Predicting scores in septic shock Romanian Journal of Anaesthesia and Intensive Care 2014 Vol 21 No 2, 95-98

Predicting scores correlations in patients with septic shock – a cohort study Anca-Meda Georgescu1, Janos Szederjesi2, Sanda-Maria Copotoiu2, Leonard Azamfirei2

1 2

Infectious Diseases Clinic, University of Medicine and Pharmacy Tirgu Mures, Romania Anaesthesiology and Intensive Care Clinic, University of Medicine and Pharmacy Tirgu Mures, Romania

Abstract Background. ICU prognostic scores were developed to measure the severity of the disease and the patients’ prognosis. The objective of this study was to assess the validity of the Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score II (SAPS II) scores in patients with septic shock. Methods. The APACHE II, SOFA and SAPS II scores were determined prospectively, in the first 24 hours after admission, for all 56 patients with septic shock who were included in this study. Data were statistically evaluated; the discriminating power regarding survivors vs deceased patients was calculated based on the receiver operating characteristic curves (ROC). Results. The overall mortality of the 56 patients with septic shock was 60.71% (34 deaths). The average APACHE II score was 25.36 ± 7.477. The average SOFA score was 7.679 ± 3.197. The average SAPS II score was 44.45 ± 16.97. For the APACHE II and SOFA scores the differences when deceased and survivors were compared were not statistically significant (APACHE II: 26.76 ± 6.742 vs 23.18 ± 8.175 respectively for SOFA: 8.029 ± 3.099 vs 7.136 ± 3.342). For the SAPS II score the values are: 49.12 ± 16.61 in deceased vs 37.23 ± 15.20 in survivors, the difference being statistically significant (p = 0.0092). The areas under ROC for the three scores are 0.622 for APACHE II, 0.575 for SAPS II and 0.705 for SOFA. Conclusions. In our study the SAPS II score was superior to the other scores for predicting survival in patients with septic shock. Keywords: sepsis: APACHE II, SOFA, SAPS II, mortality Rom J Anaesth Int Care 2014; 21: 95-98

Introduction Sepsis continues to be a major medical problem in intensive care units, due to a high mortality rate as well as to the significant financial resources required for the treatment of these patients [1, 2]. Septic shock is defined as the persistent systolic blood pressure < 90 mmHg (or more than 40 mm Hg decrease compared to the initial blood pressure) and a Adress for correspondence:

Dr. Janos Szederjesi Disciplina ATI Spitalul Clinic de Urgenţă Str. Gh. Marinescu, nr. 50 540136 Tîrgu Mureş, România E-mail: [email protected]

mean arterial pressure (MAP) < 70 mmHg despite of appropriate volume replacement [3]. Prospective large studies have generated several prognostic scores, which were often regarded as inclusion criteria with greater specificity for the septic patient, especially for the evaluation of different therapies. These scores have proved to be efficient in predicting the appropriateness of hospitalization in the ICU and the expected rate of survival. The most widely used scores in the ICU are: Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score II (SAPS II) [4-6]. Each of these score uses clinical and biological parameters determined either at the time of admission or during hospitalization. Their value continues to be

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controversial because of sometimes discordant data validation [7, 8]. Calculation methods predict statistical values for mortality with little if any usefulness when evaluating the survival chance of an individual patient. The objective of this study was to assess the validity of these scores in terms of mortality in patients with septic shock admitted to the ICU.

Methods The study was approved by the Ethics Committee of the University of Medicine and Pharmacy, Tirgu Mures. The study performed from January to July 2014 prospectively evaluated a series of consecutive patients admitted to the ICU Clinic from the Emergency Clinical County Hospital of Tirgu Mures, diagnosed with septic shock according to international criteria: sepsis-induced persistent hypotension (systolic blood pressure < 90 mmHg or mean arterial pressure < 70 mmHg, or a decrease in systolic blood pressure > 40 mmHg) despite adequate fluid resuscitation [3]. The investigators collected the following information: demographical data, site of infection, clinical and lab data included in the APACHE II, SOFA and SAPS II scores determined for these patients within the first 24 hours of hospitalization. They gathered the following measurements for the APACHE II score: AaDO2 or a PaO2 (depending on FiO2), rectal temperature, mean arterial pressure, arterial blood pH, heart rate, respiratory rate, sodium, potassium, creatinine, hematocrit, white blood cells and Glasgow Coma Score [4]. For the SOFA score the following physiological parameters were measured: PaO2 /FiO 2 , Glasgow Coma Scale, mean arterial pressure or requirement of vasopressors, bilirubin, platelets and creatinine [5]. For evaluating the SAPS II score, the following parameters were collected: age, heart rate, systolic blood pressure, temperature, Glasgow Coma Scale, mechanical ventilation or CPAP, PaO2, FiO2, urine output, blood urea nitrogen, sodium, potassium, bicarbonate, bilirubin, white blood cells, chronic diseases and type of admission [6]. Recorded data were statistically analyzed using the 5.0A version of the PRISM 5 software created by GraphPad Software, Inc USA. The data are presented as mean ± standard deviation, median with interquartile range. The t test was used to compare the means of each two groups, assuming that the values follow a Gaussian distribution. p < 0.05 values were considered significant. The area under the receiver operating characteristic curve (ROC) helps us visualize the tradeoff between high sensitivity and high specificity for all scores. It was calculated to evaluate the capacity of the scores to discriminate mortality as an independent variable.

