[Usefulness of subarachnoid phenol-glycerin block therapy for enabling cancer patients with refractory anal pain to proceed to home-based care].

In recent years, the number of cancer patients and their families desiring palliative home-based care in Japan has increased. Subarachnoid phenol-glycerin block therapy is offered to relieve refractory anal pain in cancer patients, and to reduce the side effects of systemic administration of opioids, such as drowsiness. The effects of phenol-glycerin, which is a medicine used for neurodegenerative diseases, lasted for 1 week to 3 months. Eight patients with this manipulation showed a significant improvement in their pain level, calculated by the numerical rating scale(NRS). Five of these patients could proceed to homebased care. It is important to establish common guidelines for the management of phenol-glycerin. The participation of pharmacists in the palliative care team will contribute to further growth of home-based care.

[Usefulness of epidural catheter with distal subcutaneous reservoir for cancer pain control].

When an effective pain relief cannot be achieved by systemic administration of analgesics, neuraxial opioid therapy such as epidural (EPI) and subarachnoid (SA) catheters should be offered. During the period of 2004 to 2008, EPI (117 patients) and SA (1 patients) with an epidural catheter with subcutaneous reservoir also showed a significant improvement in their pain level calculated by numerical rating scale (NRS). Two cases of infection were caused by a subcutaneous reservoir, however, no serious infections, such as epidural abscess, were observed. Long-term catheter trouble occurred in 15 patients (12.8%) which was considered to be the catheter obstruction caused by epidural fibrosis. It is necessary to establish the common guidelines between hospital doctors and general practitioners to prevent the incidence of the catheter troubles and infections.

Removal of 2-arachidonylglycerol by direct hemoperfusion therapy with polymyxin B immobilized fibers benefits patients with septic shock.

Arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) are endocannabinoids involved in septic shock, and 8-epi prostaglandin F2alpha (F2-isoprostane) is a biomarker of oxidative stress in biological systems. Because the antibiotic polymyxin B absorbs endocannabinoids as well as endotoxins, direct hemoperfusion therapy with polymyxin B-immobilized fibers (PMX-DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and determine the proper use of PMX-DHP, we measured the changes in levels of endocannabinoids and F2-isoprostane in patients with septic shock. Twenty-six patients with septic shock, including those with septic shock induced by peritonitis, underwent laparotomy for drainage. Endocannabinoids absorption with PMX-DHP was examined in two groups of patients: patients whose mean arterial blood pressure (mABP) had increased more than 20 mm Hg (responder group; N = 13); and patients iwhose mABP did not increase or had increased no more than 20 mm Hg (non-responder group; N = 13). Levels of AEA did not change after PMX-DHP in either the non-responder or responder groups, whereas levels of 2-AG decreased significantly after PMX-DHP in the responder group, but not in the non-responder group. F2-isoprostane gradually increased after PMX-DHP treatment; on the other hand, levels of F2-isoprostane remained constant in the responder group. Patients with septic shock are under considerable oxidative stress, and 2-AG plays an important role in the cardiovascular status of these patients. The removal of 2-AG by PMX-DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long-term oxidative stress.

Does long-term continuous transcranial Doppler monitoring require a pause for safer use?

BACKGROUND: Transcranial Doppler sonography (TCD) has been used widely for long-term monitoring of cerebral blood flow without adverse reports. However, attention has not been adequately paid to the fact that an increase in the time period of TCD insonation causes brain temperature to rise due to ultrasound absorption by tissue and the skull. We measured the actual temperature rise in local brain tissue induced by TCD insonation over a long time period during in vivo animal experiments in order to verify whether or not a pause is required in long-term, continuous TCD monitoring. METHODS: We inserted thermocouples into the skull-brain interface (SBI) of 15 New Zealand White rabbits (10: TCD application group; 5: control group, TCD non-application group). The TCD probe was placed on the parietal bone, and changes in SBI temperature (SBIT) were measured for 90 min. TCD was set at maximum output level (0.2 W, 2 MHz). RESULTS: SBIT in the TCD group increased rapidly to 3.47 degrees C within 25 min and then reached a plateau. The maximum time for safe continuous TCD application is estimated to be 33 min. CONCLUSIONS: Even though there are large differences in factors, such as brain volume and environmental conditions, between rabbits and humans, there is less difference in their cerebral blood flow per brain weight, which is the parameter that is mainly associated with heat reduction. Accordingly, the findings of the present experiment suggest that long-term TCD monitoring in clinical use should include a pause after every 30 min of insonation to avoid thermal damage to the brain surface.

