Early Goal-directed Volume Resuscitation in Severe Acute Pancreatitis

Study Overview
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Brief Summary
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Acute pancreatitis (AP) is a common disorder with rising incidence varying between 35 and 80 per 100,000 in Europe and the USA. About 15% of patients develop necrotizing pancreatitis (NP) with a mortality of up to 42% and frequently prolonged hospitalisation in the survivors. Despite a fulminant pathophysiology comparable to that of sepsis, the management of NP is still re-active, symptomatic and mainly based on paradigms with low grade evidence. In sepsis beneficial effects of early goal-directed fluid resuscitation resulting in reduced mortality have been clearly shown. With regard to these data and several studies of NP demonstrating the deleterious effects of fluid loss and haemoconcentration within the first 24h after admission, early goal-directed fluid resuscitation has the potential of improving outcome also in NP. Therefore, it is the aim of this RCT to demonstrate beneficial effects of early goal-directed resuscitation using an algorithm based on modern haemodynamic parameters such as Intra-thoracic Blood Volume Index (ITBI), Extravascular Lung Water Index (ELWI) and Stroke Volume Variation (SVV) which can be easily and safely obtained due to recent progress in haemodynamic monitoring. The algorithm is aimed at maintaining adequate resuscitation (ITBI, SVV) as well as preventing pulmonary over-hydration (ELWI).The use of a similar algorithm in cardiac surgery patients resulted in a significant reduction in catecholamine use, lactate levels, duration of ventilation and ICU stay.

Detailed Description
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Resuscitation using crystalloids and/or colloids with the following goals: ITBI: 850 -1000 ml/sqm, if ELWI <=12*ml/kg 750 - 850 ml/sqm, if ELWI >12*ml/kg and/or PaO2:FiO2 <200 *ELWI <=12ml/kg, if MAP>65mmHg without catecholamines <=14ml/kg, if catecholamines required for MAP>65mmHg SVV <10% (only in controlled ventilation and sinus rhythm) MAP >65mmHg (MAP: Mean Arterial Pressure) IAPP >60mmHg (IAPP: Intra-abdominal Perfusion Pressure)

Official Title
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EAGLE: Early Goal-directed Volume Resuscitation in Severe Acute Pancreatitis: A Randomised Multi-centre Study

Conditions
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Acute Pancreatitis

Intervention / Treatment
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* Other: PiCCO-parameter-guided volume resuscitation
* Other: Control-group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of pancreatitis: Typical pain Increase in serum lipase or amylase Onset of abdominal pain within <=48h before admission APACHE II >= 8 Evidence of >= 1 predictor of severe pancreatitis: Haematocrit >44% (male) or >40% (female), respectively Blood glucose > 125 mg/dl; CRP >= 10 mg/dl; Age > 55 years; Leukocytes >= 16 G/L GOT > 250 U/L; LDH > 350 U/L Calcium < 2,0 mmol/L CK > upper normal range Balthazar-score(CT classification) Grade C-E Any organ failure Exclusion Criteria: Pregnancy NYHA >II Pre-existing disease with life expectancy < 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PiCCO-group<br>Insertion of an arterial PiCCO catheter. Resuscitation using crystalloids and/or colloids according to PiCCO-parameter-guided algorithm | Other: PiCCO-parameter-guided volume resuscitation<br>* Insertion of an arterial PiCCO catheter. Resuscitation using crystalloids and/or colloids with the following goals: ITBI: 850-1000 ml/sqm, if ELWI <=12*ml/kg; ITBI 750-850 ml/sqm, if ELWI >12*ml/kg and/or PaO2:FiO2 <200 (*ELWI<=12ml/kg, if MAP>65mmHg without catecholamines; ELWI<=14ml/kg, if catecholamines required for MAP>65mmHg); SVV<10% (only in controlled ventilation and sinus rhythm); MAP>65mmHg (MAP: Mean Arterial Pressure); IAPP >60mmHg (IAPP: Intra-abdominal Perfusion Pressure)<br>|
| Other: 2<br>Control: Haemodynamic management without ITBI and ELWI using any other haemodynamic monitoring tool, with the exception of the PiCCO-system. | Other: Control-group<br>* Haemodynamic management without ITBI and ELWI using any other haemodynamic monitoring tool, with the exception of the PiCCO-system. Main haemodynamic goals: CVP 8-12 mmHg; MAP >65mmHg;IAPP >60mmHg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in APACHE II >=4 within 4 days as compared to baseline (admission to ICU) |  | 4 days after admission to the ICU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | ICU-, 28-days- and in hospital mortality | 
| APACHE-II-Score |  | 4d; 7d; 28d | 
| Number of ICU-days |  | Admission to transfer or death | 
| Percentage of organ failure within each group |  | Time of ICU-stay | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe pancreatitis, acute pancreatitis, haemodynamic monitoring, PiCCO