ketoacidosis - a short overview of pathophysiology ... · ketoacidosis - a short overview of...

ketoacidosis - a short overview of pathophysiology,presentations and treatment

2015 Critical Care Symposium Manchester

(ICU, Herlev Hospital, Copenhagen) ketoacidosis Critical Care Symposium 2015 1 / 76


Herlev Hospital, Copenhagen


Herlev Hospital, Copenhagen

Outline1 pathophysiology

ketoacid generation2 clinical presentations

acetonaemic vomitingdiabetic ketoacidosis, typical coursetherapeutic controversiesdiabetic ketoacidosis, complicationsalcoholic ketoacidosis

3 casesacid-base analysis at the bedsidea 16 year old girlalcohol abusemetformin

4 good byeconflicts of interest




















pathophysiology ketoacid generation








pathophysiology 0


ketone bodies

source: http://en.wikipedia.org/wiki/Ketosis


pathophysiology 1


a healthy cell


pathophysiology 2


a healthy cell


pathophysiology 3


a starving cell


pathophysiology 4


a starving cell


pathophysiology 5


a cell without insulin


pathophysiology 6


a cell without insulin


pathophysiology 7


ketoacid blood levels

source: http://en.wikipedia.org/wiki/Ketosis

clinical presentations acetonaemic vomiting








acetonaemic vomiting 1


when your small child simply will not stop vomiting

Brandel, Das acetonamische Erbrechen in der PraxisMunchMedWochenschr 1968, 110(45) 2659-60





In a susceptible child anything from a common respiratory infection oreven psychological alterations to genetic metabolic illnesses can

initiate a vicious cycle of vomiting, starvation metabolism, consequentketoacidosis and more vomiting.

In modern terminology this is better known as “cyclic vomiting”.





Treatment is simple - give glucose and fluids!

clinical presentations diabetic ketoacidosis, typical course








diabetic ketoacidosis 1


a young person in severe distress, the common presentation

- polyuria, polydipsia- general weakness

- nausea and vomiting- abdominal pain





- polyuria, polydipsia- general weakness

- nausea and vomiting- abdominal pain





- severe dehydration- circulatory compromise

- somnolence, stupor, coma- acetone smell

- Kußmaul breathing- pseudoperitonitis

- signs and symptoms pointing to another illness triggeringketoacidosis, especially an infection





- severe dehydration- circulatory compromise

- somnolence, stupor, coma- acetone smell

- Kußmaul breathing- pseudoperitonitis

- signs and symptoms pointing to another illness triggeringketoacidosis, especially an infection





- hyperglycaemia- fluid loss of 10% of body weight

- severe losses of Na+ and K+, 500 to 1000mmol- hyperosmolarity: 2 ∗ ([Na+] + [K+]) + [glucose] + [urea]

- severe metabolic, “unknown anion” acidosis- initially often low serum-Na and high serum-K values

- moderate leukocytosis





- hyperglycaemia- fluid loss of 10% of body weight

- severe losses of Na+ and K+, 500 to 1000mmol- hyperosmolarity: 2 ∗ ([Na+] + [K+]) + [glucose] + [urea]

- severe metabolic, “unknown anion” acidosis- initially often low serum-Na and high serum-K values

- moderate leukocytosis




typical treatment recommendations

- as ever: ABC - if necessary, secure the airway!- replace fluid losses, typically 2l isotonic crystalloid during the first two

hours- be prepared to replace [K+]-losses, eventually [Mg2+]

- continuous insulinadministration- shift to half strength electrolyte fluids and glucose administraton with

serum-glucose falling to below 15mmol/l




typical treatment recommendations

- as ever: ABC - if necessary, secure the airway!- replace fluid losses, typically 2l isotonic crystalloid during the first two

hours- be prepared to replace [K+]-losses, eventually [Mg2+]

