Acid-base disorders

Introduction

• Plasma pH exceeds intracellular pH by 0.6 units on average
• Water dissociation into H+ and OH- is central to our understanding of acid-base physiology
• [H+][OH-] = K’w (pKa of water)
• In aqueous solution, neutrality is attained when [H+] = [OH-]
  • Therefore, [H+]^2 = K’w
  • Neutral pH = 0.5xpK’w
  • At 37 degrees, neutral pH is 6.8 (intracellularly) and pH is relatively alkaline at 7.4

Stewart principles

• Must meet the following at equilibrium
  • [H+][OH-] = K’w
  • CO2 + H20 = H2CO3 = H+ + HCo3-
    • pH = 6.1 + log(HCO3-/PaCO2)
  • [H+][CO3^-2] = Keq[HCO3-]
  • HA- = H+ + A-
    • These are the non-volatile weak acids (HA)
    • Mostly albumin in plasma and Hb in red cells
  • Conservation of mass
    • Total concentration of non-volatile weak acids in any compartment = Atot
    • Atot = HA + A-
  • Electrical neutrality
    • All anions with pKA <4 are strong ions
    • Includes Na, K, Ca, Mg, Cl, sulphate, lactate, beta-hydroxybutyrate
    • Strong Ion Difference (SID) = Strong cations – Strong anions
  • Gibbs Donnan forces
    • Electrical and chemical gradients reach equilibrium across semi-permeable membranes
    • Erythrocytes harbour most of the trapped negative anions, attract diffusible cations (Na, K) while repelling Cl-
    • Only Cl- remains fully susceptible to Donnan effects (as transmembrane pumps do not alter its movement)

• Plasma SID goes up and down with CO2 via chloride shifts (Hamburger effect)
• Extracellular SID does NOT alter with CO2
• pH is therefore defined solely by PaCO2, SID and extracellular Atot
• For any individual, the PaCO2/pH relationship is a unique acid-base signature and ultimately a complex function of SID and Atot

• SID
  • This is a ’charge space’ occupied by weak ions from dissociating conjugate bases
  • Includes H+, OH-, HCO3-, CO3^2-, A-
  • Total net charge must always equal SID
  • HCO3- and A- (‘buffer base anions’) make up almost the entire SID
• SIDa = apparent SID calculated from strong ion concentrations in plasma
• SIDe = [HCO3-] x [A-] = effective SID = buffer base
• Discrepancy between SIDa and SIDe implies presence of unmeasured ions in plasma

• At any given PaCO2, a falling SID or rising Atot = metabolic acidosis
• At any given PaCO2, a rising SID or falling Atot = metabolic alkalosis
• Acute respiratory disturbances move data points to the left
  in respiratory alkalosis and to the right in respiratory
  acidosis
• Metabolic disturbances shift the entire curve up or down
  as demonstrated to the right with BE values

• Renal participation
  • Traditionally considered bicarb reabsorption in proximal tubule and excretion of fixed acids through titration of urinary buffers (phosphate and ammonium)
  • From the Stewart perspective, the kidneys regulate extracellular SID but manipulating urinary SID
    • Modifyging tubular NH4+ as an adjustable cationic partner for Cl- and other urinary strong anions
    • Modifying Atot by phosphate excretion

Stewart (Boston) vs. Copenhagen

• Copenhagen school uses base excess as integrates SID and Atot with PaCO2 remarkably well as compared to Boston school plasma SID which alters with PaCO2

Buffer systems

• At physiological pH
  • Haemoglobin
  • Phosphate
  • Plasma proteins
  • Bicarbonate

Renal influence on acid-base

• Regulate bicarb secretion and synthesis
• Renal compensation begins within 30 minutes but takes hours to days
• Bicarbonate is filtered and must be reabsorbed
  • 85% reclaimed at PCT in a sodium-dependent and carbonic anhydrase dependent process
    • If tubular disease inhibits PCT H+ release, a proximal renal tubular acidosis results
• The remaining 15% of reclamation occurs in the DCT via sodium-independent process
  • Again carbonic anyhydrase dependent
  • H+ is then trapped in the lumen bu inorganic phosphate or ammonia (NH4+)
  • Failure of H+ secretion results in distal renal tubular acidosis
• New bicarb can be synthesised via sodium-dependent process in distal tubule
  • Glutamine to ammonia (NH4+) and bicarbonate

