Two Cases of Chronic Subdural Hematoma with Spontaneous Intracranial Hypotention Treated with Hematoma Drainage Followed by Epidural Blood Patch Under Intracranial Pressure Monitoring.

Both chronic subdural hematoma (CSDH) and spontaneous intracranial hypotension (SIH) cause headaches. However, the etiologies are different: SIH headache is caused by decreased intracranial pressure (ICP), whereas CSDH headache results from increased ICP. Moreover, CSDH is treated by hematoma drainage, while SIH is treated by epidural blood patch (EBP). Treatment for the cases of combined SIH and CSDH is not well-established. Herein, we report two cases wherein ICP was monitored and safely controlled by EBP after hematoma drainage. Case 1: A 55-year-old man with progressive consciousness disturbance was diagnosed with bilateral CSDH. He underwent bilateral hematoma drainage; however, the headache became apparent during standing. We diagnosed SIH by diffuse pachymeningeal enhancement on brain MRI and epidural contrast medium leakage on CT myelography. Due to the re-enlargement of bilateral CSDH, we performed EBP after hematoma drainage and ICP monitor insertion. Finally, the headache and bilateral CSDH were resolved. Case 2: A 54-year-old man with persistent headache was diagnosed with bilateral CSDH. He underwent multiple hematoma drainage sessions. However, headache on standing persisted. We diagnosed SIH by diffuse pachymeningeal enhancement on brain MRI and epidural contrast medium leakage on CT myelography. Due to the re-enlargement of the left CSDH, we performed EBP after left hematoma drainage and ICP monitor insertion. Finally, the headache and bilateral CSDH were resolved. EBP after hematoma drainage and ICP monitoring was useful for SIH with bilateral CSDH. By monitoring ICP before EBP, the ICP was safely controlled and CSDH was resolved.

Different characteristics of cell volume and intracellular calcium ion concentration dynamics between the hippocampal CA1 and lateral cerebral cortex of male mouse brain slices during exposure to hypotonic stress.

The mechanism of brain edema is complex and still remains unclear. Our aim was to investigate the regional differences of cell volume and intracellular Ca2+ concentration ([Ca2+ ]i ) dynamics during hypotonic stress in male mouse hemi-brain slices. Brain slices were loaded with the fluorescence Ca2+ indicator fura-2, and cell volume and [Ca2+ ]i in the lateral cerebral cortex (LCC) and hippocampal CA1 (CA1) region were measured simultaneously during exposure to hypotonic stress using Ca2+ insensitive (F360) and Ca2+ sensitive fluorescence (F380), respectively. Brain cell swelling induced by hypotonic stress was followed by a regulatory volume change that coincided with an increase in [Ca2+ ]i . The degrees of change in cell volume and [Ca2+ ]i were significantly different between the LCC and CA1. The increase in cell volume and [Ca2+ ]i in the LCC, but not in the CA1, was decreased by the transient receptor potential channel blockers LaCl3 and GdCl3 . The increase in [Ca2+ ]i in both the LCC and CA1, was significantly decreased by the intracellular Ca2+ modulators thapsigargin and xestospongin C. The K+ channel activator isoflurane and Cl- channel blocker NPPB significantly decreased [Ca2+ ]i in the LCC. This study demonstrated that, between cells located in the LCC and in the CA1, the characteristics of brain edema induced by hypotonic stress are different. This can be ascribed to the different contribution of volume sensitive G-protein coupled receptor and stretch sensitive Ca2+ channels.

Dexmedetomidine-based intravenous anesthesia of a pediatric patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency: A case report.

RATIONALE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, resulting in deficits in nicotinamide adenine dinucleotide phosphate production, an important intracellular antioxidant enzyme. G6PD-deficient subjects present with a susceptibility of erythrocytes to oxidative stress and hemolysis, and should avoid drugs or stressors that have oxidative actions. Dexmedetomidine is an anesthetic agent with antioxidant actions. PATIENT CONCERNS AND DIAGNOSES: A 5-year-old boy with G6PD deficiency. The patient was diagnosed with G6PD deficiency at birth. His red blood cell levels were indicating Class II G6PD activity by the World Health Organization (WHO) classification, but had no history of hemolytic anemia. INTRAVENTIONS: Because of the patient's anxiety and hyperactivity prior to an operation for upper labial frenum resection, we performed perioperative management using intravenous sedation with dexmedetomidine, which provides upper airway patency and has an antioxidant action. OUTCOMES: There was no abnormal breathing observed during anesthesia, and arousal was smooth with stable hemodynamics. The patient had no symptoms of hemolytic anemia up to 1 week postsurgery. CONCLUSION: Antioxidant sedatives such as dexmedetomidine may be useful for reducing the risk of hemolysis after surgery in infant G6PD deficiency cases.

