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THAM A a Buffer
Tham Solution (tromeThamine injection) is a sterile, non-pyrogenic 0.3 M solution of tromeThamine, adjusted to a pH of approximately 8.6 with glacial acetic acid. It is administered by intravenous injection, by addition to ACD blood for priming cardiac bypass equipment and by injection into the ventricular cavity during cardiac arrest.
Each 100 mL contains tromeThamine 3.6 g (30 mEq) in water for injection. The solution is hypertonic 389 mOsmol/L (calc.). pH 8.6 (8.4-8.7).
The solution contains no bacteriostat, antimicrobial agent or added buffer (except acetic acid for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded.
Tham solution is a parenteral systemic alkalizer and fluid replenisher.
TromeThamine, USP (sometimes called “tris” or “tris buffer”) is chemically designated 2-amino-2-(hydroxymethyl)-1, 3-propanediol, a solid readily soluble in water, also classified as an organic amine buffer. It has the following structural formula:
Water for Injection, USP is chemically designated H20.
Tham – Clinical Pharmacology
When administered intravenously as a 0.3 M solution, tromeThamine act as a proton acceptor and prevents or corrects acidosis by actively binding hydrogen ions (H+). It binds not only cations of fixed or metabolic acids, but also hydrogen ions of carbonic acid, thus increasing bicarbonate anion (HCO3‾). TromeThamine also acts as an osmotic diuretic, increasing urine flow, urinary pH, and excretion of fixed acids, carbon dioxide and electrolytes. A significant fraction of tromeThamine (30% at pH 7.40) is not ionized and therefore is capable of reaching equilibrium in total body water. This portion may penetrate cells and may neutralize acidic ions of the intracellular fluid.
The drug is rapidly eliminated by the kidney; 75% or more appears in the urine after eight hours. Urinary excretion continues over a period of three days.
Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production).
Water balance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of electrolytes in the body compartments and sodium (Na+) plays a major role in maintaining physiologic equilibrium.
Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis.
Sodium bicarbonate is despite its side effects, considered the standard alkali therapy in metabolic acidosis. THAM is an alternative alkalizing agent; however, there are limited data on the use of THAM in metabolic acidosis. The aim of this study was to compare the efficacy and adverse effects of a single dose of sodium bicarbonate and THAM in intensive care unit (ICU) patients with mild metabolic acidosis.
18 adult ICU patients with mild metabolic acidosis (serum bicarbonate < 20 mmol/L) were randomized to a single dose of either sodium bicarbonate or THAM, administered over a 1-hour period, and titrated to buffer the excess of acid load.
Sodium bicarbonate and THAM had equivalent alkalinizing effect during the infusion period. This was still present 4 hours after start of infusion of sodium bicarbonate, and until 3 hours after start of infusion of THAM. Serum potassium levels decreased after sodium bicarbonate infusion, and remained unchanged after THAM. After sodium bicarbonate, sodium increased, and after THAM, serum sodium decreased.
Sodium bicarbonate and THAM had a similar alkalinizing effect in patients with mild metabolic acidosis; however, the effect of sodium bicarbonate was longer lasting. Sodium bicarbonate did decrease serum potassium, and THAM did not; THAM is therefore not recommended in patient with hyperkalemia. As sodium bicarbonate leads to an increase of serum sodium and THAM to a decrease, THAM may be the alkalinizing agent of choice in patients with hypernatremia. Similarly, because sodium bicarbonate increases PaCO2 and THAM may even decrease PaCO2, sodium bicarbonate is contraindicated and THAM preferred in patients with mixed acidosis with high PaCO2 levels.
- [PubMed – indexed for MEDLINE]
Pharmacology & Dosing
More on Acid–Base Disorders
N Engl J Med 1998; 339:1005-1006, October 1, 1998
- THAM is a biologically inert amino alcohol of low toxicity that buffers carbon dioxide and acids in vitro and in vivo. At 37°C, the pKa (the negative logarithm of the acid ionization constant) of THAM is 7.8, making it a more effective buffer than sodium bicarbonate in the physiologic range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of one proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system by accepting a proton, generating sodium bicarbonate, and decreasing the partial pressure of carbon dioxide. It rapidly distributes to the extracellular space and slowly penetrates the intracellular space, except in the case of erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike sodium bicarbonate, which requires an open system to eliminate carbon dioxide in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and it maintains its buffering ability during hypothermia.
