Randall M. Schell

Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass

Inadequate cerebral oxygenation during cardiopulmonary bypass may lead to postoperative cognitive dysfunction in patients undergoing cardiac operations. A psychological test battery was administered to 255 patients before cardiac operation and just before hospital discharge. Postoperative impairment was defined as a decline of more than one standard deviation in 20% of tests. Variables significantly (p < 0.05) associated with postoperative cognitive impairment are baseline psychometric scores, largest arterial-venous oxygen difference, and years of education. Jugular bulb hemoglobin saturation is significant if it replaces arterial-venous oxygen difference in the model. Factors correlated with jugular bulb saturation at normothermia were cerebral metabolic rate of oxygen consumption (r = -0.6; p < 0.0005), cerebral blood flow (r = 0.4; p < 0.0005), oxygen delivery (r = 0.4; p < 0.0005), and mean arterial pressure (r = 0.15; p < 0.05). Three measures were significantly related to desaturation at normothermia and at hypothermia as well: greater cerebral oxygen extraction, greater arterial-venous oxygen difference, and lower ratio of cerebral blood flow to arterial-venous oxygen difference. We conclude that cerebral venous desaturation occurs during cardiopulmonary bypass in 17% to 23% of people and is associated with impaired postoperative cognitive test performance.

Cerebral blood flow and metabolism during cardiopulmonary bypass

Although much has been learned about cerebral physiology during CPB in the past decade, the role of alterations in CBF and CMRO2 during CPB and the unfortunately common occurrence of neuropsychologic injury still is understood incompletely. It is apparent that during CPB temperature, anesthetic depth, CMRO2, and PaCO2 are the major factors that effect CBF. The systemic pressure, pump flow, and flow character (pulsatile versus nonpulsatile) have little influence on CBF within the bounds of usual clinical practice. Although cerebral autoregulation is characteristically preserved during CPB, untreated hypertension, profound hypothermia, pH-stat blood gas management, diabetes, and certain neurologic disorders may impair this important link between cerebral blood flow nutrient supply and metabolic demand (Figure 5). During stable moderate hypothermic CPB with alpha-stat management of arterial blood gases, hypothermia is the most important factor altering cerebral metabolic parameters. Autoregulation is intact and CBF follows cerebral metabolism. Despite wide variations in perfusion flow and systemic arterial pressure, CBF is unchanged. Populations of patients have been identified with altered cerebral autoregulation. To what degree the impairment of cerebral autoregulation contributes to postoperative neuropsychologic dysfunction is unknown. It must be emphasized that not the absolute level of CBF, but the appropriateness of oxygen delivery to demand is paramount. However, the assumption that the control of cerebral oxygen and nutrient supply and demand will prevent neurologic injury during CPB is simplistic. A better understanding of CBF, CMRO2, autoregulation and mechanism(s) of cerebral injury during CPB has lead to a scientific basis for many of the decisions made regarding extracorporeal perfusion.

Cerebral monitoring: jugular venous oximetry.

The internal jugular vein exits the skull and continues its course, within the carotid sheath, beneath the sternocleidomastoid muscle in a posterolateral approximation to the carotid artery. The jugular bulb is the dilated portion of the jugular vein just below the base of the skull and is the preferred site for blood sampling (see Figure 1). Although blood in the jugular bulb is derived from both cerebral hemispheres (approximately 70% ipsilateral and 30% contralateral) (6–8), it is generally accepted that most patients have a dominant side of venous drainage, usually the right (9,10). The two lateral sinuses that drain to the jugular bulbs differ in size in 88% of patients (11), and mixing of cerebral venous blood within the sinuses is incomplete (1,12)

Focal cerebral ischemia in rats. Effect of hypervolemic hemodilution with diaspirin cross-linked hemoglobin versus albumin on brain injury and edema.

