Timing of endoscopic retrograde cholangiopancreatography in the treatment of acute cholangitis of different severity

Table 1 Characteristics of the patients

Patient characteristics	Total, n = 683	Time to ERCP divided by 24 h			Time to ERCP divided by 48 h
		ERCP ≤ 24 h, n = 134	ERCP > 24 h, n = 549	P value	ERCP ≤ 48 h, n = 314	ERCP > 48 h, n = 369	P value
Age in yr1	66 (53-78)	64 (56-75.5)	66 (52-78)	0.803	65 (54-79)	66 (51-79)	0.518
Male sex, n (%)	391 (57.2)	76 (56.7)	315 (57.4)	0.890	171 (54.5)	220 (59.6)	0.174
Body temperature in °C1	37.5 (36.8-38.4)	37.2 (36.7-38.1)	37.5 (36.9-38.5)	0.003	37.4 (36.8-38.28)	37.6 (36.9-38.5)	0.009
Abnormal WBC count2, n (%)	399 (58.4)	95 (70.9)	304 (55.4)	0.001	195 (62.1)	204 (55.3)	0.072
Platelet count as /µL1	198 (148-251)	205 (142-256)	196.5 (149-250)	0.806	195 (148-249.8)	200 (148-251.5)	0.844
AST in U/L1	150 (83-305)	175 (97-406)	145 (80-289)	0.063	164 (95-311)	139 (76-302)	0.08
ALT in U/L1	166 (82-300)	194 (118-337)	156 (79-292)	0.02	188 (101-311)	142 (69-277)	0.004
ALK-P in U/L1	205 (133-327)	198 (123-321)	209 (133-327)	0.486	190 (123-329)	211 (140-324)	0.208
Amylase in U/L1	65 (41-170) (n = 307)	68 (42-634) (n = 66)	65 (40-145) (n = 241)	0.126	68 (41-367) (n = 138)	62 (40-139) (n = 169)	0.118
Lipase in U/L1	37 (26-144) (n = 487)	46 (25-1297) (n = 97)	36 (26-99) (n = 390)	0.104	41 (26-339) (n = 232)	35 (26-76) (n = 255)	0.094
Bilirubin in mg/dL1	3.7 (2.3-6.3)	4.1 (2.6-5.8)	3.7 (2.3-6.3)	0.395	3.8 (2.4-6.2)	3.7 (2.3-6.5)	0.878
PT/INR1	1.1 (1.1-1.2)	1.1 (1.1-1.3)	1.1 (1.1-1.2)	0.685	1.1 (1.1-1.2)	1.2 (1.1-1.3)	0.001
Creatinine in mg/dL1	0.93 (0.73-1.24)	0.96 (0.78-1.45)	0.93 (0.72-1.20)	0.040	0.95 (0.75-1.28)	0.93 (0.72-1.21)	0.389
Albumin in g/dL1	3.56 (3.05-3.98) (n = 133)	3.83 (3.24-4.0) (n = 23)	3.48 (3.05-3.98) (n = 110)	0.218	3.69 (3.21-3.96) (n = 43)	3.46 (2.98-3.99) (n = 90)	0.334
Cardiovascular dysfunction, n (%)	29 (4.2)	15 (11.2)	14 (2.6)	< 0.001	18 (5.7)	11 (3.0)	0.076
Neurological disturbance, n (%)	35 (5.1)	9 (6.7)	26 (4.7)	0.351	16 (5.1)	19 (5.1)	0.975
Respiratory dysfunction, n (%)	48 (7)	19 (14.2)	29 (5.3)	< 0.001	24 (7.6)	24 (6.5)	0.562

¹Expressed as median (interquartile range).

²Abnormal WBC count is defined as WBC < 4000/µL or > 12000/µL.

ALK-P: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BT: Body temperature; ERCP: Endoscopic retrograde cholangiopancreatography; PT/INR: Prothrombin time/international normalized ratio; WBC: White blood cell count.

