Case 22 BIS

Major lumbar spinal procedures such as microlumbar discectomy at L4–5 demand careful integration of physiology, pharmacology, and neuromonitoring. When the patient has morbid obesity (BMI 46) and uncontrolled type 2 diabetes (HbA1c 9.5%), virtually every anesthetic drug, every physiologic system, and every electroencephalographic output becomes altered. Depth-of-anesthesia monitoring using the Bispectral Index (BIS) becomes not only helpful but essential. In routine practice, BIS provides a surrogate estimate of hypnotic depth based on: Cortical EEG power Phase coupling Synchronicity Spectral distribution Burst suppression High-frequency contamination (usually EMG) Artifact filtering (SQI) However, in obesity and diabetes, BIS must be interpreted differently. Obesity pushes BIS upward (higher baseline, more EMG, sympathetic overactivity). Diabetes pushes BIS downward (lower cortical power, microvascular dysfunction, volatile sensitivity). This chapter provides the most detailed integrated analysis of how: Morbid obesity Uncontrolled diabetes Induction agents Opioids Muscle relaxants Volatile anesthetics Dexmedetomidine Non-narcotic adjuncts N₂O Magnesium NSAIDs Basic physiology interact with every BIS-derived parameter: The entire anesthetic regimen: Glycopyrrolate 0.2 mg Midazolam 1 mg Fentanyl 200 µg Dexona 8 mg Propofol 150 mg Atracurium 40 mg + infusion 30 mg/hr Dexmedetomidine 30 µg Magnesium sulfate 1 g Paracetamol 1 g Diclofenac 100 mg suppository Morphine 5 mg IM at end was applied over a 3-hour surgical timeline, during which BIS progressed through the pattern you documented: This chapter explains — step by step — why these BIS values occurred, how obesity and diabetes altered each parameter, how each drug contributed, and what these findings teach us about future anesthetics. Pathophysiology of Morbid Obesity & Its Influence on BIS, SEF, SR, TP, EMG, and SQI Morbid obesity alters nearly every physiologic system affecting EEG generation, drug distribution, and neuromuscular activity. The following subsections describe, in detail, how obesity modifies each of the BIS-derived parameters. HOW OBESITY AFFECTS BIS 1) Higher Baseline BIS Morbid obesity increases: Sympathetic activity Anxiety Resting EMG tone Beta frequency EEG activity Thus pre-induction BIS is often 96–99, even when the patient appears calm. 2) Larger Volume of Distribution Highly lipophilic drugs (propofol, fentanyl, midazolam, dexmedetomidine) accumulate in adipose tissue. Result: Slower offset More gradual BIS rise during emergence Delayed cortical reactivation 3) Increased Cardiac Output Obese patients maintain higher resting CO. Effect: Faster brain delivery of induction drugs Rapid BIS drop after propofol or sevoflurane Sharper initial EEG suppression 4) Decreased Functional Residual Capacity (FRC) Reduced FRC causes: Erratic volatile uptake Variable EtSevo → fluctuating cortical suppression BIS values that swing when ventilation changes HOW OBESITY AFFECTS SEF SEF = 95th percentile frequency. Obesity creates: High EMG leak → falsely high SEF readings High sympathetic tone → elevated beta activity (14–22 Hz) Higher airway pressures in prone → transient cortical activation Thus SEF often appears high even if BIS indicates adequate depth. HOW OBESITY AFFECTS SR (SUPPRESSION RATIO) Obesity usually protects against SR: Higher CO₂ → increased cerebral blood flow Higher metabolic reserve Less volatile sensitivity Unless overdosed, obese patients rarely show burst suppression. HOW OBESITY AFFECTS TP (TOTAL POWER) Obesity generally increases TP because: Higher CO₂ → higher cerebral blood flow More robust cortical amplitude High EMG contaminates low frequencies → increases apparent total power However, this is offset by diabetes (see next section). HOW OBESITY AFFECTS EMG This is the most important obesity effect. Morbid obesity → Higher baseline muscle tension Neck/thorax mass increases work of breathing Prone position activates paraspinal muscles Facial musculature remains tonically active Thus EMG is often 20–40 throughout surgery unless deep paralysis is maintained. This is exactly what your monitor showed. HOW OBESITY AFFECTS SQI Obesity reduces SQI because: Skin folds cause poor electrode contact Sweating dislodges adhesion Forehead oiliness in metabolic syndrome reduces conductivity Fat pad over brow introduces micro-movement artifacts That your patient maintained SQI 95–100 throughout indicates excellent electrode preparation. TABLE 1 — Effects of Morbid Obesity on BIS Parameters Reference De Baerdemaeker L, Mortier E. General anesthesia in obesity. Curr Opin Anaesthesiol. 2005;18:21–28. Ebert TJ. Sympathetic activation in obesity. Anesth Analg. 2000;91:759–766. Bennett C. EMG interference on BIS. Anesth Analg. 