Published papers

Critically ill patients are commonly associated with systemic inflammatory response syndrome (SIRS) and are at a greater risk of developing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Under these conditions, large amounts of various cytokines are produced, which either directly or indirectly induce tissue injury and finally organ dysfunctions, through the activation of neutrophils and as a result of release of cytotoxic molecules, especially neutrophil elastase (NE). In the present study, we determined plasma neutrophil elastase-alpha-1 antitrypsin complex (NE-AT) and elastase digests of cross-linked fibrin (e-XDP) in critically ill patients to elucidate the significance of NE in the initiation and progression of ALI and ARDS in the presence or absence of SIRS. We found significantly increased levels of plasma NE-AT in the patients with ARDS, especially when the definition of SIRS was met. Among ALI/ARDS groups, plasma NE-AT, but not e-XDP, correlated significantly with the decrease in PaO2/FIO2 ratio and the duration of ALI/ARDS. Furthermore, NE-AT, but not e-XDP, significantly increased in subgroups whose PaO2/FIO2 ratio decreased by more than 20%. Such correlations and differences between the subgroups were not observed in the non-ALI patients. From these results, we speculate that NE-AT, but not e-XDP, may be predictive of progressive lung injury in the early stage of ALI and ARDS. © 2007 Elsevier Masson SAS. All rights reserved.

Background and objective: Vascular endothelial growth factor (VEGF) is known to contribute to the development of pulmonary oedema, and has been suggested to have a protective role against lung injury. To determine the role of VEGF in acute lung injury (ALI) and ARDS, VEGF levels were measured in lung epithelial lining fluid (ELF) collected from patients with ALI/ARDS. Methods: Forty patients with ALI/ARDS underwent bronchoscopic microsampling to collect ELF on days 0 (onset of ALI/ARDS), 1, 3, 5, 7 and 10, unless the patient was extubated or had died. Twelve patients, who underwent bronchoscopy for examination of small, peripheral pulmonary nodules, served as controls. Results: The initial (day 0) levels of VEGF in ELF of the ALI/ARDS patients who survived and those who did not were 5.5 ng/mL (IQR: 2.3-19.7) and 1.7 ng/mL (IQR: 0.0-6.4), respectively. On days 0, 5, 7 and 10, the VEGF levels in ELF were significantly greater in survivors than in non-survivors (P < 0.05). VEGF levels on days 1 and 3 did not differ between survivors and non-survivors. There was no significant difference in ELF VEGF levels between control subjects and patients with ALI/ARDS at any time point. Lung injury score was inversely correlated with VEGF concentration in ELF (P < 0.001). Conclusions: In patients with ALI/ARDS, elevated VEGF levels in ELF may predict a better outcome. Increased production of VEGF in the injured lung may contribute to resolution of inflammation in the lung. © 2007 The Authors.

The aim of the present study was to examine whether neutrophil and its elastase activity played consequential roles in the progression of gut barrier dysfunction during acute alveolar hypoxia by using a specific neutrophil elastase inhibitor, sivelestat. With our institutional approval, 20 male rabbits (weight, 2.0-2.5 kg) were randomly allocated into two groups: control (n = 11) or sivelestat group (n = 9; bolus, 10 mg/kg, followed by 10 mg/kg per hour). At 4 h of alveolar hypoxia exposure (fraction of inspired oxygen, 0.10) under mechanical ventilation, the white blood cell counts and their function to produce oxygen radicals were measured. Intestinal permeability and myeloperoxidase activity were also assessed concurrently with the examination of histological changes of gut mucosa. The examination of sham animals (n = 4) exposed to normoxia was performed under the same study protocol. The circulating leukocyte counts and the neutrophil chemiluminescence were not different between the groups, whereas the neutrophil elastase activity was significantly increased in the control but not in the sivelestat and sham groups. Permeability, leukocyte accumulation, and myeloperoxidase activity of ileal wall in the control group were significantly elevated, accompanied by apparent destruction of gut mucosa compared with the sivelestat group (P < 0.05). Despite no significant differences in systemic inflammatory responses, the neutrophil elastase activity is a key element in the progression of functional and structural injury of gut mucosa during acute alveolar hypoxia. ©2007The Shock Society.

