Nutrition Therapy and Critical Illness

Practical Guidance for the ICU, Post-ICU, and Long-Term Convalescence Phases

Arthur Raymond Hubert van Zanten; Elisabeth De Waele; Paul Edmund Wischmeyer


Crit Care. 2019;23(368) 

In This Article

Nutrition Therapy After Hospital Discharge and Convalescence

We must continue to consider whether patients leaving the hospital following an ICU stay will be able to consume adequate oral calories and protein to optimally recover at home or in rehabilitation facilities. Further, we must all take a moment to read and revel in the defining achievement that is the Minnesota Starvation Study and learn from its landmark lessons.[7] Even healthy subjects require significant calories (typically 3000–4500 kcal/day) and proteins up to 1.5–2.5 g/kg/day, to recover from the marked muscle loss that occurs following starvation.

In patients who have lost significant strength and muscle mass following an ICU stay, a considerable period of significantly increased calorie and protein delivery is required for recovery and likely needed for months to years.[63] Is it possible this lack of understanding has led to the extremely poor long-term outcomes and QoL.

How many of our care protocols, or our patients, will be able achieve this well-described goal without assistance from oral protein and nutrition supplementation? A large body of data demonstrates that oral nutrition supplement (ONS) must become fundamental to our post-hospital discharge care in ICU survivors. Meta-analyses in various hospitalized patients demonstrate ONS reduces mortality, reduces hospital complications, reduces hospital readmissions, shortens length of stay, and reduces hospital costs.[64–67] A large hospital database analysis of ONS use in 724,000 patients matched with controls not receiving ONS showed a 21% reduction in hospital LOS and for every $1 (US) spent on ONS, $52.63 was saved in hospital costs.[68] Finally, a recent large RCT of 652 patients studied the role of post-hospital high-protein ONS (HP-ONS) with β-hydroxy β-methylbutyrate (HP-HMB) versus placebo ONS in elderly malnourished (Subjective Global Assessment [SGA] class B or C) hospitalized adults. This definitive post-hospital trial demonstrates HP-ONS with HMB reduces 90-day mortality ~ 50% relative to placebo (4.8% vs. 9.7%; relative risk 0.49, 95% confidence interval [CI], 0.27–0.90; p = 0.018). The number-needed-to-treat in the post-hospital discharge setting to prevent 1 death was 20.3 (95% CI 10.9–121.4).[69] As patients recovering from sepsis and the ICU will not consume sufficient calories and protein to recover optimally, the use of HP-ONS is essential and is strongly recommended for all ICU survivors post-hospital discharge for at least 3 months (and likely up to 2 years) following hospital discharge. In some patients, even prolonged tube feeding or parenteral nutrition should be considered.

Key Role for Anabolic/Anticatabolic Agents

ICU survivors are also challenged by persistent catabolism and hypermetabolism for months to years. The HP-ONS trial and another recent review emphasize that anabolic and anticatabolic interventions, such as propranolol, oxandrolone, and other agents targeted at restoring lean muscle mass may be essential components to allow for meaningful recovery of QoL and survival post-ICU.[69,70] Targeted nutrition that includes adequate protein delivery and "muscle-recovery targeted" anabolic/anticatabolic agents combined with exercise potentially lead to meaningful improvements in QoL.[71]


The data for the routine use of anabolic/anticatabolic agents in burn care is covered by a recent review.[70] Much can be learned from the vast experience with propranolol to reverse persistent hypercatabolism of critical illness.[72] This data showed that propranolol is the only intervention that will make a severely burned patient anabolic in the face of the largest and most severe catabolic insult humans can survive. Low-dose modern cardio-selective beta blockers to reverse catabolism are inadequate as was recently shown to have no impact on energy expenditure of ICU patients.[73] More research is warranted to evaluate the effect of propranolol in post-ICU patients.

Testosterone and Oxandrolone

Perhaps even more compelling is the growing body of literature for the safety, clinical efficacy, and benefit of testosterone and oxandrolone in a range of patients. It is well known that oral oxandrolone, among the most anabolic of the testosterone agents, is also among the safest as it shows minimal liver enzyme use with prolonged use. Oxandrolone has been shown to reduce mortality in burn-injured patients.[74] Concerns around potential cardiovascular risk and potential thrombotic risk have recently been dispelled in large observational studies such as the recent publication of > 43,000 subjects showing testosterone-deficient individuals (which virtually all ICU patients are within 7 days) on supplementation had a 33% reduction in all-cause cardiovascular events and a 28% reduced stroke risk.[75] A key recent meta-analysis showed that testosterone could improve exercise tolerance in heart failure patients.[76] It should be considered to check testosterone levels in patients in ICU 7 days or more, as they are often severely low or undetectable. Replacement may be done with testosterone cyprionate (~ dose 200 mg IM q 2 weeks), testosterone patch (~ dose 4 mg patch), or oxandrolone orally (~ dose 10 mg BID).

This is an area in desperate need of clinical trials outside of the burn setting as a meta-analysis of these pharmacological interventions to reduce ICU-acquired weakness did not find strong signals of benefit, except for the prevention of hyperglycemia during ICU stay.[77]