British Journal of Anaesthesia 1996; 77: 781–783
Effect of halothane, isoflurane and desflurane on lower oesophageal
sphincter tone
D. CHASSARD, J. P. TOURNADRE, K. R. BERRADA, B. BRYSSINE AND P. BOULETREAU
Summary
We have studied the effects of volatile anaesthetics
on lower oesophageal sphincter (LOS) tone in
three groups of eight pigs allocated randomly to
receive end-tidal concentrations of 0.5, 1.0 and 1.5
MAC of desflurane, isoflurane or halothane for 15
min. LOS and oesophageal barrier pressures (BrP :
LOSP – gastric pressure) were measured using a
manometric method. The decrease in BrP paralleled the decrease in LOS pressure and was significant at 0.5 MAC for isoflurane and at 1.0 MAC for
halothane. At 1.5 MAC, BrP values were approximately 62% of baseline values for halothane, 37%
for isoflurane and 83% for desflurane. Inter-group
comparisons showed that BrP did not differ at
baseline and at 0.5 MAC. At 1.0 MAC the effect of
isoflurane on BrP was significantly different from
desflurane (P 0.001) and halothane (P 0.02)
whereas the effect of desflurane on BrP was not
significantly different from halothane. At 1.5 MAC
the effect of isoflurane on BrP was significantly different from desflurane (P 0.01) and halothane (P
0.05) whereas the effect of desflurane on BrP was
not significantly different from halothane. We conclude that desflurane maintained BrP and this may
be clinically important in patients at high risk of
regurgitation. (Br. J. Anaesth. 1996; 77: 781–783)
Key words
Anaesthetics volatile, halothane. Anaesthetics volatile,
isoflurane.
Anaesthetics
volatile,
desflurane.
Gastrointestinal tract, lower oesophageal sphincter. Pig.
Induction and maintenance of anaesthesia can be
achieved in patients breathing spontaneously by
administration of volatile anaesthetic agents.
Halothane is used widely in children for induction of
anaesthesia via a face mask1 (a situation with a high
risk of pulmonary aspiration2). Halothane, isoflurane
and desflurane are used for maintenance of anaesthesia.3 The lower oesophageal sphincter (LOS) can
be altered by anaesthetics. It has been reported previously that thiopentone,4 opioids, neuromuscular
blocking agents and benzodiazepines5 affect the
competency of the LOS. During anaesthesia it is
important to be aware of these effects because a
decrease in LOS tone is associated with an increased
risk of regurgitation.6 7 Therefore, it is clinically
relevant to evaluate the effects of these anaesthetics
on LOS tone. Anaesthetics which decrease lower
oesophageal pressure (LOSP) decrease the efficacy
of the oesophageal barrier pressure (BrP : LOSP –
gastric pressure) leading to regurgitation of gastric
contents during the perioperative period.4
Therefore, this study was designed to compare the
effects of halothane, isoflurane and desflurane on
LOS tone in pigs using a manometric method.
Materials and methods
After obtaining approval from our institutional animal
care committee, we studied 24 pigs (weight 22–25 kg).
Ketamine 8 mg kg91 was given i.m. as premedication
and propofol 2 mg kg91 i.v. for tracheal intubation.
Neuromuscular blocking agents were not given during
the study. The lungs of the pigs were ventilated
mechanically by an Ohmeda ventilator incorporated
into a Modulus CD integrated anaesthetic machine
(Madison, WI, USA) with a tidal volume of 15 ml kg91
at a ventilatory frequency of 12–15 bpm. Ventilation
was adjusted to obtain normocapnia at baseline (endtidal carbon dioxide partial pressure of 4.6–5.6 kPa),
the fractional inspired concentration of oxygen was set
at 0.60 and pulse oximetry (SpO2 ) was monitored continuously using the Ohmeda oximeter attached to the
tail of the pig. After measurement of baseline values for
LOS pressures, pigs were allocated randomly to one of
three groups: halothane (n : 8), isoflurane (n : 8) or
desflurane (n : 8). The inhaled anaesthetic was introduced and end-tidal concentrations were maintained
at 0.5, 1 and 1.5 MAC for 15 min. End-tidal concentrations of each volatile agent were fixed according to
previous studies in pigs. End-tidal concentrations of
0.5, 1.0 and 1.5 MAC were 0.60%, 1.20% and 1.80%
for halothane,8 1.05%, 2.10% and 3.10% for isoflurane9 and 5%, 10% and 15% for desflurane.10
Halothane, isoflurane and desflurane were vaporized
using Ohmeda vaporizers (Fluotec 5, Isotec 5 and Tec
6; Steeton, WY, USA). End-tidal anaesthetic concentrations were measured using a calibrated respiratory
gas analyser (Ohmeda, Madison, WI, USA).
