Story - Is chloride a poison?

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  • 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!