Table 2 Characteristics of endoscopic retrograde cholangiopancreatography

Patient characteristics	Total, n = 683	Time to ERCP divided by 24 h			Time to ERCP divided by 48 h
		ERCP ≤ 24 h, n = 134	ERCP > 24 h, n = 549	P value	ERCP ≤ 48 h, n = 314	ERCP > 48 h, n = 369	P value
Time to ERCP in h1	53.8 (28.4-90.7)	17.7 (9.0-20.4)	67.6 (43.6-98.9)	-	26.0 (18.8-40.1)	88.5 (67.2-114.6)
Indications of ERCP, n (%)
Common bile duct stones	508 (74.4)	107 (79.9)	401 (73)	0.106	256 (81.5)	252 (68.3)	< 0.001
Malignant obstruction	70 (10.2)	7 (5.2)	63 (11.5)	0.032	19 (6.1)	51 (13.8)	< 0.001
Stent dysfunction	61 (8.9)	8 (6.0)	53 (9.7)	0.180	17 (5.4)	44 (11.9)	0.003
Benign stricture	31 (4.5)	8 (6.0)	23 (4.2)	0.375	15 (4.8)	16 (4.3)	0.783
Others	13 (1.9)	4 (3.0)	9 (1.6)	0.296	7 (2.2)	6 (1.6)	0.565
Treatment during ERCP, n (%)
ES	558 (81.7)	112 (83.6)	446 (81.2)	0.529	269 (85.7)	289 (78.3)	0.013
EPBD	5 (0.7)	0	5 (0.9)	0.589	2 (0.6)	3 (0.8)	1
Stone retrieval	502 (73.5)	108 (80.6)	394 (71.8)	0.038	250 (79.6)	252 (68.3)	0.001
Clearance without stone	37 (5.4)	5 (3.7)	32 (5.8)	0.336	16 (5.1)	21 (5.7)	0.732
Removal of old stents	60 (8.8)	6 (4.5)	54 (9.8)	0.049	17 (5.4)	43 (11.7)	0.004
Stent insertion	187 (27.4)	35 (26.1)	152 (27.7)	0.715	70 (22.3)	117 (31.7)	0.006
Biliary stricture dilatation	7 (1.0)	1 (0.7)	6 (1.1)	1	1 (0.3)	6 (1.6)	0.132
Others	3 (0.4)	0	3 (0.5)	1	0	3 (0.8)	0.254
ERCP failure, n (%)	7 (1.0)	0	7 (1.3)	0.356	1 (0.3)	6 (1.6)	0.132

¹Expressed as median (interquartile range). EPBD: Endoscopic papillary balloon dilation; ERCP: Endoscopic retrograde cholangiopancreatography; ES: Endoscopic sphincterotomy.

Table 3 Primary and secondary outcomes

Outcomes	Total	Time to ERCP divided by 24 h			Time to ERCP divided by 48 h
		ERCP ≤ 24 h	ERCP > 24 h	P value	ERCP ≤ 48 h	ERCP > 48 h	P value
Overall	n = 683	n = 134	n = 549		n = 314	n = 369
30-d mortality, n (%)	7 (1.02)	0	7 (1.3)	0.356	0	7 (1.9)	0.017
ICU admission, n (%)	37 (5.4)	15 (11.2)	22 (4)	0.001	22 (7.0)	15 (4.07)	0.091
LOHS in d1	7 (5-10)	6 (4-10)	7 (5-10)	0.018	6 (4-9)	8 (6-11)	< 0.001
30-d readmission, n (%)	87 (12.7)	16 (11.9)	71 (12.9)	0.757	40 (12.7)	47 (12.7)	0.999
Grade III AC	n = 170	n = 39	n = 131		n = 72	n = 98
30-d mortality, n (%)	6 (3.5)	0	6 (4.6)	0.338	0	6 (6.1)	0.039
ICU admission, n (%)	26 (15.3)	12 (9.0)	14 (2.6)	0.002	16 (22.2)	10 (10.2)	0.031
LOHS in d1	7 (7-14)	10 (6-16.5)	9 (7-12)	0.637	9 (6-15)	9 (7-12)	0.448
30-d readmission, n (%)	23 (13.5)	4 (3)	19 (14.5)	0.602	10 (13.9)	13 (13.3)	0.906
Grade II AC	n = 179	n = 39	n = 140		n = 88	n = 91
30-d mortality, n (%)	0	0	0	-	0	0	-
ICU admission, n (%)	5 (2.8)	2 (5.1)	3 (2.1)	0.299	3 (3.4)	2 (2.2)	0.679
LOHS in d1	7 (5-10)	6 (4-9.5)	7 (5.8-10)	0.047	6 (4.8-9)	8 (6-11)	0.001
30-d readmission, n (%)	24 (13.4)	4 (10.3)	20 (14.3)	0.514	8 (9.1)	16 (17.6)	0.096
Grade I AC	n = 334	n = 56	n = 278		n = 154	n = 180
30-d mortality, n (%)	1 (0.3)	0	1 (0.36)	1	0	1 (0.56)	1
ICU admission, n (%)	6 (1.8)	1 (1.8)	5 (1.8)	1	3 (1.9)	3 (1.7)	1
LOHS in d1	6 (5-9)	6 (4-8.3)	7 (5-9.8)	0.005	6 (4-7)	7 (6-11)	< 0.001
30-d readmission, n (%)	40 (12)	8 (14.3)	32 (11.5)	0.56	22 (14.3)	18	0.229

