Hirotsugu Okamoto

Kitasato University, Edo, Tokyo, Japan

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Publications (82)142.74 Total impact

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    ABSTRACT: Purpose: Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. Methods: The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. Results: The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p < 0.001), and to 4 (1-8) after FENtd (p < 0.001). The effects of FENiv, as evaluated by ΔNRS, CGI-I, and SS, were significantly greater than those of FENtd (p < 0.001, each), but not by the frequency and the severity of adverse effects, with the exception of dizziness. ΔNRS, and severity of adverse effects (drowsiness, dizziness, nausea, dry mouth, and pruritus) of FENiv correlated significantly with those of FENtd (rs > 0.04, each). Conclusions: The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.
    No preview · Article · Dec 2015 · Journal of Anesthesia
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    ABSTRACT: We report three cases of airway management with elective surgical cricothyroidotomy (SCT) for anesthetic management during surgical repair of maxillofacial injury involving basal skull fracture or nasal-bone fracture. In all patients, general anesthesia was induced, a supraglottic airway (SGA) device inserted, and SCT performed. Tracheal intubation was performed through SCT site, and the SGA device was removed. After surgery of maxillofacial fixation, the SGA device was re-inserted and the tracheal tube was removed. No major complications, such as subglottic stenosis or voice change, occurred. SCT holds potential as an alternative to tracheostomy because of ease of performance, fewer complications, and better cosmetic outcomes.
    Full-text · Article · Oct 2015
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    ABSTRACT: Aims: Lymphangiogenesis is frequently observed during inflammation, and this inflammation-induced lymphangiogenesis (IL) is a phenomenon actively involved in the pathophysiology of inflammation. We explored the roles of an inducible prostaglandin E synthase, mPGES-1, in IL elicited by lipopolysaccharide (LPS). Main methods: Peritonitis was induced in mice by intraperitoneal injection of LPS (E. coli 0111-B4; 25μg/mouse every 2days), and IL was evaluated by LYVE-1 immunostaining of whole-mount diaphragm tissues. Key findings: Compared to vehicle-treated wild-type (WT) mice, lymphatics in the diaphragms of mice injected with LPS were widened and the number of LYVE-1-positive ladder-structured lymphatics increased temporally. This. increase in lymphangiogenesis was accompanied by increased expression of vascular endothelial growth factor (VEGF)-C/D in the diaphragms. In mice treated with celecoxib, a cyclooxygenase-2 inhibitor, IL was suppressed with reduced expression of VEGF-C/D. This was also observed in mPGES-1 knockout mice (KO). Immunoreactive COX-2 and mPGES-1 were detected in. both CD11b-postive and CD3ε-postive calls in the diaphragm. When. FITC-dextran was injected into the peritoneal cavities, the amount of residual. FITC-dextran was reduced significantly in WT mice injected with LPS, and this. reduction was significantly decreased in mPGES-1 KO mice. Significance: The present results suggest that mPGES-1 plays a significant role in lymphangiogenesis during inflammation, and represents a novel target for controlling IL.
    No preview · Article · Oct 2015 · Life sciences
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    ABSTRACT: A 41-year-old woman with concomitant severe obesity, obstructive sleep apnea syndrome, and asthma was scheduled for endoscopic cholecystectomy. She was 165.8 cm tall and weighed 141.2 kg, with BMI of 51.4. We were concerned with difficulty in ventilation and intubation at the time of anesthesia induction and intra- and post-operative ventilatory failure. After sedation with fentanyl and droperidol together with intraoral local anesthesia with lidocaine (Xylocaine Viscous®), the intubating laryngeal mask (ILMA) was inserted while awake, and after the confirmation of adequate ventilation, the bronchoscope was inserted into the guide. Although she received no nerve block, she did not choke at the time of intubation. Because of airway pressure elevation during surgery, volumecontrolled ventilation was changed to pressure-controlled ventilation, and, because of a worsening P/F ratio, the recruitment procedure was performed during surgery, with a consequent improvement in the ratio. Although the use of the reservoir and NPPV equipment after extubation was considered, her respiratory status was stable, and she returned to her room with oxygen mask.
