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Obstetric AnesthesiologySection Editor: Cynthia A. Wong

Intraoperative Awareness During General Anesthesia

for Cesarean Delivery

Kay Robins, FRCA*

Gordon Lyons, FRCA, MD

Intraoperative awareness is defined as the spontaneous recall of an event occurringduring general anesthesia. A move away from rigid anesthetic protocols, whichwere designed to limit drug transmission across the placenta, has reduced theincidence of awareness during cesarean delivery to approximately 0.26%. Never-theless, it remains an undesirable complication with potential for the developmentof posttraumatic stress disorder. Assessing depth of anesthesia remains a challengefor the anesthesia provider as clinical signs are unreliable and there is no sensitiveand specific monitor. Bispectral Index monitoring with the goal of scores 60 hasbeen recommended to prevent awareness. Induction drugs vary in their ability toproduce amnesia and the period of hypnotic effect is affected by the rate at which

they are redistributed. After initiation of anesthesia, volatile anesthetics should beadministered to a target of 0.7 minimum alveolar anesthetic concentration, whichhas been shown to consistently achieve mean Bispectral Index scores 60. Becauseof its rapid uptake, nitrous oxide remains an important adjunct to reduce the riskof awareness during emergency cesarean delivery. In the absence of fetal compro-mise, there is no rationale for an inspired oxygen concentration above 0.33. Deeperlevels of anesthesia reduce the incidence of awareness; current evidence does notsuggest an increased risk of tocolysis or fetal morbidity.(Anesth Analg 2009;109:88690)

THE DILEMMA OF OBSTETRIC ANESTHESIA

The objectives of general anesthesia for cesarean

delivery are to keep mother and fetus adequately oxy-genated, while limiting fetal drug transmission andmaintaining maternal comfort. Crawford1 called thisconflict the dilemma of obstetric anesthesia and anal-gesia and said it epitomized the challenge and theattraction of the specialty. The balance of this conflict haschanged over the years. Intraoperative recall duringgeneral anesthesia was unreported with the spontaneous

breathing and ether of Mendelsons day, but thischanged with the introduction of succinylcholine in thelate 1950s when endotracheal intubation and muscle

relaxation were popularized. Initially, anesthesia wasprovided largely by thiopental and nitrous oxide2 andwas associated with an incidence of awareness up to26%.3 A reluctance to load with a volatile anesthetic, andconcern about lack of care for an anesthetized newborn

from an undeveloped neonatal service, might havehelped make this frequent incidence of recall seem an

acceptable side effect.The addition of halothane 0.5% (0.66 minimum alveo-

lar anesthetic concentration [MAC]) to the anestheticmoved the balance further in the maternal direction,reducing awareness to around 1%,4 and throughout the1970s, this was widely regarded as an acceptable inci-dence. The balance shifted further toward maternalcomfort when it was demonstrated that awareness atcesarean delivery could be reduced by more generousdoses of thiopental and more liberal use of a volatileanesthetic.5 This practice became more widely dissemi-nated in the 1990s, a time in which access to neonatal

resuscitation support became more widely available.Additionally, anesthesia providers were taking advan-tage of the electronic monitoring revolution (includingmeasurement of end-tidal gas concentrations), which of-fered a dynamic alternative to the traditional recipeapproach. Today, the incidence of awareness duringanesthesia in the United States is believed to be between0.1% and 0.2% of all patients undergoing general anes-thesia, representing 20,00040,000 cases per year.6 Therisk appears to be higher when muscle relaxants areused and during cesarean delivery.7 In Australia and

New Zealand, the Australian and New Zealand Collegeof Anesthesia (ANZCA) Trial studied 1095 cesarean

From the *Department of Anaesthesia, York Hospital, York; andDepartment of Obstetric Anaesthesia, St. James University Hospi-tal, Leeds, UK.

Accepted for publication April 24, 2009.

Address correspondence and reprint requests to Kay Robins,FRCA, Department of Anaesthesia, York Hospital, York YO61 1PS,UK. Address e-mail to [email protected].

