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Critical Care
Published in: Critical Care 1/2019

Open Access 01-12-2019 | Septicemia | Research

Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors

Authors: Carlo Custodero, Quran Wu, Gabriela L. Ghita, Stephen D. Anton, Scott C. Brakenridge, Babette A. Brumback, Philip A. Efron, Anna K. Gardner, Christiaan Leeuwenburgh, Lyle L. Moldawer, John W. Petersen, Frederick A. Moore, Robert T. Mankowski

Published in: Critical Care | Issue 1/2019

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Abstract

Background

Sepsis survivors often develop chronic critical illness (CCI) and demonstrate the persistent inflammation, immunosuppression, and catabolism syndrome predisposing them to long-term functional limitations and higher mortality. There is a need to identify biomarkers that can predict long-term worsening of physical function to be able to act early and prevent mobility loss. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-accepted biomarker of cardiac overload, but it has also been shown to be associated with long-term physical function decline. We explored whether NT-proBNP blood levels in the acute phase of sepsis are associated with physical function and muscle strength impairment at 6 and 12 months after sepsis onset.

Methods

This is a retrospective analysis conducted in 196 sepsis patients (aged 18–86 years old) as part of the University of Florida (UF) Sepsis and Critical Illness Research Center (SCIRC) who consented to participate in the 12-month follow-up study. NT-proBNP was measured at 24 h after sepsis onset. Patients were followed to determine physical function by short physical performance battery (SPPB) test score (scale 0 to12—higher score corresponds with better physical function) and upper limb muscle strength by hand grip strength test (kilograms) at 6 and 12 months. We used a multivariate linear regression model to test an association between NT-proBNP levels, SPPB, and hand grip strength scores. Missing follow-up data or absence due to death was accounted for by using inverse probability weighting based on concurrent health performance status scores. Statistical significance was set at p ≤ 0.05.

Results

After adjusting for covariates (age, gender, race, Charlson comorbidity index, APACHE II score, and presence of CCI condition), higher levels of NT-proBNP at 24 h after sepsis onset were associated with lower SPPB scores at 12 months (p < 0.05) and lower hand grip strength at 6-month (p < 0.001) and 12-month follow-up (p < 0.05).

