Dept Of Anesthesiology & Critical Care, University Of Pennsylvania School Of Medicine

Yet another awareness under anesthesia article

This article on awareness with recall during general anesthesia (AWR) by Errando et al (Br J Anaesth 2008;101:178-185) has a number of interesting observations.  First, it is from a country (Spain) other than the United States. Second, it is prospective with a calculated power to detect a 95% confidence interval of 0.09 – 0.37%.  Third, it covers a fairly long time in two separate data collection periods (April 1995 – April 1997 and then December 1998 – November 2001).  Interviews were done in the PACU immediately post op.  If there was evidence of awareness then the patients were interviewed again at 7 days and 30 days (in my opinion this is a design flaw compared to the current standard of interview regardless of initial response).   Patients going to the ICU were excluded, as were patients less than 15 years old and those having cardiac surgery.  Patients aware because erroneous administration of neuromuscular blocker prior to a hypnotic drug were classified as not having AWR.  The interviews were formally structured.  The interviewers did not know the anesthetic given.

          Data from 4001 patients cared for by 42 different anesthesiologists at one institution was reported.  The incidence of patients reporting AWR 7 days after elective surgery was 0.6% (22 of 3477 pts).  Of interest was a difference in awareness depending on anesthesia type.  Patients who received only nitrous oxide oxygen for maintenance had an AWR rate of 5% (4 of 79 pts), with total intravenous anesthesia the reported AWR was 1.1% (14/1239), but when halogenated anesthetic drugs were used the AWR was only 0.59% (9/1514).  Patients receiving a benzodiazepine pre medication (dose and type not provided) had significantly less recall than those who received an opioid pre medication.  Twenty two patients with AWR provided descriptions of the experience.  11 reported hearing noise; 18 reported hearing conversations.  Twelve patients tried to move and 14 tried to communicate but could not.  Eleven patients had pain; five reported being cut with a scalpel and five felt suturing.  Nine reported feeling the tracheal tube in their mouth.  Eleven felt panic at the time they were awake and two had a sensation of eminent death.  Few if any of the patients discussed the event with their anesthesiologist though 16 told their surgeon.  Six episodes occurred at the beginning of surgery, two during and seven at the end.  From an analysis of the anesthesia record, in only 2 patients was awareness suspected by those caring for the patient.  Three of the patients had difficult intubation.  In fifteen patients there were errors in hypnotic drug dose and in two there were equipment failures.  My observations – their numbers of aware patients may have been even higher if they had included the CT patients.  These are high numbers compared to many of the recent United States studies; however their data comes from an earlier period (1995 – 2001).  In any event awareness under anesthesia is not just a United States phenomenon.  Their data on anesthesia type having an effect, a potential role for benzodiazepine pre medication and their descriptions of what it is like to be aware during surgery makes this paper worth reading. 

David S. Smith, M.D., Ph.D.

Anesthesia awareness -- successful defense

This article by Lax JA and Attorri MD (Anesthesia Awarenss:  There is room for skepticism, Respiratory Therapy 2008;3:12) is particularly interesting in that it was written by two lawyers who recently, successfully defended an anesthesiologist against the claim of awareness under anesthesia.  They provide insight from the point of view of those who need to defend physicians.  It is clear from their success in the courtroom and the clarity of their article that they have a good grasp of the key issues.  Of particular importance in deceloping their defense was a careful, detailed review of just what the patient claimed to have remembered and its possible relationship to external location and time.   It is unclear to me why this timely article was published in Respiratory Therapy (http://www.nkms.com/articles/jal.article.excerpt.pdf ).  At a brief three pages it is worth reading.

David S. Smith, M.D., Ph.D.

Intraoperative awareness - potential causes and decreasing the risk

AIMS is a large, anonymous, multicenter, reporting system of anesthesia incidents that is in widespread use in Australia and parts of Asia.  Bergman et al examined the data base when there were 8372 abstracted reports collected between 1988 and 2001.  The authors queried on the keyword “awareness.”  Using specific definitions of awareness they found 81 reports of which there were 50 cases of definite awareness and 31 with a high probability of awareness.  They could find no obvious cause for awareness in 13 (16%) of the cases. Low inspired volatile agent concentration appeared to be responsible for 36 (44%) of the 81 cases.  In 14 of these cases there was no agent monitor present.  Five of these cases appeared to be due to prolonged attempts at intubation and four cases were due to reducing delivered anesthetic secondary to hypotension or cardiovascular instability.  Thirty two cases were due to inadvertent paralysis of an awake patient.  Case review suggested that inattention or distraction were contributory in 20 cases, haste in 14 and fatigue in 5.

