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Remifentanil-TCI and propofol-TCI for conscious sedation during fibreoptic intubation in the acromegalic patient

Cafiero, T.*; Esposito, F.; Fraioli, G.; Gargiulo, G.; Frangiosa, A.*; Cavallo, L. M.; Mennella, N.; Cappabianca, P.

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European Journal of Anaesthesiology: August 2008 - Volume 25 - Issue 8 - p 670-674
doi: 10.1017/S0265021508004195



In the patient with acromegaly, excess growth hormone is associated with mandibular enlargement resulting in prognathism, which, combined with an enlarged face, macroglossia, hypertrophic pharyngeal tissue and subglottic abnormalities, can render mask ventilation and endotracheal intubation difficult or even impossible [1-4]. Fibreoptic-guided intubation of the trachea to secure the airway before induction of general anaesthesia must be anticipated [5,6].

Because awake tracheal intubation is a painful and uncomfortable procedure, topical anaesthesia and sedation are required to optimize patient comfort [7]. Target-controlled infusion (TCI) allows the blood concentration to be targeted as accurately as possible for the individual patient and so allows the titration of dose to achieve the required clinical effect as simply as possible. It has been demonstrated that propofol and remifentanil, delivered by TCI devices, allow easy achievement of the proper level of anaesthesia and stable haemodynamics without overshooting [8,9].

In this prospective study we have evaluated awake fibreoptic intubation conditions during conscious sedation with propofol and remifentanil, both administered as TCI in the acromegalic patient.


The study was approved by the Ethics Committee and informed written consent was obtained from all patients. From January 2005 to December 2006, we studied 20 patients, aged 38–72 yr, ASA physical status II–IV. All patients with acromegaly underwent elective endonasal endoscopic transsphenoidal pituitary surgery. The reason for conscious intubation was explained to the patient and was documented in the charts. The fibreoptic intubation was performed by the same physician experienced with the fibreoptic technique.

The main end-point was to obtain conscious sedation in order to optimize the patient's comfort and to control the haemodynamic response to the fibrescopic procedure, based on a pre-determined protocol but titrating the two drugs based on the individual response and on the clinical needs. We ensured that the patient could obey commands until the positioning of the tracheal tube.

In the operating room an 18-G catheter was inserted in a peripheral vein with two T-connectors for intravenous fluid and drug administration. In the operating room electrocardiogram (ECG) and pulse oximetry were monitored continuously. Systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP) were monitored non-invasively (DINAMAP) at 2-min intervals. All patients were premedicated with midazolam 0.03 mg kg−1 and 5 μg kg−1 of atropine before fibreoptic intubation. We can speculate that the low dose of midazolam at 0.03 mg kg−1 improved the amnesic effect. Before airway manipulation, every patient received topical anaesthesia with nebulization of 4% lidocaine of the posterior tongue, soft palate and lateral oropharyngeal areas. A bite block was inserted to protect the bronchoscope.

Propofol was administered by the Diprifusor® TCI system incorporated in a syringe pump (TE-372 Terufusion TCI/TIVA, Terumo) based on the kinetic parameters published by Marsh and colleagues [10]. The patient's age and weight were entered into the TCI unit enabling target propofol concentration to be set.

Remifentanil was administered using a syringe pump (Alaris PK, Admiral, Glasgow). We chose the Minto pharmacokinetic model, which does take into account some covariables such as height, weight and age [11], enabling target remifentanil concentration to be set. Patients received O2 therapy whenever the SPO2 was below 92%.

The fibreoptic intubation technique can be followed by the entire team on high-resolution monitors connected to the endoscopic videocamera, so that the anaesthesiologist can modulate the drug infusion according to the various steps of the procedure.

The effect-site concentrations of anaesthetic drugs displayed on the device were recorded during the study period. While maintaining spontaneous ventilation, the fibreoptic bronchoscope was advanced through the mouth until the vocal cords were visualized. Propofol and remifentanil plasma concentrations were increased during airway manipulation to 2.0 μg mL−1 and 3.0 ng mL−1, respectively. After localization of the laryngo-epiglotteal region, 5 mL of lidocaine 4% was sprayed on the vocal cords through the suction port of the bronchoscope. Then propofol and remifentanil plasma concentrations were further increased to 3.5 μg mL−1 and 5.0 ng mL−1 prior to endotracheal tube insertion and changed by steps of 1 ng or μg mL−1 according to the clinical needs.

