BACKGROUND. The rewarming period of hypothermic cardiopulmonary bypass (CPB) is associated with reduced jugular bulb venous oxygen saturation (SjO2). This study investigates the effects of normocapnia vs. hypercapnia on changes in SjO2 during rewarming from hypothermic CPB for coronary artery bypass graft in patients classified as American Society of Anesthesiologists physical status 111.
Anesthesia was induced and maintained with fentanyl, midazolam, and continuous infusion of etomidate. Hypothermic CPB (27 degrees C) was managed according to alpha-stat conditions. The SjO2 percentage was measured using a fiberoptic catheter placed in the right jugular bulb via the right internal jugular vein. Data were recorded before and during the rewarming period. Patients were assigned to a normocapnic (PaCO2: 36-40 mmHg, n = 10) or hypercapnic (PaCO2: 45-50 mmHg, n = 10) PaCO2 regimen during rewarming.
The maximum reduction of SjO2 occurred during rewarming with the jugular bulb temperature at 35-36 degrees C. In contrast, SjO2 did not change during rewarming from hypothermia in hypercapnic patients.
These results show that mild hypercapnia prevents the desaturation of SjO2 seen with the normocapnic group during the rewarming period from hypothermic CPB. These data suggest that mild hypercapnia during rewarming from CPB is associated with a better balance between cerebral oxygen supply and demand.
This article is accompanied by an Editorial View. Please see: Hindman BJ: Jugular venous hemoglobin desaturation during rewarming on cardiopulmonary bypass: What does it mean, what does it matter? Anesthesiology 1998; 89:3–5.
NEUROLOGIC and neuropsychological dysfunction after coronary artery bypass graft using hypothermic cardiopulmonary bypass (CPB) affects 6–80% of patients. [1–4]Although some patients recover from the initial neuropsychological deficits, persisting deficits may occur in 10–30% of the patients and last for months or even longer. [4–10]Neuropsychological complications appear to be related to the occurrence of gas or particulate matter embolization and to global impaired cerebral oxygenation.
Studies in laboratory animals have shown cerebral venous hemoglobin desaturation with rapid rewarming. This is related to an increase in cerebral metabolic rate for oxygen that is temporarily not accompanied by an adequate increase in CBF. This mismatch may indicate an abnormality in flow-metabolism coupling, leaving the cerebral vasculature unable to vasodilate adequately in response to increases in the cerebral metabolic rate for oxygen. It is unclear whether elevated arterial carbon dioxide tension (PaCO(2)) can antagonize this constrictive effect.
This study investigated the effects of elevated PaCO(2) on jugular bulb venous hemoglobin desaturation during rewarming of patients made hypothermic for CPB for coronary artery bypass graft.
Materials and Methods
After institutional review board approval and informed patient consent were received, we enrolled 20 patients (American Society of Anesthesiologists physical status III) who were undergoing coronary artery bypass graft in the study. Patients with preexisting neurological dysfunction were not included. All patients were pre-medicated with flurazepam (1 mg/kg given orally) on the evening before surgery. Sixty minutes before induction of anesthesia, a premedication using dehydrobenzperidol (0.07 mg/kg) and fentanyl (1.5 [micro sign]g/kg) were given by subcutaneous injection. Anesthesia was induced with fentanyl (10–25 [micro sign]g/kg given intravenously), etomidate (50 [micro sign]g/kg given intravenously), and pancuronium (100 [micro sign]g/kg given intravenously) for neuromuscular blockade. After endotracheal intubation, all patients were normoventilated using oxygen in air (FIO2: 0.3–0.5). Anesthesia was maintained with fentanyl (<30 [micro sign]g/kg intravenously) and midazolam (150 [micro sign]g/kg intravenously) discontinuously as clinically required and with continuous infusion of etomidate (7 [micro sign]g [middle dot] kg-1[middle dot] min-1intravenously). During CPB the etomidate infusion was continued. Catheters were placed into one radial artery and one internal jugular vein for simultaneous measurements of mean arterial blood pressure, drug infusion, and blood sampling.
