Avidan et al.  1present a novel method of treating heparin resistance in patients about to undergo cardiopulmonary bypass (CPB). Implicit but undocumented is the premise that patients with heparin resistance, defined as failure of the activated clotting time (ACT) to increase above the institutional protocol after a standard dose of heparin, are in danger of insufficient anticoagulation to tolerate CPB safely.

The issue is more than academic. If patients with heparin resistance are indeed endangered by a low ACT, correcting the low ACT is lifesaving. If patients with heparin resistance are not endangered by the low ACT, intervention presents risk without benefit.

A heparin dose of 300 U/kg is considered the minimum dose required for safe CPB, although one study reported routine use of 150 U/kg without ill effect.2On the other hand, the Society of Cardiovascular Anesthesiologists survey3quoted by Avidan et al .1revealed a wide range of institutional ACT protocols. Some institutions omit ACT measurements entirely.4No prospective study indicates that any protocol is safer or more dangerous than others when administering conventional doses of heparin.

Commonly used target ACTs have little substance to corroborate them. Young et al.  5proposed their recommended 400 s on the basis of nine monkeys whose CPB circuits were primed with monkey blood and then five children who did fine with ACTs above 400 s. Bull et al.  6recommended 480 s on the basis on a computer simulation with no patient data; their report contained no rationale for selecting 480 s as an optimal target.

Several studies demonstrate the lack of correlation between bad outcome and uncorrected low heparinized ACTs before or during CPB.2,4,7 

The value of the study by Avidan et al.  1is that it presents an alternative treatment for heparin resistance. The use of recombinant human antithrombin will allow clinicians to increase the heparinized ACT without danger of additional heparin or blood transfusion. Instead, the patient endures the lesser risk of anaphylactic reaction and the cost of the drug. The alternative not discussed by Avidan et al.  is to ensure that the heparin went intravascular (a heparin level will suffice) and then ignore the ACT. This last alternative has no documented risks.

If Avidan et al.  are aware of studies more recent than the antiquated studies quoted here that might invalidate this conclusion, it would be educational to discuss them.

Heparin resistance is a disease carried in ACT tubes. Once assured that the standard dose of heparin went intravascular, we may spare patients the dreaded consequences of treating heparin resistance (delay of CPB, more heparin, blood products, recombinant antithrombin) if we manage them without the ACT.

Oregon Anesthesiology Group, Providence Milwaukie Hospital, Portland, Oregon. samuel.metz@comcast.net

1.
Avidan MS, Levy JH, Scholz J, Delphin E, Rosseel PMJ, Howie MB, Gratz I, Bush CR, Skubas N, Aldea GS, Licina M, Bonfiglio LJ, Kajdasz DK, Ott E, Despotis GJ: A phase III, double-blind, placebo-controlled, multicenter study on the efficacy of recombinant human antithrombin in heparin-resistant patients scheduled to undergo cardiac surgery necessitating cardiopulmonary bypass. Anesthesiology 2005; 102:276–84
2.
Dauchot PJ, Berinza-Moettus L, Rabinovitch P, Ankeney JL: Activated coagulation and activated partial thromboplastin times in assessment and reversal of heparin induced anticoagulation for cardiopulmonary bypass. Anesth Analg 1983; 62:710–9
3.
Despotis GJ, Gravlee G, Filos K, Levy J: Anticoagulation monitoring during cardiac surgery: A review of current and emerging techniques. Anesthesiology 1999; 91:1122–51
4.
Metz S, Keats AS: Low activated coagulation time during cardiopulmonary bypass does not increase postoperative bleeding. Ann Thorac Surg 1990; 49:440–4
5.
Young JA, Kisker CT, Doty DB: Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer. Ann Thorac Surg 1978; 26:231–40
6.
Bull BS, Korpman RA, Huse WM, Briggs BD: Heparin therapy during extracorporeal circulation. J Thorac Cardiovasc Surg 1975; 69:675–84
7.
Culliford AT, Gitel SN, Starr N, Thomas ST, Baumann FG, Wessler S, Spencer FC: Lack of correlation between activated clotting time and plasma heparin during cardiopulmonary bypass. Ann Surg 1981; 193:105–11