Enhanced recovery pathways in pancreatic surgery: State of the art

Table 1 Enhanced recovery pathway interventions for pancreatic surgery

Element	Description
Preoperative
Patient education	Dedicated counseling providing patients with information and goals for recovery
Optimization of organ dysfunction	Optimization of patient comorbidities and patient conditioning
Oral immunonutrition	Oral immunonutrients should be taken for 5-7 d prior to surgery
Selective biliary drainage	Endoscopic biliary drainage only indicated if serum bilirubin > 14.5 mg/dL, in case of cholangitis or planned neoadjuvant treatment
Avoid mechanical bowel preparation	Oral bowel preparation should not be used
Minimize fasting	Intake of clear fluids up to 2 h before anesthesia, and solid food until 6 h before.
Carbohydrate loading	A carbohydrate drink should be given the morning before surgery
Intraoperative
Thromboembolic disease prophylaxis	Low molecular weight heparin should be administered
Antimicrobial prophylaxis	Antibiotic prophylaxis should start 30-60 min before incision
Epidural and opioid sparing analgesia	Avoid opioids. Multimodal analgesia including thoracic epidural analgesia, acetaminophen, NSAIDs. Early transition to oral analgesics
PONV prophylaxis	Multimodal nausea and vomit prophylaxis
Avoid hypothermia	Active cutaneous warming
Balanced intravenous infusions	Avoid fluid overload. Maintain near-zero fluid balance. Potential benefit in the use of goal directed fluid therapy.
Postoperative
Avoid nasogastric intubation	Nasogastric tube should be removed at the end of surgery
Glycemic control	Avoid hyperglycemia with frequent blood sugar monitoring and insulin infusion when necessary
Early removal of urinary drainage	Bladder catheter should be removed within postoperative day 2
Early removal of perianastomotic drain	Early drain removal in patients at low risk for pancreatic fistula
Early oral feeding	Patients should be allowed a normal diet without restrictions as tolerated
Gastrointestinal stimulation	Oral laxative and chewing-gum should be started early after surgery
Early stop of intravenous infusions	Intravenous fluids should be stopped as soon as patients are able to tolerate oral liquids
Early mobilization	Scheduled active mobilization should start from postoperative day 1
Audit	Systematic audit on care processes and outcomes

NSAID: Non-steroidal anti-inflammatory drugs; PONV: Postoperative nausea and vomit.

Table 2 Study design and characteristics

Study	Year	Design	Sample size		Type of resection
			ERP	Control
Porter et al[53]	2000	Retrospective cohort	80	68	PD, TP
Vanounou et al[54]	2007	Retrospective cohort	145	64	PD
Kennedy et al[55]	2007	Retrospective cohort	92	44	PD, TP
Balzano et al[56]	2008	Retrospective cohort	252	252	PD
Kennedy et al[57]	2009	Retrospective cohort	71	40	LP
Nikfarjam et al[58]	2013	Retrospective cohort	20	21	PD
Abu Hilal et al[59]	2013	Retrospective cohort	24	20	PD
Braga et al[60]	2014	Retrospective cohort	115	115	PD
Kobayashi et al[61]	2014	Retrospective cohort	100	142	PD
Nussbaum et al[62]	2014	Retrospective cohort	50	100	LP
Nussbaum et al[63]	2014	Retrospective cohort	100	142	PD
Coolsen et al[64]	2014	Retrospective cohort	1441	86	PD
Shao et al[65]	2015	Retrospective cohort	325	310	PD
Sutcliffe et al[66]	2015	Retrospective cohort	65	65	PD
Joliat et al[67]	2015	Prospective cohort2	74	87	PD
Morales Soriano et al[68]	2015	Retrospective cohort	41	44	PD
Richardson et al[69]	2015	Retrospective cohort	22	44	LP

¹Includes 47 patients treated with an enhanced recovery-like pathway;

²Only the ERP group was prospective. PD: Pancreaticoduodenectomy; TP: Total pancreatectomy; LP: Left pancreatectomy.

Table 3 Enhanced recovery pathway elements used in comparative studies

Study	Preoperative				Intraoperative					Postoperative								Total number of ERP elements
	Patient education and counselling	No mechanical bowel preparation	Shorter preoperative fasting	Carbohydrate loading	Prophylactic antibiotics	Thromboembolic disease prophylaxis	Epidural/multimodal analgesia	Prevention of nausea and vomiting	Prevention of hypothermia	Early nasogastric tube removal	Early removal of urinary catheter	Early discontinuation of IV fluids	Glycemic control	Standardized perianastomotic drain management	Early oral feeding	Early mobilization	Stimulation of GI function
Porter et al[53]										√	√			√	√			4
Vanounou et al[54]	√				√	√	√			√	√			√				7
Kennedy et al[55]					√	√	√			√	√	√		√	√	√		9
Balzano et al[56]	√				√	√	√			√				√	√	√		8
Kennedy et al[57]					√	√	√			√	√	√		√	√	√		9
Nikfarjam et al[58]	√		√		√	√	√			√	√	√		√	√	√	√	12
Abu Hilal et al[59]			√			√						√		√	√	√	√	7
Braga et al[60]	√	√	√		√	√	√	√	√	√		√		√	√	√		13
Kobayashi et al[61]	√	√	√							√				√	√			6
Nussbaum et al[62]					√	√				√	√	√		√	√	√		8
Nussbaum et al[63]					√	√	√			√	√	√		√	√	√		9
Coolsen et al[64]	√		√	√	√	√	√		√	√	√	√		√	√	√	√	14
Shao et al[65]							√			√				√	√			4
Sutcliffe et al[66]	√	√	√	√	√	√	√	√	√	√				√	√	√		13
Joliat et al[67]	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	17
Morales Soriano et al[68]		√	√		√		√	√	√	√	√			√	√	√		11
Richardson et al[69]	√		√	√		√				√	√	√		√	√	√		10

