Invest Clin 64(1): 41 - 52, 2023 https://doi.org/10.54817/IC.v64n1a04

Corresponding author: Junxing Huang. Department of Gastroenterology, Taizhou People’s Hospital, Taizhou

225300, Jiangsu Province, P. R. China. Email: rxmvndfubck@163.com

Effects of somatostatin in combination

with early hemoperfusion on inflammatory,

hemorheological and oxidative parameters

during the treatment of acute pancreatitis.

Hengyong Zhai, Bin Yang, Yiwei Fu, Dongli Zhang, Yujiang Li and Junxing Huang

Department of Gastroenterology, Taizhou People’s Hospital, China.

Keywords: somatostatin; hemoperfusion; acute pancreatitis; inflammatory response;

stress response.

Abstract. We aimed to evaluate the effects of somatostatin combined with

early hemoperfusion on inflammatory and stress responses during acute pan-

creatitis (AP) treatment. A total of 159 AP patients treated from September

2016 to January 2020 were randomly divided into three groups A-C (n=53). In

addition to routine treatment, groups A-C were additionally given somatostatin,

early hemoperfusion, and somatostatin combined with early hemoperfusion, re-

spectively. Their inflammatory factors, stress response, intestinal mucosal bar-

rier, hemorheological indices, recovery time, length of stay, clinical efficacy,

and adverse reactions were compared. The levels of serum interleukin-10 (IL-

10), catalase and glutathione peroxidase rose in the three groups after ten days

of treatment, compared with values before treatment, being the highest rise in

group C. The levels of IL-18, tumor necrosis factor-α, soluble intercellular adhe-

sion molecule-1, procalcitonin, high mobility group protein B1, lipid hydrogen

peroxide, advanced oxidation protein products, epinephrine, cortisol, D-lactic

acid, diamine oxidase, and endotoxin decreased after ten days of treatment

compared with those before treatment, which were lowest in group C (P<0.05).

After ten days of treatment, the levels of hemorheological indices were signifi-

cantly lower than those before treatment (P<0.05). Compared with groups A

and B, group C had a shorter recovery time of urine amylase, bowel sound and

passing gas, remission time of abdominal pain, length of stay, and a higher to-

tal response rate (P<0.05). During AP treatment, somatostatin combined with

early hemoperfusion effectively relieved inflammatory and stress responses,

protected the intestinal mucosal barrier function and improved the hemorheol-

ogy, thereby promoting the recovery and benefiting the prognosis of patients.

42 Zhai et al.

Investigación Clínica 64(1): 2023

Efectos de la somatostatina en combinación con hemoperfusión

precoz sobre parámetros inflamatorios, hemorreológicos y

oxidativos durante el tratamiento de la pancreatitis aguda.

Invest Clin 2023; 64 (1): 41 – 52

Palabras clave: somatostatina; hemoperfusión; pancreatitis aguda; respuesta

inflamatoria; respuesta al estrés.