Copyright 2009 International Anesthesia Research Society

DOI: 10.1213/ane.0b013e3181af83c1

Focused Reviews

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deliveries and interviewed 763 women postoperatively;

two women had recall giving an incidence of 0.26%.

8

DEFINITIONS AND SCOPE

Awareness is defined as the spontaneous postop-erative recall of an event that occurred during generalanesthesia (Table 1).9 One difficulty with explicitmemory of perioperative events is distinguishing be-tween recall of genuine intraoperative events andemergence phenomena, because voices, the baby cry-ing, and wound pain are part of the postoperativeexperience. A wider definition of recall takes in aspectrum that ranges from dreams, through recall of

specific events, to full consciousness with paralysisand pain. Dreaming is often thought to be indicativeof light anesthesia but more likely occurs duringemergence from anesthesia and recovery.10 Crawford1

took the view that unpleasant dreams did reflectawareness and that the two should always be linked.Anecdotal reports have shown that, even when thecontent can be linked to intraoperative events, dreamsare not necessarily unpleasant.5

INDUCTION OF ANESTHESIA

Monitoring cerebral function to detect awareness

has advanced considerably in recent years, but theperfect monitor has yet to be developed. The mostwidely studied brain function monitor, Bispectral In-dex (BIS) monitoring, is easy to initiate but even rapidapplication may delay delivery of the fetus in anemergency cesarean delivery. A BIS monitor was usedin 32% of 1095 general anesthetics studied as part ofthe ANZCA trial. Of note, 30% of Category 1* and 37%of Category 4* cesarean deliveries were monitored.8

Clearly, the limiting factor in the use of monitoring

was not the urgency of the procedure. Another con-sideration is whether, within the context of an emer-gency cesarean delivery, a BIS score target 60 isattainable predelivery. When the target anestheticconcentration is 0.8 MAC or above, it seems that meanBIS scores 60 can be achieved,11,12 but without acommitment to this level of volatile anesthetic deliv-ery at the outset, the rationale for BIS monitoring islost. Intraoperative brain function monitoring duringcesarean delivery has yet to become a mandatoryrequirement by any governing or regulatory agency.

The risk of recall is increased with a rapid sequenceinduction of anesthesia as tracheal intubation andsurgical incision follow in rapid sequence. There may

be insufficient time to allow adequate uptake anddistribution of volatile anesthetic to prevent aware-ness12 before redistribution causes brain levels of theinduction drug to decrease. The choice and dose ofinduction drug then becomes critical. Many regardthiopental as the drug of choice but a single inductiondose is soon redistributed with rapid recovery ofconsciousness. Recommended doses range from 3 to 7mg/kg; in the ANZCA Trial the mean dose was 4.9mg/kg.8,1317 Not surprisingly, larger doses of hyp-notic drug result in a lower incidence of recall.5 Thewide variation in recommended dose may reflect howanesthesiologists view their role in the conflict be-tween fetal drug transmission and maternal comfort.There is general agreement that doses 4 mg/kg areunlikely to lead to fetal depression, and that doses inexcess of 7 mg/kg are liable to do so.1 The degree ofconcern for maternal awareness might be expected todecide where, between those limits, the choice lies. Atlow doses, thiopental is mildly amnesic18 but it doesnot produce retrograde amnesia.19

Although thiopental remains the drug of choice, anew generation of anesthesiologists is largely un-trained in its use. Propofol is now the most widelyused IV drug in anesthesia but there are concerns overits capacity to produce neonatal depression and ad-equate depth of anesthesia. Celleno et al. examined thematernal electroencephalogram with either thiopental5 mg/kg or propofol 2.4 mg/kg. Half of the propofolgroup had rapid low voltage (89 Hz) waves on theirelectroencephalogram suggestive of a light plane ofanesthesia compared with 10% of the thiopentalgroup.20 Another disadvantage of propofol is its longeffect-site equilibration time, which slightly prolongsthe period from injection to hypnosis. Other studieshave provided no evidence for the superiority ofthiopental compared with propofol.21 However, se-vere maternal bradycardia has been reported withpropofol combined with succinylcholine.22 Propofolhas a greater amnesic effect than thiopental23 throughinterference with long-term memory.24 Althoughthere are no data on which dose is best to avoid

awareness, 2.5 mg/kg is commonly used.