- continuous insulinadministration- shift to half strength electrolyte fluids and glucose administraton with

serum-glucose falling to below 15mmol/l




a typical course in a young adult




a typical course in a young adult




DKA cases during one year at Central Hospital Skaraborg, Skovde, 2004/2005





clinical presentations therapeutic controversies










choice of fluid therapy and hyperchloraemic acidosis

isotonic “normal” saline versus balanced solutions

this leads to excessive chloride administraton and consequenthyperchloraemic acidosis



























initial bolus dose of insulin

this is not generally recommended any more

in paediatrics it is actually recommended against

















Equivalence testing revealed no clinically relevant differences inintravenous fluid administration change, rate of change of glucose, oranion gap. Administration of an initial bolus dose of insulin was not

associated with significant benefit to patients with DKA anddemonstrated equivalent changes in clinically relevant endpoints when

compared to patients not administered the bolus.















clinical presentations diabetic ketoacidosis, complications










when all goes wrong in a young adult

a young adult with known type 1 diabetes mellitusimpulsive behaviour, in an angry fit just ignores her insulin needs

admitted with severe diabetic ketoacidosis




when all goes wrong in a young adulta young adult with known type 1 diabetes mellitus

impulsive behaviour, in an angry fit just ignores her insulin needsadmitted with severe diabetic ketoacidosis




when all goes wrong in a young adulta young adult with known type 1 diabetes mellitus

impulsive behaviour, in an angry fit just ignores her insulin needsadmitted with severe diabetic ketoacidosis





slow resolution of the ketoacidotic derangementno resolution of the hyperchloraemic component

increasingly inadequate respiratory response10 hours after admission to ICU severe vomiting, aspiration,

respiratory and cardiac arrestsevere persistent central nervous damage inspite of CPR in an ICU

environment





slow resolution of the ketoacidotic derangementno resolution of the hyperchloraemic component

increasingly inadequate respiratory response10 hours after admission to ICU severe vomiting, aspiration,

respiratory and cardiac arrestsevere persistent central nervous damage inspite of CPR in an ICU

environment




comorbidity and atypical presentations in the aging diabetic patient

a 57 year old lady at six in the morning

40 years of type 1 diabetes mellitusinjects insulin only once daily

nausea and vomiting for a whole dayrefuses to get medical attention, her husband finally manages to drive

her to hospitalwalks through the door, becomes restless

anaesthesiologist immediately contacted and present (me .... )15 minutes after walking in, severe bradacardia and circulatory arrest























ABC! - intubation, ventilation, adrenalin, fluids

first blood gas analysis:pH 6.86, SBE -27mEq/l, PCO2 5kPa (38mmHg)

Ringers solution and trometamol- Na-bicarbonate given





ABC! - intubation, ventilation, adrenalin, fluids

first blood gas analysis:pH 6.86, SBE -27mEq/l, PCO2 5kPa (38mmHg)

Ringers solution and trometamol- Na-bicarbonate given




































a dreaded complication in paediatric cases: cerebral oedema

Cerebral oedema is reported to be the leading cause of paediatricmortality due to diabetic ketoacidosis, affecting about 1% of all cases61 of 6977 hospital patients with DKA had clinically apparent cerebral

oedema, with 13 of 15 deaths occuring in this group.

Glaser N, Barnet P, Mccaslin I, Nelson D, Trainor J, Louie J, Kaufman F, Quayle K, Roback M,Malley R, Kuppermann N

Risk factors for cerebral edema in children with diabetic ketoacidosis, NEnglJMed 2001,344:264-9





Cerebral oedema is reported to be the leading cause of paediatricmortality due to diabetic ketoacidosis, affecting about 1% of all cases61 of 6977 hospital patients with DKA had clinically apparent cerebral

oedema, with 13 of 15 deaths occuring in this group.

