Therapeutic anticoagulation for splanchnic vein thrombosis in acute pancreatitis: A national survey and case-vignette study

BACKGROUND Splanchnic vein thrombosis(SVT)is a major complication of moderate and severe acute pancreatitis.There is no consensus on whether therapeutic anticoagulation should be started in patients with acute pancreatitis and SVT.AIM To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis.METHODS A total of 139 pancreatologists of the Dutch Pancreatitis Study Group and Dutch Pancreatic Cancer Group were approached to complete an online survey and case vignette survey.The threshold to assume group agreement was set at 75%.RESULTS The response rate was 67%(n=93).Seventy-one pancreatologists(77%)regularly prescribed therapeutic anticoagulation in case of SVT,and 12 pancreatologists(13%)for narrowing of splanchnic vein lumen.The most common reason to treat SVT was to avoid complications(87%).Acute thrombosis was the most important factor to prescribe therapeutic anticoagulation(90%).Portal vein thrombosis was chosen as the most preferred location to initiate therapeutic anticoagulation(76%)and splenic vein thrombosis as the least preferred location(86%).The preferred initial agent was low molecular weight heparin(LMWH;87%).In the case vignettes,therapeutic anticoagulation was prescribed for acute portal vein thrombosis,with or without suspected infected necrosis(82%and 90%),and thrombus progression(88%).Agreement was lacking regarding the selection and duration of long-term anticoagulation,the indication for thrombophilia testing and upper endoscopy,and about whether risk of bleeding is a major barrier for therapeutic anticoagulation.CONCLUSION In this national survey,the pancreatologists seemed to agree on the use of therapeutic anticoagulation,using LMWH in the acute phase,for acute portal thrombosis and in the case of thrombus progression,irrespective of the presence of infected necrosis.

Direct oral anticoagulants for the treatment of splanchnic vein thrombosis:A state of art

Splanchnic vein thrombosis(SVT)is a manifestation of venous thromboembolism in an unusual site.Portal,mesenteric,and splenic veins are the most common vessels involved in SVT which occurs mainly in patients with liver cirrhosis,although non-cirrhotic patients could be affected as well.Thrombosis of hepatic veins,also known as Budd-Chiari syndrome,is another manifestation of SVT.Prompt diagnosis and intervention are mandatory in order to increase the recalization rate and reduce the risk of thrombus progression and hypertensive complications.Traditional anticoagulation with heparin and vitamin-K antagonists is the treatment of choice in these cases.However,recent studies have shown promising results on the efficacy and safety of direct oral anticoagulants(DOACs)in this setting.Available results are mainly based on retrospective studies with small sample size,but first clinical trials have been published in the last years.This manuscript aims to provide an updated overview of the current evidence regarding the role of DOACs for SVT in both cirrhotic and non-cirrhotic patients.

Diagnosis and management of splanchnic ischemia

Splanchnic or gastrointestinal ischemia is rare and randomized studies are absent. This review focuses on new developments in clinical presentation, diagnostic approaches, and treatments. Splanchnic ischemia can be caused by occlusions of arteries or veins and by physiological vasoconstriction during low-flow states. The prevalence of significant splanchnic arterial stenoses is high, but it remains mostly asymptomatic due to abundant collateral circulation. This is known as chronic splanchnic disease (CSD). Chronic splanchnic syndrome (CSS) occurs when ischemic symptoms develop. Ischemic symptoms are characterized by postprandial pain, fear of eating and weight loss. CSS is diagnosed by a test for actual ischemia. Recently, gastro-intestinal tonometry has been validated as a diagnostic test to detect splanchnic ischemia and to guide treatment. In single- vessel CSD, the complication rate is very low, but some patients have ischemic complaints, and can be treated successfully. In multi-vessel stenoses, the complication rate is considerable, while most have CSS and treatment should be strongly considered. CT and MR-based angiographic reconstruction techniques have emerged as alternatives for digital subtraction angiography for imaging of splanchnic vessels. Duplex ultrasound is still the first choice for screening purposes. The strengths and weaknesses of each modality will be discussed. CSS may be treated by minimally invasive endoscopic treatment of the celiac axis compression syndrome, endovascular antegrade stenting, or laparotomy-assisted retrograde endovascular recanalization and stenting.The treatment plan is highly individualized and is mainly based on precise vessel anatomy, body weight, co- morbidity and severity of ischemia.

Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis

Portal hypertension is a clinical syndrome which leads to several clinical complications, such as the formation and rupture of esophageal and/or gastric varices, ascites, hepatic encephalopathy and hepato-renal syndrome. In cirrhosis, the primary cause of the increase in portal pressure is the enhanced resistance to portal outflow. However, also an increase in splanchnic blood flow worsens and maintains portal hypertension. The vasodilatation of arterial splanchnic vessels and the opening of collateral circulation are the determinants of the increased splanchnic blood flow. Several vasoactive systems/substances, such as nitric oxide, cyclooxygenase-derivatives, carbon monoxide and endogenous cannabinoids are activated in portal hypertension and are responsible for the marked splanchnic vasodilatation. Moreover, an impaired reactivity to vasoconstrictor systems, such as the sympathetic nervous system, vasopressin, angiotensin II and endothelin-1, plays a role in this process. The opening of collateral circulation occurs through the reperfusion and dilatation of preexisting vessels, but also through the generation of new vessels. Splanchnic vasodilatation leads to the onset of the hyperdynamic circulatory syndrome, a syndrome which occurs in patients with portal hypertension and is characterized by increased cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure. Understanding the pathophysiology of splanchnic vasodilatation and hyperdynamic circulatory syndrome is mandatory for the prevention and treatment of portal hypertension and its severe complications.

Influence of splanchnic vascular infusion on the content of endotoxins in plasma and the translocation of intestinal bacteria in rats with acute hemorrhage necrosis pancreatitis

The main reason for the death of the patient with acute hemorrhage necrosis pancreatitis (AHNP) is pancreatic infection and multi-organ failure caused by endotoxemia and intestinal bacterial translocation[1-7]. However, the pathogenesis of endotoxemia and intestinal bacterial translocation remains a question[8-10]; moreover, no effective method of prevention and cure for it has been found till now[11 -15] In the present study, we infused low dose dopamine and low molecular weight dextran through the catheters to abdominal aorta and portal vein, and observed its influence on the endotoxin concentration in plasma and the rate of translocation of intestinal bacteria in AHNP rats.

Splanchnic vein thrombosis in necrotizing acute pancreatitis: Detection by computed tomographic venography

AIM: To assess the diagnostic accuracy of computed tomographic venography(CTV) for splanchnic vein thrombosis(SVT) detection in necrotizing acute pancreatitis(AP) patients.METHODS:Forty-three patients with necrotizing AP who underwent both CTV and digital subtraction angiography(DSA)within 3 d were analyzed in this retrospective comparative study.All CTV procedures were performed with a dual-source CT scanner.The presence and location of SVT were determined via blinded imaging data analyses.RESULTS:According to the DSA results,17(39.5%)of the total 43 patients had SVT.The sensitivity,specificity,positive and negative predictive values of CTV for SVT detection were 100%(95%CI:77.1%-100%),92.3%(95%CI:73.4%-98.7%),89.5%(95%CI:65.5%-98.2%)and 100%(95%CI:82.8%-100%),respectively.CONCLUSION:CTV is an effective examination for SVT detection in patients with necrotizing AP with high positive and negative predictive values.

Modulation of splanchnic circulation:Role in perioperativemanagement of liver transplant patients

Splanchnic circulation is the primary mechanism thatregulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods(e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure.

Effect of laparoscopic abdominal surgery on splanchnic circulation: Historical developments

With the developments in medical technology and increased surgical experience, advanced laparoscopic surgical procedures are performed successfully. Laparoscopic abdominal surgery is one of the best examples of advanced laparoscopic surgery (LS). Today, laparoscopic abdominal surgery in general surgery clinics is the basis of all abdominal surgical interventions. Laparoscopic abdominal surgery is associated with systemic and splanchnic hemodynamic alterations. Inadequate splanchnic perfusion in critically ill patients is associated with increased morbidity and mortality. The underlying pathophysiological mechanisms are still not well understood. With experience and with an increase in the number and diversity of the resulting data, the pathophysiology of laparoscopic abdominal surgery is now better understood. The normal physiology and pathophysiology of local and systemic effects of laparoscopic abdominal surgery is extremely important for safe and effective LS. Future research projects should focus on the interplay between the physiological regulatory mechanisms in the splanchnic circulation (SC), organs, and diseases. In this review, we discuss the effects of laparoscopic abdominal surgery on the SC.