Resumen. Nuestro objetivo fue evaluar los efectos de la somatostatina

combinada con hemoperfusión temprana sobre las respuestas inflamatorias y

de estrés durante el tratamiento de la pancreatitis aguda (PA). Un total de 159

pacientes con PA tratados entre septiembre de 2016 y enero de 2020 se divi-

dieron aleatoriamente en tres grupos A-C (n=53). Con base en el tratamien-

to de rutina, los grupos A-C recibieron además somatostatina, hemoperfusión

temprana y somatostatina combinada con hemoperfusión temprana, respecti-

vamente. Se compararon sus factores inflamatorios, respuesta al estrés, barre-

ra de la mucosa intestinal, índices hemorreológicos, tiempo de recuperación,

tiempo de estancia, eficacia clínica y reacciones adversas. Los niveles séricos

de interleucina-10 (IL-10), catalasa y glutatión peroxidasa aumentaron en los

tres grupos después de 10 días de tratamiento, comparados con los valores

antes del tratamiento, siendo más elevados en el grupo C. Los niveles de IL-

18, factor de necrosis tumoral α, molécula de adhesión intercelular 1 soluble,

procalcitonina, proteína B1 del grupo de alta movilidad, peróxido de hidrógeno

lipídico, los productos proteicos de oxidación avanzada, epinefrina, cortisol,

ácido D-láctico, diaminooxidasa y endotoxina disminuyeron después de 10 días

de tratamiento en comparación con los previos al tratamiento, que fueron más

bajos en el grupo C (P<0,05). Después de 10 días de tratamiento, los índices

hemorreológicos fueron significativamente menores que los previos al trata-

miento (P<0,05). En comparación con los grupos A y B, el grupo C tuvo un

tiempo de recuperación más corto de amilasa en orina, sonido y escape in-

testinal, tiempo de remisión del dolor abdominal y tiempo de estancia, y una

tasa de respuesta total más alta (P<0,05). Durante el tratamiento de la AP, la

somatostatina combinada con hemoperfusión precoz alivia eficazmente las res-

puestas inflamatorias y de estrés, protege la función de la barrera de la mucosa

intestinal y mejora la hemorología, favoreciendo la recuperación y beneficiando

el pronóstico de los pacientes.

Received: 27-06-2022 Accepted: 30-09-2022

INTRODUCTION

Acute pancreatitis (AP) is a common

acute abdominal disease typified by the

acute episode of severe persistent upper ab-

dominal pain. Due to multiple etiological

factors, pancreatic enzymes in the pancreas

are activated, causing local inflammatory

responses in pancreatic tissues, such as au-

todigestion, edema, bleeding, and necrosis.

With the progression of AP, systemic inflam-

matory response syndrome occurs in severe

cases, accompanied by organ dysfunction

and even death 1. Recently, the imbalance

Treatment of acute pancreatitis by somatostatin plus early hemoperfusion 43

Vol. 64(1): 41 - 52, 2023

between inflammatory and oxidative stress

responses is considered a crucial cause for

the onset and exacerbation of AP. There-

fore, balancing the inflammatory response

and eliminating oxygen-free radicals are the

key to AP treatment 2. Somatostatin can

inhibit the secretion and biological activ-

ity of pancreatic enzymes and exert thera-

peutic effects by suppressing autodigestion.

Blood purification treatment can protect

organ function by restoring the blood’s in-

ternal environment to normal 3. Currently,

somatostatin is often combined with early

hemoperfusion in the clinical treatment of

AP patients. However, the effects on inflam-

matory and stress responses remain largely

unknown. In this study, the clinical efficacy

of somatostatin combined with early hemo-

perfusion on AP patients was assessed, and

the changes in their inflammatory and stress

responses were analyzed, aiming to investi-

gate the possible mechanism of action and

to provide a scientific basis for clinical treat-

ment.

MATERIALS AND METHODS

Baseline clinical data

This study has been approved by the

ethics committee of our hospital and a writ-

ten informed consent has been obtained

from all patients. A total of 159 AP patients

treated in our hospital from September

2016 to January 2020 were selected and di-

vided into groups A, B, and C (n=53) using

a random number table. In group A, the pa-

tients were 34-76 years old, with an average

of 51.26 ± 8.93 years. There were 32 males

and 21 females. The body mass index (BMI)

was 22.15 ± 1.48 kg/m2 on average, and the

duration from onset to admission was 3-71

h, averaging 24.62 ± 5.39 h. Regarding the

severity of the disease, there were 28 mild,

21 moderate-severe, and four severe cases.

As to the pathogenesis, there were 15 cases

of biliary pancreatitis, 22 cases of alcoholic

pancreatitis, and 16 cases of overeating-

induced pancreatitis. About complications,

hyperlipidemia occurred in 11 cases, diabe-

tes mellitus in 14 cases, and hypertension

in 28 cases. In group B, the patients were

33-74 years old, with an average of 50.94 ±

8.87 years. There were 29 males and 24 fe-

males. BMI was 21.89 ± 1.45 kg/m2 on aver-

age, and the duration from onset to admis-

sion was 2-72 h, averaging 24.73 ± 5.41 h.