- The initial loading dose of THAM acetate (0.3 M) for the treatment of acidemia may be estimated as follows: THAM (in milliliters of 0.3 M solution) = lean body weight (in kilograms) × the base deficit (in millimoles per liter). The maximal daily dose is 15 mmol per kilogram per day for an adult (3.5 liters of a 0.3 M solution in a patient weighing 70 kg).
“For those who are still using bicarb in your prime. There is some literature that states the occurrence of acidosis at the start of bypass is an iatrogenic event, that is due to the choices of asanguineous fluids in the prime and not due to hypotension or dilutional acidosis.
Therefore, if you switch your crystalloid solutions to balanced crystalloids, you will not need to add bicarbonate to your priming fluids. The center I had worked at in Halifax has been using balanced crystalloids for more than 30 years without the use of bicarb in their crystalloid only prime and we never had any issues with acidosis after going on bypass … verified after the first 10 minute blood gas.
If you use a synthetic colloid/crystalloid prime, that is another matter because all the colloids are acidic in nature (with the exception of Hextend).
Balanced crystalloids (Normosol R, Plasmalyte A, and Plasmalyte 148) are isotonic solutions that contain either sodium hydroxide or hydrochloric acid to normalize their pH. They also contain large amounts of unmeasured anions in the form of Acetate (27 mEq/L) and Gluconate (23 mEq/L) which create a SID value of 47 mEq/L. Crystalloids with a SID value > 24 mEq/L will lead to a progressive alkalotic state after the start of bypass.
Acetate is normally produced in the gut and as a by-product of tissue metabolism. The normal value for acetate in blood is between 0.01-0.07 mmol/L, and is quickly converted into acetyl co-enzyme A and eventually oxidized in the liver into CO2 and water.
Due to its high SID value *, balanced crystalloids have a tendency for acid base balance to move on the alkaline side of the pH scale without the addition of sodium bicarbonate during bypass.
They therefore appear to be the best choice for CPB priming solutions for most CPB cases because they avoid the development of acidosis at the start of bypass and do not require the addition of a buffer like bicarbonate.”
- Morgan TJ, Ventakesh B et al: Crystalloid strong ion difference determines metabolic acid base change during acute normovolaemic hemodilution – Intensive Care Med 2004; 30:1432-37
- Alston RP, Cormack L et al : Metabolic acidosis developing during cardiopulmonary bypass is related to a decrease in strong ion difference – Perfusion 2004, May;19(3):145-52
- Liskaser F, Story DA et al: Effect of pump prime on acidosis, strong ion difference and unmeasured ions during cardiopulmonary bypass – Anesth Intensive Care September 2009;37(5):767-72
Gerard J Myers
Halifax, Nova Scotia
Acetate is a common additive to IV solutions. It is used as a bicarbonate substitute because it is stable in solution and is converted to bicarbonate in the liver. So, you can give a lot of acetate-containing solutions without worrying about dilution of the serum bicarbonate.
- One mEq of acetate is equivalent to one mEq of bicarbonate, so give it in the same mEq dose.
There are no side effects that I know of except the usual hypernatremia if you give a lot of it.
In adults, the conversion of acetate to bicarbonate takes 5-10 minutes at normothermia, so don’t expect to see the immediate buffering change like with bicarbonate use. Wait a little while to allow the conversion to take place. Of course, the colder the patient, the longer the conversion time because the liver chemistry is slowed by hypothermia. Also, patients with cirrhosis or some other liver disease may have a harder time with the conversion.
In children, particularly babies, the liver function is less efficient than an adult. The conversion in a baby may require 6 hours. So, the use of acetate in infants is not going to work very well or quickly. So, if your program does both adults and peds, save whatever sodium bicarbonate you have left for the peds and use the acetate in the adults.
Gary Grist RN CCP
Kansas City, Mo.
* SID Values