Journal of Surgical Oncology 2014;110:197–202
Enhanced Recovery in the Resection of Colorectal Liver Metastases DECLAN F. J. DUNNE, MBChB(Hons),1,2* VINCENT S. YIP, FRCS,1 ROBERT P. JONES, PhD,1,2 EWAN A. MCCHESNEY, MBChB,3 DANIEL T. LYTHGOE, MSc,4 EFTYCHIA E. PSARELLI, MSc,4 LOUISE JONES, MSc,1 CARMEN LACASIA-PURROY, FRCS,1 HASSAN Z. MALIK, FRCS,1 GRAEME J. POSTON, MS,1,2 AND STEPHEN W. FENWICK, FRCS1 1
Liverpool Hepatobiliary Centre, University Hospital Aintree, Liverpool, United Kingdom Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom University of Liverpool Medical School, University of Liverpool, Liverpool, United Kingdom 4 CRUK Liverpool Cancer Trials Unit, Liverpool, United Kingdom 2
3
Background: There is limited evidence for the use of enhanced recovery after surgery (ERAS) in patients undergoing hepatectomy, and the impact of the evolution of ERAS over time has not been examined. This study sought to evaluate the effect of an evolving ERAS program in patients undergoing hepatectomy for colorectal liver metastases (CRLM). Methods: A multimodal ERAS program was introduced in 2/2008. Consecutive patients undergoing hepatectomy for CRLM between 2/2008 and 9/ 2012 were included in the study. Data were collected prospectively. Retrospective analysis compared an early ERAS cohort (2/2008–4/2010) with a later cohort with a matured ERAS program (5/2010–8/2012). Results: Length of stay reduced as experience of ERAS increased (Log‐rank x2 ¼ 10.43, P ¼ 0.001). Although median length of stay remained unchanged (6 days), the probability of hospitalization beyond 10 days was 25% in the early cohort compared with 7% in the later cohort. Critical care utilization reduced over time (75.5% vs. 54.7%, P < 0.0001). Complications occurred in 38.2%, with no difference in between cohorts. One postoperative death occurred in the early cohort ( 0.20). There were more males in the late cohort (70.9% vs. 57.3%), (P ¼ 0.01). The later cohort had a non‐significant trend towards greater neoadjuvant chemotherapy use, and a significant increase in combining resection with intraoperative microwave ablation (Table II).
Adherence to the ERAS Pathway Adherence to the pathway was poorly recorded during the early cohort, consequently it was not possible to assess adherence to the pathway during this period. Following the introduction of the unified care record this was reliably reported. The results are summarized in Table III.
Hospital Length of Stay Although median hospital length of stay was identical for the two cohorts (6 days), length of stay was reduced in the latter cohort (Log‐ Journal of Surgical Oncology
rank x2 ¼ 10.43, P ¼ 0.001). The Kaplan–Meier curve (Fig. 1) demonstrates that beyond 6 days, the length of stay curves separate. For example, the probability of staying in hospital beyond 10 days was 25% for the early cohort compared to 7% for the latter cohort. On multivariable analysis major resection, increased age, earlier cohort, and pulmonary comorbidities were all associated with an increased length of stay (Table IV).
Critical Care One hundred ninety six of 304 (64.5%) patients had planned admissions to critical care. No patient triaged to ward care required subsequent unplanned admission to critical care. Across the two cohorts the elective use of critical care diminished from 108 of 143 (75.5%) patients to 88 of 161 (54.7%) patients (P < 0.0001). Patients undergoing major resection were more likely to be admitted electively to critical care 82 of 101 (81.2%) vs. 114 of 203 (56.2%) minor resections (P < 0.0001). On multivariable analysis the early cohort had 2.7 times the odds of the late cohort of being admitted to critical care (OR 2.71 (95% CI: 1.63, 4.50), P < 0.0005) and those undergoing major resection 3.6 times the odds of those undergoing minor resection (OR 3.55 (95% CI: 1.98, 6.37), P < 0.0005).
