January 2014 E-Journal Club


We started posting an online summary of our nutrition support journal clubs late in 2003, so we have now crossed the 10 year mark for our E-Journal Club.  The impetus for starting the e-journal club came from clinicians who attended our traineeship and requested some updates about new literature.  It has been a great experience to meet and work with so many wonderful professionals over the years, and we are indebted to them for providing the feedback that has helped to improve our programs.  I also wanted to take the opportunity to thank everyone who has sent emails of appreciation and encouragement over the years.  The feedback has been vital to keep us keeping on when we have had more “opportunities” than we have hours in the day and to help show the powers that be, that this is time well spent.

January Citation:

Puthucheary ZA, Rawal J, McPhail M, et al.  Acute skeletal muscle wasting in critical illness. JAMA. 2013;310(15):1591-600.


This study evaluated and quantified the acute muscle loss, changes in muscle protein synthesis/breakdown and key signaling molecules that regulate protein homeostasis in adults with critical illness.  The population studied were 63 mixed ICU patients with sepsis (49.2%) and trauma (25.4%) being the most common diagnosis and smaller numbers of patients with intracranial bleeding (7.9%), acute liver failure (8%) and cardiogenic shock (9.5%).

Data from critically ill patients were compared to similar data from 8 healthy volunteers, who were assessed while both fed and fasted. Muscle mass was assessed on ICU days 1, 3, 7 and 10 by ultrasound and biopsy of thigh muscles. Muscle biopsies were analyzed for both the fiber cross-sectional area and quantification of the ratio of protein to DNA. Muscle protein synthesis and turnover were measured on ICU days 1 and 7 by stable amino acid isotope incorporation into muscle.

Inclusion and Exclusion Criteria:

Inclusion criteria:

Age >18 years, anticipated vent time >48 hours, anticipated ICU time >7 days, and anticipated to survive.

Exclusion criteria:

Not met inclusion criteria, pregnant, lower limb amputated, primary neuromuscular pathology, disseminated cancer.

Major Results:

The investigators evaluated 91 patients from 2009 to 2011 and 63 met all criteria.  Ultimately, 42 patients underwent both serial biopsies and ultrasound while 21 underwent ultrasound alone.  There were 28 patients that had thigh muscle loss assessed by all 3 methods (ultrasound, muscle fiber cross section and protein/DNA ratio) on day 1 and 7.  Only 11 patients underwent isotope infusions on days 1 and 7.  Nasogastric feeding was started in “9 of the 11 patients on day 1 and in all patients by day 7” (no quantification of how much protein and calories were actually received and no mention of nutrition in the other 52 patients).

Rectus femoris cross-sectional area decreased significantly from day 1 to day 7 (p=0.002) and continued to decrease to day 10 (p<0.001).  In those assessed by all 3 methods (n=28), ultrasound cross-sectional area  reflected a decrease in muscle of 10.3%, however the muscle loss was greater as measured by fiber cross-sectional area (17.5%), and the ratio of protein to DNA suggested muscle loss of 29.5%.  There was a significant association between change in rectus femoris cross-sectional area and ICU length of stay (p<0.001), but weakly associated with total length of stay.

The decrease in rectus femoris cross-sectional area was positively associated with degree of organ failure, mean C-reactive protein level, and total protein delivered during the study period.

Muscle protein fractional synthetic rate was depressed to rates observed by fasting controls day 1, but increased to rates observed by fed controls on day 7.  On day 1 and 7, leg protein breakdown was elevated compared to leg protein synthesis, indicating a net catabolic balance.

There were serial muscle biopsies in 37 pts, and of these, 14 had evidence of muscle necrosis by day 7 and 20 by day 10 (6 patients may have had some necrosis from a previous biopsy).

There was no significant association between any of the measured biochemical components of the anabolic and catabolic signaling pathways and muscle or protein homeostasis.

Author’s Conclusions:

Muscle wasting occurred early and rapidly during the first week of critical illness and was more severe among patients with multiorgan failure compared with single organ failure.


This study contributes to our store of knowledge regarding muscle mass and metabolism in critical illness. There have been a limited number of metabolic studies in critically ill patients in recent years, and there is a need for evaluation of different nutrition regimens on muscle metabolism (in addition to those on patient outcomes).  In an era where we are more carefully considering muscle mass and muscle function in assessment of nutrition, the concept that ultrasound may underestimate muscle loss in critically ill patients will be important to know for future studies.

Unfortunately, this study leads to more questions than answers about the role of nutrition on muscle metabolism.  The finding that thigh muscles had greater decrease in cross section when more protein was provided appears counterintuitive.  However, it must be remember that patients were not randomized to different protein intakes.  The association between protein and muscle loss means that they happened together, but it would be wrong to say that giving more protein increases muscle breakdown, based on this study.  It may be simply that patients who were perceived to be more catabolic, or who were more malnourished were given more protein.  There was no control for malnutrition on admission in this study.  There was also no information provided about how much protein, what percentage of nutrition goals, or total cumulative nutrition deficit that occurred during this study.  In fact, the authors only mention the presence of enteral nutrition in 11 out of the 63 patients, hence it is rather surprising the role of nutrition is mentioned whatsoever in this study.

We have known for a long time that nutrition alone does not completely reverse muscle catabolism in the most acute phase of critical illness.  One reason is that the body reprioritizes protein synthesis away from muscle to hepatic protein synthesis of acute phase reactants (not measured in this study).  There is a need for studies to consider the effect of the timing and amount of nutrition on both muscle and hepatic protein synthesis, as well as patient outcome.

Our Take Home Message (s)

1.   Ultrasound may underestimate muscle loss during critical illness.

2.   Randomized studies will be required to understand the optimal timing and amount of nutrition to optimize patient outcome, and improve nutritional and muscle recovery after critical illness.

3.   Details of all corticosteroids and paralytics should be included in these studies.

4.   The actual amounts of nutrients infused and percentage of nutrition needs provided should be detailed in research involving nutrition support.


Other News on the UVAHS GI Nutrition Website: (

Upcoming Webinars 2014:

–March 11:  Nutrition Support in Pancreatitis–Carol Parrish, MS, RDN
–April 29:  Micronutrient Issues in Gastric Bypass–Kelly O’Donnell, MS, RD, CNSC


Check out What’s New:

–“ Resources for the Nutrition Support Clinician

Latest Practical Gastroenterology article:

–Karosanidze T. Magnesium – So Underappreciated.  Practical Gastroenterology 2014;XXXVIII(1):28.


Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD


PS – Please feel free to forward on to friends and colleagues.