Continuous hemofiltration combined with norepinephrine in the treatment of septic shock

Jia-Feng Chen,Dong-Liang Hao,Rong-Chang Huo,Qiang Fu,Qing-Hai Zhang

1Intensive care unit,Changle People's hospital,Weifang 262400,Shandong,China.

2Intensive care unit,Weifang People's hospital,Weifang 261000,Shandong,China.

Abstract Objective:To observe the effect of continuous hemofiltration combined with norepinephrine in the treatment of septic shock,and to explore the value of blood purification in the treatment of septic shock.Methods:From November 2018 to December 2020,100 patients with septic shock in the Intensive care unit of our hospital were selected and randomly divided into observation group and control group,with 50 cases in each group.The control group was given conventional treatment,while the observation group was given continuous hemofiltration combined with norepinephrine intervention.The clinical efficacy,Scv02,MAP and oxygenation index (PO2/FiO2)of the two groups were compared.The levels of interleukin-6 (IL-6),procalcitonin (PCT) and the total number of leukocytes and other inflammatory factors were compared 72 hours after treatment,and the 28-day mortality of the two groups was counted.Results:The total effective rate of the observation group (92.00%) was significantly higher than that of the control group (86.00%),the difference was statistically significant (p<0.05);the 28-day mortality of the two groups was 8.00% in the observation group and 14.00% in the control group,the difference was statistically significant (χ2=4.629,p=0.038);Before treatment,the Scv02,MAP and PO2/FiO2levels of the two groups were significantly higher than those of post-therapy.There was no significant difference between the two groups (p>0.05);After 48 hours of treatment,the levels of Scv02,MAP and PO2/FiO2in the two groups were significantly increased,while the levels of scv02,map,PO2/FiO2in the observation group were more significantly increased than those in the control group (p<0.05);Before treatment,the levels of IL-6,PCT and total white blood cells in the two groups were significantly higher than those of post-therapy (p<0.05) After 72 hours of treatment,the levels of IL-6,PCT and the total number of white blood cells in the two groups decreased significantly,while the levels of IL-6,PCT and the total number of white blood cells in the observation group decreased more significantly than those in the control group (p<0.05).Conclusion:Continuous blood purification combined with norepinephrine can effectively reduce the level of serum inflammatory factors in patients with septic shock,improve hemodynamic indexes,improve survival rate,which is worthy of clinical application.

Key words:Sepsis,Shock,Continuous hemofiltration,Norepinephrine,Inflammation

Background

Sepsis refers to the dysfunction of organs that endanger life due to the imbalance of response to infection.When the infection of sepsis patients is aggravating,it will lead to circulatory failure and shock,which is called septic shock [1].Septic shock is a serious stage of further development of sepsis,which is caused by insufficient tissue perfusion.There are still hypotension and tissue hypoperfusion after full fluid resuscitation,which will seriously threaten the safety of patients' lives.Continuous blood purification(CBP) is a general term of all continuous and slow water and solute removal methods.It can effectively reduce the level of inflammatory media in the blood and improve the hemodynamic state of patients [2].Noradrenaline has a strong excitatory effect on adrenergic α receptor,which causes vasoconstriction and blood pressure rise;meanwhile,it also excites β receptor,but it has less effect on β1receptor in heart,which has little effect on β2receptor,so it is widely used in patients with severe hypotension and decreased resistance of peripheral blood pipe.This study aims to observe the synergistic effect of continuous hemofiltration and noradrenaline in sepsis shock patients,evaluate the value of blood purification in the treatment of sepsis shock,and provide more clinical basis for the treatment of septic shock.

Materials and methods

Data Sources

From November 2018 to December 2020,100 patients with septic shock were selected as the research objects.Diagnostic criteria [1]:(1) systemic reaction caused by infection;(2) SBP<90mmHg,MAP <70mmHg,organ dysfunction or tissue hypoperfusion;(3) coagulation dysfunction,international standardized ratio >1.5;(4)bilirubin ＞34.2 μmol/L,platelet count ＜ 100×109/L,urine volume <0.5ml/(kg·h),serum creatinine >177 μmol/L.Inclusive criteria:The patients were over 18 years old and received continuous blood purification for more than 72 hours.The family members knew the contents of the study and signed the informed consent.The patients with brain tumor,breast-feeding disease,severe cardiovascular disease and other diseases were excluded.The patients were randomly divided into observation group and control group with 50 cases in each group.There were 36 males and 14 females in the observation group,with an average age of (45.74 ±6.12) years old ranging from 37 to 62 years old,including 11 patients with postoperative abdominal infection,8 patients with severe pancreatitis,4 patients with acute cholecystitis,19 patients with severe pneumonia and 8 patients with large area burn.In the control group,there were 34 males and 16 females,with an average age of (46.39 ± 7.01) years old ranging from 36 to 61 years old,including 14 patients with postoperative abdominal infection,7 patients with severe pancreatitis,6 patients with acute cholecystitis,16 patients with severe pneumonia and 7 patients with large area burn.There was no significant difference in gender,age and other basic information between the two groups (p>0.05).This study was reviewed and approved by the ethics committee of our hospital.