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Dunne et al.
TABLE II. Demographic Summary
Age (IQR) Gender (F:M) Cardiovascular comorbidities Pulmonary comorbidities Neoadjuvant chemotherapy Bilobar metastases Major resection Resection combined with ablation
Overall (304)
Early (143)
Late (161)
P value
67 (59.5–73) 108:196 (35.5%:64.5%) 130 (42.7%) 44 (14.5%) 131 (43.2%) 125(41.1%) 101 (33.2%) 36 (11.8%)
66 (59–73) 61:82 (42.7%:57.3%) 56 (39.1%) 17 (11.9%) 55 (38.5%) 63(44.1%) 48 (33.6%) 10(7.0%)
67 (60–74) 47:114 (29.1%:70.9%) 74 (45.9%) 27 (16.8%) 76 (47.2%) 62(38.5%) 53 (32.9%) 26(16.1%)
0.204 0.012 0.253 0.248 0.133 0.351 0.905 0.020
Across the cohorts there was no difference in critical care admission in those undergoing major hepatectomy (early 83%, late 79%; P ¼ 0.600). Patients admitted to critical care had a median critical care length of stay of 1 day in both cohorts (95% CI: 1, 2; Log‐rank x2 ¼ 0.37, P ¼ 0.54,). On multivariable analysis there was no difference in critical care length of stay (HR 1.1 (95% CI: 0.83, 1.47; P ¼ 0.513).
fewer patients suffered Clavien–Dindo Grade 3 or 4 complications in the latter cohort (early 9 of 46 (19.6%), late 3 of 53 (5.6%), P ¼ 0.034). This was not confirmed in the multivariable model (P ¼ 0.102). Eighteen patients (5.9%) were readmitted within 30 days of discharge. Readmission rates were unchanged across the cohorts (early 6 of 139 (4.3%), late 12 of 161(7.5%), P ¼ 0.267). Surgical re‐intervention was required in 11 patients (3.6%), with no difference across the cohorts (early 7 of 140 (5.0%, late 4 of 161 (2.5%), P ¼ 0.530).
Morbidity Prospective morbidity data was available in 301 of 304 patients. At least one complication of Clavien–Dindo grade 1–4 occurred in 115 of 301 (38.2%) patients. No significant difference in the overall complication rate between the cohorts was observed. Complications were more likely in those undergoing major compared to minor resection (51 of 99, [51.5%] vs. 64 of 202, [31.7%], P ¼ 0.001). These results were confirmed on multivariable analysis, with age and cardiopulmonary comorbidity as covariates. Patients undergoing major resection were 2.4 times more likely to suffer a complication than those undergoing minor resection (OR 2.40 [95% CI: 1.44, 3.99], P ¼ 0.001). Clavien–Dindo grade 3–4 complications occurred in 33 of 301 (11.0%) patients. This was not difference between cohorts (early 19 of 141 (13.5%), late 14 of 160 (8.8%), P ¼ 0.190), or hepatectomy extent (major 12 of 99 (12%), minor 21 of 202 (10%), P ¼ 0.653). In patients undergoing major hepatectomy no difference in overall complications was observed (early 52%, late 51%, P ¼ 0.903), although
Mortality One postoperative death following aspiration pneumonia occurred in the early cohort. The mortality of 1 in 304 patients (0.3%) is lower than previously published series [11].
DISCUSSION This study is the largest series of ERAS following hepatectomy, and suggests that as experience evolves there is a progressive reduction in hospitalization and critical care utilization. This is without any increase in morbidity and mortality. The mortality of just 1 patient in a consecutive series of 304 hepatectomies for colorectal liver metastases (CRLM) demonstrates that this surgery should be seen as safe when delivered by experienced high volume centers. The findings of this study are in keeping with previously reported smaller series of enhanced recovery in mixed cohorts of patients undergoing liver surgery [7–9,12].
