Anesthetic Management of a Patient With Restless Legs Syndrome: A Case Report.

Restless legs syndrome (RLS) is a neurological sensory disorder associated with sensory and motor symptoms that most commonly occur at night and during periods of rest. It is characterized by altered or abnormal sensations primarily in the legs and the urge to move the associated limbs. Perioperative procedures, including general anesthesia, can cause exacerbations of RLS. This is a case report of a suspected RLS exacerbation in a 22-year-old woman who had no formal diagnosis of RLS despite reporting symptoms that met all essential diagnostic criteria by the International RLS Study Group. Despite her previous diagnoses of dehydration induced-muscle pain or nocturnal cramps, we suspected her to have RLS. The patient underwent general anesthesia for a bilateral sagittal split ramus osteotomy using a combined inhalational and intravenous anesthetic technique with sevoflurane, propofol, remifentanil, and dexmedetomidine. After successful completion of the surgery and returning to the ward, she began moving her lower extremities and complaining of unpleasant sensations in both ankles. Bed rest exacerbated the suspected RLS symptoms despite a continuous infusion of dexmedetomidine. The RLS symptoms continued to worsen and spread to her upper extremities. After increasing the dexmedetomidine infusion from 0.2 to 0.4 µg/kg/h, almost all symptoms improved, and she slept for 3 hours. Upon awakening, the unpleasant sensations were completely relieved by walking and stretching. The patient was formally diagnosed with RLS by a neurologist after discharge. In this case, an infusion of dexmedetomidine was helpful in successfully managing a suspected exacerbation of RLS.

Regular dipyridamole therapy produces sustained protection against cardiac ischemia-reperfusion injury: is it time to revisit PARIS?

BACKGROUND: Increased activated Akt and eNOS expression coincide with this persistent cardioprotection. Emergent coronary reperfusion therapies are rarely carried out before considerable myocardial injury has occurred. Moreover, reperfusion after prolonged ischemia produces paradoxical ischemia-reperfusion injury, attenuating the efficacy of reperfusion therapies. This has provided impetus for identifying chronic therapies to protect against ischemia-reperfusion injury in those at risk. We previously found that regular dipyridamole therapy produces a chronic preconditioning-like effect mediated through adenosine A1 receptors. METHODS: To determine how long this chronic preconditioning effect of dipyridamole remains present after discontinuing therapy, guinea pigs received 4 mg/kg/day in their water for 6 weeks. Ischemia-reperfusion was performed at 0, 2, 3, and 4 days after dipyridamole discontinuation (0 day, 2 days, 3 days and 4 days; n=8 per group). Left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), coronary flow (CF), infarct size, and western blot analyses for Akt and endothelial nitric oxide synthase (eNOS) were studied. RESULTS: After ischemia-reperfusion, 0 day, 2 days and 3 days, but not 4 days, had significantly higher LVDP and lower LVEDP compared to control. Myocardial infarct size was significantly reduced at 0 day, 2 days and 3 days, but not 4 days, compared to control. Western blot analyses demonstrated upregulation of phospho-Akt and phospho-eNOS expression at 0 day, 2 days, and 3 days, but not 4 days. CONCLUSIONS: A chronic preconditioning-like cardioprotection by regular dipyridamole treatment persists for 3 days after discontinuing therapy. Increased activated Akt and eNOS expression may play a role in this persistent cardioprotection.

Induction of autophagy restores the loss of sevoflurane cardiac preconditioning seen with prolonged ischemic insult.

Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 min ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 µM) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45+CAP). To inhibit autophagy, 3-methyladenine (10 µM) was administered during sevoflurane administration in SEVO-45+CAP. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained before ischemia to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, II), Akt and glycogen synthase kinase 3ß (GSK3ß) expression using Western blot analysis. The effect of autophagy on calcium-induced mitochondrial permeability transition pore (MPTP) opening in isolated calcein-loaded mitochondria was assessed. Electron microscopy was used to detect autophagosomes. Infarct size was significantly reduced in SEVO-30, but not in SEVO-45. Chloramphenicol restored sevoflurane preconditioning lost by 45 min ischemia. There were more abundant autophagozomes and LC3-II expression was significantly increased in SEVO-45+CAP. Induction of autophagy before ischemia enhanced GSK3ß phosphorylation and inhibition of calcium-induced MPTP opening. These effects were abolished by 3-methyladenine. Pre-ischemic induction of autophagy restores sevoflurane preconditioning lost by longer ischemic insult. This effect is associated with enhanced inhibition of MPTP by autophagy.

