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Anesth Analg 2000;90:576-578
© 2000 International Anesthesia Research Society

PEDIATRIC ANESTHESIA

The Potency of Succinylcholine in Obese Adolescents

John B. Rose, MD*, Mary C. Theroux, MD{dagger}, and Michael S. Katz, MD{dagger}

*Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, and Department of Anesthesiology and Pediatrics, University of Pennsylvania, School of Medicine; and {dagger}Department of Anesthesiology and Critical Care Medicine, Alfred I. duPont Hospital for Children, Wilmington, Delaware, and Department of Anesthesiology, Thomas Jefferson Medical College, Philadelphia, Pennsylvania

Address correspondence and reprint requests to Mary C. Theroux, MD, Department of Anesthesiology, Alfred I. duPont Hospital for Children, PO Box 269, Wilmington, DE 19899. Address e-mail to mtheroux{at}nemours.org


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We constructed a single-dose response curve for succinylcholine in 30 obese adolescents during thiopental-fentanyl anesthesia administration by using 100 µg/kg, 150 µg/kg, or 250 µg/kg IV. The maximal response (percent depression of neuromuscular function) of the adductor pollicis to supramaximal train-of-four stimuli was recorded by using a Datex (Helsinki, Finland) relaxograph. Linear regression and inverse prediction were used to determine doses of succinylcholine to produce 50% (ED50), 90% (ED90), and 95% (ED95) depression of neuromuscular function. The ED50, ED90, and ED95 were 152.8 µg/kg (95% confidence interval: 77.8–299.5), 275.4 µg/kg (95% confidence interval: 142–545.7), and 344.3 µg/kg (95% confidence interval: 175.3–675.3), respectively. This ED50 is similar to the dose reported for similarly aged, nonobese adolescents, 147 µg/kg. The previously reported ED95 for succinylcholine in nonobese adolescents, 270 µg/kg, is within the 95% confidence interval generated for ED95 in our study.

Implications: The potency estimates for succinylcholine in obese (body mass index > 30 kg/m2) adolescents are comparable to those in similarly aged nonobese adolescents when dosing is calculated based on total body mass and not lean body mass. When a rapid sequence induction of anesthesia is considered in an obese adolescent, the dose of succinylcholine should be based on actual (not lean) body mass.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Obesity occurs in 15%–25% of American adolescents (1). The correct dose for many anesthetics in obese children is not known. Succinylcholine (SCH) is one of these drugs. The use of large-dose (3–8 times the SCH dose that produces a 95% depression of neuromuscular function [ED95]) nondepolarizing muscle relaxants for rapid tracheal intubation is suitable in lean adolescents (2–4). However, the dosing of these drugs in obese children has not been determined. The onset of neuromuscular blockade (NMB) may be delayed if dosing is based on ideal body weight, and recovery may be prolonged if dosing is based on actual body weight (5). SCH may be preferred over nondepolarizing muscle relaxants for rapidly securing the airway in obese adolescents. Some speculate the potency of SCH is greater in obese patients because of a decreased volume of distribution (6). We conducted this study to determine the potency of SCH in obese adolescents.


   Methods
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 Abstract
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 Methods
Results
 Discussion
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After institutional review board approval, informed (written) parental consent and patient assent were obtained for each child before protocol enrollment. Children with a body mass index (BMI) > 30 kg/m2 between 9 and 15 yr of age were eligible for the study (7). Children with neuromuscular diseases, liver or renal disease, malignant hyperthermia susceptibility, pseudocholinesterase deficiency, and aminoglycoside therapy were excluded. Patients 1–20 were assigned (by a computer-generated table of random numbers) to receive either SCH 100 µg/kg or SCH 250 µg/kg. The SCH dose that produces a 50% depression of neuromuscular function (ED50) was then estimated to be close to 150 µg/kg, and Patients 21–30 received this dose.

