Fluid resuscitation in acute pancreatitis

Acute pancreatitis remains a clinical challenge, despite an exponential increase in our knowledge of its complex pathophysiological changes. Early fluid therapy is the cornerstone of treatment and is universally recommended; however, there is a lack of consensus regarding the type, rate, amount and end points of fluid replacement. Further confusion is added with the newer studies reporting better results with controlled fluid therapy. This review focuses on the pathophysiology of fluid depletion in acute pancreatitis, as well as the rationale for fluid replacement, the type, optimal amount, rate of infusion and monitoring of such patients. The basic goal of fluid epletion should be to prevent or minimize the systemic response to inflammatory markers. For this review, various studies and reviews were critically evaluated, along with authors’ recommendations, for predicted severe or severe pancreatitis based on the available evidence.     

Is aggressive intravenous fluid resuscitation beneficial in acute pancreatitis? A meta-analysis of randomized control trials and cohort studies

BACKGROUND There is conflincting evidence on the intravenous fluid (IVF) strategy for acute pancreatitis (AP).We perform a metaanalysis of the available evidence.AIM To investigate if aggressive IVF therapy in AP patients is beneficial to decrease mortality and improve outcomes.METHODS Metaanalysis of available randomized controlled trials and cohort studies comparing aggressive IVF vs non-aggressive IVF resuscitation.RESULTS There was no significant difference in mortality between the aggressive (n=1229)and non-aggressive IVF (n=1397) patients.Patients receiving aggressive IVF therapy had higher risk for acute kidney injury and acute respiratory distress syndrome.There also was no significant difference in the overall incidence of systemic inflammatory response syndrome,persistent organ failure,pancreatic necrosis when comparing both study groups.CONCLUSION Early aggressive IVF therapy did not improve mortality.Moreover,aggressive IVF therapy could potentially increase the risk for acute kidney injury and pulmonary edema leading to respiratory failure and mechanical ventilation.Studies are needed to investigate which subset of AP patients could benefit from aggressive IVF therapy.     

重症急性胰腺炎急性反应期液体复苏体会

目的 探讨重症急性胰腺炎急性反应期液体复苏的经验与体会.方法 回顾性分析97例重症急性胰腺炎患者在急性反应期的液体复苏过程;观察复苏时间及治疗过程中出现呼吸衰竭、肾功能不全等并发症情况;对比输入胶体与晶体液的情况.结果 对照组(A组,未输注胶体液)51例,呼吸衰竭19例,肾功不全16例,心功能不全10例,死亡5例.治疗组(B组,输注胶体液)46例,呼吸衰竭9例,肾功能不全8例,心功能不全3例,死亡2例.早期液体输入量及呼吸衰竭、肾功能衰竭等并发症均明显低于对照组.结论 重症急性胰腺炎急性期液体复苏时及时补充胶体液能减少液体输入量,缩短复苏时间,早期限制性液体输入降低肺损伤等并发症的发生.     

Systematic review and meta-analysis of fluid therapy protocols in acute pancreatitis: type,rate and route

BackgroundAdequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols in patients with AP.MethodsMEDLINE, Embase, Science Citation Index and clinical trial registries were searched for randomised clinical trials published before May 2020, assessing types of fluids, routes and rates of administration.ResultsA total 15 trials (1073 participants) were included. Age ranged from 38 to 73 years; follow-up period ranged from 0.5 to 6 months. Ringer lactate (RL) showed a reduced number of severe adverse events (SAE) when compared to normal saline (NS) (OR 0.48; 95%CI 0.29–0.81, p = 0.006); additionally, NS showed reduced SAE (RR 0.38; 95%IC 0.27–0.54, p < 0.001) and organ failure (RR 0.30; 95%CI 0.21–0.44, p < 0.001) in comparison with hydroxyethyl starch (HES).High fluid rate fluid infusion showed increased mortality (OR 2.88; 95%CI 1.41–5.88, p = 0.004), increased number of SAE (RR 1.42; 95%CI 1.04–1.93, p = 0.030) and higher incidence of sepsis (RR 2.80; 95%CI 1.51–5.19, p = 0.001) compared to moderate fluid rate infusion.ConclusionsIn patients with AP, RL should be preferred over NS and HES should not be recommended. Based on low-certainty evidence, moderate-rate fluid infusion should be preferred over high-rate infusion.     

