Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping

Abstracts

JUSTIFICATIVA E OBJETIVOS: A endarterectomia carotídea com pinçamento transitório altera a relação entre o fluxo sangüíneo cerebral e a demanda metabólica cerebral de oxigênio, com conseqüente geração de uma tendência a hipóxia oliguêmica ou desacoplamento hemometabólico. O objetivo do presente estudo foi identificar as alterações do hemometabolismo cerebral, avaliados através das alterações da saturação da oxihemoglobina no bulbo da veia jugular interna (SjO2), durante endarterectomia carotídea com pinçamento, correlacionando essas alterações com fatores com potencialidade de interferir com as mesmas, principalmente a pressão de CO2 expirada (P ET CO2) e a pressão de perfusão cerebral (PPC). MÉTODO: Participaram do estudo 16 pacientes com doença estenosante unilateral e submetidos a pinçamento arterial transitório durante endarterectomia carotídea. Os parâmetros monitorizados (saturação da oxihemoglobina no bulbo da veia jugular interna, stump pressure e a pressão de CO2 expirado) foram analisados nos seguintes momentos: M1 - pré-pinçamento; M2 - 3 minutos pós-pinçamento; M3 - pré- despinçamento; M4 - pós-despinçamento. RESULTADOS: A comparação entre a SjO2 (%, Média ± DP) nos períodos estudados evidenciou uma diferença entre a registrada nos momentos M1 (52,25 ± 7,87) e M2 (47,43 ± 9,19). Essa redução inicial estabilizou-se durante o pinçamento transitório, com diminuição na comparação entre M2 e M3 (46,56 ± 9,25), sem significado estatístico (p = ns). Na fase pós-despinçamento, M4 (47,68 ± 9,12), a média da SjO2 apresentou uma elevação, quando comparada com os momentos de pinçamento M2 e M3, ainda inferior ao momento pré-pinçamento M1 (M4 x M1 - p < 0,04). Essa diminuição da SjO2 foi acompanhada de diminuição significante da pressão de perfusão cerebral (stump pressure). Os fatores que influenciam essa tendência ao desacoplamento hemometabólico cerebral apresentaram um forte índice de correlação com a P ET CO2. A comparação entre a PPC e a SjO2 apresentou um fraco índice de correlação, sem significância estatística. CONCLUSÕES: Nas condições deste estudo a aferição da SjO2 é um modo de monitorização clínico efetivo e de rápida resposta na evidenciação das alterações da relação FSC/CCO2; o pinçamento carotídeo transitório implica em tendência ao desacoplamento hemometabólico cerebral e conseqüentemente, hipóxia oliguêmica; a PPC de forma isolada, não avalia a situação hemometabólica cerebral (relação entre FSC e o CCO2); a hipocapnia pode levar a situações de desacoplamento hemometabólico; a monitorização da P ET CO2 é forma inócua e eficiente de monitorizar a PaCO2, evitando situações de hipocapnia inadvertidas, com seus efeitos deletérios sobre a relação FSC/CCO2, durante pinçamento carotídeo transitório.

CIRURGIA; CIRURGIA; MONITORIZAÇÃO; MONITORIZAÇÃO

SCIENTIFIC ARTICLE

Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping^*

Análisis del comportamiento del hemometabolismo cerebral durante endarterectomia carotídea con pinzamiento transitorio

Gastão Fernandes Duval Neto, TSA, M.D.^I; Augusto H. Niencheski, M.D.^II

^IProfessor Doutor Adjunto

^IICirurgião Vascular Periférico

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: Carotid endarterectomy with temporary clamping changes cerebral blood flow and cerebral metabolic oxygen demand ratio with consequent oligemic hypoxia or hemometabolic uncoupling. This study aimed at identifying changes in brain hemometabolism, evaluated through changes in oxyhemoglobin saturation in internal jugular vein bulb (SvjO₂) during carotid endarterectomy with clamping, and at correlating these changes with potentially interfering factors, mainly end tidal CO₂ pressure (P_ETCO₂) and cerebral perfusion pressure (CPP).

METHODS: Sixteen patients with unilateral carotid stenotic disease scheduled to carotid endarterectomy with carotid arterial clamping were enrolled in this study. Parameters including internal jugular bulb oxyhemoglobin saturation, stump pressure and end tidal CO₂ pressure were measured at the following moments: M₁ - pre-clamping; M₂ - 3 minutes after clamping; M₃ - pre-unclamping; M₄ - post-unclamping).