In terms of the severity of the disease, there

were 29 mild, 19 moderate-severe, and five

severe cases. Regarding the pathogenesis,

there were 14 cases of biliary pancreatitis,

21 cases of alcoholic pancreatitis and 18 cas-

es of overeating-induced pancreatitis. As to

complications, hyperlipidemia occurred in

13 cases, diabetes mellitus in 11 cases and

hypertension in 29 cases. In group C, the pa-

tients were 34-75 years old, with an average

of 51.32 ± 9.04 years. There were 31 males

and 22 females. BMI was 22.07 ± 1.46 kg/

m2 on average, and the duration from onset

to admission was 2-71 h, with an average of

24.58 ± 5.37 h. In terms of the severity of

the disease, there were 31 mild, 17 mod-

erate-severe, and 5 severe cases. As to the

pathogenesis, there were 17 cases of biliary

pancreatitis, 19 cases of alcoholic pancre-

atitis, and 17 cases of overeating-induced

pancreatitis. Concerning complications,

hyperlipidemia occurred in 14 cases, diabe-

tes mellitus in 12 cases and hypertension in

27 cases. The three groups had comparable

baseline clinical data (P>0.05) (Table 1).

Inclusion and exclusion criteria

Inclusion criteria: 1) Patients who met

the diagnostic criteria in the Expert Con-

sensus on TCM Diagnosis and Treatment

of Acute Pancreatitis (2017) developed by

the Society of Digestive Diseases, China As-

sociation of Traditional Chinese Medicine 4;

2) those admitted within 72 h after onset;

3) those treated for the first time; 4) those

without contraindications to hemoperfusion

or history of drug allergy; 5) those admitted

for over 14 d; 6) those with complete clinical

data; 7) those who and whose families volun-

tarily signed the informed consent.

44 Zhai et al.

Investigación Clínica 64(1): 2023

Exclusion criteria: 1) Patients compli-

cated with dysfunction of vital organs such

as the heart, liver, or kidney, acute/chronic

infectious diseases, or endocrine diseases

that may affect the stress state; 2) those

with a history of acute/chronic pancreatitis;

3) those with diabetes mellitus, hyperten-

sion, tumors or trauma; 4) those with mental

disorders or language dysfunction; 5) those

who were transferred to another hospital or

quit halfway, received other therapeutic reg-

imens or had poor compliance; 6) pregnant

or lactating women.

Treatment methods

All patients were deprived of water and

food immediately after admission, and con-

ventional therapies were performed, such as

gastrointestinal decompression, the supple-

ment of blood volume, anti-infection, as well

as correction of water-electrolyte and acid-

base disorders. For group A, somatostatin

(NMPN H20066708, Yangtze River Pharma-

ceutical Group, China) was applied based on

conventional therapy: 6 mg of somatostatin

was diluted in 500 mL of normal saline and

continuously intravenously pump-infused (4

mL/L) (Sigma-Aldrich Labware, USA). For

group B, early hemoperfusion was performed

based on conventional therapy: The vascular

access was constructed using a femoral vein

single-needle double-cavity catheter and

connected to a hemodialysis machine (Phil-

ips, USA). The blood was anticoagulated

with low-molecular-weight heparin (Sigma-

Aldrich, USA) at an initial dose of 5000

U, with 250 U additionally supplemented

hourly. Hemoperfusion was conducted us-

ing a HA330 resin hemoperfusion cartridge

(Zhuhai Livzon Diagnostics Inc., China) at

a flow rate of 150-200 mL/min for 2 h, 3-5

times daily as needed. For group C, soma-

tostatin in combination with early hemoper-

fusion was employed based on conventional

Table 1

Baseline clinical data.

Group A

(n=53)

Group B

(n=53)

Group C

(n=53)

Statistical

value P

Age (year) 51.26±8.93 50.94±8.87 51.32±9.04 F=0.282 0.892

BMI (kg/m2) 22.15±1.48 21.89±1.45 22.07±1.46 F=0.762 0.324

Duration from onset

to admission (h)

24.62±5.39

24.73±5.41

24.58±5.37

F=0.823

0.192

Severity χ2=0.723 0.948

Mild 28 29 31

Moderate-severe 21 19 17

Severe 4 5 5

Pathogenesis χ2=0.649 0.958

Biliary pancreatitis 15 14 17

Alcoholic pancreatitis 22 21 19

Overeating-induced pancreatitis 16 18 17

Complication χ2=0.818 0.936

Hyperlipidemia 11 13 14

Diabetes mellitus 14 11 12

Hypertension 28 29 27

BMI: Body mass index.

Treatment of acute pancreatitis by somatostatin plus early hemoperfusion 45

Vol. 64(1): 41 - 52, 2023

therapy, and the dosage and method were

the same as those for the other two groups.

