Biguanides and lactic acidosis:unraveling the complex relationship

Biguanides,such as metformin,have long been established as frontline medications for the management of type 2 diabetes due to their glucose-lowering effects and favorable safety profiles.However,concerns regarding the risk of lactic acidosis associated with biguanide use have sparked considerable debate and scrutiny.This research article aims to provide a comprehensive analysis of the relationship between biguanides,particularly metformin,and lactic acidosis.We delve into the underlying mechanisms,epidemiological evidence,risk factors,clinical manifestations,diagnostic considerations,and management strategies related to biguanide-induced lactic acidosis.Additionally,we explore recent research developments,controversies,and future directions in this critical area of pharmacovigilance and clinical practice.

糖尿病乳酸性酸中毒(Diaberic lactic acidosis DLA)的治疗

糖尿病患者可因体内乳酸累积而发生乳酸性酸中毒,如不及时诊断和治疗,可发生死亡。乳酸是葡萄糖的中间代谢产物。葡萄糖的分解代谢包括葡萄糖的有氧氧化和葡萄糖的无氧酵解。前者是葡萄糖在正常有氧条件下彻底氧化产生二氧化碳和水,它是体内糖分解产能的主要途径,大多数组织能获得足够的氧气以供有氧氧化之需而很少进行无氧糖酵解;而后者是葡萄糖在无氧条件下分解成为乳酸,它虽然已非主要代谢途径而且产能有限,但仍是重要的代谢方式并具有病理生理意义。

Lactic acidosis during telbivudine treatment for HBV: A case report and literature review

All oral nucleoside analogues against hepatitis B virus,with an exception of telbivudine,have been reported causing lactic acidosis(LA).Here we report the first case of chronic hepatitis B developing severe refractory LA during telbivudine monotherapy.A 36-year-old man of Chinese origin received telbivudine antiviral treatment for chronic hepatitis B.After 11 mo of therapy,he developed anorexia,nausea,and vomiting with mild muscle weakness.The patient was found with elevated serum creatine phosphokinase up to 3683 U/L(upper limit of normal 170 U/L)and marked LA.LA did not resolve immediately following discontinuation of telbivudine.His condition began to improve after hemodialysis treatment for 16 times and usage of glucocorticosteroid.The patient fully recovered after 16 wk of treatment.This is the first documented case with severe LA caused by telbivudine monotherapy.Besides serum creatine phosphokinase,blood lactate level should also be closely monitored in patients receiving telbivudine.

Pyruvate is a prospective alkalizer to correct hypoxic lactic acidosis

Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase(PDH) activator with several unique beneficial biological properties, including anti-oxidant and antiinflammatory effects and the ability to activate the hypoxia-inducible factor-1(HIF-1α)-erythropoietin(EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients.

EVALUATION OF MITOCHONDRIAL ENCEPHALOMYOPATHY WITH LACTIC ACIDOSIS AND STROKE-LIKE EPISODES WITH MAGNETIC RESONANCE IMAGING AND PROTON MAGNETIC RESONANCE SPECTROSCOPY

Objective To study the characteristics of spectra on proton magnetic resonance spectroscopy （^1H-MRS） and its value in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes （MELAS）. Methods Seven clinically diagnosed patients with MELAS underwent magnetic resonance imaging （MRI） and ^1H-MRS examinations. The ^1H-MRS techniques, characteristics of the spectra, and its correlation with the laboratory tests were analyzed. Reaults Cerebral abnormalities were revealed in all 7 patients on conventional MR images, and most abnormal signals were observed in bilateral occipital, parietal, and temporal lobes. We found 4 cases with basal ganglia involvement, 2 cases with mild frontal lobe lesions, and 1 case with involvement of lateral cerebral peduncles and thalami. Additionally, 1 patient was involved with left insular lobe. Spectra from prominent lesions in brain parenchyma showed lactate doublet peak in 6 patients, 3 of whom were also noted lactate peak in ventricular cerehrospinal fluid （CSF）. Conclusion ^1H-MRS may provide more direct information about the metabolism changes, which aids to affirm the diagnosis, and may replace the conventional invasive method of quantifying lactate in CSF.

