The onset time of a neuromuscular blocking drug is an important factor in determining the speed and ease of tracheal intubation. Succinylcholine, a short acting depolarizing muscle relaxant with rapid onset of action (60 sec) has numerous adverse effects, so there has been a continual search for a non depolarizing muscle relaxant (NDMR) that can replicate the onset of succinylcholine (Engbaek and Viby-Mogensen, 1999). Onset time of most of NDMRs are between 3-5 min, so various strategies have been used to shorten their onset time, including increasing the dose and priming (Ortiz-Gomez et al., 2005; Schmidt et al., 2005). These alternates may provoke a long duration of muscle paralysis or muscle weakness before induction of anesthesia.
Since the onset time of neuromuscular blocking drugs is determined by muscle blood flow and cardiac out put (Donati, 1988; Ezri et al., 2003) various studies using induction agents that maintain cardiac out put and blood pressure have been suggested that onset time of muscle relaxants and intubating condition were improved (Leykin et al., 2005; Fuchs-Buder et al., 1996; Hans et al., 1999).
In the study by Tan et al. (2002) combination of propofol with ephedrine provided better intubating conditions than propofol alone when followed by rocuronium.
In another study by Albert et al. (2000), low dose ephedrine combined with propofol improved intubating condition after cisatracurium.
Since in our country rocuronium a NDMR with faster onset of action is not available and vecuronium, mivacurium and cisatracurium are scarce or very expensive, we used atracurium, the most frequent muscle relaxant available in our operating rooms. We tested the hypothesis that combining propofol with ephedrine as induction agent will improve intubating condition after atracurium administration by priming technique.
MATERIALS AND METHODS
This randomized clinical trial was performed in Dr. Shariati Hospital of Tehran University of Medical Sciences in 2006. After approval from hospital Ethics committee, each patients informed consent were obtained. Seventy ASA physical status I or II patients aged 18-65 years, who were scheduled for elective surgery under general anesthesia were studied.
Exclusion criteria included the presence of cardiovascular or neuromuscular
diseases, any medications known to affect neuromuscular function, anticipated
airway difficulties and risk of pulmonary aspiration. On arrival in the operating
room, ECG electrodes were applied and oxygen saturation was monitored by pulse
oxymeter. An 18-G IV cannula was inserted into a vein of the patients
hand and 5 mL kg-1 lactated Ringers solution was infused. Base
line Heart Rate (HR) and non Invasive Blood Pressure (NIBP) were measured and
2 μg kg-1 fentanyl (Amp 10 mL , Fentanyl-Janssen, Belgium)
was injected as premedication. Patient were preoxynated by mask and oxygen for
5 min then priming dose of atracurium (Amp 10 mg mL-1 Mayne Pharma
Plc, UK) 0.05 mg kg-1 was injected intravenously. After 2.5
min, intubating dose of atracurium 0.5 mg kg-1 was injected during
30 sec. The patients were randomly assigned to receive 140 μg kg-1
ephedrine (Amp 1 mL = 50 mg, Ephedrin Streuli, Switzerland) in ephedrine
group (n = 35) or saline (saline group, n = 35) plus propofol (Amp 20 mL, Propofol
1%. Fresenius, Germany) 2.5 mg kg-1 in equal volume as induction
agent just before the intubating dose of atracurium.
During priming interval the patients were also oxygenated and monitored for signs of discomfort, palpebral ptosis, diplopia or respiratory difficulty. Orotracheal intubation was attempted 30 sec after the intubating dose of atracurium and was considered successful only if performed within a 20 sec interval.
Randomization was based on computer-generated codes that were concealed until interactions were assigned. The coded syringes were prepared by an independent anesthetist in equal volume and shape there fore both the anesthesiologist and the patient was blinded to the group assignment.
Tracheal intubation was performed and assessed by an anaesthesiologist with at least 5 years of clinical experience, who was blinded to the group allocation. Intubating conditions were graded according to the criteria of Cooper (Cooper et al., 1992), which comprise jaw relaxation, vocal cord position and response to intubation. Jaw relaxation: 0 = poor, 1 = minimal, 2 = moderate and 3 = good; vocal cord position: 0 = closed, 1 = closing, 2 = moving and 3 = open and response to intubation: 0 = severe coughing and bucking, 1 = mild coughing, 2 = light diaphragmatic movement and 3 = none. A score of 8 and 9 was considered excellent, 6-7 good, 3-5 poor and 0-2 bad.