Results Fifty six patients were included in the study with an average age of 69 (range 32-88), 29 females (51.8%) and 27 males (48.2%). Fourteen were surgical patients (25%) and 42 were non-surgical patients (75%). The overall mortality of the patients with septic shock was 60.7% (34 deaths). The average APACHE II score was 25.36 ± 7.477. The average SOFA score was 7.679 ± 3.197. The average SAPS II score was 44.45 ± 16.97. The values of these scores reported to survivors and deceased are highlighted in Figures 1, 2, 3.

Fig. 1. Mean and standard deviations of the APACHE II score for survivors and the deceased

Fig. 2. Mean and standard deviations of the SOFA score for survivors and the deceased

Fig. 3. Mean and standard deviations of the SAPS II score for survivors and the deceased

Predicting scores in septic shock

For the APACHE II and SOFA scores, the differences between the deceased and survivors were not statistically significant (APACHE II: 26.76 ± 6.742 vs 23.18 ± 8.175 respectively for SOFA: 8.029 ± 3.099 vs 7.136 ± 3.342). For the SAPS II score the values are: 49.12 ± 16.61 in deceased vs 37.23 ± 15.20 in survivors (p = 0.0092). The values of the areas under ROC for the three scores are presented in Table 1 while the graphs of the three curves in Figure 4. Table 1. The areas under the curve values for APACHE II, SOFA and SAPS II scores Score

AUC

SE

95% CI

APACHE II

0,622

0,0787

0,483-0,748

SOFA

0,575

0,0791

0,436-0,706

SAPS II

0,705

0,0723

0,568-0,819

AUC: Area under curve; SE: Standard Error; CI: Confidence Interval

100 AP ACHE II-AUC=0 .6 22 SOFA-AUC =0 .57 5 SAPS II-AUC= 0.70 5

Sensitivity

80 60 40

APACH E II SOFA SAPS II

20 0 0

20

40 60 80 100-Specificity

100

Fig. 4. Receiver operating curves for the APACHE II, SOFA and SAPS II scores

Discussion Simplified Acute Physiology Score II (SAPS II) is a complex score calculated during the first 24 hours of hospitalization in the ICU. Rating values obtained from areas under the curve chart show SAPS II score to be superior in predicting patients’ survival as compared with the other two scores (APACHE II and SOFA). A ROC value above 0.7 qualifies a score in discriminating survivors vs deceased although strong discrimination occurs in a ROC over 0.8. ROC values obtained with SOFA and APACHE II were below 0.7. The results of our study differ from those of Kim [8] who identified the SOFA score as being the most predictive in patients poisoned with organophosphates. An explanation for the observed difference may stem

from the more complex nature of septic shock as compared with poisoning both in onset and evolution. Moreover, the simplicity of the SOFA score, in particular the absence of parameters related to associated diseases makes it more relevant to organ dysfunctions, unlike SAPS II and APACHE II that evaluate multiple organ dysfunction specific to the critically septic patient. While the APACHE II score is a predictor for morbidity, the SAPS score is a predictor of mortality. The use of these scores as predictors must take into account the heterogeneity of the population tested. There are, on one hand, significant geographical variables [9], the homogenization trend of confirmation by excluding certain population groups (for example, age, length of admission in ICU) [10] and on the other different statistical methods for assessing prediction [11]. The parameters taken into account may lead to evaluation errors. Tunnell demonstrated what are the most common bias causes when applying scores in the ICU: heart rate, arterial pressure, respiratory rate, oxygenation, pH value and blood glucose [12]. For these reasons and taking into account the above mentioned limitations, ICU scores can be taken into consideration only to evaluate ICU performance in order to improve the quality of medical care even if the existence of a single output – mortality may influence both the decision for ICU admission as well as the time of discharge. Obviously, this criterion can be influenced by the case-mix and the level of care in a specific ICU as well. A high case-mix, specific to highperforming ICU services is the consequence of complex pathologies, with unfavourable prognostic scores. The limitations of the study are the low number of studied cases that were concentrated within a single center. Moreover, the study does not take into account deaths that could have occurred immediately after discharge. These scores are complementary and have certain limitations. They do not provide individual prediction but may assist therapeutic and managerial decisions. For a complex pathology such as sepsis, a more complex score could be more informative. In conclusion, the SAPS II score was superior to the APACHE II and SOFA scores for predicting survival in patients with septic shock but a combination of factors must be taken in consideration to estimate the prognosis in the ICU. Acknowledgements The research has been carried out within the project “The evaluation of the soluble receptor for urokinase-type plasminogen activator receptor (suPAR) as a biomarker in sepsis”, no. 23/2013, funded through internal research grants by the Tirgu Mures University of Medicine and Pharmacy, Romania. Conflict of interest Nothing to declare