Mucosal necrosis of the small intestine in myopathy,encephalopathy,lactic acidosis,and stroke-like episodes syndrome

This report presents a case of massive mucosal necrosis of the small intestine in a patient with mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes(MELAS),which particularly affects the brain,nervous system and muscles.A 45-year-old Japanese female,with an established diagnosis of MELAS,presented with vomiting.Computed tomography showed portomesenteric venous gas and pneumatosis intestinalis.She underwent a resection of the small intestine.A microscopic study showed necrosis of the mucosa and vacuolar degeneration of smooth muscle cells in the arterial wall.Immunohistochemistry showed anti-mitochondrial antibody to be highly expressed in the crypts adjacent the necrotic mucosa.The microscopic and immunohistochemical findings suggested the presence of a large number of abnormal mitochondria in MELAS to be closely linked to mucosal necrosis of the small intestine.

Oral alkali therapy and the management of metabolic acidosis of chronic kidney disease:A narrative literature review

Chronic metabolic acidosis is a common complication seen in advanced chronic kidney disease(CKD). There is currently no consensus on its management in the Republic of Ireland. Recent trials have suggested that appropriate active management of metabolic acidosis through oral alkali therapy and modified diet can have a deterring impact on CKD progression. The potential benefits of treatment include preservation of bone health and improvement in muscle function; however,present data is limited. This review highlights the current evidence,available primarily from randomised control trials(RCTs) over the last decade,in managing the metabolic acidosis of CKD and outlines ongoing RCTs that are promising. An economic perspective is also briefly discussed to support decision-making.

Metformin Induced Lactic Acidosis What Is the Effective Treatment?

Metformin is known to be an effective treatment for patients with type 2 diabetes mellitus. Metformin induced lactic acidosis (MALA) is a serious illness which should identify and treat urgently. In this review article, we will present our own data and review the literature to highlight the importance of recognizing MALA;causes, presentations and the proper treatment, even though there are few published studies discussing MALA treatment modalities. The two cases that we presented here were patients admitted to the ICU and undergoing hemodynamic instability, which improved after removal of Metformin and clearance of associated lactic acidosis with SLED and CVVH. A case could be made for SLED and CVVH as modalities of choice for patients with MALA and hemodynamic instability, but further research is needed in this direction.

Lactic Acidosis and Atrial Tachycardia: Unusual Presentations of Disseminated Burkitt-Like Lymphoma

Lactic acidosis is a rare complication of malignancies and is seen more frequently in high grade lymphoma and leukemia. Although, its pathogenesis is not well understood, it remains a surrogate of poor prognosis. Herein, we present a case of Burkitt-like lymphoma presenting with metabolic abnormalities including lactic acidosis and hypoglycemia along with atrial tachycardia. We will discuss the different mechanisms involved in these metabolic disturbances and we will provide insight on novel therapeutic strategies based on our understanding of the underlying pathophysiology.

Metformin Intoxication: A Case of a Combination of Severe Hypoglycaemia and Severe Lactic Acidosis (LA)

Metformin is a worldwide used and effective antihyperglycemic agent. It is generally well tolerated but contraindicated in severe renal dysfunction. Metformin does not cause hypoglycaemia, however this case describes hypoglycaemia after an overdose. Another well-known, but rare and potentially life-threatening complication of metformin is the occurrence of LA, the so-called metformin-associated lactic acidosis (MALA). The severe consequences of an overdose of metformin, as well as the pathophysiologic mechanisms and the clinical consequences of LA in combination with severe hypoglycaemia are described in this report. Early recognition and swift clinical intervention is of paramount importance in case of auto-intoxication with metformin to prevent a lethal outcome.

Diarrhea and Acute Renal Injury Culminating in Metformin-Induced Lactic Acidosis

Background: Metformin (M) is an effective first-line hypoglycemic agent in obese type 2 diabetes mellitus due to its low cost and safety profile. The Case: A 66-year-man presented with shock due to lactic acidosis induced by M-supersaturation subsequent to acute renal failure following infective diarrhea. The drug has been used, by this patient, for >10 years without complication. Physical examination, laboratory tests, radiological investigations and blood cultures did not show evidence of new cardiac, hepatic and septic insult. Despite discontinuation of M and 2-days of aggressive hydration, bicarbonate infusions and pressors;toxic levels of the drug persisted and shock-state culminated in severe and oliguric renal failure with serum urea and creatinine up to 50 mmol/L and 1270 umol/L, respectively. Hence, continuous venovenous hemodiafiltration (CVVHDF) was used, for 16-hours, to remove the drug, correct his acidosis and support his severe renal complications. Hours after the procedure;drug level, lactic acidosis and its associated shock improved followed by gradual renal recovery. The patient was discharged after 6 days and serum creatinine reached his base line (180 umol/L) 2 weeks later. The drug was not recommended for his future use. Conclusion: M-induced lactic acidosis, should be considered in assessment of shock in M-treated patients and management of unstable patients indicates early-use of CVVHDF.

