Objective:To evaluate the efficacy and clinical application value of mouse nerve growth factor combined with neostigmine in the treatment of nerve injury in patients bitten by Bungarus multicinctus by a prospective single-blind controlled clinical study.Methods:A total of 60 patients after bitten by Bungarus multicinctus admitted to the Emergency Department of Ganzhou People’s Hospital from June 2020 to June 2022 were consecutively enrolled.The youngest was 14 years old and the oldest was 83 years old.There were 35 males(58.33%)and 25 females(41.67%).There were 29 cases admitted to the hospital within 4 hours after the bite,and 15 cases in the treatment group,aged(56.07±12.03)years,6 females and 9 males.There were 14 cases in the control group,aged(54.07±14.05)years,7 females and 7 males.There were 31 patients admitted to hospital more than or equal to 4 hours after the bite.There were 18 patients in the treatment group,aged(53.50±20.27)years,including 6 females and 12 males.The control group included 13 cases,aged(51.00±17.65)years,7 males and 6 females.Due to the high correlation between the degree of poisoning injury and the duration of poisoning,we divided the patients into two groups according to the time from the bite to the receiving of standard medical assistance,which was less than 4 hours and more than or equal to 4 hours.The two groups were divided into the treatment group and the control group according to whether the patients were treated with rat nerve growth factor combined with neostigmine.All cases received routine monitoring after admission,and were treated according to the routine treatment of snakebite,including adequate targeted antivenom,necessary debridement,tetanus antitoxin injection,necessary prophylactic antibiotics,and ventilator support for patients with respiratory depression.The treatment group was given intramuscular injection of neostigmine 1mg q8 h and mouse nerve growth factor 18ug/d on the basis of conventional treatment.The control group was only given conventional treatment.The age,sex,Body mass index(BMI),admission heart rate,white blood cell count(WBC),alanineaminotra ferase(ALT),serum albumin(SA),creatinine(Cr),serum potassium(K),D-dimer(DD),high sensitivity C-Reactive Protein(Hs-CRP),Myasthenia Gravis Composite(MGC)scores of all enrolled cases were recorded together.Myasthenia gravis Complex Scale(MGC)scores were performed for all patients at admission,4 hours,8 hours,and24 hours.Muscle strength was continuously assessed and the recovery time of muscle strength was recorded.Results:1.Comparison of MGC score,muscle strength recovery time,and length of stay of patients in different groups: Four hours after admission,MGS scores of the three groups decreased except for the ≥4h control group,which decreased by 2.43±2.53 in the < 4h control group,4.27±2.22 in the < 4h treatment group and 15.94±12.02 in the≥4h treatment group,respectively.Regardless of the ≥4h group or the < 4h group,the MGS score of the treatment group was lower than that of the control group at the same time(P < 0.05),the difference between the two groups of ≥4h was 14.52 points,and the difference between the two groups of < 4h was 1.91 points.In both control and treatment groups,patients with < 4h had lower MGS scores than patients with ≥4h(P< 0.001 for all).After that,the MGS scores of all groups showed a continuous downward trend,until the MGS scores of both groups were 0 when 24 hours was less than 4 hours.There was no statistically significant difference in the scores of the < 4h group and the two groups 8 hours after admission,but the MGS scores of the two groups were lower than those of the same treatment ≥4h group(P < 0.05).For patients≥4h,MGS scores in the treatment group were lower than those in the control group(P < 0.001)during 4 to 24 hours after admission.The muscle strength recovery time of patients ≥4h was evaluated,which was 24(20)h in the treatment group and 48(24)h in the control group,respectively,after excluding the influence of MGS score on admission,there was still a difference between the groups(P < 0.001).There was no difference in the length of hospital stay among the four groups,and the median length of hospital stay was 2 days.2.The trend of MGS score transformation over time was observed in all groups after treatment,and all groups showed a linear trend(all P <0.05).For patients < 4 hours,the MGS score of the control group was basically 0 within8 hours of admission,while that of the treatment group was only 4 hours.For patients with 4 hours or more,the control group did not show significant changes in MGS score after 4 hours of treatment,and then showed a downward trend,and it was still more than 10 points at 24 hours,while the treatment group rapidly dropped to about 5 points after 4 hours of treatment,and there was still a small decline from then to 24 hours.3.Correlation analysis between MGS score and muscle strength recovery time: MGS score was positively correlated with muscle strength recovery time at 4h after admission(r=0.54,p=0.00);MGS score at 8h after admission was positively correlated with muscle strength recovery time(r=0.72,p=0.00).24 h after admission,MGS score was positively correlated with muscle strength recovery time(r=0.64,p=0.00).Muscle strength recovery time was positively correlated with duration of onset(r=0.91,p=0.00).4.Correlation between duration of onset and prognosis: Duration of onset was strongly positively correlated with admission MGS score(r=0.908,P < 0.001).After admission,the duration of onset was positively correlated with MGS scores at 4,8,and 24 hours after admission,and the correlation coefficient increased after controlling for experimental grouping.The relationship between duration of onset and MGS score after admission in the treatment group showed a linear trend,while the linear trend was not obvious in the control group.The results of correlation analysis showed that the duration of onset was positively correlated with the recovery time of muscle strength(r=0.757,P < 0.001),and the correlation coefficient increased with the control group,showing a strong correlation(r= 0.892).Conclusion:1.In the patients admitted less than 4 hours after admission,most of the patients had a good prognosis without sequelae after conventional treatment.Neostigmine combined with mouse nerve growth factor had no significant effect on the long-term prognosis,but it could shorten the duration of muscle weakness,reduce MGC score,promote nerve repair and muscle strength recovery.2.High MGC score at admission was found in patients admitted to hospital for more than or equal to 4 hours.The MGC scores of the treatment group at 4 hours,8 hours and 24 hours after admission were statistically significant compared with the control group.Compared with the observation group,the treatment group can shorten the time of muscle weakness,reduce MGC score,promote nerve repair and muscle strength recovery in a certain period of time.The muscle strength of the treatment group recovered faster than that of the control group during the whole course of the disease.Neostigmine combined with mouse nerve growth factor can shorten the duration of myasthenia,reduce MGC score and neuromuscular blockade in severe patients with delayed treatment after bitten by Bungarus multicinctus.3.The later the starting time of treatment(the time from injury to admission),the longer the recovery time of muscle strength;The higher the MGC score at admission,the longer the recovery time of muscle strength.4.The combination of mouse nerve growth factor and neosmine can shorten the time of muscle weakness after bite,promote the recovery of injured nerves,and improve the clinical symptoms caused by nerve snake venom. |