story - is chloride a poison?
TRANSCRIPT
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Dave StoryMBBS, MD, BMedSci, FANZCA
Professor and Chair of AnaesthesiaHead of Anaesthesia, Perioperative and Pain Medicine Unit (APPMU)
Melbourne Medical SchoolThe University of Melbourne
Is Chloride a Poison?
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Conflict of Interest
I think I have no conflict of interest associated with this presentation
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Problems of (saline) chloride
• Metabolic acidosis • Reduced urine output• Abdominal pain• ? Gut hypoperfusion• Altered mental state• Worse survival animal studies
Wilkes, Clin Sci, 2003
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Chloride is an acidArrhenius, 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
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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)
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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
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Acidosis Mechanism?
–Dilution of bicarbonate ?– Strong-ion acidosis?
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Dilution?
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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, 2002Miller’s Anesthesia
H+ / HCO3
CO2
SID
Weak acids
Kw + Ka
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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
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Sodium-Chloride difference
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Human studies
18 volunteers, 50 ml/Kg over 1 hr, crossoverPrimary endpoint osmolality NS HartEnd mOsm/L 289 285End pH 7.38 7.44End Na+, mmol/L 141 139First U, min 106 75Subjective mental 13/18 0/18Abdo pain 10/18 1/18
Abdo pain assoc with pHWilliams, Anesth Analg 1999
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Anesthesiology 2013
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Cognitive Change?
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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
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ICU kidneys
JAMA, 2012
ProspectiveBefore and After“Great Fluid Shift”
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Annals of Surgery 2012
3:1 propensity-matched926 Plasmalyte 2,778 Saline
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Chloride and Surgery
Anaesthesia and Analgesia, 2013
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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
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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
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Are some are more balanced than others?
Postoperative Plasmalyte Hartmann’s pSBE; mmol/L -0.9 (2.3) -1.7 (2.2) 0.17Lactate; mmol/L 1.9 (1.13) 2.9 (1.76) 0.02pH 7.34 (0.05) 7.33 (0.05) 0.44Na+; mmol/L 139 (2.2) 138 (2.9) 0.09Cl; 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
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Small furry animals
Healey, J Trauma, 1998
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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
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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
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Thanks!
Of course I use saline!