BJA Advance Access originally published online on June 15, 2007
British Journal of Anaesthesia 2007 99(2):276-281; doi:10.1093/bja/aem147
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Comparison of two induction regimens using or not using muscle relaxant: impact on postoperative upper airway discomfort
1 Department of Anesthesia, Henri Mondor Hospital (APHP), 51 avenue du Maréchal de Lattre-de-Tassigny, 94100 Créteil cedex, France
2 Department of Anesthesia, Dupuytren Hospital, Limoges, France
* Corresponding author: Service d'anesthésie reanimation, Hôpital Henri-Mondor, 51 avenue du Maréchal de Lattre-de-Tassigny, 94100 Créteil cedex, France. E-mail: xavier.combes{at}hmn.ap-hop-paris.fr
Accepted for publication April 20, 2007.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
Background: Muscle relaxants facilitate tracheal intubation, but they are often not used for short peripheral surgical procedures. The consequences of this practice on the upper airway are still a matter of controversy. We therefore compared the incidence of post-intubation symptoms in a randomized study comparing patients intubated with or without the use of a muscle relaxant.
Methods: A total of 300 adult patients requiring tracheal intubation for scheduled peripheral surgery were randomly assigned in a double-blind study to an anaesthetic protocol that either included or did not include a muscle relaxant (rocuronium). The primary end-point was the rate of post-intubation symptoms 2 and 24 h after extubation. The secondary end-points were the intubation conditions score (Copenhagen Consensus Conference), the rate of difficult intubations (Intubation Difficulty Scale), and the incidence of adverse haemodynamic events.
Results: Post-intubation symptoms were more frequent in patients intubated without the use of a muscle relaxant, whether 2 h (57% vs 43% of patients; P < 0.05) or 24 h (38% vs 26% of patients; P < 0.05) after extubation. Intubation conditions were better when the muscle relaxant was used. In patients intubated without a muscle relaxant, difficult intubation was more common (12% vs 1%; P < 0.05), as were arterial hypotension or bradycardia requiring treatment (12% vs 3% of patients; P < 0.05).
Conclusions: The use of a muscle relaxant for tracheal intubation diminishes the incidence of adverse postoperative upper airway symptoms, results in better tracheal intubation conditions, and reduces the rate of adverse haemodynamic events.
Keywords: anaesthetic techniques, induction; complications, intubation tracheal; complications, sore throat; pharmacology, rocuronium
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
The main indication for administering a muscle relaxant during anaesthesia is to facilitate laryngoscopy and tracheal intubation.1 The muscle relaxant paralyses the vocal cords and limits post-intubation coughing and bucking.2 However, since the availability of propofol, satisfactory intubating conditions for short surgical procedures have been achieved without a muscle relaxant, and thus without any risk of residual postoperative paralysis.3–8
The practice of administering a muscle relaxant to facilitate tracheal intubation may appear self-evident; however, it has never been rigorously evaluated and results are conflicting. For instance, in one randomized controlled trial, postoperative vocal cord dysfunction was higher when tracheal intubation was performed without than with a muscle relaxant, whereas in a non-randomized prospective study, there was no difference in post-intubation pharyngolaryngeal symptom frequency between patients who had or had not received a muscle relaxant.9 10
The primary aim of the present randomized controlled trial was to evaluate post-intubation pharyngolaryngeal symptoms (hoarseness and sore throat) in patients undergoing elective surgery under general anaesthesia with tracheal intubation, with or without the use of a non-depolarizing muscle relaxant (rocuronium). Secondary end-points were ease of intubation and haemodynamic responses.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
Patients
This was a prospective, randomized, double-blind study which was approved by the Ethics Committee of Dupuytren Hospital (Limoges, France). A total of 300 adult patients (ASA status I or II) undergoing elective surgery under general anaesthesia were enrolled in the study. Written informed consent was obtained from all patients. All patients underwent oro-tracheal intubation for a peripheral surgical procedure, in the supine position with head and neck in neutral positions, which was expected to last less than 120 min. Exclusion criteria were factors predictive of difficult intubation, a BMI above 30 kg m–2, a history of allergy to muscle relaxants, the need for a nasogastric tube, and ear-nose-and-throat surgery. Patients were also excluded if they reported any preoperative sore throat or hoarseness at history taking.
