Original Articles

ORIGINAL ARTICLE – Effect of two different doses of fentanyl on intubating conditions with sevoflurane inhalation without neuromuscular blocking agents in adults

Mansoor Aqil*, Aziz-ul-Haq**, Amjad Rasheed***, Rana Altaf **.

*Associate Professor of Anesthesiology, College of Medicine, King Saud University, Consultant anesthetist, King Khalid University Hospital and King Abdul Aziz University Hospital, Riyadh (Saudi Arabia).

**Consultant anesthetist, *** Specialist anesthetist

KingAbdulAzizUniversityHospital, Riyadh (Saudi Arabia).

Correspondence: Dr. Mansoor Aqil,Associate Professor of Anesthesiology, College of Medicine, King Saud University, Consultant anesthetist, King Khalid University Hospital and King Abdul Aziz University Hospital, P.O. box 245, Riyadh 11411, (Saudi Arabia); Email: mansooraqil@yahoo.com; Phone:0096614775703 (office); 00966507221058 (mobile); Fax: 0096614786100 Ext. 7525


Purpose: To compare the effect of two different doses of fentanyl on intubating conditions, after inhalational induction with sevoflurane in adults, without using neuromuscular blocking agents.

Methods: In this prospective, randomized, double blind study, fifty six adult patients with ASA status I–II, without any airway problem and scheduled to undergo elective surgical procedures under general anesthesia requiring endotracheal intubation were selected. Patients with allergy to any of the drugs used, body mass index > 30 kg/m2 and anticipated difficult airway were excluded from the study. Patients were premedicated with midazolam 0.1mg/kg and ranitidine 150 mg PO two hours prior to surgery and received 0.2 mg of glycopyrrolate intravenously just before the start of inhalational induction. The patients were randomly divided into two groups.  Group-I patients received fentanyl 2 µg/kgand those in Group-II received 3 µg/kg intravenously one minute after the start of inhalational induction with 8% sevoflurane in 50% nitrous oxide and oxygen. After 4 minutes of start of inhalational induction, conditions for tracheal intubationwere assessed based upon a set of criteria.

Results: Tracheal intubation was successful in all patients.Meantime to loss of consciousness was 47 sec in Group-I  and 46 secin Group-II. Optimalintubating conditions were higher in the Group-II (89% vs. 54% P <0.01).The incidence of post-intubation coughing was lower in the Group-II as compared to Group-I (11% vs.39%) with P <0.02.

Conclusions: We conclude that both doses of fentanyl along with inhalational induction with sevoflurane nitrous oxide mixture provided adequate conditions for tracheal intubation without using neuromuscularblocking agents. However, increasing the dose to fentanyl to 3µg/kg furtherimproved the intubating conditions. Tracheal intubationusing sevoflurane and fentanyl may be an alternative totraditional tracheal intubation with neuromuscular blockingagents.

Keywords: Intubating conditions; Inhalational induction; Endotracheal intubation; Sevoflurane;   Fentanyl

Citation: Aqil M, Haq AU, Rasheed A, Altaf R. Effect of two different doses of fentanyl on intubating conditions with sevoflurane inhalation without neuromuscular blocking agents in adults. Anaesth Pain & Intensive Care 2009;13(2);52-56


Inhalational induction has been a classical technique. It used to be slow and stormy with ether and hence was replaced by IV induction. During the recent past, the introduction of sevoflurane has offered an attractive alternative to IV induction and promised a resurgence of the forgotten technique (1). It has a pleasant smell with minimum irritation to the airways and the induction with it is rapid due to its low blood: gas solubility coefficient of 0.69. These qualities make it close to an ideal anesthetic agent (2-5). Advantages of inhalationalinduction are lack of pain with drug injection, confirmationthat the patient can be ventilated at the time of induction of anesthesia, the use of a single agent for both induction and maintenance and avoidance of neuromuscular blocking agents for trachealintubation. However, induction time for adequate depth of anesthesiafor tracheal intubation with sevoflurane is long when comparedto traditional IV induction with muscle relaxants (6–7). Addition of nitrous oxide (N2O) reduces the MAC of sevoflurane and also shortens the time of induction (8,9). Opioids reduce the MAC of sevoflurane (10). Fentanyl is an opioid with quick onset and has a short half-life. We assumed that addition of fentanyl would speed up inhalational induction with sevoflurane and provide an adequate depth of anesthesia to allow tracheal intubation.  The objective of this study was to compare the effects of two different doses of fentanyl on intubating conditions in adults, following inhalational induction with sevoflurane.


