In this prospective, randomized, double-blind, placebo-controlled study, we attempted to define the dose of succinylcholine that provides excellent intubation conditions in patients within 60 s during simulated rapid-sequence induction of anesthesia. Anesthesia was induced in 180 patients with 2 μg/kg fentanyl and 2 mg/kg propofol. After loss of consciousness, patients were randomly allocated to receive 0.3, 0.5, 1.0, 1.5, or 2.0 mg/kg succinylcholine or saline solution (control group). Tracheal intubation was performed 60 s later. A blinded investigator performed all laryngoscopies and graded intubating conditions. Intubating conditions were excellent in 0.0%, 43.3%, 60.0%, 63.3%, 80.0%, and 86.7% of patients after 0.0, 0.3, 0.5, 1.0, 1.5, and 2.0 mg/kg succinylcholine, respectively. The incidence of excellent intubating conditions was significantly more frequent (P < 0.001) in patients receiving succinylcholine than in the controls and in patients who received 2.0 mg/kg succinylcholine (P < 0.05) than in those who received 0.3 mg/kg succinylcholine. The calculated doses of succinylcholine (and their 95% confidence intervals) that are required to achieve excellent intubating conditions in 50% and 80% of patients at 60 s are 0.39 (0.29–0.51) mg/kg and 1.6 (1.2–2.0) mg/kg, respectively. It appears that there are no advantages to using doses of succinylcholine larger than 1.5 mg/kg.
IMPLICATIONS: Doses as large as 2.0 mg/kg of succinylcholine do not guarantee excellent intubating conditions within 60 s in 90% of patients. The calculated doses of succinylcholine (and their 95% confidence intervals) that are required to achieve excellent intubating conditions in 50% and 80% of patients at 60 s are 0.39 (0.29&#x2013;0.51) mg/kg and 1.6 (1.2&#x2013;2.0) mg/kg, respectively.
Department of Anesthesiology and Pain Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; Departments of Anesthesia and Surgery, King Saud University, Riyadh, Saudi Arabia
The results of this study were presented at the American Society of Anesthesiologists Annual Meeting, October 22–26, 2005, Atlanta, GA.
Accepted for publication July 22, 2005.
Address correspondence and reprint requests to Mohamed Naguib, MB, BCh, MSc, MD, Department of Anesthesiology and Pain Medicine, The University of Texas M. D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 409, Houston, TX 77030–4009. Address e-mail to email@example.com.
Succinylcholine remains the drug of choice for rapid sequence induction of anesthesia. The most commonly used dose of succinylcholine is 1.0 mg/kg. The reported incidence of acceptable intubating conditions (excellent plus good grades combined) after administration of 1.0 mg/kg succinylcholine varies from 91.8% to 98% (1–5). The dose of succinylcholine needs to be individualized, however, depending on the clinical situation. In some situations “acceptable” conditions for tracheal intubation are not ideal. In the patient with increased intracranial pressure or the patient with a full stomach, for example, any intubating conditions short of excellent may not be suitable. The reported incidence of excellent intubating conditions after administration of 1.0 mg/kg succinylcholine in simulated rapid sequence induction varies from 63% to 80% (1,3–5). The reported incidence of excellent intubating conditions after administration of larger doses (1.5 mg/kg) of succinylcholine ranges from 55% to 85% (6,7).
In this prospective, randomized, double-blind, placebo-controlled study, we attempted to define the dose of succinylcholine that provides excellent intubation conditions in 90% of patients within 60 s during a simulated rapid sequence induction of anesthesia.
After obtaining institutional approval (King Khalid University Hospital, Riyadh, Saudi Arabia) and informed patient consent, we enrolled 180 adult patients of both sexes who were ASA physical status I, aged 30.9 ± 10.2 yr (mean ± sd), and weighed 69.6 ± 12.3 kg. All patients underwent elective procedures; had no neuromuscular, renal, or hepatic disease; and no patient was taking any drug known to interfere with neuromuscular function. Exclusion criteria included a history of drug or alcohol abuse, gastroesophageal reflux or hiatal hernia, cardiovascular disease, reactive airway disease, allergies to any of the study drugs, administration of sedative or narcotic drugs in the previous 24 h, renal or hepatic impairment, or anticipated difficult intubation. No premedication was administered. An IV infusion of lactated Ringer's solution was started before induction of anesthesia. Standard monitoring was used.
