Prediction of In-Hospital Mortality in Patients with Myocardial Infarction Using APACHE II System

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1 Chi nese Med i cal Jour nal (Taipei) 2001;64: Orig i nal Prediction of In-Hospital Mortality in Patients with Myocardial Infarction Using APACHE II System Hung-Ting Chiang Shoa-Lin Lin Hsiang-Chin Hsu Shue-Ren Wann Ming-Ho Kung Chun-Peng Liu In ten sive Care Unit and Di vi sion of Car di ol ogy, Kaohsiung Vet erans Gen eral Hos pi tal, Kaohsiung, Na tional Yang-Ming Uni ver sity School of Med i cine; and Na tional De fense Med i cal Cen ter, Tai wan, R.O.C. Key Words APACHE; in ten sive care unit; myo car dial in farc tion; mor tal ity Background. The acute physiology and chronic health eval u a tion (APACHE) scoring system has been validated in many dif fer ent pa - tient populations, however, patients with myo car dial in farc tion (MI) were not in cluded in the orig i nal data base. To eval u ate the abil ity of APACHE scor ing sys tem in pre dict ing in-hospital mor tal ity, 694 pa - tients with MI were stud ied. Methods. Data had been col lected pro spec tively in an ICU com puter database in the past 3 years. Patients ad mit ted in cor o nary care unit with acute MI or acute cor o nary syn drome who had pre vi ous his tory of MI were all included. Patients were divided into survivor and nonsurvivor data sets. Mul ti ple lo gis tic re gres sion anal y sis was eval u ated on the variables of APACHE II score to determine which variables could predict in-hospital mortality. A logistic regression model was used to study the mor tal ity curves. The differences of APACHE II scores be tween sur vi vors and non-survivors were com pared. Cor re la - tion be tween ob served and pre dicted mor tal ity was also as sessed. Results. Ac cord ing to the sta tis ti cal anal y sis, the non-survivors tended to have sig nif i cantly greater APACHE II scores than those of sur vi vors. The APACHE II values of non-survivors and survivors were ± 9.41 ver sus ± 7.14 (p < 0.001), re spec tively. Using mul ti ple lo gis - tic regression analysis, we found that age, creatinine, coma scale, so - dium and APACHE II score were ca pa ble of pre dict ing the in-hospital mor tal ity (p < 0.05). With use of the lo gis tic model, a good cor re la tion of pre dicted mor tal ity rate to ob served mor tal ity rate was found (r = 0.992). This study demonstrated that lower APACHE II scores predicted sur - vival while high scores pre dicted mor tal ity. Mor tal ity rate in creased sig - nificantly when APACHE II score was > 25. An APACHE II score greater than pre dicted a more than 50% in- hospital mor tal ity. Conclusions. This study demonstrates that the APACHE II scor ing sys tem is ca pa ble of pre dict ing mor tal ity in pa tients with MI, which makes this mo dal ity more ap pli ca ble in the busy in ten sive care unit. [Chin Med J (Tai pei) 2001;64: ] There is a grow ing need for a dis ease se ver ity in dex in the intensive care unit. Sev eral prognostic meth ods have been sug gested for pa tients with acute myo car dial infarction (MI) but none have reached wide-spread ac cep tance. 1-3 The Acute Phys i ol ogy and Chronic Health Eval u a tion II (APACHE II) sys tem for Re ceived: October 27, Ac cepted: April 18, Cor re spon dence to: Hung-Ting Chiang, MD, Di vi sion of Car di ol ogy, De part ment of In ter nal Med i cine, Kaohsiung Vet erans Gen eral Hos pi tal, 386, Dar-Chung 1 st Road, Kaohsiung 813, Tai wan. Fax: ;

