Anesth Analg 2004;99:1573-1574
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000134860.73875.CF
GENERAL ARTICLES
Prolonged Postoperative Disorientation After Methylene Blue Infusion During Parathyroidectomy
Kevin K. Bach, MD*,
Fred W. Lindsay, MD*,
Lamont S. Berg, MD
, and
Red S. Howard, MD PhD
Department of *Otolaryngology and
Anesthesiology, Naval Medical Center San Diego, California
Address correspondence and reprint requests to Red Howard, Department of Anesthesiology, Naval Medical Center, 34800 Bob Wilson Dr., San Diego, CA 92134. Address e-mail to rhoward{at}ucsd.edu
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Abstract
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Methylene blue 7.5 mg/kg is frequently given at our institution during parathyroidectomy. The dye preferentially stains the parathyroids so as to provide better surgical visualization. Other than causing a pseudocyanosis, the technique is generally considered to be rather innocuous. We report a case of a patient who, after this procedure, had a postoperative course that was unusual because of slowly resolving altered mental status.
IMPLICATIONS: We report the case of a patient who, after a large dose of methylene blue, had a postoperative course that was unusual because of slowly resolving altered mental status.
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Introduction
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Large (7.5 mg/kg) doses of methylene blue are frequently given at our institution during parathyroidectomy. The dye preferentially stains the parathyroids so as to provide better surgical visualization. The technique has been previously reported (1,2), and, other than causing a pseudocyanosis, it is generally considered to be rather innocuous. We report a case of a patient who, after this procedure, had a postoperative course that was unusual because of slowly resolving altered mental status.
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Case Report
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The patient was a 59-yr-old, 6’1", 115-kg man scheduled for a parathyroidectomy because of hypercalcemia secondary to parathyroid adenoma. He had no previous exposure to general anesthesia. The patient was a recovered alcoholic (alcohol-free for 20 yr) with a history of anxiety, depression, noninsulin-dependent diabetes, hypertension, first-degree atrioventricular block, hyperlipidemia, and hiatal hernia. His medications included paroxetine, glyburide, metformin, verapamil, Lasix, potassium, simvastatin, and rabeprazole. The patient had stopped taking metformin 2 days before the surgery, and his preoperative glucose was 113 mg/dL. He was given metoclopramide 10 mg and midazolam 2 mg, but the start of his surgery was then delayed for 2 h by an unrelated emergency. During this time, he napped with supplemental oxygen while being monitored by pulse oximetry. Subsequently, he appeared alert and oriented and was given an additional 2 mg of midazolam just before the anesthetic induction with propofol, succinylcholine, and vecuronium. Anesthesia was maintained with nitrous oxide and sevoflurane. During the case, he received Ancef 1 g, alfentanil 2500 mg, and 1500 mL of lactated Ringer’s solution. An IV infusion of 700 mg of methylene blue was given approximately midway through the 2-h surgery. At the end of the case, the patient was given neostigmine 4 mg, with glycopyrrolate 0.8 mg and ondansetron 4 mg. His trachea was extubated in the operating room. Upon arrival in the postanesthesia care unit, his vital signs were normal and stable. During the next hour, the patient was awake and responsive but demonstrated a marked aphasia. Neurological examination found no other deficit, although there was a suggestion of clonus with forced dorsiflexion of his feet. During the next hours, the aphasia improved somewhat, but the patient’s speech remained slow, and he was not oriented to time or place. The patient’s glucose at this time was again 113 mg/dL, electrolytes were normal (sodium = 139 mEq/L), and an arterial blood gas was normal. The blood sample was not chocolate-colored, and methylene blue-induced methemoglobinemia was considered unlikely because the patient showed no ventilatory signs of hypoxia. A radiographic head scan was obtained and was reported as normal. The patient was transferred to the ward for observation. His mentation gradually improved over the next 2 postoperative days. On the first postoperative day, his spouse described his mental condition as similar to being inebriated, and the patient subsequently described himself as having been loopy. On the second postoperative day, the patient’s mentation had returned to preoperative levels, although his urine had not yet cleared its blue coloration. He was discharged without further complication.
