1 Service d'Anesthésiologie et de Réanimation Chirurgicale, 2 Département d'Epidémiologie, Biostatistique et Recherche Clinique and 3 Service des Explorations Fonctionnelles, Hôpital Bichat, Assistance Publique, Hôpitaux de Paris, 46 rue Henri Huchard, F-75018 Paris, France
* Corresponding author. E-mail: jean.guglielminotti{at}bch.ap-hop-paris.fr
Accepted for publication May 16, 2005.
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Abstract |
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Methods. Fifteen, ASA III, non-smoking patients undergoing elective colonoscopy were studied. Anaesthesia was induced and maintained with a blood target-controlled propofol infusion. Cough reflex threshold was measured with citric acid. Increasing concentrations of nebulized citric acid (2.5, 5, 10, 20, 40, 80, 160, 320, and 640 mg ml1) were delivered during inspiration until a cough was evoked. The citric acid concentration eliciting one cough (C1) was defined as the cough reflex threshold. C1 was log transformed for statistical analysis (Log C1). Log C1 was measured before anaesthesia and during the recovery period with estimated decreasing propofol concentrations of 1.2, 0.9, 0.6, and 0.3 µg ml1.
Results. Log C1 (median; interquartile range) measured with propofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 µg ml1 were 1.9 (0.6), 1.9 (1.0), 1.9 (1.1), 1.9 (0.6), and 1.9 (0.7) mg ml1 (NS), respectively. However, light sedation was observed with propofol concentrations of 1.2 and 0.9 µg ml1.
Conclusion. This study indicates that residual sedation after propofol anaesthesia for colonoscopy does not adversely affect the cough reflex.
Keywords: anaesthetics i.v., propofol ; citric acid ; colonoscopy ; complications, aspiration ; complications, pneumonia ; cough
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Introduction |
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Propofol is often used in general anaesthesia for day-case surgery. In this setting, early recovery of airway reflexes is essential to allow safe resumption of fluid intake before hospital discharge. However, propofol is a potent depressant of airway reflexes at hypnotic concentrations,4 5 but the effects of low concentrations of this drug, such as those observed during recovery from general anaesthesia, have not been assessed. We therefore conducted this study to assess the effect of the low propofol concentrations observed during recovery from general anaesthesia on the cough reflex sensitivity assessed by the cough reflex threshold to an inhaled irritant.
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Methods |
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ASA III non-smoking patients undergoing elective colonoscopy under general anaesthesia were scheduled for the study. Any of the following excluded the patient from the study: age less than 18 or more than 55 yr, diabetes mellitus, central nervous system disease, epilepsy, medication with psychotrops or ACE inhibitors, pregnancy, anaesthesia or tracheal intubation during the preceding month, allergic rhinitis, upper airways or bronchopulmonary infection during the preceding month, chronic respiratory disease (asthma, COPD, bronchiectasis), chronic cough (more than 3 months per yr during 2 consecutive yr) or chronic upper airways disease.
The patients did not receive any pre-anaesthetic medication and no anaesthetic drug other than propofol was administered during colonoscopy. Anaesthesia was induced and maintained with a blood target controlled propofol infusion (Diprifusor® device, Astra-Zeneca Laboratory, France). The software running the device uses the Marsh pharmacokinetic model.6 It has a precision of 18.2% (median absolute prediction error) and a bias of 7% (median prediction error).7 The initial blood target for induction was 6 µg ml1. Thereafter, the target was modified according to the depth of anaesthesia as assessed by the motor response to endoscopic stimulation and arterial pressure and heart rate variations. During anaesthesia, patients were spontaneously breathing with supplemental oxygen administered through nasal prongs to keep pulse oxygen saturation above 95%. Airway management was limited to manual jaw thrust and mandibular advancement. After anaesthesia, the patient was transferred to the post anaesthesia care unit while the propofol infusion was maintained with a blood target concentration of 1.2 µg ml1.
