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HPB : The Official Journal of the International Hepato Pancreato Biliary Association logoLink to HPB : The Official Journal of the International Hepato Pancreato Biliary Association
. 2009 Mar;11(2):140–144. doi: 10.1111/j.1477-2574.2009.00025.x

The effect of a multimodal fast-track programme on outcomes in laparoscopic liver surgery: a multicentre pilot study

Jan H Stoot 1, Ronald M van Dam 1, Olivier R Busch 2, Richard van Hillegersberg 3, Marieke De Boer 4, Steven WM Olde Damink 1,5, Marc H Bemelmans 1, Cornelis HC Dejong 1,5, on behalf of the Enhanced Recovery After Surgery (ERAS) Group
PMCID: PMC2697877  PMID: 19590638

Abstract

Objectives:

This study was conducted to evaluate the added value of an enhanced recovery after surgery (ERAS) programme in laparoscopic liver resections for solid tumours.

Methods:

Patients undergoing laparoscopic liver resection between July 2005 and July 2008 were included. Indications for resections included presumed benign and malignant liver lesions. Primary outcome was total length of hospital stay (LOS). Secondary outcomes were functional recovery, complications, conversions, blood loss and duration of operation.

Results:

Thirteen patients were treated by laparoscopic liver resections in the ERAS programme in one centre (group 1). Their outcomes were compared with outcomes of 13 laparoscopic procedures performed either before the introduction of the ERAS programme during 2003–2005 in the same centre or during the same period in other centres using traditional care (group 2). Median total LOS was 5.0 days (range 3–10 days) in group 1 and 7.0 days (3–12 days) in group 2. This difference was not statistically significant. Functional recovery occurred 2 days earlier in group 1 (median 3.0 days [range 1–7 days] vs. median 5.0 days [range 2–8 days]; P < 0.044). There were no significant differences in complications, conversions or duration of operation. Blood loss was significantly less in the ERAS group (median 50 ml [range 50–200 ml] vs. median 250 ml [range 50–800 ml]; P < 0.002).

Conclusions:

This exploratory, multicentre, fast-track laparoscopic liver resection study is the first such study conducted. Although small, the study suggests that a multimodal enhanced recovery programme in laparoscopic liver surgery is feasible, safe and may lead to accelerated functional recovery and reductions in LOS.

Keywords: laparoscopic liver surgery, functional recovery, fast-track surgery, multimodal enhanced recovery programme

Introduction

Laparoscopic surgical procedures have been popularized because they allow for rapid recovery, shorter postoperative hospital stays and improved cosmetic outcomes. In gastrointestinal surgery, the minimally invasive approach is extensively used in many operations and has become the gold standard for some of these procedures, such as cholecystectomy and adrenalectomy.1,2 For solid tumours in the liver, the laparoscopic technique is used more and more frequently in expert centres and the results, mostly from cohort studies, suggest benefits, notably in terms of shorter postoperative stays.3 With respect to improved recovery and outcome,a multimodal enhanced recovery after surgery (ERAS) programme has recently shown promising results in many open elective colorectal operations, as well as in liver surgery.4,5 This multimodal recovery programme is evidence-based and combines several interventions in perioperative care to reduce the stress response and organ dysfunction, with a focus on enhancing recovery.5,6 The key elements of this protocol include the provision of preoperative counselling, perioperative i.v. fluid restriction, optimal pain relief, preferably without the use of opioid analgesia, early oral nutrition and enforced mobilization, and the absence of nasogastric tubes and drains.68 In other fields of elective surgery, similar programmes have been shown to reduce hospital stay by several days.9,10 However, to our knowledge, the added value of a fast-track ERAS programme in laparoscopic liver surgery has hitherto not been explored. At the Maastricht University Medical Centre (MUMC), the ERAS programme for liver surgery started 2 years after the laparoscopic programme for left lateral sectionectomies. Therefore, a pilot study was conducted to find out whether the ERAS programme was feasible and safe and whether it improved recovery after laparoscopic liver surgery.

