Awareness Under Anaesthesia

Definitions and Terminology

• Miller's Anesthesia, 10e, p. 683

Incidence

• Overall incidence of AWR (awareness with explicit recall): approximately 1-2 per 1,000 general anaesthetics when formally assessed
• The incidence of intraoperative consciousness without recall is substantially higher
• AWR carries a high incidence of posttraumatic stress disorder (PTSD)
• Approximately 2% of closed claims in the ASA Closed Claims Project database relate to awareness
• Miller's Anesthesia, 10e, p. 682; Morgan & Mikhail, 7e, p. 2347

High-risk surgical contexts:

Risk Factors

Patient-related

• Female sex (claims for recall more likely in women, especially without a volatile agent)
• Long-term substance abuse (increased anaesthetic requirements)
• Difficult airway (intubation difficulties may delay or interrupt anaesthetic delivery)
• High ASA status / haemodynamic instability (anaesthesia deliberately lightened)
• Obesity (altered pharmacokinetics)
• Prior awareness

Surgical / procedural

• Cardiac surgery (reduced agent tolerated due to cardiovascular compromise)
• Obstetric surgery under GA (low volatile agent concentration used to preserve uterine tone and avoid neonatal depression)
• Major trauma (haemodynamic instability limits dosing)
• Neuromuscular blockade - muscle relaxants mask the motor signs of inadequate depth and prevent the patient from signalling; implicated as a major contributor to AAGA

Anaesthetic / technical

• Vaporiser malfunction or empty
• Drug labelling / administration errors (e.g., paralytic given before induction agent)
• Total intravenous anaesthesia (TIVA) without EEG monitoring - no exhaled agent as a check
• Under-dosing (especially opioids used as the sole agent without hypnotics)

Mechanisms

1. Explicit episodic recall - suppressed by the amnesic effects of most inhalational and IV agents, even at sub-hypnotic doses (hippocampus, amygdala, prefrontal cortex)
2. Consciousness/hypnosis - mediated through thalamocortical circuits; requires disruption of cortico-subcortical connectivity
3. Movement - spinal reflex suppression (basis of MAC)
4. Autonomic responses - heart rate, blood pressure changes to nociception

• Miller's Anesthesia, 10e, p. 5346

Key neuroscience

• GABA-ergic drugs (propofol, volatile agents) act largely through thalamocortical hyperpolarisation - the resulting alpha-delta EEG pattern is the primary monitoring target
• Orexinergic and aminergic arousal systems (locus coeruleus, VTA, DRN) are suppressed by anaesthesia but can "break through" when dosing is inadequate
• Dopaminergic stimulation of the VTA can reverse anaesthetic-induced unconsciousness
• Miller's Anesthesia, 10e, pp. 691-693

Clinical Features of an Awareness Episode

• Auditory - hearing voices or sounds (most common sensory modality recalled)
• Tactile - feeling of pressure, touch, or surgical manipulation
• Pain - pain during surgery (the most distressing form)
• Paralysis - inability to move or communicate despite being conscious
• Emotional - fear, helplessness, panic

Sequelae

• PTSD - sleep disturbances, nightmares, social difficulties, flashbacks
• Anxiety and depression
• Medico-legal consequences - significant litigation risk

Detection

Intraoperative signs (unreliable in isolation)

• Tachycardia, hypertension, sweating, lacrimation
• Movement - the most obvious sign, but masked by NMB

Isolated Forearm Technique (IFT)

• Miller's Anesthesia, 10e, p. 5402

EEG-based monitoring

• Derived from: relative alpha/beta ratio, bicoherence, and burst suppression
• Scale: 0 (isoelectric) to 100 (fully awake)
• Target range for general anaesthesia: 40-60
• BIS monitors 4 EEG components: low-frequency activity, high-frequency beta activation, suppressed waves, and burst suppression

• Different patients may become aware at BIS values anywhere from 40 to 90
• Administration of NMB reduces EMG contamination of the signal, causing BIS to fall artifactually even in awake patients ("false-negative" scenario)
• Performance is weaker in the elderly (acceptable anaesthesia at relatively high index values)
• Evidence from RCTs: EEG monitoring reduces AWR by more than half compared to clinical monitoring alone, but advantage is much less when compared to end-tidal agent concentration monitoring

