Consensus of primary care in acute pancreatitis in Japan

Table 1 Principles of treatment for patients with acute pancreatitis at initial and early stage

Management	Physical check lists	Examination	Treatment
Within 24 h after onset
Initial vigorous intravenous hydration Severity stratification Assessment of etiology All patients with severe acute pancreatitis should be transferred to a high special unit or intensive therapy unit.	Consciouness status Abdominal findings Blood pressure Pulse rate Respiratory rate Body temperature Urinary volume Pulse oximetry (SpO2)	CBC and blood chemistry Chest and abdominal x-ray Abdominal US Abdominal CT and/or MRI Arterial blood gas analysis	Secure and maintain venous route Initial fluid resuscitation (60-160 mL/kg body weight/day) For the first 6 h, fluid resuscitation of about 1/2-1/3 of the amount required for the first 24 h Analgesics and oxygen, as required Protease inhibitors Antibiotics for severe cases and infection of the bile duct Consider CRAI CHDF in severe cases Urgent therapeutic ERCP or EST in patients with cholangitis or with disturbed bile flow (refer to a specialist unit where facilities and expertise are available for ERCP and EST)
From 24 to 48 h after onset
Re-evaluation of severity All patients with severe acute pancreatitis should be transferred to a high special unit or intensive therapy unit.	Consciouness status Abdominal findings Blood pressure Pulse rate Respiratory rate Body temperature Urinary volume Pulse oximetry (SpO2)	CBC and blood chemistry Chest and abdominal x-ray Arterial blood gas analysis Abdominal CE-CT, as required	Similar to the above-mentioned treatment In addition Correction of fluid resuscitation Enteral feeding in patients without clear signs and symptoms of ileus and gastrointestinal bleeding
After 48 h of onset
Fundamental conservative therapy in moderate and mildcases All patients with severe acute pancreatitis should be transferred to a high special unit or intensive therapy unit.	Consciouness status Abdominal findings Blood pressure Pulse rate Respiratory rate Body temperature Urinary volume Pulse oximetry (SpO2)	CBC and blood chemistry Chest and abdominal x-ray Arterial blood gas analysis Abdominal CE-CT, as required	Similar to the above-mentioned treatment In addition Correction of fluid resuscitation Enteral feeding in patients without clear signs and symptoms of ileus and gastrointestinal bleeding

SpO₂: Blood oxygen saturation level, CBC: Complete blood count; US: Ultrasonography; CT: Computed tomography, MRI: Magnetic resonance imaging; CE-CT: Contrast-enhanced computed tomography; ERCP: Endoscopic retrograde cholangiopancreatography; EST: Endoscopic sphincterotomy; CRAI: Continuous regional arterial infusion of protease inhibitors and antibiotics; CHDF: Continuous hemodiafiltration.

Table 2 Criteria for grading the severity of acute pancreatitis

Prognostic factors	Clinical signs	Laboratory data
Prognostic factor I (2 points for each positive factor)	Shock	BE ≤ -3 mEq/L
	Respiratory failure	Ht ≤ 30% (after hydration)
	Mental disturbance	BUN ≥ 40 mg/dL or
	Severe infection	creatinine ≥ 2.0 mg/dL
	Hemorrhagic diathesis
Prognostic factor II (1 point for each positive factor)		PaO2 ≤ 60 mmHg (room air) FBS ≥ 200 mg/dL Total protein ≤ 60 g/L LDH ≥ 700 IU/L Ca ≤ 7.5 mg/dL Prothrombin time ≥ 15 s Platelet count ≤ 1 × 105 /mm3 CT grade IV or V1
Prognostic factor III	SIRS score ≥ 3 (2 points) Age≥ 70 yr (1 point)

BE: Base excess, Ht: Hematocrit, BUN: Blood urea nitrogen; FBS: Fasting blood sugar; LDH: Lactate dehydrogenase; SIRS: Systemic inflammatory response syndrome.

¹CT grade IV or V: Presence of diffuse and uneven density in the pancreatic parenchyma or the presence of inflammatory changes extending beyond the border of the pancreas. Severity score: Sum of the points for the positive prognostic factors is defined as the severity score. Standardized criteria: Severe: Presence of more than one prognostic factor I, and/or the presence of more than two prognostic factor II (severity score ≥ 2 points). Moderate: Presence of one prognostic factor II (severity score = 1 point). Mild: Acute pancreatitis without prognostic factor I or II (severity score = 0 point).

Table 3 Stage classification of acute pancreatitis and mortality rate in nationwide survey in 2003 in Japan

Stage	Severity score	Severity	No of patients(%)1	Died2	Mortality rate
Stage 0	0 point	Mild	943 (53.3)	1	0.10%
Stage 1	1 point	Moderate	280 (15.8)	2	0.70%
Stage 2	2-8 points	Severe I	455 (25.7)	17	3.70%
Stage 3	9-14 points	Severe II	63 (3.6)	16	25.40%
Stage 4	≥ 15 points	Most severe	27 (1.5)	16	59.30%
Total			1768 (100)	52	2.90%

¹In 2004, nationwide survey of patients with acute pancreatitis who visited the hospitals in the year 2003 (from January 1 to December 31) was performed by stratified random sampling method. From the first survey, the total number of patients treated for acute pancreatitis in Japan in the year 2003 was estimated as 35 300 (95% confidence interval, 30 500-40 000). Clinical records of 1768 patients with acute pancreatitis were obtained in the second survey for analysis of etiology and outcome.

²Number of patients who died of acute pancreatitis or related complications.

Table 4 Recommended doses of protease inhibitors for acute pancreatitis[47]

	Mild and moderate	Severe
Protease inhibitor	FOY	FOY ＋ UTI
	FUT	FUT ＋ UTI
	UTI
Initial dose2 (during the first 12 h)	Maximum usual one- day dose1 by continuous intravenous infusion	Maximum usual one- day dose1 by continuous intravenous infusion
Until d 32	Above dose for 24 h	Above dose for 24 h
First wk2	Gradually reduce the above dose or intermittent administration	Above dose for 24 h
Second wk2	Reduce the dose or cease	Maintain or gradually reduce the above dose
Third wk2	Reduce the dose or cease	Maintain or gradually reduce the above dose

FOY: Gabexate mesilate, FUT: Nafamostat mesilate, UTI: Ulinastatin.

¹Administer the one-day dose during the initial 12 h.

²Severity stratification should be made repeatedly, and the doses of protease inhibitors must be increased or decreased depending on the severity. The usual daily dosage for acute pancreatitis of FOY, FUT and UTI approved by the health insurance is 200-600 mg, 10-60 mg and 50 000-150 000 units, respectively. Since, however, severe acute pancreatitis often complicates disseminated intravascular coagulation (DIC) and shock, it is recommended to give these reagents in doses that are approved for these disorders in severe acute pancreatitis (daily dosage for severe acute pancreatitis of FOY, FUT and UTI is 20-39 mg/kg body weight/d, 1.44-4.8 mg/kg body weight per day, and 10 000-300 000 units /d, respectively).