    No preview · Article · Apr 2015 · Masui. The Japanese journal of anesthesiology
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    ABSTRACT: Sodium bisulfite (NaHSO3) was clinically used as a preservative agent for local anesthetics but was later suspected to be neurotoxic. However, recent studies reported that NaHSO3 reduces the neurotoxicity of local anesthetics. The purpose of this study was to examine the effects of NaHSO3 with and without procaine on axonal transport in cultured mouse dorsal root ganglion (DRG) neurons. Experiment 1 served to determine the dose-dependent effects of NaHSO3 on axonal transport (DRG neurons were treated with 0.01, 0.1, 1, 10, or 20 mM of NaHSO3), whereas experiment 2 investigated the effect of 0.1 mM NaHSO3 on the action of local anesthetics on axonal transport (DRG neurons were treated with 1 mM procaine alone, or with 0.1 mM NaHSO3 plus 1 mM procaine). As an additional experiment, DRG neurons were also treated with 1 mM chloroprocaine alone, or with 0.1 mM NaHSO3 plus 1 mM chloroprocaine. In these experiments, we analyzed the percent change in the number of anterogradely and retrogradely transported organelles and recorded changes in neurite morphology using video-enhanced microscopy. In experiment 1, NaHSO3 at more than 1 mM caused cell membrane damage and complete inhibition of axonal transport, whereas 0.1 mM NaHSO3 maintained axonal transport at 40% to 60% of control with intact cell membrane. In experiment 2, 1 mM procaine alone maintained axonal transport at 90% to 100%. However, application of 1 mM procaine-0.1 mM NaHSO3 solution resulted in deformation of neurites and with complete cessation of axonal transport. Likewise, although 1 mM chloroprocaine maintain axonal transport at 80% to 100%, 1 mM chloroprocaine-0.1 mM NaHSO3 arrested axonal transport. NaHSO3 resulted in a dose-dependent damage to the cell membrane and axonal transport, especially when used in combination with procaine or chloroprocaine.
    No preview · Article · Dec 2014 · Regional Anesthesia and Pain Medicine
  • Hiromi Matsuda · Masayasu Arai · Hirotsugu Okamoto
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    ABSTRACT: We described the anesthetic management of a 17-year-old male patient with Fukuyama congenital muscle dystrophy (FCMD) who underwent surgical repair for scoliosis under total intravenous anesthesia. The patient had severe constructive lung disease (%VC 18.6%). Left ventricular wall motion was reduced (left ventricular ejection fraction 40%). Propofol and remifentanil were continuously infused to maintain anesthesia, but we did not use any muscle relaxant throughout the course. We used arterial pressure-based cardiac output and stroke volume variation as a guide for circulatory management. We could not find any congestion on chest X-ray after the surgery. The emergence and recovery from the anesthesia was rapid and muscle strength was enough, and we could extubate the patient just after the end of the surgery. No respiratory and cardiac complications occurred during the postoperative period. Even though he was in the young age in FCMD, respiratory and cardiac complications were severely impaired. For successful anesthetic management in FCMD patient, we should take care of rapid emergence from anesthesia and also we should not impair muscle strength for good postoperative respiratory function. Appropriate hemodynamic monitoring to avoid postoperative cardiac congestion is also required.
    No preview · Article · Jun 2014 · Masui. The Japanese journal of anesthesiology
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    ABSTRACT: It is known that acute liver dysfunction is one of the complications after Fontan operation. We tend to overlook it because their laboratory abnormalities are typically mild and hepatic dysfunction is an uncommon complication in children after cardiac surgery. However, this complication is likely to be an important indicator of poor prognosis. We report a patient who showed a prominent elevation of liver enzymes after Fontan operation. A year and 5 month old boy was scheduled for Fontan operation due to hypoplastic left heart syndrome. We used arterial pressure, central venous pressure and rSO2 probes (INVOS 5100, Somanetics Corp., USA) attaching on his head, abdomen and leg for circulatory management. The operation was performed with the heart beating. The blood removal tubes were inserted to the superior vena cava and inferior vena cava and the blood sending tube was inserted to the innominate artery when Norwood stage 1 was performed. After making an extracardiac conduit and a fenestration, we tried to take off the oxygenator with dopamine 5 microg x kg(-1) x min(-1), dobutamine 3 microg x kg(-1) x min(-1), isosorbide 2.5 microg x kg(-1) x min(-1). The central venous pressure was increased to 22-25 mmHg and systematic arterial pressure was unstable around 50 mmHg. We suggested the surgeons to expand the fenestration because the low flow through it was found on TEE examination, and introduced 15 ppm of nitric monoxide (NO) to decrease pulmonary vascular resistance and to control the central venous pressure at the same time. rSO2 was decreased to 50 temporarily when the oxygenator was taken off, however it was returned to 70 just after expanding the fenestration. On the first postoperative day, the patient showed marked elevations in GOT 17,305 U x l(-1), GPT 8,110 U x l(-1), gradually peaking out to GOT 105 U x l(-1), GPT 1,348 U x l(-1) by the seventh postoperative day. Hepatic dysfunction is related mainly to hemodynamic disturbances and is also related to the abdominal rSO2 and the high central venous pressure.
