Keywords
electroencephalography - general anesthesia - neurophysiological monitoring - pain
Introduction
Processed electroencephalography (EEG)-based monitors such as Bispectral Index (BIS
Medtronic, Dublin, Ireland), State, Response Entropy (SE/RE; GE Health Care, Helsinki,
Finland), and Patient State Index (PSI; SedLine, Masimo, Irvine, California, United
States) are commonly utilized depth of anesthesia (DOA) monitors for titrating hypnosis.[1]
[2] These DOA monitors measure relatively high-frequency EEG power rather than low-frequency
activity. Hence, they mainly focus on the EEG changes associated with various depths
of hypnosis and not the EEG changes associated with noxious stimuli.
Recently, there has been a renewed interest in utilizing the EEG/processed EEG to
assess pain response to noxious stimuli.[3]
[4]
[5] Although the EEG response to noxious stimuli was first reported in the early 90s,
it has seldom received attention for pain assessment.[6]
[7]
[8] Beta arousal (increase in β power in 12–25 Hz band), alpha dropout (decreased α
power in 8–12 Hz), and delta arousal (increased delta power in 0.5–4 Hz) are the three
EEG patterns reported in the literature in response to noxious stimuli.[2]
[3]
Increased cortical depolarization to noxious stimuli during the light plane of anesthesia
produces a beta arousal pattern. The alpha dropout and delta arousal patterns are
observed during adequate DOA with inadequate analgesia. Exaggerated GABAergic negative
feedback loops in the brainstem and thalamic regions convert intense noxious stimulation
to slow-wave activity, producing delta arousal. Cortical hyperpolarization due to
sufficient intrinsic inhibitory GABAergic drug effects is responsible for alpha dropout.
Both delta arousal and alpha dropout need to be treated with analgesics without altering
the DOA, while beta arousal should be treated with increasing the DOA along with analgesics.[3]
We are submitting multiple observations that explore the intriguing phenomenon of
the transient burst suppression pattern (BSP) in density spectral array (DSA) display
of SedLine Masimo, which is associated with intense noxious stimulation at various
stages of spine surgery under an adequate depth of general anesthesia (GA) using sevoflurane/total
intravenous anesthesia (propofol and fentanyl). This observation has not been reported
in the literature.
Case Series
Case1
A 61-year-old male with diabetes, hypertension, and a history of coronary artery bypass
grafting for triple-vessel disease was diagnosed with L2–3 central disc prolapse.
He underwent L2 laminectomy, and L2–3 discectomy under sevoflurane anesthesia (PSI
ranged 25–35) with bilateral erector spinae block at the L2-L3 level. As the block
worked well, the patient's hemodynamics remained stable throughout the surgery. During
discectomy, the surgeon retracted the nerve root (intense noxious stimuli), which
resulted in a sudden transient drop in PSI along with BSP in DSA ([Fig. 1A]) of SedLine Masimo along with a transient increase in blood pressure and heart rate
([Fig. 1B]). The response was treated with fentanyl (30 μg) and propofol (30 mg), which resulted
in the disappearance of BSP with normalization of vital signs.
Fig. 1 (A) Case no 1: SedLine Masimo, showing the transient drop in patient state index (PSI)
along with burst suppression pattern (pink arrows) in the density spectral array (DSA)
at the time of root handling (noxious stimuli) during L2-L3 discectomy. (B) Shows the vital trends; at the time of root stimulation, there is a transient elevation
in blood pressure (BP) and heart rate (pink line). (C) Case no 2: SedLine Masimo – DSA display showing transient burst suppression pattern
(vertical black lines) in a patient undergoing C6 corpectomy at the time of cage placement
(noxious stimuli). (D) Case no 3: SedLine Masimo – DSA display showing multiple transient burst suppression
patterns (vertical black lines) for a few minutes at the time of ventral untethering
at T6 (cord retraction with root stretching lead to noxious stimuli).