2009;108:104–110. Laflamme M. Obesity and EEG response. Acta Anaesthesiol Belg. 2007;58:65–70. Uncontrolled Diabetes Mellitus (HbA1c 9.5%) and Its Impact on BIS Parameters Chronic uncontrolled hyperglycemia alters neuronal metabolism, cerebral perfusion, autonomic responses, EEG amplitude, and susceptibility to anesthetics. Diabetes has the opposite effect of obesity on many BIS parameters. HOW DIABETES AFFECTS BIS 1) Lower Baseline EEG Amplitude Microvascular ischemia reduces neuronal metabolic activity, lowering: Alpha power Beta power Overall cortical amplitude Thus BIS tends to be lower than expected for any given hypnotic concentration. 2) Increased Sensitivity to Volatiles Diabetics show exaggerated cortical suppression from: Sevoflurane Isoflurane Desflurane Propofol synergism Thus BIS drops faster and deeper during induction. 3) Autonomic Neuropathy → BIS-Hemodynamic Dissociation HR and BP changes do not accurately reflect depth. Thus BIS becomes more important for titration. HOW DIABETES AFFECTS SEF 1) Lower baseline SEF Due to reduced alpha/beta production. 2) Unstable SEF during anesthesia Small changes in anesthetic concentration → large changes in SEF. 3) Faster SEF suppression by volatiles Diabetics have enhanced volatile sensitivity → SEF drops before BIS. HOW DIABETES AFFECTS SR 1) Diabetic brains enter suppression more easily Reduced metabolic reserve → more sensitive to anesthetics → more prone to suppression. 2) Volatile + Propofol synergy → increased SR risk Even moderate MAC levels can cause EEG quiescence. Your case maintained SR = 0 because: N₂O supplemented hypnotic effect Sevo was kept modest Dexmedetomidine smoothed depth EMG kept artifacts low BP was stable HOW DIABETES AFFECTS TP (TOTAL POWER) 1) Low TP is common Chronic hyperglycemia → reduced cortical amplitude → lower TP. 2) Hypotension worsens TP Diabetics have impaired autoregulation → small drops in MAP produce large TP reductions. In your case, MAP was maintained well; TP remained 64–69. HOW DIABETES AFFECTS EMG Two opposing effects: 1) Autonomic neuropathy reduces EMG responsiveness Lower variability during early emergence. 2) Sudden EMG surge when reflexes return The diabetic patient may appear outwardly still, then suddenly have EMG bursts. This explains EMG ~49 pre-extubation. HOW DIABETES AFFECTS SQI Diabetes typically: Does not significantly impair EEG electrode adhesion May help SQI due to dryer skin If neuropathy reduces sweating, artifacts decrease Your SQI remained high. TABLE 2 — Effects of Uncontrolled Diabetes on BIS Parameters Reference Callaghan BC, et al. Diabetic neuropathies. Lancet Neurol. 2012;11:521–534. Ozanne SE. Neural consequences of diabetes. Diabetes. 2007;56:2987–2994. Mizuno J, et al. Diabetes and EEG physiology. Clin Neurophysiol. 2016;127:1221–1229. HOW OBESITY AND DIABETES INTERACT TO ALTER BIS Morbid obesity and uncontrolled diabetes have opposing effects on several BIS components. The anesthesiologist must understand the push–pull relationship between these two disease states to interpret BIS in such patients. Combined Effects on BIS Net result: BIS becomes more variable, requiring careful interpretation of SEF, EMG, and TP. Combined Effects on SEF Net result: SEF fluctuations 10–22 Hz common even with stable anesthesia. Combined Effects on SR Net result: Moderate anesthetic dosing avoids SR; your case maintained SR = 0. Combined Effects on TP Net result: TP becomes moderately reduced but stable (as in your TP 64–69). Combined Effects on EMG Net result: EMG 30 during surgery → EMG 49 at emergence (your case) is typical. Combined Effects on SQI Net result: SQI depends on correct electrode placement. Your SQI of 95–100 was ideal. Reference Pilge S, et al. EEG monitoring of anesthesia. Best Pract Res Clin Anaesthesiol. 2006;20:109–118. Bennett C. Impact of EMG on BIS. Anesth Analg. 2009;108:104–110. Purdon PL, et al. Neurophysiology of anesthetic EEG changes. J Neurosci. 2015;35:1105–1117. How Premedication Alters BIS in a Morbidly Obese, Uncontrolled Diabetic Patient Premedication behaves very differently in a BMI 46, HbA1c 9.5% patient because obesity and diabetes create opposing effects on the BIS signal: Obesity increases EMG and sympathetic tone → BIS goes UP Diabetes reduces cortical power → BIS goes DOWN Thus, the pre-induction BIS is always a tug-of-war between EMG contamination (obesity) and low amplitude EEG (diabetes). Let's analyze each premedication drug strictly in terms of BIS, SEF, SR, TP, EMG, and SQI, without tables. Glycopyrrolate 0.2 mg — How It Alters BIS in This Physiology Although glycopyrrolate does not cross the blood–brain barrier, it significantly affects BIS indirectly through sympathetic activation. Effects in Morbid Obesity Morbidly obese patients have chronically elevated sympathetic tone and increased baseline EMG from: Overworked upper airway muscles Tonic activation of frontalis and masseter muscles Increased work of breathing even while resting When