Intravenous Lipid Emulsion Given to Volunteers does not Affect Symptoms of Lidocaine Brain Toxicity

Intravenous lipid emulsion has been suggested as treatment for local anaesthetic toxicity, but the exact mechanism of action is still uncertain. Controlled studies on the effect of lipid emulsion on toxic doses of local anaesthetics have not been performed in man. In randomized, subject‐blinded and two‐phase cross‐over fashion, eight healthy volunteers were given a 1.5 ml/kg bolus of 20% Intralipid^® (200 mg/ml) or Ringer's acetate solution intravenously, followed by a rapid injection of lidocaine 1.0 mg/kg. Then, the same solution as in the bolus was infused at a rate of 0.25 ml/kg/min. for 30 min. Electroencephalography (EEG) was recorded, and 5 min. after lidocaine injection, the volunteers were asked to report subjective symptoms. Total and un‐entrapped lidocaine plasma concentrations were measured from venous blood samples. EEG band power changes (delta, alpha and beta) after the lidocaine bolus were similar during lipid and during Ringer infusion. There were no differences between infusions in the subjective symptoms of central nervous system toxicity. Lidocaine was only minimally entrapped in the plasma by lipid emulsion, but the mean un‐entrapped lidocaine area under concentration–time curve from 0 to 30 min. was clearly smaller during lipid than Ringer infusion (16.4 versus 21.3 mg × min/l, p = 0.044). Intravenous lipid emulsion did not influence subjective toxicity symptoms nor affect the EEG changes caused by lidocaine.     

咪达唑仑联合丙泊酚麻醉对腹腔镜胆囊切除术后患者恢复的影响

目的 探究咪达唑仑联合丙泊酚对腹腔镜胆囊切除术后患者恢复的影响。方法 选择2019年4月至2021年1月期间入院行腹腔镜胆囊切除术的患者162例，根据不同麻醉方式的将其分为对照组（实施咪达唑仑麻醉）和观察组（实施咪达唑仑联合丙泊酚麻醉），各81例。对比两组手术前后应激指标水平，术前（T₀）、术后24 h（T₁）及48 h（T₂）的MoCA评分，T₀、术后第1天（T₃）、2天（T₄）的术后相关恢复情况。结果 观察组患者的术后Cor、NE水平及睁眼、拔管、定向力恢复时间、不良反应发生率均低于对照组（P<0.05）；T₁、T₂时观察组的MMSE评分、T₃、T₄时的睡眠质量评分均高于对照组（P<0.05）。结论 咪达唑仑联合丙泊酚用于腹腔镜胆囊切除术安全性高，患者术后恢复良好。     

布托啡诺超前镇痛在瑞芬太尼麻醉腹腔镜胆囊切除术中的应用

目的评价布托啡诺超前镇痛对瑞芬太尼麻醉下胆囊切除术的镇痛效果。方法选择40例腹腔镜下胆囊切除术患者,ASAⅠ～Ⅱ级。随机分为2组（n=20）,布托啡诺超前镇痛组（I组）：麻醉前静脉注射布托啡诺30μg／kg超前镇痛;对照组：麻醉前静脉注射生理盐水。在手术结束后0．5、2,4、8、16、24h测定VAS评分（视觉模拟评分）,观察镇痛效果;同时记录术中瑞芬太尼用量、拔管时间、拔管后清醒评分及术后嗜睡、恶心、呕吐、瘙痒等不良反应发生率。结果术后VAS评分及术中瑞芬太尼用量I组〈Ⅱ组（P〈0．05）;拔管时间及拔管后清醒评分Ⅰ组〉Ⅱ组但无统计学意义（P〉0．05）;两组术后不良反应发生率均较低。结论布托啡诺超前镇痛能够弥补瑞芬太尼麻醉腹腔镜手术术后镇痛不足的缺点,安全有效,值得临床采用。     

