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Posterior Reversible Encephalopathy Syndrome After Combined General and Spinal Anesthesia with Intrathecal Morphine

Eran, Ayelet MD*; Barak, Michal MD

doi: 10.1213/ane.0b013e31818f635e
Neurosurgical Anesthesiology and Neuroscience: Case Report

We describe a patient who was in a stupor for several days after combined general-spinal anesthesia. Both clinical manifestations and magnetic resonance imaging findings were consistent with posterior reversible encephalopathy syndrome and resolved after the patient recovered spontaneously.

IMPLICATIONS: We describe a case in which a patient developed posterior reversible encephalopathy syndrome after combined general-spinal anesthesia. The patient recovered spontaneously within days and the magnetic resonance findings resolved.

From the Departments of *Radiology and †Anesthesiology, Rambam Health Care Campus and the Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.

Accepted for publication July 28, 2008.

Address correspondence and reprint requests to Dr. Michal Barak, Department of Anesthesiology, Rambam Health Care Campus, POB 9602, Haifa 31096, Israel. Address e-mail to

Posterior reversible encephalopathy syndrome (PRES), a neurologic syndrome, is associated with a variety of underlying co-morbid conditions, with identifiable neuroimaging abnormalities.1 We describe a case of PRES that occurred after combined general-spinal anesthesia, in which intrathecal morphine was used.

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A 51-yr-old female patient was admitted to hospital for a video-assisted thoracoscopic wedge resection of a lesion in her right lung. Her medical history included essential hypertension treated with enalapril (angiotensin converting enzyme inhibitor) and heavy smoking. Several weeks earlier, she had complained of weakness and had an extensive work-up. Her weight was 64 kg and her height was 1.68 m. Her blood count revealed mild anemia (hemoglobin = 11.5 g/dL), and chest radiographs showed a 1.5 cm lesion in the middle lobe of the right lung. Otherwise, her physical examination and tests, including blood electrolytes, renal and liver function tests, electrocardiogram, transthoracic echocardiography, positron emission tomography scan, and pulmonary function tests, were normal. Because of the low probability of malignancy, it was decided to remove the lung lesion in a video-assisted thoracoscopic procedure under combined general-spinal anesthesia.

On the day of the surgery, the patient received valium 10 mg and metoclopramid 10 mg per os an hour before surgery. In the operating room, the patient was monitored with electrocardiogram, noninvasive arterial blood pressure, and pulse oximeter. Her arterial blood pressure was 125/78 and heart rate was 75 bpm. General anesthesia was induced using propofol 150 mg and fentanyl 0.2 mg IV; muscle relaxation was achieved with vecuronium 10 mg. She was tracheally intubated and her lungs were ventilated with 80%–100% oxygen and 1.0–1.5 volume % isoflurane. After placing the patient in the lateral position, lumbar spinal anesthesia was performed using a 25 pencil-point needle and 0.5 mg preservative-free morphine. The operation was uneventful and lasted 1 h and 10 min; the patient was stable, her arterial blood pressure ranged between 110/60 and 144/88, her heart rate was 65–85 bpm and oxygen saturation was above 96%. At the end of surgery, muscle relaxation was reversed with myostigmine 2.5 mg and atropine 1 mg IV. After the surgery, the patient did not regain consciousness. She was in a stupor and in an agitated state. She opened her eyes but did not communicate with others and was sometimes combative when approached. Her vital signs and body temperature were normal. Her blood glucose and electrolytes were within normal limits. Thorough neurologic examination showed no localized neurologic deficit. The diagnosis of postoperative delirium was suggested and the patient was sedated with a continuous infusion of propofol 50–150 mg/h.

There was no change in her status for two more days and further investigation was performed, with the differential diagnoses of meningitis, encephalitis, cerebral vascular accident, brain malignancy, or psychiatric disorder. Lumbar puncture was done with normal opening pressure. The cerebrospinal fluid was clear and laboratory analysis was normal. This excluded the possibility of meningitis or encephalitis. Computed tomography (CT) of the head showed areas of low attenuation in the occipital lobe bilaterally, suggesting occipital infarct or ischemia. The CT was repeated after 24 h and the diagnosis of ischemia was withdrawn. For further delineation of the insult, magnetic resonance imaging (MRI) was performed. It showed cortical and subcortical increased fluid-attenuated inversion recovery (FLAIR) intensity in the occipito-parietal and upper frontal regions bilaterally (Fig. 1A), as well as sulci effacement and cortical and leptomeningeal enhancement (Fig. 1B). There was no evidence of diffusion restriction within the lesions, which are consistent with encephalitis.