TABLE III. Adherence to ERAS Pathway (from 1st May 2010) N ¼ 161 Preoperative Anesthetic assessment CPET Planned critical care admission Epidural PCA Epidural removed by Day 3 Normal diet by: Postoperative Day 1 Postoperative Day 2 Postoperative Day 3 Postoperative Day 4 Walking by: Postoperative Day 1 Postoperative Day 2 Postoperative Day 3 Postoperative Day 4 Discharged by: Postoperative Day 4 Postoperative Day 5 Postoperative Day 6
Journal of Surgical Oncology
Yes
No
Missing data
151 112 103 127 53 115
0 49 58 34 108 12
10 0 0 0 0 0
111 135 145 148
37 13 3 0
13 13 13 13
74 119 137 146
73 28 10 1
14 14 14 14
33 73 104
128 88 57
0 0 0
Enhanced Recovery in Liver Surgery
Fig. 1. A Kaplan–Meir curve showing length of stay, and the difference between cohorts.
The reduction in high dependency utilization, without an increase in critical care readmission, reflects appropriate pre‐operative stratification of patients. Other series have reported median high dependency stays of 2 days for minor resections and 3 days for major hepatectomies [13], compared to this studies median length of stay of 1 day. The CPET based risk stratification was based on work by Older et al., who first pioneered CPET in postoperative care stratification. [14,15] The success of this stratification is illustrated by the absence of any patient stratified to ward care subsequently requiring unplanned critical care admission. In colorectal surgery ERAS has shown to be associated with a reduction in healthcare cost [1]. This is primarily driven by a reduction in complications and hospital length of stay. The morbidity and hospital length of stay reported in is in keeping with published literature utilizing ERAS following hepatectomy [7–9,12]. When compared to series not using ERAS the morbidity is lower and length of stay shorter [16–18]. This suggests the reduction in costs seen in colorectal surgery as a result of ERAS may be replicated in liver surgery, and would be a useful focus of further study. As the ERAS program evolved there was a progressive reduction in length of stay, without significant change in complication rates. The length of stay reduction in the latter cohort is due to a reduction in the significant minority of patients with a prolonged length of stay,
201
consequently skewing the data less. Given that complications would typically be the cause of a prolonged admission, and that complication rates are static across the cohort, it suggests that complications are impacting hospital length of stay less as ERAS evolves. The reducing hospital length of stay in conjunction with progressive reduction in critical care utilization suggests that ERAS will be associated with lower healthcare costs, and that these benefits accrue with time. A true study of the economic impact of ERAS in patients undergoing hepatectomy would be a useful focus for further study. This is particularly important given the extensive support network the ERAS program requires including the use of CPET, and a dedicated pain team. The strengths of this study include the study size, homogeneity of the study group, and analysis of the effects of ERAS evolution. The lack of adherence data within the early cohort is unfortunate as it would be useful to establish whether the improvements seen were due to evolution of the ERAS program, or due to less variability and the standardization of care. The improvements are likely to be multifactorial, with improving adherence a significant contributor. Indeed when looking at the adherence rate in the latter cohort (Table III) it is evident that a significant cohort of patients do not achieve early postoperative targets including commencing normal diet, mobilizing, and epidural removal by Day 3. Establishing the reasons for failing to achieve these ERAS targets may enable further revisions to the program and allow further improvements in perioperative outcomes, or highlight a cohort of patients where these targets are unachievable. Epidural anesthesia is itself controversial particularly in hepatectomy within an ERAS program [19,20]. The use of intrathecal morphine has been suggested as an alternative, which can deliver early mobilization with excellent pain control. This study is not a randomized assessment of ERAS against a control group as such comparison of ERAS versus standard care directly is not possible. No large randomized controlled trial has examined ERAS in hepatectomy, but all published series, and small trials have reported benefits in favor of ERAS [6–8]. Furthermore, randomized studies of ERAS versus standard care are subject to internal bias, where adoption of ERAS practice across an institution affects the approach of healthcare professionals to any control arm [7]. The findings of this study make it difficult to ethically justify the management of patients outside of an enhanced recovery program, and consequently inappropriate to conduct a trial in this context. In other areas of surgical practice enhanced recovery has led to reduced hospitalization and reduced hospital costs [1]. This study suggests that enhanced recovery after hepatectomy for CRLM is feasible, and is associated with low morbidity and mortality. Enhanced recovery after hepatectomy for CRLM should be a standard of care for all patients.