2 502 Hung-Ting Chiang, et al. Chi nese Med i cal Jour nal (Taipei) Vol. 64 No. 9 eval u at ing the se ver ity of dis ease was ini tially de - scribed in The sys tem is well doc u mented and its per for mance has been val i dated in many dif fer ent pa - tient pop u la tions; 5-14 how ever, pa tients with MI were not in cluded in the orig i nal da ta base. 4 Com par i son of APACHE II with prog nos tic meth ods es pe cially con - structed for use in acute myo car dial in farc tion, such as the Sim plified Acute Phys i ol ogy Score (SAPS), have been proved to be ac cu rate in pre dict ing the out come of acute MI pa tients and can be used in multicenter stud - ies. 15,16 Ludwigs and Hulting re ported that the APACHE II scor ing sys tem could ac cu rately pre dict the in-hospital mor tal ity in pa tients with acute MI. 5 As these in ves ti ga tions were stud ied in pa tients with acute MI, the goal of this study was to eval u ate the per for - mance of APACHE II in all kinds of MI pa tients, and to de ter mine which vari ables of APACHE II scor ing sys - tem are ca pa ble to pre dict the in-hospital mor tal ity. Study patients Methods Acute MI was di ag nosed when at least two of the fol low ing three cri te ria were pres ent: typ i cal se vere chest pain, electrocardiographic changes (new Q waves), and in creased car diac en zyme con cen tra tion (MB isoenzyme level was 5% of the to tal creatine kinase level). Dur ing the past 3-years, all con sec u tive pa tients ad mit ted to the med i cal in ten sive care unit with a di ag no sis of MI (ICD-9CM codes of 410, 410.1, ) were in cluded in the study, i.e., pa - tients with acute MI or acute cor o nary syn drome who had his tory of old MI were also in cluded. If a pa tient was ad mit ted in our in ten sive care unit more than once, only data from the first ad mis sion were eval u - ated. Six hun dred and ninety four pa tients, 583 men and 111 women, aged from 34 to 90 (mean ± SD, 66.3 ± 11.7) years were en rolled in this study. The worst data of all vari ables were ob tained dur ing the first 24 hours in the in ten sive care unit; the APACHE II score was de ter mined re spec tively in all pa tients. All of the data (100%) of all pa tients were col lected with out any be ing lost. The def i ni tion of in-hospital mor tal ity was those who died during hos pi tal iza tion or within 48 hours af ter dis charge from the hos pi tal. Data collection The APACHE II score was ob tained from 15 phys i - o logic vari ables, age con di tion, and chronic health sta - tus. The phys i o logic data in cluded mean blood pres - sure, spon ta ne ous re spi ra tory rate, ox y gen a tion (when - ever the FiO 2 > 0.5 re cord ar te rial ox y gen dif fer ence; if FiO 2 0.5, re cord alveoloar te rial ox y gen par tial pres - sure), ar te rial ph, se rum so dium, po tas sium, creatinine, hematocrit, white blood cell count, body tem per a ture, heart, and Glas gow coma scale. To fa cil i tate anal y sis of the dis tri bu tion of the APACHE II scores in the pa tient pop u la tion, the scores were pooled and strat i fied in nine lev els in APACHE II, each be ing 5 points wide, as in the initial study. 4 If more than one data were as - sessed, the worst score of each vari able was ob tained dur ing the first 24 hours, the sum of to tal scores of all vari ables was used as the APACHE II score. Un der the rules of the APACHE sys tem, any un mea sured value was as sumed to be nor mal and the weighted score for the un mea sured item was zero. 4 Sta tis ti cal anal y sis The data of quan ti ta tive vari ables in APACHE II was sum ma rized as mean ± SD. Among the vari ables of APACHE II, mul ti ple lo gis tic re gres sion anal y sis was ini tially used to as sess which vari ables were ca - pa ble of pre dict ing mor tal ity. Af ter the vari ables were de ter mined, the val ues of these vari ables were com pared be tween sur vi vors and non-survivors us - ing Mann-Whitney U test. A p-value less than 0.05 was con sid ered to be sta tis ti cally sig nif i cant. Ad di - tionally, the lo gis tic model was used to cal cu late the pre dict ing curve of mor tal ity rate from the ac tual APACHE II curve by fit ting the for mula, Ln[P/(1-P)] = A (A PACHE II score) - B (P was the out come of pre dict ing mor tal ity rate, A and B were ob tained af - ter cal cu la tion). 4 Results In this se ries, 76 of 694 (10.95%) pa tients died.