25

World-wide, there is little doubt that propofol is used for

*Category 1: emergency cesarean delivery indicated because ofpresence of condition which is of immediate threat to the life of the

woman or fetus; Category 4: elective procedure, cesarean deliverycan be scheduled to suit the woman and staff.

Table 1. Terminology of Awareness37,44

Consciousness State in which information frompatients surroundings can beprocessed

Recall Ability to retrieve stored memoriesAmnesia Absence of recall. Event not

retained in long-term memoryWakefulness/

responsivenessUnequivocal communication with

an anesthetized patient withoutsubsequent recall

Explicit memory Recall of specific intraoperativeclinical events

Priming Presentation of material to ananesthetized patient

Learning Evidence of communication ordetection of priming throughpostoperative tests but withoutrecall

Implicit memory Postoperative evidence of primingbut without recall

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cesarean delivery despite these concerns and, to date,without the accumulation of adverse reports.8,23

Ketamine is used as an induction drug 2% of thetime.8 It is associated with less responsiveness andrecall than thiopental when used at a dose of 1mg/kg,26 but the sympathomimetic effects limit itsuse in preeclampsia, and when there are concernsabout hypertension. The associated hallucinations andemergence phenomena are another problem, although

both are dose related and possibly occur less fre-quently in obstetric patients.27 Ketamine may be of useto reduce hypotension at induction in the setting ofhemodynamic instability.

Benzodiazepines are used infrequently as sole induc-tion drugs, although they may be used occasionally tosupplement an induction sequence.8 Midazolam pro-duces more profound amnesia than propofol,28 impair-ing both explicit and implicit memory,29but the onset ofhypnosis is slow and neonatal depression is slow toresolve. It does not produce retrograde amnesia.28

MAINTENANCE OF ANESTHESIA

The rapid redistribution of induction drugs under-lines the importance of introducing an adequate vola-tile anesthetic as soon after induction as is practical. Insome centers, the skin is prepared and the drapesapplied before induction of anesthesia. Although thismight be in the best interests of a fetus in need ofimmediate delivery, emergency surgery and inad-equate uptake of the volatile anesthetic are known riskfactors for awareness.12 Depth of anesthesia can beconsidered in terms of the MAC that is required to

achieve anesthesia in 50% of the patients. MAC may bereduced in pregnancy by 25%40%, possibly because ofincreased pain thresholds or analgesia administered inlabor. Lower BIS scores were observed for similar anes-thetic concentrations in pregnant compared with non-pregnant patients. A comparison between parturientswith and without prior labor undergoing cesarean de-livery found that prior labor was associated with lowerintraoperative BIS values during sevoflurane/nitrousoxide general anesthesia.30

The rapid uptake of nitrous oxide makes it a usefuladjunct despite being a weak anesthetic. The choice ofconcentration is secondary to that of the inspiredoxygen requirement. The administration of 100% oxy-gen may improve 1-min Apgar scores31 but oxygen-free radicals have been detected in newborns aftermaternal administration of high oxygen concentra-tions,32 and resuscitation of neonates with oxygen wasassociated with poorer Apgar scores than air.33 Acommon recommendation is that 50% oxygen should

be given,13,1517 but 33% has been shown to result insimilar outcome provided there is no fetal compro-mise.34 Nitrous oxide has little influence on monitors

of cerebral function35,36 but a concentration of 70%contributes around 0.5 MAC and, if less is given, acorresponding increase in volatile anesthetic is neededto compensate.

