Beware of beta! A case of salbutamol-induced lactic acidosis in severe asthma

Abstract

A 22-year-old woman presented with symptoms and signs consistent with acute severe asthma. After significant doses of beta-agonist, she developed a significant lactic acidosis. Significant issues arose in this patient's history with regards to purchase of medications, compliance and follow-up with respiratory service. Beta-adrenergic receptors when stimulated have been hypothesised to increase lipolysis, producing free fatty acids, which inhibit the conversion of pyruvate to coenzyme A within the Krebs cycle. Additional pyruvate is generated through stimulation of glycolysis and glycogenolysis through simultaneous catecholamine surge. This increased pyruvate load is shunted through anaerobic glycolysis, producing increased lactate. Steroid use during an asthma attack enhances the beta-2 receptor sensitivity, further potentiating lactate production. The hyperadrenergic state in this young asthmatic likely resulted in pyruvate and therefore lactate rise and thus metabolic acidosis as mentioned before. This piece highlights a physiological phenomenon that may occur in the context of iatrogenic hyperadrenergism.

Prevalence and risk factors of lactic acidosis in children with acute moderate and severe asthma, a prospective observational study

“…In paediatric case reports, lactate concentration in asthma-related lactic acidosis ranged from 5.9 to 9.2 mmol/l [ 8 ]. Koul documented lactic acidosis with a peak lactate range (5.2–13 mmol/l) 2–8 h after the beginning of aerosol therapy in 4 children 11 to 17 years of age.…”

“…Even if lactic acidosis during asthma is a self-limited condition, it has an impact on assessment and management of respiratory distress. Compensatory hyperventilation of lactic acidosis is often mistaken as a sign of respiratory worsening and leads to inappropriate escalation of bronchodilator therapy, increasing morbidity and mortality [ 8 , 9 ].…”

The more you give, the worse it gets

“…However, once this pathway is saturated, pyruvate is shunted and metabolised through the anaerobic pathway into lactate [ 6 ]. This hyperadrenergic state also enhances lipolysis, resulting in free fatty acids that inhibit the entrance of pyruvate into the Krebs cycle via inhibition of pyruvate dehydrogenase, thus shunting pyruvate into the anaerobic pathway [ 6 , 7 ]. Moreover, systemic corticosteroid use frequently induces a state of hyperglycaemia, which potentially provides more substrate for lactic acid production [ 5 ].…”

“…Moreover, systemic corticosteroid use frequently induces a state of hyperglycaemia, which potentially provides more substrate for lactic acid production [ 5 ]. Corticosteroids also enhance β 2 -receptor sensitivity, perpetuating the vicious cycle of a hyperadrenergic state and increased lactate production [ 7 ].…”

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

“…Forty-two articles [4, reported on 47 patients (Table 1), who were found to have a blood lactic acid level ≥5.0 mmol/L on treatment with a short-acting (N = 46) or a long-acting (N = 1) ß 2 -agonist, which subsequently decreased by ≥3.0 mmol/L or to ≤2.5 mmol/L ( Figure 2). This was noticed 3 to 56, median 13 h later: in 24 cases after discontinuing [4,[9][10][11][14][15][16]18,19,22,24,25,29,[32][33][34]36,38,40,41,47,48], in 17 cases after reducing [12,13,20,22,23,26,28,30,31,35,37,39,42,43,45], and in 6 cases (all of these patients were affected by asthma) without modifying [8,12,17,21,27,46], the dosage of the selective ß 2 -agonist. None of the patients was managed with further drugs potentially associated with hyperlactate...…”