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The Cochrane Database of Systematic... Jul 2020Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious risks to the mother (unconsciousness, pulmonary aspiration) and baby (hypoxia, acidosis, neurological injury).
OBJECTIVES
To assess the effects of prophylactic interventions for hypotension following spinal anaesthesia for caesarean section.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (9 August 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials, including full texts and abstracts, comparing interventions to prevent hypotension with placebo or alternative treatment in women having spinal anaesthesia for caesarean section. We excluded studies if hypotension was not an outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and extracted data from eligible studies. We report 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included 125 studies involving 9469 women. Interventions were to prevent maternal hypotension following spinal anaesthesia only, and we excluded any interventions considered active treatment. All the included studies reported the review's primary outcome. Across 49 comparisons, we identified three intervention groups: intravenous fluids, pharmacological interventions, and physical interventions. Authors reported no serious adverse effects with any of the interventions investigated. Most trials reported hypotension requiring intervention and Apgar score of less than 8 at five minutes as the only outcomes. None of the trials included in the comparisons we describe reported admission to neonatal intensive care unit. Crystalloid versus control (no fluids) Fewer women experienced hypotension in the crystalloid group compared with no fluids (average risk ratio (RR) 0.84, 95% confidence interval (CI) 0.72 to 0.98; 370 women; 5 studies; low-quality evidence). There was no clear difference between groups in numbers of women with nausea and vomiting (average RR 0.19, 95% CI 0.01 to 3.91; 1 study; 69 women; very low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (60 babies, low-quality evidence). Colloid versus crystalloid Fewer women experienced hypotension in the colloid group compared with the crystalloid group (average RR 0.69, 95% CI 0.58 to 0.81; 2009 women; 27 studies; very low-quality evidence). There were no clear differences between groups for maternal hypertension requiring intervention (average RR 0.64, 95% CI 0.09 to 4.46, 3 studies, 327 women; very low-quality evidence), maternal bradycardia requiring intervention (average RR 0.98, 95% CI 0.54 to 1.78, 5 studies, 413 women; very low-quality evidence), nausea and/or vomiting (average RR 0.89, 95% CI 0.66 to 1.19, 14 studies, 1058 women, I² = 29%; very low-quality evidence), neonatal acidosis (average RR 0.83, 95% CI 0.15 to 4.52, 6 studies, 678 babies; very low-quality evidence), or Apgar score of less than 8 at five minutes (average RR 0.24, 95% CI 0.03 to 2.05, 10 studies, 730 babies; very low-quality evidence). Ephedrine versus phenylephrine There were no clear differences between ephedrine and phenylephrine groups for preventing maternal hypotension (average RR 0.92, 95% CI 0.71 to 1.18; 401 women; 8 studies; very low-quality evidence) or hypertension (average RR 1.72, 95% CI 0.71 to 4.16, 2 studies, 118 women, low-quality evidence). Rates of bradycardia were lower in the ephedrine group (average RR 0.37, 95% CI 0.21 to 0.64, 5 studies, 304 women, low-quality evidence). There was no clear difference in the number of women with nausea and/or vomiting (average RR 0.76, 95% CI 0.39 to 1.49, 4 studies, 204 women, I² = 37%, very low-quality evidence), or babies with neonatal acidosis (average RR 0.89, 95% CI 0.07 to 12.00, 3 studies, 175 babies, low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (321 babies; low-quality evidence). Ondansetron versus control Ondansetron administration was more effective than control (placebo saline) for preventing hypotension requiring treatment (average RR 0.67, 95% CI 0.54 to 0.83; 740 women, 8 studies, low-quality evidence), bradycardia requiring treatment (average RR 0.49, 95% CI 0.28 to 0.87; 740 women, 8 studies, low-quality evidence), and nausea and/or vomiting (average RR 0.35, 95% CI 0.24 to 0.51; 653 women, 7 studies, low-quality evidence). There was no clear difference between the groups in rates of neonatal acidosis (average RR 0.48, 95% CI 0.05 to 5.09; 134 babies; 2 studies, low-quality evidence) or Apgar scores of less than 8 at five minutes (284 babies, low-quality evidence). Lower limb compression versus control Lower