Several textbooks recommend that the MAC ofvolatile drug administered predelivery should be ap-proximately 0.51,15 despite evidence that this policy isassociated with an incidence of awareness close to1%.5 This finding is consistent with predelivery BIS

scores at 0.5 MAC in 50% nitrous oxide that rangebetween 57 and 64.12 In a small sample, anesthesiawith 0.2% end-tidal isoflurane in 50% nitrous oxidegave BIS scores between 70 and 80 with evidence oflearning but not spontaneous recall.37 When MAC wasincreased to 0.8 in nonobstetric patients, BIS scores

between 40 and 60 were achieved but the incidence ofawareness was still 0.21%.38 One point to consider iswhether the target MAC should represent the MACfor the volatile drug alone or include the contributionof nitrous oxide. Because the effect of nitrous oxide onmemory is uncertain, prudent advice would be to

regard the target MAC as that of the volatile drugalone.39 However, increasing the concentration of thevolatile drug introduces a new conflict as all volatiledrugs are tocolytic and uterine contractility and tonedecrease in a dose-dependent manner. The uterus willcontract in response to oxytocin, however, providedMAC is 0.81.0.40 These operational limits shouldprovide sufficient scope for adequate anesthesia with-out penalty.

In pregnancy, reduced functional residual capacityand increased minute ventilation increase the rate ofequilibration of blood and inspired concentration of

the volatile anesthetic, although the pregnancy-induced increase in cardiac output counteracts this tosome degree. Equilibration between inspired and

brain concentrations may take 4 12 min depending onthe volatile anesthetic. Uptake of volatile anesthetictherefore needs to be accelerated. McCrirrick et al.41

described an overpressure technique with initialvaporizer settings in excess of MAC to speed equili-

bration, but measurement of end-tidal vapor concen-trations has offered a more dynamic approach. Indeed,investigators found no difference in the incidence ofrecall when noncesarean patients were randomized to

adjustment of the vaporizer setting to deliver a targetend-tidal concentration or BIS monitoring with atarget BIS score 60.38 Unfortunately, because thisstudy was underpowered, equivalence between thetwo techniques cannot be assumed. Isoflurane andsevoflurane are favored because of rapid uptake; forthe former, the target end-tidal concentration should

be in excess of 0.7%,11 and for the latter, an end-tidalconcentration of 1.5% achieved mean predelivery BISscores of60.12

After delivery, the concentration of nitrous oxidemay be increased and opioids may be administered.

This will result in a reduction in reflex activity but notnecessarily a reduction in the incidence of recall. The

Gin T, Chan MTV. Pregnancy reduces the bispectral index

during isoflurane anesthesia (abstract). Anesthesiology 1997;87:A305.

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volatile anesthetic should be continued until comple-tion of the operation, but in the event of uterine atony,it can be reduced and a small dose of midazolam orketamine substituted. Suggested techniques to reducethe risk of awareness during cesarean delivery aresummarized in Table 2.

BRAIN FUNCTION MONITORING

Routine brain function monitoring of patients under-going general anesthesia is controversial, although inone study, it was shown to result in an 82% reduction inthe incidence of awareness in patients undergoing pro-cedures considered at high risk for awareness, includingcesarean delivery.9 However, a low BIS score does notguarantee unconsciousness.42 Whether routine monitor-ing of brain function in the specific setting of generalanesthesia for cesarean delivery can reduce the incidenceof awareness has not been studied.

THE FETUS

Catecholamine secretion during light anesthesiapromotes uterine vasoconstriction and tocolysis. De-pressant effects from transplacental drug transmissionare usually responsible for a lower 1-min Apgar scorein neonates after general anesthesia compared withneuraxial techniques, but by 5 min, differences havelargely disappeared. Provided neonatal resuscitativesupport is available, the effects of general anesthesiaare wholly reversible and the uterine incision todelivery time is more important than the induction todelivery time for good neonatal outcome. Evidence islacking that an awareness avoidance approach togeneral anesthesia has untoward neonatal effects be-yond the first few minutes of life.

