ORIGINAL PAPER
Further Pieces of Evidence to the Pulmonary Originof Sevoflurane Escaping to the Operating Room During GeneralAnaesthesia
Zhanhong Xu • Min Dong • Ran Dong •
Shuyan Li • Shangjin Cui
� Springer Science+Business Media New York 2014
Abstract The purpose of this study was to investigate
whether the previously described per oral escape of sevo-
flurane during general anaesthesia is influenced by the
method of cuff inflation and the intra-cuff pressures
achieved. A total of 30 patients undergoing intracranial
surgery participated in the study. Cuffs were inflated under
manual control of the pilot balloon (n = 15) or using a
standardised pressure gauge (n = 15). Sevoflurane con-
centration at the patients’ mouth was captured by absorbers
and quantified by chromatography. We also addressed
whether plateau pressure, breathing frequency, end-tidal
volume, compliance or alveolar concentration of the vol-
atile anaesthetic monitored throughout the anaesthesia was
related to the sevoflurane concentration at the patient’s
mouth. Mean (± SD) intra-cuff pressures achieved by
empirical inflations were significantly higher compared
with the gauge-controlled inflations (53 ± 17 versus
27.7 ± 1.8 cm H2O, P \ 0.001). Despite these pressure
differences, the mean (± SD) concentrations of sevoflu-
rane at the patients’ mouth were comparable (1.77 ± 2.24
versus 2.04 ± 2.31 ppm, P = 0.78). Of the monitored
parameters, only the mean alveolar sevoflurane concen-
tration seemed to be related to the magnitude of escape
(r = 0.51, P \ 0.05). The results provide further evidence
that sevoflurane captured at the patients’ mouth originates
from the lung, and the escape is possibly due to the pre-
viously described presence of longitudinal folds in the
polyvinyl chloride cuff wall, which are not eliminated by
increasing the intra-cuff pressure beyond the recommended
cuff pressure of 25 cm H2O, at least not in the pressure
range covered by this study.
Keywords Method of cuff inflation � Sevoflurane �The intra-cuff pressures
Introduction
Volatile anaesthetics remain the preferred choice for the
maintenance of general anaesthesia. While their use is
intended for patients undergoing surgery, numerous studies
highlight simultaneous exposure of the staff and in par-
ticular, the anaesthesiologist [1, 2]. Since possible health
hazards from long-term exposure to trace concentrations of
inhalational anaesthetics cannot yet be definitely excluded
[3], the National Institute of Occupational Safety and
Health (NIOSH) recommends not to exceed a threshold
value of 2 parts per million (ppm) for volatile anaesthetic
agents without concomitant nitrous oxide exposure [4]. In
order to minimise occupational exposure, better under-
standing of the sources of airborne anaesthetics remains of
paramount importance. We have previously reported that
the concentration of the commonly used volatile anaes-
thetic agent sevoflurane was highest in the proximity of the
intubated patient’s mouth [5]. This observation contradicts
the core function of the cuff, which is to seal the upper-
airway and maximise positive pressure ventilation and
prevent the aspiration of fluid or pharyngeal contents.
Z. Xu � R. Dong � S. Li
The First Affiliated Hospital of Harbin Medical University,
Harbin 150001, China
M. Dong
The Affiliated Hospital of Guilin Medical University,
Guilin 541001, China
S. Cui (&)
State Key Laboratory of Veterinary Biotechnology, Harbin
Veterinary Research, Institute of Chinese Academy of
Agricultural Sciences, Harbin 150001, China
e-mail: [email protected]
123
Cell Biochem Biophys
DOI 10.1007/s12013-014-0080-8
Ideally, this sealing occurs at intra-cuff pressures that do
not exceed the safety margin of 25–30 cm H2O, at which
the risk of blocking mucosal capillary blood flow by
compression and the occurrence of various post-procedural
complications is minimal [6, 7]. Nevertheless, numerous
in vitro studies highlight the possibility of fluid micro-
leakage and its dependence on intra-cuff pressure [8–11].
However, less is known about whether the inflation pro-
cedure influences the per oral escape of the volatile
anaesthetic.