    No preview · Article · Apr 2014 · Masui. The Japanese journal of anesthesiology
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    ABSTRACT: We described a case of 19-year-old female who developed re-expansion pulmonary edema (RPE) after removal of a huge ovarian tumor. Altered lung volume after the surgery was observed by chest X-ray. Preoperatively, the lung was highly compressed by the tumor. Patient was intubated under general anesthesia and was ventilated by pressure controlled mode with only 5 cmH2O of positive end-expiratory pressure (PEEP). P/F ratio was changed from 163 to 444 after removal of the tumor. At the end of the surgery, P/F ratio decreased to 263 with yellow frothy sputum in the endotracheal tube and we diagnosed re-expansion pulmonary edema based on appearing yellow frothy sputum and chest X-ray. No recruitment procedure was carried out through the course except positive pressure ventilation with 5 cmH2O of PEEP in the intensive care unit after surgery. Twelve hours after the surgery, we could not confirm the recovery of lung volume on chest X-ray; however the patient was extubated because of P/F ratio increasing to 507. After 8 days of the surgery, the chest X-ray showed recovery of the lung volume to almost normal size. In this case, the compressed lung needed almost 1 week to recover the lung volume. This change in chest X-ray might indicate inadequate recovery of lung volume by recruitment maneuver and this should be avoided in order not to allow development of unfavorable clinical course of RPE.
    Full-text · Article · Apr 2014 · Masui. The Japanese journal of anesthesiology
  • Yuriko Niki · Akifumi Kanai · Keika Hoshi · Hirotsugu Okamoto
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    ABSTRACT: Trigeminal nerve block is widely used for trigeminal neuralgia (TN), though with much painful procedure and potential serious complications. The pain of TN occurs most frequently in the second and the third divisions of the trigeminal nerve, which are distributed in intraoral mucous membrane as well as face skin. Here, we examined the response to intraoral application of 8% lidocaine (LDC) in patients with oral TN pain in a double-blind, placebo (PBO)-controlled crossover study. Twenty-four outpatients with oral TN pain were randomized to receive intraoral application of either 8% LDC or saline PBO to the painful area. Following 7-days period, patients were crossed over to receive the alternative treatment. The pain was assessed with a numerical rating scale (NRS) before and 15 minutes after treatment. Patients used a descriptive scale to grade pain outcome and were asked to note any recurrence and the latency for recurrence after therapy. Intraoral LDC, but not PBO, significantly decreased the NRS from 5 (4, 8) (median [25, 75 percentiles]) to 1 (0, 4) (P = 0.001). Of the 24 patients, 19 described marked or moderate relief of pain after LDC but only three described the same after PBO application. The effect of LDC and PBO persisted for 2.8 (0.3, 3.0) and 0 (0, 0) hours, respectively. Intraoral application of 8% LDC produced prompt analgesia without serious side effects in patients with TN who presented with severe intraoral pain.
    No preview · Article · Feb 2014 · Pain Medicine
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    ABSTRACT: A patient complicated with interstitial pneumonia required emergency posterior lumbar spinal fusion. The blood gas analysis showed relatively benign values (PaO2 81 torr, PaCO2 44 torr, under room air), but the honeycombing lungs were noted in the bilateral lung fields on CT, and the KL-6 level was high (1,000 U x ml(-1)), for which the acute exacerbation of interstitial pneumonia was suspected. Sivelestat sodium administration was initiated during the surgery and continued postoperatively. During surgery, setting the FIO2 at 0.34, the P/F ratio and intra-airway pressure could be maintained at 500 and 25 mmHg, respectively. To reduce postoperative respiratory complication, anesthesia was maintained with desflurane, which is dissipated easily, and 0.5% ropivacaine 15 ml was subcutaneously injected to the surgical field at the time of wound closure to reduce the total doses of intraoperative fentanyl and postoperative analgesics. After the completion of surgery, the endotracheal tube was removed with head elevated position, and the patient was transported back to the ward. No acute exacerbation occurred thereafter, and the patient was discharged 67 days after surgery. The prediction of acute exacerbation of interstitial pneumonia is difficult. Moreover, there is no established preventive method, although the mortality is high. Therefore, physicians should be thoroughly informed about the currently available evidence, including developmental factors.