Current practice of anticoagulant in the treatment of splanchnic vein thrombosis secondary to acute pancreatitis

Background:Severe acute pancreatitis is a common diagnosis in emergency general surgery and can be a cause of significant morbidity and mortality.A consequence of severe acute pancreatitis is thrombus in the splanchnic veins.These thrombi can potentially lead to bowel ischemia or hepatic failure.However,another complication of severe acute pancreatitis is retroperitoneal bleeding.At this time,it is unclear if treating patients for splanchnic vein thrombosis in the context of severe acute pancreatitis is associated with any outcome benefit.A systematic review might clarify this question.Data sources:A two-fold search strategy(one broad and one precise)looked at all published literature.The review was registered on PROSPERO(ID:CRD42018102705).MEDLINE,EMBASE,PubMed,Cochrane and Web of Science databases were searched and potentially relevant papers were reviewed indepen-dently by two researchers.Any disagreement was reviewed by a third independent researcher.Primary outcome was reestablishment of flow in the thrombosed vein versus bleeding complications.Results:Of 1462 papers assessed,a total of 16 papers were eligible for inclusion.There were no ran-domized controlled trials,2 were case series,5 retrospective single-center studies and 9 case reports.There were a total of 198 patients in these studies of whom 92(46.5%)received anticoagulation therapy.The rates of recanalization of veins in the treated and non-treated groups was 14%and 11%and bleeding complications were 16%and 5%,respectively.However,the included studies were too heterogeneous to undertake a meta-analysis.Conclusions:The systematic review highlights the lack evidence addressing this clinical question.There-fore a randomized controlled trial would be appropriate to undertake.

Stability of cirrhotic systemic hemodynamics ensures sufficient splanchnic blood flow after living-donor liver transplantation in adult recipients with liver cirrhosis

AIM： To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation （LDLT）, and to clarify how systemic hemodynamics impact on local graft circulation after LDLT.METHODS： Systemic hemodynamics, indocyanine green （ICG） elimination rate （K,cG） and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry （PDD） and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output （CO） to blood volume （BV） and mean transit time （MTT）, defined as the time required for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative graft function.RESULTS： Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance （TPR） were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and M＇IT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased KICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow.CONCLUSION： We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes.

Effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats

IM To investigate the effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats.METHODS Twentyeight male SpragueDawley rats were divided into two groups: intrahepatic portal hypertension (IHPH, n=14) by injection of CCl4 and prehepatic portal hypertension (PHPH, n=14) by stenosis of the portal vein. Animals of each group were divided into two subgroups: injection of octreotide and injection of normal saline. Seven agematched normal rats served as controls. The mean systemic arterial pressure (MSAP) and free portal venous pressure (FPP) were measured. The splanchnic blood flow was detected by injection of toad blood red cell labelled with 51Cr and 125I·T3. The concentration of plasma glucagon was determined by radioimmunoassay.RESULTS Octreotide significantly decreased both the splanchnic blood flow and FPP in portal hypertensive rats, and markedly increased splanchnic vascular and portal venous resistance. Octreotide did not significantly lower the plasma glucagon levels in both the peripheral and the portal veins.CONCLUSION The decreased splanchnic blood flow induced by octreotide in portal hypertensive rats results mainly from direct vasoconstriction but less from decreased plasma glucagon level.

