12 декабря 2018г.
In the early phase of severe acute pancreatitis (AP), limited to the first 72 hours from the onset of the medical condition, a key role is played by a complex of therapeutic measures conducted in the intensive care unit (ICU). At the same time extremely important is, an objective prognostic evaluation of the course morbidity of the disease and the effectiveness of the complex intensive treatment conducted under ICU conditions. In this connection an important factor in assessing the severity of the condition in patients with AP deserves attention, as an indicator of intra-abdominal pressure (IAP), since intra-abdominal hypertension (IAH) and abdominal hypoperfusion are closely related to the development and progression of early multi-organ failure (MOF).
Acute severe pancreatitis (AP) is commonly referred to as a mixed (resuscitative-surgical) profile. Recently, however, more and more arguments have been put forward in favor of treating AP as an immunological process, as a result of which it becomes possible to solve serious clinical problems.
The characteristics of ADP, allow considering it from the immunology standpoint, include:
· pathological process bimodality (at first aseptic and then infectious) with high clinical significance of infectious complications, which are the main mortality cause;
· the regular development of pancreatic necrosis, which is the central pathological process in AP, determines the pathological immune response and has a vivid clinical expression;
· diagnostic significance of various immunological and biochemical "markers" (cytokines, receptors, immune competent cells and products of their vital activity), which allow to make both an objective assessment of the severity of AP and the prognosis of its course, answering the most important clinical questions (expected mortality, sepsis development probability, need for intensive care, surgical treatment, etc.);
· Sensitivity of patients with AP to immuno-oriented therapy (IT), the effectiveness of different methods is not the same at different periods of the medical condition. In this case, IT is able to solve both as independent tasks (for example, to prevent purulent complications and infections in general), and to serve as a complex treatment component, improving the tolerability of surgical interventions, the destructive focus sanitation effectiveness, eradication of pathogens and so on.
The severity of the course and the prognosis of AP is primarily determined by the prevalence of the inflammatory process in the pancreas and peripancreatic mass, the onset of the Systemic Inflammation Response Syndrome (SIRS) and multiple organ failure (MOF), necrotic tissue infection, secondary immune deficiency (using SAPS scales, APACHE II -III, MODS, SOFA, Ranson, Marshall, etc.). Sensitivity of patients with AP to immuno-oriented therapy (IT), the effectiveness of various methods of intensive care and extracorporeal therapy (ET) is not the same in different periods of the disease. Immunotherapy with this pathology is able to solve both as independent tasks
prevention of purulent complications and generalization of infection) and to serve as a component of the therapeutic complex, improving the tolerability of surgical interventions, the destructive focus sanitation effectiveness, eradication of pathogens, and also to be used to suppress secretory activity of the pancreatic glands with immunosuppressants (delagil, 5-fluorouracil).
Research objective: to determine the clinical significance of the index of IAP in predicting the course of the medical condition and evaluating the effectiveness of intensive therapy in patients with severe AP. To assess the changes in the immune status in patients with AP characterized by different phenotypes of immune deficiency depending on the severity of IAP and the effectiveness of immunotherapy after performing the surgical intervention.
Material and methods. Conducted was a treatment analysis with the results of 76 patients with severe AP who have been hospitalized in the clinic within the first 4 days of the onset of the medical condition. From 76 patients, 61 (80.3%) patients underwent rehabilitation laparoscopy and 4 (5.3%) had laparotomy, sanitation and drainage of the abdominal cavity. The prevalence of retroperitoneal tissue damage (RTD) was assessed by ultrasound, computer tomography with by the use of bolus contrast, and also information obtained during the surgical intervention.
Depending on the severity of the course of AP, all patients were divided into 4 groups: in 26 (34.2%) patients, signs of organ dysfunction were not expressed and were transient in nature (group 1), in 18 (23.7%) - functional insufficiency of one organ (group 2), 15 (19.7%) - two organs (group 3) and 17 (22.4%) - three or more organs. The evaluation of organ dysfunction was performed according to the criteria of A.Baue et al. (2000). All patients received complex treatment in conditions of ICU, the main components of which included: adequate analgesia (including epidural analgesia) and oxygenation, massive infusion therapy, nasogastric and / or naso-intestinal intubation, incipient enteroalimentation, antibacterial and antisecretory therapy. Plasma exchange was performed in 16 (21.0%) patients, and hemophilia in 7 (9.2%).
In patients with admission, as well as within 1-7 days after admission to the dynamics of treatment IAP has been measured according to the method by I. L. Kron et al. (1984). The degree of IHA was determined in accordance with the gradation of M.L. Malbrain et al. (2005). The value of abdominal perfusion pressure (APP) was calculated as the difference between mean arterial pressure (MAP) and IAP, as well as the level of the filtration gradient (FG), which was determined by the difference between SBP and doubled IAP. The severity of the patients' condition was assessed according to the APACHE II scale. The indicators of IHA were compared among patients of different groups and compared with the scores of the APACHE II scale. Also in a comparative aspect, the level of mortality in each of the groups of patients was assessed. All AP patients underwent evaluation of the immune status, which included a standard definition of the total number of leukocytes, lymphocytes, CD3+ lymphocytes, CD3+ CD4+ lymphocytes, CD3+ CD8+ lymphocytes, with definition of the immunoregulatory index, CD 19+ lymphocytes, CD3- CD16+ Lymphocytes by cytofluorimetry flow, immunoglobulin G, A, M serum in g/l by nephelometry, the functional activity of neutrophils in the NBT test, the CIC.
