story - is chloride a poison?

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!