Optimizing Nutritional Status of Patients Prior to Major Surgical Intervention

Background

The American College of Surgeons National Surgical Quality Improvement Program database developed a preoperative mortality predictor (PMP) for general surgery. PMP identified nine variables as predictors of death, among them “inpatient status, poor functional status, age, cancer, comorbidities, and weight loss.”³

Hiram Studley in 1936 established the association between preoperative weight loss and postoperative mortality rate in patients with peptic ulcer disease.^4,5 The understanding of the impact of nutritional status on surgical outcomes showed slow progress until the 2018 joint consensus statement of the Perioperative Quality Initiative (POQI) workgroup and American Society for Enhanced Recovery (ASER).⁶ Since then, recognition of the effect of age, mobility status, comorbidities, presence of malignancies, and performance status on outcomes has promoted the search for evidence-based preventive and therapeutic interventions.³

Fowler et al. compared historical references and showed that progressive aging among surgical patients has increased and is expected to continue in the future.⁷ The impact of aging on mechanical muscle function was evaluated by Hvid et al. in young and older healthy active men, comparing muscular function after short-term disuse followed by retraining. After equal time for recovery, younger men showed restored function while older men had an impaired ability to restore function, confirming a similar early study by Suetta et al.^8,9

Subsequently, establishment of strategies to prevent and address modifiable factors in surgical patients took the form of initiatives such as the Enhanced Recovery After Surgery (ERAS®) program promoted by the ERAS® Society and the European Society for Clinical Nutrition and Metabolism. The American Society for Parenteral and Enteral Nutrition is currently working on ERAS® nutrition guidelines.

Nutrition and Frailty in the Surgical Patient

The surgical stress response is a hypermetabolic and hypercatabolic state characterized by protein catabolism, primarily relying on skeletal muscle mass, resulting in a net loss of skeletal muscle mass. Surgeries requiring cardiopulmonary bypass are among the most stressful, and cardiac surgery has the highest rates of iatrogenic malnutrition globally.^16,17,18 Due to the protein-wasting nature of the surgical stress response, preexisting cachexia, sarcopenia, or malnutrition is a major risk factor for postoperative morbidity and mortality. Impaired functional status is also a major risk factor for poor postoperative outcomes.¹⁹ Kassin et al. identified that among the factors affecting 30-day hospital readmission in general surgery patients, “failure to thrive/malnutrition” has a frequency of 10.4%.²⁰

Preoperative Fasting Effect

Extended preoperative fasting is still prevalent in the preoperative setting despite the wealth of evidence against this practice. The American Society of Anesthesiologists Task Force on Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration issued updated guidelines in 2017. In patients evaluated and cleared for antecedents of gastroesophageal reflux disease, dysphagia, or other motility and metabolic disorders (ie, diabetes), “clear liquids may be ingested for up to 2 hours before procedures requiring general anesthesia, regional anesthesia, or procedural sedation and analgesia.”²¹

In 2003, a systematic review of the effect of different preoperative fasting regimens on perioperative complications and patient wellbeing showed “no evidence that the volume or pH of the participants’ gastric contents differed significantly depending on whether the groups were permitted a shortened preoperative fluid fast or continued a standard fast.”²²

ERAS® guidelines for clinical nutrition in surgery²³—including ERAS® Cardiac,²⁴ ERAS® Esophagectomy,²⁵ and European Society for Clinical Nutrition and Metabolism—all recommend limiting the duration of preoperative fasting.^6,26

Surgical Procedure Stress Response

The physiological response to cell injury that surgical intervention entails manifests as an acute stress response. Initial neuroendocrine response with the release of stress hormones, adrenocorticotrophic hormone, cortisol, vasopressin, and growth hormone predispose increased free water retention and hyperglycemia. The effect on glucose homeostasis expressed by increased glycogenolysis and gluconeogenesis, along with insulin resistance, leads to a hyperglycemic state known to increase postoperative complications. It is important to recognize a biphasic hypermetabolic response expressed as an initial ebb phase and flow phase that follows. The ebb starts within hours of the injury and lasts until 2 to 3 days after, manifesting with “a reduction of cardiac output, oxygen consumption, basal metabolic rate, and glucose tolerance.”²⁷ The flow phase follows the ebb phase and can last from days to weeks, and it is characterized by an “increase in cardiac output, respiratory rate, oxygen consumption, hyperglycemia, skeletal muscle catabolism, and a negative nitrogen balance.”²⁷ As the patient evolves through these phases into a recovery state or a chronic stress state, significant variability occurs in nutrition requirement, intake absorption, and substrate utilization.^27,28

Surgery-induced Hyperglycemia

The anabolic effect of insulin promotes glycogenesis and the uptake of glucose into the muscle and adipose tissue. This effect in the context of surgical injury is offset by increased insulin requirements and insulin resistance, leading to an overall catabolic state and residual persistent hyperglycemia. Persistent hyperglycemia in addition to immobilization leads to a multiplying effect of increased insulin resistance and decreased muscular synthesis, thus enhancing the catabolic effect.

