Adjustment of excess acidity of stored blood (blood preserved with anticoagulant citrate dextrose [ACD] solution) used to prime pump-oxygenator during cardiac bypass surgery.
May use as an alkalinizing agent in cardiac arrest; only limited data indicate that buffers may improve outcome of cardiac arrest.
Restoration of oxygen content with appropriate ventilation with oxygen, support of some tissue perfusion and cardiac output with good chest compressions, and then rapid return of spontaneous circulation (ROSC) are mainstays of restoring acid-base balance during cardiac arrest.
May be beneficial in cardiac arrest, but generally use only after more proven methods for ACLS (e.g., defibrillation, cardiac compression, support of ventillation including intubation, vasopresssor therapy) have been ineffective.
Non-carbon dioxide generating buffers (e.g., tromethamine) may minimize some adverse effects of sodium bicarbonate (e.g., carbon dioxide generation, hyperosmolarity, hypernatremia, hypoglycemia, intracellular acidosis, myocardial acidosis, overshoot alkalosis) in certain CPR situations; however, clinical experience is limited.
May be preferable to sodium bicarbonate in treatment of severe metabolic acidosis in patients in whom sodium or carbon dioxide elimination is restricted.
May not be preferable to sodium bicarbonate in treatment of patients intoxicated with salicylates, barbiturates, or other weak acids.
Has been used in the treatment of metabolic acidosis associated with status asthmaticus† and neonatal respiratory distress syndrome†.
Maintain ventilation by artificial means if respiratory acidosis accompanies metabolic acidosis; not recommended in patients with respiratory acidosis alone, since the drug may depress ventilation by decreasing carbon dioxide tension.
Dosage and Administration
Administration
Administer by slow IV infusion, by addition to the pump-oxygenator ACD blood or other priming fluid, or by injection into the ventricular cavity during cardiac arrest.
Do not administer for >1 day, except in life-threatening situations.
May be used along with standard resuscitative measures.
Containers are for single use only.
Commercially available tromethamine (Tham®) is a 0.3 M solution of the drug. Do not extemporaneously prepare solutions in a concentration >0.3 M.
IV Administration
Infuse the drug slowly via a large needle into the largest antecubital vein or via an indwelling catheter placed in a large vein of an elevated limb. IV catheters are recommended.
Rate of Administration
Administer slowly.
Dosage
Dosage depends on severity and progression of acidosis.
Carefully supervise dosage and rate of administration to avoid overtreatment (alkalosis). Determine blood pH, arterial oxygen pressure (PaO2), carbon dioxide tension (PaCO2), bicarbonate, glucose and electrolyte concentrations, and urinary output before, during, and following administration of the drug. Monitor dosage and progress of treatment, as needed.
Consider the possibility of some accumulation of drug, especially in patients with impaired renal function.
Dosage is the least amount of a 0.3 M solution that is required to increase blood pH to within normal limits (7.35–7.45) and correct acid-base derangements.
Dosage calculations are based on base deficit as determined by means of the Siggaard-Andersen nomogram. Calculate dosage of tromethamine in metabolic acidosis using the following empiric formula as a guide:
mL of 0.3 M tromethamine solution = body weight (in kg) × base deficit (in mEq/L) × 1.1
(Factor of 1.1 accounts for an approximate reduction of 10% in buffering capacity due to presence of sufficient acetic acid to lower pH of 0.3 M solution to approximately 8.6.)
Thus, total dose of tromethamine solution for a 70-kg adult having a base deficit of 5 mEq/L is 385 mL of 0.3 M solution (approximately 13.9 g of tromethamine). Need for additional doses is determined by serial measurements of existing base deficit.
Pediatric Patients
Acidosis
Metabolic Acidosis Associated with Respiratory Distress Syndrome
IV
Neonates and Infants: Initial dose based on initial pH and weight of child at birth. Usually, initial dose is about 1 mL per kg for each pH unit below 7.4. Additional doses may be given according to changes in PaO2, blood pH, and PaCO2.