Thoracic epidural anesthesia:Effects on splanchnic circulation and implications in Anesthesia and Intensive care

AIM: To evaluate the currently available evidence on thoracic epidural anesthesia effects on splanchnic macro and microcirculation, in physiologic and pathologic conditions.METHODS:A Pub Med search was conducted using the Me SH database.Anesthesia,Epidural was always the first MeS H heading and was combined by boolean operator AND with the following headings:Circulation,Splanchnic;Intestines;Pancreas and Pancreatitis;LiverFunction Tests.EMBASE,Cochrane library,ClinicalT rials.gov and clinicaltrialsregister.eu were also searched using the same terms.RESULTS:Twenty-seven relevant studies and four ongoing trials were found.The data regarding the effects of epidural anesthesia on splanchnic perfusion are conflicting.The studies focusing on regional macro-hemodynamics in healthy animals and humans undergoing elective surgery,demonstrated no influence or worsening of regional perfusion in patients receiving thoracic epidural anesthesia(TEA).On the other hand most of the studies focusing on micro-hemodynamics,especially in pathologic low flow conditions,suggested that TEA could foster microcirculation.CONCLUSION:The available studies in this field are heterogeneous and the results conflicting,thus it is difficult to draw decisive conclusions.However there is increasing evidence deriving from animal studies,that thoracic epidural blockade could have an important role in modifying tissue microperfusion and protecting microcirculatory weak units from ischemic damage,regardless of the effects on macro-hemodynamics.

Hepatosplanchnic circulation in cirrhosis and sepsis

Hepatosplanchnic circulation receives almost half of cardiac output and is essential to physiologic homeostasis.Liver cirrhosis is estimated to affect up to 1% of populations worldwide,including 1.5% to 3.3% of intensive care unit patients.Cirrhosis leads to hepatosplanchnic circulatory abnormalities and end-organ damage.Sepsis and cirrhosis result in similar circulatory changes and resultant multi-organ dysfunction.This review provides an overview of thehepatosplanchnic circulation in the healthy state and in cirrhosis,examines the signaling pathways that may play a role in the physiology of cirrhosis,discusses the physiology common to cirrhosis and sepsis,and reviews important issues in management.

From portal to splanchnic venous thrombosis:What surgeons should bear in mind

The present study aims to review the evolution of surgical management of portal(PVT) and splanch-nic venous thrombosis(SVT) in the context of liver transplantation over the last 5 decades. PVT is more commonly managed by endovenous thrombectomy, while SVT requires more complex technical expedients. Several surgical techniques have been proposed, such as extensive eversion thrombectomy, anastomosis to collateral veins, reno-portal anastomosis, cavo-portal hemi-transposition, portal arterialization and combined liver-intestinal transplantation. In order to achieve satisfactory outcomes, careful planning of the surgical strategy is mandatory. The excellent results that are ob-tained nowadays confirm that, even extended, splanch-nic thrombosis is no longer an absolute contraindication for liver transplantation. Patients with advanced portal thrombosis may preferentially be referred to specialized centres, in which complex vascular approaches and even multivisceral transplantation are performed.

Effect and Clinical Value of Splanchnic Nerve Block of Hemodynamics in ACST

The condition of acute cholangitis of severe type (ACST) develops very rapidly and the prognosis is poor. The main clinical feature is that there is an obvious dynamic variation, which is the principal factor for the early occurrence of shock and death. In this study the Japanese long ear rabbits were used and biliary tract pressure increasing and splanchnic nervous plexus blocking experiments were conducted. Our results indicate that 0.6% of lidocaine can be used to block the right celiac plexus. It can avoid the decrease of blood pressure due to the pressure increase of the binary tract, and the decrease of blood pressure due to the pressure increase of the binary tract can be corrected by local anesthesia. 8 cases in conformity with the ACST diagnostic standards received the right renal capsule block injection for the purpose of stopping the celiac plexus, 6 cases of whom had a return of blood pressure to various extent, suggesting that the splanchnic nervous activity in the occurrence of ACST is of great significance. The technique may provide a new approach for the clinical treatment of ACST.