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Discussion
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There was a suggestion that the patient was manifesting a prolonged sensitivity to midazolam, and a flumazenil challenge was considered. This was not performed because he was not somnolent during this protracted period of resolving aphasia, and one year before this surgery, he had a colonoscopy, presumably with midazolam sedation without untoward effect.
There has been only one other report of mental toxicity of methylene blue after parathyroidectomy in the literature (3). It that case, the patient displayed agitated behavior for two days after surgery, whereas our patient’s affect remained calm and pleasant throughout his hospital course. In both cases, the implication of methylene blue toxicity was made by exclusion and by the prolonged time course of its resolution.
Large doses of methylene blue may be given perioperatively for procedures other than parathyroidectomy (4). With this increasing use in the operating room, the dye should not be considered pharmacologically inert. Its use, at smaller doses, in the treatment of methemoglobinemia is well established (5). More recently, methylene blue has reportedly been an effective pressor agent in septic (6) and anaphylactic shock (7) and for catecholamine-refractory vasoplegia after cardiopulmonary bypass (8). Neuropsychological effects have been reported, and the reports range from it causing simple confusion (9,10) to its use as an antidepressant (11) and in the treatment of ifosfamide-induced encephalopathy (12). Perhaps such psychiatric effects should not be surprising because its chemical structure has the same tricyclic scaffold as phenothiazines, which are historical derivatives of methylene blue (13).
We report this case for consideration in patients who have been given methylene blue for parathyroidectomy and who subsequently manifest an unusual emergence from anesthesia.
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References
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- Meekin GK. Introperative use of methylene blue to localize parathyroid adenoma. Laryngoscope 1998; 108: 772–3.[Medline]
- Traynor S, Adams JR, Andersen P, et al. Appropriate timing and velocity of infusion for the selective staining of parathyroid glands by intravenous methylene blue. Am J Surg 1998; 176: 15–7.[Medline]
- Martindale SJ, Stedeford JC. Neurological sequelae following methylene blue injection for parathyroidectomy. Anaesthesia 2003; 58: 1041–2.
- Obermeyer RJ, Knauer EM, Millie MP, et al. Intravenous methylene blue as an aid to intraoperative localization and removal of the adrenal glands during laparoscopic adrenalectomy. Am J Surg 2003; 185: 531–4.
- Clifton J 2nd, Leikin JB. Methylene blue. Am J Ther 2003; 19: 289–91.
- Evgenov OV, Bjertnaes LJ. Administration of methylene blue in human septic shock: renaissance of an old drug? Crit Care Med 2003; 31: 1601–2.[ISI][Medline]
- Evora PR, Oliveira Neto AM, Duarte NM, Vincente WV. Methylene blue as treatment for contrast medium-induced anaphylaxis. J Postgrad Med 2002; 48: 327.
- Leyh RG, Kofidis T, Struber M, et al. Methylene blue: the drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass? J Thorac Cardiovasc Surg 2003; 56: 1426–31.
- Nadler JE, Green H, Rosenbaum A. Intravenous injection of methylene blue in man with reference to its toxic symptoms and effect on the electrocardiogram. Am J Med Sci 1934; 188: 15–21.
- Faulding Pharmaceutical Co. Methylene blue injection, USP 1%. Package insert 2002.
- Naylor GJ, Smith AH, Connelly P. A controlled trial of methylene blue in severe depressive illness. Biol Psychiatry 1987; 22: 657–9.[Medline]
- Zulian GB, Tullen E, Maton B. Methylene blue for ifosfamide encephalopathy. N Engl J Med 1995; 332: 1239–40.[Free Full Text]
- Shen WW. A history of antipsychotic drug development. Compr Psychiatry 1999; 40: 407–14.[Medline]
Accepted for publication May 20, 2004.
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Dose-response and postoperative confusion following methylene blue infusion during parathyroidectomy
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C. Siebert, S. Kroeber, and N. Lutter
Prolonged Postoperative Disorientation After Methylene Blue Infusion During Parathyroidectomy
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Abstract
Introduction
