Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Tham: 30 mEq/100 mL (500 mL [DSC])
Pharmacology
Mechanism of Action
Acts as a proton acceptor, which combines with hydrogen ions, liberating bicarbonate buffer, to correct acidosis. It buffers both metabolic and respiratory acids, limiting carbon dioxide generation. Also an osmotic diuretic.
Pharmacokinetics/Pharmacodynamics
Absorption
30% of dose is not ionized
Distribution
Distributes quickly into extracellular space; at steady state distributes into a volume slightly greater than total body water; penetrates slowly intracellularly
Excretion
Urine (>75%) within 8 hours
Half-Life Elimination
5.6 hours
Use: Labeled Indications
Correction of metabolic acidosis associated with cardiac bypass surgery or cardiac arrest; to correct excess acidity of stored blood that is preserved with acid citrate dextrose (ACD); indicated in infants needing alkalinization after receiving maximum sodium bicarbonate (8-10 mEq/kg/24 hours)
Contraindications
Hypersensitivity to tromethamine or any component of the formulation; uremia or anuria; chronic respiratory acidosis (neonates); salicylate intoxication (neonates)
Dosage and Administration
Dosing: Adult
Note: Tham solution is no longer available in the US.
Dose depends on buffer base deficit; when deficit is known: tromethamine (mL of 0.3 molar [M] solution) = body weight (kg) x base deficit (mEq/L) x 1.1
Metabolic acidosis with cardiac arrest:
IV: 3.6 to 10.8 g (111 to 333 mL of 0.3 M solution); additional amounts may be required to control acidosis after arrest reversed
Open chest: Intraventricular: 2 to 6 g (62 to 185 mL of 0.3 M solution). Note: Do not inject into cardiac muscle
Acidosis associated with cardiac bypass surgery: IV: Average dose: 9 mL/kg of 0.3 M solution (2.7 mEq/kg); 500 mL is adequate for most adults; maximum dose: 500 mg/kg over at least 1 hour
Excess acidity of acid citrate dextrose (ACD) blood in cardiac bypass surgery: 15 to 77 mL of 0.3 M solution added to each 500 mL of ACD blood
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Tham solution is no longer available in the US. Dose dependent upon severity and progression of acidosis; doses should be administered slowly to prevent overtreatment. Tromethamine is available as a 0.3 M solution (THAM); doses are based on this concentration and expressed as volumes (mL/kg). Each mL of THAM = 0.3 mmol = 36 mg = 0.3 mEq
Metabolic acidosis: Infants, Children, and Adolescents: IV: Empiric dosage based upon base deficit: Dose (mL) of THAM = body weight (kg) x base deficit (mEq/L) x 1.1*
Usual range: 1 to 2 mEq/kg/dose; maximum dose in 24 hours: 15 mEq/kg/24 hours (15 mmol/kg/24 hours) (Kliegman 2007; Nahas 1998)
*Factor of 1.1 accounts for an approximate reduction of 10% in buffering capacity due to the presence of sufficient acetic acid to lower the pH of the 0.3 M solution to approximately 8.6
Metabolic acidosis with cardiac arrest: Limited data available: Note: Routine use of buffering agents during cardiac arrest not recommended (AHA [Klienman 2010]): Infants, Children, and Adolescents: THAM: IV: 1 mL/kg should raise bicarbonate concentration by 1 mEq/L (Fuhrman 2011)
Administration
IV: Correction of metabolic acidosis in cardiac bypass surgery: Administer by slow IV infusion over at least 1 hour (maximum rate: 500 mg/kg over at least 1 hour); rapid administration may result in prolonged hypoglycemia.
Correction of ACD blood acidity in cardiac bypass surgery: Add to each 500 mL of ACD blood used to prime the pump-oxygenator.
Correction of metabolic acidosis in cardiac arrest: If chest is open, instill directly into ventricular cavity; do NOT inject into cardiac muscle. If chest is not open, inject into a large peripheral vein.
Vesicant (with IV administration); ensure proper needle or catheter placement prior to and during administration; avoid extravasation.
Extravasation management: If extravasation occurs, stop IV administration immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.
Storage
Store at 20°C to 25°C (68°F to 77°F). Protect from freezing.
Drug Interactions
Alpha-/Beta-Agonists (Indirect-Acting): Alkalinizing Agents may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy
Amantadine: Alkalinizing Agents may increase the serum concentration of Amantadine. Monitor therapy
Amphetamines: Alkalinizing Agents may decrease the excretion of Amphetamines. Management: Consider alternatives to using amphetamines and alkalinizing agents in combination. If these agents must be used together, patients should be monitored closely for excessive amphetamine effects. Consider therapy modification
Flecainide: Tromethamine may increase the serum concentration of Flecainide. Monitor therapy
Mecamylamine: Alkalinizing Agents may increase the serum concentration of Mecamylamine. Monitor therapy
Memantine: Alkalinizing Agents may increase the serum concentration of Memantine. Monitor therapy
QuiNINE: Alkalinizing Agents may increase the serum concentration of QuiNINE. Monitor therapy
Adverse Reactions
Frequency not defined.
Cardiovascular: Localized phlebitis, venospasm
Endocrine & metabolic: Hyperkalemia, hypervolemia, hypoglycemia (usually doses >500 mg/kg administered over <1 hour)
Hepatic: Hepatic necrosis (resulted during delivery via umbilical venous catheter)
Local: Local irritation
Respiratory: Apnea, pulmonary edema, respiratory depression
Warnings/Precautions
Concerns related to adverse effects:
- Extravasation: Vesicant; ensure proper needle or catheter placement prior to and during administration; avoid extravasation. May cause tissue inflammation and necrosis.
- Hypoglycemia: May cause hypoglycemia with extremely large doses.
- Respiratory depression: May cause respiratory depression; monitor closely especially if patient not intubated.
Disease-related concerns:
- Renal impairment: Use with caution in patients with renal impairment; reduce dose and monitor pH carefully.
Other warnings/precautions:
- Duration of therapy: Drug should not be given for a period of longer than 24 hours unless for a life-threatening situation.
Monitoring Parameters
Serum electrolytes (especially potassium, blood glucose); renal function, arterial blood gases, ECG monitoring, fluid status, ventilation rate
Check infusion site frequently during administration.
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal studies have not been conducted.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling), difficulty breathing, slow breathing, shallow breathing, shortness of breath, excessive weight gain, swelling of arms or legs, or severe injection site pain, burning, edema, blisters, or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