Materials and methods

Patients undergoing laparoscopic liver resections for solid liver tumours between July 2003 and July 2008 were enrolled in the study. Preoperative assessment consisted of standard plasma liver function tests, preoperative radiological evaluation with abdominal ultrasonography, contrast-enhanced computed tomography (CT) and/or selective magnetic resonance imaging (MRI) and/or CT-positron emission tomography (CT-PET). Multidisciplinary consent was also required. All lesions <10 cm in diameter and judged amenable to laparoscopic resection were included (left lateral sectionectomy or anterolateral small lesions of the right side of the liver). All but one lesion were limited to lateral liver segments (II, III, V, VI). One lesion was located centrally in segment IV. Indications for surgery included presumed benign and malignant liver lesions. For patients with presumed benign disease, the indications were suspicion of a hepatocellular adenoma or cystadenoma or, in cases where the nature of the tumour was uncertain, the presence of symptoms and risk of bleeding. Indications for liver metastases were synchronous or metachronous liver tumours from colorectal malignancies. Patients were informed about the operative procedure and consent was obtained.

The ERAS perioperative programme was instituted in the surgical unit in Maastricht at the beginning of 2002, initially for patients undergoing elective colonic resections.11 The protocol for this multimodal, evidence-based, enhanced recovery programme for colonic surgery requires extensive preoperative counselling, no premedication, no preoperative fasting but carbohydrate-containing liquids until 2 hours before surgery, mid-thoracic epidural anaesthesia and short-acting anaesthetics, perioperative oxygen supplementation, avoidance of perioperative fluid overload, non-opioid pain management, no routine use of nasogastric tubes, early removal of bladder catheters, standard laxatives and prokinetics, and early and enhanced postoperative feeding and mobilization.5,11 This protocol was modified in 2005 to cover all aspects of liver surgery, including laboratory liver function tests, and to avoid excessive fluids (preoperative and perioperative central venous pressure [CVP] <5 mmHg).4

Until May 2005, traditional care was given before, during and after liver surgery. Therefore, the 5-year period during which laparoscopic liver surgery for solid tumours has been performed at MUMC was divided into two periods, representing the 2 years before the ERAS programme was implemented and the 3 years immediately following its implementation. As the number of patients in the MUMC control group (patients undergoing surgery with traditional perioperative care) was too small to allow us to draw firm conclusions, other major liver centres in the Netherlands, which were not familiar with the ERAS programme and which applied a traditional care protocol, were contacted in order to enrol additional laparoscopic liver resection patients. These included the Academic Medical Centre (AMC), Amsterdam, the University Medical Centre Utrecht (UMCU), Utrecht, and the University Medical Centre Groningen (UMCG), Groningen.

The following recovery data were defined (and patients were considered functionally recovered when all criteria were met): normal or decreasing serum bilirubin; good pain control on oral analgesics only; absence of i.v. fluids and tolerance of solid food, and mobilization to preoperative level.4,8 Patients were considered fit for discharge, or functionally recovered, on the postoperative day when all four criteria were met. Patients were discharged if all four criteria were met and if they were willing to go home.4 A discharge that occurred later than functional recovery was defined as a delayed discharge.

Primary outcome was total length of hospital stay (LOS), defined as the number of nights spent in hospital after surgery, including nights after readmission within 90 days of surgery. Secondary outcomes were functional recovery, complications, conversions, blood loss and length of operation. In addition, the following data were recorded: preoperative indication(s) for surgery; perioperative blood transfusions; use of nasogastric tubes; use of drains; restart of oral fluids; restart of oral solid food; histology of the resected liver specimen, and diameter of the lesions and resection margins.

Complications were defined according to the grading system devised by Clavien et al.12 Grade I complications are generally non-life-threatening complications without lasting disability. Grade II complications are potentially life-threatening, but without residual disability. Grade III complications involve residual disability, including organ resections or persistence of life-threatening conditions. Grade IV complications refer to deaths as a result of complications.