            This study covers a later period than did the closed claims analysis study of awareness (Domino KM et al: Anesthesiology 1999;90:053-61).  In my opinion, at least in the United States, the 1988 – 2001 period is reasonably similar to current practice yet awake paralysis persists and in Bergman et al awake paralysis was the most common cause for awareness.  Picking up the wrong syringe (a paralytic instead of the desired drug) was a recurrent cause of awareness.  Keeping syringes of paralytic drugs away from other drugs might help reduce this problem.  The authors expressed particular concern about the incidents of awareness with no apparent cause.   Two of the 13 cases had agent analyzers and apparently adequate doses of volatile agent.  Two cases occurred during ECT when no volatile agent is typically used.

            Neither this study nor the closed claims study allows calculation of incidence since the total number of cases from which these reports are drawn is not known.  In addition reporting is voluntary and the threshold for reporting most likely varied from practitioner to practitioner.  Finally if patient report was the major source of information then there was most likely underreporting as most patients do not volunteer awareness information unless repeatedly asked.  However, despite these weaknesses, this paper provides an intensive study of a serious of events providing conclusions as to cause and approaches for decreasing the risk of the occurrence of awareness.

            The authors presented eight suggestions based on their data that they feel will help reduce awareness (table 4 modified):  1) Check the anesthesia machine before each use; ensure a correctly mounted and filled vaporizer. 2) When using a volatile agent use an end-tidal agent monitor.  Use a low level alarm set for a sufficient volatile agent concentration to prevent awareness. 3)  Provide further hypnotic doses for repeated intubation attempts. 4) Be aware of the potential for awareness in hypovolemic patients receiving low concentrations of anesthetic.  Restore appropriate anesthetic concentration as soon as possible. 5) Routinely use a peripheral nerve stimulator and ensure sufficient anesthetic concentration until muscle power returns. 6) When using total intravenous anesthetics, ensure a patent intravenous line and periodically check the infusion pump to confirm drug administration. 7) Clearly label all drug syringes immediately when they are drawn up.  Check this label carefully before administration.  Do not rely on recognition of syringe size to confirm its contents.  Consider newer methods of ensuring that the correct drug is given. 8) Consider a depth of anesthesia monitor, if not routinely then for selected cases.

Bergman IJ et al: Awareness during general anesthesia: a review of 81 cases from the Anesthetic incident monitoring study (AIMS).  Anaesthesia 2002;57:549-556

David S. Smith, M.D., Ph.D.

Awareness - the ASA closed claim study - a detailed review

Some background information for those unfamiliar with the ASA closed claims project (this background information is taken from the closed claim website http://depts.washington.edu/asaccp/ASA/index.shtml ): Since 1985 the ASA has sponsored this project. At the time the project was initiated, professional liability insurance was expensive for anesthesiologists and in some states difficult to obtain. The intention of the Closed Claims Project was to identify causes of loss, improve patient safety, and thereby relieve the insurance problem for anesthesiologists.  The project consists of an in-depth investigation of 7328 closed insurance claims resulting from anesthetic mishaps. Data is gathered in the form of detailed case summaries collected by ASA member anesthesiologists from insurance company claim files. Claims for dental injury, a very common, well understood, and in most cases minor injury, are excluded. Claims in which the basic sequence of events and/or nature of the injury cannot be reconstructed from the information in the insurance files are also been excluded. This results in most cases being collected from mishaps resulting in lawsuits, as files in these cases contain the most extensive information. Cases are collected from throughout the United States on a continuous basis.  The database consists of standardized summaries of each case, including patient information (e.g. age, physical status), surgical procedure and positioning, anesthetic evaluation and technique, events leading to the injury or claim, type and severity of injury, outcome of litigation, and physician evaluations of potential for prevention and appropriateness of anesthesia care. The database also includes a brief narrative summary of each claim, describing the sequence of events and adding any pertinent information not contained in the standardized data collection form.

            In my opinion the closed claims project provides a unique resource of intensively studied case experiences in which there was an outcome that was not satisfactory to the patient or their family.  It does not allow the calculation of incidence as the denominator is not known.  Because of the length of time from law suit to settlement, the data in the closed claims project tends to be old.  Thus new areas of risk or trends in settlement costs are, in my opinion, difficult to determine from this data.