靶控输注异丙酚复合瑞芬太尼在老年人腹腔镜胆囊切除术中的应用

目的探讨异丙酚复合瑞芬太尼靶控输注（Target—controlled infusion,TCI）全凭静脉麻醉用于老年人腹腔镜胆囊切除术（Laparoscopic Cholecystectomy,LC）的可行性及安全性。方法择期LC手术老年患者56例,美国麻醉医师协会（American Society of Anesthesiologists,ASA）分级Ⅰ-Ⅱ级,心肺功能正常。随机等分为静吸麻醉组（I组）和静脉全麻组（T组）,两组均以咪选唑仑、异丙酚、芬太尼、雏库溴铵诱导后做气管插管。麻醉维持：静吸麻醉组（Ⅰ组,n=28例）采用3％异氟醚吸入诱导,1％-2．5％维持,间断辅以瑞芬太尼静注;全凭静脉组（T组,n=28例）将瑞芬太尼和异丙酚混合液持续恒速输入,诱导时设定瑞芬太尼血浆靶浓度为4—8ns／ml,异丙酚为3～5μg／ml,术中根据血压、心率调整靶浓度．术中监测心率（heart rate,HR）、收缩压（systolic blood pressure,SBP）、舒张压（diastolic blood pressure,DBP）、平均动脉压（mean arterial pressure,MAP）等指标及手术结束至自主呼吸、睁眼、拔除气管导管、恢复定向能力的时间等。结果两组间的拔管时间、清醒程度有显著差异。静吸麻醉组（Ⅰ组）在气腹后10min的HR、SBP、DBP及术毕明显高于术前基础值（P〈0．05或P〈0．01）,而全凭静脉组术中无明显变化,术后恶心呕吐发生率也明显低于静吸组。结论异丙酚复合瑞芬太尼靶控输注静脉麻醉用于老年人腹腔镜胆囊切除术可达满意的麻醉深度,具有苏醒快,围术期血压、心率变化幅度小,能降低术后恶心呕吐的发生,患者安全系数高等优点,且无吸入麻醉药的手术室空气污染,优于异氟醚吸人麻醉方法。     

Comparative Pharmacokinetics Study after Oral Administration of Geniposide in Normal Rats and Adjuvant‐induced Arthritis Rats by UPLC‐MS/MS

A simple and rapid ultra‐performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC‐ESI‐MS/MS) method for quantitative analysis of geniposide (GE) in rat plasma was developed, validated and applied to determine the level of GE in rat plasma after oral administration of GE in adjuvant‐induced arthritis (AA) and normal rats. The investigation showed that there were significant differences in the groups between the normal rat and AA rat in pharmacokinetics parameters, such as the area under the time versus drug concentration curve (AUC _(0‐∞)) (3.77 ± 0.68 versus 2.27 ± 0.42, p < 0.05), the apparent volume of distribution (V) (140.41 ± 2.07 versus 136.51 ± 1.03, p < 0.05), the mean residence time (MRT) (3.98 ± 0.90 versus 3.80 ± 0.50, p < 0.05) and the clearance from the total body (CL) (16.10 ± 2.87 versus 26.44 ± 4.94, p < 0.05). The results indicated that AA could alter the pharmacokinetics of the drug and these experimental findings could be useful for the further study of the clinical applications of GE.     

Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers

This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non‐smoking healthy male Chinese population. Four polymorphisms CYP1A2*1C (G‐3860A), G‐3113A, CYP1A2*1F (C‐163A) and CYP1A2*1B (C‐5347T) were screened in 238 unrelated male volunteers. Then, a single oral 200‐mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7‐dimethylxanthine/caffeine ratios (17X/137X) after administration of 100‐mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high‐performance liquid chromatography. The activity of CYP1A2 was lower in volunteers with the ‐3113 AA genotype compared with those with the ‐3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the ‐3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP1A2*1F polymorphisms were associated with increased CYP1A2 activity in volunteers with ‐3860G/‐3113G/5347C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.     

A Human Experimental Bone Pain Model

The aim of this study was to develop a human experimental bone pain model. Fourteen healthy men were included in two study sessions. Pressure pain threshold (PPT) was estimated using probes of different sizes. Computer‐controlled and hand‐held algometry were applied to the skin area covering right and left medial tibia before and after local anaesthesia (LA) of the skin and reproducibility was evaluated. Pain experience (McGill questionnaire) was compared between healthy volunteers and 12 patients with vertebral fractures. Computer‐controlled algometer: No differences in PPT between study sessions for 6 and 8‐mm probes (p = 0.43 and 0.32) were seen. There was a difference in PPT before and after LA for the 6‐mm probe (p = 0.008), but not for the 8‐mm probe (p = 0.26). Hand‐held algometer: A difference in PPT between study sessions was observed for 4‐ and 8‐mm probes (p = 0.03 and 0.007), but not for 2, 6 and 10‐mm probes (p = 0.19, 0.05 and 0.25). No differences in PPT were seen before and after LA for 2, 4, 8 and 10‐mm probes (p = 0.35, 0.15, 0.08 and 0.53), but LA significantly influenced PPT with the 6‐mm probe (p = 0.01). Similar words were chosen in the McGill pain questionnaire by healthy volunteers and patients, qualitatively describing the deep pain sensation. The pain evoked by hand‐held algometer and the 2‐mm probe was not influenced by LA, and PPT was reproducible between sessions and is recommended for studies of experimentally evoked bone‐associated pain.     

