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Anesthesiology:
Clinical Investigations

The “Intubating Dose” of Succinylcholine: The Effect of Decreasing Doses on Recovery Time

Kopman, Aaron F. M.D.*; Zhaku, Bledi B.A.†; Lai, Kane S. M.D.‡

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Abstract

Background: The usually cited “intubation dose” of succinylcholine is 1.0 mg/kg. In the majority of patients, this dose will produce apnea of sufficient duration that significant hemoglobin desaturation may occur before neuromuscular recovery takes place in those whose ventilation is not assisted. This study was undertaken to examine the extent to which reducing this dose would decrease the duration of action of succinylcholine.
Methods: During stable desflurane/oxygen/opioid anesthesia and after adequate twitch stabilization, neuromuscular function was recorded with an acceleromyographic monitor. Supramaximal stimuli were delivered at 0.10 Hz. Patients received 0.40, 0.60, or 1.0 mg/kg succinylcholine, and twitch height was monitored for at least 20 min thereafter.
Results: The onset times to maximal effect were 105 ± 23 s, 81 ± 19 s, and 71 ± 22 s, respectively. The lowest dose (0.40 mg/kg) did not reliably produce 100% twitch depression. The times to 90% twitch recovery at the adductor pollicis in the three groups were 6.6 ± 1.5 min, 7.6 ± 1.6 min, and 9.3 ± 1.2 min, respectively.
Conclusions: Reducing the dose of succinylcholine from 1.0 mg/kg to 0.60 mg/kg shortens the duration of effect at the adductor pollicis by more than 90 s. The authors believe that even this modest decrease in the duration of drug-induced paralysis is often worth pursuing.
THE utility of succinylcholine as a tool in facilitating tracheal intubation was first described 50 yr ago. 1,2 In these early reports, doses averaging less than 0.50 mg/kg were usually employed (range, 10–50 mg). One of the advantages seen for succinylcholine was a “short duration of respiratory arrest even when an overdosage is administered as a result of error in judgment.” However, Foldes noted that a problem with doses of this magnitude was that they “…allow only 60–90 s for [intubation] when a single intravenous dose is administered.”2 Perhaps as a consequence, doses of 1.0 mg/kg or greater have come to be accepted as usual and customary for succinylcholine-abetted intubation. 3
Recently, second thoughts about the margin of safety associated with succinylcholine in doses ≥ 1.0 mg/kg have been expressed. Based on theoretical considerations, Benumof et al. suggested that “…in the large majority of patients with 1 mg/kg of succinylcholine-induced apnea, significant life threatening hemoglobin desaturation will occur before functional recovery” in subjects whose ventilation is not assisted. 4 Heir et al., in a study of adult volunteers, were able to demonstrate the validity of this position. 5 They remarked that “a smaller dose of succinylcholine would have decreased the duration of muscle paralysis…but the results would have been less clinically relevant.”
Nevertheless, the clinical utility of succinylcholine in doses of less than 1.0 mg/kg deserves to be reexamined. With nondepolarizing neuromuscular blockers of low potency (and, hence, fast onset), satisfactory conditions for tracheal intubation can be achieved with doses approximating only 1.5 times the ED95. 6 Because the ED95 of succinylcholine is less than 0.30 mg/kg, 7 doses as small as 0.40 mg/kg might also provide clinically acceptable conditions for intubation in the majority of individuals. An article in the current issue of the Journal by Naguib et al. strongly supports this hypothesis. 8 These authors found that 0.60 mg/kg succinylcholine was sufficient to achieve acceptable intubating conditions at 60 s in 95% of patients anesthetized with 2 μg/kg fentanyl and 2 mg/kg propofol. Even doses as low as 0.30 mg/kg produced good or excellent conditions for intubation in 92% of patients, as compared to only 30% of individuals receiving a saline placebo.
The possibility of an earlier return of neuromuscular function following low-dose succinylcholine has much to recommend it, especially in situations in which the anesthesiologist is less than certain of complete control of a patient's airway. Unfortunately, only a limited amount of objective information is available to document the extent to which recovery is expedited by using doses of succinylcholine of less than 1.0 mg/kg. We undertook this study to determine the degree to which smaller than conventional doses of succinylcholine reduced the duration of neuromuscular block.
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Methods

