Introduction
While I feel very fortunate for the training and experience that I have received over the years, I feel equally fortunate for having colleagues who are experts in every sense of the word in various aspects of critical care transport. In this month’s column, I would like to introduce you to once such expert. Jeff Thomas, RN, BSN, CEN, NREMT-P is a flight nurse specialist with Survival Flight at the University of Michigan. He has extensive experience and expertise in acid-base management and advanced ventilatory techniques.
Over the past year, I have received no less than five requests for topics related to acid-base balance. My goal is to go beyond the basics of interpreting an ABG based upon pH, PaO2 and PCO2. Once the clinician masters this concept, what is important is appropriate, evidence-based management at the bed side and in the air.
Scenario
A critical care transport team is called to the bedside of a 64-year-old female who was diagnosed with sepsis and ARDS. She is profoundly acidotic and hypotensive and is being transferred to tertiary care to be evaluated as a candidate for extra corporeal membrane oxygenation (ECMO). She has an arterial pH of 7.05, a PaO2 of 46 mmHg, a PCO2 of 104 mm Hg and a base deficit of -14. She has a blood pressure reading of 88/46 by arterial line and a central venous pressure (CVP) of 16. She has received 5 liters of crystalloid over the last 6 hours and is on a norepinephrine infusion at 20 mcg/min. The referring physician is hesitant to administer sodium bicarbonate although he recognizes a metabolic component to this patient’s acidosis. What are management options at this time?
Tham (Tromethamine/tris-hydroxymethyl aminomethane) is a physiologic buffer agent used in the critical care setting. Although this drug has been marketed since 1959, the widespread use of Tham in the treatment of acidosis has been negligible compared with that of sodium bicarbonate. In this article, we will review Tham as a physiological agent, the standard drug dose range, cost and effect of the drug in the critically ill patient.
Tham vs. Sodium Bicarbonate
It is impossible to initiate a discussion about Tham without first addressing this drug in the context and contrast to the standard alkalinization therapy of sodium bicarbonate. As opposed to sodium bicarbonate — which requires an “open system” to elicit the chemical buffering effect (CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+) by requiring alveolar or extracorporeal Carbon Dioxide (CO2) exchange — Tham utilizes its properties as a proton acceptor to generate bicarbonate and decrease the partial pressure of carbon dioxide in the arterial blood without the need for primary organ function.1 This process of acid neutralization without the sodium or CO2 load of sodium bicarbonate can make Tham the ideal drug for a focused patient population.
Dose
Tham is supplied in glass 500 cc bottles containing 3.6 Grams/100cc (30 mq/ml). In adults and children, the standard dose calculation is figured as: Lean Body Weight (kg) x Base Deficit x 1.1 (an adjustment for the pH adjustment necessary in drug manufacturing to attain a solution pH of 8.6) = Milliliters of Tham dosage.2, 3
Tham infusions must also be limited to a total of 15 ml/kg over 1 hour and maximum daily dose should not exceed 50 ml/kg/day.1, 3, 4
Cost
A cost review was conducted in conjunction with the University of Michigan Pharmacy Services.
Comparative costs of therapy are as follows:
- Tham-500 cc Bottle = Negotiated hospital cost: $148; Patient cost: $564
- Sodium Bicarbonate 8.4% 50 cc vial = Negotiated hospital cost: $0.46; Patient cost: $8
Risk/Benefit Evaluation of Tham
As a drug that is primarily eliminated by the renal system (75 percent of the drug appears in the urine after 8 hours)5, administration of Tham must be weighed against the risks of toxicity in the setting of anuria and uremia1. In addition, there are theoretical risks of hypokalemia, hypoglycemia and respiratory depression associated with the infusion of Tham in at risk populations5. As with sodium bicarbonate, the extremes in osmolarity of this drug and the alkaline nature of this infusion make it extremely toxic to peripheral soft tissue and organs distal to the peripheral or central infusion site (especially in the neonatal population).1 However, the risks of Tham administration can be tempered against the advantages.
Summary
The theoretical risks and increased cost of Tham administration can be tempered with the clear and patient driven advantages of this drug. As a buffer agent in the setting of permissive hypercapnea and acute lung injury, Tham can be utilized to achieve significant improvement in pH balance.6 In addition, the physiological burdens of hypernatremia and increased carbon dioxide production that are placed on the patient with sodium bicarbonate therapy can be tempered by the implementation of Tham in the critical care arena. Although this should not be considered a first line therapy, in specific populations Tham can be a useful adjunct to attain clinical stability.
Resources
1. Capan, L., Nahas, G.G., et al. “Guidelines for the Treatment of Acedaemia with Tham,” Drugs, Volume 55 (2), pp 191-224 (34), 1998.
2. “Tromethamine: Pediatric Drug Information,” Up-to-Date, www.utdol.com, Licensed to the University of Michigan, copyright 2009.
3. “Drugdex Evaluations: Tromethamine, Micormedex Healthcare Series,” Licensed to the University of Michigan, copyright 2009.
4. “Tromethamine: Drug Information,” Up-to-Date, www.utdol.com, Licensed to the University of Michigan, copyright 2009.
5. Homldahl, M., Wiklund, L., et. al.,"The place of THAM in the management of acidemia in clinical practice.” Acta Anesthesiologica Scaninavica, 524-527 (55), 2000.
6. Kellum, J., Gehlbach, B., Schmidt, G., “Bench-to-bedside review: Treating acid-base abnormalities in intensive care unit-the role of buffers.” Critical Care, 259-265 (8), 2004.
