Metabolic Acidosis

Abnormal ↑ in blood fixed acid concentration. Metabolic acidoses are:

• Classified by the change in AG into:
  • HAGMA
  • NAGMA
• Graded by the change in SBE
  • Mild: SBE -4-9
  • Moderate: SBE -10-14
  • Severe: SBE <-14

Aetiology

Causes of Metabolic Acidosis

High Anion Gap	Normal Anion Gap
Lactate: Type A ↓ Perfusion. Type B Metabolic. D-lactate	Renal base loss: Renal Tubular Acidosis ↓ Aldosterone Cushings Adrenal insufficiency Addison’s disease Aldosterone antagonists Toluene Carbonic anhydrase inhibitors
Toxins: Citrate Alcohols Methanol Ethylene glycol Salicylates Pyroglutamic Iron
Ketoacidosis: Diabetic Alcoholic Starvation	GIT base loss: Secretion drainage Pancreatic Biliary Small bowel fistula Diarrhoea
Renal: Due to failure to excrete organic anions: Sulphate Hippurate Phosphate Uraemic acidosis occurs in CKD Severe acidosis typically demands GFR <20ml/min. AKI has a more variable acidosis Hyperkalaemia is typically the determinant of dialysis, rather than acidosis.	Mineral acid gain: Chloride gain TPN Hyperalimentation.

The extent of acidosis caused by diarrhoea depends on the ionic content of the stools. Cl^- is freely exchanged for HCO_3^- in the intestinal wall, so (somewhat paradoxically) anything that ↑ Cl^- secretion into the lumen culminates in an ↑ loss of HCO_3^- and a hyperchloraemic acidosis.

The greatest effect is seen in secretory diarrhoea, particularly cholera, and the least effect in inflammatory diarrhoea.

Causes of a negative anion gap include:

• Excess unmeasured cation
  • Lithium
  • Magnesium
  • Calcium
  • Cationic drugs
    • Polymyxin B
• Halides
  Incorrectly read as chloride by the electrode.

Pathophysiology

Adverse effects of metabolic acidosis include:

• B
  • ↑ PVR and PAP
  • Hyperventilation
• C
  • ↓ Inotropy
  • Dysrhythmia
  • ↓ SVR and hypotension
  • Venoconstriction
  • ↓ Catecholamine response
• D
  • Confusion
• E
  • ↑ Metabolic rate
  • ↑ BSL
  • Bone loss
• F
  • ↓ RBF
  • Hyperkalaemia
• G
  • ↓ Splanchnic blood flow
  • Nausea/vomiting
• H
  • Coagulopathy

Management

• Treat cause
• Consider alkalinisation if:
  • NAGMA
  • Severe metabolic consequences

Specific Therapy:

• Pharmacological
  • Sodium bicarbonate
    ↑ SID due to chloride-free sodium, counteracting NAGMA.
    • Indications:
      • Strong indications
        • Severe NAGMA
        • Severe hyperkalaemia
        • TCA
        • Salicylate overdose
          Urinary alkalinisation.
      • Controversial indications:
        • Severe HAGMA
          • Toxic alcohols
        • Pulmonary hypertension
    • Considerations:
      • Significant volume load
      • ↑ PaCO₂, worsening respiratory acidosis
        1029mmol/L in 1M solution.
      • Significant ↑ in VCO₂ and PCO₂ unless administered slowly
      • May lead to significant intracellular acidosis due to diffusion of CO₂ across the cell membrane
        i.e. Measured improvement in pH may not be physiologically beneficial.
  • Sodium carbonate
    • Usually combined with sodium bicarbonate (‘carbicarb’)
    • ↓ CO₂ production but produces NaOH
      • NaOH causes local vessel destruction on peripheral administration
  • Sodium lactate
    • Bicarbonate precursor
    • Requires intact lactate metabolism as bicarbonate is produced during metabolism of lactate to pyruvate
  • THAM
    • Weak base and buffer with pKa of 7.7
    • Effective for both respiratory and metabolic acidoses
    • Complications:
      • Consumes CO₂
        May cause apnoea given rapidly.
      • Accumulates in AKI
      • May ↓ BSL
      • Coagulopathy
      • Potassium disturbances

There are several equations that estimate the dose of sodium bicarbonate required to reverse a metabolic acidosis.

They are all inaccurate, but if you need to pick one consider:
\(Dose = W \times 0.3 \times ([HCO_3^-]_{Target} - [HCO_3^-]_{Current})\)

Where:

• \(Dose\) is bicarbonate dose in mmol
• \(W\) is weight in kg
• \([HCO_3^-]\) is serum bicarbonate concentration in mmol/L

Key Studies

Alkalinising Solutions:

• Metabolic acidosis is common in the critically unwell, and brings a raft of physiological harms

• Alkalinising the serum may not be the solution

  • May worsen intracellular acidosis
  • Correcting cause of acidosis should be the priority

• Bicarbonate probably has a role in NAGMA, but not in HAGMA
  Metabolism of organic acids regenerates HCO₃^-.

• BICAR-ICU (2018)

  • 389 adult Frenchpersons with metabolic acidosis (pH <7.2) and lactataemia or OSFA >4
  • Multicentre (26), unblinded, allocation concealed, randomised trial
  • 80% power for 15% ARR ↓ (!) in composite of death or organ failure from 45% control group mortality
  • Bicarbonate vs. control
    • Bicarbonate
      • 4.2% bicarbonate targeting pH >7.3, up to 1L/24 hours
    • Control
      No placebo.
  • No difference in primary outcome (66% vs. 71%) overall, though difference in defined subgroup of patients with AKI
    Note unpowered for this.
  • Secondary outcomes demonstrated ↓ RRT in bicarbonate group (35% vs. 52%)
  • 24% of the control group received bicarbonate, and >100 patients were excluded because they had already been given bicarbonate
  • No differential between source of acidosis (excluding AKI, which presumably had a uraemic contibution)

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References

1. Brandis, K. Acid-base pHysilogy. 2015.
2. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.