Effect of Volatile Anesthetics on Brain pO2 during Hypoxic Hypoxia
Huagang Hou1, Oleg Y. Grinberg1, Stalina A. Grinberg1, Nadeem Khan1, Jeffrey F. Dunn2, Harold M. Swartz1
1EPR Center for the Study of Viable
Systems, Dartmouth
Medical School, Hanover, NH 03755, USA
2Biomedical NMR
Laboratory, Dartmouth
Medical School, Hanover, NH 03755, USA
INTRODUCTION
The effects of various
anesthetics under a range of FIO2 (0.21-1.0) on brain oxygenation
have been measured using EPR Oximetry.
While overall the deleterious effects of
hypoxia on various aspects of brain function are well recognized, presumably
due
to decreased cerebral PtO2, the role of oxygen in
pathophysiology of brain remains empirical and incomplete.
This is due in part,
to a lack of quantitative data on the relationship between cerebral PtO2
and the deleterious effects that are observed.
It has been shown that the
brain can maintain energy balance down to a PtO2 of 8.8 mm Hg, when
under ketamine/xylazine anesthesia.
In clinical conditions, isoflurane and
halothane are more widely used. Since anesthesia has varying effects on CBF and
CMRO2,
it is likely that volatile anesthetics will have different
effects on brain PtO2 during hypoxia. The aim of this study was to
investigate
brain PtO2 during hypoxia, using two different volatile
anesthetics, isoflurane and halothane, making repeated measurements by
utilizing EPR oximetry.
METHODS
12 male Sprague-Dawley rats,
250-350 g, were used. One week prior to the PtO2 measurements, rats
were anesthetized with ketamine/xylazine
(80/8 mg/kg, i.m.), and LiPc crystals
were placed via a spinal needle directly into the brain at a depth of 2.0 mm
from the surface of the skull,
through 1.0 mm drilled holes located 3.0 mm from
the midline and 1.0 mm in front of the bregma. Rats with LiPc crystals in their
brain were randomly
assigned to either isoflurane or halothane experimental
groups and accordingly were anesthetized with 3.0% isoflurane or 2.5% halothane
in 26% O2/balance nitrogen. After an adequate level of anesthesia
was achieved, endotracheal intubation was carry out using laryngoscopy
and an
“over-the-needle” 14 gauge catheter. Femoral arterial and venous catheters
(PE-50 tubing) filled with heparinized saline were inserted
and all wound sites
were infiltrated with 2.0% lidocaine. The arterial catheter was connected to a
pressure transducer for continuous blood
pressure monitoring and periodic blood
gas measurements, while the venous catheter was used for administration of
drugs and fluids.
Total surgical preparation time was 30-40 min (measured from
the start of induction). Following surgery, the inspired anesthetic agent
concentration was reduced to either 0.7 MAC isoflurane (0.9-1.0%) or 0.7 MAC
halothane (0.7-0.8%) in 26% O2/balance nitrogen. Next,
we paralyzed
the rats with pancuronium (0.2 mg/kg/h), then ventilated with a small animal
ventilator. These doses/concentrations were
chosen to produce comparable acute
levels of anesthesia based on the literature. Rectal temperature was
controlled at 37.0
± 0.5°C via a heated pad.
All six animals in each group
underwent the same protocol. The only difference between the two groups was the
anesthetic. FIO2
was maintained at 0.35 during vascular and airway
access, and then animals were allowed to stabilize for 10-15 min before
beginning data collection.
Then the rats were exposed for 30 minutes each to
FIO2 of 0.26, 0.21, 0.15 and 0.10. Fluid balance was maintained with
1.0 ml /hr of saline (i.v.).
Blood pressure was continuously monitored by a
pressure transducer. Blood pressure was not controlled pharmacologically in
order
to avoid drugs with direct effects on the cerebral vasculature. Arterial
blood gas analysis was done with a blood gas analyzer using 0.1 ml of blood
collected from the femoral artery. Samples were collected 10 min before
commencing a change of FIO2 and at the termination of the
experiment.
At the end of the experiment, the rats were euthanized. Gross and
microscopic examination (H & E staining) of the tissue around
the implanted LiPc confirmed that crystals were in the cerebral cortex and that there was no
significant inflammatory infiltrate or necrosis around the LiPc.
