Methylene blue to treat protamine-induced anaphylaxis reactions. An experimental study in pigs

ABSTRACT Objective: To examine if methylene blue (MB) can counteract or prevent protamine (P) cardiovascular effects. Methods: The protocol included five heparinized pig groups: Group Sham -without any drug; Group MB - MB 3 mg/kg infusion; Group P - protamine; Group P/MB - MB after protamine; Group MB/P - MB before protamine. Nitric oxide levels were obtained by the nitric oxide/ozone chemiluminescence method, performed using the Nitric Oxide Analizer 280i (Sievers, Boulder, CO, USA). Malondialdehyde plasma levels were estimated using the thiobarbiturate technique. Results: 1) Groups Sham and MB presented unchanged parameters; 2) Group P - a) Intravenous protamine infusion caused mean arterial pressure decrease and recovery trend after 25-30 minutes, b) Cardiac output decreased and remained stable until the end of protamine injection, and c) Sustained systemic vascular resistance increased until the end of protamine injection; 3) Methylene blue infusion after protamine (Group P/MB) - a) Marked mean arterial pressure decreased after protamine, but recovery after methylene blue injection, b) Cardiac output decreased after protamine infusion, recovering after methylene blue infusion, and c) Sustained systemic vascular resistance increased after protamine infusion and methylene blue injections; 4) Methylene blue infusion before protamine (Group MB/P) - a) Mean arterial pressure decrease was less severe with rapid recovery, b) After methylene blue, there was a progressive cardiac output increase up to protamine injection, when cardiac output decreased, and c) Sustained systemic vascular resistance decreased after protamine, followed by immediate Sustained systemic vascular resistance increase; 5) Plasma nitrite/nitrate and malondialdehyde values did not differ among the experimental groups. Conclusion: Reviewing these experimental results and our clinical experience, we suggest methylene blue safely prevents and treats hemodynamic protamine complications, from the endothelium function point of view.

Clemastine to prevent adverse effects of protamin sulfate after coronary artery bypass graft surgery

Heparin is the only widely used pharmacologic agent for anticoagulation during coronary artery bypass graft surgery [CABG]. Failure of adequate and prompt heparin reversal by protamine sulfate can result in hemodynamic instability. Protamine has various side effects. Clemastine as an H1 receptor blocking agent shows positive inotropic effect but not some side effects of non-sedative antihistamines such as cardiac arrhythmia. The aim of this study was to evaluate the effect of clemastine on several hemodynamic responses after protamine sulfate administration in patients subjected to CABG. In a prospective randomized controlled trial, 60 patients aged 34-87, with the ASA class II to IV and cardiac ejection fraction >/= 50% who subjected to elective CABG were enrolled to two equal groups. Patients in group 1 received normal saline [2ml] intravenously as placebo before the operation was completed. Patients in group 2 received clemastine 2 mg [2ml] intravenously at the same time as group 1. After the operation all patients received slowly infusion of protamine sulfate within 7 minutes, through peripheral vein. Change of MAP in 5 minutes after protamine administration was clinically significant in group 1. No drop in MAP in 5 and 10 minutes after protamine administration was seen in group 2. There was a significant increase in heart rate in 5 and 10 minutes after protamine administration in group 1. There was no significant rise in heart rate before and after protamine administration in group 2. Clemastine can prevent MAP decrease after protamine administration in patients subjected to coronary artery bypass graft surgery

Cambios hemodinamicos durante la administración de protamina y eliminación de sus efectos adversos por inhibición de la ciclo-oxigenasa / Hemodymamic changes during protamine administration and elimination of this adverses effect for inhibition ciclooxygenase

La hipótesis que los efectos adversos producidos al revertir la heparina por protamina puedan ser eliminados o disminuídos al suministrar Indometacina, se trató de comprobar en 16 pacientes clasificados en dos grupos. En el grupo I (placebo) n=8, fe=0.60%; 6 masculinos y 2 femeninos; a 4 de ellos se les realizó puentes aorto coronarios u al resto reemplazo de la válvula mitral. Se determinaron los efectos hemodinámicos y la diferencia arterio-venosa de oxígeno al administrar la protamina endovenosa. El grupo II (n= 8); fe= 0.47%; 5 masculinos y 3 femeninos, fueron tratados con Indometacina (50 mgs. V.O. TID); las intervenciones efectuadas fueron puentes aorto-coronarios 5, y reemplazo valvular aórtico 2, realizándose las mismas medidas que al grupo I. Cuando se administró la protamina (1,5 mgs. por total de heparina) en 5 minutos y se compararon las variables hemodinámicas de los dos grupos, no se encontraron diferencias estadísticamente significativas en los tiempos T3, T4 y T5. Al tomar en cuenta los 2 grupos se observa que la presión arterial media aumenta en el grupo I (76 ñ 8 a 82 ñ 4) y disminuyó en el grupo II (80 ñ 7 a 73 ñ 14). La presión venosa central, la presión media en arteria pulmonar, la presión capilar pulmonar y el gasto cardíaco aumentan en ambos grupos; la resistencia vascular sistémica disminuye en ambos grupos, siendo más acentuada en el grupo II (2.181 ñ 1.283 a 996 ñ 521). La resistencia vascular pulmonar comparada con su mismo grupo mostró variación estadísticamente significativa en el grupo II, con p < 0.05 en relación a su valor base T0 (166 ñ 108 a 96 ñ 51)..