Respiratory compensation

• Never reaches normal pH as feedback loops linked to alveolar ventilation continually force the CO2 in the direction that reverses the pH perturbation
• Loops driven by CSF and plasma pH acting on central and peripheral chemoreceptors respectively
• Central chemoreceptors dampen the initial response as SID equilibration between plasma and CSF is gradual, whereas PaCO2 equilibration is immediate

Acidosis

• Physiological effects
  • Raises serum K 0.5 for every pH drop of 0.1
  • Increases off loading of O2 to tissues
  • May decrease Ca by direct binding (opposite to expected effect of acidosis when consider hypocalcaemia a result of respiratory alkalosis in hyperventilation)
  • Depresses myocardial contractility (pH <7.1)
  • Decreases clotting
  • Arterial vasodilation
  • Vasoconstriction of pulmonary arteries and veins
  • Increased sodium channel blocking toxicity

Alkalosis

• Symptoms usually due to reduced iCa
• Metabolic effects
  • Decreases ventilatory drive
  • Blunts respiratory response to raised CO2 (may be clinically relevant in chronic respiratory acidosis)
  • Shifts Hb-O2 to left (reduced delivery to tissues)
  • Decreased K
  • Increases ammonium in CNS and may precipitate hepatic encephalopathy

Hypocapnoea

• No proven benefits
• Negatives
  • CNS – Lowers seizure threshold, impairs psychomotor fx and increases metabolic demands
  • CVS – Vasoconstriction, decreases myocardial O2 delivery
  • Resp – Increased capillary permeability, reduced compliance, inhibits normal pulmonary hypoxic vasoconstriction, worsens intrapulmonary shunt, increases airway resistance
  • Metabolic – Inhibits negative feedback on lactate production normally present at low pH
  • Particulary harmful in infants (risk of cerebral haemorrhage)
  • Cerebral vasoconstriction and risk of infarction

Anion gap

• Measures the unmeasured anions (plasma proteins, phosphate, sulfate and organic ions e.g. lactate and conjugate bases of ketoacids)
• Do not need to correct sodium for albumin in calculating AG (as dilutes chloride by the same factor)
• Normal = 12+-4 (or 7+- 4 if using ion-specific electrodes in measurement)
  • Most important is whether changes from patients baseline
• If >15 must consider abnormal

• Can also rise if unmeasured cations are significantly decreased (e.g hypocalcaemia/hypomagnesaemia)
• Metabolic and respiratory alkalosis can raise AG by 2-3 due to lactate production due to increased glycolysis
• Penicillin can increase the AG as they are themselves unmeasured anions
• If AG raised, there must be a metabolic acidosis (if unmeasured cations not decreased)

A narrow or negative AG

• May result from increase in:
  • Unmeasured cations e.g lithium, calcium, magnesium
  • Unmeasured positively charged proteins e.g. myeloma, PGUS
• Or significant decrease in unmeasured anions such as:
  • Hypoalbuminaemia
  • Should correct for abnormal albumin as this constitutes a large portion of the anion gap
    • = AG + 0.25 x (Albumin ref – Albumin meas)
    • Add 2.5 for every 10 albumin is reduced below normal value (30)
• Bromide toxicity causes false elevations of chloride unless ion-specific electrodes are used resulting in narrow/negative AG
• Triglycerides >600mg/dL falsely elevate chloride levels and lower sodium levls resulting in narrow or negative AG

