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Published in: Intensive Care Medicine 12/2014

Open Access 01-12-2014 | Original

Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS

Authors: Andrew D. Shaw, Karthik Raghunathan, Fred W. Peyerl, Sibyl H. Munson, Scott M. Paluszkiewicz, Carol R. Schermer

Published in: Intensive Care Medicine | Issue 12/2014

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Abstract

Purpose

Recent data suggest that both elevated serum chloride levels and volume overload may be harmful during fluid resuscitation. The purpose of this study was to examine the relationship between the intravenous chloride load and in-hospital mortality among patients with systemic inflammatory response syndrome (SIRS), with and without adjustment for the crystalloid volume administered.

Methods

We conducted a retrospective analysis of 109,836 patients ≥18 years old that met criteria for SIRS and received fluid resuscitation with crystalloids. We examined the association between changes in serum chloride concentration, the administered chloride load and fluid volume, and the ‘volume-adjusted chloride load’ and in-hospital mortality.

Results

In general, increases in the serum chloride concentration were associated with increased mortality. Mortality was lowest (3.7 %) among patients with minimal increases in serum chloride concentration (0–10 mmol/L) and when the total administered chloride load was low (3.5 % among patients receiving 100–200 mmol; P < 0.05 versus patients receiving ≥500 mmol). After controlling for crystalloid fluid volume, mortality was lowest (2.6 %) when the volume-adjusted chloride load was 105–115 mmol/L. With adjustment for severity of illness, the odds of mortality increased (1.094, 95 % CI 1.062, 1.127) with increasing volume-adjusted chloride load (≥105 mmol/L).

