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Department of Anesthesiology, Inonu University, School of Medicine, Malatya, Turkey
Address correspondence and reprint requests to Mahmut Durmus, MD, Inonu University, School of Medicine, Department of Anesthesiology, Elazig Yolu 13.km, 44069-Malatya, Turkey. Address e-mail to mdurmus{at}inonu.edu.tr
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Abstract |
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IMPLICATIONS: We evaluated in a double-blinded manner the dose requirements for remifentanil with thiopental without muscle relaxants for obtaining acceptable intubation condition. Our results show that remifentanil 4 µg/kg administered before thiopental provided excellent or satisfactory intubation condition in 94% of patients.
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Introduction |
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We designed a prospective, randomized, double-blinded study to evaluate the dose requirements for remifentanil with thiopental without muscle relaxants for obtaining clinically acceptable intubation conditions.
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Methods |
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All patients were premedicated with midazolam 0.03 mg/kg IV approximately 10 min before the induction of anesthesia. All patients were given 7 mL/kg of saline 0.9% before the induction of anesthesia and were randomly designated to receive remifentanil 2, 3, or 4 µg/kg (Groups I–III, respectively; n = 35 per group) by means of individually prepared envelopes. Remifentanil syringes were prepared by an independent anesthesiologist in a total volume of 10 mL with 0.9% saline. Therefore, all anesthesia personnel were blinded to the dose of remifentanil.
In the operating room, after a bolus dose of remifentanil that was administered over 30 s, anesthesia was induced with thiopental 5 mg/kg over 40 s. Injection of all syringes was performed by an assistant behind a drape so that the anesthesiologist performing the intubation was blinded to drug doses. Patients were ventilated manually with 100% oxygen until intubation and mechanically thereafter with a Drager® Cato Edition (end-tidal carbon dioxide partial pressure 35–40 mm Hg; Lubeck, Germany). Ninety seconds after completion of drug administration, laryngoscopy and intubation were attempted by the same experienced anesthesiologist using a Macintosh 3 laryngoscope blade and a 7.0- or 8.0-mm endotracheal tube (for women and men, respectively). The endotracheal tube cuff was inflated slowly. The anesthesiologist performing the intubation assessed and scored each patient’s condition at laryngoscopy and tracheal intubation using these criteria (7): (a) excellent: flaccid relaxation of jaw muscles, mouth wide open, good cord visualization, cord well separated-abducted, and no bucking at intubation; (b) satisfactory: mouth easily opened, jaw muscles well relaxed, good cord visualization, slight cord movement when touched but abducted, and minimal bucking at intubation; (c) fair: conditions less favorable, jaw muscles not well relaxed, cord visualization fair but allowing intubation, and bucking on intubation; (d) unsatisfactory: poor relaxation of jaw and resistance to opening mouth, poor cord visualization or none, cord abducted if viewed, superior pharyngeal constrictor muscle activity, and patient unable to be intubated or, if intubated, marked bucking and body movement. Patients who could not be intubated on the first attempt were given succinylcholine 1 mg/kg IV, and intubation was completed. Anesthesia was maintained with 1%–2% sevoflurane and 66% N2O (end tidal). Hypotension (mean arterial blood pressure [MAP] < 25% from baseline for 60 s) was treated with ephedrine 5–10 mg IV, or bradycardia (heart rate [HR] < 50 bpm for 60 s if hypotension occurred) was treated with atropine 20 µg/kg IV.
HR, systolic arterial blood pressure (SAP), MAP, and diastolic arterial blood pressure (DAP) were recorded as baseline, which is the mean of three resting measurements in the operating room before any instrumentation, after the induction, and 1, 3, 5, 10, and 15 min after the intubation.
Parametric data were analyzed by one-way analysis of variance. Differences in hemodynamic data among groups were analyzed with two-way analysis of variance. Differences from baseline within groups were evaluated using paired-sample t-test. 
2 test or Fisher’s exact test, when appropriate, was used for nonparametric data. P < 0.05 was considered as significant.
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Discussion |
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Neuromuscular blocking drugs and their antagonists have potential side effects (e.g., postoperative myalgia, nausea, and vomiting) that may result in slower recovery. Also, in many surgeries, muscle relaxation is undesirable or not required. However, tracheal intubation without neuromuscular block is not without hazard. If intubation is attempted under inadequate conditions, trauma to the airway or inadequate ventilation can result. In addition, remifentanil can cause severe bradycardia, muscle rigidity, apnea, and an increased risk of postoperative nausea and vomiting. These effects can be hazardous in hypovolemic or elderly patients or patients with clinically significant cardiovascular disease (8).
