Efficacy Of Clemastine Fumarate Injection On Prevention And Treatment Of Histamine Release Induced By Drugs In Perioperative Period

Background and ObjectiveThe release of histamine can be induced by many factors in the perioperative period such as drugs,latex,blood and blood products,etc.The release of histamine and other vasoactive substances induced by these substances can cause skin reaction,hypotension,tachycardia,or even severe life-threatening adverse reaction.So,effective prevention and treatment of histamine release during perioperative period is very necessary.Clemastine fumarate is a new kind of H1 receptor antagonist,which has a faster onset and stronger effect,long duration in the treatment of anaphylactic reaction.Clemastine can not only antagonize histamine at H1 receptor level,but also reduce histamine release from mast cells.In this paper,atracurium and protamine which can easily induce histamine release during perioperative period are selected to evaluate the efficacy of clemastine fumarate injection on prevention and treatment of histamine release during perioperative period.MethodsPart Ⅰ:Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱpatients,aged 20～60 yr,with body mass index of 17～26 kg/m 2 scheduled for elective modified radical mastectomy,were divided into 2 groups(n=40 each)using a random number table:control group(group C)and clemastine fumarat group(group CF).Clemastine fumarate 2 mg was injected intramuscularly at 20 min before induction of anesthesia.Anesthesia was induced with iv midazolam 0.1 mg/kg,etomidate 0.3 mg/kg,fentanyl 4～6 μg/kg and atracurium 0.8 mg/kg.The patients were tracheally intubated and mechanically ventilated.Anesthesia was maintained with inhalation of 2%sevoflurane.Before administration of clemastine fumarate(T0),at 20 min after administration(T1),immediately before administration of atracurium(T2),and at 2,5,10 and 20 min after administration of atracurium(T3～6),blood samples were taken from the radial artery for determination of plasma histamine concentrations,and the peak airway pressure was recorded.The degree of cutaneous color was observed and scored.The occurrence of histaminemia and adverse cardiovascular events was recorded.Steward recovery scores and Ramsay sedation scores were recorded at 10 min after removal of the laryngeal mask airway.PartⅡ:Sixty patients scheduled for OP-CABP were randomly divided into 2 groups(n=30 each group).Clemastine fumarate(2mg/2ml,Group CF)or normal saline(2ml,Group C)was injected intramuscularly 20 minutes before intravenously injecting protamine for neutralizing heparin.SP,DP,MAP,HR,CVP were observed and plasma histamine level was measured at 0.5 min before intravenously injecting protamine(T0)and 2 minute(T1),5 minute(T2),10 minute(T3),20 minute(T4)and 30 minute(T5)after protamine injection.The time period and the pauses during protamine injecting process and the requirement of vasoactive drugs were recorded.ResultsPart Ⅰ:The incidence of histaminemia was 60%and 8%in C and CF groups,respectively.Compared with group C,the plasma histamine concentrations,incidence of histaminemia,degree of cutaneous color,and incidence of hypotension and tachycardia were significantly decreased(P<0.05),and no significant change was found in the peak airway pressure,Steward recovery scores and Ramsay sedation scores in group CF(P<0.05).Part Ⅱ:Compared with group C,HR was decreased at T1,SP,DP,MAP and CVP was significantly increased at T1,2 in group CF(P<0.05 or 0.01).The time period and the pauses of protamine intravenous injection and the consumption of norepinephrine were significantly shorter or less in group CF than those in Group C(P<0.01).Compared with group C,The plasma histamine concentrations were decreased at T1～T3 in Group CF(P<0.05 or 0.01).ConclusionPart I:For atracurium-induced release of histamine in the patients undergoing surgery under general anesthesia,clemastine fumarate 2 mg injected intramuscularly before operation can not only antagonize histamine at H1 level,but also reduce histamine release.Clemastine fumarate 2 mg exerts no influence on recovery from anesthesia and produces good antihistamine efficacy.PartPart Ⅱ:H1 histamine receptor blocker clemastine fumarate is able to antagonize protamine-induced disturbance on hemodynamics in patients undergoing OP-CABG.