            The ASA closed claims analysis of awareness during anesthesia was published in 1999 and included claims for adverse outcomes that occurred between 1961 and 1995.  A total of 4183 claims were in the database.  Seventy nine claims were for awareness with a greater proportion occurring in the 1990s compared to earlier decades.  The proportion of claims in the database was similar to burns, aspiration pneumonia and myocardial infarction.  Compared to other claims awareness more often involved women, patients younger than 60 years of age, and elective surgery.  The severity of injury for awareness claims was lower than for the other claims.  Eighteen of the claims were for awake paralysis and 61 claims were for recall during general anesthesia. 

            Claims for awake paralysis were related to intravenous infusion errors or syringe swaps.  Succinylcholine drips accounted for 10 of the 18 claims (unlabelled, mislabeled, failure to check the label).  The period of risk was preinduction or during induction when a muscle relaxant was given instead of a sedative or hypnotic.

            The highest frequency of recall during general anesthesia was during the maintenance phase (49 of 61 claims).  Recollection included recollection of conversation, feeling surgery without pain, pain, paralysis, tracheal intubation, and severe panic.  Eighty four percent sustained temporary emotional distress; 10% developed posttraumatic stress disorders.  Recurrent nightmares were described in 16% of claims and psychotherapy was described in 13%.

            Factors associated with recall during general anesthesia included: nitrous – narcotic relaxant technique  without volatile anesthetic (11 of 61 claims), hypotension requiring discontinuation of the anesthetic agent (11 instances), inadequate dose of anesthetic for no obvious reason (8), difficult intubation (5), failure to adjust anesthetic dose for morbid obesity (8), vaporizer leak (5) and failure to turn on the vaporizer (3).  In 10 cases no obvious factor could be determined.  The classic cues for light anesthesia were absent in most cases.  Five factors were significantly associated with claims for recall compared to other general anesthesia claims: no volatile anesthetic agent, female gender, obstetric or gynecologic procedure, intraoperative opioid, and intraoperative muscle relaxant.  After adjusting for risk factors and application of multiple logistic analyses – female gender and anesthetic techniques using intra operative opioid and muscle relaxants without a volatile anesthetic increased the relative frequency of claims of recall.  OB/Gyn procedures were not an independent risk factor. (From Domino KB et al: Awareness during anesthesia: A closed claims analysis. Anesthesiology 1999;90:1053-1061.)

            DSS comments: The separation of “awake paralysis” from “recall” is not done in most subsequent studies.  Notice the frequency of a drug error with respect to the occurrence of awake paralysis.  Changes in practice (decreased use of succinylcholine infusions) may decrease this incidence.  However bags of non depolarizing muscle relaxants for infusion present the same potential risk unless clearly labeled and kept away from other intravenous solutions until the time of use.  Several of the instances of awake paralysis occurred because of a syringe swap or mislabeled syringe.  An argument might be made to keep syringes containing muscle relaxant separate from antibiotics, anxiolytics, narcotics and anesthesia induction drugs.  Finally using nitrous oxide without a volatile agent was associated with a large number of instances of recall.  Fortunately that practice has almost disappeared (at least at Hospital of the University of Pennsylvania).

David S. Smith, M.D., Ph.D.

What is the role of BIS or other brain activity monitor in decreasing the incidence of awareness?

Reviews of cases in which awareness has occurred have identified cases in which, had BIS monitoring been used, the inadequate level of anesthesia might have been recognized (1).  However there appear to be cases in which awareness occurred despite BIS monitoring.  This is true for the b-aware and b-unaware trials as well as case reports (2, 3, 4).

1) Bergman IJ et al: Awareness during general anesthesia: a review of 81 cases from the anaesthesia incident monitoring study. Anaesthesia 2002;57:549-556

2) Myles PS: Bispectral index monitoring to prevent awareness during anaesthesia: the B Aware randomized controlled trial. Lancet 2004;363:1757-63

3) Finkel KJ et al: Sensitivity of BIS and MAC in the B-Unaware Trial.  ASA Annual Meeting, San Francisco A728

4) Mychaskiw G, et al: Explicit intraoperative recall at a bispectral index of 47. Anesth Analg 2001;92:808-9

David S. Smith, M.D., Ph.D.

What can an anesthesiologist do as part of their daily practice to decrease the probability that one of their patients will experience awareness under anesthesia?