To obtain insights, we sought to answer the following
questions:
(1) Does the release of sevoflurane differ when the
endotracheal balloon is inflated under manual con-
trol (palpation of the pilot balloon) versus when it is
set to the recommended tracheal cuff pressure of
25–30 cm H2O with the help of a pressure gauge?
(2) If yes, can differences in intra-cuff pressure explain
the differences in sevoflurane release?
(3) And can associations of sevoflurane release at the
patient’s mouth provide hints to the origin of the
release?
Methods
Subjects
A total of 30 patients undergoing craniotomy for the
removal of intra-cerebral tumours participated in the study.
Participants were both women and men with a mean
(± SD) age of 58 ± 12 years. All patients gave written
consent to participation, and the study protocol was
approved by the local Investigational Review Board and
Ethics Committee (registration number: DEOEC RKET/
IKET 2483-2006).
Procedures-Cuff Inflation
Tracheal tubes were armoured RuschFlex tracheal tubes
with a low-pressure cuff made of polyvinyl chloride (PVC)
(Teleflex Medical GmbH, Kernen, Germany). Size of the
tube chosen for men and women was 8.5 and 7.5, respec-
tively. The so-called barrel cuff makes this model partic-
ularly suitable for sealing. In both the groups, the position
of the endotracheal tube was ascertained under visual
control using the black indicator mark on the tube, which
was to be positioned between the vocal cords.
In the first series involving 15 patients, tracheal cuffs
were inflated under controlled conditions using the Rusch
Endotest system (Teleflex Medical GmbH, Kernen, Ger-
many), which is an easy-to use and read pressure gauge
able to fill, read, monitor and adjust the cuff pressure of the
low-pressure endotracheal tube. Using this equipment,
intra-cuff pressure was set to a pressure between 25 and
30 cm H2O.
In the second series involving another 15 patients, tra-
cheal cuffs were inflated empirically, i.e. while estimating
intra-cuff pressure based on the hardness of the pilot bal-
loon. In these latter cases, the anaesthesiologists/assistants
were not made aware of the intended control of intra-cuff
pressure, which was obtained by a trained independent
person.
General Anaesthesia Using Sevoflurane
For the induction of anaesthesia, we used propofol
(1–2.5 mg/kg), whereas for maintenance we used the
combination of fentanyl-rocuronium and sevoflurane. Ro-
curonium was given via perfusor to ensure sustained
compliance and airway pressure throughout the anaesthe-
sia. The sevoflurane-air mixture was administered via an
anaesthesia machine (Zeus, Drager Medical AG & Co. KG,
Lubeck, Germany) using a low-flow technique (2 L/min
fresh gas flow). All operations were performed in recently
built operating theatres equipped with modern ventilation
and air-conditioning systems. The operating theatre was
also equipped with a scavenging system compliant with
international standards.
Air was continuously circulated in the room and chan-
ged or refilled at a rate of approximately 50 m3/min.
Monitored Parameters of Ventilation
During anaesthesia, we monitored peak pressure, plateau
pressure, minute volume and alveolar concentration of
sevoflurane in order to explore possible relations to the
degree of anaesthetic escape and thereby obtain hints to the
origin of the release.
Quantification of Volatile Sevoflurane
For the detection of sevoflurane, we used a detection setup
that consisted of a portable air sampling pump (224-51TX
Air Sampling Pump, SKC, Dorset, England), an integrated
tube system and an absorber ampoule coupled to the tube
system. During the sampling, the distal part of the tube
containing the absorber was placed in the close proximity
of the patient’s mouth. A suction pump attached to the
sample collector ensured that samples were flowing
through the absorber where the anaesthetic was collected
for later quantification. Sampling of sevoflurane at the
patient’s mouth was restricted to the time period starting
from reaching steady state conditions to the beginning of
skin closure.
Cell Biochem Biophys
123
After the termination of sample collection, the ampoule
containing the absorber was hermetically sealed and sent to
the laboratory for chromatographic assessment, as descri-
bed previously in detail [5, 12]. The chromatographic
assessment was performed by an independent chemist
(Cs.P.), who was blinded to the origin of the sample and
other key variables of the study. The concentration cap-
tured by chromatography (in ppm) is considered to be a
surrogate of the time-weighted average present over the
entire sampling period.
Data Analysis
Data shown are mean ± SD, unless otherwise indicated.
