Early Diagnosis and Prognosis of Surgical Sepsis with Simple Laboratory Criteria in the Elderly Patients: Clinical and Laboratory Substantiation

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Introduction
Until 2016, sepsis was characterized as a systemic inflammatory response to infection [1, 2]. Despite the worldwide popularization of the ACCP/SCCM consensus (Sepsis II), some authors still question the perfection and practical significance of the initial criteria for systemic inflammatory response syndrome (SIRS) [1, 2, 4] due to the fact that such criteria do not reflect the full spectrum of the systemic response of the macroorganism, do not indicate its nature and the life-threatening situation [3, 5].In addition, there are no indicators of CARS (compensatory anti-inflammatory syndrome)manifestations in the diagnostic criteria of the "Sepsis II" consensus, which significantly determines the tactics of medical care and the outcome of the disease [1, 2].
In 2016, the scientific community was presented with the recommendations of the working group "The Third International Consensus on the definition of sepsis and septic shock" (Sepsis III), in which sepsis was defined as a systemic reaction to infection only with the mandatory formation of any organ dysfunction [6]. The Consensus Working Group also clarified that there is no gold standard for validating sepsis according to the old and new criteria, and clinical and laboratory information should identify all elements of sepsis and at the same time be quite simple and accessible for practice both at the outpatient stage and during the stay of patients in the hospital [5, 6].
The leukocyte (or hematological) indices used earlier to determine the degree of intoxication did not take into account all the features of the modern definition of sepsis, while modern information tests for assessing toxemia in practical healthcare are not systematically prescribed [3, 4]*.
* Order of the Ministry of Health of the Russian Federation of 10.05.2017 N 203n – "On approval of criteria for assessing the quality of medical care" The
use of tests such as the determination of procalcitonin, presepsis and blood lactate levels allows you to verify the presence of bacterial infection, sepsis and multiple organ dysfunction.
However, it can be assumed with a high degree of probability that the determination of the level, in particular, of lactate in the blood in the daily regime in Russia is available only in a limited number of medical institutions, which causes not always reliable indicators of the incidence of surgical sepsis in the population [1, 5].
The purpose of our work was to form a laboratory indicator reflecting the presence and severity of sepsis in different periods of its course on the basis of a simple laboratory study (a general detailed blood test), taking into account the degree of pro - inflammatory response to infection (SIRS), an anti-inflammatory component (CARS), the presence of a particular sign of multiple organ failure (one of the criteria of SOFA-Sepsis-related Organ Failure Assessment).
Materials and methods
A statistical study of 3,500 people, patients who underwent inpatient treatment in the department of surgical infection of the GBUZ "Hospital for War Veterans" in the period from 2016 to 2019 was conducted. Patients with the presence of malignant neoplasms were excluded from the study group. The study group consisted of 152 patients. The average age of the patients ranged from 71 to 87 years (the average number of years was 75.09 ±2.25). All patients, except for general and biochemical blood tests, were performed a procalcitonin test (PCT), the level of blood lactate was determined. The first group included 96 patients with surgical infection and clinical and laboratory manifestations of SIRS (up to 2 points). Taking into account the results of the PCT, the diagnosis of sepsis was excluded (group 1 "SIRS").The second group consisted of patients (39 clinical observations), in whom the diagnosis of secondary sepsis in the long term was verified by autopsy and verified by the presence of septicopyemic foci, the results of crops and the results of laboratory tests (lactate level of more than 2.5 mg/l) (group 2 - the prevalence of "CARS / SIRS").The third group of observations consisted of patients with severe sepsis (17 clinical observations), in whom the diagnosis of sepsis and the presence of multiple organ failure was verified upon admission to the hospital and confirmed by the results of laboratory tests (lactate level more than 2.5 ng/ml, PCT – more than 2 ng/ml) (group 3 - the prevalence of "SIRS /CARS").The general parameters of the study groups are shown in table 1.
Table 1-General information about patients with surgical infection included in the study group
Table 1-General information about patients with surgical infection included in the study group

Basic parameters /
Main parameters Number of patients, ( % ) /
Number of patients, ( % )
Gender (male /female) /
Gender (male /female) 64/ 88
Average age /
Average age 75,09 ±2,25
Main clinical diagnosis: /
Main clinical diagnosis
Obliterating atherosclerosis of the vessels of the lower extremities, chronic arterial insufficiency stage 4b / Obliterating
atherosclerosis of the vessels of the lower extremities, chronic arterial insufficiency stage 4b 73
Abscesses, phlegmons, destructive forms of erysipelas /
Abscesses, phlegmons, erysipelas 30
Cerebrovascular pain, bedsores of 3-4 degrees /
Cerebrovascular disease, bedsores of 3-4 degrees 24
Chronic osteomyelitis /
Chronic osteomyelitis 9
Acute severe pancreatitis, infected parapancreatitis /
Acuteseverepancreatitis, inflatedparapancreatitis 16
Average number of bed days /
Average number of bed days 18.84 ±1.57
Lethality /
Mortality rate 90 (59,2)
Total /
Total 152
Total number of patients with surgical infection /
Total number of patients with surgical infection 3 500