RESULTS: The comparison among SvjO₂ (%, mean ± SD) in all studied periods has shown differences between those recorded in moments M₁ (52.25 ± 7.87) and M₂ (47.43 ± 9.19). This initial decrease stabilized during temporary clamping, showing decrease in the comparison between M₂ and M₃ (46.56 ± 9.25), without statistical significance (p = ns). At post-unclamping, M₄ (47.68 ± 9.12), SvjO₂ was increased as compared to M₂ and M₃ clamping stages, however it was still lower than that of pre-clamping stage M₁.(M₄ x M₁ - p < 0.04) This SvjO₂ decrease was followed by significant cerebral perfusion pressure (stump pressure) decrease. Factors influencing this brain hemometabolic uncoupling trend were correlated to P_ETCO₂. The comparison between CPP and SvjO₂ showed weak correlation devoid of statistical significance.

CONCLUSIONS: In the conditions of our study, SvjO₂ measurement is a fast and effective way of clinically monitoring changes in CBF/CMRO₂ ratio. Temporary carotid clamping implies in a trend towards brain hemometabolic uncoupling and, as a consequence, to oligemic ischemia; cerebral perfusion pressure does not assesses brain hemometabolic status (CBF and CMRO₂ ratio); hypocapnia, may lead to brain hemometabolic uncoupling; P_ETCO₂ monitoring is an innocuous and efficient way to indirectly monitor PaCO₂ preventing inadvertent hypocapnia and its deleterious effects on CBF/CMRO₂ ratio during temporary carotid clamping.

Key Words: MONITORING: jugular bulb oxyhemoglobin saturation, brain oximetry; SURGERY, Vascular: carotid endarterectomy

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La endarterectomia carotídea con pinzamiento transitorio altera la relación entre el flujo sanguíneo cerebral y la demanda metabólica cerebral de oxígeno, con consecuente generación de una tendencia a hipóxia oliguemica o desacoplamiento hemometabólico. El objetivo del presente estudio fue identificar las alteraciones del hemometabolismo cerebral, evaluados por medio de las alteraciones de la saturación de la oxihemoglobina en el bulbo de la vena yugular interna (SjO₂), durante endarterectomia carotídea con pinzamiento, correlacionando esas alteraciones con factores con potencialidad de interferir con las mismas, principalmente la presión de CO₂ expirada (P_ETCO₂) y la presión de perfusión cerebral (PPC).

MÉTODO: Participaron del estudio 16 pacientes con enfermedad estenosante unilateral y sometidos al pinzamiento arterial transitorio durante endarterectomia carotídea. Los parámetros monitorizados (saturación de la oxihemoglobina en el bulbo de la vena yugular interna, stump pressure y la presión de CO₂ expirado) fueron analizados en los siguientes momentos: M₁ - pre-pinzamiento; M₂ - 3 minutos pos-pinzamiento; M₃ - pre-despinzamiento; M₄ - pos-despinzamiento.

RESULTADOS: La comparación entre la SjO₂ (%, Media ± DP) en los períodos estudiados evidenció una diferencia entre la registrada en los momentos M₁ (52,25 ± 7,87) y M₂ (47,43 ± 9,19). Esa reducción inicial estabilizó durante el pinzamiento transitorio, con disminución en la comparación entre M₂ y M₃ (46,56 ± 9,25), sin significado estadístico (p = ns). En la fase pos despinzamiento, M₄ (47,68 ± 9,12), la media de la SjO₂ presentó una elevación, cuando comparada con los momentos de pinzamiento M₂ e M₃, más inferior al momento pre-pinzamiento M₁ (M₄ x M₁ - p < 0,04). Esa disminución de la SjO₂ fue acompañada de disminución significante de la presión de perfusión cerebral (stump pressure). Los factores que influencian esa tendencia al desacoplamiento hemometabólico cerebral presentaron correlación con la P_ETCO₂. La comparación entre la PPC y la SjO₂ presentó un bajo índice de correlación, sin significación estadística.

CONCLUSIONES: En las condiciones de este estudio la aferición de la SjO₂ es un modo de monitorización clínico efectivo y de rápida respuesta en la evidenciación de las alteraciones de la relación FSC/CCO₂; el pinzamiento carotídeo transitorio implica en una tendencia al desacoplamiento hemometabólico cerebral y consecuentemente, hipóxia oliguemica; la PPC de forma aislada, no evalúa la situación hemometabólica cerebral (relación entre FSC y el CCO₂); la hipocapnia puede llevar a situaciones de desacoplamiento hemometabólico; la monitorización de la P_ETCO₂ es forma inocua y eficiente de monitorizar la PaCO₂, evitando situaciones de hipocapnia inadvertidas, con sus efectos deletéreos sobre la relación FSC/CCO₂, durante pinzamiento carotídeo transitorio.

