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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.52 no.2 Campinas Mar./Apr. 2002
Temperature and acid-base balance in coronary bypass grafting with cardiopulmonary bypass, under hypothermia and normothermia*
Temperatura y alteraciones en el equilibrio ácido-base de pacientes sometidos a cirugía cardíaca con circulación extracorpórea, bajo normotermia e hipotermia
Hugo Leonardo de Moura Luz, M.D.I; José Otávio Costa Auler Junior, TSA, M.D.II
IAluno Graduando do 3°
ano da Faculdade de Medicina da Universidade de São Paulo; Bolsista do
Programa Institucional de Bolsas de Iniciação Científica do CNPq
- Bolsa PIBIC/CNPq - 1999/2000
IIProfessor Titular da Disciplina de Anestesiologia da Faculdade de Medicina da Universidade de São Paulo; Diretor do Serviço de Anestesiologia do InCor - HCFMUSP
BACKGROUND AND OBJECTIVES: Cardiopulmonary
bypass (CPB) is related to several changes in normal physiology. The multiple
causes of these changes interact and are a potential risk for postoperative
organic dysfunction. This study aimed at investigating changes in acid-base
and metabolic balance during cardiopulmonary bypass with hypothermia and at
comparing them to those observed in patients submitted to normothermal cardiopulmonary
METHODS: Participated in this study 30 adult patients of both genders, aged 41 to 78 years, scheduled for coronary bypass grafting with CPB, under normothermia or hypothermia. The following parameters were evaluated: hemoglobin and blood gases concentration, pH, bicarbonate, base excess, anion gap, lactate ion, tissue oxygenation parameters and flow and systemic vascular resistance.
RESULTS: There were no statistically significant differences in arterial pH, arterial bicarbonate, Na+ and Cl- plasma concentrations, anion gap, carbon dioxide partial pressure and arterial oxygen content between Normothermia and Hypothermia Groups. A time-effect was observed for all variables except for base excess and anion gap. Base excess and K+ concentration were lower in the hypothermia group. Serum lactate increased in both groups when comparing time before CPB to after CPB, with higher levels in the hypothermia group.
CONCLUSIONS: Mild hypothermia does not seem to substantially change acid-base balance as compared to normal temperature during CPB. Plasma lactate, however, has significantly increased in patients under hypothermia, suggesting inadequate oxygen transport to periphery during the proposed observation period. Low temperature, although mild, does not seem to offer the expected degree of cell protection to CPB blood flow.
Key words: ACID-BASE BALANCE; HYPOTHERMIA; MONITORING: temperature; SURGERY, Cardiac: cardiopulmonary bypass
JUSTIFICATIVA Y OBJETIVOS: La circulación
extracorpórea (CEC) se asocia a varios cambios en la fisiología normal.
Las múltiplas causas de estas alteraciones interaccionan y representan
un número de rutas potenciales para la disfunción orgánica pós-operatoria.
El objetivo de este trabajo es investigar las alteraciones de sus parámetros
indicadores durante a circulación extracorpórea en hipotermia y compararlas
a aquellas ocurridas en normotermia.
MÉTODO: Fueron seleccionados 30 pacientes adultos, de ambos sexos, con edades entre 41 y 78 años, indicados para la revascularización quirúrgica del miocárdio, operados con auxilio de CEC, bajo normotermia o hipotermia. Fueron evaluados los siguientes parámetros: concentración de hemoglobina y de los gases sanguíneos, pH, bicarbonato, exceso de bases, hiato aniónico, íon lactato, parámetros de oxigenación tecidual y los índices de flujo y de resistencia vascular sistémica.
RESULTADOS: No hubo diferencia estadísticamente significativa entre los grupos normotermia e hipotermia, en relación al pH arterial, al bicarbonato arterial, a las concentraciones plasmáticas de los íons sodio y cloreto, al anion gap, a la presión parcial de gás carbónico y al contenido arterial de oxígeno. Hubo efecto de tiempo en todas esas variables excepto para las variables exceso de bases y anion gap. El exceso de bases y la concentración de potasio mostraran valores inferiores en el grupo hipotérmico. El lactato sérico aumentó en los dos grupos del tiempo antes para el después la CEC siendo que el grupo hipotermia presentó valores más elevados.
