Occurrence Of Lactic Acidosis Research Articles

Prescription trend and lactic acidosis in patients prescribed metformin before and after the revision of package insert for allowing metformin administration to patients with moderately decreased kidney function based on real-world data from MID-NET® in Japan.

This study was conducted to understand the impact of package insert (PI) revision in Japan on 18 June 2019 to allow metformin use for patients with moderately decreased kidney function (30 ≤ estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2). A new user cohort design was employed to examine the prescription trend and the occurrence of lactic acidosis in patients prescribed metformin before and after PI revision using the Medical Information Database Network (MID-NET®). From 12 May 2016 to 31 March 2020, 5,874 patients (before, n = 4,702; after, n = 1,172) were identified as new metformin users, including 1,145 patients (before, n = 914; after, n = 231) with moderately decreased kidney function. Although no marked changes in metformin prescription were observed before and after PI revision, the daily metformin dose at the first prescription decreased after PI revision. For both before and after PI revision, less than 10 cases of lactic acidosis occurred in all patients prescribed metformin, and no lactic acidosis was observed in patients with moderately decreased kidney function. The results of this study are useful for understanding the safety of metformin use in patients with decreased kidney function and suggest no worse impacts of PI revision in Japan, indicating no further safety concerns on metformin use in patients with moderately decreased kidney function under the situation with careful use and safety monitoring of metformin.

Blood lactate levels, base excess values and lactic acidosis predict short-term and long-term survival in patients admitted to the ICU after and out-of-hospital cardiac arrest

Abstract Funding Acknowledgements Type of funding sources: None. Background Global hypoperfusion causes tissue hypoxia, resulting in overproduction of lactate because of impaired mitochondrial oxidation, causing lactic acidosis (LA). Base excess (BE) is defined as the amount of acid or base required to return the pH to 7.4 in the setting of a normal Paco2 and is therefore related to the degree of acid production following injury. Purpose Our hypothesis was that lactate levels, BE levels and occurrence of LA on admission could help in early risk stratification in patients admitted to the ICU after an out-of-hospital cardiac arrest (OHCA). Methods we enrolled 171 consecutive patients resuscitated from an OHCA and admitted to ICU at our center from September 2017 to April 2021. Blood gas analysis on admission was available for 140 patients [77%male, mean age 60 (18-90) years, 54% with first shockable rhythm, median number of shocks delivered 1 (0-14), median dose of adrenaline administered 3 mg (0-12), 26% received amiodarone, median cardiac arrest duration 38 min (IQR 22-74 min)]. Patients with low lactate levels were compared with patients with high lactate levels (cutoff 2 mmol/l as per standard practice), patients with low BE levels were compared with patients with high BE levels (cutoff -8.5 mmol/l, median value) and patients with LA were compared with patients without LA (defined as pH &amp;lt;7.36 and lactate&amp;gt;2mmol/). Survival with good neurological outcome (CPC 1-2) at ICU discharge and 30-day survival were investigated for each group with chi-squared test. Then, one-year survival was investigated for each group with Kaplan-Meier analysis. Results Patients with low BE (&amp;lt; -8.5 mmol/l) had a significantly lower survival with good neurological outcome at ICU discharge (p=0.0017), lower survival at 30 days (p &amp;lt; 0.0001) and 365 days (p&amp;lt;0.0001) compared to patients with high BE (&amp;gt; - 8.5 mmol/l). Low lactate levels (&amp;lt; 2 mmol/L) were associated with higher survival with good neurological outcome at ICU discharge (p&amp;lt; 0.0001), higher survival at 30 days (p &amp;lt; 0.0001) and 365 days (p = 0.0002) compared to higher lactate levels (&amp;gt; 2 mmol/l). The occurrence of LA on admission was significantly associated with lower survival with good neurological outcome at ICU discharge (p=0.001), lower 30-days survival (p=0.001) and 365-days survival (p&amp;lt;0.0001). Conclusion high blood lactate levels, low base excess and lactic acidosis predict short-term and long-term survival in patients admitted to the ICU after an OHCA. These results could help clinician in the identification of populations with different risk profile with the first blood gas analysis obtained at ICU admission.