limb compression was more effective than control for preventing hypotension (average RR 0.61, 95% CI 0.47 to 0.78, 11 studies, 705 women, I² = 65%, very low-quality evidence). There was no clear difference between the groups in rates of bradycardia (RR 0.63, 95% CI 0.11 to 3.56, 1 study, 74 women, very low-quality evidence) or nausea and/or vomiting (average RR 0.42, 95% CI 0.14 to 1.27, 4 studies, 276 women, I² = 32%, very-low quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (130 babies, very low-quality evidence). Walking versus lying There was no clear difference between the groups for women with hypotension requiring treatment (RR 0.71, 95% CI 0.41 to 1.21, 1 study, 37 women, very low-quality evidence). Many included studies reported little to no information that would allow an assessment of their risk of bias, limiting our ability to draw meaningful conclusions. GRADE assessments of the quality of evidence ranged from very low to low. We downgraded evidence for limitations in study design, imprecision, and indirectness; most studies assessed only women scheduled for elective caesarean sections. External validity also needs consideration. Readers should question the use of colloids in this context given the serious potential side effects such as allergy and renal failure associated with their administration.
AUTHORS' CONCLUSIONS
While interventions such as crystalloids, colloids, ephedrine, phenylephrine, ondansetron, or lower leg compression can reduce the incidence of hypotension, none have been shown to eliminate the need to treat maternal hypotension in some women. We cannot draw any conclusions regarding rare adverse effects associated with use of the interventions (for example colloids) due to the relatively small numbers of women studied.
Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Antiemetics; Cesarean Section; Colloids; Crystalloid Solutions; Ephedrine; Female; Humans; Hypotension; Intraoperative Complications; Isotonic Solutions; Ondansetron; Phenylephrine; Postoperative Nausea and Vomiting; Pregnancy; Randomized Controlled Trials as Topic; Vasoconstrictor Agents; Walking
PubMed: 32619039
DOI: 10.1002/14651858.CD002251.pub4 -
Neurology Jun 2022Stroke management in the context of primary mitochondrial disease is clinically challenging, and the best treatment options for patients with stroke-like episodes remain...
BACKGROUND AND OBJECTIVES
Stroke management in the context of primary mitochondrial disease is clinically challenging, and the best treatment options for patients with stroke-like episodes remain uncertain. We sought to perform a systematic review of the safety and efficacy of l-arginine use in the acute and prophylactic management of stroke-like episodes in patients with mitochondrial disease.
METHODS
The systematic review was registered in PROSPERO (CRD42020181230). We searched 6 databases from inception to January 15, 2021: MEDLINE, Embase, Scopus, Web of Science, CINAHL, and ClinicalTrials.gov. Original articles and registered trials available, in English, reporting l-arginine use in the acute or prophylactic management of stroke-like episodes in patients with genetically confirmed mitochondrial disease were eligible for inclusion. Data on safety and treatment response were extracted and summarized by multiple observers. Risk of bias was assessed by the methodologic quality of case reports, case series, and a risk-of-bias checklist for nonrandomized studies. Quality of evidence was synthesized with the Oxford Centre for Evidence-Based Medicine Levels of Evidence and Grade of Recommendations. The predetermined main outcome measures were clinical response to l-arginine treatment, adverse events, withdrawals, and deaths (on treatment and/or during follow-up), as defined by the author.
RESULTS
Thirty-seven articles met inclusion criteria (0 randomized controlled trials; 3 open-label; 1 retrospective cohort; 33 case reports/case series) (N = 91 patients; 86% m.3243A>G). In the case reports, 54% of patients reported a positive clinical response to acute l-arginine, of which 40% were concomitantly treated with antiepileptic drugs. Improved headache at 24 hours was the greatest reported benefit in response to IV l-arginine in the open-label trials (31 of 39, 79%). In 15 of 48 patients (31%) who positively responded to prophylactic l-arginine, antiepileptic drugs were either used (7 of 15) or unreported (8 of 15). Moderate adverse events were reported in the follow-up of both IV and oral l-arginine treatment, and 11 patients (12%) died during follow-up or while on prophylactic treatment.
