THAM (tromethamine, tris-hydroxymethyl aminomethane)

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THAM is a biologically inert amino alcohol of low toxicity which buffers carbon dioxide and acids in vitro and invivo. At 37^o C, the pK of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood. It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system and maintains its buffering power in the presence of hypothermia.

The use of THAM is well documented in treating acidosis following cardiac bypass. Its use in ARDS is lightly reported, but it is useful in treating acidosis that accompanies permissive hypercapnia. THAM administration may permit correction of severe acidosis temporarily until vital homeostasis returns to normal. THAM administration should follow established guidelines, along with concurrent monitoring of acid-base status, ventilation and plasma electrolytes and glucose.

 

Indications

• Treatment of metabolic acidosis refractory to bicarbonate therapy
• To facilitate permissive hypercapnia in patients with severe ARDS during acute ventilator management

Patient Eligibility

• Patients must be in an ICU or PACU and administration of therapy must be per protocol, unless cleared by an ICU attending

Monitoring

• Q 1h ABG, potassium and glucose till stable then q 4h
• Q 6h basic
• Q 6h osmolarity with osmole gap for 24h and as indicated

Dosing

THAM acetate 0.3 mol/L (pH8.6) is well tolerated and is the only formulation available in the US. In large doses, THAM may induce respiratory depression requiring ventilatory assistance, hypokalemia secondary to pH changes and hypoglycaemia requiring glucose administration. It is supplied in 500 ml bottles.

1. Initial loading dose THAM acetate
   • 0.3 mol/L (in ml) = lean body-weight (kg) x base deficit (mmol/L)
   • 25-50% of the calculated dose is given IV over 5-10 minutes and the balance administered over 1 hour
   • One bottle (500 ml) for a 70kg person with base deficit -8.0, half the dose over 5-10 minutes, remainder of the hour
2. Rate of administration should not exceed 15 ml/kg in 1 hour, not to exceed 50 ml/kg/day
   • 70 kg person, max rate short term 1000 ml/hr, max daily dose 3500 ml = 150 ml/hr
3. THAM is excreted renally at similar rates as creatinine.
   • IR (ml/hr) = 0.2 x CLCR(ml/min) x PTHAM (mmol/L)
   • (If ClCr is 30 ml/min, the maximum THAM infusion rate should be 35 ml/h to keep plasma THAM less than 6mmol/l)

Endpoints

Goal pH 7.25 – 7.30; Orders must be rewritten daily