    No preview · Article · Feb 2014 · Masui. The Japanese journal of anesthesiology
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    ABSTRACT: Receptor activity-modifying protein 1 (RAMP1) forms a complex with calcitonin receptor-like receptor (CLR) to produce the receptor for calcitonin gene-related peptide (CGRP). CGRP, a 37-aa neuropeptide, is widely distributed in neuronal tissues and exerts its biological effects via CLR/RAMP1; however, the pathophysiological roles of CLR/RAMP1 remain to be clarified. To study the functions of CLR/RAMP1, we generated RAMP1-knockout (RAMP1(-/-)) mice. Compared with those of wild-type (WT) mice, wound healing and wound-induced angiogenesis were significantly suppressed in RAMP1(-/-) mice, with reduced expression of vascular endothelial growth factor (VEGF)-A. Formation of the lymphatic vessels that drain interstitial fluids was also suppressed in RAMP1(-/-) mice, with reduced expression of VEGF-C and VEGFR-3 in wound granulation tissues. RAMP1 was expressed in endothelial cells (ECs) in the preexisting skin blood vessels, but was not observed in ECs in newly formed blood or lymphatic vessels. Macrophages in the wound granulation tissues expressed RAMP1 and produced substantial amounts of VEGF-C in response to CGRP in vitro. RAMP1(-/-) bone marrow chimeric mice showed delayed wound healing with reduced angiogenesis/lymphangiogenesis in wound granulation tissues. These findings suggest that RAMP1 plays a crucial role in wound healing and wound-induced angiogenesis and lymphangiogenesis and that it is a promising target for controlling angiogenesis and lymphangiogenesis.-Kurashige, C., Hosono, K., Matsuda, H., Tsujikawa, K., Okamoto, H., Majima, M. Roles of receptor activity-modifying protein 1 in angiogenesis and lymphangiogenesis during skin wound healing in mice.
    No preview · Article · Dec 2013 · The FASEB Journal
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    ABSTRACT: A 36-year-old man (185 cm tall, weighing 85 kg) was scheduled for fixation of a right carpal bone fracture. He had no operative history, and his preoperative laboratory data were normal. A laryngeal mask was inserted after intravenous propofol and fentanyl administration without a muscle relaxant. Anesthesia was maintained by sevoflurane in a mixture of air and oxygen. A tourniquet was placed on the right upper arm. One hour after the operation, his heart rate increased to 90-100 beats x min(-1) from 70-80 beats x min(-1) at the start of the operation, and tachycardic continued, even after release of the tourniquet. Although end-tidal CO2 was 50-60 mmHg, his body temperature remained 37.6 degrees C, and neither muscle stiffness nor brown urine was observed. The duration of the operation and the duration of anesthesia were 2 hours 40 min and 4 hours, respectively. The patient went back to the ward without myalgia after removal of the laryngeal mask. On the postoperative day one, the patient had brown urine. On the postoperative day 2, he experienced myalgia of the upper and lower extremities and masseter muscle. On the postoperative day 3, myoglobinuria was detected. As in this case, although evident symptoms of malignant hyperthermia are not always observed during operations, some cases show obvious symptoms during the postoperative period. Thus, it is important to be aware of the symptoms of malignant hyperthermia postoperatively for early diagnosis and treatment.
    No preview · Article · Mar 2013 · Masui. The Japanese journal of anesthesiology
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    ABSTRACT: Background: Vasopressin V1a receptor (V1aR) null mice have insufficient acid-base balance, but the target cell for V1aR signaling which results in the urinary acidification has not been identified. Methods: By using a quantitative in situ hybridization technique and a double-staining technique with an anti-AQP3 antibody in mice, we investigated the axial distribution and acidosis-induced expression of V1aR mRNA along the nephron. We also investigated the acidosis-induced morphological change in the tubule cells from wild-type and V1aR-null (V1aR(-/-)) mice. Results: In the normal condition, V1aR mRNA was moderately expressed in the medullary thick ascending limb (MTAL) and highly expressed in the intercalated cell (IC) throughout the collecting duct (CD). However, no expression was observed in the proximal tubule, thin limbs of Henle's loop, and the principal cell of the CD. Importantly, V1aR mRNA was upregulated significantly both in the TAL and the IC of the CD in the inner stripe of the outer medulla (MTALis and IC of OMCDis, respectively) when mice were treated with NH4Cl (0.28 mol/L) for 6 days. Acidosis-induced hypertrophy, which was completely attenuated in V1aR(-/-) mice, was observed only in the IC of OMCDis (P < 0.005). In addition, urinary excretion of ammonia (NH3/NH4 (+)) was significantly decreased on day 3 (P < 0.05) and day 6 (P < 0.005) in the V1aR(-/-) mice treated with NH4Cl. Conclusion: In conclusion, the IC of OMCDis may be the target cell stimulated by the vasopressin V1aR axis and contribute to urinary acidification, at least during metabolic acidosis.
