Jugular Venous Bulb Oxygen Saturation in Patients with Preexisting Diabetes Mellitus or Stroke during Normothermic Cardiopulmonary Bypass

After obtaining the approval of the ethical committee of our institution and written informed consent from the patients, 19 age-, weight-, and height-matched control patients (control group), 10 diabetic patients (DM group), and 9 patients with preexisting stroke (stroke group) undergoing elective coronary artery bypass graft surgery were studied. The clinical data of DM and stroke groups are shown in tables 1–3. The stroke group had no diabetic disease. None of the patients had pulmonary, renal, or hepatic disease.

All patients received 10 mg oral diazepam 1 h before administration of anesthesia. A cannula was inserted in the left radial artery to monitor arterial blood pressure. Anesthesia was induced with 25 μg/kg intravenous fentanyl, 0.2 mg/kg midazolam, and 0.2 mg/kg vecuronium, and the trachea then was intubated. After induction of anesthesia, the pulmonary arterial catheter (Vigilance Swan–Ganz CCO Thermodilution Catheter; Baxter, Irvine, CA) was inserted through the right internal jugular vein. For continuous monitoring of jugular vein oxygen saturation (Sjv^O2), a 4.0-French fiberoptic oximetry catheter (Dual-lumen Oximetry Catheter; Baxter) was passed to the right jugular bulb retrogradely from the internal jugular vein using a modified Seldinger technique. Proper position of the top of the catheter was verified by radiograph. This catheter was connected to an analysis system (Explorer; Baxter) and calibrated in vivo  by drawing a blood sample from the catheter. The arterial and jugular venous blood gases were analyzed (Stat Profile Ultima; NOVA Biomedical, Boston, MA). All patients were ventilated with 50% oxygen and 50% nitrogen. End-tidal carbon dioxide concentration was monitored (Ultima; Datex, Helsinki, Finland) and maintained between 35 and 45 mmHg. After induction of anesthesia, 4 mg · kg⁻¹· h⁻¹propofol was infused using a syringe pump and continued until the patients were placed in the intensive care unit. Relaxation was maintained with an intermittent administration of vecuronium. No volatile anesthetics were administrated. The tympanic membrane temperature also was monitored continuously (Mon-a-Therm; Mallinckrodt, St. Louis, MO) as an indicator of brain temperature.

Cardiopulmonary bypass was primed with a crystalloid, non–glucose-containing lactate Ringer’s solution, and a nonpulsatile pump flow rate of 2.2–2.5 l · min⁻¹· m⁻²was maintained. A membrane oxygenator and a 40-μm arterial line filter were used, and arterial oxygen tension (Pa^CO2) uncorrected for temperature was adjusted to normocapnic levels (35–45 mmHg) by varying fresh gas flow to the membrane oxygenator. The target tympanic temperature was 35°C.

Hematocrit was maintained at more than 20% during CPB, with the addition of blood as needed. Phenylephrine infusions were used during CPB to maintain mean arterial pressure of 50–90 mmHg.

Cerebral perfusion pressure (CPP) was defined as mean arterial pressure minus internal jugular venous pressure. Internal jugular pressure was measured by monitoring pressure at the distal end of the Sjv^O2catheter. All hemodynamic transducers were referenced to atmospheric pressure at the level of the external auditory meatus.

After the end of CPB, catecholamines, such as dopamine and dobutamine, were infused to maintain the cardiac index above 2.2 l · min⁻¹· m⁻². No patients needed infusion of epinephrine or norepinephrine to maintain the cardiac index above 2.2 l · min⁻¹· m⁻².

Antegrade blood cardioplegia was administrated intermittently from the aortic root at 37°C. Distal coronary and proximal anastomoses were performed during a single aortic cross-clamping.

Hemodynamic parameters, arterial and jugular venous blood gases, and internal jugular venous pressure were measured (1) after the induction of anesthesia and before the start of surgery, (2) just after the beginning of CPB, (3) 20 min after the beginning of CPB, (4) 40 min after the beginning of CPB, (5) 60 min after the beginning of CPB, (6) just after the cessation of CPB, and (7) at the end of the operation.

