Outcome Prediction for Critically Ill Egyptian Cirrhotic Patients in Liver Intensive Care Unit

Transcription

1 Med. J. Cairo Univ., Vol. 85, No. 4, June: , Outcome Prediction for Critically Ill Egyptian Cirrhotic Patients in Liver Intensive Care Unit AMANY ABDEL-MAQSOD, M.D.; HEBA SEDRAC, M.D.; MERVAT NAGUIB, M.D. and NOUMAN ELGAREM, M.D. The Department of Internal Medicine, Faculty of Medicine, Cairo University Abstract Background: Decompensation in patients with chronic liver disease leading to hospitalization, usually develops after an acute insult such as variceal bleeding, hepatorenal syndrome, or spontaneous bacterial peritonitis. Mortality rates among cirrhotic patients admitted to intensive care units are high. Prediction of prognosis in critically ill cirrhotic patients helps in prioritizing ICU admission especially with limited resources. Objective: Comparing the predictive value of Child Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), acute physiology, age, chronic health evaluation II (APACHEII) scores in critically ill cirrhotic patients. Patients and Methods: This study retrospectively reviewed the medical records of 301 patients who had been admitted to hepatic ICU in a tertiary care hospital from July 2007 to March The CTP, MELD and APACHE II scores were computed for each patient within the first 24 hours of admission. Patients were classified as either survivors or non survivors. ROC (receiver operator characteristic curve) was used to find out the best cut off and validity of each scoring system for prediction of mortality. Results: Survivors 129 (42.9%) had significantly lower CTP, MELD and APACHEII scores (10.2 ± 1.9, 21.8±6.8, 22.7±4.5) compared to non survivors (11.3± 1.4, 31.4±8.9, 26.6±5.2) p< MELD score had the highest sensitivity (86.6%) compared to CTP (75.6%) and APACH II (72%). The predictive accuracy of MELD score was the highest (AUC = 0.81) compared to CTP and APACHII scores (AUC = 0.67, 0.71) respectively. Need for vasopressors and mechanical ventilation were associated with higher mortality (OR 9.9; 95% CI ) for the former and (OR 8; 95% CI )for the later. Conclusion: In critically ill cirrhotic patients MELD score had the highest sensitivity and predictive accuracy for mortality. In addition, need for mechanical ventilation or vasopressors were associated with poor outcome. Key Words: ICU Critically ill Liver cirrhosis Scoring system. Correspondence to: Dr. Mervat Naguib, mervat.naguib@kasralainy.edu.eg Introduction LIVER cirrhosis is associated with significant morbidity and mortality, mainly due to its complications which occur in up to 40% of patients with advanced cirrhosis at 5 years of diagnosis [1]. The common causes of hospital admission in cirrhotic patients are variceal bleeding, hepatorenal syndrome, or infection such as spontaneous bacterial peritonitis. Despite some recent evidences suggest improving outcomes in acutely ill patients with cirrhosis, in part due to the better understanding of disease processes and improving ICU care, the overall prognosis for patients with cirrhosis admitted to ICU remains poor with mortality rates ranging from 44 to 81% [2,3]. Many scoring systems have been suggested as predictors of mortality in critically ill cirrhotics, some are general others are liver specific scores [4-7]. Early prediction of outcome allows creating appropriate management plan and help in prioritizing ICU admission in the presence of limited beds. Egypt is a developing country, with a high prevalence of cirrhosis [8]. The ability to reliably risk stratify our critically ill patients would be extremely helpful in discussing goals of critical care with patients and their families. The aim of the present study was to compare the prognostic value of two hepatic specific scores (CTP and MELD) and APACHE II in predicting hospital mortality of patients with liver cirrhosis admitted to hepatic ICU. Material and Methods This study retrospectively reviewed the medical records of 301 patients who had been admitted to hepatic ICU in a tertiary care hospital from July 1571