Observation indices

Before and after 10 d of treatment, 5

mL of peripheral cubital venous blood was

drawn and centrifuged, and the serum was

collected.

Inflammatory factors interleukin-10

(IL-10), IL-18, tumor necrosis factor-α

(TNF-α), soluble intercellular adhesion mol-

ecule-1 (sICAM-1), procalcitonin (PCT) and

high mobility group protein B1 (HMGB1) in

the serum were detected by enzyme-linked

immunosorbent assay (ELISA), according to

the instructions of corresponding kits (Ab-

cam, USA).

Stress response indices: Oxidative indi-

ces (lipid hydrogen peroxide (LHP) and ad-

vanced oxidation protein products (AOPPs))

and antioxidative indices (catalase (CAT)

and glutathione peroxidase (GSH-Px)) were

determined using immunofluorescence as-

say kits (Thermo Fisher Scientific, USA). Ad-

ditionally, stress hormones epinephrine (E)

and cortisol (COR) were determined by ra-

dioimmunoassay kits (North Bioengineering

Institute, Beijing, China).

Intestinal mucosal barrier indices D-

lactic acid (D-LAC), diamine oxidase (DAO),

and endotoxin (ET) in the serum were de-

tected by ELISA kits (Abcam, USA).

Hemorheological indices: before treat-

ment and after 10 d of treatment, the plate-

let adhesion rate, plasma-specific viscosity,

whole blood-specific viscosity (high). and

thrombus length were observed.

Urine amylase was detected by an ELISA

kit (Abcam, USA), and its recovery time was

recorded. The recovery time of bowel sound

and exhaust, remission time of abdominal

pain, together with the length of stay were

also recorded.

After treatment for 10 d, clinical effi-

cacy and adverse reactions were observed.

Evaluation criteria for clinical efficacy:

Cured: The laboratory test indices returned

to normal, and the clinical symptoms disap-

peared. Markedly effective: The laboratory

test indices were improved significantly, and

the clinical symptoms were significantly re-

lieved. Effective: The laboratory test indi-

ces and clinical symptoms were improved.

Ineffective: The laboratory test indices had

no improvement or even worsened, and the

clinical symptoms were not changed or even

exacerbated. Total response rate = (cured +

markedly effective + effective cases)/total

cases × 100%.

Statistical analysis

All data were statistically analyzed by

the SPSS 20.0 software (IBM Inc., USA). The

quantitative data were expressed as means

± standard deviations (x

 ± s). Multigroup

comparisons were performed by one-way

analysis of variance, and those at different

time points were conducted with repeated

measures analysis of variance. In the case of

statistical significance, intergroup compari-

sons at the same time point were carried out

by the independent t test, and the paired t

test was used for intragroup comparisons

at various time points. The numerical data

were represented as percentage (%) and sub-

jected to the χ2 test. P<0.05 was considered

statistically significant.

RESULTS

Levels of inflammatory factors

Before treatment, the levels of inflam-

matory factors IL-10, IL-18, TNF-α, sICAM-1,

PCT and HMGB1 had no statistically signifi-

cant differences among the three groups

(P>0.05). At 10 d after treatment, the level

of serum IL-10 rose in the three groups com-

pared with that of before treatment, higher

in group C than that in groups A and B. In

contrast the levels of other indices declined

in the three groups, lower in group C than

those in groups A and B, showing statistical-

ly significant differences (P<0.05) (Table 2).

46 Zhai et al.

Investigación Clínica 64(1): 2023

Levels of stress response indices

No statistically significant differences

were found in the levels of stress response

indices LHP, AOPPs, CAT, GSH-Px, E, and

COR among the three groups before treat-

ment (P>0.05). At 10 d after treatment,

the levels of serum CAT and GSH-Px rose

in the three groups compared with those

before treatment, higher in group C than

those in groups A and B, whereas the levels

of LHP, AOPPs, E, and COR declined in the

three groups, lower in group C than those

in groups A and B, displaying statistically

significant differences (P<0.05) (Table 3).

Levels of intestinal mucosal barrier

indices

Before treatment, there were no sta-

tistically significant differences in the lev-

els of intestinal mucosal barrier indices D-

lac, DAO and ET among the three groups

(P>0.05). At 10 d after treatment, the levels

of these indices declined in the three groups

compared with those before treatment, and

the differences were statistically significant

(P<0.05). At 10 d after treatment, group

C had significantly lower levels of serum D-

lac, DAO and ET than the other two groups

(P<0.05) (Table 4).

