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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.56 no.3 Campinas May/June 2006
Hemodynamic effects of aortic occlusion during inhalational anesthesia with isoflurane and sevoflurane. Experimental study in dogs*
Efectos hemodinámicos de la oclusión de la aorta durante anestesia por inhalación con isoflurano y sevoflurano. Estudio experimental en perros
Artur Udelsmann, TSAI; Derli Conceição MunhozII; Álvaro Edmundo Simões Ulhoa CintraIII; José Eduardo Tanus dos SantosIV
Doutor do Departamento de Anestesiologia da FCM-UNICAMP
IIProfessora Doutora do Serviço de Anestesiologia do HC-UNICAMP
IIIPós-Graduando do Departamento de Cirurgia da FCM-UNICAMP
IVProfessor Doutor do Departamento de Farmacologia da FMRP-USP
OBJECTIVES: Aortic flow suppression and release during aortic procedures
promote major hemodynamic disorders. This study aimed at evaluating these disorders
in dogs anesthetized with isoflurane or sevoflurane.
METHODS: This study involved 41 dogs divided in two groups according to the anesthetic agent used for maintenance with 1 MAC: GI (n = 21) isoflurane; GS (n = 20) sevoflurane. Aorta was occluded by intra-arterial infra-diafragmatic cuff inflation for 30 minutes. Hemodynamic parameters were observed in moments M1 (control), M2 and M3, 15 and 30 minutes after aortic occlusion, M4 and M5, 15 and 30 minutes after cuff deflation.
RESULTS: During aortic occlusion there has been increased mean blood pressure (MBP), central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP) and systemic vascular resistance (SVR), without increase in pulmonary vascular resistance (PVR) and cardiac output (CO). CO was more stable with isoflurane as compared to sevoflurane where it has decreased after occlusion. Heart rate has initially decreased followed by increase during occlusion, being more expressive in GS as compared to GI, however without statistically significant difference between groups. Systolic volume was not importantly changed; left and right ventricular function have similarly increased after occlusion for both groups. With flow release, MBP, CVP, PAP, PCWP and SVR have decreased, and PVR has increased for both groups; ventricular function has abruptly decreased.
CONCLUSIONS: This study has shown that isoflurane is a better indication for such interventions for promoting less hemodynamic changes.
Key Words: ANESTHETICS, General: isoflurane, sevoflurane; ANIMALS: dogs; SURGERY, Vascular: aortic occlusion
Y OBJETIVOS: La supresión del flujo aórtico y su posterior
liberación en intervenciones quirúrgicas de la aorta, ocasionan
importantes disturbios hemodinámicos. El objetivo de este estudio fue
el de evaluar esas alteraciones en perros anestesiados con isoflurano o sevoflurano.
MÉTODO: Se estudiaron 41 perros, divididos en dos grupos según el anestésico empleado en el mantenimiento con 1 CAM: GI (n = 21) isoflurano; GS (n = 20) sevoflurano. Se realizó la oclusión aórtica por insuflación de globo intraarterial infradiafragmático por 30 minutos. Los parámetros hemodinámicos fueron observados en los momentos M1 (control), M2 y M3, 15 y 30 minutos después de la oclusión aórtica, M4 y M5, 15 y 30 minutos después de la desinsuflación del globo.
RESULTADOS: Durante la oclusión de la aorta, se observó el aumento de la presión arterial promedio (PAM), de la presión venosa central (PVC), de la presión de arteria pulmonar (PAP), de la presión de capilar pulmonar (PCP) y de la resistencia vascular sistémica (RVS) sin aumento de la resistencia vascular pulmonar (RVP) y del débito cardíaco (DC). El DC se mantuvo más estable con el isoflurano comparado al sevoflurano, con el cual presentó disminución después de la oclusión. La frecuencia cardiaca tuvo disminución inicial que después aumentó durante la oclusión, siendo en GS más expresiva que en GI, sin embargo, sin diferencia significativa entre los grupos. El volumen sistólico no tuvo grandes alteraciones; el trabajo sistólico de los ventrículos izquierdo y derecho aumentó después de la oclusión de forma similar en los dos grupos. Con la liberación del flujo PAM, PVC, PAP, PCP y RVS bajaron, la RVP aumentó en los dos grupos; el trabajo ventricular disminuye abruptamente.
CONCLUSIONES: El estudio demostró que el isoflurano es el más indicado en esas intervenciones quirúrgicas por causar menores alteraciones hemodinámicas.
Surgical vascular procedures involving aneurysm correction are high-risk procedures, both due to the technique and to patients, mostly elderly with other co-morbidities 1,2.
