Does serotonin reuptake inhibitor therapy increase the risk of post-sphincterotomy bleeding in patients undergoing endoscopic retrograde cholangio-pancreatography?

Table 1 Complications of sphincterotomy and risk factors for hemorrhage

Complications of sphincterotomy	Risk factors for hemorrhage
Pancreatitis - 1.0%-15.7% (Most common complication)	Presence of coagulopathy
Hemorrhage - 2%-7%	Use of anti-coagulation
Cholangitis - 1% - (Fever, chills, elevated liver enzymes, and/or positive blood culture within 48 h after the procedure)	Cholangitis
Cholecystitis - (Clinical and radiographic evidence of an inflamed gallbladder)	Low endoscopist case volume

Table 2 Bleeding grading system

Mild	Moderate	Severe
Transfusion is not required, with evidence of bleeding	Transfusion of 4 units or less is required	Transfusion of 5 units or more is required
Hemoglobin drop of less than 3 g/dL	No surgical intervention	Angiographic or surgical intervention
Immediate bleeding - seen in 30% patients (8) - endoscopic venous oozing which stopped with epinephrine
Delayed bleeding - occur up to 2 wk after the procedure - hematemesis, melena, haematochezia
Severe bleeding - 0.1%-0.5%

Adapt from Cotton et al[3].

Table 3 Serotonin reuptake inhibitors medications included in the study

Serotonin reuptake inhibitors	Serotonin-norepinephrine reuptake inhibitors
Citalopram (Celexa)	Desvenlafaxine (Pristiq)
Escitalopram (Lexapro, Cipralex)	Duloxetine (Cymbalta)
Paroxetine (Paxil, Seroxat)	Levomilnacipran (Fetzima)
Fluoxetine (Prozac)	Milnacipran (Ixel, savella)
Fluvoxamine (Luvox)	Tofenacin (Elamol, tofacine)
Sertraline (Zoloft, lustral)	Venlafaxine (Effexor)

Table 4 Patient demographics n (%)

Factor	Overall (n = 447)		SRI (n = 219)		No SRI (n = 228)		P value
	n	Summary	n	Summary	n	Summary
Age (yr)	445	64.4 ± 17.9	219	64.0 ± 16.8	226	64.7 ± 19.0	0.681
Male	447	112 (25.1)	219	47 (21.5)	228	65 (28.5)	0.0863
BMI	442	29.5 ± 7.5	218	29.7 ± 7.6	224	29.3 ± 7.4	0.591
Smoking	435	216 (49.7)	216	114 (52.8)	219	102 (46.6)	0.203
Alcohol use	432	161 (37.3)	215	69 (32.1)	217	92 (42.4)	0.0273
Cardiovascular disorder	447	111 (24.8)	219	53 (24.2)	228	58 (25.4)	0.763
Depression	445	160 (36.0)	219	99 (45.2)	226	61 (27.0)	< 0.0013
Renal disease	447	55 (12.3)	219	30 (13.7)	228	25 (11.0)	0.383
Intestinal disease	447	66 (14.8)	219	29 (13.2)	228	37 (16.2)	0.373
History of UGI bleed	389	1 (0.26)	207	0 (0.0)	182	1 (0.55)	0.474

¹ANOVA; ²Kruskal-Wallis test;

³Pearson's χ² test;

⁴Fisher's exact test. Intestinal diseases: Peptic ulcer, inflammatory bowel disease. Values presented as Mean ± SD or n (%). SRI: Serotonin reuptake inhibitor.

Table 5 Patients lab values

Factor	Overall (n = 447)		SRI (n = 219)		No SRI (n = 228)		P value
	n	Summary	n	Summary	n	Summary
PPI	447	111 (24.8)	219	51 (23.3)	228	60 (26.3)	0.462
Platelets	435		213		222		0.591
140-400		432 (99.3)		212 (99.5)		220 (99.1)
> 400		3 (0.69)		1 (0.47)		2 (0.90)
INR	391		190		201		-
0.9-1.2		391 (100.0)		190 (100.0)		201 (100.0)
PTT	361		171		190		-
24.7-32.7 s		361 (100.0)		171 (100.0)		190 (100.0)

¹Kruskal-Wallis test;

²Pearson's χ² test. Values presented as Mean ± SD or n (%). SRI: Serotonin reuptake inhibitor.

Table 6 Number of endoscopic retrograde cholangiopancreatography

Number of ERCPs	Overall (n = 447)	SRI (n = 219 )	No SRI (n = 228)	P value
1	432 (96.6)	214 (97.7)	218 (95.6)	0.231
2	13 (2.9)	3 (1.4)	10 (4.4)
3	2 (0.45)	2 (0.91)	0 (0.0)

¹Kruskal-Wallis test. Values presented as n (%).SRI: Serotonin reuptake inhibitor; ERCP: Endoscopic retrograde cholangiopancreatography.

Table 7 Indications for endoscopic retrograde cholangiopancreatography

	Overall (n = 447)	SRI (n = 219)		No SRI (n = 228)	P value
	Summary		n (%)	n (%)
Abnormal CT	16 (3.8)		9 (4.3)	7 (3.3)	0.571
Abdominal pain	90 (21.2)		43 (20.6)	47 ( 21.9)	0.751
Abnormal LFT	62 (14.6)		32 (15.3)	30 (14.0)	0.691
Biliary dilation	8 (1.9)		6 (2.9)	2 (0.93)	0.172
Bile duct stones	187 (44.1)		96 (45.9)	91 (42.3)	0.451
Complications of prior biliary surgery	6 (1.4)		4 (1.9)	2 (0.93)	0.442
Jaundice	49 (11.6)		16 (7.7)	33 (15.3)	0.0131
Cholangitis	9 (2.1)	209	4 (1.9)	5 (2.3)	0.992

¹Pearson's χ² test;

²Fisher's exact test. Values presented as n (%). CT: Computed tomography; LFT: Lung function testing; SRI: Serotonin reuptake inhibitor.

Table 8 Bleeding and management

	Overall (n = 447)	SRI (n = 219)		No SRI (n = 228)		P value
	n (%)	n	Summary	n	Summary
Post-sphincterotomy bleeding	46 (10.3)	219	18 (8.2)	228	28 (12.3)	0.161
Injected with epinephrine	25 (54.3)	18	7 (38.9)	28	18 (64.3)	0.0911

¹Pearson's χ² test;. Values presented n (%). SRI: Serotonin reuptake inhibitor.