CONCLUSIONES: Hipotermia leve parece no modificar substancialmente el equilibrio ácido-base, cuando comparado a valores normales de temperatura, durante a CEC. Entretanto, el íon lactato se elevó significativamente en los pacientes operados sobre hipotermia, sugiriendo que el transporte de oxígeno para la periferia no fue adecuado durante el período de observación propuesto. La disminución de la temperatura, aun cuando discreta, parece no haber conferido el grado de protección celular esperada al flujo sanguíneo de la CEC.
Cardiopulmonary bypass (CPB) is associated to several physiological changes. The multiple causes of these changes interact and are potential routes for postoperative organic dysfunction 1.
During hypothermia, pH variations are biochemically independent of PaCO2 variations 2.
Increased pH with decreased temperature, regardless of any changes in bicarbonate, hemoglobin or plasma protein changes, has been shown as early as in 1948 3. In case of abnormal temperatures - and hypothermia is the best example - pH changes may only mean cell and blood physiology adaptation 4. The imidazol-histidin complex, in addition to determining blood neutrality with mild alkalinity over waters pH, maintains, during temperature variations, an oscillation range, which is parallel and similar to water 5. Physiological advantages of alpha-stat type control in men, who are homothermal animals, may be observed in experimental studies 6,7.
Cardiopulmonary bypass is always followed by a certain degree of myocardial dysfunction, even in the absence of hypothermia 1,8. Regardless of temperature or of the protocol to determine acid-base (pH-stat or alpha-stat) during CPB, pH of 7.4 and PaCO2 above 35 mmHg is desirable at the end of rewarming for a safe pump disconnection. Acidosis may additionally depress myocardial contraction, decreasing inotropic action and increasing pulmonary vascular resistance.
Considering cardiopulmonary bypass physiological changes in cardiac surgery patients and possible changes in acid-base and metabolic balance, this study aimed at investigating changes in indicated parameters during cardiopulmonary bypass in hypothermia and at comparing them to those obtained in patients submitted to CPB under normothermia.
After the Ethics Committee approval, this study was prospectively performed with patients submitted to myocardial revascularization under cardiopulmonary bypass in the Heart Institute, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, from October 1999 to June 2000.
Participated in this study 30 adult patients of both genders, aged 41 to 78 years, scheduled for myocardial revascularization. Exclusion criteria were diabetes mellitus, renal failure or liver diseases.
Patients were distributed in two groups, according to the temperature used during cardiopulmonary bypass. Normothermia Group (N) - patients submitted to CPB in normothermia (t = 37 ºC) and Hypothermia Group (H) - patients submitted to CPB in hypothermia (t between 32 and 33 ºC). Patients temperature was monitored with a nasopharyngeal sensor and continuously obtained during surgery. The study was performed in the intraoperative period and the following moments were evaluated:
M1 - Before cardiopulmonary bypass;
M2 - 15 minutes after CPB;
M3 - 30 minutes after CPB;
M4 - 60 minutes after CPB;
M5 - At the end of CPB (standardized in 15 minutes after protamine administration).
Arterial and venous blood samples were collected to measure hemoglobin (Hb), blood gases concentration and acid-base balance; arterial and venous oxygen partial pressures (PaO2 and PvO2), arterial and venous oxygen saturation (SaO2 and SvO2), arterial and venous carbon dioxide partial pressures (PaCO2 and PvCO2); arterial and venous pH (pHa and pHv), arterial and venous bicarbonate (Art bic and ven bic), and excess arterial and venous bases (BEa and BEv).
The anion gap was also calculated (VN = 10 to 12 mmol. L-1) to check possible metabolic pH changes. Since the formula is AG = Na+ - (CI - + HCO3+), plasma sodium ion (flame photometry, VN = 133 to 145 mmol.L-1) and chloride (calorimetric method, VN = 98 to 119 mmol. L-1) were dosed.