Intraoperative epiaortic ultrasonography confirmed that none of the patients had moderate or severe atherosclerotic lesions in the ascending aorta.

All data were expressed as the mean ± SD. After the study was completed, we evaluated the sample size. The sample size calculation was based on the hypothesis that the Sjv^O2value in diabetic or stroke patients would be decreased by 10% compared with that in control patients. The sample size provides 80% power to detect a 20% difference between groups with a 5% probability of an a-type error. Changes in mean values were compared with the baseline values using an analysis of covariance. Contrast was used to compare the differences among the three groups at each time point. Statistical significance was set at P < 0.05.

All calculations were performed on a Macintosh computer with SPSS (Chicago, IL) and Stat View 4.5 software packages (Abacus Concepts, Berkeley, CA).

Postoperative neurologic dysfunction did not develop in any patient. There was no significant difference in preoperative blood pressure among the three groups (data not shown). Table 4shows the time course for changes in variable parameters among three groups. Mean arterial pressure, cardiac index, hemoglobin, q]Pa^CO2, internal jugular pressure, and CPP among the three groups did not differ significantly at any time.

Figure 1shows the time course for changes in Sjv^O2among the three groups. Sjv^O2did not differ among the three groups after anesthesia induction and before surgery, just after the beginning of CPB, 60 min after the beginning of CPB, just after the end of CPB, or at the end of the operation. Significant differences between the control group and the diabetic and stroke groups were observed, however, at 20 min and 40 min after the beginning of CPB (at 20 min: control group 62.2 ± 6.8%, diabetes group 48.4 ± 5.1%, stroke group 45.9 ± 6.3%; at 40 min: control group 62.6 ± 5.2%, diabetes group 47.1 ± 5.2%, stroke group 48.8 ± 4.1%[values expressed as the mean ± SD];P < 0.05). Also, Sjv^O2values in diabetic and stroke groups were decreased at 20 min and 40 min after onset of CPB compared with before the start of surgery. There was no significant difference in Sjv^O2values between the diabetic group and the stroke group during at any point of the study.

The principal findings of this study are that (1) patients with preexisting DM or stroke had a reduced Sjv^O2compared with those in the control group during normothermic CPB, and (2) the reduced Sjv^O2was not attributable to either the mean arterial pressure or Pa^CO2but rather to the preexisting DM or stroke.

Many studies have attempted to determine preoperative factors that may be used to predict major perioperative neurologic events in patients undergoing coronary artery bypass graft surgery. In addition to age, history of preexisting symptomatic neurologic disease and history of DM were considered to be concurrent risk factors in many studies. 5,6To date, few clinical studies have examined patients with DM or preexisting stroke. One of the many possible causes of postoperative stroke in patients with DM or preexisting stroke is the impaired cerebrovascular circulatory and vasodilatory reserve. Dandona et al.  7reported that 56% of awake diabetic patients failed to increase cerebral blood flow (CBF) after a 5% CO²inhalation challenge. Maeda et al.  8reported that the CBF reactivity to CO²measured by transcranial Doppler ultrasonography in patients with asymptomatic small infarctions was significantly lower than that of control subjects. Cook et al.  9reported that low Sjv^O2, which indicates lower CBF in relation to cerebral metabolic rate, was observed more often in normothermic CPB than in hypothermic CPB in patients without preexisting DM or stroke. Thus, we considered whether patients who had risk factors for cerebral circulatory disturbances such as DM or stroke might have reduced Sjv^O2more often than patients without these risk factors during normothermic CPB.