Kotagal et al. evaluated a cohort of 40,836 surgical patients from the Surgical Care and Outcomes Assessment Program for diabetes mellitus status, perioperative hyperglycemia, and adverse events. Patients with diabetes had a higher rate of adverse events compared with non-diabetes mellitus patients. Patients with hyperglycemia had an increased risk for events compared with normoglycemic patients, and patients without diabetes mellitus had a dose-response relationship between blood glucose level and adverse events.²⁹ The ERAS® guidelines recognize this issue and recommend evaluation of hemoglobin A1c in preoperative evaluation of surgical candidates.

Surgical Inflammatory Response

The surgical injury triggers a systemic inflammatory response susceptible for being evaluated and followed up by biomarkers such as interleukin-6 and C-reactive protein (CRP). Watt and colleagues in a systematic review involving 14,362 patients undergoing elective procedures showed that interleukin-6 and CRP responses were associated with the magnitude of the operative injury and the invasiveness of the operative procedure.”⁴ Postoperative levels of CRP have shown a strong correlation with complications in patients with major abdominal surgery.³⁰ The dual measurement of albumin and CRP in patients with advanced esophageal cancer may offer prognostic parameters in evaluating patients being considered for palliative surgery.³¹

Nutrition Assessment by Registered Dietitian

Patients who are identified at malnutrition risk should be referred to a Registered Dietitian to perform a formal nutrition assessment along with nutrition-focused physical exam (NFPE) to assess body composition and, if present, to diagnose and quantify degree of malnutrition.^{6,36,37,38,39} Labs are reviewed, including micronutrient levels that need correction, to help with appetite or other symptoms.

Assessment of Frailty and Sarcopenia

Having identified the malnutrition risk and completed the nutrition assessment and NFPE to diagnose malnutrition, assessment then pivots to identify the extent of frailty in these patients. Handgrip strength using a hand dynamometer and six-minute walk test are both objective and easy to administer.^40,41 Measured and calculated gait speed also adds to the assessment.⁴² A hand dynamometer is the gold standard for determining decreased functional status, but a simple handshake during the NFPE, where the clinician instructs patients to squeeze tightly, will suffice if these devices are not available.

At HMH, the outpatient transplant dietitians use some of these objective measures along with two subjective questions, based on the Fried Frailty Phenotype, to then categorize a patient as frail, pre-frail, or not frail.^43,44 A treatment plan including nutrition and physical therapy is implemented and, in some cases, surgery is not recommended until progress is made. The algorithm in Figure 1 depicts clinical practice guidelines for frailty that are followed by the HMH outpatient transplant team.

Figure 1

Elderly, obese, and chronically ill frail patients need special consideration of their lean body mass (LBM).⁶ Pairing nutrition assessment and frailty assessment provides insight into a patient’s LBM status, but objective measures of LBM with innovative use of computed tomography and ultrasound for assessment of muscle mass and body composition are emerging in recent literature and are proposed for use in preoperative risk stratification.^6,45 Weerink et al. evaluated the influence of preoperative sarcopenia using low psoas muscle mass on postoperative complications in surgical oncology patients and showed increased risk of postoperative complications and 30-day mortality.⁴⁶

Nutritional Interventions

Pharmaconutrients are indicated as a complement or substitute of oral nutrition in patients at risk for malnutrition or malnourishment. In the surgical population, the prevalence of malnutrition is increased due to “undernutrition” associated with extended nil per os orders and increased nutritional requirements from the surgical stress and heightened catabolic state. Oral nutrition should always be considered early and first, if possible, in the postoperative period.^2,55 In an international and multi-institutional study, Heyland et al. showed that when enteral feeding is started late, 38.8 hours after admission, patients received only 61.2% of calories and 57.6% of protein prescribed, with 74% of patients not meeting at least 80% of their energy target.⁶¹ Undernutrition is particularly present in cardiac surgery^62,63 and in patients subject to esophagectomy. Patients undergoing esophagectomy could remain nutritionally compromised in the months/years that follow and may never return to baseline.⁶⁴

Oral Nutrition Supplementation

Oral nutrition supplements are indicated for patients with a preserved functional and structural intact gastrointestinal tract that cannot meet adequate nutritional goals for their calculated or measured requirements. The formulations vary from standard to caloric dense and standard to high protein formulations. IMN formulas are defined as containing arginine, omega-3 fatty acids, and a complex carbohydrate such as maltodextrin. IMN formulations have been recommended in the preoperative and postoperative period in patients undergoing elective surgery.^{23,24,25,47,48} Berkelmans et al. performed an international multicenter trial with patients undergoing minimally invasive esophagectomy, testing direct start of oral feeding versus standard of care and the effect on primary (functional recovery) and secondary outcomes (anastomotic leak, pneumonia rate, and surgical complications). It showed no compromise of functional recovery without an increased incidence of postoperative complications.⁶⁵