Figure 1

Figure 1

Gradually, the patient regained consciousness and became responsive. The sedation was stopped on the sixth postoperative day. The patient recovered fully and was discharged home 10 days after surgery, with no neurological deficit. On follow-up MRI of the brain 2 mo later, there was nearly complete resolution of the previously described imaging findings, with only minimal residual cortical FLAIR hyperintensity and enhancement (Figs. 2A and B). The patient underwent rigid bronchoscopy 6 mo later. General anesthesia was induced and maintained with propofol. Remifentanil and atracurium were also administered. The procedure and anesthesia were uneventful.

Figure 2

Figure 2

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PRES was first described in 19961 as a combination of neurological abnormalities and imaging findings developing in patients with acute medical illness or treatment with immune-suppressive drugs. The syndrome was initially recognized in association with severe hypertension, renal disease, autoimmune disease, viral or bacterial infection, malignancy, immunosuppressive therapy, trauma, or pregnancy.1–10 Eventually PRES became linked to a diverse array of causes (Table 1). The clinical presentation is diverse and typically reflects the global encephalopathy. The most common clinical symptoms are headache, vomiting, altered behavior ranging from drowsiness to stupor, seizures, somnolence, and mental abnormalities, including confusion and diminished speech.1,2 Temporary restlessness and agitation may alternate with lethargy. Given the nonspecific clinical features, diagnosis is mostly by exclusion and relies on imaging findings. Neuroimaging abnormalities at CT and MRI typically show focal regions of symmetrical white matter edema, most commonly affecting the parietal and occipital lobes, the posterior aspect of the frontal lobes might also be affected.11,12 On MRI, involvement of cortex, subcortical white matter and deep white matter can be depicted on FLAIR images. Diffusion weighted imaging is crucial to exclude ischemic insult and consistently demonstrates vasogenic edema in the corresponding regions of abnormalities.13 Less common imaging finding include brainstem, cerebellum and basal ganglia involvement, contrast enhancement, hemorrhage, and restricted diffusion on MRI.14

Table 1

Table 1

The pathophysiological mechanism of the syndrome is not yet completely understood and is controversial.15 Treatment seeks to discontinue the causal factor, if known, such as controlling arterial blood pressure and stopping chemotherapy. As the name of the syndrome implies, it is usually reversible, with patient recovery and resolution of the imaging finding being the rule. Nevertheless, the syndrome might be recurrent or result in permanent damage.16–18

Our patient had clinical symptoms consistent with PRES. The CT and MRI studies support that diagnosis. The course of her illness, with spontaneous recovery and disappearance of MRI findings, confirm the diagnosis of PRES. After establishing the diagnosis, we searched for the cause. Hypertension and electrolyte disturbances were not present in our case. Our patient was not treated with immunosuppressive therapy, nor did she suffer from a viral or bacterial infection. The occurrence of PRES has been described in pregnant patients,5,6 but our patient was not pregnant. She received several anesthetic and analgesic drugs on the day of surgery, none of which is described as causing PRES. There is one report of PRES that occurred 6 days after general anesthesia in a patient who received chemotherapy,18 but the association of PRES with anesthesia in that case is not well established. Triquenot-Bagan et al.19 described PRES after abdominal aortic surgery, which occurred in a context of unusually severe arterial hypertension due to renal ischemia.

We tend to believe that the morphine, which was administered intrathecally, might have caused the PRES in our patient. However, because only a few cases have been reported, the connection between anesthesia-spinal or general and PRES is a speculation. The most commonly reported side effects of intrathecal morphine are nausea, vomiting, urinary retention, and pruritus.20 Severe neurological complications after the use of neuroaxial morphine, such as myoclonus, motor dysfunction, or vertigo, were previously described.21–24 These reports may raise questions about the neurotoxic effect of intrathecal morphine injection. The occurrence of PRES after spinal anesthesia was described by Ho and Chan25 in a parturient patient, in which 12 mg 0.5% hyperbaric bupivacaine was used and PRES developed a few days later. There are several cases of parturient patients who developed PRES, attributed to preeclampsia, eclampsia, or to gestational hormonal changes taking place before or after delivery.5,6,26–29 Therefore, the case report by Ho and Chan25 might be related to the parturient status and not to the spinal anesthesia. According to the number of case reports about pregnancy and PRES, there may be a pathophysiological connection between the two, not yet understood.

The relatively new diagnosis of PRES should be known to anesthesiologists, particularly those who specialize in obstetric anesthesia, where PRES seems to be more prevalent. Clinicians should be aware of this profound but poorly understood entity and the clinical conditions which have been associated with its development, because recognizing the diagnosis could assist in managing the affected patient.

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