D. CHASSARD, MD, J. P. TOURNADRE, MD, K. R. BERRADA, MD,
B. BRYSSINE, MD, P. BOULETREAU, MD, Service d’AnesthésieRéanimation, Hôpital de l’Hôtel-Dieu, 69002, Lyon, France.
Accepted for publication: August 2, 1996.
Correspondence to D. C.
782
LOS PRESSURE MEASUREMENT
LOS and gastric pressures were measured with the
pig supine using perfused polyethylene catheters
connected to pressure transducers. Transducers
were zeroed to the mid-chest position and calibrated
using a water column before each measurement.
Pressures were recorded using a multiple channel
recording system. The first readings for LOSP were
obtained 8–10 min after induction of anaesthesia.
The method for LOS pressure measurements has
been described previously11: catheters were perfused
constantly with water by a low-compliance infusion
pump at 1 ml min91 (compliance 200 mm Hg
min91). The high-pressure zone was detected with a
pull-through technique.
DATA ANALYSIS
Results were expressed as mean (SD). Statistical significance was determined by one-way analysis of
variance for repeated measures for intra-group comparisons and by two-way analysis of variance for
repeated measures for inter-group comparisons
(CSS statistica; Statsoft, Tulsa, OK, USA). When significance was found, a post hoc test (Newman–Keuls
test) was used to determine where the differences lay.
P 0.05 was considered statistically significant.
Results
The effects of halothane, isoflurane and desflurane
on lower oesophageal pressures and barrier pressures
are shown in figure 1 and table 1.
Despite the fact that the mean values of LOSP in
the isoflurane group were 24% and 22% greater than
the mean values in the desflurane and halothane
groups, respectively, there was no significant difference in LOSP at baseline between the three groups
(halothane 19.4 (5.6) mm Hg; isoflurane 24.1 (6.4)
mm Hg; desflurane 19.7 (3.8) mm Hg). Both
halothane and isoflurane produced a dose-related
decrease in LOSP whereas desflurane had no effect.
This decrease was apparent at 1 MAC for halothane
and isoflurane whereas none of the three anaesthetics decreased LOSP significantly at 0.5 MAC. At 1.5
MAC, LOSP values were approximately 72% of
Figure 1 Effects of isoflurane, halothane and desflurane on
lower oesophageal sphincter pressure (LOSP) at equipotent
concentrations (mean, SD). **P 0.01 compared with baseline.
British Journal of Anaesthesia
Table 1 Effects of isoflurane, halothane and desflurane at 0.5, 1
and 1.5 MAC on oesophageal barrier pressure (mm Hg : lower
oesophageal sphincter pressure9gastric pressure) (mean (SD)).
*P 0.05, **P 0.01 compared with baseline; †P 0.05
compared with desflurane and halothane (see text for P values
0.05)
Isoflurane
Halothane
Desflurane
Baseline
0.5 MAC
1.0 MAC
1.5 MAC
15.4
(5.0)
13.1
(5.5)
12.0
(5.8)
10.2
(5.2)*
12.4
(6.2)
11.4
(4.9)
5.6
(3.8)**†
9.4
(5.0)*
11.1
(5.8)
5.8
(5.4)**†
8.3
(5.2)**
10
(6.0)
baseline values for halothane, 56% for isoflurane and
86% for desflurane.
BrP decreased in parallel with the decrease in
LOSP and this was significant at 0.5 MAC for isoflurane and 1.0 MAC for halothane. At 1.5 MAC, BrP
values were approximately 62% of the baseline
values for halothane, 37% for isoflurane and 83% for
desflurane. Inter-group comparisons showed that
BrP was not different at baseline and at 0.5 MAC. At
1.0 MAC the effect of isoflurane on BrP was significant different from desflurane (P 0.001) and
halothane (P 0.02) whereas the effect of desflurane
on BrP was not significantly different from
halothane. At 1.5 MAC the effect of isoflurane on
BrP was significantly different from desflurane (P 0.01) and halothane (P 0.05) whereas the effect of
desflurane on BrP was not significantly different
from halothane.