High Anion Gap Metabolic Acidosis

• Exogenous poisoning
  • Methanol – Formate
  • Ethylene glycol – Oxalate and organic ions
  • Salicylate
  • Isoniazid – Lactate
  • Hippurate (seen with toluene toxicity and renal impairment
  • Pyroglutamic acid – GSH synthetase deficiency seen with sepsis, starvation, pregnancy, hepatic/renal impairment and paracetamol, flucloxacillin and vigabatrin
  • Paraldehyde

CAT MUDPILES

• Carbon monoxide, cyanide
• Alcohol/starvation/diabetic ketoacidosis
• Toluene
• Methanol/metformin
• Uraemia – Phosphate/sulfate
• DKA
• Paracetamol, phenformin, propylene glycol, paraldehyde
• Iron, isoniazid
• Lactic acidosis
• Ethylene glycol
• Salicylates

Delta gap

• Increase in AG / Decrease in bicarbonate
• <0.4 = Lone NAGMA (Hyperchloraemic) i.e. AG should not be elevated at all
  • HCl is additional acid and Cl- is part of AG calculation so AG doesn’t rise but bicarb drops
• 0.4-0.8 = Consider combined HAGMA and NAGMA
• 1-2 = Uncomplicated HAGMA
• >2 = Concomitant metabolic alkalosis or compensation for chronic respiratory acidosis i.e. bicarb inordinately elevated

Osmolar gap

• Osmolar gap = Measured Osmolality – Calculated Osmolarity
• Calculated osmolarity = 2 x Na + Glucose + Urea (+ Ethanol if known)
• Osmole = The amount of a substance that yields, in ideal solution, that number of particles that wound depress the freezing point by 1.86 deg K
• Osmolality = Number of osmoles of solute per kg of solvent
• Osmolarity = Number of osmoles of solute per litre of solution

• >10 abnormal as small gap exists due to osmolar effects of chloride, K, sulfate, phosphate, calcium, Mg, lactate, ammonia, serum proteins and lipids
• Exogenous agents
  • Acetone
  • Ethanol
  • Ethylene glycol
  • Methanol
  • Glycerol, sorbitol
  • Glycine
  • Isopropyl alcohol
  • Mannitol
  • Propylene glycol (diluent in IV diazepam/phenytoin)

• Non-toxicological causes of raised osmolar gap
  • Alcoholic ketoacidosis
  • Chronic renal failure
  • Diabetic ketoacidosis
  • Hyperlipidaemia
  • Hyperproteinaemia
  • Hypermagnesaemia
  • Severe lactic acidosis
  • Shock
  • Trauma and burns

• A normal osmolar gap does NOT exclude toxic alcohol intoxication as even small concentrations can cause significant illness
  • Also, late in the clinical course, alcohols are already metabolised to non-osmotically active compounds
• Can multiply osmolar gap by MW of suspected alcohol to work out concentration of it
  • Ethanol 4.6
  • Ethylene glycol 6.2
  • Isopropyl alcohol 6.0
  • Methanol 3.2
  • Propylene glycol 7.2

Lactate gap

• = Lactate (measured by oxidase method) – lactate (dehydrogenase method)
• = Lactate (gas) – Lactate (lab)
• Glycolate is measured by gas machine as lactate therefore get elevated lactate gap in ethylene glycol toxicity

VBG vs. ABG

• Venous pCO2 is a sensitive screen for hypercarbia (>45mmHg) but if elevated then there is wide variation and ABG is warranted
  • Therefore, to rule out is very good
• Venous lactate is clinically very useful but may be significantly higher than arterial
• VBG pH = ABG pH +- 0.02-0.035
• SpO2 usually within 2-5% of SaO2 (measured)
  • Discrepancy increases with hypoxia and poor circulation
  • May overestimate SaO2 if <92%
  • CO will falsely elevated SpO2
  • PaO2 rapidly declines below SpO2 <92% as per Hb-O2 dissociation curve
• No evidence for VBG assessment of acid-base status in mixed acid-base disorders, cardiac arrest or shock state

etCO2

• Proportionally approximates PaCO2 in healthy individuals with normal VQ
  • Arterial levels typically 5mmHg higher than alveolar samples
• Can include air from physiological dead space or environmental air that enters sample and in both cases etCO2 will be lower than PaCO2
• Not useful in COAD due to incomplete expiration of gases due to air trapping

etCO2 capnography

• 4 phases
  • I: Inspiratory baseline
  • II: Expiratory upstroke
  • III: Expiratory (alveolar) plateau
  • 0: Inspiratory downstroke
  • Alpha angle = Transition from II to III
  • Beta angle = Transition from III to 0
• If horizontal alveolar plateau, etCO2 correlates with alveolar CO2