3 Sep tem ber 2001 APACHE II in MI Pa tients 503 Using mul ti ple lo gis tic re gres sion anal y sis, we found that age, creatinine, coma scale, so dium and APACHE II score were ca pa ble of pre dict ing in-hospital mor tal - ity (p < 0.05). Ac cord ing to the APACHE II sys tem, the data of age (66.2 ± 10.3 vs ± 10.0, p < 0.01), creatinine score (0.96 ± 1.37 vs 2.22 ± 1.48, p = ), coma scale (1.15 ± 2.77 vs 5.32 ± 4.64, p < ), se rum so dium (0.36 ± 0.78 vs 0.68 ± 1.06, p = ) and APACHE II score (13.35 ± 7.14 vs ± 9.41, p < 0.001) were sig nif i cantly smaller in sur vi - vors than those of non-survivors (Ta ble 1). By lo gis tic model, the pre dicted mor tal ity rate of APACHE II could be cal cu lated; the curves of the ob - served real mor tal ity rate and pre dicted mor tal ity rate are plot ted in Fig. 1. Sta tis ti cal anal y sis de picted that the re la tion ship be tween the APACHE II score and mor tal ity rate was ex po nen tial. The for mula of the pre - dict ing curve of APACHE II was Ln[P/(1-P)] = (score) (P was the out come of pre dicted mor tal - ity rate). The cor re la tion co ef fi cient be tween ob served and pre dicted mor tal ity rate was From the above for mula, the pre dicted deaths could be cal cu lated from multiplying the num ber of pa tients by the mor tal ity rate. The re la tion ship be tween ob served-death and pre - dicted-death can be re ferred to in Ta ble 2. At the point of 50% mor tal ity rate, the APACHE II score was Table 1. Comparison of APACHE II variables between survivors and non-survivors Characteristics Allpatients Survivors (n = 618) Nonsurvivors (n = 76) p value APACHE II ± ± ± 9.41 < Age 66.3 ± ± ± 10.0 < 0.01 Sex (M/F) 583/ /101 67/ Creatinine 1.10 ± ± ± GCS 1.61 ± ± ± 4.64 < Sodium 0.39 ± ± ± Arterial PH 0.43 ± ± ± Potassium 0.29 ± ± ± Hematocrit 0.37 ± ± ± WBC 0.27 ± ± ± BT 0.35 ± ± ± MBP 1.63 ± ± ± Pulse 1.84 ± ± ± Respiratory Rate 1.42 ± ± ± A-aDO ± ± ± PaO ± ± ± Chronic Health 0.15 ± ± ± GCS = Glasgow coma scale; WBC = white blood cell; BT = body temperature; MBP = mean blood pressure; A-aDO 2 = alveoloarterial oxygen difference. Table 2. Relation of APACHE II score to observed and predicted death in patients with myocardial infarction Score n Observed death Predicted death Mortality rate (%) ~ ~ ~ ~ ~ ~ ~

4 504 Hung-Ting Chiang, et al. Chi nese Med i cal Jour nal (Taipei) Vol. 64 No. 9 In other words, if the APACHE II score was greater than 28.58, there would be a more than 50% mor tal ity rate. No pa tient with an APACHE II score of < 5 died; the mor tal ity rate for pa tients with scores < 7.5 was 2.12%. The mor tal ity rate for pa tients with score be - tween was There were 510 pa tients (73.5%) in the first 3 groups, their APACHE II scores were less than 17.5 and their mor tal ity rates were less than 9.92%. The mor tal ity rate would be greater than 90% if the APACHE II score was greater than 42.22, the mor tal ity rate would be 93.51% if the score was > This study dem on strated that lower APACHE II scores predicted survival and high scores predicted mor tal ity; the greater the APACHE II score, the higher the mor tal ity rate. Discussion The APACHE sys tem has many ad van tages: (A) it is based on ob jec tive phys i o logic vari ables; (B) its sim - plic ity ren ders it in de pend ent of the user; (C) it can be used ei ther con cur rently or ret ro spec tively; and (D) it is one of the most re li able ICU ad just ers when com pared with other case-mix ad just ers. 12 The im por tance of the Fig 1. The APACHE II scores are plot ted against the ob - served mor tal ity rate (dot ted line) and the pre dicted mor tal ity rate (con tin u ous line). The pre dic tive prob a bil ity of death was cal cu lated ac cord ing to the APACHE II equa tion by lo gis tic model (r = 0.992, p < 0.001). Please note that there is an ex po nen tial re la tion ship be tween APACHE II score and mor tal - ity rate: the greater the APACHE II score, the higher the mor tal ity