This prospective, randomized, double blind study was carried out at King Abdul Aziz University Hospital, Riyadh (Saudi Arabia) from January-December 2007. After approval from the hospital ethical committee and informed consent, 56ASA class I–II, adult patients between the ages of 18to 65 years, scheduled for elective surgery under general anesthesiaand endotracheal intubation were included in the study. We excluded patients with allergies to any of the drug used in this study, risk of pulmonary aspiration,anticipated difficult airway, body mass index > 30 kg/m2 and ASA classificationIII or higher.

All the patients were explained three breath vital capacity inhalational induction on pre operative visit. An IV line was established in all the patients 6 hours before surgery and DW5%+0.45% NaCl infusion started according to the hourly fluid requirements. All the patients were premedicated with oral midazolam 0.1 mg/Kg and oral ranitidine 150 mg two hours before surgery. Patients were randomly assigned to one of two groups (numbersout of an envelope). The patientand the first investigator were blinded to the dose of fentanyl which was diluted to a volume of 10ml by an anesthetist who was not included in the study.

In the operating room, monitors like electrocardiogram and pulse oximeter, non-invasiveBP at the interval of one minute were attached. All patientsreceived IV glycopyrrolate 0.2 mg as an antisialogue and asprophylaxis against bradycardia. Inhalational anesthetic inductionwas started with a circle breathing circuit primed with 8% sevofluranein 50% N2O and 50% oxygen with total flow of 8 L/min. Anesthesiawas induced using the three breath vital capacity techniquewith 2 L reservoir bag. The anesthesia machine used was Datex Ohmeda® anesthetic deliveryunit (AS/3-ADU). One minute after start of inhalational induction, patients in Group-I received 2 µg/kg and Group-II patients received 3 µg/kg of fentanyl IV respectively. After confirmation of loss of lid lash reflex, ventilationwas assisted manually with positive pressure ventilation to keep end tidal carbon dioxide concentration (EtCO2) in the range between 30–35 mmHg. Four minutes after the start of inhalational induction, laryngoscopywas performed using Macintosh blade. A 7-mm endotracheal tube (ETT) was used for female patients and 8-mm ETT was used for male patients. After confirmation of proper ETT position, anesthesia was continued using sevoflurane inN2O and O2.

The parameters assessed were vocal cord opening, jaw relaxation, coughingand patient movement and were graded as shown in Table 1.

Table 1: Grading of various parameters studied.







Vocal cord opening open less than 30 degree open fully closed

Jaw relaxation fully relaxed with no jaw stiffness mildly stiff if stiffness wasfelt but did not affect mouth opening moderately stiff ifthere was difficulty in mouth opening but it could be overcomewith manual force severely stiff if there was difficultywith mouth opening
Coughing no cough mild cough for less than ten seconds moderate cough; ten to20 sec severe cough >20 sec

Patient movement wasdefined as any movement of the arms, legs or thorax.

Time to successful tracheal intubation was defined as the periodbetween removal of the facemask and detection of CO2 on capnograph.

Intubating conditions were defined as given in Table 2.

Table 2: Definitions of intubating condition.

Intubating condition


Optimal The jawwas fully relaxed with partially to fully open vocal cords andno coughing at tracheal intubation
Good The jaw was partiallyrelaxed and/or there was mild coughing after tracheal intubation
Marginal Moderate coughing after tracheal intubation,or if the jaw was moderately stiff
Poor The jaw was severely stiff,the vocal cords were closed or there was severe coughingafter tracheal intubation

Other variables measured included: 1) heartrate, BP, EtCO2, Et sevoflurane (Sev)concentration and SpO2 measured every minute; 2) time to lossof consciousness and 3) time to successful tracheal intubation.Hypotension was defined as systolicBP <80 mmHg and if noted was corrected with inj. ephedrine 5 mg IV doses. Bradycardia was defined as heart rate <60/min. Hypoxemia was defined as SpO2<90%.

Parametric data were analyzed using the Student’s t test. Non-parametricdata were analyzed using the Mann-Whitney rank sum test. Proportionswere analyzed using Fisher’s exact test. Hemodynamic responseswere analyzed using repeated measures ANOVA. Sigma Stat 2.0.(SPSS, Chicago, IL, USA) was used for statistical analysis.P value <0.05 was considered statistically significant.