The endotracheal tube (reinforced endotracheal tube id. 7 or 7.5 mm) was successively advanced into the trachea. We use the rotation of the tube to reduce the difficulty in advancing the tube over the fibrescope. The proper endotracheal tube placement was assessed by viewing the carina, and confirmed by auscultation of breath sounds and end-tidal CO2 monitoring. The tube was positioned approximately 3 cm above the carina and the cuff inflated. Changes in heart rate (HR) and MAP were recorded at pre-determined times in relation to the fibreoptic intubation manoeuvres: during fibrebronchoscope introduction, during tracheal intubation, and at 1 and 3 min after. Coughing and limb movement were also evaluated by the investigators.

On the first postoperative day, patients completed a post-procedure standardized questionnaire asking about explicit intraoperative recall of pain or discomfort, if any, of the fibrescopic procedure itself. The level of discomfort was graded using a 4-step scale: 3 = no recall, 2 = slight memories, 1 = perfect recall with no discomfort, 0 = perfect recall with extreme discomfort.

For statistical analysis we used ANOVA for repeated measures and a value of P < 0.05 was considered statistically significant.


There were 11 males and nine females, aged 47 ± 10 yr (range 38–72), weighing 88 ± 15 kg (range 58–115). The mean body mass index was 29 ± 2 (range 24–35). Nine subjects were ASA class II; eight were ASA class III; three were ASA class IV, due to severe complications from acromegaly, such as hypertension, diabetes mellitus and chronic obstructive pulmonary disease (COPD).

The first attempt with fibrescope was successful in 16 of 20 patients. Mallampati class, thyromental distance (range), number of cases of intubation at first attempt with a fibrescope and number of cases of impingement in each Mallampati class, and coughing during tracheal intubation are listed in Table 1. A cough response was associated with the passage of the tracheal tube in 12 patients (60%). Tracheal intubation was successfully accomplished at the second attempt in two patients. In one occasion more than two attempts were required to achieve tracheal intubation in a patient with the tongue too large to allow the advancement of the fibrescope into the trachea.

Table 1
Table 1:
Mallampati class, thyromental distance, number of cases of intubation at first attempt with fibrescope, number of cases of impingement in each Mallampati class and coughing during tracheal intubation.

Mean duration of fibreoptic procedure, remifentanil (ng mL−1) and propofol effect-site concentrations (μg mL−1), and mean doses with range during fibreoptic intubations are shown in Table 2. The mean time required to complete the tracheal intubation procedure, from the initial insertion of the fibrescope to the assessment of the correct positioning of the orotracheal tube, was 4.4 min.

Table 2
Table 2:
Mean duration of fibreoptic procedure, remifentanil (ng mL−1), propofol effect-site concentrations (μg mL−1), remifentanil (μg) and propofol (mg) dose during fibreoptic intubation.

During the fibreoptic procedure the target concentrations of remifentanil and propofol ranged between 1.0 and 5.0 ng mL−1, and between 1.5 and 3.5 μg mL−1, respectively. A significant increase in blood pressure and HR compared with baseline values was found only during the tracheal intubation (P < 0.05) as shown in Table 3.

Table 3
Table 3:
Haemodynamic changes during fibreoptic manoeuvres and tracheal intubation, and at 1 and 3 min after tracheal intubation.

All patients described their anaesthetic experience as satisfactory. Among them, 17 patients (85%) had no recall on the first postoperative day; slight memories were described by two patients (10%). Perfect recall with no discomfort on airway manipulation was described by one patient (5%).

Oxygenation was sufficient in all patients throughout the study period (SPO2 > 94%) and no bradypnoea or apnoea was recorded in all patients. After surgery the trachea was extubated successfully in the operating room without respiratory distress.


The incidence of difficult intubation in acromegalic patients is approximately four to five times higher compared with non-acromegalic populations. It has been demonstrated that fibreoptic intubation may prove difficult or fail in acromegalic patients undergoing general anaesthesia [12].

