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Assessment of The Cough Reflex After Propofol Anaesthesia For Colonos
Assessment of The Cough Reflex After Propofol Anaesthesia For Colonos
Cough reflex is the main mechanism of airway defence. It assess the effect of the low propofol concentrations observed
protects the lungs from inhalation of foreign particles and during recovery from general anaesthesia on the cough
clears the airways of retained secretions. However, residual reflex sensitivity assessed by the cough reflex threshold to
concentration of anaesthetics and residual sedation observed an inhaled irritant.
after general anaesthesia may depress this reflex.1–4 This
impairment may lead to adverse respiratory events like
aspiration pneumonia or retained secretions. Methods
Propofol is often used in general anaesthesia for day-case The study was conducted in the Anaesthesia Department
surgery. In this setting, early recovery of airway reflexes is of Bichat Hospital, a 1200-bed University Hospital. It was
essential to allow safe resumption of fluid intake before approved by the Ethics Committee of Saint-Antoine
hospital discharge. However, propofol is a potent depressant Hospital and written informed consent was obtained from
of airway reflexes at hypnotic concentrations,4 5 but the each patient.
effects of low concentrations of this drug, such as those ASA I–II non-smoking patients undergoing elective
observed during recovery from general anaesthesia, have colonoscopy under general anaesthesia were scheduled for
not been assessed. We therefore conducted this study to the study. Any of the following excluded the patient from the
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Cough reflex after propofol for colonoscopy
study: age less than 18 or more than 55 yr, diabetes mellitus, C1 was measured before anaesthesia (blood propofol
central nervous system disease, epilepsy, medication with concentration of 0 mg ml 1) and during the recovery
psychotrops or ACE inhibitors, pregnancy, anaesthesia or period with decreasing blood target propofol concentra-
tracheal intubation during the preceding month, allergic tions of 1.2, 0.9, 0.6, and 0.3 mg ml 1. Blood concentra-
rhinitis, upper airways or bronchopulmonary infection tions were estimated with the Diprifusor software, but
during the preceding month, chronic respiratory disease were not measured. Each measurement at a given concen-
(asthma, COPD, bronchiectasis), chronic cough (more than tration was performed once and was started 5 min after
3 months per yr during 2 consecutive yr) or chronic upper the blood and brain propofol concentrations had reached
airways disease. equilibrium.
The patients did not receive any pre-anaesthetic medica- Before each challenge, sedation was assessed with
tion and no anaesthetic drug other than propofol was admin- the Observer’s Assessment of Awareness/Sedation Scale
istered during colonoscopy. Anaesthesia was induced and (OAA/S).10 It is a five point scale, which takes into
maintained with a blood target controlled propofol infusion account responsiveness, speech, facial expression, and
(Diprifusor device, Astra-Zeneca Laboratory, France). The eyes (see Appendix). It ranges from 5 to 1, a score of 5
software running the device uses the Marsh pharmacokinetic corresponding to an alert state and a score of 1 to a deep
model.6 It has a precision of 18.2% (median absolute pre- sleep state. The same unblinded investigator assessed the
diction error) and a bias of 7% (median prediction error).7 OAA/S score and conducted the cough challenge.
The initial blood target for induction was 6 mg ml 1. There- Fifteen subjects were required to show a 50% increase
after, the target was modified according to the depth of of Log C1 at a propofol concentration of 1.2 mg ml 1
anaesthesia as assessed by the motor response to endoscopic when compared with the preoperative value (nQuery
stimulation and arterial pressure and heart rate variations. Advisor software, Statistical Solutions Company, Saugus,
During anaesthesia, patients were spontaneously breathing MA, USA). C1 was Log transformed for statistical analysis
with supplemental oxygen administered through nasal (Log C1). A Wilcoxon sign rank test was used for compar-
prongs to keep pulse oxygen saturation above 95%. Airway isons. Results were expressed as the median (interquartile
management was limited to manual jaw thrust and mandi- range).
bular advancement. After anaesthesia, the patient was trans-
ferred to the post anaesthesia care unit while the propofol
infusion was maintained with a blood target concentration of Results
1.2 mg ml 1.
From July 2001 to October 2002, 17 patients were included.
The cough reflex threshold was determined by delivering
Two patients withdrew their consent on the day of colono-
increasing concentrations of nebulized citric acid (2.5, 5, 10,
scopy. So, 15 patients were studied and their characteristics
20, 40, 80, 160, 320, and 640 mg ml 1) during inspiration
are presented in Table 1.
until cough was evoked. The concentration eliciting one
OAA/S scores measured before colonoscopy and with
cough (C1) was defined as the cough reflex threshold8 pro-
propofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 mg ml 1
vided that cough was also elicited by the immediately
were 4 (2), 5 (1), 5 (0), 5 (0), and 5 (0), respectively. Scores
greater concentration.9 The order of administration of citric
measured at 1.2 and 0.9 mg ml 1 were significantly different
acid solutions was always the same, from the lowest to
from the score measured at 0 mg ml 1 (P=0.002 and
the highest concentration. No saline was interspersed with
P=0.016, respectively).
increasing concentrations of citric acid. If cough was not
Log C1 measured with estimated propofol concentrations
evoked with the concentration of 640 mg ml 1, C1 was
of 1.2, 0.9, 0.6, 0.3, and 0 mg ml 1 were 1.9 (0.6), 1.9 (1.0),
arbitrarily defined as 1280 mg ml 1. All measurements
1.9 (1.1), 1.9 (0.6), and 1.9 (0.7) mg ml 1, respectively. Log
were performed in the morning to minimize the diurnal
C1 value measured at 1.2 mg ml 1 did not differ from that
variation of the cough reflex, as the threshold is increased
measured at 0 mg ml 1 (P=0.10). Individual variations of
in the afternoon.