TABLE IV. Final Multivariable Cox Regression Model for Hospital Length of Stay 95% CI Variable Cohort Early Late Resection Minor Major Age Pulmonary co‐morbidity No Yes
Journal of Surgical Oncology
HR
se
P
Lower
Upper
— 1.41
— 0.17
— 0.004
— 1.11
— 1.78
— 0.78 0.99
— 0.10 0.00
— 0.045 0.006
— 0.61 0.98
— 0.99 1.00
— 0.75
— 0.13
— 0.089
— 0.54
— 1.04
202
Dunne et al.
ACKNOWLEDGMENTS The authors would like to thank key members of the enhanced recovery team for their support including Peter Groom, Claire Burston, and Clare Bryne. Without their support this study would not have been possible. No funding support was received in the conduction of this study.
REFERENCES 1. Adamina M, Kehlet H, Tomlinson GA, et al.: Enhanced recovery pathways optimize health outcomes and resource utilization: A meta‐analysis of randomized controlled trials in colorectal surgery. Surgery 2011;149:830–840. 2. Lassen K, Soop M, Nygren J, et al.: Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations. Arch Surg 2009;144: 961–969. 3. Leibman BD, Dillioglugil O, Abbas F, et al.: Impact of a clinical pathway for radical retropubic prostatectomy. Urology 1998;52:94–99. 4. Niino T, Hata M, Sezai A, et al.: Optimal clinical pathway for the patient with type B acute aortic dissection. Circ J 2009;73:264–268. 5. Spanjersberg WR, Reurings J, Keus F, et al.: Fast track surgery versus conventional recovery strategies for colorectal surgery. Cochrane Database Syst Rev 2011;CD007635. http://www.ncbi. nlm.nih.gov/pubmed/?term¼21328298 6. Hall TC, Dennison AR, Bilku DK, et al.: Enhanced recovery programmes in hepatobiliary and pancreatic surgery: A systematic review. Ann R Coll Surg Engl 2012;94:318–326. 7. Jones C, Kelliher L, Dickinson M, et al.: Randomized clinical trial on enhanced recovery versus standard care following open liver resection. Br J Surg 2013;100:1015–1024. 8. Ni CY, Yang Y, Chang YQ, et al.: Fast‐track surgery improves postoperative recovery in patients undergoing partial hepatectomy for primary liver cancer: A prospective randomized controlled trial. Eur J Surg Oncol 2013;39:542–547.
