A Comparative Blind Study for Assessment of Intubating Conditions Using Propofol and Remifentanil with and Without Muscle Relaxant

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1 A Comparative Blind Study for Assessment of Intubating Conditions Using Propofol and Remifentanil with and Without Muscle Relaxant Dr. Ashraf A. Hassan*,Hefny M Hefny *Department of Anesthesia, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. ABSTRACT Background: Remifentanil is a powerful and ultra-short acting opiate, with a rapid onset of action. It is hydrolyzed by non-specific blood and tissue esterases and it has a half life of approximately 3 min compared with 58.5 min for alfentanil after 4 hours infusion. Thus, remifentanil can be administered without fear of accumulation over time. Intubation without neuromuscular blocking agents has been used in a number of different studies. Based on the pharmacokinetic profile of remifentanil, it was hypothesized that it may be very useful in facilitating tracheal intubation. The aim of our study is to determine the quality of intubation using remifentanil 3µg/kg and propofol 2 mg/kg compared with the standard use of muscle relaxants. Methods: We studied 100 healthy adult patients (ASA physical status I, II), undergoing elective surgery requiring tracheal intubation. They are arranged in two equal groups: one group with muscle relaxation given for intubation, while the other group no relaxant was given. Anesthesia was induced with 3µg.kg -1 of remifentanil over 3 min. followed by propofol 2mg.kg -1 as a bolus over 30 seconds for both groups. Laryngoscopy was performed after assisted ventilation with 50% N2O and 6-8% desflurane in O2till a bispectral index value (BIS) of < 40% was reached. The trachea was intubated with an appropriate-sized cuffed tube. The study parameters were; MAP, HR, and SpO 2 which were measured before induction, then every minute until the tube is fixed. A blinded operator scored the ease of intubation using a special scoring system. Adverse events such as laryngospasm, bronchospasm, chest wall rigidity, coughing or post-operative sore throat were recorded if occurred. Results: intubation conditions were clinically acceptable in both groups with no statistical difference. Conclusions: From this study we conclude that the use of propofol and remifentanil in the given doses provided excellent intubation condition without the need for muscular relaxation. Key words: remifentanil, propofol, intubation. INTRODUCTION The ease of endotracheal intubation has been recently shown to affect the incidence of laryngeal injuries (1). Thus, routine use of muscle relaxants has become the gold standard in routine anesthesia practice to facilitate smooth tracheal intubation. However, the use of muscle relaxants is not free of complications, for example they are implicated in many cases of anaphylaxis (2), the concerns about their prolonged effects; especially in elderly, or in patients with organ dysfunction, and lastly their potential trigger of malignant hyperthermia. Remifentanil is a powerful and ultrashort acting opiate, with a rapid onset of action. It is hydrolyzed by non specific blood and tissue esterases, it has a half life of approximately 3 min. compared with 58.5min. for alfentanil after 4 hours infusion (3,4). The terminal half life is less than 10 min at the site of action with a rapid termination of effect (5,6). These properties of remifentanil produce a rapid onset with a time to peak plasma concentration effect of 60 90s.only (7). The offset of remifentanil is quick and dramatic, with the loss of effective analgesia occurring within minutes of cessation of infusion. Thus, remifentanil can be administered without fear of accumulation over time. Intubation without neuromuscular blocking agents, has been used in a number of different studies (8,9,10). Given the pharmacokinetic profile of remifentanil, it was hypothesized that it may be very useful in facilitating tracheal intubation.