Demographic data was similar for both groups (Table 3). Inductionof anesthesia with sevoflurane/N2O was successfulin all patients in both groups. Meantime to loss of consciousness was 47 sec in Group-I  and 46 secin Group-II (Table 4). No patientin either group coughed or moved during laryngoscopy. Mean timeto successful tracheal intubation was similar at 32 sec for Group-I and 31 sec for Group-II. The incidence of post-intubationcoughing was higher in Group-I (39%vs.11%) with P<0.02. Optimal intubation conditions were higher in Group-II (89%vs.54%) with P <0.01. Both groups had a high incidence of good to optimal intubatingconditions (Group-I 89% and Group-II 100%). The incidenceof hypotension during induction was 7% in each group and responded to a 5mg bolus of IV ephedrine (Table 5).No patient in any group developed bradycardia, hypoxemia or any other complication during tracheal intubation (Table 5).


The results of our study show that good to optimum conditions for tracheal intubation canbe achieved within four minutes of anesthetic induction with8% sevoflurane in 50% N2O and fentanyl in the dose of 2-3 µg/kg. However, patients who received fentanyl in the dose of 3 µg/kg had better intubatingconditions compared to those who received fentanyl in the dose of 2 µg/kg. Bothgroups had a high proportion of good to optimal conditionsfor tracheal intubation (89% and 100% respectively). Ourresults are similar to Alaxander and co-workers’ study in which propofol and alfentanil was used for tracheal intubation without neuromuscular blocking agents and it provided good to excellent intubating conditions in 85% of the patients (11). Iamaroon A and colleagues compared intubation conditions with sevoflurane (6% ET Sev.) with 50% N2O and that achieved with propofol in combination with succinylcholine. They observed comparable results.(12). Our results were very similar to the results of this study.

Adding narcotic analgesics during inhalation induction with 8% sevoflurane in 50% N2O improves intubating conditions and allows intubation slightly earlier provided there is no hypoventilation (10). Nathan and colleagues used alfentanil along with 8% sevoflurane and 50% N2O and it allowed intubation slightly earlier compared to the placebo group (10). They also found that increasing the dose of alfentanil provided better intubating conditions compared to the patients who received a lower dose. These results are comparable to our results.

To our knowledge the optimum dose of fentanyl that improves the intubating conditions in patients requiring inhalational induction has not been studied. Hwan S and colleagues used another narcotic analgesic ramifentanil in the dose of 2 µg/kg along with sevoflurane-N2O and achieved optimal intubating conditions at three minutes (13). Our comparison of fentanyl in two different doses demonstrated that the incidence of post intubating coughing was higher in Group-I than in Group-II, who received fentanyl in the dose of 3 µg/kg compared to 2 µg/kg.

There are contradictory results in literature regarding the incidence of hypotension during inhalational induction. In our study, we observed that the incidence of hypotension was 7% in both the groups which is lower than the previous finding in which the authors found a higher incidence of hypotension (27%) when sevoflurane was used with ramifentanil for the same objective (13). One factor leading to hypotension during induction is volume depletion due to preoperative fasting. The reason of decreased incidence of hypotension in our study may be due to the fact that we avoided volume depletion by infusing maintenance fluid during fasting period. However, in some studies, no hemodynamic instability was found during inhalational induction with sevoflurane (10,14).

Potential problems with the use of fentanyl during anesthetic induction include hypoventilation that is likely to slow the process of inhalational induction (10,15).  Muzi and colleagues found that when narcotic analgesic was given before sevoflurane induction, it actually increased time to successful tracheal intubation due to hypoventilation leading to slowing the process of delivery of anesthetics to the lungs (16). We avoided hypoventilation caused by fentanyl by manually assisting the ventilation. We prevented expected severe bradycardia associated with administration of fentanyl following sevoflurane induction (17) with glycopyrrolate administered as prophylaxis before induction of anesthesia in patients in both groups (Table 5).

An advantage of the sevoflurane/fentanyl induction techniqueis the avoidance of neuromuscular blocking agents. Succinylcholine is commonly used to facilitate tracheal intubation. However, it is associated with side effects and may be contraindicated in some patients (18). Non depolarizing muscle relaxants with a rapid onset of action can be used as an alternative to succinylcholine, but these drugs may also be associated with undesirable effects like prolonged neuromuscular blockade, or inability to rapidly reverse the paralysis in cases of difficult intubation of difficult ventilation. Inhalational induction has advantage over IV induction in patients with anticipated difficult intubation (19-20). Spontaneousventilation is preserved until fentanyl is administered.Should airway obstruction arise during induction of anesthesia,induction may be terminated and the patient allowed to wake up.If ventilation difficulties arise after fentanyl administration,its effects can be reversed with naloxone.  This technique is especially important in surgical procedures in which use of muscle relaxants is to be avoided if intraoperative assessment of the integrity of the neuromuscular transmission is required by the surgeon.


