Experimental evidence suggest that various types of anaesthetics indirectly suppress cortical responses to painful or other ascending stimuli by an action on the spinal cord29
. The mechanism for this effect is not completely understood, but compelling evidence exists that spinal cord anaesthesia, through a decrease in the ascending somatosensory transmission, depresses the activity of reticulo-thalamo-cortical mechanisms that regulate arousal12, 13
. On the other hand, acute sensory deafferentation in various animal models is associated with reduced activity of the midbrain reticular formation and cerebral cortex10, 11
. In humans, epidural and spinal anaesthetics depress consciousness and reduce anaesthetic requirements for different anaesthetic endpoints1-3, 5 7
. However, resetting the brain's arousal system by deafferentation of sensory input implies a dose-dependent effect — which has not previously been clearly demonstrated.
Sensory block levelduring epidural anaesthesia significantly predicted sedation depth in our volunteers, as measured by both objective and subjective methods. Loss of afferent sensory input during epidural anaesthesia was associated with a downregulation of brainstem neural activity as this was evaluated using auditory evoked potentials (BAEP). The latency of BAEP III showed a significant correlation with the level of sensory block. Wave III is generated by neural elements around the nucleus of inferior colliculus, which receives somesthetic input from the spinothalamic tract and medial lemniscus19, 20
, while it appears to induce cortical activation by acting through both cholinergic and serotonergic systems21
. Auditory circuits in the brainstem interact with reticular nuclei providing the anatomical basis for the defence alertness reaction, sensory information control, and even sleep regulation17-18
Taken into account the very limited BAEP response to general anaesthetics22-25
, even at anaesthetic depths associated with EEG burst suppression30
, we believe that the significant correlation of sensory block with the latency of brainstem potential III involves a selective effect of sensory deafferentation on the activity of the midbrain region inside and in the vicinity of inferior colliculus. Despite the fact that sensory input (including auditory stimulation) from the unblocked areas of the body might have counteracted any deafferentation effect on BAEP in unmedicated volunteers, brainstem conduction showed a significant positive correlation with the block level and sedation depth. These findings support the original hypothesis that sensory block affects, in a dose-dependent manner, brainstem transmission.
The effect of epidural anaesthesia on BAEP has been evaluated previously by others31
who found that lidocaine epidural anaesthesia prolonged the peak latencies and delayed brainstem transmission. However, a similar pattern of BAEP inhibition after intravenous lidocaine administration32
suggested that systemic absorption rather than anaesthetic block itself was responsible for the effect on brainstem neural activity. To avoid the potential effect of systemically absorbed anaesthetic on BAEP, we used chloroprocaine which is metabolized by plasma cholinesterase and has an elimination half-life ranging from 10 seconds to 3 minutes33, 34
. Using multiple small epidural boluses enabled us to assess the sensory block level during its evolution, as well as its regression. Comparison of sedation depth at the same block between those two phases of the anaesthetic did not reveal any difference. Thus, despite our lack of a placebo-controlled experimental condition, we believe that repetitive assessments of the block level, during both evolution and regression of the sensory block, reduced the likelihood that systemic chloroprocaine or elapsed study time confounded our findings.
Since the activity of cholinesterase in the cerebrospinal fluid (CSF) is greately diminished compared to the plasma35
, there still remains a theoretical possibility that part of the chloroprocaine absorbed into the CSF could flow in the cephalad direction and exert its effects directly on the brainstem. However, in that case, a rather homogeneous than selective effect on BAEP would be a more likely outcome. Our findings do not support this possibility.
Responsiveness of the volunteers was maintained at an OAA/S score of 4 or 5. These data are in agreement with previous findings7
. Prediction probability analysis showed that sensory block level predicts OAA/S score with similar strength as VRS. PK
is a nonparametric measure of association that is recommended as a performance measure for anaesthetic depth indicators and observed depth scales of any degree of coarseness or fineness28
. It is important to understand that the PK
statistic is not prediction as we typically think of it. Instead, PK
is the probability that for any two data pairs selected from the data set, the order of one variable (e.g.
, block level) will correctly “predict” the order of the other variable (e.g.
, VRS). In a sense, the PK
value is the proportion of times that the higher VRS score is paired with the higher block level. We believe that the use of self-reported sedation did not introduce bias in our results because the volunteers were not aware of the purpose of the study or the basic hypothesis. Consistent with this theory, PK
values of sensory block level were identical for the VRS and OAA/S score.
The bispectral index predicted sedation depth as defined by the VRS and OAA/S score. The PK
value of sensory block level for BIS was lower than for the other sedation depth indicators; however, it was significantly different from 0.50 which is the PK
value indicating no association. This is a new finding and contrasts with results of a previous placebo-controlled trial which concluded that BIS was an insensitive indicator of sedation and was affected only 60 minutes after the injection of spinal anaesthetic7
. This late sedation was ascribed to delayed cephalad spread of the local anaesthetic. On the other hand, in a non-randomized trial, the same investigators found that the largest deviation of BIS from the baseline value occurred 30 minutes after spinal injection and coincided with the highest block level7
In conclusion, we found that sedation during epidural anaesthesia depends on the level of sensory block and is associated with detectable alterations in the brainstem auditory evoked responses. Sensory deafferentation during neuraxial anaesthesia may modulate CNS alertness through mechanisms related to brainstem neural activity.