Journal of Surgical Oncology
9. Schultz NA, Larsen PN, Klarskov B, et al.: Evaluation of a fast‐track programme for patients undergoing liver resection. Br J Surg 2013;100:138–143. 10. Dindo D, Demartines N, Clavien P‐A: Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–213. 11. Adam R, Bhangui P, Poston G, et al.: Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg 2010;252:774–787. 12. van Dam RM, Hendry PO, Coolsen MME, et al.: Initial experience with a multimodal enhanced recovery programme in patients undergoing liver resection. Br J Surg 2008;95:969–975. 13. Junejo MA, Mason JM, Sheen AJ, et al.: Cardiopulmonary exercise testing for preoperative risk assessment before hepatic resection. Br J Surg 2012;99:1097–1104. 14. Older P, Hall A, Hader R: Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly . Chest 1999;116:355. 15. Older P, Hall A: Clinical review: How to identify high‐risk surgical patients. Crit Care 2004;8:369–372. 16. Jarnagin WR, Gonen M, Fong Y, et al.: Improvement in perioperative outcome after hepatic resection: Analysis of 1,803 consecutive cases over the past decade. Ann Surg 2002;236:397– 406;discussion 406–407. 17. Reddy SK, Barbas AS, Turley RS, et al.: A standard definition of major hepatectomy: Resection of four or more liver segments. HPB (Oxford) 2011;13:494–502. 18. Zimmitti G, Roses RE, Andreou A, et al.: Greater complexity of liver surgery is not associated with an increased incidence of liver‐ related complications except for bile leak: An experience with 2,628 consecutive resections. J Gastrointest Surg 2013;17:57–64;discussion p. 64–65. 19. Tzimas P, Prout J, Papadopoulos G, et al.: Epidural anaesthesia and analgesia for liver resection. Anaesthesia 2013;68:628–635. 20. Sakowska M, Docherty E, Linscott D, et al.: A change in practice from epidural to intrathecal morphine analgesia for hepato‐ pancreato‐biliary surgery. World J Surg 2009;33:1802–1808.
Enhanced Recovery in the Resection of Colorectal Liver Metastases DECLAN F. J. DUNNE, MBChB(Hons),1,2* VINCENT S. YIP, FRCS,1 ROBERT P. JONES, PhD,1,2 EWAN A. MCCHESNEY, MBChB,3 DANIEL T. LYTHGOE, MSc,4 EFTYCHIA E. PSARELLI, MSc,4 LOUISE JONES, MSc,1 CARMEN LACASIA-PURROY, FRCS,1 HASSAN Z. MALIK, FRCS,1 GRAEME J. POSTON, MS,1,2 AND STEPHEN W. FENWICK, FRCS1 1
Liverpool Hepatobiliary Centre, University Hospital Aintree, Liverpool, United Kingdom Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom University of Liverpool Medical School, University of Liverpool, Liverpool, United Kingdom 4 CRUK Liverpool Cancer Trials Unit, Liverpool, United Kingdom 2
3
Background: There is limited evidence for the use of enhanced recovery after surgery (ERAS) in patients undergoing hepatectomy, and the impact of the evolution of ERAS over time has not been examined. This study sought to evaluate the effect of an evolving ERAS program in patients undergoing hepatectomy for colorectal liver metastases (CRLM). Methods: A multimodal ERAS program was introduced in 2/2008. Consecutive patients undergoing hepatectomy for CRLM between 2/2008 and 9/ 2012 were included in the study. Data were collected prospectively. Retrospective analysis compared an early ERAS cohort (2/2008–4/2010) with a later cohort with a matured ERAS program (5/2010–8/2012). Results: Length of stay reduced as experience of ERAS increased (Log‐rank x2 ¼ 10.43, P ¼ 0.001). Although median length of stay remained unchanged (6 days), the probability of hospitalization beyond 10 days was 25% in the early cohort compared with 7% in the later cohort. Critical care utilization reduced over time (75.5% vs. 54.7%, P < 0.0001). Complications occurred in 38.2%, with no difference in between cohorts. One postoperative death occurred in the early cohort ( 0.20). There were more males in the late cohort (70.9% vs. 57.3%), (P ¼ 0.01). The later cohort had a non‐significant trend towards greater neoadjuvant chemotherapy use, and a significant increase in combining resection with intraoperative microwave ablation (Table II).
Adherence to the ERAS Pathway Adherence to the pathway was poorly recorded during the early cohort, consequently it was not possible to assess adherence to the pathway during this period. Following the introduction of the unified care record this was reliably reported. The results are summarized in Table III.
Hospital Length of Stay Although median hospital length of stay was identical for the two cohorts (6 days), length of stay was reduced in the latter cohort (Log‐ Journal of Surgical Oncology
rank x2 ¼ 10.43, P ¼ 0.001). The Kaplan–Meier curve (Fig. 1) demonstrates that beyond 6 days, the length of stay curves separate. For example, the probability of staying in hospital beyond 10 days was 25% for the early cohort compared to 7% for the latter cohort. On multivariable analysis major resection, increased age, earlier cohort, and pulmonary comorbidities were all associated with an increased length of stay (Table IV).
