Metformin and contrast media — A dangerous combination?

Metformin-Associated Lactic Acidosis in a Patient with Normal Renal Function.

<h2>Metformin-associated lactic acidosis (M-ALA) is considered to be one of the complications caused by intravascular contrast media (CM) administration in diabetics especially those with coexisting renal or cardiac impairment. We focused on the necessity and duration of metformin suspension in diabetics with normal or impaired renal function scheduled for CT scan with IV contrast. Searching PubMed, Web of Science, and Scopus databases, we reviewed the latest relevant guidelines as well as articles published from 1994 to 2015. There is no global consensus among different guidelines on the duration of the Metformin suspension before CT scan with IV contrast. Also, lack of substantial evidence supporting M-ALA encourages specialists to take a less conservative approach.</h2> It is safe to continue Metformin in patients with normal renal function who have no co-morbidities. In cases of equivocal renal function (30&lt;GFR&lt;60 mL/min/1.73 m²) and also in patients with normal renal function and other co-morbidities, the decision should be made based on the patient’s clinical status. In case of severe renal failure, the use of metformin should be reassessed. Due to the probability of contrast associated nephropathy, laboratory follow up seems to be necessary for all patients.

Background Metformin associated lactic acidosis (MALA) is a serious adverse event with a high mortality rate of 30–50%. Early recognition of MALA and timely starting treatment may reduce its morbidity and mortality. Objective The aim of this study was to explore clinical parameters to identify patients with MALA in patients with suspected sepsis induced lactic acidosis in the emergency department ED. Setting A retrospective single centre study was conducted at the Deventer Teaching Hospital in the Netherlands. Method Patients with lactate concentration > 4.0 mmol/l admitted at the ED between 2010 and 2017 with suspected sepsis or confirmed MALA and referred to the Intensive Care Unit were included. Baseline characteristics (pH, lactate, creatinine and CRP) of MALA patients were compared with patients with suspected sepsis induced lactic acidosis. Creatinine and lactate concentration were selected as potential relevant parameters. Main outcome measure Sensitivity and specificity of the highest tertiles of the creatinine and the lactate concentrations separately, in combination, and both combined with metformin use, were calculated. Results Thirteen MALA and 90 suspected sepsis induced lactic acidosis patients were included. Lactate (14.7 vs 5.9 mmol/l, p < 0.01) and creatinine concentration (642 vs 174 μmol/l, p < 0.01) were significantly higher in the MALA group and arterial pH (7.04 vs 7.38, p < 0.01) and CRP (90 vs 185 mg/l, p < 0.01) were significantly lower. The combined parameters lactate ≥ 8.4 mmol/l, creatinine ≥ 256 μmol/l had a sensitivity of 85% and a specificity of 95% for identifying MALA in suspected sepsis induced lactic acidosis patients in the ED. When combined with metformin use the specificity increased to 99%. Conclusion When managing lactic acidosis in the ED the diagnosis MALA should be considered in patients with a creatinine concentration ≥ 256 μmol/l and lactate concentration ≥ 8.4 mmol/l.

Nurturing a Research-active Clinical Oncology Workforce: A Trainee Perspective

The administration of intravenous (IV) contrast media during computed tomography (CT) examinations is essential to enhance diagnostic accuracy in various clinical scenarios. Traditionally, older age is considered a risk factor for the development of post-contrast Acute Kidney Injury (PC-AKI); however, there is limited information available for the super-elderly population (aged ≥ 85). This study aims to investigate the incidence and risk factors associated with PC-AKI in individuals aged 85 and older undergoing CT scans with IV contrast. A retrospective cohort study, including all hospitalized patients aged 85 or older who underwent CT scans between the years 2005 and 2021. Patients were categorized into IV contrast and non-IV contrast groups. Baseline demographic and clinical data, along with kidney function parameters, were collected. The final cohort included 7,078 patients who underwent CT scans, with 40% receiving IV contrast. The overall AKI occurrence within 72 h post-CT was 5.72%, slightly elevated in the non-IV contrast group (6.25% vs. 4.94%, p = 0.02). However, multivariate analysis revealed no significant difference between the groups (OR 1, CI 0.8-1.2, p = 0.92), even after stratifying by kidney function. A secondary analysis, using a less strict AKI definition, supported these findings. Baseline creatinine levels emerged as prominent risk factor associated with PC- AKI. The current study provides reassurance regarding the safety of contrast-enhanced CT scans in super-elderly patients, particularly those with baseline normal to mild kidney dysfunction. These findings may contribute to the ongoing discussion on the risk-benefit balance of contrast-enhanced CT scans in the super-elderly population.

