Ward-based goal-directed fluid therapy (GDFT) in acute pancreatitis

INTERVENTION: Patients admitted with acute pancreatitis will be randomised using sealed envelope (www.sealedenvelope.com) to one of the following groups for the first 48 hours of the hospital stay: Standard care: The amount and rate of fluid therapy (balanced electrolyte solution) will be based on the blood pressure, heart rate and urine output as per clinician choice. Ward based GDFT: GDFT will be carried out for 48 hours after admission. It can take up to 48 hours for the severity of pancreatitis to manifest. GDFT will be based on a standard algorithm which uses the stroke volume (SV) derived from non‐invasive cardiac output monitoring using the Cheetah NICOM. The fluid administration will be as follows: Maintenance fluid should be administered at 1.5 ml/kg/hr as a balance crystalloid solution. On admission SV is recorded and an initial bolus of 250ml of IV fluid (balanced electrolyte solution) is given over 5 to 10 minutes. If there is a sustained rise in stroke volume for 15 minutes or more, this indicates fluid responsiveness and a repeat 250ml bolus will be given. If there is a rise in SV of more than 10%, the patient is deemed to be fluid responsive and the process of administering a fluid bolus repeated. If there is not a rise in SV of 10% or more then the patient is deemed fluid unresponsive and no further fluid bolus is administered. SV monitoring continues four hourly and if it decreases by more than 10% a further fluid bolus is administered as above. Total duration of follow‐up is 3 months. CONDITION: Specialty: Surgery, Primary sub‐specialty: Other; UKCRC code/ Disease: Oral and Gastrointestinal/ Disorders of gallbladder, biliary tract and pancreas ; Digestive System ; Acute pancreatitis PRIMARY OUTCOME: Feasibility assessed at the end of the study period by the following criteria:; 1. A consent rate of at least 30% is achieved; 2. The ability to recruit 50 patients to the study at the two sites over 17 months; 3. GDFT can be successfully performed within 6 hours of diagnosis of acute pancreatitis and can be continued until at least 48 hours after admission in a minimum of 80% of participants randomised to GDFT; 4. The complication rate in the intervention group is not more than 10% higher than that of the control group at 90 days INCLUSION CRITERIA: Acute pancreatitis will be confirmed by international consensus criteria for diagnosis of acute pancreatitis i.e. two of the following three features: 1. Abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back) 2. Serum amylase or lipase activity at least three times greater than the upper limit of normal 3. Characteristic findings of acute pancreatitis on contrast‐enhanced computed tomography (CECT) and less commonly magnetic resonance imaging (MRI) or transabdominal ultrasonography SECONDARY OUTCOME: A number of outcome measures will also be collected in order to assess safety and determine the optimum primary outcome and for a subsequent larger randomised controlled trial in which both clinical and cost effectiveness shall be assessed:; 1. Mortality, recorded up to the end of the 3 month follow‐up period; 2. Health‐related quality of life (HRQoL), assessed by EQ‐5D‐5L questionnaire at admission (estimated from information prior to onset of acute pancreatitis), 7 days, 30 days and 90 days following the attack of pancreatitis; 3. Outcomes including treatment‐related adverse events and serious adverse events as well as proportion of people with severe acute pancreatitis, necrotising pancreatitis, infected pancreatic necrosis, requiring intensive therapy unit (ITU) stay, requiring renal replacement therapy, requiring ventilation, surgical interventions for complications related to pancreatitis, positive blood cultures, duration of ventilation, length of ITU and hospital stay, time to return to pre‐pancreatitis activities, number of work days lost (in those who work), and costs (NHS and PSS (personal social services) perspective, collected until discharge and at 30 and 90 days follow‐up; 4. Routine blood tests including inflammatory markers (C‐reactive protein, WCC), liver function tests, clotting, renal function and arterial blood gases, recorded daily for up to 7 days after acute onset of pancreatitis and twice weekly until discharge (if longer admission than 7 days); 5. Serum samples collected by venesection for markers of endothelial injury, collected at the start of intervention (t=0), 6, 12, 24 and 48 hours; 6. Microcirculatory changes assessed using sublingual videomicroscopy (Cytocam‐IDF) at baseline and post‐intervention (48 hours)