Excellent and good conditions were considered clinically acceptable while fair or poor conditions were considered unacceptable. The primary outcome was the number of patients with clinically acceptable intubating conditions.
Non Invasive Blood Pressure (NIBP) and heart rate were recorded as base line (before premedication), 1 min after propofol injection and 1 min after tracheal intubation. The presence of arrhythmias on the ECG monitor and other complications during priming interval were also recorded.
Statistical analysis: For sample size calculation we considered excellent and good condition as acceptable and poor and bad as non acceptable condition. Sample size was calculated to detect 25% difference in percentile of acceptable tracheal intubation condition with α = 0.05 and statistical power of 0.8.
Statistical analysis was performed With SPSS package version 11.5. Normality of distribution was tested by Kolmogorov-Smirnov test. Data were analyzed by independed sample t-test, repeated measures ANOVA, chi-square or fisher exact test when appropriate. p<0.05 was considered statistically significant.
There were no significant differences in demographic data between the two groups,
(Table 1) (Independent sample t-test, Chi square). All intubations
were successful and performed within a 20 sec interval and there were no statistically
significant differences in intubating conditions between the two groups (Table
|| Comparing demographic data between the study groups
|*Data are presented as mean±SD
|| Comparing intubating conditions between the study groups
|*Data are presented as number (percent) of patients
||Comparing jaw relaxation, vocal cord position and response
to intubation between the study groups
|**NS: Non Significant, *Data are presented as number (%) of
Jaw relaxation and response to intubation was better in ephedrine group (
p = 0.014 and p = 0.049, respectively) but vocal cord positions did not differ
significantly between the two groups (Table 3). The baseline
values of MAP and HR did not differ between the two groups (independent sample
t-test). There were not statistically significant differences in MAP between
and within two groups (repeated measures ANOVA). Differences in HR was statistically
significant between the two groups (repeated measures ANOVA, between subject
effects, p = 0.01), but within subject test did not show significant difference
in each group. The only complications were 2 cases of self-limiting sinus tachycardia
of less than 130 beats min-1 in the ephedrine group.
In this study we compared propofol-ephedrine with propofol-saline on intubating condition after priming with atracurium. We used ephedrine because it is a weak sympathomometic agent which produces venoconstriction more than arterial constriction, improving venous return, increasing cardiac out put and thus muscle blood flow. The circulating time to the target organ and its blood flow partly determine the onset time of the neuromuscular block that can improve intubating condition (Lawson and Meyer, 2001).
The main finding of this study is that combination of propofol-ephedrine compared with propofol-saline did not improve intubating condition after priming by atracurium. This finding is not correlated with the study by Tan et al. (2000) which comparing propofol-ephedrine with propofol alone on intubating condition after rocuronium. They resulted that intubating condition was better in ephedrine group.
In the study by Albert et al. (2000) propofol-ephedrine compared with propofol-saline on intubating condition after cisatracurium and intubating condition was better in ephedrine group.
In present, Jaw relaxation and response to intubation was better in ephedrine group but Vocal cord positions did not differ significantly between the two groups. In Tan et al. (2002) study Vocal cord position and response to intubation were significantly better in the propofol-ephedrine group, although jaw relaxation was similar.
The differences in present study with Tan et al. (2002) and Albert et al. (2000) studies may be due to our different type of muscle relaxant and using premedication that may help for better intubating condition in both groups but other factors should be included.
We had no statistically significant differences in MAP between and within two groups. HR was statistically but not clinically (more than 30% of normal) higher in ephedrine group. Within subject test did not show significant difference in HR of each group. In Tan et al. (2002) study MAP and HR were significantly increased in the propofol-ephedrine group that was not correlated with present study.
These differences may be due to using premedication in present study, however histamine release of atracurium may be partially responsible.
Further study may be needed to evaluate the effects of different doses of ephedrine on intubating condition after priming by atracurium or other NDMRs.
In conclusion ephedrine in dose of 140 μg kg-1 combining with propofol for intubation after priming by atracurium did not improve intubating condition and induced no clinically acceptable hemodynamic responses.
Authors would like to special thanks to Dr. Fatemeh Esfahani, the consultant of Research Development Center of Dr. Shariati Hospital, for statistical review.