Direct evidence for inhibition of mitochondrial permeability transition pore opening by sevoflurane preconditioning in cardiomyocytes: comparison with cyclosporine A.

To assess whether sevoflurane preconditioning is associated with inhibition of mitochondrial permeability transition pore (MPTP), the effects of sevoflurane were compared with those of cyclosporine A, a known inhibitor of MPTP opening. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (control). Sevoflurane preconditioning was elicited by administration of 2% sevoflurane for 10 min with 10 min washout before ischemia (sevoflurane). A preconditioning-like cardioprotection was also induced by administering cyclosporine A (0.2 µM) for 15 min, starting 5 min before ischemia and for 10 min after the onset of reperfusion (cyclosporine A). Left ventricular developed and end-diastolic pressures, coronary flow and infarct size were measured. Expressions of Akt and glycogen synthase kinase 3ß (GSK3ß), known mediators of inhibition of MPTP opening, were determined by Western blot analysis. GSK3ß inhibition was achieved with LY294002. The effects of sevoflurane and cyclosporine A on calcium-induced MPTP opening in isolated calcein-loaded mitochondria were assessed. After ischemia-reperfusion, sevoflurane and cyclosporine A had higher left ventricular developed pressure. Infarct size was significantly reduced in sevoflurane and cyclosporine A vs. control. This was abolished by LY294002 in sevoflurane, but not in cyclosporine A. Akt and GSK3ß phosphorylation after reperfusion were significantly increased in sevoflurane and cyclosporine A. Ca²âº-induced reduction in calcein fluorescence was significantly attenuated in sevoflurane and cyclosporine A. Preconditioning agents, sevoflurane and cyclosporine A increase the threshold of calcium-induced MPTP opening to a similar extent. This effect by sevoflurane, but not cyclosporine A is at least partially mediated by GSK3ß inactivation.

Changes in blood pressure during induction of anesthesia and oral and maxillofacial surgery by type and timing of discontinuation of antihypertensive drugs.

The purpose of this study was to evaluate the effects of an antihypertensive drug class and the timing of discontinuation of antihypertensive therapy on blood pressure during oral and maxillofacial surgery for 129 patients on antihypertensive therapy receiving general anesthesia. Blood pressures at loss of response to stimulation and 5-15 minutes after intubation were significantly lower than those before induction, although the type of antihypertensive therapy did not affect changes in blood pressure. No significant correlation was observed between systolic blood pressure (SBP) on the ward and change in SBP during surgery, though patients with higher blood pressure on the ward tended to exhibit larger differences between SBP on the ward and the lowest SBP during surgery. Frequency of use of vasopressors during surgery was significantly higher in patients who discontinued antihypertensive therapy on the day before surgery than in those who continued antihypertensive therapy on the day of surgery. These findings suggest that appropriate preoperative antihypertensive therapy is important for minimizing change in blood pressure during surgery and preventing perioperative complications. Patients undergoing antihypertensive therapy should be carefully monitored perioperatively by observation for interactions between antihypertensive and anesthetic agents and minimizing interruption schedules for antihypertensive therapy.

Cardioprotection by regular ethanol consumption: potential mechanisms and clinical application.

