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Poor Cardiorespiratory Fitness Is a Risk Factor for Sepsis in Patients Awaiting Liver Transplantation

Wallen, Matthew P., PhD1; Woodward, Aidan J., MBBS2,3; Hall, Adrian, MBBS4; Skinner, Tina L., PhD1; Coombes, Jeff S., PhD1; Macdonald, Graeme A., PhD2,3,5

doi: 10.1097/TP.0000000000002360
Original Clinical Science—Liver
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Background. Patients with advanced liver disease are at increased risk of infection and other complications. A significant proportion of patients also have poor fitness and low muscle mass. The primary aim of this study was to investigate if cardiorespiratory fitness and body composition are risk factors for sepsis and other complications of advanced liver disease.

Methods. Patients being listed for liver transplantation underwent cardiopulmonary exercise testing to determine ventilatory threshold (VT). Computed tomography was used to measure skeletal muscle and subcutaneous and visceral adipose tissue indexes. All unplanned hospital admissions, deaths or delistings before transplantation were recorded.

Results. Eighty-two patients (aged 55.1 [50.6–59.4] years, median (interquartile range); male 87%] achieved a median VT of 11.7 (9.7–13.4) mL·kg−1·min−1. Their median model of end-stage liver disease, incorporating serum sodium score was 18 (14–22); and 37 had hepatocellular carcinoma. There were 50 admissions in 31 patients; with 16 admissions for sepsis in 13 patients. Patients with sepsis had a significantly lower VT (sepsis, 9.5 [7.8–11.9]; no sepsis, 11.8 [10.5–13.8] mL·kg−1·min−1; P = 0.003]. No body composition variables correlated with sepsis, nor were there any significant associations between VT and unplanned admissions for other indications. Multivariate logistic regression demonstrated that VT was independently associated with a diagnosis of sepsis (P = 0.03). Poisson regression revealed that VT was a significant predictor for the number of septic episodes (P = 0.02); independent of age, model of end-stage liver disease, incorporating serum sodium score, hepatocellular carcinoma diagnosis, presence of ascites, and β-blocker use.

Conclusions. Poor cardiorespiratory fitness is an independent risk factor for the development of sepsis in advanced liver disease.

1Centre for Research on Exercise, Physical Activity and Health (CRExPAH), School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Queensland, Australia.

2School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

3Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

4Department of Anaesthesia, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

5Translational Research Institute, Brisbane, Queensland, Australia.

Received 9 March 2018. Revision received 28 June 2018.

Accepted 3 July 2018.

M.W., A.H., and T.S. have no personal or funding interests to disclose. A.W. has received funding from the Royal Australasian College of Physicians for unrelated work. A.W. is also supported by the Princess Alexandra Hospital’s Research Support Scheme postgraduate scholarship. J.C. has received an unrestricted research grant from Coca Cola and funding from Renew Corp, Pfizer, Cyanotech, Terumo, Gatorade, Numico, Northfields and Baxter for unrelated work. J.C. has also received honorariums to present at meetings from Novartis, Amgen and Roche. G.M. is on an advisory board for AbbVie and has received funding to speak on behalf of MSD and Gilead for unrelated work.

M.W. conceived and designed the research, performed and analyzed the data, and wrote the article. A.W. performed data collection, contributed to writing and revised the article. A.H. performed data collection and revised the article. T.S. contributed to writing and revised the article. J.C. conceived and designed the research, advised on the research performance, contributed to writing and revised the article. G.M. conceived and designed the research, advised on the performance of the research and revised the article.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Graeme A. Macdonald, PhD, FAASLD, Department of Gastroenterology and Hepatology, The Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba, Queensland, 4011, Australia. (g.macdonald@uq.edu.au).

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