Critical Care One hundred ninety six of 304 (64.5%) patients had planned admissions to critical care. No patient triaged to ward care required subsequent unplanned admission to critical care. Across the two cohorts the elective use of critical care diminished from 108 of 143 (75.5%) patients to 88 of 161 (54.7%) patients (P < 0.0001). Patients undergoing major resection were more likely to be admitted electively to critical care 82 of 101 (81.2%) vs. 114 of 203 (56.2%) minor resections (P < 0.0001). On multivariable analysis the early cohort had 2.7 times the odds of the late cohort of being admitted to critical care (OR 2.71 (95% CI: 1.63, 4.50), P < 0.0005) and those undergoing major resection 3.6 times the odds of those undergoing minor resection (OR 3.55 (95% CI: 1.98, 6.37), P < 0.0005).
200
Dunne et al.
TABLE II. Demographic Summary
Age (IQR) Gender (F:M) Cardiovascular comorbidities Pulmonary comorbidities Neoadjuvant chemotherapy Bilobar metastases Major resection Resection combined with ablation
Overall (304)
Early (143)
Late (161)
P value
67 (59.5–73) 108:196 (35.5%:64.5%) 130 (42.7%) 44 (14.5%) 131 (43.2%) 125(41.1%) 101 (33.2%) 36 (11.8%)
66 (59–73) 61:82 (42.7%:57.3%) 56 (39.1%) 17 (11.9%) 55 (38.5%) 63(44.1%) 48 (33.6%) 10(7.0%)
67 (60–74) 47:114 (29.1%:70.9%) 74 (45.9%) 27 (16.8%) 76 (47.2%) 62(38.5%) 53 (32.9%) 26(16.1%)
0.204 0.012 0.253 0.248 0.133 0.351 0.905 0.020
Across the cohorts there was no difference in critical care admission in those undergoing major hepatectomy (early 83%, late 79%; P ¼ 0.600). Patients admitted to critical care had a median critical care length of stay of 1 day in both cohorts (95% CI: 1, 2; Log‐rank x2 ¼ 0.37, P ¼ 0.54,). On multivariable analysis there was no difference in critical care length of stay (HR 1.1 (95% CI: 0.83, 1.47; P ¼ 0.513).
fewer patients suffered Clavien–Dindo Grade 3 or 4 complications in the latter cohort (early 9 of 46 (19.6%), late 3 of 53 (5.6%), P ¼ 0.034). This was not confirmed in the multivariable model (P ¼ 0.102). Eighteen patients (5.9%) were readmitted within 30 days of discharge. Readmission rates were unchanged across the cohorts (early 6 of 139 (4.3%), late 12 of 161(7.5%), P ¼ 0.267). Surgical re‐intervention was required in 11 patients (3.6%), with no difference across the cohorts (early 7 of 140 (5.0%, late 4 of 161 (2.5%), P ¼ 0.530).
Morbidity Prospective morbidity data was available in 301 of 304 patients. At least one complication of Clavien–Dindo grade 1–4 occurred in 115 of 301 (38.2%) patients. No significant difference in the overall complication rate between the cohorts was observed. Complications were more likely in those undergoing major compared to minor resection (51 of 99, [51.5%] vs. 64 of 202, [31.7%], P ¼ 0.001). These results were confirmed on multivariable analysis, with age and cardiopulmonary comorbidity as covariates. Patients undergoing major resection were 2.4 times more likely to suffer a complication than those undergoing minor resection (OR 2.40 [95% CI: 1.44, 3.99], P ¼ 0.001). Clavien–Dindo grade 3–4 complications occurred in 33 of 301 (11.0%) patients. This was not difference between cohorts (early 19 of 141 (13.5%), late 14 of 160 (8.8%), P ¼ 0.190), or hepatectomy extent (major 12 of 99 (12%), minor 21 of 202 (10%), P ¼ 0.653). In patients undergoing major hepatectomy no difference in overall complications was observed (early 52%, late 51%, P ¼ 0.903), although
Mortality One postoperative death following aspiration pneumonia occurred in the early cohort. The mortality of 1 in 304 patients (0.3%) is lower than previously published series [11].