Anaesthesia
Patients were randomized into two groups of 150 patients. Patients were randomly assigned to one of the two groups by a physician not involved in the patient's care, using numbered sealed envelopes. All patients were premedicated with hydroxyzine 50–100 mg orally 1 h before induction of anaesthesia. Standard clinical monitoring was performed. After preoxygenation through a face mask for 4 min, anaesthesia was induced with propofol (2.5 mg kg–1), alfentanil (15 µg kg–1), and rocuronium (0.6 mg kg–1) for the muscle relaxant group and with propofol (2.5 mg kg–1), alfentanil (40 µg kg–1), and saline for the control group. All drugs were prepared by an independent staff anaesthetist not involved in the study. The muscle relaxant (rocuronium) and the saline solution were prepared in identical syringes and in identical volumes. If the anaesthesia induced was not deep enough, the anaesthetist in charge of the patient could administer an iterative bolus of propofol 0.5 mg kg–1. If intubating conditions were unsatisfactory due to poor muscle relaxation, the second anaesthetist in attendance could administer succinylcholine (1 mg kg–1) to patients in the control group or rocuronium (0.25 mg kg–1) to patients in the muscle relaxant group. A Guedel airway was used for all patients during anaesthesia.
Tracheal intubation was attempted 90 s after the administration of either rocuronium or saline. Intubation was always performed by an experienced anaesthetist, using endotracheal tubes (Lo-Contour; Mallinckrodt, Athlone, Ireland) with a high residual volume, a low-pressure cuff, and an internal diameter of 7.5 mm for female patients and 8.0 mm for male patients. The cuff was connected to a manometer (Mallinckrodt) and inflated to a cuff pressure of 20–30 cm H2O. Thereafter, cuff pressure was under continuous control.
Mechanical ventilation was controlled, with end-tidal carbon dioxide maintained at 4.5 (0.5)%. Anaesthesia was maintained with an average end-tidal isoflurane concentration of 0.5–1.5%. Boluses of alfentanil (15 µg kg–1) were given to maintain surgical analgesia. I.V. acetaminophen and morphine were used for postoperative analgesia in the recovery room.
Assessment of intubating conditions
Oro-tracheal intubation conditions were assessed using the score recommended by the 1994 Copenhagen Consensus Conference on Good Clinical Research Practice in Pharmacodynamic Studies of Neuromuscular Blocking agents.11 Intubation criteria include four variables: jaw relaxation and resistance to laryngoscopy blade, the position and movement of vocal cords, the movement of the limbs, and coughing. Each of these variables was rated as excellent, good, or poor. Intubating conditions were considered excellent if all variables were excellent, good if all variables were good or excellent, and poor if any variable was poor.
The Intubation Difficulty Scale (IDS) was used to determine the incidence of difficult intubations (IDS > 5).12 The IDS is the sum of the seven following parameters: number of tracheal intubation attempts, number of operators who attempted intubation, alternative techniques used, glottic exposure (as defined by the Cormack and Lehane class), intensity of (normal or increased) lifting force applied during laryngoscopy, necessity for external laryngeal manipulation, and position of the vocal cords (Table 1). Difficult intubation was defined by an IDS value above 5.
|
Assessment of haemodynamics
After induction of anaesthesia, heart rate and non-invasive arterial pressure measurements were recorded every 3 min for 15 min, then every 15 min. The anaesthesiologist in charge of the patient could use ephedrine to correct for arterial hypotension and atropine for severe bradycardia.
Assessment of post-intubation pharyngolaryngeal symptoms
An independent observer asked the patients whether they experienced any pharyngolaryngeal discomfort. The question ‘are you hoarse or do you have a sore throat?’ was asked first in the post-anaesthetic care unit 2 h after extubation, then on the ward 24 h after extubation. If the answer was yes, the severity of the complaint was assessed on a 101-point numerical rating scale (0 = no discomfort, 100 = extreme discomfort).
