Systematic review and meta-analysis of the impact of deviations from a clinical pathway on outcomes following pancreatoduodenectomy

Table 1 Summary of studies included in the analysis along with details of the clinical pathway, compliance and comparison between groups

Ref.	Study design	n	Age (yr)	Number of clinical pathway factors	Overall compliance (%)	Comparison groups (% of compliance)	NOS
Braga et al[16], 2014	Prospective	115	69 (61-74)	12 (4 Pre- + 3 Intra- + 5 Post-op)	NA	No group stratification	-
Zouros et al[17], 20161	Prospective	75	65.9 ± 10.5	5 (Post-op)	NA	100% (n = 53) vs < 100% (n = 22)	7
Kagedan et al[18], 20171	Retrospective	82	65 (56-74)	4 (Post-op)	NA	100% (n = 134) vs < 100% (n = 134)	6
Tremblay St-Germain et al[20], 2017	Retrospective	83	65 (29-85)	8 (Post-op)	NA	No group stratification	-
Agarwal et al[23], 2018	Prospective	394	55 (18-81)	13 (6 Pre + 4 Intra- + 3 Post-op)	84	≥ 80% (n = 278) vs < 80% (n = 116)	-
Williamsson et al[24], 20191	Retrospective	160	66-69	8 (Post-op)	52	≥ 50% (n = 134) vs < 50% (n = 26)	7
Karunakaran et al[6], 20201	Retrospective	162	59 (19-84)	8 (Post-op)	53	≥ 50% (n = 98) vs < 50% (n = 64)	7
Roulin et al[10], 2020	Prospective	390	65.3 ± 11.6	19 (7 Pre + 3 Intra- + 9 Post-op)	62 (30 for post-operative components)	≥ 70% (n = 85) vs < 70% (n = 305)	-
Tankel et al[21], 2020	Prospective	97	68 (17-85)	7 (Post-op)	NA	No group stratification	-
Capretti et al[22], 20201	Prospective	205	64.7 ± 13.7	16 (5 Pre + 5 Intra- + 6 Post-op)	68.4	100% (n = 52) vs < 100% (n = 152)	7
St-Amour et al[19], 2020	Retrospective	89	68 (61-73)	NA	63 (36 for post-op)	≥ 67% vs < 67%	-

¹Included in the meta-analysis. NOS: Newcastle–Ottawa scale; NA: Not available.

Table 2 Summarising the morbidity, mortality and readmission rates along with length of stay and impact of deviations on these outcomes

Ref.	Length of stay1 (d)	Complications (%)		Mortality (%)	Readmissions (%)	Impact of deviations/non-compliance to clinical pathway
		Overall	≥ CD 3
Braga et al[16]	14.6 ± 9.8	60	20	3.5	12.2	Significantly lower deviations in patients with uneventful post-operative course; Lower compliance correlated with severity of postoperative complications; Low compliance to early oral feeding most likely to be associated with postoperative complications
Zouros et al[17]	9.7 ± 5.6	34.7	14.7	4	6.7	< 100% compliance associated with significantly higher rates of postoperative complications (72.7% vs 20.8%; P < 0.001)
Kagedan et al[18]	9 (7-14)	NA	NA	0.8	16	< 100% compliance associated with longer length of stay (13 vs 7 d, P < 0.001) and greater mean total cost of the index postoperative hospitalization ($20392.81 CAD vs $10562.28 CAD, P < 0.002)
Tremblay St-Germain et al[20]	8 (4-35)	67.5	29	0	222	Failure to remove urinary catheter by POD 3, and initiate solid diet ≤ POD 4 (P < 0.01 and P < 0.001, respectively), more likely to have prolonged length of stay (> 8 d)
Agarwal et al[23]	12 (4-78)	63.2	33.2	3.5	7.8	< 80% compliance associated with significantly increased major complications (44% vs 28.7%, P < 0.004), CR-POPF (32.7% vs 20.8%, P < 0.012), longer length of stay [15 (4-61) vs 11 (5-78), P < 0.001)], re-explorations (17.2% vs 6.8%, P < 0.002), escalation of antibiotics (24.1% vs 14.7%, P < 0.025) and mortality (6.8% vs 2.1%, P = 0.021)
Williamsson et al[24]	12 (6-97)	69.4	21.25	1.25	16.252	< 50% compliance associated with delayed discharge [10 (6-77) vs 23 (8-97) d] and higher incidence of CD ≥ 3A complications [21 (16%) vs 13 (50%)]; ≥ 90% (n = 13) compliance had a median discharge of POD 8 (7-9) and no complication ≥ CD3A
Karunakaran et al[6]	10.8 ± 5.8	71	23.5	6.2	23.72	< 50% compliance significantly higher risk of complications [DGE (79.7% vs 19.4%, P = 0.0001); POPF (22.2% vs 8.1%, P < 0.025); CD 3/4 complications (37.5% vs 6.1%, P < 0.0001)], longer length of stay (14 vs 10.8 d, P < 0.0001), 90-d readmissions (40.7% vs 14.3%, P = 0.0001) and mortality (14.1% vs 1%, P < 0.003)
Roulin et al[10]	14 (9-22)	83.7	36.9	3.1	11.3	< 70% compliance significantly increased length of stay [15 (10-23) vs 11 (7-16) d, P < 0.001], and overall (88.9% vs 78.8%, P < 0.029) and major (43.6 vs 28.2, P < 0.012) complications (especially respiratory and infectious)
Tankel et al[21]	14 (6-100)	NA	21.6	2.1	28.9	< 100% compliance had a longer length of stay ≥ 14 d
Capretti et al[22]	14.1 ± 8.6	54.6	15.6	1	3.4	Sum of failed ERP components/deviations significantly correlated with postoperative complications
St-Amour et al[19]	NA	NA	NA	NA	NA	No significant effect of ERAS® compliance on time to receipt of adjuvant chemotherapy from surgery, or disease-free survival

¹Expressed either as median (range) or mean (± SD).

²90-d readmissions (as opposed to others reporting 30-d readmissions). CD: Clavien-dindo; CAD: Canadian dollars; CR-POPF: Clinically-relevant post-pancreatectomy pancreatic fistula; DGE: Delayed gastric emptying; ERAS: Enhanced recovery after surgery; ERP: Enhanced recovery pathway; NA: Not available; POD: Post-operative day.