Effects of high-dose propofol on succinylcholine-induced fasciculations and myalgia

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Effects of high-dose propofol on succinylcholine-induced fasciculations and myalgia
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  Effects of high-dose propofol on succinylcholine-inducedfasciculations and myalgia A. K ARARMAZ , S. K AYA , S. T URHANOGLU  and M. A. O ZYILMAZ Department of Anesthesiology, Dicle University Hospital, Diyarbakir, Turkey Background:  The purpose of this prospective study was todetermine the effects of high-dose propofol on the incidenceof fasciculations and myalgia, and to evaluate changes in creat-ine kinase levels following the administration of succinylcho-line in 90 women who underwent laparoscopy. Methods:  Patients were randomly assigned to one of threegroups. Induction of anesthesia was performed with thiopen-tone 5mgkg  1 in Group I (n ¼ 30), propofol 2mgkg  1 in GroupII (n ¼ 30), and propofol 3.5mgkg  1 in Group III (n ¼ 30). Thensuccinylcholine 1mgkg  1 was administered to the patients forintubation. Results:  Fasciculation was absent in 20 % of Group III patients,and no vigorous fasciculation occurred in this group. Further-more, the severity of fasciculation in Group III was signifi-cantly lower than in the other two groups ( P ¼ 0.01). Seventyper cent of patients had no myalgia in Group III, 39.2 %  inGroup II and 37 % in Group I ( P ¼ 0.007). Severity of myalgiawas also significantly lower in Group III compared with theother two groups ( P ¼ 0.011). Post-operative creatine kinaselevels were significantly higher than their baseline values inGroups I and II ( P < 0.0001). Conclusion:  Administration of propofol 3.5mgkg  1 is effectivein reducing fasciculations and myalgia after succinylcholine.  Accepted for publication 10 October 2002 Key words:  Anesthetics: propofol; complications: fascicula-tions, myalgia; neuromuscular relaxants: suxamethonium. #  Acta Anaesthesiologica Scandinavica 47 (2003) S UCCINYLCHOLINE possesses the unique properties ofrapid onset and short duration of action. How-ever, it has some disadvantages, such as fasciculation,postoperative myalgia and increased serum creatinekinase (CK).The mechanism of fasciculation is well established.However, various reasons, including the involvementof free radicals, have been suggested as the cause ofpostoperative muscle pain, and accordingly a varietyof agents including antioxidants have been experi-mented with to attenuate these reasons (1). Propofol isafree-radicalscavengerlike a -tocopherol(2).Manatakiet al. (3) found that continuous propofol adminis-tration was effective in preventing succinylcholine-induced postoperative myalgia. However, a singledose of propofol used to prevent postoperativemyalgia produces conflicting results (4, 5).We designed a randomized study to determine theeffect of high-dose propofol in the induction ofanesthesia on fasciculations, postoperative myalgiaand CK levels. Materials and methods Ninety patients of ASA grades I or II who underwentlaparoscopy for gynecologic conditions were studiedwith their informed consent; the approval of the DicleUniversity Ethics Committee was also obtained.Exclusioncriteriaincludedcardiovascularpathologiessuchascoronaryarterydisease,valvularheartdisease,arrhythmia, hypotension or hypertension, neuromus-cular disease, increased intraocular and intracranialpressure, malignant hyperthermia, hyperkalemia,dehydration, and the use of medications known tointeract with neuromuscular function. No agent wasgiven for premedication. ECG, non-invasive bloodpressure, peripheral oxygen saturation, and end-tidalcarbon dioxide levels were also monitored.By using computer-generated random numbers,patients were assigned to one of three groups: thio-pentone 5mgkg  1 was administered in Group I Alper Kararmaz, Specialist Doctor of Anesthesiology; SedatKaya, Specialist Doctor of Anesthesiology; Selim Turhanoglu,Assistant Professor of Anesthesiology; and Mehmet AliOzyilmaz, Assistant Professor of Anesthesiology.  