Mean sevoflurane concentrations were compared using
Mann–Whitney U test, while differences in balloon pres-
sure were tested with Student’s unpaired t test. Differences
were considered statistically significant if P \ 0.05. Given
the broad range and none normal distribution of sevoflu-
rane concentrations measured at the patients’ mouth the
relationship with the different functional parameters of
ventilation was explored following logarithmic transfor-
mation of the respective datasets. Calculations were carried
out using the Statistical for Windows software (StatSoft,
Tulsa, OK, USA).
Results
Baseline Characteristics of the Two Patient Cohorts
Baseline characteristics of the two patient cohorts are
shown in Table 1. Under controlled conditions, intra-cuff
pressures were successfully inflated to a pressure between
25 and 30 cm H2O. The mean (± SEM) pressure in the
group of 15 patients was 27.7 ± 0.5 cm H2O. In contrast,
when cuffs were inflated under manual control, only intra-
cuff pressures were significantly higher (53 ± 4.4 cm H2O,
P \ 0.001).
Sevoflurane concentrations captured at the patients’
mouth showed a considerable variation in both the groups
(Fig. 1). However, when comparing the two mean sevo-
flurane concentrations between the two groups, there were
no statistically significant differences. Thus, when inflating
the endotracheal cuffs under manometer or manual control,
the mean (± SD) sevoflurane concentrations at the
patients’ mouth were 2.04 ± 2.31 and 1.77 ± 2.24 ppm,
respectively (P = 0.78). Given that the sevoflurane data
did not show normal distribution, we have also calculated
the medians and interquartile ranges for each group
(Fig. 1).
When investigating the relationship between different
parameters of ventilation and the concentration of sevo-
flurane measurable at the patient’s mouth, we found no
association with peak or plateau pressure, ventilation rate
and end-tidal volume (Table 2). Of the different parameters
of ventilation, only the mean alveolar concentration of
sevoflurane showed a relationship to the concentration of
Table 1 Key baseline characteristics
Group 1
(manual
control)
Group 2
(manometer
control)
Number of subjects 15 15
Gender distribution (M/F) 8/7 9/6
Body mass index (kg/m2) 25.6 ± 4.8 26.4 ± 6.2
Intra-cuff pressure(cm H2O) 53 ± 17 27.7 ± 1.8
Sevoflurane concentration
at patient’s mouth (ppm)
1.77 ± 2.24 2.04 ± 2.31
Minute volume (ml) 7,155 (750) 7,015 (970)
Data shown are mean ± SD
Fig. 1 Concentration of volatile sevoflurane captured at the patients’
mouth (in ppm), when cuffs of endotracheal tubes were inflated either
empirically (manual control of the pilot balloon) or to an optimal
pressure under guidance by a pressure gauge. Data show the
minimum, maximum and median concentration as well as the
respective interquartile ranges (bars) for the two scenarios. Mean
intra-cuff pressures (± SD) measured were 53 ± 17 and
27.7 ± 1.8 cm H2O, respectively (P = 0.78)
Table 2 Associations between numerous ventilation parameters and
the concentration of sevoflurane measured at the patients’ mouth
Sevoflurane concentration at patient’s mouth
versus N R P Plateau pressure
Minute
volume
30 30
-0.10 -0.12
0.6 0.5
Cell Biochem Biophys
123
sevoflurane detectable at the patients’ mouth (R2 = 0.27,
P = 0.004). The relationship following logarithmic trans-
formation of the respective parameters is illustrated in
Fig. 2.
Discussion
The present study asked the question whether the mode of
cuff inflation and the related intra-cuff pressures have
implications for the concentration of sevoflurane measur-
able at the patient’s mouth during general anaesthesia. Our
findings highlight that when cuffs are inflated empirically,
intra-cuff pressure frequently exceeds the recommended
limits from 25 to 30 cm H2O. This observation is in line
with numerous reports from independent groups [13–15].
This finding is important, in particular, when considering
time-demanding operations where prolonged intubation
with unnecessarily high intra-cuff pressures may pose risks
for post-procedural complications via unwanted impact on
the tracheal tissue [6, 7]. To avoid these complications,
cuff inflation should be performed under guidance by a
manometer to ensure the ideal cuff pressure of 25–30 cm
H2O.