2 1572 Outcome Prediction for Critically Ill Egyptian Cirrhotic Patients 2007 to March The collected data included; Demographic data, cause of admission, Length of ICU stay, need of vasopressors for hemodynamic support of shocked patients and use of mechanical ventilation for respiratory failure. In addition, CTP, MELD, and APACHEII scores have been calculated for each patient. The outcome was either ICU death or discharge due to improvement. CTP was calculated depending on total bilirubin, serum albumin, INR, ascites and hepatic encephalopathy [9]. MELD score was calculated with the following formula: MELD = 3.78 [serum bilirubin mg/dl] [INR] [serum creatinine mg/dl] [10]. APACHEII score was calculated based on the initial values of 12 routine physiologic measurements, age, and previous health status [11]. Statistical analysis: Analysis of data was done by using SPSS (statistical program for social science version 16) as follow; quantitative variables were described as mean, SD and range and qualitative variables as number and percentage. Unpaired t-tests and chi-square analysis were used to assess the differences between groups. Results are expressed as mean ± Standard deviation (SD) with a p-value less than 0.05 was considered statistically significant. Discrimination was tested using the receiver operating characteristic (ROC) curves and by comparing areas under the curve (AUCs). AUCs between 0.7 and 0.8 were classified as "acceptable" and between 0.8 and 0.9 as "excellent" discrimination. For the different scoring systems tested, the sensitivity, specificity, positive and negative predictive values were calculated according to the most predictive cut off that had the best discriminative ability to predict mortality. Calibration was assessed using the Hosmer-Lemeshow goodness of fit statistic which divides subjects into deciles based on predicted probabilities of death and then computes a chi-square from observed and expected frequencies. Lower chi-square values and higher p-values are associated with a better fit. A good fit was defined as p>0.05 [12]. Results Baseline characteristics of cirrhotic patients admitted to ICU: Mean age of the studied patients was (57.9 ±8.7) years and 76.1% of them were males. The mean length of ICU stay was 5.3 ±4.2 days. The most common causes of ICU admission were Hepatic encephalopathy (43.5%), variceal bleeding (22.3%) and hepatorenal syndrome (14.3%). Most of patients had advanced stage of liver cirrhosis; 78.4% of them were CTP stage C and 21.6% were stage B. Moreover, MELD score of this group was (27.3 ± 9.4). 26.2% of them needed mechanical ventilation and 21.9% received vasopressors (Table 1). The overall ICU mortality rate was 57.1%. Table (1): Characteristics of cirrhotic patients admitted to intensive care unit (ICU). Variable (unit) All (n =301) Age (years) 57.9±8.7 Sex n (%): Male 229 (76.1) Female 72 (23.9) Length of ICU stay (days) 5.3±4.2 Cause of ICU admission n(%) Hepatic encephalopathy 131 (43.5) Variceal bleeding 67 (22.3) Hepatorenal syndrome 43 (14.3) Non hepatic causes* 40 (13.3) Spontaneous bacterial peritonitis 10 (13.3) Post-cardiac arrest 7 (2.3) Acute-on-chronic liver failure 2 (0.7) Obstructive jaundice 1 (0.3) CTP (Mean±SD) 10± 1.7 Class B n (%) 65 (21.6) Class C n (%) 236 (78.4) MELD (Mean±SD) 27.3±9.4 APACHE II (Mean±SD) 24.9±5.3 Need for Mechanical ventilation n (%) 79 (26.2) Need for vasopressors n (%) 66 (21.9) * Non hepatic causes included pneumonia and sepsis from other causes not related to SBP. Patients were divided according to the outcome into 2 groups: Survivors and non-survivors. The CTP, MELD, and APACHE II scores were significantly higher in the non-survived group (Table 2). The mean length of ICU stay was (5.2±3.7) days in non survivors and (5.5 ±4.9) days in survivors with no significant difference (p=0.607). Of the non survivors, 73 (92.4%) needed mechanical ventilation and 64 (97%) required vasopressors compared to 6 (7.6%) and 2 (3%) respectively of survivors (p<0.001). Table (2): Comparison of CTP, MELD, APACHE II scores and length of ICU stay between survivors and non survivors. Non survivors Survivors Variable no=172 no=129 p-value Mean±SD Mean±SD CTP 11.3± ± 1.9 <0.001* MELD 31.4± ±6.8 <0.001 * APACHE II 26.6± ±4.5 <0.001 * *=Significant. p>0.05=non significant.