rate. APACHE score is to an a lyze dif fer ent groups of pa - tients; it can be used to com pare per for mances of dif - fer ent in ten sive care units in multi-center stud ies. This study used the APACHE II sys tem to eval u ate its abil - ity to pre dict in-hospital mor tal ity in a spe cific group of MI pa tients. The APACHE II scores in this study were gen er ally lower than those scores found in gen eral ICUs. 4,17 This find ing is not un ex pected, be cause the car dio vas cu lar sys tem was of ten the only or gan sys tem in volved in this study. Other rea sons for lower scores in our pa tients are: (A) Most pa tients with MI in this se - ries had nor mal neu ro log i cal con di tion and alert con - scious ness. The Glas gow Coma Scale was scored as 0 in these pa tients, which lead to no neu ro log i cal points be ing scored; (B) Pa tients rel a tively less fre quently un - der went an elec tive sur gery in our se ries. This study dem on strated that lower APACHE scores pre dicted sur vival and high scores pre dicted mor tal ity in all kinds of MI pa tients. Mor tal ity rate in - creased sig nif i cantly when APACHE II score was > 25. From Fig. 1, a sig nif i cant S-shape re la tion ship be - tween APACHE II score and mor tal ity was found. Our re sult de picted that the higher the score, the greater the mortality, which is consistent with Moreau s re port, which de scribed the as sess ment of acute MI in 76 pa - tients us ing APACHE II scores. 15 Be sides, sim i lar ex - pe ri ence that the greater the APACHE II score, the higher the mor tal ity was also noted in repiratory fail - ure pa tients from our in ten sive unit. 18 By mul ti ple lo gis tic re gres sion anal y sis, we found that the creatinine, so dium, Glas gow coma scale, and the APACHE II score were ca pa ble of pre dict ing the in-hospital mor tal ity rate. We be lieve that the de - pressed car diac per for mance af ter MI will re sult in de - te ri o ra tion of hemodynamic, re nal or cen tral ner vous func tion, which may cause changes in these vari ables. Ab nor mal ities in the above or gan-system func tions rea son ably ex plained that these vari ables could pre - dict in-hospital mor tal ity. Myo car dial in farc tion may lead to var i ous non - spe cific or gan fail ures that APACHE II can de tect: hypotension, re spi ra tory dis tress, re nal fail ure, and encephalopathy. By de tect ing these, APACHE II com - pen sates for the lack of spe cific in for ma tion such as site and size of in farc tion or pres ence and types of arrhythmias. Be sides, the APACHE II sys tem takes

5 Sep tem ber 2001 APACHE II in MI Pa tients 505 into ac count the leu ko cyte count. Ev i dence is grow ing for a role of granu lo cytes in the mech a nism of myo - car dial ischemia through myo car dial cap il lary plug - ging, the so-called no-reflow phe nom e non, and ox y - gen rad i cal pro duc tion. 19 Re cently, the ini tial leu ko - cyte count was found to be the most im por tant pre dic - tor of ven tric u lar fi bril la tion in pa tients with AMI, 20 where WBC count was found to be sig nif i cantly cor - re lated with pre ma ture ven tric u lar beats and ven tric u - lar tachy car dia. Finally, age, a ma jor prog nos tic fac tor in myo car dial in farc tion, en ters into the cal cu la tion of APACHE II. 21,22 In con clu sion, this study dem on strates that the APACHE II scor ing sys tem is ca pa ble of pre dict ing in-hospital mor tal ity in pa tients with MI, which makes this mo dal ity more ap pli ca ble in the busy in - ten sive care unit. Acknowledgment This study was sup ported by Vet erans Gen eral Hos pi tal- Kaohsiung, Grant No. VGHKS References 1. Killip T, Kimball JT. Treat ment of myo car dial in farc tion in a cor o nary care unit: a two-year ex pe ri ence with 250 pa tients. Am J Cardiol 1967;20: Fedullo AJ, Swinburne AJ, Wahl GW, Bixby K. Acute cardi - o gen ic pul mo nary edema treated with me chan i cal ven ti la - tion. Chest 1991;99: