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Heparin nitroglycerin interaction during cardiac surgery — Does it exist?
42 HEPARIN NITROGLYCERIN EXIST ?
INTERACTION
DURING CARDIAC SURGERY
- DOES IT
P. Neidhart, B. Tatti, R. Wesolowski Departement of Anesthesiology University Hospital of Geneva 1211 Geneva 4, Switzerland
INTRODUCTION (HEP) administration during The goal of heparin cardiopulmonary bypass (CPB) is to achieve sufficient suppression of coagulation so that thrombogenesis will not occur. The adequacy of anticoagulation during CPB and its reversal (by protamine) is usually monitored with the activated clotting time (ACT). Recent reports suggest that the in vivo activity of HEP, measured by the activated partial thromboplastin time, is reduced when nitroglycerin (NG) is administred concomitantly with HEP (1). Because NG is used extensively during cardiac surgery (2), we investigated, whether in vivo NG-HEP interaction occurs during CPB, and if it is sufficiently important to interfere with a given HEP administration schedule. PATIENTS AND METHODS After approval by the institutional review board, 21 patients undergoing cardiac surgery with CPB of at least 70 min were randomly assigned to receive NG as a continuous iv. infusion, either before CPB (group A: n=l 1 pat) or during CPB (group B: n = 10 pat). Patients were not eligible for the study if 1, they were receiving medication known, or thought to interfere with HEP or its monitoring with ACT e.g. heparin, aspirin, and 2. there was a contraindication to randomisation to either of the two groups e.g. unstable angina. Induction and maintenance of anaesthesia (midazolamfentanyl-pavulon-air/Os) was similar for all patients. In group A, i.v. NG was started immediately after induction of anaesthesia at a dose of 20-200 kg/min and maintained up to the start of CPB. In group B, i.v. NG was started at the beginning of CPB and maintained up to the end. The loading dose of HEP (HEP,,) for both groups was calculated according to the Hepcon/System (HemoTec Inc), in order to obtain a target of 3 units (u) HEP/ml calculated blood volume. An additional 12500 u of HEP was added to the prime volume of 2.5 1crystalloid solution. The HEP-effect was assessed by two different methods of the automated ACT : the hemochron 400 and the HemoTec ACT. The HEP-plasma levels were measured by the Hepcon/System at the following times : after induction of anaesthesia (TJ, 5 min after administration of HEP,, (Tn), 5 min after crossclamping of the aorta (To), every 30 mm thereafter (To_ ) and finally 7-10 min after protamine reversal (Tv). Hupplemental HEP (5’000 or 10’000 u) was administred when the HC or the ACT was below 300 set before CPB or below 450 set during CPB. The last HEP-level measured by the Hepcon/System before termination of CPB was used to calculate the protamine dose necessary to reverse HEP. A dose ratio of Img protamine per 100~ HEP was used. In order to compare the HEP consumed by patient we “normalised” the units of HEP added during CPB (HEP & and the total units given (HEP,,,) for the different length of CPB, by dividing HEP units by CPB-time in min. The results are expressed as mean + SD. They were compared by Student’s t-test for unpaired data. P
RESULTS : Group A received 8i3.5 mg NG i.v. before the start of CPB (including T ) and group B 22*11 mg during CPB (T -TX). As presente 3 ‘in the table, similar doses of HE8 were administered before and added during CPB in both groups. The mean values for the hemochron after heparin loading (409klll set vs 432+69 set), at aortic cross clamp (515?143 set vs 623*154 set) and during CPB (To_, : 51 lk95 set vs 570t72 set) were not significantly different between group A and B respectively. The protamine dose given for adequate HEP reversal was similar in both groups (18.2k4.1 ml vs 22.Ot3.5 ml). This dose best correlated with HEP loading dose (r = 0.74 and r = 0.70 for group A and B respectively). TABLE : Comparison by proteanins between
of heparin adminbtration schedule and re.ve~~I the two group8 (for abbreviation see text).
GROUP (n=ll)
CPB
HEPadd HEPtot
GROUP (n=lO)
20300f3600
(units) (units/min) (units/tin)
PROTAMINE
(“xl)
B
125fSO
150f40
(min)
HEPID
A
2ssou~8Oo
68f47
61f44
2QOf97
356fSQ
18.0f4.1
22.0fS.6
DISCUSSION The doses of heparin required to achieve adequate heparinisation before CPB were similar whether NG was used before CPB or not. In addition heparin doses required to maintain adequate heparinisation during CPB were similar whether NG was used or not. Therefore we conclude that during cardiac surgery, where high doses of heparin have to be administered, the concomitant use of NG does not seem to influence the heparin requirement.