AVOIDING LITIGATION

Intraoperative awareness is one of several majorpatient concerns when undergoing general anesthesia;Klafta and Roizen43 showed that up to 54% of patientsworry about the possibility of pain, paralysis, andmental distress during surgery. Current advice is thatpatients considered to be high risk should be informedof the possibility of awareness, when circumstancespermit.44 It may not be appropriate to do this before

an emergency cesarean delivery when anxiety can beextreme. When possible, a preoperative discussion

may help align expectation with experience and re-duce the risk of litigation.45

When awareness occurs, a full account with precisedetails should be recorded in the medical record forfuture reference. An apology costs nothing and mightavert legal proceedings; denial is unhelpful. Symp-toms consistent with posttraumatic stress disorder,sleep disturbance, nightmares, irritability, and lack ofconcentration that can interfere with work, may fol-

low. Counseling is recommended, but its efficacy isunknown. The anesthesiologist may also be distressed

by the incident.46

Hull and Thorburn47believe that awareness cannotoccur without negligence and equated light anesthesiawith inadequate anesthesia. An analysis of 81 inci-dents of awareness found that 32 occurred because ofavoidable drug and equipment errors.46 The alterna-tive view is that a low incidence of awareness duringgeneral anesthesia for cesarean delivery is unavoid-able, but the difficulty of mounting a successful de-fense is acknowledged.47

REFERENCES

1. Crawford JS. Principles and practice of obstetric anaesthesia. 5thed. Oxford: Blackwell Science, 1984

2. Hamer Hodges RJ, Bennet JR, Tunstall ME, Knight RF. Generalanaesthesia for operative obstetrics. Br J Anaesth 1959;31:15263

3. Crawford JS. Awareness during operative obstetrics undergeneral anaesthesia. Br J Anaesth 1971;43:179 82

4. Moir DD. Anesthesia for Caesarean section: an evaluation of amethod using low concentration of halothane and 50 percent ofoxygen. Br J Anaesth 1970;42:13642

5. Lyons G, Macdonald R. Awareness during Caesarean section.Anaesthesia 1991;46:624

6. Sebel PS. The incidence of awareness during anesthesia: amulticenter United States study. Anesth Analg 2004;99:8339

7. Sandin R, Enlaund G, Samuelson P, Lennmarken C. Awarenessduring anaesthesia: a prospective case study. Lancet 2000;355:70711

8. Paech MJ, Scott KL, Clavisi O, Chua S, McDonnell N. TheANZCA Trials Group. A prospective study of awareness andrecall associated with general anaesthesia for caesarean section.Int J Obstet Anesth 2008;17:298303

9. Myles PS, Leslie K, McNeil J, Forbes A, Chan MTV. Bispectralindex monitoring to prevent awareness during anaesthesia: theB-Aware randomised controlled trial. Lancet 2004;363:175763

10. Leslie K, Skrzypek H, Paech MJ, Kurowski I, Whybrow T.Dreaming during anesthesia and anesthetic depth in electivesurgical patients: a prospective cohort study. Anesthesiology2007;106:3342

11. Yeo SN, Lo WK. Bispectral index in assessment of adequacy ofgeneral anaesthesia for lower segment caesarean section. An-

aesth Intensive Care 2002;30:36 4012. Chin K, Yeo S. Bispectral index values at sevoflurane concen-

trations of 1% and 1.5% in lower segment cesarean delivery.Anesth Analg 2004;98:1140 4

13. Malinow AM. General anesthesia for cesarean delivery. In:Norris MC, ed. Obstetric anesthesia. 2nd ed. Philadelphia:Lippincott Williams & Wilkins 1998;37598

14. Kuczkowski KM, Reisner LS, Liu D. Anesthesia for cesareansection. In: Chestnut DH, ed. Obstetric anesthesia, principlesand practice. 3rd ed. Philadelphia: Mosby Elsevier 2004;42146

15. Biribo MA. Anesthesia for cesarean section. In: Birnbach D, GattS, Datta S, eds. Textbook of obstetric anesthesia. Philadelphia:Churchill Livingstone 2000;239 44

16. Paech MJ General anesthesia for cesarean section. In: PalmerCM, DAngelo R, Paech MJ, eds. Handbook of obstetric anes-thesia. Oxford: Bios 2002;10513

17. Yentis S, May A, Malhotra S. Analgesia, anaesthesia and preg-nancy. 2nd ed. Cambridge: Cambridge University Press, 2007

Table 2. Techniques to Avoid Awareness

Beware drug and equipment errorsBrain function monitoring (e.g., Bispectral Index

monitoring to achieve scores 60)Thiopental dose 57 mg/kgTarget end-tidal volatile anesthetic monitoring to achieve

concentration 0.8 MACa

Highest concentration of nitrous oxide compatible withmaternal and fetal oxygen requirements

Opioid analgesia after deliveryConsider benzodiazepines after deliveryaThere is no evidence of fetal morbidity with increased depth of anesthesia.

