Persistent Low Serum Zinc is Associated with Recurrent Sepsis in Critically Ill Patients - A Pilot Study

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 May 5

PMID 28472045

Citations 25

Authors

Janine Hoeger

Tim-Philipp Simon

Thorben Beeker

Gernot Marx

Hajo Haase

Tobias Schuerholz

Affiliations

Soon will be listed here.

Abstract

Zinc is an essential trace element for both pathogens and hosts. Hypozincemia is a well known phenomenon in sepsis patients and represents the innate immune systems attempt to deprive pathogens of zinc. However little is known about course, restitution and prognostic value of serum zinc levels in sepsis patients. We performed a prospective observational single-center study set in a tertiary care university hospital intensive care unit. Serum zinc levels were singularly measured of healthy controls and sequentially of surgical sepsis patients and surgical patients over a 8-day period. Throughout the study period, we report significantly decreased serum zinc levels in surgical and surgical sepsis patients compared to healthy controls. Lower serum zinc levels in surgical sepsis patients were associated with a higher susceptibility to a recurrent sepsis episode. Furthermore, surgical sepsis patients with a higher number of organ dysfunctions and increased in-hospital mortality at day 28 and 90 showed lower serum zinc levels at admission. We report serum zinc levels as a promising biomarker in the diagnosis and evaluation of sepsis patients. However, it is still unclear whether these findings are caused by an over-amplified redistribution of zinc during acute-phase response, or whether the critically ill patients were zinc deficient before sepsis.

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References

Pepersack T, Rotsaert P, Benoit F, Willems D, Fuss M, Bourdoux P . Prevalence of zinc deficiency and its clinical relevance among hospitalised elderly. Arch Gerontol Geriatr. 2004; 33(3):243-53. DOI: 10.1016/s0167-4943(01)00186-8. View

Liuzzi J, Lichten L, Rivera S, Blanchard R, Aydemir T, Knutson M . Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci U S A. 2005; 102(19):6843-8. PMC: 1100791. DOI: 10.1073/pnas.0502257102. View

Hood M, Skaar E . Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol. 2012; 10(8):525-37. PMC: 3875331. DOI: 10.1038/nrmicro2836. View

Mertens K, Lowes D, Webster N, Talib J, Hall L, Davies M . Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. Br J Anaesth. 2015; 114(6):990-9. DOI: 10.1093/bja/aev073. View

Yamasaki S, Sakata-Sogawa K, Hasegawa A, Suzuki T, Kabu K, Sato E . Zinc is a novel intracellular second messenger. J Cell Biol. 2007; 177(4):637-45. PMC: 2064209. DOI: 10.1083/jcb.200702081. View

Haase H, Rink L . Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr. 2009; 29:133-52. DOI: 10.1146/annurev-nutr-080508-141119. View

Shankar A, Prasad A . Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998; 68(2 Suppl):447S-463S. DOI: 10.1093/ajcn/68.2.447S. View

van Zanten A, Sztark F, Kaisers U, Zielmann S, Felbinger T, Sablotzki A . High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial. JAMA. 2014; 312(5):514-24. DOI: 10.1001/jama.2014.7698. View

Knoell D, Julian M, Bao S, Besecker B, Macre J, Leikauf G . Zinc deficiency increases organ damage and mortality in a murine model of polymicrobial sepsis. Crit Care Med. 2009; 37(4):1380-8. PMC: 2905048. DOI: 10.1097/CCM.0b013e31819cefe4. View

10.

Besecker B, Exline M, Hollyfield J, Phillips G, DiSilvestro R, Wewers M . A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission. Am J Clin Nutr. 2011; 93(6):1356-64. PMC: 3095505. DOI: 10.3945/ajcn.110.008417. View

11.

Nowak J, Harmon K, Caldwell C, Wong H . Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis. Pediatr Crit Care Med. 2012; 13(5):e323-9. PMC: 3438373. DOI: 10.1097/PCC.0b013e31824fbd90. View

12.

Hoeger J, Simon T, Doemming S, Thiele C, Marx G, Schuerholz T . Alterations in zinc binding capacity, free zinc levels and total serum zinc in a porcine model of sepsis. Biometals. 2015; 28(4):693-700. DOI: 10.1007/s10534-015-9858-4. View

13.

Rink L, Kirchner H . Zinc-altered immune function and cytokine production. J Nutr. 2000; 130(5S Suppl):1407S-11S. DOI: 10.1093/jn/130.5.1407S. View

14.

Angus D, Lidicker J, Clermont G, Carcillo J, Pinsky M . Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001; 29(7):1303-10. DOI: 10.1097/00003246-200107000-00002. View

15.

Wang T, DerHovanessian A, De Cruz S, Belperio J, Deng J, Soo Hoo G . Subsequent infections in survivors of sepsis: epidemiology and outcomes. J Intensive Care Med. 2013; 29(2):87-95. PMC: 4393330. DOI: 10.1177/0885066612467162. View

16.

Shanbhogue L, Paterson N . Effect of sepsis and surgery on trace minerals. JPEN J Parenter Enteral Nutr. 1990; 14(3):287-9. DOI: 10.1177/0148607190014003287. View

17.

Bone R, Balk R, Cerra F, Dellinger R, Fein A, Knaus W . Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992; 101(6):1644-55. DOI: 10.1378/chest.101.6.1644. View

18.

Rittirsch D, Flierl M, Ward P . Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008; 8(10):776-87. PMC: 2786961. DOI: 10.1038/nri2402. View

19.

Wacker C, Prkno A, Brunkhorst F, Schlattmann P . Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013; 13(5):426-35. DOI: 10.1016/S1473-3099(12)70323-7. View

20.

Wong H, Shanley T, Sakthivel B, Cvijanovich N, Lin R, Allen G . Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 2007; 30(2):146-55. PMC: 2770262. DOI: 10.1152/physiolgenomics.00024.2007. View