Conclusions

Among patients with SIRS, a fluid resuscitation strategy employing lower chloride loads was associated with lower in-hospital mortality. This association was independent of the total fluid volume administered and remained significant after adjustment for severity of illness, supporting the hypothesis that crystalloids with lower chloride content may be preferable for managing patients with SIRS.
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Literature
1.
go back to reference Lobo DN, Lewington AJ, Allison SP (2013) Basic concepts of fluid and electrolyte therapy. Bibliomed, Melsungen Lobo DN, Lewington AJ, Allison SP (2013) Basic concepts of fluid and electrolyte therapy. Bibliomed, Melsungen
2.
go back to reference Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011. II. Cardiovascular, infections, pneumonia and sepsis, critical care organization and outcome, education, ultrasonography, metabolism and coagulation. Intensive Care Med 38:345–358PubMedCentralPubMedCrossRef Antonelli M, Bonten M, Chastre J, Citerio G, Conti G, Curtis JR, De Backer D, Hedenstierna G, Joannidis M, Macrae D, Mancebo J, Maggiore SM, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2012) Year in review in Intensive Care Medicine 2011. II. Cardiovascular, infections, pneumonia and sepsis, critical care organization and outcome, education, ultrasonography, metabolism and coagulation. Intensive Care Med 38:345–358PubMedCentralPubMedCrossRef
5.
go back to reference Wan L, Bellomo R, May CN (2007) The effects of normal and hypertonic saline on regional blood flow and oxygen delivery. Anesth Analg 105:141–147PubMedCrossRef Wan L, Bellomo R, May CN (2007) The effects of normal and hypertonic saline on regional blood flow and oxygen delivery. Anesth Analg 105:141–147PubMedCrossRef
6.
go back to reference Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Raibbandari D, Taylor CB, Webb SA, CHEST Investigators, Australiand and New Zealand Intensive Care Society Clinical Trials Group (2012) Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 367:1901–1911PubMedCrossRef Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Raibbandari D, Taylor CB, Webb SA, CHEST Investigators, Australiand and New Zealand Intensive Care Society Clinical Trials Group (2012) Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 367:1901–1911PubMedCrossRef
7.
go back to reference SAFE Study Investigators, Finfer S, McEvoy S, Bellomo R, McArthur C, Myburgh JA, Norton R (2011) Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 37:86–96PubMedCrossRef SAFE Study Investigators, Finfer S, McEvoy S, Bellomo R, McArthur C, Myburgh JA, Norton R (2011) Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 37:86–96PubMedCrossRef
8.
go back to reference McFarlane C, Lee A (1994) A comparison of Plasmalyte 148 and 0.9 % saline for intra-operative fluid replacement. Anaesthesia 49:779–781PubMedCrossRef McFarlane C, Lee A (1994) A comparison of Plasmalyte 148 and 0.9 % saline for intra-operative fluid replacement. Anaesthesia 49:779–781PubMedCrossRef
9.
go back to reference Scheingraber S, Rehm M, Sehmisch C, Finsterer U (1999) Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 90:1265–1270PubMedCrossRef Scheingraber S, Rehm M, Sehmisch C, Finsterer U (1999) Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 90:1265–1270PubMedCrossRef
10.
go back to reference Reid F, Lobo DN, Williams RN, Rowlands BJ, Allison SP (2003) (Ab)normal saline and physiological Hartmann’s solution: a randomized double-blind crossover study. Clin Sci 104:17–24PubMedCrossRef Reid F, Lobo DN, Williams RN, Rowlands BJ, Allison SP (2003) (Ab)normal saline and physiological Hartmann’s solution: a randomized double-blind crossover study. Clin Sci 104:17–24PubMedCrossRef
11.
go back to reference Waters JH, Gottlieb A, Schoenwald P, Popovich MJ, Sprung J, Nelson DR (2001) Normal saline versus lactated Ringer’s solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesth Analg 93:817–822PubMedCrossRef Waters JH, Gottlieb A, Schoenwald P, Popovich MJ, Sprung J, Nelson DR (2001) Normal saline versus lactated Ringer’s solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesth Analg 93:817–822PubMedCrossRef
12.
go back to reference Williams EL, Hildebrand KL, McCormick SA, Bedel MJ (1999) The effect of intravenous lactated Ringer’s solution versus 0.9 % sodium chloride solution on serum osmolality in human volunteers. Anesth Analg 88:999–1003PubMed Williams EL, Hildebrand KL, McCormick SA, Bedel MJ (1999) The effect of intravenous lactated Ringer’s solution versus 0.9 % sodium chloride solution on serum osmolality in human volunteers. Anesth Analg 88:999–1003PubMed
13.
go back to reference 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 256:18–24PubMedCrossRef 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 256:18–24PubMedCrossRef
14.
go back to reference Cieza JA, Hinostroza J, Huapaya JA, Leon CP (2013) Sodium chloride 0.9 % versus lactated Ringer in the management of severely dehydrated patients with choleriform diarrhoea. J Infect Dev Ctries 7:528–532PubMedCrossRef Cieza JA, Hinostroza J, Huapaya JA, Leon CP (2013) Sodium chloride 0.9 % versus lactated Ringer in the management of severely dehydrated patients with choleriform diarrhoea. J Infect Dev Ctries 7:528–532PubMedCrossRef
15.
