Case Reports  |   August 2003
Albuterol-induced Lactic Acidosis
Author Affiliations & Notes
  • Edwin B. Liem, M.D.
  • Stephen C. Mnookin, M.D.
  • Michael E. Mahla, M.D.
  • *Assistant Professor, Outcomes Research™ Institute and Department of Anesthesiology, University of Louisville. †Anesthesia Consultant, Anesthesiology Associates of Tallahassee, P.A. ‡Professor of Anesthesiology and Neurosurgery, Associate Professor for Education, Department of Anesthesiology, University of Florida.
  • Received from the Outcomes Research™ Institute and Department of Anesthesiology, University of Louisville, Louisville, Kentucky; and the Department of Anesthesiology and Neurosurgery, University of Florida, Gainesville, Florida.
Article Information
Case Reports
Case Reports   |   August 2003
Albuterol-induced Lactic Acidosis
Anesthesiology 8 2003, Vol.99, 505-506. doi:
Anesthesiology 8 2003, Vol.99, 505-506. doi:
LACTIC acidosis occurring in association with β-2 agonist treatments such as salbutamol, 1,2 ritodrine, 3 meta-proterenol, 4 and albuterol 5 has been reported, and its mechanism remains poorly understood. Lactic acidosis in the setting of severe asthma has been attributed to the production of lactate by overworked respiratory muscles. 6 However, the increased work of breathing seems an unlikely factor in patients who are anesthetized, paralyzed, and mechanically ventilated, and this phenomenon has not been previously reported in anesthetized patients. We report a case of severe lactic acidosis in a patient undergoing thoracoscopic sympathectomy under general anesthesia who received repeated albuterol nebulizer treatments for bronchospasm.
Case Report
A 39-yr-old white woman was scheduled for thoracoscopic sympathectomy at the University of Florida, Shands Hospital, to alleviate reflex sympathetic dystrophy. The patient had a history of mild asthma for which she was never intubated or hospitalized in the past. Her home medications included loratadine (Claritin-D®; Schering-Plough, Kenilworth, NJ), fluticasone (Flonase®; Glaxo Smith Kline, Philadelphia, PA), amitriptyline (Elavil®; AstraZeneca, Wilmington, DE), and albuterol-metered-dose inhalers that she used one to two times per week. The patient was allergic to sulfa drugs, mexiletine, and benzoin. Previous operations, all without complications, included cholecystectomy, appendectomy, carpal tunnel release, and removal of a ganglion cyst on right wrist. Physical examination revealed a 97-kg woman in no apparent distress with clear breath sounds on auscultation; her hematocrit was 0.37.
Preoperative medications included an albuterol nebulizer treatment (2.5 mg) and intravenous midazolam (2 mg). The patient was then taken to the operating room; initial vital signs were heart rate of 100 beats per minute, blood pressure 145/75 mmHg, and arterial oxygen saturation of 100% on room air. The patient was then preoxygenated for 2 min, and general anesthesia was induced with 350 mg sodium thiopental, 10 mg pancuronium, and 50 μg sufentanil. Anesthesia was maintained with a sufentanil infusion and isoflurane. The patient was easily mask-ventilated. Tracheal intubation was attempted with a 39, and then a 37, French double-lumen endotracheal tube, but this was unsuccessful because of the patient's small mouth opening. Thus, we placed a 7.0-mm single-lumen endotracheal tube with a bronchial blocker (Univent, Fuji Systems Corporation, Tokyo, Japan).
The patient then developed severe bronchospasm, which was confirmed with auscultation and by observation of slow-rising expiratory phases on the capnography waveform. Initial tidal volumes were approximately 800 ml, mechanical ventilation rate was 12 breaths per minute, and peak inspiratory pressure readings were approximately 55 cm H2O. Repeated albuterol nebulizer treatments were given for 45 min. Subsequently, the peak inspiratory pressure decreased to 30 cm H2O, and the bronchospasm resolved. During this first episode of bronchospasm, the patient's mean arterial blood pressure remained at 70 mmHg or higher; furthermore, her arterial oxygen saturation remained 95% or higher except for a few brief periods of desaturation. The lowest recorded arterial oxygen saturation of 90% occurred during the initial onset of the bronchospasm. An arterial catheter was placed in the left radial artery, and the patient was placed in the left lateral position. On positioning, correct placement of the endotracheal tube was verified via  fiberoptic bronchoscopy. Albuterol treatments were continued for 30 min, and then the right lung was deflated for surgical access.