:
References 1. Co1 J. et al Propylene glycol-induced heparin nitrodvcerin infusion. Am 110: 171-173 (19861 2. Barn& R.E. et al : Heparin nitroglycerin in&c&n. 71:QQl (leS9)
:
Heart
r&stance
during
Anesthesiology
INTERACTION
DURING CARDIAC SURGERY
- DOES IT
P. Neidhart, B. Tatti, R. Wesolowski Departement of Anesthesiology University Hospital of Geneva 1211 Geneva 4, Switzerland
INTRODUCTION (HEP) administration during The goal of heparin cardiopulmonary bypass (CPB) is to achieve sufficient suppression of coagulation so that thrombogenesis will not occur. The adequacy of anticoagulation during CPB and its reversal (by protamine) is usually monitored with the activated clotting time (ACT). Recent reports suggest that the in vivo activity of HEP, measured by the activated partial thromboplastin time, is reduced when nitroglycerin (NG) is administred concomitantly with HEP (1). Because NG is used extensively during cardiac surgery (2), we investigated, whether in vivo NG-HEP interaction occurs during CPB, and if it is sufficiently important to interfere with a given HEP administration schedule. PATIENTS AND METHODS After approval by the institutional review board, 21 patients undergoing cardiac surgery with CPB of at least 70 min were randomly assigned to receive NG as a continuous iv. infusion, either before CPB (group A: n=l 1 pat) or during CPB (group B: n = 10 pat). Patients were not eligible for the study if 1, they were receiving medication known, or thought to interfere with HEP or its monitoring with ACT e.g. heparin, aspirin, and 2. there was a contraindication to randomisation to either of the two groups e.g. unstable angina. Induction and maintenance of anaesthesia (midazolamfentanyl-pavulon-air/Os) was similar for all patients. In group A, i.v. NG was started immediately after induction of anaesthesia at a dose of 20-200 kg/min and maintained up to the start of CPB. In group B, i.v. NG was started at the beginning of CPB and maintained up to the end. The loading dose of HEP (HEP,,) for both groups was calculated according to the Hepcon/System (HemoTec Inc), in order to obtain a target of 3 units (u) HEP/ml calculated blood volume. An additional 12500 u of HEP was added to the prime volume of 2.5 1crystalloid solution. The HEP-effect was assessed by two different methods of the automated ACT : the hemochron 400 and the HemoTec ACT. The HEP-plasma levels were measured by the Hepcon/System at the following times : after induction of anaesthesia (TJ, 5 min after administration of HEP,, (Tn), 5 min after crossclamping of the aorta (To), every 30 mm thereafter (To_ ) and finally 7-10 min after protamine reversal (Tv). Hupplemental HEP (5’000 or 10’000 u) was administred when the HC or the ACT was below 300 set before CPB or below 450 set during CPB. The last HEP-level measured by the Hepcon/System before termination of CPB was used to calculate the protamine dose necessary to reverse HEP. A dose ratio of Img protamine per 100~ HEP was used. In order to compare the HEP consumed by patient we “normalised” the units of HEP added during CPB (HEP & and the total units given (HEP,,,) for the different length of CPB, by dividing HEP units by CPB-time in min. The results are expressed as mean + SD. They were compared by Student’s t-test for unpaired data. P
RESULTS : Group A received 8i3.5 mg NG i.v. before the start of CPB (including T ) and group B 22*11 mg during CPB (T -TX). As presente 3 ‘in the table, similar doses of HE8 were administered before and added during CPB in both groups. The mean values for the hemochron after heparin loading (409klll set vs 432+69 set), at aortic cross clamp (515?143 set vs 623*154 set) and during CPB (To_, : 51 lk95 set vs 570t72 set) were not significantly different between group A and B respectively. The protamine dose given for adequate HEP reversal was similar in both groups (18.2k4.1 ml vs 22.Ot3.5 ml). This dose best correlated with HEP loading dose (r = 0.74 and r = 0.70 for group A and B respectively). TABLE : Comparison by proteanins between
of heparin adminbtration schedule and re.ve~~I the two group8 (for abbreviation see text).
GROUP (n=ll)
CPB
HEPadd HEPtot
GROUP (n=lO)
20300f3600
(units) (units/min) (units/tin)
PROTAMINE
(“xl)
B
125fSO
150f40
(min)
HEPID
A
2ssou~8Oo
68f47
61f44
2QOf97
356fSQ
18.0f4.1
22.0fS.6
DISCUSSION The doses of heparin required to achieve adequate heparinisation before CPB were similar whether NG was used before CPB or not. In addition heparin doses required to maintain adequate heparinisation during CPB were similar whether NG was used or not. Therefore we conclude that during cardiac surgery, where high doses of heparin have to be administered, the concomitant use of NG does not seem to influence the heparin requirement.
:
References 1. Co1 J. et al Propylene glycol-induced heparin nitrodvcerin infusion. Am 110: 171-173 (19861 2. Barn& R.E. et al : Heparin nitroglycerin in&c&n. 71:QQl (leS9)
:
Heart
r&stance
during
Anesthesiology