Medication‐Induced Hyperlactatemia and Lactic Acidosis: A Systematic Review of the Literature

Abstract

Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are diagnoses of exclusion and have the potential to be overlooked. The purposes of this systematic review are to identify published reports of medication-induced lactate level elevations to aid clinicians in diagnosing and comprehending the underlying mechanism of this rare adverse drug effect and to provide management strategies. The PubMed database was searched for case reports, case series, retrospective studies, and prospective studies describing cases of medication-induced lactate level elevation, including lactic acidosis and hyperlactatemia, published between January 1950 and June 2017. A standardized search strategy was used, and the articles identified underwent two rounds of independent evaluation by two reviewers to assess for inclusion. Articles were included if they described at least one patient older than 12 years with hyperlactatemia or lactic acidosis caused by a medication with United States Food and Drug Administration (FDA) approval and if alternative etiologies for an elevated lactate level were ruled out. Metformin and nucleoside/nucleotide reverse transcriptase inhibitors were excluded since the pathophysiology and incidence of lactic acidosis have been well established for these agents. Overall, 1918 articles were identified, and 101 met inclusion criteria. A total of 286 patients experienced medication-induced lactate level elevations, from which 59 unique medications were identified. The most commonly identified agents were epinephrine and albuterol. Medication-induced lactate level elevation was classified as lactic acidosis (64.0%), hyperlactatemia (31.1%), or not specified (4.9%). The doses ingested included FDA-labeled doses (86%), intentional overdoses (10.8%), or prescribed doses exceeding the FDA-labeled dose (3.1%). Medications were continued without a change (40.8%), were permanently discontinued (34.4%), were continued with a dosage reduction (11.6%), or were initially withheld then resumed after lactate level normalized (2.9%); medication management for the remaining 10.0% was not reported. Forty-six patients died (16%). Six deaths were attributed by treating clinicians to be secondary to medication-induced lactic acidosis. Management strategies were heterogeneous, and treatment included supportive care, exogenous bicarbonate therapy, medication specific antidotes, and decontamination strategies. Unexplained lactate level elevations should prompt clinicians to assess for medication-induced lactate level elevations. Pharmacists are members of the health care team that are well positioned to serve as experts in the diagnosis and management of medication-induced lactate level elevations. KEY WORDS adverse drug reactions, hyperlactatemia, systematic review, lactate, lactic acidosis. (Pharmacotherapy 2019;39(9):946-963)

Lactate/Albumin Ratio as a Predictor of In-Hospital Mortality in Septic Patients Presenting to the Emergency Department

“…Our study supports existing literature on the use of the L/A ratio as a prognostic marker in patients with sepsis with fair discriminative value. Although lactate is a well-studied prognostic biomarker, its interpretation is complex due to the pathophysiology that can lead to serum lactate elevations (13)(14)(15)(16)(17)(18). Moreover, normal lactate levels may be falsely misinterpreted as a good prognosis in high-risk patients.…”

“…The current recommendation is to obtain a serum lactate level within the first hour of presentation in all patients with suspected sepsis, and to repeat the measurement within 2-4 h if the initial lactate is more than 2 mmol/L (12). However, lactic acidosis has been described in patients on metformin and albuterol (13), patients with diabetic ketoacidosis (14), malignancies (15), intoxication (16), hepatic or renal dysfunction (17,18), and lastly, as a consequence of receiving epinephrine (13). In these cases, it is challenging to rely solely on lactate levels for prognostication.…”

Selective ß2-Adrenoceptor Agonists and Relevant Hyperlactatemia: Systematic Review and Meta-Analysis

“…Our analysis complements the results of a very recent review which included patients ≥13 years of age with hyperlactatemia associated with the administration of both selective and non-selective ß 2 -agonists [2].…”

“…The potential of selective ß 2 -agonists to produce hypocalcemia, hypomagnesemia, hypophosphatemia, and especially hypokalemia and hyperglycemia is well recognized but often overlooked in clinical practice [2,[67][68][69]. The present review of the literature points out that relevant hyperlactatemia is also common (about 20%) on high dose treatment with these agents.…”

“…Excess (≥2.5 mmol/L) blood lactic acid level and, less frequently, lactic acidosis, may result from poor tissue oxygen delivery, from inherited or acquired metabolic defects and from drugs such as biguanides, some antiretrovirals, the antibiotic linezolid, and the hypnotic sedative propofol [1,2].…”