Methods

After the diagnosis of septic shock,the patients in the control group began to receive basic treatment such as volume expansion and anti shock,standardized antibiotics,immune regulation and nutritional treatment,and dopamine was used as a pressor drug according to the clinical situation of the patients;the patients with surgical conditions timely asked the relevant surgical experts to actively deal with the surgical conditions;the patients in the observation group were treated on the basis of the control group,continuous blood purification combined with norepinephrine was given within 1 hour after diagnosis:Gambro prismaflex blood purification machine,prismaflex M100 set filter,and the filter membrane area was 1.0m2.After cardiopulmonary bypass was established through femoral vein catheterization,hemofiltration replacement fluid (Huaren Pharmaceutical Co.,Ltd.,H20083401) was used as replacement fluid,with the replacement speed of 2000ml/h and blood flow speed of 200 ml/min.At the arterial end of the hemofiltration line,citrate was used for anticoagulation;at the venous end of the hemofiltration line,10% calcium gluconate injection was pumped to maintain the ionic calcium level in vitro (hemofiltration line) at 0.2-0.4 mmol/L and in vivo at 1.0-1.2mmol/L.

Observation index

The clinical effects of the two groups were compared.Remarkable effect:the patient's state of consciousness returned to normal after treatment,and his condition was stable within 24 hours.After the patient was separated from vasoactive drugs,SBP>90mmHg,MAP>70mmHg,and urine volume>30ml/h;Effective:the patient's consciousness improved after treatment,and his condition was stable within 48 hours,and still needed vasoactive drugs to maintain SBP>90mmHg,and urine volume increased but did not reach 30ml/h;Ineffective:the SBP of the patient was less than 90mmHg,the state of consciousness and urine volume of the patient remained unchanged,and even deteriorated or died [3].Total effective rate=(Remarkable effect+effective)/ total cases×100%.At the same time,the mortality of the two groups (death cases/total cases×100%) was counted.

The changes of Scv02,MAP and oxygenation index(PO2/FiO2) were recorded before and 48 hours after treatment.

Before and 48 hours after treatment,10ml of fasting venous blood was collected and placed in a vacuum anticoagulant tube.After shaking evenly,the blood was centrifuged at 3000R/min.the plasma was separated and stored in a refrigerator at-20℃.The levels of IL-6,PCT and total number of leukocytes were detected by ELISA.The reagents were purchased from Shanghai biyuntian Biotechnology Co.,Ltd.

Statistical analysis

Allthe measurement datainthis studywereexpressed bythe expression (),and themeasurementdata of each group were repeated at least three times.The data were analyzed by Graphpad prism 6 software.T test of independent samples was used to compare the mean of the two groups;the count data was expressed as %,and the comparison was performed by chi square test,p<0.05,which was considered that the difference was statistically significant.

Results

The to tal e ffective r ate of th e o bservation g roup was higher t han that of t he c ontrol group.The effective rate of the observation group (92.00%) was significantly higher than that of the control group(86.00%),the difference was statistically significant(p<0.05).Compared with the 28-day mortality of the two groups,4 cases died in the observation group,the mortality was 8.00% (4/50);7 cases died in the control group,the mortality was 14.00% (7/50).The mortality of the observation group was lower than that of the control group (χ2=4.629,p=0.038) (Table 1).

The clinical in dexes were s ignificantly i mproved after 48 hours of treatment.The clinical indexes of the two groups before and after treatment were compared Before treatment,there was no significant difference in Scv02,MAP and oxygenation index(PO2/FiO2)between the two groups (p>0.05);After 48 hours of treatment,Scv02,MAP and oxygenation index(PO2/FiO2) of the two groups increased significantly,compared with the control group,the above clinical indexes of the observation group increased more significantly,and the difference was statistically significant (p<0.05).

