Received: 21 August 2001Accepted: 29 April 2002Published online: 20 June 2002© Springer-Verlag 2002

Abstract Objective: To evaluate theimpact of transesophageal echocar-diographic (TEE) studies on furtherpatient management and incidenceand degree of left ventricular (LV)dysfunction in patients with lethalsevere brain injury. Design and setting: Retrospective, clinical studyin two surgical intensive care units ina university hospital. Patients: In 51patients with severe brain injury ulti-mately leading to brain death, the re-sults of TEE studies were reviewedfor evidence of newly developed LVdysfunction (i.e., regional wall mo-tion abnormalities) and its impact onpatient management. Measurementsand results: Seven patients (13.7%)had a diminished LV function global(fractional area change <50%). Fourof these patients (7.8%) exhibited aseverely reduced LV function (frac-tional area change <35%). Regionalwall motion abnormalities and pre-served global function were found ineight patients (15.7%). Patient man-

agement was altered in all patientswith diminished LV function: imple-mentation of advanced hemodynam-ic monitoring (n=5), institution oradjustment of inotropes and adjust-ment of fluid management (n=7). Inpatients exhibiting a severely re-duced LV function and deterioratingcardiovascular status, brain death di-agnosis was established by one clini-cal examination in conjunction withlaboratory tests, thus shortening theinterval required for brain death diagnosis by about 12 h. Conclusions: Severe LV dysfunc-tion occurred in about 8% of our pa-tients with severe brain injury ulti-mately leading to brain death. TEEmay be helpful in guiding cardio-vascular resuscitation ultimatelyleading to improved organ procure-ment rates.

Keywords Transesophageal echocardiography · Left ventricularfunction · Brain death

Intensive Care Med (2002) 28:1084–1088DOI 10.1007/s00134-002-1355-x O R I G I N A L

E. HüttemannC. SchelenzK. ChatzinikolaouK. Reinhart

Left ventricular dysfunction in lethal severebrain injury: impact of transesophageal echocardiography on patient management

Introduction

The pool of donor organs available for transplant is inad-equate to meet the ever increasing demand. The develop-ment of strategies aimed at expanding donor pools andmaximizing organ harvest are therefore critically needed.Early donor recognition, rapid and accurate diagnosis ofbrain death, physiological maintenance of potential or-gan donors, and coordination with local organ procure-ment organizations are all important issues in organ do-nor management. One critical aspect of brain death man-

agement is left ventricular (LV) dysfunction leading tocardiac failure and ultimately death before diagnosis ofbrain death is established or organ procurement complet-ed. In animals the acute hemodynamic changes resultingfrom catecholamine release occurring during brain deathinduce myocardial ischemia in 75% of brain dead ani-mals, causing myocyte necrosis [1, 2]. Studies of in-duced brain death in a dog model have shown a deterio-ration of right and LV systolic function by 34% and20%, respectively [3]. Electrocardiographic abnormali-ties are found in 50–100% of patients with cerebral le-

E. Hüttemann (✉ ) · C. SchelenzK. ReinhartDepartment of Anesthesiology and Intensive Care Medicine, Friedrich Schiller University, Bachstrasse 18, 07740 Jena, Germanye-mail: Egbert.Huettemann@med.uni-jena.deTel.: + +49-3641-933943Fax: +49-3641-933256

K. ChatzinikolaouDepartment of Intensive Care, Hippocration General Hospital, 55133 Thessaloniki, Greece

sions (stroke, intracranial hemorrhage, subarachnoidhemorrhage) depending on the analysis and evaluationdesign [4, 5, 6, 7]. Left ventricular dysfunction as evi-denced by a diminished LV ejection fraction (global hy-pokinesia) and new regional wall motion abnormalitiesare found in about 6.5–22.5% and 8.1–45% of brain-dead patients [5, 8, 9, 10, 11, 12]. The impact of echocar-diographic studies on patient management independentlyof donor screening has not yet been evaluated. We there-fore analyzed retrospectively the incidence and degree ofLV dysfunction and the impact of echocardiographic in-formation on further patient management (e.g., hemody-namic monitoring, pharmacotherapy, fluid management,timing of brain death diagnosis, organ procurement).