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References 1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 29: 530-538 2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29: 1303-1310 3. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41: 580-637 4. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13: 818-829 5. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22: 707-710 6. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993; 270: 2957-2963 7. Hargrove J, Nguyen HB. Bench-to-bedside review: outcome predictions for critically ill patients in the emergency department. Crit Care 2005; 9: 376-383 8. Kim YH, Yeo JH, Kang MJ, Lee JH, Cho KW, Hwang S, et al. Performance assessment of the SOFA, APACHE II scoring system, and SAPS II in intensive care unit organophosphate poisoned patients. J Korean Med Sci 2013; 28: 1822-1826 9. Moreno RP, Metnitz PG, Almeida E, Jordan B, Bauer P, Campos RA, et al. SAPS 3 – From evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med 2005; 31: 1345-1355 10. Vincent JL, Moreno R. Clinical review: scoring systems in the critically ill. Crit Care 2010; 14: 207 11. Kramer AA, Zimmerman JE. Assessing the calibration of mortality benchmarks in critical care: The Hosmer-Lemeshow test revisited. Crit Care Med 2007; 35: 2052-2056 12. Tunnell RD, Millar BW, Smith GB. The effect of lead time bias on severity of illness scoring, mortality prediction and standardised mortality ratio in intensive care – a pilot study. Anaesthesia 1998; 53: 1045-1053

Corelaţii între scorurile de prognostic la pacienţii cu şoc septic – un studiu de cohortă Rezumat Premize. Scorurile de prognostic utilizate în Terapie Intensivă au fost dezvoltate cu scopul de a cuantifica severitatea boli şi prognosticul pacientului. Obiectivul acestui studiu a fost de a aprecia validitatea scorurile utilizate în prezent (APACHE II, SOFA şi SAPS II) în cazul pacienţilor cu şoc septic. Metodă. Au fost calculate în primele 24 de ore de la internare, scorurile APACHE II, SOFA şi SAPS II pentru toţi cei 56 de pacienţi, cu şoc septic, care au fost înrolaţi prospectiv în studiu. Datele obţinute au fost evaluate statistic iar puterea de diferenţiere dintre supravieţuitori vs decedaţi a fost calculată conform curbelor ROC (receiver operating characteristic). Rezultate. Mortalitatea generală a celor 56 de pacienţi cu şoc septic a fost de 60,71% (34 decese). Scorul mediu APACHE II a fost de 25,36 ± 7,477, scorul mediu SOFA a fost de 7,679 ± 3,197 iar scorul mediu SAPS II de 44,45 ± 16,97. Pentru scorurile APACHE II şi SOFA diferenţele dintre supravieţuitori şi decedaţi nu au fost semnificative statistic (APACHE II: 26,76 ± 6,742 vs 23,18 ± 8,175 respectiv pentru SOFA: 8,029 ± 3,099 vs 7,136 ± 3,342). Scorurile SAPS II medii au fost în cazul decedaţilor de 49,12 ± 16,61 vs 37, 23 ± 15,20 în cazul supravieţuitorilor, cu o diferenţă semnificativă statistic între grupuri (p = 0,0092). Ariile de sub curbele ROC pentru cele trei scoruri au fost 0,622 pentru APACHE II, 0,575 pentru SAPS II şi 0,705 pentru SOFA. Concluzii. În studiul nostru scorul SAPS II a fost superior celorlalte scoruri în ce priveşte capacitatea de predicţie a supravieţuirii la pacientul cu şoc septic. Cuvinte cheie: sepsis, APACHE II, SOFA, SAPS II, mortalitate