Advanced Acid/Base on the PICU David Schmidt SUMMA / Clinician Scientists Training Program

Stewart 101

Definitions

•  Ions, Kations, Anions •  Strong electrolytes and weak electrolytes •  Acid •  pH

Governing principles •  Law of Electrical Neutrality •  Law of Mass Conservation •  Law of Mass Action

Acid Base Chemistry

H2O! "# H + +OH $

Kd = [H+][OH $ ]H2O

Kd  =  the  dissocia-on  constant  Dependent  on  temp,  molecular  structure  

Strong vs weak electrolytes (e.g. acids)

KA =[H + ][A! ][HA]

HA! "# H + + A$

HA  =  an  acid  H+  =  a  hydrogen  ion  that  lost  an  electron  A-­‐  =  a  deprotonated  acid  Ka  =  the  dissocia-on  constant  for  the  acid  (a)  

NaCl(s) H 2O! "!! Na+ +Cl#(aq)S  =  solid  Aq  =  aqueous  

Proteins = acids and bases

Alberts,  NCBI  Bookshelf  

Albumin  (weak  acid)  IgA  (weak  acid)  IgG  (weak  ka-on)  

Stewart’s Message: [H+] and [HCO3

-] are dependent

Strong Ion Difference (SID)

•  Completely dissociated ions at body pH 1 organic acids with a pKa <4 (’strong acids’) 2 strong electrolytes

•  Q: Law of electrical neutrality?

•  Unmeasured anions: e.g. lactate, ketones, SO42-

•  Unmeasured kations: e.g. lithium, Mg, Ca

pKa  =  acid  dissocia-on  constant  

SID = [strongkations]![stronganions]"[Na+ ]+[K + ]![Cl! ]

Weak non-volatile acids

HA! "# H + + A$

ATOT = HA+ A!

Meet the Stewart players

•  Strong ion difference •  Non-volatile weak acids •  pCO2

These determine •  H+ •  HCO3- by •  Law of Electrical Neutrality •  Law of Mass Conservation •  Law of Mass Action

The formulas that govern acid base status

HA! "# H + + A$

SID+[H + ]![HCO3! ]![CO3

2! ]![A! ]![OH ! ]= 0

For  each  acid  (including  water)  

CO32-­‐  =  carbonate    

A-­‐  =  total  anionic  weak  non-­‐vola-le  acids  

CO2 +H2OCA! "# H2CO3! "# H + +HCO3

$

SID & pH

PCO2  is  held  constant  at  40  mm  Hg.  ATOT  20  mEq/L  

Morgan  TJ.  Clin  Biochem  Rev.  2009  May  13;30(2):41–54.    

SID & pH

PCO2  is  held  constant  at  40  mm  Hg.  SID  =  42mEq/L  

Morgan  TJ.  Clin  Biochem  Rev.  2009  May  13;30(2):41–54.    

Summary

•  Strong ion difference •  Non-volatile weak acids •  pCO2

These determine •  H+ •  HCO3-

Stewart Acid Base Physiology

Stewart Acid Base Status

www.acidbase.org    Paul  Elbers,  MD  ©  

Stewart Acid Base Status

www.acidbase.org    Paul  Elbers,  MD  ©  

Stewart Acid Base Status

www.acidbase.org    Paul  Elbers,  MD  ©  

Hyperchloremic SID acidosis

•  0.9% saline •  Rapid infusion

–  reduces SID (metabolic acidosis) –  reduces ATOT (metabolic alkalosis) SID change predominates over ATOT

•  SID changes may also be induced by low Cl- fluids

–  0.45% saline –  mannitol –  5% dextrose

Morgan.  Clin  Biochem  Rev  2009  

Fluids & Stewart Acid Base

•  The balanced crystalloid SID lower than plasma (acidotic) to counteract ATOT dilutional alkalosis

•  Experimentally: SID 24 mEq/L

•  E.g. Ringer’s lactate (SID=28), Hartmann’s (SID=27)

Morgan  TJ.  Crit  Care.  2005  Apr;9(2):204–11.    