• Flat etCO2 trace
  • Disconnection
  • Loss of output
  • Airway not in trachea
  • Capnography obstruction
• Increased etCO2
  • Increased CO2 production e.g. fever, sodibic administration, tourniquet release, venous CO2 embolism, overfeeding
  • Increased pulmonary perfusion
  • Hypoventilation (bronchial intubation, iatrogenic MV, partial airway obstruction or rebreathing (full filter)

• Decreased etCO2
  • Reduced CO2 production (hypothermia)
  • Reduced pulmonary perfusion (reduced CO, PE, hypotension, hypovolaemia, cardiac arrest)
  • Hyperventilation
• Elevated inspiratory plateau
  • CO2 rebreathing (soda lime exhaustion)

• Oesophageal intubation
  • <6 waveforms of decreasing height
• Right main bronchus intubation
  • Bifid, etCO2 can increase, decrease or stay the same
• Curare cleft in partially paralysed patient on ventilator
  • Small dip in alveolar plateau towards end
• Phase IV in pregnancy
  • Quick upstroke before phase 0
• Alpha angle
  • >90 degrees in VQ mismatch
• Beta angle
  • >90 degrees if rebreathing

Compensatory mechanisms

1. Bicarb change in acute respiratory acidosis by physiochemical conversion is almost immediate
2. Bicarb change in chronic respiratory acidosis by renal conservation takes days
3. Respiratory compensation for acute metabolic acidosis/alkalosis takes 12-24 hours to reach steady-state. Limit is around PaCO2 of 10 (12 in Tintinalli). This is due to resistant to airflow and increased CO2 generation by muscles of respiration
4. If bicarb and Co2 move in opposite directions  = mixed disorder
5. pH <7.10 impairs ventilation and subsequent compensation for any acidosis

Compensatory mechanisms
 – 1-2-3-4-5 rule

Simple rules

• Uncompensated respiratory disturbance = SBE -3 to +3
• Compensated respiratory disturbance = pH is normal 
  • or SBE = 0.4x (PaCo2 – 40)
• Metabolic acidosis
  • PaCO2 = last 2 digits of pH
  • PaCo2 = 40 + SBE
• Metabolic alkalosis
  • PaCO2 = last 2 digits of pH
  • PaCO2 = 40 + SBE

Potassium and acid-base

• H+ movement into cells in setting of acidosis, results in extrusion of K+
• For each 0.10 change in pH, serum K+ will change by 0.5mmol/L in inverse direction
• In acidosis, low serum K represents massively low total body potassium (e.g. diabetic ketoacidosis)

Clinical features of metabolic acidosis

• Primary disorder symptoms predominate
• Common to all are nausea, dyspnoea, drowsiness, abdominal pain, headache and generalised weakness
• Reduced cardiac contractile function (likely impaired oxidative phosphorylation, intracellular acidosis and altered intracellular calcium concentrations)
• Threshold for VF falls and defibrillation threshold rises
• SBP, hepatic and renal perfusion decline
• Pulmonary vascular resistance rises
• Response to catecholamines is attenuated

Lactic acidosis

• Lactate >8 predicts fatality
• Lactate >10 = 83% mortality
• Clearance of lactate allows evaluation of response to therapy
• Produced at 0.8mmol/kg/hr and continuously metabolised by liver, kidney, skeletal muscle, brain and red blood cells
• Pyruvate + NADH + H+ =(LDH)= Lactate + NAD+
  • Pyruvate from glycolysis (85%) and proteolysis (15%)
• Type A = Impaired tissue oxygenation
• Type B = Normal tissue oxygenation but impaired lactate metabolism
• Must consider as syndrome with its own differential
• Ethanol should never be considered the sole cause of any significant metabolic acidosis