Conclusions

NT-proBNP levels during the acute phase of sepsis may be a useful indicator of higher risk of long-term impairments in physical function and muscle strength in sepsis survivors.
Literature
1.
Rhee C, Dantes R, Epstein L, Murphy DJ, Seymour CW, Iwashyna TJ, Kadri SS, Angus DC, Danner RL, Fiore AE, et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014. JAMA. 2017;318(13):1241–9.PubMedPubMedCentral
2.
Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010;36(2):222–31.PubMedPubMedCentral
3.
Efron PA, Mohr AM, Bihorac A, Horiguchi H, Hollen MK, Segal MS, Baker HV, Leeuwenburgh C, Moldawer LL, Moore FA, et al. Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery. Surgery. 2018;164(2):178–84.PubMedPubMedCentral
4.
Mira JC, Cuschieri J, Ozrazgat-Baslanti T, Wang Z, Ghita GL, Loftus TJ, Stortz JA, Raymond SL, Lanz JD, Hennessy LV, et al. The epidemiology of chronic critical illness after severe traumatic injury at two level-one trauma centers. Crit Care Med. 2017;45(12):1989–96.PubMedPubMedCentral
5.
Davidson GH, Hamlat CA, Rivara FP, Koepsell TD, Jurkovich GJ, Arbabi S. Long-term survival of adult trauma patients. JAMA. 2011;305(10):1001–7.PubMed
6.
Gardner AK, Ghita GL, Wang Z, Ozrazgat-Baslanti T, Raymond SL, Mankowski RT, Brumback BA, Efron PA, Bihorac A, Moore FA, et al. The development of chronic critical illness determines physical function, quality of life, and long-term survival among early survivors of sepsis in surgical ICUs. Crit Care Med. 2019;47(4):566–73.PubMed
7.
Walkey AJ, Hammill BG, Curtis LH, Benjamin EJ. Long-term outcomes following development of new-onset atrial fibrillation during sepsis. Chest. 2014;146(5):1187–95.PubMedPubMedCentral
8.
Yende S, Linde-Zwirble W, Mayr F, Weissfeld LA, Reis S, Angus DC. Risk of cardiovascular events in survivors of severe sepsis. Am J Respir Crit Care Med. 2014;189(9):1065–74.PubMedPubMedCentral
9.
Mankowski RT, Yende S, Angus DC. Long-term impact of sepsis on cardiovascular health. Intensive Care Med. 2019;45(1):78–81.PubMed
10.
Dos Santos C, Hussain SN, Mathur S, Picard M, Herridge M, Correa J, Bain A, Guo Y, Advani A, Advani SL, et al. Mechanisms of chronic muscle wasting and dysfunction after an intensive care unit stay. A pilot study. Am J Respir Crit Care Med. 2016;194(7):821–30.PubMed
11.
Chow SL, Maisel AS, Anand I, Bozkurt B, de Boer RA, Felker GM, Fonarow GC, Greenberg B, Januzzi JL Jr, Kiernan MS, et al. Role of biomarkers for the prevention, assessment, and management of heart failure: a scientific statement from the American Heart Association. Circulation. 2017;135(22):e1054–91.PubMed
12.
Turner KL, Moore LJ, Todd SR, Sucher JF, Jones SA, McKinley BA, Valdivia A, Sailors RM, Moore FA. Identification of cardiac dysfunction in sepsis with B-type natriuretic peptide. J Am Coll Surg. 2011;213(1):139–46 discussion 146-137.PubMed
13.
Fox AA, Marcantonio ER, Collard CD, Thoma M, Perry TE, Shernan SK, Muehlschlegel JD, Body SC. Increased peak postoperative B-type natriuretic peptide predicts decreased longer-term physical function after primary coronary artery bypass graft surgery. Anesthesiology. 2011;114(4):807–16.PubMedPubMedCentral
14.
Charpentier J, Luyt CE, Fulla Y, Vinsonneau C, Cariou A, Grabar S, Dhainaut JF, Mira JP, Chiche JD. Brain natriuretic peptide: a marker of myocardial dysfunction and prognosis during severe sepsis. Crit Care Med. 2004;32(3):660–5.PubMed
15.
Li Y, Ge S, Peng Y, Chen X. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis. Burns Trauma. 2013;1(3):109–21.PubMedPubMedCentral
16.
de Bold AJ. Cardiac natriuretic peptides gene expression and secretion in inflammation. J Investig Med. 2009;57(1):29–32.PubMed
17.
Li N, Zhang Y, Fan S, Xing J, Liu H. BNP and NT-proBNP levels in patients with sepsis. Front Biosci (Landmark Ed). 2013;18:1237–43.
18.
Brueckmann M, Huhle G, Lang S, Haase KK, Bertsch T, Weiss C, Kaden JJ, Putensen C, Borggrefe M, Hoffmann U. Prognostic value of plasma N-terminal pro-brain natriuretic peptide in patients with severe sepsis. Circulation. 2005;112(4):527–34.PubMed
19.
Roch A, Allardet-Servent J, Michelet P, Oddoze C, Forel JM, Barrau K, Loundou A, Perrin G, Auffray JP, Portugal H, et al. NH2 terminal pro-brain natriuretic peptide plasma level as an early marker of prognosis and cardiac dysfunction in septic shock patients. Crit Care Med. 2005;33(5):1001–7.PubMed
20.
Wang F, Wu Y, Tang L, Zhu W, Chen F, Xu T, Bo L, Li J, Deng X. Brain natriuretic peptide for prediction of mortality in patients with sepsis: a systematic review and meta-analysis. Crit Care. 2012;16(3):R74.PubMedPubMedCentral
21.
Cheng H, Fan WZ, Wang SC, Liu ZH, Zang HL, Wang LZ, Liu HJ, Shen XH, Liang SQ. N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: a retrospective study. J Crit Care. 2015;30(3):654 e659–14.
22.
