Nutrition Support Blog: Skeletal Muscle Wasting in Critical Illness
November 7, 2013
Survival is only the first part of the battle that confronts critically ill patients. There is increased recognition that loss of skeletal muscle and muscle weakness in the ICU is an enormous issue for patients and our whole healthcare system. Muscle weakness during and after critical illness delays weaning from mechanical ventilation, prolongs recovery, compromises functional status and increases the need for rehabilitation after hospitalization. Muscle breakdown during critical illness contributes to weakness and the loss of functional status that can last for many months after recovery from the initial insult. Elderly patients are particularly susceptible to muscle wasting, take much longer to recover, and are more likely to lose independence or suffer falls or other injury when muscle wasting occurs. Recognition of the vast resources that will be required to rehabilitate the survivors of critical illness has spurred research into the mechanisms of muscle loss, with the hope of developing therapies that will prevent or help restore muscle mass.
A new study published in the Journal of the American Medical Association investigated muscle metabolism and the mechanisms that cause muscle wasting in critical illness.1 http://jama.jamanetwork.com/article.aspx?articleid=1752755
The researchers found that that muscle biopsies revealed that muscle breakdown was significantly greater than suggested by ultrasound measurement of muscles. Ultrasound of the thigh muscles on day 7 reflected a 10.9% decrease in cross section, but the biopsy demonstrated nearly 29.5% decrease (via protein to DNA ratio). The investigators found that muscle protein synthesis was severely decreased on day 1, but increased to that of a healthy fed person by day 7.
One puzzling aspect of the study is the nutrition component. The article reports that NG feeding was started in 9 of the 11 patients on day 1, and in all of the patients by day 7. The results mention that the decrease in the rectus femoris muscle at day 10 was positively associated with the total protein delivered during the study period. The clinical implications section mentions the association between increased protein delivery with increased muscle loss, and in the video presentation (see below), one investigator suggests that we must rethink continuous delivery of nutrition support in the ICU. http://jama.jamanetwork.com/multimediaPlayer.aspx?mediaid=6068893
However, the paper and supplemental tables do not provide any details about the amount of calories or protein delivered to the patients. There is copious data that ICU patients routinely receive only a portion of ordered enteral nutrition, especially during the first days of admission (see our October e-journal club). There is no way to know how much protein patients actually received or how the amount of protein provided compared to the size of the patients (grams/kg, rather than absolute amounts), or existing nutrition status between patients – especially critical considering the very small number of patients studied. Most importantly, patients were not randomized to different amounts of nutrition, or to different regimens (continuous or otherwise), so no cause and effect statements can be made regarding nutrition delivery and muscle loss.
It is not particularly surprising that muscle protein synthesis was decreased on day 1 of critical illness. After all, the “ebb” phase of critical illness was described in 1932.2 The priority of the body in the initial stage of illness is increased hepatic protein synthesis of acute phase reactants3, which was not measured at all in this study. Negative nitrogen balance during the first week of critical illness has been repeatedly demonstrated over the past 30 years. It is also not surprising that muscle protein synthesis was increased on day 7, when the initial shock phase of illness had subsided, insulin resistance was less intense, and perhaps, nutrition support was provided in increased amounts.
Although research is increasing our insights into muscle breakdown, it may not be possible, or even desirable to affect muscle breakdown in the earliest, most intense phase of critical illness. We may find that this early cell breakdown process is essential for removing damaged intracellular components, and preparing for recovery. Providing full nutrition may be most important in the later, recovery period of illness. After all, to a well-organized mind, catabolism is but the first step on the path to anabolism.*
“The worst pain a man can suffer: to have insight into much and power over nothing” - Herodotus 484-425 BC
*borrowed (and very badly paraphrased) from JK Rowling
1. Puthucheary ZA, Rawal J, McPhail M, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16; 310(15):1591-600.
2. Cuthbertson DP. Observations on the disturbance of metabolism produced by injury to the limbs. Q J Med 1932; 1: 233–246
3. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999; 340(6):448-454.