• Type A
  • Shock
  • Severe hypoxaemia
  • Severe anaemia
  • CO poisoning
• Type B1 (underlying disease)
  • Sepsis, liver failure thiamine deficiency, malignancy, phaeo diabetes
• Type B2 (drug or toxin)
  • Adrenaline, salbutamol, propofol, ethanol, methanol, paracetamol, nitroprusside, salicylates, ethylene/propylene glycol, biguanides, cyanide, isoniazid
• Type B3 (inborn metabolism)
  • G6PD deficiency, pyruvate carboxylase deficiency

Triple acid-base disturbance

• Metabolic acidosis, metabolic alkalosis and respiratory acidosis alkalosis is seen with sepsis and salicylate poisoning
• Must check delta gap and expected pCO2 in all metabolic acidoses to ensure concomitant processes are not present

NAGMA

• Some texts refer to this as hyperchloraemic metabolic acidosis but in reality, may have sodium deficiency and normal chloride with subesquent NAGMA
  • What matters is the relationship of Na:Cl (should be 140:100)
• Due to:
  • GIT loss of base
    • Severe diarrhoea, villous adenoma, pancreatic/biliary fistulas, chronic laxative abuse or NG drainage
  • Renal loss of base
    • Renal tubular acidosis
    • Diuretics
  • N/saline resuscitation

NAGMA – Potassium-based differential

• Hyperkalaemic
  • Resolving diabetic ketoacidosis
  • Early uraemic acidosis
  • Early obstructive uropathy
  • RTA – type IV
  • Hypoaldosteronism
  • HCl infusion
  • Potassium-sparing diuretics

• Hypokalaemic
  • RTA type I and II
  • Acetazolamide
  • Acute diarrhoea with loss of bicarbonate and K
  • Ureterosigmoidostomy
  • Ileal conduit
  • Dilution acidosis (NaCl)

NAGMA – Urinary anion gap

• Na + K – Cl
• >20 considered abnormal
  • Gap increased due to increased urinary ammonium
  • Low or negative
    • GI loss of base (lower GI losses)
  • Normal
    • Renal loss of base (Type II RTA)
  • Elevated
    • Altered urinary acidification
    • Type I and IV RTA

NAGMA– Renal tubular acidosis

• Tubular dysfunction with intact glomerular filtration
• Classic/Distal/Type I
  • Failure of distal portion to acidify urine
  • Urine pH >5.5 despite acidaemia
  • Typically hyperchloraemic metabolic acidosis with alkaline urine +- stone formation
• Proximal/Type 2
  • Impaired bicarb reabsorption proximally
  • Fanconi’s syndrome with impaired reabsorption at proximal tubule of glucose, amino acids, bicarbonate, phosphate and uric acid
• Type 4 RTA
  • Impaired cation exchange in distal tubule with reduced H+ and K+ secretion (so presents as hyperkalaemic unlike the other two)
  • Most patients have renal disorders but GFR >20

NAGMA

• If using potassium-based differential, need to correct K for accurate use given low pH
• All diuretics cause a contraction alkalosis and subsequent metabolic acidosis seen with potassium-sparing diuretics may not be evident (as cancel each other out)
  • Probably due to secondary hyperaldosteronism
  • Crucial to check PCO2 compensation with normal AG to ensure no other respiratory acid-base disturbance is occurring