    Full-text · Article · Mar 2013 · Clinical and Experimental Nephrology

  • No preview · Article · Feb 2013 · Circulation Journal
  • Hisae Ando · Masayasu Arai · Masaya Toda · Hirotsugu Okamoto

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    ABSTRACT: Background: Epinephrine can potentially worsen the neurotoxic effects of local anesthetics when used for spinal or epidural anesthesia. The vasoconstrictive property of epinephrine reduces dural blood flow, which in turn reduces the clearance of local anesthetics from the subarachnoid space. This study examined the histological and neurofunctional effects of intrathecally administered lidocaine combined with epinephrine in rats. Methods: Sixty-two rats were divided into 9 treatment groups: 5% or 7.5% lidocaine in 10% glucose solution with or without 0.1 or 0.5 mg/mL epinephrine, or epinephrine alone at 0.1 or 0.5 mg/mL in 10% glucose, or 10% glucose alone. Hind-limb motor function was evaluated immediately after drug injection by walking behavior. Sensory function was assessed by the response to radiant heat stimulation at just before and 1 week after the injection. Seven days after the injection, L3 spinal cord with anterior and posterior roots, the dorsal ganglion, and cauda equina were harvested and examined histologically. Results: Histological lesions were limited to the posterior root just at entry into the spinal cord in rats injected with 7.5% lidocaine, with and without epinephrine. No histological abnormalities were noted in other areas or other groups. There was no significant change in sensory threshold in all groups. Significantly, prolongation of gait recovery time was noted in 5% and 7.5% lidocaine with epinephrine groups compared with 5% or 7.5% lidocaine alone. Conclusions: Intrathecal epinephrine prolonged the action of intrathecal lidocaine but did not worsen lidocaine-induced histological damage and functional impairment.
    No preview · Article · Dec 2012 · Regional anesthesia and pain medicine
  • Norihito Hayashi · Akifumi Kanai · Takashi Okamoto · Hirotsugu Okamoto
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    ABSTRACT: Three patients with severe neck and radicular pain due to cervical disc herniation was not relieved of pain by common drug medication such as NSAIDs and anticonvulsants. Patients underwent oral mini-pulse therapy of betamethasone as the initial dose of 8 mg x day(-1) in the form of 8 tablets of 0.5 mg in a single dose twice a day (after breakfast and after lunch). The daily dose was reduced by half every 4 days, and the therapy was continued for 16 days. In all patients, the pain disappeared completely within the opening 10 days of the therapy, and the pain did not relapse after the therapy. All adverse events of betamethasone including irritation, insomnia and overeating disappeared without medication within several days.
    No preview · Article · Dec 2012 · Masui. The Japanese journal of anesthesiology
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    ABSTRACT: Background: Vasopressin V1a receptor null (V1aR(-/-)) mice recently showed incomplete urinary concentration due to higher urine volume during control and water diuresis (euhydration), but showed normal response during dehydration (Aoyagi et al., Am J Physiol 295: F100-7, 2008). Methods: Water balance, plasma vasopressin, plasma and urine osmolality, and aquaporin 2 (AQP2) expression in the kidney of wild-type (WT) and V1aR(-/-) mice were therefore further examined using improved methods of urine collection (urinary bladder urine). Results: V1aR(-/-) mice demonstrated a lower urine osmolality (3,360 ± 138 vs. 3,610 ± 47 mOsm/kgH2O) and a higher plasma osmolality (354.3 ± 1.3 vs. 342.5 ± 1.5 mOsm/kgH2O) after dehydration for 24 h compared to WT mice (P < 0.05). In contrast, the plasma vasopressin concentration was significantly (P < 0.001) higher in the V1aR(-/-) mice (48.8 ± 4.8 vs. 22.1 ± 2.4 pg/ml). On the other hand, although the AQP2 protein expression in the kidney was increased after dehydration, the basal (control) and dehydration-induced AQP2 protein levels were significantly lower in V1aR(-/-) mice compared to WT mice (by Western blotting). Staining by an anti-AQP2 antibody in the luminal membrane of the collecting ducts was increased in both V1aR(-/-) and WT mice after dehydration, but was relatively weaker in the V1aR(-/-) mice (by immunohistochemistry). Moreover, urinary excretion of AQP2 protein, an index of the luminal AQP2 expression, was significantly (P < 0.05) lower in the V1aR(-/-) mice. Conclusion: V1aR signaling may be fundamentally important for the expression of AQP2 in the collecting ducts during control conditions and dehydration.
