Skip to main content

Advertisement

SpringerLink
Log in

Effects of restricting perioperative use of intravenous chloride on kidney injury in patients undergoing cardiac surgery: the LICRA pragmatic controlled clinical trial

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Purpose

The administration of chloride-rich intravenous (IV) fluid and hyperchloraemia have been associated with perioperative renal injury. The aim of this study was to determine whether a comprehensive perioperative protocol for the administration of chloride-limited IV fluid would reduce perioperative renal injury in adults undergoing cardiac surgery.

Methods

From February 2014 through to December 2015, all adult patients undergoing cardiac surgery within a single academic medical center received IV fluid according to the study protocol. The perioperative protocol governed all fluid administration from commencement of anesthesia through to discharge from the intensive care unit and varied over four sequential periods, each lasting 5 months. In periods 1 and 4 a chloride-rich strategy, consisting of 0.9% saline and 4% albumin, was adopted; in periods 2 and 3, a chloride-limited strategy, consisting of a buffered salt solution and 20% albumin, was used. Co-primary outcomes were peak delta serum creatinine (∆SCr) within 5 days after the operation and KDIGO-defined stage 2 or stage 3 acute kidney injury (AKI) within 5 days after the operation.

Results

We enrolled and analysed data from 1136 patients, with 569 patients assigned to a chloride-rich fluid strategy and 567 to a chloride-limited one. Compared with a chloride-limited strategy and adjusted for prespecified covariates, there was no association between a chloride-rich perioperative fluid strategy and either peak ∆S Cr, transformed to satisfy the assumptions of multivariable linear regression [regression coefficient 0.03, 95% confidence interval (CI) −0.03 to 0.08); p = 0.39], or stage 2 or 3 AKI (adjusted odds ratio 0.97, 95% CI 0.65–1.47; p = 0.90].

Conclusions

A perioperative fluid strategy to restrict IV chloride administration was not associated with an altered incidence of AKI or other metrics of renal injury in adult patients undergoing cardiac surgery.

Trial Registration: Clinicaltrials.gov Identifier: NCT02020538.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA (2008) Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant 23:1970–1974

    Article  PubMed  Google Scholar 

  2. Ricci Z, Cruz D, Ronco C (2007) The RIFLE criteria and mortality in acute kidney injury: a systematic review. Kidney Int 73:538–546

    Article  PubMed  Google Scholar 

  3. Robert AM, Kramer RS, Dacey LJ et al (2010) Cardiac surgery-associated acute kidney injury: a comparison of two consensus criteria. Ann Thorac Surg 90:1939–1943

    Article  PubMed  Google Scholar 

  4. Xu JR, Zhu JM, Jiang J et al (2015) Risk factors for long-term mortality and progressive chronic kidney disease associated with acute kidney injury after cardiac surgery. Med (Baltimore) 94:e2025

    Article  CAS  Google Scholar 

  5. Parke RL, McGuinness SP, Gilder E, McCarthy LW, Cowdrey KA (2015) A randomised feasibility study to assess a novel strategy to rationalise fluid in patients after cardiac surgery. Br J Anaesth 115:45–52

    Article  CAS  PubMed  Google Scholar 

  6. Scheingraber S, Rehm M, Sehmisch C, Finsterer U (1999) Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 90:1265–1270

    Article  CAS  PubMed  Google Scholar 

  7. Wilkes NJ, Woolf R, Mutch M et al (2001) The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesth Analg 93:811–816

    Article  CAS  PubMed  Google Scholar 

  8. Chowdhury AH, Cox EF, Francis ST, Lobo DN (2012) A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte(R) 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg 256:18–24

    Article  PubMed  Google Scholar 

  9. Yunos NM, Bellomo R, Story D, Kellum J (2010) Bench-to-bedside review: chloride in critical illness. Crit Care 14:226

    Article  PubMed  PubMed Central  Google Scholar 

  10. McCluskey SA, Karkouti K, Wijeysundera D, Minkovich L, Tait G, Beattie WS (2013) Hyperchloremia after noncardiac surgery is independently associated with increased morbidity and mortality: a propensity-matched cohort study. Anesth Analg 117:412–421

    Article  PubMed  Google Scholar 

  11. Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M (2012) Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 308:1566–1572

    Article  CAS  PubMed  Google Scholar 

  12. Young P, Bailey M, Beasley R et al (2015) Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial. JAMA 314:1701–1710

    Article  CAS  PubMed  Google Scholar 

  13. Kidney disease: Improving global outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2:1–138

    Article  Google Scholar 

  14. Roques F, Nashef SA, Michel P et al (1999) Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients. Eur J Cardiothorac Surg 15:816–822

    Article  CAS  PubMed  Google Scholar 

  15. Thakar CV, Arrigain S, Worley S, Yared J-P, Paganini EP (2005) A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol 16:162–168