Moreno R, Morais P. Out come pre dic tion in in ten sive care: re sults of a pro spec tive, multicenter, Por tu guese study. In - tens Care Med 1997;23: Knaus WA, Zimmerman JE, Wag ner DP, Draper E A, Law - rence DE. Acute phys i ol ogy and chronic health eval u a tion: a phys i o log i cally based clas si fi ca tion sys tem. Crit Care Med 1981;9: Ludwigs U, Hulting J. Acute Phys i ol ogy and Chronic Health Eval u a tion II scor ing sys tem in acute myo car dial in farc tion: a pro spec tive val i da tion study. Crit Care Med 1995;23: Berger MM, Marazzi A, Free man J, Chiolero R. Eval u a tion of the con sis tency of Acute Phys i ol ogy and Chronic Health Eval u a tion (APACHE II) scor ing in a sur gi cal in ten sive care unit. Crit Care Med 1992;20: John son MH, Gordon PW, Fitz ger ald FT. Strat i fi ca tion of prog no sis in granulocytopenic pa tients with hematologic ma lig nan cies us ing the APACHE II se ver ity of ill ness score. Crit Care Med 1986;14: Bion JF, Aitchison TC, Edlin SA, Ledingham IM. Sick ness scor ing and re sponse to treat ment as pre dic tors of out come from crit i cal ill ness. Intens Care Med 1988;14: Knaus WA, LeGall JR, Wag ner DP, Draper EA, Loirat P, Cam pos RA, et al. A com par i son of in ten sive care in the U.S.A. and France. Lan cet 1982;2: Bion JF, Edlin SA, Ransay G, McCabe S, Ledingham IM. Val i da tion of a prog nos tic score in crit i cally ill pa tients un - der go ing trans port. Br Med J 1985;291: Jacobs S, Chang RW, Lee B, Lee B. Au dit of in ten sive care: a 30 month ex pe ri ence us ing APACHE II se ver ity of dis ease clas si fi ca tion sys tem. Intens Care Med 1988;14: Gross PA, Beyt BE, Decker MD, Gar i baldi RA, Hierholzer WJ Jr, Jarvis WR. De scrip tion of case-mix ad just ers by the se ver ity of ill ness work ing group of the so ci ety of hos pi tal epidemiologists of Amer ica (SHEA). In fect Con trol Hosp Epidemiol 1988;9: Turner JS, Potgieter PD, Lin ton DM. Sys tems for scor ing se - ver ity of ill ness in in ten sive care. S Afr Med J 1989;76: Kruse JA, Thill-Baharozian MA, Carlson RW. Com par i son of clin i cal as sess ment with APACHE II for pre dict ing mor - tal ity risk in pa tients ad mit ted to a med i cal in ten sive care unit. JAMA 1988;260: Moreau R, Soupison T, Vauquelin P, Derrida S, Beaucour H, Sicot C. Com par i son of two sim pli fied se ver ity scores (SAPS and APACHE II) for pa tients with acute myo car dial in farc tion. Crit Care Med 1989;17: Teskey RJ, Cal vin JE, McPhail I. Dis ease se ver ity in the cor - o nary care unit. Chest 1991;100: Giangiuliani G, Mancini A, Gui D. Val i da tion of a se ver ity of ill ness score (APACHE II) in a sur gi cal in ten sive care unit. Intens Care Med 1989;15: Hsu CW, Wann SR, Chiang HT, Lin CH, Kung MH, Lin SL. Com par i son of the APACHE II and APACHE III scor ing sys - tems in pa tients with re spi ra tory fail ure in a med i cal in ten - sive care unit (ab stract). J Emerg Crit Care Unit 2000; 11(suppl I): Engler R. Con se quences of ac ti va tion and adenosine- medi - ated in hi bi tion of granu lo cytes dur ing myo car dial ischemia. Fed Proc 1987;46: Maisel AS, Filpin FA. Le Win ter M. Ini tial leu ko cyte count dur ing acute myo car dial in farc tion in de pend ently pre dicts early ven tric u lar fi bril la tion. Cir cu la tion (ab stract) 1985; 72(suppl III): Le Gall JR, Loirat P, Alperovitch A, Glaser P, Granthil C, Mathieu D, et al. A sim pli fied acute phys i ol ogy score for ICU pa tients. Crit Care Med 1984;12: Knaus WA, Draper EA, Wag ner D, Zimmerman JE. APACHE II: a se ver ity of dis ease clas si fi ca tion sys tem. Crit Care Med 1985;13:

6 506 Hung-Ting Chiang, et al. Chinese Medical Journal (Taipei) 2001;64: APACHE II APACHE 694 APACHE II multivariate logistic regression analysis APACHE II logistic regression model APACHE II APACHE II (24.64 ± 9.41 vs ± 7.14, p < 0.001) logistic regression model APACHE II % APACHE II APACHE

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