Evidence of an association between intravenous contrast media (CM) and persistent renal dysfunction is lacking for patients with pre-existing acute kidney injury (AKI). This study was designed to determine the association between intravenous CM administration and persistent AKI in patients with pre-existing AKI. A retrospective propensity-weighted and entropy-balanced observational cohort analysis of consecutive hospitalized patients ≥ 18years old meeting Kidney Disease Improving Global Outcomes (KDIGO) creatinine-based criteria for AKI at time of arrival to one of three emergency departments between 7/1/2017 and 6/30/2021 who did or did not receive intravenous CM. Outcomes included persistent AKI at hospital discharge and initiation of dialysis within 180days of index encounter. Our analysis included 14,449 patient encounters, with 12.8% admitted to the intensive care unit (ICU). CM was administered in 18.4% of all encounters. AKI resolved prior to hospital discharge for 69.1%. No association between intravenous CM administration and persistent AKI was observed after unadjusted multivariable logistic regression modeling (OR 1; 95% CI 0.89-1.11), propensity weighting (OR 0.93; 95% CI 0.83-1.05), and entropy balancing (OR 0.94; 95% CI 0.83-1.05). Sub-group analysis in those admitted to the ICU yielded similar results. Initiation of dialysis within 180days was observed in 5.4% of the cohort. An association between CM administration and increased risk of dialysis within 180days was not observed. Among patients with pre-existing AKI, contrast administration was not associated with either persistent AKI at hospital discharge or initiation of dialysis within 180days. Current consensus recommendations for use of intravenous CM in patients with stable renal disease may also be applied to patients with pre-existing AKI.

Background: Metformin-associated lactic acidosis (MALA) and metformin-induced lactic acidosis (MILA) remain controversial entities. Metformin toxic effect depends on accumulation to lead to lactic acidosis (LA), particularly during an episode of acute kidney injury (AKI). In MILA, no other condition contributing to LA is found. The aims of this study were to describe the characteristics and prognosis of AKI associated with LA in metformin users and to clarify the role of this drug in the different types of LA.Methods: We performed a French multicenter retrospective study in diabetic patients treated by metformin presenting with LA in a context of AKI in 2015. 126 nephrology units (NU) and 23 intensive care units (ICU) were contacted. We individualized MILA and MALA patients in order to illustrate the role of metformin.Results: We included 173 patients (109 MILA, 64 MALA). 103 patients presented without hemodynamic instability (82 MILA and 21 MALA) whereas 70 patients were shocked including 27 MILA. The shock was associated with death with an odds ratio (OR) of 12.92 (p < .001). Digestive disorders (DD) were strongly associated with MILA (p = .0001). MALA was significantly associated with shock (p < .0001). The mortality rate was higher in MALA (26%) when compared with MILA (7%). Dialysis performed in 133 patients was significantly associated with shock, kalemia, lactate and serum creatinine levels. In multivariate analysis, metformin level was independently associated with pH or lactate level only in MILA patients.Conclusions: MILA is associated with DD and death is due to severe refractory acidosis leading to cardiovascular collapse attributed to metformin accumulation mainly via AKI. MALA patients are more frequently shocked and death is related to their underlying condition, metformin accumulation increasing LA.

BackgroundMetformin has been widely used as a first-line agent to treat type 2 diabetes mellitus. Lactic acidosis is a rare but serious adverse effect in patients treated with metformin. Recent studies noted a correlation between metformin accumulation and lactic acidosis. Continuous renal replacement therapy for the treatment of metformin-associated lactic acidosis has been documented in some case reports; however, there is currently no specific treatment for metformin-associated lactic acidosis.Case presentationA 70-year-old Japanese woman with type 2 diabetes mellitus presented to an emergency room with metformin-associated lactic acidosis. She was found to be hypotensive and laboratory examinations revealed severe lactic acidosis: pH 6.618, partial pressure of carbon dioxide in arterial blood 17.3 mmHg, bicarbonate 1.7 mmol/L, and lactate 18 mmol/L. Severe acidemia persisted despite supportive care including intravenously administered fluids, sodium bicarbonate, antibiotics, and vasopressors. Continuous renal replacement therapy was initiated in our intensive care unit. After dialysis for 3 days, her lactate level and pH value completely normalized. The concentration of metformin detected was 77.5 mg/L, which is one of the highest in metformin-associated lactic acidosis successfully treated without overdose.ConclusionsThe present case had one of the highest metformin concentrations in metformin-associated lactic acidosis successfully treated with continuous renal replacement therapy, and serum metformin concentrations may be useful for the diagnosis of metformin-associated lactic acidosis. Metformin-associated lactic acidosis is a rare but important etiology of lactic acidosis. Continuous renal replacement therapy is advantageous for the treatment of hemodynamically unstable patients with metformin-associated lactic acidosis.

