Empirical protamine dosage

Correspondence

909

Empirical profamine dosage We were interested in the article by Dutton el al. (Anaesthesia 1983; 38: 2 6 8 ) in which they advocate a titration technique to determine the protamine dose required to reverse heparinisation at the end of cardiopulmonary bypass. This concept is obviously reasonable since the correct dose of any drug must be that which produces the required effect. We would, however, question their extrapolation of in virro findings to the in vivo situation. In one of the cases reported they suggest that a protamine dose of 2 mgjkg would have been an overdose and could have resuked in an adivated clotting time (ACT) of 270 seconds measured with a Haemochron 400. It had not been our impression that the use of a standard 3 mglkg empirical dose of protamine leads to an excessive ACT, and examination of the records of 51 consecutive patients operated on in a &week period this year supports this view. Thirty-four patients had coronary artery bypass grafts, 16 had valve replacements, there was one repair of an atrial septa1 defect, onc cardiac transplant and one replacement of the ascending aorta. An initial ACT was measured after the induction of anaesthesia. Heparin, 3 mgjkg, was given and the ACT again measured. Additional heparin was needed in six patients to bring the ACT to greater than 350 seconds. Sixty mg of heparin was added to the 2.5 litre crystalloid prime volume. The ACT was checked shortly after the start of cardiopulmonary bypass and at 30-minute intervals during the bypass. Eleven patients required supplements of heparin to maintain an ACT of greater than 350 seconds. After the bypass stopped and venous decannulation, 3 mg/kg of protamine was given at a controlled rate of 0.2 to 0.4 pg/kg/min. The ACT was measured 10 minutes after the infusion of this protamine was completed. A further I mg/kg prolamine was given at the time of closure of the sternotomy. In order to identify the effect of variation in the protamine/total heparin dose ratio, regression analysis of this variable was performed both against the change in ACT from before the first dose of heparin to after the 3 mg/kg of prolamine ( r = 0.01, 46 patients not on anticoagulants prior to surgery) and also against the ACT after prolamine (r=0.204, all 51 patients or r = 0.192, 46 patients not on anticoagulants.) None of these correlation coefficients nor the slopes of the regression lines, differed significantly from zero. The mean duration of anticoagulation was 126 minutes (SD 37.7 minutes). Other results are summarised in Tables I and 2 In only tive out of all 51 patients was there any nse in the ACT over the bypass period. Our final mean ACT for all cases of 124 seconds is very similar to that obtained by Dutton and colleagues. This together with our failure to demonstrate a significant relationship between protamine/heparin dose ratio and

Table 1. Forty-six patrents not o n ankoagulants prror to surgery ~~

A C T (sec) 'ifter prutdminr

Change rn AC r (sec) Protamine'hemnn dose ratio

Mean

SD

1237 -It 8 756

f2i

~

158

615

T a w 2. A11 51 patkents ~

Mean

su

123 8 -175

1204

~~

ACT (sec) after protarnine Change m ACT (sec) Protamme/hepdnn dose ratio "(,

756

244 588

the change in ACT, or between the dose ratio and the ACT after prolamine, suggests to us that a protocol using an empirical dose of 3 mdkg of protamine would give clinically satisfactory reversal of anticoagulation. Thc additional complication and cost of in vilro protamine litration is then unnecessary. Department of Anaesthesia, Addenhrooke's Hospital. New Site. Carnhridge

J. KNFEWAW M. S~ELLEY

D.W. BETHUNE J. CULLIS R.D. LATI.=

A reply

Thank you for the opportunity of replying to the letter from Dr Kneeshaw and colleagues. We d o not take issue with the empirical use of comparatively small doses of protamine sulphate for the reversal of h e p arinisation after cardiopulmonary bypass, Their concern is also about our extrapolation of in vitro findings to the in vivo situation. No matter how one calculates a protamine dose in these circumstances, one is ultimately dependent upon in vifro data to determine its effectiveness. We feel that the facility to predict reliably an effective dose of protamine prim to administration is a logical approach to this problem, and it is particularly helpful following lengthy bypass procedures during which supplementary doses of heparin may have been administered. Our main objective was to indicate the adequacy of small doses of protamine and also to illustrate the need to modify the size of these doses by taking into account the decay in heparin activity. It is our opinion that any complication or additional cost of the titration procedure is quite justifiable. Department of Anaesthesia, Vicroria InJirmary, Giasgow, G42 9TY Department of Anaesthesia, West Infirmary, Glasgow, GI1 6h'T

D.A. DUTTON

A.P. HOTHERSALL A.D. MCLAREN