Detrimental effect of high volume fluid administration in acute pancreatitis – A retrospective analysis of 391 patients

BackgroundEarly fluid resuscitation is recommended for the therapy of acute pancreatitis in order to prevent complications. There are, however, no convincing data supporting this approach.MethodsWe reviewed 391 consecutive cases of confirmed acute pancreatitis. Admitting physicians had been advised to administer an aggressive fluid resuscitation in the early phase of disease, if possible. We tested whether disease severity according to the revised Atlanta Classification, local complications, and maximum C-reactive protein levels were predictable by the initial volume therapy in logistic and linear regression models, respectively. We also determined which parameters on admission encouraged a more aggressive fluid resuscitation.ResultsThe recorded fluid administered within the first 24 h was 5300 [3760; 7100] ml (median [1st; 3rd quartile]). More aggressive volume therapy was associated with disease severity and a higher rate of local complications. There was a linear relationship between administered volume and the maximum C-reactive protein. The amount of administered fluid was significantly attributed to age, hematocrit, and white blood cell count on admission. When adjusted for these parameters the impact of administered volume on outcome was still present but attenuated.ConclusionsWe found detrimental effects of fluid therapy on major outcome parameters throughout the whole range of administered volume. More volume was administered in younger patients and in patients with evidence of hemoconcentration and inflammation. The adverse effects of volume therapy persisted after elimination of these parameters. Caution should therefore be advised with regards to volume therapy in patients with acute pancreatitis.     

限制性液体复苏在急性上消化道出血致失血性休克中的临床应用

目的:探讨限制性液体复苏在急性上消化道出血致失血性休克中的临床应用.方法:回顾性分析57例急性上消化道出血致休克患者的病历资料,其中常规液体复苏组27例,限制性液体复苏组30例,对复苏后2组患者的血乳酸、血气剩余碱值(BE)、血红蛋白及血小板计数等指标进行统计学分析.结果:限制组患者复苏后的血红蛋白、血小板计数、血乳酸、BE值与常规组相比较,差异均有统计学意义(P＜0.05).结论:对于急性上消化道出血致失血性休克患者,早期限制性液体复苏可有效维持重要脏器的血流灌注,改善全身灌注指标.     

Detailed fluid resuscitation profiles in patients with severe acute pancreatitis

Background and aim

Appropriate and timely initial fluid resuscitation in acute pancreatitis (AP) is critical. The aim of this retrospective study was to evaluate fluid therapy on an hour-by-hour basis in relation to standard indices of adequate resuscitation during AP.

Methods

Emergency room shock charts, fluid balance sheets and intensive care (ICU) charts for all patients with AP admitted to ICU in a large acute hospital were examined. Vital signs, clinical course and fluid administered during the first 72 h after admission were tabulated against urine output, central venous pressure (CVP) and inotrope/vasopressor therapy.

Results

Sixty-three consecutive patients with AP were initially evaluated. Inter-hospital transfers with established organ dysfunction (n = 11) or where records had insufficient detail (n = 22) were excluded. In the remaining 30 patients, in-hospital death occurred in 7. The cumulative volume of crystalloid given was significantly less at 48 h in patients who died in hospital (3331 ± 800 ml vs. survivors, 7287 ± 544 ml; P < 0.001). Non-survivors had a higher CVP, and received more inotropes/vasopressors.

Conclusion

In severe AP-associated organ failure, fluid resuscitation profiles differ between survivors and non-survivors. CVP alone as a crude indicator of adequate resuscitation may be unreliable, potentially leading to the use of inotropes/vasopressors in the inadequately filled patient.     