2 A lot of results compared alfentanil and (11) remifentanil for intubation have been recorded. Also,some studies have been performed to describe the effect of using different doses of remifentanil with propofol in order to assess intubation conditions (5,12). The aim of our study is to determine the quality of intubation using remifentanil 3 µg.kg -1 with propofol 2 mg.kg -1 ; and to compare it with the standard use of muscle relaxants. METHODS After obtaining ethics committee approval and written consent, we studied 100 healthy adult patients aged from years (ASA physical status 1, 2), undergoing elective surgery requiring tracheal intubation in Zayed Military Hospital-Emirates. The airway was assessed using a modified Mallampati test, as described by Samson & Young (13). Exclusion criteria were; a history of esophageal reflux or hiatus hernia, previous difficulty with intubation or difficult airway as suspected when there is one or more of the following: Mallampati classification > 2, interincisor distance <3.5 cm or thyromental distance < 6.5cm, and when there is renal or hepatic impairment. Patients were undergoing surgery for orthopaedic, urology, plastic and general surgery and were all premedicated with midazolam 0.02mg Kg -1 i.v. 10 min. before induction. Patients then were randomly arranged in two equal groups (50 patients each). For the first group muscle relaxants were planned to be given to facilitate tracheal tube insertion, but in the other group muscle relaxants were not used for intubation. Once in the operating room, monitoring of ECG, heart rate (HR), peripheral arterial hemoglobin oxygen saturation (SpO 2 ), and non invasive mean arterial blood pressure (NMAP) were commenced. Bispectral index (BiS, Aspect Medical Systems, USA) to monitor the depth of anesthesia was also used. Induction of general anesthesia. In the muscle relaxant group, after 3 min. of pre-oxygenation, anesthesia induction started with 3 µg Kg -1 of remifentanil i.v. injection over 3 min. followed by i.v. injection of propofol 2mg Kg -1 over 30 seconds; then cisatracurium injected i.v. in a dose of 0.2 mg Kg -1, followed by face mask assisted ventilation with 8% desflurane in 50% N2O in oxygen for 2 min. In muscle relaxants free group, anesthesia was induced with 3 µg kg -1 of remifentanil over 3 min. followed by propofol 2mg.kg -1 as a bolus over 30 s, then face mask assisted ventilation with 8% desflurane in 50% N 2 O in oxygen was applied. Induction was considered complete if BiS index value was less than 40. Endotracheal intubation. After the induction was considered complete another anesthesiologist was called to proceed through the process of endotracheal intubation; he was blinded to which group he was intubating to avoid personal bias. Laryngoscopy was done using blade sizes of 3 or 4 of Macintosh larngoscopy. Patient trachea was intubated using low pressure cuff tracheal tube 7.5 mm for men and 7.0 for women. The cuff was inflated smoothly to Cm H 2 O, controlled with help of intra cuff pressure guide (Mallinckrodot Medical, Athlone, Ireland. ETT cuff air pressure gauge). Anesthesia was maintained with 6-8% desflurane in 50% N 2 O in oxygen. Ventilation was assisted to maintain normocapnia. Parameters of study In our study, MAP, HR, and SpO 2 were measured before induction, then every minute until the tube is fixed. The operator scored the ease of intubation using the scoring system shown in table 1. The view of the larynx was assessed with the modified Cromack and Lethane classification (14). Adverse events such as laryngospasm, bronchospasm, chest wall rigidity, airway trauma, coughing in response to laryngoscopy, tube insertion or inflation of cuff were recorded. Postoperative horsiness or throat pain was recorded by direct patient questionnaire next morning. Inductionrelated hypotension which was defined as > 20% reduction of mean arterial blood pressure from the pre-operative basal levels-was recorded too. Induction related hypotension if happened was treated by i.v. fluids and / or ephedrine 5 to 10 mg i.v. boluses.

