospital after discharge from the intensive care unit.  Anaesth Intensive Care. 1999;  27 185-189
• 9 Esteban A, Gordo F, Solsona J F et al.. Withdrawing and withholding life support in the intensive care unit: a Spanish prospective multi-centre observational study.  Intensive Care Med. 2001;  27 1744-1749
• 10 Wunsch H, Harrison D A, Harvey S, Rowan K. End-of-life decisions: a cohort study of the withdrawal of all active treatment in intensive care units in the United Kingdom.  Intensive Care Med. 2005;  31 823-831
• 11 Ferrand E, Robert R, Ingrand P, Lemaire F. Withholding and withdrawal of life support in intensive-care units in France: a prospective survey. French LATAREA Group.  Lancet. 2001;  357 9-14
• 12 Smedira N G, Evans B H, Grais L S et al.. Withholding and withdrawal of life support from the critically ill.  N Engl J Med. 1990;  322 309-315
• 13 Wood G G, Martin E. Withholding and withdrawing life-sustaining therapy in a Canadian intensive care unit.  Can J Anaesth. 1995;  42 186-191
• 14 Varelas P N, Conti M M, Spanaki M V et al.. The impact of a neurointensivist-led team on a semiclosed neurosciences intensive care unit.  Crit Care Med. 2004;  32 2191-2198
• 15 Suarez J I, Zaidat O O, Suri M F et al.. Length of stay and mortality in neurocritically ill patients: impact of a specialized neurocritical care team.  Crit Care Med. 2004;  32 2311-2317
• 16 Mayer S A, Kossoff S B. Withdrawal of life support in the neurological intensive care unit.  Neurology. 1999;  52 1602-1609
• 17 Diringer M N, Edwards D F, Aiyagari V, Hollingsworth H. Factors associated with withdrawal of mechanical ventilation in a neurology/neurosurgery intensive care unit.  Crit Care Med. 2001;  29 1792-1797
• 18 Beauchamp T L, Childress J F. Principles of Biomedical Ethics. New York; Oxford University Press 2001
• 19 Prendergast T J, Puntillo K A. Withdrawal of life support: intensive caring at the end of life.  JAMA. 2002;  288 2732-2740
• 20 Manno E M, Wijdicks E F. The declaration of death and the withdrawal of care in the neurologic patient.  Neurol Clin. 2006;  24 159-169
• 21 Larriviere D, Bonnie R J. Terminating artificial nutrition and hydration in persistent vegetative state patients: current and proposed state laws.  Neurology. 2006;  66 1624-1628
• 22 Bacon D, Williams M A, Gordon J. Position statement on laws and regulations concerning life-sustaining treatment, including artificial nutrition and hydration, for patients lacking decision-making capacity.  Neurology. 2007;  68 1097-1100
• 23 Cook D, Rocker G, Giacomini M, Sinuff T, Heyland D. Understanding and changing attitudes toward withdrawal and withholding of life support in the intensive care unit.  Crit Care Med. 2006;  34 S317-S323
• 24 Sprung C L, Cohen S L, Sjokvist P et al.. End-of-life practices in European intensive care units: the Ethicus Study.  JAMA. 2003;  290 790-797
• 25 Sinuff T, Adhikari N K, Cook D J et al.. Mortality predictions in the intensive care unit: comparing physicians with scoring systems.  Crit Care Med. 2006;  34 878-885
• 26 Pochard F, Azoulay E, Chevret S et al.. French intensivists do not apply American recommendations regarding decisions to forgo life-sustaining therapy.  Crit Care Med. 2001;  29 1887-1892
• 27 Faber-Langendoen K, Lanken P N. Dying patients in the intensive care unit: forgoing treatment, maintaining care.  Ann Intern Med. 2000;  133 886-893
• 28 Becker K J, Baxter A B, Cohen W A et al.. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies.  Neurology. 2001;  56 766-772
• 29 Hemphill III J C, Newman J, Zhao S, Johnston S C. Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage.  Stroke. 2004;  35 1130-1134
• 30 Wijdicks E F, Hijdra A, Young G B, Bassetti C L, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology. 2006;  67 203-210
• 31 Geocadin R G, Buitrago M M, Torbey M T, Chandra-Strobos H, Williams M A, Kaplan P W. Neurologic prognosis and withdrawal of life support after resuscitation from cardiac arrest.  Neurology. 2006;  67(1) 105-108
• 32 Tuhrim S, Dambrosia J M, Price T R et al.. Intracerebral hemorrhage: external validation and extension of a model for prediction of 30-day survival.  Ann Neurol. 1991;  29 658-663
• 33 Hemphill III J C, Bonovich D C, Besmertis L, Manley G T, Johnston S C. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage.  Stroke. 2001;  32 891-897