Table 2

Levels of inflammatory factors.

Index Group A

(n=53)

Group B

(n=53)

Group C

(n=53) F P

IL-10 (x

 ± s, ng/L)

Before treatment 9.87±1.02 10.11±1.06 9.98±1.03 1.018 0.236

10 days after treatment 15.18±1.46* 14.97±1.52* 20.36±2.19*ab 14.325 0.0001

IL-18 (x

 ± s, ng/L)

Before treatment 463.27±45.81 459.13±46.07 461.49±45.87 0.564 0.637

10 days after treatment 170.32±18.49* 167.91±17.85* 138.46±14.52*ab 10.318 0.0001

TNF-α (x

 ± s, ng/L)

Before treatment 185.41±20.36 182.53±20.78 179.85±19.96 0.847 0.259

10 days after treatment 93.62±11.28* 94.15±10.86* 72.03±6.78*ab 9.653 0.0001

sICAM-1 (x

 ± s, ng/mL)

Before treatment 24.95±2.61 25.13±2.68 24.87±2.59 0.501 0.612

10 days after treatment 13.27±1.45* 12.96±1.37* 5.13±0.64*ab 34.698 0.0001

PCT (x

 ± s, ng/mL)

Before treatment 6.48±0.73 6.52±0.69 6.47±0.71 0.359 0.704

10 days after treatment 3.79±0.42* 3.85±0.40* 1.68±0.23*ab 28.076 0.0001

HMGB1 (x

 ± s, ng/mL)

Before treatment 15.24±1.67 15.18±1.63 14.97±1.58 0.755 0.391

10 days after treatment 10.18±1.13* 9.97±1.08* 5.26±0.61*ab 28.634 0.0001

Compared with before treatment, *P<0.05; compared with group A, aP<0.05; compared with group B, bP<0.05.

HMGB1: High mobility group protein B1; IL: interleukin; PCT: procalcitonin; sICAM-1: soluble intercellular adhe-

sion molecule-1; TNF-α: tumor necrosis factor-α.

Treatment of acute pancreatitis by somatostatin plus early hemoperfusion 47

Vol. 64(1): 41 - 52, 2023

Table 3

Levels of stress response indices.

Index Group A

(n=53)

Group B

(n=53)

Group C (n=53) F P

LHP (x

 ± s, μmol/L)

Before treatment 23.78±2.59 24.05±2.63 23.91±2.60 0.523 0.495

10 days after treatment 14.26±1.47* 13.98±1.42* 7.52±0.83*ab 26.491 0.0001

AOPPs (x

 ± s, μmol/L)

Before treatment 8.41±0.92 8.37±0.89 8.45±0.93 0.472 0.651

10 days after treatment 5.39±0.56* 5.44±0.57* 2.96±0.31*ab 27.628 0.0001

CAT (x

 ± s, U/L)

Before treatment 17.04±2.12 16.88±2.09 16.96±2.11 0.381 0.696

10 days after treatment 25.63±2.87* 24.75±2.83* 33.18±3.76*ab 10.612 0.0001

GSH-Px (x

 ± s, g/L)

Before treatment 27.16±2.95 26.97±2.89 27.14±2.93 0.435 0.758

10 days after treatment 36.52±3.78* 35.68±3.71* 49.36±5.07*ab 13.786 0.0001

E (x

 ± s, ng/mL)

Before treatment 0.72±0.11 0.69±0.10 0.70±0.09 1.369 0.147

10 days after treatment 0.45±0.06* 0.43±0.05* 0.18±0.02*ab 24.757 0.0001

COR (x

 ± s, ng/mL)

Before treatment 251.16±27.38 249.57±26.81 250.43±27.19 0.602 0.763

10 days after treatment 142.09±15.26* 138.64±14.92* 87.58±9.61*ab 20.941 0.0001

Compared with before treatment, *P<0.05; compared with group A, aP<0.05; compared with group B, bP<0.05.

AOPPs: Advanced oxidation protein products; CAT: catalase; COR: cortisol; E: epinephrine; GSH-Px: glutathione

peroxidase; LHP: lipid hydrogen peroxide.

