There is no evidence supporting a specific nutritional strategy for CCPs and patients with PICS. The persistence of inflammation, hypercatabolism and anabolic resistance leads to a state of sarcopenia/cachexia; the “anabolic nutrition” strategy is the best option for combating this situation, together with resistance exercises. In addition to other actions, “anabolic nutrition” proposes a caloric supply of 25–30kcal/kg/day and a protein supply of 1.5–2g/kg/day.6–9 Special attention should focus on glycemic control (glycemia <150 mg/dl, minimizing its variability), with the avoidance of an excessive caloric supply.10

Enteral nutrition (EN) is recommended as first-line nutrition support strategy in patients with a functioning gastrointestinal tract. Feeding initially is via a nasogastric tube (NGT); the nasojejunal route offers no objective advantages in this regard.11,12 Enteral nutrition, initially on a continuous basis, can be applied intermittently to facilitate other therapeutic actions (e.g., active exercise, early mobilization, etc.).13 In any case, it is advisable to have an EN administration protocol based on volumetric objectives and controlled by nursing staff.14

Percutaneous endoscopic gastrostomy (PEG) should be considered in patients that tolerate EN via NGT if a prolonged duration of feeding is expected (>30 days). It should be considered in the second-third week in those patients with inadequate intake and a moderate to severe risk of malnutrition. The decision to perform PEG should be made on an individualized basis, taking into account the patient preferences, diagnosis and life expectancy.15 In the recovery phase, CCPs should be evaluated for safety of feeding via the oral route and the suspension of feeding via NGT or PEG once the nutritional targets have been reached.

No data are available regarding the most adequate nutritional formula in CCPs/PICS, though in general a hyperproteic polymeric diet is indicated. Some authors advise the use of formulas enriched with pharmaconutrients, based on studies that describe improvements in terms of immune function and inflammation, together with a decrease in infections and shortened stay and duration of MV.16 The chosen nutritional formula should afford sufficient protein, avoid excessive calories and ensure an adequate provision of micronutrients.

Trace elements (TEs) such as Cu, Mn, Zn and Fe, and certain vitamins (Vi) such as vitamin E, C and E, and β-carotene, are crucial as coenzymes and antioxidants.17 These elements are usually deficient in CCPs as a result of redistribution, hemodilution, insufficient intake and treatments such as continuous renal replacement therapy. There is a negative correlation between micronutrient deficit and the severity of the disease process.18 In a systematic review, Manzanares et al. sought to determine whether TE and Vi replacement is of benefit. The authors concluded that high doses of TEs and Vi improve the clinical outcomes in critical patients, particularly in the more serious cases.19 However, there is an important gap in knowledge regarding the normal levels, the dosage and the effect of each TE considered isolatedly. What does seem clear is that the existing commercial mixtures are unable to cover the requirements.20

Controversy remains regarding the administration of pharmaconutrients such as arginine, glutamine, leucine, beta-hydroxy-beta-methylbutyrate and creatine, despite their acknowledged immunological, enteroprotective and anabolic actions. There are no studies of sufficient quality to clearly establish the usefulness of these nutrients in critical patients in general and in CCPs in particular.21–23

The endocrine-metabolic scenario, together with concomitant factors such as disuse, make a determinant contribution to sarcopenia, cachexia and immune depression in CCPs and PICS.24 Hormone replacement therapy could correct the consequences of the endocrine anomalies, though studies involving the administration of growth hormone, thyroxin and corticosteroids in CCPs have found such measures to be ineffective.25 In rare instances, a lack of effective hypothalamic-pituitary stimulation can result in functional insufficiency requiring replacement with corticosteroids and thyroxin.

Chronic critical patients suffer bone metabolic disorders (elevated reabsorption) – the recognizable risk factors being cytokines, immobilization, endocrine alterations, the administration de corticosteroids, electrolyte and micronutrient disturbances (Mg, P, K, vitamin C, K and D) and secondary hyperparathyroidism. Nevertheless, the clinical benefits of administering bisphosphonates, calcium and vitamin D are subject to controversy – though there is agreement regarding the administration of vitamin D in highly deficient patients.26–28

Prolonged immobilization and disuse are crucial contributors to the appearance of sarcopenia and weakness. A systematic review revealed no impact upon short- and middle term mortality, though improved mobility and muscle strength was recorded.29 In contrast, other studies have highlighted the benefits of an early rehabilitation program guided by objectives consistent with the patient condition.30 In general, early mobilization is advised, with resistance exercises or neuromuscular electrical stimulation – though the indicated duration and frequency are not clear.

Other pharmacological treatments with anabolic effects are currently under study, such as ghrelin, insulin-like growth factor type 1 and muscle modulators such as the myostatin inhibitors and melanocortin-4 receptor antagonists. Due to its anabolic and appetite-stimulating properties, ghrelin improves the symptoms and muscle weakness of chronic patients with cachexia,31 and therefore could afford benefits in the rehabilitation of CCPs.