Case report

Bispectral Index in a 3-year old undergoing deephypothermia and circulatory arrest

LUIS ZABALA M DM D*, MOHAMMED IQBAL AHMED M B B S ,M B B S ,

F R C AF R C A† AND WILLIAM T. DENMAN M B CM B C hh B , F R C AB , F R C A‡

*Clinical Fellow, Tufts University School of Medicine, Resident in Anesthesia, New EnglandMedical Center, †Assistant Professor in Anesthesia, Tufts University School of Medicine,Attending Anesthesiologist, New England Medical Center and ‡Associate Professor ofAnesthesia, Tufts University School of Medicine, Attending Anesthesiologist, New EnglandMedical Center, Boston, MA, USA

SummaryWe report a 3-year-old girl who presented with Scimitar syndrome

and underwent hypothermic circulatory arrest for correction of

anomalous pulmonary veins and an atrial septal defect. In this case

the Bispectral Index (BIS) correlated significantly with the gradual

onset of hypothermia and circulatory arrest. However, BIS remained

low during the rewarming phase of cardiopulmonary bypass, in spite

of adequate pump flows and stable haemodynamics. We postulate

that this significant lag in BIS during the rewarming phase of deep

hypothermic circulatory arrest may represent neuronal bewilderment

or perhaps stunning, and differs from previous studies that show

significant increase in BIS during rewarming from mild hypothermia.

Keywords: Scimitar syndrome; Bispectral Index; hypothermia; circu-

latory arrest; cardiopulmonary bypass

Introduction

Scimitar syndrome is a rare congenital disease,

responsible for 3–5% of all cases of partial anomal-

ous pulmonary venous drainage. This syndrome is

characterized by partial or complete anomalous

connection of the right pulmonary veins to the

inferior vena cava (IVC). Neill and associates in 1960

described the ‘scimitar sign’ because of a crescent-

like shadow in the right lower lung field seen on

chest X-ray, when drainage of the right pulmonary

veins is into the IVC (1). Associated anomalies

include systemic arterial supply to the lower lobe of

the right lung, hypoplastic right pulmonary artery

and lung, and dextrocardia. Surgical correction is

possible with the help of cardiopulmonary bypass

(CPB). The increase risk of awareness associated

with cardiac surgery and the inconsistent effects of

CPB on electroencephalogram (EEG) has prompted

the use of other devices to guide the depth of

anaesthesia.

Clinical and volunteer studies have shown that

Bispectral Index (BIS) accurately monitors the effect

of anaesthetics on the brain. In spite of the majority

of studies being performed in adults, recent work

has shown that clinical end-points and response are

Correspondence to: William T. Denman, Department of Anesthesia,750 Washington Street no. 298, Boston, MA 02111, USA(email: wdenman@lifespan.org).

Paediatric Anaesthesia 2003 13: 355–359

� 2003 Blackwell Publishing Ltd 355

similar in children (2). The use of hypothermic

circulatory arrest has made congenital heart disease

surgery much more successful. As hypothermia

is induced, BIS decreases and burst suppression

becomes more prominent as EEG activity is

diminished. During the period of hypothermic

arrest, brain metabolism is greatly decreased but

not absent. Therefore metabolism continues in an

environment of hypoxia. This exposes the brain to

changes in oxygen extraction, hypoxia, acidosis and

elevated levels of metabolites that have been asso-

ciated with significant neurological damage. Studies

have demonstrated altered cerebral metabolism after

hypothermic circulatory arrest, comprising dec-

reased transcranial oxygen extraction and decreased

cerebral blood flow as a response of the brain to an

ischaemic insult (3,4). Although it is clear that the BIS

is not intended as an ischaemia monitor nor as a

predictive device, BIS correlates with EEG activity

which is affected by neuronal activity and metabolic

demands.

Case report

A 3-year-old female child, weighing 11.5 kg with a

history of chronic cough and recurrent right lower

lobe pneumonia was diagnosed with Scimitar syn-

drome at 12 months of age. She had undergone

several cardiac catheterizations to define the pul-

monary pressures and to delineate the pulmonary

venous anatomy. Most recent catheterization dem-

onstrated that there were three separate pulmonary

veins from the right lung draining into the inferior

vena cava-right atrial junction and an atrial septal

defect. The main pulmonary artery was hypoplastic

and there was a sequestration of the right lower lobe.

Haemodynamic measurements documented a left to

right shunt of greater than 2 to 1. She was admitted

for surgical correction of partial anomalous pulmon-

ary venous drainage with intracardiac baffling of her

anomalous right-sided pulmonary veins to the left

atrium.