Acta Anaesthesiol Scand 2003;  47:  180 — 184  Copyright #  Acta Anaesthesiol Scand 2003 Printed in Denmark. All rights reserved ACTA ANAESTHESIOLOGICA SCANDINAVICA ISSN 0001-5172 180  (n ¼ 30), propofol 2mgkg  1 in Group II (n ¼ 30), andpropofol 3.5mgkg  1 in Group III (n ¼ 30) for theinductionofanesthesia.Allpatientsreceivedsuccinyl-choline 1mgkg  1 immediately after the inductionagent. Fasciculations and intubation conditions wereevaluated by the same investigator, who was unawareof which induction agent was given to the patients.All induction agents were applied to the left arm ofthe patient, which was covered with a green sheet toprevent the viewing of the independent observer. Pro-pofol and thiopentone were injected over a period of60s. Fasciculations were graded according to Minguset al. (6): no fasciculations ¼ 0; mild,finefasciculationsof the eyes, neck, face, or fingers without limb move-ment ¼ 1; moderate fasciculations occurring on morethan two sides or obvious limb movement ¼ 2; andvigorous or severe, sustained and widespread fas-ciculations ¼ 3. The adequacy of relaxation for intub-ationwasevaluatedasfollows:wellrelaxed,nopatientmovement during intubation, vocal cords notmoving ¼ satisfactory; minor patient movement orvocal cords moving ¼ fair; and obvious patientmovement, bucking, or coughing during intuba-tion ¼ poor (7). Systolic blood pressure (SBP) anddiastolic blood pressure (DBP) were recorded beforeanesthesia, immediately after the induction ofanesthesia, and at 5-min intervals during anesthesia.Anesthesia was maintained with 60 % nitrous oxidein oxygen supplemented with sevoflurane, cisatra-curium and fentanyl as required.All patients were interviewed by another blindedinvestigator who was unaware of the induction agentused at the 24th postoperative hour. Muscle pain notrelated to surgical intervention was graded accordingto Harvey et al. (7): absence of muscle pain ¼ nomyalgia; minor stiffness limited to one area of thebody ¼ mild;musclepainorstiffnessnoticedspontan-eously by the patient, which may require analgesictherapy ¼ moderate; and generalized, severe, orincapacitating discomfort ¼ severe. Intramuscularinjection was not performed during the pre or post-operative period. Blood samples to determine CKlevels were taken before the induction of anesthesiaand at 24h postoperatively.Postoperative care was standardized for all patients.Pain related to surgical intervention was treated withpethidine 1mgkg  1 i.v., as necessary.Statistical analysis was performed using SPSS 10.0for Windows (SPSS Inc., Chicago, IL, USA). Sample-size calculation was performed based onthe results ofManataki et al. (3). In that study, the incidence ofpostoperative myalgia was 76 % , and we aimed atdetecting a decrease to less than 40 % with high-dosepropofol. With a power of 80 % and type 1 error of5 % , we calculated that 30 subjects were required pergroup. The incidence of patients in each fasciculationand postoperative myalgia score and adequacy ofrelaxation for intubation were analyzed using thechi-squared test. The Kruskal—Wallis test was used tocompare the severity of fasciculations and myalgiabetween the groups. Correlations between thefasciculation score and postoperative myalgia weredetermined by using Spearman’s correlation. Hemo-dynamic variables including SBP and DBP wereanalyzed by the ANOVA test. ANOVA and Student’s t -test were used to analyze CK levels between thegroups and intergroup differences. A value of P < 0.05 was considered statistically significant. Results There were no significant differences between thethree groups with respect to age, weight and durationof surgery (Table1). Data were collected intraopera-tively for 90 patients, but