Early outcome predictors of post cardiac arrest patients. Abouelela Amr 1, Imam Mohamed 2.

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1 Early outcome redictors of ost cardiac arrest atients Abouelela Amr 1, Imam Mohamed 1 Alexandria University, critical care medicine deartment, Alexandria, Egyt Alexandria university, hysical medicine, Rheumatology and Rehabilitation deartment, Alexandria, Egyt amrela1@yahoo.com; imam_mohamed@hotmail.com Abstract: When ulse and blood ressure return after cardioulmonary resuscitation (CPR), the brain may have already been critically injured. When severe, a ost resuscitation anoxic-ischemic encehaloathy leaves atients comatose. Awakening generally takes lace within days after CPR, and neurological imairment is exected if a atient fails to do so. These atients are often left in a severely cognitively disabled and fully deendent state; some remain in a minimally conscious or vegetative state, and very few awaken neurologically. The aim of this research was to evaluate the efficacy of some clinical, radiological, electrohysiological and laboratory tests as early redictors of the outcome in ost arrest atients. This study was carried out on 5 atients- in critical care deartment of Alexandria university main hosital in Egyt- who survived after successful cardioulmonary resuscitation for at least 1 hours after the event. All atients were subjected to the routine ICU care with emhasis on neurological examination and investigations in the form of CT brain, SomatoSensory Evoked Potential and serial serum creatinine measurement. Outcome evaluation was done using Glasgow- Pittsburgh Cerebral Performance Categories (GP-CPC). Patients were categorized into two grous: grou 1 (favourable outcome) including GP- CPC1and ; grou (unfavourable outcome) included GP-CPC, and 5. Regarding the neurological assessment of atients, it was found that out of atients (16.7%) develoed myoclonus in grou I versus 7 atients out of (%) in grou II with no significant difference between the grous. The (SEP) results were significantly better in grou I comared to grou II (=.1*). Significant higher creatinine level was recorded in day in grou II being 1.6±1.1 versus 1.1±.78 in grou I (P =.5*). No significant statistical difference was found between the grous regarding the CT results. As a conclusion from this study, the duration of cardiac arrest, the SSEP and the changes in serum creatinine are the arameters which carry the highest ability to differentiate between atients with good rognosis from those with bad rognosis. No gold standard single test can be used to redict the rognosis in ost cardiac arrest atients. [Abouelela Amr, Imam Mohamed. Early outcome redictors of ost cardiac arrest atients. Journal of American Science 1; 8(1):-8]. (ISSN: 155-1).. Keywords: SSEP, ost-arrest, Outcome redictors, GP-CPC 1. Introduction With the advent of emergency medicine and imrovements in the rovision of emergency medical services, the number of atients who survive a cardioresiratory arrest has increased. However, many of these survivors never regain consciousness(1) and rogress to a ersistent vegetative state.() Even when atients are resuscitated in the hosital, fewer than one in five atients survive to discharge.() Considerable research has been carried out to identify those comatose atients who will recover sufficiently to live a meaningful life.() An accurate rediction of neurological outcome not only has ethical and legal imlications but is also in the interest of the atient and his or her family. The ability to redict very oor outcome would relieve ressure on the finite resources of intensive care. At resent, such outcome redictions are based on clinical history and hysical examination, electrohysiological findings, neuro-imaging tests and levels of biochemical markers in the serum and cerebrosinal fluid (CSF). (5). Material and Methods this study was carried out- in critical care deartment of Alexandria university main hosital in Egyt- on 5 atients who survived after successful cardioulmonary resuscitation for at least 1 hours after the event and for whom informed consents were obtained from the next of kin in the critical care deartment in the main hosital of Alexandria University. Aroval of local ethical committee was also obtained. Exclusion criteria: 1- Patients with significant neurological insult before the cardiac arrest. - Patients with significant renal insufficiency before the cardiac arrest. - Patients under the age of 16. The aim of this research was to evaluate the efficacy of some clinical, radiological,