Glaser N, Barnet P, Mccaslin I, Nelson D, Trainor J, Louie J, Kaufman F, Quayle K, Roback M,Malley R, Kuppermann N

Risk factors for cerebral edema in children with diabetic ketoacidosis, NEnglJMed 2001,344:264-9





”Risk factors associated with cerebral edema would be: age inferior to5, recent DM diagnosis, long-standing symptoms, hypocapnia, severe

acidosis, bicarbonate treatment for acidosis, excessive volumereplacement in the first 4 hours and insulin administration in the first

hour of fluid replacement“

Wolfsdorf JI, Craig ME, Daneman D, Dunger D, Edge JA, Lee WRW, Rosenbloom A, SperlingMA, Hanas R ISPAD Clinical Practice Consensus Guidelines 2006-2007 - Diabetic Ketoacidosis

Pediatric Diabetes 2007, 8:28-43





”Risk factors associated with cerebral edema would be: age inferior to5, recent DM diagnosis, long-standing symptoms, hypocapnia, severe

acidosis, bicarbonate treatment for acidosis, excessive volumereplacement in the first 4 hours and insulin administration in the first

hour of fluid replacement“

Wolfsdorf JI, Craig ME, Daneman D, Dunger D, Edge JA, Lee WRW, Rosenbloom A, SperlingMA, Hanas R ISPAD Clinical Practice Consensus Guidelines 2006-2007 - Diabetic Ketoacidosis

Pediatric Diabetes 2007, 8:28-43




a dreaded complication in paediatric cases: cerebral oedemathe conventional view

Diabetic Ketoacidosis and Cerebral Edema Elliot J. Kranehttp://pedsccm.org/FILE-CABINET/Metab/DKA-CEdema.html




a dreaded complication in paediatric cases: cerebral oedemaMRI imaging, though, suggests vasogenic oedema due to ischaemia

as the pathogenetic mechanism initiating cerebral oedema.

https://clinicaltrials.gov/ct2/show/NCT01365793





Purpose

The investigators will conduct a randomized controlled trial comparingfour different intravenous (IV) fluid treatment protocols for pediatric

diabetic ketoacidosis (DKA). Two rates of rehydration will becompared; a more rapid rate and a slower rate. Within each of thesetwo basic rehydration protocols, the investigators will vary the type of

rehydration fluid used (0.9% saline or 0.45% saline). The investigatorswill compare the different treatments by conducting assessments of

neurological injury, by measuring the frequency of significant cerebraledema, and by measuring long-term neurocognitive function.

https://clinicaltrials.gov/ct2/show/NCT01365793

clinical presentations alcoholic ketoacidosis








alcoholic ketoacidosis 1


when the stomach just will not take more ethanol









As in the small child with cyclic vomiting, these patients are caught ina vicious circle of vomiting, starvation metabolism and more vomiting.

As with the paediatric patients, the decisive point is recognising thisclinical presentation.

cases acid-base analysis at the bedside








a bedside approach 1

”Base Excess partitioning“

a good approximation - a bedside Stewart approachas described David Story


D. A. Story, H. Morimatsu, R. BellomoStrong ions, weak acids and base excess: a simplified Fencl-Stewart approach to clinical

acid-base disordersBritish Journal of Anaesthesia 92(1):54-60 (2004)


a bedside approach 2

BE [mEq/l]Na- Cl effect: - ([Na+]-[Cl-]) + 35 mEq/l(1) [mEq/l]albumin effect: - (42 - albumin)g/l*0.25mEq/g [mEq/l]

=

result: unknown anion effect [mEq/l]


sodium, potassium, chloride, lactate and bicarbonate in mmol/l, BE in mEq/l, albumin in g/l,PCO2 in kPa

(1) The exact base value is dependent on your local normal value ranges! just calculate thedifference between your normal values for sodium and chloride!

cases a 16 year old girl








a 16 year old girl 1


measured values:pH 7.28PCO2 2.2 [kPa]Na+ 131 [mmol/l]K+ 4.6 [mmol/l]Cl– 105 [mmol/l]lactate 1.3 [mmol/l]albumin 40 [g/l]

calculated values:SBE -18 [mEq/l]HCO–

3 8 [mmol/l]



no surprise

a common case of diabetic ketoacidosis in an adolescent whostruggles to come to terms with being chronically dependent on

medical treatment

although a rather mild one:BE: -18 [mEq/l]Na- Cl effect: - (131 - 105)+ 35 mEq/l [mEq/l]albumin effect: - (42 - 40)g/l*0.25mEq/g [mEq/l]

=

unknown anion effect: -9.5 [mEq/l]




no surprise


medical treatment


=





no surprise


medical treatment


=





no surprise


medical treatment


=






If you use the analysis module on acidbase.org, you get this kind of output.