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18. Veselis RA, Reinsel R, Feschenko VA, Wronski M. The compara-tive amnesic effects of midazolam, propofol, thiopental andfentanyl at equisedative concentrations. Anesthesiology 1997;87:74964

19. Dundee JW, Pandit SK. Studies on drug induced amnesia withintravenous anaesthetic agents in man. Br J Clin Pract 1972;26:1646

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28. Ghoneim MM, Block RI, Sum Ping ST, El-Zahaby HM, HinrichsJV. The interactions of midazolam and flumazenil on humanmemory and cognition. Anesthesiology 1993;79:118392

29. Bulach R, Myles PS, Russnak M. Double-blinded randomizedcontrolled trial to determine extent of amnesia with midazolamgiven immediately before general anaesthesia. Br J Anaesth2005;94:3005

30. Yoo KY, Jeong CW, Kang MW, Kim SJ, Chung ST, Shin MH, LeeJ. Bispectral index values during sevoflurane-nitrous oxidegeneral anesthesia in women undergoing cesarean delivery: acomparison between women with and without prior labor.Anesth Analg 2008;106:182732

31. Piggott SE, Bogod DG, Rosen M, Rees GAD. Isoflurane witheither 100% oxygen or 50% nitrous oxide in oxygen for caesar-ean section. Br J Anaesth 1990;61:25562

32. Khaw KS, Wang CC, Ngan Kee W, Pang CP, Rogers MS. Theeffects of high inspired oxygen fraction during elective caesar-ean section under spinal anaesthesia on maternal and fetaloxygenation and lipid peroxidation. Br J Anaesth 2002;88:1823

33. Saugstad OM, Rootwelt T, Aalen O. Resuscitation of asphyxi-ated newborn infants with room air or oxygen: an internationalcontrolled trial: the Resair 2 Study. Pediatrics 1998;102:e1

34. Lawes EG, Newman B, Campbell MJ, Irwin M, Dolenska S,Thomas TA. Maternal inspired oxygen concentration and neo-natal status for caesarean section under general anaesthesia.Comparison of effects of 33% or 50% oxygen in nitrous oxide.Br J Anaesth 1988;61:2504

35. Barr G, Jakobsson JG, Owall A, Anderson RE. Nitrous oxidedoes not alter bispectral index: a study with nitrous oxide assole agent and as adjunct to intravenous anaesthesia. Br JAnaesth 1999;82:82730

36. Anderson RE, Jakobsson J. Entropy of EEG during anaestheticinduction: a comparative study with propofol or nitrous oxideas sole agent. Br J Anaesth 2004;92:16770

37. Lubke G, Kerssens C, Gershon R, Sebel P. Memory formationduring general anesthesia for emergency cesarean sections.Anesthesiology 2000;92:102934

38. Avidan MS, Zhang L, Burnside BA, Finkel J, Searleman AC,Selvidge JA, Saager L, Turner MS, Rao S, Bottros M, Hantier C,

Jacobsohn E, Evers AS. Anesthesia awareness and the bispectralindex. N Engl J Med 2008;358:1097108

39. Sneyd JR, Mathews DM. Memory and awareness during anaes-thesia. Br J Anaesth 2008;100:7423

40. Yildiz K, Dogru K, Dalgic H, Serin IS, Sezer Z, Madenoglu H,Boyad A. Inhibitory effects of desflurane and sevoflurane onoxytocin-induced contractions of isolated pregnant humanmyometrium. Acta Anaesthesiol Scand 2005;49:13559

41. McCrirrick A, Evans GH, Thomas TA. Overpressure isofluraneat caesarean section: a study of arterial isoflurane concentra-tions. Br J Anaesth 1994;72:1224

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