The cough reflex threshold was determined by delivering increasing concentrations of nebulized citric acid (2.5, 5, 10, 20, 40, 80, 160, 320, and 640 mg ml1) during inspiration until cough was evoked. The concentration eliciting one cough (C1) was defined as the cough reflex threshold8 provided that cough was also elicited by the immediately greater concentration.9 The order of administration of citric acid solutions was always the same, from the lowest to the highest concentration. No saline was interspersed with increasing concentrations of citric acid. If cough was not evoked with the concentration of 640 mg ml1, C1 was arbitrarily defined as 1280 mg ml1. All measurements were performed in the morning to minimize the diurnal variation of the cough reflex, as the threshold is increased in the afternoon.
For the challenge, the patient was in the sitting position and wore a nose-clip and was asked to exhale to functional residual capacity and then inhale to total lung capacity through a mouthpiece (single-breath inhalation technique). Each concentration of tussive agent was inhaled five times with a 30-s pause between each inhalation. A breath-activated jet nebulizer was used (Nebulizer dosimeter MEDIPRON F.D.C. 88, MEDIPROM, Paris, France) which delivered a constant volume of solution (8 mg breath1). Citric acid solutions were prepared by the Pharmacy of Bichat Hospital. Normal saline was used as solvent. Solutions were used no more than 48 h after their preparation.
C1 was measured before anaesthesia (blood propofol concentration of 0 µg ml1) and during the recovery period with decreasing blood target propofol concentrations of 1.2, 0.9, 0.6, and 0.3 µg ml1. Blood concentrations were estimated with the Diprifusor® software, but were not measured. Each measurement at a given concentration was performed once and was started 5 min after the blood and brain propofol concentrations had reached equilibrium.
Before each challenge, sedation was assessed with the Observer's Assessment of Awareness/Sedation Scale (OAA/S).10 It is a five point scale, which takes into account responsiveness, speech, facial expression, and eyes (see Appendix). It ranges from 5 to 1, a score of 5 corresponding to an alert state and a score of 1 to a deep sleep state. The same unblinded investigator assessed the OAA/S score and conducted the cough challenge.
Fifteen subjects were required to show a 50% increase of Log C1 at a propofol concentration of 1.2 µg ml1 when compared with the preoperative value (nQuery Advisor software, Statistical Solutions Company, Saugus, MA, USA). C1 was Log transformed for statistical analysis (Log C1). A Wilcoxon sign rank test was used for comparisons. Results were expressed as the median (interquartile range).
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Results |
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Log C1 measured with estimated propofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 µg ml1 were 1.9 (0.6), 1.9 (1.0), 1.9 (1.1), 1.9 (0.6), and 1.9 (0.7) mg ml1, respectively. Log C1 value measured at 1.2 µg ml1 did not differ from that measured at 0 µg ml1 (P=0.10). Individual variations of Log C1 values are presented in Figure 1. One patient was not able to cough with the highest concentration tested (640 mg ml1) at each of the five challenges.
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Discussion |
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Previous studies have suggested that postoperative impairment of the cough reflex may lead to aspiration pneumonia or retained secretions. Indeed, an increase of the cough reflex threshold was observed in medical patients who developed aspiration pneumonia or recurrent pneumonia.11 12 Moreover, a decrease of the cough threshold induced by ACE inhibitors may be protective against aspiration pneumonia.13 Consequences of cough reflex depression after general anaesthesia may be worse in patients with pulmonary disease like COPD patients. Indeed, cough contributes to up to 60% of total pulmonary clearance in COPD patients but only to 8% in healthy patients.14
Little is known about the effects of anaesthetics on the cough reflex and especially the effect of subhypnotic concentrations of anaesthetics like those observed in the recovery period. Nishino and Tagaito reported that enflurane and propofol depress the cough reflex.2 3 However, both studies addressed the effects of high, hypnotic concentrations of these drugs, that is 0.7 MAC enflurane and 3 µg ml1 propofol concentrations. Dilworth and colleagues reported an increase of the cough reflex threshold elicited by citric acid and capsaicin until the first day after upper abdominal surgery. Drugs administered during anaesthesia may have been responsible for that increase.8
In the present study, we investigated the effect of lingering concentrations of propofol and the associated residual sedation observed in the post anaesthesia care unit, in view of the high risk of adverse respiratory events during the early postoperative period.15 16 We observed a small but significant decrease of the OAA/S score indicating light levels of sedation with blood propofol concentrations of 1.2 and 0.9 µg ml1. However, we did not observe any effect of low propofol concentration on the cough reflex threshold. The cough reflex appears more resistant to the effect of anaesthetic agents than pharyngeal reflexes. Indeed, venous blood propofol concentration of 0.9 µg ml1 deeply impairs pharyngeal reflexes.4 Differential sensitivity of both reflexes towards the same anaesthetic drug seems to be related to a differential sensitivity of each neural pathway in the brain.3 However, we cannot rule out that our negative results were related to a type II statistical error. Since the number of subjects included in the study was calculated to demonstrate a 50% increase in Log C1, a smaller Log C1 change may not have been detected.