LACTIC ACIDOSIS IN TYPE 2DIABETES PATIENT WITH AND WITHOUT RENAL IMPAIRMENT TREATED WITH METFORMIN

Metformin is a widely used antihyperglycemic agent recommended by both the American Diabetes Association and the European Association for the Study of Diabetes as the first-line type 2 diabetes treatment in all patients receiving a new diagnosis, regardless of age Lactic acidosis (LA) is a rare event, with an estimated incidence of 4.3 cases per 100,000 person-years in metformin users LA is caused by the buildup of lactic acid in the bloodstream. It is characterized by an arterial lactate level ?5 mmol/L and a blood pH ?7.35, and occurs when oxygen levels in the body drop (hypoxia). The occurrence of LA in type 2 diabetes is of great concern because the mortality rate of LA can be as high as 50% .To determine whether the use of metformin in type 2 diabetic patients with various kidney functions is associated with an increased risk of lactic acidosis (LA). Lactic acidosis occurs in patients taking metformin who have renal failure. In our study, metformin was used in CKD stage 1 to 3b patients. Most of them were in stage 3. There is statistically significant association between stages of kidney disease and serum lactate level(P&lt;0.05) .There Is statistically significant association between stages of kidney disease and arterial blood gas analysis.

A Study of Associations Between Plasma Metformin Concentration, Lactic Acidosis, and Mortality in an Emergency Hospitalization Context.

To determine the plasma metformin concentration threshold associated with lactic acidosis and analyze the outcome in metformin-treated patients with lactic acidosis hospitalized in an emergency context. A retrospective, observational, single-center study. Emergency department and ICUs at Amiens University Hospital (Amiens, France). All consecutive patients with data on arterial lactate and pH up to 12 hours before or after a plasma metformin assay within 24 hours of admission, over a 9.7-year period. None. The study population consisted of 194 metformin-treated diabetic patients (median age: 68.6; males: 113 [58.2%]); 163 (84%) had acute kidney injury, which was associated variously with dehydration (45.4%), sepsis (41.1%), cardiogenic shock (20.9%), and diabetic ketoacidosis (16%). Eighty-seven patients (44.8%) had lactic acidosis defined as an arterial blood pH less than 7.35 and a lactate concentration greater than or equal to 4 mM, and 38 of them (43.7%) died in the ICU. A receiver operating characteristic curve analysis showed that a metformin concentration threshold of 9.9 mg/L was significantly associated with the occurrence of lactic acidosis (specificity: 92.9%; sensitivity: 67.1%; area under the receiver operating characteristic curve: 0.83; p < 0.0001). Among lactic acidosis-positive patients, however, in-ICU death was less frequent when the metformin concentration was greater than or equal to 9.9 mg/L (33.9% vs 61.3% for < 9.9 mg/L; p = 0.0252). After adjustment for the Simplified Acute Physiology Score II, in-ICU death was positively associated with prothrombin activity less than 70% and negatively associated with the initiation of renal replacement therapy at admission. In metformin-treated patients admitted in an emergency context, a plasma metformin concentration greater than or equal to 9.9 mg/L was strongly associated with the presence of lactic acidosis. This threshold may assist with the delicate decision of whether or not to initiate renal replacement therapy. Indeed, the outcome of lactic acidosis might depend on the prompt initiation of renal replacement therapy-especially when liver failure reduces lactate elimination.

Propofol Infusion Is a Feasible Bridge to Extubation in General Pediatric Intensive Care Unit.

Objective: The current literature on propofol infusion as a bridge to extubation in critically ill children is limited to children with burns and congenital cardiac disease. We hypothesize that propofol infusion is a feasible bridge to extubation in mechanically ventilated, critically ill children.Design: Retrospective chart review.Setting: Pediatric intensive care unit of a tertiary care teaching hospital.Patients: Children < 21 years, admitted to our Pediatric intensive care unit (PICU), requiring mechanical ventilation (MV) for at least 48 h and at least two sedative infusions and who received propofol infusion for 4 to 24 h during anticipated extubation from January 2014 to May 2017.Interventions: None.Measurements and Main Results: We assessed extubation success as primary outcome. We defined extubation success as no re-intubation within 24 h after extubation. We also assessed for occurrence of adverse effects of propofol infusion (1) hemodynamic instability [more than 10% change from pre-propofol baseline heart rate (HR) and mean arterial pressure (MAP) measured 4 h before and during propofol infusion, need for any inotrope and/or fluid bolus] and (2) occurrence of lactic acidosis in absence of any documented sepsis. We compared hemodynamic parameters before and during infusion using Wilcoxon Rank Sum Test (significant p-value ≤ 0.05). We evaluated 35 critically ill, mechanically ventilated children. The median age, weight and duration of MV were 3.8 (IQR: 1.25–10.5) years, 12 (IQR: 6–16.2) kilograms and 111 (IQR: 78–212) h, respectively. Of the 35 patients, 15 (43%) were post-surgical (10 general and 5 cardiac) and the remaining 20 (57%) were non-surgical respiratory failure cases. The median (IQR) propofol infusion dose and duration were 64.7 (53.2-81.1) mcg/kg/min and 7.8 h respectively. Only one patient got re-intubated within 24 h of extubation and was later diagnosed with vascular ring. During propofol infusion, 7/35 (20%) patients exhibited transient drop in MAP > 10% from baseline, but none had lactic acidosis or required an inotrope or fluid bolus.Conclusions: In critically ill, mechanically ventilated patients, propofol infusion used over a short duration (<12 h) was found to be a feasible bridge to extubation. No patient had significant hypotension or lactic acidosis during the infusion.