Background:Hemodilution has had limited success as a treatment of cerebral ischemia. When using a non-oxygen-binding fluid, the therapeutic efficacy of hemodilution-induced Increases in blood flow are offset by concomitant decreases in oxygen content. Methods:The effect of hemodilution, with diaspirin cross-linked hemoglobin (DCLHb), on brain injury and edema was assessed during middle cerebral artery occlusion (180 min) and reperfusion (120 min) in rats (blood volume increased by “30% and n = 10 for each group): (1) 44/B: 8.0 ml of donor blood was given; (2) 30/albumln: hematocrit was decreased to 30% with 10% albumin; (3) 30/DCLHb: hematocrit was decreased to 30% with 10% DCLHb; or (4) 9/DCLHb: hematocrit was decreased to 9% with DCLHb. infarct size was analyzed with 2,3,5-triphenyltetrazollum chloride, and edema by microgravimetry. Results:Brain injury (percent of the hemispheric area ipsi-lateral to ischemia, mean ± SD) was greater in the 44/B group (44 ± 4) versus the 30/albumin group (37 ± 3). in addition, brain injury was greater in the 44/B and 30/albumin groups versus the 30/DCLHb group (27 ± 4); which was in turn greater than the 9/DLCHb group (18 ± 3). Specific gravity was greater (less brain water) in all hemodiluted groups versus the 44/B group. Conclusions:These results support a hypothesis that hemodilution decreases focal cerebral ischemic injury, and when an oxygen-binding fluid is used, there is a dose-dependent effect of hemodilution on ischemia. in addition, these results suggest that hemodilution, as achieved with DCLHb, was more effective in reducing ischemic brain damage than was the same degree of hemodilution as achieved with albumin.

Focal Cerebral Ischemia in Rats: Effect of Hemodilution with α-α Cross-Linked Hemoglobin on CBF

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced increases in CBF are offset by concomitant decreases in oxygen content. The effect of hemodilution, with diaspirin α-α cross-linked hemoglobin (DCLHb), on CBF during middle cerebral artery occlusion was assessed. Rats were hemodiluted to one of the following hematocrits (Hct): (a) 44/Hct, (b) 37/Hct, (c) 30/Hct, (d) 23/Hct, (e) 16/Hct, or (f) 9/Hct. After 10 min of ischemia, CBF was determined with 14C-iodoantipyrine. Coronal brain sections were evaluated for areas with a CBF of 0–10 and 11–20 ml 100 g−1 min−1. In addition, oxygen delivery was calculated. In the center of the ischemic zone, both areas of low CBF were less in the 30/Hct, 23/Hct, and 16/Hct groups compared with the 44/Hct and 37/Hct groups; and both areas were less in the 9/Hct group compared with the other five groups (p < 0.05). For the hemisphere contralateral to occlusion, there was a direct correlation between hematocrit and oxygen delivery. However, for the hemisphere ipsilateral to occlusion, oxygen delivery increased as hematocrit decreased (44/Hct, 8.6 ± 0.3 vs. 9/Hct, 13.6 ± 0.4 [mean ± SD, ml 100 g−1 min−1]). The results of this study support a hypothesis that hemodilution with DCLHb decreases the extent of focal cerebral ischemia.

Temporary Cerebral Ischemia: Effects of Pentastarch or Albumin on Reperfusion Injury

