| BackgroundEpilepsy is a common neurological disease,and its treatment is mainly drug therapy.The common antiepileptic drugs(AEDs)include traditional AEDs and new AEDs.Epilepsy drug treatment may bring a lot of adverse reactions and related blood indicators of abnormalities,such as blood ammonia,blood lipid,blood sodium and blood homocysteine concentrations,and affect the treatment of epilepsy patients and quality of life.With the long-term use of antiepileptic drugs,the incidence of cardiovascular and cerebrovascular diseases in patients with epilepsy is higher than that in normal people.Epilepsy may also be induced,increase the frequency of seizures,easy to affect the long-term effect of antiepileptic treatment.At present,studies have found that traditional AEDs have more common adverse effects on blood metabolic indicators than new AEDs,including hyperammonemia,elevated blood lipids,hyponatremia,and hyperhomocysteine.However,different studies at home and abroad suggest that the impact of AEDs,especially the new AEDs,on hematological metabolic indicators is still unclear,so more clinical studies are needed to evaluate the impact of AEDs on hematological metabolism to guide clinical diagnosis and treatment.ObjectiveThis study compared blood ammonia(Ammo)levels,lipid levels,including total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-c),low density lipoprotein cholesterol(LDL-c),sodium levels(Na+)and homocysteine(Hcy)levels before and after the medication in the patients with epilepsy who had taken AEDs for at least 12 months.At the same time,the differences of the above-mentioned hematological metabolic indicators of different genders,AEDs monotherapy,multidrug therapy and AEDs types were evaluated.MethodsAccording to the new clinical definition of epilepsy proposed by the International League Against Epilepsy(ILAE)in 2014,two groups of clinically diagnosed epilepsy patients were included in this study:163 patients in the blood ammonia group and 221 patients in the blood lipid,sodium and homocysteine group.Subjects with chronic active illness and taking medications known to affect hematological metabolic indicators were excluded.Age,sex,drug use,medical history were collected in the two groups.According to the number of oral AEDs,patients were divided into two subgroups of AEDs monotherapy and multidrug therapy;according to the type of AEDs,patients were divided into two subgroups of enzyme inducing antiepileptic drugs(EIAEDs)and non-enzyme inducing antiepileptic drugs(NEIAEDs).At the same time,the hematologic indexes of patients exposed to sodium valproate(VPA),Carbamazepine(CBZ),Oxcarbazepine(OXC),Lamotrigine(LTG),topiramate(TPM),Levetiracetam(LEV)in the AEDs monotherapy group were compared.After obtaining the informed consent of the patients,blood samples from the two groups were obtained through intravenous blood sampling before and after medication(at least 12 months),and the levels of blood ammonia,blood lipid,blood sodium and blood homocysteine were measured.Statistical analysis software SPSS 25.0 was used to compare the blood metabolism indexes,analyze the influence of AEDs on metabolism,and explore the influence of age,gender,AEDs quantity and type on blood metabolism.ResultsStatistical analysis showed that the blood ammonia level(19.09±8.18umol/L)after taking AEDs was higher than that before(15.79±6.89umol/L),and the difference was statistically significant(P=0.023);the incidence of hyperammonemia after medication was 11.04%,which was higher than that before(4.29%),and the difference was statistically significant(P=0.022);the TC level(4.45±0.86mmol/L)was higher than that before(4.19±0.79mmol/L),and the difference was statistically significant(P<0.001);the TG level(1.33±0.79mmol/L)was higher than that before(1.21±0.75mmol/L),and the difference was statistically significant(P=0.012);the HDL-c level(1.33±0.34mmol/L)was higher than that before(1.27±0.31mmol/L),and the difference was statistically significant(P=0.003);the LDL-c level(2.46±0.74mmol/L)was higher than that before(2.33± 1.48mmol/L),and the difference was statistically