The ASA practice advisory for intraoperative awareness contains the following suggestions (1): 1) Be alert for patients who give a history of substance use or abuse or who are taking high doses of opioids, prior episodes of intraoperative awareness, a history of difficult intubation, and patients with limited hemodynamic reserve. 2) Determine potential risk factors such as planned cardiac surgery, cesarean delivery, trauma or emergency surgery, the need for reduced anesthetic doses in the presence of muscle paralysis, planned use of muscle relaxants during anesthesia maintenance, or planned used of nitrous oxide – opioid anesthesia.  3)  Use a pre operative check list to assure that the anesthesia machine and associated equipment including agent analyzers are functioning, make sure that anesthetic agent vaporizers are properly filled and functioning, confirm that the appropriate anesthetic drugs have been prepared.  Verify proper functioning of venous access, infusion pumps, and confirm that all connections are tight.  Back – flow check valves help insure that drugs being administered are going into the patient and not into an infusion bag. 4) Use multiple modalities to monitor depth of anesthesia.  Patient movement can be an important indicator that anesthetic depth is not adequate.  Heart rate and blood pressure may also indicate that more anesthetic drugs are needed; however awareness can occur without changes in these vital signs.  Many feel that brain function monitoring will help detect and decrease the incidence of awareness under anesthesia, however, use of these monitors are only an adjunctive part of the ASA practice advisory.  The advisory takes the position that brain function monitoring is not routinely indicated for general anesthesia patients and that the decision to use it should be made on a case by case basis. 5)  Consider the use of benzodiazepines.  However as noted in an earlier section of this Blog, 2 mg of midazolam is not adequate in many patients.  My interpretation of the studies is that the midazolam, if used to induce amnesia, probably should be given on a mg/kg basis with a dose of at least 0.05 mg/kg.

1)                  American Society of Anesthesiologists Task Force on Intraoperative Awareness: Practice advisory for intraoperative awareness and brain function monitoring.  Anesthesiology 2006;104:847-864

David S. Smith, M.D., Ph.D.

Will midazolam or other benzodiazepines prevent memory of intraoperative events?

The answer is maybe and sometimes.  Most investigators have agreed that giving a benzodiazepine has little effect on memory of events that have occurred before the drug was given (retrograde amnesia).  In contrast most investigators believe that midazolam has a variable antegrade effect on explicit memory; that is the patient has no recall of events occurring after the drug is given.  The amnesic dose of midazolam is not well defined.  In part this is due to variable definitions of the term amnesia; in part due to a large number of poorly designed under powered studies that fail in some degree to address the specific question, and, finally, the amnesia after a specific dose of midazolam is some poorly defined function of the intensity of the stimulation; that is stronger stimuli may produce recall.  As a general rule, doses of midazolam titrated to levels of sedation at which the patient no longer responds to name appear to have a very high probability of producing amnesia (these doses are on the order of 0.1 mg/kg i.v.).  Miller et al (1) examined amnesia after three different dose levels of midazolam (0.07, 0.10 and 0.13 mg/kg) along with fentanyl 0.1 mg for dental extraction with local anesthesia.  Fifteen percent of patients with the lowest dose of midazolam remembered some part of the tooth extraction and 10% of patients in the two higher dose groups had recollection.   Ghoneim et al (2) determined the amnesic effects of midazolam (0.03 or 0.06 mg/kg i.v.) in volunteers receiving a subanesthetic dose of isoflurane (0.2% end tidal).  Both doses of midazolam abolished recall of word lists.  In contrast Miller et al (3) found a high level of intraoperative awareness with recall in a group of patients infused with 100 mcg/kg/min propofol and alfentanil (0.5 mcg/kg/min) and given various doses of midazolam for arthroscopic surgery.  Six of 90 patients had awareness with recall.  Of these, four of 21 patients did not receive midazolam, one of 24 received 0.015 mg/kg and one of 22 received 0.045 mg/kg midazolam i.v.  Bulach et al (4) examined the effects of 2, 5, or 10 mg midazolam on retrograde and antegrade memory for events when it was given just prior to general anesthesia.  There was no retrograde amnesia.  The degree of antegrade amnesia was a function of dose with 5 or 10 mg doses producing better amnesia than the 2 mg dose.  My conclusions are as follows: 1) amnesia after midazolam is variable, 2) amnesia is considerably more likely when the drug is titrated to a level of sedation at which the patient is not longer responding to their name, 3) a fixed dose of 2 mg will produce amnesia in some patients, 4) a dose based on body weight will probably be more effective particularly when doses are in the range of 0.05 – 0.1 mg/kg.

