Predictors of 30-day mortality in medical patients with severe sepsis or septic shock

Objectives. To evaluate independent predictors of 30-day mortality in patients with severe sepsis or septic shock. Background. Severe sepsis and septic shock are associated with increased mortality. Admission APACHE II score is the gold standard for assessing prognosis in critically ill, but several other predictors of mortality have been evaluated. Methods. We retrospectively evaluated clinical and laboratory data in adult patients with severe sepsis or septic shock as predictors of 30-day mortality. Results. Thirty-day mortality was 62.7%. Nonsurvivors in comparison to survivors were significantly more likely to be treated with noradrenalin, renal replacement therapy, mechanically ventilated, to have suffered a fungal infection, had lower admission arterial pH, increased admission Acute Physiology, Age, Chronic Health Evaluation (APACHE) II score and a higher peak lactate level (5.6 ± 6.2 vs 3.1 ± 1.75, p=0.021). Binary logistic regression demonstrated that only peak inhospital serum lactate level was a significant independent predictor of 30-day mortality (OR 1.367, 95% CI 1.041 to 1.795, p=0.025). Conclusion. Only peak in-hospital lactate significantly and independently predicts 30-day mortality in severe sepsis or septic shock medical patients. ANDREJA SINKOVIC ( ) •


Introduction
The incidence of severe sepsis is increasing within the last decade, reaching 50-100 cases /100.000people in the general population and approximately 30% in intensive care units.(1,2) Mortality of patients with sepsis depends on the sepsis stage and co-morbidities.It ranges from 10-20% in patients with uncomplicated sepsis to 20-50% in severe sepsis and up to 80% in patients with septic shock.(1) Admission Acute Physiology, Age, Chronic Health Evaluation (APACHE) II score is a standard predictor of mortality in critically-ill patients, including septic patients.(3) It is applicable in the majority of critically-ill patients and extensively validated in several countries due to its simplicity as a predictor of mortality.(4,5) The score is obtained from the patient's age and the worst values of 12 physiological parameters within the first 24 hours such as body temperature, mean arterial blood pressure, pulse, arterial pO 2 , serum creatinine, potassium, sodium, hematocrit, white blood cell count, Glasgow coma scale, respiratory rate.The higher the APACHE II score, the higher the mortality rate.A variety of other predictors of mortality in patients with sepsis was evaluated in clinical studies, including inflammatory markers such as C-reactive protein (CRP), lactate clearance, cardiac biomarkers such as troponin and ejection fraction (EF), individual organ system failures, presence of multi-organ failure syndrome (MOFS), etc. (6) These stu-dies were performed in heterogeneous patient populations, ranging from lower risk patients with sepsis to high risk septic shock patients, included from wards to surgical or medical intensive care units (ICU).(4)(5)(6)(7)(8)(9) The primary objective of this study was to investigate which patient characteristics are related to outcome in medical patients with severe sepsis or septic shock.