Calculating the Strong ion gap

•  A- = albumin * constant + phosphate * constant •  SID = Na + K + Mg + Ca – Cl – A- •  SIG = SID – lactate – bicarb

•  Anion gap = Na + K – Cl – bicarb – lactate •  AGc = AG / (2.5x reference albumin – pt albumin)

5 Minutes of ICU Acid Base

Acidosis •  Sympathoadrenal activation •  Right-shift Hb dissociation

curve (+Haldane effect) •  Hyperkalemia (shift) •  SMC Cathecolamine

responsiveness decreases

Alkalosis •  Left-shift Hb dissociation

curve •  Hypocalcemia (plasma

protein binding) - cardiac - neuromuscular

•  Reduced cerebral blood flow

•  Increased peripheral vascular resistance

•  Coronary vasospasm •  Bronchoconstriction

The physiological effects of pH changes

Morgan  &  Mikhail’s  Clinical  Anesthesiology  5e  (AccessMedicine)  

Prognostic value

•  Metabolic acidosis predicts mortality, lactate > other causes

•  Increased anion gap acidosis predicts morbidity & mortality

•  Metabolic acidosis = 2x mortality risk [adults] •  Hyperchloremic acidosis associated with ICU stay, renal

dysfunction, mortality [adults]

Lucking  SE,  Maffei  FA,  Tamburro  RF.  Pediatric  Cri-cal  Care  Study  Guide.  Springer;  2012.    Gunnerson  KJ,  Saul  M,  He  S,  Kellum  JA.  Crit  Care.  2006  Feb;10(1):R22.    McCluskey  SA,  Karou-  K,  Wijeysundera  D,  Minkovich  L,  Tait  G,  Beadle  WS.  Anesthesia  &  Analgesia.  2013  Nov  6.    

Balasubramanyan N, Havens PL, Hoffman GM. Unmeasured anions identified by the Fencl-Stewart method predict mortality better than base excess, anion gap, and lactate in patients in the pediatric intensive care unit. Critical Care Medicine. 1999 Aug 1;27(8):1577. -  n=255, retrospective cohort -  inclusion: PICU + acid base status measured -  ATOT determination superior to AG/BE/lactate for predicting

mortality -  Discussion: Possibly same with AGc ? Multiple

measurements, error

AGc  =  albumin  corrected  anion  gap  

Dubin A, Menises MAM, Masevicius FD, Moseinco MC, Kutscherauer DO, Ventrice E, et al. Comparison of three different methods of evaluation of metabolic acid-base disorders*. Critical Care Medicine. 2007 May;35(5):1264–70 -  n=953, prospective observational cohort -  inclusion: ICU -  Stewart detected metabolic alterations in 14% of patients

with normal HCO3- / BE

-  SIG and AGc are correlated R2=.97 -  Stewart and AGc perfomed as good in detecting metabolic

acidosis, and were superior to the traditional approach

SIG  =  strong  ion  gap  AGc  =  albumin  corrected  anion  gap  

No Consequence for Clinical Practice ?

•  Traditional approach is more intuitive and well known, supported by robust experience and evidence

•  Provision of clear epidemiological evidence for Steward approached Dx / Tx is not given yet (sample size of research…)

Rastegar  A.  Clinical  Journal  of  the  American  Society  of  Nephrology.  2009  Jul;4(7):1267–74.    

5 Minutes of Periop Cardio Acid/Base

Murray DM, Olhsson V, Fraser JI. Defining acidosis in postoperative cardiac patients using Stewart’s method of strong ion difference*. Pediatric Critical Care Medicine. 2004 May;5(3):240–5. -  n=44, prospective -  inclusion: PICU post-cardiac Sx -  Daily acid-base status -  Metabolic acidosis: lactate, UA, SID -  CPB results in more SID acidosis -  Stewart detection of acids is superior: 13% of normal BE

samples had UA. However, AGc almost as good by ROC AUC

UA  =  unmeasured  acids,  part  of  ATOT  AGc  =  albumin  corrected  anion  gap  ROC  AUC  =  receiver  operated  characteris-cs  area  under  the  curve  

Hatherill M. Hyperchloraemic metabolic acidosis following open cardiac surgery. Archives of Disease in Childhood. 2005 Dec 1;90(12):1288–92. -  n=97, prospective -  inclusion: PICU post-cardiac Sx -  Metabolic acidosis: lactate, UA, SID (less SID than Murray) -  No association with CPB time, ventilation, but complexity of

surgery -  No association with PICU length of stay -  Chloride from CPB priming / renal hypoperfusion?