a 16 year old girl 3 - a few months later 1


measured values:pH 7.31PCO2 4.5 [kPa]Na+ 127 [mmol/l]K+ 4.7 [mmol/l]Cl– 89 [mmol/l]lactate [mmol/l]albumin 37 [g/l]


3 18 [mmol/l]




measured values: old newpH 7.28 7.31PCO2 2.2 4.5 [kPa]Na+ 131 127 [mmol/l]K+ 4.6 4.7 [mmol/l]Cl– 105 89 [mmol/l]lactate 1.3 [mmol/l]albumin 40 37 [g/l]

calculated values:SBE -18 -8 [mEq/l]HCO–

3 8 18 [mmol/l]




BE: -18 -8 [mEq/l]Na- Cl effect: + 35 mEq/l - (131 - 105) + 35 mEq/l - (127 - 89) [mEq/l]albumin effect: + (40-42g/l)*0.25mEq/g + (37-42g/l)*0.25mEq/g [mEq/l]

= =

unknown anioneffect:

-9.5 -12.25 [mEq/l]

cases alcohol abuse







cases alcohol abuse

alcohol abuse 1


measured values:pH 7.51PCO2 3.1 [kPa]Na+ 127 [mmol/l]K+ 2.8 [mmol/l]Cl– 86 [mmol/l]lactate 5.0 [mmol/l]albumin 15 [g/l]

calculated values:SBE -3.5 [mEq/l]HCO–

3 19 [mmol/l]

cases alcohol abuse

alcohol abuse 2

too much alcohol and too much water in a 60 year old ladyhepatic coma / alcoholic liver cirrhosis

BE: -3.5 [mEq/l]Na- Cl effect: - (127 - 86)+ 35 mEq/l [mEq/l]albumin effect: - (42 - 15)g/l*0.25mEq/g [mEq/l]

=



cases alcohol abuse

alcohol abuse 2

too much alcohol and too much water in a 60 year old ladyhepatic coma / alcoholic liver cirrhosis

BE: -3.5 [mEq/l]Na- Cl effect: - (127 - 86)+ 35 mEq/l [mEq/l]albumin effect: - (42 - 15)g/l*0.25mEq/g [mEq/l]

=



cases alcohol abuse

alcohol abuse 3



cases alcohol abuse

alcohol abuse 4



cases alcohol abuse

alcohol abuse 5



cases alcohol abuse

alcohol abuse 6



cases metformin







cases metformin

metformin 1


measured values:pH 6.83PCO2 1.1 [kPa]Na+ 140 [mmol/l]K+ 6.0 [mmol/l]Cl– 108 [mmol/l]lactate 13 [mmol/l]albumin 45 [g/l]

glucose 19.6 [mmol/l]


3 1.4 [mmol/l]

cases metformin

metformin 2

58 year old maleadmitted to intensive care after several days with diarrhoea and

reduced fluid intakediabetes mellitus type 2, metformin-treated

BE: -30 [mEq/l]Na- Cl effect: - (140 - 108)+ 35 mEq/l [mEq/l]albumin effect: - (42 - 45)g/l*0.25mEq/g [mEq/l]

=



cases metformin

metformin 2

58 year old maleadmitted to intensive care after several days with diarrhoea and

reduced fluid intakediabetes mellitus type 2, metformin-treated

BE: -30 [mEq/l]Na- Cl effect: - (140 - 108)+ 35 mEq/l [mEq/l]albumin effect: - (42 - 45)g/l*0.25mEq/g [mEq/l]

=



cases metformin

metformin 3



cases metformin

metformin 4



cases metformin

metformin 5


everything is getting better - or is it?

cases metformin

metformin 6


unresolved and severe unknown anion acidosisactally, the nurse noted a smell of acetone

(which the doctor dismissed)

cases metformin

metformin 7


normalising the pH by increasing the SID (Na-Cl difference)also known as ‘buffering ’

good bye conflicts of interest








conflicts of interest


my two conflicts of interest!

http://www.acidbase.org/presentations/











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