Fifteen minutes after one lung ventilation was initiated, with the patient receiving 100% fraction of inspired oxygen, arterial blood gases were pH 7.24, Pco245 mmHg, Po2102 mmHg, HCO318.3 mm, base excess −8.5 mm, and lactate 5.1 mm. Fifteen minutes later, arterial blood gases were pH 7.22, Pco246 mmHg, Po2105 mmHg, HCO318.2 mm, base excess −8.9 mm, and lactate 5.9 mm. The patient's heart rate was 100–110 beats per minute, and her mean arterial blood pressure was stable and remained near 70 mmHg throughout the rest of the procedure. Her core body temperature was maintained between 35.5° and 36.0°C. During the procedure, there were no signs of ischemia on the electrocardiogram. Furthermore, the patient had good peripheral pulses and was hemodynamically stable, with a total blood loss of 200 ml and a urine output of 500 ml. Total intravenous fluids given during surgery were 4,000 ml normal saline.
At the conclusion of surgery, just before emergence, the patient had bronchospasm again and repeated albuterol treatments were given. She was eventually extubated and was sent to the postanesthesia recovery unit in no apparent distress.
With the patient receiving a 2-l nasal canula, her initial vital signs in the postanesthesia recovery unit were heart rate 117 beats per minute, arterial pressure 123/70 mmHg, respiration rate 13 breaths per minute, and arterial oxygen saturation 97%. The patient was given another albuterol nebulizer treatment in the postanesthesia recovery unit, and 1 h later her arterial blood gases were pH 7.14, Pco242 mmHg, Po286 mmHg, HCO313.8 mm, base excess −14.1 mm, lactate 7.5 mm, Na+139 mm, K+3.4 mm, Cl109 mm, blood urea nitrogen 3.2 mm, creatinine 53 μm, glucose 11.4 mm, and hematocrit 0.30. Her anion gap was 19.6 mm. The patient was in no distress, and her respiratory rate was 15 breaths per minute. She was taken to the surgical intensive care unit, where her lactate levels were followed, but no more albuterol treatments were administered. Her lactate level peaked at 7.8 mm. Sodium bicarbonate was administered, and 12 h later her lactate level was 1.8 mm. The patient was discharged in good health on postoperative day 2.
Lactic acidosis can occur in two different clinically distinguishable categories. The first (type A) occurs when oxygen delivery to the tissues is compromised. The second (type B) occurs when either lactate production is increased or lactate removal is decreased without obvious oxygen delivery problems. 7,8 
In a study by Phillips et al.  , 9 healthy volunteers without respiratory distress who were given intravenous infusions of either salbutamol or rimiterol had dose-related increases in lactic acid levels. In the absence of any clinical signs of circulatory shock or severe hypoxia in the current patient, we hypothesize that she had type B lactic acidosis.
β-2 Receptor activation produces excess glycogenolysis and lipolysis. 10 Increased glycogenolysis eventually leads to increased concentrations of pyruvate. Pyruvate is converted to acetyl CoA, which enters the citric acid cycle. If pyruvate does not enter this aerobic pathway, it is converted to lactate instead, thereby potentially causing lactic acidosis. In addition, an increased lipolysis also increases acetyl CoA concentration through a different pathway. An increased acetyl CoA concentration potentially further inhibits pyruvate oxidation to acetyl CoA and leads to excess pyruvate. Finally, β-2 receptor stimulation will also inhibit the pyruvate dehydrogenase complex, and this might even further limit the rate that pyruvate is oxidized to acetyl CoA. 10 
We believe that the lactic acidosis in the current patient was caused by the repeated use of albuterol. We hypothesize that the cause was excess β-2 stimulation through the mechanisms described above, and that one should be aware of the possibility that severe lactic acidosis might develop, even in patients who are anesthetized and mechanically ventilated, with repeated and prolonged use of β-2 agonist drugs.
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