All patients were premedicated orally with midazolam 20 mg, metoclopramide 0.1 mg/kg, and ranitidine 0.5 mg/kg. Forty minutes later, an IV catheter was placed, and blood specimens for determination of pseudocholinesterase (PCHE) concentration and dibucaine number (Db) were obtained. In the operating room, routine noninvasive monitors were established for all patients. NMB was monitored with a Datex (Helsinki, Finland) electromyograph on the arm opposite the IV catheter. After preoxygenation for 2 min, anesthesia was induced IV with thiopental 4–5 mg/kg and fentanyl 2–3 µg/kg. Anesthesia was maintained with 60%–70% nitrous oxide in oxygen and thiopental 1 mg/kg IV as required. A baseline response of the adductor pollicis muscle to supramaximal train-of-four (TOF) stimuli of the ulnar nerve at 10-s intervals was recorded for 30 s. Then, the SCH study dose was administered through the "T" connector hub of a rapidly infusing IV line. The first response of the TOF was compared with the first response of the baseline TOF to quantify neuromuscular function. Once the maximal response (no further decrease in TOF amplitude) was recorded, a second dose of SCH (total = 2 mg/kg IV) was administered. The patient’s trachea was intubated when no response to TOF stimuli was recorded.

The following data were obtained for each patient: maximal response (percent depression of neuromuscular function), PCHE, Db, age, weight, height, and BMI. Demographic variables of study groups were compared by using analysis of variance. Dose and percent depression of neuromuscular function were converted into log of the dose and probit of the response, respectively. An F test for lack of fit to ascertain whether a linear regression function was appropriate for the data was performed (8). A P value of 0.29 indicated that the regression function was linear. Therefore, a linear regression was done for the variables log of the dose versus probit of the response. No patient had a 0% or 100% response. Inverse prediction for ED50, ED90 (effective dose to depress 90% of the baseline twitch), and ED95 was completed. Ninety-five percent confidence intervals were also performed.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The dose groups were comparable in age, weight, BMI, Db, and PCHE (Table 1). No patient had a core temperature <35.5°C or >37.0°C. The PCHE was greater than the upper limit of normal (7–19 µmol/L) in 12 of 25 subjects tested. Maximal depression (mean and SD) of neuromuscular function after IV SCH 100 µg/kg, 150 µg/kg, and 250 µg/kg are reported in percentage depression when compared with baseline and in Probits (Table 1).


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  		Table 1. Demographic Data, Dibucaine Number, Pseudocholinesterase, % Maximal Twitch Depression in (Probits as well as Percentages), Final Electromyelogram (EMG) Baseline when Compared with Initial EMG Baseline, and Tmax
 
Relative efficacy was assessed for the following three different calculations of dose vs probit of effect: dose in µg/kg of body weight versus probit of effect (Method 1); dose in µg/body surface area in m2 versus probit of effect (Method 2); and dose in µg/BMI versus probit of effect (Method 3). Specifically, bivariate correlations were calculated between each dosing method and probit of percent depression. The resulting coefficients (Method 1 = 0.825, Method 2 = 0.791, and Method 3 = 0.332) were dependent because each was computed by using the same sample of subjects and the same outcome (percent depression). Consequently, the formula for dependent correlations was used to evaluate whether the three correlation coefficients differed among themselves. Results showed that Methods 1 and 2 were superior to Method 3 (P < 0.0003 and P < 0.0026, respectively). In contrast, there was no difference between Methods 1 and 2 (P = 0.354). Thus, these results indicate that either Method 1 or 2 can be used with equal effectiveness to create the dose-response relationship. Because dosing based on body weight is the simplest method, we decided to use Method 1. The estimated ED50, ED90, and ED95 with lower and upper 95% confidence intervals in µg/kg are 152.8 (77.8 and 299.5), 275.4 (142 and 545.7), and 344.3 (175.3 and 675.3), respectively (Table 1 and Figure 1).



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  		Figure 1. Linear regression of the log of the dose of succinylcholine versus the probit of the maximal response (% twitch depression).

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
We have shown that the potency of SCH in obese adolescents, as estimated by the ED50 of 158 µg/kg, is similar to the value of 147 µg/kg reported previously for lean adolescents (6). The ED95 of SCH in lean adolescents, 270 µg/kg, occurs within the 95% confidence intervals generated for obese adolescents in the present study (6). Of further interest is our finding that PCHE levels may be increased in obese adolescents. We have no explanation for this observation; however, similar results have been noted in studies of obese adults (9).

In a previous report, Brown et al. (6) stated that the volume of distribution for SCH is decreased in obese children. They speculated that the dose requirement for SCH to achieve similar levels of paralysis is smaller in obese children when compared with the dose required for lean children (6). Our results showed that the dose requirement in obese adolescents is similar to that reported previously in nonobese adolescents. This is particularly true with the ED50, which is the estimated variable with the least error.