DISCUSSION
The available evidence is of poor methodologic quality and classified as Level 5. IV and oral l-arginine confers no demonstrable clinical benefit in either the acute or prophylactic treatment of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, with more robust controlled trials required to assess its efficacy and safety profile.
Topics: Acidosis, Lactic; Anticonvulsants; Arginine; Humans; Mitochondrial Diseases; Mitochondrial Encephalomyopathies; Retrospective Studies; Stroke
PubMed: 35428733
DOI: 10.1212/WNL.0000000000200299 -
Life (Basel, Switzerland) May 2023Anticoagulation is recommended to maintain the patency of the circuit in continuous renal replacement therapy (CRRT). However, anticoagulation-associated complications... (Review)
Review
Regional Citrate Anticoagulation in Continuous Renal Replacement Therapy: Is Metabolic Fear the Enemy of Logic? A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
BACKGROUND
Anticoagulation is recommended to maintain the patency of the circuit in continuous renal replacement therapy (CRRT). However, anticoagulation-associated complications can occur. We performed a systematic review and meta-analysis to compare the efficacy and safety of citrate anticoagulation to heparin anticoagulation in critically ill patients treated with CRRT.
METHODS
Randomised controlled trials (RCTs) evaluating the safety and efficacy of citrate anticoagulation and heparin in CRRT were included. Articles not describing the incidence of metabolic and/or electrolyte disturbances induced by the anticoagulation strategy were excluded. The PubMed, Embase, and MEDLINE electronic databases were searched. The last search was performed on 18 February 2022.
RESULTS
Twelve articles comprising 1592 patients met the inclusion criteria. There was no significant difference between the groups in the development of metabolic alkalosis (RR = 1.46; (95% CI (0.52-4.11); = 0.470)) or metabolic acidosis (RR = 1.71, (95% CI (0.99-2.93); = 0.054)). Patients in the citrate group developed hypocalcaemia more frequently (RR = 3.81; 95% CI (1.67-8.66); = 0.001). Bleeding complications in patients randomised to the citrate group were significantly lower than those in the heparin group (RR 0.32 (95% CI (0.22-0.47); < 0.0001)). Citrate showed a significantly longer filter lifespan of 14.52 h (95% CI (7.22-21.83); < 0.0001), compared to heparin. There was no significant difference between the groups for 28-day mortality (RR = 1.08 (95% CI (0.89-1.31); = 0.424) or 90-day mortality (RR 0.9 (95% CI (0.8-1.02); = 0.110).
CONCLUSION
regional citrate anticoagulation is a safe anticoagulant for critically ill patients who require CRRT, as no significant differences were found in metabolic complications between the groups. Additionally, citrate has a lower risk of bleeding and circuit loss than heparin.
PubMed: 37240843
DOI: 10.3390/life13051198 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2020Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of...
BACKGROUND
Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of choice. However, despite the use of acetylcysteine, some patients who ingest very large doses of paracetamol or who reach hospital late in the course of their poisoning, develop acute liver failure. Some will develop metabolic acidosis indicating mitochondrial toxicity.
OBJECTIVE
We review the experimental and clinical data reported with the use of cimetidine, fomepizole, and calmangafodipir in the treatment of paracetamol toxicity to determine if these treatments alone or in combination with acetylcysteine might be of benefit.
METHODS
We searched Ovid Medline 1946-2020, Embase 1947-2020, Scopus 2004-2020, Cochrane Databases of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov 1997-2020 for records including the concepts of paracetamol poisoning and cimetidine, fomepizole, calmangafodipir, and acetylcysteine. We included basic science studies in animals and all available study types in humans. We reviewed the reference lists of included articles to search for references missed in the original search. We registered the protocol in PROSPERO.