Is the use of metformin in patients undergoing dialysis hazardous for life? A systematic review of the safety of metformin in patients undergoing dialysis.

Metformin may have clinical benefits in dialysis patients; however, its safety in this population is unknown. This systematic review evaluated the safety of metformin in dialysis patients. MEDLINE, Embase, CENTRAL, PsycINFO and the Cochrane Library were searched for randomised controlled trials and observational studies evaluating metformin use in dialysis patients. Three authors reviewed the studies and extracted data. The primary outcomes were mortality, occurrence of lactic acidosis and myocardial infarction (MI) in patients taking metformin during dialysis treatment for ≥12 months (long term). Risk of bias was assessed using Risk Of Bias In Nonrandomised Studies of Interventions (ROBINS-1). Overall quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Fifteen observational studies were eligible; 7 were prospective observational studies and 8 were case reports/case series. No randomised controlled trials were identified. The 7 prospective observational studies (n = 194) reported on cautious metformin use in patients undergoing maintenance dialysis. Only 3 provided long-term follow-up data. In 2 long-term studies of metformin therapy (≤1000 mg/d) in patients undergoing peritoneal dialysis (PD), 1 reported 6 deaths (6/83; 7%) due to major cardiovascular events (3 MI) and the other reported no deaths (0/35). One long-term study of metformin therapy (250 mg to 500 mg thrice weekly) in patients undergoing haemodialysis reported 4 deaths (4/61; 7%) due to major cardiovascular events (2 MI). These findings provide very low-quality evidence as they come from small observational studies. The evidence regarding the safety of metformin in people undergoing dialysis is inconclusive. Appropriately designed randomised controlled trials are needed to resolve this uncertainty.

Metformin is not associated with lactic acidosis in patients with diabetes undergoing coronary artery bypass graft surgery: a case control study

BackgroundMetformin associated lactic acidosis (MALA) is a rare but lethal complication. There is no consensus regarding when to stop and resume metformin in patients who undergo coronary artery bypass grafting (CABG). This study aimed to determine if uninterrupted metformin administration in patients with diabetes undergoing CABG increases the risk of lactic acidosis.MethodsOver a span of 12 months (2015–2016), 127 patients with type 2 diabetes underwent isolated CABG. Of those, 41 patients (32%) continued taking metformin and 86 patients (68%) took other antidiabetic agents. Patients taking metformin took the drug until the day of surgery and resumed taking it 3 h after extubation.ResultsThere were no differences in clinical outcomes or complications between groups. Serial measurement of cardiac, liver, and kidney biomarkers were similar between groups. The mean peak lactic acid level was significantly higher in the non-metformin users (5.4 ± 2.6 vs. 7.4 ± 4.1 mmol/l; P = 0.001). Multivariable logistic regression analysis identified the need for vasopressor administration as an independent predictor of lactic acidosis (odds ratio: 7.3, 95% confidence interval: 2.5–20.6; P < 0.001).ConclusionIn the absence of risk factors associated with persistent lactic acidosis, such as shock or acute kidney or liver injury, continued peri-operative metformin administration was not associated with the occurrence of lactic acidosis in patients undergoing CABG. Elevated lactic acid levels seem to be directly related to tissue anoxia caused by escalating vasopressor support after surgery.

Hyperlactatemia and the Outcome of Type 2 Diabetic Patients Suffering Acute Myocardial Infarction.