Intravenous contrast medium (ICM) rarely induces anaphylactic reactions, including urticaria, hypotension and respiratory failure. Even the most modern ICM may cause such adverse events. Thrombocytopenia has been reported as an extreme rare consequence of ICM. Here we report on a case of a 72-year-old male patient with a self-limiting severe acute thrombocytopenia following administration of intravenous non-ionic low-osmolarity contrast medium. No such low platelet count has ever been reported. We also present a review of the literature.

Non-cardiac pulmonary edema following intravenous (IV) contrast medium is a rare form of severe allergic response; however, association of cardiopulmonary arrest with it is even an extremely uncommon occurrence. It is a very serious and life threatening reaction, and it must be immediately recognized and promptly treated to avoid poor outcome. I, report a case of a 77-year-old female who developed an immediate acute pulmonary edema of non-cardiac origin resulting in cardiopulmonary arrest on computed tomography (CT) scan table following IV non-ionic contrast media injection of Optiray 320 during spiral CT of abdomen for a routine outpatient urological disorder for follow-up with a miraculous outcome. There was no known previous reaction or allergy to IV contrast. A prolonged cardiopulmonary resuscitation (CPR) more than 4 h was required to revive and stabilize the patient’s critical condition with complete recovery without any sequel. Take home message is to be familiar with and recognize these catastrophic complications of IV contrast and be prepared to manage them appropriately and immediately to save the patients’ life. A routine use of IV Benadryl prior to contrast injection may be beneficial in high risk patients. Due to serious untoward reactions of IV contrast, it may be prudent to discover or invent a new inert substance or improved CT scanning techniques without any contrast. “Thou shall not harm”. J Med Cases. 2018;9(1):5-7 doi: https://doi.org/10.14740/jmc2955e

N-Acetylcysteine (NAC) may confer protection against post-contrast acute kidney injury (PC-AKI), although evidence is sparse and conflicting. The objective was to analyse the evidence on the efficacy and safety of NAC vs no administration of NAC in preventing PC-AKI in patients with pre-existing kidney impairment undergoing a non-interventional radiological examination requiring intravenous (IV) contrast media (CM) administration. We carried out a systematic review including randomised controlled trials (RCTs) published in MEDLINE, EMBASE, and Clinicaltrials.gov up to May 2022. The primary outcome was PC-AKI. Secondary outcomes included the requirement of renal replacement therapy, all-cause mortality, serious adverse events, and length of hospital stay. We conducted the meta-analyses using the Mantel-Haenszel method and following a random-effects model. NAC was not associated with a significant reduction in PC-AKI (RR 0.47, 95%CI 0.20 to 1.11; 8 studies; 545 participants; I2: 56%; low certainty), all-cause mortality (RR 0.67, 95%CI 0.29 to 1.54; 2 studies; 129 participants; very low certainty), or length of hospital stay (mean difference 9.2days, 95%CI - 20.08 to 38.48; 1 study; 42 participants; very low certainty). The impact on other outcomes could not be determined. NAC may not reduce the risk of PC-AKI or all-cause mortality in people with kidney impairment who receive an IV CM prior to radiological imaging, although the certainty of the evidence is very low or low. Our review concludes that prophylactic administration of N-acetylcysteine may not significantly reduce the risk of acute kidney injury in patients with kidney impairment receiving an intravenous contrast media prior to non-interventional radiological imaging, which may support decision making in this common clinical scenario. • N-Acetylcysteine may not significantly reduce the risk of acute kidney injury in patients with kidney impairment receiving an intravenous contrast media prior to non-interventional radiological imaging. • All-cause mortality and length of hospital stay would not be decreased with the administration of N-Acetylcysteine in this setting.