Do dopamine receptors mediate part of MAC?

BACKGROUND: Depletion of central nervous system catecholamines, including dopamine, can decrease MAC (the minimum alveolar concentration of an inhaled anesthetic required to suppress movement in response to a noxious stimulus in 50% of test subjects); release of central nervous system catecholamines, including dopamine, can increase MAC; and increased free dopamine concentrations in the striatum can decrease MAC. Such findings suggest that dopamine receptors might mediate part of the capacity of inhaled anesthetics to provide immobility in the face of noxious stimulation. METHODS: We measured the effect of blockade of D2 dopamine-mediated transmission with 0.3 mg/kg or 3.0 mg/kg droperidol on the MAC of cyclopropane, desflurane, halothane, isoflurane, or sevoflurane in rats, and the effect of 3.0 mg/kg droperidol on the dose or concentration of etomidate (an anesthetic known to act principally by enhancing the response of gamma-aminobutyric acid(A) receptors to gamma-aminobutyric acid) required to suppress movement in response to noxious stimulation. RESULTS: Blockade of D2 dopamine-mediated transmission with droperidol does not decrease the MAC of cyclopropane, desflurane, halothane, isoflurane, or sevoflurane or its equivalent for etomidate in rats. CONCLUSIONS: These data, plus data from studies by others about D1 dopamine receptors, indicate that dopamine receptors do not mediate the immobility produced by inhaled anesthetics.

Insulin secretion and glucose utilization are impaired under general anesthesia with sevoflurane as well as isoflurane in a concentration-independent manner.

PURPOSE: The dose-dependent effects of sevoflurane and isoflurane anesthesia on glucose tolerance were compared in humans. METHODS: A prospective, randomized clinical study was conducted in 30 patients. The 30 patients were divided randomly into three sevoflurane anesthesia groups (0.5, 1.0, and 1.5 minimum alveolar concentration [MAC]) and three isoflurane anesthesia groups (0.5, 1.0, and 1.5 MAC). Induction of anesthesia was accomplished by inhalation of the volatile agent and nitrous oxide. After induction, anesthesia was maintained at the designated MAC for 15 min without surgical stimulation. The intravenous glucose tolerance test (IVGTT) was performed in these 30 patients while they were under general anesthesia and again several days after surgery in 5 of these patients while they were awake, as a control. RESULTS: The insulinogenic index (change in concentration of immunoreactive insulin/change in glucose concentration), the acute insulin response, and rates of glucose disappearance were significantly lower in all anesthesia groups than in the control group. However, the insulinogenic index, acute insulin response, and the glucose disappearance rate did not differ significantly among the six anesthesia groups. CONCLUSION: Sevoflurane anesthesia impairs glucose tolerance to the same degree as does isoflurane anesthesia. Glucose intolerance during sevoflurane or isoflurane anesthesia is independent of agent and dosage up to 1.5 MAC.

Comparative effects of bupivacaine and ropivacaine on intracellular calcium transients and tension in ferret ventricular muscle.

BACKGROUND: Recent evidence suggests that ropivacaine exerts markedly less cardiotoxicity compared with bupivacaine; however, the mechanisms are not fully understood at the molecular level. METHODS: Isolated ferret ventricular papillary muscles were microinjected with the Ca-binding photoprotein aequorin, and intracellular Ca transients and tension were simultaneously measured during twitch in the absence and presence of bupivacaine or ropivacaine. RESULTS: Bupivacaine and ropivacaine (10, 30, and 100 microm) reduced peak systolic [Ca]i and tension in a concentration-dependent manner. The effects were significantly greater for bupivacaine, particularly on tension (approximately twofold). The percentage reduction of tension was linearly correlated with that of [Ca]i for both anesthetics, with the slope of the relationship being approximately equal to 1.0 for ropivacaine and approximately equal to 1.3 for bupivacaine (slope difference, P < 0.05), suggesting that the cardiodepressant effect of ropivacaine results predominantly from inhibition of Ca transients, whereas bupivacaine suppresses Ca transients and the reaction beyond Ca transients, i.e., myofibrillar activation, as well. BAY K 8644, a Ca channel opener, abolished the inhibitory effects of ropivacaine on Ca transients and tension, whereas BAY K 8644 only partially inhibited the effects of bupivacaine, particularly the effects on tension. CONCLUSION: The cardiodepressant effect of bupivacaine is approximately twofold greater than that of ropivacaine. Bupivacaine suppresses Ca transients more markedly than does ropivacaine and reduces myofibrillar activation, which may at least in part underlie the greater inhibitory effect of bupivacaine on cardiac contractions. These results suggest that ropivacaine has a more favorable profile as a local anesthetic in the clinical settings.

