Minimal alveolar concentration of sevoflurane for induction of ... - BJA

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Methods
The study was approved by the local Institute’s Ethical Committee
(Huazhong University of Science and Technology) and
registered with ClinicalTrials.gov (ref: NCT01662622). After
written informed consent, we enrolled 31 subjects aged
45–65 yr, undergoing upper abdominal surgery using general
anaesthesia from March to May 2012 at Tongji Hospital,
Tongji Medical College, Huazhong University of Science and
Technology, Wuhan, China. All participants had an ASA physical
status classification of I or II. Patients were excluded from
the study if they had one of the following criteria: any neurological
disease or having received central nervous system–
active drugs; a cardiac ejection fraction ,40%; previous
history of difficult intubation or anticipated difficult intubation;
daily alcohol consumption; and obesity (defined as a body
mass index .30 kg m –2 ). Those without informed consent
were also excluded.
As premedication, 0.1 g of phenobarbital and 0.5 mg of atropine
were administered by i.m. injection. After arrival in the
operating theatre, standard monitoring, including electrocardiography,
non-invasive arterial pressure, and pulse oximetry,
was established. The i.v. infusion rate of lactated Ringer’s injection
was 15 ml kg 21 h 21 via an 18 G venous catheter. A neuromuscular
monitor (TOF-watch SX; Organon, Dublin, Ireland)
was placed over the ulnar nerve at the wrist.
Electrical activity of the brain was measured and recorded
with a Narcotrend Monitor (unprocessed EEG) and S/5 Compact
Anaesthesia Monitor [burst suppression ratio (BSR)].
Sensors of the Narcotrend Monitor (MonitorTechnik, Bad Bramstedt,
Germany, version 4.0) and Entropy Module (S/5 Compact
Anaesthesia Monitor, Datex-Ohmeda, Helsinki, Finland) were
attachedto the forehead of each subject according to the manufacturer’s
recommendation. Impedances were measured for
each set of electrodes to ensure adequate electrode contact
defined as 6 kV for the Narcotrend Monitor and 7.5 kV for the
Entropy Module. To calculate BSR, suppression is defined as
periods .0.5 s during which EEG voltage is ,5 mV. Time in a
suppressed state is measured and BSR is reported as the fraction
of the epoch during which the EEG is suppressed. BSR is
averaged over at least 15 epochs (60 s). The presence of burst
suppression was defined as BSR .0. 17 A BSR of 100% implies
isoelectric EEG.
General anaesthesia was induced by tidal volume breathing
of 8% sevoflurane in 100% oxygen at 6 litre min 21 with
a semi-closed face mask. Cisatracurium 0.15 mg kg 21 was
administered after loss of the lash reflex, 18 with manual ventilation
until the amplitude of T1 decreased to zero. Tracheal
intubation was performed and switched to mechanical ventilation
with a fresh gas flow of 2 litre min 21 . Oxygen, carbon
dioxide, and sevoflurane were sampled with a 19 G tube connected
to the distal end of the tracheal catheter. Gas concentration
and partial pressure were analysed by a gas analyser
(S/5 Compact Anaesthesia Monitor) with a sample flow rate
of 200 ml min 21 . The end-tidal partial pressure of carbon
dioxide was maintained at 4.7 kPa. An oesophageal temperature
probe was inserted and a warming unit was used if
Niu et al.
necessary to maintain 36.5 to 37.58C. Surgery started at
least 30 min after inhalation induction, so that the determined
sevoflurane concentration was stable for at least
15 min and the difference of inspired and end-tidal concentrations
was ,10%. 4 A cuff-based continuous arterial pressure
monitor was used; an audible alarm was set to indicate
mean arterial pressure (MAP) reduction of .20% of baseline
values. Phenylephrine 0.1 mg was administered i.v. if necessary
to maintain MAP. Neither Entropy nor Narcotrend
alarms were set.
MAC was determined using the Dixon up-and-down method.
To avoid awareness, the first subject received end-tidal
sevoflurane concentration of 1.7% (1 MAC). As shown in
Figure 1, the presence or absence of isoelectric EEG of the previous
subject determined the end-tidal sevoflurane concentration
of the following subject. End-tidal concentration of
sevoflurane for the next subject was decreased by 0.2% (isoelectric
EEG) or increased by 0.2% (non-isoelectric EEG). A
crossover response was defined as the consecutive inclusion
of a subject who presented isoelectric EEG, followed by
another who did not. The value of a pair was the average of
the end-tidal concentration used for the two subjects of this
pair. The MACie was determined by averaging the values of
six consecutive pairs. For each subject, a 30 min interval was
given to allow equilibration between arterial and brain tensions.
2 The isoelectric EEG was considered as significant
when the isoelectric state lasted .1 min. 19 The maximal BSR
was recorded if isoelectric EEG was not reached. Then, the endtidal
concentration of sevoflurane was maintained until 3 min
after incision. Heart rate (HR) and MAP were recorded at 2 and 1
min before skin incision, and then at 3 min after surgical incision.
The pre-incision value was defined as the mean value of
the 2 and 1 min before skin incision. Adrenergic reflexes (an increase
in either HR or MAP .15% above the pre-incision
values) 5 cases were counted.
Statistical analysis
Patient characteristic data were collected and presented as
mean (SD) or as number (%) where appropriate. The MACie
was calculated as the mean of six independent crossovers of
end-tidal sevoflurane concentration as shown in Figure 3.
Up-and-down sequences were analysed by the probit test
(SPSS for Windows 12.0; SPSS, Inc., Chicago, IL, USA), which
enabled MACie and MACbs with 95% confidence limits of the
mean to be derived. 20 Data were also analysed with logistic
regression for the probability of isoelectric EEG and burst suppression
vs end-tidal concentration, the maximum-likelihood
estimation, and goodness-of-fit.
Subjects were divided into an isoelectric EEG (ie+) group
and a non-isoelectric EEG (ie2) group. The frequency of
phenylephrine injection and incidence of positive adrenergic
reflexes were compared between groups by two-tailed
Fisher’s exact test. Numerical data were analysed by Student’s
t-test or the Mann–Whitney U-tests where appropriate.
P-values of ,0.05 were considered statistically significant.
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