RESULTS
We completed all search strategies on 20 August 2019, 27 January 2020, and 15 June 2020. These produced 6,826 citations. We identified and deleted 2,843 duplicate resulting in a total of 3,856 unique citations. After applying inclusion and exclusion criteria, 89 studies remained. The largest numbers of studies described the past use of cimetidine, and the more recent use of fomepizole. There is good animal evidence that cimetidine blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. Early case reports were inconclusive regarding the benefit to humans in paracetamol poisoning. Two comparative trials found no benefit of cimetidine in paracetamol poisoning, but few patients had severe poisoning. There is good animal evidence that fomepizole blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. There are no comparative trials of fomepizole for acute paracetamol poisoning. Case reports are inconclusive due to multiple other interventions including the use of acetylcysteine in all cases. The benefit of fomepizole as adjunct treatment has not been demonstrated. Calmangafodipir, a drug mimicking superoxide dismutase, has emerged as a potential treatment for severe paracetamol toxicity because the formation of superoxide free radicals appears to explain part of the mitochondrial toxicity of extremely large paracetamol overdoses. Calmangafodipir has reached Phase I/II trial of safety in humans with acute paracetamol overdose. Planning for a Phase III study of efficacy is currently underway.
CONCLUSIONS
The vast majority of patients with acute paracetamol overdose enjoy excellent outcomes with acetylcysteine alone. Although cimetidine and fomepizole inhibit CYP 2E1 in animals, there is insufficient evidence to recommend their use either as a primary treatment or adjunct therapy in paracetamol poisoning. Calmangafodipir remains investigational.
Topics: Acetaminophen; Acetylcysteine; Acidosis; Animals; Antidotes; Cimetidine; Drug Overdose; Edetic Acid; Fomepizole; Humans; Mitochondria; Pyridoxal Phosphate
PubMed: 32762579
DOI: 10.1080/15563650.2020.1798979 -
Maedica Dec 2023ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic...
ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic acidosis. A systematic review was conducted with the aim to evaluate the effect of STAN method compared with isolated CTG on perinatal and neonatal outcomes. A search of electronic databases (PubMed, Cochrane, Scopus) was conducted to identify randomized controlled trials (RCTs) in English language. Outcomes considered operative deliveries, fetal blood sampling (FBS), metabolic acidosis, perinatal and neonatal death, neonatal seizures, neonatal encephalopathy, transfer to the neonatal intensive care unit (NICU) and Apgar score. Seven RCTs were included in the present review. The first two RCTs showed that the combination of STAN and CTG was a better option than using CTG alone, because there was a documented reduction in the rate of operative deliveries due to fetal distress and metabolic acidosis. The following studies showed no statistically significant changes with the combination of methods, except from a reduction in FBS. The findings from the RCTs were inconclusive. Most studies did not demonstrate a superiority of the combination regarding operative deliveries and neonatal outcomes but there were many methodological differences between the trials.
PubMed: 38348066
DOI: 10.26574/maedica.2023.18.4.684 -
The Cochrane Database of Systematic... Feb 2017Cardiotocography (CTG) records changes in the fetal heart rate and their temporal relationship to uterine contractions. The aim is to identify babies who may be short of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiotocography (CTG) records changes in the fetal heart rate and their temporal relationship to uterine contractions. The aim is to identify babies who may be short of oxygen (hypoxic) to guide additional assessments of fetal wellbeing, or determine if the baby needs to be delivered by caesarean section or instrumental vaginal birth. This is an update of a review previously published in 2013, 2006 and 2001.
OBJECTIVES
To evaluate the effectiveness and safety of continuous cardiotocography when used as a method to monitor fetal wellbeing during labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 November 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials involving a comparison of continuous cardiotocography (with and without fetal blood sampling) with no fetal monitoring, intermittent auscultation intermittent cardiotocography.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study eligibility, quality and extracted data from included studies. Data were checked for accuracy.