3 Amany Abdel-Maqsod, et al Predictors of ICU mortality: The highest mortality was among patients presented with fulminant hepatic failure (100%). also patients with hepatorenal syndrome had higher mortality (86%) than those with hepatic encephalopathy (50.4%) and GIT bleeding (40.3%). Logistic regression model for odds ratio (OR) of mortality showed that patient needed vasopressors were 10 times likely to die (OR 9.9; 95% CI ). Also, patients required mechanical ventilation had a high probability of death (OR 8; 95% CI ). CTP, MELD, and APACHE II scores had significant effect on outcome, however, the lower limit of the 95% CI is 1 or near one (Table 3). Thus, we analyzed the three scores with Hosmer- Lemeshow goodness-of-fit tests. For the three scores, calibration was good with best p-value was for MELD score (Table 4). Table (3): Univariate analysis of variables affecting outcome. Variable Odds Ratio 95%CI p-value CTP * MELD <0.001 * APACHE II * Need for <0.001 * Mechanical ventilation Need for vasopressors * *=Significant. p>0.05=non significant. CI : Confidence Interval Table (4): Hosmer-Lemeshow goodness-of-fit tests results for the 3 scores. Score Chi-square value p-value CTP * MELD * APACHE II * *A good fit was defined as p>0.05. The predictive values of the various scoring systems calculated at the cutoff point giving the best discriminative ability to predict mortality. MELD score had the highest sensitivity (86.6%) followed by CTP (75.6%) and lastly APACHE II (72%). However, specificity of the three scores was rather low; CTP (52.7%), MELD (60%), APACHE II (59%). Discrimination power of MELD as assessed by AUC was excellent, while that of APACHE II AUC was acceptable (Table 5). Table (5): Comparison of the predictive values of the scoring systems. Variable CTP MELD APACHE II Cutoff point AUC (CI) ( ) ( ) ( ) Sensitivity 75.6% 86.6% 72% Specificity 52.7% 60% 59% Positive predictive 68.0% 74% 70% value Negative predictive value 61.8% 77% 61% Discussion Many prognostic indicators have been suggested for prediction of outcomes in critically ill cirrhotic patients and the work is still running [2,13,14]. In this study, mortality was associated with higher MELD, APACHI II and CTP scores. MELD score was superior compared to other scores with excellent discrimination, and APACHE II was better than CTP. This agrees previous studies in which the ICU-specific score (APACHE II) was superior to CTP [14,15]. This may be explained by the fact that most ICU cirrhotic patients have multiple organ system dysfunction, in which the liver failure may have little effect on the outcome. In addition, some of liver-specific parameters are assessed in APACHE II [3]. In spite of being independent predictor of poor long-term survival, CTP includes subjective variables which may lead to its poor performance in acute settings [6]. Although newer scoring systems, such as SOFA have replaced APACHE II in some ICUs, APACHE II still widely used, first, so much documentation is based on it. Second, APACHE II score is not recalculated during admission, while SOFA needs to follow the patient's condition. Lastly, some important variables which could affect outcome such as age, reason for admission, co-morbidity, total leucocytic count, hyponatrmia, acid-base status that are commonly disturbed in critically ill cirrhotic patient are not assessed in SOFA but included in APACHE [16,17]. In spite, the higher accuracy of APACHE II compared to CTP in our study, the sensitivity of both scores were close. One study reported the correlation of CTP but not APACHE II score with ICU mortality [18]. However, this study done in mechanically ventilated patients and involved smaller number of cohort than that investigated in our study.