Adults
Acidosis
Metabolic Acidosis Associated with Cardiac Bypass Surgery
IV
Total single dose of a 0.3 M solution for most adults is 500 mL. A single dose of up to 1000 mL may be necessary in unusually severe cases. Do not administer individual doses >500 mg/kg per hour (about 1078 mL of 0.3 M solution per hour for a 70-kg adult).
Acidity of ACD Blood in Cardiac Bypass Surgery
IV
Usually, add 15–77 mL of a 0.3 M solution to each 500 mL of ACD blood, depending on the pH of the blood. Clinical experience indicates that 62 mL of a 0.3 M solution added to 500 mL of ACD blood usually is adequate.
Metabolic Acidosis Associated with Cardiac Arrest
IV
If chest is not open, administer 111–333 mL of a 0.3 M solution into a large peripheral vein. Additional tromethamine may be required to control acidosis that persists after resuscitation.
Intraventricular
If chest is open, 62–185 mL of a 0.3 M solution has been injected into the ventricular cavity (not into the cardiac muscle).
Prescribing Limits
Pediatric Patients
Do not administer for >1 day, except in life-threatening situations.
Adults
Do not administer for >1 day, except in life-threatening situations.
Acidosis
Metabolic Acidosis Associated with Cardiac Bypass Surgery
IV
Maximum (individual dose) 500 mg/kg per hour.
Special Populations
Renal Impairment
Use with caution. (See Renal and Electrolyte Effects under Cautions.)
Geriatric Patients
Select dosage with caution, usually initiating therapy at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. (See Geriatric Use under Cautions.)
If an adverse effect occurs, discontinue infusion, evaluate patient, institute appropriate therapeutic countermeasures, and save remainder of fluid for examination (if deemed necessary).
Respiratory Effects
Possible respiratory depression, as a result of increased blood pH and reduced carbon dioxide concentrations associated with administration of large doses of tromethamine;also in those with chronic hypoventilation or in those receiving other drugs that depress respiration.
Carefully adjust dosage so that blood pH does not increase above normal; have facilities readily available to provide mechanical ventilation during administration of tromethamine. May be used with mechanical ventilatory support if respiratory acidosis is present concomitantly with metabolic acidosis.
Local Effects
Possible local irritation and tissue inflammation or infection at the site of injection, febrile response, chemical phlebitis, venospasm, hypervolemia, and IV thrombosis.
Administer slowly through a large needle or indwelling catheter to minimize venous irritation. Use with caution to prevent perivascular infiltration, since extravasation may result in inflammation, necrosis, and sloughing of overlying skin.
If perivascular infiltration occurs, discontinue tromethamine immediately and initiate appropriate countermeasures. Infiltration of the affected area with 1% procaine hydrochloride (to which hyaluronidase has been added) will often reduce venospasm and also will dilute any tromethamine remaining locally in tissues. Local infiltration of an α-adrenergic blocking agent (e.g., phentolamine mesylate) into the vasospastic area has been recommended.Perform nerve block of autonomic fibers to the affected area, if necessary.
Metabolic Effects
Possible transient decreases in blood glucose concentration. When larger than recommended doses are used or when administration is too rapid, hypoglycemia may persist for several hours.
Administer tromethamine slowly and in amounts sufficient only to correct the existing acidosis; avoid overdosage and alkalosis.
Frequently determine blood glucose concentrations during and following therapy.
Renal and Electrolyte Effects
Possible hyperkalemia and accumulation of tromethamine in patients with renal disease or reduced urinary output; use with extreme caution, montior ECG, and frequently determine serum potassium concentrations.
Possible hydropic degeneration of renal tubular cells in adults who received hypertonic solution (1.5 M) of tromethamine.
Fluid and/or Solute Overload
Possible fluid and/or solute overload following IV administration resulting in dilution of serum electrolyte concentrations, overhydration, congested conditions, or pulmonary edema.