Preservation of the cough reflex after propofol anaesthesia may be clinically relevant for the management of ambulatory patients. It may allow early and safe resumption of oral fluid intake before hospital discharge, that is without aspiration of fluid into the trachea. Colonoscopy is the most frequent procedure conducted under general anaesthesia in France. More than 800 000 procedures are performed each year in France accounting for 10% of all anaesthetics.17 Owing to the number of cases and the ambulatory nature of the procedure, safety is a primary concern. So, knowing that the concentrations of propofol observed in the recovery period do not impair airway protective reflexes is rather reassuring for the management of the patient. These results could also be extended to all procedures conducted under propofol sedation with or without topical anaesthesia or local anaesthetic infiltration, that is with no or little systemic resorption of local anaesthetics (cataract and ocular surgery, dental extractions, extracorporeal shock-wave lithotripsy, angiography, cosmetic surgical procedures, in vitro fertilization procedures, etc.).
In this study, patients only received propofol without upper airway instrumentation. Our findings can therefore not be extrapolated to other anaesthetic protocols using different anaesthetic agents or airway manipulation, as opioids, volatile agents, and muscle relaxants impair upper airway function.2 3 18 Similarly, upper airway reflexes are depressed after tracheal intubation or laryngeal mask airway insertion.19 20 We chose not to insert a laryngeal mask airway or a tracheal tube because that is not the usual practice in our Institution. The patients in this study were young non-smoking patients and the procedure was a colonoscopy, which does not interfere with lung function. In contrast, patients with abnormal upper airway function, for example diabetic patients, smokers or elderly, may have a different postoperative course.21 23 However, these conditions are associated with an increase of the cough reflex threshold. If we had included these patients, we may have overlooked an increase of the cough reflex threshold caused by low propofol concentrations because of the high basal threshold of the patients. The surgical procedure may also influence the cough threshold, as described after upper abdominal surgery.8
Measurement of the cough threshold evoked by a tussive agent like citric acid is the gold standard for assessing the cough reflex sensitivity. It has been used to assess the effect of many conditions on this reflex, for example asthma,24 smoking,22 chronic obstructive lung disease,25 or diabetes.21 It is also routinely used to test the efficacy of anti-tussive drugs.9 Capsaicin is the other tussive agent used in cough challenge. Theoretically, the results may have been different if capsaicin had been used instead of citric acid. However, this is probably not the case. Indeed, doseresponse curves to citric acid and capsaicin are similar in humans.26 Moreover, studies that have used both citric acid and capsaicin as tussive agent in serial cough challenges have shown similar evolution of the cough reflex threshold whatever the tussive agent used.8
In conclusion, propofol concentrations observed during recovery from general anaesthesia for colonoscopy and associated sedation do not appear to adversely affect the cough reflex.