Statistical analysis
To detect a decrease in the incidence of pharyngolaryngeal symptoms from 60% to 45%, we calculated that we needed 150 patients per study arm (power of the study, 0.8; type I error, 0.05). The non-parametric Mann–Whitney U-test was used to compare continuous variables. The 
2 test, or the Fisher's exact test for small samples, was used to compare the incidence of pharyngolaryngeal symptoms and of arterial hypotension or bradycardia requiring treatment between the two groups. Two-way analysis of variance was used to compare repeat heart rate and arterial pressure measurement. Results are reported as means (SD). P < 0.05 was considered statistically significant. Data were analysed using SAS software version 9.1.3 (©SAS Institute Inc., Cary, NC, USA).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
Of the 300 patients included in the study, seven (three in the rocuronium arm and four in the control arm) left the hospital before they could be questioned a second time on their pharyngolaryngeal symptoms. Six of these seven patients were interviewed by phone. The seventh (from the rocuronium arm) could not be reached. Patient characteristics were similar in both arms, and postoperative analgesic requirement did not differ between the two groups (Table 2).
|
Post-intubation laryngotracheal symptoms
The incidence of post-intubation pharyngolaryngeal symptoms was significantly lower in the muscle relaxant group than in the control group. This was the case both 2 h after extubation [43% (64/150) vs 57% (86/150) of patients, P < 0.05] and 24 h after extubation [26% (38/149) vs 38.0% (57/150) of patients, P < 0.05]. When symptoms were present, symptom intensity did not differ between the two groups.
Ease of intubation
The number of patients presenting excellent or good intubating conditions was significantly higher in the muscle relaxant group than in the control group according to the Copenhagen Consensus Conference score (Table 3). The frequency of difficult intubations, as given by an IDS score > 5, was significantly higher in the control group. Whereas 18 patients in the control group had an IDS > 5, only one patient in the muscle relaxant group did (P < 0.05). We have reported in Table 4 the distribution of the subcomponents of the IDS. Moreover, 20 patients in the control group required a muscle relaxant (succinylcholine) because of unsatisfactory intubation conditions due to inadequate vocal cord paralysis. No patient in the muscle relaxant group required an additional dose of rocuronium. Patients who were difficult to intubate (IDS > 5) were more likely to present post-intubation symptoms at 2 h [79% (15/19) vs 48% (135/281) of patients, P < 0.05] and at 24 h [58% (11/19) vs 30% (84/281) of patients, P < 0.05].
|
|
Haemodynamics
Mean systolic arterial pressure and mean heart rate decreased in both groups after anaesthesia induction, but significantly more so in the control group (Fig. 1). There was a significant difference between the two groups (P < 0.05) in the need to resort to ephedrine or atropine. Ephedrine (3–9 mg) had to be administered for arterial hypotension in 13 control patients (mean cumulative dose: 10 mg) and three patients in the muscle relaxant group (mean cumulative dose: 6 mg). Atropine was given for brachycardia to five control patients (mean cumulative dose: 0.75 mg) and to one patient in the muscle relaxant group (individual dose: 1 mg).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
The results of the current study have established that omitting a muscle relaxant before tracheal intubation increases the rate of pharyngolaryngeal symptoms during the 24 h after extubation. Moreover, they confirm that intubation without a muscle relaxant increases difficult intubation and adverse haemodynamic events.3 6 13 Serious pharyngolaryngeal lesions secondary to tracheal intubation are uncommon. However, a sore throat and hoarseness have been reported by up to 50% of patients in the first few hours after extubation.14–17 Many factors, such as cuff pressure, gastric tube insertion, type of surgery, gender, head and neck positions, and endotracheal tube size, are known to contribute to these symptoms.14 16 18–20 In our study, cuff pressure was monitored and remained under 30 cm H2O, no patient had a gastric tube, and ear-nose-and-throat surgery was an exclusion criterion. The sex ratio and distribution of tube sizes did not differ between the two arms of our study. Thus, most of the known confounding factors were controlled.