Early management of acute pancreatitis: A review of the best evidence

In the 20th century early management of acute pancreatitis often included surgical intervention, despite overwhelming mortality. The emergence of high-quality evidence (randomized controlled trials and meta-analyses) over the past two decades has notably shifted the treatment paradigm towards predominantly non-surgical management early in the course of acute pancreatitis. The present evidence-based review focuses on contemporary aspects of early management (which include analgesia, fluid resuscitation, antibiotics, nutrition, and endoscopic retrograde cholangiopancreatography) with a view to providing clear and succinct guidelines on early management of patients with acute pancreatitis in 2017 and beyond.     

Effects of 7.5% hypertonic saline on fluid balance after radical surgery for gastrointestinal carcinoma

AIM: To investigate the effects of 7.5% hypertonic saline on positive fluid balance and negative fluid balance, after radical surgery for gastrointestinal carcinoma. METHODS: Fifty-two patients with gastrointestinal carcinoma undergoing radical surgery were studied. The patients were assigned to receive either Ringer lactate solution following 4 mL/kg of 7.5% hypertonic saline (the experimental group, n = 26) or Ringer lactate solution (the control group, n = 26) during the early postoperative period in SICU. Fluid infusion volumes, urine outputs, fluid balance, body weight change, PaO2/FiO2 ratio, anal exhaust time as well as the incidence of complication and mortality were compared between the two groups. RESULTS: Urine outputs on the operative day and the first postoperative day in experimental group were significantly more than in control group (P<0.000001, P=0.000114). Fluid infusion volumes on the operative day and the first postoperative day were significantly less in experimental group than in control group (P= 0.000042, P= 0.000415). The volumes of the positive fluid balance on the operative day and during the first 48 h after surgery, in experimental group, were significantly less than in control group (P<0.000001). Body weight gain post-surgery was significantly lower in experimental group than in control group (P<0.000001). The body weight fall in experimental group occurred earlier than in control group (P<0.000001). PaO2/FiO2 ratio after surgery was higher in experimental group than in control group (P= 0.000111). The postoperative anal exhaust time in experimental group was earlier than in control group (P= 0.000006). The overall incidence of complications and the incidence of pulmonary infection were lower in experimental group than in control group (P= 0.0175, P= 0.0374). CONCLUSION: 7.5% hypertonic saline has an intense diuretic effect and causes mobilization of the retained fluid, which could reduce fluid infusion volumes and positive fluid balance after radical surgery for gastrointestinal carcinoma, as well as, accelerate the early appearance of negative fluid balance after the surgery, improve the oxygen diffusing capacity of the patients' alveoli, and lower the overall incidence of complications and pulmonary infection after the surgery.     

Clinical management and outcomes of acute pancreatitis: Identifying areas for quality improvement in a tertiary Asian setting

BackgroundThis study aims to review the clinical management of patients with acute pancreatitis in a tertiary institute in Singapore, and to identify areas qualiy improvement based on validation against the recommendations in the IAP/APA and the Japanese guidelines.Methods391 patients from a prospective electronic database were included and reviewed for compliance to the International Association of Pancreatology (IAP)/American Pancreatic Association (APA) guidelines (2013) and the Japanase Guidelines (2015).ResultsThe 90 day mortality was 8.4% for moderately severe and 11.9% for severe pancreatitis. The accuracy of SIRS in predicting severe acute pancreatitis on admission was 72.1% and at 48 h 80.8%. Only 61.1% patients had ultrasound scan during their admission of whom 32.9% had it within 24 h of admission. 18.3% patients with initial diagnosis of idiopathic pancreatitis had EUS. 50% received Ringer lactate for initial fluid resuscitation. 38.7% received antibiotics as prophylaxis. 21.4% with severe acute pancreatitis had early enteral nutrition. Only 21.4% patients with biliary pancreatitis had index admission cholecystectomy.ConclusionThe compliance to existing guidelines for management of acute pancreatitis is variable. Identifying gaps and implementing measures to address them allows for continued improvement in the management of patients with acute pancreatitis.     

