Nutrition in ICU and the Refeeding Syndrome Prof

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Part II Anaesthesia Refresher Course – 2020 06 University of Cape Town Nutrition In ICU and the refeeding syndrome Prof. Lance Michell Associate Professor (Emeritus), Division of Critical Care Dept Anaesthesia and Perioperative Medicine, Groote Schuur Hospital University of Cape Town

The role of nutrition in managing ICU patients

Providing adequate nutrition to the patient in the ICU is an essential part of the care but many aspects remain controversial. On the one hand the provision of nutrition is often, in practice, ignored as we struggle with the more pressing problems of oxygenation and circulation. On the other hand, dramatic claims made in the past that an excess of nutrients or that the provision of special “pharmaco- nutrients” could improve outcome have fallen away as larger trials have failed to show a special benefit.

Critically ill patients often arrive in ICU already nutritionally depleted due to pre-existing illness and then go into marked negative energy balance due to the hypermetabolic response. Observational studies have shown a survival benefit if adequate protein and energy is provided and a cluster randomised study of ICU’s following a nutrition protocol as opposed to “usual care” has shown a trend towards a survival benefit.1,2 For obvious reasons prospective randomized trials of “nutrition” vs “no nutrition” have not been done.

The most recent trend in this field is one of caution and a “less-is-more” approach particularly in the early phase of critical illness. Awareness is also growing that some ICU patients can be harmed by a covert refeeding syndrome.

The recommendations in this lecture are largely based on the 2019 guidelines of the European Society of Enteral and Parenteral nutrition.3

Metabolic dysfunction in critical illness

Many ICU patients are admitted following a major insult, such as sepsis, trauma or major surgery that causes a massive inflammatory response which includes profound metabolic changes. During the initial shock phase following an insult, tissue hypoxia reduces energy expenditure. This is followed by an acute phase where there is an increase in metabolic rate with an increase in energy expenditure of 25 to 50% above resting energy expenditure. Glucose is the main source of energy with some derived from fat stores. Carbohydrate stores in the body are very limited, mainly glycogen in the liver, which is rapidly depleted. At the same time relative insulin resistance develops resulting in an increased blood glucose level that may impair the immune response and particularly the function of neutrophils.

To provide this energy source there is a massive breakdown of structural protein, particularly skeletal muscle with the resulting amino-amides being converted to glucose - mainly in the liver. This can result a loss of muscle mass at a rate of 2% per day.4 This contributes to the long-term weakness and disability commonly suffered by ICU survivors which is part of the post intensive care syndrome (PICS).

The liver also synthesizes different proteins, becoming a net albumin importer and increasing its production of acute phase proteins including clotting factors and opsonins. Albumin levels drop rapidly in acute illness and no longer reflect the nutritional status.

All these changes are governed by a network of hormones including cortisol, glucagon and catecholamines as well as the inflammatory cytokines such as TNF, IL-1 and IL-6. This metabolic response is different to the metabolic response to starvation that includes a reduction in metabolic rate, the consumption of fat stores and the conservation of protein.

During the acute phase, nutrition can only reduce, but not reverse protein catabolism until recovery begins and the patient become anabolic. Nutrition in ICU and the refeeding syndrome Prof. L Michell

Nutritional Assessment

Ideally all ICU patients should be assessed by a dietician prior to admission. Assessment starts with a nutritional history including recent intake of micronutrients and alcohol consumption. Physical examination should particularly look for evidence of muscle wasting. Ideal body mass index (BMI) should be calculated. The subjective global assessment uses patient history and a specific physical examination to determine nutritional status. Actual and Height can be easily measured in the supine patient, but body mass is best obtained from a recent premorbid measurement as resuscitation fluid will increase mass. The body mass index (BMI) can be calculated:

BMI = Mass (Kg) / Height (meters)2

A BMI of less than 18.5 is indicative of malnutrition and less than 17 is associated with severe malnutrition. For ICU patients the modified NUTRIC score gives an indication of nutritional risk and is associated with mortality.5

Nutritional requirements

Energy: The main focus of nutrition is to provide for the patient’s energy and protein needs. This is easier said than done as energy expenditure varies between patients and from day to day. Also, providing full requirements in the early acute phase increases complications, both gastrointestinal intestinal and metabolic.

Hypocaloric feeding in the first few days of critical illness results in less hyperglycaemia and better gastrointestinal tolerance without worsening outcome and ESPEN recommends no more than 70% of requirements in the early acute phase.