We chose rocuronium as the muscle relaxant, even though intubating conditions are considered inferior to those with succinylcholine.21 This is because succinylcholine cannot be used in a blinded study design because of muscle fasciculations.22 Succinylcholine was, however, administered to some of the control patients who required a muscle relaxant for tracheal intubation. The incidence and severity of postoperative hoarseness and sore throat have not been shown to differ significantly between succinylcholine and rocuronium.21
Traditionally, the combination of propofol with a rapid-onset opioid is considered to give rise to satisfactory conditions for a high rate of successful intubation. The most effective drug combinations are those that include either alfentanil or remifentanil as the opioid.3 23–25 However, relatively high amounts of opioid are needed. When alfentanil is used, an initial bolus of 40 µg kg–1 seems to provide the best intubation conditions.8 23 25 26 If the dosage is below 40 µg kg–1, up to 35% of patients may have their vocal cords closed during laryngoscopy.25 A minimum dose of remifentanil (3 µg kg–1) is also mandatory for successful intubation.3 6 We have deliberately chosen not to administer the same dose of alfentanil in the two groups. Indeed, when muscle relaxant is used, 40 µg kg–1 of alfentanil is clearly not mandatory. Thus, we cannot state that we have strictly compared intubation with or without muscle relaxant but rather two different induction regimens using or not using muscle relaxants.
We assessed overall intubating conditions using the Copenhagen Consensus Conference score and actual ease of intubation using IDS.11 12 The IDS score shows a good correlation with time to intubate and with the difficulties experienced by the operator.12 According to this score, intubation was difficult in 12% of patients when a muscle relaxant was not used instead of 1% when rocuronium was used. Our study, thus clearly confirms that tracheal intubation is more difficult when muscle relaxants are omitted during anaesthesia induction.
We confirm that occurence of post-intubation symptoms occurrence depends on the level of muscle relaxation during laryngoscopy. This was already suggested by the higher rates of hoarseness and vocal cord sequelae recorded by Mencke and colleagues9 in patients intubated without administration of a muscle relaxant. We observed symptom incidence rates of 57% at 2 h after extubation and 38% at 24 h without muscle relaxant compared with 43% and 26%, respectively, with muscle relaxant. These rates are higher than the rates of 36% and 16% recorded by Mencke and colleagues.9
Even if the results of Mencke and colleagues are similar to ours, many study conditions were different. We included sore throats together with hoarseness assessment, whereas Mencke and colleagues assessed only hoarseness. Moreover, in patients not receiving muscle relaxant, we used a fairly high dose of alfentanil, whereas Mencke and colleagues used low-dose fentanyl. In addition, the study of Mencke and colleagues was performed in patients undergoing ear surgery which implies neck rotation. This position has been shown to influence tracheal mucosal pressure.20 As observed by Mencke and colleagues,9 we report that the patients who experienced intubation difficulties had more frequent post-intubation symptoms.
As shown in previous studies, there is a ‘price to pay’ for the use of a higher dosage of opioids in combination with propofol as observed in our study, as this combination can induce a high incidence of adverse haemodynamic events, such as hypotension and bradycardia.3 6 13 The mean decrease in arterial pressure and heart rate during the first 15 min after anaesthesia induction was significantly greater in control patients than in patients who received rocuronium. As a consequence, the anaesthetist, who was blinded to the assignment of patients, had to administer ephedrine or atropine to 12% of control patients but only 3% of patients in the rocuronium group.
A first and potential important limitation of our results might be related to the study design. Indeed, the anaesthetist who performed intubation could have identified the group to which a patient was assigned in several cases, such as in patients where succinylcholine rescue administration was needed and in other patients with marked post-induction arterial hypotension and bradycardia. Nevertheless, the postoperative laryngotracheal symptoms assessment, which was the main goal of our study, was performed in a complete double-blind manner by an independent observer totally unaware of events during the perioperative period.
A second potential limitation of our study was the lack of monitoring to ensure that neuromuscular block was optimal in all patients in the rocuronium arm. However, even if monitoring does indeed improve intubation conditions, it has not been shown to have any direct effect on the incidence of vocal cord injuries or of post-intubation hoarseness.27 In addition, the administration of analgesics for postoperative pain may have led to underestimation of post-intubation symptoms. However, since the postoperative morphine requirement was similar in both arms of the study, this was probably not a confounding factor.