significant(P=0.004);the Na+level(141.61±3.73mmol/L)was lower than that before(142.15±2.98mmol/L),and the difference was statistically significant(P=0.015);the incidence of mild hyponatremia after treatment was 3.61%,which was higher than before(0.45%),and the difference was statistically significant(P=0.037);the Hcy level(18.66±6.18umol/L)was higher than that before(15.35±5.13umol/L),and the difference was statistically significant(P=0.001);the incidence of moderate hyperhomocysteine was 15.38%after treatment,which was higher than before(7.23%),and the difference was statistically significant(P=0.006).The blood ammonia level of male patients with epilepsy after medication(21.86±9.68umol/L)was higher than that before(17.13±7.39umol/L),and the difference was statistically significant(P=0.041);the TC level of male patients(4.37±0.73mmol/L)was higher than that before(4.24±0.80mmol/L),and the difference was statistically significant(P=0.033);the HDL-C level of male patients(1.27±0.29mmol/L)was higher than that before(1.19±0.24mmol/L),and the difference was statistically significant(P=0.012);the Na+level of male patients(141.71±3.17mmol/L)was lower than that before(142.42±1.96mmol/L),and the difference was statistically significant(P=0.025);the Hcy level of male patients(21.11±7.68umol/L)was higher than that before(16.83±9.77umol/L),and the difference was statistically significant(P=0.001).The TC level of female patients with epilepsy after medication(4.35±0.85mmol/L)was higher than that before(4.13±0.65mmol/L),and the difference was statistically significant(P=0.004);the TG level of female patients(1.36±0.89mmol/L)was higher than that before(1.13±0.72mmol/L),and the difference was statistically significant(P=0.030);the LDL-c level of female patients(2.47±0.83mmol/L)was higher than that before(2.30±0.75mmol/L),and the difference was statistically significant(P=0.046).The median of blood ammonia difference(after-before medication)of epilepsy patients after taking EIAEDs was-10.00umol/L,and the median of blood ammonia difference after taking NEIAEDs was 0.00umol/L,and the difference was statistically significant(P=0.038).Intra-group comparison of EIAEDs and NEIAEDs groups was studied respectively,the blood ammonia level(18.98±6.35umol/L)after taking NEIAEDs was higher than that before(15.21±6.53umol/L),and the difference was statistically significant(P=0.045).The TC level(4.35±0.78mmol/L)after taking EIAEDs was higher than that before(4.16±0.80mmol/L),and the difference was statistically significant(P=0.047);the TG level(1.13±0.72mmol/L)after taking EIAEDs was higher than that before(0.96±0.75mmol/L),and the difference was statistically significant(P=0.047);the LDL-c level(2.39±0.60mmol/L)after taking EIAEDs was higher than that before(2.23±0.43mmol/L),and the difference was statistically significant(P=0.033).The HDL-c level(1.31±0.32mmol/L)after taking NEIAEDs was higher than that before(1.23±0.35mmol/L),and the difference was statistically significant(P=0.024);the Na+level(141.63±2.19mmol/L)after taking NEIAEDs was lower than that before(142.31±1.65mmol/L),and the difference was statistically significant(P=0.038);the Hcy level(19.13±7.18umol/L)after taking NEIAEDs was higher than that before(15.34±9.77umol/L),and the difference was statistically significant(P=0.006).The medians of the difference of blood ammonia level(after-before medication)between the VPA group,the CBZ group,the OXC group,the LTG group,the TPM group and the LEV group were 2.00umol/L,-10.00umol/L,0.00umol/L,1.50umol/L,-1.00umol/L and 0.50umol/L respectively,and the difference between the VPA group and the CBZ group was statistically significant(P=0.032).Within each single drug group,the blood ammonia level after medication with VPA was higher than before,and the difference was statistically significant(after:28.75± 14.04umol/L,before:16.92±5.00 umol/L,P=0.030);the HDL-c level after medication with VPA was higher than before,and the difference was statistically significant(after:1.28±0.29mmol/L,before:1.19±0.22mmol,P=0.036);the TC level after medication with CBZ was higher than before,and the