Editorials

phase (see Supplementary Fig. 1 in [8]). Most of the remaining patients (47%) died of cardiovascular collapse or organ failure, which suggests that the intrinsic frailty of elderly patients may also have contributed to this high early mortality. In summary, exclusion of patients who are older than 75 years from CPR is not warranted on the basis of age alone. Elderly victims of cardiac arrest can have an excellent long-term outcome, but this concerns mainly a minority of patients with favorable characteristics. The retrospective study by Grimaldi et al (8) provided important clues to identify the ideal elderly patient to be resuscitated, although achieving this goal will need further investigation in larger prospective studies.

3. D e a s y C , B ra y JE, S m ith K, e t a l; V A C A R S te e rin g C o m m itte e : O u to f-h o s p ita l c a rd ia c a rre s ts in th e o ld e r a g e g ro u p s in M e lb o u rn e , A u s tra lia . R esuscitation 2 0 1 1 ; 8 2 : 3 9 8 - 4 0 3 4. S a n d ro n i C , C a ric a to A : O u tc o m e s in e ld e rly p a tie n ts re s u s c ita te d fro m c a rd ia c a rre s t: Is a g e an in d e p e n d e n t p re d ic to r ? C rit C are M ed 2 0 1 4 ; 4 2 :4 5 3 - 4 5 4 5. S e d e r D B , P atel N, M c P h e rs o n J, e t al: G e ria tr ic e x p e rie n c e fo llo w in g c a rd ia c a rre s t a t six in te rv e n tio n a l c a rd io lo g y c e n te rs in th e U n ite d S ta te s 2 0 0 6 - 2 0 1 1 : In te rp la y o f a g e , d o -n o t-re s u s c ita te o rd e r, a nd o u tc o m e s . C rit C are M e d 2 0 1 4 ; 4 2 : 2 8 9 - 2 9 5 6. C h a n P S , S p e rtu s JA, N a lla m o th u B K : L o n g -te rm o u tc o m e s in e ld e rly s u rv iv o rs o f c a rd ia c a rre s t. N E n g l J M e d 2 0 1 3 ; 3 6 8 : 2 4 3 8 - 2 4 3 9 7. H A C A S tu d y G ro u p : M ild th e ra p e u tic h y p o th e rm ia to im p ro ve th e n e u ro ­ lo g ic o u tc o m e a fte r c a rd ia c arrest. N E ngl J M ed 2 0 0 2 ; 3 4 6 : 5 4 9 - 5 5 6 8. G rim a ld i D, D u m a s F, P e rie r M -C , e t a l: S h o rt- a n d

L ong-T erm

O u tc o m e in E ld e rly P a tie n ts A fte r O u t-o f-H o s p ita l C a rd ia c A rre s t: A C o h o rt S tu d y . C rit Care M e d 2 0 1 4 ; 4 2 : 2 3 5 0 - 2 3 5 7

REFERENCES

9. 3 C S tu d y G ro u p : V a s c u la r fa c to rs a n d ris k o f d e m e n tia : D e s ig n o f th e

1. M c N a lly B, R o b b R, M e h ta M , e t a l; C e n te rs fo r D is e a s e C o n tro l and

P re v e n tio n : O u t-o f-h o s p ita l c a rd ia c

a rre s t s u rv e illa n c e - C a r -

T h re e -C ity S tu d y a n d b a s e lin e c h a ra c te ris tic s o f th e s tu d y p o p u la tio n .

N e u ro e p id e m iolog y 2 0 0 3 ; 2 2 : 3 1 6 - 3 2 5

d ia c A rre s t R e g is try to E n h a n c e S u rv iv a l (C A R E S ), U n ite d S ta te s ,

1 0 . B o u g o u in W , L a m h a u t L, M a rijo n E, e t al: C h a ra c te ris tic s a n d p ro g ­

O c to b e r 1, 2 0 0 5 - D e c e m b e r 3 1 , 2 0 1 0 . M M W R S u rv e ill Sum m 2 0 1 1 ; 6 0 :1 -1 9

a p p ro a c h fro m th e P a ris S u d d e n D e a th E x p e rtis e C e n te r (P aris-

2. U n ite d

N a tio n s -D e p a rtm e n t

P o p u la tio n

of

E c o n o m ic

D iv is io n : M a g n itu d e a n d s p e e d

and

S o c ia l

A ffa irs -

n o s is o f s u d d e n c a rd ia c d e a th in G re a te r P a ris : P o p u la tio n -b a s e d S D E C ). Intensive Care M ed 2 0 1 4 ; 4 0 : 8 4 6 - 8 5 4

o f p o p u la tio n a g e in g .