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Appendix |
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Acknowledgments |
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References |
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2 Nishino T, Hiraga K, Mizuguchi T, Honda Y. Respiratory reflex responses to stimulation of the tracheal mucosa in enflurane-anesthetized humans. J Appl Physiol 1988; 65: 106974
3 Tagaito Y, Isono S, Nishino T. Upper airway reflexes during a combination of propofol and fentanyl anesthesia. Anesthesiology 1998; 88: 145966[CrossRef][ISI][Medline]
4 Sundman E, Witt H, Sandin R, et al. Pharyngeal function and airway protection during sub hypnotic concentrations of propofol, isoflurane, and sevoflurane. Anesthesiology 2001; 95: 112532[CrossRef][ISI][Medline]
5 Barker P, Langton JA, Wilson IG, Smith G. Movements of the vocal cords on induction of anesthesia with thiopentone or propofol. Br J Anaesth 1992; 69: 235[Abstract]
6 Marsh B, White M, Morton N, Kenny GNC. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: 418[Abstract]
7 Coetzee JF, Glen JB, Wium CA, Boshoff L. Pharmacokinetic model selection for target controlled infusions of propofol. Assessment of three parameter sets. Anesthesiology 1995; 82: 132845[CrossRef][ISI][Medline]
8 Dilworth JP, Pounsford JC, White RJ. Cough threshold after upper abdominal surgery. Thorax 1990; 45: 2079[Abstract]
9 Morice AH, Kastelik JA, Thompson R. Cough challenge in the assessment of cough reflex. Br J Clin Pharmacol 2001; 52: 36575[CrossRef][ISI][Medline]
10 Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the Observer's Assessment of Awareness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol 1990; 10: 24451[ISI][Medline]
11 Sekizawa K, Ujiie Y, Itabashi S, Sasaki H, Takishima T. Lack of cough reflex in aspiration pneumonia. Lancet 1990; 335: 12289[ISI][Medline]
12 Niimi A, Matsumoto H, Ueda T, et al. Impaired cough reflex in patients with recurrent pneumonia. Thorax 2003; 58: 1523
13 Arai T, Yasuda Y, Takaya T, et al. ACE inhibitors and reduction of the risk of pneumonia in elderly people. Am J Hypertens 1999; 12: 77883[CrossRef][ISI][Medline]
14 Lauque D, Aug F, Puchelle E, et al. Efficiency of mucociliary clearance and cough in bronchitis. Bull Eur Physiopathol Respir 1984; 20: 1459[ISI][Medline]
15 Asai T, Koga K, Vaughan RS. Respiratory complications associated with tracheal intubation and extubation. Br J Anaesth 1998; 80: 76775
16 Rose DK, Cohen MM, Wigglesworth DF, DeBoer DP. Critical respiratory events in the postanesthesia care unit. Patient, surgical and anesthetic factors. Anesthesiology 1994; 81: 4108[ISI][Medline]
17 Clergue F, Auroy Y, Pequignot F, Jougla E, Lienhart A, Laxenaire MC. French survey of anesthesia in 1996. Anesthesiology 1999; 91: 150920[CrossRef][ISI][Medline]
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. Anesthesiology 2000; 92: 97784[CrossRef][ISI][Medline]
19 De Larminat V, Montravers P, Dureuil B, Desmonts JM. Alteration in swallowing reflex after extubation in intensive care unit patients. Crit Care Med 1995; 23: 48690[CrossRef][ISI][Medline]
20 Tanaka A, Isono S, Ishikawa T, Nishino T. Laryngeal reflex before and after placement of airway interventions: endotracheal tube and laryngeal mask airwayTM. Anesthesiology 2005; 102: 205[CrossRef][ISI][Medline]
21 Behera D, Das S, Dash RJ, Jindal SK. Cough threshold in diabetes mellitus with and without autonomic neuropathy. Respiration 1995; 62: 2638[ISI][Medline]
22 Dicpinigaitis PV. Cough reflex sensitivity in cigarette smokers. Chest 2003; 123: 6858
23 Newnham DM, Hailton SJC. Sensitivity of the cough reflex in young and elderly subjects. Age Ageing 1997; 26: 1858[Abstract]
24 Pounsford JC, Birch MJ, Saunders KB. Effect of bronchodilators on the cough response to inhaled citric acid in normal and asthmatic subjects. Thorax 1985; 40: 6627[Abstract]
25 Wong CH, Morice AH. Cough threshold in patients with chronic obstructive pulmonary disease. Thorax 1999; 54: 624
26 Laude EA, Higgins KS, Morice AH. A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man. Pulm Pharmacol 1993; 6: 1715[CrossRef][ISI][Medline]
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