MAIN RESULTS
We included 13 trials involving over 37,000 women. No new studies were included in this update.One trial (4044 women) compared continuous CTG with intermittent CTG, all other trials compared continuous CTG with intermittent auscultation. No data were found comparing no fetal monitoring with continuous CTG. Overall, methodological quality was mixed. All included studies were at high risk of performance bias, unclear or high risk of detection bias, and unclear risk of reporting bias. Only two trials were assessed at high methodological quality.Compared with intermittent auscultation, continuous cardiotocography showed no significant improvement in overall perinatal death rate (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.59 to 1.23, N = 33,513, 11 trials, low quality evidence), but was associated with halving neonatal seizure rates (RR 0.50, 95% CI 0.31 to 0.80, N = 32,386, 9 trials, moderate quality evidence). There was no difference in cerebral palsy rates (RR 1.75, 95% CI 0.84 to 3.63, N = 13,252, 2 trials, low quality evidence). There was an increase in caesarean sections associated with continuous CTG (RR 1.63, 95% CI 1.29 to 2.07, N = 18,861, 11 trials, low quality evidence). Women were also more likely to have instrumental vaginal births (RR 1.15, 95% CI 1.01 to 1.33, N = 18,615, 10 trials, low quality evidence). There was no difference in the incidence of cord blood acidosis (RR 0.92, 95% CI 0.27 to 3.11, N = 2494, 2 trials, very low quality evidence) or use of any pharmacological analgesia (RR 0.98, 95% CI 0.88 to 1.09, N = 1677, 3 trials, low quality evidence).Compared with intermittent CTG, continuous CTG made no difference to caesarean section rates (RR 1.29, 95% CI 0.84 to 1.97, N = 4044, 1 trial) or instrumental births (RR 1.16, 95% CI 0.92 to 1.46, N = 4044, 1 trial). Less cord blood acidosis was observed in women who had intermittent CTG, however, this result could have been due to chance (RR 1.43, 95% CI 0.95 to 2.14, N = 4044, 1 trial).Data for low risk, high risk, preterm pregnancy and high-quality trials subgroups were consistent with overall results. Access to fetal blood sampling did not appear to influence differences in neonatal seizures or other outcomes.Evidence was assessed using GRADE. Most outcomes were graded as low quality evidence (rates of perinatal death, cerebral palsy, caesarean section, instrumental vaginal births, and any pharmacological analgesia), and downgraded for limitations in design, inconsistency and imprecision of results. The remaining outcomes were downgraded to moderate quality (neonatal seizures) and very low quality (cord blood acidosis) due to similar concerns over limitations in design, inconsistency and imprecision.
AUTHORS' CONCLUSIONS
CTG during labour is associated with reduced rates of neonatal seizures, but no clear differences in cerebral palsy, infant mortality or other standard measures of neonatal wellbeing. However, continuous CTG was associated with an increase in caesarean sections and instrumental vaginal births. The challenge is how best to convey these results to women to enable them to make an informed decision without compromising the normality of labour.The question remains as to whether future randomised trials should measure efficacy (the intrinsic value of continuous CTG in trying to prevent adverse neonatal outcomes under optimal clinical conditions) or effectiveness (the effect of this technique in routine clinical practice).Along with the need for further investigations into long-term effects of operative births for women and babies, much remains to be learned about the causation and possible links between antenatal or intrapartum events, neonatal seizures and long-term neurodevelopmental outcomes, whilst considering changes in clinical practice over the intervening years (one-to-one-support during labour, caesarean section rates). The large number of babies randomised to the trials in this review have now reached adulthood and could potentially provide a unique opportunity to clarify if a reduction in neonatal seizures is something inconsequential that should not greatly influence women's and clinicians' choices, or if seizure reduction leads to long-term benefits for babies. Defining meaningful neurological and behavioural outcomes that could be measured in large cohorts of young adults poses huge challenges. However, it is important to collect data from these women and babies while medical records still exist, where possible describe women's mobility and positions during labour and birth, and clarify if these might impact on outcomes. Research should also address the possible contribution of the supine position to adverse outcomes for babies, and assess whether the use of mobility and positions can further reduce the low incidence of neonatal seizures and improve psychological outcomes for women.