Participants and methods
We performed a retrospective cohort analysis of all adult patients with severe sepsis or septic shock treated in a medical ICU in 2008, 2009 and 2010.The study was approved by the Ehical institutional review board (No. 156/13) and is in accordance with the declaration of Helsinki.In all, 102 patients (63 men, 39 women, mean age 65.1 ± 13.3 years) were included.The criteria for severe sepsis were fulfilled if in patients with sepsis there was at least one organ failure or a sign of tissue hypoperfusion.In septic shock patients there were signs of sepsis in addition to acute circulatory failure with decreased systolic blood pressure < 90 mm Hg or mean arterial blood pressure < 65 mm Hg without any other known causes in spite of adequate infusion of fluids.(10) Patient treatment followed guideline goals.(11)  We registered demographic, admission and in-hospital laboratory and clinical data, treatments and 30-day mortality.
Among laboratory data we registered admission and peak arterial pH, CRP, serum creatinine, lactate, troponin I and serum glucose as well as nadir serum glucose and albumin.Among clinical data on admission we registered prior chronic diseases such as chronic cardio-vascular, pulmonary, hepatic, hematological, renal chronic disea-se, admission mean arterial pressure, pulse, APACHE II score, ratio between arterial oxygen pressure and fraction of inspired oxygen (paO 2 /FiO 2 ) .Among organ failures we registered acute cardiovascular, respiratory, renal and hepatic failure.Acute respiratory failure was defined as arterial hypoxia with paO 2 /FiO 2 < 300, acute renal failure was defined as oliguria with increased serum creatinine, acute hepatic failure as an increase in serum bilirubin > 35 mmol/L and acute cardio-vascular failure as arterial hypotension (decrease of systolic arterial blood pressure < 90 mmHg or mean arterial blood pressure < 65 mmHg).(10) We also registered positivity of hemocultures, site of infection -pneumonia, urinary tract infection and infection of other sites -in particular of pancreas, gall bladder, meninges, skin or joints.We registered causative microorganisms of infection associated with sepsis as gram-negative and gram-positive bacteria, viruses or fungi, but we also registered microorganisms (gram-negative, gram-positive bacteria, viruses or fungal infection) identified in positive hemocultures.Among in-hospital data we registered echocardiographic parameters (ejection fraction and left ventricular end-diastolic diameter) and treatments such as the use of noradenaline, inotropic support by dobutamine, mechanical ventilation, iv.diuretics, insulin and renal replacement therapy by continuous veno-venous hemofiltration (CVVH).
Our aim was to evaluate the independent predictive role of demographic, clinical and laboratory data, treatments, individual organ failures and MOFS between survivors and nonsurvivors within 30 days in our patients with severe sepsis and septic shock.

Statistical analysis
Statistical analysis was performed using SPSS statistical package, version 19 (SPSS Inc., Chicago, IL, USA) for Windows.Data were expressed as means ± standard deviations or percentages.Differences between the groups were tested by the two-sided Student's t-test for means ± standard deviations and by the χ 2 -test for percentages.A p-value < 0.05 was considered statistically significant.The binary logistic regression model was used to predict relation to 30-day mortality.Goodness of fit of the model was assessed using the Hosmer-Lemeshow test.
In terms of association with outcome, binary logistic regression demonstrated that peak in-hospital lactate level was the most significant independent predictor of 30-day mortality (OR 1.367, 95% CI 1.041 to 1.795, p = 0.025) (table 3).

Discussion
We

Table 1 .
Admission clinical and laboratory data in all septic patients, survivors and nonsurvivors.
APACHE, acute physiology, age, chronic health evaluation; G -, gram-negative; G +, gram-positive; SD, standard deviation.p < 0.05 was statistically significant and was calculated by the two-sided Student's t-test for means ± standard deviations and by the χ 2 -test for percentages.

Table 2 .
In-hospital data of all septic patients, survivors and nonsurvivors.
CRP, C-reactive protein; ICU, intensive care unit; LVEDD, left ventricular end-diastolic diameter; SD, standard deviation.p < 0.05 was statistically significant and was calculated by the two-sided Student's t-test for means ± standard deviations and by the χ 2 -test for percentages come were retrieved from patient medical records.

Table 3 .
(11,24)logistic regression to estimate independent predictors of 30-day mortality in septic patients.Second, a number of pointof-care machines enable rapid, bedside determination of lactate levels.There seem to be no significant differences between point-of-care and laboratory lactate results.(24)Point-of-carelactatedeterminationmakessense,especially when goal-directed therapy principles are to be observed.(24,25)Third,apartfromrecognition of critically ill patients, lactate tracking can be used as a tool to evaluate the efficacy of treatment not only in sepsis, but in variety of settings.(11,24)Third,the information that elevated lactate levels provide, is easily integrated into treatment strategies, no additional conversions or calculations are needed.To conclude, the results of our study confirm the importance of measuring lactate levels on a regular basis in critically ill patients with severe sepsis and septic shock.Increased levels of lactate enable recognition of patients who are at highest risk of dying.The method is simple and can be performed at the bedside.The information that elevated lactate levels provide to the clinician is easily integrated into existing treatment strategies.No additional conversions or calculations are needed in order to appreciate the results.Peak in-hospital lactate level was the only significant independent predictor of 30-day mortality in our patients with severe sepsis and septic shock.