Cardiovascular complications responsible for the higher incidence of morbidity and mortality after aortic interventions may be present both in the intra and the postoperative period. Factors affecting results include the action of anesthetic agents on coronary circulation and on cardiovascular system. Surgery-induced stress, hemodynamic changes caused by aortic cross-clamping and unclamping, coagulation disorders, pulmonary disorders and the anesthetic procedure itself also influence results 3,4.
Results have been favorable thanks to diagnostic enhancements, surgical technique improvement, better understanding of primary disease pathophysiology and of those affecting several organs, better hemodynamic control, adequate intra and postoperative monitoring and modern anesthetic techniques 5.
Aortic cross-clamping and unclamping during surgical correction promote major physiological changes. Patients' response to this stress depends on numerous variables, including ventricular function, volemia, presence and intensity of ischemic disease and cross-clamping level 3,6.
Several authors report decrease, increase or absence of cardiac index or left ventricular function changes, or of both, without heart rate variations. There are progressive cardiac function changes after cross-clamping and ischemia and acute dysfunction may be present as a consequence of preload increase by decreased cardiac compliance, in addition to afterload 3,6,7.
Anesthetic agents may influence the pathogenesis of cardiac changes during aortic cross-clamping and unclamping, promoting cardiovascular changes and mediator hormones release 3.
Halogenated agents promote vasodilation, which has advantages and disadvantages. They may control afterload and preload, but they may also increase the need for intravascular volume. They may also be used to treat stress-induced left ventricle filling pressure increase 8-10.
This study aimed at evaluating the influence of isoflurane and sevoflurane on cardiovascular function of dogs during aortic cross-clamping and unclamping.
After the Animal Research Ethical Committee, FCM-UNICAMP approval, 41 adult mixed-breed dogs of both genders, wei-ghing 15 to 20 kg were involved in this study. Animals were randomly distributed in two groups according to the inhalational agent:
Group I (GI) anesthetic maintenance with isoflurane.
Group S (GS) anesthetic maintenance with sevoflurane.
Hemodynamic and expired gases values were checked with Engstrom A/S-3 monitor. Brunson's proposition (1997) 11 establishing 1.28% isoflurane concentration and 2.36% sevoflurane concentration as MAC values for dogs was adopted. The experiment had two phases for both groups: the first consisted of anesthetic induction, tracheal intubation, mechanical ventilation, anesthetic maintenance with isoflurane or sevoflurane, ventilation monitoring, hemodynamic monitoring followed by aortic catheterization via left femoral artery aiming at preparing animals for infra-diafragmatic aortic occlusion with intra-arterial inflatable cuff. The second phase consisted of aortic flow occlusion for 30 minutes followed by flow release.
Animals fasted for 12 hours with free access to water. They were initially weighed and their body surfaces were calculated. Anesthesia was induced with intravenous thiopental (10 mg.kg-1) and vecuronium (0.1 mg.kg-1). Then, animals were placed in the Claude Bernard trough and the following procedures were performed:
- Tracheal intubation, installation of mechanically controlled ventilation in circle system with CO2 absorber, animal ventilation with tidal volume of 15 mL.kg-1 with a mix of compressed air and oxygen to maintain O2 saturation above 97%, checked by pulse oximetry. Respiratory rate was adjusted to maintain expired CO2 between 32 and 34 mmHg. Gases analyzer was installed at the endotracheal tube proximal edge;
- ECG at DII lead and thermometer on esophageal distal third;
- Inhalational agent administration using vaporizer specifically gauged for each halogenated agent, maintaining 1 MAC in expired gas;
- Left femoral vein dissection and catheterization for lactated Ringer's administration (5 mL.kg-1.h-1);
- Left carotid artery dissection and catheterization for mean arterial pressure monitoring (MAP);
- Left jugular vein dissection and 7F Swan-Ganz catheter insertion in the pulmonary artery to monitor cardiac output by thermodilution and for pressure monitoring; its correct position was confirmed through pressure curves morphology;
- Left femoral vein dissection and catheterization with Fogarty intra-arterial catheter positioned at the level of the infra-diaphragmatic aorta introducing it 1/3 of the muzzle-anus distance;
- Hemodynamic conditions stabilization for 15 minutes;
- Hemodynamic values monitoring at rest (M1);
- Aortic occlusion by intra-arterial cuff inflation, confirmed by the lack of right femoral pulses and disappearance of the oximetric plethysmographic wave at animal's tail;
- Hemodynamic values monitoring 15 minutes (M2) and 30 minutes (M3) after aortic occlusion;
- Intra-arterial cuff deflation and new monitoring 15 minutes (M4) and 30 minutes (M5) after;
- End of experiment and animal euthanasia with 20 mL of intravenous 19.1% potassium chloride.