INTRODUCTION

Carotid endarterectomy has been considered superior for severe and symptomatic carotid stenotic disease when compared to clinical treatment ^1,2, but this benefit is significantly lower in asymptomatic carotid stenosis ³.

Ischemic brain injuries are factors significantly contributing for increased perioperative morbidity and mortality in carotid endarterectomy with temporary intraoperative clamping. In theory, the pathophysiology of such complications is explained by thromboembolic processes ^4-6, hemodynamic changes ⁷ or both.

Global blood flow and brain metabolic oxygen demand ratio characterizes the so-called brain hemometabolism, which may be evaluated by the measurement of oxyhemoglobin saturation of venous blood samples drawn from the internal jugular vein bulb ipsilaterally to the surgically intervened carotid artery. On the other hand, regional changes between flow and brain O₂ demand, secondary to thromboembolic episodes, are not detectable with this type of monitoring ^8,9.

Anesthesiologists may significantly influence brain hemometabolism during carotid endarterectomy, especially through intraoperative mechanical ventilation control (CO₂ arterial pressure) and/or hemodynamic control (cerebral perfusion pressure) during temporary common carotid artery clamping.

This study aimed at identifying brain hemometabolism changes evaluated through oxyhemoglobin changes in jugular bulb venous oxygen saturation (SvjO₂) during carotid endarterectomy with temporary intraoperative arterial clamping, and at correlating such changes to factors potentially interfering with them, especially end-tidal CO₂ pressure (P_ETCO₂) and cerebral perfusion pressure (CPP).

METHODS

After Ethics Committee approval and informed consent, 16 patients of both genders, 65 ± 10.3 year-old, with symptomatic carotid stenotic disease scheduled to unilateral carotid endarterectomy were enrolled in the study. All obstructive lesions were symptomatic and unilateral with diameter equal to or above 70%, and diagnosed by Doppler ultrasound (Sonos 2000 - Hewlett Packard with 7.5 MHz transducer) and/or arteriography with digital subtraction of carotid and vertebral vascular beds. Carotid and vertebral arteries opposite to the stenotic vessels had no critical lesions.

Patients on drugs with cerebro-vascular actions as well as diabetic patients were excluded from the study. No patient had hemoglobin or hematocrit abnormalities that could impair oxygen transportation. Anesthesia was induced with propofol (2 mg.kg^-1) and sufentanil (0.15 µg.kg^-1) and was maintained with inhaled isoflurane associated with sufentanil boluses, in order to maintain stable anesthetic depth based on hemodynamic parameters. Muscle relaxation was achieved with atracurium (0.5 mg.kg^-1) and neuromuscular block intensity was assessed with peripheral nerve stimulator, in order to obtain no muscle responses at TOF stimulation. Patients were mechanically ventilated with tidal volumes of 8 mL.kg^-1 at 10 cycles per minute. P_ETCO₂ was used to adjust the ventilatory regimen.

Retrograde ipsilateral internal jugular vein catheterization was performed under direct vision with 17G 5.1 cm length needle (1.5 mm) through which a 19G (1.1 mm) 30 cm length radio-opaque catheter (Intracath^® and Vialon^® wire guide - Becton-Dickinson, USA) was inserted. Cephalad catheter progression was slowly and carefully performed until elastic resistance corresponding to upper internal jugular vein bulb wall was perceived. When this occurred, catheter was removed approximately 5 mm maintaining smooth and continuous aspiration until continuous venous flow was obtained, a maneuver that indicates catheter detachment from bulb wall. The jugular bulb catheter was connected to the 3-way stop-cock and continuously flushed with heparinized saline solution (2500 U in 250 ml saline solution), at 1 mL.h^-1.

Sampling consisted of gentle aspiration of 3 ml jugular bulb venous blood in 90 s in order to prevent contamination with extra-cranial venous blood. Samples were collected at pre-established observation moments.