Methods

Patients

We retrospectively examined the data of all 62 patients admitted toour intensive care unit between September 1994 and June 2000 inwhom brain death diagnosis was established according to the cri-teria of the German Medical Council, and in whom transesophage-al echocardiography (TEE) was performed. Eleven of these pa-tients were not eligible for analysis for they did not undergo a TEEstudy or known cardiac history or severe chest trauma. The studypopulation thus consisted of 51 patients (31 men, 20 women) withlethal severe brain injury resulting from various lesions (Table 1).On admission their mean Acute Physiology and Chronic HealthEvaluation II (APACHE II) score was 19.1 (range 6–34) and meanGlasgow Coma Score 7.6 (range 3–15). TEE was performed in 26patients because of hemodynamic instability (evidenced by hypo-tension and/or need for inotropes or vasopressors) and/or exclu-sion of potential disease states (i.e., aortic pathology) before thediagnosis of brain death was established. At the time of study thisgroup of patients received analgosedatives, i.e., propofol, thiopen-tone, or methohexital, and opioids (fentanyl or sufentanil). In theother 25 patients TEE was performed for donor organ assessmentafter brain death diagnosis. All patients were mechanically venti-lated in a pressure controlled mode with a positive end-expiratorypressure of 5–10 cmH2O.

Transesophageal echocardiography

All TEE studies were performed using commercially availablesystems (Sonos 1000, Sonos 2500, Agilent, Andover, Mass., USA)equipped with a 5- or 6.2-MHz multiplane TEE probe. A compre-hensive TEE study was performed including fractional areachange (FAC) determination from a standard short-axis view ofthe LV at midpapillary muscle level. LV short-axis FAC (%FAC=LVEDA – LVESA/LVEDA × 100; mean 56.5 range 18–76)was used as a measure of LV performance (LV end-diastolic area,LVEDA; LV end-systolic area, LVESA). TEE images were record-ed continuously on videotape (SVHS). Off-line analysis was per-formed by arithmetic means of three consecutive beats at end-ex-piration. Enddiastole was defined as the LV short axis correspond-ing to the peak of the R wave on the recorded electrocardiography.The endsystolic area was defined as the smallest ventricular area.By convention of the American Society of Echocardiography, thepapillary muscles were included in the ventricular area. Regionalwall motion was assessed according to the 16-segment model bymultiplane imaging. Wall motion abnormalities were graded(1=normal, 2=mild hypokinesis, 3=severe hypokinesis, 4=akine-

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sis, 5=dyskinesis) based on inward motion and wall thickening[13].

Brain death diagnosis

Brain death was diagnosed according to the established braindeath criteria of the German Medical Council [14]. This protocolrequires ensuring irreversibility by reevaluation after 12 h (inadults and children with a minimum age of 2 years and supratento-rial lesions) or by laboratory tests (electroencephalography,evoked potentials, or lack of intracranial perfusion evidenced byfour-vessel intracranial angiography, radioisotope scanning, ortranscranial Doppler).

Results

Evidence of LV dysfunction was found in seven brain-dead patients (13.7%). Global systolic LV function wasmoderately impaired (35≤FAC<50%) in three of theseand severely impaired (FAC <35%) in four. In 12(15.7%) new wall motion abnormalities (NWMA) werefound (Table 2). Due to the new information provided byTEE patient management was changed in all patientswith LV dysfunction (100%; Table 3). The echocardio-graphic findings led to implementation of advanced he-modynamic monitoring devices (pulmonary artery cathe-ter, n=3); fiberoptic femoral artery catheter for measure-ment of intrathoracic blood volume by means of the dou-ble indicator dilution technique, n=2), adjustment or in-stitution of inotropes (dobutamine, enoximone), and ad-justment of fluid management (n=7). Furthermore, in thefour patients exhibiting a severely reduced LV functionthe TEE information in conjunction with a deteriorating

Table 1 Diagnosis of the 51 patients enrolled in the study

Diagnosis n Age (years)

Mean Range

Severe head injury 28 35.4 8–68(contusion, edema, hemorrhage)Subarachnoid hemorrhage 12 49.2 23–69Intracranial hemorrhage 7 59.2 40–66Cerebral infarction 4 41.8 35–48Overall 51 42.4 8–69

Table 2 Left ventricular function and regional wall motion abnor-malities (RWMA) in 51 brain-dead patients (FAC fractional areashortening

n FAC (range)

FAC <35% 4 18–2635≤FAC<50% 3 38–42FAC≥50% 51 50–76RWMA 8Total 51

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cardiovascular status led to diagnosis of brain death byaid of laboratory tests thus avoiding a 12-h wait for clini-cal confirmation. Ventricular fibrillation occurred in twopatients, leading to cardiac arrest; in both cases organprocurement was nevertheless completed since both pa-tients were already in or on the way to the operatingroom. Cardiac autopsy was performed in two of the pa-tients with myocardial dysfunction evidenced by echo-cardiography. Histopathological examinations revealedsubendocardial myocyte injury and contraction band ne-crosis.

