Alexandria Journal of Anaesthesia and Intensive Care

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 , 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 . 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 value (BIS) of < 40% was reached. The trachea was intubated with an appropriate-sized cuffed tube. The study parameters were; MAP, HR, and SpO2 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 approximately 3 min. compared with The ease of endotracheal intubation has 58.5min. for alfentanil after 4 hours been recently shown to affect the incidence infusion(3,4). The terminal half life is less of laryngeal injuries(1). Thus, routine use of than 10 min at the site of action with a rapid muscle relaxants has become the gold termination of effect(5,6). These properties of standard in routine anesthesia practice to remifentanil produce a rapid onset with a facilitate smooth tracheal intubation. time to peak plasma concentration effect of However, the use of muscle relaxants is not 60 – 90s.only(7). The offset of remifentanil is free of complications, for example they are quick and dramatic, with the loss of implicated in many cases of anaphylaxis (2), effective analgesia occurring within minutes the concerns about their prolonged effects; of cessation of infusion. Thus, remifentanil especially in elderly, or in patients with can be administered without fear of organ dysfunction, and lastly their potential accumulation over time. trigger of . Intubation without neuromuscular blocking Remifentanil is a powerful and ultra- agents, has been used in a number of different short acting opiate, with a rapid onset of studies(8,9,10). Given the pharmacokinetic profile action. It is hydrolyzed by non specific blood of remifentanil, it was hypothesized that it may and tissue esterases, it has a half life of be very useful in facilitating tracheal intubation.

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A lot of results compared alfentanil and cisatracurium injected i.v. in a dose of 0.2 remifentanil for intubation (11) have been mg Kg-1, followed by face mask assisted recorded. Also,some studies have been ventilation with 8% desflurane in 50% N2O performed to describe the effect of using in oxygen for 2 min. different doses of remifentanil with propofol in In muscle relaxants free group, order to assess intubation conditions (5,12). anesthesia was induced with 3 µg kg-1 of The aim of our study is to determine the remifentanil over 3 min. followed by quality of intubation using remifentanil 3 propofol 2mg.kg-1 as a bolus over 30 s, then µg.kg-1 with propofol 2 mg.kg-1; and to face mask assisted ventilation with 8% compare it with the standard use of muscle desflurane in 50% N2O in oxygen was relaxants. applied. Induction was considered complete if BiS index value was less than 40. METHODS After obtaining ethics committee approval Endotracheal intubation. and written consent, we studied 100 healthy After the induction was considered adult patients aged from 18-45 years (ASA complete another anesthesiologist was physical status 1, 2), undergoing elective called to proceed through the process of surgery requiring tracheal intubation in Zayed endotracheal intubation; he was blinded to Military Hospital-Emirates. The airway was which group he was intubating to avoid assessed using a modified Mallampati test, as personal bias. Laryngoscopy was done described by Samson & Young (13). Exclusion using blade sizes of 3 or 4 of Macintosh criteria were; a history of esophageal reflux or larngoscopy. Patient trachea was intubated hiatus hernia, previous difficulty with using low pressure cuff tracheal tube 7.5 intubation or difficult airway as suspected mm for men and 7.0 for women. The cuff when there is one or more of the following: was inflated smoothly to 20-30 Cm H2O, Mallampati classification > 2, interincisor controlled with help of intra cuff pressure distance <3.5 cm or thyromental distance < guide (Mallinckrodot Medical, Athlone, 6.5cm, and when there is renal or hepatic Ireland. ETT cuff air pressure gauge). impairment. Anesthesia was maintained with 6-8% Patients were undergoing surgery for desflurane in 50% N2O in oxygen. orthopaedic, urology, plastic and general Ventilation was assisted to maintain surgery and were all premedicated with normocapnia. 0.02mg Kg-1 i.v. 10 min. before induction. Patients then were randomly Parameters of study arranged in two equal groups (50 patients In our study, MAP, HR, and SpO2 were each). For the first group muscle relaxants measured before induction, then every minute were planned to be given to facilitate until the tube is fixed. The operator scored the tracheal tube insertion, but in the other ease of intubation using the scoring system group muscle relaxants were not used for shown in table 1. The view of the larynx was intubation. assessed with the modified Cromack and Once in the operating room, Lethane classification (14). of ECG, heart rate (HR), peripheral arterial Adverse events such as laryngospasm, hemoglobin oxygen saturation (SpO2), and bronchospasm, chest wall rigidity, airway non invasive mean arterial blood pressure trauma, coughing in response to (NMAP) were commenced. Bispectral index laryngoscopy, tube insertion or inflation of (BiS, Aspect Medical Systems, USA) to cuff were recorded. Postoperative horsiness monitor the depth of anesthesia was also or throat pain was recorded by direct patient used. questionnaire next morning. Induction- related hypotension which was defined as > Induction of general anesthesia. 20% reduction of mean arterial blood In the muscle relaxant group, after 3 min. pressure from the pre-operative basal of pre-oxygenation, anesthesia induction levels-was recorded too. Induction related started with 3 µg Kg-1 of remifentanil i.v. hypotension if happened was treated by i.v. injection over 3 min. followed by i.v. injection of fluids and / or ephedrine 5 to 10 mg i.v. propofol 2mg Kg-1 over 30 seconds; then boluses.