Table 4

Levels of intestinal mucosal barrier indices.

Index Group A (n=53) Group B (n=53) Group C (n=53) F P

D-lac (x

 ± s, mg/L)

Before treatment 3.96±0.58 4.12±0.63 4.07±0.62 1.265 0.173

10 days after treatment 1.97±0.29* 2.05±0.31* 1.15±0.18*ab 14.356 0.0001

DAO (x

 ± s, IU/mL)

Before treatment 16.42±1.75 15.96±1.72 16.28±1.73 0.956 0.147

10 days after treatment 9.38±0.96* 9.24±0.93* 5.04±0.51*ab 28.927 0.0001

ET (x

 ± s, EU/mL)

Before treatment 10.13±1.24 9.98±1.07 10.02±1.16 0.548 0.506

10 days after treatment 6.87±0.65* 6.75±0.62* 3.29±0.38*ab 36.439 0.0001

Compared with before treatment, *P<0.05; compared with group A, aP<0.05; compared with group B, bP<0.05.

DAO: Diamine oxidase; D-LAC: D-lactic acid; ET: endotoxin.

48 Zhai et al.

Investigación Clínica 64(1): 2023

Levels of hemorheology indices

Before treatment, there were no statis-

tically significant differences in the plate-

let adhesion rate, plasma-specific viscosity,

whole blood-specific viscosity (high), and

thrombus length among the three groups

(P>0.05). At 10 d after treatment, the

hemorheology indices significantly declined

in the three groups compared with those be-

fore treatment (P<0.05). They declined suc-

cessively in group A, B and C, and the differ-

ences were statistically significant between

any two groups (P<0.05) (Table 5).

Recovery time and hospital stay length

In group C, the recovery time of urine

amylase, bowel sound and exhaust, remis-

sion time of abdominal pain, and length of

stay were all significantly shorter than those

of groups A and B (P<0.05). However, there

were no significant differences between

groups A and B (Table 6).

Clinical treatment outcomes and adverse

reactions

The total clinical response rate was

significantly higher in group C than that in

Table 5

Levels of hemorheology indices.

Index Group A

(n=53)

Group B

(n=53)

Group C

(n=53) F P

Platelet adhesion rate (x

 ± s, %)

Before treatment 79.58±13.42 80.37±14.15 79.94±13.86 0.285 0.649

10 days after treatment 52.91±8.27* 43.21±6.86*a 31.28±5.73*ab 7.592 0.0001

Plasma specific viscosity (x

 ± s, %)

Before treatment 2.24±0.25 2.19±0.23 2.21±0.24 1.063 0.186

10 days after treatment 1.89±0.18* 1.54±0.16*a 1.17±0.12*ab 15.478 0.0001

Whole blood specific viscosity

(high) (x

 ± s, mPa·s)

Before treatment 6.52±0.73 6.49±0.71 6.50±0.72 0.314 0.821

10 days after treatment 5.14±0.62* 4.08±0.53*a 3.21±0.34*ab 16.871 0.0001

Thrombus length (x

 ± s, mm)

Before treatment 56.87±17.24 55.97±17.16 56.48±17.22 0.249 0.788

10 days after treatment 43.29±11.56* 31.28±8.45*a 20.31±4.69*ab 9.510 0.0001

Compared with before treatment, *P<0.05; compared with group A, aP<0.05; compared with group B, bP<0.05.

Table 6

Recovery time and hospital stay length.

Item Group A

(n=53)

Group B

(n=53)

Group C

(n=53) F P

Recovery time of urine amylase (x

 ± s, d) 7.49±0.89 7.26±0.85 5.73±0.64ab 10.688 0.0001

Recovery time of bowel sound (x

 ± s, d) 5.76±0.73 5.83±0.79 2.45±0.31ab 23.975 0.0001

Recovery time of exhaust (x

 ± s, d) 6.04±0.81 6.07±0.82 2.69±0.42ab 18.709 0.0001

Remission time of abdominal pain (x

 ± s, d) 3.58±0.45 3.65±0.46 1.87±0.29ab 21.427 0.0001

Hospital stay length (± s, d) 18.61±2.29 18.78±2.34 15.24±1.76ab 6.834 0.0001

Compared with group A, aP<0.05; compared with group B, bP<0.05.