glycopyrrolate blocks parasympathetic activity, this sympathetic dominance becomes unopposed. This increases frontal EMG, which BIS translates as higher cortical activation, even though the patient is not more awake. Thus in obesity, glycopyrrolate frequently produces a false BIS rise and false SEF rise. BIS may climb 3–10 points simply due to excess muscle activation. Effects in Uncontrolled Diabetes In contrast, diabetic autonomic neuropathy blunts the cardiovascular and sympathetic response. This means the expected EMG surge may not occur. Thus in diabetes, glycopyrrolate may have little or no effect on BIS. Combined Effect in This Patient Because obesity enhances EMG and diabetes dampens sympathetic reactivity, the BIS response is mild: BIS tends to rise slightly or remain unchanged SEF rises a little due to beta contamination EMG rises modestly TP and SR remain unchanged SQI remains high unless sweating is present The key point is: glycopyrrolate does not sedate or stimulate the brain; it changes the BIS primarily by increasing EMG. Midazolam 1 mg — BIS Effects in an Obese Diabetic Brain Midazolam is the first drug that produces true EEG changes. Its BIS effect is amplified by diabetes and prolonged by obesity. Effects in Morbid Obesity Obesity increases the volume of distribution significantly. A dose of 1 mg produces mild sedation but lasts longer because the drug redistributes into fat slowly. In terms of BIS: EMG decreases, making BIS more reliable Anxiety is reduced BIS may drop 5–10 points but not profoundly SEF decreases slightly due to GABAergic slowing Effects in Uncontrolled Diabetes Midazolam’s cortical effects are much more noticeable in diabetics: Diabetes reduces alpha and beta EEG power Midazolam further diminishes fast frequencies The BIS drop from a small dose appears larger TP falls because diabetic brains produce lower amplitude waves Thus even 1 mg can produce a noticeable BIS reduction. Net BIS Interpretation In this patient: BIS decreases modestly SEF clearly drops TP decreases EMG falls, making the BIS reading more accurate SR remains zero The most important point: diabetes makes midazolam appear more potent on EEG than in healthy individuals. Fentanyl 200 µg — Why the BIS Change Is Subtle in This Physiology Opioids do not cause hypnosis. They should not significantly reduce BIS — and they don’t. But fentanyl modifies the BIS indirectly. Effects in Morbid Obesity Obese patients tend to hypoventilate, especially after opioid administration. Rising CO₂ stimulates cortical activation. Paradoxically, fentanyl can cause a slight BIS increase if CO₂ rises. However, fentanyl also: Lowers nociceptive tone Reduces EMG Blunts sympathetic responses during laryngoscopy Thus, the BIS effect is mixed. Effects in Uncontrolled Diabetes Diabetics are more opioid-sensitive because of: Small-fiber neuropathy Lower nociceptive thresholds Possible reduced clearance Pain pathways dampen quickly, and fentanyl reduces cortical arousal. Thus fentanyl can cause a subtle BIS decrease in diabetics. What Happens in This Patient Because obesity pushes BIS up and diabetes pushes BIS down, the net effect is minimal. BIS may fall by 3–5 points, but not more. SEF remains stable, SR 0, TP slightly reduced, EMG decreases modestly. Fentanyl’s main contribution is reducing EMG noise and preventing BIS spikes during laryngoscopy. NON-HYPNOTIC ADJUNCTS AND BIS Even though dexamethasone, magnesium, paracetamol, and diclofenac do not directly sedate, they strongly influence EEG stability, especially in patients where nociceptive surges cause unpredictable BIS fluctuations. Dexamethasone 8 mg — The BIS Stabilizer Dexamethasone stabilizes BIS primarily by decreasing nociceptive cortical activation. In Obesity Obese patients have higher inflammatory tone. Steroids reduce this, indirectly decreasing: Subcortical arousal Beta-activity from pain EMG associated with discomfort Thus BIS becomes smoother and less reactive. In Diabetes Dexamethasone does not affect EEG directly. It does not significantly change BIS unless pain pathways are involved. Net Effect BIS stabilizes SEF decreases slightly TP remains stable EMG falls SQI improves because the patient moves less This drug’s effect is subtle but clinically helpful. Magnesium Sulfate 1 g — The Most Underestimated BIS Drug Magnesium has a profound BIS-cleaning effect because it reduces: NMDA-mediated excitatory activity Nociceptive transmission Sympathetic tone Muscle activity (by potentiating NMBAs) In Obesity Because obese patients have high EMG baseline, magnesium reduces EMG significantly. This makes BIS more accurate, not necessarily lower. In Diabetes Diabetics often have subclinical magnesium deficiency. Restoring magnesium reduces neural irritability, which: Lowers SEF Lowers cortical noise Stabilizes BIS against incision-related fluctuations Net Effect on BIS BIS may fall