Samransamruajkit R, Uppala R, Pongsanon K, Deelodejanawong J, Sritippayawan S, Prapphal N. Clinical outcomes after utilizing surviving sepsis campaign in children with septic shock and prognostic value of initial plasma NT-proBNP. Indian J Crit Care Med. 2014;18(2):70–6.PubMedPubMedCentral
23.
Hur M, Kim H, Lee S, Cristofano F, Magrini L, Marino R, Gori CS, Bongiovanni C, Zancla B, Cardelli P, et al. Diagnostic and prognostic utilities of multimarkers approach using procalcitonin, B-type natriuretic peptide, and neutrophil gelatinase-associated lipocalin in critically ill patients with suspected sepsis. BMC Infect Dis. 2014;14:224.PubMedPubMedCentral
24.
Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM, Damske BA, Parrillo JE. Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med. 1984;100(4):483–90.PubMed
25.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250–6.PubMed
26.
Gardner-Thorpe J, Love N, Wrightson J, Walsh S, Keeling N. The value of Modified Early Warning Score (MEWS) in surgical in-patients: a prospective observational study. Ann R Coll Surg Engl. 2006;88(6):571–5.PubMedPubMedCentral
27.
Muckart DJ, Bhagwanjee S. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients. Crit Care Med. 1997;25(11):1789–95.PubMed
28.
Davies MG, Hagen PO. Systemic inflammatory response syndrome. Br J Surg. 1997;84(7):920–35.PubMed
29.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.PubMed
30.
Loftus TJ, Mira JC, Ozrazgat-Baslanti T, Ghita GL, Wang Z, Stortz JA, Brumback BA, Bihorac A, Segal MS, Anton SD, et al. Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients. BMJ Open. 2017;7(7):e015136.PubMedPubMedCentral
31.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.PubMed
32.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29.PubMed
33.
Januzzi JL Jr, Chen-Tournoux AA, Christenson RH, Doros G, Hollander JE, Levy PD, Nagurney JT, Nowak RM, Pang PS, Patel D, et al. N-terminal pro-B-type natriuretic peptide in the emergency department: the ICON-RELOADED Study. J Am Coll Cardiol. 2018;71(11):1191–200.PubMed
34.
McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14(8):803–69.PubMed
35.
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49(2):M85–94.PubMed
36.
Innes E. Handgrip strength testing: a review of the literature. Aust Occup Ther J. 1999;46(3):120–40.
37.
Zhang Z, Zhang Z, Xue Y, Xu X, Ni H. Prognostic value of B-type natriuretic peptide (BNP) and its potential role in guiding fluid therapy in critically ill septic patients. Scand J Trauma Resusc Emerg Med. 2012;20:86.PubMedPubMedCentral
38.
Khoury J, Arow M, Elias A, Makhoul BF, Berger G, Kaplan M, Mashiach T, Ismael-Badarneh R, Aronson D, Azzam ZS. The prognostic value of brain natriuretic peptide (BNP) in non-cardiac patients with sepsis, ultra-long follow-up. J Crit Care. 2017;42:117–22.PubMed
39.
Pavasini R, Guralnik J, Brown JC, di Bari M, Cesari M, Landi F, Vaes B, Legrand D, Verghese J, Wang C, et al. Short physical performance battery and all-cause mortality: systematic review and meta-analysis. BMC Med. 2016;14(1):215.PubMedPubMedCentral
40.
Rantanen T, Guralnik JM, Foley D, Masaki K, Leveille S, Curb JD, White L. Midlife hand grip strength as a predictor of old age disability. JAMA. 1999;281(6):558–60.PubMed
41.
Bohannon RW. Hand-grip dynamometry predicts future outcomes in aging adults. J Geriatr Phys Ther. 2008;31(1):3–10.PubMed
42.
Yamashita T, Kohara K, Tabara Y, Ochi M, Nagai T, Okada Y, Igase M, Miki T. Muscle mass, visceral fat, and plasma levels of B-type natriuretic peptide in healthy individuals (from the J-SHIPP Study). Am J Cardiol. 2014;114(4):635–40.PubMed
43.
44.
Stana F, Vujovic M, Mayaki D, Leduc-Gaudet JP, Leblanc P, Huck L, Hussain SNA. Differential regulation of the autophagy and proteasome pathways in skeletal muscles in sepsis. Crit Care Med. 2017;45(9):e971–9.PubMed
45.
Mofarrahi M, Sigala I, Guo Y, Godin R, Davis EC, Petrof B, Sandri M, Burelle Y, Hussain SN. Autophagy and skeletal muscles in sepsis. PLoS One. 2012;7(10):e47265.PubMedPubMedCentral
46.
Teener JW, Rich MM. Dysregulation of sodium channel gating in critical illness myopathy. J Muscle Res Cell Motil. 2006;27(5–7):291–6.PubMed
47.
Rocheteau P, Chatre L, Briand D, Mebarki M, Jouvion G, Bardon J, Crochemore C, Serrani P, Lecci PP, Latil M, et al. Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy. Nat Commun. 2015;6:10145.PubMedPubMedCentral
48.
Solverson KJ, Grant C, Doig CJ. Assessment and predictors of physical functioning post-hospital discharge in survivors of critical illness. Ann Intensive Care. 2016;6(1):92.PubMedPubMedCentral
Metadata
Title
Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors
Authors
Carlo Custodero
Quran Wu
Gabriela L. Ghita
Stephen D. Anton
Scott C. Brakenridge
Babette A. Brumback
Philip A. Efron
Anna K. Gardner
Christiaan Leeuwenburgh
Lyle L. Moldawer
John W. Petersen
Frederick A. Moore
Robert T. Mankowski
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2505-7

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