4 1574 Outcome Prediction for Critically Ill Egyptian Cirrhotic Patients MELD score which is a liver-specific prognostic model has been evaluated in critically ill cirrhotics and it has been a significant predictor of overall mortality in multiple ICU cohorts of cirrhotic patients [19,20]. Although it was better than APACHE II and CTP in some studies [14,21], APACHE II was more powerful predictor of prognosis in others [22]. In the present study, MELD score had a better prognostic value than APACHE II and CTP. Moreover, it had better sensitivity, positive and negative predictive values compared to that of APACHE II. These results compare well with what was previously reported that MELD is a better predictor than APACHE II or CTP in critically ill cirrhotic [3]. The good performance of MELD score may be related to having bilirubin and creatinine as components, so it is related to more than one organ dysfunction which is common ICU finding. In addition, MELD contains only objective variables which reduce intra and inter-observer variability [23]. The need for mechanical ventilation and use of vasopressors were two simple and reproducible parameters related to mortality among the studied patients. Mechanical ventilation has been associated with ICU mortality rates of 83-95% in patients with cirrhosis [24]. Circulatory failure with need for vasopressors is a component of the novel scoring system, chronic liver failure-sequential organ failure assessment (CLIF-SOFA), for prediction of mortality in critically ill cirrhotics [25]. Moreover, it has been related to the outcome in decompensated liver cirrhosis [26]. Potential limitations of our study should also be mentioned. Our study was performed in an academic referral hospital; therefore our results may not be applicable to institutions with different patient populations. Second, because of the retrospective nature of this study, some laboratory data were unavailable. Lastly, we would like to stress that all scoring systems have limitations and should be applied cautiously to individual patients. In conclusion, MELD score was the most powerful predictor of mortality for cirrhotic patients admitted to ICU followed by APACHE II score and lastly CTP. Moreover, need for Mechanical ventilation or vasopressors correlated well with poor outcome. The presence of fulminant hepatic failure or hepatorenal syndrome was associated with the worst outcome. References 1- ESCORSELL MAÑOSA A. and ORDEIG A.: Acute on chronic liver failure. Gastroenterol. Hepatol., 33: , GALBOIS A., TROMPETTE M.L., DAS V., BOËLLE P.Y., CARBONELL N., THABUT D., et al.: Improvement in the prognosis of cirrhotic patients admitted to an intensive care unit, a retrospective study. Eur. J. Gastroenterol. Hepatol., 24: , CHOLONGITAS E., SENZOLO M., PATCH D., SHAW S., HUI C., and BURROUGHS A.K. Review article: Scoring systems for assessing prognosis in critically ill adult cirrhotics. Aliment Pharmacol. Ther., 24: , KIM J.Y., LIM S.Y., JEON K., KOH Y., LIM C.M., KOH S.O., et al.: External Validation of the Acute Physiology and Chronic Health Evaluation II in Korean Intensive Care Units. Yonsei Med. J., 54: , NASSAR A.P., MALBOUISSON L.M. and MORENO R. Evaluation of Simplified Acute Physiology Score 3 performance: A systematic review of external validation studies. Crit Care, 18: R117, MATSUMURA Y., NAKADA T., ABE R., OSHIMA T. and ODA S.: Serum procalcitonin level and SOFA score at discharge from the intensive care unit predict postintensive care unit mortality: A prospective study. PLoS One, 9 (12): e114007, KIM H.J. and LEE H.W.: Important predictor of mortality in patients with end-stage liver disease. Clin. Mol. Hepatol., 19: , HANAFIAH M.K., GROEGER