After 4 8 h ours o f tr eatment,th e i nflammatory indexes d ecreased s ignificantly.There was no significant difference in the levels of IL-6,PCT and WBC between the two groups before treatment (p>0.05);After 48 hours of treatment,the levels of IL-6,PCT and WBC in the two groups were significantly decreased,compared with the control group,the levels of inflammatory factors in the observation group were significantly decreased,and the difference was statistically significant (p<0.05).See Table 3

Table 1 Comparison of clinical efficacy and mortality between the two groups［n(%)］

Table 2 Comparison of clinical indexes between the two groups before and after treatment

Table 3 Comparison of the levels of inflammatory factors between the two groups before and after treatment (n，)

Table 3 Comparison of the levels of inflammatory factors between the two groups before and after treatment (n，)

Discussion

Sepsis is a life-threatening organ dysfunction caused by the host's maladjustment of response to infection,which can cause shock,leading to tissue hypoxia,release a large number of free radicals and inflammatory factors at the same time,leading to tissue reperfusion injury and microcirculation disturbance,and seriously threaten the life and health of patients [4].The mean arterial pressure (MAP)≥65mmHg and serum lactate level>2mmol/L were required to be maintained by vasoconstrictors [1].Continuous hemofiltration therapy mainly through three ways:diffusion,convection and adsorption,can slowly and continuously remove the inflammatory mediators in patients' plasma,maintain the homeostasis of the internal environment,improve the metabolism of the body,and has little effect on patients' hemodynamics,which plays an important role in maintaining the balance of pro-inflammatory and anti-inflammatory factors;Another important role of continuous hemofiltration therapy is to effectively manage the volume level of patients,maintain the stability of internal environment,and ensure the normal metabolism of patients [5,6].The cascade "waterfall"release of inflammatory mediators is intertwined with the excessive release of pro-inflammatory and anti-inflammatory factors in the process of occurrence.Therefore,early treatment and timely control of inflammatory state is the key to the treatment of sepsis patients [7].

Noradrenaline is a classic catecholamine with positive muscle force and vasoconstriction.In recent years,noradrenaline has attracted more and more attention in the application of infectious diseases and perioperative hypotension [8].Noradrenaline can improve the resistance of the whole body,promote the contraction of the small artery,increase the diastolic pressure of the aorta,and expand the coronary artery.It can ensure the sufficient supply of blood and oxygen in the heart,reduce the hyperlactation caused by hypoxemia,maintain the balance of the patient's internal environment and accelerate the elimination of lactate [9,10].Therefore,in this study,the author has observed the continuous blood purification and noradrenaline treatment in the early stage of septic shock patients,which are more common in ICU,in order to provide more clinical basis for the diagnosis and treatment of septic shock patients.

The total effective rate of the observation group(92.00%) was significantly higher than that of the control group (86.00%),the difference was statistically significant (p<0.05);in this study,we randomly divided the patients with septic shock into the control group and the observation group,the control group was given conventional treatment,while the observation group was given conventional treatment,after entering the group,the patients were given continuous hemofiltration combined with noradrenaline.The results showed that after 48 hours of treatment,the total effective rate of the observation group (92.00%)was significantly higher than that of the control group(86.00%),the difference was statistically significant(p<0.05);the 28-day mortality rate of the two groups was 8.00% in the observation group and 14.00% in the control group,the difference was statistically significant (χ2=4.629,p=0.038),which suggested that continuous blood transfusion should be given in the early stage.Purification combined with norepinephrine treatment can improve the total effective rate of such patients,which is similar to the results reported by relevant scholars [5].In addition,we recorded the changes of Scv02,MAP and oxygenation index(PO2/FiO2) in two groups.The results showed that:before treatment,there was no significant difference in Scv02,MAP and PO2/FiO2between the two groups (p>0.05);after 48 hours of treatment,Scv02,MAP and PO2/FiO2of the two groups increased significantly,compared with the control group,the above clinical indicators of the observation group increased more significantly,the difference was statistically significant(p<0.05),which reflects the advantages of continuous hemofiltration therapy combined with norepinephrine in improving the clinical manifestations of patients.The levels of inflammatory factors in septic shock patients are closely related to the occurrence and progress of shock process.IL-6 is secreted by B cells,T cells and macrophages,which regulates the growth and differentiation of a variety of cells and plays an important role in immune response and acute phase response.PCT has a good correlation with infection and sepsis,and has been widely used in the diagnosis and treatment of sepsis Stratification,treatment monitoring and prognosis evaluation,dynamic monitoring of PCT level change trend can judge the progress of the disease and prognosis [11];Our research results show that,after 72 hours of treatment,the levels of IL-6,PCT and WBC in the two groups were significantly decreased,compared with the control group,the level of inflammatory factors in the observation group decreased more significantly,the difference was statistically significant (p<0.05),suggesting that for the treatment of early continuous hemofiltration combined with norepinephrine treatment can significantly reduce the level of inflammatory factors,block the cascade "waterfall"release of inflammatory mediators,and reduce the level of inflammation in patients with toxic shock.

In conclusion,the clinical effect of early continuous blood purification combined with norepinephrine in the treatment of septic shock patients is better than that of the conventional treatment group,which can more effectively block the cascade "waterfall" release of inflammatory mediators,reduce the body inflammation level of such patients,alleviate the disease of patients,and promote the rehabilitation of patients,which is worthy of clinical reference.