five patients (two in Group Iand three in Group II) were discharged within 24h ofthe operation and were not followed up. As a result,only 85 patients were questioned postoperatively.The incidence and severity of fasciculations areshown in Fig.1. There were no significant differencesbetween Groups I and II regarding the severity andincidence of fasciculation. Fasciculations were absentin 20 % of Group III patients and no vigorous fascicu-lation occurred in this group. Furthermore, the sever-ity of fasciculation in Group III was significantlylower than in the other two groups ( P ¼ 0.01). Intubat-ing conditions were similar and generally adequate inall the groups. The incidence of myalgia in each myal-gia score is shown in Fig.2. No patients sufferedsevere myalgia. Although no statistically significantcorrelations were found between fasciculation andpostoperative myalgia among the patients, both theincidence and severity of myalgia were significantlylower in Group III compared with the other two Table1 Physical characteristics of patients and duration of surgery asmean (SD).Group I(n ¼ 30)Group II(n ¼ 30)Group III(n ¼ 30)Age (years) 27 (5.2) 28 (6.1) 29 (5.7)Weight (kg) 65 (4.2) 63 (3.3) 67 (4.6)Duration of surgery (min) 34 (5.4) 30 (7.2) 35 (6.4)Group I: thiopentone 5mgkg  1 , Group II: propofol 2mgkg  1 ,Group III: propofol 3.5mgkg  1 . Propofol for preventing myalgia 181  groups ( P ¼ 0.011 for severity of myalgia). No inter-group differences were determined in hemodynamicvariables. Hypotension requiring treatment (SBP < 90)occurred in none of the patients. Post-operative CKlevelsincreasedsignificantlycomparedwiththeirbase-line levels in Groups I and II (Table2). Post-operativeCK levels in Group III were significantly lower thanin the other two groups ( P < 0.0001). Discussion As muscle pain after the use of succinylcholine wasfirst reported in 1954, it has been a common clinicalproblem. To solve this problem, many techniques andalternative agents have been employed (8). Hartmanetal.(9)showedthatantidromicallyconductedaxonaldepolarizations initiated by succinylcholine bindingon prejunctional nicotinic cholinergic receptorscaused fasciculations. Although the exact underlyingpathophysiology has not been clarified completely, ithas been reported that several mechanisms includingincreased myoplasmic calcium concentrations, mem-brane phospholipid degradation, released free fattyacids, and free radicals were responsible for muscledamage and postoperative myalgia (1, 10—12). Thesefindings have led to the employment of several agentsincluding non-depolarizing drugs, aspirin,  m -toco-pherol,pretreatment with lidocaine,diazepam,diphe-nylhydantoin,andpropofoltominimizepostoperativemuscle pain. Murphy et al. (2) showed that propofolhas an antioxidant effect like  a -tocopherol, and itaccumulates in biomembranes far more readily. Con-sidering this antioxidant effect of propofol, in 1993propofol was used to attenuate postoperative myalgiain two different studies (5, 13). However, these studiesfailed to demonstrate any useful effects of propofol onpostoperativemyalgia.Manatakietal.(3)showedthatpropofol effectively prevented succinylcholine-induced myalgia and CK elevation when used forboth the induction and maintenance of anesthesia.They suggested that a single dose of propofol atinduction is not sufficient to sustain effective levelsof the drug in the serum, and is insufficient in pre-venting postoperative muscle pain and CK elevation.Accordingly, we thought that by using high-dose 05101520250123Fasciculation scaleGroup IGroup IIGroup III Number of patients * Fig.1. Number of patients showing fasciculations. *P ¼ 0.002. No fasciculations ¼ 0; mild, fine fasciculations of the eyes, neck, face,or fingers without limb movement ¼ 1; moderate fasciculationsoccurring on more than two sides or obvious limb movement ¼ 2;and vigorous or severe, sustained and widespread fasciculations ¼ 3.Group I: thiopentone 5mgkg  1  , Group II: propofol 2mgkg  1  ,Group III: propofol 3.5mgkg  1 . 