Log C1 values are presented in Figure 1. One patient was
For the challenge, the patient was in the sitting position
not able to cough with the highest concentration tested
and wore a nose-clip and was asked to exhale to functional
(640 mg ml 1) at each of the five challenges.
residual capacity and then inhale to total lung capacity
through a mouthpiece (single-breath inhalation technique).
Each concentration of tussive agent was inhaled five
Table 1 Demographic and anaesthetic characteristics of the 15 patients. Results
times with a 30-s pause between each inhalation. A breath- are expressed as median (interquartile range) unless otherwise stated
activated jet nebulizer was used (Nebulizer dosimeter
Age (yr) 40 (19)
MEDIPRON F.D.C. 88, MEDIPROM, Paris, France) which Weight (kg) 64 (14)
delivered a constant volume of solution (8 mg breath 1). Height (cm) 167 (12)
Citric acid solutions were prepared by the Pharmacy of Male patients 6/15 (40%)
Duration of anaesthesia (min) 25 (17)
Bichat Hospital. Normal saline was used as solvent. Solu- Dose of propofol received (mg) 290 (232)
tions were used no more than 48 h after their preparation.
407
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Guglielminotti et al.
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Cough reflex after propofol for colonoscopy
Measurement of the cough threshold evoked by a tussive 8 Dilworth JP, Pounsford JC, White RJ. Cough threshold after
agent like citric acid is the gold standard for assessing the upper abdominal surgery. Thorax 1990; 45: 207–9
cough reflex sensitivity. It has been used to assess the effect 9 Morice AH, Kastelik JA, Thompson R. Cough challenge in the
assessment of cough reflex. Br J Clin Pharmacol 2001; 52: 365–75
of many conditions on this reflex, for example asthma,24
10 Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the
smoking,22 chronic obstructive lung disease,25 or diabetes.21 Observer’s Assessment of Awareness/Sedation Scale: study with
It is also routinely used to test the efficacy of anti-tussive intravenous midazolam. J Clin Psychopharmacol 1990; 10: 244–51
drugs.9 Capsaicin is the other tussive agent used in cough 11 Sekizawa K, Ujiie Y, Itabashi S, Sasaki H, Takishima T. Lack of
challenge. Theoretically, the results may have been different cough reflex in aspiration pneumonia. Lancet 1990; 335: 1228–9
if capsaicin had been used instead of citric acid. However, 12 Niimi A, Matsumoto H, Ueda T, et al. Impaired cough reflex in
this is probably not the case. Indeed, dose–response curves patients with recurrent pneumonia. Thorax 2003; 58: 152–3
13 Arai T, Yasuda Y, Takaya T, et al. ACE inhibitors and reduction of
to citric acid and capsaicin are similar in humans.26 More-
the risk of pneumonia in elderly people. Am J Hypertens 1999; 12:
over, studies that have used both citric acid and capsaicin as 778–83
tussive agent in serial cough challenges have shown similar 14 Lauque D, Aug F, Puchelle E, et al. Efficiency of mucociliary
evolution of the cough reflex threshold whatever the tussive clearance and cough in bronchitis. Bull Eur Physiopathol Respir
agent used.8 1984; 20: 145–9
In conclusion, propofol concentrations observed during 15 Asai T, Koga K, Vaughan RS. Respiratory complications associated
recovery from general anaesthesia for colonoscopy and with tracheal intubation and extubation. Br J Anaesth 1998; 80:
767–75
associated sedation do not appear to adversely affect the
16 Rose DK, Cohen MM, Wigglesworth DF, DeBoer DP. Critical
cough reflex. respiratory events in the postanesthesia care unit. Patient, surgical
and anesthetic factors. Anesthesiology 1994; 81: 410–8
Acknowledgements 17 Clergue F, Auroy Y, Pequignot F, Jougla E, Lienhart A, Laxenaire
MC. French survey of anesthesia in 1996. Anesthesiology 1999; 91:
We would like to thank Dr V. Leclerc (Société Aster-Cephac) and
Dr A. C. Cremieux (Centre d’Investigation Clinique, Hôpital Bichat) for 1509–20
their help in conducting this study. 18 Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R,
Eriksson LI. The incidence and mechanisms of pharyngeal and
upper esophageal dysfunction in partially paralyzed humans.
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Appendix
Assessment categories included in the OAA/S.10
5 Response readily to name spoken in normal tone Normal Normal Clear, no ptosis
4 Lethargic response to name spoken with a normal tone Mild slowing or thickening Mild relaxation Glazed or mild ptosis
3 Responds only after name is called loudly and/or repeatedly Slurring or prominent slowing Marked relaxation Glazed and marked ptosis
2 Response after gentle hand stimulation Few recognizable words
1 Responds only after mild prodding or shaking
0 Does not respond to mild prodding or shaking
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