3 Statistical Analysis Intubation score data were considered categorical variables; they were analyzed using X 2 - test. P<0.05 was considered significant. The mean arterial blood pressure and heart rate values were analyzed for differences among pre-induction, postinduction and post-intubation values using repeated-measures analysis of variance (ANOVA test). P value <0.05 was considered statistically significant. RESULTS A hundred patients were enrolled into the study. Fifty patients enrolled in each group. Patient characteristics are shown in table 2; while surgical procedures done presented in table 3. Intubation was completed successfully in all patients with no intubation failures in both groups. Clinically acceptable intubation scores were observed in 49 patients (98%) of relaxant group and in 48 patients (96%) in relaxant free group with no significant difference. Laryngoscopic view before external laryngeal pressure proved to be difficult (McCormack grades 3 or 4) in 3 patients of relaxant group (6%) and 11 patients in relaxant free group (22%) P <0.05 (Table 4). nduction related hypotension was noticed in 20% of relaxant group and 22% of relaxant free group with no significant difference between the two groups. Bradycardia which is defined as a pulse rate < 60 beats /min. occurred in 6% of patients of relaxant group and 8% of patients of relaxant free group with no significant difference between the two groups. egarding SpO 2, it was above 97% in all patients of the study with no single recording of hypoxia during the period of the study. Two patients (4%) of relaxant free group coughed during cuff inflation while one patient (2 %) of relaxant group coughed during cuff inflation with no significant difference between the two groups. ostoperative throat pain recorded in 5 patients (10%) of relaxant group and in 6 patients (12%) in relaxant free group with no significant difference between the two groups. Table (1): Scoring conditions for tracheal intubation. (15). Intubation score Clinically acceptable Clinically unacceptable Intubation condition Excellent Good Poor Laryngoscopic condition Resistance to laryngoscopy None Slight Active Vocal cords Position Movement Abducted None Intermediate Moving Closed Closing Cough upon tube insertion or cuff inflation None Slight Sustained Intubation conditions: excellent all qualities are excellent; good qualities are excellent or good. Excellent and good intubation conditions are summarized as clinically acceptable intubation conditions. Table (2): Patient characteristics. Relaxant group Relaxant free group P Gender (M/F) 30/20 30/20 Not significant Age (yr) 33 ± ± 11 Not significant Body weight (kg) 72 ± ± 12 Not significant Height (cm) 167 ± ± 10 Not significant The data are means ± SD.

4 Table (3): Surgical procedures. Relaxant group Relaxant free group P Duration (min) 113±26 (mean+/-sd) 122±30 (mean+/-sd) Not significant (Mean ± SD) Type (number %) Abdominal 75% 0% Orthopedic 7% 50% Plastic 2% 42% Urology 16% 8% Table (4): Intubation scores. Relaxant group Relaxant free P Intubation score Clinically acceptable 49 (98%) 48 (96%) Not significant Excellent 38 (76%) 30 (60%) * Good 11 (22%) 18 (36%) * Clinically unacceptable 1 (2%) 2 (4%) * The data are absolute numbers with relative frequencies. * = significant P < DISCUSSION The ease of tracheal intubation alters laryngeal morbidity (16) after induction of anesthesia. Tracheal intubation is usually facilitated by the help of muscle relaxant; the later if used properly allow complete relaxation. On the other hand, relaxants are the class of anesthetic-adjuvant mainly responsible for life threatening allergic episodes (17). Because the relaxant free intubation is getting more popular (18), the challenge is to provide satisfactory intubation conditions while avoiding the use of muscle relaxants. Many studies in the literature have concluded that intubation was possible without neuromuscular blocking agent( 8,9,10). The choice of propofol as an induction agent in the present study was based on its ability to relax laryngeal muscles and to decrease upper air way reflexes (19,20). Copremedication with midazolam usually enhances propofol related hypnosis (21). Keaveney and knell reported good intubating conditions with 60% success rate with propofol 2,5 mg/kg (22) alone. Alexander et al found that using a dose of 2µg/kg of remifentanil did not provide conditions for tracheal intubation as reliable as those obtained with alfentanil 50 µg/kg and propofol 2mg/kg (11). In this observational study, the use of relaxant free technique did not appear to be associated with poor conditions for tracheal intubation which were evaluated using an intuabtion score previously proposed as a tool for better description of the quality of relaxation during intubation (23). In our study, poor intubation conditions were observed in only 2 patients (4%) of relaxant free group which was statistically insignificant compared to the relaxant group. This result differs from other studies (15,24,25). Most studies found sustained coughing in up to 18% of patients in which muscle relaxants were not used. In a recent study, Menche et al found poor intubation conditions in one