All laparoscopic hepatic resections were performed by two consultant surgeons, one expert in hepatobiliary surgery and one with specific expertise in advanced laparoscopic surgery. Patients were placed in the ‘French’ position (supine position with legs apart) under general anaesthesia. The surgeon stood between the legs with an assistant on each side.13 Liver resections were defined according to anatomical planes (Couinaud's classification). An open introduction of the subumbilical port was used to produce the CO2 pneumoperitoneum. In all cases, a 30-degree laparoscope was used and abdominal pressure was monitored and maintained at 12–14 mmHg. Three to four extra trocars were placed in a semi-circle, slightly higher and paramedian of the umbilical trocar, to facilitate the procedure.13 Inspection of the liver was performed both visually and with laparoscopic ultrasound in order to confirm the number of lesions in relation to main anatomical structures. The falciform, left triangular ligament and lesser omentum were divided. Hepatic transection of the parenchyma and minor crossing vessels and biliary radicals was performed with a harmonic scalpel (Ultracision; Ethicon Endo-Surgery, Johnson & Johnson, Piscataway, NJ, USA). A vascular stapler (EndoGIA; Covidien Surgical Devices, New Haven, CT, USA) was used to divide the portal pedicles and hepatic veins. Resected specimens were placed in a plastic bag (Endocatch; Covidien Surgical Devices) and removed through a separate, preferably suprapubic, incision. In cases where a laparotomy had been performed in the past, a small subumbilical incision was made for retrieval of the specimen.

Statistical analysis

Continuous variables are expressed as median (range). Age, tumour diameter, hospital stay, functional recovery, delay in discharge, blood loss and duration of surgery were analysed using the Mann–Whitney U-test. Sex, American Society of Anesthesiologists (ASA) classification, indication for surgery, type of resection, liver pathology, complications, conversions, intake of fluid and solid food and the use of nasogastric tubes and drains were analysed using the chi-squared or Fisher's exact test as appropriate. A P-value <0.05 was considered statistically significant. Data were analysed using spss Version 13.0 for Windows (SPSS, Inc., Chicago, IL, USA).

Results

A total of 26 patients were treated by laparoscopic liver resection during the 5-year period in the four participating hospitals. Thirteen patients were treated by laparoscopic liver resections (left lateral sectionectomy [II, III] or segmentectomy [IV, V, VI] under the ERAS programme (group 1). All of these were operated at a single centre (MUMC). Thirteen patients were operated in traditional perioperative care settings in the four participating hospitals during the same period (group 2). Three laparoscopic procedures were performed at MUMC from 2003–2005 before the ERAS programme was instituted. Ten patients were operated laparoscopically in traditional perioperative care settings at the AMC (n = 4), UMCU (n = 2) and UMCG (n = 4).

Demographics and clinical data are reported in Table 1. Median total LOS was reduced by 2 days in the ERAS group, but this difference did not attain statistical significance (Table 2). There were no readmissions in either group. There were two minor complications (grade I) in the ERAS group and two (grade I) in the traditional care group. In group 1, one patient had a urinary tract infection, which was treated by antibiotics, and another had constipation and remained in hospital longer. In group 2, one patient was treated for a hypokalaemia and another for atrial fibrillation. There were no deaths. The rate of conversions was similar in both groups (Table 2). In group 2 (traditional care), conversion occurred because of a preoperatively undetected lesion in segment IV in one patient and suboptimal visualization in another. The conversions in the ERAS group occurred because of the uncertain nature and size of the lesion and its proximity to the left liver vein in one patient and because of suboptimal visualization in another. Blood loss was significantly less in the ERAS group (P < 0.002). However, there was no difference in blood transfusions. Only one patient from group 2 (traditional care) received two units of packed cell while in hospital. No significant difference was observed in operation time. Oral fluid intake was resumed within 24 hours of surgery in almost all patients in the ERAS group, as well as in the traditional care group (median 1 day [range 0–2 days] vs. median 1 day [range 0–6 days], respectively; P = 0.861). The median time to successful resumption of normal diet was 1 day (range 1–2 days) in the ERAS group, compared with 2 days (range 1–6 days) in the controls (P = 0.223). Nasogastric decompression tubes were not used after surgery in the ERAS group. In the control group, nasogastric tubes were in place after surgery in five of 13 patients for 1–5 days (P = 0.257). This included two reinsertions because of delayed gastrointestinal function on day 1. In the ERAS group, no drains were used after surgery. In the control group, six patients received a drain, which was removed 2–4 days after surgery (P = 0.015).