Some studies have described the alterations in cerebral circulation in patients with DM or preexisting stroke during hypothermic CPB. 3,4Croughwell et al.  4reported that the CBF of their diabetic group was constant despite an increase in temperature from 27 to 37°C, in contrast to an 83% increase in CBF in the control group. This was contradictory to the fact that the cerebral metabolic rate of oxygen consumption in both groups increased in parallel with rewarming. Goto et al.  3found that patients with preexisting small cerebral infarctions had reduced Sjv^O2compared with controls during CPB, especially during the rewarming period. They speculated that the imbalance in CBF and cerebral metabolic rate of oxygen consumption might have resulted from impaired cerebral circulatory disturbance in patients with preexisting stroke, and they considered the fact that patients with risk factors for cerebral circulatory disturbance were unable to preserve effective CBF if systemic hypoperfusion occurred. From the results of our study, we also concluded that patients with DM or stoke may be at a much higher risk of cerebral oxygenation abnormality than otherwise normal patients.

In the current study, multiple linear regression analysis indicated that either DM or preexisting stroke was a single determining factor of Sjv^O2value during normothermic CPB. CPP, Pa^CO2, and arterial oxygen tension did not differ among groups. Sjv^O2did not correlate with CPP during normothermic CPB in the control group. There have been some reports describing the correlation between CPP and Sjv^O2during CPB. Grubhofer et al.  10reported that an increase in CPP in response to administering phenylephrine (from 47 to 93 mmHg) induced increases in Sjv^O2by 4.9% during hypothermic CPB. Furthermore, they considered this finding to suggest impaired cerebral autoregulation, and they recommended administration of phenylephrine to increase CPP in patients with lower Sjv^O2during CPB. In contrast, Hessel 11commented that the poor correlation between slopes obtained during the rise versus the decline in arterial pressure (r = 0.10) in the report of Grubhofer et al.  10was disturbing. We suspect that the differences between our study and the one by Grubhofer et al.  10could be a result of the different species studied, anesthetic conditions, management of CPB, preoperative baseline mean arterial pressure, or mean arterial pressure during CPB.

The finding that control patients with normothermic CPB did not show any reduction in Sjv^O2is inconsistent with findings both of Cook et al.  9and of our previous studies. 12,13It is possible that many factors such as age, species, anesthetic drugs, Pa^CO2, arterial oxygen tension, and blood viscosity influence Sjv^O2during normothermic CPB. Sjv^O2in our control group had tended to increase over time during CPB. Cook et al.  9reported that the increase in Sjv^O2appeared to be adapting to CPB flow conditions with time.

Croughwell et al.  14reported that reduced Sjv^O2during CPB was a risk factor for cerebral ischemia. There has been some controversy, however, regarding interpretation of Sjv^O2during CPB. 15,16Dexter and Hindman 15recently reported that a high Sjv^O2value during hypothermic CPB indicated impaired oxygen transfer from hemoglobin to the brain. They also found that during normothermia, increased oxygen extraction reduced Sjv^O2, but that this reduction does not indicate an imbalance in either CBF or metabolism. In contrast, Hanel et al.  17reported that maximal reduction in the Sjv^O2value did not occur when blood–brain temperature gradients were at their maximum but rather occurred when the temperature gradients were small. To date, it is not clear whether reduced Sjv^O2during hypothermic or normothermic CPB indicates an imbalance in CBF and metabolism.

Whether Sjv^O2influences neurologic outcome after cardiac surgery remains unclear. 18Murkin et al.  19suggested that neurologic outcome may be poorer in patients with higher Sjv^O2during CPB. Patients with risk factors for cerebral circulatory disturbance, however, have not been studied extensively in terms of whether the state of cerebral oxygenation as measured by the Sjv^O2value has some effect on their neurologic outcome. Using a routine postoperative neurologic assessment, we did not detect any neurologic disorders in any of the patients. The possibility exists, however, that an extensive assessment of neurologic and cognitive function might have detected minor neurologic abnormalities. Further studies are needed to determine if any correlation exists between Sjv^O2reduction and neurologic disorders.

In conclusion, reduced Sjv^O2was observed more frequently in patients with preexisting DM or stroke during normothermic CPB. It is possible that cerebral circulation during normothermic CPB is altered in patients with risk factors for cerebrovascular disorder.