third of patients intubated without muscle relaxants (16). We believe that this difference in poor intubation score can be explained by the properly timed intubation because we used bisepctral index monitor which gave us a firm idea about the anesthesia depth when it was good enough (< 40%) for intubation, which guaranteed that the patient was in the proper surgical anesthesia plane before we try any stimulation by laryngoscopy and intubation. The only concern is that it may be associated with hypotension and bradycardia but in our study we did not experience any significant difference between the two groups in this respect. This may be explained by the sequence of drug administration because we think that the administration of remifentanil before propofol is more likely to avoid hypotention and bradycardia. This sequence is crucial

5 because it decreases the synergistic effect and consequently the drop of peripheral systemic resistance. Timing is very important because the remifentanil peak plasma level is reached within 90 seconds. However, peak target effector site concentration, which determines the effect, is clinically delayed. Thus, giving 3µg/kg of remifentanil before propofol over slower rate resulted in hemodynamic stability and better intubating conditions. The use of remifentanil over 3 minutes keeps good level of consciousness to keep proper contact with the patient for at least 2 minutes because loss of consciousness occurred after 3 minutes meanwhile the SpO 2 remained unchanged. We found in this study that the minimum dose of remifentanil required to provide reliable intubating conditions without muscle relaxants is 3µg/kg.The sequence and the rate of administration are very important to avoid any drop in the mean arterial blood pressure (MAP) and heart rate (HR) experienced in the previous studies (24). The decrease in MAP was not clinically significant; no patient was treated for hypotension or bradycardia. The time interval measurement of the MAP and the HR every minute for 12 minutes confirmed that the hemodynamic response after this technique is quiet stable. Stevens and Wheatly used this technique in ambulatory surgery and had 28% of drop in Mean arterial pressure (MAP) after remifentanil 4µg/kg (9). Alexander et al found that remifentanil 4-5 µg/kg reliably provided good to excellent conditions for intubation after propofol 2mg/kg (8).Also, Grant et al, studied 3, 4 and 5 µg/kg of remifentanil to assess intubating conditions. In both studies, significant reduction of heart rate and mean arterial pressure were observed (10), the decrease of the MAP prompted the administration of ephedrine. In our study, two patients (4%) of relaxant free group coughed during cuff inflation while one patient (2 %) of relaxant group coughed during cuff inflation with no significant difference between the two groups. We recommend that endotracheal cuff inflation should be slow. Muscle rigidity was not noticed with any of the study patients. This was in accordance with Steven and Wheatly study (9). In a previous study, muscle rigidity was reported in 7% of patients after an infusion of remifentanil 1µg/kg/min and propofol 0.5 to 1mg/kg (26). The better result in our study may be accounted for by the use of midazolam and the slow injection of remifentanil over 3 minutes. The short duration of action of the remifentanil would avoid prolonged apnea encountered with alfentanil. This is very advantageous in the event of difficult whether predicted or unpredicted intubation cases. It allows assessment of the airway by larygoscopy and also equally importantif oxygenation is maintained- the decision whether or not to awaken the patient can then be comfortably made. This technique of relaxant free intubation can have a place in cases where intubation is necessary but neuromuscular block is not required to facilitate surgical techniques. We can also use this protocol when muscle relaxants are contraindicated (e.g. myopathies) or when succinylcholine can not be used. (e.g. hyperkalmia, burns, plasma cholinesterase deficiency, or penetrating eye injury). Also, the technique is indicated if the use of neostigmine as a reversal agent is undesirably associated with an increase of salivation and post operative nausea and vomiting. The combination of remifentanil and propofol may allow the rapid return of spontaneous ventilation and thus rapid extubation. The use of this technique is also interesting in ambulatory surgery which requires safe and reliable drugs. Nowadays, there is no question about remifentanil as a drug that may significantly alter anesthesia practice. It will take some patience, experience and imagination to translate its theoretical advantages into better care for patients. From this work it can be concluded that 3 µg kg -1. remifentanil injected over 3 minutes followed by 2mg.Kg -1 propofol over 30 seconds can be a safe and reliable alternative for endotracheal intubation without the use of muscle relaxant and incorporating a muscle relaxant did not add much to facilitate endotracheal intubation. REFERENCES 1- Katoh T, Nakajima Y, Moriwaki G. Sevoflurane requirements for tracheal

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