Mulvihill-Smith syndrome is a rare disease that belongs to progeroid syndromes. This syndrome is characterized by a senile face with an underdeveloped lower half, short stature, microcephaly, multiple pigmented nevi, immunodeficiency, hearing loss, and high-pitched voice. We report anesthetic management of a 27-year-old woman, 138 cm and 27 kg, with this syndrome, who underwent removal of mandibular cyst, partial resection of tongue and keratoplasty. Anesthesia was induced with fentanyl, propofol and vecuronium. There was difficulty in maintaining adequate ventilation with a face mask for children, and we used a mask for infants. Her Cormack grade was rated 3 but her trachea could be intubated assisted by BURP procedure. Anesthesia was maintained with sevoflurane, nitrous oxide and oxygen supplemented with fentanyl. The changes of blood pressure during anesthesia were extraordinary, suggesting the presence of advanced arteriosclerosis. The postoperative course was uneventful, with stable hemodynamics, and the patient was discharged from the hospital on 9th postoperative day. Anesthesia for Mulvihill-Smith syndrome should be performed with caution for the potential risk of difficult airway and unstable hemodynamics.

The purpose of the present study was to determine the effects of magnesium sulfate (MgSO4) on the neuromuscular function and spontaneous breathing of patients under sevoflurane and spinal anesthesia. Twenty-two patients with a history of arrhythmia undergoing elective knee surgery were randomly assigned to two groups: group M (n = 11), administered with MgSO4 40 mg·kg-1, and group S (n = 11), administered with saline. A combination of spinal anesthesia with 2% sevoflurane inhalation was applied to all patients under spontaneous breathing. Tidal volume (Vt), respiratory rate (RR) and end-tidal carbon dioxide (ETCO2) were measured before the MgSO4 or saline injection and measurements were repeated at 5, 15, 30, and 45 min after the injection. Neuromuscular function was continuously monitored with an acceleromyograph to record the acceleration of the adductor pollicis by stimulating the ulnar nerve at a frequency of 0.1 Hz. The Vt, RR, and ETCO2 showed little change in either group, and there was no significant difference between, the groups. The single-twitch response showed significant differences between the two groups (P = 0.0006). The present study indicated that the MgSO4 had a minimal effect on spontaneous breathing in patients undergoing sevoflurane and spinal anaesthesia, but that it attenuated the safety margin of neuromuscular function. © JSA 2007.

Cardiopulmonary bypass (CPB) is believed to cause postoperative lung dysfunction. To more closely examine the inflammatory processes occurring in the airways during CPB, we serially measured inflammatory mediators, with the assistance of a new bronchoscopic microsample probe, in 11 patients undergoing repair of aortic arch aneurysms. Epithelial lining fluid (ELF) and arterial blood were sampled simultaneously after induction of anesthesia, at the time of pulmonary reperfusion, and at the end of surgery. A decrease in the Pao2/Fio2 ratio was observed at the end of surgery (P = 0.029). Although the ELF concentrations of interleukin (IL)-8, IL-6, and neutrophil elastase had increased significantly at the end of surgery (median = 23,200, 1818, and 12,900 μg/mL, respectively), they did not correlate with the degree of hypoxemia. Neutrophil elastase increased significantly at the time of pulmonary reperfusion, before IL-8 and IL-6, and independently of blood transfusions. At the end of surgery, IL-6 in ELF correlated with total blood transfusion volume (ρ = 0.731, P = 0.011). These results indicate that a neutrophil-derived inflammatory response is activated in the airway in the early phase of CPB. © 2006 by International Anesthesia Research Society.