    Full-text · Article · Sep 2012 · Clinical and Experimental Nephrology
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    ABSTRACT: The aim of this study was to compare the neurotoxicity of intrathecal procaine, bupivacaine, levobupivacaine, and ropivacaine in an animal model. The study comprised two experiments. In the concentration experiment, rats (n = 78) were administered 0.12 μL·g(-1) body weight (BW) of 2% or 20% procaine, 0.5% or 5% bupivacaine, 0.5% or 5% levobupivacaine, or 0.5% or 5% ropivacaine. Based on the findings, the doses were increased by volume in the subsequent volume experiment using 0.12, 0.24, or 0.48 μL·g(-1) BW of 6% procaine, 6% levobupivacaine, or 6% ropivacaine (n = 79). Walking behaviour and sensory threshold were analyzed, and a histological examination of the spinal cord, posterior and anterior roots, and cauda equina was performed. The concentration experiment showed abnormalities only in the 5% bupivacaine group, and these abnormal findings were in the posterior root (PR) and posterior column (PC). The volume experiment revealed that procaine 0.24 μL·g(-1) was neurotoxic, mainly affecting the PR. At 0.48 μL·g(-1), severe injury was observed in the PR and PC in all six procaine rats and four of six levobupivacaine rats, while milder injury was limited to the PR in one of six ropivacaine rats, which differed significantly from the former two groups (P = 0.006 and P = 0.014, respectively). Electron microscopy showed axonal degeneration. All four local anesthetics seemed to cause identical neurotoxic lesions commencing in the PR and extending to the PC by axonal degeneration. Bupivacaine appeared to be the most neurotoxic of the four drugs, and the neurotoxicity at higher doses increased by volume with procaine > levobupivacaine > ropivacaine.
    No preview · Article · Mar 2012 · Canadian Anaesthetists? Society Journal
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    ABSTRACT: Intrathecally administered fentanyl rarely causes drug tolerance or formation of inflammatory masses and might therefore be a suitable treatment option for chronic pain. However, the neurotoxicity of intrathecally administered fentanyl remains to be clarified. We examined the histological changes, neurodysfunction, and side effects of intrathecal fentanyl in rats. The rats received fentanyl at 0.12 µL/g body weight (0, 50, 1000, 2000, and 5000 µg/mL in saline) via an intrathecal catheter. Seven days after the injection, the spinal cord with both roots were removed for histological examination. The neurological function was evaluated by monitoring walking behavior and latencies to radiant heat. Side effects were also recorded. No histological abnormalities were observed in the spinal cord, anterior and posterior roots, cauda equina nerves, or arachnoid membrane. Formation of white neomembrane was noted around the catheter in some animals, but there was no significant difference in the incidence among the groups. The sensory threshold was significantly higher at 1 and 2 hours after injection in the 50 and 5000 µg/mL groups, respectively. However, there was no significant difference in the sensory threshold among the five groups at 7 days postinjection. All of the rats walked normally within 4 hours even after injection of 5000 µg/mL fentanyl. The incidence of apnea, muscular rigidity, and bradycardia increased significantly at ≥ 1000 µg/mL dose. The side effects of intrathecally administered fentanyl were concentration-dependent, although no neuronal tissue damage, inflammation, or irreversible neurodysfunction were observed even at 5000 µg/mL.
    No preview · Article · Apr 2011 · Pain Medicine

Publication Stats

419 Citations
142.74 Total Impact Points


  • 2002-2015
    • Kitasato University
      • Department of Anesthesiology
      Edo, Tokyo, Japan
  • 1992-2000
    • Kyushu University
      • Department of Anesthesiology and Critical Care Medicine
      Fukuoka-shi, Fukuoka-ken, Japan