Common carotid artery catheterization distally to clamping site (common and external carotid) was performed under direct vision with a 5-French Swan-Ganz catheter (BIOMEDICA^® USA) to measure mean arterial blood pressure, which was considered cerebral perfusion pressure (CPP), which was measured by a BIOMONITOR 7^® (Bese - Bio Engenharia de Sistema e Equipamentos S.A. - Belo Horizonte, MG), zeroed at the mid-axillary line. For measuring distal (cranial) mean blood pressure, the catheter cuff was inflated. Stump pressures lesser than 25 mmHg from baseline were considered indication for temporary shunt, and patients were excluded from the study.

Radial artery was catheterized with 18G catheter for continuous mean blood pressure monitoring (Biomonitor 7^® - Bese - Bio Engenharia de Sistema e Equipamento S.A. - Belo Horizonte, MG) and blood sampling for gas analysis (PaCO₂).

Arterial (radial artery) and venous (internal jugular vein bulb) blood samples were simultaneously collected at the ratio of 2 mL of arterial to 1 mL venous blood, at the observation moments. One ml of venous sample was used to measure SvjO₂ in a hemoximeter (Hemoximeter™ OMS3^® - Radiometer^® - NV, Denmark 1991), and the 2-mL arterial sample was sent to arterial blood gases analysis (178 pH/Blood Gas Analyzer - Corning Glass Works^® - Corning Limited, Halstead, Essex, England). Arterial hemoglobin saturation was kept stable throughout the procedure.

Measurements were performed at the following moments: M₁ - previously to carotid clamping, M₂ - 3 minutes after carotid clamping, M₃ - immediately before carotid unclamping, and M₄ - 3 minutes after carotid unclamping.

Statistical analysis included Student's t, Fisher and Pearson's r correlation coefficients as appropriate. Significance level was 5% (p < 0.05).

RESULTS

Mean patients' age was 65 ± 10.3 years. No patient had procedure-related neurological complications in the 48-hour postoperative period of observation in the intensive care unit).

MBP and SvjO₂ were maintained stable as shown in table I.

Brazilian Journal of Anesthesiology, 2004; 54: 2: 162 - 177

Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping

Gastão Fernandes Duval Neto; Augusto H. Niencheski

Jugular oxyhemoglobin saturation (SvjO₂) - comparisons of SvjO₂ (% mean ± SD) detected in studied periods showed statistically significant differences between M₁ (52.25 ± 7.87) and M₂ (47.43 ± 9.19) (p < 0.02). This decrease stabilized during temporary clamping with mild non-significant decrease in the comparison between M₂ and M₃ (46.56 ± 9.25). At M₄ mean SvjO₂ was increased as compared to M₂ and M₃ (47.68 ± 9.12), but still lower than M₁ (M₄ x M₁ - p < 0.04) (Figure 1).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 162 - 177

Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping

Gastão Fernandes Duval Neto; Augusto H. Niencheski

Cerebral perfusion pressure - comparisons of CPP (mmHg, mean and SD) showed statistically significant differences between M₁ (70.31 ± 12.46) and M₂ (39.00 ± 6.68) (p < 0.001). This decrease stabilized during temporary carotid clamping, while keeping statistically significant difference when M₂ was compared to M₃ (50.75 ± 10.66) (p < 0.01). At M₄ (63.50 ± 10.49), CPP has significantly increased (p < 0.03), however remaining below M₁ (p < 0.05), that is, not reaching pre-clamping pressures (Figure 2).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 162 - 177

Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping

Gastão Fernandes Duval Neto; Augusto H. Niencheski

Correlation between SvjO₂ (%) and CPP (mmHg) - figure 3 shows linear regression between studied variables, with a weak correlation coefficient and without statistical significance (r = 0.089; p = ns).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 162 - 177

Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping

Gastão Fernandes Duval Neto; Augusto H. Niencheski

Correlation between PaCO₂ and P_ETCO₂ - figure 4 shows linear regression with strong positive and statistically significant correlation (r = 0.94; p < 0.0001) between PaCO₂ and P_ETCO₂. No changes were seen in such parameters in the opposite direction, that is increased PaCO₂ has always corresponded to increased P_ETCO₂.