In fact, induction of general anaesthesia causes the soft palate, tongue and epiglottis to approximate to the posterior pharyngeal wall [13], making the location of the glottis and insertion of a fibrescope into the trachea difficult [14].

For this reason, awake intubation is the safest way to manage the acromegalic patient's airway.

During an awake fibreoptic intubation the patient can maintain the tonicity of the airway muscles. Such condition provides more safety and makes the localization of the vocal cords easier. Nevertheless, adequate sedation will improve intubating conditions and minimize mucosal bleeding. Obviously, such considerations are of great importance in the acromegalic patient. Finally, the cooperation from the patient can be enhanced by both adequate explanation of the procedure and adequate sedation to alleviate anxiety.

The goal of the present study was to evaluate the combination of propofol and remifentanil, both administered as TCI, for sedation during fibreoptic intubation in the acromegalic patient. Remifentanil, due to its rapid onset and offset of action, offers relevant clinical advantages compared to the other opioids in providing the opioid component of conscious sedation and analgesia during awake tracheal fibreoptic intubation [15]. Since the same drugs used during the fibrescopic intubation were administered along the whole procedure, we can speculate that the subsequent operation did not affect the recall. It has been previously demonstrated that remifentanil, manually infused, either as a single drug or supplemented with midazolam or propofol improved intubating conditions during awake fibreoptic intubation [16-19].

Nevertheless, in order to rapidly obtain the optimal analgesia, the manually controlled infusion of remifentanil is often preceded by a bolus dose. The initial bolus is often associated with respiratory depression and apnoea and, in old patients, with hypotension and bradycardia [20]. Therefore, we think that the TCI is of utmost importance since the effect-site concentration can be titrated precisely to the needs of the individual patient, maintaining a more stable remifentanil effect-site concentration with the use of an internal pharmacokinetic model.

With regard to the administration of remifentanil as single drug, as also discussed by Puchner and colleagues, the tracheal intubation may be associated with a higher incidence of recall [16]. Therefore, it is advisable to associate the remifentanil with a hypnotic drug. In this study, using a TCI of propofol and remifentanil, fibreoptic intubation was performed with complete amnesia of the procedure for the patient.

The use of remifentanil- and propofol-TCI in patients undergoing awake fibreoptic intubation has been reported only in a case report [21]. The authors stated that this regimen was rapidly titratable, aided suppression of airway reflexes, maintained patient comfort and cooperation and did not compromise spontaneous respiration.

In our clinical investigation, which is the first report on remifentanil- and propofol-TCI in the acromegalic patient, the anaesthetic procedure provided satisfactory conscious sedation allowing for successful oral fibreoptic intubation in all patients. Adequate analgosedation was achieved in all patients with reduced anaesthetic doses, and in a relatively short period of time. The reduced doses have to be related to the infusion technique of the drugs (TCI). As a matter of fact, propofol reduces remifentanil requirements for suppression of responses to laryngoscopy and intubation in a synergistic manner [22].

We have to underline that the advancement of the fibrescope into the trachea was sometimes withheld to allow for reaching a deeper level of analgosedation. Regarding the fibreoptic procedure, it is advisable to concomitantly rotate and slide the tube over the bronchoscope to facilitate its introduction, as previously demonstrated [23,24].

In conclusion, we have found that the association of remifentanil and propofol both administered, as TCI, is effective for conscious sedation during fibreoptic intubation in the acromegalic patient. This is probably because few of these drugs are required when using TCI, as well as its smooth mode of administration and reduction of workload with potential clinical benefits for the patient.


