Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients

Bandarn Suetrong, Chawika Pisitsak, John H Boyd, James A Russell, Keith R Walley, Bandarn Suetrong, Chawika Pisitsak, John H Boyd, James A Russell, Keith R Walley

Abstract

Background: Acute kidney injury and hyperchloremia are commonly present in critically ill septic patients. Our study goal was to evaluate the association of hyperchloremia and acute kidney injury in severe sepsis and septic shock patients.

Methods: In this retrospective cohort study in a provincial tertiary care hospital, adult patients with severe sepsis or septic shock and serum chloride measurements were included. Serum chloride was measured on a daily basis for 48 hours. Primary outcome was development of acute kidney injury (AKI) and association of AKI and serum chloride parameters was analyzed.

Results: A total of 240 patients were included in the study, 98 patients (40.8 %) had hyperchloremia. The incidence of acute kidney injury (AKI) was significantly higher in the hyperchloremia group (85.7 % vs 47.9 %; p < 0.001). Maximal chloride concentration in the first 48 hours ([Cl-]max) was significantly associated with AKI. In multivariate analysis, [Cl-]max was independently associated with AKI [adjusted odds ratio (OR) for AKI = 1.28 (1.02-1.62); p = 0.037]. The increase in serum chloride (Δ[Cl-] = [Cl-]max - initial chloride concentration) demonstrated a dose-dependent relationship with severity of AKI. The mean Δ[Cl-] in patients without AKI was 2.1 mmol/L while in the patients with AKI stage 1, 2 and 3 the mean Δ[Cl-] was 5.1, 5.9 and 6.7 mmol/L, respectively. A moderate increase in serum chloride (Δ[Cl-] ≥ 5 mmol/L) was associated with AKI [OR = 5.70 (3.00-10.82); p < 0.001], even in patients without hyperchloremia [OR = 8.25 (3.44-19.78); p < 0.001].

Conclusions: Hyperchloremia is common in severe sepsis and septic shock and independently associated with AKI. A moderate increase in serum chloride (Δ[Cl-] ≥5 mmol/L) is associated with AKI even in patients without hyperchloremia.

Keywords: Acute kidney injury; Chloride; Hyperchloremia; Sepsis; Septic shock.

Figures

Fig. 1
Fig. 1
Flow chart of the patients with severe sepsis and septic shock in the study. [Cl-]max maximal chloride concentration in the first 48 hours, AKI acute kidney injury, CRF chronic renal failure
Fig. 2
Fig. 2
Increase in serum chloride and AKI severity. The mean increase in serum chloride (Δ[Cl-]) in AKI stage 1, 2 and 3 is significantly higher than in patients without AKI (p < 0.05) and these data suggest a dose-response relationship between Δ[Cl-] and AKI stage. Δ[Cl-] increase in serum chloride, AKI acute kidney injury,