• 34 Tamargo R J, Walter K A, Oshiro E M. Aneurysmal subarachnoid hemorrhage: prognostic features and outcomes.  New Horiz. 1997;  5 364-375
• 35 Rosengart A J, Schultheiss K E, Tolentino J, Macdonald R L. Prognostic factors for outcome in patients with aneurysmal subarachnoid hemorrhage.  Stroke. 2007;  38 2315-2321
• 36 Frankel M R, Morgenstern L B, Kwiatkowski T et al.. Predicting prognosis after stroke: a placebo group analysis from the National Institute of Neurological Disorders and Stroke rt-PA Stroke Trial.  Neurology. 2000;  55 952-959
• 37 Steiner T, Mendoza G, De Georgia M, Schellinger P, Holle R, Hacke W. Prognosis of stroke patients requiring mechanical ventilation in a neurological critical care unit.  Stroke. 1997;  28 711-715
• 38 Towne A R, Pellock J M, Ko D, DeLorenzo R J. Determinants of mortality in status epilepticus.  Epilepsia. 1994;  35 27-34
• 39 Treiman D M, Meyers P D, Walton N Y et al.. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group.  N Engl J Med. 1998;  339 792-798
• 40 Holtkamp M, Othman J, Buchheim K, Meierkord H. Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit.  J Neurol Neurosurg Psychiatry. 2005;  76 534-539
• 41 Gilligan T, Raffin T A. Withdrawing life support: extubation and prolonged terminal weans are inappropriate.  Crit Care Med. 1996;  24 352-353
• 42 Ethical and moral guidelines for the initiation, continuation, and withdrawal of intensive care. American College of Chest Physicians/ Society of Critical Care Medicine Consensus Panel.  Chest. 1990;  97 949-958
• 43 Faber-Langendoen K, Bartels D M. Process of forgoing life-sustaining treatment in a university hospital: an empirical study.  Crit Care Med. 1992;  20 570-577
• 44 Donatelli L A, Geocadin R G, Williams M A. Ethical issues in critical care and cardiac arrest: clinical research, brain death, and organ donation.  Semin Neurol. 2006;  26 452-459
• 45 Kirchhoff K T, Anumandla P R, Foth K T, Lues S N, Gilbertson-White S H. Documentation on withdrawal of life support in adult patients in the intensive care unit.  Am J Crit Care. 2004;  13 328-334
• 46 Gedge E, Giacomini M, Cook D. Withholding and withdrawing life support in critical care settings: ethical issues concerning consent.  J Med Ethics. 2007;  33 215-218
• 47 Treece P D, Engelberg R A, Crowley L et al.. Evaluation of a standardized order form for the withdrawal of life support in the intensive care unit.  Crit Care Med. 2004;  32 1141-1148
• 48 Lee D K, Swinburne A J, Fedullo A J, Wahl G W. Withdrawing care. Experience in a medical intensive care unit.  JAMA. 1994;  271 1358-1361
• 49 Manno E M. Nonheart-beating donation in the neurologically devastated patient.  Neurocrit Care. 2005;  3 111-114
• 50 Uniform Determination of Death Act. 12 Uniform Laws Annotated (U.L.A.) 589 (West 1993 and West Supp 1997)
• 51 Powner D J, Hernandez M, Rives T E. Variability among hospital policies for determining brain death in adults.  Crit Care Med. 2004;  32 1284-1288
• 52 Greer D M, Varelas P N, Haque S, Wijdicks E F. Variability of brain death determination guidelines in leading US neurologic institutions.  Neurology. 2008;  70 284-289
• 53 Practice parameters for determining brain death in adults (summary statement). The Quality Standards Subcommittee of the American Academy of Neurology.  Neurology. 1995;  45 1012-1014
• 54 Guidelines for the determination of death. Report of the medical consultants on the diagnosis of death to the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research.  JAMA. 1981;  246 2184-2186
• 55 Wijdicks E F. Brain death worldwide: accepted fact but no global consensus in diagnostic criteria.  Neurology. 2002;  58 20-25
• 56 Wijdicks E F. The diagnosis of brain death.  N Engl J Med. 2001;  344 1215-1221
• 57 Wijdicks E F. Determining brain death in adults.  Neurology. 1995;  45 1003-1011
• 58 Al-Shammri S, Nelson R F, Madavan R, Subramaniam T A, Swaminathan T R. Survival of cardiac function after brain death in patients in Kuwait.  Eur Neurol. 2003;  49 90-93
• 59 Wijdicks E FM. Neurologic states resembling brain death. In: Wijdicks EFM Brain Death. Philadelphia, PA; Lippincott Williams and Wilkins 2001: 115-134
• 60 Lopez-Navidad A, Caballero F, Domingo P et al.. Early diagnosis of brain death in patients treated with central nervous system depressant drugs.  Transplantation. 2000;  70 131-135