Topics: Cardiotocography; Cesarean Section; Female; Heart Auscultation; Heart Rate, Fetal; Humans; Infant; Infant Mortality; Infant, Newborn; Labor, Obstetric; Pregnancy; Randomized Controlled Trials as Topic; Seizures
PubMed: 28157275
DOI: 10.1002/14651858.CD006066.pub3 -
Frontiers in Endocrinology 2023The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons. (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUNDS
The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons.
METHODS
This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework.
RESULTS
Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups.
CONCLUSION
In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fractures, Bone; Hypoglycemia; Hypovolemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37701900
DOI: 10.3389/fendo.2023.1238399 -
Clinical Toxicology (Philadelphia, Pa.) Nov 2022Metformin poisoning with lactic acidosis is an uncommon yet clinically serious condition related to the inhibition of normal aerobic metabolism. Toxicity may occur after...
INTRODUCTION
Metformin poisoning with lactic acidosis is an uncommon yet clinically serious condition related to the inhibition of normal aerobic metabolism. Toxicity may occur after an acute overdose although it is much more common after a systemic insult, such as acute kidney injury, in the setting of chronic use. Hemodialysis is currently the preferred extracorporeal treatment modality (Grade 1D evidence) although some patients may be too hemodynamically unstable to tolerate it. Continuous renal replacement therapy is considered an alternative if hemodialysis is unavailable but an evaluation of survival amongst this specific treatment class is lacking.
OBJECTIVES
To assess overall survival and provide an updated review of the toxicokinetic elimination parameters of patients receiving continuous renal replacement therapy for metformin poisoning.
METHODS
A comprehensive search was performed using the EMBASE and MEDLINE libraries from inception until November 30, 2021. Data was extracted and findings were summarized. Toxicokinetic parameters were analyzed and confirmed for accuracy when data permitted.
RESULTS
Eighty-three reports met inclusion criteria. These consisted of only low-quality evidence including 75 case reports, four case series, and four descriptive retrospective reviews. Overall survival among patients suffering from metformin toxicity who received continuous extracorporeal treatment was 85.8%. When stratified between metformin-induced lactic acidosis and metformin-associated lactic acidosis, survival was 75.0% and 87.4%, respectively. Available continuous renal replacement therapy toxicokinetic parameters were quite heterogeneous. Errors in previously published toxicokinetic calculations were noted in only two instances. The overall average and median peak metformin concentrations were 70.5 mg/L and 41.9 mg/L, respectively. The average and median extracorporeal clearance rates were 39.0 mL/min and 42.1 mL/min (range 9.0-58.7 mL/min). The average and median elimination half-life parameters were 27.5 h and median 23.0 h. Elimination half-life ranged from seven to 74 h. There was no meaningful relationship between peak metformin concentration and continuous extracorporeal treatment half-life at lower concentrations, though at very high concentrations (over 200 mg/L), there was a trend towards a half-life below 20 h. There is insufficient data to robustly evaluate overall survival in relation to the extracorporeal clearance rate. Finally, there was no relevant relationship between maximal lactate concentration and survival, nor nadir pH and survival, for patients with either type of metformin toxicity.
CONCLUSIONS
This retrospective systematic analysis of published cases treating metformin related lactic acidosis with continuous renal replacement therapy notes an overall slightly greater survival percentage compared to previous publications of individuals requiring modality of renal replacement therapy. Because of publication bias, these results should be interpreted with caution and serve as hypothesis generating for future research. Prospective study focusing on the most clinically meaningful endpoint - survival - will help elucidate if continuous modalities are non-inferior to intermittent hemodialysis in metformin toxicity.
