Effects Of Promethazine Hydrochloride On Fentanyl Induced Cough

Objective Fentanyl induced cough (Fentanyl induced cough, FIC) greatlyincreases the risk during general anesthesia induction.Many clinical methodsand drug have been applied to inhibition of FIC. It has not been reported thatwhether clinical commonly used antitussive promethazine can inhibit FIC ornot so far. The aim of this study was to observe the effect of intravenousinjection of small dose of promethazine hydrochloride on fentanyl inducedcough(FIC) during general anesthetic induction, looking for a new method toinhibit FIC during general anesthetic induction. Observing the changes of theplasma histamine concentration after intravenous injection of fentanyl orpreinjection of promethazine hydrochloride after intravenous injection offentanyl during general anesthetic induction to investigate the role of histaminein FIC and to explore that whether promethazine hydrochloride prevents FIC bypreventing the release of histamine.MethodsFirst part: This article detailed a double-blind, randomized study. Two hundredelective operation patients undergoing general anesthesia were selected andrandomly allocated to4groups before operations: control group, experimentalgroup1,2and3. Four drugs (0.9%NS,0.5mg/ml promethazine hydrochloride,1mg/ml promethazine hydrochloride,1.5mg/ml promethazine hydrochloride)with a dose of0.1ml/kg were injected before induction respectively. All patientswere inducted by intravenous injection of fentanyl3μg/kg, followed withpropofol1-1.5mg/kg and cisatracurium0.2mg/kg2min later. The depth ofanesthesia and muscle relaxation were maintained with inhalation of sevoflure(1-1.5MAC) and intravenous infusion of remifentanil0.1-0.2μg/kg/min,cisatracurium0.3mg/kg/h by syringe pumps continuously. The occurrence ofcough was recorded, including onset time, frequency and intensity of coughwithin two minutes after injection of fentanyl. The value of blood pressure and heart rate was recorded at four time points: before preinjection of promethazinehydrochloride（T0）, before injection of fentanyl（T1）, before endotrachealintubation（T3） and after intubation（T4）. The time from the end of operationto extubation, occurrence of nausea and vomiting postoperatively wererecorded.Second part: According to the results of the first part, the dose of promethazinehydrochloride in experiment group2was chosen in this part. Thirty calculouscholecystitis patients undergoing laparoscopic holecystectomy after generalanesthesia were divided randomly into two groups: fentanyl group(group F) andpromethazine+fentanyl group(group FP).Patients in two groups were receivedfentanyl3μg/kg,0.1mg/kg promethazine hydrochloride+3μg/kg fentanylrespectively, and other anaesthesias methods were the same as before.2ml ofperipheral venous blood were taken before injection of drugs（t0）,2min afterinjection of drugs（t1）,2min after intubation（t2）for measurement of plasmahistamine concentration.Results First part(1)General information in4groups：There were no significant differencesamong all the groups in age, sex, weight, height, the kinds of disease anddepartment（p>0.05）.(2)Blood pressure and heart rates in four groups: Comparison amonggroups:There were no significant differences among all the groups in systolicblood pressure, diastolic blood pressure and heart rate at T0, T1, T2, T3.Diastolic blood pressure in control group, experimental group2and3wassingnificantly higher than that in experimental group1at T4（p<0.05）. Heartrate in experimental group3was singnificantly higher than that in controlgroup, experimental group1and2at T4（p<0.05）. Comparison in groups:systolic blood pressure, diastolic blood pressure and rate in these four groups atT3were significantly lower than those at T0, T1, T2and T4, but there were no significant differences in systolic blood pressure, diastolic blood pressure andheart rate at T0, T1, T2, T3in groups（p>0.05）.(3)Incidence of FIC in four groups:Comparison among groups: In control group,16patients had FIC(32%), andthe number of mild, moderate, severe cough was11,3,2respectively. Inexperimental group1,8patients had FIC(16%), and the number of mild,moderate, severe cough was4,2,2respectively. In experimental group2,6patients had FIC(12%), and the number of mild, moderate, severe cough was1,2,3respectively. In experimental group3,5patients had FIC(10%), and thenumber of mild, moderate, severe cough was2,0,3respectively. The totalincidence of cough in experimental group1,2,3was significantly lower thanthat in control group（p<0.05）. The incidence of mild cough in experimentalgroup1,2,3was significantly lower than that in control group（p<0.05）. Therewere no significant differences among all the groups in the incidence ofmoderate cough and severe cough（p>0.05）. Comparison in groups: Theincidence of mild cough was significantly higher than that of moderate andsevere cough in control group（p<0.05）, and there was no significant differencebetween incidence of moderate cough and that of severe cough in control group（p>0.05）. There were no significant differences in experimental group1,2,3in the incidence of moderate cough and severe cough（p>0.05）.(4) Average occurrence time of FIC in four groups was12.60,12.89,13.36,12.25s respectively. There were no significant differences among all the groups（p>0.05）.(5)Extubation time after waking: The time from the end of surgery to trachealextubation in control group, experimental group1,2,3was7.40±1.80min,7.52±1.81min,7.44±1.89min,7.32±2.11min respectively. There were nosignificant differences among all the groups（p>0.05）.(6)The occurrence of postoperative nausea and vomiting: The number of postoperative nausea in control group, experimental group1,2,3was1,1,1and2respectively. The number of postoperative vomiting in the four groupswas7,10,4and4respectively. There were no significant differences among allthe groups（p>0.05）.Second part(1) There were no significant differences among all the groups in generalinformation（p>0.05）.(2)The plasma histamine concentration in group F at T0, T1, T2was8.53±2.04,7.24±2.14,7.57±1.83ng/ml. The plasma histamine concentration in group FP atT0, T1, T2was8.23±2.58,7.33±1.89,7.23±2.02ng/ml. There were nosignificant differences in both groups at these time points and there were alsono significant differences between the two groups（p>0.05）.Conclusion(1)Pre-injection of promethazine hydrochloride with0.05,0.1, and0.15mg/kgdecreased the incidence of FIC. The three doses of promethazine hydrochloridehad light effects on blood pressure during induction, but had no significanteffects on the extubation time, postoperative complications.(2)Injection of fentanyl3μg/kg during anesthesia induction had no significanteffect on plasma histamine concentration. Preinjection promethazinehydrochloride0.1mg/kg before3μg/kg fentanyl injection had also nosignificant effect on plasma histamine concentration.