2 electrohysiological and laboratory tests as early redictors of the outcome in ost arrest atients. All atients in the study were subjected to the following: I. Thorough history taking and comlete hysical examination with emhasis on the eriarrest factors and neurological examination..ii. Investigations: 1- Arterial blood gases after cardiac arrest and as needed. - Somatosensory evoked otential (SSEP) to 8 hours ost cardiac arrest. (6) - Comuterized Tomograhic Scan (CT) of the brain to 8 hours ost cardiac arrest.(7) - Laboratory investigations: A. comlete blood count, liver function tests, serum electrolytes and coagulation tests. B. Serum creatinine at time of cardiac arrest, hours and 8 hours after. (8) Outcome of the atients was assessed at 8 days using Glasgow- Pittsburgh Cerebral Performance Categories (GP-CPC) using five oints scale: (9) GP-CPC 1: conscious, alert, and oriented with normal cognitive functions GP-CPC : conscious and alert with moderate cerebral disability GP-CPC : conscious with severe disability GP-CPC : comatose or in ersistent vegetative state GP-CPC 5: certified brain death or dead by traditional criteria. Patients were categorized into two grous: grou 1 (favourable outcome) including GP-CPC1and ; grou (unfavourable outcome) included GP-CPC, and 5. The Mann Whitney U test, Student's t test and Chi square test were used to comare the grous.. Results The age distribution (table1) in grou I was ranging from 6 to 8 years with a mean of 6.88 ± 1.65 while in grou II it was ranging from 7 to 76 years with a mean of 59.9 ± There was no statistical significant difference between the grous regarding the age distribution. There was 15 male atients and 9 female atients in grou I versus 18 male and 1 female in grou II with no statistical significant difference between the grous regarding the Sex. (Table 1) Multile diagnoses were there in both grous ranging from tye I and Tye II resiratory failure, cardiogenic shock, setic shock and metabolic disorders as acute oisoning and heatic cell failure. (Table1) The duration of cardiac arrest(table ) in grou I was ranging from to 18 minutes with a mean of 9.67 ±.55 which was significantly shorter than the duration of arrest in grou II Which was ranging from to minutes with a mean of 1. ± 5.88 (P=.8* ). The cardiac arrest rhythm(table ) in grou I was asystole in 8 atients, ulseless electrical activity in 11 atients and ventricular fibrillation in 5 atients while in grou II it was asystole in 1 atients, ulseless electrical activity in 1 atients and ventricular fibrillation in 6 atients with no statistical significant difference between the grous regarding rhythm in arrested atients. The number of DC shock among the atients with ventricular fibrillation atients (5 atients in grou I & 6 atients in grou II ) was significantly less in grou I ranging from 1 to shock with a mean of ±.71 versus to 5 shock with a mean of. ± 1.7 (P=.* )(table) Regarding the neurological assessment of atients (table), it was found that out of atients (16.7%) develoed myoclonus in grou I versus 7 atients out of (%) in grou II with no significant difference between the grous. GCS was ranging from to 11 with a mean of 7.6 ±. in grou I versus to 11 with a mean of 7.5 ±. in grou II with no significant difference between the grous. Puillary light reflex was resent in 1 out of atients (5.%) in grou I versus 1 out of atients (%) in grou II with no significant difference between the grous. Somatosensory Evoked Potential (SEP) results were significantly different between the grous (table ). In the atients with favorable outcome out of atients (8.%) showed normal resonse, out of atients (16.7%) showed delayed resonse while no atient in this grou showed oor resonse while in the other grou with unfavorable outcome only 6 atients out of (%) showed normal resonse, 1 atients out of (%) showed delayed resonse and oor resonse was recorded in the remaining 1 atients (%). The (SEP) results were significantly better in grou I comared to grou II (=.1*) CT brain (table 5) in grou I was unremarkable in 15/ atients (6.5%), global ischemia was detected in 5/ atients (.8%) while the remaining / atients showed signs of focal ischemia (16.7%). In grou II 16/ atients (5.%) had unremarkable CT, 8/ atients (6.7%) had a CT findings matched with global ischemia and 6/ atients (%) showed CT findings of focal ischemia. No significant statistical difference was found between the grous regarding the CT results. Regarding serum creatinine level (Table 6) & (Figure 1), there was no significant difference in the level between both grous in day and day 1 after