Treatment

• If inadequate respiratory compensation, treat this first
• Buffer therapy
  • Bicarb therapy produces CO2 which may worsen intracellular acidosis (esp. CNS) and may worsen respiratory acidosis abruptly
  • Also imposes osmotic and sodium load, causes hypokalaemia, decreases iCa
  • Bicarbonate therapy may be appropriate for:
    • Severe hypobicarbonataemia (<4): Insufficient buffer may lead to massive increase in acidaemia with small increase in acidosis
    • Severe acidaemia (<7-7.1) in causes of HAGMA with signs of shock, myocardial irritability as therapy of underlying cause requires adequate organ perfusion
    • Severe hyperchloraemic acidosis: Replacement of HCo3 lost in urine or gut
    • Hyperkalaemia
    • Rhabdo
    • Severe sodium channel blocker toxicity, salicylate toxicity, cyanide toxicity and toxic alcohols
  • Dose is 0.5mmol/kg for each mmol/L rise in bicarb desired
    • Goal is >8 or clinical improvement
    • Give as slowly as clinically possible

Metabolic alkalosis

• Clinical features
  • Underlying disorder + nausea, weakness, dizziness, myalgia, palpitations, paraesthesias, muscle spasm or twitching
  • Tetany, neuromuscular abnormalities and seizures are common
  • Reduced H+ causes reduced plasma Ca, K, Mg and phosphate through protein binding (no longer have H+ to bind)
  • Particularly concerning in COPD patients as oxygen dissociation curve shifts to the left with impaired tissue oxygen delivery, depresses respiratory drive
    • Many patients with COPD are on diuretics which cause a contraction alkalosis (RAS activation with increased bicarbonate reabsorption at PCT, increased H+ secretion in DCT and K+ secretion in DCT with subsequent hypokalaemia seen in contraction alkalosis)

• Need both an initiating process and maintenance process
• Initiating
  • Addition of HCO3 = Citrate or NaHCO3
  • Loss of acid = Kidneys or GI
• Maintenance – Impaired renal bicarb excretion either through reduced filtering or increased reabsorption at tubules
  • Chloride depletion
  • Potassium depletion
  • Reduced GFR
  • Volume contraction

• Chloride-responsive (loss of chloride – urinary Cl <10)
  • Vomiting, diarrhoea, previous diuretic therapy and chloride-wasting CF or enteropathy lead to contraction alkalosis with RAS activation and hyperaldosteronism
  • Resultant increase in serum bicarbonate overcomes reabsorption processes with subsequent alkaline urine with urinary Cl <10 (except with diuretics)
  • Result is hypovolaemic, hypokalaemic, hypochloraemic metabolic alkalosis with low urinary Cl that responds to normal saline

• Non-chloride responsive (urinary chloride >20)
  • Usually associated excess RAS activation and hypertension without volume or chloride loss
  • Urinary chloride >10 and alkalosis not responsive to NaCl
  • Metabolic alkalosis is primarily driven by hypokalaemia and until this is fixed, will not resolve
  • Causes
    • Hypertensive: Renal artery stenosis, renin-secreting tumours, adrenal hyperplasia, hyperaldosteronism, Cushing’s, Liddle’s syndrome, licorice or fludrocortisone
    • Normotensive: Bartter’s and Gitelman’s syndromes, acute diuretic use

Treatment of metabolic alkalosis

• Usually does not require urgent therapy
• If suspected chloride-responsive, give NaCl
• If severe (HCO3 >45), consider HCl administration (100mmol/L solution) at 0.1mmol/kg/hr through CVL

Respiratory acidosis

• 5-10% of patients with severe emphysema will demonstrate CO2 retention and inadequate response to chronically elevated pCO2 >60-70 and subsequently respond only to hypoxic drive via carotid and aortic body chemoreceptors
• Firstly, compare PCO2 with level of ventilation (if high MV and PCO2 of 40 = impaired ventilation)
• Compensation
  • Acute: HCO3 rises 1 for 10; pH drops 0.8 for 10
  • Chronic: HCO3 rises 4 for 10; pH drops 0.03 for 10

• Effects
  • Sweating, vasodilation, confusion, tachycardia, impaired myocardial contractility, mydriasis