Simultaneous determination of endocannabinoids (arachidonylethanolamide and 2-arachidonylglycerol) and isoprostane (8-epiprostaglandin F2alpha) by gas chromatography-mass spectrometry-selected ion monitoring for medical samples.

This article describes the overall procedure for the simultaneous determination of endocannabinoids (arachidonylethanolamide and 2-arachidonyglycerol) and isoprostane by gas chromatography-mass spectrometry in the selected-ion monitoring SIM mode (GC-MS-SIM) for medical samples. It also describes the general points of this method which a scientist who wants to assay a new, unidentified prostanoids and related compounds in medical samples would need to be clarified. The similar structures of prostaglandins, thromboxane, their metabolites, isoprostane, and arachidonyl compounds, allow them to be assayed after the simultaneous preparation of a single sample. The dimethyl isopropylsilyl ether forms of derivatized compounds are suitable for multiple GC-MS-SIM assay because of their molecular stability, and because they produce positive, strong, and large fragments on MS.

Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca2+ in rat ventricular muscle.

BACKGROUND: Bupivacaine exhibits a cardiodepressant effect, the molecular mechanism(s) of which have yet to be fully understood. Bupivacaine may directly act on contractile proteins and thereby decrease myofibrillar Ca2+ sensitivity. METHODS: Rat ventricular muscle was used. First, the effect of bupivacaine was examined on tetanic contractions in isolated intact myocytes. Next, Triton X-100-treated ventricular trabeculae were used to investigate the effect of bupivacaine on the pCa (= -log [Ca2+ ])-tension relation as well as on maximal Ca2+ -activated tension. Furthermore, to test whether bupivacaine inhibits the pathway downstream from Ca2+ binding to troponin C, tension was elicited in the skinned preparations by lowering the Mg-adenosine triphosphate (MgATP) concentration in the absence of Ca2+. The effect of bupivacaine on the pMgATP (= -log [MgATP])-tension relation was examined. RESULTS: In myocytes, 3 microm bupivacaine significantly (P < 0.01) increased intracellular Ca2+ concentration required for 5% cell shortening from the resting cell length. In skinned preparations, bupivacaine shifted the pCa-tension relation to the lower pCa side; the midpoint of the pCa curve (pCa50) was significantly (P < 0.05) changed by 10 and 100 microm bupivacaine. A highly correlated linear relation (R = 0.81; P< 0.0005) was present between pCa50 and maximal Ca2+ -activated tension. Bupivacaine (10 and 100 microm) significantly (P < 0.05) shifted the midpoint of the pMgATP-tension relation to the higher pMgATP side. CONCLUSIONS: Bupivacaine decreases myofibrillar Ca2+ sensitivity in ventricular muscle, and this is coupled with the compound's inhibitory effect on the pathway beyond Ca2+ binding to troponin C, possibly on the actomyosin interaction. The current results may partly explain the overall cardiodepressant effect of bupivacaine in vivo.

[One-lung anesthesia was successfully maintained by means of Fogarty Catheter in infants].

We experienced one-lung anesthesia using Fogarty catheter as a selective bronchial blocker in two infants. First case was a one-year and ten month-old female who underwent partial resection of the right middle lobe for her giant lung cyst under general anesthesia. Second case was an eight-month-old male who underwent thoracoscopic resection of his left mediastinal tumor under general anesthesia. One-lung anesthesia was successfully established with Fogarty catheters for both cases. Size of the catheter and its balloon was decided beforehand by measuring the diameter and length of the trachea and both bronchi based on the image obtained from computerized tomography (CT) in both cases. Therefore, surgical field was well visible during operation. There was no accidental episode in perioperative period. Bronchoscopy with ultra-thin fiberscope and X-ray fluoroscopy is useful to decide the position of Fogarty catheter and its balloon. Our means is recommendable for maintenance of one-lung anesthesia in infant.