Brazilian Journal of Anesthesiology, 2004; 54: 2: 162 - 177

Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping

Gastão Fernandes Duval Neto; Augusto H. Niencheski

Correlation between SvjO₂ and PaCO₂ - linear regression illustrated in figure 5 shows a moderate correlation between PaCO₂ and SvjO₂ (r = 0.69; p < 0.0001).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 162 - 177

Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping

Gastão Fernandes Duval Neto; Augusto H. Niencheski

Correlation between SvjO₂ and P_ETCO₂ - linear regression shown in figure 6 shows a moderate correlation between P_ETCO₂ and SvjO₂ (r = 0.72; p < 0.0001), which is consistent with previous correlation (Figure 6).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 162 - 177

Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping

Gastão Fernandes Duval Neto; Augusto H. Niencheski

DISCUSSION

Patients submitted to carotid endarterectomy are at risk of developing perioperative brain complications, which are very often clinically evidenced during the anesthetic recovery period. These complications may be attributed to two major pathophysiological mechanisms: hemodynamic, by changing cerebral blood flow as a consequence of temporary carotid clamping, or by thromboembolic phenomena secondary to surgical handling of arterial vascular system, resulting in atheromatous plaque displacement and, eventually, brain microembolism ^4-7.

The brain is dependent on glucose mitochondrial aerobic oxidation to produce the necessary energy for its normal cellular functioning. Approximately 50% of this energy is used in maintaining and restoring ionic gradients necessary for depolarization and repolarization of neuronal membranes and the remaining 40% are spent in maintaining cell integrity. On the other hand, the brain has little glucose reserve and low adenosine triphosphate concentration (ATP). For this reason, the maintenance of adequate cerebral blood flow (CBF) to supply tissue metabolic demands (brain oxygen consumption - CMRO₂) is critical for the anatomicofunctional integrity of central nervous system neurons.

Although brain represents only 2% of body weight, its high metabolic index requires 15% of cardiac output to maintain a perfect brain oxygen supply/consumption ratio (CBF/CMRO₂).

CBF/CMRO₂ ratio, that is, the hybrid association between hemodynamic and metabolic phenomena is clinically evaluated as a whole, and called brain hemometabolism. Although varying CBF and CMRO₂, the ratio between these two variables is maintained within narrow limits. In fact, tissue CMRO₂ participates in brain vascular resistance control through CO₂ production, thus regulating CBF. This phenomenon is called brain hemometabolic coupling (BHMC) ¹⁰.

Brain O₂ release (BRO₂) may be described by the following equation:

BRO₂ = CBF x CaO₂

Where

CaO₂ - arterial oxygen content

On the other hand, CMRO₂ may be calculated by the following equation:

CMRO₂ = CBF x (CaO₂ - CvjO₂)

Where

CvjO₂ - jugular bulb venous oxygen content

The difference between arterial and jugular bulb venous oxygen content is expressed as (CaO₂ - CvjO₂) or D_ajvO₂. Thus, the above equation may be modified as follows:

D_ajvO₂ = CMRO₂ / CBF

It is possible to calculate D_ajvO₂ through CBF and CMRO₂ or, in a more practical and clinical manner, through the arterial and jugular oxygen content.

DajO₂ = CaO₂ - CjO₂

Blood (arterial or venous) oxygen content results from the addition of volumes of oxygen bound to hemoglobin and dissolved in plasma.

CaO₂ = Hb_a x1.39 x SaO₂ + PaO₂ . 0.003

CjO₂ = Hb_jv x 1.39 x SvjvO₂ + PjvO₂ . 0.003

PaO₂ - O₂ arterial pressure

PjvO₂ - jugular bulb venous O₂ pressure

Hb_a - arterial hemoglobin concentration

Hb_jv - jugular venous hemoglobin concentration

0.003 - O₂ solubility coefficient

O₂ content (CaO₂ - CjvO₂) is the total amount of this gas carried by a certain blood volume and resulting in the following formula:

DajO₂ = [(SaO₂.Hb_a) - (SvjO₂.Hj_j)],1.39 - [PaO₂ - PjO₂].0.003

100

Considering the low O₂ plasma solubility (solubility coefficient = 0.003) it is acceptable to disregard the participation of O₂ dissolved in plasma in calculating blood oxygen content. Arterial hemoglobin is similar to venous hemoglobin allowing the consideration of just one value. Thus:

DajvO₂ = (SaO₂ -SvjO₂) x Hb x 1.39

DajvO₂ has been used to establish the presence or absence of an auto-regulation system of the functioning CBF/CMRO₂ ratio.

As previously presented, provided Hb is kept stable and SaO₂ is the highest (close to 100%), DajvO₂ becomes a direct reflex of SvjO₂ (since SaO₂, Hb and 1.39 are constant). SvjO₂ and DajvO₂ may also represent the amount of O₂ extracted from CBF in a time unit. In fact, brain O₂ extraction (ECO₂) is a function of the difference of arterio-jugular content over arterial content.

