Clinical trial NCT00894907: Early Goal-directed Volume Resuscitation in Severe Acute Pancreatitis
Official title: EAGLE: Early Goal-directed Volume Resuscitation in Severe Acute Pancreatitis: A Randomised Multi-centre Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Pancreatitis
Keywords: Severe pancreatitis
acute pancreatitis
haemodynamic monitoring
PiCCO
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
First posted: 2009-05-07
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of pancreatitis:

   * Typical pain
   * Increase in serum lipase or amylase
2. Onset of abdominal pain within \<=48h before admission
3. APACHE II \>= 8
4. 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:

1. Pregnancy
2. NYHA \>II
3. Pre-existing disease with life expectancy \< 3 months

Primary outcomes:
measure: Increase in APACHE II >=4 within 4 days as compared to baseline (admission to ICU)
timeFrame: 4 days after admission to the ICU
Secondary outcomes:
measure: Mortality
timeFrame: ICU-, 28-days- and in hospital mortality
measure: APACHE-II-Score
timeFrame: 4d; 7d; 28d
measure: Number of ICU-days
timeFrame: Admission to transfer or death
measure: Percentage of organ failure within each group
timeFrame: Time of ICU-stay
Other outcomes:
Locations:
city: Munich
country: Germany
facility: 2nd Medical Department; Klinikum Rechts der Isar
Study officials:
References:
citation: Huber W, Umgelter A, Reindl W, Franzen M, Schmidt C, von Delius S, Geisler F, Eckel F, Fritsch R, Siveke J, Henschel B, Schmid RM. Volume assessment in patients with necrotizing pancreatitis: a comparison of intrathoracic blood volume index, central venous pressure, and hematocrit, and their correlation to cardiac index and extravascular lung water index. Crit Care Med. 2008 Aug;36(8):2348-54. doi: 10.1097/CCM.0b013e3181809928.