The ability to ventilate the lungs was tested before induction of anesthesia by applying positive airway pressure via a tightly fitting mask. Thereafter, all patients inhaled 100% oxygen from the anesthesia circuit via a facemask, and 2 μg/kg fentanyl was administered IV. Administration of oxygen was continued for 3 min and then 2 mg/kg propofol was administered IV. When the patient lost consciousness, one of the following was administered through a rapidly flowing IV line: 0.3, 0.5, 1.0, 1.5, or 2.0 mg/kg succinylcholine or saline solution (control group). Succinylcholine and placebo (saline) were prepared in coded syringes to achieve double blinding. The coded syringes were prepared by a pharmacist using a randomization schedule provided in sealed envelopes according to a computer-generated list. All other personnel were blinded as to the patient's treatment group. Each patient was randomly assigned to a particular dosage group or to the control group (n = 30 in each group).
Because observation of fasciculations would identify the drug administered as succinylcholine, the anesthesiologist performing and grading the intubation was positioned with his back to the patient until just before beginning the intubation sequence. The tracheal intubation sequence was begun between 40 and 45 s after administration of succinylcholine. The head was positioned, laryngoscopy was started at 50 s using a size 3 Macintosh blade, and tracheal intubation was subsequently performed 60 s after succinylcholine administration. Cuffed endotracheal tubes of 7-mm and 8-mm sizes were used in female and male patients, respectively. The scheme for grading conditions for tracheal intubation was based on accepted criteria for good clinical research practice (Table 1) (8). Intubating conditions were graded as excellent if all variables were excellent. If all the variables were not excellent, intubating conditions were graded as good unless any variable was graded poor. If any variable was poor, the intubating conditions were graded as poor. The investigator performing the intubation and grading intubation conditions was an experienced anesthesiologist and was blinded as to which group the patient had been assigned.
Before induction of anesthesia, surface electrodes were placed over the ulnar nerve at the wrist. After loss of consciousness, the ulnar nerve was stimulated at the wrist with square wave stimulus set at a current of 60 mA and a duration of 0.2 ms. Each stimulus was delivered in a train-of-four (TOF) sequence and repeated every 12 s using a Myotest peripheral nerve stimulator (Biometer International, Odense, Denmark). An investigator counted the number of tactile TOF responses immediately after administration of the study drug. Onset time was defined as the time from the end of injection of the study drug until maximum block of the TOF response. The duration of action was the time from injection until return of the tactile TOF response. Thereafter, the investigatory intervention was terminated, and anesthesia continued as appropriate for surgery. Each patient was monitored for any adverse effects.
Demographic data were analyzed with analysis of variance or χ2 test as appropriate. If analyses of variance results were significant, the Dunnett post hoc test was used to compare the study groups and the control group. The Duncan multiple range test was used to compare the onset time and duration of block among the different succinylcholine dosage groups. Intubating conditions and TOF counts were analyzed with a Kruskal-Wallis test for multiple comparisons using the Bonferroni adjustments. Statistical analyses were performed using the BMDP statistical software package (release 7.01; University of California Press, Berkeley, CA; 1994) and StatXaxt for Windows (version 4.0.1; CYTEL Software Corporation, Cambridge, MA; 1999). The doses of succinylcholine that were required to achieve excellent intubation conditions in 50% and 80% of patients at 60 s were calculated by probit analysis using the pharmacologic software programs of Tallarida and Murray (9). Logistic regression analysis was performed to test the influence of body mass index (BMI), age, and dose as predictors for excellent intubating conditions. Unless otherwise specified, results are expressed as means and sd or medians and interquartile ranges (25%–75%) and are considered significant at P < 0.05.
There were no significant differences among the six groups regarding baseline demographics (Table 2). All patients underwent successful tracheal intubation except for seven patients in the control group. Intubating conditions were excellent in 0.0%, 43.3%, 60.0%, 63.3%, 80.0%, and 86.7% of patients after 0.0, 0.3, 0.5, 1.0, 1.5, and 2.0 mg/kg succinylcholine, respectively (Fig. 1 and Table 2). The incidence of excellent intubating conditions was significantly more frequent (P < 0.001) in patients receiving succinylcholine than in those in the control group and in the 2.0 mg/kg succinylcholine group (P < 0.05) than in the 0.3 mg/kg succinylcholine group. Probit analysis yielded calculated doses of succinylcholine (and their 95% confidence intervals) that are required to achieve excellent intubating conditions in 50% and 80% of patients at 60 s of 0.39 (0.29–0.51) mg/kg and 1.6 (1.2–2.0) mg/kg, respectively (Fig. 2). Logistic regression model adjusted for age and BMI predicted that the dose was a significant predictor for excellent intubating conditions.
TOF response was abolished at ≤60 s in 6, 18, 25, 24, and 26 patients after administration of succinylcholine doses of 0.3, 0.5, 1.0, 1.5, and 2.0 mg/kg, respectively (Table 2). There were no significant differences in the onset times among the different doses of succinylcholine studied (Table 3). The duration of action of succinylcholine was dose dependent and was significantly longer after doses of 1.5 and 2.0 mg/kg than after doses of 0.3, 0.5, and 1.0 mg/kg (Table 3).