[Successful trial for introduction of the WHO surgical safety checklist].

BACKGROUND: The WHO Surgical Safety Checklist was published in 2008 as an attempt to decrease complications and death from surgery. This checklist was implemented and evaluated using questionnaires in an intermediate size general hospital. We attempted to confirm how the WHO checklist has been implemented and assessed as a medical safety system. METHODS: Using questionnaires, we surveyed anesthesiologists, surgeons and operating room nurses at Kosei Chuo General Hospital regarding the effectiveness of the WHO Surgical Safety Checklist on three occasions (immediately following implementation, after half a year, after one year). RESULTS: Immediately after its implementation, 50% of the anesthesiologists, surgeons and operating room nurses evaluated the checklist positively. That percentage decreased after half a year, and then increased significantly to 85% after one year following the use of our amended checklist. CONCLUSIONS: According to our questionnaires, after the adoption of our checklist, which amended the WHO Surgical Safety Checklist, positive evaluation increased significantly after one year, compared with evaluation immediately following implementation. At least one year was required for the checklist to be favorably received by anesthesiologists, surgeons and operating room nurses. We anticipate that the WHO Surgical Safety Checklist, amended to meet the circumstances of individual facilities, will be effectively implemented and firmly established.

Evaluation of the protective effects of cyclosporin a and FK506 on abnormal cytosolic and mitochondrial Ca²âº dynamics during ischemia and exposure to high glutamate concentration in mouse brain slice preparations.

We examined the protective effects of the immunosuppressants cyclosporin A (CsA) and FK506 on abnormal cytosolic Ca²âº ([Ca²âº]c) and mitochondrial Ca²âº concentration ([Ca²âº]m) dynamics induced by ischemia or high L-glutamate concentration in mouse brain slice preparations. We used fura-4F and rhod-2 as indicators for [Ca²âº]c and [Ca²âº]m, respectively, in their acetoxymethylester form. Slice preparations loaded with either of these two indicators were exposed to ischemic artificial cerebrospinal fluid (oxygen- and glucose-deprived medium) for 12 min or to aerobic medium with high L-glutamate concentration (isotonic 20 mM L-glutamate) for 5 min. CsA (1 - 10 µM) showed significant protective effects on the maximum increase in ischemia-induced [Ca²âº]c and [Ca²âº]m. FK506 (10 µM) showed significant protective effects on the [Ca²âº]m increase, but not on the ischemia-induced [Ca²âº]c increase. Both immunosuppressants showed almost equal protective effects on the [Ca²âº]c and [Ca²âº]m increases induced by high L-glutamate concentration. These results suggest that the protective effects of CsA and FK506 on Ca²âº overloading may be dependent upon the common pharmacological sites of actions relating to their effects as immunosuppressants. The small, but significant depressant effects of these drugs could give us important clues for rescuing critical brain damage induced by Ca²âº overloading.

Cyclophilin D-sensitive mitochondrial permeability transition in adult human brain and liver mitochondria.

The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the central nervous system (CNS) and other organs. Pharmacological inhibition or genetic knockout of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. If these findings in animal models are translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic target. The objective of this study was to validate the presence of a CypD-sensitive mPT in adult human brain and liver mitochondria. In order to perform functional characterization of human mitochondria, fresh tissue samples were obtained during hemorrhage or tumor surgery and mitochondria were rapidly isolated. Mitochondrial calcium retention capacity, a quantitative assay for mPT, was significantly increased by the CypD inhibitor cyclosporin A in both human brain and liver mitochondria, whereas thiol-reactive compounds and oxidants sensitized mitochondria to calcium-induced mPT. Brain mitochondria underwent swelling upon calcium overload, which was reversible upon calcium removal. To further explore mPT of human mitochondria, liver mitochondria were demonstrated to exhibit several classical features of the mPT phenomenon, such as calcium-induced loss of membrane potential and respiratory coupling, as well as release of the pro-apoptotic protein cytochrome c. We concluded that adult viable human brain and liver mitochondria possess an active CypD-sensitive mPT. Our findings support the rationale of CypD and mPT inhibition as pharmacological targets in acute and chronic neurodegeneration.

Inadequate gas supply to patients with an adjustable pressure-limiting valve in the fully opened position.

With spontaneous ventilation, sufficient exhaust resistance at the adjustable pressure-limiting (APL) valve when fully opened ensures that the reservoir bag fills and adequately supplies gas to patients. A lack of exhaust resistance with the APL valve fully open caused inadequate gas supply to patients with four types of anesthesia machines: SA2 (Dräger), Excel-210 SE (GE), Fabius (Dräger), and Cato (Dräger). Mechanically, the SA2 and Excel-210 SE APL valve systems, which are of the spring-loaded disc type positioned horizontally, cannot maintain sufficient exhaust resistance with the APL valve fully open. As for the Fabius and Cato, an exhaust valve independent of the APL valve should maintain sufficient exhaust resistance continuously. However, accumulated viscous substances on the thin diaphragm of the exhaust valve contributed to hindrance of diaphragm closure.

