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Anesthesiology:
Editorial Views

The Right Dose of Succinylcholine

Donati, François Ph.D., M.D., F.R.C.P.C.

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SUCCINYLCHOLINE is considered to be endowed with two great qualities: It provides intense paralysis rapidly, and its effect is likely to wear off before an adequately preoxygenated patient becomes hypoxic. However, this claim was challenged because calculations showed that at the recommended dose, 1 mg/kg, preoxygenated patients were likely to become hypoxic before spontaneous breathing resumed. 1 Two articles in this issue of the Journal address the questions that come next: Would a smaller dose be just as effective, and if so, would this dose have a short enough duration of action? Naguib et al.2 suggest that acceptable intubating conditions can be obtained in 95% of patients with just 0.56 mg/kg of succinylcholine. Kopman et al.3 report that decreasing the dose by 40% from 1.0 to 0.6 mg/kg decreases the duration of action by approximately 90 s.
Succinylcholine is used to facilitate tracheal intubation, especially in emergency situations when the risk of aspiration of gastric contents is present. In this context, manual ventilation can increase the risk of aspiration, so it is important to limit the duration of paralysis so the patient can breathe again in case of failure to intubate. The question of the right dose to obtain adequate intubating conditions has not been addressed until now, probably because the problem is not as simple as it appears. Monitoring the twitch response at the adductor pollicis is of limited use because of different onset times, intensities of blockade, and duration of action at different muscles. In addition, depth of anesthesia affects the quality of intubating conditions.
Thus, the only way to determine the best dose is to assess intubating conditions in a large number of patients. The assessor must be blinded and must follow a well-accepted scoring system, such as the one proposed by the 1994 Copenhagen consensus conference. 4 Ideally, a group not receiving any neuromuscular blocking agent should be included, to take into consideration the effect of the anesthetic. Still, many variables must be fixed by the investigators, and the choices should be adapted to the drug and situation to be studied. The dose and timing of administration of narcotics, the dose of induction agent, and the interval between injection of the neuromuscular blocking agent and intubation are all important. 5 Succinylcholine is meant to be used for rapid-sequence intubation. Therefore, Naguib et al.2 quite appropriately chose a relatively light anesthetic and a short induction-intubation interval, 60 s. The authors chose not to give any nondepolarizing drug to prevent fasciculations. Doing so would have increased the dose of succinylcholine required, 6 so the results of the study do not apply to the situation when a defasciculant is given.
Table 1
Table 1
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As expected, the quality of the intubating conditions increased with dose. Acceptable conditions were found in only 30% of patients receiving no succinylcholine, but in 98% of subjects administered 1 mg/kg. From their data, the authors concluded that 0.56 mg/kg was expected to provide acceptable conditions in 95% of patients. However, the 95% figure and the definition of acceptable were picked arbitrarily. If one is content with acceptable conditions 9 times out of 10, then 0.3 mg/kg is more than enough. However, if one aims for 99% of patients with acceptable conditions, more than 1 mg/kg is needed. The term acceptable is also arbitrary, as it includes excellent and good conditions. Only those with excellent conditions do not move at all, and this occurs in only 55% and 60% with doses of 0.3 and 0.5 mg/kg, respectively. The proportion increases to 80% with 1 mg/kg, but this is not perfect. Despite the subjective nature of intubation quality assessment, it is interesting to note that all large-scale studies agree on the conditions provided by succinylcholine, 1 mg/kg (Table 1).
Clearly, high doses should be chosen, unless the associated duration of action is too long. Benumof et al.1 calculated that preoxygenated healthy adult patients can withstand an 8-min period of apnea until desaturation to 90% occurs, but the average duration to 90% twitch height recovery after succinylcholine, 1 mg/kg, is greater (10 min). They concluded that “significant-to-life threatening hemoglobin desaturation will occur before functional recovery”1 if an airway fails to be secured. Kopman et al., 3 in this issue of the Journal, obtained a similar recovery value (9.3 min), longer than the 8-min critical period. A 40% reduction in dose to 0.6 mg/kg corresponded to a 7.6-min duration, which at first sight brings the patient into the safe zone.
But before we all adopt the 0.6-mg/kg dose, let us look at the duration of apnea and not the twitch height at the thumb. At least two studies demonstrated that, on average, breathing resumes before the subject becomes hypoxic after a 1-mg/kg dose. Heier et al.7 obtained a mean duration of apnea of 5.2 min in 12 volunteers. Hayes et al.8 measured a mean time to first diaphragmatic movement of 4.7 min in 100 patients. These are much shorter than the 9- to 10-min duration at the adductor pollicis, probably because the diaphragm recovers before the adductor pollicis does. 9 Upper airway muscles might recover later, but in the case of a failed intubation, the anesthesiologist is expected to be present to maintain patency of the airway. On the basis of these results, it is tempting to recommend a dose of 1 mg/kg, which provides excellent intubating conditions in 80% of subjects, more often than the lower doses, and a safe duration of apnea.
Careful inspection of the data suggests that although this is true, on average, not all patients are average. Functional residual capacity may be reduced and/or oxygen consumption increased and/or preoxygenation not optimal. 1 Also, succinylcholine does not have the same effect in all subjects, even if their plasma cholinesterase activity is within the normal range. Kopman et al.3 found a 5-min range for all levels of recovery. In Hayes et al. ’s study, 8 manual ventilation had to be applied in 11% of cases to prevent hypoxia, and in Heier et al. ’s study, 7 one subject was apneic for 9 min! The safety of succinylcholine is limited by these relatively sensitive patients, and interestingly, a decrease in dose does not have a marked effect on the upper range of duration (10, 10.5, and 11 min in Kopman et al. ’s study 3 for 0.4, 0.6, and 1 mg/kg, respectively). This is not unexpected, because the half-life of succinylcholine is less than 1 min. 10 Doubling the dose of any drug should prolong its duration of action by one half-life, because it takes one half-life for the concentration to decrease by 50%, that is, to bring it down to that corresponding to a single dose.
What should we conclude? The traditional 1-mg/kg dose is not a bad choice, after all. It is perfect in average patients, providing excellent intubating conditions, and oxygenation can be maintained during the apnea period. But not all patients are average. A reduction of dosage, to 0.5–0.6 mg/kg, will not compromise intubating conditions dramatically, but neither will it shorten the period of apnea below the safe level in all subjects. Succinylcholine has limitations because of its variability. No single dose is perfect.
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References