Objective: The purpose of this study was to assess perioperative platelet function with 2 types of monitors (a whole-blood aggregometer [WBA analyzer; Mebanix, Tokyo, Japan]) and the Sonoclot monitor [Sienco, Wheat Ridge, CO]) in patients undergoing hypothermic cardiopulmonary bypass (CPB). Design: Prospective, observational study. Setting: Single-center study at a university hospital. Participants: Twenty-six patients who underwent coronary artery bypass grafting or valve replacement under hypothermic CPB without platelet transfusion or fresh frozen plasma administration. Interventions: Blood sampling was performed at the following time periods: after anesthetic induction, after CPB, and on the first postoperative day. These samples were assessed with the WBA analyzer and the Sonoclot. Measurements and Main Results: Significant attenuation of adenosine diphosphate-induced platelet aggregation was detected shortly after CPB by 2 WBA analyzer-derived parameters: a decrease in the filtration pressure rate and an increase in the platelet aggregatory threshold index. Platelet aggregation returned to the preoperative level on the next day. There was no correlation between the amount of postoperative mediastinal drainage and defects in platelet aggregation. On the other hand, time to peak obtained by the Sonoclot did not show any significant changes. Conclusions: Whole-blood aggregation measured with the WBA analyzer detected transient platelet dysfunction shortly after CPB, whereas the Sonoclot was less sensitive to this change. © 2006 Elsevier Inc. All rights reserved.

Rationale: Proinflammatory cytokines play an important role in ventilator-induced lung injury (VILI). High-mobility group box-1 (HMGB1) is a macrophage-derived proinflammatory cytokine that can cause lung injury. Objectives: This study tested the hypothesis that HMGB1 is released in intact lungs ventilated with large VT. A second objective was to identify the source of HMGB1. A third objective was to examine the effects of blocking HMGB1 on the subsequent development of VILI. Methods: Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained from rabbits mechanically ventilated for 4 h with a small (8 ml/kg) versus a large (30 ml/kg) VT. BALF was also obtained from rabbits with intratracheal instillation of anti-HMGB1 antibody before the initiation of large VT ventilation. Measurements and Main Results: The concentrations of HMGB1 in BALF were fivefold higher in the large than in the small VT group. Immunohistochemistry and immunofluorescence studies revealed expression of HMGB1 in the cytoplasm of macrophages and neutrophils in lungs ventilated with large VT. Blocking HMGB1 improved oxygenation, limited microvascular permeability and neutrophil influx into the alveolar lumen, and decreased concentrations of tumor necrosis factor-α in BALF. Conclusions: These observations suggest that HMGB1 could be one of the deteriorating factors in the development of VILI.

Esophagetomy is considered as one of the most invasive surgical procedures. Despite marked advances in surgical techniques, anesthetic management and intensive care, the morbidity and mortality remain still high compared with the other types of surgery. Excessive inflammatory response after surgery induces over-production of inflammatory cytokines, leading to the development of vital organ failures. Anesthesiologists should pay much attention to perioperative management of patients undergoing esophagectomy since they are potentially at high risks of respiratory and cardiovascular complications caused by excessive stress with cervical thoracic and abdominal procedures. During surgery, many interventions such as effective epidural anesthesia, restrictive fluid management lung protective strategy, maintenance of hemodynamic stability and steroid therapy should be considered. Perioperative respiratory management including early extubation, intensive physical therapy, early mobilization and rehabilitation with enteral nutrition are all important to prevent postoperative complications and to shorten the length of hospital stay. However, some patients need longer-term mechanical ventilation due to preoperative respiratory dysfunction and reduced cough reflex by surgical manipulations. A multimodal treatment is warranted to improve the outcomes after esophagectomy.

We report the anesthetic management of a female neonate with congenital cyst adenoid malformation (CCAM) type III of the lung who underwent the lower right lobe resection 22 days after birth. General anesthesia was induced with propofol and rocuronium. The trachea was intubated with a 3.0 standard tube. Anesthesia was maintained with sevoflurane in an air/oxygen mixture and fentanyl. Intraoperative anesthetic course was uneventful except transient desaturation during lung compression. Immediately, the saturation was restored by interruption of lung compression. One lung ventilation was not necessary in this operation. Postoperative course was uneventful. Patient was discharged home on the 28th postoperative day.

C1 inhibitor (INH) deficiency is characterized by the presence of angioedema of the extremities, face, airway and the gastrointestinal tract. Airway obstruction is the most common cause of mortality. A 78-year-old woman presented with repeated episodes of angioedema. These episodes were triggered by general anesthesia, dental extraction, venipuncture, vaccination and loxoprofen. The familiy history of similar symptoms was negative. C1 inhibitor concentrate was administered perioperatively for prophylaxis of attacks. Operation was performed under neurolept anesthesia and combined spinal-epidural anesthesia in order to avoid airway manipulation. Postoperative pain was controlled by patient-controlled epidural anesthesia to prevent attacks triggered by pain. The patient had angioedema on both lower extremities perioperatively but did not develop further attacks. Anesthesia was safely performed in a patient with C1 inhibitor deficiency scheduled for total hip arthroplasty.