Results and consideration. It was found that in patients of groups 1-3 in the first day, the indices of IAP did not differ significantly between each other and did not exceed 15 mm Hg. (1st level of IAH). In patients of the 4th group, the level of IAP in these term was significantly higher and reached 18.7 ± 1.2 mm Hg. (2nd degree of VPG). In patients of the 1 st group, the tendency to decrease of IAP was observed already from 2-3 days. In patients of the 2nd group, the level of IAP increased slightly by the 3 rd day, and then gradually decreased and by the 7th day did not exceed 10.3 ± 0.9 mm Hg. In patients of the 3rd group by the 5th day, the level of IAP increased to 17.6 ± 1.5 mm Hg. (2nd degree of IAP) and did not have a significant tendency to decrease by the 7th day (16.3 ± 1.3 mm Hg). In patients of the 4th group, during the 2nd-4th day, the second degree of IAP remained (17.9 ± 1.5 - 19.6 ± 1.4 mm Hg), but by the 7th day the level of IAP elevated to 23.8 ± 1.9 mm Hg. (3rd degree of IAP.
On the base of treatment in patients with 1-2 groups, ranging from 2-3 days, it a clear regression of indicators was observed on the APACHE II scale. At the same time in patients of 3rd and 4th group, despite intensive therapy, there was an increase in values of the APACHE II scale, which on 5-7 days increased from 17,4±1,2 to 20.7±1,7 - 25,3±1,2 points respectively from 21.8±1.6 to 23,5±1,4 - 27,2±1,3 points. This marked a direct correlation between the level of IAP and the indicators of the APACHE II scale. It was also established by a significant decrease of NPD values (66,3±1.7 mm Hg.St.) FG (44,2±1,6 mm Hg.) patients of the 4th group, which was accompanied by the development of renal-hepatic failure. In addition, it was found that at high values of IAP, as a rule, in patients with severe AP occurred common forms of lesions RTD , whereas at low IAP values were observed restricted to (local) forms of retroperitoneoscopy.
Of the 76 patients with severe AP with lethal outcome occurred in 17 (22.4 per cent). In the 1st group there were no lethal outcomes. In the 2nd group of 18 patients, 2 died (11,1%), in the 3rd group of 15 patients, died 5 (33,3%). The highest mortality level (58,8%) was noted in 4-th group of patients (10 out of 17 patients have died). Thus in the 3-4th groups of patients with early mortality (up to 14 days of onset) 28.1% (9 out of 32 patients died).
Thus, the results obtained by us showed that the group of patients with severe AP is not homogeneous. In 57.9% of patients with severe AP, organ dysfunction regresses and/or has a transitory character and on base of a complex treatment to the 3rd-4th day from the onset of the medical condition, the condition of patients gradually stabilizes, and the mortality rate does not exceed 4.5% (1st -2nd group of patients). In the event that during the specified periods the MOF persists or progresses, the lethality reaches 46.9% (3rd – 4th group of patients).
In immunological monitoring of patients with the third and fourth clinical groups with the most pronounced intraperitoneal hypertension in the subpopulation composition of lymphocytes, a definite regularity was revealed: up to 28 ± 3% CD3+ CD4+ lymphocytes decreased, and CD3+ CD16+ lymphocytes on contrast increased by 17 ± 2% . At reference values of CD3+ CD4+ lymphocytes in these patients, a significant decrease in the number of CD3- CD16+ lymphocytes to a level of 2 ± 0.5% was observed. All patients in the third and fourth clinical groups showed absolute lymphopenia on the base of leukocytosis to 28.0 ± 2.5 * 109/l and a high CIC content of 260 ± 32 c.u. While in the first and second clinical groups, changes in immune status were not so pronounced.
Conclusions: the evaluation of the dynamics of IAP along with the scores of the APACHE II scale objectively reflects the severity of AP, which allows predicting the course and outcome of the medical condition. At the same time, the degree of correlation between these parameters is greatest in patients with severe AP with a 3-4 degree of IHA and a common lesion of the RTD . It is also of fundamental importance that the monitoring of IAP allows for the timely stratification of the most severe category of patients with AP with the IHA and the early progression of organ dysfunctions. This category of patients primarily needs to perform emergency sanitary video laparoscopy and early decompression interventions on the RTD , as well as the entire complex of intensive care (including extracorporeal methods) aimed at correcting the resulting disorders and preventing fatal complications.
However, in AP patients with persistent IHA and early progression of organ dysfunction, it is important to provide control over the inflammatory reaction characterizing the current ADP. Study of the immune status in patients with ADP confirms the presence of severe secondary immune deficiency and the need to appoint pathogenetic immunotherapy depending on the term of development and severity of ADP with a high risk of severe septic complications. Still relevant is the search of new therapeutic options taking into account characteristics of innate and adaptive immune response during different phases of severe acute pancreatitis and searching for complex subcellular approaches to its treatment.