A simple formula for full energy requirements is 25-30 Kcal/Kg ideal body weight that can be calculated using the height and sex of the patient. Conventionally the caloric content of enteral feeds is quoted as total calories while that of parenteral solutions is quoted as “protein free calories” – so the lower figure is advised for parenteral prescriptions. More complex formulae, such as the Harris- Benedict equation that consider age and sex, can be used to calculate resting energy expenditure to which a 25% stress factor can be added. More scientifically a metabolic monitor that uses indirect calorimetry to measure energy expenditure can be used. This is attached to the ventilator and calculates energy expenditure and respiratory quotient from the measured oxygen consumption and carbon dioxide production. Any non-nutritional energy source such as glucose and propofol infusions should be considered when calculating requirements. Obese patients require additional nutrients and the energy and protein prescription should be based on an adjusted body mass of ideal body mass plus one third of the difference between actual and ideal mass.

Carbohydrate and Fat: Both carbohydrate and fat should be used to provide non-protein energy. Glucose is the only carbohydrate used in parenteral solution while enteral feeds contain a variety of starches. Lipid should make up 30-50% of the energy supply and include a blend of medium chain triglycerides, mono- and omega-3 unsaturated lipids. While small studies on omega-3 fatty acids in ARDS and Sepsis showed promise, larger studies have been unable to show an outcome benefit. Blood glucose levels should be maintained in the 6 to 10 mmol range using an insulin infusion and/or by reducing the carbohydrate intake.

Protein requirements are thought to be higher in the critically ill and the current recommendation is 1.3 grams/Kg ideal body weight. It need not be restricted in the early acute phase. Protein intake should not be decreased in acute renal failure but should be reduced in severe hepatic failure.

Glutamine: This non-essential amino acid was thought to be beneficial in the critically ill, but a large study showed that high doses in multiple organ failure caused harm. It may be of benefit in trauma and burns patients but should not be administered to patients in hepatic or renal failure.7

Vitamins Patients should receive the recommended daily allowance of vitamins that are included in most enteral feeds. However, vitamins do not have magical properties in critical illness. Vitamin C is an anti-oxidant but a large study of antioxidants in multiple organ failure failed to show benefit.7 There may be a benefit with modest doses but the promise of mega doses of Vitamin C and D in an observational study reducing mortality in septic shock has not been borne out in prospective

06 - 2 Nutrition in ICU and the refeeding syndrome Prof. L Michell randomized trials.

Vitamin D levels should be measured and if low, a single dose of 50000 IU administered.

Thiamine should be administered to all patients with a history of heavy alcohol intake and to patients at risk of the refeeding syndrome.

Trace elements should be supplemented in patients on parenteral nutrition. Plasma zinc should be monitored in long-term ICU patients particularly if they have high gastrointestinal fluid losses and supplemented if low.

Dietary Fiber is important for proper bowel function and to slow the rate of absorption of carbohydrates. It may reduce the incidence of diarrhea and constipation. Fiber containing feeds should be introduced once bowel motility has become established.

Water and Electrolytes: Most of the daily adjustments to the nutrition prescription are related to this fluctuating requirement. Generally, ICU patients require potassium, magnesium and phosphate replacement (see section on the refeeding syndrome) and sodium and water restriction. After resuscitation, fluid restriction and diuretics may be used to improve pulmonary function hence the need for more concentrated feeding solutions. Over-restriction causes hypernatremia which may require addition water to be temporally added. Low potassium feeds are required in renal failure. In patients with high upper gastrointestinal losses sodium intake may have to be increased.

Enteral Nutrition

There is good evidence that early (24-48 hours after admission) institution of enteral feeds is beneficial with a decrease in organ failure, infections and mortality.6 This may be due restoration of gut barrier function and gut-associated lymphoid tissue function. Low volumes of feed are as beneficial as full volume and are better tolerated.8 Enteral feeds also reduce the risk of stress related gastrointestinal feeding. The downside of enteral feeding is that vomiting and the risk of aspiration is increased.

There is a huge variety of enteral feeds. They all come pre-packed in sterile containers usually 500ml in volume. Polymeric feeds contain whole nutrients, are cheaper and are indicated where bowel function is expected to be normal. Semi-elemental feeds mainly consist of polypeptides, small complex carbohydrates and medium chain triglyceride fats. There main indication is when bowel function is impaired and absorption compromised, particularly when the bowel may be edematous after resuscitation or due to hypoalbuminemia. Theoretically they are indicated in pancreatitis.