In conclusion, the use of a muscle relaxant for tracheal intubation diminishes the incidence of adverse postoperative upper airway symptoms, results in better tracheal intubation conditions, and reduces the rate of adverse haemodynamic events. The use of a muscle relaxant should therefore be maintained as a standard during anaesthesia induction.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
This work was performed in the Departments of Anesthesia of Henri Mondor (Créteil) and Dupuytren (Limoges) hospitals. Support was from departmental sources only.
|
Footnotes |
|---|
Presented as an abstract at the annual meeting of the American Society of Anesthesiologists, San Francisco, October 2003. 
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledgementsReferences |
|---|
1 Clergue F, Auroy Y, Pequignot F, Jougla E, Lienhart A, Laxenaire MC. French survey of anesthesia in 1996. Anesthesiology (1999) 91:1509–20.[CrossRef][Web of Science][Medline]
2 Rimaniol JM, Kersuzan Y, Duvaldestin P. Intubating conditions using cisatracurium after induction of anaesthesia with thiopentone. Anaesthesia (1997) 52:998–1000.[CrossRef][Web of Science][Medline]
3 Alexander R, Olufolabi AJ, Booth J, El-Moalem HE, Glass PS. Dosing study of remifentanil and propofol for tracheal intubation without the use of muscle relaxants. Anaesthesia (1999) 54:1037–40.[CrossRef][Web of Science][Medline]
4 Andel H, Klune G, Andel D, et al. Propofol without muscle relaxants for conventional or fiberoptic nasotracheal intubation: a dose-finding study. Anesth Analg (2000) 91:458–61.
5 Erhan E, Ugur G, Gunusen I, Alper I, Ozyar B. Propofol—not thiopental or etomidate—with remifentanil provides adequate intubating conditions in the absence of neuromuscular blockade. Can J Anaesth (2003) 50:108–115.[Web of Science][Medline]
6 Grant S, Noble S, Woods A, Murdoch J, Davidson A. Assessment of intubating conditions in adults after induction with propofol and varying doses of remifentanil. Br J Anaesth (1998) 81:540–3.
7 McNeil IA, Culbert B, Russell I. Comparison of intubating conditions following propofol and succinylcholine with propofol and remifentanil 2 micrograms kg–1 or 4 micrograms kg–1. Br J Anaesth (2000) 85:623–5.
8 Stevens JB, Vescovo MV, Harris KC, Walker SC, Hickey R. Tracheal intubation using alfentanil and no muscle relaxant: is the choice of hypnotic important? Anesth Analg (1997) 84:1222–6.[Abstract]
9 Mencke T, Echternach M, Kleinschmidt S, et al. Laryngeal morbidity and quality of tracheal intubation: a randomized controlled trial. Anesthesiology (2003) 98:1049–56.[CrossRef][Web of Science][Medline]
10 Baillard C, Adnet F, Borron SW, et al. Tracheal intubation in routine practice with and without muscular relaxation: an observational study. Eur J Anaesthesiol (2005) 22:672–7.[CrossRef][Web of Science][Medline]
11 Viby-Mogensen J, Engbaek J, Eriksson LI, et al. Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents. Acta Anaesthesiol Scand (1996) 40:59–74.[Web of Science][Medline]
12 Adnet F, Borron SW, Racine SX, et al. The intubation difficulty scale (IDS). Proposal and evaluation of a new score characterizing the complexity of endotracheal intubation. Anesthesiology (1997) 87:1290–7.[CrossRef][Web of Science][Medline]
13 Trabold F, Casetta M, Duranteau J, et al. Propofol and remifentanil for intubation without muscle relaxant: the effect of the order of injection. Acta Anaesthesiol Scand (2004) 48:35–9.[CrossRef][Web of Science][Medline]
14 Jensen PJ, Hommelgaard P, Sondergaard P, Eriksen S. Sore throat after operation: influence of tracheal intubation, intracuff pressure and type of cuff. Br J Anaesth (1982) 54:453–7.