End-tidal anaesthetic agent concentration

• Maintaining end-tidal volatile agent ≥ 0.7-1.0 MAC is the most reliable and evidence-based approach to preventing awareness in patients receiving inhalational agents
• NAP5 (UK 5th National Audit Project, 2014) confirmed TIVA without EEG monitoring was a major independent risk factor for AAGA

Prevention

1. Pre-operative
   • Identify high-risk patients; discuss awareness as part of informed consent where appropriate
   • Clarify technique (GA vs. regional/sedation) to set appropriate expectations
2. Induction
   • Confirm adequate hypnotic dose before giving NMB - never give paralytic before induction agent
   • Check vaporiser level and function
   • Confirm IV access functioning
3. Maintenance
   • Target end-tidal volatile agent ≥ 0.7-1.0 MAC (best evidence for inhalational agents)
   • Use EEG/BIS monitoring for TIVA and high-risk patients
   • If inhalational delivery interrupted, re-dose IV agents promptly
   • Benzodiazepines (or scopolamine) provide explicit amnesia when depth is uncertain
4. Practice recommendations (Morgan & Mikhail, 7e):
   • Routinely monitor brain (EEG) when using TIVA
   • Evaluate known risk factors; increase agent concentration when identified
   • Re-dose IV agents when inhalational delivery is disrupted

Management After an Awareness Event

1. Acknowledge and listen - obtain a detailed account of the experience during postoperative rounds; most patients are dissatisfied when their concerns are dismissed
2. Answer questions honestly and empathetically
3. Explain what happened where possible (e.g., technical fault, deliberate lightening for cardiovascular reasons)
4. Refer for psychological support - PTSD is a real risk; early mental health involvement is recommended
5. Document thoroughly
6. Incident reporting - root cause analysis where appropriate

Special Note: Regional Anaesthesia

• Mulholland & Greenfield's Surgery, 7e

Recent Evidence

Bispectral Index (BIS) Monitoring

What Is BIS?

• Morgan & Mikhail's Clinical Anesthesiology, 7e, p. 234; Barash, 9e, p. 2151; Schwartz's Principles of Surgery, 11e, p. 476

Technical Basis

Hardware Setup

1. A single-use adhesive sensor is applied to the patient's forehead, capturing frontal lobe EEG activity via 4 electrodes
2. The sensor connects to the BIS monitor via a single connector
3. The device checks electrode impedance and alerts to poor contact or gel bridging before beginning data acquisition
4. A signal quality index (SQI) or equivalent is displayed to show reliability of the reading

EEG Signal Processing

• Schwartz's Surgery, 11e, p. 476; Miller's Anesthesia, 10e, p. 5399

What BIS Actually Captures

1. Awake: high-frequency beta and gamma activity, low amplitude
2. Induction/light anaesthesia: frontal alpha oscillations emerge and increase in amplitude (anteriorisation of alpha); beta activation may briefly increase
3. Surgical anaesthesia: dominant alpha-delta pattern - large amplitude, slow
4. Deep anaesthesia: burst suppression - alternating periods of near-silence and high-amplitude bursts
5. Overdose: isoelectric EEG

• Miller's Anesthesia, 10e, p. 5346

Drug-Specific Effects on BIS

• Barash, 9e, p. 2152; Morgan & Mikhail, 7e, p. 234

Key Landmark Trials

B-Aware Trial (Myles et al., Lancet 2004)

• High-risk surgical population; BIS vs. standard care
• Result: BIS significantly reduced AWR
• Criticism: Control arm was "standard care" (no ETAG monitoring); fragility index very low (a single additional event would change the result)

B-Unaware Trial (Avidan et al., NEJM 2008)

• High-risk patients; BIS (target 40-60) vs. ETAG monitoring (0.7-1.3 MAC)
• Result: No significant difference in AWR between BIS and ETAG groups
• Significance: First major trial to challenge BIS superiority