Evaluation of putative inhibitors of mitochondrial permeability transition for brain disorders--specificity vs. toxicity.

Inhibition of mitochondrial permeability transition (mPT) has emerged as a promising approach for neuroprotection and development of well-tolerated mPT inhibitors with favorable blood-brain barrier penetration is highly warranted. In a recent study, 28 clinically available drugs with a common heterocyclic structure were identified as mPT inhibitors e.g. trifluoperazine, promethazine and nortriptyline. In addition, neuroprotection by structurally unrelated drugs e.g. neurosteroids, 4-hydroxy-tamoxifen and trimetazidine has been attributed to direct inhibition of mPT. The regulation of mPT is complex and highly dependent on the prevailing experimental conditions. Several features of mPT, such as swelling, depolarization or NADH oxidation, can also occur independently of the mPT phenomenon. Here, in isolated rodent brain-derived and human liver mitochondria, we re-evaluate drugs promoted as potent mPT inhibitors. We address the definition of an mPT inhibitor and present strategies to reliably detect mPT inhibition in vitro. Surprisingly, none of the 12 compounds tested displayed convincing mPT inhibition or effects comparable to cyclophilin D inhibition by the non-immunosuppressive cyclophilin inhibitor D-MeAla(3)-EtVal(4)-Cyclosporin (Debio 025). Propofol and 2-aminoethoxydiphenyl borate (2-APB) inhibited swelling in de-energized mitochondria but did not increase calcium retention capacity (CRC). Progesterone, trifluoperazine, allopregnanolone and 4-hydroxy-tamoxifen dose-dependently reduced CRC and respiratory control and were thus toxic rather than beneficial to mitochondrial function. Interestingly, topiramate increased CRC at high concentrations likely by a mechanism separate from direct mPT inhibition. We conclude that a clinically relevant mPT inhibitor should have a mitochondrial target and increase mitochondrial calcium retention at concentrations which can be translated to human use.

Nicorandil decreases cardiac events during and after noncardiac surgery.

STUDY OBJECTIVE: To assess whether nicorandil reduces the likelihood of cardiac events during and after intermediate risk surgery. DESIGN: Multicenter study. SETTING: 13 hospitals in Japan. PATIENTS: Intermediate-risk patients were identified by the presence of risk factors such as angina, a history of myocardial infarction, heart failure, diabetes mellitus, and abnormal electrocardiography (ECG). INTERVENTIONS: Nicorandil was given to these patients during the operation. MEASUREMENTS AND MAIN RESULTS: Cardiac events during the operation and the following 5 days were monitored. The frequency of cardiac events in nicorandil-treated patients was compared with those in nontreated patients. Eighty-four patients received nicorandil during surgery and 237 patients received standard care. Cardiac events in the nicorandil-treated group occurred less frequently both during the operation (odds ratio, 0.15; 95% confidence interval, 0.03-0.76; P=0.02) and after it (odds ratio, 0.24; 95% confidence interval, 0.06-0.90; P=0.04). CONCLUSIONS: Nicorandil reduces the frequency of cardiac events in patients undergoing noncardiac surgery, both during and after the operation.

Are the incidences of cardiac events during noncardiac surgery in Japan the same as in the United States and Europe?

In Japan, an ever-present problem in the preoperative evaluation of patients with ischemic heart disease is that although such evaluations are based on Western data, these data serve as the basis for determining perioperative risk in Japanese patients. To remedy this problem, the Cardiac Ischemia and Anesthesia Research Committee was formed in 1997 and has conducted studies of perioperative complications in noncardiac surgery in Japan. In two retrospective studies in 1997, the proportions of patients with ischemic heart disease were 3.9% and 3.1%, approximately one tenth the rates reported in Europe and the United States. The incidences of perioperative cardiac complications in patients with ischemic heart disease were 16.4% and 13.2%, not widely divergent from rates reported in Europe and the United States. To investigate the baseline characteristics involved in perioperative complications, we conducted a prospective study of 237 patients classified as having intermediate risk for perioperative cardiac complications according to the American College of Cardiology/American Heart Association Guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery. We found that the prominent factor in intraoperative cardiac complications was the presence of hypertension (odds ratio = 2.911). Factors contributing to postoperative cardiac complications included those reflecting coronary lesion severity and cardiac dysfunction (history of heart failure; odds ratio = 6.884, coronary risk index grade; odds ratio = 2.884, and a history of intervention; odds ratio = 4.774).