1 1 . N ie ls e n N, W e tte rs le v J, C ro n b e rg T, e t al: T a rg e te d te m p e ra tu re m a n ­

2 0 0 2 . A va ila b le at: h ttp ://w w w .u n .o rg /e s a /p o p u la tio n /p u b lic a tio n s / w o r ld a g e in g l 9 5 0 2 0 5 0 / . A c c e s s e d Ju n e 1 0 , 2 0 1 4

a g e m e n t a t 3 3 d e g re e s C v e rs u s 3 6 d e g re e s C a fte r c a rd ia c a rre s t. N E n g l J M e d 2 0 1 3 ; 3 6 9 :2 1 9 7 - 2 2 0 6

When Is “Dead” Actually Dead?* Divya Gupta, M D Advanced Heart Failure and Transplant Division of Cardiology Emory University School of Medicine Atlanta, GA

ho would ever think that the simple concept of “death” could actually be so complicated? Through debate and trial, we have legally and medically defined the permanent end to life. Organ dona­ tion and procurement is a major topic that spurs controversy behind the definition and timing of death. Although brain death was first defined in 1968, the Uniform Brain Death Act of 1978 nationally acknowledged that although a person may have a pulse, their irreversible lack of brain function was grounds to declare them legally dead (1-3). The legal defini­ tion of death was expanded to include the “irreversible cessa­ tion of circulatory and respiratory function” by the Uniform

*S e e a ls o p. 2 3 5 8 . K ey W o rd s; a u to re s u s c ita tio n ; b ra in d e a th ; c irc u la to ry d e a th ; d e a th ; o rg a n d o n a tio n T h e a u th o r h a s d is c lo s e d th a t s h e d o e s n o t have a n y p o te n tia l c o n flic ts o f in te re s t. C o p y rig h t © 2 0 1 4 b y th e S o c ie ty o f C ritic a l C a re M e d ic in e a n d L ip p in c o tt W illia m s & W ilk in s

D O I: 1 0 .1 0 9 7 /C C M .0 0 0 0 0 0 0 0 0 0 0 0 0 4 4 2

Critical Care Medicine

Determination of Death Act of 1981 (2); irreversible being the operative word. In the 1800s, when checking for a pulse and looking for chest rise to assess respiration were some of the only rudimen­ tary methods of determining death, concern for autoresusci­ tation or the “Lazarus phenomenon” plagued society. Coffins were built with escape mechanisms in place as a provisional measure (2). Interestingly, our methods of determining death have become more sophisticated; however, organ procurement remains haunted by this concern when dealing with donation after circulatory death (DCD). The “dead donor rule” causes us to take pause: it is unethical to cause death by organ procure­ ment and unethical for organ procurement to precede death (4). To assure such travesties did not take place, the Institute of Medicine in 1997 mandated monitoring the deceased for 5 minutes after the stated time of death to confirm irreversibility prior to procurement (4-6). How exactly can we declare circulatory death and what is the appropriate amount of time to wait after time of death to confirm a person’s demise is irreversible? We have clearly defined brain death and can test for brain activity, reflexes, and spontaneous respiration. Concerning organ donation, the continued flow of blood and oxygen to organs despite death allows for greater leeway when timing confirmation of brain death and organ procurement. However, circulatory death is just that, the end of circulation to organs, starting the clock on ischemic injury. In an effort to decrease w w w . c c m jo u r n a l. o r g

