Abstract
Background
Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature.
Methods
A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when >80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system.
Results
A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (>80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy.
Conclusions
These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed.
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Introduction
Enhanced Recovery After Surgery (ERAS) is a multimodal and perioperative management pathway. ERAS offers to reduce the response to surgical stress and has been shown to decrease postoperative complications and length of stay (LoS) after several types of surgery [1, 2].
The first ERAS guidelines for liver surgery were published in 2016 [3]. Since then, several publications have shown that implementation of ERAS in liver surgery improves postoperative outcomes [4, 5]. Three recent meta-analyses showed that ERAS in liver surgery decreased postoperative complications, LoS, and costs [6,207].
Summary and recommendation: Use of an omental flap to cover the cut surface of the liver might reduce the risk of delayed gastric emptying after left-sided liver resection.
Evidence level: Low.
Grade of recommendation: Weak.
Stimulation of bowel movement
Shimada et al. [208] found in a multicenter RCT that daikenchuto (TU-100, traditional herbal medicine) significantly decreased the median time to first bowel movement by 5 h in 231 patients who underwent hepatectomy for cancer. Although significant, this 5-h difference is probably not clinically relevant as complication rates were similar in both groups. Another RCT assessing the effect of daikenchuto after hepatectomy found that the daikenchuto group had shorter time to bowel movement and oral intake, but complications were similar [209]. You et al. [210] performed a 3-arm RCT to assess ileus rates in patients with HCC undergoing liver resection. Simo decoction (traditional Chinese herbal medicine) with acupuncture was compared to gum chewing and no specific postoperative intervention (control group). Both interventions were found to diminish the time to first stool compared to the control group, whereas only the group with simo decoction and acupuncture had a shorter length of hospital stay. In a RCT of 68 patients undergoing liver surgery, the group with laxatives had reduced time to passage of stool but similar secondary outcomes, such as DGE, LoS, or time to functional recovery [211]. Jang et al. [212] showed in a prospective case–control study including 42 patients that gum chewing permitted to decrease the time to first flatus and the xerostomia rate, but did not have an effect on LoS or analgesic use.
Summary and recommendation: Postoperative laxatives, gum chewing, herbal medicine, or decoction after hepatectomy might reduce the time to first flatus or stool but do not impact the morbidity rate. Current data do not permit the recommendation of the routine use of postoperative laxatives, gum chewing, herbal medicine, or decoction to stimulate bowel movement after liver surgery.
Evidence level: Moderate.
Grade of recommendation: Weak.
Early and scheduled mobilization
Bed rest is associated with multiple established deleterious effects including muscle atrophy, thromboembolic disease, and insulin resistance [213,214,215]. A RCT involving 120 patients undergoing liver resection showed a significantly faster postoperative gastrointestinal function and shorter length of hospital stay after performing early activity (from postoperative day 1) [216]. An early postoperative mobilization program based on supervised exercises improved functional capacity in patients undergoing major elective abdominal oncologic surgery [217].
So far, however, no consensus has been defined regarding the type, frequency, and intensity of physical therapy in liver surgery [218].
Summary and recommendation: Early mobilization (out of bed) after liver surgery should be established from the operative day until hospital discharge. No recommendation can be made regarding the optimal duration of mobilization.
Evidence level: Moderate.
Grade of recommendation: Strong.
Postoperative nausea and vomiting (PONV) prophylaxis
PONV occurs frequently after major surgery (25–30%). The multimodal approach and opioid reduction provided by ERAS enable the majority of patients to eat early after hepatectomy [219]. Known risk factors, such as previous PONV, female gender, younger age, non-smoker, and use of volatile anesthetic agents and opioids, should be evaluated before the operation [220]. The 5-HT3 antagonists are the primary treatment because of their safe side effect profile. Low-dose dexamethasone is a good additive preventative agent and facilitates hepatic regeneration [221]. Of note, there is no supplementary advantage of using higher doses [221]. However, dexamethasone should be used with caution in diabetics as it can transiently worsen glycemic control [222]. Antihistamines, butyrophenones, and phenothiazines can also be used as second-line therapy [88]. The international consensus group on PONV recommends using 2 antiemetic drugs to decrease PONV and to improve efficacy [88]. Table 3 summarizes potential antiemetic drugs with doses and timing of use.
Summary and recommendation: A multimodal approach to postoperative nausea and vomiting should be used. Patients should receive postoperative nausea and vomiting prophylaxis with at least 2 antiemetic drugs such as dexamethasone and ondansetron.
Evidence level: High.
Grade of recommendation: Strong.
Fluid management
Blood loss and transfusion rates remain central risk factors leading to higher morbidity and mortality after liver resections [223,224,225]. A Cochrane review showed that a lower central venous pressure (CVP) decreased blood loss, but without significant difference in red blood cell transfusion requirements, intraoperative morbidity, or long-term survival benefits [226]. Another systematic review and meta-analysis also confirmed that low CVP was associated with less blood loss [227].
Regarding fluid management for major hepatic surgery, there is currently no protocol available providing the optimum amount of fluid to be given to patients. The current concept must focus on the maintenance of central euvolemia, thereby preventing any excess of salt or water. Goal-directed fluid therapy (GDFT), targeting adequate cardiac output and end-organ perfusion, has attracted much attention. A meta-analysis of 32 RCT including about 3000 patients testing the impact of GDFT during major surgery, i.e., not only liver surgery, demonstrated significant benefits in reducing morbidity and mortality [228]. A RCT published in 2015 found that stroke volume variation (SVV)-guided GDFT compared to standard fluid resuscitation decreased the intraoperative infused fluid volume without decreasing postoperative complications [229]. On multivariable analysis, higher intraoperative fluid volume was an independent risk factor for 30-day morbidity. Recently, Weinberg et al. [230] showed in an RCT that a restrictive GDFT did not decrease LoS and fluid-related complications compared to conventional care within an ERAS pathway for major liver resection. Of note, only 24 patients were included in each arm.