ECO₂ = (CaO₂ - CjO₂)

CaO₂

If the same previously considered simplifications are applied, we have:

ECO₂ = (SaO₂ - SvjO₂)

SaO₂

When maximum arterial blood Hb (100%) is almost reached, as it was the case in this study (Figure 1), extraction is directly represented by jugular blood hemoglobin saturation, that is, by SvjO₂.

ECO₂ = 1 - SvjO₂

It is clear from the above that SvjO₂ is a function of CBF and CMRO₂ ratio. So, continuous or intermittent SvjO₂ monitoring is a fast and simple way to monitor brain hemometabolic status during carotid clamping in endarterctomies.

In such conditions, direct SvjO₂ analysis identifies and quantifies brain hemometabolic status (global brain oxygenation) in a certain moment. This monitoring does not evaluate regional ischemic or perfusional hemometabolic changes ^8,9.

In general, DajvO₂ is stable around 4 to 8 ml of O₂ per 100 mL of CBF. If CMRO₂ remains constant, DajvO₂ changes may reflect CBF changes. On one hand, DajvO₂ < 4 mL of O₂ per 100 mL^-1 CBF confirms that O₂ supply is higher than demand (luxuriant CBF); on the other hand, DajvO₂ > 8 mL of O₂ per 100 mL^-1 CBF suggests demand greater than flow, which characterizes a clinical situation of oligemic brain ischemia ^11-14.

When CMRO₂ is increased without simultaneous CBF increase, brain increases arterial blood O₂ extraction resulting in decreased O₂ content or effluent brain venous blood oxyhemoglobin saturation (internal jugular vein bulb), that is widening of DajvO₂ or narrowing of SvjO₂. Normal SvjO₂ range between 55% and 75% is lower than systemic venous blood saturation ^14,15.

Since SvjO₂ is a global measure, its monitoring is highly specific but poorly sensitive for ischemia, that is, normal SvjO₂ may not reflect areas of focal brain ischemia, but low SvjO₂ is indicative of low global cerebral blood flow ¹⁵.

A study ¹⁶ suggests that minimum SvjO₂ level to promote neurological injuries is bellow 50%. When lower SvjO₂ levels are detected, therapeutic interventions to increase CBF or decrease CMRO₂ are indicated.

There are clinical situations, among them temporary carotid clamping, potentially able to generate brain hemometabolism uncoupling, which are clinically characterized by SvjO₂ decrease due to relative increase in oxygen extraction by brain tissues. This phenomenon, as previously seen, may be called oligemic ischemia.

In our study, figure 1 represents an analysis of SvjO₂ behavior of the whole population of studied patients (n = 16) in pre-established observation moments. This analysis has shown that in comparing SvjO₂ values (%, Mean ± SD) found in M₁ (pre clamping) and M₂ (3 minutes after clamping), there has been a statistically significant decrease.

The period between M₂ and M₃ (clamping period) has shown a mild trend to SvjO₂ decrease, without statistical significance. These findings represent clinically changes in CBF:CMRO₂ ratio, which tends to stabilize during the total clamping period. This phenomenon is evidenced by comparing moments M₂ and M_3, suggesting that stabilization may be attributed to the interference of CBF auto-regulation mechanisms.

In comparing SvjO₂ in moments M₃ (previously to unclamping) and M₄ (after unclamping) a significant increase was found there, showing improvement in CBF:CMRO₂ ratio with reestablishment of carotid blood flow, although this increase does not reach normal values even when M₄ is compared to M₁ (p < 0.04).

Results in figure 1 suggest that carotid clamping during endarterectomy results in a trend to significantly change CBF:CMRO₂ ratio, that is, brain metabolism, with the possibility of generating a situation of hemometabolic uncoupling or oligemic ischemia. The downward trend of SvjO₂ during this procedure suggests that collateral or retrograde cerebral blood flow through contralateral carotid and/or vertebral arteries, may not be sufficient to keep stable the ratio. Several factors may potentiate this change in CBF:CMRO₂ ratio, among them cerebral perfusion pressure and CO₂ arterial pressure.

In our study, the short period between carotid clamping and/or unclamping and SvjO₂ changes demonstrates its sensitivity to global brain perfusion changes when MBP, Hb concentration and SaO₂ are kept stable and within the normal range. Therefore, SvjO₂ may help in detecting brain ischemic episodes during carotid endarterectomy with carotid clamping and may be included among evaluation parameters for the installation of shunts during clamping, especially in some special situations where there is previous difficulty in maintaining CBF auto-regulation, such as diabetes.