3 cardiac arrest as it was in day, 1.6±.5 in grou I versus 1.±.6 in grou II while in day 1 it was 1.8±.55 in grou I versus 1.1±.75. Significant higher creatinine level was recorded in day in grou II being 1.6±1.1 versus 1.1±.78 in grou I (P =.5*). Table (1): Comarison between the two studied grous regarding demograhic data and diagnoses Age Sex Male Female Diagnosis ARDS Resiratory failure Bronchial asthma Cardiogenic shock Heatic failure Sesis (Setic shock) MI Pancreatitis Polytrauma Pulmonary embolism Poisoning (6.5%) 9 (7.5%) 6 "n=" (6.%) 1 (.%).1 Table (): Comarison between the two studied grous regarding circumstances of cardiac arrest (duration, rhythm, number of DC shock ) Duration of arrest Rhythm Asystole PEA VF Number of DC Shock (.%) 11 (5.8%) 5 (.8%) "n=" * 1 (.%) 1 (.%) 6 (.%) Table () Comarison between the two studied grous regarding clinical Data (neurological signs): myoclonus, Glasgow Coma Scale (GCS) & uillary light reflex (PLR) Myoclonus Yes No GCS PLR Yes No (16.7%) (8.%) (5.%) 11 (5.8%) "n=" 7 (.%) (76.7%) (.%) 18 (6.%).99 Table () Comarison between the two studied grous regarding electrohysiological arameter (SSEP) SSEP Poor Delayed Normal (.) (16.7%) (8.%) "n=" 1 (.%) 1 (.%) 6 (.%).87.*.1* 5

4 Table (5): Comarison between the two studied grous regarding radiological arameter (CT brain) CT brain Focal ischaemia Global ischaemia Unremarkable (16.7%) 5 (.8%) 15 (6.5) "n=" 6 (.%) 8 (6.7%) 16 (5.%) Table (6) Comarison between the two studied grous regarding the creatinine level at different eriod of follow u. Days "n=" *.79 creatinine level Unfavourable Favourable 1 Figure 1. Level of ceratinine at different eriod of follow u.. Discussion The age distribution in this study does not reflect any significant correlation with the outcome as in grou I the mean was 6.88 ± 1.65 while in grou II it was 59.9 ± This result was in agreement with Berger and Kelley including 55 in hosital cardioulmonary arrests in non-critical atients demonstrated age was not an indeendent redictor of survival (1). In contrast to Schultz et al study which reviewed 75 ost-arrest atients and showed a significant difference in survival between atients under the age of 6 years and those over the age of 8 years (15% v %, resectively)(11). The mean duration of cardiac arrest (table ) in grou I was 9.67 ±.55 which was significantly shorter than grou II Which was 1. ± 5.88 (P=.8*). Schultz et al concluded that the duration of the cardioresiratory arrest was related to outcome as they reorted survival rates of 8% for less than 1 minutes duration and % for longer than 1 minutes (11). Saklaven et al confirmed a shorter duration of arrest was associated with a better outcome and that this correlated with a witnessed arrest or resuscitation by a health rofessional indicating earlier effective intervention (1). The cardiac arrest rhythm did not show any significant correlation with the outcome in our study.in contrast to our study was Andreasson et al as They showed a survival rate of 6% from VT/VF arrest, % from asystole, and 1% from a PEA arrest. Monitored atients had a survival rate of 5% while unmonitored atients had a survival rate of 7%.(1) This difference may be attributed to the different outcome end oint used in both studies as Andreasson et al used the mortality as the end oint outcome while in our study GP-CPC, and 5 were included in the oor outcome grou. The number of DC shock among the atients with ventricular fibrillation atients (5 atients in grou I & 6 atients in grou II ) was significantly less in grou I with a mean of ±.71versus. ± 1.7 (P=.*). This result was in agreement with Denton and Thomas study who also correlated the number of DC shocks with oor outcome(1). Insite literature showed that myoclonus is a very ominous sign for very oor rognosis and death, In our study, it was found that out of atients (16.7%) develoed myoclonus in grou I versus 7 atients out of (%) in grou II with no significant difference between the grous. Myoclonus in comatosed atients following ROSC was reorted to be an agonal sign by Wijdicks et al as all atients with myoclonus died(15). However, since that reort this finding has been contradicted in a number of case reorts. Morris et al reorted three survivors with mild disability and in a litereature review found five similar cases(16). In a rosective study done by Zandbergen EG etal involving 7 atients, myoclonic status eileticus at hours after arrest was associated with no false ositives (95% CI) (17) GCS mean was 7.6 ±. in grou I versus 7.5 ±. in grou II with no significant difference between the grous. These results are in agreement 6