• 61 Wijdicks E FM. Confirmatory testing of brain death in adults. In: Wijdicks EFM Brain Death. Philadelphia, PA; Lippincott Williams and Wilkins 2001: 61-90
• 62 Santamaria J, Orteu N, Iranzo A, Tolosa E. Eye opening in brain death.  J Neurol. 1999;  246 720-722
• 63 Jain S, DeGeorgia M. Brain death-associated reflexes and automatisms.  Neurocrit Care. 2005;  3 122-126
• 64 Goetting M G, Contreras E. Systemic atropine administration during cardiac arrest does not cause fixed and dilated pupils.  Ann Emerg Med. 1991;  20 55-57
• 65 Schmidt J E, Tamburro R F, Hoffman G M. Dilated nonreactive pupils secondary to neuromuscular blockade.  Anesthesiology. 2000;  92 1476-1480
• 66 Huttemann E, Schelenz C, Sakka S G, Reinhart K. Atropine test and circulatory arrest in the fossa posterior assessed by transcranial Doppler.  Intensive Care Med. 2000;  26 422-425
• 67 Lang C J. Apnea testing by artificial CO2 augmentation.  Neurology. 1995;  45 966-969
• 68 Sharpe M D, Young G B, Harris C. The apnea test for brain death determination: an alternative approach.  Neurocrit Care. 2004;  1 363-366
• 69 al Jumah M, McLean D R, al Rajeh S, Crow N. Bulk diffusion apnea test in the diagnosis of brain death.  Crit Care Med. 1992;  20 1564-1567
• 70 Levesque S, Lessard M R, Nicole P C et al.. Efficacy of a T-piece system and a continuous positive airway pressure system for apnea testing in the diagnosis of brain death.  Crit Care Med. 2006;  34 2213-2216
• 71 Buchner H, Schuchardt V. Reliability of electroencephalogram in the diagnosis of brain death.  Eur Neurol. 1990;  30 138-141
• 72 Rimmele T, Malhiere S, Ben Cheikh A et al.. The electroencephalogram is not an adequate test to confirm the diagnosis of brain death.  Can J Anaesth. 2007;  54 652-656
• 73 Monteiro L M, Bollen C W, van Huffelen A C, Ackerstaff R G, Jansen N J, van Vught A J. Transcranial Doppler ultrasonography to confirm brain death: a meta-analysis.  Intensive Care Med. 2006;  32 1937-1944
• 74 Ducrocq X, Hassler W, Moritake K et al.. Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography: Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology.  J Neurol Sci. 1998;  159 145-150
• 75 Dominguez-Roldan J M, Jimenez-Gonzalez P I, Garcia-Alfaro C, Rivera-Fernandez V, Hernandez-Hazanas F. Diagnosis of brain death by transcranial Doppler sonography: solutions for cases of difficult sonic windows.  Transplant Proc. 2004;  36 2896-2897
• 76 Boissy A R, Provencio J J, Smith C A, Diringer M N. Neurointensivists' opinions about death by neurological criteria and organ donation.  Neurocrit Care. 2005;  3 115-121
• 77 Munari M, Zucchetta P, Carollo C et al.. Confirmatory tests in the diagnosis of brain death: comparison between SPECT and contrast angiography.  Crit Care Med. 2005;  33 2068-2073
• 78 Facco E, Munari M, Gallo F et al.. Role of short latency evoked potentials in the diagnosis of brain death.  Clin Neurophysiol. 2002;  113 1855-1866
• 79 Combes J C, Chomel A, Ricolfi F, d'Athis P, Freysz M. Reliability of computed tomographic angiography in the diagnosis of brain death.  Transplant Proc. 2007;  39 16-20
• 80 Leclerc X, Taschner C A, Vidal A et al.. The role of spiral CT for the assessment of the intracranial circulation in suspected brain-death.  J Neuroradiol. 2006;  33 90-95
• 81 Quesnel C, Fulgencio J P, Adrie C et al.. Limitations of computed tomographic angiography in the diagnosis of brain death.  Intensive Care Med. 2007;  33 2129-2135
• 82 Joffe A R. Limitations of brain death in the interpretation of computed tomographic angiography.  Intensive Care Med. 2007;  33 2218
• 83 Leclerc X. Groupe de relecture . CT angiography for the diagnosis of brain death: recommendations of the French Society of Neuroradiology (SFNR).  J Neuroradiol. 2007;  34 217-219
• 84 Lovblad K O, Bassetti C. Diffusion-weighted magnetic resonance imaging in brain death.  Stroke. 2000;  31 539-542
• 85 Matsumura A, Meguro K, Tsurushima H et al.. Magnetic resonance imaging of brain death.  Neurol Med Chir (Tokyo). 1996;  36 166-171
• 86 Helms A K, Torbey M T, Hacein-Bey L, Chyba C, Varelas P N. Standardized protocols increase organ and tissue donation rates in the neurocritical care unit.  Neurology. 2004;  63 1955-1957
• 87 Williams M A, Lipsett P A, Rushton C H et al.. The physician's role in discussing organ donation with families.  Crit Care Med. 2003;  31 1568-1573