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Kumar et al. Mini-invasive Surg 2018;2:41 I http://dx.doi.org/10.20517/2574-1225.2018.49 Page 7 of 12

PONV
Prevention and treatment of PONV is of utmost importance to allow early oral intake and keep the patient
within an ERAS pathway. Risk factors include previous PONV, young female patient, nonsmoker, use of
[5]
volatile anesthetic or opioids . Given their favorable side effect profile, 5-HT3 antagonists such as Ondan-
[85]
setron, remain the treatment of choice . Low dose dexamethasone has equivalent antiemetic action but
[85]
has to be used with caution in diabetics . Metoclopramide is a weak antiemetic and a dose of 10 mg may
[86]
not effectively reduce PONV . Therefore, the international ERAS society and the international consensus
group on PONV recommend a multimodal prophylaxis including at least two antiemetic drugs to reduce
PONV [5,87] .

Perioperative steroid administration
Preoperative steroid in patients undergoing hepatic surgery is controversial and its use is limited. Al-
though supported by experimental studies [88,89] , beneficial effects stemming from its immunologic and anti-

inflammatory action has not been consistent [90,91] . Although pre-operative steroid administration has not
been associated with a reduction of post-operative complications in two recent meta-analysis of RCTs [90,91] ,
[92]
it resulted in significantly lower levels of serum bilirubin and interleukins on POD 1 . The mechanism
of action may be due to a protection against warm ischemia-reperfusion injury, lower IL’s release, better
[93]
tissue perfusion, stabilization of cell membrane and lower lysosomal protease release . A negative effect
of steroids in liver regeneration remains a concern, as IL-6 and TNF-α are important initiators of hepatic
[95]
[94]
regeneration . However, Glanemann et al. showed in an animal model that steroids had no negative
impact on liver regeneration. Although the use of preoperative steroids (methylprednisolone) can not be
strongly recommended in liver surgery, they may be used only before hepatectomy in non-diabetic patients
with normal liver parenchyma in order to decrease liver injury and intraoperative stress.

OUTCOMES OF ERAS PROTOCOLS COMPARED WITH TRADITIONAL CARE
[7]
In the inaugural experience with a multimodal ERAS program after open liver surgery, Van Dam et al.
reported a significant reduction in the LOS without increasing morbidity or mortality. Many later retro-
spective studies and meta-analyses comparing ERAS with traditional care have confirmed the safety and
[9]
feasibility of ERAS in liver resection [96-98] . A recent meta-analysis by Wang et al. showed that hospital
stay was significantly shorter for ERAS patients in both RCTs and non-RCTs, being reduced by a mean
of 2.65 days and 1.81 days, respectively (P < 0.001). This benefit was increased if laparoscopic surgery was
[9]
applied, with a mean reduction of 3.64 days (P < 0.001) . Time to bowel function recovery has been con-
sistently found significantly shorter when an ERAS protocol is applied [9,99] . With regards to morbidity, a
meta-analysis of 4 RCTs found that complications were significantly reduced in ERAS patients compared
[99]
[9]
to traditional care patients (20.9% vs. 31.4%; P = 0.02) . This was later confirmed by Wang et al. , who
found significantly less overall morbidity in both RCTs and non-RCTs (OR = 0.57 and 0.66 respectively; P
= 0.01). However, when categorized according to the Dindo-Clavien classification, although ERAS group
had significantly fewer grade I complications (RR = 0.51; P = 0.003), there were no differences in grade II-V
[97]
complications (RR = 0.94; P = 0.80) [100] . Similarly, a RCT by Jones et al. found a significantly reduced rate
of medical complications (7% vs. 27%; P = 0.02), but not surgical complications (15% vs. 11%; P = 0.612). In
addition, three meta-analyses of RCTs found no significant differences regarding 30-day mortality and
readmission rates between ERAS and traditional care approaches [9,101,102] . With regards to QOL evaluation,
two RCTs have found a statistically significant improvement in QOL by one month after surgery in ERAS
patients [98,103] . Finally, although the benefits in outcomes of ERAS protocols have been translated in signifi-
cant cost saving in colorectal surgery, from around $2,800 to $5,900 per patient, this has not been widely
[4]
confirmed in liver surgery yet . Although a recent retrospective cost-benefit analysis of ERAS in liver
surgery from Switzerland found a total mean cost reduction of €3,080 per patient compared to traditional
care, this difference did not reach statistical significance (P = 0.467) [104] . The main outcomes of ERAS proto-
cols reported in the literature are summarized in Table 2.