Lactate ion was determined only for arterial blood in moments pre-CPB and post-CPB by the UV enzymatic method.
Tissue oxygenation and systemic vascular flow and resistance were calculated by adequate formulas for the three CPB periods:
· oxygen content
(CaO2, VN = 17 to 20 ml/dl and CvO2, VN = 12 to 15 ml/dl), CaO2 = (Hb.SaO2.1.34/100) + (PaO2.0.0031);
· arteriovenous oxygen difference (DavO2, VN = 4 to 5 ml/dl), DavO2 = CaO2-CvO2;
· oxygen extraction (EO2, VN = 24 to 28%), EO2 = (CaO2-CvO2)/CaO2;
· oxygen transport index (iTO2, VN = 550 to 650 ml/min.m2), iTO2 = (CaO2Flow)/(BodyArea.100);
· oxygen consumption index (iVO2, VN = 115 a 165 ml.min-1.m2), iVO2=(DavO2.Flow)/(BodyArea.100);
· flow index, iFlow=Flow/SupCorp;
· systemic vascular resistance index, iRVS = (MBP.80.1000)/(Flow/SupCorp).
Statistical analysis consisted of mean profile analysis of each group (normothermia and hypothermia) 11. The variable studied was the deviation of the measurement compared to pre-CPB value, that is, response in time x (minutes) is the difference between the value observed in time x and pre-CPB value.
Post-CPB observations were not considered since they occurred in different times depending on the patient. The statistical model adopted has contemplated possible correlations between observations in the same patient; for such, a non-structured correlation was used 9. Some interesting hypothesis were tested, such as, equal behavior between groups in moments studied (mean profiles coincidence test) 10. Significance level was 5%.
Table I shows demographic values for both normothermia (n = 14) and hypothermia (n = 16) groups. No statistical differences were observed between groups.
Mean CPB time and lowest temperature during CPB are shown in table II. CPB duration was longer for group H.
Mean blood pressure, arterial flow and systemic vascular resistance were evaluated during the three predetermined CPB moments (15, 30 and 60 minutes) for both groups and mean values are shown in table III. Mean blood pressure and arterial flow were used to calculate other variables and were not statistically analyzed. Even without statistical analysis, peripheral vascular resistance was higher in group H during CPB.
Variables PaO2, PvO2, PvCO2, CvO2, DavO2, iTO2 and EO2 were not statistically analyzed and were only used to calculate other data.
Mean arterial partial CO2 pressures are shown in figure 1. Curves show parallelism and coincidence among them. The mean deviation increased in both groups in the interval between 15 and 30 CPB minutes without significant changes in the following period.
O2 arterial content was similar for both groups and curves were coincident, showing no statistically significant differences between groups, with lower values for the hypothermia group. Between 30 and 60 minutes increase in arterial oxygen content was observed in both groups. Although not submitted to statistical analysis, oxygen consumption was, in average, higher in the normothermia group during CPB.
Blood pH and base excess were analyzed in arterial and venous blood and results are shown in table VII. Data on ion sodium, ion chloride and bicarbonate concentrations were obtained to calculate ion gap (AG). Lactate concentrations measured pre and post-CPB are also shown in table VII.
Arterial sodium ion concentration had a similar variation in both groups with statistically coincident curves. A significant increase in the mean deviation occurred in the interval between 30 and 60 minutes after CPB.
Potassium ion had a similar variation in serum concentration; however, mean values were statistically different between both groups with higher values during CPB for the normothermia group. An increase of the mean values was observed along time, showing a time-effect.
Chloride anion concentration has also shown parallel and coincident curves and temporal changes that were statistically significant only between 30 and 60 minutes after CPB.
Arterial pH had a similar variation between groups and mean profile curves along time (Figure 2) were coincident. Between 15 and 30 minutes of CPB a decrease of the mean values was observed although not statistically significant between 30 and 60 minutes, the last value being equal to that of 15 minutes.
