Severe acute pancreatitis: Clinical course and management

Table 1 Severe acute pancreatitis: Gut barrier dysfunction causes local changes and systemic complications

Local	Systemic consequences
Mucosal ischemia[10,15,16]	Priming of neutrophils[20-22]
Disruption of mucosal epithelial integrity[17]	Endotoxemia[14,23,24]
Reperfusion injury of mucosal epithelia[18]	Bacterial translocation[25-27]
Increase of intestinal permeability[19]	Cytokine overproduction[1,2,28]
Gram-negative intestinal bacterial	Impaired systemic immunity[29,30]
overgrowth[11]
Impaired mucosal immunity[11]

Table 2 Clinical course of AP/SAP

Clinical		Pathophysiologic process
Early: d 1-10 after HA	Hypovolemia Abdominal pain	Fluid sequestration Liberation of pro- and anti-
ESAP in about 20% of SAP	Dysfunction Pulmonary Renal	inflammatory cytokines Endotoxemia
	Cardiocirculatory	Liberation of vasoactive substances
	Liver	Disturbance of blood coagulation
	Intestine	Translocation of endotoxin and bacteria
Late > 2 wk after HA	Local and systemic	Bacterial translocation
	septic complications	CARS
	IN, SPN	Anti-inflammatory reaction Immunosuppression

AP: Acute pancreatitis; SAP: Severe acute pancreatitis; ESAP: Early severe acute pancreatitis; HA: Hospital admission; IN: Infected necrosis; SPN: Sterile pancreatic necrosis; CARS: Compensatory antiinflammatory syndrome.

Table 3 Severe acute pancreatitis-early organ failure

Admission		Dynamic of organ failure			Hospital mortality
ESAP (n = 47)	SOF	25 (53%)	Reversible 9 develop MOF 14 (30%)		42%
	MOF	22 (47%)	Reversible 1 progress to MOFS 21 (95%)
SAP (n = 111)	OF (-)	30 (27%)
	SOF	26 (23%)			14%
	MOF	55 (50%)

ESAP: Early severe acute pancreatitis; SOF: Single organ failure; MOF: Multiorgan failure; SAP: Severe acute pancreatitis; OF: Organ failure. Reversibility or assistance in spite of maximum intensive care treatment of early organ failure or early organ failure syndrome (n = 158)[48].

Table 4 Frequency of pancreatic infection in 427 patients¹ with necrotizing pancreatitis²

		NP (%)	AP (%)
Infected necrosis	99	23.2	6.9
Pancreatic abscess	40	9.4	2.8
Infected pseudocyst
after AP	7	1.6	0.5
Total	146	34.2	10.1

¹Pancreatic necrosis/extrapancreatic fatty tissue necrosis, pancreatic abscess, postacute pseudocyst. ²5/1982-12/1996 Department of General Surgery, University of Ulm.

Table 5 Severe acute pancreatitis: Clinical systems to predict prognosis

	Cut-off	Time	Reference
Ranson	> 2 points	> 48 h	SGO 1974[71]
Apache II	> 9 points	daily	Br J Surg 1990[65]
Balthazar	C, D, E	> first week	Radiology 1990[69]
Marshall score	> 3 points	72 h	Crit Car Med 1995[45]
MOF/Goris	> 1 point	48 h	Arch Surg 1985[46]
SOFA	> 4 points	48 h/d	Crit Car Med 1996[41]

MOF: Multiorgan failure; SOFA: Sepsis-related organ failure assessment.

Table 6 Early prediction of infected necrosis, infected necrosis + MODS and death using biochemical parameters

	Cut-off	Sensitivity(%)	Specificity(%)	Accuracy(%)
Prediction of infected necrosis
PCT	≥ 1.4 ng/mL	75	68	69a
CRP	≥ 400 mg/L	29	92	76
Prediction of infected necrosis and MODS
PCT	≥ 3.8 ng/mL	80	93	92a
CRP	≥ 410 mg/L	35	93	87
Prediction of death
PCT	≥ 3.8 ng/mL	82	88	88a
Prediction of IN and MODS or death
PCT	≥ 3.8 ng/mL	76	94	92a
CRP	≥ 400 mg/L	35	92	84

PCT: Randomized controlled trial; CRP: C reactive protein; MODS: Multiorgan dysfunction syndrome; IN: Infected necrosis. Receiver operating curve-analysis based on d 3 and 4 onset of symptoms,

^aP < 0.05-0.004, Rau, Annals of Surgery 2007[72].