OBJECTIVES: Spinal cord deficits are devastating complications after surgery for thoracic and thoracoabdominal aortic aneurysms. We developed a regional spinal cord cooling system using an epidural catheter containing cold saline within an isolated counter-current lumen to prevent such complications and reviewed the clinical results. METHODS: We enrolled 37 patients with thoracic (n = 13) and thoracoabdominal (n = 24) aortic aneurysms that were repaired using the regional spinal cord cooling system under mild hypothermia with a partial femoro-femoral bypass. RESULTS: Although 2 patients died before hospital discharge (hospital mortality, 5.4%), none developed neurological deficits such as paraplegia or paraparesis. CONCLUSIONS: The outcomes of surgery for thoracic and thoracoabdominal aortic aneurysms under regional spinal cord hypothermia using a custom-designed epidural catheter were excellent. Although our patient cohort was small, the results indicate that our technique might help to improve the outcomes of thoracic and thoracoabdominal aortic repair. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

Doxapram is the only dedicated respiratory stimulant used to aid recovery of breathing after major surgery. Doxapram acts on peripheral chemoreceptors and although the central action of doxapram has been suggested, its detailed neuronal mechanism is unknown. We assessed doxapram-induced changes in spontaneous cervical nerve (C4) inspiratory activity and the firing of action potentials in pre-inspiratory and inspiratory neurones in the medulla. Experiments were performed in neonatal rat brainstem-spinal cord preparations, which can produce respiratory rhythm for several hours under in vitro conditions. Doxapram application (for 15 min) increased the frequency and amplitude of C4 activity dose-dependently. Doxapram induced changes in the electrophysiological properties of pre-inspiratory and inspiratory neurones. Our results suggest that respiratory activity enhancement was likely to be induced via effects on the potassium channels of pre-inspiratory and inspiratory neurones and indicate the central actions of doxapram. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Moyamoya disease is the result of progressive steno-occlusive changes in the internal carotid arteries followed by formation of bilateral abnormal vascular networks. The disease may present with cerebral ischemia causing cerebral hemorrhage in the perioperative period. There are few reports of cardiac surgeries in patients with moyamoya disease, and the management during cardiopulmonary bypass for moyamoya disease has not been established We gave general anesthesia for mitral valve plasty in patient with the moyamoya disease. A 52-year-old woman underwent mitral valve plasty. She had been diagnosed with moyamoya disease and during the cardiopulmonary bypass, we used a-stat blood gas management with mild hypothermia and maintained Paco2 around 40 mmHg. We maintained the perfusion flow of CPB above 3.0 l • min-1 • m-2 and the mean perfusion pressure above 70 mmHg. In additioa we used the pulsatile perfusion assist with intraaortic balloon pumping to maintain cerebral circulation. Postoperative course was uneventful without apparent neurologic deficit, and she was discharged from hospital on 10th postoperative day.

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease, also known as Bland-White-Garland (BWG) syndrome. Mitral valve regurgitation secondary to papillary muscle dysfunction due to myocardial ischemia and progressive left ventricular dysfunction are major clinical manifestations of BWG syndrome. We report perioperative management of a five-year-old patient with BWG syndrome who underwent the Takeuchi procedure making an ¡baffle using anterior pulmonary artery wall. General anesthesia was maintained with inhalation of sevoflurane in 25-40% oxygen and continuous infusion of remifentanil. Since a decrease in pulmonary artery pressure could induce coronary steal phenomenon, we ventilated the patient with minimally required FIO2 to maintain SpO2 98-100%, and maintained PaCO2 between 40 and 50 mmHg to avoid myocardial ischemia before the induction of cardiopulmonary bypass (CPB). We started continuous infusions of nitroglycerin and milrinone after the initiation of CPB, which were continued through the post-CPB period. The patient was transferred to the ICU and the postop-erative course was uneventful. There are two key points in the management of BWG syndrome : the balance between systemic and pulmonary artery pressure in pre-CPB period, and left ventricular support including both inotropes and vasodilators in post-CPB period. key words : anomalous origin of the left coronary artery from the pulmonary artery, Bland-White-Garland syndrome, mitral valve regurgitation, Takeuchi procedure.