Table 1.

Clinical and pathological features

Group 1 Group 2 P-value
ERAS programme Traditional care
(n = 13) (n = 13)
Age, years* 55 (34–82) 45 (26–70) 0.104
ASA score I/II/III/IV 3/9/1/0 6/6/1/0 0.688
Patient sex, M/F 3/10 2/11 1.0
Indication for surgery: malignant/benign 8/5 3/10 0.111
Types of liver resection
Left lateral sectionectomy 9 9
Monosegmentectomy (or metastasectomy) 3 3 1.0
Multiple segmentectomy (≥2 segments) 1 1
Liver pathology: malignant/benign 5/8 2/11 0.160
Tumour size, cm* 4.1 (1.0–10.5) 6.0 (1.4–8.0) 0.765
*

Continuous variables are expressed as median (range)

P-values by Fisher's exact test, except

Mann–Whitney U-test

ERAS, Enhanced Recovery After Surgery; ASA, American Society of Anaesthesiologists; M, male; F, female

Table 2.

Primary and secondary outcomes. No readmissions were recorded in either group

Group 1 Group 2 P-value
ERAS programme Traditional care
(n = 13) (n = 13)
Primary outcome
Total LOS, days* 5.0 (3–10) 7.0 (3–12) 0.305
Secondary outcomes
Functional recovery, days* 3 (1–7) 5 (2–8) 0.044
Complications, n (grade) 2 (I) 2 (I) 1.0
Conversions, n 2 2 1.0
Blood loss, ml* 50 (50–200) 250 (50–800) 0.002
Operation time, min* 118 (85–192) 180 (51–340) 0.293
*

Continuous variables are expressed as median (range)

P-values by Fisher's exact test, except

Mann–Whitney U-test

ERAS, Enhanced Recovery After Surgery; LOS, length of stay

In both groups, functional recovery was achieved a median of 2 days earlier than actual discharge. In the ERAS group, patients met the discharge criteria on median postoperative day 3 (range 1–7 days), compared with the traditional care group, which met the discharge criteria on median postoperative day 5 (range 2–8 days). The difference between the groups in functional recovery proved to be statistically significant (P < 0.044), as did the difference in delay in discharge (P < 0.032).

In group 1, resected specimens included two hepatocellular adenomas, two focal nodular hyperplasias (FNHs), an angiomyolipoma, a haemangioma, a presumed metastasis which proved to be an inflammatory pseudotumour after chemotherapy, an intra-hepatic accessory gallbladder with inflammation, a hepatocellular carcinoma and four metastases of colorectal origin. Resection margins were free of disease in 12 cases; one resected adenoma extended to the resection margin. In group 2, resected specimens included three adenomas, six FNHs and two haemangiomas and, in two patients, three metastases of colorectal origin. Resection margins were free of disease in eight patients, were not reported (benign tumour) in four and involved a haemangioma in the resection surface in one.

No late complications were recorded in group 1 during the follow-up period (median 3 months, range 1–23 months). In the follow-up period (median 6 months, range 1–27 months) in group 2, one patient developed colorectal metastases in the lungs and liver (segments VI and VII) and simultaneous acute myeloid leukaemia. No palliative chemotherapy was given to this patient because of his clinical condition and he died 12 months postoperatively.

Discussion

This study investigated the added value of an enhanced recovery programme in laparoscopic liver surgery. To the best of our knowledge, this represents the first such study to be conducted (although it is only a small pilot study). The results suggest that initiation of a multimodal enhanced recovery programme in laparoscopic liver surgery is feasible. It also shows that it is safe to implement an evidence-based enhanced recovery programme, as there were only two minor complications in the ERAS group and two conversions in each group. The difference in median LOS of 2 days did not attain significance, but this probably reflects the small number of patients in this study. Importantly, the current study provides evidence that an enhanced recovery programme is associated with expedited functional recovery. Patients in the laparoscopic ERAS group fulfilled discharge criteria 2 days earlier than control patients.

