Carbicarb, Na bicarbonate, THAM

Compare and contrast the pharmacology of carbicarb, Sodium bicarbonate and THAM.

Carbicarb:
Another potential and perhaps more effective alternative to Na bicarbonate is an equimolar mixture of sodium carbonate (Na2CO3) and sodium bicarbonate called "Carbicarb". Sodium carbonate in the mixture reacts with carbonic acid (H2CO3) to generate bicarbonate via the following reaction:

CO3(2-) + H2CO3 = 2 HCO3-

Thus, the carbonate component of Carbicarb consumes H2CO3 (or CO2) while the HCO3 component and the newly generated HCO3 will form CO2 when protons are buffered. Consequently, the total amount of CO2 which is generated is two-thirds the amount that would be generated by an equimolar amount of HCO3 alone. The mixture of sodium carbonate and Na bicarbonate is utilized instead of sodium carbonate alone because a solution of pure sodium carbonate is too caustic to be intravenously infused. The risks of hypertonicity and hypervolemia are similar to those of sodium bicarbonate.
Carbicarb has been evaluated in animals, with inconsistent benefit compared with Na bicarbonate. One human study of 36 surgical patients with metabolic acidosis compared the effects of sodium bicarbonate with Carbicarb. No benefit was observed.

 

Na Bicarbonate

Bicarbonate is an anion and cannot be given alone. Its therapeutic use is as Na bicarbonate. An 8.4% solution is a molar solution (i.e. it contains 1 mmol of HCO3^- per ml) and is the concentration clinically available in Malaysia. This solution is very hypertonic (osmolality is 2,000 mOsm/kg). 

The main use of alkali therapy include to counteract the extracellular acidemia and thus avoiding the side effects of acidosis, in emergency treatment of hyperkalaemia and to promote alkaline diuresis.

 

The severity of the undesirable effects will depend on the amount of bicarbonate used:

hypernatraemia

hyperosmolality

volume overload

rebound or ‘overshoot’ alkalosis

hypokalaemia

impaired oxygen unloading due to left shift of the oxyhaemoglobin dissociation curve

acceleration of lactate production by removal of acidotic inhibition of glycolysis

CSF acidosis

hypercapnia

can cause paradoxical acidosis in the presence of a low output

THAM (tris-hydroxymethyl aminomethane)

 

THAM  is an amino alcohol which buffers protons by virtue of its amine (NH2) moiety via the following reactions:

 

THAM-NH2 + H+ = THAM-NH3+

Unlike bicarbonate which generates CO2, THAM consumes CO2:

THAM-NH2 + H2O + CO2 = THAM-NH3+ + HCO3-

The urinary clearance of protonated THAM salts is slightly greater than urinary clearance of creatinine. To the extent THAM-NH3+ is excreted in the urine with chloride, this represents net acid excretion. However, if THAM-NH3+ is excreted with HCO3-, then no net acid excretion occurs. Thus, THAM can increase the buffering capacity of blood without generating CO2 but is less effective in anuric patients.

Reported toxicities of THAM include hyperkalemia, hypoglycemia, extravasation related necrosis, hepatic dysfunction.and respiratory depression; the last complication may be due to the ability of THAM to rapidly increase the pH and decrease the PCO2 in the central nervous system. 

 

THAM has been used to treat severe acidemia due to sepsis, permissive hypercapnia, diabetic ketoacidosis, renal tubular acidosis, gastroenteritis, and drug intoxications. However, THAM has not been evaluated in clinical trials involving patients with lactic acidosis. Thus, the efficacy and safety of THAM in such patients is unknown.