Recent investigations have proposed that, after temporary ischemia, pentastarch may reduce microvascular permeability and reperfusion injury. However, this hypothesis has not been tested in the brain. Accordingly, after 180 min of temporary middle cerebral artery occlusion, the effect of pentastarch or albumin on blood-brain barrier permeability and cerebral injury was investigated in isoflurane-anesthetized rats. One of the following was maintained for the final 60 min of occlusion and throughout reperfusion: control-hematocrit was not manipulated; pentastarch-hematocrit was decreased to approximately 30% with pentastarch; or albumin-hematocrit was decreased (approximately 30%) with albumin. Part A (n = 21): 30 min of reperfusion was allowed, and blood-brain barrier permeability was determined with the indicator dye Evans Blue. Part B (n = 14): in different animals, 120 min of reperfusion was allowed, and cerebral injury (2,3,5-triphenyltetrazolium chloride stain) and edema (specific gravity) were assessed. Part C (n = 4): in different animals, the blood-brain barrier was evaluated by electron microscopy. Evans Blue (micrograms per gram brain tissue, mean +/- SD) was greater in the control (20.8 +/- 9.0) and albumin (15.5 +/- 7.3) groups versus the pentastarch (4.7 +/- 2.7) group (P less than 0.05). Brain injury (percent of hemisphere ipsilateral to occlusion) was less and specific gravity greater in the pentastarch (33 +/- 8 and 1.040 +/- 0.003 respectively) versus the albumin group (45 +/- 6 and 1.035 +/- 0.003). This study supports the hypothesis that during temporary cerebral ischemia, pentastarch decreases brain injury and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparing two strategies of cardiopulmonary bypass cooling on jugular venous oxygen saturation in neonates and infants

BACKGROUND Cerebral protection during deep hypothermic circulatory arrest is predicted on efficient and complete cerebral cooling. Institutions approach cooling quite differently. We compared two different cooling strategies in terms of measured jugular venous bulb saturations in 39 infants undergoing deep hypothermic cardiopulmonary bypass to evaluate the effect of institutional cooling practices on jugular venous bulb saturation, an indirect measure of cerebral cooling efficiency. METHODS The patients were grouped based on the method of core cooling. In group A (n = 17), core cooling was achieved rapidly by setting the water bath temperature of the heat exchanger at 4 degrees to 5 degrees C, and the patient was cooled until rectal temperature and nasopharyngeal temperature were 15 degrees C or lower. In group B (n = 22), the heat exchanger was initially set at 18 degrees C and slowly lowered to 12 degrees C. Hypothermic temperatures of 12 degrees C were maintained until the nasopharyngeal temperature was 18 degrees C or less and the rectal temperature was 20 degrees C or lower. Once cooling was complete, blood samples were analyzed by cooximetry for determination of arterial oxygen saturation and jugular venous bulb saturation. RESULTS In group A, the measured jugular venous bulb saturation was 98.0% +/- 0.9% and the oxygen saturation to jugular venous bulb saturation difference was 0.3% +/- 0.5%, measured at the time that institutional cooling objectives were achieved (total cooling time, 15.0 +/- 0.45 minutes). In group B, jugular venous bulb saturation was 86.2% +/- 12% and the oxygen saturation to jugular venous bulb saturation difference was 10.8% +/- 12.2%, measured at the time that institutional cooling objectives were achieved (total cooling time, 17.5 +/- 1.1 minutes (p < 0.01). CONCLUSIONS Differences in cardiopulmonary bypass cooling techniques may alter the rate at which jugular bulb saturations rise. We believe this represents an indirect measure of the efficiency of brain cooling and therefore of cerebral protection.

Proton magnetic resonance spectroscopy in the evaluation of children with congenital heart disease and acute central nervous system injury

We studied nine infants and children, aged 1 week to 42 months, with severe acute central nervous system injuries associated with cardiac disease or corrective operations by means of single-voxel proton magnetic resonance spectroscopy to determine whether this technique would be useful in predicting neurologic outcome. Proton magnetic resonance spectroscopic data were acquired from the occipital gray and parietal white matter (8 cm3 volume, stimulated echo-acquisition mode sequence with echo time of 20 msec and repetition time of 3.0 seconds) a median of 9 days after operation (range 3 to 42 days). Data were expressed as ratios of areas under metabolite peaks, including N-acetyl compounds, choline-containing compounds, creatine and phosphocreatine, and lactate. Four patients had cerebral insults before operation, one had both a preoperative and a perioperative insult, three had perioperative insults, and one had a prolonged cardiac arrest 2 days after operation. Outcomes (Glasgow Outcome Scale scores) were assigned at discharge and 6 to 12 months after injury. Six patients were in a vegetative state or had severe impairment at discharge, and two still had severe impairment at 6- to 12-month follow-up. Proton magnetic resonance spectroscopy showed lactate in these two patients, along with markedly reduced ratios of N-acetyl compounds to creatine compounds. The other four patients with severe impairment recovered to a level of mild disability at follow-up. Proton magnetic resonance spectroscopy showed no lactate in these four patients; however, one patient showed moderately reduced ratio of N-acetyl compounds to creatine compounds. The three patients who had mild or moderate impairment at discharge showed no lactate and mild or no changes in metabolite ratios; follow-up revealed normal or mild outcomes. Overall, we found that the presence of lactate and markedly reduced ratios of N-acetyl compounds to creatine compounds were predictive of severe outcomes at discharge and long-term follow-up, whereas no lactate and mild or no changes in ratios suggested potential for recovery with at least a mild disability. Continuing investigations are in progress to determine the optimal selection of candidates and timing of proton magnetic resonance spectroscopic studies.