Improved Anti‐Emetic Efficacy of 5‐HT3 Receptor Antagonists in Cancer Patients with Genetic Polymorphisms of ABCB1 (MDR1) Drug Transporter

Chemotherapy‐induced nausea and vomiting (CINV) remains a major adverse effect decreasing quality of life in patients with cancer. Genetic variations among patients may be responsible for part of the lack of efficacy of anti‐emetic drugs. The aim of this study was to investigate how the genetic variants of the drug transporter ABCB1 (MDR1) gene affect anti‐emetic treatment with 5‐HT₃ receptor antagonists. Patients (n = 239) receiving moderately or highly emetogenic chemotherapy and ondansetron or granisetron were included in the study. Anti‐emetic responses were recorded daily. The primary end‐point of the assessment was the total control rates of CINV in the acute and delayed phases after chemotherapy. Genotyping was performed by PCR‐RFLP. In the acute phase, patients with ABCB13435TT, 1236TT or 2677TT genotypes had a higher control rate of CINV than other genotype groups: (64.7% in 3435TT versus 45.7% in 3435CC+CT, p = 0.016; 65.1% in 1236TT versus 46.4% in 1236CC+CT, p = 0.027; 66.7% in 2677TT versus 46.5% in other genotypes, p = 0.021). Subjects carrying homozygous variant alleles together (TT‐TT‐TT) showed a significantly higher protection from nausea and vomiting (67.7% in TT‐TT‐TT versus 47.1% in other genotypes, p = 0.032). After the logistic regression analysis with adjustment for other known covariates, the total control rate was significantly higher in the 3435TT genotype group during the acute phase (p = 0.021). No significant change was found between the total control rates among genotypes in the delayed phase. Each of three 3435TT, C1236TT, 2677TT genotypes of ABCB1 and their combination was associated with about 50% higher anti‐emetic response to 5‐HT₃ receptor antagonists in the acute phase of chemotherapy in patients with cancer receiving moderately or highly emetogenic chemotherapy. ABCB1 (MDR1) genotypes may contribute to predict the anti‐emetic efficacy of 5‐HT₃ antagonists.     

Intravenous Lipid Emulsion Entraps Amitriptyline into Plasma and Can Lower its Brain Concentration – An Experimental Intoxication Study in Pigs

Intravenous lipid emulsion has been suggested as treatment for severe intoxications caused by lipophilic drugs, including tricyclic antidepressants. We investigated the effect of lipid infusion on plasma and tissue concentrations of amitriptyline and haemodynamic recovery, when lipid was given after amitriptyline distribution into well‐perfused organs. Twenty anaesthetized pigs received amitriptyline intravenously 10 mg/kg for 15 min. Thirty minutes later, in random fashion, 20% Intralipid^® (Lipid group) or Ringer's acetate (Control group) was infused 1.5 ml/kg for 1 min. followed by 0.25 ml/kg/min. for 29 min. Arterial and venous plasma amitriptyline concentrations and haemodynamics were followed till 75 min. after amitriptyline infusion. Then, frontal brain and heart apex samples were taken for amitriptyline measurements. Arterial plasma total amitriptyline concentrations were higher in the Lipid than in the Control group (p < 0.03) from 20 min. on after the start of the treatment infusions. Lipid emulsion reduced brain amitriptyline concentration by 25% (p = 0.038) and amitriptyline concentration ratios brain/arterial plasma (p = 0.016) and heart/arterial plasma (p = 0.011). There were no differences in ECG parameters and no severe cardiac arrhythmias occurred. Two pigs developed severe hypotension during the lipid infusion and were given adrenaline. In conclusion, lipid infusion, given not earlier than after an initial amitriptyline tissue distribution, was able to entrap amitriptyline back into plasma from brain and possibly from other highly perfused, lipid‐rich tissues. In spite of the entrapment, there was no difference in haemodynamics between the groups.     