Table 4 Postoperative length of stay and readmission rates

Study	Postoperative length of stay (d)			Readmission rates
	ERP	Usual care	P value	ERP	Usual care	P value
Porter et al[53]	12	15	0.001	10 (15)	9 (11)	0.620
Vanounou et al[54]	8	8	0.357	13 (9)	4 (6)	0.508
Kennedy et al[55]	7	13	< 0.001	7 (8)	3 (7)	> 0.05
Balzano et al[56]	13 (7-110)	15 (7-102)	< 0.001	18 (7)	16 (6)	0.865
Kennedy et al[57]	Mean 7	Mean 10	0.037	5 (7)	10 (25)	0.027
Nikfarjam et al[58]	8 (7-16)	14 (8-29)	< 0.001	3 (15)	0	0.107
Abu Hilal et al[59]	8 (7-13)	13 (10-20)	0.015	1 (1)	2 (8)	0.583
Braga et al[60]	11 (5-51)	13 (8-54)	0.226	14 (12)	12 (10)	0.835
Kobayashi et al[61]	22 ± 12	36 ± 24	< 0.001	2 (2)	2 (2)	0.689
Nussbaum et al[62]	6 (5-9)	7 (5-9)	0.026	15 (30)	20 (20)	0.219
Nussbaum et al[63]	11 (8-18)	13 (10-18)	0.015	31 (31)	36 (25)	0.850
Coolsen et al[64]	14 (7-83)	20 (9-132)	< 0.050	11 (13)	14 (14)	NR
Shao et al[65]	14 ± 7	18 ± 8	< 0.001	43 (13)	44 (14)	0.725
Sutcliffe et al[66]	9 (4-70)	10 (4-114)	0.160	9 (15)	5 (8)	0.260
Joliat et al[67]	15 (11-24)	19 (14-29)	0.029	NR	NR	NR
Morales Soriano et al[68]	14 ± 1.3	19 ± 2	0.014	9 (10)	4 (9)	> 0.05
Richardson et al[69]	3 (3-4)	6 (5-10)	< 0.001	2 (9)	8 (18)	0.476

Data for length of stay are reported as median (range or interquartile range) or mean ± SD. Data for readmission are reported as number of patients (%). ERP: Enhanced recovery pathway.

Table 5 Morbidity and mortality rates

Study	Complication rates			Mortality rates
	ERP	Usual care	P value	ERP	Usual care	P value
Porter et al[53]	56 (70)	52 (76)	0.210	2 (3)	1 (1)	0.870
Vanounou et al[54]	77 (54)	40 (62)	0.207	2 (1)	1 (2)	0.918
Kennedy et al[55]	34 (37)	19 (44)	> 0.05	1 (1)	1 (2)	> 0.05
Balzano et al[56]	119 (47)	148 (59)	0.014	9 (4)	7 (3)	0.798
Kennedy et al[57]	11 (16)	15 (38)	> 0.05	1 (1)	1 (2)	> 0.05
Nikfarjam et al[58]	NR	NR		NR	NR	-
Abu Hilal et al[59]	8 (40)	6 (67)	0.077	0	0	-
Braga et al[60]	69 (60)	76 (66)	0.339	4 (4)	4 (4)	1
Kobayashi et al[61]	39 (39)	54 (60)	0.004	0	1.1	0.957
Nussbaum et al[62]	13 (26)	24 (24)	0.842	0	0	-
Nussbaum et al[63]	43 (43)	53 (41)	0.792	1 (1)	4 (3)	0.651
Coolsen et al[64]	46 (53)	48 (49)	> 0.05	4 (5)	6 (6)	> 0.05
Shao et al[65]	127 (39)	173 (55.8)	< 0.001	40 (12)	53 (17)	NR
Sutcliffe et al[66]	15 (34)	15 (41)	0.650	2 (3)	2 (3)	1
Joliat et al[67]	50 (68)	71 (82)	0.046	3 (4)	4 (5)	1
Morales Soriano et al[68]	12 (30)	24 (55)	0.029	0	2 (2)	> 0.05
Richardson et al[69]	6 (27)	17 (39)	0.421	0	0	-

Data are reported as number of patients (%). ERP: Enhanced recovery pathway.