الفهرس 
SYSTEMIC INFLAMATORY RESPONSEOnly 14 pages are availabe for public view
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Abstract
Low systemic vascular resistance commonly occurs during and after cardiopulmonary bypass and is easy to accept as a bothersome side effectof bypass Treatment is usually required to maintain adequate perfusion pressure during CPB and to establish satisfactory haemodynamics. Ocassionaly patients may develop a more severe and persistent fall in systemic vascular resistance named Vasoplegic syndrome.
This hypotension occurring during cardiopulmonary bypass is in part because of induction of the inflammatory response for which nitric oxide and guanylate cyclase play a central role.
Metghylene blue is believed to act through competition with nitric oxide in binding to the iron heme moiety of soluble guanylate cyclase resulting in enzyme activation.This inhibits the increase in the levels of c GMP,and therby precludes the vasorelaxant effect of nitric oxide.
Several studies have used the methylene blue drug with different doses ranging from (1.5-3mg)and at different times during the course of the CPB (pre,on bypass and post bypass) with favorable results in almost every and each studies it is worth saying that this drug has been used in treatment of vasoplegic syndromes associated with liver transplantation, sepsis and evevn as a compassionate therapy in children developing severe sepsis.
Fourty patients were included in this study undergoing CABG, where half of them received the methylene blue drug in adose 1.5 mg/Kg after induction and the other half did not.Data was collected regarding haemodynamics (SVR,MAP,….etc), laboratory data ,hospital and icu length of stay.
Results were favorable in the study group where showed higher and better mean arterial pressure,systemic vascular resistance,cardiac output,the need for inotropes reflected by the lower length of stay and icu and that goes with most of the Reported results.
Although pulmonary vascular resistance was higher in the study group ,it never reached the degree of pulmonary hypertension.Laboratory results showed no marked difference except for the elevation in the alanine aminotransferase that returned on the second postoperative day to comparable levels with the control group.
It can be concluded that the prebypass usage of methylene blue in a dose of 1.5 mg/Kg markedly attenuates the postbypass vasodilatation and hypotension with favourable effects on haemodynamics of cariac output and decreasing the length of hospital stay .inflammatory response after cardiopulmonary bypass, as in other situations, encourages the use of inhibitory drugs such as methylene blue (MB) as a therapeutic option as declared by Gomes et al,1994,and Evora et al ,2000. This drug has been used for treating vasoplegia in isolated cases with Levin et al,2001 group being the first to report a reduction in postoperative mortality .
The primary goal of this study was to prevent the development of VS during the intraoperative and post¬operative periods in high-risk patients by administering MB after induction of anesthesia. This approach prevented VS com-pletely in patients in our study treated with MB (study group) while 25% of the control group(5 out of 20) developed VS(p < 0.001),with no need for norepinephrine in the study group while in the control group a total sum of 14406±2880.39µg was given with (p value<0.001) .Thus, despite the small size of the patient population, this study has succeeded in showing that this approach does work and does significantly limit the development of VS ,and this goes in agreement with Andrade et al,1996,where 6 patients developed VS during cardiac surgery where the aim of this study was to restore blood pressure and SVR .In this study the SVR pre MB vs post MB was 868 vs 1693 dyne/sec/〖cm〗^2after after receiving 1.5 mg/Kg methylene blue over one hour.The same conclusion was found by Leyh et al,2003 where 54 patients with N.E resistant vasoplegic syndrome post CPB out of 1111 patients who underwent cardiac surgery over 12 months and received a dose of 2 mg/Kg.
Also our study goes with Levin et al,2004 showed 638 consecutive cardiac surgeries over 5 months where patients developed VS were randomized to receive methylene blue at a dose 1.5 mg/Kg over one hour.The results presented by Ozal et al,2005 , where 100 patients at high risk for development of VS undergoing CABG were randomized to receive 2mg/Kg preoperatively where (0/50) in the study group vs (13/50) 26% developed VS, goes with our study .