BAG-RECALL Trial (Avidan et al., NEJM 2011)

• Also BIS vs. ETAG (≥0.7 MAC); high-risk population
• Result: Replicated B-Unaware - no benefit of BIS over ETAG monitoring

Mashour et al. RCT (2019 - MYLES study)

• 18,836 unselected patients; BIS vs. ETAG alarms
• Result: No significant difference overall. However, ~30% BIS equipment failure; when failures excluded in post-hoc analysis, BIS group had lower awareness rates

TIVA-specific evidence

• The only large trial specifically examining propofol-based TIVA showed a marked reduction in AWR from 0.65% to 0.14% with BIS guidance - the strongest evidence for BIS utility
• Miller's Anesthesia, 10e, p. 5408-5409

Meta-analysis summary (Miller's, 10e, citing 52 studies, 41,331 participants)

• BIS monitoring more than halves AWR vs. clinical monitoring alone (OR 0.36, 95% CI 0.21-0.60)
• No significant advantage vs. end-tidal agent (ETAG) monitoring
• Evidence graded low certainty due to rarity of AWR events

Limitations and Pitfalls

False Negatives (patient conscious, BIS in "safe" range)

False Positives (patient unconscious, BIS elevated)

Elderly-specific concerns

• Reduced cortical thickness and dendritic spine density
• Flattened power spectrum (20% shallower slope)
• More variable, low-amplitude EEGs
• Higher likelihood of burst suppression at lower doses
• "Paradox of age" - entropy indices and BIS tend to be higher at loss of behavioural response compared to younger patients

• Miller's Anesthesia, 10e, p. 5393

Children (< 12 months)

• BIS derived from adult EEG databases; neonatal EEG patterns are markedly different
• Neonates show "tracé alternant"; classic alpha oscillations do not develop until ~4 months
• BIS is poorly validated in neonates and young infants

BIS in TIVA

• There is no exhaled gas monitor to confirm drug delivery (unlike volatile agents)
• Target-controlled infusions rely on pharmacokinetic modelling - individual variation is substantial
• Syringe pump errors, line disconnections, and IV failures can go undetected

• Morgan & Mikhail, 7e, p. 234; NAP5 UK findings (referenced in Barash, 9e)

BIS and Postoperative Delirium / Cognitive Outcomes

• Deep anaesthesia (sustained low BIS / burst suppression) has been associated with postoperative delirium and cognitive decline in elderly patients
• ENGAGES RCT (JAMA 2019): 1,232 patients ≥60 years undergoing major surgery with volatile agents; EEG-guided vs. usual care - found no reduction in delirium with EEG-guided anaesthesia
• BALANCED study: Compared BIS target 50 (lighter) vs. BIS target 35 (deeper) - found no significant difference in mortality
• Whether deep anaesthesia causes cognitive harm or simply reveals patients with more sensitive brains remains unresolved

Practical Recommendations

1. TIVA: Use BIS (or equivalent EEG monitor) routinely - strongest indication
2. High-risk patients for awareness: Cardiac surgery, obstetrics, major trauma - consider BIS as adjunct to ETAG monitoring
3. Standard inhalational anaesthesia: ETAG monitoring at ≥0.7-1.0 MAC is as effective as BIS for preventing AWR; BIS adds marginal benefit
4. Ketamine-based anaesthesia: BIS is unreliable; do not titrate to BIS value
5. Elderly patients: Treat BIS values cautiously; look at the raw EEG or spectrogram directly rather than trusting the number alone
6. Always check SQI: A low signal quality index invalidates the displayed BIS value
7. Inspect raw EEG/spectrogram: A BIS of 50 in one patient is not equivalent to BIS 50 in another; the raw EEG gives qualitatively richer information than the single number

BIS vs. Other Depth-of-Anaesthesia Monitors

• Morgan & Mikhail, 7e, p. 240

Bronchospasm in Anaesthesia

Definition and Clinical Significance

• 40 closed malpractice claims from bronchospasm events
• 88% involved brain damage or death
• Only 50% of patients with non-allergic bronchospasm had prior asthma or COPD - it can occur in anyone
• Adverse respiratory events account for 28% of claims related to anaesthesia-induced brain damage and death in the USA
• In France, 7% of anaesthesia-related deaths were attributed to bronchospasm
• A non-allergic mechanism was involved in nearly 80% of perioperative bronchospasm cases