Excessive administration of crystalloids should be avoided as much as blood loss during liver surgery. To guide fluid management during surgery, the measurement of SVV has been proposed to replace CVP monitoring [231]. A randomized prospective trial comparing SVV monitoring versus CVP recording in 90 patients undergoing laparoscopic liver surgery showed a reduced conversion rate as well as reduced blood loss in favor of the SVV approach [232]. The choice for intravenous fluid therapy in liver surgery is still under debate. A systematic review covering 43 RCT compared 18 fluid types (9 crystalloids and 9 colloids) in major abdominal surgery concluded that the best approach was balanced crystalloids (e.g., Ringer’s lactate) as maintenance fluid and colloids as volume expander (e.g., human albumin) [233]. Concerning the postoperative period, a recent retrospective study showed that a weight gain ≥3.5 kg on postoperative day 2 was an independent risk factor for major complication after liver surgery [234]. This suggests that postoperative weight fluctuation should be carefully monitored and potentially minimized.
Summary and recommendation: Low central venous pressure (below 5 cm H2O) with close monitoring is recommended during hepatic transection. As maintenance fluid balanced crystalloid should be preferred over 0.9% saline or colloids. Goal-directed fluid therapy optimizes cardiac output and end-organ perfusion. This may be particularly beneficial after the intraoperative liver resection during a low central venous pressure state to restore tissue perfusion. Patients who have comorbidities and reduced cardiac function may benefit most.
Evidence level: High.
Grade of recommendation: Strong.
Monitoring/audit
Monitoring the outcomes after implementation of ERAS allows performing a precise audit. Outcome monitoring therefore represents the first step to establish an audit of quality. A recent study reported the successful implementation of a nationwide audit for liver surgery in the Netherlands [235]. This audit on postoperative outcomes after liver surgery was intended to evaluate the quality of centers performing these operations and to reach or maintain the best surgical quality. Otherwise, no study specifically designed for liver surgery has been published yet. A Cochrane systematic review on the effects of audit and feedback analyzed 140 studies [236]. It was found that audit and feedback generally induce improvements. The audit was more efficient when the baseline performance was low. The structure of the audit or feedback played a role. It was, for example, of interest to identify specific targets and put in place a plan of action. Another review by Ivers et al. [237] revealed that the body of evidence showing that audit improves outcomes was substantial, but that progress and evolution in this field were not present in recent literature. To a larger scale such as healthcare system, Grimshaw et al. [238] recommended the implementation of laboratories to better understand the science behind audit and feedback and to improve audit and feedback and their impact. One article highlighted the importance of undertaking actions over just measurement [239]. Recently, the Clinical Performance Feedback Intervention Theory issued from a systematic review and meta-synthesis postulated that an effective feedback was a cyclical process and that every missing links stop** the “cycle” cause effect loss of the feedback [240]. This theory includes recommendations for optimally designing or implementing an audit intervention. Practical suggestions on how to effectively display or deliver feedback have also been published [241].
Summary and recommendation: Substantial literature exists supporting that audit and feedback improve outcomes in health care and surgery. Regular audit and feedback should be implemented and performed in liver surgery to monitor and improve postoperative outcomes and compliance to the ERAS program.
Evidence level: Moderate.
Grade of recommendation: Strong.
Discussion
This systematic review and modified Delphi consensus elaborated 25 recommendations based on the best available evidence published until mid-2020. Nine items had a high level of evidence: preoperative smoking and alcohol cessation, preoperative nutrition, wound catheter and TAP block, prophylactic nasogastric intubation, prophylactic abdominal drainage, postoperative artificial nutrition and early oral intake, postoperative glycemic control, PONV prophylaxis, and fluid management.
Regarding differences with 2016 recommendations, more evidence regarding use of steroids before hepatectomy has been published since. It is now routinely recommended in non-diabetic patients. Routine drainage after hepatectomy without biliary reconstruction is not recommended in the present guidelines, whereas in 2016 no conclusive evidence and no recommendation for or against the use of drain were given. In addition, 3 novel items were introduced: prehabilitation, preoperative biliary drainage, and preoperative smoking and alcohol cessation. The novelties of these guidelines are the addition of the 3 novel items mentioned hereabove and the reassessment of the previously published items based on the most recent literature data.
It is not clear if patients with cirrhosis undergoing liver surgery should be managed differently within an ERAS program. Preliminary data showed that ERAS was safe in these patients [242, 243]. Further robust data are needed, and it remains unclear if ERAS pathways should be adapted in cirrhotic patients undergoing liver surgery.
It is important to mention that the compliance (adherence) to all ERAS items is paramount. It has been clearly shown that higher compliance to the ERAS pathway allows to have better postoperative outcomes compared to lower compliance [244, 245].
In conclusion, these guidelines for perioperative care after liver surgery were developed based on the best available evidence and recommend management for 25 perioperative items.
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Acknowledgements
The authors would like to thank Cécile Jaques and Alexia Trombert, Biomedical Information Specialists (Medical Library, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland), for support with the systematic literature search.
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Prof. Nicolas Demartines is implementation chair of the ERAS Society. The other authors declare that they have no conflict of interest.
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Joliat, GR., Kobayashi, K., Hasegawa, K. et al. Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations 2022. World J Surg 47, 11–34 (2023). https://doi.org/10.1007/s00268-022-06732-5
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DOI: https://doi.org/10.1007/s00268-022-06732-5