As to arterial bases excess, deviation curves for both groups were parallel and non-coincident and no changes along time have been detected (Figure 3).
Arterial bicarbonate had similar variation along time for both groups. No statistically significant differences were observed between mean values of each curve, that is, they were coincident. Between 15 and 30 minutes after CPB an increase of the mean value was observed. Between 30 and 60 minutes no statistically significant changes were detected, however, when compared to 15 minutes, the 60 minutes mean value was statistically the same.
Anion gap (Figure 4) did not differ between groups (means at 15, 30 and 60 minutes were not statistically different). The estimated mean deviation (± standard deviation) (T) was equal to -4.06 ± 0.76.
As to lactate, pre-CPB values did not differ between groups, the same being not true for post-CPB values (p = 0.0137). Mean deviations for each group are different (p = 0.0159). There has been a significant lactate increase in the hypothermia group.
Our study has not found statistically significant differences between groups in arterial pH, plasma bicarbonate, sodium and chloride ion concentrations and oxygen arterial content. The CO2 partial pressure, which is an indicator of possible pH changes caused by ventilatory changes, did not show statistically significant differences between groups. Base excess and anion gap curves have not shown a time-effect, as opposed to other variables.
In spite of the equality between both groups for those parameters, a statistically significant lower mean value of potassium plasma concentration and arterial base excess was observed in the hypothermia group.
Total and balanced venous anesthesia techniques are similar in acid-base and lactate ion balance changes during cardiopulmonary bypass with moderate hypothermia 11. CPB allows for a relative manipulation of arterial flow and systemic arterial pressure indices through the perfusion pump, in addition to the infusion of vasoactive drugs. In our study, the flow was maintained above 2 L.min-1.m-2 during hypothermia to provide an adequate protection against unexpected increases in oxygen consumption or decreases in oxygen release.
Arterial lactate concentration was increased in the post-CPB period as compared to pre-CPB, suggesting that, in spite of hypothermia, arterial flow has been inadequate. There has also been a significant post-CPB difference in such parameter between groups, with a higher mean value in the hypothermia group, which could indicate the influence of temperature. The explanation for such undesirable effect would be an increase in systemic vascular resistance leading to a decreased tissue perfusion with a simultaneous increase in anaerobic metabolism and building up of acid metabolytes 12. Even without statistical analysis, peripheral vascular resistance in this study was higher during CPB in the hypothermia group. Oxygen consumption, although not submitted to statistical analysis, showed higher mean values in the normothermia group during CPB. It has been reported in the literature that during CPB performed by the moderate hypothermia technique, body oxygen consumption is decreased when temperature is decreased and that, in addition, flow decrease to 1.2 L.min.m2 under moderately hypothermal conditions does not change oxygen consumption 13.
There were no statistically significant differences between groups of the arterial pH, arterial bicarbonate, sodium and chloride ion plasma concentrations, anion gap, carbon dioxide partial pressure and arterial oxygen content. Except for base excess and anion gap, all other variables showed a time dependent effect.
Base excess and potassium concentration varied differently between groups, with lower values for the hypothermia group as compared to the normothermia group throughout cardiopulmonary bypass. Serum lactate increased in both groups at pre-CPB and post-CPB with higher values in the hypothermia group. Mild hypothermia, as used in this study, does not seem to substantially change acid-base balance, as compared to normal temperature values during cardiopulmonary bypass. Lactate ion, however, which reflects cell aerobic metabolism, was significantly higher in patients under hypothermia. This increase may suggest that oxygen transportation to periphery was not adequate during the proposed observation period. A decrease in temperature, although mild, does not seem to have provided adequate cell protection against calculated blood flow of cardiopulmonary bypass.
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Dr. José Otávio Costa Auler Junior
Av. Dr. Enéas de Carvalho Aguiar, 255 Bloco 3 - 8º Andar - Cerqueira César
05403-900 São Paulo, SP
Submitted for publication April 23, 2001
Accepted for publication September 18, 2001