In continuing this study, some clinical parameters, cerebral perfusion pressure (CPP) and end tidal CO₂ pressure (P_ETCO₂) were evaluated, which may potentially influence brain hemometabolism changes during temporary carotid clamping.

Stump pressure (carotid stump pressure) represents mean blood pressure measured in the internal carotid artery, distally to the common and the external carotid clamping sites. This measurement represents the pressure retrogradely transmitted along the ipsilateral carotid artery, by ipsilateral vertebral artery and/or by contralateral carotid artery ¹⁷.

Cerebral perfusion pressure (CPP) may be calculated by the following equation:

CPP = MBP - ICP (or CVP)

Where

MBP - mean blood pressure

ICP - intracranial pressure

CVP - central venous pressure.

Considering that in our patients ICP was normal and stump pressure has been measured directly in the internal carotid artery, it was considered representative of cerebral perfusion pressure (CPP).

Brain perfusion pressure is a monitor often used as indicator of brain perfusion quality during carotid clamping and, according to some vascular surgeons and anesthesiologists, it may be taken into consideration for the indication of intraoperative carotid shunt. However, the literature ^18-20 is controversial about its usefulness as a sole method to assess the quality of brain perfusion during this type of surgical procedure, based on the following assumptions:

1. Lack of conclusive data evidencing the relationship between CPP and the incidence of perioperative morbidity/mortality;

2. Controversy about normal pressure level;

3. Evidence of major influence of anesthetic techniques on this type of monitor.

A study ²¹ has shown that stump pressure does not correlate well with CBF because significant EEG changes, suggestive of brain ischemia generated by critical regional CBF levels, may be detected with pressures above 50 mmHg. On the other hand, there may be situations of absence of EEG signals suggestive of brain ischemia, with stump pressures below 50 mmHg.

The major objective of CBF auto-regulation system is to maintain a stable CBF/CMRO₂ ratio during variations of their component factors, maintaining optimal conditions for normal neuronal function performance.

CBF is a function of CPP and cerebro-vascular resistance (CVR) ratio, that is:

CBF = CPP - CVR

Where

CVR - cerebro-vascular resistance

It is important to stress that CVR is dependent on two variables - blood viscosity and brain arterial vascular diameter.

Based on the above-mentioned equation, one may conclude that CPP alone does not reflect CBF; so, it does not represent CBF/CMRO₂ ratio.

In a recent study ²² that compared CPP monitoring to SvjO₂ and consequent brain perfusion control and prophylaxis during carotid endarterectomy with temporary clamping, the latter parameter was considered superior.

Table I and figure 2 represent, respectively, MBP and CPP evolution during the study period. It is note-wise that even with stable MBP, CPP has significantly changed after carotid clamping. CPP decrease after clamping suggests the possibility of CBF/CMRO₂ ratio changes with consequent brain hemometabolism change.

Figure 3 shows a linear regression between CPP to SvjO₂. A weak non-significant correlation coefficient can be observed between them. Thus, considering SvjO₂ as a sensitive method for CBF/CMRO₂ ratio evaluation, one may conclude that isolated mean arterial pressure measurement at the vascular stump distal to clamping is not a safe monitor to evaluate the stability of the CBF/CMRO₂ ratio. As a consequence, it should not be considered, by itself, a major parameter for the indication of temporary carotid shunt.

The second evaluated factor was the interference of P_ETCO₂ on brain hemometabolism.

CBF changes secondary to PaCO₂ variations without simultaneous changes in tissue pH seem to be a way to maintain brain hemometabolic coupling. Increased PaCO₂ increases CBF, allowing an effective washout of the metabolically produced CO₂, the opposite being true during hypocapnia ²³.

Hypocapnia results in vasoconstriction that may reach the threshold for brain tissue hypoxia and anaerobic metabolism, causing adverse effects on brain cell activity. Additionally, hypocapnia causes left-shift of the Hb dissociation curve, exacerbating brain tissue hypoxia by impairing O₂ release. These phenomena result in increased H⁺ ions and consequent decrease in brain tissue pH ²⁴.