Discussion

Unfortunately, 17–25% of potential organ donors are lostdue to medical failure [15, 16]. Complications related toprolonged supportive care, as a consequence of delays inthe diagnosis of brain death, reduce the availability andsuitability of potentially transplantable organs [17, 18].Multiple complications occur in many of these patients.In a retrospective analysis of 114 solid organ donors overa 6-year period, the following hemodynamic complica-tions were recorded: hypotension (81%), arrhythmias(27%), cardiac arrest requiring cardiopulmonary resusci-tation (25%), and pulmonary edema (19%). Six patientshad to be excluded from the analysis because they suf-fered cardiovascular collapse before their organs couldbe retrieved [19]. In a series of 28 patients 6 had cardiacarrest before certification of brain death [20]. In an in-vestigation evaluating the effect of hormonal therapy (T3replacement) in brain-dead patients, 4 of 26 potential do-nors developed ventricular fibrillation and had to be ex-cluded from the donor pool [21]. In yet another study,one-half of the brain-dead patients exhibited cardiac ar-rest [22]. Thus organs are lost due to cardiac arrest in asmall but significant proportion of cases. In general, atri-al and ventricular arrhythmias as well as conduction de-fects occur frequently in organ donors [23]. In additionto cofactors such as electrolyte, or arterial blood gas dis-orders, hypotension, and hypothermia, contributing fac-tors include the myocardial injury, due to the mecha-nisms discussed below. Ultimately all brain-dead indi-viduals undergo terminal arrhythmias which are resistantto therapy [23]. Cardiopulmonary resuscitation should beperformed at least for a limited period of time and espe-

cially if the donor is already in the operating room. Al-though this may preclude the use of the heart for trans-plantation, the other organs may still be used.

The relationship between intracranial hypertensionand myocardial injury has been studied in patients withconditions such as subarachnoid hemorrhage and intra-cranial tumors [24]. Subendocardial myocyte necrosisand pseudoacute myocardial infarcts have been docu-mented in patients with these central nervous system pa-thology but normal coronary arteries [25]. Extensivestudies of experimental brain death have identified twomajor types of tissue injury in brain death in animals [1].Myocardial histological and electrocardiographic chang-es are directly related to acute release of catecholaminestriggered by the sudden increase in intracranial pressure[1]. Metabolic derangement results from significant hor-monal depletion which is caused by the inhibition of mi-tochondrial aerobic metabolism [1, 26]. The two patho-physiological events occur in close temporal proximity,the latter within hours or days of the initial insult. Exper-imentally induced brain death in baboons is associatedwith acute intracranial hypertension that triggers an ex-cessive sympathetic and parasympathetic activity. Tran-sient parasympathetic activity is rapidly replaced by abrisk response to endogenous circulating catecholaminesreleased at nerve endings. During the initial phases of in-tracranial hypertension the release of endogenous cate-cholamines at the cardiac and vascular levels induces amassive increase in systemic vascular resistance andmean arterial pressure [1, 27]. These hemodynamicchanges acutely increase myocardial wall stress, result-ing in subendocardial coronary insufficiency. The histo-logical features are foci of myocardial necrosis scatteredthroughout the atria and ventricles and are more pro-nounced in the subendocardial LV areas. Contractionsbands, coagulative necrosis, and myocytolysis are seen,accompanied by interstitial edema and mononuclear cellsinfiltrates [1, 2].

TEE has been shown to provide high-quality imagingof cardiac donor hearts and a more complete assessmentof the cardiac structures than transthoracic echocardiog-raphy (TTE) [10]. Given our experience in a surgical in-tensive care setting (e.g., constraints regarding optimalpositioning, dressings, mechanical ventilation withPEEP), we generally prefer TEE to TTE since the greateramount of time required for a TEE study is more thancompensated for by the better visualization than in TTE.

Given the evidence from numerous studies in variouspopulations of critically ill patients evaluating the impactof TEE on patient management, (transesophageal) echo-cardiography has been advocated to become an integralpart of diagnostic evaluation of critically ill patients [28].The potential impact of therapeutic interventions aimedat normalization of cardiac output to optimize organfunction in patients with lethal severe brain injury orbrain-dead patients is illustrated by two investigations.