¹Expressed as median (interquartile range). AC: Acute cholangitis; ERCP: Endoscopic retrograde cholangiopancreatography; ICU: Intensive care unit; LOHS: Length of hospital stay.

Table 4 Univariate and multivariate analyses of the factors associated with 30-d mortality

Variables		Univariate analysis		Multivariate analysis
		OR (95%CI)	P value	OR (95%CI)	P value
Age	≥ 75 yr	1.772 (0.393-7.991)	0.456
	< 75 yr
		Reference
Common bile duct stones	Yes	0.254 (0.056-1.146)	0.075
	No
		Reference
Malignant biliary obstruction	Yes	6.817 (1.494-31.109)	0.013	7.718 (0.664-89.660)	0.102
	No
		Reference
Fever, BT ≥ 39 °C	Yes	1.045 (0.124-8.777)	0.968
	No
		Reference
Abnormal WBC count	Yes	1.789 (0.345-9.289)	0.489
	No
		Reference
Hyperbilirubinemia, ≥ 5 mg/dL	Yes	1.382 (0.307-6.228)	0.673
	No
		Reference
Hepatic dysfunction, PT-INR > 1.5	Yes	8.896 (1.645-48.119)	0.011	2.257 (0.275-18.553)	0.449
	No
		Reference
Hematological dysfunction, PLT < 100 × 103/µL	Yes	4.885 (0.919-25.649)	0.063
	No
		Reference
Renal dysfunction, Cr > 2.0 mg/dL	Yes	4.548 (0.862-23.998)	0.074
	No
		Reference
Respiratory dysfunction, PaO2/FiO2 ratio > 300	Yes	10.517 (2.284-48.431)	0.003	1.644 (0.172-15.676)	0.666
	No
		Reference
Neurological dysfunction, conscious disturbance	Yes	15.094 (3.241-70.298)	0.001	2.773 (0.380-20.238)	0.315
	No
		Reference
Cardiovascular dysfunction1	Yes	18.750 (3.990-88.112)	< 0.001	17.756 (0.994-317.241)	0.050
	No
		Reference
Severity of AC	Grade III	18.732 (2.239-156.728)	0.007	3.603 (0.274-47.356)	0.329
	Grade II + I
		Reference
ICU admission	Yes	7.326 (1.373-39.101)	0.02	2.463 (0.204-29.703)	0.478
	No
		Reference
Time to ERCP	Every 1-d delay	1.950 (1.252-3.038)	0.003	2.081 (1.154-3.753)	0.015

¹Defined as hypotension requiring dopamine ≥ 5 µg/kg per min, or any dose of norepinephrine. AC: Acute cholangitis; BT: Body temperature; ERCP: Endoscopic retrograde cholangiopancreatography; ICU: Intensive care unit; PT/INR: Prothrombin time/international normalized ratio; WBC: White blood cell count.