1. 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

2. 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

3. Awake - Movie released in 2007

4. Campagna et al, New England Journal of Medicine, 2003

5. 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

6. 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

7. 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.

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

9. 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:
Even during seemingly adequate GA, implicit memory (perception without conscious recall) may be retained, along with the ability to subconsciously process auditory stimuli

10. 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

11. 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 Feb;108(2):

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

13. 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

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

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

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

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

19. 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

20. 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.

21. 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

22. 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

23. 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

24. 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

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

26. 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

29. 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

32. 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

33. 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)

34. 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.

35. 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)

36. 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

37. “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

38. The Bispectral Index Declines During Neuromuscular Block in Fully Awake Persons Anesth Analg 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.”

40. 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’

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

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

43. 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

45. 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, ; P = 0.99)

46. 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

47. 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

48. 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

49. Questions?