ORIGINAL ARTICLE
Effect of intravenous dezocine on fentanyl-induced cough during general anesthesia induction:a double-blinded,prospective,randomized,controlled trial
Zhen-Tao Sun •Chun-Yao Yang •Zhi Cui •
Jie Zhang •Xue-Ping Han
rent
Received:15June 2011/Accepted:7September 2011/Published online:21September 2011ÓJapane Society of Anesthesiologists 2011
Abstract
Purpo To evaluate the suppressive effect of intrave-nous dezocine on fentanyl-induced cough during the induction of general anesthesia.
Methods A total of 120patients,American Society of Anesthesiologists (ASA)physical status I–II,were ran-domized into two equally sized groups (n =60).The two groups were given either intravenous dezocine 0.1mg/kg or a matching placebo (equal volume of 0.9%saline)10min before the induction of g
eneral anesthesia.Patients were induced with midazolam 0.1mg/kg,fentanyl 5l g/kg,propofol 1–1.5mg/kg,and suxamethonium 1.5mg/kg.The injection time of fentanyl was less than 2s in all patients.The occurrence of cough was recorded 2min after fentanyl bolus.
Results No patient in the dezocine group had cough,and 42patients in the control group had cough.This dif-ference was statistically different between the two groups (P =0.000).
Conclusion The results demonstrate that intravenous dezocine 0.1mg/kg 10min prior to induction was effective in suppressing fentanyl-induced cough in our patients.Keywords Fentanyl ÁCough ÁDezocine ÁGeneral anesthesia ÁSuppress
Introduction
Fentanyl,an opioid analgesic,is widely ud as a pre-induction adjunct due to its inten analgesia,short dura-tion of action,and cardiovascular stability,but cough as well as truncal rigidity elicited by fentanyl is undesirable.Cough induced during the induction of general anesthesia has the potential to elevate cerebral,ocular,or abdominal pressure,which may lead to a health-threatening condition in the patients [1].Although fentanyl-induced cough is transient and not vere in most patients,the verity should not be ignored in patients with pneumothorax,cerebral aneurysm brain tr
cpa是什么auma,brain hernia,open eye injury,arterial aneurysm rection,and hypernsitive airway dia.Animal experiments have demonstrated that the u of a low-efficacy opioid in association with high-efficacy opioid will not only enhance the analgesic effect but also antagonize a number of undesirable adver effects,such as pruritus and naua caud by the higher efficacy opioid [2].Pre-emptive fentanyl prior to the administration of fentanyl is able to effectively suppress fentanyl-induced cough [3].Dezocine is an analgesic agent and a full agonist of j -receptor and partial agonist of l -receptor without classic l -receptor dependence.As the effect of dezocine on fentanyl-induced cough is still unknown,we designed a prospective,randomized,double-blinded,and placebo controlled study to investigate the effect of dezocine on fentanyl-induced cough in patients during the induction of general anesthesia.
Patients and methods
Ethical approval for this study was provided by the Ethical Committee of the First Affiliated Hospital of Zhengzhou
Z.-T.Sun ÁC.-Y.Yang ÁZ.Cui ÁJ.Zhang ÁX.-P.Han (&)Department of Anesthesia,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan,China e-mail:xuepinghan@live
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J Anesth (2011)25:860–863DOI 10.1007/s00540-011-1237-x
University,Zhengzhou,Henan,China.Informed connt was obtained from all patients enrolled in this randomized, prospective,controlled study.A total of120American Society of Anesthesiologists(ASA)physical status I–II patients(age range20–60years,weight45–90kg)sched-uled for elective surgery under general anesthesia were enrolled in this study.Exclusive criteria included known allergies,sinus bradycardia,vere neurological,respira-tory or cardiovascular dias,narcotic drug dependence and recent history of opioid application,a history of smoking,hepatic and renal dysfunction,gallbladder sur-gery,pregnancy,lactation and delivery surgery,upper airway infection within2weeks of surgery.Such condi-tions may cau spontaneous cough.
Patients meeting the inclusive criteria during the pre-anesthetic evaluation were randomly assigned into two groups of60patients each using a computer-generated table of random numbers.