Monitored values were: heart rate (HR beat.min-1), mean blood pressure (MBP mmHg), cardiac output (CO L.min-1), systolic volume (SV mL.beat-1), mean pulmonary artery pressure (PAP mmHg), central venous pressure (CVP mmHg), pulmonary capillary wedge pressure (PCWP mmHg), left ventricular sistolic work (LVSW g.min-1), right ventricular sistolic work (RVSW g.min-1), and cardiac (CI L.min-1.m-2), systolic (SI mL.beat-1.m2), systemic vascular resistance (SVRI dina.s.cm-5.m-2), pulmonary vascular resistance (PVRI dina.s.cm-5.m-2), left ventricular work (LVWI g.min-1.m-2) and right ventricular work (RVWI g.min-1.m-2) index.
Mann-Whitney test was used to check homogeneity between groups. Chi-square test was used for gender distribution. ANOVA was used for hemodynamic variables. Significance level was 5% (p < 0.05).
Groups were homogeneous in weight and gender distribution (Table I).
CO and CI in GS were significantly decreased in M2 after aortic occlusion as compared to GI (p = 0.0361 and 0.0358, respectively) starting to recover as from M3. There has been no change in CO and CI in GI throughout the experiment (Figures 1 and 2).
There has been no significant difference in HR throughout the experiment between groups, however, it was lower in GS in M2 as compared to M1 (p = 0.0188) followed by increase in M3 (p 0.0006). In GI it has increased between M2 and M3 (p = 0.0006) and between M3 and M4 (p = 0.0289) (Figure 3).
There was no difference in MAP between groups, however in both groups it has increased with occlusion in M2 (p = 0.0001) and in M3 (p = 0.0003), decreasing after clearing in M4 (p = 0.0001) and continuing to decrease in GS between M4 and M5. There was no significant difference in CVP between groups; it has increased immediately after occlusion in M2 (p = 0.0001) and remained stable until M3, significantly decreasing in M4 for both groups (Figures 6 and 7).
There has been no difference in PAP between groups. it has significantly increased in M2 for both groups (p = 0.0001), continued to increase in M3 only for GS (p = 0.0004) and decreased in M4 for both groups (p = 0.0004).
There has been no difference in PCPW between groups, it has significantly increased in M2 for both groups (p = 0.0001), continued increasing in M3 only for GS (p = 0.0121) till decreased in M4 for both GI and GS (p = 0.0001) (Figures 8 and 9).
SVR and SVRI have significantly increased in M2 after aortic occlusion for both groups (p = 0.0085 and 0.02, respectively), however increases in GS were significantly higher as compared to GI (p = 0.0001). In M3 they have decreased only in GS (p = 0.0203 and 0.0132, respectively) remaining stable for GI. After clearing in M4 they have decreased for both groups (p = 0.0012 and 0.0001) remaining with a minor difference until the end of experiment (Figures 10 and 11).
There was no difference in PVR between groups throughout the experiment. It has increased for both groups between M4 and M5 (p = 0.0307). PVRI had similar behavior and has increased between M4 and M5 only for GS (Figures 12 and 13).
LVW and LVWI have significantly increased in M2 for both groups, however they have been significantly higher for GI (p = 0.0157 and 0.0264). After clearing both parameters have decreased for both groups in M4 (p = 0.0001 for both), with further LVF decrease in GS (p = 0.0001) and ending the experiment with a significantly lower value in M5. LVFI has decreased for both groups between M4 and M5 ending as such in M5 without difference between groups (Figures 14 and 15).
RVF was higher for GI immediately after obstruction (M2) (p = 0.0388), remaining stable in this group until M3. It has significantly increased for GS between M2 and M3 (p = 0.0098). There was no difference in RVWI between groups, however there has been a significant increase in M2 for GI (p = 0.045) and between M2 and M3 for GS (p = 0.0007). Both RVSW and RVSWI have significantly decreased in M4 immediately after clearing (p = 0.0013 and 0.0009) (Figures 16 and 17).
Aortic occlusion, especially at the supraceliac level, promotes major hemodynamic changes (increased blood pressure, vascular wall abnormalities, increased ventricular wall tension, decreased cardiac output, decreased renal blood flow, decreased ejection fraction, increased pulmonary capillary wedge pressure and coronary blood flow) and metabolic changes (decreased total oxygen consumption and carbon dioxide production, increased venous mixed oxygen saturation, decreased oxygen extraction, increased catecholamines, respiratory alkalosis). The mechanisms of such responses remain controversial. In addition to increased afterload, proposed etiologies include preload changes, blood volume distribution, myocardial performance and sympathetic nervous system activation 3.