difference was statistically significant(after:4.35±0.78mmol/L,before:4.16±0.80mmol/L,P=0.047);the TG level after medication with CBZ was higher than before,and the difference was statistically significant(after:1.13±0.72mmol/L,before:0.96±0.75mmol/L,P=0.047);the LDL-c level after medication with CBZ was higher than before,and the difference was statistically significant(after:2.39±0.60mmol/L,before:2.23±0.43mmol/L,P=0.033);the Na+level after medication with OXC was lower than before,and the difference was statistically significant(after:141.07±2.57mmol/L,before:142.21±1.97mmol/L,P=0.044);the Na+level after medication with LTG was lower than before,and the difference was statistically significant(after:141.11±2.22mmol/L,before:142.51±1.14mmol/L,P=0.008);the Hcy level after medication with LTG was higher than before,and the difference was statistically significant(after:15.85±8.64umol/L,before:12.36±3.39umol/L,P=0.027).The results of the correlation analysis between drug dose and hematological indicators showed that the dose of VPA was positively correlated with the concentration of blood ammonia(r=0.802,P=0.001),and the correlation was highly correlated.The dose of OXC was negatively correlated with the concentration of Na+(r=-0.445,P=0.048),and the correlation was low.Epilepsy patients taking VPA drugs were selected as the study subjects,in which the VPA dose of the normal blood ammonia group was 782.35±235.73mg/d,and the VPA dose of the hyperammonemia group was 1263.63±226.72mg/d,the difference was statistically significant(P<0.001).Patients with epilepsy taking OXC were selected as the study subjects.OXC dose was 0.77±0.20g/d in the blood Na+normal group,and VPA dose was 1.05±0.15g/d in the hyponatremia group,and the difference was statistically significant(P=0.005).Conclusions1.AEDs have an effect on hematologic metabolic indexes.After taking AEDs,the levels of ammonia,TC,TG,HDL-C,LDL-C and Hcy in the blood increase,while the level of Na+in the blood decreases;the incidences of hyperaminemia,hyponatremia and hyperhomocysteinemia in epileptic patients after taking AEDs are significantly higher than before;2.The changes of serum metabolic indexes in male and female patients are different.The levels of blood ammonia,TC,HDL-C and Hcy after taking AEDs in male patients are significantly higher than before,while the level of Na+is significantly lower than before;the levels of TC,TG and LDL-C after taking AEDs in female patients are significantly higher than before.Tests for blood ammonia,Na+and Hcy levels are more needed for males,while tests for TG and LDL-C levels are more needed for females;3.There are differences in the changes of serum metabolic indexes between patients taking EIAEDs and NEIAEDs.The levels of TC,TG and LDL-C in patients taking EIAEDs are significantly higher than before,while the levels of blood ammonia,HLD-C and Hcy in epilepsy patients taking NEIAEDs are significantly higher than before,and the level of Na+is significantly lower than before.Tests for blood lipid levels are more needed in patients taking EIAEDs;4.Different types of monotherapy have different effects on hematologic indexes.Blood ammonia and HDL-C levels increase after VPA treatment,TC,TG and LDL-C levels increase after CBZ treatment,Na+level decreases after OXC treatment,Na+level decreases and Hcy level increases after LTG treatment.Patients taking the above drugs should pay more attention to the detection of changes in the corresponding indicators and adjust drugs timely;5.The dose of VPA is positively correlated with the level of serum ammonia,while the dose of OXC is negatively correlated with the level of blood Na+.The higher dose of VPA and OXC,the higher risk of hyperammonemia and hyponatremia respectively;6.The mean dose of VPA in hyperammonemia group of epileptic patients treated with VPA is significantly higher than that in normal group of blood ammonia;the mean dose of OXC in the hyponatremia group of epileptic patients treated with OXC is significantly higher than that in the normal group of blood sodium. |
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