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Page 4 of 15 Gidumal et al. Plast Aesthet Res 2021;8:42 https://dx.doi.org/10.20517/2347-9264.2021.27

expectations and improving their understanding of treatment course are recommended as an early part of
enhanced recovery protocol and represents a target for improvement [8,20,21] .

Assessment of preoperative nutritional status
Up to 57% of head and neck cancer patients suffer from malnutrition caused by catabolic tumor cytokines,
mechanical obstruction within the aerodigestive tract, and anorexia from alterations in neurotransmitters
and immunoregulatory hormones [8,22] . Malnutrition leads to an immunocompromised state and predisposes
patients to postoperative complications such as poor wound healing, infection, poor survival outcomes, and
increased risk of locoregional recurrence [8,23] .

Originally developed in 1984 to screen surgical candidates for malnutrition prior to gastrointestinal surgery,
Onodera’s prognostic nutritional index (PNI) has gained significant traction as a preferred nutritional
[24]
screen prior to head and neck surgery . PNI uses a simple formula [Figure 2] to calculate a nutritional
score with just two variables: serum albumin and total lymphocyte count. A PNI ≤ 40 is associated with a
significantly increased risk of postoperative complications Clavien-Dindo grade II and IIIa as well as
prolonged hospital stay . Furthermore, a PNI score under 40 has been shown as a stronger and more
[25]
consistent prognostic indicator for postoperative complications due to malnutrition than body mass
index . In addition to the surgical setting use, PNI has also been used successfully to predict worse
[25]
outcomes after chemotherapy, demonstrating the wide-ranging applicability of the metric as an indicator of
malnutrition . While other validated nutritional screens have also been employed to screen for nutritional
[26]
status in head and neck populations, no single metric of malnutrition has yet been established as the
[26]
standard of care . Interestingly, despite the supporting evidence, many institutions do not utilize PNI
routinely in clinical practice. It is believed that all patients presenting as candidates for head and neck
surgery should be screened using PNI, and patients should be referred to a dietician for further evaluation
and management.

Preoperative immunonutrition
When possible, patients who suffer from malnutrition may benefit from a brief delay prior to surgery to
undergo nutritional prehabilitation, a practice that has been shown to improve postoperative outcomes. The
administration of immunonutrition, nutritional formulas containing essential nutrients to promote
[27]
adequate immune response after medical treatment or surgery, has demonstrated improved outcomes . In
addition to supplementing caloric intake to combat malnutrition, immunonutritional formulas are often
comprised of a variety of immunoactive additives, including L-arginine, omega-3 fatty acids, and RNA
nucleotides. L-arginine, in particular, has garnered the most attention for its beneficial impact on wound
healing and infection prevention prior to surgery.

L-arginine (now “arginine”), an amino acid, is an essential component of both the urea cycle and the nitric
oxide cycle . Although arginine is synthesized in the kidney from citrulline, additional dietary arginine is
[28]
needed for growth, wound repair, and infection prevention . Arginine improves wound healing through
[29]
two mechanisms: the generation of nitric oxide as well as the upregulation of growth hormone and insulin-
like growth factor. Firstly, nitric oxide (NO), the chemical that forms the basis for many vasodilatory
medications such as nitroglycerin, is generated from arginine in the nitric acid cycle. The biological effects
of NO on vascular tone have been shown to improve blood flow to free flaps in both healthy and diseased
individuals, with effects lasting for weeks after administration [30,31] . Secondly, dietary arginine administration
has been shown to elevate serum levels of growth hormone and insulin-like growth factor (IGF-1). These
hormones are key components of the anabolic response required for wound healing and are associated with
increased collagen production [31,32] . The improved wound healing afforded by arginine administration has