Treatment of acute pancreatitis by somatostatin plus early hemoperfusion 49

Vol. 64(1): 41 - 52, 2023

groups A and B, and the difference was sta-

tistically significant (P<0.05). No statisti-

cally significant difference was found in the

incidence rate of adverse reactions among

the three groups (P>0.05) (Table 7).

DISCUSSION

In recent years, the theories of pan-

creatic autodigestion, pancreatic microcir-

culation disorder, the excessive response of

inflammatory mediators and intestinal bac-

terial translocation have been recognized as

the pathogeneses of AP 5. Therefore, patients

with AP are often treated by relieving the

pancreatic autodigestion and inflammatory

response, and improving the pancreatic mi-

crocirculation and intestinal flora balance.

As a peptide hormone containing 14 amino

acids, somatostatin has been confirmed to

possess a potent inhibitory effect on the

secretion of gastric acid and pepsin. It can

also inhibit pancreatic autodigestion via

various ways, the most direct of which is to

inhibit pancreatic secretion by reducing the

content of pancreatic enzyme, thereby weak-

ening its digestive function. Moreover, the

Oddi’s sphincter preventing the discharge of

pancreatic juice out of the body, is also re-

laxed, thus promoting the discharge of pan-

creatic juice 6. Toxic substances in human

blood, including endogenous and exogenous

poisons and their metabolites, are adsorbed

by hemoperfusion through a large number of

active adsorbents in a circulation perfusion

device placed outside the body, so that the

toxic substances are effectively discharged

out of the body, and not ingested by organs,

thus purifying the blood 7.

Massive secretion of pancreatic en-

zymes leads to autodigestion of the pancre-

as and its surrounding tissues and organs,

during which a large number of inflamma-

tory mediators are quickly released in lo-

cal lesions and penetrate the bloodstream,

thereby inducing a strong systemic inflam-

matory response 8. Then the inflammatory

response worsens the damage to the pan-

creas and its surrounding tissues. TNF-α re-

leased by monocyte-macrophages upon the

stimulation of various factors is considered

the primary mediator inducing the inflam-

matory response. During pancreatic injury,

TNF-α promotes the release of a variety of

inflammatory mediators through activating

multiple cells, thus leading to chain reac-

tions 9. The pro-inflammatory cytokine IL-

18 produced by the activation of monocytes

and macrophages can bind to the receptor

to induce the expressions of various ILs and

Table 7

Clinical treatment outcomes and adverse reactions.

Item Group A

(n=53)

Group B

(n=53)

Group C

(n=53) χ2P

Total response rate (%) 67.92 60.38 90.57ab 15.799 0.015

Cured (case) 6 5 11

Markedly effective (case) 12 10 19

Effective (case) 18 17 18

Ineffective (case) 17 21 5

Incidence rate of adverse reactions (%) 7.55 9.43 5.66 0.541 0.763

Acute respiratory distress syndrome (case) 2 3 2

Upper gastrointestinal bleeding (case) 1 0 1

Shock (case) 1 2 0

Compared with group A, aP<0.05; compared with group B, bP<0.05.

50 Zhai et al.

Investigación Clínica 64(1): 2023

chemokines, ultimately inducing the inflam-

matory cascade 10 As an anti-inflammatory,

cytokine IL-10 is able to inhibit the prolif-

eration and differentiation of immune cells,

thereby hindering the progress of inflamma-

tory respons 11 The inflammatory factor sI-

CAM-1 with the function of immunoglobulin

can act on leukocytes to promote their adhe-

sion, aggregation and penetration through

endothelial cells, so that they can reach the

site of inflammation, thereby enhancing

the inflammatory response 12 When trauma

or infection becomes worse, large amounts

of PCT will be released into the blood, and

its level is positively correlated with the se-

verity of disease 13. The late inflammatory

mediator HMGB1 can enhance the inflam-

matory response through various pathways,

ultimately amplifying the inflammation 14.

In this study, somatostatin and early he-

moperfusion could effectively suppress the

secretion and release of pro-inflammatory

factors in patients with AP, and promote the

release of anti-inflammatory factors, thereby

inhibiting the inflammatory response. More-

over, somatostatin combined with early he-

moperfusion had a more significant effect,

indicating that there is a synergistic effect

between somatostatin and hemoperfusion,

which effectively lowers the severity of AP in

patients, consistent with the results of mul-

tiple previous reports 15.