A total of 45 patients (aged 20–64 yr, American Society of Anesthesiologist's physical status I and II) undergoing elective surgical procedures were included in the study. All patients were free from neuromuscular disease and had a body mass index ≤ 30. The protocol was approved by our hospital's Human Subject Review Committee, and consent was obtained. Anesthesia was induced with alfentanil 15–40 μg/kg plus propofol 2.0–2.5 mg/kg intravenous, and laryngeal mask placement or tracheal intubation was accomplished without the use of neuromuscular blocking drugs. Anesthesia was maintained with desflurane in oxygen (4.0–5.0%, end-tidal) and intermittent doses of fentanyl as required. Ventilation was controlled, and end-tidal partial pressure of carbon dioxide was maintained between 34 and 40 mmHg.
Following induction of anesthesia, the evoked response of the adductor pollicis muscle to ulnar nerve stimulation at the wrist was recorded in all subjects. The monitor/stimulator used was the TOF-Watch SX® acceleromyograph (Organon Teknika B.V.; Boxtel, The Netherlands). The study arm was immobilized, and the thumb was placed under a small preload with a single strand of an elastic rubber band. 9 All data were transferred to a personal computer using a TOF-Link® fiber-optic cable and were saved using TOF-Watch SX Monitor® software. Just before calibration of the TOF-Watch® unit, a 5-s 50-Hz supramaximal tetanic stimulus was administered at the ulnar nerve. Previous work in our department has demonstrated that the period required for baseline stabilization is shortened considerably by this procedure. 10
Immediately thereafter, the acceleration transducer was taped to the volar aspect of the thumb at the interpharyngeal joint, and calibration of T1 was performed. Single stimuli were then administered at 10-s intervals. After initial T1 calibration, an additional 5 min of stimulation (0.10 Hz) was allowed for baseline stabilization. A second T1 calibration was performed, and a single dose of succinylcholine was administered as a rapid intravenous bolus. One of three doses was given: 0.40, 0.60, or 1.0 mg/kg. No further neuromuscular blocking agents were administered. Twitch height was then followed for not less than 20 min. In accordance with the recommendations of the Copenhagen Consensus Conference, all twitch height data recorded during recovery from neuromuscular block were “normalized” to the final T1 value. 11
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Statistics
All summary data are presented as mean ± SD. The recovery intervals from bolus to 10%, 25%, and 90% twitch recovery were calculated and compared using an unpaired Student t test. Demographic data were examined using chi-square analysis and Fisher exact P value. The Bonferroni inequality correction was applied. Observed differences were considered significant if P < 0.05.
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Results

Table 1
Table 1
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Although the male/female sex distribution between the three groups was not perfectly balanced (Table 1), these differences did not reach statistical significance. It should be noted that in the 1.0-mg/kg group in which female patients outnumbered male patients by 3 to 1, the 90% recovery times were essentially the same regardless of sex (9.3 vs. 9.2 min, on average).
Table 2
Table 2
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Fig. 1
Fig. 1
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Table 2 and figure 1 summarize our neuromuscular observations. Although we demonstrate that reducing the dose of succinylcholine from 1.0 to 0.6 mg/kg results in a statistically significant average reduction in duration of action (T1 times to 90% recovery of 9.3 ± 1.2 min vs. 7.6 ± 1.6 min, P < 0.01), there was considerable overlap in individual recovery times between these groups. It should be noted that the duration of action of even a modest dose of succinylcholine (0.60 mg/kg) might still be longer than is generally appreciated. In 4 of 15 patients in this group, the time to 10% twitch height recovery took 6 min or longer.
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Discussion