The child was premedicated with oral midazolam

(8 mg). General anaesthesia was induced using sevo-

flurane and nitrous oxide with oxygen. Following

placement of an intravenous line, atracurium 8 mg

and fentanyl 50 lg were given to facilitate tracheal

intubation. The trachea was intubated with a 4.0-mm

diameter uncuffed orotracheal tube; correct place-

ment was confirmed by auscultation and capnogra-

phy. The left radial artery was cannulated with a

22-g catheter and central venous access was obtained

via the right internal jugular vein. Endtidal gases,

electrocardiogram, pulse oximetry, invasive blood

pressure, central venous pressure, temperature, and

BIS were monitored throughout surgery. The child’s

mother had informed the staff that the patient had

complained of recall or awareness during a prior

cardiac catheterization. It was not possible to corro-

borate this information but in light of this informa-

tion BIS monitoring was instituted. The patient was

placed in a right lateral decubitus position and 1 mg

of preservative free morphine was given epidurally

via the caudal route. Anaesthesia was maintained

with isoflurane 1.6% vaporizer setting and fentanyl

8 lgÆkg)1 h)1 via an infusion preceding CPB. Car-

diopulmonary bypass was instituted 63 min after

skin incision. Anaesthesia was maintained during

CPB with isoflurane 0.5% vaporizer setting through

bypass circuit and a fentanyl infusion 5 lgÆkg)1 h)1.

Following the onset of bypass and cooling, a

progressive decrease in BIS was recorded during

induction of hypothermia. Sodium thiopentone

60 mg and ketamine 48 mg were given intraven-

ously for cerebral protection, 45 min prior to the

onset of circulatory arrest, with isoelectric activity

occurring at the onset of circulatory arrest. Total

time for hypothermic circulatory arrest was 41 min,

during which surgical repair was performed. Fol-

lowing the period of arrest, CPB and rewarming to

normothermia was initiated. The BIS monitor con-

tinued recording isoelectric activity for 60 min after

CPB was resumed (Figure 1). A dopamine infusion

(5 lgÆkg)1 min)1) was started for haemodynamic

support while weaning from CPB. Total bypass time

was 155 min. The procedure was well-tolerated and

the patient was transported to the paediatric inten-

sive care unit sedated and tracheally intubated. The

last BIS recording prior to transport was 48. The

patient’s trachea was extubated once the patient was

fully awake. The patient was discharged home with

no evidence of any neurological sequelae and con-

tinues well.

Discussion

The Scimitar syndrome is characterized by partial

or complete anomalous connection of the right

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� 2003 Blackwell Publishing Ltd, Paediatric Anaesthesia, 13, 355–359

pulmonary veins to the IVC. The surgical correction

consists of baffling the anomalous venous channel

into the left atrium through an atrial septal defect.

All intracardiac repairs require extracorporeal circu-

lation by means of CPB with or without deep

hypothermic circulatory arrest. The assessment of

the depth of anaesthesia in infant and children is

difficult during cardiac surgery.

Multiple studies have demonstrated how the BIS

responds to the effect of anaesthetics on the brain,

especially in adults. However, BIS is still being

validated fully in the paediatric population.

In this case we saw a result different from that of

Laussen et al. in children being rewarmed from mild

hypothermic bypass (5). In their study they found a

significant increase in BIS during rewarming from

mild hypothermic CPB in 15 children undergoing

atrial septal defect repair. However, no significant

change in BIS was noted with the induction of mild

hypothermia (tympanic temperature 31.1 ± 3.0 �C).

This is in contrast with our case where significant

decline in BIS was noted when the temperature

reached below 30 �C, during induction of deep

hypothermia (tympanic temperature 13 �C). It is

important to point out that in our case marked

decrease in BIS was noted well before pharmaco-

logical neuroprotective measures were instituted,

implying that there is significant association between

temperature and BIS as reported previously by

Mathew et al. (6).

Several studies have addressed the utility of BIS

during CPB under conditions of normothermia and

hypothermia. EEG and BIS are known not to be

affected by the transition to CPB (7), but little is

known about the effects of various degrees of

temperature change on the BIS and how they might

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Circulatory arrest

Figure 1Changes in the Bispectral Index with induced hypothermia and circulatory arrest.

BIS IN DEEP HYPOTHERMIA AND CIRCULATORY ARREST 357

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represent accurate levels of sedation under condi-

tions of hypothermia.

Electroencephalogram is one technique commonly

used to determine if cerebral metabolism has been

suppressed (8), but recent studies have reported

burst suppression on EEG recordings while jugular

bulb mixed venous values are still low (9), which

raises the question of significant cerebral activity

during EEG silence.