1. 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

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

3. Kopman AF, Zhaku B, Lai KS. The “intubating dose” of succinylcholine: The effect of decreasing doses on recovery time. A nesthesiology 2003; 99: 1050–4

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

5. Donati F: Tracheal intubation: Unconsciousness, analgesia and muscle relaxation (editorial). Can J Anesth 2003; 50: 99–103

6. Szalados JE, Donati F, Bevan DR: Effect of d-tubocurarine pretreatment on succinylcholine twitch augmentation and neuromuscular blockade. Anesth Analg 1990; 71: 55–9

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

8. 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

9. Dhonneur G, 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

10. Roy JJ, Donati F, Boismenu D, Varin F: Concentration-effect relation of succinylcholine chloride during propofol anesthesia. A nesthesiology 2002; 97: 1082–92

11. Andrews JI, Kumar N, van den Brom RH, Olkkola KT, Roest GJ, Wright PM: A large simple randomized trial of rocuronium versus succinylcholine in rapid-sequence induction of anaesthesia along with propofol. Acta Anaesthesiol Scand 1999; 43: 4–8

12. Sparr HJ, Mellinghoff H, Blobner M, Nolge-Schomburg G: Comparison of intubating conditions after rapacuronium (Org 9487) and succinylcholine following rapid sequence induction in adult patients. Br J Anaesth 1999; 82: 537–41

13. Blobner M, Mirakhur RK, Wierda JM, Wright PM, Olkkola KT, Debaene B, Pendeville P, Engbaek J, Rietbergen H, Sparr HJ: Rapacuronium 2.0 or 2.5 mg kg-1 for rapid-sequence induction: Comparison with succinylcholine 1.0 mg kg-1. Br J Anaesth 2000; 85: 724–31

14. Fleming NW, Chung F, Glass PS, Kitts JB, Kirkegaard-Nielsen H, Gronert GA, Chan V, Gan TJ, Cicutti N, Caldwell JE: Comparison of the intubation conditions provided by rapacuronium (ORG 9487) or succinylcholine in humans during anesthesia with fentanyl and propofol. A nesthesiology 1999; 91: 1311–7

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