Patients in the enhanced recovery group had less blood loss. This may have resulted from the implementation of the ERAS protocol, which prescribes a low CVP and the avoidance of excessive perioperative fluids. However, although this outcome issignificant, it remains unclear whether it resulted solely from the implementation of ERAS. This difference in blood loss may also have been clouded by the learning curve effect because the patients operated in group 2 (traditional care) were the first patients to be treated laparoscopically in the participating centres.

Most authors recommend that laparoscopic procedures on liver resections of solid tumours should preferably begin with the left lateral segments or anterolateral small lesions of the right side.13,14 Tumours of the left lateral side, particularly benign tumours, constitute only a small fraction of the minor resections in most units. This is probably one of the reasons for the small number of patients in this pilot study. It was also considered unethical to prospectively compare effects in an intervention (ERAS) group with effects in a control group receiving traditional care in Maastricht because the ERAS protocol includes several evidence-based care elements aimed at reducing surgical stress and postoperative catabolism.68

Studies on colorectal laparoscopy and fast-track programmes have shown conflicting results regarding the additional outcomes of minimally invasive surgery performed within a perioperative ERAS programme. In a single-centre study, the laparoscopic approach seemed to improve the outcome in terms of LOS, whereas other studies, including a randomized controlled trial, showed no additional effect of laparoscopy on LOS.1517 Therefore, it has been suggested that there is a need for further randomized trials to evaluate the additional effects of laparoscopy within fast-track recovery programmes in colorectal surgery.5,15,16 At present, there is only limited evidence available about the effects on LOS of a multimodal, fast-track setting in liver surgery.4

In the current study, a difference between the date of functional recovery of patients undergoing liver resection and the day of actual discharge was observed, as we previously reported in a colonic ERAS programme.11 A significant difference of a median of 2 days in time to full functional recovery was observed between the ERAS-treated group and the traditional care group. It is remarkable that, despite the preoperative counselling in the ERAS programme, a difference between functional recovery and actual day of discharge was still observed. This implies that the difference in LOS may be even more pronounced if patients do actually go home as soon as they are functionally recovered according to predefined criteria.8,11 Delay in discharge and presence of complications were associated with increased LOS. For future studies, functional recovery may be a better criterion with which to investigate differences in outcome of surgical treatments. Establishing the effect of ERAS programmes on outcomes in laparoscopic liver surgery in a more structured manner is a challenge yet to be met.

Acknowledgments

The authors thank the patients who agreed to participate in the study and the surgeons, anaesthetists and nurses who helped to implement the protocol.

The Enhanced Recovery After Surgery initiative was funded principally by Nutricia Healthcare (Zoetermeer, the Netherlands), which also sponsored preparatory meetings with an unrestricted grant. CHCD was supported by a grant from the Dutch Organization for Scientific Research (NWO Clinical Fellowship 907-00-033).

Conflicts of interest

None declared.