Dewandre et al. reported that after a significant

decrease at the induction of anaesthesia, BIS was not

further modified during CPB and mild hypothermia

(10), suggesting that they could not find any reason

to preclude the use of BIS to assess the hypnotic

effects of anaesthetics during normothermic or mild

hypothermic CPB. Doi et al. reported the effects of

hypothermia on BIS in 12 adults undergoing cardiac

surgery. They describe a wide variation in BIS values

during induced hypothermia, some of which despite

burst suppression recordings on raw EEG, showed

BIS values that overlapped with those recorded prior

to induction of anaesthesia (7). These studies may

suggest that BIS may play a significant role in

determining consciousness during the cooling phase

of mild hypothermic CPB in adults.

It is known that CPB may change the pharmaco-

kinetics and pharmacodynamics of anaesthetic

drugs by many mechanisms. Drug absorption,

distribution, metabolism and elimination are all

affected by the haemodilution, temperature and

hypotension. Under these conditions plasma drug

concentration could be lower than those required to

suppress awareness. The high lipid solubility of

ketamine and thiopentone and their relatively high

volume of distribution may be more readily taken

up by bypass equipment, decreasing plasma con-

centrations. The effect of back diffusion into the

plasma of these drugs from large tissue stores

appears to be more significant for continuous infu-

sion technique than that of single dose injections.

Deep hypothermic circulatory arrest may also have a

significant effect on the elimination clearance of

these drugs, by decreasing hepatic blood flow

during the arrest period. These effects could parti-

ally explain changes in anaesthetic depth level seen

by BIS during the different phases of CPB and

circulatory arrest.

In our case confounding variables such as induced

deep hypothermia, cerebral perfusion pressure and

the use of neuroprotective agents may influence the

decrease of BIS, rather than any single variable

alone.

Our observation of no significant increase in BIS

during rewarming is inconsistent with results

reported previously by Laussen et al. derived from

rewarming during mild hypothermic CPB in chil-

dren undergoing atrial septal defect repair (5).

Several studies have described a delay in return of

cerebral metabolism to baseline values during

rewarming, in contrast to a very prompt recovery

of cerebral blood flow (11,12). A possible explanation

for this phenomenon has been addressed by the term

‘luxury perfusion’, where the cerebral blood flow is

inappropriately high for the brain temperature

during early reperfusion. This may suggest that the

cerebral derangements during a period of profound

hypothermic arrest are much more significant than

those taking place under conditions of mild hypo-

thermia, and that metabolic rate is temperature

appropriate (13). Electrophysiological studies have

demonstrated an association between EEG recovery

times and duration of circulatory arrest (14,15). This

and the altered kinetics of neuroprotective agents

during bypass and circulatory arrest would explain

the delay in neuronal activity seen on BIS despite

adequate cerebral blood flow.

Godet et al. reported the effects of profound

hypothermia and circulatory arrest on BIS in 10

consecutive adult patients undergoing aortic arch

repair. They demonstrated a lack of normalization of

BIS during rewarming and conclude that BIS is

probably inappropriate to monitor the depth of

anaesthesia during rewarming under hypothermic

circulatory arrest (16).

Recent case reports may imply that BIS is mark-

edly sensitive to cerebral blood flow, suggested by

the decrease in BIS during decreased cerebral blood

flow as a result of gas embolism (17) and insidious

cardiac arrest (18) with rapid recovery during cereb-

ral reperfusion, under conditions of normothermia.

This is in contrast with the absence of recovery in BIS

during profound hypothermia and circulatory arrest,

which may suggest that the recovery in BIS may be

related to the ideal relationship between cerebral

blood flow and cerebral metabolic rate.

In conclusion, we describe a 3-year-old girl who

underwent hypothermic circulatory arrest for cor-

rection of anomalous pulmonary veins and an atrial

358 L. ZABALA ET AL.

� 2003 Blackwell Publishing Ltd, Paediatric Anaesthesia, 13, 355–359

septal defect. BIS monitoring was used to aid in

titrating anaesthetic agents pre- and post-hypother-

mic circulatory arrest. BIS correlates significantly

with induction of hypothermia, probably related to

the decrease in metabolic activity and a response to

EEG effects of pharmacological agents used as

neuroprotective measures. The lack of response of

BIS during rewarming may represent derangements

in cerebral metabolism, characterized by changes in

oxygen extraction, cerebral blood flow, active trans-

port mechanisms and metabolite buildup. More

formal studies will be needed to establish the role

and mechanism of cerebral monitoring during

rewarming following deep hypothermia and circu-

latory arrest in children.

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Accepted 10 February 2003

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