Intraductal pressure in experimental models of acute and chronic pancreatitis in mice

Background/ObjectivesPancreatic intraductal pressure is related to the development of pancreatitis, including post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis. In this study, we investigate pancreatic intraductal pressure in various mouse models of acute and chronic pancreatitis.MethodsPost-ERCP pancreatitis was induced by retrograde infusion of normal saline or radiocontrast at the constant rate of 10 or 20 μL/min. Obstructive pancreatitis was induced by ligation of the pancreatic duct followed by a single injection of caerulein and the changes of intraductal pressure were recorded in day 3 for obstructive acute pancreatitis and day 14 for obstructive chronic pancreatitis. Non-obstructive pancreatitis was induced by repetitive intraperitoneal injections of caerulein. The changes of intraductal pressure were recorded right after the last caerulein injection for non-obstructive acute pancreatitis and after the completion of 4-week caerulein injections for non-obstructive chronic pancreatitis.ResultsElevated pancreatic intraductal pressure was observed in both normal saline and radiocontrast infusion groups and was furtherly indicated that was positively correlated with the viscosity of solution but not genders. In the models of obstructive pancreatitis, a rise in intraductal pressure was observed in both acute and chronic pancreatitis; whereas in the models of non-obstructive pancreatitis, a rise in intraductal pressure was only observed in chronic, but not acute pancreatitis.ConclusionsDuring ERCP, the elevations in pancreatic intraductal pressure are induced by increasing rate or viscous solution of infusion. During different forms of experimental acute and chronic pancreatitis, obstructive or non-obstructive etiologies of pancreatitis also induces the elevations in pancreatic intraductal pressure.     

Infusionstherapie im Rettungsdienst

For preclinical treatment of emergency patients, only a few infusion solutions are necessary. Preclinical fluid therapy is especially indicated in patients with hypovolemic shock, including the four subgroups of hypovolemia, and in patients with cardiogenic shock. Further indications are patients with anaphylactic, neurogenic, and septic shock. Fluid replacement means the compensation of interstitial and intracellular fluid deficits, whereas volume replacement means the maintenance of intravascular volume and avoidance of hypovolemia. Balanced crystalloid solutions have properties similar to that of human plasma. With respect to high oxygen demand during lactate metabolization and lack of an increase in plasma lactate concentration, the addition of acetate and/or malate is superior to lactate. The volume effect of hyperosmolar or hyperosmolar-hyperoncotic saline solutions is short and may end abruptly. For maintenance of normovolemia, HES solutions are in widespread use. In the preclinical setting, renal side effects of HES are clinically insignificant, and the hemostatic side effects of HES 130 are hardly relevant. For the therapy of the most relevant emergency situations, ambulances and rescue helicopters should be equipped with a balanced crystalloid solution, 10% HES 130, and a hyperosmolar or hyperosmolar-hyperoncotic saline solution. With respect to the individual situation of the patient, the main goals of infusion and circulatory therapy are the following: SAP >90 mmHg, HR <100/min; patients with craniocerebral trauma SAP >120 mmHg; permissive hypotension SAP 70–80 mmHg.     

New tools for optimizing fluid resuscitation in acute pancreatitis

Acute pancreatitis(AP)is a frequent disease with degrees of increasing severity responsible for high morbidity.Despite continuous improvement in care,mortality remains significant.Because hypovolemia,together with microcirculatory dysfunction lead to poor outcome,fluid therapy remains a cornerstone of the supportive treatment.However,poor clinical evidence actually support the aggressive fluid therapy recommended in recent guidelines since available data are controversial.Fluid management remains unclear and leads to current heterogeneous practice.Different strategies may help to improve fluid resuscitation in AP.On one hand,integration of fluid therapy in a global hemodynamic resuscitation has been demonstrated to improve outcomein surgical or septic patients.Tailored fluid administration after early identification of patients with high-risk of poor outcome presenting inadequate tissue oxygenation is a major part of this strategy.On the other hand,new decision parameters have been developed recently to improve safety and efficiency of fluid therapy in critically ill patients.In this review,we propose a personalized strategy integrating these new concepts in the early fluid management of AP.This new approach paves the way to a wide range of clinical studies in the field of AP.     