The work assumed the statement about the stages (including parallel) course of the septic process in the presence of multiple organ failure (prevalence of SIRS /CARS) and the development of immune insufficiency with the formation of septicopyemic foci and secondary multiple organ failure (prevalence of CARS / SIRS).The general group of indicators initially included: blood procalcitonin (as a marker of the presence of surgical infection); blood lactate (as a marker of the presence of severe sepsis); the level of creatinine, blood bilirubin, the absolute number of platelets (as a marker of SOFA); the absolute number of leukocytes, neutrophils, the number of rod-nuclear shift of neutrophils (as signs of SIRS); the absolute number of lymphocytes, monocytes (as signs of CARS); the level of potassium in the blood, hematocrit. It should be noted that when evaluating the indicators, it was the absolute values of blood parameters that were taken into account (in contrast to the classical hematological indices) (except for the shift of the leukocyte formula to the left).
The main objective of the study was to find a complex hematological indicator correlated with the level of procalcitonin in the blood (PCT), lactate and mortality (target parameters).
Methods of statistical research: one-factor analysis of variance, correlation analysis.
The work was carried out in several stages:
1. Formation of the main group of indicators of general and biochemical (hematological) blood tests to assess the degree of their influence on the level of PCT and lactate, death (method - single-factor analysis of variance-DOA).
2. Determination of variants of the score assessment of sepsis based on verified reliably significant criteria.
3. Determination of the correlation of the selected blood parameters, ball parameters depending on the level of PCT, blood lactate, as well as the forecast (method - correlation analysis).
4. Determination of the sensitivity and specificity of the score indicators for the assumption of the presence of sepsis and the prognosis of the disease.
5. Formation of conclusions and results.
Statistical processing of the results of the study was carried out using the programs "Microsoft Excel", "Statistica 6.0". The required sample size was calculated using the Lopez-Jimenez F formula. Statistical characteristics of the studied parameters and a test for the normality of the distribution (Kolmogorov-Smirnov criteria, Shapiro-Wilk W-test) are determined. The differences between the groups were also determined using nonparametric methods (the Mann-Whitney test).
The correlation analysis was performed using the coefficients Gamma (Gamma, G) and Spearman (R). The following classification of the correlation strength was used depending on the value of the correlation coefficient G (R): G(R)≤0.25-weak correlation, 0.25<G (R)<0.75 – moderate (average) correlation, G≥0.75 (R) - strong correlation. The critical level of significance of statistical hypotheses in this study was assumed to be 0.05, since the probability of a difference is more than 95%.
At the first stage, during the DOA, only those indicators were determined that had a significantly significant effect on the target parameters (PCT, lactate level, mortality) - the absolute number of lymphocytes, the absolute number of monocytes, the level of blood potassium. During the DOA, there was a less significant effect on the PCT of the absolute number of platelets, the number of leukocytes and the n/a shift. However, taking into account the fact that these parameters are taken into account when evaluating SIRS and SOFA, they were also taken into account for further work.
Taking into account the fact that the potassium level is only a biochemical indicator, its number was estimated only in terms of correlation with sepsis markers without taking it into account in the score assessment.
During the DOA, the indicators of the degree of influence on the PCT and the mortality of the absolute number of leukocytes and neutrophils were identical. Taking into account the fact that the number of white blood cells is an indicator that includes the number of both granulocytes (neutrophils) and agranulocytes (monocytes)), a more specific indicator was specified in the work - the absolute number of neutrophils.

About the authors

Taras Vasilyevich Ykovenko

North-Western State Medical University named after I. I. Mechnikov

Email: Taras.Yakovenko@szgmu.ru

h.D., Associate Professor of the Department of Hospital Surgery

Russian Federation, St. Petersburg, Russian Federation

Konstantin Nikolaevich Movchan

North-Western State Medical University named after I. I. Mechnikov

Email: MovchanK@spbmiac.ru

M.D., Professor of the Department of Surgery named after N. D. Monastyrsky

Russian Federation, St. Petersburg, Russian Federation

Alexandr Nikolaevich Tkachenko

North-Western State Medical University named after I. I. Mechnikov

Email: altkachenko@mail.ru

M.D., Professor of the Department of Traumatology and Orthopedics

Russian Federation, St. Petersburg, Russian Federation

Olga Igorevna Yakovenko

North-Western State Medical University named after I. I. Mechnikov

Author for correspondence.
Email: Olga.Yakovenko@szgmu.ru

Ph.D., assistant of the Department of Surgery named after N. D. Monastyrsky

Russian Federation, St. Petersburg, Russian Federation

References

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