Topics: Humans; Acidosis, Lactic; Metformin; Retrospective Studies; Prospective Studies; Hypoglycemic Agents
PubMed: 36239608
DOI: 10.1080/15563650.2022.2127363 -
Burns : Journal of the International... Jun 2018The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in...
BACKGROUND
The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in various vehicles that augment skin absorption thus allowing greater efficacy. Polyethylene glycol (PEG) and Propylene glycol (PropG) are among the most commonly used vehicles, and both have been used in numerous medications and cosmetic products over the past few decades. Rarely, burn patients treated with agents containing these glycols present with a life threatening systemic toxidrome of hyperosmolar metabolic acidosis. We present a systematic review of outcomes in burn patients treated with similar agents.
METHODS
Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters), from database inception to August 4th, 2016. All publications of clinical burn patient studies included at least one arm receiving a glycol based topical therapy.
RESULTS
A total of 61 studies involving 10,282 patients and 4 different antimicrobial medications fulfilled the inclusion criteria. Nine burn patients (0.09%) were documented to present with hyperosmolar metabolic acidosis during topical silver sulfadiazine treatment. Propylene glycol isolated from their blood accounted for the high osmole gap.
CONCLUSION
This first systematic review found very few cases of documented hyperosmolar metabolic acidosis, all within one study that had set to specifically explore this toxidrome. High index of suspicion with frequent osmolar gap monitoring may help identify future toxicities in a timely manner.
Topics: Acidosis; Anti-Infective Agents, Local; Glycols; Humans; Osmolar Concentration; Pharmaceutical Vehicles; Polyethylene Glycols; Propylene Glycol
PubMed: 28797572
DOI: 10.1016/j.burns.2017.06.006 -
Pharmacology 2023Metformin-treated patients may experience severe hyperlactatemia or lactic acidosis (LA). LA often requires intensive-care-unit (ICU) treatment, and mortality rates are...
INTRODUCTION
Metformin-treated patients may experience severe hyperlactatemia or lactic acidosis (LA). LA often requires intensive-care-unit (ICU) treatment, and mortality rates are high. Here, we investigate the impact of renal dysfunction and renal replacement therapy (RRT) on the outcomes of critically ill patients with metformin-associated LA (MALA). Furthermore, we assessed associations between mortality and metformin dose, metformin plasma/serum concentrations, lactate level, and arterial pH. Finally, we investigated whether the recommended classification in MALA, metformin-unrelated LA, metformin-induced LA, and LA in metformin therapy appears useful in this regard.
METHODS
We performed a retrospective analysis based on a systematic PubMed search for publications on hyperlactatemia/LA in metformin-treated ICU patients from January 1995 to February 2020. Case-level data including demographics and clinical conditions were extracted, and logistic regression analyses were performed.
RESULTS
A total of 92 ICU patients were reported. Two of these patients had no comorbidities interfering with lactate metabolism. In the overall group, arterial pH, lactate levels, and metformin plasma/serum concentrations were similar in survivors versus non-survivors. Ingested daily metformin doses and plasma/serum creatinine levels were significantly higher in survivors versus non-survivors (p = 0.007 vs. p = 0.024, respectively). Higher plasma/serum creatinine levels, higher lactate levels, and lower arterial pH were all associated with patients receiving RRT (all p < 0.05). Overall mortality was 22% (20 out of 92 patients) and did not differ between the RRT and non-RRT groups.
CONCLUSION
Mortality is high in ICU patients with metformin-associated hyperlactatemia/LA. Unexpectedly, higher ingested metformin dose and plasma/serum creatinine were associated with a better outcome. Survival was similar in patients with or without need for RRT.
Topics: Humans; Hyperlactatemia; Acidosis, Lactic; Retrospective Studies; Creatinine; Metformin; Intensive Care Units; Lactates; Hypoglycemic Agents
PubMed: 36652938
DOI: 10.1159/000528252