DISCUSSION This study is the largest series of ERAS following hepatectomy, and suggests that as experience evolves there is a progressive reduction in hospitalization and critical care utilization. This is without any increase in morbidity and mortality. The mortality of just 1 patient in a consecutive series of 304 hepatectomies for colorectal liver metastases (CRLM) demonstrates that this surgery should be seen as safe when delivered by experienced high volume centers. The findings of this study are in keeping with previously reported smaller series of enhanced recovery in mixed cohorts of patients undergoing liver surgery [7–9,12].
TABLE III. Adherence to ERAS Pathway (from 1st May 2010) N ¼ 161 Preoperative Anesthetic assessment CPET Planned critical care admission Epidural PCA Epidural removed by Day 3 Normal diet by: Postoperative Day 1 Postoperative Day 2 Postoperative Day 3 Postoperative Day 4 Walking by: Postoperative Day 1 Postoperative Day 2 Postoperative Day 3 Postoperative Day 4 Discharged by: Postoperative Day 4 Postoperative Day 5 Postoperative Day 6
Journal of Surgical Oncology
Yes
No
Missing data
151 112 103 127 53 115
0 49 58 34 108 12
10 0 0 0 0 0
111 135 145 148
37 13 3 0
13 13 13 13
74 119 137 146
73 28 10 1
14 14 14 14
33 73 104
128 88 57
0 0 0
Enhanced Recovery in Liver Surgery
Fig. 1. A Kaplan–Meir curve showing length of stay, and the difference between cohorts.
The reduction in high dependency utilization, without an increase in critical care readmission, reflects appropriate pre‐operative stratification of patients. Other series have reported median high dependency stays of 2 days for minor resections and 3 days for major hepatectomies [13], compared to this studies median length of stay of 1 day. The CPET based risk stratification was based on work by Older et al., who first pioneered CPET in postoperative care stratification. [14,15] The success of this stratification is illustrated by the absence of any patient stratified to ward care subsequently requiring unplanned critical care admission. In colorectal surgery ERAS has shown to be associated with a reduction in healthcare cost [1]. This is primarily driven by a reduction in complications and hospital length of stay. The morbidity and hospital length of stay reported in is in keeping with published literature utilizing ERAS following hepatectomy [7–9,12]. When compared to series not using ERAS the morbidity is lower and length of stay shorter [16–18]. This suggests the reduction in costs seen in colorectal surgery as a result of ERAS may be replicated in liver surgery, and would be a useful focus of further study. As the ERAS program evolved there was a progressive reduction in length of stay, without significant change in complication rates. The length of stay reduction in the latter cohort is due to a reduction in the significant minority of patients with a prolonged length of stay,
201
consequently skewing the data less. Given that complications would typically be the cause of a prolonged admission, and that complication rates are static across the cohort, it suggests that complications are impacting hospital length of stay less as ERAS evolves. The reducing hospital length of stay in conjunction with progressive reduction in critical care utilization suggests that ERAS will be associated with lower healthcare costs, and that these benefits accrue with time. A true study of the economic impact of ERAS in patients undergoing hepatectomy would be a useful focus for further study. This is particularly important given the extensive support network the ERAS program requires including the use of CPET, and a dedicated pain team. The strengths of this study include the study size, homogeneity of the study group, and analysis of the effects of ERAS evolution. The lack of adherence data within the early cohort is unfortunate as it would be useful to establish whether the improvements seen were due to evolution of the ERAS program, or due to less variability and the standardization of care. The improvements are likely