Duration of Administration
Do not administer for >1 day, except in life-threatening situations. Clinical experience generally limited to short-term use.
General Precautions
Laboratory Monitoring
Determine blood pH, PaCO2, and bicarbonate, glucose, and electrolyte concentrations before, during, and following administration of tromethamine.
Hematologic Effects
Possible increased blood coagulation time.
Hepatic Effects
Hemorrhagic necrosis of the liver reported in seriously ill neonates who received hypertonic (1.2 M) preparations of tromethamine via the umbilical vein.
Hydropic degeneration of hepatic cells reported in adults who received hypertonic solution (1.5 M) of tromethamine.
Specific Populations
Pregnancy
Category C.
Lactation
Not known whether distributed into human milk. Use with caution.
Pediatric Use
Safety and efficacy based on extensive (over 30 years) clinical experience documented in medical literature and by safety surveillance.
May be used in the treatment of severe cases of metabolic acidosis with concurrent respiratory acidosis in neonates and infants with respiratory failure, because unlike sodium bicarbonate, tromethamine does not elevate PaCO2.
Also may be used in neonates and infants with hypernatremia and metabolic acidosis to avoid the additional sodium given with the bicarbonate.
Because osmotic effects of tromethamine are greater and large continuous doses of the drug are required, sodium bicarbonate is preferred to tromethamine in the treatment of acidosis in neonates and infants with respiratory distress syndrome (RDS).
Possible occurrences of hepatocellular necrosis associated with IV infusions of tromethamine via low-lying umbilical venous catheters.
Hypoglycemia may occur in premature and even in full-term neonates.
Contraindicated in neonates with chronic respiratory acidosis and salicylate intoxication.
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. Other reported clinical experience has not identified differences in response between geriatric patients and younger adults.
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. (See Geriatric Patients under Dosage and Administration.)
Substantially eliminated by kidneys; risk of toxic reactions may be greater in patients with impaired renal function. Monitor renal function and adjust dosage accordingly since geriatric patients are more likely to have decreased renal function.
Renal Impairment
Substantially eliminated by kidneys; risk of toxic reactions may be greater in patients with impaired renal function. (See Renal and Electrolyte Effects under Cautions.)
Common Adverse Effects
Adverse effects may include respiratory depression, local irritation, tissue inflammation, injection site infection, febrile response, chemical phlebitis, venospasm, hypervolemia, IV thrombosis, extravasation (with possible necrosis and sloughing of tissues), transient decreases in blood glucose concentrations, hypoglycemia, and hepatocellular necrosis with infusion via low-lying umbilical venous catheters. (See Warnings under Cautions.)
Interactions
No formal drug interaction studies performed to date.
Pharmacokinetics
Distribution
Extent
Not known whether distributed into human milk.
Elimination
Metabolism
Not appreciably metabolized.
Elimination Route
Excreted principally in urine (rate depends on infusion rate). Urinary excretion continues over a period of 3 days; 75% or more appears in the urine after 8 hours.
Weak base. Prevents or corrects acidosis by actively binding with hydrogen ions and their associated acid anions; the resulting salts are excreted in urine.
Combines with lactic, pyruvic, and other metabolic acids and with carbonic acid.
Approximately 70% of tromethamine present in plasma at pH 7.4 is in ionized (protonated) form; if pH is decreased from pH 7.4, ionized fraction of drug is increased. Ionized fraction of tromethamine reacts only with acid in extracellular fluids; fraction of drug that remains un-ionized at physiologic pH may be capable of penetrating cell membrane to combine with intracellular acid.
Does not appear to affect ventilatory rate; may reduce tidal volume leading to a decrease in minute ventilation and carbon dioxide output; may decrease arterial oxygen saturation by about 5%.
Weak osmotic diuretic; increases flow of alkaline urine containing increased amounts of electrolytes.
Advice to Patients
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