Discussion
We have demonstrated that a marked reduction in
BrP occurred at 1 and 1.5 MAC of isoflurane and
halothane whereas no changes were seen during
administration of desflurane at equipotent MAC
values.
Volatile anaesthetics have variable effects on
LOSP and BrP. One study in humans reported that
halothane and enflurane in combination with nitrous
oxide decreased LOSP.12 However, nitrous oxide
was introduced before halogenated agents and it
induced a more significant decrease in LOS pressure
than after the introduction of halogenated agents. In
addition, both agents were given at an inspiratory
concentration of 2% without monitoring end-tidal
anaesthetic concentrations. Giving the same inspiratory concentration of enflurane and halothane leads
to different end-tidal concentrations (1.0 MAC is
0.29% for halothane in 50% nitrous oxide in oxygen
and 0.57% for enflurane in 50% nitrous oxide in
oxygen for humans). In contrast, one study performed in dogs showed that 1 h of exposure to
0.5–1% enflurane had no effect on LOSP.13
However, this study was inconclusive because the
MAC of the halogenated agent was not corrected for
species (1.0 MAC of enflurane in dogs is 2.10%).
MAC values greater than 1.5 were impossible to
obtain because of the design of the desflurane vaporizer. The Tec 6 vaporizer is manufactured for use in
humans. MAC 2.0 is 12–14% in humans whereas it
is approximately 20% in swine. The Tec 6 vaporizer
Inhaled anaesthetics and lower oesophageal sphincter
does not allow inspiratory concentrations greater
than 18%. Despite this, desflurane did not cause a
significant decrease in BrP pressure at 1.5 MAC
whereas isoflurane and halothane decreased BrP
pressure at 1.0 MAC. There is no previous study on
the effect of desflurane on BrP pressure to compare
with our data. Failure of desflurane to affect BrP
cannot be attributed to the difference in blood–
muscle gas equilibration because BrP was measured
after end-tidal concentrations of anaesthetic had
been stable for 15 min. In humans, the
blood–muscle partition coefficient of desflurane
(2.02) is lower than those of halothane (3.4) and
isoflurane (2.92).14 15 Therefore, difference in equilibration between LOS muscle and end-tidal gas concentrations cannot explain the difference found. The
absence of an effect of desflurane on LOS could be
because of sympathetic nervous system activation
which is known to occur when desflurane is administered alone.16 In clinical practice, we usually use
nitrous oxide to maintain anaesthesia. Because this
agent decreases LOSP, its use may have attenuated
the LOS responses observed during desflurane
anaesthesia. Confirmation of this hypothesis
requires a different study design.
The choice of anaesthetic technique and animal
are probably important factors in the study of the
effects of inhaled anaesthetics on LOS. Thus
potential criticisms of our study design include the
use of ketamine and propofol before administration of inhalation anaesthesia. However, ketamine
is assumed not to influence LOSP.11 In pigs, we
showed recently that ketamine i.m. followed by
propofol at a higher dose than that used in this
study (5 mg kg91 instead of 2 mg kg91) had no
effect on LOS.17 In addition, all animals received
the same induction dose. As in humans, the musculature of the porcine LOS consists of smooth
muscle fibres.18 Moreover, it has been shown that
the porcine LOS exhibits responses to various
stimuli similar to that in humans.19 Therefore,
these results obtained in pigs could be applied to
humans.
The lungs of all animals were ventilated mechanically before measurement of baseline LOS pressure
and before introduction of the halogenated agents.
This allowed us to obtain constant tidal volumes
throughout the study. This is important because the
pressure at the oesophago–gastric junction is created
not only by contraction of the smooth muscles of the
LOS but also by the striated muscle of the crural
diaphragm.20 All changes in pulmonary volumes
could influence LOS recording. However, LOS
pressures were measured at the end of expiration, a
technique which minimizes the influence of respiration on LOS pressure recording.4 Therefore, to compare LOS pressure from baseline to 1.5 MAC, the
lungs of pigs were ventilated mechanically during
baseline measurements.
In summary, in this animal study we have shown
that in contrast with desflurane, both halothane and
isoflurane decreased oesophageal barrier pressure.
This finding may be clinically important in patients
with a high risk of regurgitation.
