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As noted earlier, ERAS aims to target several areas in an effort to minimise
the impact of the surgical stress and maintain homeostasis. The main areas
will be highlighted below, namely; preparing the patient for the surgical
stress, minimising insulin resistance, maintaining fluid balance, maximising
multimodal analgesia and improving postoperative deconditioning.

1.3.1. Preparing the patient for surgical stress

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A number of pre-existing factors can impact the patient’s response to the
surgical stress, such as; comorbidities, premorbid status and psychological
preparedness. In an ageing population such as in Australia, the large
proportion of patients requiring surgery is often the elderly population. With
this comes patients associated with a number of comorbidities including

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ischaemic heart disease, diabetes and chronic obstructive airway disease. It is
well established that the more significant comorbidities present, the higher
the risk of complication (25). Furthermore, with the surge of obesity there is
an additional significant stress placed on organ systems in the perioperative
period with reduction in functional ability. Smoking, alcohol, anaemia, poor
nutritional status and poor glycaemic control can further negatively affect
postoperative infection rate, immune function and tissue healing (16).
Furthermore, preoperative anxiety and emotional distress have been reported
to have significant impact on postoperative recovery. Studies have reported
associations with higher complication rates, greater postoperative pain and
delayed rehabilitation (16).

In light of these factors, fundamental preoperative ERAS elements involve a
risk assessment, optimisation of pre-existing organ function and education.
This is achieved via a multidisciplinary team involved in the preoperative
period including anaesthetists, surgeons, physicians, dietitians,
physiotherapists, nurses, and, when required, psychologists.

1.3.2. Minimising insulin resistance

Several ERAS elements are aimed to minimise surgical stress by moderating
perioperative insulin sensitivity. These include preoperative carbohydrate
loading, adherence to pre-operative fasting guidelines (cessation of food for
six hours and clear fluids for two hours), early oral feeding, glycaemic control
and epidural anaesthesia.

The use of preoperative oral carbohydrate solutions have been reported to
increase insulin sensitivity 50% and reduce postoperative insulin resistance
by 50% (26). Furthermore, carbohydrate loading also shifts cellular

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metabolism to a more anabolic state. This allows better use of postoperative
nutritional care, with less risk of hyperglycaemia and improved retention of
protein ultimately leading to a reduction in LOS (27). Another effort to
minimise insulin resistance in ERAS is to recommence nutrition early
postoperatively. The benefits of which were noted in a study by Soop et al.
(28) which commenced complete enteral feeding immediately after the
operation in colorectal surgery. They not only found that ERAS was
associated with minimal postoperative insulin resistance, enteral nutrition
was provided without hyperglycaemia with an overall nitrogen balance of
0.1g nitrogen per day (28).

1.3.3. Maintaining fluid balance

Following the initiation of the surgery, the release of catabolic hormones and
inflammatory mediators facilitate salt and water retention to preserve
intravascular volume, maintain blood pressure and provide gluconeogenic
substrates for metabolism and cell function. Salt and water overload of more
than 2.5kg weight gain (2.5L cumulative fluid overload) has been shown to
lead to ‘gut oedema'(29). This in turn may lead to postoperative ileus and can
impact the integrity of the anastomosis (30,31). Furthermore, studies have
demonstrated that when patients are not maintained in a state of near-zero
fluid balance, the rise in complications may increase LOS (30).

ERAS therefore targets the maintenance of fluid and electrolyte balance and
tissue perfusion via several modalities in the perioperative period. Adequate
preoperative hydration and avoidance of bowel preparation aim to keep the
patient close to normovolaemia prior to surgery. Intraoperatively, the use of
additional monitoring devices such as pulse pressure variation, stroke volume

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variation, oesophageal Doppler and pulse contour wave analysis can guide
fluid therapy. This is particularly valuable during challenging periods such as
haemorrhage or poor cardiac function (32). In addition, maintenance of
normothermia maintains central and peripheral perfusion. Postoperatively,
the early recommencement of oral fluids also allows control of homeostasis.

1.3.4. Maximising multimodal analgesia

Surgery itself can lead to cell disruption leading to a rise in a number of
intracellular chemical mediators (e.g. potassium, cytokines and chemokines)
that activate and sensitise peripheral nociceptors (16). Acute surgical pain can
be somatic, visceral or neuropathic depending on the type of surgery (33).
The rationale for multimodal analgesia is based on the multifactorial nature
and complexity of surgical pain pathways (16). Therefore, control of pain is
achieved via different classes of medications acting on multiple sites (33).

In ERAS, multimodal analgesia aims not only to improve postoperative pain
control and minimise surgical stress but also to diminish the multi-organ
dysfunction induced by unrelieved pain, reduce opioid side effects, facilitate
early resumption of normal diet and early mobilisation, ultimately improving
overall recovery. Previously this was achieved via epidurals and
non-steroidal anti-inflammatories (NSAIDs), however in recent times due
their adverse effects there has been a shift towards spinals/transversus
abdominis plane (TAP) blocks or IV lidocaine (34).

1.3.5. Minimising postoperative deconditioning

Prolonged bed rest for up to several weeks in hospital was historically
standard practice up until the 1940s (35). However, studies have reported that
individuals confined to bed rest tend to exhibit a linear decline in exercise

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capacity (36). Complications include postoperative muscle and
cardiovascular deconditioning, complications attributed to immobility (e.g.
pulmonary and thromboembolic events), decreased insulin sensitivity, and
reduced gastrointestinal recovery (35,37). In fact, some of these effects can
be exhibited within only two days of physical inactivity (35,37). While ERAS
programmes do not specify specific types of exercise, it does highlight the
importance of a structured mobilisation plan with daily targets beginning as
early as the day of surgery.

While each of these interventions individually may only have a small effect,
collectively they are believed to have a synergistic effect. When implemented
successfully, ERAS has been associated with significant reduction in LOS
(38). This benefit has been observed without a concurrent rise in
complications or readmissions (38). While ERAS is evidence-based, the
translation into clinical care has been slow due to the challenge it places on
the traditional surgical dogmas. In fact, recent studies have demonstrated that
some of the traditional approaches to surgical care such as preoperative bowel
clearance, use of NGT, drains placed into cavities, enforced bed rest and use
of graduated diets have been found to be unnecessary, and in some cases even
harmful (38). The subsequent advancement of ERAS programmes has led to
the publication of guidelines on the perioperative care focused on colonic,
rectal/pelvic and pancreatic and gastric surgery (39–41). Previous versions of
these guidelines have been shown to impact on daily practice across multiple
studies.

One such study, was published by Greco et al. (42), a meta-analysis of RCTs
to assess the impact of ERAS pathway on overall morbidity, single

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postoperative complications, LOS and readmission following colorectal
surgery. Out of 2,376 patients in 16 RCTs, they found a shortened hospital
stay (weighted mean difference (WMD): -2.28 days, 95% CI: 3.09 to1.47)
without increasing readmission rate. They also noted a reduction in overall
morbidity (RR: 0.60, 95% CI: 0.46 to 0.76).

Furthermore, in 2011 Gustafsson et al. (43), demonstrated in an international,
multicentre study, better compliance to an evidence based ERAS protocol led
to improved outcomes in terms of complications, LOS and readmissions.
ERAS patients treated with less than 50% compliance had a complication rate
of almost 50%, while those achieving at least 90% compliance had less than
20% complications. Similar improvements have been reported in a
meta-analysis of RCTs (44).

While there is a significant body of evidence in favour of ERAS in specialties
such as colorectal, urology and cardiothoracic surgery there is limited
evidence in the benefits of ERAS in PD (24). 

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