Patients schedule for surgery were unpremedicated and had fasted.Upon arrival at the operating room,patients were cannulated with an intravenous(IV)cannula(22G)on the dorsum of the right forear
m.Monitoring of each patient was accomplished by electrocardiogram,non-invasive blood pressure[systolic(SBP)and diastolic blood pressure (DBP)],pul oximetry(SpO2),and end-tidal carbon dioxide measurement(M1205A;Philips,Eindhoven,the Netherlands).All patients were randomly assigned to receive either dezocine0.1mg/kg or a matching placebo (equal volume of0.9%saline)10min before the induction of anesthesia.The application of anesthesia was standard-ized in the two groups.The patients werefirst induced with midazolam0.1mg/kg,fentanyl5l g/kg,propofol 1–1.5mg/kg,and suxamethonium1.5mg/kg.The injec-tion time of fentanyl was limited to under2s;propofol and suxamethonium were administered2min later,after the fentanyl bolus.All medications were provided by the hospital pharmacy(dezocine:SN10042021;Yangtze River Pharmaceutical,Co.,Jiangsun,China;fentanyl:SN100302 Yichang Humanwell Pharmaceutical Co.,Hubei,China), identical,and administered intravenously.
A blinded obrver,who had no knowledge of the pre-medication given to the patients,recorded the occurrences of coughing2min after administration of the fentanyl bolus.It has been reported that cough occurs within1min of the fentanyl bolus iv[4],so we choo2min after the administration of the fentanyl bolus.SBP,DBP,heart rate (HR),and SpO2were recorded before the administration of dezocine or normal saline(T0)and2min(T1)later after fentanyl injection.Assisted mask ventilation oxy
gen was applied if desaturation was obrved(SpO2\89%).Other side effects related to fentanyl and dezocine,such as truncal rigidity and apnea,were also recorded after the fentanyl injection.
All data were reported as the mean±standard deviation (SD)or as percentages.The demographic data were ana-lyzed with the unpaired Student’s t test.Comparison between two groups was performed for overall incidence of cough by Fisher’s exact test with Bonferroni correction. General linear model repeated-measures analys were applied to compare differences of vital signs between groups before and after the fentanyl injection.The software package SPSS ver.14.0(SPSS,Chicago,IL)was ud for statistical analysis.A P\0.05was considered to be sta-tistically significant.
Results
All patients completed this study as required by the proto-col.The demographic data were compared in both groups, and no statistically significant difference between the two groups was found with regard to x,age,and weight. (Table1).The hemodynamic data(BP,HR,and SpO2) were also simila,r and there was no significant difference between groups in the baline value or after fentanyl injection(Table2).No patient in the dezocine group had cough,and42patients in the placebo group(0v
s.70%)had cough;this difference was statistically significant (P=0.000)(Table3).None of the patients suffered from hypoxemia(SpO2\89%),desaturation,apnea,truncal rigidity,or other adver effects after fentanyl injection. Discussion
steal过去式Cough is an inten body reflex irritation,and it may cau instantaneous changes in the internal environment of a patient on perioperative anesthesia.Tweed and Dakin reported cas requiring immediate tracheal intubation for excessive cough prior to the induction of general anesthesia [5].In our study,dezocine completely suppresd fentanyl-induced cough.The incidence of cough elicited by fentanyl during general anesthesia induction has been reported to vary between18and65%[6].The incidence of fentanyl-induced cough among our patients was70%,which may Table1Patient characteristics
Patient
characteristics
Dezocine group
(n=60)
Placebo group
(n=60)
P value
Age(years)46.6±10.348.2±10.60.4 Sex(Male/female)36/2432/280.5 Weight(kg)63.5±7.664.6±9.50.5 Values are mean±SD.No statistical difference was obrved between dezocine and placebo groups
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due to the small sample size in our study and the fast injection of fentanyl.The injection time of fentanyl is an important factor that affects cough frequency[7].The threshold of fentanyl-induced cough may be readily reached with a rapid intravenous injection.Many factors have been associated with fentanyl-induced cough,such as drug dosage and concentration,order of drug administra-tion,intravenous injection rate and site[8],individual physical condition,age,x,weight,dia history, smoking,and family genetics.A number of techniques have been applied to reduce the incidence of fentanyl-induced cough,including the u of betamethasone(8.3vs. 35%),dexamethasone(6.3vs.21.3%)[9],ephedrine (21vs.65%)[10],lidocaine(13.1%)[11],ketamine (7.2
vs.21.6%)[12],and propofol(6.7%)[13],a change the order of administering the drugs,the speed of fentanyl administration,and fentanyl concentration.The u of the drugs in the earlier studies was unable to completely prevent fentanyl-induced cough,and some of them are very limited in terms of their clinical application.For example, betamethasone and dexamethasone are steroids and should be ud under strict conditions;ephedrine can cau hemodynamic changes;lidocaine does not have a signifi-cant influence on the verity of cough;ketamine is scar-cely ud in adult general anesthesia,especially in patients with hypertension,elevation of intracranial pressure,and intraocular pressure.In a study involving the pre-injection of propofol as a measure to suppress fentanyl-induced cough,the incidence of cough in the propofol group(rec-ommended do1.5mg/kg)was approximately6.7%[13]. An overdo of propofol may caufluctuation of hemo-dynamics.Patients who are nsitive to the effects of muscle relaxants cannot be given vecuronium bromide early,as breathing difficulties may ari.Other rearch has suggested that prolongation of the effective duration of fentanyl and dilution of the fentanyl do before adminis-tration are not convenient practices in some emergent sit-uations.In our study,dezocine had the effect of analgesia and had a synergistic effect on fentanyl;as such,it was able to completely prevent cough.In a subquent study,we found that dezocine suppresd the fentanyl induced cough just before the fentanyl bolus,thereby removing the necessity to wait10min before administering the fentanyl. Conquently,i
t may be possible to u dezocine as an advance analgesia.The limitation of the study is we did not compare the verity of cough between the two groups[14] becau we obrved no cough in dezocine group;there-fore we just recorded the incidence of cough despite the verity.
