Dave Story
MBBS, MD, BMedSci, FANZCA
Professor and Chair of Anaesthesia
Head of Anaesthesia, Perioperative and Pain Medici...
Conflict of Interest
I think I have no conflict of interest associated with this
presentation
Problems of (saline) chloride
• Metabolic acidosis
• Reduced urine output
• Abdominal pain
• ? Gut hypoperfusion
• Altered...
Chloride is an acid
Arrhenius, 1870s
Swedish Chemist
Electrolytic theory for ions
(Almost failed PhD but later Nobel Prize...
IV fluids
N. Saline Hartmann’s Plasmalyte
Osmolality 308 274 294
Sodium 154 129 140
Chloride 154 109 98
Potassium 0 5 5
Ca...
Iatrogenic hyperchloraemic
metabolic acidosis
• Influential publication
– Major gynaecologic surgery
– Saline vs Hartmann’...
Acidosis Mechanism?
–Dilution of bicarbonate ?
–Strong-ion acidosis?
Dilution?
Strong ion acidosis- Stewart
Bicarbonate and hydrogen ions dependent factors
Bicarbonate is a marker not a mechanism
Base-...
In acid-base: hyperchloraemia is relative
26 ICU patients traditional hyperchloremic acidosis:
base-excess < -2 mmol/L
ani...
Sodium-Chloride difference
Human studies
18 volunteers, 50 ml/Kg over 1 hr, crossover
Primary endpoint osmolality
NS Hart
End mOsm/L 289 285
End pH 7...
Anesthesiology 2013
Cognitive Change?
Renal Effects
Dog Kidneys
• NaCl = 15% decrease RBF
• Na Acetate = 25% increase in RBF
Wilcox, J Clin Invest, 1983
Humans:...
ICU kidneys
JAMA, 2012
Prospective
Before and After
“Great Fluid Shift”
Annals of Surgery 2012
3:1 propensity-matched
926 Plasmalyte
2,778 Saline
Chloride and Surgery
Anaesthesia and Analgesia, 2013
Chlorides ain’t chlorides
Reference range for central laboratory assays:
97 to 107 mmol/l
OR
100 to 110 mmol/l
Central lab...
While all solutions are balanced,
are some more balanced than others?
Association of Plasmalyte-148 or Hartmann’s
with met...
Are some are more balanced than others?
Postoperative
Plasmalyte Hartmann’s p
SBE; mmol/L -0.9 (2.3) -1.7 (2.2) 0.17
Lacta...
Small furry animals
Healey, J Trauma, 1998
Kellum and the septic rats
18 hours
-ceacal ligation and puncture
10 ml/kg then 5 ml/kg for 4 hrs
Zhou, Crit Care Med, 201...
Conclusions: problems of (saline) chloride
• Metabolic acidosis- SID
• Reduced urine output – Poisons kidneys
• Gut hypope...
Thanks!
Of course
I use saline!
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Story - Is chloride a poison?

  1. 1. Dave Story MBBS, MD, BMedSci, FANZCA Professor and Chair of Anaesthesia Head of Anaesthesia, Perioperative and Pain Medicine Unit (APPMU) Melbourne Medical School The University of Melbourne Is Chloride a Poison?
  2. 2. Conflict of Interest I think I have no conflict of interest associated with this presentation
  3. 3. Problems of (saline) chloride • Metabolic acidosis • Reduced urine output • Abdominal pain • ? Gut hypoperfusion • Altered mental state • Worse survival animal studies Wilkes, Clin Sci, 2003
  4. 4. Chloride is an acid Arrhenius, 1870s Swedish Chemist Electrolytic theory for ions (Almost failed PhD but later Nobel Prize) General definition of acid: substance when added to solution increases H+ concentration Predates Bronsted-Lowry: H+ donor
  5. 5. IV fluids N. Saline Hartmann’s Plasmalyte Osmolality 308 274 294 Sodium 154 129 140 Chloride 154 109 98 Potassium 0 5 5 Calcium 0 2.5 3 Magnesium 0 0 1.5 Other 0 29(lactate) 27(acetate) 23(gluconate)
  6. 6. Iatrogenic hyperchloraemic metabolic acidosis • Influential publication – Major gynaecologic surgery – Saline vs Hartmann’s – 30ml/kg/hr over 2 hours • Saline: pH 7.28, BE -6.5mmol/L • Hartmann’s: pH 7.40, BE -0.5 mmol/L Scheingraber, Anesthesiology 1999
  7. 7. Acidosis Mechanism? –Dilution of bicarbonate ? –Strong-ion acidosis?