5 with Zandbergen et al systematic review which showed that GCS of 5 or less in the first hours was not helful in redicting outcome(18). In view of the brainstem reflex activity which has been examined as a redictor of individual outcome. The simlest clinical examination is the uillary resonse to light. Numerous studies have raised doubts about the secificity of uillary resonsivity due to small numbers of atients who make a good recovery desite no resonse to light. In the resent study, Puillary light reflex was resent in 1 out of atients (5.%) in grou I versus 1 out of atients (%) in grou II with no significant difference between the grous. The discreancy of results of different studies regarding the redictive outcome of uillary light reflex is mainly raised from the different timing in erforming the examination ost cardiac arrest. In our study, Significant different between the grous were recorded regarding the somatosensory evoked otential. In the atients with favorable outcome (8.%) showed normal resonse, (16.7%) showed delayed resonse while no atient in this grou showed oor resonse while in the other grou with unfavorable outcome only (%) showed normal resonse, (%) showed delayed resonse and oor resonse was recorded in (%) of atients.most of the studies showed similar results to what be reached as Madel et al study ublished in 199, of 66 atients investigated with SSEP between and 8 hours after ROSC. In 17 atients with favourable outcome a normal resonse was demonstrated whereas in 9 with a oor outcome the evoked resonse was delayed or absent. However, further studies have qualified these initial findings. A study of SEP in 6 atients demonstrated an abnormal SEP was associated with a oor rognosis but a normal SEP did not redict recovery(1). Nakabayashi et al, Chen et al, and Sandroni et al demonstrated a 1% negative redictive value for a good outcome (ersistent disability after awakening or comlete recovery) with delayed or absent SEPs but a oor ositive redictive value for normal SEPs. Nakabayashi demonstrated that of 1 atients with normal cortical resonse on SSEP, eight recovered consciousness. Chen demonstrated that bilaterally absent or low amlitude SSEP redicted brain death or ersistent unconsciousness while with a normal SSEP the rate of comlete recovery was only % (19,,1). Madl C et al suggested that a recording of the N7 eak is more accurate in redicting individual outcome than hysician review of clinical data. However, SSEP is difficult to record reliably in an intensive care environment. The anaesthetic and sedative agents used in atient management can themselves deress or extinguish the evoked otentials, and status eileticus will interfere with SSEP recording(). No significant statistical difference was found between the grous regarding the CT results in the current study. Few studies have tried to use neuroimaging to redict outcome in comatose atients. Torbey et al carried out a retrosective review of 5 atients who had CT of the brain. They showed that loss of distinction between grey and white matter on CT redicted oor outcome esecially at the basal ganglia level and roduced a qualitative analysis that suggested a cut-off for loss of distinction and guaranteed oor outcome. This was based on a small samle and has yet to be validated(7). It aears that [magnetic resonance imaging] MRI can certainly identify the most severely affected atients fairly easily, but whether it's going to be redictive in a rosective data set would need to be validated. Regarding serum creatinine level, there was no significant difference in the level between both grous in day and day 1 after cardiac arrest while Significant higher creatinine level was recorded in day in grou II being 1.6±1.1 versus 1.1±.78 in grou I (P =.5* ). These findings are artially different from Dietrich Haser et al study which showed that changes in serum creatinine may contribute to the rediction of outcome in atients with cardiac arrest. Whereas a decline in serum creatinine (>. mg/dl) in the first hours after cardiac arrest indicates good rognosis, the risk of unfavourable outcome is markedly elevated in atients with constant or increasing serum creatinine(8). As a conclusion from this study, the duration of cardiac arrest, the SSEP and the changes in serum creatinine are the arameters which carry the highest ability to differentiate between atients with good rognosis from those with bad rognosis. No gold standard single test can be used to redict the rognosis in ost cardiac arrest atients. More accurate rognostication can otentially be achieved by using several methods to investigate neurological injury. I believe that in the near future we will see more studies using incororated indices using multile neurological, laboratory and radiological tools to increase the sensitivity and secificity in rediction of neurological outcome. Acknowledgements: I would like to thank all members of staff and ersonnel of deartment of Critical Care Medicine and the deartment of hysical medicine of Alexandria University for heling me to accomlish this work. 7