In this experimental study with dogs submitted to ischemia and reperfusion, CO, CI, SV, SI, SVR, SVRI, PVR, PVRI, LVSW and LVSWI were significantly different according to the inhalational agent. As compared to baseline conditions, these variables were less affected by isoflurane as compared to sevoflurane.
The experiment resulted in considerable increase in SVR, followed by marked increase in MBP, CVP, PAP and PCWP without increase in PVR, CO and CI. CO and CI were more stable under isoflurane as compared to sevoflurane. HR was changed with both drugs with less variation with isoflurane. SV and SI have not significantly changed, however they were always higher with isoflurane.
Increased SVR may be explained by proximal vasoconstriction in response to excessive blood flow blocked in the ventral region and also by distal vasoconstriction as initial reflex response to sudden blood flow decrease in the extremities, resulting in tissue ischemia and cellular anoxia. Aortic cross-clamping is associated to increased adrenergic sympathetic activity promoting arteriolar vasoconstriction and capillary flow decrease (increase in SVR) 12. SVR has further increased with sevoflurane as compared to isoflurane. CVP values showed increased volemia upstream to the occlusion, promoting higher cardiac muscle effort and higher need to adjust coronary flow faced to increased preload. High pulmonary artery and pulmonary capillary wedge pressures are reflexes of increased blood flow and of decreased ventricular chambers capacity to eject such volume.
There were no significant differences between drugs in MBP, CVP, PAP and PCWP. MBP depends on SVR and CO and remained high throughout arterial occlusion. Highest MBP value was observed during HR recovery, during ischemia. The highest CO variation in the sevoflurane group was probably due to decreased HR. We suppose that HR was decreased with the increase in afterload, but with extremities hypotension, in an attempt to compensate low blood flow to these areas associated to regional vasoplegia and to the presence of protective mechanisms, HR has again increased.
SV was virtually unchanged with cross-clamping as a consequence of volemia redistribution, increased preload, myocardial compensation (increased contractility) and HR variations.
LVSW and RVSW had similar changes in both groups. These results are in line with other studies where it has been observed that blood shift results in increased left ventricular preload 6,13. Other authors, however, attribute this to increased aortic flow impedance with increased afterload 6,14.
Rennin activity, which increases with supra-renal or infra-renal aortic occlusion, may contribute to hypertension. Increased epinephrine and norepinephrine concentrations after aortic occlusion may help increase myocardial contractility to adapt to high afterload and preload 6,15,16.
Isoflurane had a higher vasodilating effect as compared to sevoflurane since during occlusion in GS there has been further increase both in SVR and HR and these results are in line with other studies 17-19.
There has been multifactorial genesis decrease in MBP, CVP, PAP and PCWP after blood flow release 3. Volemia was readapted to vasoplegic distal vascular bed, probably as result of tissue hypoxia, of the action of vasodepressor agents produced by ischemic tissues and of myogenic response 3,20.
Abdominal aorta release is often associated to decreased SVR, venous return and MBP 21. There is immediate hemodynamic response to aortic flow release following a reflex or mechanical phenomenon.
Vasoactive metabolites, high potassium concentration, lactic acid and myocardial depressing factors accumulated during aortic obstruction and promptly released in circulation may exacerbate hemodynamic effects 22.
Increased HR was a consequence of the attempt to compensate MBP after preload decrease and peripheral dilatation. CVP decrease has affected volume supply to maintain CO, which has slowly decreased. PVR has increased in this stage for both groups. Ventricular function, as expected, has markedly decreased with flow release.
The effects of volatile anesthetics during ischemia and reperfusion, protecting or decreasing cellular aggressions, are still not totally understood. Experimental studies by other authors have shown that hemodynamic parameters changed during aortic obstruction have returned to normal after flow release 9.
On the other hand, clinical experiments have shown that depending on left ventricular filling, hemodynamic variables may remain unchanged, may increase or decrease 23,24.
It was possible to conclude that in experimental conditions in dogs anesthetized with isoflurane or sevoflurane in equipotent concentrations, hemodynamic changes were lower in the isoflurane group as compared to the sevoflurane group. These results are opposed to other authors 25, also in animal studies, where no differences were found between isoflurane and sevoflurane. Although one cannot categorically state, aortic occlusion performed at a lower level as compared to our study might have contributed for such.
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Submitted for publication
4 de agosto de 2005
Accepted for publication 8 de fevereiro de 2006
* Received from Laboratório de Anestesia Experimental do Núcleo de Medicina e Cirurgia Experimental da Faculdade de Ciências Medicas da Universidade de Campinas (FCM-UNICAMP).