Propofol is superior to barbiturates in decreasing muscle tone and abolishing laryngeal responses to tracheal intubation or to laryngeal mask insertion (9,10). The possible development of severe hypotension is a limiting factor for using propofol (3,4), whereas thiopental may provide more favorable intubation conditions according to a study by Hovorka et al. (6) causing less hemodynamic decrease.
In the present study, the induction of anesthesia with thiopental 5 mg/kg and remifentanil 2–4 µg/kg resulted in significant decreases in SAP, MAP, DAP, and HR values. Increasing the dose of remifentanil provides acceptable intubation conditions for premedicated patients but results in an 18% decrease in MAP that can be seen with any inhaled or IV induction regimen.
In addition to acceptable intubation conditions, the usual increase in cardiovascular responses after tracheal intubation was not observed in any groups in this study. Glass et al. (1) reported that remifentanil alone as an induction anesthetic with doses of 
10 µg/kg produces a 10%–40% reduction in MAP with a mild decrease in HR. In a study by Barclay and Kluger (11), remifentanil 2 µg/kg with target-controlled infusion of propofol attenuated the hemodynamic responses to tracheal intubation, whereas the larger doses (4 µg/kg) failed to confer any additional advantage. O’Hare et al. (12) found thiopental 5–7 mg/kg of succinylcholine and remifentanil 1 µg/kg administered as a bolus after the induction of anesthesia generally prevents the pressor response after intubation, except for a small increase in DAP. In our study, remifentanil 2 µg/kg suppressed hemodynamic responses to intubation, but we did not obtain excellent or satisfactory intubation conditions with this dose. For this purpose, relatively large doses of remifentanil must be used.
Although remifentanil more than 1 µg/kg is associated with clinically significant muscle rigidity, no patients manifested signs of opioid-induced muscle rigidity in our study (1,13). When co-administered with a hypnotic drug, remifentanil may not cause muscle rigidity (1,8). Furthermore, the pretreatment with benzodiazepines may be effective in preventing opioid induced muscle rigidity (14).
These techniques can be advantageous in cases where neuromuscular blocking drugs are contraindicated. Because of the pharmacokinetic properties with the potential to allow rapid recovery and return of spontaneous ventilation (15) after appropriate doses for satisfactory conditions and suppressing the hemodynamic responses to tracheal intubation, remifentanil seems to be a more practical opioid of choice in this setting compared with other opioids. One study compared the intubating conditions at 60 seconds and hemodynamic effects after propofol 2.5 mg/kg preceded by remifentanil 3–4 µg/kg or alfentanil 30 µg/kg after diazepam premedication (2). All patients received atropine 0.01 mg/kg immediately before the induction of anesthesia. Excellent intubating conditions were significantly more frequent in patients receiving remifentanil 4 µg/kg compared with alfentanil (55% versus 20%). In another study, the rate of excellent intubation conditions was 95%–100% after propofol 2 mg/kg and remifentanil 3 or 4 µg/kg (14). Hence, the current results are in conformity with other reports supporting an increased use of non-muscle relaxing techniques for endotracheal intubation in suitable cases.
In summary, our results suggest that remifentanil 4 µg/kg administered before thiopental 5 mg/kg provided excellent or satisfactory intubation conditions with acceptable hemodynamic changes. This technique may be appropriate when neuromuscular block is undesirable.
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  L. Bouvet, A. Stoian, S. Jacquot-Laperriere, B. Allaouchiche, D. Chassard, and E. Boselli Laryngeal injuries and intubating conditions with or without muscular relaxation: an equivalence study: [Lesions laryngees et conditions d'intubation avec ou sans relaxation musculaire : une etude d'equivalence] Can J Anesth, October 1, 2008; 55(10): 674 - 684. [Abstract] [Full Text] [PDF]
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S. Taha, S. Siddik-Sayyid, M. Alameddine, C. Wakim, C. Dahabra, A. Moussa, M. Khatib, and A. Baraka Propofol is superior to thiopental for intubation without muscle relaxants: [Le propofol est superieur au thiopental pour l'intubation sans myorelaxants] Can J Anesth, March 1, 2005; 52(3): 249 - 253. [Abstract] [Full Text] [PDF]
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T. M. Hemmerling, P. Beaulieu, K. E. Jacobi, D. Babin, and J. Schmidt Neuromuscular blockade does not change the incidence or severity of pharyngolaryngeal discomfort after LMA anesthesia: [Le blocage neuromusculaire ne modifie pas l'incidence ou la severite de l'inconfort pharyngo-larynge apres l'anesthesie avec un ML] Can J Anesth, August 1, 2004; 51(7): 728 - 732. [Abstract] [Full Text] [PDF]
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