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organ ischemia but ascertain irreversible circulatory death, Dhanani et al (7) set out to determine the feasibility of con­ ducting a study to investigate when is “dead” conclusively dead. In this issue of Critical Care Medicine, Dhanani et al (7) were able to monitor continuous electrocardiograms and invasive arterial blood pressure for 30 minutes after the time of death in all enrolled subjects after withdrawal of care (7). They found that although cardiac electrical activity could continue for up to 38 minutes, this was always pulseless in nature. Also, although invasive arterial blood pressure activ­ ity could recur, this was not the case if the cessation period was greater than a minute and a half. When there was return of arterial pressure waves, systolic pressures were consistently less than 30 mm Hg—significantly less than what is required for cerebral perfusion (8). It is not surprising that a subject whose life support is removed would actually be dead at the documented time of death. The electrical activity and incon­ sequential arterial pulse wave do not denote life. These indi­ viduals have been dwindling in front of healthcare providers and loved ones without any hope for recovery, hence the deci­ sion to withdraw care. Electroencephalogram was obtained in only four sub­ jects making it difficult to conclusively determine anything from these data. All brain activity ceased prior to losing arte­ rial waveform and electrical cardiac activity in three of these subjects. One of the four patients, however, had delta and theta waves present for 26 minutes after arterial blood pres­ sure activity had ceased. This brings up an interesting ethical dilemma—if a person does not have circulatory or respiratory function but has documented brain activity, are they dead? Safar documented that after 5 minutes of cardiac arrest, a per­ son’s neurologic function could not recover completely. Even after 3 minutes, blood stasis may not allow adequate cerebral perfusion even if circulation began (9). Many factors such as age, blood glucose level, hematocrit, and blood gas level will influence a patient’s outcome from this injury, as well (9). Fur­ ther evaluation needs to be conducted regarding brain activity in this situation. What if an individual undergoes cardiopulmonary resusci­ tation (CPR)? Lazarus phenomenon has only been documented in case reports and only after uncontrolled circulatory death in which CPR was used (10-12). Auto-positive end-expiratory pressure and impaired venous return have been blamed for the delay in circulatory response in some instances (10). A review of case reports would deem 10 minutes of observation after stopping resuscitative efforts would be adequate to confirm permanent circulatory cessation (10); however, little has been studied regarding this scenario. Fewer organ donations originate from this population of deceased because of the timing involved in gaining consent from family and perfusing the organs for transplantation. Efforts should be made to streamline the pro­ cess so that these organs may benefit someone, as well. The increasing demand for organs and the stagnant sup­ ply pushed clinicians to successfully use DCD organs to bridge the gap with comparable outcomes to those of organs obtained 2 448

w w w .c c m jo u r n a l.o r g

from the brain-dead donors (13). Now, DCD organs account for up to 20% of organ donations in some regions (4). Unfor­ tunately, a large gap remains between the supply and demand of donor hearts. Currently, DCD hearts are not used for trans­ plantation, as there is very little experience in humans. Boucek et al (14) published a case series of pediatric DCD heart trans­ plants. Three infants received DCD hearts and survived at least 3.5 years with comparable results to their age-matched controls who received hearts from brain-dead donors. Obser­ vation period after cessation of circulatory function was even reduced during this study from 3 minutes to 1.25 minutes to reduce warm ischemic injury since no cases of autoresuscita­ tion had been reported after 60 seconds in children or adults. Death is not a single moment but a process (9, 15). With regard to controlled circulatory collapse, we have been wit­ nessing and battling the dying process until the decision to withdraw care. It would seem that once time of death has been determined for these individuals, we are “beating a dead horse” by waiting for autoresuscitation and increasing warm ischemic time without any true chance of reversibility. Uncontrolled circulatory collapse warrants further studies to optimize tim ­ ing of gaining consent and organ perfusion. Overall, greater consideration should be given to minimizing the observa­ tion period after circulatory death to reduce warm ischemic injury, allow more DCD organs, and improve outcomes. Stud­ ies assessing this situation are rare, and most protocols stem from case reports. Dhanani et al (7) have tasked themselves with answering these questions via a scientifically and ethically sound manner to improve our understanding of when does life truly end.

REFERENCES 1. Uniform Law Commission: Determination of death act summary, 2014. Available at: http://www.uniformlaws.org/ActSummary.aspx? title=Determination°/o20of°/o20Death°/o20Act. Accessed June 20, 2014 2. United States President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research: Defining Death: A Report on the Medical, Legal and Ethical Issues in the Determination of Death. Washington, DC, The Commission: For sale by the Supt. of Docs., U.S. G.P.O., 1981 3. A definition of irreversible coma. Report of the ad hoc committee of the Harvard Medical School to examine the definition of brain death. JAMA 1968; 2 0 5 :3 3 7 -3 4 0 4. Ethics Committee, American College of Critical Care Medicine; Society of Critical Care Medicine: Recommendations for nonheart­ beating organ donation. A position paper by the Ethics Committee, American College of Critical Care Medicine, Society of Critical Care Medicine. Crit Care Med 2001; 2 9 :1 82 6-1 831 5. Zamperetti N, Bellomo R, Ronco C: Defining death in non-heart beat­ ing organ donors. J Med Ethics 2003; 2 9 :1 8 2 -1 8 5 6. Potts JT, Herdman R, Institute of Medicine (U.S.), Division of Health Care Services: Non-Heart-Beating Organ Transplantation: Medical and Ethical Issues in Procurement. Washington, DC, National Academy Press, 1 997 7. Dhanani S, Hornby L, Ward R, et al; on behalf of the Canadian Critical Care Trials Group and in collaboration with the Bertram Loeb Chair and Research Consortium in Organ and Tissue Donation: Vital Signs After Cardiac Arrest Following Withdrawal of Life-Sustaining Therapy: A Multicenter Prospective Observational Study. Crit Care Med 2014; 4 2 :2 3 5 8 -2 3 6 9 8. Kovach AG, Sandor P: Cerebral blood flow and brain function during hypotension and shock. Annu Rev Physiol 1976; 3 8 :5 7 1 -5 9 6 November 2014 * Volume 42 • Number 11