In rapid sequence induction of anesthesia, 0.39 (0.29–0.51) mg/kg and 1.6 (1.2–2.0) mg/kg succinylcholine would be required to achieve excellent intubating conditions in 50% and 80 of patients with normal airway anatomy anesthetized with 2 μg/kg fentanyl and 2 mg/kg propofol%, respectively.
Consistent with our results, Stewart et al. (7) reported that, after induction of anesthesia with 5 mg/kg thiopental, 23 (85%) of 27 patients receiving 1.5 mg/kg succinylcholine, and 18 (56%) of 32 patients receiving 0.5 mg/kg succinylcholine had excellent intubating conditions at 60 s. Iamaroon et al. (6) reported that, in patients anesthetized with 5 mg/kg thiopental, the incidence of excellent intubating conditions at 60 s after 1.5 mg/kg succinylcholine was 55% as assessed by the intubationist. In the present study, increasing the succinylcholine dose from 1.5 to 2.0 mg/kg resulted in only 6.7% improvement in the incidence of excellent intubating conditions (from 80% to 86.7%). There is probably no advantage to exceeding a dose of succinylcholine of 1.5 mg/kg, as the results in this group were not significantly different from those of the 2.0 mg/kg group. Our data also suggest that the dose required to achieve excellent intubating conditions in 90% of patients is larger than 2.0 mg/kg succinylcholine. It is possible that increasing succinylcholine dosage to 3 mg/kg, for instance, would have increased the incidence of excellent intubating conditions to 90%. The question remains, is there any justification to using doses of this magnitude? In fact, no dose of succinylcholine would guarantee excellent intubating conditions within 60 s in 100% of patients because of the limiting effects of the circulation time and muscle blood flow (10–12). In patients anesthetized with 2.0–2.5 mg/kg propofol, a succinylcholine dose of 3.0 mg/kg failed to produce uniform excellent intubating conditions within 60 s (13).
Our data confirm our previous findings that a succinylcholine dose of ≈0.5 mg/kg is adequate for achieving clinically acceptable (excellent or good) conditions for routine tracheal intubation within 60 s (5). Intubating conditions depend on several factors, including the depth of anesthesia, the interval between drug administration and laryngoscopy, the dose of the neuromuscular blocking drug given, the anatomy of the airway, and the experience of the intubationist.
There were few differences in onset times for the doses of succinylcholine (0.3 to 2.0 mg/kg) used in this study (Table 3). The mean onset times were 72 s with 0.3 mg/kg and 52 s with 2.0 mg/kg succinylcholine. Koscielniak-Nielsen et al. (14) reported that the mean onset times during fentanyl-thiopental-oxygen anesthesia, measured by mechanomyography, were 79.5 s and 71 s after administration of 0.3 mg/kg and 1 mg/kg succinylcholine, respectively. Kopman et al. (15) reported that the mean onset times, measured by acceleromyographic monitor, were 105 s and 71 s after administration of 0.4 mg/kg and 1.0 mg/kg succinylcholine, respectively, in patients anesthetized with desflurane-oxygen-opioid anesthesia.
In the present study, the duration of succinylcholine-induced block was dose dependent and ranged from 4.4 min for the 0.3 mg/kg dose to 7.5 min for the 2.0 mg/kg dose. These results are consistent with previously published results of other investigators (15–18). Katz and Ryan (17), using mechanomyographic monitoring, found in patients who were anesthetized with 150–500 mg thiamylal and whose anesthesia was maintained with nitrous oxide supplemented by thiamylal, meperidine, trichloroethylene, or halothane, that the mean times to 10% recovery of the twitch tension after succinylcholine doses of 0.5, 1.0, and 2.0 mg/kg were 5.5, 10.2, and 13.1 min, respectively. Corresponding times reported by Walts and Dillon (16) and Vanlinthout et al. (18) were 4.6, 8.1, and 10.7 min, and 4.8, 8.5, and 13.0 min, respectively. Kopman et al. (15) reported that, during desflurane-oxygen-opioid anesthesia, times to 10% recovery of twitch height after administration of succinylcholine doses of 0.6 mg/kg and 1.0 mg/kg were, on average, 5.1 and 6.2 min, respectively.
In conclusion, it appears that there are no advantages to using succinylcholine doses larger than 1.5 mg/kg in a rapid sequence induction of anesthesia. Succinylcholine doses as large as 2.0 mg/kg do not guarantee excellent intubating conditions within 60 s in 90% of patients.
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