When comparing the two modes of inflation, the con-
centration of sevoflurane measured at the patients’ mouth
did not show significant differences. These concentrations
were comparable with those previously found at the
patient’s mouth, which at the same time represents the zone
of the highest concentration during anaesthesia [5, 16]. Our
observations have underscored that inflating the cuff with
pressures exceeding 25–30 cm H2O did not diminish sig-
nificantly the mean sevoflurane concentrations at the
patients’ mouth and hence did not achieve complete sealing
in the trachea.
In in vitro investigations performed in bench-top mod-
els, Young et al. [8] as well as Dullenkopf et al. [6]
described considerable fluid leakage past the endotracheal
cuff, which was detectable even at 60 cm H2O. The fluid
leakage could be ascribed to the presence of longitudinal
folds within the cuff wall.
Importantly, fold formation is particularly common in
cuff walls made of PVC [6]. Since the endotracheal cuffs
used in the present study are also made of PVC and the
higher cuff pressures (* 60 cm H2O) accompanying
purely empirical inflations did not eliminate the per oral
escape of sevoflurane, and it seems reasonable to assume
that the involvement of contributing factors is similar to
those described in bench-top models.
Anticipating considerable differences in trachea calibre
between men and women, we used tubes with size of 8.5
and 7.5, respectively. Despite this consideration, (i.e.
trying to account for differences in gender-specific anat-
omy of the upper-airways) a fairly broad range of sevo-
flurane concentration was measured at the patients’
mouth. Even when focusing on patients who received the
same balloon inflated to the same intra-cuff pressure,
there was considerable variation in the measured sevo-
flurane concentrations, which seems to point the addi-
tional factors influencing the escape of sevoflurane.
Indeed, numerous studies indicate that the relationship
between the diameter of the trachea and the cuff (or tra-
cheal tube) size [17] together with the material and shape
of the cuffs [18, 19] has an influence on the rise of folds
in the cuff wall. The study by Hwang et al. [20] clearly
demonstrates that larger versus smaller balloons inflated
in the same trachea are associated with more folds within
the cuff wall. Thus, when trachea diameter is smaller than
anticipated just by gender, the same tracheal cuff may
turn out to be too large for the individual patient leading
to increased number of longitudinal folds, and thereby a
more pronounced escape of sevoflurane during the
anaesthesia.
To explore potential further hints to the underlying
mechanisms of the apparent escape of the volatile anaes-
thetic, we also investigated the association between sevo-
flurane concentration at the patients’ mouth and various
key parameters of the actual ventilation. Of these latter
ones plateau pressure, compliance, end-tidal volume and
breathing frequency did not seem to be modifiers of
sevoflurane escape. The only parameter that could be
related to the sevoflurane concentration at the patient’s
mouth was the alveolar sevoflurane concentration. This
latter observation provides further support to the previously
raised notion that the origins of the volatile anaesthetic at
the patient’s mouth are the ventilated lungs.
Fig. 2 Association between sevoflurane concentrations measured at
the patients’ mouth and the alveolar concentrations of the volatile
anaesthetic in 30 intubated patients undergoing craniotomy for the
removal of intracranial tumours. Note that the relationship was
visualised with log-transformed data (base 10)
Cell Biochem Biophys
123
Sevoflurane concentrations at the patient’s mouth as
captured by the absorber (average overtime) exceeded the
clinically significant threshold value of 2 ppm in some
cases [4]. In theory, exposure of the personnel is expected
to decrease with increased distance from the patient’s
mouth (dilution), yet several studies [3, 21, 22] failed to
demonstrate this consistently. What is more, staff members
working outside the area of protective laminar airflow were
actually the subject of the highest level of exposure [23].
Importantly, location and/or placement of instrument tables
and containers may abolish the laminar airflow and create
turbulence, which in turn can lead to a 15-fold higher
exposure level compared to that in areas of laminar air flow
[19]. Intuitively, obtaining complete sealing of airways
during endotracheal intubation could be an important
contributor to the elimination of leakage. Our study sug-
gesting that more pronounced inflation cannot per se
eliminate or diminish the magnitude of leakage, when
using PVC balloons calls on further comparative investi-
gations addressing whether non-PVC balloon material
could contribute to further reduction or even elimination of
this source of airborne sevoflurane.
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