References

    1. Poukkanen M, Vaara ST, Pettilä V, et al. Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units. Acta Anaesthesiol Scand. 2013;57:863–72. doi: 10.1111/aas.12133.
    1. Lopes JA, Jorge S, Resina C, et al. Acute kidney injury in patients with sepsis: a contemporary analysis. Int J Infect Dis. 2009;13:176–81. doi: 10.1016/j.ijid.2008.05.1231.
    1. Vanmassenhove J, Lameire N, Dhondt A, Vanholder R, Van Biesen W. Prognostic robustness of serum creatinine based AKI definitions in patients with sepsis: a prospective cohort study. BMC Nephrol. 2015;16:112. doi: 10.1186/s12882-015-0107-4.
    1. Lopes JA, Fernandes P, Jorge S, et al. Long-term risk of mortality after acute kidney injury in patients with sepsis: a contemporary analysis. BMC Nephrol. 2010;11:9. doi: 10.1186/1471-2369-11-9.
    1. Linder A, Fjell C, Levin A, Walley KR, Russell JA, Boyd JH. Small acute increases in serum creatinine are associated with decreased long-term survival in the critically ill. Am J Respir Crit Care Med. 2014;189:1075–81. doi: 10.1164/rccm.201311-2097OC.
    1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637. doi: 10.1097/CCM.0b013e31827e83af.
    1. Hahn RG. Should anaesthetists stop infusing isotonic saline? Br J Anaesth. 2014;112:4–6. doi: 10.1093/bja/aet292.
    1. Hammond NE, Taylor C, Saxena M, et al. Resuscitation fluid use in Australian and New Zealand Intensive Care Units between 2007 and 2013. Intensive Care Med. 2015;41:1611–9. doi: 10.1007/s00134-015-3878-y.
    1. Finfer S, Liu B, Taylor C, et al. Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care. 2010;14:R185. doi: 10.1186/cc9293.
    1. Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013;369:1243–51. doi: 10.1056/NEJMra1208627.
    1. O'Dell E, Tibby SM, Durward A, Murdoch IA. Hyperchloremia is the dominant cause of metabolic acidosis in the postresuscitation phase of pediatric meningococcal sepsis. Crit Care Med. 2007;35:2390–4. doi: 10.1097/01.CCM.0000284588.17760.99.
    1. Noritomi DT, Soriano FG, Kellum JA, et al. Metabolic acidosis in patients with severe sepsis and septic shock: a longitudinal quantitative study. Crit Care Med. 2009;37:2733–9. doi: 10.1097/CCM.0b013e3181a59165.
    1. Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest. 1983;71:726–35. doi: 10.1172/JCI110820.
    1. Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9 % saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2012;256:18–24. doi: 10.1097/SLA.0b013e318256be72.
    1. Williams EL, Hildebrand KL, McCormick SA, Bedel MJ. The effect of intravenous lactated Ringer's solution versus 0.9 % sodium chloride solution on serum osmolality in human volunteers. Anesth Analg. 1999;88:999–1003.
    1. Zhou F, Peng ZY, Bishop JV, Cove ME, Singbartl K, Kellum JA. Effects of fluid resuscitation with 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Crit Care Med. 2014;42:e270–8. doi: 10.1097/CCM.0000000000000145.
    1. Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012;308:1566–72. doi: 10.1001/jama.2012.13356.
    1. Zhang Z, Xu X, Fan H, Li D, Deng H. Higher serum chloride concentrations are associated with acute kidney injury in unselected critically ill patients. BMC Nephrol. 2013;14:235. doi: 10.1186/1471-2369-14-235.
    1. Ryan S, Maria H, Rahul N, Gagan K. Hyperchloremia after fluid resuscitation in severe sepsis - does it predict renal outcomes? Chest. 2014;146:232A. doi: 10.1378/chest.1994006.
    1. Neyra JA, Canepa-Escaro F, Li X, et al. Association of hyperchloremia with hospital mortality in critically ill septic patients. Crit Care Med. 2015;43:1938–44. doi: 10.1097/CCM.0000000000001161.
    1. Kellum JA, Lameire N. KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: A KDIGO summary (Part 1) Crit Care. 2013;17:204–19. doi: 10.1186/cc11454.
    1. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–70. doi: 10.7326/0003-4819-130-6-199903160-00002.
    1. Young P, Bailey M, Beasley R, et al. 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. 2015;314:1701–10. doi: 10.1001/jama.2015.12334.