Incidence

• Bronchospasm develops in approximately 9% of asthmatics in the perioperative period
• 25% of asthmatics may wheeze after induction of anaesthesia
• 1.7% of asthma patients sustain a poor respiratory outcome perioperatively
• The most critical time is during airway instrumentation (induction and intubation)
• The majority of events occur during induction and maintenance of anaesthesia

Risk Factors

Patient factors

• Asthma (most important) - especially active, poorly controlled asthma
• COPD / chronic bronchitis
• Active smoking (heavy tobacco use)
• Atopy - eczema, allergic rhinitis (especially in children)
• Upper respiratory tract infection (URI) - doubles the risk; preoperative nocturnal dry cough is associated with a 10-fold increased risk
• Recent wheeze or exacerbation

Procedure/technique factors

• Endotracheal intubation (most common trigger - direct airway irritation)
• Light plane of anaesthesia during intubation or surgical stimulation
• Aspiration of gastric contents
• Use of histamine-releasing drugs (morphine, meperidine/pethidine, atracurium)
• Anticholinesterase reversal agents (neostigmine/pyridostigmine - increase ACh and bronchomotor tone) without preceding anticholinergic
• Desflurane inhalation induction
• High spinal/epidural anaesthesia (blocks sympathetic T1-T4, leaving unopposed parasympathetic tone)

Pathophysiology

1. Reflex vagal (parasympathetic) pathways - airway irritation (ETT, secretions, aspiration) stimulates submucosal receptors → ACh release → M3 muscarinic receptor activation → IP3/Ca²⁺ mobilisation → smooth muscle contraction
2. Inflammatory/allergic mediators - histamine, leukotrienes, serotonin, endothelin-1
3. Inadequate anaesthetic depth - surgical or airway stimulation at light planes of anaesthesia

Clinical Presentation

Symptoms and signs (ventilated patient):

Differential Diagnosis

Preoperative Optimisation (Asthmatic/High-Risk Patient)

1. Postpone elective surgery in patients with active wheeze, URI, or recent exacerbation - ideally wait 4-6 weeks after URI
2. Continue all bronchodilators up to the day of surgery - do not withhold inhalers
3. Optimise with: nebulised/inhaled short-acting beta-2 agonists (SABA), inhaled corticosteroids; oral prednisolone course if poorly controlled
4. Patients on chronic steroids >5 mg/day prednisolone: give perioperative steroid supplementation, taper to baseline within 1-2 days
5. Avoid H2 blockers (e.g., ranitidine) in acute bronchospasm - H2 receptor activation normally produces bronchodilation; H2 blockade leaves unopposed H1 bronchoconstriction
6. Consider regional anaesthesia when appropriate - avoids airway instrumentation entirely (though does not eliminate bronchospasm risk, and high spinal may worsen it)

Intraoperative Management

Choice of Anaesthetic Agents

Blunting the Intubation Reflex

1. Deepen anaesthesia - additional bolus of induction agent
2. Ventilate with 2-3 MAC volatile agent for 5 minutes before intubation
3. IV lidocaine 1-2 mg/kg (1-2 minutes before intubation)
4. Intratracheal lidocaine (but can itself trigger bronchospasm if plane of anaesthesia is inadequate - use with caution)
5. Anticholinergic (glycopyrrolate/atropine) - blocks reflex bronchospasm but may cause tachycardia

Neuromuscular Blockade Considerations

• Atracurium and mivacurium: significant histamine release - avoid or use very slowly in asthmatics
• Succinylcholine: rarely causes marked histamine release but is generally safe
• Rocuronium, vecuronium: minimal histamine release - preferred
• Reversal with neostigmine: can precipitate bronchospasm; must co-administer appropriate anticholinergic (glycopyrrolate preferred over atropine as it has less tachycardia)
• Sugammadex: avoids acetylcholine increase altogether - preferred reversal agent in reactive airway disease (rare allergic reactions reported)