01020304050607080No myalgiaMildModerateSevereMyalgia scoreGroup IGroup IIGroup III % of patients * Fig.2. Incidence of myalgia after surgery. *P ¼ 0.007. Group I:thiopentone 5mgkg  1  , Group II: propofol 2mgkg  1  , Group III: propofol 3.5mgkg  1 .Table2 Creatine kinase concentration (IU) as mean (SD) before and 24h after administration of succinylcholine, and  P   for comparison with thepreoperative value (Student’s  t  -test).Pre-operative(IU)Post-operative(IU) P  Group I (n ¼ 28) 94.03 (18.86) 171.61 (57.95) 0.0001Group II (n ¼ 27) 91.43 (16.69) 175.11 (60.37) 0.0001Group III (n ¼ 30) 95.23 (13.63) 103.73 (30.68)* 0.08* P  < 0.0001 for comparison with the other two groups (ANOVA).Group I: thiopentone 5mgkg  1 , Group II: propofol 2mgkg  1 , Group III: propofol 3.5mgkg  1 . A. Kararmaz et al. 182  propofol, this effective level might be obtained. Ourresults showed that high-dose propofol reduces boththe incidence and severity of postoperative myalgia.We believe that the antioxidant effect of propofol maycause this beneficial result. However, propofol can noteliminate postoperative myalgia. Increasing evidencesuggests that there may be a baseline incidence ofpostoperative myalgia in laparascopic surgery that isunrelated to the choice of muscle relaxant, and post-operative myalgia is multifactorial in srcin, with suc-cinylcholine being only one contributing factor (13).Postoperative myalgia is most frequently observedon the first postoperative day in young women whoare ambulatory soon after surgery (13—15). Hence, wethoughtthatwomenwhohadundergonelaparoscopywould be an appropriate study group for investigat-ing succinylcholine-induced muscle pain.Drugs administered for preventing fasciculationsand myalgia have a number of disadvantages. Pre-treatment with small doses of non-depolarizing drugsmay attenuate some adverse effects of succinylcho-line, but preadministration of these drugs may causecomplications including diplopia, a feeling ofimpending doom, difficulties with breathing andswallowing, and prolonged neuromuscular paralysis(6, 16). Aspirin and  a -tocopherol must be given orallyand preoperatively, and do not prevent the elevationofCK(1).Propofolisahypnoticagentusedfrequentlyfor the induction of anesthesia. The cardiovasculardepressive effects of large doses of propofol may bea drawback in clinical use. By increasing the injectiontime, the hypotensive effects of propofol may beminimized. In addition, Billard et al. (17) reportedthat hemodynamic changes were unaffected by theadministration of 2mgkg  1 or 3.5mgkg  1 of propo-fol. Our results are compatible with those of Billardet al. and no hypotension that was clinically signifi-cant and required treatment (SBP  < 90) occurred inour study.Pre-treatment with non-depolarizing muscle relax-ants was generally preferred to prevent succinyl-choline-induced fasciculations. However, there arealternative treatment strategies. Randell et al. (18)demonstrated that isoflurane in nitrous oxide inhibitssuccinylcholine-induced muscle fasciculations in chil-dren. Propofol has been shown to decrease muscletone in a dose-dependent manner in clinical use, andthis effect is attributed not only to central nervoussystem depression but also to a block in skeletalmuscle sodium channels (19). Additionally, theadministration of propofol without neuromuscularblockade provides adequate conditions for trachealintubation (20). In previous studies (3, 5, 13) in whichpropofol was administered at an induction dose(2mgkg  1 ), it did not attenuate fasciculations, andthis finding correlated with Group II in our study,but propofol 3.5mgkg  1 might interfere more withmuscle relaxation, even though it did not acton the neuromuscular junction. In our study, high-dose propofol attenuated both the incidence andseverity of muscle fasciculations, as well as CKelevation.In conclusion, we believe that propofol 3.5mgkg  1 administered for induction of anesthesia is capable ofreducing the incidence of succinylcholine-inducedfasciculations and postoperative myalgia. References 1. McLoughlin C, Elliot P, McCarthy G, Mirakhur RK. Musclepains and biochemical changes following suxamethoniumadministration after six pretreatment regimens.  