Metformin associated lactic acidosis in Auckland City Hospital 2005 to 2009

AIM： To determine the incidence, clinical characteristics and outcomes of patients with metformin associated lactic acidosis （MALA）.METHODS： Auckland City Hospital drains a population of just over 400000 people. All cases presenting with metabolic acidosis between July 2005 and July 2009 were identifed using clinical coding. A retrospective case notes review identifed patients with MALA. Prescribing data for metformin was obtained from the national pharmaceutical prescribing scheme.RESULTS： There were 42 cases of metabolic lactic acidosis over 1718000 patient years. There were 51000 patient years of metformin prescribed to patients over the study period. There were thirty two cases of lactic acidosis due to sepsis, seven in patients treated with metformin. Ten cases of MALA were identified. The incidence of MALA was estimated at 19.46 per 100000 patient year exposure to metformin. The relative risk of lactic acidosis in patients on metformin was 13.53 （95%CI： 7.88-21.66） compared to the general population. The mean age of patients with MALA was 63 years, range 40-83 years. A baseline estimated glomerular fltration rate was obtained in all patients and ranged from 23-130 mL/min per 1.73 m^2. Only two patients had chronic kidney disease G4.Three patients required treatment with haemodialysis. Two patients died.

In vitro investigation of the effect of dairy propionibacteria on rumen pH,lactic acid and volatile fatty acids

Ruminal acidosis is a prevalent disorder in ruminants such as dairy cows and feedlot beef cattle, caused primarily by the inclusion of a high percentage of readily fermentable concentrates in the diet. The disorder presents as an accumulation of lactic acid, a decrease of pH in the rumen and a subsequent imbalance of the rumen fermentation process with detrimental impacts on the animal＇s health and productivity. Dairy propionibacteria, a group of bacteria characterised by utilization of lactic acid as the favoured carbon source, with propionic acid produced as a by-product, were evaluated in this study as potential direct-fed microbials for use in controlling ruminal acidosis. Acidosis was simulated by introduction of high concentrations of lactic acid into rumen fluid samples and a multi-strain in vitro analysis was conducted, whereby changes in pH and lactic acid metabolism were compared in identical acidified rumen samples, following inoculation with various propionibacteria. This was followed by a study to evaluate the effect of bacterial inoculation dosage on acid metabolism. The results indicated that lactic acid levels in the rumen fluid were significantly reduced, and propionic acid and acetic acid concentrations both significantly increased, following addition of propionibacteria. Significant ＇between strains＇ differences were observed, with Propionibacterium acidopropionici 341, Propionibacterium freudenreichfi CSCC 2207, Propionibacterium jensenfi NCFB 572 and P. jensenii 702 each producing more rapid reduction of lactic acid concentration than P. freudenreich# CSCC 2206, P. acidopropionici ATCC 25562 and Propionibacterium thoenii ATCC 4874. Furthermore, the efficacy of this application was dosage related, with the rates of reduction in lactic acid levels and production of propionic acid, both significantly greater for the higher （10^10 cfu mL-1） compared with lower （10^5 cfu mL-1） dosage inoculation. The results confirmed that the introduction of propionibacteria could promote more rapid reduction of lactic acid levels than would occur without their addition, demonstrating their potential in controlling ruminal acidosis.