1. Messick JM Jr, Cucchiara RF, Faust RJ. Airway management in patients with acromegaly. Anesthesiology 1982; 56(2): 157.
2. Southwick JP, Katz J. Unusual airway difficulty in the acromegalic patient—indications for tracheostomy. Anesthesiology 1979; 51(1): 72–73.
3. Cafiero T, Gargiulo G, Spaziante R et al. Anesthesiologic problems in transsphenoidal surgery of GH-secreting and ACTH-secreting adenomas. Minerva Anestesiol 1986; 52(12): 455–461.
4. Hakala P, Randell T, Valli H. Laryngoscopy and fibreoptic intubation in acromegalic patients. Br J Anaesth 1998; 80(3): 345–347.
5. Dougherty TB, Cronau LH Jr. Anesthetic implications for surgical patients with endocrine tumors. Int Anesthesiol Clin 1998; 36(3): 31–44.
6. Ovassapian A, Doka JC, Romsa DE. Acromegaly – use of fiberoptic laryngoscopy to avoid tracheostomy. Anesthesiology 1981; 54(5): 429–430.
7. Ovassapian A, Krejcie TC, Yelich SJ, Dykes MH. Awake fibreoptic intubation in the patient at high risk of aspiration. Br J Anaesth 1989; 62: 13–16.
8. Passot S, Servin F, Allary R et al. Target-controlled versus manually controlled infusion of propofol for direct laryngoscopy and bronchoscopy. Anesth Analg 2002; 94(5): 1212–1216.
9. De Castro V, Godet G, Mencia G, Raux M, Coriat P. Target controlled infusion for remifentanil in vascular patients improves hemodynamics and decreases remifentanil requirement. Anesth Analg 2003; 96: 33–38.
10. Marsh B, White M, Morton N, Kenny GNC. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: 41–48.
11. Minto CF, Schnider TW, Egan TD et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 1997; 86(1): 10–23.
12. Hakala P, Randell T, Valli H. Laryngoscopy and fibreoptic intubation in acromegalic patients. Br J Anaesth 1998; 80: 345–347.
13. Nandi PR, Charlesworth CH, Taylor SJ, Nunn JF, Dore CJ. Effect of general anaesthesia on the pharynx. Br J Anaesth 1991; 66(2): 157–162.
14. Asai T, Shingu K. Difficulty in advancing a tracheal tube over a fibreoptic bronchoscope: incidence, causes and solutions. Br J Anaesth 2004; 92(6): 870–881.
15. Beers R, Camporesi E. Remifentanil update: clinical science and utility. CNS Drugs 2004; 18(15): 1085–1104.
16. Puchner W, Egger P, Puhringer F, Lockinger A, Obwegeser J, Gombotz H. Evaluation of remifentanil as single drug for awake fiberoptic intubation. Acta Anaesthesiol Scand 2002; 46(4): 350–354.
17. Machata AM, Gonano C, Holzer A et al. Awake nasotracheal fiberoptic intubation: patient comfort, intubating conditions, and hemodynamic stability during conscious sedation with remifentanil. Anesth Analg 2003; 97(3): 904–908.
18. Neidhart G, Kovacs AF, Bremerich DH, Kessler P. Remifentanil-propofol for bronchoscopic fiber optic intubation under capnographic control. Anaesthesist 2000; 49(6): 523–526.
19. Reusche MD, Egan TD. Remifentanil for conscious sedation and analgesia during awake fiberoptic tracheal intubation: a case report with pharmacokinetic simulations. J Clin Anesth 1999; 11(1): 64–68.
20. Hall AP, Thompson JP, Leslie NAP, Fox AJ, Kumar N, Rowbotham DJ. Comparison of different doses of remifentanil on cardiovascular response to laryngoscopy and tracheal intubation. Br J Anaesth 2000; 84: 100–102.
21. Donaldson AB, Meyer-Witting M, Roux A. Awake fibreoptic intubation under remifentanil and propofol target-controlled infusion. Anaesth Intensive Care 2002; 30(1): 93–95.
22. Mertens MJ, Olofsen E, Engbers FH, Burm AG, Bovill JG, Vuyk J. Propofol reduces perioperative remifentanil requirements in a synergistic manner: response surface modeling of perioperative remifentanil-propofol interactions. Anesthesiology 2003; 99(2): 347–359.
23. Jones HE, Pearce AC, Moore P. Fibreoptic intubation. Influence of tracheal tube tip design. Anaesthesia 1993; 48: 672–674.
24. Schwartz D, Johnson C, Roberts J. A maneuver to facilitate flexible fiberoptic intubation. Anesthesiology 1989; 71: 470–471.


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