Table 3 Impact of TEE on patient management in patients withglobal left ventricular dysfunction (n=7)

n

Diagnosis of brain death by confirmatory laboratory tests 4Institution of advanced hemodynamic monitoring 5Institution or adjustment of inotropes (dobutamine, enoximone) 7

and adjustment of fluid management

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One study established and refined a strategy for optimiz-ing donor management based on comprehensive invasivemonitoring, and this resulted in an expansion of the do-nor pool by approximately 30% [29]. Recently it hasbeen shown that cases of some brain death induced myo-cardial dysfunction may be reversible, and that low-dosedobutamine stress echocardiography may identify re-versible myocardial dysfunction, thus rendering TEEparticularly useful [30]. Thus these data and the impacton patient management in our study (pharmacotherapy,fluid therapy, monitoring) support the use of early TEEfor guiding cardiovascular resuscitation in patients withacute cerebral lesions and cardiovascular instability.

Additionally, establishment of brain death diagnosiswith the aid of laboratory investigations may be consid-ered in countries where a 12-h wait for clinical confir-mation of brain death is mandatory in order to shortenthe interval required for the definitive confirmation ofbrain death. The latter is especially important if LVfunction is considerably reduced, leading to a low out-put syndrome which threatens organ function, and en-hances the risk of sudden cardiac deterioration (e.g.,

ventricular fibrillation). The timely diagnosis of LV dys-function in patients with lethal severe brain injury mayimprove patient management and thereby ultimately or-gan procurement rates.

In about 12% of the patients in our study we foundevidence of LV dysfunction. The reported incidence ofLV dysfunction in brain-dead patients as evidenced bydiminished LV ejection fraction (global hypokinesia) andnew regional wall motion abnormalities of about6.5–22.5% and 8.1–45%, respectively, corresponds wellwith the incidence of LV dysfunction in our population.However, in this retrospective study we could not deter-mine by history what proportion of the patients had pre-existing coronary artery disease or myocardial dysfunc-tion. None of the patients included had known cardiacdisease, and most were younger than 40 years of age. Itis unlikely therefore that a significant number of patientshad myocardial dysfunction prior to the onset of braininjury. Due to the rather small size and the retrospectivedesign of our study our findings warrant further studieson the impact of timely diagnosis of LV dysfunction inpatients with severe brain injury.

References

1. Novitzky D, Wicomb WN, Cooper DK,Rose AG, Reichart B (1984) Electro-cardiographic hemodynamic and endo-crine changes occurring during experi-mental brain death in the Chacma ba-boon. J Heart Transplant 4:63–69

2. Novitzky D, Wicomb WN, Cooper DK,Rose AG, Reichart B (1986) Preven-tion of myocardial injury during braindeath by total cardiac sympathectomyin the Chacma baboon. Ann ThoracSurg 41:520–524

3. Kendall SW, Bittner HB, PeterseimDS, Campbell KA, Van Trigt P (1997)Right ventricular function in the donorheart. Eur J Cardiothorac Surg 11:609–615

4. Brouwers PJ, Wijdicks EF, Hasan D,Vermeulen M, Wever EF, Frericks H,van Gijn J (1989) Serial electrocardio-graphic recording in aneurysmal sub-arachnoid hemorrhage. Stroke20:1162–1167

5. Mayer SA, LiMandri G, Sherman D, Lennihan L, Fink ME, Solomon RA,DiTullio M, Klebanoff LM, BeckfordAR, Homma S (1995) Electrocardio-graphic markers of abnormal left ventric-ular wall motion in acute subarachnoidhemorrhage. J Neurosurg 83:889–896

6. Melin J, Fogelholm R (1983) Electro-cardiographic findings in subarachnoidhemorrhage. A population study. ActaMed Scand 213:5–8

7. Pollick C, Cujec B, Parker S, Tator C(1988) Left ventricular wall motion ab-normalities in subarachnoid hemor-rhage: an echocardiographic study.J Am Coll Cardiol 12:600–605

8. Gilbert EM, Krueger SK, Murray JL,Renlund DG, O’Connell JB, Gay WA,Bristow MR (1988) Echocardiographicevaluation of potential cardiac trans-plant donors. J Thorac Cardiovasc Surg95:1003–1007