Chronic intestinal ischemia and splanchnic blood-flow:Reference values and correlation with body-composition

AIM:To determine the splanchnic blood flow and oxygen uptake in healthy-subjects and patients and to relate the findings to body-composition.METHODS:The total splanchnic blood flow (SBF) and oxygen uptake (SO2U) were measured in 20 healthy volunteers (10 women) and 29 patients with suspected chronic intestinal ischemia (15 women),age 40-85 years,prior to and after a standard meal.The method is based on the Fick principle using the continuous infusion of an indicator (99mTechnetium-labelled mebrofenin) and catheterization of an artery and the hepatic vein.An angiography of the intestinal arteries was performed during the same investigation.A whole-body dual-energy x-ray absorptiometry scan was performedin healthy volunteers to determine body composition.RESULTS:Angiography revealed no atherosclerotic lesions in the intestinal arteries.The mean baseline SBF was 1087mL/min (731-1390),and this value increased significantly to 1787 mL/min after the meal in healthy volunteers (P<0.001).The baseline SBF in patients was 1080 mL/min,which increased to 1718 mL/min postprandially (P<0.001).The baseline SBF was independent of age,sex,lean body mass and percentage of body fat.The mean meal-induced increase in SBF was equal to 282mL/min + 5.4mL/min × bodyweight,(P=0.025).The SO2U in healthy volunteers and patients was 50.7mL/min and 48.0mL/min,respectively,and these values increased to 77.5 mL/min and 75mL/min postprandially,respectively.Both baseline and postprandial SO2U were directly related to lean body mass.Age and sex exerted no impact on SO2U.CONCLUSION:A direct correlation between body weight and the postprandial increase in SBF was observed.The effect of body weight should be considered in the diagnosis of chronic intestinal ischemia.

Physiopathology of splanchnic vasodilation in portal hypertension

In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.

High risk of thrombosis recurrence in people with idiopathic or only locally caused non-cirrhotic splanchnic vein thrombosis: it is time for guidelines’ revision

Portal hypertension caused by non-cirrhotic(and non neoplastic)splanchnic vein thrombosis(NC-SVT)is responsible for 5–10%of portal hypertension cases in the western world(1).Chronic myeloproliferative neoplasms(MPN)or systemic prothrombotic disorders are in cause in about 40%of subjects,while in about 30%a local condition,such as recent abdominal surgery or infection/inflammation triggers the event.The local condition,however,can only be the precipitating cause,since a thorough screening allows identifying the co-occurrence of systemic thrombophilia in about 30%of such cases.Hence,screening is mandatory even in cases where the cause of NC-SVT seems obvious.Nevertheless,about 30%of cases of NC-SVT remains unexplained and defined idiopathic(1).

Responses in splanchnic and mammary amino acid metabolism to short-term graded removal of methionine in lactating goats

Four multi-catheterized lactating goats were used in a 4×4 Latin square experiment to investigate the responses of amino acid metabolism in portal-drained viscera(PDV),liver,and mammary glands to short-term varying supplies of methionine(Met).During the last 45 h in each experimental period,goats were fasted for 12 h and then abomasally infused with an amino acid(AA)mixture plus glucose for 33 h.Treatments consisted of graded removal of Met from an infused AA mixture to achieve Met content in the infusate of 100%(complete),60%,30%,or 0%that in casein.Graded Met removal decreased the pro-duction of milk,milk protein,lactose,and fat linearly whilst also decreasing arterial Met concentration linearly(P<0.05).Meanwhile,net PDV uptake and liver removal of Met decreased linearly(P<0.05)due to decreased Met affinity of PDV and liver(P<0.05).Net mammary uptake of Met(P>0.1)was maintained as Met supply declined.This was achieved through increased mammary affinity(P<0.05)and increased mammary blood flow(P<0.05)totally offsetting the negative effect of decreased circu-lating Met concentration.Graded removal of Met from the infusate linearly decreased mammary uptake-to-milk output ratios of Met(P<0.05)and tended to decrease essential amino acid(EAA)linearly(0.05<P<0.1).Treatments also linearly decreased circulating concentration of prolactin and linearly increased insulin concentration(P<0.05).In conclusion,results of the present study indicated there were several mechanisms used to mitigate a Met deficiency,including reduced catabolism of Met in PDV,liver,and peripheral tissue(including mammary glands)and a linear increase in mammary blood flow.The observed decreases in milk protein production as Met supply decreased appear to be a result of regulatory events which may have been driven by decreased circulating prolactin,rather than as a result of decreased mammary Met uptake.

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.