二甲双胍相关性乳酸酸中毒的不良反应及事件分析

目的探讨二甲双胍相关性乳酸酸中毒(metformin associated lactic acidosis,MALA)不良反应及事件发生的规律及特点,以提高临床用药安全性。方法检索中国知网、万方数据和维普网,检索日期截至2023年9月30日,对国内MALA相关公开发表的不良反应及事件病例进行回顾性分析。结果收集40例MALA不良反应及事件,其中男20例、女20例。平均年龄60.2岁,60岁及以上占57.5%(23/40)。27例(67.5%)患者存在诱发MALA的危险因素,其中14例(35.0%)患者超说明书最大剂量用药;另有13例(32.5%)患者考虑至少有诱发不良反应的一种危险因素,包括饮酒行为、冠心病、心功能不全或心肌梗死病史、脑梗死病史、合并肾功能不全、合并肝功能不全或感染诱发等。经治疗,31例患者好转,9例患者死亡,MALA发病时的相关实验室数据与预后存在一定关系。结论未见MALA的发生有明显性别差异,高龄患者发生MALA的风险更高。MALA的发生可能与合并的危险因素相关。对于MALA风险较高的患者,如在超剂量用药、肝肾功能不全、急性胃肠道疾病、严重缺氧、心力衰竭、重度感染、手术、饮酒和使用造影剂的情况下,应避免或停止使用二甲双胍。对于老年及轻中度肾功能不全的患者,可适量应用二甲双胍,但要密切监测患者的肾功能,加强随访,必要时监测血乳酸水平及时调整或停药。

经鼻高流量湿化治疗仪治疗慢阻肺急性加重期伴呼吸性酸中毒患者的效果

目的:分析经鼻高流量湿化治疗仪应用于慢阻肺急性加重期伴呼吸性酸中毒的治疗效果,探讨其对患者血气指标及肺功能的影响。方法:回顾性分析2022年1月—2023年10月在北京市昌平区医院呼吸与危重症学科治疗的100例慢阻肺急性加重伴呼吸性酸中毒患者的临床资料。根据治疗方式的不同分为两组,各50例。观察组接受经鼻高流量湿化氧疗,对照组接受无创正压通气治疗。比较两组的血气指标、肺功能指标、治疗效果及不良反应发生情况。结果:观察组治疗总有效率高于对照组,差异有统计学意义(P<0.05)。治疗前,两组血气指标、肺功能指标比较,差异无统计学意义(P>0.05);治疗后,两组pH值、氧分压(PaO_(2))、氧合指数(OI)均高于治疗前,二氧化碳分压(PaCO_(2))低于治疗前,且观察组pH值、PaO_(2)、OI高于对照组,PaCO_(2)低于对照组,差异有统计学意义(P<0.05)。治疗后,两组第1秒用力呼气容积(FEV_(1))、用力肺活量(FVC)、呼气峰流速值(PEF)、第1秒用力呼气容积/用力肺活量(FEV_(1)/FVC%)均高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论:经鼻高流量湿化氧疗、无创正压通气治疗都是慢阻肺急性加重期伴呼吸性酸中毒辅助通气的有效方法,而经鼻高流量湿化氧疗可有效提高治疗效果,改善患者血气指标及肺功能,不良反应少,安全性更高。

目标导向液体治疗在腹腔镜肝脏手术中的应用效果

目的探讨对腹腔镜肝脏手术患者实施目标导向液体治疗(GDFT)后获得的临床效果。方法选取2020年3月至2023年8月烟台市烟台山医院收治的62例腹腔镜肝脏手术患者作为研究对象,按照随机数字表法分为参照组(31例)与研究组(31例),参照组采用常规方法治疗,研究组采用GDFT治疗。比较两组的简易精神状态检查量表(MMSE)评分、血流动力学指标水平、尿素氮(BUN)水平、乳酸(Lac)水平。结果术前1 d,两组患者MMSE评分比较,差异无统计学意义(P>0.05);术后1、3 d,研究组患者MMSE评分高于参照组,差异有统计学意义(P<0.05)。研究组患者切肝时(T_(2))及手术完毕时(T_(3))心脏指数(CI)高于参照组;T_(2)时中心静脉压(CVP)水平高于参照组,T_(3)时CVP水平低于参照组,差异有统计学意义(P<0.05);入室时(T_(0))、T_(3)时及术后24 h,两组患者BUN水平比较,差异无统计学意义(P>0.05);T_(0)时,两组患者Lac水平比较,差异无统计学意义(P>0.05);T_(3)及术后24 h,研究组患者Lac水平低于参照组,差异有统计学意义(P<0.05)。结论临床对腹腔镜肝脏手术患者合理给予GDFT治疗,对于患者重要脏器血流灌注稳定性以及患者的血流动力学水平维持表现出的作用明显,可以保护患者的脑组织,对于患者的术后认知功能改善有促进作用。