INTRODUCTION- Metformin is a commonly prescribed anti diabetic drug, with rare but potentially severe toxicity. Metformin associated lactic acidosis (MALA) is one of the most dreaded complication of metformin use, with an incidence of less than 10 events per 100,000 patient years of exposure. MALA is defined as pH less than 7.35 and lactate more than 5 mmol/L. MALA is a difficult diagnosis to make as it is a diagnosis of exclusion, however it is reported to be quite lethal with a mortality rate as high as 50%. DESCRIPTION OF CASE- A 70 year old female with Diabetes Mellitus (DM), Anemia and hypertension presented to the emergency department with altered mental status and malaise. Her home medications included metoprolol, amlodipine, hydrochlorothiazide, losartan, metformin, insulin glargine and aspart. She was quickly intubated due to concern for airway protection. On presentation, she was hypotensive, bradycardic, hypothermic, and her labs were significant for lactate 14, pH 6.68, serum bicarbonate less than 5, creatinine 10.29, Blood urea nitrogen 133, white blood cell count 27k and blood glucose level 180. She was treated empirically for sepsis, however no source of infection was identified. Cardiogenic shock was ruled out as her echocardiogram demonstrated an ejection fraction more than 55% and mild left ventricular diastolic dysfunction. She remained in a severe shock state, requiring all vasopressors available, and intermittent dialysis was attempted along with a bicarbonate infusion. Goals of care discussions occurred, and she expired in the Intensive Care Unit within 36 hours of presentation. Metformin levels were not readily available to be sent, so this lab was not collected during the patient's course. DISCUSSION- MALA can occur acutely in an overdose but typically has a more gradual onset in patients with hepatic or renal dysfunction due to decreased excretion. The lactic acidosis from metformin is primarily type B but can be compounded by type A when the drug's lactic acid production leads to cardiovascular collapse, tissue hypoperfusion and hepatic dysfunction. In our case, we did not have metformin levels, however MALA appears to be a possible explanation of this patient's presentation. Furthermore, the level of metformin required to cause toxicity has not been clearly defined. IMPORTANCE OF CASE- With metformin's wide usage for DM and Polycystic Ovary Syndrome, and its recent potential as an anti-aging medication, the awareness around MALA should be increased as it can be a devastating condition as demonstrated by this case.

The importance of early haemodiafiltration in the treatment of lactic acidosis associated with the administration of metformin.

MP56-01 RENAL FUNCTIONAL CHANGES AFTER CYSTECTOMY: WHO IMPROVES AND WHO DOES NOT?

Contrast media-induced nephropathy (CIN) is an increasing cause of hospital-acquired acute kidney injury and leads to a significant increase in mortality. There is uncertainty whether the use of iso-osmolar contrast media as opposed to the use of low-osmolar contrast media would be associated with a lower incidence of CIN. Therefore, we compared the nephrotoxicity of isoosmotic contrast media iodixanol with the low-osmotic contrast media iopromid in patients receiving contrast media during coronary angiography. In this prospective double-blind study we examined 221 patients with normal renal function who received up to 1,000 ml of contrast media during coronary angiography, and compared the effect of iodixanol and iopromid on inducing contrast media nephropathy. Patients received 800 ml fluid orally before contrast media administration and 1,000 ml saline i.v. thereafter. Creatinine clearance, serum creatinine and urine-N-acetyl-beta-D-glucosaminidase (NAG) concentration was obtained 24 h before and 48 h after contrast media administration. Decrease of 20% of the creatinine clearance, increase of 25% of serum creatinine and increase of 20% of the urine concentration of NAG was defined as CIN. Incidence of CIN assessed by decreased creatinine clearance was 22.2% in the iopromid group and 19.7% in the iodixanol group. CIN defined by increased serum creatinine was 6.9% in the iopromid group and 8.6% in the iodixanol group. The difference between these two groups was not significant. Subgroup analysis of the diabetic patients or the patients that received high dose of contrast media revealed no significant difference in the incidence of CIN between the two contrast media. The iso-osmolar and the low-osmolar contrast media exhibited the same incidence of CIN in our study population. If fluid administration is sufficient, the selection of either iopromid or iodixanol has no impact on the risk of developing CIN in patients with normal renal function, even when they are diabetic or receive a high dose of more than 500 ml contrast media.