Data collected by a research by Andrew et al,2006 stands with our study ,where they used methylene blue in a dose 3mg/Kg after the onset the CPB, as 30 patients were randomized ,and data was collected prebypass,at the onset and every 20 minutes for 60 minutes on bypass and once at the postbypass period.
In our study preoperative MB administration stabilized SVR starting 40 minutes from baseline till the end of the study 48 hours in the ICU with (p value<0.001). In fact, despite the administration of norepinephrine boluses in the control group according the study protocol , the mean SVR was still higher in the study group (1550±89.44 dynes • sec-1 • cm-5 vs 1347±93.77dynes • sec-1 • cm-5 ) and at the CPB time interval, ( 1137±100dynes • sec-1 • cm-5 vs 983±65.41dynes • sec-1 • cm-5 ),and at ICU admission and(1262±78.98dynes • sec-1 • cm-5 vs1138±54.398dynes • sec-1 • cm-5 ) (p < 0.001) that goes in agreement with Andrew et al,2006 , Ozal et al,2005 ,Leyh et al,2003 and Andrade et al,1996 .
The mean arterial pressure(MAP) showed significant increase in the study group more than the control group starting from the CPB studied time interval showed ( 80±10 vs 75±12 mmHg)with (P value<0.001),also the cardiac output (COP)showed marked improvement in the study group starting from the post CBP time interval (4.41±0.42 vs 3.89±0.05 l/min) with (p value<0.001).
These results go with the data percieved by previous researches by Ozal et al,2005,Andrew et al,2006 ,and Leyh et al,2003 and Levin et al,2004 .
All these parameters are translated as shorter ICU length of stay in the study group (1.8±0.25 days vs 3.65±0.81 days) with (p value<0.01),while the hospital length of stay(4.3±0.66 vs 6.30±1.17 days) with (p value<0.001), and this agrees with the study by Ozal et al,2005 that showed shorter ICU length of stay and the hospital length of stay in the study group with (p values<0.001) as well.
Although there was significant difference in the central venous pressure being higher in the study group( 3.9±1.33cm .H2o vs 2.59±0.10cm .H2o) with (p value<0.001),this was not translated into a decrease in the total volume infused (crystalloids,colloids or packed RBC’s) partly as the administration of aprotinin, aminocaproic acid, , and the management of ane¬mia were not controlled for in the present study and because of the liberal usage of volume expanders in the ICU. In this study the need for crystalloid(p=0.076),need for colloid(p=0.625) and the need for packed RBC’s (p=0.143) that goes with other lititure by Andrew et al,2006 .
This was in contrast with the results reported by Ozal et al,2005 study where there was significant decrease in the volume expanders and the need for crystalloid (p = 0.024), colloid (p =0.027), and packed red blood cells (p < 0.001) in the study group.
Methylene blue causes vasoconstriction including the pulmonary vessels causing increase in the pulmonary vascular resistance 221.3±9 dynes • sec-1 • cm-5 in our study group vs 124.4±7.05 dynes • sec-1 • cm-5 after 40 minutes(p value <0.001)while after 48 hours 178±59.3 dynes • sec-1 • cm-5 vs 94.7±5.39 dynes • sec-1 • cm-5 (p =0.86) while at the study by Ozal and colleagues 2005 showed no marked difference although elevated PVRI 472±28 vs 465±23 dynes • sec-1 • cm-5 /m2 were recorded maybe due the drug was administrated 1 hour preoperatively at the I.C.U. in Ozal study.Although mean pulmonary pressure was comparable after induction(with p value=0.086 in our study,the after CPB studied time interval showed significant increase in the study group more than the control group (25.6±5.14 vs 21.05±1.5 mmHg) with p value<0.001,but the values returned comparable after 40 hours with values(20.37±2.94 vs 19.26±0.49 mmHg) with( p value=0.134), but it was noticed that the mean pulmonary never increased more than 25.73±4.09mmHg in its highest value.