Pharmacogenetics,Plasma Concentrations,Clinical Signs and EEG During Propofol Treatment

A variety of techniques have been developed to monitor the depth of anaesthesia. Propofol's pharmacokinetics and response vary greatly, which might be explained by genetic polymorphisms. We investigated the impact of genetic variations on dosage, anaesthetic depth and recovery after total intravenous anaesthesia with propofol. A total of 101 patients were enrolled in the study. The plasma concentration of propofol during anaesthesia was measured using high‐performance liquid chromatography. EEG was monitored during the surgical procedure as a measure of anaesthetic depth. Pyrosequencing was used to determine genetic polymorphisms in CYP2B6, CYP2C9, the UGTIA9‐promotor and the GABRE gene. The correlation between genotype and to plasma concentration at the time of loss of consciousness (LOC), the total induction dose, the time to anaesthesia, eye opening and clearance were investigated. EEG monitoring showed that the majority of the patients had not reached a sufficient level of anaesthetic depth (subdelta) at the time of loss of consciousness despite a high induction dose of propofol. Patients with UGT1A9‐331C/T had a higher propofol clearance than those without (p = 0.03) and required a higher induction dose (p = 0.03). The patients with UGT1A9‐1818T/C required a longer time to LOC (p = 0.03). The patients with CYP2C9*2 had a higher concentration of propofol at the time of LOC (p = 0.02). The polymorphisms in the metabolizing enzymes and the receptor could not explain the large variation seen in the pharmacokinetics of propofol and the clinical response seen. At LOC, the patients showed a large difference in EEG pattern.     

Methodological quality and risk of bias of meta-analyses of pharmacy services: A systematic review

BackgroundA suboptimal meta-analysis with misleading conclusions, frequently published in the healthcare journals, can compromise decision making in clinical practice.ObjectiveTo evaluate the reporting quality, methodological quality, and risk of bias of meta-analyses of pharmacy services.MethodsSystematic searches to identify all the meta-analyses reporting the effect of pharmacy services were performed in PubMed, Scopus, and Web of Science. The reporting quality, the methodological quality, and the risk of bias of the included meta-analyses were evaluated using PRISMA checklist, R-AMSTAR, and ROBIS, respectively.ResultsA total of 109 meta-analyses were eligible for the study. The heterogeneity, the quality of evidence, and the quality analyses were poorly reported on authors’ conclusions (14.3%, 14.7%, and 17.4%, respectively). The median scores of PRISMA and R-AMSTAR tolls were 24 (IQR 21.75–25), and 30 (IQR 27–32.5), respectively. Additionally, most of the studies were considered as high risk of bias (n = 83, 76.1%). No association between the date of publication and guideline compliance exists. PRISMA score was higher in studies published in high impact factor journals (rho = 0.313; p = 0.002), in articles that reported the quality of evidence obtained (p = 0.018), and in those that stated the need for future studies in their conclusions (p = 0.011). R-AMSTAR score was higher in studies published in high impact factor journals (rho = 0.338; p = 0.001), in those which reported the quality of evidence (p = 0.002), and in articles that described the quality analyses in their conclusions (p = 0.046). An association between the risk of bias and the recognition of the need for further studies in their conclusions (p = 0.041) was also found.ConclusionThe rapid increase of the meta-analyses of pharmacy services was not associated with higher quality. Mechanistic meta-analyses with poor conclusions are commonly published. Quality of the analyses, strength of evidence, heterogeneity, and absence of confrontation with current guidelines are rarely considered when synthetizing evidence and making recommendations.     