Durward A, Tibby SM, Skellett S, Austin C, Anderson D, Murdoch IA. The strong ion gap predicts mortality in children following cardiopulmonary bypass surgery*. Pediatric Critical Care Medicine. 2005 May;6(3):281–5. -  n=85, prospective -  inclusion: PICU post-cardiac Sx -  41% (admission) and 52% (24h) raised strong ion gap -  SIG and lactate increased with surgical complexity, but not

length of CPB or aortic cross-clamping

-  5 deaths, 4 of which persistent SIG, 2 lactaemia

Mann C, Held U, Herzog S, Baenziger O. Impact of normal saline infusion on postoperative metabolic acidosis. Pediatric Anesthesia. 2009 Nov;19(11):1070–7. -  n=119, prospective -  inclusion: PICU post-cardiac Sx -  Intervals of Saline infusion / no saline infusion -  Saline infusion post-op is associated with metabolic acidosis -  This can be calculated by chloride effect of SID

WKZ PICU: 2 patient analyses

•  pH, bicarbonate, PCO2, PO2, lactate, urea, ketones, Hb/Ht, Na, K, phosphate, albumin, glucose, osmolality

•  Pt A, pH 7.27 – mixed acidosis: low SID (high Cl), increased ATOT (explained by lactate and ketones), phosphate effect (high P). Alongside hypoalbuminemia (metabolic alkalosis).

•  Pt B, pH 7.23 – low SID acidosis (high Cl), phosphate effect (high P)

Discussion Translation WKZ Practice

David Schmidt d.e.schmidt@students.uu.nl

Figge-Fencl Stewart Modification

•  Albumin charge is approximately linear over pH 6.9-7.9 •  Can thus be calculated

Stewart modification

•  Story DA. Strong ions, weak acids and base excess: a simplified Fencl-Stewart approach to clinical acid-base disorders. British Journal of Anaesthesia. 2004 Jan 1;92(1):54–60.

The Scheingraber Gynecology Trial

•  Two groups of 12 patients undergoing major intraabdominal gynecologic surgery, saline or lactated Ringer at 30ml / kg BW/h

•  Saline caused metabolic acidosis with hyperchloremia and SID decrease

•  Infusion of both fluids results in hypoproteinemia and decreased anion gap

•  Authors consider condition benign, but argue for treatment

•  Complication of respiratory acidosis by opiate analgesics ?

Scheingraber  et  al.  Anesthesiology.  1999  May;90(5):1265–70.    Prough  DS.  Anesthesiology.  1999  May;90(5):1247–9.    

Further Repots Saline & Metabolic Acidosis

•  Stephens RCM, Mythen MG. Saline-Based Fluids Can Cause a Significant Acidosis That May Be Clinically Relevant. Critical Care Medicine. 2000 Sep 1;28(9):3375.

•  Prough DS, Bidani A. Hyperchloremic metabolic acidosis is a predictable consequence of intraoperative infusion of 0.9% saline. Anesthesiology. 1999 May;90(5):1247–9.

•  Dorje P, Adhikary G, Tempe DK. Avoiding latrogenic hyperchloremic acidosis--call for a new crystalloid fluid. Anesthesiology. 2000 Feb;92(2):625–6.

•  Constable PD. Hyperchloremic Acidosis: The Classic Example of Strong Ion Acidosis. Anesthesia & Analgesia. 2003 Apr;:919–22.

•  Eisenhut M. Causes and effects of hyperchloremic acidosis. Crit Care. 2006;10(3):413; authorreply413.