Splanchnic tissue perfusion in acute experimental pancreatitis

BACKGROUND: Gut hypoperfusion may have a role in the pathogenesis of multiple organ failure, which is a the main cause of death in severe acute pancreatitis. We hypothesized that gut hypoperfusion is present early in acute pancreatitis and that supporting the systemic hemodynamics by fluid resuscitation would prevent this. METHODS: In a pig model of randomized, controlled experimental hemorrhagic pancreatitis induced by Na-taurocholate the animals were divided into four groups (n = 6 for each): 1) pancreatitis, 2) control, 3) pancreatitis and fluid resuscitation to keep the pulmonary capillary wedge pressure at 5 to 6 mmHg, and 4) control and fluid resuscitation as in group 3. Splanchnic perfusion was assessed by means of local PCO2 gap with intestinal tonometer, oxygen delivery and consumption, lactate production, and blood flow. The follow-up time was 6 h. RESULTS: The Pco2 gap increased in pancreatitis (1.72+/-0.17, 1.94+/-0.29, 1.75+/-0.22, 2.32+/-0.33; 9.40+/-2.16, 3.72+/-1.78, 0.84+/-0.39, 1.11+/-0.21 kPa, respectively; P < 0.05). Oxygen delivery in portal-drained organs decreased in pancreatitis (2.5+/-0.3, 2.6+/-0.2, 2.8+/-0.4, 2.3+/-0.2; 1.7+/-0.3, 2.3+/-0.3, 2.4+/-0.5, 2.3+/-0.3 ml/min x kg, respectively; P < 0.05). Regional oxygen consumption did not change. Arterial plasma lactate increased (1.20+/-0.19, 1.33+/-0.16, 1.14+/-0.15, 1.43+/-0.33; 3.81+/-1.31, 1.48+/-0.48, 1.12+/-0.18, 1.18+/-0.35 mmol/l, respectively; P < 0.05). The portal venous blood flow decreased 50% in pancreatitis, but with fluid resuscitation it increased 50%. CONCLUSIONS: Splanchnic hypoperfusion is present early in acute hemorrhagic pancreatitis. The signs of hypoperfusion can be prevented with fluid resuscitation.     

Fluid resuscitation in acute medicine: what is the current situation?

The administration of intravenous fluids for resuscitation is the most common intervention in acute medicine. There is increasing evidence that the type of fluid may directly affect patient‐centred outcomes. There is a lack of evidence that colloids confer clinical benefit over crystalloids and they may be associated with harm. Hydroxyethyl starch preparations are associated with increased mortality and use of renal replacement therapy in critically ill patients, particularly those with sepsis; albumin is associated with increased mortality in patients with severe traumatic brain injury. Crystalloids, such as saline or balanced salt solutions, are increasingly recommended as first‐line resuscitation fluids for the majority of patients with hypovolaemia. There is emerging evidence that saline may be associated with adverse outcomes due to the development of hyperchloraemic metabolic acidosis, although the safety of balanced salt solutions has not been established. Fluid requirements vary over the course of critical illness. The excessive use of fluids during the resuscitative period is associated with increased cumulative fluid balance and adverse outcomes in critically ill patients. The selection of fluid depends on the clinical context in which it is administered and requires careful consideration of the dose and potential for toxicity. There is an urgent need to conduct further high‐quality randomized controlled trials of currently available fluid therapy in patients with critical illness.     

Endotherapy for pancreatic necrosis and abscess: endoscopic drainage and necrosectomy

Pancreatic necrosis and abscess are among the most severe complications of acute pancreatitis. Endoscopic drainage of pancreatic fluid collections has been increasingly performed in many tertiary care centers. The type of fluid collection that is being intervened upon determines the outcome. The development of endoscopic ultrasonography (EUS) has expanded the safety and efficacy of this modality by allowing one to access and drain more challenging fluid collections. The technique and review of current literature regarding endoscopic therapy of pancreatic necrosis and abscess will be discussed.     