Enteral Nutrition

Enteral nutrition (EN) is indicated in patients unable to meet nutritional requirements due to functional or structural limitations. In the preoperative period, EN could be a complement in patients with suboptimal oral intake, limited compliance with ONS, and patients at high risk of malnutrition or malnourished as part of the preoperative optimization.^66,67 In the postoperative period, EN could be started after admission to intensive care⁶⁸ and increased stepwise to achieve the nutritional goal over 3 to 5 days.^26,55 Berger et al. studied intestinal absorption in hemodynamic unstable cardiac surgery patients using an acetaminophen absorption test and showed decreased (but not suppressed) absorption associated with decreased pyloric motility.⁶⁹ The use of early EN is supported⁶⁸ in critically ill and surgical patients alike: in a systematic review of a hospitalized mixed-population, Marik and Zaloga showed that early EN was associated with a significantly lower incidence of infections and reduced hospital LOS.⁷⁰ In a group of patients with upper gastrointestinal cancer (54 esophageal, 38 gastric, 29 pancreatic), Barlow et al. randomly assigned patients to EN versus control (nil per os and IV fluid) and showed that EN was associated with shortened LOS and improved outcomes.^66,71

An earlier study by Gabor et al. evaluated the impact of early postoperative EN on patients with esophagectomy or esophagogastrectomy and reconstruction and found that they recovered faster in terms of ICU and hospital stay, with no impact on mortality.⁷² A major drawback of this intervention is limited compliance and inappropriate quantification of delivery of the nutritional prescription.

EN is the first choice of nutritional delivery in all patients able to tolerate it. Li et al. performed a meta-analysis of 10 studies evaluating safety and efficacy of jejunostomy versus nasoenteric tube in patients undergoing esophagectomy. Patients in the jejunostomy group had a lower incidence of postoperative pneumonia, shorter LOS, and lower risk for catheter dislocation, placing jejunostomy as the preferred EN route in these patients.⁷³

Critically ill patients are often underfed due to interruptions in EN delivery. Interventions to improve delivery include the use of energy-dense formulations and strategies such as volume-based feeding, which allow for a catch-up time. The use of energy-dense formulation (1.5 kcal/mL versus 1.0 kcal/mL), evaluated by the TARGET Investigator Group, did not affect mortality (primary outcome) but showed the delivery of similar volumes of EN in both groups, with increased calorie delivery in the 1.5 kcal/mL subgroup.⁷⁴ In the surgical critically ill patient, undernutrition is prevalent along with an increased frequency of parenteral nutrition (PN),⁶² raising the question of benefit of PN over EN. Mazaki and Ebisawa studied the benefit of EN over PN in trials that included 2,552 patients after elective gastrointestinal surgery and found a reduction of “any complications, infectious complications, anastomotic leak, intraabdominal abscess and duration of hospital stay.”⁷⁵

Parenteral Nutrition and Supplemental Parenteral Nutrition

The use of PN is indicated in the perioperative period in surgical patients who are unable to meet nutritional requirements with oral intake or EN. PN is indicated in the well-nourished patient after 7 days of admission if EN is delivering < 50% of the caloric requirements.²⁶ In the postoperative period, use of PN is indicated if EN is deemed high risk for complications (ie, high vasopressor requirements) or gastrointestinal intolerance prevents adequate nutritional delivery, and in those patients with severe malnutrition or high nutritional risk.

Supplemental parenteral nutrition (SPN) is indicated to complement EN when it is insufficient to deliver caloric requirements, always keeping EN as tolerated, to preserve gastrointestinal trophism. Heidegger et al. evaluated the effect of SPN in 153 patients targeting at 100% of energy delivery from day 4 to 8 upon admission to the ICU; they found that patients randomized to SPN versus EN had a lower occurrence of nosocomial infections after day 8.⁷⁶ A similar study by Wischmeyer et al. showed no increase in infection risk in patients receiving SPN.⁷⁷

The evolution of intravenous lipid emulsion (ILE) development and the impact on outcomes in patients receiving PN is noteworthy, from the historical use of soy-based emulsions to the latest incorporation of ILEs with a mixture of olive oil-based emulsion and fish oil (FO)-based emulsions. Manzanares et al. performed a systematic review and meta-analysis evaluating the efficacy of FO-based emulsions on clinical outcomes in critically ill patients. Ten randomized controlled studies including 733 patients were evaluated for clinical outcomes and showed that FO-based emulsions may be associated with a reduction in infections.⁷⁸

Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is indicated in critically ill patients with cardiac or respiratory failure, and the use of EN in this population has been a subject of concern for practitioners. Ferrie and colleagues evaluated 86 patients retrospectively who received ECMO at a single center: 31 patients receiving ECMO for heart failure were subject to venoarterial (VA) ECMO, with the rest receiving venovenous ECMO. All received early EN, and it was well tolerated with both modalities.⁷⁹ Umezawa et al. showed feasibility and safety in a case series of seven patients receiving VA ECMO with nutrition support for severe hemodynamic failure using early EN in a step-up manner over 4 days.⁸⁰ Karpasity reviewed published randomized trials and observational studies between July 2000 and July 2020, evaluating nutritional interventions in critically ill patients receiving ECMO therapy for nutritional adequacy and gastrointestinal complications. EN was found feasible and safe albeit with difficulties meeting nutritional goals.⁸¹