Treatment of Acute Intraoperative Bronchospasm

Step-by-step approach:

• Confirm correct ETT position (rule out endobronchial intubation)
• Check circuit for obstruction, kinking, cuff issues
• Suction through ETT to clear secretions
• Increase FiO2 to 100%
• Hand-ventilate to feel compliance and to allow adequate expiratory time (prevent air trapping)

• Increase volatile agent concentration - first-line treatment; exploits powerful bronchodilating properties
• Propofol bolus (if TIVA)

• Hydrocortisone IV 100-200 mg (or 0.25-1 g in severe cases)
• Onset 4-6 hours - not immediate; given for sustained anti-inflammatory effect
• Particularly important in patients known to respond to corticosteroids

• If bronchospasm associated with hypotension, urticaria, or cardiovascular collapse - treat as anaphylaxis:
  • IM or IV epinephrine as the cornerstone
  • IV fluids, antihistamines, hydrocortisone

Emergence and Extubation Considerations

• Patient should ideally be free of wheeze before extubation
• Deep extubation (before return of airway reflexes) reduces risk of bronchospasm on emergence
• Lidocaine 1.5-2 mg/kg IV bolus before extubation helps obtund airway reflexes
• Prefer sugammadex over neostigmine for reversal to avoid ACh-mediated bronchoconstriction
• Avoid extubating in a "light" plane

Special Considerations

Upper Respiratory Tract Infection (URI) and Timing of Surgery

• URI doubles the perioperative bronchospasm risk
• Preoperative nocturnal dry cough carries a 10-fold risk
• Airway reactivity remains elevated for up to 6 weeks after a URI
• Best practice: postpone elective surgery for 4-6 weeks after URTI if possible
• If surgery is unavoidable: prefer IV induction over inhalational; avoid ETT if possible (LMA or neuraxial)

Children

• Desflurane is contraindicated for induction in children with asthma or URI
• Sevoflurane is the preferred volatile in children with reactive airways
• IV induction should be considered in children with atopy, asthma, or eczema
• Bronchospasm in children is also a sign of anaphylaxis - remain vigilant

COPD

• Bronchospasm less prominent than in asthma but still occurs
• Volatile agents (sevoflurane, isoflurane) still reduce respiratory system resistance in COPD patients
• Avoid excessive PEEP - already air-trapped lungs worsen further

Summary Table: Perioperative Bronchospasm Management

Bronchospasm vs. Laryngospasm: A Comparative Analysis

Side-by-Side Overview

Laryngospasm in Detail

Definition and Anatomy

Reflex Arc

1. Trigger: Mechanical/chemical irritation superior to the vocal cords - secretions, blood, foreign material, passing an ETT through the larynx during extubation, splanchnic nerve stimulation
2. Afferent: Internal branch of the superior laryngeal nerve (SLN) → vagus nerve
3. Motor response: Recurrent laryngeal nerve → lateral cricoarytenoid (adduction and medial rotation of arytenoids → glottic closure) + thyroarytenoid (vocal cord shortening); SLN external branch → cricothyroid (vocal cord tensing)
4. Sustained by: Repetitive suprathreshold SLN stimulation causes heavy after-discharge activity in adductor motor output - the spasm can persist beyond the stimulus, making it a true pathological reflex rather than just an exaggerated normal response

Incidence and Risk Factors

• Overall incidence: 0.79% of all anaesthetics
• Children are at significantly higher risk (1-25%)
• More common at younger ages (infants and toddlers)

• Recent upper respiratory tract infection (URI)
• Light plane of anaesthesia during airway manipulation
• Inhalational induction (vs. IV induction)
• Secretions or blood in the airway
• Three or more airway instrumentation attempts
• Surgeries with high airway stimulation (tonsillectomy, adenoidectomy)
• Asthma / reactive airway disease / atopy / smoke exposure
• Less experienced provider

