Acute Crit Care.  2022 Aug;37(3):295-302. 10.4266/acc.2021.01767.

Muscle Growth and Anabolism in Intensive Care Survivors (GAINS) trial: a pilot randomised controlled trial

• Anstey MH
• Rauniyar R
• Fitzclarence E
• Tran N
• Osnain E
• Mammana B
• Jacques A
• Palmer RN
• Chapman A
• Wibrow B

• KMID: 2535292
• DOI: http://doi.org/10.4266/acc.2021.01767

Abstract

Background
To explore the feasibility, safety, and potential benefits of administration of the anabolic steroid nandrolone to patients in the recovery phase from critical illness weakness.
Methods
In this phase II, double blind, randomized, controlled trial, adult critically ill patients admitted to one of two tertiary Intensive Care Units in Western Australia for longer than 7 days with significant weakness were enrolled. Patients received nandrolone (200 mg males, 100 mg females) intramuscularly or placebo weekly for up to 3 weeks in addition to standard care. The primary outcome measures were improvement in grip strength, Medical Research Council muscle strength sum score, and functional activity level (Chelsea critical care assessment tool [CPAx]).
Results
A total of 22 patients was enrolled between September 2017 and May 2019. No significant adverse events were detected. Median grip strength change was non-significantly greater in the nandrolone group (8.5 vs. 13.0, P=0.185), while hospital length of stay (36 vs. 26 days, P=0.023) and duration of mechanical ventilation (377 vs. 168, P=0.032) were lower. The discharge CPAx and intensive care unit mobility scores were higher in the nandrolone group, although there was no difference in the change in CPAx score (17.0 vs. 17.7, P=0.865). There were no changes in ultrasound-detected muscle thickness between the two groups.
Conclusions
In patients with prolonged critical illness, nandrolone appears to be safe. However, a larger study, potentially combined with resistance exercise, is needed to definitively address the potential benefits of nandrolone.

Keyword

androgens; critical illness; intensive care; muscle strength; nandrolone; quality of life

Figure

• 

  Figure 1. Consort diagram. ICU: intensive care unit; SF-36: 36-item short form survey.

• 

  Figure 2. Kaplan-Meier survival curve for hospital length of stay (LOS). (Log-rank test P=0.023).

Reference

1. Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. N Engl J Med. 2014; 370:1626–35.

2. Dinglas VD, Aronson Friedman L, Colantuoni E, Mendez-Tellez PA, Shanholtz CB, Ciesla ND, et al. Muscle weakness and 5-year survival in acute respiratory distress syndrome survivors. Crit Care Med. 2017; 45:446–53.

3. Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011; 364:1293–304.

4. Gamrin L, Andersson K, Hultman E, Nilsson E, Essén P, Wernerman J. Longitudinal changes of biochemical parameters in muscle during critical illness. Metabolism. 1997; 46:756–62.

5. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013; 310:1591–600.

6. Preiser JC, Ichai C, Orban JC, Groeneveld AB. Metabolic response to the stress of critical illness. Br J Anaesth. 2014; 113:945–54.

7. Nierman DM, Mechanick JI. Hypotestosteronemia in chronically critically ill men. Crit Care Med. 1999; 27:2418–21.

8. Almoosa KF, Gupta A, Pedroza C, Watts NB. Low testosterone levels are frequent in patients with acute respiratory failure and are associated with poor outcomes. Endocr Pract. 2014; 20:1057–63.

9. Vincent JL. Metabolic support in sepsis and multiple organ failure: more questions than answers. Crit Care Med. 2007; 35(9 Suppl):S436–40.

10. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008; 154:502–21.

11. Miller JT, Btaiche IF. Oxandrolone treatment in adults with severe thermal injury. Pharmacotherapy. 2009; 29:213–26.

12. Wischmeyer PE, Suman OE, Kozar R, Wolf SE, Molinger J, Pastva AM. Role of anabolic testosterone agents and structured exercise to promote recovery in ICU survivors. Curr Opin Crit Care. 2020; 26:508–15.

13. Gold J, Batterham MJ, Rekers H, Harms MK, Geurts TB, Helmyr PM, et al. Effects of nandrolone decanoate compared with placebo or testosterone on HIV-associated wasting. HIV Med. 2006; 7:146–55.

14. Schols AM, Soeters PB, Mostert R, Pluymers RJ, Wouters EF. Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease: a placebo-controlled randomized trial. Am J Respir Crit Care Med. 1995; 152(4 Pt 1):1268–74.

15. Creutzberg EC, Wouters EF, Mostert R, Pluymers RJ, Schols AM. A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind, placebo-controlled, randomized trial. Chest. 2003; 124:1733–42.

16. Pikul J, Sharpe MD. Use of anabolic steroid therapy in critically ill ICU patients. Crit Care. 2003; 7:P014.

17. Anstey M, Desai S, Torre L, Wibrow B, Seet J, Osnain E. Anabolic steroid use for weight and strength gain in critically ill patients: a case series and review of the literature. Case Rep Crit Care. 2018; 2018:4545623.

18. Corner EJ, Wood H, Englebretsen C, Thomas A, Grant RL, Nikoletou D, et al. The Chelsea critical care physical assessment tool (CPAx): validation of an innovative new tool to measure physical morbidity in the general adult critical care population. An observational proof-of-concept pilot study. Physiotherapy. 2013; 99:33–41.

19. Tillquist M, Kutsogiannis DJ, Wischmeyer PE, Kummerlen C, Leung R, Stollery D, et al. Bedside ultrasound is a practical and reliable measurement tool for assessing quadriceps muscle layer thickness. JPEN J Parenter Enteral Nutr. 2014; 38:886–90.

20. Milton A, Schandl A, Soliman I, Joelsson-Alm E, van den Boogaard M, Wallin E, et al. ICU discharge screening for prediction of new-onset physical disability: a multinational cohort study. Acta Anaesthesiol Scand. 2020; 64:789–97.

21. Ripley DL, Gerber D, Pretz C, Weintraub AH, Wierman ME. Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury: results from a double-blind, placebo-controlled clinical pilot study. NeuroRehabilitation. 2020; 46:355–68.

22. Ali NA, O'Brien JM Jr, Hoffmann SP, Phillips G, Garland A, Finley JC, et al. Acquired weakness, handgrip strength, and mortality in critically ill patients. Am J Respir Crit Care Med. 2008; 178:261–8.

23. Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996; 335:1–7.

24. Segers J, Hermans G, Charususin N, Fivez T, Vanhorebeek I, Van den Berghe G, et al. Assessment of quadriceps muscle mass with ultrasound in critically ill patients: intra- and inter-observer agreement and sensitivity. Intensive Care Med. 2015; 41:562–3.

25. Pardo E, El Behi H, Boizeau P, Verdonk F, Alberti C, Lescot T. Reliability of ultrasound measurements of quadriceps muscle thickness in critically ill patients. BMC Anesthesiol. 2018; 18:205.

26. Johansen KL, Mulligan K, Schambelan M. Anabolic effects of nandrolone decanoate in patients receiving dialysis: a randomized controlled trial. JAMA. 1999; 281:1275–81.

27. Horstman A, Backx E, Smeets J, Marzuca-Nassr GN, van Kranenburg J, de Boer D, et al. Nandrolone decanoate administration does not attenuate muscle atrophy during a short period of disuse. PLoS One. 2019; 14:e0210823.