Background. Increased lactate production is frequent in unregulated/complicated diabetes mellitus. Methods. Three groups, each consisting of 40 patients (type 2 diabetics with myocardial infarction, DM+AMI, nondiabetics suffering myocardial infarction, MI, and diabetics with no apparent cardiovascular pathology, DM group), were tested for pH, serum bicarbonate and electrolytes, blood lactate, and CK-MB. Results. Blood lactate levels were markedly higher in AMI+DM compared to MI group (4.54 ± 1.44 versus 3.19 ± 1.005 mmol/L, p < 0.05); they correlated with the incidence of heart failure (ρ = 0.66), cardiac rhythm disorders (ρ = 0.54), oxygen saturation (ρ = 0.72), CK-MB levels (ρ = 0.62), and poor short-term outcome. Lactic acidosis in DM+AMI group was not always related to lethal outcome. Discussion. The lactate cutoff value associated with grave prognosis depends on the specific disease. While some authors proposed cutoff values ranging from 0.76 to 4 mmol/L, others argued that only occurrence of lactic acidosis may be truly predictive of lethal outcome. Conclusion. Both defective glucose metabolism and low tissue oxygenation may contribute to the lactate production in diabetic patients with acute myocardial infarction; high lactate levels indicate increased risk for poor outcome in this population comparing to nondiabetic patients. The rise in blood lactate concentration in diabetics with AMI was associated with increased incidence of heart failure, severe arrhythmias, cardiogenic shock, and high mortality rate.

Renal cell cancer (RCC): Use of metformin in the setting of renal impairment.

e15551 Background: Metformin is a biguanide that is widely used to treat type-2 diabetes and prediabetic syndromes. It has been found to inhibit RCC cell proliferation through activation of AMP-activated protein kinase (AMPK) and downstream inhibition of mammalian target of rapamycin (mTOR). Metformin is associated with potentially life threatening lactic acidosis (LA), but a clear link has not been established. We evaluated the occurrence of lactic acidosis in metformin-treated RCC patients with renal impairment. Methods: A retrospective study of 65 RCC patients treated with 250 to 2000 mg of metformin daily was conducted. Demographic data including age, gender, and ethnic background were collected. Data were collected on median metformin dose, eGFR, dialysis status, lactic acid, BUN, Na, K, Cl, and CO2 values. Results: Median metformin dose was 1000 mg daily in each group. Fifteen patients (23%) had elevated lactic acid &gt;4. The mean eGFR for patients with elevated lactic acid of &gt;4 vs. &lt;4is comparable (p=0.98). The two populations were significantly different at the BUN baseline level: patients with lactic acids &gt;4 have statistically significant smaller median baseline BUN level (median of 19.0 vs. 19.5; Wilcoxon two-sample p=0.03). Moreover, there is a marginally significant difference in age between these 2 groups (Mean of 58 vs. 62.8, Student's t-test p=0.07). Conclusions: Regardlessof lactic acid elevation, patients did not experience lactic acidosis. Complete data will be presented. [Table: see text]

Lactic Acidosis: A Short Review of Cases

Lactic acidosis, which is caused by a high anion concentration due to metabolic acidosis, occurs when the plasma lactate concentration exceeds 4 to 5 millimoles/litre (mmol/L) (normal range: 0.5-1.5 mmol/L). Lactate accumulation results from increased metabolism or decreased excretion. Lactic acidosis cases often occurs in intensive care units. In order to carry out effective treatment, the primary aim must be the reversal of the causes underlying the disease. Today, various methods are used to treat lactic acidosis. We have reviewed the occurrence of lactic acidosis in two cases in light of the current literature. Lactic acidosis can have quite serious consequences, and clinicians must be very careful while managing patients with lactic acidosis. (Yogun Bakim Derg 2011; 3: 63-6)

The propofol infusion syndrome: more puzzling evidence on a complex and poorly characterized disorder

The propofol infusion syndrome is a potentially devastating cardiovascular and metabolic derangement that has been described in both pediatric and adult patients sedated with propofol. Despite a large number of case reports that have appeared in the literature since 1992, the precise clinical features and pathophysiology of this disorder remain uncertain. Historically, the syndrome has been characterized by the occurrence of lactic acidosis, rhabdomyolysis, and circulatory collapse after several days of high-dose propofol infusion. The affected patients were typically young and critically ill, and the reported mortality was high. More recently, a number of atypical cases have been reported with favorable outcomes. These occurred after short-term or lower-dose infusions in noncritically ill patients in whom generally only a subset of the classical syndrome features was observed. It remains unclear whether these reports reflect true propofol infusion syndrome detected at an earlier and more salvageable stage, or mere associations with the use of sedative agents in general. Without better information on the true incidence of the propofol infusion syndrome, clinical guidelines on the safe use of this drug remain unsupported by good evidence.