Case 2
A 64-year-old hypertensive male presented with clinical features of compressive myelopathy
at C5–6 and C6-C7 levels due to central disc prolapse and ligamentum flavum hypertrophy
with spinal cord signal changes at the C6–7 level. He underwent a C6 corpectomy with
instrumented fusion under sevoflurane anesthesia. The patient's DOA was stable during
surgery (PSI ranged between 28 and 40). At the time of cage placement, multiple BSPs
were noted on the DSA that lasted for 8 to 10 minutes and were treated with a fentanyl
bolus without altering the DOA. Subsequently, the BSP disappeared ([Fig. 1C]).
Case 3
A 65-year-old male, a diabetic, hypertensive, and heavy smoker with severe chronic
obstructive lung disease, presented with clinical features of T6 compressive myelopathy.
Magnetic resonance imaging spine revealed severe cord compression at the T6 level
with ventral tethering. The patient underwent T5-T8 posterior fusion, followed by
T5–7 laminectomy and ventral untethering under total intravenous anesthesia using
propofol (150–200 μg/kg/min) and fentanyl (1–2 μg/kg/hr) with motor-evoked potential
monitoring. His hemodynamics and DOA were stable throughout the surgery. At the time
of ventral untethering (cord retraction and root stretch), we observed BSP on the
DSA of SedLine Masimo, which was treated with fentanyl bolus, followed by increasing
the fentanyl infusion rate. Subsequently, the BSP did not reappear ([Fig. 1D]).
Discussion
From our case series, we observed transient BSP pattern during intense noxious stimulation
in hemodynamically stable patients at various stages of spine surgeries with adequate
DOA. This pattern was observed without the delta arousal or alpha dropout pattern
on DSA. Traditionally, in a hemodynamically stable patient, during the maintenance
phase of GA, the appearance of BSP on EEG/processed EEG generally indicates excessive
hypnosis. It is usually treated with decreasing the DOA by reducing the dose of hypnotic
agents (inhalational agents/propofol). Decreasing the DOA in the presence of noxious
stimuli can lead to adverse consequences, especially in high-risk patients.
There are various physiological and pathological causes for intraoperative BSP on
EEG, such as hypoxia, severe hypotension, intraoperative stroke, severe hypothermia,
refractory status epilepticus, and raised intracranial pressure with low cerebral
perfusion pressure.[9] All these factors will cause persistent BSP pattern on EEG/processed EEG. In our
case series, all patients had sudden, transient BSP associated with noxious stimuli.
All of them underwent spine surgeries with stable hemodynamics, and none of them had
intraoperative hypotension or hypoxic events. None of them had any intracranial pathology
or woke up with neurological deficits indicative of stroke.
Animal studies have shown that the administration of N-methyl-D-aspartate receptor
antagonists in patients receiving GABAergic agonists also causes transient BSP by
increasing the DOA and accelerating the recovery through the cholinergic mechanism.[10] However, in our case series, none of them received ketamine for intraoperative analgesia.
Studies have shown that the duration of BSP has a positive correlation with postoperative
cognitive dysfunction and delirium.[9] In our case series, since the BSP was transient, none of the patients had postoperative
delirium or cognitive dysfunction.
There is no standard monitoring method for assessing pain under GA. Traditionally,
cardiovascular parameters, autonomic signs, and somatic responses have been used to
assess pain responses under GA. However, all these parameters have low sensitivity
and specificity, especially with adequate DOA. Recently, various monitors have been
used to monitor nociception based on autonomic nervous system indices, EEG-based monitoring,
and spinal reflex-based monitoring.[2]
[3] Nociception monitor with high sensitivity and specificity is yet to be elucidated.
Awareness regarding these processed EEG/DSA changes associated with intense noxious
stimuli helps the anesthesiologist titrate analgesia without altering the DOA. The
long-term clinical consequences of BSP with noxious stimulation remain unknown. Future
studies are needed to determine whether processed EEG/DSA can be utilized as a potential
biomarker of pain perception and to elucidate the long-term effects of noxious stimuli-induced
BSP and its clinical outcome.