Brain vascular reactivity to CO₂ is mediated by pH changes in the CSF surrounding the arteriolar bed, where pH depends on arterial blood pressure of free CO₂, which crosses the blood-brain barrier, and on the concentration of bicarbonate in CSF. The understanding of the double-nature of CBF chemical control (arterial CO₂ and CSF bicarbonate) is important to justify the pathophysiology of brain vasoplegia during brain metabolic acidosis followed by hemometabolic uncoupling. Some authors suggest that intracellular pH in vascular smooth muscles influences brain vascular tone, by the activation of NMDA (N-methyl-D-aspartate) receptors, which causes changes in intracellular ionic calcium concentrations ^25,26.

Brain arteriolar tone regulated by MBP modulates the effects of PaCO₂ on CBF. For example: moderate arterial hypotension blocks the ability of cerebral circulation to respond to PaCO₂ changes, while severe arterial hypotension totally abolishes this mechanism. On the other hand, PaCO₂ changes MBP-dependent CBF auto-regulation mechanism, that is, starting from a situation of hypercapnia toward hypocapnia, there is a widening of the plateau of the auto-regulation curve ^27,28.

Some studies ^29,30 have considered P_ETCO₂ measurement as a valid estimate of PaCO₂ during anesthesia, in situation of no clinical intra-cardiac shunt, pathological increase of the alveolar dead space or compensation of metabolic acid-base abnormalities. In addition, P_ETCO₂ values are 2 to 5 mmHg lower than PaCO₂.

A study aiming at comparing PaCO₂ and P_ETCO₂ during neurosurgical anesthesia has presented some contradictory results as compared to what has been stated above. Although results show a strong and statistically significant correlation between both parameters (r = 0.81; slope = 0.76; r² = 0.22), 17 out of 35 correlations observed had no statistical significance and in 18% of them, parametric changes went in opposite directions. These findings led the authors to conclude that P_ETCO₂ does not stably reflect PaCO₂ during craniotomies ³¹.

In spite of controversial data, this study has validated the correlation between PaCO₂ and P_ETCO₂, as shown in figure 4, through the strong and significant correlation coefficients observed at all moments of study (r = 0.94; p < 0.001). So, our study contradicts the above-mentioned study and preconizes P_ETCO₂ monitoring as a clinical, practical continuous and noninvasive method to control PaCO₂.

CO₂ is the most effective modulator of brain vascular resistance being considered the coupling factor between CBF and CMRO₂, that is, brain hemometabolism. Increased brain metabolic index results in increased CO₂ production, which generates a local dilatation process. Fast CO₂ spread through blood-brain barrier allows it to modulate extracellular CSF pH, thus affecting arteriolar resistance.

Decreased CBF secondary to carotid clamping suggests that during this period the auto-regulation mechanisms are at their maximal vasodilatory capacity. During this period, hyperventilation with consequent hypocapnia may result in changes or elimination of the referred mechanism, increasing the possibility of clinical brain hypoperfusion or oligemic hypoxia.

It is important to stress that the anesthetic technique used in this study, that is, the association of propofol and sevoflurane, does not significantly interfere with brain vascular reactivity to CO₂ although hyperventilation may potentiate CBF decrease secondary to propofol administration ³².

Figure 6 shows a moderate and statistically significant correlation index between P_ETCO₂ and SvjO₂. Based on these findings, we could conclude that during carotid endarterectomy with temporary clamping, hyperventilation should be avoided through continuous monitoring of CO₂ expired concentration - noninvasive method which truly represents PaCO₂, as shown in figure 5.

Based on the method and the population evaluated, we could conclude that during carotid endartererctomy with temporary clamping:

1. SvjO

   ₂ measurement is and effective monitoring method with fast response in representing CBF/CMRO

   ₂ ratio changes, once not contaminated by extra-cranial venous blood;

2. Stump pressure does not effectively evaluate brain hemometabolic situation during this type of surgical procedure;

3. The presence of even moderate hypocapnia (P

   _ETCO

   ₂ 25 - 30 mmHg) may lead to hemometabolic uncoupling situations, that is, oligemic ischemia;

4. P

   _ETCO

   ₂ monitoring is an innocuous and efficient method to indirectly monitor PaCO

   ₂, thus preventing inadvertent hypocapnia with its noxious effects on CBF/CMRO

   ₂ ratio.

REFERENCES

Apresentado (Submitted) em 22 de maio de 2003

Aceito (Accepted) para publicação em 30 de julho de 2003

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*

Recebido da (

Received from) Disciplina de Anestesiologia Faculdade de Medicina da Universidade Federal de Pelotas, RS

Publication Dates

• Publication in this collection
  29 June 2004
• Date of issue
  Apr 2004

History

• Accepted
  30 July 2003
• Received
  22 May 2003