Table 3
Table 3
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The duration of action (at the adductor pollicis) of succinylcholine-induced block that we report is virtually identical to the observations of Viby-Mogensen 12 and is quite similar to the observations of other investigators 13–15 (Table 3).
In a recent letter in the Journal, we suggested that the usually cited 1.0-mg/kg “intubation dose” of succinylcholine was unnecessarily large. 16 It was hypothesized that a smaller dose (0.50–0.60 mg/kg) might enhance overall patient safety if this reduced dose resulted in a significant reduction in the duration of succinylcholine-induced apnea. Previously published data (Table 3) suggested that reducing the dose of succinylcholine from 1.0 to 0.5 mg/kg should decrease the duration of neuromuscular block by more than 4 min. 17–19 Although all recovery intervals (T10 through T90) that we measured were shorter after 0.60 mg/kg succinylcholine compared to the 1.0 mg/kg dose, the magnitude of these differences was less than we anticipated. A 40% decrease in dose does not result in a comparable reduction in the drug's duration of effect.
Only limited information is available on how the twitch response at the adductor pollicis following succinylcholine relates to diaphragmatic and laryngeal function. Smith et al. reported that the diaphragm may require more than 1.5 times as much succinylcholine as the adductor pollicis for a comparable degree of neuromuscular block. 20 Dhonneur et al. provide what appears to be the only comparative duration data available at the adductor pollicis versus the diaphragm (n = 8). 21 Following succinylcholine 1.0 mg/kg, they report T25, T75, and T90 recovery intervals at the respective adductor pollicis of 6.9 ± 2.6, 8.3 ± 2.9, and 9.1 ± 3.0 min, values very similar to those in the present study. At the diaphragm these values were 3.7 ± 1.5, 6.5 ± 3.0, and 7.2 min. Thus, return of diaphragmatic function seems to precede that seen at the hand by about 2 min. However, in this small series at least one individual still required 14 min for 90% twitch recovery at the diaphragm.
A recent article by Hayes et al. provides highly relevant data. 22 They studied 100 patients who, following preoxygenation, received an anesthetic induction consisting of fentanyl 1 μg/kg, a sleep dose of thiopental (3–7 mg/kg), and succinylcholine 1.0 mg/kg. Ventilation was not assisted unless the oxygen saturation decreased below 90%. They noted that the first movement of the reservoir bag appeared, on average, at 4.7 (± 1.5–2.0) min and that the first recordable end-tidal carbon dioxide reading did not appear for 5.5 (± 1.5–2.0) min. Hayes et al. found that only 11% patients developed arterial desaturation, a figure much lower than that reported by Heir et al.5 However, in Hayes et al. ’s study the anesthesia mask with oxygen running was kept on the patient's face. Heir et al. removed the facemask and provided no support to the airway. The effect on the diaphragm of succinylcholine in doses of less than 1.0 mg/kg has not been studied. Current evidence suggests that the duration of action of succinylcholine at the laryngeal adductors does not appear to be significantly shorter than that at the adductor pollicis. 21,23
It is not clear how the decreased duration in action as the dose of succinylcholine is reduced should be calculated. Benumof et al. defined the time to 50% T1 recovery as the time to functional recovery and used this point for comparisons in their hemoglobin desaturation model. 4 They reasoned that this degree of recovery should permit adequate spontaneous ventilation if the airway was patent. By this standard, we estimate that succinylcholine 0.60 mg/kg decreases the duration of block by less than 90 s, compared to a dose of 1.0 mg/kg. However, Benumof et al. ’s analysis does not really reflect the problem that concerns the clinical anesthesiologist, because if the patient has a patent airway then the need for spontaneous ventilation may be of little importance. The more pressing question seems to be, At what level of neuromuscular recovery is the patient able to spontaneously maintain a patent airway? Certainly, with nondepolarizing relaxants, 50% return of twitch height is still associated with profound weakness in the muscles of the upper airway. However, even if the time to 90% return of twitch height is used as the criterion by which recovery is measured, reducing the “standard” intubation dose of succinylcholine to 0.60 mg/kg still results in less than a 2-min decrease in the drug's duration of action (at the adductor pollicis).
Decreasing the dose of succinylcholine even further (to < 0.50 mg/kg) results, as expected, in additional reductions in the drug's duration of action (Table 2). In only 6 of the 14 patients who received succinylcholine 0.40 mg/kg was complete twitch depression at the adductor pollicis achieved. The average peak effect for the group as a whole was 93%. This is a little surprising, because previous work from our department estimated that the ED95 for succinylcholine under N2O/propofol anesthesia was only 0.27 mg/kg. 7 However, our current data do not imply that the ED95 of succinylcholine approximates 0.40 mg/kg. In those patients in whom twitch was abolished, all that can be said is that the ED95 was obviously less than 0.40 mg/kg. Therefore, the average ED95 value of succinylcholine cannot be estimated from the data in Table 2. Doses of this magnitude still facilitate ease of tracheal intubation compared to placebo administration. 8 However, administration of low-dose succinylcholine mandates certain trade-offs that not all clinicians may accept. In Naguib et al. ’s series, these doses produced “excellent conditions” for intubation in only half of their patients. In situations in which complete patient immobility is required, even doses of 1.0 mg/kg may occasionally prove unsatisfactory.
In summary, reducing the dose of succinylcholine from 1.0 to 0.60 mg/kg will shorten the duration of neuromuscular effect at the adductor pollicis by 1.5 to 2 min. The extent to which this will reduce the period of profound neuromuscular block at the diaphragm, laryngeal adductors, and muscles of the upper airway remains largely untested. In the vast majority of patients, this reduced dose of succinylcholine will provide perfectly acceptable conditions for tracheal intubation when combined with a standard anesthetic induction sequence. 8 We believe that even this modest decrease in the duration of drug-induced paralysis will often be worth pursuing. Nevertheless, when complete neuromuscular block is critical, doses of 1.0 to 1.5 mg/kg may still be appropriate. Thus, there does not appear to be a single ideal “intubating dose” of succinylcholine.
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References

