Anesth Analg 2004;99:1427-1428
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000135638.60722.E3
ANESTHETIC PHARMACOLOGY
Hypoglycemia Associated with Preoperative Metoprolol Administration
Daniel R. Brown, MD PhD, and
Michael J. Brown, MD
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota
Address correspondence to Daniel R. Brown, MD, PhD, Department of Anesthesiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Address e-mail to brown.daniel{at}mayo.edu
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Abstract
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Perioperative ß1-selective-adrenergic antagonist administration has been shown to decrease morbidity and mortality in patients with cardiac disease undergoing surgical procedures. We report a case of a patient receiving the selective ß1-adrenergic antagonist, metoprolol, immediately before surgery that was associated with severe hypoglycemia. We postulate that an underlying abnormality in energy requirements or metabolism may allow for ß1-selective-adrenergic antagonists to precipitate hypoglycemia.
IMPLICATIONS: In patients with abnormal energy metabolism, which may occur with cancer, or a history of unexplained hypoglycemia, care must be taken to ensure that hypoglycemia does not occur when ß-adrenergic antagonists are administered.
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Introduction
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Perioperative ß1-selective-adrenergic antagonist administration has been shown to decrease morbidity and mortality in patients with cardiac disease undergoing surgical procedures (1). ß2-Adrenergic receptors seem to have an important role in stimulating hepatic glucose production in humans (2). Whereas nonselective ß-adrenergic antagonists have been shown to cause hypoglycemia (3), ß1-adrenergic selective antagonists have not been shown to influence glucose metabolism (4). We report a case of a patient receiving the selective ß1-adrenergic antagonist, metoprolol, immediately before surgery that was associated with severe hypoglycemia.
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Case Report
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A 50-yr-old woman, weighing 66 kg, presented for resection of an intrathoracic mass. Her medical history was unremarkable and she took no medications. She reported mild, stable shortness of breath and a 7-kg weight loss over the preceding 6 mo. She denied symptoms suggestive of a paraneoplastic syndrome, in particular those attributable to hypoglycemia. Two months before presentation, she was evaluated for abdominal pain. Her radiograph and computed tomography scan revealed a large, pleural-based mass and pleural effusion. A computed tomography-guided biopsy showed the mass to be a fibrous tumor of the pleura. Physical examination was notable for the lower two-thirds of her right chest being dull to percussion with lung sounds severely diminished to auscultation. The remainder of the physical examination was unremarkable. Preoperative laboratory evaluations were unremarkable with a fasting glucose concentration of 77 mg/dL (laboratory normal 70–100 mg/dL).
On the morning of surgery, the patient consented to participate in a research protocol investigating the effect of perioperative administration of the ß1-selective-adrenergic antagonist, metoprolol, on pulmonary function and development of supraventricular arrhythmias. She had been fasting since 20.00 the previous day. As part of the study protocol, she received IV metoprolol (10 mg) between 11.45 and 12.00 as previously described (1). Over the next 15 min, the patient became increasingly somnolent and diaphoretic. Vital signs and oxygenation remained stable. The neurologic examination was nonfocal. Blood glucose was <50 mg/dL on 2 separate samples (determinations were 26 and 32 mg/dL but were reported as <50 mg/dL in accordance with the manufacturer recommendations). Dextrose 50 g was administered IV and neurologic status returned to baseline. Repeat blood glucose was 107 mg/dL. The patient was asymptomatic over the next hour and surgery proceeded. A right pneumonectomy was performed and a 25 x 17 x 13 cm solitary fibrous tumor resected. No further hypoglycemic episodes occurred during her hospitalization and she was discharged to home 6 days later.
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Discussion
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Perioperative ß1-selective-adrenergic blockade improves outcome in patients with cardiac disease undergoing surgical procedures (1). Administration of ß-adrenergic antagonists may be associated with undesirable side effects. Hypotension and bradycardia are well recognized side effects of ß-adrenergic antagonist administration and clinicians closely monitor vital signs in an effort to detect such events. ß2 Receptors have an important role in hepatic glucose production in humans (2) and may contribute to hypoglycemia associated with unselective ß-blockade (3). Although there are several case reports of perioperative hypoglycemia in pediatric patients receiving the nonselective ß-adrenergic antagonist, propranolol (5–7), there is currently no evidence, including case reports, of altered glucose homeostasis associated with administration of ß1-selective antagonists (4). However, based on our patient’s lack of a hypoglycemic history and the temporal relationship between administration of metoprolol and subsequent symptomatic hypoglycemia, we believe that metoprolol administration may have precipitated severe hypoglycemia in our patient.
Our patient had other factors that may have contributed to the hypoglycemia we observed. The resected tumor was large and may well have been metabolically active. In addition to possible direct tumor-related increases in energy expenditure, it is possible that cancer may cause direct alterations in systemic metabolism resulting in increased energy expenditure (8). In the absence of appropriate caloric intake, such as during a preoperative fast, it is possible that net caloric requirements exceed a patient’s capabilities, resulting in hypoglycemia. However, the patient denied any symptoms of hypoglycemia during similar fasting conditions during her immediate presurgical evaluation. Furthermore, two days before surgery, a fasting glucose determination after a longer fast than the day of surgery was normal. It is possible that the patient had a primary disorder of glucose metabolism, although the lack of subjective or objective evidence of hypoglycemia makes this unlikely. The patient’s extensive workup for metastatic disease was negative suggesting that direct hepatic or endocrine involvement was also unlikely. Finally, although metoprolol is ß1-selective, at large plasma concentrations, which may transiently occur after IV administration, there may be ß2-adrenergic antagonism that could inhibit hepatic gluconeogenesis. In fasting patients with increased energy expenditure, such impaired gluconeogenesis could result in hypoglycemia.
The lack of reported cases of hypoglycemia associated with administration of ß1-selective-adrenergic antagonists suggests that hypoglycemia related solely to drug effect is rare. Overall, we believe the beneficial effects of ß1-selective-adrenergic antagonism outweigh the risks. However, in patients with abnormal energy requirements or metabolism, administration of ß1-selective-adrenergic antagonists may be associated with hypoglycemia.
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Acknowledgments
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Financial support was provided by the Mayo Foundation.
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References
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Accepted for publication May 24, 2004.
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Abstract
Introduction