Naso-gastric tube feeding is the main nutritional route used in ICU and should always be tried first unless contraindicated. Contraindications are unresuscitated shock, abdominal compartment syndrome, a stapled off GIT, upper gastrointestinal fistulae and large (> 500 ml/day) nasogastric drainage. Abdominal surgery, intestinal anastomoses (except duodenal repairs) post-surgical ileus, and lack of bowel sounds are not contraindications. The location of the feeding tube should always be checked after placement on X-ray. The patient should be nursed head up at 30-400 and the feed to should be started slowly, gradually increasing the feed rate every 4 hours. Critically ill patients commonly have gut dysfunction even if they have not had abdominal surgery.9 Regular gastric aspirates to guide the rate of increase (slow down if > 250 ml) are practiced in our units but have been shown to not reduce the incidence of aspiration in medical patients. Having a feeding protocol to guide the nurses helps to ensure that the prescribed feed is all administered. If the feed is not tolerated, then metoclopramide and/or IV erythromycin should be started but not persisted with beyond 3 days.

Oral feeding should be attempted in extubated patients. Many ICU patients are anorexic, and it is difficult to achieve full nutritional requirements using this method. Supplemental sip feeds are often better tolerated than plates of unappetizing food from the kitchen.

Naso-jejunal tube feeding is an option when there is a need to bypass the stomach and duodenum as in gastric outlet obstruction and after surgery in that area. It is also useful for patients with severe pancreatitis who often have a function gastric outlet obstruction. They are difficult to insert, are easily displaced and do not reduce the risk of vomiting. Jejunostomies should not be inserted in the critically ill as they have a high complication rate.

06 - 3 Nutrition in ICU and the refeeding syndrome Prof. L Michell Parenteral nutrition

Parenteral nutrition should only be used if the enteral route is not available or if enteral feeding is inadequate for more than seven days in the previously well nourished.10 It may also be introduced earlier in malnourished patients who are not achieving full requirements via the enteral route provided the risk of refeeding syndrome is mitigated.

The intravenous nutrition solutions consist of mixtures of amino-acids, glucose and lipid and come in a variety of formulations so most patient requirements can be provided for. Most of the solutions are available with and without electrolytes. When combined the solutions are unstable and need to be refrigerated and used within a few days. There are two systems for supplying PN. Compounded bags are made to order in a central factory. Multi-chambered bags are supplied in bags with the different administration. Trace elements and vitamins also need to be supplied in IV form. PN solutions are very hyperosmolar and the more concentrated solutions, preferred in ICU because of their lower volume, must be administered through a central venous catheter.

The main risk of parenteral nutrition is infection; either of the central venous catheter or of the bag itself as the solution is very supportive of bacterial growth. PN should be administered through a dedicated catheter or port and no additives or “piggy-back” infusions added. Each bag should not hang for more than 24 hours once spiked and the infusion set should be changed with the line using a full sterile technique. Other complications of TPN are hyperglycaemia and hyperlipidemia, hepatic dysfunction and overfeeding.

Refeeding syndrome

First described in World War II among liberated prisoners who were re-fed too rapidly, this is describes a cluster of conditions that may even be fatal. Critically ill patients are particularly at risk, perhaps because of their high metabolic rate. Risk factors are illness or stay in hospital prior to ICU admission.

During relative starvation there is a gradual decrease in the main intracellular ions: Potassium, Magnesium and Phosphate. Prior to refeeding blood levels of these electrolytes are normal, but with the reintroduction of nutrition they drop rapidly. The main culprit in refeeding syndrome is the phosphate as low levels can cause muscle weakness and affect neurological function. A decrease in blood phosphate below 0.65 mmol/l or a decrease of > 0.16 mmol/l ICU is strongly suggestive of the diagnosis.3 In extreme cases there may be arrhythmias, seizures and coma. During refeeding basal metabolic rate increases as does blood glucose level. Phosphate becomes bound to phosphorylated carbohydrates in the liver and muscles. The increase in blood glucose increases the demand for phosphate to form ATP. There is also a decrease in red blood cell 2,3-DPG resulting in reduced oxygen delivery. Thiamine is an essential co-enzyme in the oxidative decarboxylation of pyruvate and further steps in glycolytic pathway.

All critically ill patients should have their nutrients introduced gradually and their phosphate, magnesium and potassium levels closely monitored and aggressively replaced if below normal. In patients at risk of the refeeding syndrome their initial nutrition targets should be calculated on their actual, not ideal body mass.

In conclusion providing nutrition in the ICU requires a partnership between the dietician, nurse and doctor to make a daily feeding plan and ensure it is carried out.