The role of continuous jugular venous saturation monitoring during cardiac surgery with cardiopulmonary bypass.

n this issue of Anesthesia & Analgesia, Nakajima et al. (1) demonstrate a practical method of confinuI ously monitoring cerebral oxygenation during cardiac surgery. They used an oximetry catheter to monitor the blood oxygen saturation in the jugular bulb (Sjo,) of 12 patients throughout cardiac surgery with cardio ulmonary bypass (systemic flows of 2.03.0 L.min-Pm-’, a-stat blood gas management, nonpulsatile flow, and moderate hypothermia). Of potential importance is the demonstration of jugular venous “desaturation,” which we believe should more properly be referred to as “reduced saturation” during rewarming. The reduced saturation was inversely and linearly correlated with nasopharyngeal temperature despite an average systemic flow >2.5 L.rnin-l.m-, and stable hemoglobin level. This abrupt decrease in saturation indicates a major alteration in the balance of cerebral oxygen supply and demand. This study emphasizes the importance of cerebral oxygen balance rather than absolute measurements of cerebral blood flow and cerebral metabolic rate for oxygen during cardiopulmonary bypass (CPB). It identifies the rewarming period following moderate hypothermic CPB as a potential period of increased neurologic risk. In the paradigm of neurologic injury after CPB, the relative importance of incomplete global ischemia is unclear. We recently found, using intermittent sampling from the jugular venous bulb during rewarming on CPB, a 23% incidence of desaturation to an Sjo, 5 50% partial pressure of jugular venous blood (2). In the patients who did not demonstrate jugular venous desaturation, cerebral blood flow was higher and the cerebral metabolic rate for

Brain eicosanoid levels during temporary focal cerebral ischemia in rats: a microdialysis study.

After transient cerebral ischemia, the brain is vulnerable to additional injury via hypoperfusion deficits. Eicosanoids with vasoconstrictor properties, such as thromboxane A2 (TxA2), may worsen postischemic hypoperfusion. The effect of temporary middle cerebral artery occlusion (MCAo) on brain TxB2 (the stable metabolite of TxA2) was evaluated in isoflurane-anesthetized rats. Microdialysis probes were placed in the caudate nucleus and temporal cortex. Each rat underwent one of the following ischemic regimens: groups I, II, and III--MCAo was maintained for 60, 120, and 180 min, respectively, followed by 120 min of reperfusion; group IV--a sham group in which MCAo and reperfusion were simulated; group V--7 h of MCAo only. Dialysate was measured for TxB2 by radioimmunoassay. Brain levels of TxB2 did not deviate from baseline during MCAo (or in the sham group). In contrast, during reperfusion, there was a significant increase in TxB2 following 180 min of MCAo but not after 60 or 120 min or MCAo (p < 0.05). These data indicate that, in this model of cerebral ischemia, TxB2 does not increase during MCAo. However, following a threshold duration of MCAo (180 min), the vasoconstrictor TxB2 may modulate postischemic hypoperfusion. These findings may have implications in the pharmacologic treatment of postischemic hypoperfusion and reperfusion brain injury.