story - is chloride a poison?
TRANSCRIPT
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?
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 mental state• Worse survival animal studies
Wilkes, Clin Sci, 2003
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
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)
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
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-excess is a marker
Sirker et al. Anaesthesia, 2002Miller’s Anesthesia
H+ / HCO3
CO2
SID
Weak acids
Kw + Ka
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
Sodium-Chloride difference
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
Anesthesiology 2013
Cognitive Change?
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
ICU kidneys
JAMA, 2012
ProspectiveBefore and After“Great Fluid Shift”
Annals of Surgery 2012
3:1 propensity-matched926 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 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
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
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
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, 2014
n = 30 + 30
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
Thanks!
Of course I use saline!