    1. Awad S, Allison SP, Lobo DN. The history of 0.9 % saline. Clin Nutr. 2008;27:179–88. doi: 10.1016/j.clnu.2008.01.008.
    1. Kellum JA, Bellomo R, Kramer DJ, Pinsky MR. Etiology of metabolic acidosis during saline resuscitation in endotoxemia. Shock. 1998;9(5):364–8
    1. Story DA, Lees L, Weinberg L, et al. Cognitive changes after saline or plasmalyte infusion in healthy volunteers: a multiple blinded, randomized, cross-over trial. Anesthesiology. 2013;119:569–75. doi: 10.1097/ALN.0b013e31829416ba.
    1. Reid F, Lobo DN, Williams RN, Rowlands BJ, Allison SP. (Ab) normal saline and physiological Hartmann's solution: a randomized double-blind crossover study. Clin Sci (Lond) 2003;104:17–24.
    1. Hadimioglu N, Saadawy I, Saglam T, et al. The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation. Anesth Analg. 2008;107:264–9. doi: 10.1213/ane.0b013e3181732d64.
    1. Young JB, Utter GH, Schermer CR, et al. Saline versus Plasma-Lyte A in initial resuscitation of trauma patients: a randomized trial. Ann Surg. 2014;259:255–62. doi: 10.1097/SLA.0b013e318295feba.
    1. O’Malley F, Frumento RJ, Catherine MN, et al. A randomized, double-blind comparison of Lactated Ringer’s solution and 0.9 % NaCl during renal transplantation. Anesth Analg. 2005;100:1518–24. doi: 10.1213/01.ANE.0000150939.28904.81.
    1. Scheingraber S, Rehm M, Sehmisch C, et al. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology. 1999;90:1265–70. doi: 10.1097/00000542-199905000-00007.
    1. Waters JH, Gottlieb A, Schoenwald P, et al. Normal saline versus Lactated Ringer’s solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesth Analg. 2001;93:817–22. doi: 10.1097/00000539-200110000-00004.
    1. Hasman H, Cinar O, Uzun A, et al. A randomized clinical trial comparing the effect of rapidly infused crystalloids on acid-base status in dehydrated patients in the emergency department. Int J Med Sci. 2012;9:59–64. doi: 10.7150/ijms.9.59.
    1. Zunini GS, Rando KA, Cox RG. Fluid replacement in craniofacial pediatric surgery: normal saline or ringer’s lactate? J Craniofac Surg. 2011;22:1370–4. doi: 10.1097/SCS.0b013e31821c94db.
    1. Mahler SA, Conrad SA, Wang H, et al. Resuscitation with balanced electrolyte solution prevents hyperchloremic metabolic acidosis in patients with diabetic ketoacidosis. Am J Emerg Med. 2011;29:670–4. doi: 10.1016/j.ajem.2010.02.004.
    1. Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care. 2006;10:R22. doi: 10.1186/cc3987.
    1. Quilley CP, Lin YS, McGiff JC. Chloride anion concentration as a determinant of renal vascular responsiveness to vasoconstrictor agents. Br J Pharmacol. 1993;108:106–10. doi: 10.1111/j.1476-5381.1993.tb13447.x.
    1. Bullivant EM, Wilcox CS, Welch WJ. Intrarenal vasoconstriction during hyperchloremia: role of thromboxane. Am J Physiol. 1989;256:F152–7.
    1. Aksu U, Bezemer R, Yavuz B, Kandil A, Demirci C, Ince C. Balanced vs unbalanced crystalloid resuscitation in a near-fatal model of hemorrhagic shock and the effects on renal oxygenation, oxidative stress, and inflammation. Resuscitation. 2012;83:767–73. doi: 10.1016/j.resuscitation.2011.11.022.
    1. Tanaka M, Schmidlin O, Olson JL, Yi SL, Morris RC. Chloride-sensitive renal microangiopathy in the stroke-prone spontaneously hypertensive rat. Kidney International. 2001;59(3):1066–76.
    1. Yunos NM, Bellomo R, Story D, Kellum J. Bench-to-bedside review: chloride in critical illness. Crit Care. 2010;14:226. doi: 10.1186/cc9052.
    1. Yunos NM, Bellomo R, Glassford N, Sutcliffe H, Lam Q, Bailey M. Chloride-liberal vs. chloride-restrictive intravenous fluid administration and acute kidney injury: an extended analysis. Intensive Care Med. 2015;41:257–64. doi: 10.1007/s00134-014-3593-0.
    1. Krajewski ML, Raghunathan K, Paluszkiewicz SM, Schermer CR, Shaw AD. Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation. Br J Surg. 2015;102:24–36. doi: 10.1002/bjs.9651.
    1. Drummer C, Gerzer R, Heer M, et al. Effects of an acute saline infusion on fluid and electrolyte metabolism in humans. Am J Physiol. 1992;262:F744–54.

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