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. Conflict of Interest
I think I have no conflict of interest associated with this
presentation

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. 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. 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. 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. Acidosis Mechanism?
–Dilution of bicarbonate ?
–Strong-ion acidosis?

8. Dilution?

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. 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. Sodium-Chloride difference

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. Anesthesiology 2013

14. Cognitive Change?

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. ICU kidneys
JAMA, 2012
Prospective
Before and After
“Great Fluid Shift”

17. Annals of Surgery 2012
3:1 propensity-matched
926 Plasmalyte
2,778 Saline

18. Chloride and Surgery
Anaesthesia and Analgesia, 2013

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. 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. 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. Small furry animals
Healey, J Trauma, 1998

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. 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. Thanks!
Of course
I use saline!