Stress response is involved in the oc-

currence and development of AP. Pancre-

atic autodigestion-induced damage of the

pancreas and its surrounding tissues and

systemic inflammatory response can trig-

ger the body’s stress state. During this pro-

cess, the body’s oxidation/antioxidation im-

balance and massive release of oxygen free

radicals directly cause vascular endothelial

injury and vascular hyperconstriction, thus

leading to ischemia and even irreversible ne-

crosis of tissues and organs. In addition, the

secretion of various stress hormones will be

enhanced due to the up-regulated activity of

the hypothalamus-pituitary-adrenal axis 16.

Therefore, the content of oxidative factors

LHP and AOPPs, antioxidant factors CAT and

GSH-Px, and stress hormones E and COR

can objectively reflect the stress state and

the severity of the disease in patients. In this

study, the results revealed that somatostatin

and hemoperfusion could balance the oxida-

tion/antioxidation state and regulate the

neuro-endocrine function in patients with

AP through up-regulating antioxidant fac-

tors and down-regulating oxidative factors

and stress hormones, so that the patient’s

systemic stress was alleviated. Besides, the

synergistic effect of somatostatin and hemo-

perfusion was more significant. When the

intestinal mucosa epithelium and its barrier

function are damaged, the intestinal bacte-

rial ferment D-lac and the highly-active en-

donuclease DAO can enter the blood circula-

tion. At the early stage of intestinal barrier

dysfunction, ET can translocate, leading to

intestinal endotoxemia and the release of

inflammatory factors, and worsening the

systemic inflammatory response in patients.

In this study, somatostatin and hemoperfu-

sion could reduce the levels of serum D-lac,

DAO and ET in patients, indicating that both

treatment methods have a protective effect

on the intestinal mucosal barrier function in

patients with AP. Additionally, the combina-

tion of them has a better protection effect.

The results are consistent with previous

literature reports 17, i.e. somatostatin can

reduce the endotoxin level through activat-

ing the liver reticuloendothelial system and

enhancing its phagocytosis, thereby improv-

ing the endotoxemia symptoms. In addition,

such an effect is related to the ability of he-

moperfusion to scavenge endogenous and

exogenous poisons and their metabolites 18.

In this study, it was found that somatosta-

tin and hemoperfusion could improve the

hemorheological indices of patients with AP

to different degrees. It is speculated that the

reason is closely related to the ability of so-

matostatin to effectively weaken the release

of platelet-activating factors and reduce vas-

cular permeability, and the ability of hemo-

perfusion to purify the blood. Besides, in the

Treatment of acute pancreatitis by somatostatin plus early hemoperfusion 51

Vol. 64(1): 41 - 52, 2023

group C, the recovery time of urine amylase,

bowel sound and exhaust, remission time of

abdominal pain and length of stay were all

shorter than those in groups A and B, and

the total clinical response rate was higher

than that in groups A and B. It can be seen

that somatostatin combined with hemoper-

fusion is more conducive to the recovery of

patients and can improve clinical efficacy.

In conclusion, somatostatin combined

with early hemoperfusion can effectively re-

duce the inflammatory and stress responses,

protect the intestinal mucosal barrier func-

tion, and improve the hemorheology in the

treatment of AP, thereby promoting recovery

and benefitting the prognosis of patients.

Such therapy has essential practical applica-

tion value in clinical practice, which is wor-

thy of popularization in the future.

ACKNOWLEDGEMENTS

We thank all coauthors for their signifi-

cant contributions.

Conflict of interest

None to declare

Funding/Support

This study was not financially supported.

ORCID numbers of authors

• Hengyong Zhai (HZ):

0000-0002-0015-9340

• Bin Yang (BY):

0000-0002-7647-9973

• Yiwei Fu (YF):

0000-0003-2799-5450

• Dongli Zhang (DZ):

0000-0003-3031-2526

• Yujiang Li (YL):

0000-0001-9844-7043

• Junxing Huang (JH):

0000-0001-7199-4717

Authors’ contributions

HZ and JH designed this study and sig-

nificantly revised this paper; BY, YF, DZ and

YL performed this study, analyzed clinical

data and drafted this paper. All authors have

approved the submission and publication of

this paper.

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