All subjects studied received midazolam, metoclopramide, and ranitidine. Midazolam is unlikely to affect the onset, magnitude, or duration of NMB associated with SCH because these effects have not been reported with other benzodiazepines (10). Although metoclopramide inhibits PCHE activity and has been shown to increase the duration of NMB after the administration of SCH, Db levels were normal in our subjects (11–13). The H-2 receptor antagonist ranitidine is also known to affect duration, but not onset, of NMB with SCH because of the drug’s inhibitory effects on acetylcholinesterase and PCHE (13–16). These effects are most pronounced with repeated oral doses or large IV doses. Because our patients received only one dose of ranitidine and Db levels were normal immediately before the induction, we believe raniditine had little, if any, effect on our data.

In conclusion, we have shown that the potency of SCH in obese adolescents is similar to that observed in nonobese adolescents. When the anesthesiologist considers a rapid sequence induction in an obese adolescent, the dose of SCH should be based on actual (not lean) body mass.


   Acknowledgments
 
The authors thank Barbara B. Brandom, MD, and Mehernoor F. Watcha, MD, for their help preparing this article.


   Footnotes
 
Presented at the annual meeting of the International Anesthesia Research Society, Orlando, FL, March 1998.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. United States Department of Health and Human Services. The Surgeon General’s report on nutrition and health. Washington, DC: US Government Printing Office, 1988.
  2. Schultz J, Crawford M. Intubating conditions 30 seconds after rocuronium or succinylcholine in children [abstract]. Anesth Analg 1998;86:S417.
  3. Sloan MH, Lerman J, Bissonnette B. Pharmacodynamics of high-dose vecuronium in children during balanced anesthesia. Anesthesiology 1991;74:656–9.[Web of Science][Medline]
  4. Woloszczuk-Gebicka B. Intubating conditions in children following rocuronium 0.8 mg kg-1 [abstract]. Anesth Analg 1998;86:S421.
  5. Schwartz AE, Matteo RS, Ornstein E, et al. Pharmacokinetics and pharmacodynamics of vecuronium in the obese surgical patient. Anesth Analg 1992;74:515–8.[Abstract/Free Full Text]
  6. Brown TC, Meretoja OA, Bell B, Clare D. Suxamethonium: electromyographic studies in children. Anaesth Intensive Care 1990;18:473–6.[Web of Science][Medline]
  7. Hines JH, Dietz WH. Guidelines for overweight in adolescent preventive services: recommendations from an expert committee. Am J Clin Nutr 1994;59:307–16.[Abstract/Free Full Text]
  8. Neter J, Kutner MH, Nachtsheim CJ, Wasserman W. Applied linear statistical models. Chicago:McGraw-Hill, 1996:115–21.
  9. Bentley JB, Borel JD, Vaughan RW, Gandolfi AJ. Weight, pseudocholinesterase activity, and succinylcholine requirement. Anesthesiology 1982;57:48–9.[Web of Science][Medline]
  10. Eisenberg M, Balsley S, Katz RL. Effects of diazepam on succinylcholine-induced myalgia, potassium increase, creatine phosphokinase elevation, and relaxation. Anesth Analg 1979;58:314–7.[Abstract/Free Full Text]
  11. Kao YJ, Turner DR. Prolongation of succinylcholine block by metoclopramide. Anesthesiology 1989;70:905–8.[Web of Science][Medline]
  12. Kao YJ, Tellez J, Turner DR. Dose-dependent effect of metoclopramide on cholinesterases and suxamethonium metabolism. Br J Anaesth 1990;65:220–4.[Abstract/Free Full Text]
  13. Turner DR, Kao YJ, Bivona C. Neuromuscular block by suxamethonium following treatment with histamine type 2 antagonists or metoclopramide. Br J Anaesth 1989;63:348–50.[Abstract/Free Full Text]
  14. Kambam JR, Dymond R, Krestow M. Effect of cimetidine on duration of action of succinylcholine. Analg 1987;66:191–2.[Web of Science][Medline]
  15. Kambam JR, Franks JJ. Cimetidine does not affect plasma cholinesterase activity. Analg 1988;67:69–70.[Abstract/Free Full Text]
  16. Woodworth GE, Sears DH, Grove TM, et al. The effect of cimetidine and ranitidine on the duration of action of succinylcholine. Anesth Analg 1989;68:295–7.[Abstract/Free Full Text]
Accepted for publication November 2, 1999.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2000 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press