go back to reference Mahler SA, Conrad SA, Wang H, Arnold TC (2011) Resuscitation with balanced electrolyte solution prevents hyperchloremic metabolic acidosis in patients with diabetic ketoacidosis. Am J Emerg Med 29:670–674PubMedCrossRef Mahler SA, Conrad SA, Wang H, Arnold TC (2011) Resuscitation with balanced electrolyte solution prevents hyperchloremic metabolic acidosis in patients with diabetic ketoacidosis. Am J Emerg Med 29:670–674PubMedCrossRef
16.
go back to reference Berger MM, Pictet A, Revelly JP, Frascarolo P, Chiolero RL (2000) Impact of a bicarbonated saline solution on early resuscitation after major burns. Intensive Care Med 26:1382–1385PubMedCrossRef Berger MM, Pictet A, Revelly JP, Frascarolo P, Chiolero RL (2000) Impact of a bicarbonated saline solution on early resuscitation after major burns. Intensive Care Med 26:1382–1385PubMedCrossRef
17.
go back to reference Yunos NM, Kim IB, Bellomo R, Bailey M, Ho L, Story D, Gutteridge GA, Hart GK (2011) The biochemical effects of restricting chloride-rich fluids in intensive care. Crit Care Med 39:2419–2424PubMedCrossRef Yunos NM, Kim IB, Bellomo R, Bailey M, Ho L, Story D, Gutteridge GA, Hart GK (2011) The biochemical effects of restricting chloride-rich fluids in intensive care. Crit Care Med 39:2419–2424PubMedCrossRef
18.
go back to reference Raghunathan K, Shaw AD, Nathanson B, Stürmer T, Brookhart A, Stefan MS, Setoguchi S, Beadles C, Lindenauer PK (2014) Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med 42:1585–1591PubMedCrossRef Raghunathan K, Shaw AD, Nathanson B, Stürmer T, Brookhart A, Stefan MS, Setoguchi S, Beadles C, Lindenauer PK (2014) Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med 42:1585–1591PubMedCrossRef
19.
go back to reference Cho YS, Lim H, Kim SH (2007) Comparison of lactated Ringer’s solution and 0.9 % saline in the treatment of rhabdomyolysis induced by doxylamine intoxication. Emerg Med J 24:276–280PubMedCentralPubMedCrossRef Cho YS, Lim H, Kim SH (2007) Comparison of lactated Ringer’s solution and 0.9 % saline in the treatment of rhabdomyolysis induced by doxylamine intoxication. Emerg Med J 24:276–280PubMedCentralPubMedCrossRef
20.
go back to reference 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 117:412–421PubMedCrossRef 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 117:412–421PubMedCrossRef
21.
go back to reference Boniatti MM, Cardoso PR, Castilho RK, Vieira SR (2011) Is hyperchloremia associated with mortality in critically ill patients? A prospective cohort study. J Crit Care 26:175–179PubMedCrossRef Boniatti MM, Cardoso PR, Castilho RK, Vieira SR (2011) Is hyperchloremia associated with mortality in critically ill patients? A prospective cohort study. J Crit Care 26:175–179PubMedCrossRef
22.
go back to reference Mahajan V, Sajan SS, Sharma A, Kaur J (2012) Ringers lactate versus normal saline for children with acute diarrhea and severe dehydration- a double blind randomized controlled trial. Indian Pediatr 49:963–968PubMedCrossRef Mahajan V, Sajan SS, Sharma A, Kaur J (2012) Ringers lactate versus normal saline for children with acute diarrhea and severe dehydration- a double blind randomized controlled trial. Indian Pediatr 49:963–968PubMedCrossRef
23.
go back to reference Shaw AD, Bagshaw SM, Goldstein SL, Scherer LA, Duan M, Schermer CR, Kellum JA (2012) Major complications, mortality, and resource utilization after open abdominal surgery: 0.9 % saline compared to Plasma-Lyte. Ann Surg 255:821–829PubMedCrossRef Shaw AD, Bagshaw SM, Goldstein SL, Scherer LA, Duan M, Schermer CR, Kellum JA (2012) Major complications, mortality, and resource utilization after open abdominal surgery: 0.9 % saline compared to Plasma-Lyte. Ann Surg 255:821–829PubMedCrossRef
24.
go back to reference Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M (2012) Association between a chloride-liberal versus chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 308:1566–1572PubMedCrossRef Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M (2012) Association between a chloride-liberal versus chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 308:1566–1572PubMedCrossRef
25.
go back to reference Young JB, Utter GH, Schermer CR, Galante JM, Phan HH, Yang Y, Anderson BA, Scherer LA (2013) Saline versus Plasma-Lyte A in initial resuscitation of trauma patients: a randomized trial. Ann Surg 259:255–262CrossRef Young JB, Utter GH, Schermer CR, Galante JM, Phan HH, Yang Y, Anderson BA, Scherer LA (2013) Saline versus Plasma-Lyte A in initial resuscitation of trauma patients: a randomized trial. Ann Surg 259:255–262CrossRef
26.
go back to reference Al-Khafaji A, Webb AR (2004) Fluid resuscitation. Cont Ed Anaesth Crit Care Pain 4:127–131CrossRef Al-Khafaji A, Webb AR (2004) Fluid resuscitation. Cont Ed Anaesth Crit Care Pain 4:127–131CrossRef
27.
go back to reference Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, Saunders LD, Beck CA, Feasby TE, Ghali WA (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130–1139PubMedCrossRef Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, Saunders LD, Beck CA, Feasby TE, Ghali WA (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130–1139PubMedCrossRef
28.
go back to reference van Walraven C, Austin PC, Jennings A, Quan H, Forster AJ (2009) A modification of the Elixhauser comorbidity measures into a point system for hospital death using administrative data. Med Care 47:626–633PubMedCrossRef van Walraven C, Austin PC, Jennings A, Quan H, Forster AJ (2009) A modification of the Elixhauser comorbidity measures into a point system for hospital death using administrative data. Med Care 47:626–633PubMedCrossRef