9. Seiler C, Laske A, Gallino A, TurinaM, Jenni R (1992) Echocardiographicevaluation of left ventricular wall mo-tion before and after heart transplanta-tion. J Heart Lung Transplant 11:867–874

10. Stoddard MF, Longaker RA (1993)The role of transesophageal echocardi-ography in cardiac donor screening.Am Heart J 125:1676–1681

11. Kron IL, Tribble CG, Kern JA, Daniel TM, Rose CE, Truwit JD,Blackbourne LH, Bergin JD (1993)Successful transplantation of marginal-ly acceptable thoracic organs. AnnSurg 217:518–522

12. Mayer SA, Fink ME, Homma S, Sherman D, LiMandri G, Lennihan L,Solomon RA, Klebanoff LM, Beckford A, Raps EC (1994) Cardiacinjury associated with neurogenic pulmonary edema following subarach-noid hemorrhage. Neurology 44:815–820

13. Smith JS, Cahalan MK, Benefiel DJ,Byrd BF, Lurz FW, Shapiro WA, Roizen MF, Bouchard A, Schiller NB(1985) Intraoperative detection ofmyocardial ischemia in high-risk pa-tients: electrocardiography versus two-dimensional transesophageal echocar-diography. Circulation 72:1015–1021

14. Wissenschaftlicher Beirat der Bun-desärztekammer (1998) Richtlinien zurFeststellung des Hirntodes. Dtsch Arzteblatt 95:A 1861

15. Grossman MD, Reilly PM,McMahon D, Hawthorne RV, KauderDR, Schwab CW (1996) Who pays forfailed organ procurement and what isthe cost of altruism? Transplantation62:1828–1831

16. Mackersie RC, Bronsther OL, Shackford SR (1991) Organ procure-ment in patients with fatal head inju-ries. The fate of the potential donor.Ann Surg 213:143–150

17. Lucas BA, Vaughn WK, Spees EK,Sanfilippo F (1987) Identification ofdonor factors predisposing to high dis-card rates of cadaver kidneys and in-creased graft loss within one year post-transplantation-SEOPF 1977–1982.South-Eastern Organ ProcurementFoundation. Transplantation43:253–258

1088

18. Chatterjee SN, Payne JE, Berne TV(1975) Difficulties in obtaining kidneysfrom potential postmortem donors.JAMA 232:822–824

19. Nygaard CE, Townsend RN, Diamond DL (1990) Organ donor man-agement and organ outcome: a 6-yearreview from a Level I trauma center.J Trauma 30:728–732

20. Matuschak GM (1993) Presented at the13th international symposium of Inten-sive Care and Emergence Medicine.Brussels

21. Novitzky D, Cooper DK, Reichart B(1987) The value of hormonal therapyin improving organ viability in thetransplant donor. Transplant Proc19:2037–2038

22. Taniguchi S, Kitamura S, Kawachi K,Doi Y, Aoyama N (1992) Effects ofhormonal supplements on the mainte-nance of cardiac function in potentialdonor patients after cerebral death. EurJ Cardiothorac Surg 6:96–101

23. Logigian EL, Ropper AH (1985) Ter-minal electrocardiographic changes inbrain-dead patients. Neurology35:915–918

24. Burch GE, Meyers R, Abildskov J(1954) A new electrocardiographic pat-tern observed in cerebrovascular acci-dents. Circulation 9:719–723

25. Heggtveit HA (1970) The donor heart:brain death and pathological changes inthe heart. Laval Med 41:178–179

26. Novitzky D, Cooper DK, Morrell D,Isaacs S (1988) Change from aerobicto anaerobic metabolism after braindeath, and reversal following triiodo-thyronine therapy. Transplantation45:32–36

27. Novitzky D, Wicomb WN, Rose AG,Cooper DK, Reichart B (1987) Patho-physiology of pulmonary edema fol-lowing experimental brain death in theChacma baboon. Ann Thorac Surg43:288–294

28. Voga G, Krivec B (2000) Echocardiog-raphy in the intensive care unit. CurrOpin Crit Care 6:207–213

29. Potter CD, Wheeldon DR, Wallwork J(1995) Functional assessment andmanagement of heart donors: a ratio-nale for characterization and a guide totherapy. J Heart Lung Transplant14:59–65

30. Kono T, Nishina T, Morita H, Hirota Y,Kawamura K, Fujiwara A (1999) Use-fulness of low-dose dobutamine stressechocardiography for evaluating re-versibility of brain death-induced myo-cardial dysfunction. Am J Cardiol84:578–582