J., FLAXMAN A.D.and WIERSMA S.T.: Global epidemiology of hepatitis C virus infection: New estimates of age-specific antibody to seroprevalence. Hepatology, 57: , PUGH R., MURRAY-LYON I. and DAWSON J.: Transection of the oesophagus for bleeding oesophageal varices. Br. J. Surg., 60: , KAMATH P.S. and KIM W.R.: The model for end-stage liver disease (MELD). Hepatology, 45: , KNAUS W.A., DRAPER E.A., WAGNER D.P. and ZIM- MERMAN J.E.: APACHE II: A severity of disease classification system. Crit Care Med., 13: , LEMESHOW S. and HOSMER D.W.: A review of goodness of fit statistics for use in the development of logistic regression models. Am. J. Epidemiol., 115: , BAHIRWANI R., GHABRIL M., FORDE K.A., CHA- TRATH H., WOLF K.M., URIBE L., et al.: Factors that predict short-term intensive care unit mortality in patients with cirrhosis. Clin. Gastroenterol. Hepatol, 11: , CHOLONGITAS E., SENZOLO M., PATCH D., KWONG K., NIKOLOPOULOU V., LEANDRO G., et al.: Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit. Aliment Pharmacol. Ther., 23: , HO Y.P., CHEN Y.C., YANG C., LIEN J.M., CHU Y.Y., FANG J.T., et al.: Outcome prediction for critically ill cirrhotic patients: A comparison of APACHE II and Child-

5 Amany Abdel-Maqsod, et al Pugh scoring systems. J. Intensive Care Med., 19: , PAN H.C., JENQ C.C., TSAI M.H., FAN P.C., CHANG C.H., CHANG M.Y., et al.: Scoring systems for 6-month mortality in critically ill cirrhotic patients: A prospective analysis of chronic liver failure-sequential organ failure assessment score (CLIF-SOFA). Aliment Pharmacol. Ther., 40 (9): , TIAN Y.C., LIU N.J., HO Y.P., YANG C., CHU Y.Y., CHEN P.C., et al.: Prospective cohort study comparing sequential organ failure assessment and acute physiology, age, chronic health evaluation III scoring systems for hospital mortality prediction in critically ill cirrhotic patients. Int. J. Clin. Pract., 60 (2): 160-6, RABE C., SCHMITZ V., PAASHAUS M., MUSCH A., ZICKERMANN H., DUMOULIN F.L., et al.: Does intubation really equal death in cirrhotic patients? Factors influencing outcome in patients with liver cirrhosis requiring mechanical ventilation. Intensive Care Med., 30: , LEVESQUE E., HOTI E., AZOULAY D., ICHAÏ P., HABOUCHI H., CASTAING D, et al.: Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit. J. Hepatol., 56: , KARVELLAS C.J., PINK F., MCPHAIL M., AUSTIN M., AUZINGER G., BERNAL W., et al.: Bacteremia, acute physiology and chronic health evaluation II and modified end stage liver disease are independent predictors of mortality in critically ill nontransplanted patients with acute on chronic liver failure. Crit Care Med., 38: 121-6, CHOLONGITAS E., PAPATHEODORIDIS G.V., VAN- GELI M., TERRENI N., PATCH D. and BURROUGHS A.K.: Systematic review: The model for end-stage liver disease-should it replace Child-Pugh's classification for assessing prognosis in cirrhosis? Aliment Pharmacol. Ther., 22: , OLMEZ S., GÜMÜRDÜLÜ Y., TAS A., KARAKOC E., KARA B. and KIDIK A.: Prognostic markers in cirrhotic patients requiring intensive care: A comparative prospective study. Ann. Hepatol., 11: 513-8, MARIK P.E. and VARON J.: Severity scoring and outcome assessment. Computerized predictive models and scoring systems. Crit Care Clin., 15: , LEE K.C. and CHIANG A.A.: The outcome of terminal liver cirrhosis patients requiring mechanical ventilation. Zhonghua Yi Xue Za Zhi (Taipei), 59: 88-94, LEE M., LEE J.H., OH S., JANG Y., LEE W., LEE H.J., et al.: CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: A retrospective analysis. Liver Int., 35: 46-57, KAVLI M., STROM T., CARLSSON M., DAHLER- ERIKSEN B. and TOFT P.: The outcome of critical illness in decompensated alcoholic liver cirrhosis. Acta. Anaesthesiol. Scand., 56: , 2012.