to be multifactorial, with improving adherence a significant contributor. Indeed when looking at the adherence rate in the latter cohort (Table III) it is evident that a significant cohort of patients do not achieve early postoperative targets including commencing normal diet, mobilizing, and epidural removal by Day 3. Establishing the reasons for failing to achieve these ERAS targets may enable further revisions to the program and allow further improvements in perioperative outcomes, or highlight a cohort of patients where these targets are unachievable. Epidural anesthesia is itself controversial particularly in hepatectomy within an ERAS program [19,20]. The use of intrathecal morphine has been suggested as an alternative, which can deliver early mobilization with excellent pain control. This study is not a randomized assessment of ERAS against a control group as such comparison of ERAS versus standard care directly is not possible. No large randomized controlled trial has examined ERAS in hepatectomy, but all published series, and small trials have reported benefits in favor of ERAS [6–8]. Furthermore, randomized studies of ERAS versus standard care are subject to internal bias, where adoption of ERAS practice across an institution affects the approach of healthcare professionals to any control arm [7]. The findings of this study make it difficult to ethically justify the management of patients outside of an enhanced recovery program, and consequently inappropriate to conduct a trial in this context. In other areas of surgical practice enhanced recovery has led to reduced hospitalization and reduced hospital costs [1]. This study suggests that enhanced recovery after hepatectomy for CRLM is feasible, and is associated with low morbidity and mortality. Enhanced recovery after hepatectomy for CRLM should be a standard of care for all patients.
TABLE IV. Final Multivariable Cox Regression Model for Hospital Length of Stay 95% CI Variable Cohort Early Late Resection Minor Major Age Pulmonary co‐morbidity No Yes
Journal of Surgical Oncology
HR
se
P
Lower
Upper
— 1.41
— 0.17
— 0.004
— 1.11
— 1.78
— 0.78 0.99
— 0.10 0.00
— 0.045 0.006
— 0.61 0.98
— 0.99 1.00
— 0.75
— 0.13
— 0.089
— 0.54
— 1.04
202
Dunne et al.
ACKNOWLEDGMENTS The authors would like to thank key members of the enhanced recovery team for their support including Peter Groom, Claire Burston, and Clare Bryne. Without their support this study would not have been possible. No funding support was received in the conduction of this study.
REFERENCES 1. Adamina M, Kehlet H, Tomlinson GA, et al.: Enhanced recovery pathways optimize health outcomes and resource utilization: A meta‐analysis of randomized controlled trials in colorectal surgery. Surgery 2011;149:830–840. 2. Lassen K, Soop M, Nygren J, et al.: Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations. Arch Surg 2009;144: 961–969. 3. Leibman BD, Dillioglugil O, Abbas F, et al.: Impact of a clinical pathway for radical retropubic prostatectomy. Urology 1998;52:94–99. 4. Niino T, Hata M, Sezai A, et al.: Optimal clinical pathway for the patient with type B acute aortic dissection. Circ J 2009;73:264–268. 5. Spanjersberg WR, Reurings J, Keus F, et al.: Fast track surgery versus conventional recovery strategies for colorectal surgery. Cochrane Database Syst Rev 2011;CD007635. http://www.ncbi. nlm.nih.gov/pubmed/?term¼21328298 6. Hall TC, Dennison AR, Bilku DK, et al.: Enhanced recovery programmes in hepatobiliary and pancreatic surgery: A systematic review. Ann R Coll Surg Engl 2012;94:318–326. 7. Jones C, Kelliher L, Dickinson M, et al.: Randomized clinical trial on enhanced recovery versus standard care following open liver resection. Br J Surg 2013;100:1015–1024. 8. Ni CY, Yang Y, Chang YQ, et al.: Fast‐track surgery improves postoperative recovery in patients undergoing partial hepatectomy for primary liver cancer: A prospective randomized controlled trial. Eur J Surg Oncol 2013;39:542–547.
Journal of Surgical Oncology
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