利奈唑胺诱导致命性乳酸中毒:一种极易混淆为脓毒性休克的不良反应

回顾性分析北京、山东两所医院诊治的3例利奈唑胺诱导乳酸中毒患者的临床资料,并检索国内外相关文献,探讨其致病机制、危险因素、临床表现和治疗方案。3例患者因病情使用利奈唑胺抗感染治疗,在用药的不同阶段出现难以用脓毒性休克解释的乳酸中毒,停用利奈唑胺并给予床旁连续性静脉-静脉血液滤过治疗后,患者血乳酸水平明显下降,最终临床诊断为利奈唑胺诱导的乳酸中毒,但初诊医生均考虑为脓毒性休克。经积极治疗,2例患者转归良好,1例患者死亡。利奈唑胺诱导的乳酸中毒易被误诊为脓毒性休克,广大临床医生应提高对此不良反应早期诊断的认知与识别,采取有效的治疗措施,以改善患者预后。

以不典型疼痛为首发症状的先天性腹内疝1例报告及文献复习

目的:探讨先天性腹内疝患者的临床特征、诊断过程和治疗方法,总结在诊治过程中可能出现的误区,旨在提高临床医生对该病的认识。方法:收集1例先天性腹内疝患者的临床资料和辅助检查结果,分析上述资料并进行相关文献复习。结果:患者,男性,65岁,2 d前因中上腹疼痛就诊于当地医院,于当地医院检查未见明显异常,血糖>25 mmol·L^(-1),予以降糖、补液和血液净化治疗后,患者病情加重,出现意识不清、血压下降和呼吸困难,为求进一步诊治于本院就诊。入院后予以液体复苏、机械通气和支持治疗后,患者症状未见好转,由介入科行腹腔动脉和右侧股静脉造影,未见明显腹部血管病变。予以腹腔穿刺引出混合血性液体,考虑为腹腔隐匿性疾病,遂行剖腹探查术。术中诊断为腹内疝、小肠坏死和感染性休克,行小肠部分切除术、吻合术、黏连松解术和腹腔冲洗引流术。术后患者恢复良好,于术后14 d康复出院。结论:先天性腹内疝是一种非常少见的成年患者肠梗阻的原因,高度怀疑腹内疝是非典型急腹症的鉴别诊断之一,早期多学科干预可以挽救患者生命。

利奈唑胺致极重度乳酸酸中毒1例报道及文献复习

利奈唑胺是一种噁唑烷酮类抗菌药物,其作用机制主要是通过靶向细菌核糖体和干扰细菌蛋白质合成来抑制细菌生长,主要用于治疗革兰阳性菌感染,包括对万古霉素具有耐药性的屎肠球菌、金黄色葡萄球菌以及对甲氧西林具有耐药性的金黄色葡萄球菌。尽管利奈唑胺是一种有效的抗菌药物,但其可能引起的乳酸酸中毒是一种罕见且致命的不良反应。目前治疗指南推荐:①在使用利奈唑胺时监测血利奈唑胺和乳酸水平。②利奈唑胺不宜与影响线粒体功能的药物合用。③肝肾功能不全或利奈唑胺治疗>1个月的患者应监测高乳酸血症。④若出现高乳酸酸中毒,建议尽快停用利奈唑胺并纠正酸中毒。本文报告1例服用利奈唑胺治疗结核性胸膜炎后出现乳酸酸中毒的病例,经排除代谢、缺氧或器官损伤等其他原因后,确认该症状为利奈唑胺不良反应,旨在提升临床医师对利奈唑胺引起乳酸酸中毒的诊疗认知。

线粒体脑肌病伴高乳酸血症和卒中样发作的诊断与治疗策略

线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)是线粒体病最常见的临床亚型。MELAS的临床表现包括卒中样发作、头痛、癫痫、肌无力等,同时还可伴有多系统受累的表现,从而呈现出高度异质性。诊断需结合详细准确的病史、家族史,以及病理、生化和基因检测的结果。治疗需要多学科综合管理,包括药物治疗和营养运动干预。本文总结了MELAS的诊断和治疗方法,旨在帮助临床医生更全面地理解MELAS,从而做到早期诊断并规范化治疗以改善患者长期预后。