  8. 8. Dilution?
  9. 9. Strong ion acidosis- Stewart Bicarbonate and hydrogen ions dependent factors Bicarbonate is a marker not a mechanism Base-excess is a marker Sirker et al. Anaesthesia, 2002 Miller’s Anesthesia H+ / HCO3 CO2 SID Weak acids Kw + Ka
  10. 10. In acid-base: hyperchloraemia is relative 26 ICU patients traditional hyperchloremic acidosis: base-excess < -2 mmol/L anion gap < 17 mmol/L Story, Anesth Analg, 2006
  11. 11. Sodium-Chloride difference
  12. 12. Human studies 18 volunteers, 50 ml/Kg over 1 hr, crossover Primary endpoint osmolality NS Hart End mOsm/L 289 285 End pH 7.38 7.44 End Na+, mmol/L 141 139 First U, min 106 75 Subjective mental 13/18 0/18 Abdo pain 10/18 1/18 Abdo pain assoc with pH Williams, Anesth Analg 1999
  13. 13. Anesthesiology 2013
  14. 14. Cognitive Change?
  15. 15. Renal Effects Dog Kidneys • NaCl = 15% decrease RBF • Na Acetate = 25% increase in RBF Wilcox, J Clin Invest, 1983 Humans: MRI renal flow velocity • Saline: 13 % decrease in velocity • Plasmalyte: no change renal velocity Chowdhury, Ann Surg, 2012
  16. 16. ICU kidneys JAMA, 2012 Prospective Before and After “Great Fluid Shift”
  17. 17. Annals of Surgery 2012 3:1 propensity-matched 926 Plasmalyte 2,778 Saline
  18. 18. Chloride and Surgery Anaesthesia and Analgesia, 2013
  19. 19. Chlorides ain’t chlorides Reference range for central laboratory assays: 97 to 107 mmol/l OR 100 to 110 mmol/l Central laboratory changed from Hitachi to Beckman, Paired samples: Bias 2.0 mmol/l (95% LOA, –1.7 to 5.6 mmol/l) This will affect derived variables eg anion gap, SID
  20. 20. While all solutions are balanced, are some more balanced than others? Association of Plasmalyte-148 or Hartmann’s with metabolic acidosis and complications after liver resection: • Multicenter: 4 hospitals • RCT • Non-inferiority trial, • SBE NOT > 2 mmol/L more negative • Blinded • Liver resection (usually CA) • Intraoperative Hartmann’s or Plasmalyte
  21. 21. Are some are more balanced than others? Postoperative Plasmalyte Hartmann’s p SBE; mmol/L -0.9 (2.3) -1.7 (2.2) 0.17 Lactate; mmol/L 1.9 (1.13) 2.9 (1.76) 0.02 pH 7.34 (0.05) 7.33 (0.05) 0.44 Na+; mmol/L 139 (2.2) 138 (2.9) 0.09 Cl; mmol/L 106.3 (2.4) 108.1 (3.0) 0.01 Patient Outcomes No of patients with a complication 6 (20%) 17 (56%) 0.007 Length of Hospital stay days (median) 5.9 7.8 0.04 Hospital death within 30 days of surgery 0 2 (7%) 0.49
  22. 22. Small furry animals Healey, J Trauma, 1998
  23. 23. Kellum and the septic rats 18 hours -ceacal ligation and puncture 10 ml/kg then 5 ml/kg for 4 hrs Zhou, Crit Care Med, 2014 n = 30 + 30
  24. 24. Conclusions: problems of (saline) chloride • Metabolic acidosis- SID • Reduced urine output – Poisons kidneys • Gut hypoperfusion??? • Altered mental state - unlikely • Worse survival animal studies – And human studies Wilkes, Clin Sci, 2003 SPLIT: RCT Saline vs Plasmalyte Major abdominal surgery
  25. 25. Thanks! Of course I use saline!
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