The jugular bulb venous oxygen saturation (SjO2) percentage and jugular bulb temperature (JBT) were measured using a fiberoptic thermodilution catheter (Opticath[R] F 5.5; Abbott Critical Care Systems, Mountain View, CA) placed into the right jugular bulb via the right internal jugular vein. Appropriate catheter position was confirmed by x-ray control before the measurements. The catheter was calibrated in vitro before insertion. Immediately after insertion and during the observation period, accurate fiberoptic saturation values were verified by drawing blood samples from the catheter and by measuring the oxygen saturation using a co-oximeter (OSM 3, Radiometer, Copenhagen, Denmark) every 5 min.
Cardiopulmonary bypass was performed using a membrane oxygenator (Monolyth[R] Sorin, Biomedica, Saluggia, Italy) and a roller pump (Stockert Instrumente, Munich, Germany) with an arterial line filter (40 [micro sign]m). Non-pulsatile perfusion (Q') through an ascending aortic cannula of 2–3 1 [middle dot] min-1[middle dot] m-2was maintained during the study period. The pump was primed with crystalloid solution, and a hematocrit of 0.22 +/- 0.02 was maintained during extracorporal circulation. Cardiopulmonary bypass was managed according to alpha-stat acid-base conditions under moderate hypothermia (27 +/- 1 [degree sign]C). During CPB arterial perfusate temperature (APT) was measured continuously at the oxygenator outlet.
After baseline measurements at the end of hypothermia (27 [degree sign]C) were made, hemoglobin concentration, the partial tension of oxygen (PaO(2)), mean arterial blood pressure, pump flow rate (Q'), JBT, ABT, and SjO2were monitored continuously and recorded every 5 min during rewarming of CPB. In the normocapnic group (n = 10), PaCO(2) was maintained within a range of 36–40 mmHg during rewarming. In the hypercapnic group (n = 10), PaCO(2) was increased with start of rewarming and was maintained within a range of 45–50 mmHg. The PaCO(2) in both groups was maintained by adjusting gas flow to the membrane oxygenator and measured at 37 [degree sign]C uncorrected to the patient's temperature (alpha-stat management). At the beginning of rewarming, the regulator of the heater was increased to 40–42 [degree sign]C and the APT was measured continuously at any time point.
Normally PaCO(2) was increased in the hypercapnic group by reducing the gas flow of the CPB to near 600 ml/min (i.e., about 60% of the gas flow before the start of rewarming) for 5–10 min until the PaCO(2) was increased to >45 mmHg, then for 5 min to 900 ml/min, and after 10 min to 1,200 ml/min to keep the PaCO(2) between 45–50 mmHg. To prevent hypoxemia, the FIO2was increased to 70% during hypercapnic rewarming. Patients were rewarmed until their nasopharyngeal temperature was >36 [degree sign]C and bladder temperature was >35 [degree sign]C. Norepinephrine was used to keep mean arterial blood pressure >40 mmHg during hypothermia and >55 mmHg during normothermia.
Physiologic variables are given as means +/- SD. Physiological variables at given time intervals were tested for Gaussian distribution using the Kolmogorow-Smirnow test. Analysis of variance for repeated measurements was used to test for significant differences between and within groups. Post hoc data were analyzed using paired or unpaired t tests when appropriate, with Bonferroni corrections for multiple comparisons. A probability value <0.05 was considered to indicate a significant difference.
(Table 1) shows the demographic variables and CPB times. No significant differences occurred in any parameter between the groups. Table 2shows the physiologic variables in patients with normocapnia (group 1) or hypercapnia (group 2) during hypothermia and rewarming. The hemoglobin value and mean arterial blood pressure did not change during rewarming compared with baseline (i.e., at the end of hypothermic CPB) and were not different between the groups. The amount of vasoactive drugs used was not different between the groups. The JBT and APT were not significantly different between the groups. The PaCO(2) was kept constant in group 1 but was increased in group 2 according to the study protocol. The PaO(2) was not significantly different between groups. Q' (pump flow rate) was increased in both groups to a similar extent.