Anaesthesia 1992:  47  : 202—6.2. Murphy PG, Myers DS, Davies MJ, Webster NR, Jones JG.The antioxidant potential of propofol.  Br J Anaesth  1992:  68 :613—8.3. Manataki AD, Anaoutoglu HM, Tefa LK, Glatzounis GK,Papadopoulos GS. Continuous propofol administration forsuxamethonium-induced postoperative myalgia.  Anaesthesia 1999:  54 : 419—22.4. McClymont C. A comparison of the effect of the propofol orthiopentone on the incidence and severity of suxametho-nium-induced myalgia.  Anaesth Intensive Care 1994: 22 : 174—9.5. Maddineni VR, Mirakhur RK, Cooper AR. Myalgia and bio-chemical changes following suxamethonium after inductionof anesthesia with thiopentone or propofol.  Anaesthesia  1993: 48 : 626—8.6. Mingus ML, Herlich A, Eisenkraft JB. Attenuation of suxa-methonium myalgias. Effect of midazolam and vecuronium.  Anaesthesia  1990:  45 : 834—7.7. Harvey SC, Roland P, Bailey MK, Tomlin MK, Williams A.A randomized, double-blind comparison of rocuronium,d-tubocurarine, and ‘mini-dose’ succinylcholine for preventingsuccinylcholine-induced muscle fasciculations.  Anesth Analg 1998:  87  : 719—22.8. Churchill-Davidson HC. Suxamethonium (succinylcholine)chloride and muscle pains.  BMJ   1954:  1 : 74—5.9. Hartman GS, Fiamengo SA, Riker WF Jr. Succinylcholine:mechanism of fasciculations and their prevention by d -tubocurarine or diphenylhydantion.  Anesthesiology  1986: 65 : 405—13.10. Suarez-Kurtz G, Eastwood AB. Release of sarcoplasmicenzymes from frog skeletal muscle.  Am J Physiol  1981:  241 :C98—105.11. McLoughlin C, Nesbitt GA, Howe JP. Suxamethoniuminduced myalgia and the effect of pre-operative administra-tion of oral aspirin.  Anaesthesia  1988:  43 : 565—7.12. Mizogami M, Fujibayashi T, Goto Y. Succinylcholine-inducedfasciculations in denervated rat muscles as measured using31P-NMR spectroscopy: the effect of pretreatment with dan-trolene or vecuronium.  Acta Anaesthesiol Scand  1998:  42 :472—7. Propofol for preventing myalgia 183  13. Smith I, Ding Y, White PF. Muscle pain after outpatientlaparoscopy-influence of propofol versus thiopental andenflurane.  Anesth Analg  1993:  76 : 1181—4.14. Dottori O, Lof BA, Ygge H. Muscle pains after suxametho-nium.  Acta Anaesthesiol Scand  1965:  9 : 247—56.15. Newman PTF, Ormston TOG. Muscle pain followingadministration of suxamethonium: the aetiological role ofmuscle fitness.  Br J Anaesth  1966:  38 : 533—44.16. Bruce DL, Downs JB, Kulkarni P, Caplan L. Precurarizationinhibits maximal ventilatory effort.  Anesthesiology  1984:  61 :618—21.17. Billard V, Moula F, Bourgain JL, Megnigbeto A, Stanski DR.Hemodynamic response to induction and intubation: Propo-fol fentanyl interaction.  Anesthesiology  1994:  81 : 1384—93.18. Randell T, Yli-Hankala A, Lindgren L. Isoflurane inhibitsmuscle fasciculations caused by succinylcholine in children.  Acta Anaesthesiol Scand  1993:  37  : 262—4.19. Haeseler G, Stormer M, Bufler J et al. Propofol blocks humanskeletal muscle sodium channels in a voltage-dependentmanner.  Anesth Analg  2001:  92 : 1192—8.20. Scheller MS, Zornow MH, Saidman LJ. Tracheal intubationwithout the use of muscle relaxants: a technique using pro-pofol and varying doses of alfentanil.  Anesth Analg  1992:  75 :788—93.Address:  Alper Kararmaz , MDDicle University HospitalDepartment of Anesthesiology21280 DiyarbakirTurkeye-mail: alper@dicle.edu.tr A. Kararmaz et al. 184
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