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Statistical Analysis patients of relaxant group (6%) and 11 Intubation score data were considered patients in relaxant free group (22%) P categorical variables; they were analyzed <0.05 (Table 4). using X2- test. P<0.05 was considered nduction related hypotension was significant. The mean arterial blood pressure noticed in 20% of relaxant group and 22% and heart rate values were analyzed for of relaxant free group with no significant differences among pre-induction, post- difference between the two groups. induction and post-intubation values using Bradycardia which is defined as a pulse repeated-measures analysis of variance rate < 60 beats /min. occurred in 6% of (ANOVA test). P value <0.05 was considered patients of relaxant group and 8% of statistically significant. patients of relaxant free group with no significant difference between the two RESULTS groups. A hundred patients were enrolled into egarding SpO2, it was above 97% in all the study. Fifty patients enrolled in each patients of the study with no single group. Patient characteristics are shown in recording of hypoxia during the period of table 2; while surgical procedures done the study. Two patients (4%) of relaxant presented in table 3. free group coughed during cuff inflation Intubation was completed successfully while one patient (2 %) of relaxant group in all patients with no intubation failures in coughed during cuff inflation with no both groups. significant difference between the two Clinically acceptable intubation scores groups. were observed in 49 patients (98%) of ostoperative throat pain recorded in 5 relaxant group and in 48 patients (96%) in patients (10%) of relaxant group and in 6 relaxant free group with no significant patients (12%) in relaxant free group with difference. Laryngoscopic view before no significant difference between the two external laryngeal pressure proved to be groups. difficult (McCormack grades 3 or 4) in 3

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 Abducted Intermediate Closed Movement None Moving Closing Cough upon tube insertion None Slight Sustained or cuff inflation 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 ± 10 32 ± 11 Not significant Body weight (kg) 72 ± 14 70 ± 12 Not significant Height (cm) 167 ± 13 165 ± 10 Not significant The data are means ± SD.

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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 < 0.05.

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

AJAIC-Vol. (9) No. 1 Marsh 2006 Alexandria Journal of Anaesthesia and Intensive Care because it decreases the synergistic effect study(9). In a previous study, muscle rigidity and consequently the drop of peripheral was reported in 7% of patients after an systemic resistance. Timing is very infusion of remifentanil 1µg/kg/min and important because the remifentanil peak propofol 0.5 to 1mg/kg(26). The better result plasma level is reached within 90 seconds. in our study may be accounted for by the However, peak target effector site use of midazolam and the slow injection of concentration, which determines the effect, remifentanil over 3 minutes. is clinically delayed. Thus, giving 3µg/kg of The short duration of action of the remifentanil before propofol over slower remifentanil would avoid prolonged apnea rate resulted in hemodynamic stability and encountered with alfentanil. This is very better intubating conditions. The use of advantageous in the event of difficult remifentanil over 3 minutes keeps good whether predicted or unpredicted intubation level of consciousness to keep proper cases. It allows assessment of the airway contact with the patient for at least 2 by larygoscopy and also equally important- minutes because loss of consciousness if oxygenation is maintained- the decision occurred after 3 minutes meanwhile the whether or not to awaken the patient can SpO2 remained unchanged. We found in then be comfortably made. this study that the minimum dose of This technique of relaxant free remifentanil required to provide reliable intubation can have a place in cases where intubating conditions without muscle intubation is necessary but neuromuscular relaxants is 3µg/kg.The sequence and the block is not required to facilitate surgical rate of administration are very important to techniques. We can also use this protocol avoid any drop in the mean arterial blood when muscle relaxants are contraindicated pressure (MAP) and heart rate (HR) (e.g. myopathies) or when succinylcholine experienced in the previous studies(24). can not be used. (e.g. hyperkalmia, burns, The decrease in MAP was not clinically plasma cholinesterase deficiency, or significant; no patient was treated for penetrating eye injury). Also, the technique hypotension or bradycardia. The time is indicated if the use of neostigmine as a interval measurement of the MAP and the reversal agent is undesirably associated HR every minute for 12 minutes confirmed with an increase of salivation and post that the hemodynamic response after this operative nausea and vomiting. The technique is quiet stable. Stevens and combination of remifentanil and propofol Wheatly used this technique in ambulatory may allow the rapid return of spontaneous surgery and had 28% of drop in Mean ventilation and thus rapid extubation. The arterial pressure (MAP) after remifentanil use of this technique is also interesting in 4µg/kg(9). Alexander et al found that ambulatory surgery which requires safe and remifentanil 4-5 µg/kg reliably provided reliable drugs. good to excellent conditions for intubation Nowadays, there is no question about after propofol 2mg/kg(8).Also, Grant et al, remifentanil as a drug that may significantly studied 3, 4 and 5 µg/kg of remifentanil to alter anesthesia practice. It will take some assess intubating conditions. In both patience, experience and imagination to studies, significant reduction of heart rate translate its theoretical advantages into and mean arterial pressure were better care for patients. observed(10), the decrease of the MAP From this work it can be concluded that prompted the administration of ephedrine. 3 µg kg-1. remifentanil injected over 3 In our study, two patients (4%) of minutes followed by 2mg.Kg-1 propofol over relaxant free group coughed during cuff 30 seconds can be a safe and reliable inflation while one patient (2 %) of relaxant alternative for endotracheal intubation group coughed during cuff inflation with no without the use of muscle relaxant and significant difference between the two incorporating a muscle relaxant did not add groups. We recommend that endotracheal much to facilitate endotracheal intubation. cuff inflation should be slow. Muscle rigidity was not noticed with any REFERENCES of the study patients. This was in 1- Katoh T, Nakajima Y, Moriwaki G. accordance with Steven and Wheatly Sevoflurane requirements for tracheal

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