783
Acknowledgments
We thank Mr Gardette, Ohmeda, France, for loan of a Modulus
CD integrated anaesthesia machine, Me Finzi and Mr Pr Peix,
Institut de Recherches Chirurgicales (Faculté A. Carrel, Lyon) for
their technical assistance and Mark de Souza (Adelaide,
Australia) for his help in the preparation of the manuscript.
References
1. Reignier J, Ben Ameur M, Ecoffey C. Spontaneous ventilation with halothane in children. Anesthesiology 1995; 83:
674–678.
2. Cheney FW, Posner KL, Caplan RA. Adverse respiratory
events infrequently leading to malpractice suits.
Anesthesiology 1991; 75: 932–939.
3. Matta BF, Mayberg TS, Lam AM. Direct cerebrovasodilatory effects of halothane, isoflurane and desflurane during
propofol-induced isoelectric electroencephalogram in
humans. Anesthesiology 1995; 83: 980–985.
4. Smith G, Dalling R, Williams TIR. Gastro–oesophageal pressure gradient changes produced by induction of anaesthesia
and suxamethonium. British Journal of Anaesthesia 1978; 50:
1137–1142.
5. Hall AW, Moossa AR, Clark J, Cooley GR, Skinner DB. The
effect of premedication drugs on the lower oesophageal high
pressure zone and reflux status of Rhesus monkeys and man.
Gut 1975; 16: 347–521.
6. Haddad JK. Relation of gastroesophageal reflux to yield
sphincter pressures. Gastroenterology 1970; 58: 1089–1090.
7. Roewer N. Can pulmonary aspiration of gastric contents be
prevented by balloon occlusion of the cardia? A study with a
new nasogastric tube. Anesthesia and Analgesia 1995; 80:
378–383.
8. Weiskopf RB, Bogetz MS. Minimum alveolar concentrations
(MAC) of halothane and nitrous oxide in swine. Analgesia
and Anesthesia 1984; 63: 529–532.
9. Moon PF, Scalett JM, Ludders JW, Conway TA, Lamb SV.
Effect of fentanyl on the minimum alveolar concentration of
isoflurane in swine. Anesthesiology 1995; 83: 535–542.
10. Wedel DJ, Gammel SA, Milde JH, Laizzo PA. Delayed onset
of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine.
Anesthesiology 1993; 78: 1138–1144.
11. Cotton BR, Smith G. The lower oesophageal sphincter and
anaesthesia. British Journal of Anaesthesia 1984; 56: 37–46.
12. Senhati GH, Frey R, Star EG. The action of inhalation
anaesthetics upon the lower oesophageal sphincter. Acta
Anaesthesiologica Belgica 1980; 31: 91–98.
13. Caldwell MPT, Marks P, Byrne PJ, Walsh TN, Hennessy
TPJ. Hypotension induced by haemorrhage impairs lower
oesophageal sphincter function. British Journal of Surgery
1994; 81: 1517–1519.
14. Caldwell JE, Laster MJ, Magorian T, Heier T, Yasuda N,
Lynam DP, Eger EI II, Weiskopf RB. The neuromuscular
effects of desflurane, alone and combined with pancuronium
or succinylcholine in humans. Anesthesiology 1991; 74:
412–418.
15. Yasuda N, Targ AG, Eger EI II. Solubility of I-653, sevoflurane, isoflurane and halothane in human tissues. Anesthesia
and Analgesia 1989; 69: 370–373.
16. Ebert TJ, Muzi M. Sympathetic hyperactivity during desflurane anesthesia in healthy volunteers. Anesthesiology 1993; 79:
444–453.
17. Tournadre JP, Chassard D, Berrada KR, Boulétreau P.
Effects of pneumoperitoneum on lower oesophageal
sphincter. British Journal of Anaesthesia 1996; 76: 130–132.
18. Weisbrodt NW. Neuromuscular organisation of esophageal
and pharyngeal motility. Archives of Internal Medicine 1976;
136: 524–531.
19. Goyal RK, Rattan S. Neurohumoral, hormonal and drug
receptors for the lower esophageal sphincter. Gastroenterology
1978; 74: 598–619.
20. Dodds WJ, Stewart ET, Hogan WJ, Stef JJ, Arndorfer RC.
Effect of esophageal movement on intraluminal esophageal
pressure recording. Gastroenterology 1974; 67: 592–600.