Table 7 Severe acute pancreatitis-antibiotic prophylaxis is inefficient in severe acute pancreatitis; results of two randomized controlled double-blind multicentric trials

	Isenmann[79]		Dellinger[80]
	2004	P value	2005	P value
Patients (n)	114		100
Treatment (n)1	48		40
Placebo (n)	41		40
Infection of necrosis
Treatment	12%1	NS	23%2	NS
Placebo	14%1		15%2
Need for surgery
Treatment	17%1	NS	23%2	NS
Placebo	11%1		24%2
Hospital mortality
Treatment	12%1	NS	20%2	NS
Placebo	9%1		18%2

¹Statistical comparison of treatment and placebo group data 2004;

²Data 2005.

Table 8 Severe acute pancreatitis-enteral feeding reduces infection in the need for surgical intervention

Benefits of enteral nutrition	Lower infections (P = 0.004)
	Reduced surgical interventions (P = 0.05)
	Reduced LHS-2.9 d (P < 0.001)
Differences	Hospital mortality (P = 0.3)
	Non-infectious complications (P = 0.16)

LHS: Length of hospital stay. Enteral feeding vs parenteral nutrition, results of 6 RCTs, meta-analysis of 263 patients[81-86].

Table 9 Severe acute pancreatitis-surgical and non-surgical treatment: Ulm Experience: 1568 patients¹ n (%)

	Patients	Conservative	Surgery/Intervention
Interstitial-oedematous	1071 (68.3)	1056 ( 98.6)	15 (1.4)2
Necrotizing pancreatitis	359 (22.9)	95 (26.5)	264 (73.5)
Sterile necrosis	227	85 ( 37.5)	142 (62.5)
Infected necrosis	132	10 (7.6)	122 (92.4)
Pancreatic abscess	42 (2.7)	3 (7.1)	39 (92.9)
Postacute pseudocyst	96 (6.1)	22 ( 22.9)	74 (77.1)

¹5/1982-12/1999 Department of General Surgery, University of Ulm, Germany.

²Biliary tract surgery not included.

Table 10 Results of open surgical debridement of necrotizing pancreatitis using surgical debridement and local bursa lavage

		Complication		Hospital mortality
	n	Postop, n (%)	Reop, n (%)	n (%)
Pederzoli 1990[90]	191	55 (29)	34 (18 )	40 (21)
Beger 1999[92]	221	122 (55)	93 (42)	46 (21)
Mai 2000[61]	27	10 (37)	6 (22)	5 (18)
Hungness 2002[93]	26		4 (15.4)	6 (23)
Farkas 2006[94]	220	43%	48 (22)	17 (7.7)
Howard 2007[95]	102	83 (81)	69 (68)	12 (11.8)
1990-2007	787	43%	29.60%	14.70%

Table 11 Results of minimal invasive interventional treatment of necrotizing pancreatitis: Minimal invasive debridement + local lavage

	n	Infect.necrosis(%)	ApacheII	Time0-S	Earlymorbidity(%)	OP/pts	Hospitalmortality(%)
Freeny 1998[96]	34	100	-				20
Goiuzi 1999[97]	32	81	26				15
Carter 2000[98]	10	90		24 d	10	3	20
Horvath 2001[99]	6	100			33		0
Castellanos 2002[100]	15	100			40		27
Connor 2003[101]	24	58	8		88	4	25
Zhou 2003[102]	12	58		72/102			0
Connor 2005[102]	47	81	9	28 d	92	3	19
1998-2006	156 pts	83			70.6		18.3

OP: Operation per patient; O: Onset of disease; S: Surgery.