15 Jones MW, Catling S, Evans E, Green DH, Green JR. Hoarseness after tracheal intubation. Anaesthesia (1992) 47:213–6.[Web of Science][Medline]
16 Stout DM, Bishop MJ, Dwersteg JF, Cullen BF. Correlation of endotracheal tube size with sore throat and hoarseness following general anesthesia. Anesthesiology (1987) 67:419–21.[CrossRef][Web of Science][Medline]
17 Mandoe H, Nikolajsen L, Lintrup U, Jepsen D, Molgaard J. Sore throat after endotracheal intubation. Anesth Analg (1992) 74:897–900.
18 Combes X, Schauvliege F, Peyrouset O, et al. Intracuff pressure and tracheal morbidity: influence of filling with saline during nitrous oxide anesthesia. Anesthesiology (2001) 95:1120–4.[CrossRef][Web of Science][Medline]
19 McHardy FE, Chung F. Postoperative sore throat: cause, prevention and treatment. Anaesthesia (1999) 54:444–53.[CrossRef][Web of Science][Medline]
20 Brimacombe J, Keller C, Giampalmo M, Sparr HJ, Berry A. Direct measurement of mucosal pressures exerted by cuff and non-cuff portions of tracheal tubes with different cuff volumes and head and neck positions. Br J Anaesth (1999) 82:708–11.
21 Mencke T, Knoll H, Schreiber JU, et al. Rocuronium is not associated with more vocal cord injuries than succinylcholine after rapid-sequence induction: a randomized, prospective, controlled trial. Anesth Analg (2006) 102:943–9.
22 Miller R. Will succinylcholine ever disappear? Anesth Analg (2004) 98:1674–5.
23 Alexander R, Booth J, Olufolabi AJ, El-Moalem HE, Glass PS. Comparison of remifentanil with alfentanil or suxamethonium following propofol anaesthesia for tracheal intubation. Anaesthesia (1999) 54:1032–6.[CrossRef][Web of Science][Medline]
24 Erhan E, Ugur G, Alper I, Gunusen I, Ozyar B. Tracheal intubation without muscle relaxants: remifentanil or alfentanil in combination with propofol. Eur J Anaesthesiol (2003) 20:37–43.[CrossRef][Web of Science][Medline]
25 Scheller MS, Zornow MH, Saidman LJ. Tracheal intubation without the use of muscle relaxants: a technique using propofol and varying doses of alfentanil. Anesth Analg (1992) 75:788–93.
26 Harsten A, Gillberg L. Intubating conditions provided by propofol and alfentanil—acceptable, but not ideal. Acta Anaesthesiol Scand (1997) 41:985–7.[Web of Science][Medline]
27 Mencke T, Echternach M, Plinkert PK, et al. Does the timing of tracheal intubation based on neuromuscular monitoring decrease pharyngolaryngeal injury? A randomized, prospective, controlled trial. Anesth Analg (2006) 102:306–12.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. S. Meyhoff, J. Lund, M. T. Jenstrup, C. Claudius, A. M. Sorensen, J. Viby-Mogensen, and L. S. Rasmussen Should Dosing of Rocuronium in Obese Patients Be Based on Ideal or Corrected Body Weight? Anesth. Analg., September 1, 2009; 109(3): 787 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Lundstrom, A. M. Moller, C. Rosenstock, G. Astrup, M. R. Gatke, J. Wetterslev, and the Danish Anaesthesia Database Avoidance of neuromuscular blocking agents may increase the risk of difficult tracheal intubation: a cohort study of 103 812 consecutive adult patients recorded in the Danish Anaesthesia Database Br. J. Anaesth., August 1, 2009; 103(2): 283 - 290. [Abstract] [Full Text] [PDF]
|
|
E-letters:
Read all E-letters
- Comparison of two induction regimens using or not using muscle relaxant
- Krishnan Melarkode
- British Journal of Anaesthesia, 14 Aug 2007 [Full text]
- Intubation without muscle relaxant
- Valasubramaniam K Mahadevan
- British Journal of Anaesthesia, 14 Aug 2007 [Full text]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||