• Causes
  • CNS tumors, stroke, infections, pregnancy, hypoxia and toxins e.g. salicylates, theophylline toxicity, progresterone
  • Anxiety, pain and iatrogenic hyperventilation
• Reduction in plasma H+ results in free plasma anions that then bind calcium leading to paraesthesias and tetany
• Hypocapnoea also significantly reduces cerebral blood flow and oxygen delivery with left shift of O2-dissociation curve
• Chronic respiratory alkalosis can be completely compensated (unique)
• Treatment
  • Calm reassurance better than paperbag (risks hypoxia)
  • Acetazolamide for altitutude-induced respiratory alkalosis

Respiratory alkalosis

• Each 10mmHg drop in PCO2 decreases HCO3 by 1 acutely and 4 chronically
• Each 10mmHg drop in PCO2 increases pH by 0.05-0.08 acutely and 0.03 chronically

Hypoxia

Calculated PaO2, A-a gradient and P/F ratio

• Five times the FiO2 is a good rule of thumb
• PAO2 = FiO2 x (760-PaO2) – 0.8/PacO2
• A-a gradient = PAO2 – PaO2
• Normal = <15 in young adults
• A-a gradient increases by 4-8mmHg per decade = Age /4 + 4 (same as paediatric ET size)
• P/F ratio = PaO2 / FiO2
  • 300 = Minimal impairment of oxygenation
  • 200 = Moderate
  • 150 = Severe
  • 100 = Very severe

Base excess

• Amount of HCl or NaHCO3 has to be added to blood sample at PCo2 of 40 to achieve pH of 7.4 at 37 degrees
• Measure of magnitude of metabolic component 
• Issues
  • Not independent of PaCO2 in vivo (blood is a better buffer than total ECF at it contains Hb and is susceptible to Gibbs Donnan forces)
  • Does not distinguish between compensatory and primary metabolic disorder
• Standard base excess
  • Calculates BE at Hb of 50, replicating mean extracellular Hb concentration and more closely resembling the extracellular environment
  • In metabolic acidosis = Quantifies the increase in extracellular SID needed to shift the curve back to the normal position without changing Atot
  • In metabolic alkalosis = Decrease in extracellular SID needed to shift the curve back to normal position without changing the Atot

Sodium bicarbonate therapy

• Primary role is to replace bicarbonate in severe NAGMA, urinary alkalinisation or improving cardiovascular function in setting of critical acidosis
• Indications
  • Hyperkalaemia with metabolic acidosis
  • Severe NAGMA
    • Lost bicarbonate cannot be rapidly regenerated as no extra organic anions
  • Cardiac arrest with pH <7.1
  • Critical acidosis with pH <7.1 with associated haemodynamic instability
  • Salicylate toxicity
  • TCA toxicity
  • Propranolol toxicity
• Controversial
  • DKA
    • Possibly increases mortality but may play a role if pH < 6.8 and shocked to improve haemodynamics/catecholamine function
    • May slow clearance of ketones and increase lactate production
  • Severe pulmonary hypertension with RV failure to improve RV function
  • Severe ischaemic heart disease where lactic acidosis may contribute to arrhythmia risk
• Adverse effects
  • Hypernatraemia
  • Hypervolaemia
  • Hyperosmolarity (causes arterial vasodilation and hypotension)
  • Hypokalaemia
  • Ionised hypocalcaemia
  • Impaired oxygen delivery to tissues secondary to left shift in Hb-O2 dissociation curve
  • CSF acidosis
  • Removal of acidotic inhibition of glycolysis by increased activity of phosphofructokinase
  • Hypercapnoea (CO2 produced by bicarbonate passes intracellularly and worsens intracellular acidosis)
  • Tissue necrosis if extravasation should occur
  • Increased lactate production
• How does bicarb increase lactate production?
  • Increases activity of phosphofructokinase thereby removing acidotic inhibition of glycolysis
  • Impairs oxygen delivery to tissues by left-shift of Hb-O2 dissociation curve
• Need to ensure adequate ventilation to ensure CO2 produced is able to be removed

Last Updated on November 22, 2021 by Andrew Crofton