Hypertriglyceridemia and acute pancreatitis

Hypertriglyceridemia is the third most common cause of acute pancreatitis. It typically occurs in patients with an underlying disorder of lipoprotein metabolism and in the presence of a secondary condition such as uncontrolled diabetes, alcohol abuse, or medication use.The presentation of hypertriglyceridemia-induced pancreatitis is similar to that of acute pancreatitis due to other causes; however, patients with hypertriglyceridemia-induced pancreatitis are more likely to have severe disease courses and have a higher likelihood of persistent organ failure. The initial treatment of hypertriglyceridemia-induced pancreatitis is also similar to acute pancreatitis from other causes and consists of aggressive fluid resuscitation, pain control, and nutritional support. Hypertriglyceridemia is specifically treated with apheresis or insulin therapy when necessary.The prompt recognition of hypertriglyceridemia in the setting of acute pancreatitis is essential in both the initial and long-term management of this disease and are essential to prevent recurrent acute pancreatitis. The review seeks to highlight the etiology, pathogenesis, and clinical course of hypertriglyceridemia-induced acute pancreatitis.     

Optimising fluid requirements after initial resuscitation: A pilot study evaluating mini-fluid challenge and passive leg raising test in patients with predicted severe acute pancreatitis

BackgroundThe goals and approaches to fluid therapy vary through different stages of resuscitation. This pilot study was designed to test the safety and feasibility of a fluid therapy protocol for the second or optimisation stage of resuscitation in patients with predicted severe acute pancreatitis (SAP).MethodsSpontaneously breathing patients with predicted SAP were admitted after initial resuscitation and studied over a 24-h period in a tertiary hospital ward. Objective clinical assessment (OCA; heart rate, mean arterial pressure, urine output, and haematocrit) was done at 0, 4, 8, 12, 18–20, and 24 h. All patients had mini-fluid challenge (MFC; 250 ml intravenous normal saline within 10 min) at 0 h and repeated at 4 and 8 h if OCA score ≥2. Patients who were fluid responsive (>10% change in stroke volume after MFC) received 5–10 ml/kg/h, otherwise 1–3 ml/kg/h until the next time point. Passive leg raising test (PLRT) was done at each time point and compared with OCA for assessing volume status and predicting fluid responsiveness.ResultsThis fluid therapy protocol based on OCA, MFC, and PLRT and designed for the second stage of resuscitation was safe and feasible in spontaneously breathing predicted SAP patients. The PLRT was superior to OCA (at 0 and 8 h) for predicting fluid responsiveness and guiding fluid therapy.ConclusionsThis pilot study found that a protocol for intravenous fluid therapy specifically for the second stage of resuscitation in patients with predicted SAP was safe, feasible, and warrants further investigation.     

重症急性胰腺炎早期体液代谢特征和液体复苏

早期重症急性胰腺炎(SAP)胰腺局部产生的大量炎症因子、血管活性物质和有毒物质溢入循环.引发全身性炎症反应综合征(SIRS)。微血管损伤、微循环障碍以及出凝血机制异常明显增加毛细血管的通透性,使更多的血浆成分和组织液丢失,甚至出现全身毛细血管渗漏综合征(CLS)。因此,缓解血浆和组织液严重丢失是SAP早期急救治疗的关键,从而防治多器官功能衰竭(MOF)。为尽早恢复组织细胞生存代谢的微循环系统,应强调应用高渗NaCl溶液、低分子右旋糖酐、血浆或一些新型胶体复苏液实施合理的液体复苏。当然,只有综合采用液体复苏以及血液净化、高压氧疗等方法才可能获得SAP早期急救的成功。     

Akute Pankreatitis

Acute pancreatitis is a potentially fatal disease. It can be diagnosed based on present history, the patient’s clinical appearance, and, typically, laboratory and radiological findings. Each patient must be admitted to the hospital because the disease course cannot be determined at the initial presentation. Increasing severity demands an increasingly individualized therapy, but the most important interventions are rapid fluid resuscitation and analgesic therapy with opioids. Pancreatitis-specific therapeutic agents have failed to prove any advantages so far. The roles of antibiotic therapy and nutritional support have been carefully reassessed over the last years. Surgery and endoscopic interventions could be necessary and beneficial for well-selected patients. In this review, we summarize the clinically relevant issues in acute pancreatitis.