Epidemiological studies demonstrate that excessive drinking is associated with hypertension, cerebral bleeding and loss of cardiac contractility. Conversely, studies have shown that mortality rates for people who regularly drink ethanol in moderation are lower than in abstainers, primarily due to decreased fatal ischemic heart disease. Further, moderate ethanol consumers have lower rates of myocardial infarction compared with abstainers. These beneficial cardiac effects may be due to pleiotropic effects of ethanol on lipids, platelets, and fibrinolytic activity. During the past decade, studies conducted in several animal models have revealed that light to moderate regular ethanol consumption renders hearts more tolerant to myocardial ischemia-reperfusion injury; to a degree similar to cardiac ischemic preconditioning (brief episodes of ischemia dramatically limit infarct size following prolonged ischemia). Recent clinical evidence suggests that light to moderate ethanol consumption in the year prior to myocardial infarction is associated with reduced mortality following myocardial infarction. These findings suggest that light to moderate ethanol consumption not only prevents myocardial infarction but also improves survival after myocardial infarction. Proposed mechanisms of cardioprotection by regular ethanol consumption include activation of adenosine A1 receptors, alpha(1)-adrenoceptors, protein kinase C-delta and epsilon, adenosine triphosphate-dependent potassium (K(ATP)) channels, nitric oxide synthase and reduced leukocyte-endothelial cell adhesive interactions. In this review, we focus on the recent progress in elucidating the endogenous myocyte signaling mediating cardioprotection by light to moderate ethanol consumption.

Aprotinin abolishes sevoflurane postconditioning by inhibiting nitric oxide production and phosphorylation of protein kinase C-delta and glycogen synthase kinase 3beta.

BACKGROUND: It remains controversial whether aprotinin use during cardiac surgery is cardioprotective or detrimental. In contrast, volatile anesthetics may offer cardioprotection perioperatively. Increased nitric oxide, protein kinase C activation, and glycogen synthase kinase 3beta inhibition play a role in sevoflurane-induced cardioprotection. The authors investigated whether aprotinin affects sevoflurane postconditioning. METHODS: Isolated guinea pig hearts underwent 30 min of global ischemia and 120 min of reperfusion (control [CTL]). Postconditioning was elicited with sevoflurane (2%) for 2 min at reperfusion onset (POST). Aprotinin (250 kallikrein inhibitor units/ml) was administered for 5 min at reperfusion onset (POST + APRO and CTL + APRO). In additional experiments, both sevoflurane and aprotinin were given before ischemia and throughout the reperfusion period (SEVO + APRO (throughout)) to mimic clinical conditions. Left ventricular developed and end-diastolic pressures and infarct size were measured. Western blot analysis determined phosphorylated protein kinase C-delta, protein kinase C-delta, Akt, and glycogen synthase kinase 3beta expression. Nitric oxide production during reperfusion was measured by nitric oxide sensor. RESULTS: After ischemia-reperfusion, POST had significantly higher left ventricular developed (56 +/- 11 vs. 26 +/- 8 mmHg [mean +/- SD]) and lower end-diastolic pressures (20 +/- 9 vs. 47 +/- 15 mmHg) and reduced infarct size (15 +/- 3% vs. 41 +/- 10%) versus CTL. Aprotinin abolished these improvements. Expressions of phospho-Akt (activated), phospho-protein kinase C-delta (activated), and phospho-glycogen synthase kinase 3beta (inhibited) were significantly increased in POST. Aprotinin attenuated these increased expressions. Nitric oxide production after reperfusion was higher in POST than in CTL, but not in POST + APRO. CONCLUSIONS: Aprotinin abolishes sevoflurane postconditioning, associated with inhibited phosphorylation of Akt, protein kinase C-delta, and glycogen synthase kinase 3beta and reduced nitric oxide production.

[A case of anesthesia for a patient with a huge pheochromocytoma accompanying difficulty in hemodynamics control].

A 33-year-old man with diabetes mellitus developed a left pheochromocytoma, 9 cm diameters in size, of adrenalin predominance type. He underwent laparoscopic adrenalectomy. Anesthesia was induced with propofol and vecuronium, and maintained with continuous infusion of propofol. Lopivacaine was also used for epidural anesthesia. From the beginning of the operation, blood pressure was well controlled using prostaglandin E1 and landiolol continuously. However, the bleeding from the adrenal vein occurred in the middle of the operation. This incidence obliged us to alter the operation from laparoscopic to open surgery. It turned difficult to control blood pressure although antihypertensive drugs, such as prostaglandin E1, phentolamine and landiolol, were used. However, it was difficult to suppress unexpected high blood pressure and tachycardia with alteration of the operative procedure.