RESULTS
Table summarizes the data. Heart rate
and rectal temperature did not change with decreasing FIO2. The MBP value
did not vary
significantly from baseline (FIO2 = 0.21) in either
group with FIO2 = 0.35 or 0.26, but did vary significantly at FIO2
= 0.15 and 0.10.
There was a significant difference in MBP between the two
anesthetics at all FIO2, which became pronounced under
hypoxia.
These differences occurred even though they are well in the normal
cerebral regulatory ranges at the FIO2 = 0.10 in
the isoflurane group.
The PaCO2 and pH did not change significantly from
baseline in the isoflurane group, but did in the halothane group at FIO2 = 0.10.
At
FIO2 = 0.10 the PaCO2 and pH in the halothane group was
significantly lower than in the isoflurane group. With each anesthetic,
the PaO2
decreased significantly with decreasing FIO2; at the same FIO2
there were no significant differences in PaO2 between groups.
With
each anesthetic, the PtO2 decreased significantly with decreasing
FIO2.
There were no statistically significant differences in PtO2
between the groups at any FIO2.
The
general pattern of observed changes in cerebral PtO2 suggests that
the response to hypoxia under halothane does
not differ greatly from isoflurane. However, the magnitude of changes in MBP, PaCO2, and pH
varied significantly with the different agents.
These differences could have a
significant impact on the management of inhalation anesthetic when hypoxia may
occur during the procedure.
These results demonstrate the value of making
direct measurements of PtO2.
The ability to obtain such data with EPR oximetry indicates the usefulness of this method.
Table. Mean blood
pressure (mm Hg), heart rate (beats/minute), rectal temperature (°C), blood gas
(mm Hg), pH and cerebral PtO2
(mm Hg) during exposure to each anesthetic agent with different FIO2.
|
Variables FIO2 (%) |
|
0.35 0.26 0.21 0.15 0.10 0.35 |
|
Isoflurane MBP 105.6±4.5 96.3±4.7 98.0±4.0 82.2±2.6+ 67.4±11.3+ 106.5±2.8 HR 360.9±18.0 348.6±13.6 375.7±28.8 378.9±23.3 351.3±22.0 391.5±20.6 Temp. 36.8±0.2 37.1±0.2 37.3±0.2 37.2±0.2 36.7±0.3 37.2±0.3 PaO2 142.6±6.9++ 111.3±3.6++ 84.0±2.4 45.9±2.6+ + 37.7±3.8 ++ 154.5±5.5++ PaCO2 39.2±0.9 38.7±1.4 37.9±1.1 40.3±1.6 37.2±0.8 37.8±0.7 pH 7.42±0.01 7.42±0.01 7.43±0.01 7.41±0.03 7.37±0.02 7.41±0.01 PtO2 28.9± 2.8++ 22.3±2.8++ 14.4±2.5 6.8±1.3++ 2.8±0.3++ 27.3±3.5++ Halothane MBP 93.8±2.6* 84.8±2.1* 86.6±6.7* 70.1±4.7*+ + 38.7±2.1**++ 95.6±4.8*+ HR 331.2±12.0 344.0±9.4 348.7±12.1 374.4±10.6 342.9±20.3 393.2±17.5 Temp. 36.6±0.2 37.0±0.2 37.3±0.3 37.4±04 37.2±0.4 37.7±0.3 PaO2 132.9±3.9++ 106.1±5.2 ++ 76.1±3.7 46.4±3.8+ + 36.7±1.8++ 134.6±11.7++ PaCO2 40.4±1.3 40.8±1.5 40.2±2.2 41.1±1.9 34.4±0.7*+ 38.4±1.1 pH 7.42±0.01 7.41±0.01 7.43±0.01 7.41±0.02 7.26±0.04*++ 7.42±0.02 PtO2 28.0± 2.3++ 21.6±1.9++ 13.7±2.6 8.6±1.9++ 4.7±0.8 ++ 27.6±4.3 ++ |
Values are
given as means ± SE. * p< 0.05; ** p< 0.01, significant differences
as compared with isoflurane (unpaired t test).
+ p< 0.05;
++ p< 0.01,
significant differences as compared with 0.21 FIO2 in same
group (paired t test). N = 6 in each group.
ACKNOWLEDGEMENTS
This work
was supported by a NIH (NIBIB) grant PO1 EB002180, “Measurement of pO2 in
Tissues In Vivo and In Vitro,”
and used the facilities of the EPR Center for the Study of Viable
Systems supported by NIH (NIBIB) grant P41 EB002032.