Clinical Features

• Stridor (high-pitched inspiratory crowing sound) in incomplete laryngospasm - the most recognisable sign
• Complete silence in total glottic closure - no air entry at all despite vigorous respiratory effort
• Paradoxical "rocking" chest and abdominal movement - chest moves in during inspiration (paradoxical) as the patient fights against a closed glottis
• Suprasternal and supraclavicular retractions
• Loss of capnograph trace (or markedly reduced waveform)
• Reservoir bag does not move
• Rapid SpO2 fall - children desaturate particularly quickly due to low FRC
• Bradycardia - a late sign indicating significant hypoxia; especially dangerous in children (cardiac output is rate-dependent)
• If intubated: the ETT cannot be easily ventilated through; circuit pressure rises to maximum, no chest rise

Treatment Algorithm

• Remove the stimulus (suction secretions/blood from glottis and mask)
• 100% oxygen
• CPAP 15-20 cmH2O via well-fitted mask - gentle positive pressure may open incomplete laryngospasm (note: ineffective against complete true cord closure, which can resist up to 140 mmHg)
• Assertive jaw thrust (Larson's maneuver: firm pressure at the "laryngospasm notch" - the space behind the angle of the mandible between the mastoid process and condylar process of the mandible, with forward mandibular displacement) - provides painful stimulus, which may break spasm as patient cannot maintain laryngospasm while crying/vocalising

• IV propofol bolus - depresses laryngeal reflexes; useful in incomplete laryngospasm
• (Note: propofol is helpful but should not be relied upon as the definitive treatment for complete laryngospasm)

• Succinylcholine is the gold standard:
  • 0.1 mg/kg IV (sub-paralytic "lysis" dose) for postoperative laryngospasm
  • 0.25-0.5 mg/kg IV for intraoperative laryngospasm
  • 1-2 mg/kg IV (or 4-5 mg/kg IM if no IV access) for severe/complete laryngospasm with desaturation
  • As little as 5-10 mg may break laryngospasm in an adult
• Rocuronium 0.4-1.2 mg/kg IV - alternative, particularly if succinylcholine contraindicated (can be reversed with sugammadex)
• Intubate if laryngospasm does not resolve after muscle relaxation

• If total obstruction and cannot ventilate: cricothyroidotomy/needle cricothyroidotomy as last resort

Key Differences in Distinguishing Bronchospasm from Laryngospasm

A critical overlap: they can co-exist

• Laryngospasm can trigger bronchospasm (reflex via vagal stimulation)
• Both can be the first sign of anaphylaxis - if either occurs with hypotension and urticaria, treat as anaphylaxis immediately

Complications Unique to Each

Laryngospasm: Negative-Pressure Pulmonary Oedema (NPPE)

• Classically in young, muscular patients (they generate the largest negative pressures)
• Presents as frothy pink fluid in the ETT, hypoxia, bilateral crackles
• Managed with: PEEP, diuretics, supportive care
• Can develop acutely and progress to respiratory failure

Bronchospasm: Status Asthmaticus / Air Trapping

• Dynamic hyperinflation from severe air trapping
• Intrinsic PEEP (auto-PEEP) increases risk of barotrauma/pneumothorax
• Right heart strain from elevated intrathoracic pressures
• Hypoxia, hypercapnia, respiratory failure
• 88% of severe perioperative bronchospasm claims involved brain damage or death

Shared Risk Factors and Prevention

• Upper respiratory tract infection (most important - doubles bronchospasm risk, significantly raises laryngospasm risk)
• Light plane of anaesthesia during airway manipulation
• Inhalational induction vs. IV induction
• Asthma / reactive airway disease
• Young age (especially infants and toddlers)
• Secretions or blood in the airway

• IV induction preferred over inhalational in at-risk patients
• Adequate depth before any airway manipulation
• Avoid/delay elective surgery after URI (4-6 weeks ideal)
• Preoperative bronchodilators for asthmatics
• Deep extubation (or fully awake) to avoid the vulnerable "light" emergence phase
• Lidocaine IV (1-1.5 mg/kg) before extubation to blunt airway reflexes
• Sevoflurane preferred over desflurane/isoflurane for inhalational induction in reactive airway disease

Memory Aid: Site and Sound