References

  • 1.Gagner M, Pomp A, Heniford BT, Pharand D, Lacroix A. Laparoscopic adrenalectomy: lessons learned from 100 consecutive procedures. Ann Surg. 1997;226:238–246. doi: 10.1097/00000658-199709000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Trondsen E, Reiertsen O, Andersen OK, Kjaersgaard P. Laparoscopic and open cholecystectomy. A prospective, randomized study. Eur J Surg. 1993;159:217–221. [PubMed] [Google Scholar]
  • 3.Simillis C, Constantinides VA, Tekkis PP, Darzi A, Lovegrove R, Jiao L, et al. Laparoscopic versus open hepatic resections for benign and malignant neoplasms – a meta-analysis. Surgery. 2007;141:203–211. doi: 10.1016/j.surg.2006.06.035. [DOI] [PubMed] [Google Scholar]
  • 4.van Dam RM, Hendry PO, Coolsen MM, Bemelmans MH, Lassen K, Revhaug A, et al. Initial experience with a multimodal enhanced recovery programme in patients undergoing liver resection. Br J Surg. 2008;95:969–975. doi: 10.1002/bjs.6227. [DOI] [PubMed] [Google Scholar]
  • 5.Wind J, Polle SW, Fung Kon Jin PH, Dejong CH, von Meyenfeldt MF, Ubbink DT, et al. Systematic review of enhanced recovery programmes in colonic surgery. Br J Surg. 2006;93:800–809. doi: 10.1002/bjs.5384. [DOI] [PubMed] [Google Scholar]
  • 6.Fearon KC, Ljungqvist O, Von Meyenfeldt M, Revhaug A, Dejong CH, Lassen K, et al. Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clin Nutr. 2005;24:466–477. doi: 10.1016/j.clnu.2005.02.002. [DOI] [PubMed] [Google Scholar]
  • 7.Kehlet H. Manipulation of the metabolic response in clinical practice. World J Surg. 2000;24:690–695. doi: 10.1007/s002689910111. [DOI] [PubMed] [Google Scholar]
  • 8.Maessen J, Dejong CH, Hausel J, Nygren J, Lassen K, Andersen J, et al. A protocol is not enough to implement an enhanced recovery programme for colorectal resection. Br J Surg. 2007;94:224–231. doi: 10.1002/bjs.5468. [DOI] [PubMed] [Google Scholar]
  • 9.Podore PC, Throop EB. Infrarenal aortic surgery with a 3-day hospital stay: a report on success with a clinical pathway. J Vasc Surg. 1999;29:787–792. doi: 10.1016/s0741-5214(99)70204-1. [DOI] [PubMed] [Google Scholar]
  • 10.Trondsen E, Mjaland O, Raeder J, Buanes T. Day-case laparoscopic fundoplication for gastro-oesophageal reflux disease. Br J Surg. 2000;87:1708–1711. doi: 10.1046/j.1365-2168.2000.01578.x. [DOI] [PubMed] [Google Scholar]
  • 11.Maessen JM, Dejong CH, Kessels AG, von Meyenfeldt MF. Length of stay: an inappropriate readout of the success of enhanced recovery programmes. World J Surg. 2008;32:971–975. doi: 10.1007/s00268-007-9404-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Clavien PA, Sanabria JR, Strasberg SM. Proposed classification of complications of surgery with examples of utility in cholecystectomy. Surgery. 1992;111:518–526. [PubMed] [Google Scholar]
  • 13.Cherqui D, Husson E, Hammoud R, Malassagne B, Stephan F, Bensaid S, et al. Laparoscopic liver resections: a feasibility study in 30 patients. Ann Surg. 2000;232:753–762. doi: 10.1097/00000658-200012000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Gigot JF, Glineur D, Santiago AJ, Goergen M, Ceuterick M, Morino M, et al. Laparoscopic liver resection for malignant liver tumours: preliminary results of a multicentre European study. Ann Surg. 2002;236:90–97. doi: 10.1097/00000658-200207000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Basse L, Jakobsen DH, Bardram L, Billesbolle P, Lund C, Mogensen T, et al. Functional recovery after open versus laparoscopic colonic resection: a randomized, blinded study. Ann Surg. 2005;241:416–423. doi: 10.1097/01.sla.0000154149.85506.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.MacKay G, Ihedioha U, McConnachie A, Serpell M, Molloy RG, O'Dwyer PJ. Laparoscopic colonic resection in fast-track patients does not enhance short-term recovery after elective surgery. Colorectal Dis. 2007;9:368–372. doi: 10.1111/j.1463-1318.2006.01123.x. [DOI] [PubMed] [Google Scholar]
  • 17.Raue W, Haase O, Junghans T, Scharfenberg M, Muller JM, Schwenk W. Fast-track’ multimodal rehabilitation programme improves outcome after laparoscopic sigmoidectomy: a controlled prospective evaluation. Surg Endosc. 2004;18:1463–1468. doi: 10.1007/s00464-003-9238-y. [DOI] [PubMed] [Google Scholar]

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