(Figure 1) shows SjO2at baseline, nadir, and at the end of rewarming. In group 2, SjO2did not change during rewarming from hypothermia, and no patient showed a SjO2<50%. However, in group 1 SjO (2) was reduced to a nadir of 45 +/- 4%. Fifteen minutes after the start of rewarming, a maximum reduction of SjO2was seen in group 1, when JBT and APT were 36.5 +/- 1.1 [degree sign]C and 37.5 +/- 0.5 [degree sign]C (Table 2).
Our data show that the degree of jugular bulb venous hemoglobin saturation during rewarming from CPB is related to the level of PaCO(2). During normocapnia jugular bulb venous hemoglobin desaturation (SjO2<50%) occurred, with the lowest values seen at 36 [degree sign]C JBT. This suggests a mismatch between global cerebral oxygen demand and CBF during the rewarming period. In contrast, desaturation did not occur with hypercapnic acid base management. This suggests that hypercapnic cerebrovascular dilation is effective in reversing the imbalance of oxygen demand and supply during the rewarming period. However, an increased carbon dioxide level could increase the embolic load to the brain.
Previous studies have shown that rewarming from hypothermic CPB is frequently associated with decreases in SjO2(SjO2<50%). [6,14–17]These may be related to postoperative cognitive dysfunction. The imbalance may be due to differences in the speed of rewarming within the various tissues and compartments. Studies in rabbits have shown that rewarming from hypothermic CPB decreases cerebral venous hemoglobin saturation as a result of increases in the cerebral metabolic rate for oxygen that are temporarily greater than the increase in CBF. Therefore oxygen extraction was increased and SjO2was decreased. This suggests that the rewarming process activates cerebral function despite the fact that the brain temperature is still within the hypothermic range and that cerebral venous hemoglobin desaturation is related to inadequate cerebrovascular dilation as neuronal functional activity increases.
Cerebral venous oxygenation is a function of the position of the oxygen - hemoglobin dissociation curve and the venous oxygen pressure, and decreases in SjO2are not necessarily related to pathological conditions. According to a theoretical model of oxygen transfer from the blood to the brain, oxygen transfer depends closely on hemoglobin oxygen affinity. Warm blood with decreased oxygen affinity (increased P50= the oxygen partial pressure at which hemoglobin oxygen saturation equals 0.5) facilitates oxygen transfer from “warm” hemoglobin to the cold brain. This results in desaturation and is expected to occur at the beginning of rewarming, when the temperature gradient between the blood and the brain is most pronounced. In contrast, desaturation in normocapnic patients occurred during minimal temperature differences (JBT: 36.5 +/- 1.1 [degree sign]C vs. APT: 37.3 +/- 0.7 [degree sign]C) between the blood and the brain (i.e., 15 min after the start of rewarming, just before or when normothermia is reached;Table 2). However, the JBT probably represents only the area of the brain near the vessels with high perfusion, and the temperature of areas that are less perfused are lower, indicating a temperature gradient in these areas. Twenty-five minutes after the start of rewarming, the JBT is higher than the APT (Table 2). This difference may be related to the fact that the two different temperature measurement devices were not independently calibrated.
The P50theory cannot explain the association between cerebral venous hemoglobin desaturation and the neuropsychological impairment found in human studies in which the arterial-jugular-venous oxygen difference and jugular venous hemoglobin desaturation at the end of rewarming was associated with postoperative neuropsychological impairment. Similarly, this model cannot explain the reversal of jugular venous hemoglobin desaturation with hypercapnia during rewarming (group 2).
The fact that mild hypercapnia (45–50 mmHg) during alpha-stat management reversed jugular bulb venous hemoglobin oxygen desaturation seen with the classical alpha-stat approach (36–40 mmHg) tends to support the vascular response issue largely because the pH shift produced with mild hypercapnia is not great enough to facilitate unloading. Thus the difference in SjO2between the two groups is unlikely related to differences in the cerebral metabolic rate for oxygen, which was not measured in the present study.
In conclusion, these data show that under normocapnia the cerebral vascular reserve to vasodilate may not be exhausted during the rewarming period from hypothermic CPB. Further, these data show that mild hypercapnia during rewarming from hypothermic CPB reverses jugular bulb venous hemoglobin desaturation, possibly suggesting a better balance between oxygen supply and demand.