We conclude that 3 µg/kg fentanyl with 8% sevoflurane in 50% N2O – oxygen mixture, provide optimal intubating condition in four minutes. Tracheal intubationusing sevoflurane, N2O and fentanyl can be used as an alternative totraditional tracheal intubation with neuromuscular blockingagents.


  1.  Ti LK, Chow MY, Lee TL. Comparison of sevoflurane with propofol for laryngeal mask airway insertion in adults. Anesth Analg. 1999;88:908–12
  2. Fredman B, Nathanson MH, Smith I, Wang J, Klein K, White PF. Sevoflurane for out patient anaesthesia: a comparison with propofol. Anesth Analg. 1995;81:823-8.
  3.  Smith I, Nathanson M, White PF. Sevoflurane–a long awaited volatile anaesthetic. Br J Anaesth. 1996;76:435–45.
  4.  Philip BK, Lombard LL, Roaf ER, Drager LR, Calalang I, Philip JH. Comparison of vital capacity induction with sevoflurane to intravenous induction with propofol for adult ambulatory anesthesia. Anesth Analg. 1999;89:623–7.
  5.  Strum DP, Eger EI II. Partition coefficients for sevoflurane in human blood, saline, and olive oil. Anesth Analg 1987;66:654–6.
  6. Joo HS, Perks WJ. Sevoflurane versus propofol for anesthetic induction: a meta-analysis. Anesth Analg. 2000;91:213–9.
  7. Fox AJ, Rowbotham DJ. Clinical review. Recent advances in Anaesthesia. BMJ 1999;319:557-560.
  8. Watson KR, Shah MV. Clinical comparison of `single agent’ anaesthesia with sevoflurane versus target controlled infusion of propofol. Br J Anaesth. 2000;85:541-546
  9.  Muzi M, Robinson BJ, Ebert TJ, O’Brien TJ. Induction of anesthesia and tracheal intubation with sevoflurane in adults. Anesthesiology 1996;85:536–43
  10.  Nathan N, Vandroux D, Benrhaiem M, Marquet P, Mari P, Feiss P. Low alfentanil target-concentrations improve hemodynamic and intubating conditions during induction with sevoflurane. Can J Anaesth. 2004;51(4):382–387.
  11. 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
  12.  Arissara Iamaroon, Siriporn Pitimana-aree, Chatchai Prechawai, Jutarat Anusit, Kanchana Somcharoen, and Onanong Chaiyaroj. Endotracheal Intubation with Thiopental/Succinylcholine or Sevoflurane-Nitrous Oxide Anesthesia in Adults: A Comparative Study. Anesth Analg. 2001;92:523–8.
  13. Hwan S. Joo, William J. Perks , and Susan E. Belo. Sevoflurane with remifentanil allows rapid tracheal intubation without neuromuscular blocking agents. Can J Anaesth. 2001;48:646-650
  14.  Wappler F; Frings DP; Scholz J; Mann V; Koch C; Schulte am Esch J. Inhalational induction of anaesthesia with 8% sevoflurane in children: conditions for endotracheal intubation and side-effects. Eur J Anaesthesiol  2003;20(7):548-54
  15. Michelsen LG, Hug CC. The pharmacokinetics of ramifentanil and fentanyl. J Clin Anesth 1996;8:679–82.
  16.  Muzi M, Colinco MD, Robinson BJ, Ebert TJ. The effects of premedication on inhaled induction of anesthesia with sevoflurane. Anesth Analg. 1997;85:1143–8.
  17. Wang JY, Winship SM, Thomas SD, Gin T, Russell GN. Induction of anaesthesia in patients with coronary artery disease: a comparison between sevoflurane-remifentanil and fentanyl-etomidate. Anaesth Intensive Care 1999;27:363–8.
  18. Savarese JJ, Caldwell JE, Lien CA, Miller RD. Pharmacology of muscle relaxants and their antagonists. In: Miller RD, ed. Anesthesia. 5th ed. Philadelphia: Churchill Livingstone, 2000:412–90
  19. Cros AM, Chopin F, Lopez C, Kays C. Anesthesia induction with sevoflurane in adult patients with predictive signs of difficult intubation. Ann Fr Anesth Reanim. 2002;21(4):249-55
  20. WoodsAW and Allam S. Tracheal intubation without the use of neuromuscular blocking agents. Br J Anaesth. 2005; 94(2):150-158