地佐辛降低手术患者全麻苏醒期躁动的临床效果

目的 探讨地佐辛对全麻苏醒期躁动的影响。方法 选取全麻手术患者140例,根据病历单双号随机分为观察组(73例)和对照组(67例)。观察组患者在手术结束前30 min给予5 mg地佐辛静脉注射;对照组给予5 mL 0.9% NaCl溶液静脉滴注。对两组患者拔管前5 min、拔管时及拔管后5 min进行躁动评分和镇静评分;于拔管后10 min对两组患者舒适度进行评价;记录两组患者拔管时间、睁眼时间以及呼吸恢复时间。结果 拔管前5 min、拔管时以及拔管后5 min观察组患者躁动评分分别为(1.11±0.13)分、(1.13±0.11)分和(0.44±0.05)分,均明显低于对照组,差异有统计学意义(P < 0.05);观察组患者镇静评分分别为(1.82±0.14)分、(2.18±0.30)分及(2.63±0.21)分,均明显高于对照组,差异有统计学意义(P < 0.05)。拔管后10 min观察组患者Bcs舒适度得分为(2.73±0.21)分,明显高于对照组,两组比较差异有统计学意义(P < 0.05)。观察组患者拔管时间、睁眼时间以及呼吸恢复时间与对照组比较,差异无统计学意义(P > 0.05)。结论 术前给予地佐辛静脉注射可以有效降低手术患者全麻苏醒期躁动,提高患者舒适度,并且不会抑制患者的呼吸,临床应用安全。     

Pharmacogenomics and Efficacy of Risperidone Long‐Term Treatment in Thai Autistic Children and Adolescents

The purpose of this study was to evaluate the association of pharmacogenomic factors and clinical outcome in autistic children and adolescents who were treated with risperidone for long periods. Eighty‐two autistic subjects diagnosed with DSM‐IV and who were treated with risperidone for more than 1 year were recruited. Pharmacogenomics and clinical outcome (CGI‐I, aggressive, overactivity and repetitive score) were evaluated. Almost all patients showed stable symptoms on aggressive behaviour (89.02%), overactivity (71.95%), repetitive (70.89%) behaviour and all clinical symptoms (81.71%). Only 4.48% of patients showed minimally worse CGI‐I score. Patients in the non‐stable symptom group had DRD2 Taq1A non‐wild‐type (TT and CT) frequencies higher than the clinically stable group (p = 0.04), whereas other gene polymorphisms showed no significant association. Haplotype ACCTCAT (rs6311, rs1045642, rs1128503, rs1800497, rs4436578, rs1799978, rs6280) showed a significant association with non‐stable clinical outcome (χ² = 6.642, p = 0.010). Risperidone levels showed no association with any clinical outcome. On the other hand, risperidone dose, 9‐OH risperidone levels and prolactin levels were significantly higher in the non‐stable compared to the stable symptom group (p = 0.013, p = 0.044, p = 0.030). Increased appetite was the most common adverse drug reaction and associated with higher body‐weight, whereas it was not significantly associated with genetic variations and non‐genetic information. In conclusion, risperidone showed efficacy to control autism, especially aggressive symptoms in long‐term treatment. However, Taq1A T – carrier of dopamine 2 receptor gene – is associated with non‐stable response in risperidone‐treated patients. This study supports pharmacogenomics testing for personalized therapy with risperidone in autistic children and adolescents.     

Calcitriol Attenuates Weight‐Related Systemic Inflammation and Ultrastructural Changes in the Liver in a Rodent Model

The role of vitamin D in maintaining calcium homoeostasis and bone mineralization is well‐established. The aim of the current investigation was to evaluate the effect of calcitriol treatment on inflammation, insulin resistance and liver changes induced by increased body‐weight. Four groups of mice (n = 11 each) were maintained on either low‐fat diet (LFD) or high‐fat diet (HFD) with and without 1α, 25‐dihydroxyvitamin D3 (calcitriol) for 16 weeks. Body‐weight of animals was recorded at the start of the study and every 4 weeks thereafter. At the end of the experiment, blood samples were collected for the determination of biochemical parameters, and liver tissues were harvested for the histopathological evaluation. A significant gradual decrease in weight was observed in HFD‐fed mice treated with calcitriol compared with a steady increase in controls (p < 0.01). Furthermore, calcitriol treatment reduced concentrations of various inflammatory markers including TNF‐α, CRP and IL‐6 (p < 0.05). Treated animals also exhibited lower levels of C‐peptide and insulin (539.4 ng/ml versus 718.9 ng/ml and 0.77 ng/ml versus 1.7 ng/ml, respectively; p < 0.05), which are consistent with improved insulin resistance. Liver histology and ultrastructural studies showed a marked accumulation of fat droplets in approximately 60–70% of hepatocytes of mice fed on HFD, while calcitriol administration rendered the whole structure more normal. Overall, our data signify an important effect of calcitriol on inflammation under HFD conditions and a protective effect on the liver structure.     