Editorials 9. Safar P: Cerebral resuscitation after cardiac arrest: A review. Circulation 1986; 74:IV138-IV153 10. Adhiyaman V, Adhiyaman S, Sundaram R: The Lazarus phenomenon. J R Soc Med 2007; 1 0 0 :5 5 2 -5 5 7 11. Bray JG Jr: The Lazarus phenomenon revisited. Anesthesiology 1993; 78:991 12. Sheth KN, Nutter T, Stein DM, et al: Autoresuscitation after asystole in patients being considered for organ donation. Crit Care Med 2012; 4 0 :1 5 8 -1 6 1

13. Cho YW, Terasaki PI, Cecka JM, et al: Transplantation of kidneys from donors whose hearts have stopped beating. N Engl J Med 1998; 3 3 8 :2 2 1 -2 2 5 14. Boucek MM, Mashburn C, Dunn SM, et al; Denver Children's Pediatric Heart Transplant Team: Pediatric heart transplantation after declaration of cardiocirculatory death. N Engl J Med 2008; 3 5 9 :7 0 9 -7 1 4 15. Hornby K, Hornby L, Shemie SD: A systematic review of autoresusci­ tation after cardiac arrest. Crit Care Med 2010; 38:1 2 4 6 -1 2 5 3

Predicting Death and Disability, Is It Really Possible? A Medical ICU Prognostication Model Study* Mohammed F. Rehman, DO Departments of Neurology and Neurosurgery Henry Ford Hospital/Wayne State University School of Medicine Detroit, Ml

Mohammed Salman Siddiqui, DO Department of Internal Medicine Beaumont Health System/ Oakland University School of Medicine Royal Oak, Ml

istorically, research on prognosis of critically ill patients has focused on prognostic accuracy of ill­ ness and severity scoring system early in course of critical illness. To improve on the demonstrated weaknesses in physicians’ ability to judge, with certainty, who will or will not survive critical illness, several studies were undertaken to help in prognostication of critically ill patients. These studies com­ pared the utility of various scoring systems such as Acute Phys­ iology and Chronic Health Evaluation system score (1, 2), the Simplified Acute Physiology Score (3), and the Mortality Pre­ diction Model (4) to prognosticate outcomes within 24 hours of admission to the ICU. When these scores became unreli­ able, scoring systems were developed to predict specific organ dysfunction at the time of the admission (the Logistics Organ Dysfunction Score) (5) followed by serial measurements over

H

*See also p. 2387. Key Words: intensive care units; mortality and morbidity; prediction model The authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

DOI: 10.1097/CCM.0000000000000577

Critical Care Medicine

the length of the ICU stay such as Multiple Organ Dysfunc­ tion Score (6) and Sequential Organ Failure Assessment Score (7). However, despite these scoring systems, prognostication of critically ill patients remains highly elusive. To tackle this problem, an idea emerged of combining the functional scoring systems (such as the ones described above) along with observational prediction of mortality and morbid­ ity specifically by the caretakers (namely attending physicians, fellows, residents, nurses, and sometimes family members of the patients) with help of serial questionnaires and surveys pre­ dicting short- and long-term mortality and morbidity. A timely article by Meadow et al (8) in this issue of Critical Care Medi­ cine attempted to provide much needed insight into power and limitations of daily prognostication of death in the medical ICU (MICU) for outcomes in patients with more than 72 hours of stay in a single-center ICU patient cohort of 350 MICU (MICU) patients. On each MICU day, caretakers (attending physician, fellow, resident, and primary nurse) were asked one question— “do you think this patient will die in hospital, or survive to be discharged”? These responses were correlated with patient’s 6-month mortality and morbidity (Barthel score for survivors). Despite the limitations (nonuniformity of the caretak­ ers who were at different levels of expertise and training and a single-center study), this article clearly showed the relative inaccuracy that is prevalent in prediction models in terms of predicting survival and mortality. Results of the study revealed that there was disagreement in 41% of the providers regard­ ing outcomes when asked about the survivability of the patient after 72 hours. Furthermore, the unpredictable nature of the prediction model was evident as 44% of all patients predicted to die prior to discharge survived during their hospital course making a case for relative caution when withdrawal of care is done based on prediction models. The enlightening thing of this article was that less than 4% of MICU patients who required 72 hours of MICU care and had a corroborated pre­ diction of death before discharge were alive at 6 months and functioning with a Barthel score more than 70. This could be w w w .c c m jo u r n a l.o r g

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When is "dead" actually dead?.

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