Dr Trevor Kavanagh MB BCh BAO FCAI FRCPC When is an anesthetic not an anesthetic? Accidental Awareness under General Anesthesia Dr Trevor Kavanagh MB BCh BAO FCAI FRCPC

Learning objectives Understand what AAGA is and why/how it can occur Recognize what patients may report if they experience AAGA and possible psychological sequelae Realize that reporting of AAGA can be delayed by days (or longer) and the person they report it to may be their family doctor. What to do if someone reports an episode of AAGA to you

Awake - Movie released in 2007

Campagna et al, New England Journal of Medicine, 2003

What Is the State of General Anesthesia? General anesthesia ≠ Sleep Classic triad of reversible loss of consciousness, analgesia and muscle relaxation Currently used volatile anesthetic agents induce hypnosis and muscle relaxation Importantly they also cause anterograde amnesia

Anesthetized but not paralysed Anesthetized decerebrate rats may still show some responses to surgical stimuli, even without cortical and forebrain structures These rats could not be described as aware yet still exhibit subcortical responses to painful stimuli While anesthetized: REFLEX MOVEMENT ≠ AWARENESS BREATHING ≠ AWARENESS

Stages of Awareness Gradual suppression of cognitive function by GA 4 stages of perception during GA: 1. Conscious awareness with explicit memory 2. Conscious awareness without explicit memory 3. Subconscious awareness with implicit memory 4. No awareness Griffith D, Jones JB. Awareness and memory in anaesthesised patients. Br J anaesth 1990; 65: 603-7 Implicit memory and hypnosis. Study performed over 40 years (1965, when Bernie Levinson ) ago showed that hypnosis could extract memories of intraoperative events in 4/10 patients. The results could not be replicated 30 years later.

Vocabulary (the public, press, and media call it "anesthesia awareness" The ASA has decided to use the term “Unintended Intraoperative Recall"

Awareness A serious complication of general anesthesia with potential adverse psychological sequelae 50% of patients are concerned about awareness McCleane and cooper, Anesthesia 1990; 45:153-5 65% of patients do not tell anesthesiologist Moerman et al. Anesthesiology 1993; 79:454-464 Even during seemingly adequate GA, implicit memory (perception without conscious recall) may be retained, along with the ability to subconsciously process auditory stimuli

Awareness First successful public demonstration of general anesthesia also involved the first case of awareness during anesthesia The man anesthetized with ether by William Morton on 16 October 1846, Edward Gilbert Abbott, later stated that he was aware

Risk factors Retrospective case control study of 271 cases of awareness Type of surgery Patient characteristics Anesthetic factors Ghoneim MM, Block RI, Haffarnan M, Mathews MJ. Awareness during anesthesia: risk factors, causes and sequelae: a review of reported cases in the literature. Anest Analg. 2009 Feb;108(2):527-35.

High risk surgery Overall incidence of awareness under GA ~ 0.1% Cesarean section under GA ~ 0.9% (P<0.0001) Cardiac surgery 0.4-1.1% Trauma surgery >10% -Myles et al, 2003

Patient risk factors History of awareness – Genetic resistance to anesthetics • Female (P<0.05) Obesity ?Higher ASA status Impaired cardiovascular status Difficult intubation Severe end-stage lung disease Heavy alcohol use Chronic benzodiazepine or opioid usage

Anesthetic risk factors Equipment malfunction Insufficient dosing No opioid used at induction TIVA IV line disconnect Cannula extravasation Larger interindividual variation in dosing requirements

Other potential causes Patient expectations – regional anesthesia with sedation Drug errors – awake paralysis Vaporizer on anesthetic machine running out of anesthetic agent

Awareness 3rd commonest cause of litigation against anesthesiologists in the UK Accounts for ~ 20% of all claims

Awareness / Recall: Epidemiology Sweden: 11785 patients 0.18% (paralysed) vs 0.1% (not) Sandin Lancet 2000 55;707 Australia: 10811 patients 0.11% Myles, BJA 2000;84:6-10 USA: 19575 patients 0.13% Sebel et al, Anesth Analg. 2004 Sep;99(3):833 = 26000 cases/yr in USA High-risk patients having muscle relaxant GA with incidence as high as 1%

NAP 5 Looked at 2.8 million cases of general anesthesia over a 1 year period in the UK Overall incidence of awareness 1 in 20,000 ~1:8,000 when muscle relaxant given (93% of reported cases of awareness) ~1:136,000 when no muscle relaxant used ~1:670 for Cesarean delivery under GA

NAP 5 More common in cases of awareness: RSI ↑ X 6 TIVA ↑ X 2.3 Muscle relaxant use Depth of anesthesia (EEG-based) monitoring ↑ X 1.5 About 7.5 thousand surgeries in RMH/year =~1 case of awareness every 2 years or so.