    Article  PubMed  Google Scholar 

  16. Yunos NM, Kim IB, Bellomo R et al (2011) The biochemical effects of restricting chloride-rich fluids in intensive care. Crit Care Med 39:2419–2424

    Article  CAS  PubMed  Google Scholar 

  17. Nichol A, Bailey M, Egi M et al (2011) Dynamic lactate indices as predictors of outcome in critically ill patients. Crit Care 15:R242

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zwarenstein M, Treweek S, Gagnier JJ et al (2008) Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ 337:a2390

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nadeem A, Salahuddin N, El Hazmi A et al (2014) Chloride-liberal fluids are associated with acute kidney injury after liver transplantation. Crit Care 18:625

    Article  PubMed  PubMed Central  Google Scholar 

  20. Shaw AD, Bagshaw SM, Goldstein SL et al (2012) Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg 255:821–829

    Article  PubMed  Google Scholar 

  21. Shaw AD, Raghunathan K, Peyerl FW, Munson SH, Paluszkiewicz SM, Schermer CR (2014) Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS. Intensive Care Med 40:1897–1905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang Z, Xu X, Fan H, Li D, Deng H (2013) Higher serum chloride concentrations are associated with acute kidney injury in unselected critically ill patients. BMC Nephrol 14:235

    Article  PubMed  PubMed Central  Google Scholar 

  23. Raghunathan K, Shaw A, Nathanson B et al (2014) Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med 42:1585–1591

    Article  CAS  PubMed  Google Scholar 

  24. Yunos NM, Bellomo R, Glassford N, Sutcliffe H, Lam Q, Bailey M (2015) Chloride-liberal vs. chloride-restrictive intravenous fluid administration and acute kidney injury: an extended analysis. Intensive Care Med 41:257–264

    Article  CAS  PubMed  Google Scholar 

  25. Burdett E, Dushianthan A, Bennett-Guerrero E et al (2012) Perioperative buffered versus non-buffered fluid administration for surgery in adults. Cochrane Database Syst Rev 12:4089

    Google Scholar 

  26. Sen A, Keener CM, Sileanu FE et al (2017) Chloride content of fluids used for large-volume resuscitation is associated with reduced survival. Crit Care Med 45:e146–e153

    Article  CAS  PubMed  Google Scholar 

  27. McIlroy DR, Farkas D, Argenziano M, Umann T, Sladen R (2013) Incorporating oliguria into the diagnostic criteria for acute kidney injury after on-pump cardiac surgery: impact on incidence and outcomes. J Cardiothorac Vasc Anesth 27:1145–1152

    Article  PubMed  Google Scholar 

  28. Semler MW, Wanderer JP, Ehrenfeld JM et al (2016) Balanced crystalloids versus saline in the intensive care unit: the SALT randomized trial. Am J Respir Crit Care Med. doi:10.1164/rccm.201607-1345OC

    Google Scholar 

Download references

Acknowledgements

D. McIlroy and J. Kasza had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The statistical analysis was jointly conducted by J. Kasza (biostatistician) and D. McIlroy. The study was jointly funded by grants from the Australian and New Zealand College of Anaesthetists and the Society of Cardiovascular Anesthesiologists/International Anesthesia Research Society. Neither of the funding bodies had any input into the design and conduct of the study, collection, management, analysis, and interpretation of data, nor preparation, review, or approval of the manuscript.

Author information

Authors and Affiliations

  1. Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, 55 Commercial Road, Melbourne, VIC, 3004, Australia

    David McIlroy, Dhiraj Bhatia & Lisa Wutzlhofer

  2. Monash University, Commercial Road, Melbourne, VIC, 3004, Australia

    David McIlroy & Silvana Marasco

  3. Intensive Care Unit, Alfred Hospital, Melbourne, VIC, Australia

    Deirdre Murphy

  4. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    Jessica Kasza

  5. Department of Surgery, Alfred Hospital, Melbourne, VIC, Australia

    Silvana Marasco

Authors
  1. David McIlroy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deirdre Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jessica Kasza
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dhiraj Bhatia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lisa Wutzlhofer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Silvana Marasco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David McIlroy.

Ethics declarations

Conflicts of interest

All of the authors declare that they have no potential conflicts of interest related to the submitted manuscript.

Additional information

Take-home message:

In a pragmatic trial in adults undergoing cardiac surgery, limiting the chloride content of perioperative IV fluid did not reduce AKI.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McIlroy, D., Murphy, D., Kasza, J. et al. Effects of restricting perioperative use of intravenous chloride on kidney injury in patients undergoing cardiac surgery: the LICRA pragmatic controlled clinical trial. Intensive Care Med 43, 795–806 (2017). https://doi.org/10.1007/s00134-017-4772-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-017-4772-6

Keywords

Search

Navigation