1. Hampton LJ, Little DM, Fuller EM: The use of succinylcholine to facilitate endotracheal intubation. A nesthesiology 1953; 14: 382–9

2. Foldes FF: The use of succinylcholine for endotracheal intubation. A nesthesiology 1953; 14: 93–6

3. Bevan DR, Donati F: Muscle relaxants, Clinical Anesthesia, 3rd edition. Edited by Barash PG, Cullen BF, Stoelting RK. Philadelphia, Lippincott-Raven, 1997, p 390

4. Benumof JL, Dagg R, Benumof R: Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine. A nesthesiology 1997; 87: 979–82

5. Heir T, Feiner JR, Lin J, Brown R, Caldwell JE: Hemoglobin desaturation following succinylcholine-induced apnea: A study of the recovery of spontaneous ventilation in healthy volunteers. A nesthesiology 2001; 94: 754–9

6. Kopman AF, Klewicka MM, Neuman GG: Reexamined: The recommended “intubating dose” for nondepolarizing blockers of rapid-onset. Anesth Analg 2001; 93: 954–9

7. Kopman AF, Klewicka MM, Neuman GG: An alternate method for estimating the dose-response relationships of neuromuscular blocking drugs. Anesth Analg 2000; 90: 1191–7

8. Naguib M, Samarkandi A, Riad W, Alharby SW: The optimal dose of succinylcholine revisited. A nesthesiology 2003; 99: 1045–9

9. Kopman AF, Klewicka MM, Neuman GG: The relationship between acceleromyographic train-of-four fade and single twitch depression. A nesthesiology 2002; 96: 583–7

10. Kopman AF, Klewicka MM, Neuman GG: The staircase phenomenon: Implications for calibration and stabilization of the accelograph neuromuscular monitor A nesthesiology 2001; 95: 403–7

11. Viby-Mogensen J, Enbgbæk J, Eriksson LI, Gramstad L, Jensen E, Jensen FS, Koscielniak-Nielsen Z, Skovgaard LT, Østergaard D: Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents. Acta Anaesthiol Scand 1996; 40: 59–74

12. Viby-Mogensen, J: Correlation of succinylcholine duration of action with plasma cholinesterase activity in subjects with the genotypically normal enzyme A nesthesiology 1980; 53: 517–20

13. Miguel R, Witkowski T, Nagashima H, Fragen R, Bartkowski R, Foldes FF, Shanks CA: Evaluation of neuromuscular and cardiovascular effects of two doses of rapacuronium (ORG 9487) versus mivacurium and succinylcholine. A nesthesiology 1999; 91: 1648–54

14. Wierda JMKH, van den Broek L, Proost JH, Verbaan BW, Hennis PJ: Time course of action of endotracheal intubating conditions of Org 9487, a new short-acting steroidal muscle relaxant: A comparison with succinylcholine. Anesth Analg 1993; 77: 579–84

15. Hayes A, Breslin D, Reid J, Mirakhur RK: Comparison of recovery following rapacuronium, with and without neostigmine, and succinylcholine. Anaesthesia 2000; 55: 859–63

16. Kopman AF: The intubation dose of succinylcholine (letter). A nesthesiology 2002; 96: 516

17. Walts LF, Dillon JB: Clinical studies on succinylcholine. A nesthesiology 1967; 28: 372–6

18. Vanlinthout LEH, Egmond JV, De Boo T, Lerou JGC, Wevers RA, Booij LHD: Factors affecting magnitude and time course of neuromuscular block produced by suxamethonium. Br J Anesth 1992; 69: 29–35

19. Katz RL, Ryan JF: The neuromuscular effects of suxamethonium in man. Br J Anaesth 1969; 41: 381–90

20. Smith CE, Donati F, Bevan DR: Potency of succinylcholine at the diaphragm and at the adductor pollicis muscle. Anesth Analg 1988; 67: 625–30

21. Dhonneur GD, Kirov K, Slavov V, Duvaldestin P: Effects of an Intubating dose of succinylcholine and rocuronium on the larynx and diaphragm: An electromyographic study in humans A nesthesiology 1999; 90: 951–5

22. Hayes AH, Breslin DS, Mirakhur RK, Reid JE, O'Hare RA: Frequency of haemoglobin desaturation with the use of succinylcholine during rapid sequence induction of anaesthesia. Acta Anaesthesiol Scand 2001; 45: 746–9

23. Meistelman C, Plaud B, Donati F: Neuromuscular effects of succinylcholine on the vocal cords and adductor pollicis muscles. Anesth Analg 1991; 73: 278–82

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