瑞芬太尼全麻复合硬膜外麻醉在食管癌根治术中的应用

目的观察和分析瑞芬太尼全麻复合硬膜外麻醉在食管癌手术中的应用效果。方法60例择期行食管癌根治术患者,ASA I～Ⅱ级,随机分组分为3组,瑞芬太尼组（R组）、瑞芬太尼＋硬外组（RE组）和芬太尼＋硬外组（FE组）。RE组和FE组全麻诱导前行硬膜外麻醉,麻醉维持：RE组和R组静脉输注瑞芬太尼,FE组静脉输注芬太尼。记录术中阿片类用药量、术后拔管时间、血压和心率变化、OAA／S评分、VAS评分及躁动情况。结果与R组比较,RE组术中瑞芬太尼用药量减少．术后VAS评分和躁动概率降低。与FE组比较,RE组术后OAA／S评分明显升高（P〈0．05）。结论瑞芬太尼全麻复合硬膜外麻醉能减少术中阿片类药物用量,术后苏醒快,苏醒质量好,镇痛效果好,是较好的麻醉方式。     

盐酸右美托咪定联合七氟烷对小儿眼科手术术后镇静的影响

目的 探讨右美托咪定联合七氟烷对小儿眼科手术术后镇静的影响。方法 选择2014年1月-2016年8月在安康市中医医院进行眼科手术的患儿200例,将其随机分为两组,每组100例,A组患儿接受七氟烷联合生理盐水术后镇静,B组患儿接受七氟烷联合右美托咪定术后镇静,比较两组患儿的手术情况以及术后VAS疼痛评分、Ramsay镇静评分以及PAED躁动评分,记录两组患儿术后不良反应的发生情况并进行统计学分析。结果 两组患儿的手术时间差异不显著,B组患儿术后清醒较A组晚,差异有统计学意义（P<0.05）。B组患儿术后拔管质量评分低于A组,差异有统计学意义（P<0.05）;且B组术后使用镇痛剂的患儿明显较A组少,差异有统计学意义（P<0.05）。T1、T2及T3时刻,B组患儿的VAS评分显著小于A组患儿,差异有统计学意义（P<0.05）;T1及T2时B组患儿的Ramsay评分显著高于A组患儿,差异有统计学意义（P<0.05）;B组患儿PAED评分明显低于A组,差异有统计学意义（P<0.05）。B组患儿术后恶心呕吐、呼吸抑制、术后躁动的发生率显著低于A组患儿,差异有统计学意义（P<0.05）;且B组患儿术后发生不良反应的总发生率显著低于A组患儿,差异有统计学意义（P<0.05）。结论 右美托咪定联合七氟烷用于小儿眼科手术术后镇静的临床疗效显著且安全性较好,可以显著缓解患儿苏醒期的躁动程度,降低患儿术后发生不良反应的发生率,值得临床推广应用。     

No antidotal effect of intravenous lipid emulsion in experimental amitriptyline intoxication despite significant entrapment of amitriptyline

Abstract: Intravenous lipid emulsion has been used in the resuscitative treatment of intoxications caused by local anaesthetics and tricyclic antidepressants with seemingly beneficial results. We studied the effect of intravenous lipid emulsion on the plasma concentration of amitriptyline and haemodynamic recovery in a pig model of amitriptyline intoxication. Twenty pigs were anaesthetized (1% isoflurane in 21% O₂) and given amitriptyline 15 mg/kg intravenously for 15 min. In random fashion immediately thereafter, either 20% lipid emulsion (ClinOleic^®, Lipid group) or Ringer’s acetate (Control group) was infused for 30 min.; first 1.5 ml/kg for 1 min., followed by 0.25 ml/kg/min. for 29 min. The amitriptyline concentration in total and lipid‐poor plasma and haemodynamic parameters were measured until 30 min. after the infusions. Lipid infusion prevented the decrease in plasma total amitriptyline concentration, resulting in a 90% higher (p < 0.001) total concentration and significantly (p = 0.014) lower free fraction of plasma amitriptyline in the Lipid group (1.1%) compared with the Control group (3.0%) at 30 min. Haemodynamic recovery from the intoxication as measured by heart rate, arterial pressure or cardiac output was similar in both groups. However, five pigs in the Lipid group and two pigs in the Control group died. In conclusion, a marked entrapment of amitriptyline by intravenous lipid emulsion was observed but this did not improve the pigs’ haemodynamic recovery from severe amitriptyline intoxication. Care should be exercised in the antidotal use of lipid emulsion until controlled human studies indicate its efficacy and safety.     