29.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMedCrossRef Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMedCrossRef
30.
go back to reference Kratz A, Ferraro M, Sluss PM, Laewandrowski KB (2004) Laboratory reference values. N Engl J Med 351:1548–1563PubMedCrossRef Kratz A, Ferraro M, Sluss PM, Laewandrowski KB (2004) Laboratory reference values. N Engl J Med 351:1548–1563PubMedCrossRef
31.
go back to reference National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Weidemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AFJ, Hite RD, Harabin AL (2006) Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 354:2564–2575CrossRef National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Weidemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AFJ, Hite RD, Harabin AL (2006) Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 354:2564–2575CrossRef
32.
go back to reference Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lidorff-Larsen K, Rasmussen MS, Lanng C, Wallin L, Iversen LH, Gramkow CS, Okholm M, Blemmer T, Svendsen PE, Rottensten HH, Thage B, Riis J, Jeppesen IS, Teilum D, Christensen AM, Graungaard B, Pott F (2003) Danish study group on perioperative fluid therapy. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 238:641–648PubMedCentralPubMedCrossRef Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lidorff-Larsen K, Rasmussen MS, Lanng C, Wallin L, Iversen LH, Gramkow CS, Okholm M, Blemmer T, Svendsen PE, Rottensten HH, Thage B, Riis J, Jeppesen IS, Teilum D, Christensen AM, Graungaard B, Pott F (2003) Danish study group on perioperative fluid therapy. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 238:641–648PubMedCentralPubMedCrossRef
33.
go back to reference Stewart RM, Park PK, Hunt JP, McIntyre RCJ, McCarthy J, Zarzabal LA, Michalek JE, National Institutes of Health National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network (2009) Less is more: improved outcomes in surgical patients with conservative fluid administration and central venous catheter monitoring. J Am Coll Surg 208:725–735PubMedCrossRef Stewart RM, Park PK, Hunt JP, McIntyre RCJ, McCarthy J, Zarzabal LA, Michalek JE, National Institutes of Health National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network (2009) Less is more: improved outcomes in surgical patients with conservative fluid administration and central venous catheter monitoring. J Am Coll Surg 208:725–735PubMedCrossRef
34.
go back to reference Van de Louw A, Shaffer C, Schaefer E (2014) Early intensive care unit-acquired hypernatremia in severe sepsis patients receiving 0.9 % saline fluid resuscitation. Acta Anaesthesiol Scand 58:1007–1014. doi:10.1111/aas.12368 CrossRef Van de Louw A, Shaffer C, Schaefer E (2014) Early intensive care unit-acquired hypernatremia in severe sepsis patients receiving 0.9 % saline fluid resuscitation. Acta Anaesthesiol Scand 58:1007–1014. doi:10.​1111/​aas.​12368 CrossRef
35.
go back to reference Wilkes NJ, Woolf R, Mutch M, Mallett SV, Peachey T, Stephens R, Mythen MG (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 93:811–816PubMedCrossRef Wilkes NJ, Woolf R, Mutch M, Mallett SV, Peachey T, Stephens R, Mythen MG (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 93:811–816PubMedCrossRef
36.
go back to reference Kellum JA, Song M, Almasri E (2006) Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest 130:962–967PubMedCrossRef Kellum JA, Song M, Almasri E (2006) Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest 130:962–967PubMedCrossRef
37.
go back to reference Kellum JA, Song M, Venkataraman R (2004) Effects of hyperchloremic acidosis on hemodynamics and circulating inflammatory molecules in experimental sepsis. Chest 125:243–248PubMedCrossRef Kellum JA, Song M, Venkataraman R (2004) Effects of hyperchloremic acidosis on hemodynamics and circulating inflammatory molecules in experimental sepsis. Chest 125:243–248PubMedCrossRef
38.
go back to reference Cambier C, Detry B, Beerens D, Florquin S, Ansay M, Frans A, Clerbaux T, Gustin P (1998) Effects of hyperchloremia on blood oxygen binding in healthy calves. J Appl Physiol 85:1267–1272PubMed Cambier C, Detry B, Beerens D, Florquin S, Ansay M, Frans A, Clerbaux T, Gustin P (1998) Effects of hyperchloremia on blood oxygen binding in healthy calves. J Appl Physiol 85:1267–1272PubMed
39.
go back to reference Pedoto A, Caruso JE, Nandi J, Oler A, Hoffmann SP, Tassiopoulos AK, McGraw DJ, Camporesi EM, Hakim TS (1999) Acidosis stimulates nitric oxide production and lung damage in rats. Am J Respir Crit Care Med 195:397–402CrossRef Pedoto A, Caruso JE, Nandi J, Oler A, Hoffmann SP, Tassiopoulos AK, McGraw DJ, Camporesi EM, Hakim TS (1999) Acidosis stimulates nitric oxide production and lung damage in rats. Am J Respir Crit Care Med 195:397–402CrossRef
Metadata
Title
Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS
Authors
Andrew D. Shaw
Karthik Raghunathan
Fred W. Peyerl
Sibyl H. Munson
Scott M. Paluszkiewicz
Carol R. Schermer
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 12/2014
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-014-3505-3

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