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*Department of Anesthesia and Intensive Care Medicine, City of Vienna Hospital Lainz; and
Ludwig Boltzmann Institute for Economics of Medicine in Anesthesia and Intensive Care, Vienna, Austria
Address correspondence and reprint requests to Herbert Krenn, MD, PhD, Department of Anesthesia and Intensive Care Medicine, City of Vienna Hospital Lainz, Wolkersbergenstraße 1, A-1130 Vienna. Address e-mail to krh{at}ana.khl.magwien.gv.at
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Abstract |
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Implications: We describe a case of neurological symptoms after the intrathecal use of an opioid. These symptoms were not reversible by the use of an opioid-antagonist.
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Introduction |
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We report a case of a 72-yr-old woman who received 0.1 mg morphine intrathecally for a gynecological surgery and thereafter developed severe side effects. Naloxone was successful in reversing the nausea and vomiting, but had no effect on the respiratory depression or neurological eye symptoms (nystagmus, double vision, and convulsive movements of the eye lids).
We discuss the possible causes for this failure of reversing respiratory depression with naloxone and propose an interaction between morphine and metoclopramide.
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Case Report |
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The operative procedure was performed with the patient in a lithotomy position (duration, 40 min) without complications. During surgery, she was requested to perform a Valsalva maneuver and cough actively to test the surgical repair. At the end of the operation, the patient reported shortness of breath and nausea. Without showing any evidence of high spinal anesthesia, she received 10 mg metoclopramide IV and oxygen via a face mask (4 L/min oxygen). Up to this point, no abnormal vital parameters had been detected.
On arrival in the recovery room, the patient had increased shortness of breath and nausea, followed by several spells of vomiting. She received 1 mg granisetron (IV; 5HT3-antagonist) and 1 h later another 10 mg dose of IV metoclopramide without reducing the nausea and vomiting or decreasing the shortness of breath. SaO2 ranged between 96% to 99% on 4 L/min oxygen via a face mask, and the respiratory rate was normal.
Noninvasive blood pressure, heart rate, and biochemical parameters (complete blood cell count, electrolytes, glucose, creatinine, urea nitrogen) and arterial blood gases were within normal limits.
Two hours postoperatively, the respiratory depression increased, and the patient showed signs of Cheyne-Stokes breathing with breath-to-breath intervals of up to 90 s. She continued to complain of nausea and vomiting and was treated with IV ondansetron 8 mg and 0.4 mg naloxone. One minute after the injection of naloxone, the nausea and vomiting ceased. However, there seemed to be no change in respiratory depression. Additionally, the patient reported double vision and nystagmus, and convulsive movements of the eyelids were observed. These symptoms, together with a clinical examination, led to the suspicion of a morphine overdose. The patient received another dose of 0.4 mg naloxone IV which was followed by 1.2 mg naloxone as an infusion for 4 h without reported reversal of the side effects.
An acute magnetic resonance imaging of the brain and spine was performed and found to be normal. The patient was transferred to an intermediate care unit for close monitoring. Sixteen hours postoperatively, the respiratory depression and neurological symptoms resolved without further therapy. Twenty-four hours postoperatively, the patient was comfortable and showed no signs of respiratory depression or neurological abnormalities.
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Discussion |
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In this case, respiratory abnormalities in combination with nausea and vomiting were detected within 90 minutes after the injection of intrathecal morphine. The administration of IV naloxone is considered standard treatment of opioid-induced side effects; however, cases of resistance to opioid antagonists requiring spinal fluid exchange (8–11) have been reported. The incidence of severe side effects is dose-dependent, with elderly patients at the highest risk (3). Glass (12) reported a case of respiratory depression after a 0.4-mg intrathecal morphine administration.
In this case report, we show that an intrathecal morphine dose as low as 0.1 mg was sufficient to induce pronounced symptoms of severe nausea and vomiting, Cheyne-Stokes respiration, convulsive eye movements, nystagmus, and double vision. The rapid development of symptoms may be explained by the positioning and the coughing and Valsalva maneuvers. However, the ineffectiveness of the opioid antagonist remains curious. Naloxone 2 mg reversed the nausea and vomiting, although respiratory depression and neurologic symptoms persisted. These symptoms could have been caused by a leakage of cerebrospinal fluid. However, the early onset of symptoms, the use of a 27-gauge needle, and the resolution of symptoms within 24 hours make this explanation unlikely. A possible explanation might be an interaction of the antiemetic drugs administered to this patient. Metoclopramide 10 mg was administered intraoperatively, followed by another 10 mg postoperatively. In addition, two selective 5HT3-antagonists were administered during the first two hours after surgery. Although no interactions between opioids and 5HT3-antagonists have been reported (13), it is known that metoclopramide can potentiate opioid analgesia dopamine 2-receptor antagonism (14,15), and although no reports to date suggest an effect of metoclopramide on opioid reversal by naloxone, we speculate that this was the etiology of prolonged respiratory depression and eye symptoms in the current case report.
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This article has been cited by other articles:
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  J. Fichna, A. Janecka, J. Costentin, and J.-C. Do Rego The Endomorphin System and Its Evolving Neurophysiological Role Pharmacol. Rev., March 1, 2007; 59(1): 88 - 123. [Abstract] [Full Text] [PDF]
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