Answering your questions on ten-minute transport of lactate test specimens and incomplete TDM orders.

Ten-minute transport of lactate test specimens

Q Recently, we changed lactate procedures and are now using the Beckman Synchron CX system lactate reagent. The instructions provided read: "Tubes of blood should be kept closed at all times in a vertical, stopper-up position. Keep samples on ice. Plasma should be physically separated from contact with cells within 15 minutes of sample collection, and analyzed without delay."

The supervisor for the lab section performing this test requires blood specimens to be in the lab within 10 minutes of collection. We have a difficult time getting blood samples from the patient to the testing area within 10 minutes. How can I help speed completion of this time-sensitive test?

A Lactate (lactic acid) is the product of anaerobic glycolysis, and is used clinically to detect situations in which there is decreased oxygen delivery or increased oxygen demand. Specimens for lactate are particularly subject to preanalytic variation; red cells are capable of anareobic glycolysis and can generate lactate after collection. According to Tietz, at room temperature glycolysis can increase normal lactate concentration by 20% in 3 minutes, and by 70% in 30 minutes.(1) Thus, if no preservatives are used, lactate will be falsely elevated unless specimens are promptly centrifuged and serum or plasma are separated from the cells.

There are several ways to prevent glycolysis and allow less pressured transport and handling of specimens. Chilling tubes to near 0 [degrees] C in ice water prevents any significant change in lactate for up to 2 hours.(2) Use of an inhibitor of glycolysis, such as iodoacetateor fluoride, will prevent glycolysis for up to 2 hours even at room temperature. The most effective way to prevent glycolysis is to denature enzymes by using a protein precipitant. In our laboratory, we use a combination of sodium fluoride and ice water to inhibit glycolysis. I would recommend reviewing your specimen collection manual to assure that you are taking proper steps to prevent glycolysis; if so, then it is not necessary to follow the 15 minute requirement stated in your manual.

A change of 20-70% may seen dramatic, but this increase is relative to a normal baseline. If average lactate concentration is approximately 1.0 mmol/L, this would increase lactate to 1.7 mmol/L 30 minutes after collection if stored at room temperature. In patients with high anion gap acidosis, baseline lactate levels are often 10-15 mmol/L; an increase of 0.7 mmol/L would represent an error of less than 10%, a clinically insignificant difference.

- D. Robert Dufour References

1. Burtis, CA, Ashwood, ER, ed. Tietz Textbook of Clinical Chemistry, 2nd ed. Philadelphia: W.B. Saunders, 1994:977.

2. Kaplan, LA, Pesce, A J, ed. Clinical Chemistry: Theory, Analysis, Practice, 3rd ed. St. Louis: Mosby, 1996:482.

Incomplete TDM orders

Q When performing therapeutic drug monitoring, should the lab require the times of the last and next dose on the test order form prior to testing? If these times are unknown, and/or the time of specimen collection is unknown, should the lab reject the test order as incomplete?

A For most purposes, if the relationship between the last dose and the specimen collection time is not known, TDM test results cannot be interpreted correctly, and the results are useless. In such cases, it is inappropriate for the lab to perform the test, and test results might produce an incorrect interpretation and action that is detrimental to the patient. The time of the next dose after specimen collection is usually not necessary.

There are instances, however, where dosing and specimen collection times may not be needed. if, for instance, the physician is interested in knowing whether the patient is taking the drug, an analysis showing that the drag is present may provide all the information that is needed. With some drugs with very long half lives, such as antiepileptic and antidepressant drugs, the range of values' between peak and trough times is small, and the specimen may be collected at any time.

- Daniel M. Baer