Low incidence with large numbers = Big problem In the US, general anesthesia is administered to ~21 million patients per year Between 20,000 and 40,000 cases of anesthesia awareness per year Sentinel-event alert disseminated by the Joint Commission on Accreditation of Healthcare Organizations

Patient reporting of awareness Often not immediately postop. Patients may first report intraoperative memories days to over a week later Surgical, nursing staff or family doctor may be the first person the patient reports their experience to

Consequences of Awareness The most common complaints from patients following awareness were: Auditory perception Loss of motor power 62% of patients reported no pain Severe pain reported in 17% Inability to move and feelings such as helplessness, anxiety and panic were significantly related to the persistence of late psychological symptoms Awareness During Anesthesia: Risk Factors, Causes and Sequelae: A Review of Reported Cases in the Literature. Ghoneim et al, anes Analg.,Vol. 108, No. 2, Feb 2009

Consequences of Awareness PTSD seen in 20-30% of cases of awareness. Awareness During Anesthesia: Risk Factors, Causes and Sequelae: A Review of Reported Cases in the Literature. Ghoneim et al, anes Analg.,Vol. 108, No. 2, Feb 2009

Monitoring Clinical signs Volatile anesthetic agent monitoring Cerebral monitors (BIS)

Bispectral Index (BIS) monitor (Aspect Medical Systems) The BIS monitor uses a proprietary algorithm to process a single frontal EEG signal and generates a dimensionless number that provides a measure of the patient’s level of consciousness

Intraoperative Monitoring Practice advisory for intraoperative awareness and brain function monitoring A Report by the American Society of Anesthesiologists Task Force on Intraoperative Awareness Intraoperative Monitoring Intraoperative awareness cannot be measured during the intraoperative phase of general anesthesia, because the recall component of awareness (memory) can only be determined postoperatively by obtaining information directly from the patient Anesthesiology 2006; 104:847–64

B-Aware Trial Prospective, randomized, double-blind, multi-center study (mostly Australia) 2503 high risk patients assigned to one of two groups: – Standard Practice; n=1238 – BIS guided (target 45-60); n=1227 Myles et al. Anesthesiology 2003; 99:A3

Patients interviewed at 3 intervals: 6 h, at 36 h and 30 days Bispectral index monitoring to prevent awareness during anesthesia: the B-Aware RCT Myles, Lancet 2004 Patients interviewed at 3 intervals: 6 h, at 36 h and 30 days Awareness Rate: BIS=2 (0.17%) vs Routine=11 (0.91%) Odds Ratio 0.18 (NNT is 138)

Conclusions and Comments BIS monitoring   risk of awareness by 82% in high-risk adults having relaxant GA. Cost = US$ 16 per surgical procedure, (NNT of 138), i.e. To prevent one case of awareness in a high-risk population is about US$ 2208.

But… No difference in painful awareness (if 2 patients removed from routine group) 36 ”possible awareness” episodes reported (20 BIS & 16 routine ) and when included no difference between groups Same incidence of intra-operative dreaming, (62 BIS and 83 routine)

Anesthetists’ Attitudes Toward Awareness and Depth of Anesthesia Monitoring Depth of anesthesia monitoring may in fact increase the risk of awareness if it leads to reduced administration of anesthetic drugs and leads to insufficient anesthesia – Myles et al, 2003

“Wide variation in the awake values and considerable overlap between consciousness and unconsciousness... further improvement is required” AAI vs BIS during propofol-remifentanil anesthesia. Kreuer Br J anesth 2003; 91: 336 THE TWIGHLIGHT ZONE

The Bispectral Index Declines During Neuromuscular Block in Fully Awake Persons Anesth Analg. 2003 Aug;97(2):488-91, Messner M, et al “There were no significant changes in the raw EEG …. recorded EEG parameters (power, median frequency) remained stable in a range compatible with the awake state. The suppression ratio was zero at all times.”

B-Unaware Trial 2000 patients at high risk of awareness Single-center, prospective, randomized controlled trial with blinded patient interviews and analysis BIS-guided Versus an ETAG-guided protocol 2 patients had definite awareness in each group ‘Reliance on BIS technology may provide patients and anesthetists with a false sense of security about the reduction in the risk of anesthesia awareness’

BIS vs Brain Metabolism Quantitative EEG Correlations with Brain Glucose Metabolic Rate during Anesthesia in Volunteers Alkire, Anesthesiology 1998

Causes of Decreased Cortical activity Sleep Sedative Drugs Metabolic Hypothermia Uraemia Acidosis Illnesses Any CNS disease Sepsis

BIS and memory BIS correlates to cortical activity Memory engrams are encoded subcortically in the hippocampus which is not measured by BIS monitoring Different types of memory (e.g., auditory, fear-associated, short-term, and long-term) are mediated by different neuronal pathways in different regions of the brain, so the anesthetic doses required to suppress each type of memory may differ

BAG RECALL Study Prospective randomized multicentre study 6041 patients randomized to BIS-guided anesthesia Vs ETAG guided anesthetic protocol 7 of 2861 patients (0.24%) in the BIS group Vs 2 of 2852 (0.07%) in the ETAC group had definite awareness 19 cases of definite or possible awareness (0.66%) occurred in the BIS group Vs 8 (0.28%) in the ETAC group (a difference of 0.38 %; 95% CI, 0.03 - 0.74; P = 0.99)

How can awareness be minimised? Equipment check Minimize distractions during induction of anesthesia Use of protocol based anesthetic delivery with alarms set when anesthetic agent delivery drops too low Brain Function Monitors (BIS), as they currently exist, have not been shown to reduce the incidence of awareness

What to do if someone reports an episode of awareness under anesthesia Don’t dismiss their report Contact the anesthesia dept. of the hospital where their surgery took place They may need referral to a psychologist PTSD counseling Forewarned is forearmed – this can help us prevent the occurrence again in the future

When is an anesthetic not an anesthetic? When it does not prevent memory of intraoperative events An uncommon event that may have profound consequences Much progress has been made to monitor this in the OR but further advances are required

Questions?