Dabigatran Concentration: Variability and Potential Bleeding Prediction In “Real–Life” Patients With Atrial Fibrillation

Routine laboratory monitoring is currently not recommended in patients receiving dabigatran despite its considerable variation in plasma concentration. However, in certain clinical situations, measurements of the dabigatran effect may be desirable. We aimed to assess the variability of dabigatran trough and peak concentration and explore the potential relationship between dabigatran concentration and adverse events. We included 44 patients with atrial fibrillation who started treatment with dabigatran 150 mg (D150) or 110 mg (D110) twice daily. They contributed 170 trough and peak blood samples that were collected 2–4 and 6–8 weeks after dabigatran initiation. Plasma dabigatran concentration was measured by LC‐MS/MS and indirectly, by selected coagulation tests. D110 patients were older (74 ± 7 versus 68 ± 6 years), had lower creatinine clearance (68 ± 21 versus 92 ± 24 mL/min) and higher CHA₂DS₂‐VASc score (3.1 ± 1.3 versus 2.3 ± 0.9) compared to D150 patients (all p < 0.05), but both had similar dabigatran concentrations in both trough and peak samples. Dabigatran concentrations varied less in trough than in peak samples (17.0 ± 13.6 versus 26.6 ± 19.2%, p = 0.02). During the 12‐month follow‐up, 4 patients on D150 and 6 on D110 suffered minor bleeding. There was no major bleeding or thromboembolic event. Patients with bleeding had significantly higher average trough dabigatran concentrations (93 ± 36 versus 72 ± 62 μg/L, p = 0.02) than patients without bleeding, while peak dabigatran values had no predictive value. Dabigatran dose selection according to the guidelines resulted in appropriate trough concentrations with acceptable repeatability. High trough concentrations may predispose patients to the risk of minor bleeding.     

靶控输注异丙酚复合瑞芬太尼在老年人腹腔镜胆囊切除术的应用

目的探讨异丙酚复合瑞芬太尼靶控输注（TCI）全凭静脉麻醉用于老年人腹腔镜胆囊切除术（LC）的可行性及安全性。方法择期LC手术老年患者56例,美国麻醉医师协会（ASA）分级I-Ⅱ级,年龄60～81岁,心肺功能正常,随机等分为静吸麻醉组（I组）和静脉全麻组（T组）各28例。I组以异丙酚、瑞芬太尼、阿曲库铵诱导后做气管插管,术中吸入1%～2.5%异氟醚维持麻醉。T组瑞芬太尼和异丙酚靶控输注,术中根据血压、心率调整靶浓度。术中监测HR、SBP、DBP、MAP等指标及记录手术结束至自主呼吸、睁眼、拔除气管导管、恢复定向能力的时间。结果两组间的拔管时间、清醒程度有显著差异。静吸麻醉组（I组）在气腹后5min的HR、SBP、MBP明显高于术前基础值（P〈0.05或P〈0.01）。而T组术中无明显变化,术后恶心呕吐发生率也明显低于I组。结论异丙酚复合瑞芬太尼靶控输注静脉麻醉用于老年人LC手术可达满意的麻醉深度,具有苏醒快,围术期血压、心率变化幅度小,能降低术后恶心呕吐的发生,且无吸入麻醉药的手术室空气污染等优点,优于传统的静吸复合麻醉。     

升压药物预注射对全凭静脉麻醉下腹部手术患者升压反应性和术后恢复的影响

目的 探讨全凭静脉麻醉下腹部手术中预注射不同升压药物对患者升压反应性、手术指标、不良反应指标、脑电双频指数(bispectral index,BIS)及复苏时间的影响。方法 选择中国人民解放军联勤保障部队第九八八医院择期行下腹部手术患者300例,按照不同预注射药物分为生理盐水组、麻黄碱组、去氧肾上腺素组,各100例,所有患者均行全凭静脉麻醉。记录麻醉诱导前(T0)、注射药物后1 min(T1)、注射药物后3 min(T2)、注射药物后5 min(T3)、注射药物后7 min(T4)、注射药物后9 min(T5)时患者收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均动脉压(mean arterial pressure,MAP)、心率(heart rate,HR)、心输出量(cardiac output,CO)、外周血管阻力(systemic vascular resistence,SVR)、每搏量变异度(stroke volume variation,SVV)等血流动力学指标;记录患者术中低血压、高...