The mechanisms of fentanyl-induced cough have been reported to be opioid receptors[15],C-fiber receptors, rapidly adapting pulmonary stretch receptors,histamine, and the citrate in fentanyl injectionfluid.
Dezocine is a new bridge central amino tetralin,a mixed opioid agonist/antagonist analgesic,a completely j-recep-tor agonist,and a partial l-receptor agonist without classic l-receptor dependence liability.As a result of various countries’drugs admittance system,dezocine may not be accesd in every country and available for u in all hos-pitals.However,dezocine is widely applied as an advance and postoperative pain analgesic agent in many countries. The results of animal experiments have demonstrated that the u of a low-efficacy opioid in association with a high-efficacy opioid will not only enhance the analgesic effect but also antagonize some of undesirable side effects,such as pruritus and naua,of the higher efficacy opioid. This double benefit effect may due to the opioid receptors agonized and antagonized.In has been reported that pre-emptive fentanyl25l g(0.5ml)1min before the admin-istration of fentanyl125or150l g significantly reduced the i
ncidence of fentanyl-induced cough in both pre-emptive groups[3.5%for the125l g fentanyl group and7.5%for the150l g fentanyl group compared to the saline group (18.5%)].The frequency along with dosage implies that partial l receptor agonists did not reach the cough thresh-old,indicating that partial l pre-agonized receptors cannot
Table2Changes in vital signs after treatment in both groups
out there
Group SBP(mmHg)DBP(mmHg)HR(bpm)SpO2(%) T0T1T0T1T0T1T0T1
Dezocine117.6±17.3118.5±15.169.3±10.469.6±13.377.7±10.476.9±10.698.4±1.898.8±1.4 Placebo117.6±14.3114.3±16.372.7±9.673.9±11.280.63±9.679.3±11.098.4±1.598.3±1.5
SBP Systolic blood pressure,DBP diastolic blood pressure,HR heart rate,SpO2pul oximeter oxygen saturation,T0Time before administration of dezocine or normal saline injection,T12min after fentanyl injection
No statistical difference was obrved between the dezocine and placebo groups
Table3Incidence of coughing in both groups
Group Total(n)Cough(n)Ratio(%)
Dezocine6000
Placebo604270
P value=0.000(dezocine vs.placebo group)
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2016高考语文completely suppress cough.Dezocine therefore suppress fentanyl-induced cough by other mechanisms.
In the context of fentanyl-induced cough,we speculate that the possible mechanism of dezocine suppressing fen-tanyl-induced cough could be as follows.(1)dezocine is a partial l-receptor agonist that either caus no cough or possibly induces cough when above the cough threshold;it also occupies the l-receptor,preventing the combination of fentanyl with l-receptor.(2)Dezocine agonizes j recep-tors,which in turn antagonize fentanyl-activated l recep-tors,thereby inducing cough.(3)Dezocine counteracts the action of fentanyl by a central gating mechanism of cough suppression,predominantly via C-fibers receptors.(4) Dezocine inhibits the relea of histamine by antagonizing and suppressing cough reflex.Some rearchers have pro-pod that opioid receptors
exist in the brain and spinal cord and that the differences in intensity of the analgesic and side effects of narcotic drugs are related to opioid receptors in different parts of brain.In1990,Karlsson and his co-workers[16]found that opioid drugs affected l and j receptors on guinea pig trachea and bronchial trees, resulting in inhibition of bronchial cough and reflex con-traction of the role.In this ca,it is not impossible to surmi that opioid receptors also exist in humans and mediate the antitussive effect.
Conclusions
Our results demonstrate that IV dezocine0.1mg/kg 10min before fentanyl is an effective and clinically feasible method for suppressing fentanyl-induced cough during general anesthesia induction.
Acknowledgments This work was supported the Department of Anesthesia,The First Affiliated Hospital of Zhengzhou University, Zhengzhou,Henan,China.
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