Update on the propofol infusion syndrome in ICU management of patients with head injury

The propofol infusion syndrome is a rare condition characterized by the occurrence of lactic acidosis, rhabdomyolysis and cardiovascular collapse following high-dose propofol infusion over prolonged periods of time. Patients with traumatic brain injury are particularly at risk of developing this complication because large doses of propofol are commonly used to control intracranial pressure, whereas vasopressors are administered to augment cerebral perfusion pressure. In this review, we provide an update on the literature with particular emphasis on patients with traumatic brain injury. Several new case reports and reviews, as well as a number of experiments, have contributed significantly to our increased understanding of the cause of the syndrome. At the basis of the syndrome lies an imbalance between energy utilization and demand resulting in cell dysfunction, and ultimately necrosis of cardiac and peripheral muscle cells. Uncertainty remains whether a genetic susceptibility exists. Nonetheless, the growing number of case reports has made it possible to identify several risk factors. Propofol infusion syndrome is a rare but frequently lethal complication of propofol use. In patients with risk factors, such as traumatic brain injury, it is suggested that an infusion rate of 4 mg/kg per hour should not be exceeded. Early warning signs include unexplained lactic acidosis, lipemia and Brugada-like ECG changes. When these occur, propofol infusion should be discontinued immediately.

Frequency of concentrate supplementation for cattle fed barley straw. 2. Ruminal dilution rates, pH and metabolite concentrations

Five ruminally cannulated crossbred steers (474 ± 30 kg) were fed diets containing 70% barley straw and 30% concentrate in an unbalanced 5 × 5 Latin square design experiment to in vestigate the effects of frequency of feeding concentrate (daily, alternate days or every third day) with different dietary protein concentrations (7.9 and 11.5%) on ruminal liquid and particulate dilution rates, pH and metabolite concentrations. Dilution rates of cobalt-ethylene diamine tetraacetic acid (Co- EDTA) and chromium-mordanted fibre did not differ when low- and high-protein concentrates were fed. Supplemental protein increased (P &lt; 0.05) mean ruminal ammonia concentrations (3.3 vs. 1.6 mM), but had no influence on ruminal concentrations of organic acids. Frequency of concentrate feeding had no influence on dilution rate of digesta markers, pH or on mean ruminal concentrations of ammonia, lactic acid, propionic acid, isobutyric acid, valeric acid and isovaleric acid. Mean concentrations of total volatile fatty acids, acetic acid and butyric acid were, however, reduced (P &lt; 0.05) when steers were fed concentrates on alternate days. The reduced (P &lt; 0.01) ruminal acetic:propionic acid ratios observed in steers fed concentrates on alternate days were consistent with reduced heat productions. Positive relationships (P &lt; 0.05) were obtained between heat production of steers and ruminal concentrations of isobutyric and valeric acids. It was concluded that the low-protein diet did not provide sufficient protein to meet microbial requirements and that under controlled feeding conditions cattle can be fed concentrate on alternate days or every third day without the occurrence of lactic acidosis. Additional research is warranted to examine the relationships between reduced heat production of steers fed concentrates on alternate days and ruminal concentration and production of organic acids. Key words: Cattle, straw, protein, feeding frequency, rumen metabolites, lactic acid

SOME PHYSIOLOGICAL AND METABOLIC EFFECTS OF SODIUM NITROPRUSSIDE AND CYANIDE IN THE DOG

The cardiovascular and acid-base changes following equivalent i.v. bolus doses of sodium nitroprusside (SNP) and potassium cyanide (KCN) have been studied in two groups of anaesthetized dogs. In a third group, the metabolic changes produced by i.v. infusion of SNP 1.5 mg kg-1 at a constant rate over 1 h have been studied. In contrast to a decrease in arterial pressure following SNP, hypertension and tachycardia occurred after the administration of KCN, with hyperventilation and an increase in packed cell volume. During infusion of SNP, increases in plasma cyanide concentrations were associated with an increase in arterial base deficit, plasma lactate and excess lactate and a decrease in oxygen consumption. The occurrence of lactic acidosis with SNP 1.5 mg kg-1 suggests that this may be the maximum safe dose for short term infusion. However, all these changes reversed spontaneously following discontinuation of SNP, indicating that base deficit is an adequate metabolic monitor during administration of SNP.