1. Miller RI: Duration of amnesia associated with midazolam/fentanyl intravenous sedation. Oral Maxillofac Surg 1989;47:155-158

2. Ghoneim MM et al: Interaction of subanaesthetic concentration of isoflurane with midazolam: effects on responsiveness, learning and memory. BJA 1998;80:581-587

3. Miller DR: Midazolam and awareness with recall during total intravenous anaesthesia. Can J Anaesth 1996;43:946-53

4. Bulach R: Double-blind randomized controlled trial to determine extent of amnesia with midazolam given immediately before general anaesthesia. BJA 2005;94:300-5

David S. Smith, M.D, Ph.D.

what are the known causes of awareness during general anesthesia?

Bergman et al (1) examined 81 cases from the Australian voluntary, anonymous reporting data base in which awareness during surgery was reported.  The found that 50 cases were definitely aware and 31 cases had a high probability of awareness.  In 13 of the cases the patients appeared to have received an adequate anesthetic.  Where cause could be determined, in 32 cases there was an error in drug handling that resulted in paralysis of an awake patient and in 16 cases there was failure to deliver volatile anesthetic.  Other causes included prolonged attempts at tracheal intubation (5 cases) and deliberate withdrawal of the volatile anesthetic due to hemodynamic instability (4 cases).

Reference:  1) Bergman IJ et al: Awareness during general anesthesia: a review of 81 cases from the anaesthesia incident monitoring study. Anaesthesia 2002;57:549-556

David S. Smith, M.D., Ph.D.

What is the true incidence of awareness during general anesthesia?

  The trailer for the movie Aware claims an incidence of 1 in 700; this is much too high for a general population of patients. A number of studies have produced values ranging from 1/1000 to as high as 1/115 in a population at very high risk for awareness (1-5). A very recent study on a large private practice population suggests that the incidence may be as low as 1 in 14,000 (6) but the results of that study have been challenged for a number of methodological reasons (7,8).

References:

1. Myles PS et al: Patient satisfaction after anaesthesia and surgery: results of a prospective survey of 10811 patients.  BJA 2000;84:6-10

2. Sebel PS et al: The incidence of awareness during anesthesia: A multicenter United States study. Anesth Analg 2004;99:833-9

3. Wennervirta J et al: Awareness and recall in outpatient anesthesia. Anesth Analg 2002;95:72-7

4. Sandin RH et al: Awareness during anaesthesia: a prospective study. Lancet 2000;355:707-711

5. Sandin R, Nordstrom O: Awareness during total I.V. anaesthesia. BJA 1993;71:782-787

6. Pollard RJ et al: Intraoperative awareness in a regional medical system. Anesthesiology 2007;106:269-74

7. Leslie K: Awareness in a community-based anesthesia practice (letter). Anesthesiology 2007;107:671-672

8. Sebel PS et al: Don't ask, don't tell (letter). Anesthesiology 2007;107:672

David S. Smith, M.D., Ph.D.

What is awareness under anesthesia – how is it detected?

Awareness under anesthesia is a complex and a not completely defined phenomenon.  The fact that different definitions are used by various investigators further confuses the issue.  The “awareness” that attracts the most attention is when the patient is awake but paralyzed during what is supposed to be a general anesthetic.  This experience of being operated on while awake but unable to move or otherwise communicate is usually agonizing and typically leaves lasting psychological scars; fortunately “awake but paralyzed” during surgery is very rare.  In less severe episodes the patient may have sleep disturbances or “bad” dreams which they may not specifically link to the intraoperative experience.  In a number of experimental situations “awareness” without recall has been demonstrated.  There are case reports of patients receiving an anesthetic based on a very high narcotic dose who have had episodes of auditory recollection but no pain.  Most frequently awareness with recall is detected after the fact, when a patient reports that they were awake and recalls events that occurred during their surgery.  In patients who have not received muscle relaxants, movement may suggest that the level of administered anesthetic is not adequate and allow correction before awareness with recall occurs.  Intraoperative discovery that anesthetic drug delivery has been compromised may help identify a patient at risk for post operative awareness and recall.  Clinical situations that require lower than usual anesthetic drug doses such as patients in shock, caesarian sections under general anesthesia, etc. may also identify a patient who may be at risk.

David S. Smith, M.D., Ph.D.