6 Corresonding Author: Dr. Amr M. Abouelela Deartment of Critical Care Medicine Faculty of Medicine, Alexandria University, Egyt Authors Dr. Amr Mohamed Abouelela Lecturer of Critical Care Medicine. Critical Care Medicine Deartment. Faculty of Medicine, University of Alexandria. Raml station, PO box 156- Alexandria- Egyt. Cell Phone: amrela1@yahoo.com Dr. Mohammed Hassan Imam Assistant rofessor of hysical medicine hysical medicine, Rheumatology and Rehabilitation deartment Faculty of Medicine, University of Alexandria Raml station, PO Box 156, Alexandria- Egyt Cell Phone: imam_mohamed@hotmail.com References 1. Madl C, Grimm G, Kramer L, et al (199). Early rediction of individual outcome after cardioulmonary resuscitation. Lancet 1: Saltuari L, Marosi M (199). Coma after cardiac arrest: Will he recover all right? Lancet : 15.. Peberdy MA, Kaye W, Ornato JP (). Cardioulmonary resuscitation of adults in the hosital: a reort of 1,7 cardiac arrests from the National Registry of Cardioulmonary Resuscitation. Resuscitation 58: Berek K, Jeschow M, Aichner F (1997). The rognostication of cerebral hyoxia after outof- hosital cardiac arrest in adults. EurNeurol 7: Goh W.C, Heath P., Ellis S.J, et al (). Neurological outcome rediction in a cardioresiratory arrest survivor.br J Anaesth 88: Ahmed I (1988). Use of somatosensory evoked resonses in the rediction of outcome from coma. Clin Electroencehalogr 19: Torbey MT, Selim M, Knorr J, et al (). Quantitative analysis of the loss of distinction between gray and white matter in comatose atients after cardiac arrest. Stroke. 1: Dietrich H, Stehan von H, Christian S, et al (9). Changes in serum creatinine in the first hours after cardiac arrest indicate rognosis: an observational cohort study. Critical Care 1: Cummins RO, Chamberlain DA, Abramson NS et al: Recommended guidelines for uniform reorting of data from out-of-hosital cardiac arrest: the Utstein Style. Task Force ofthe American Heart Association, the Euroean Resuscitation Council, the Heart and StrokeFoundation of Canada, and the Australian Resuscitation Council. 1. Berger R, Kelley M (199). Survival after in-hosital cardioulmonary arrest of noncritically ill atients. A rosective study. Chest16: Schultz SC, Cullinane DC, Pasquale MD, et al (1996). Predicting in-hosital mortality during cardioulmonary resuscitation. Resuscitation : Saklayen M, Liss H, Markert R (1995). In-hosital cardioulmonary resuscitation. Survival in 1 hosital and literature review. Medicine7: Andreasson AC, Herlitz J, Bang A, et al (1998). Characteristics and outcome among atients with a susected in-hosital cardiac arrest. Resuscitation 9:. 1. Denton R, Thomas AN (1997). Cardioulmonary arrest: a retrosective review. Anaesthesia 5: Wijdicks EF, Parisi JE, Sharbrough FW (199). Prognostic value of myoclonus status in comatose survivors of cardiac arrest. Ann Neurol 5: Morris HR, Howard RS, Brown P (1998). Early myoclonic status and outcome after cardioresiratory arrest. J Neurol Neurosurg Psychiatry 6: Zandbergen EG, Hijdra A, Koelman JH, et al (6). Prediction of oor outcome within the first days of ostanoxic coma. Neurology 66: Zandbergen EG, de Haan RJ, Stoutenbeek CP, et al (1998). Systematic review of early rediction of oor outcome in anoxic-ischaemic coma. Lancet 5: Nakabayashi M, Kurokawa A, Yamamoto Y, et al (1). Immediate rediction of recovery of consciousness after cardiac arrest. Intensive Care Med 7: Chen R, Bolton CF, Young B (1996). Prediction of outcome in atients with anoxic coma: a clinical and electrohysiologic study. Crit Care Med : Sandroni C, Barelli A, Piazza O, et al (1995). What is the best test to redict outcome after rolonged cardiac arrest? Eur J Emerg Med : 7.. Madl C, Kramer L, Domanovits H, et al (). Imroved outcome rediction in unconscious cardiac arrest survivors with sensory evoked otentials comared with clinical assessment. Crit Care Med 8: /11/11 8