Regional anesthesia has been widely applied as an excellent method for perioperative analgesia. Recent studies suggested that regional anesthesia is a promising approach to minimize the risk of surgical site infection and postoperative cancer recurrence, subsequently providing the benefits to the long-term outcome. In particular, it is of great interest that regional anesthesia might be able to reduce cancer recurrence. In cancer patients, innate immunity against cancer could be depressed, resulting in the predisposition to evoke metastasis. Besides, during the perioperative periods, tumor immunity is significantly depressed due to surgical pain, activation of sympathetic nervous system, inflammatory responses, and others. In this review article, we discuss the tumor immunity during the perioperative period, with focus on the alterations of tumor immunity and regional anesthesia.

A 22-year-old female was scheduled to undergo posterior thoracolumbar spinal fusion. She had been diagnosed with congenital antithrombinIII (AT-III) deficiency by the onset of pulmonary embolism and deep vein thrombosis after the first operation at the age of 18. Thereafter she had taken warfarin, 5 mg daily, until 4 days before the surgery. Preoperatively, we administered AT-III products to regulate AT-III activity. The posterior spinal fusion was performed successfully without surgical complications. Postoperatively, we continued administration of AT-III products to maintain AT-III activity above 75%. We also used low dose unfractionated heparin with AT-III by continuous intravenous infusion. Heparin was administered with dose adjustment to achieve a target activated partial thromboplastin time of 45 to 60 seconds. After the activated partial thromboplastin time was stabilized in the target range, we started warfarin therapy (target international normalized ratio, 1.5 to 2.5) on postoperative day 16 and stopped administration of heparin on postoperative day 19. There was no thrombosis complications during the perioperative period. Good anticoagulant management was achieved in a patient with congenital AT-III deficiency undergoing posterior spinal fusion.

Aim: To investigate perinatal outcomes, the analgesic efficacy and maternal satisfaction in nulliparous women receiving fentanyl intravenous patient-controlled analgesia (i.v.-PCA). Material and Methods: A total of 1401 nulliparous women with a singleton pregnancy who received fentanyl i.v.-PCA (i.v.-PCA group, n = 290) or no analgesia (control group, n = 1111) in labor between 2005 and 2010 were reviewed. Fentanyl i.v.-PCA was implemented on maternal request during the first stage of labor over 35 weeks of gestation, and discontinued at full cervical dilatation. Perinatal outcomes were compared between the i.v.-PCA and the control groups. The numerical rating scale (NRS) levels during labor were also examined in the i.v.-PCA group. Additionally, parturients received fentanyl i.v.-PCA in 2010 (n = 73) were asked about overall satisfaction using a scale poor, moderate, good and excellent on postpartum day 0-3. Results: Women receiving i.v.-PCA showed significantly longer labor and more need of oxytocin augmentation, compared with the control. Cesarean section was significantly less frequent in the i.v.-PCA group compared with the control (11.0% v.s. 24.1%, respectively), with the vacuum-assisted delivery rate comparable between groups. Neonatal outcomes (i.e. Apgar score <7 at 1 min or 5 min, umbilical artery pH <7.20) were comparable between groups, irrespective of mode of delivery. Significant reduction of NRS levels was noted until 3 h after induction of i.v.-PCA, compared to the baseline. Of the women who expressed their satisfaction, 72% (48/67) exhibited 'excellent' or 'good' for pain relief by i.v.-PCA. Conclusion: Fentanyl i.v.-PCA could be a useful approach for labor pain relief in nulliparas when regional blocks are unavailable. © 2012 Japan Society of Obstetrics and Gynecology.

Following the introduction of the Ciaglia technique, PDT has become increasingly popular due to its relatively easy procedure to secure the airway. Multiple prospective studies and meta-analyses have compared PDT and ST to define the superior procedure. The results favor PDT with respect to wound infection and cosmetic sequelae. To ensure the safety of the procedure, it is indispensable to strictly observe the indications and contraindications of PDT without being preoccupied by only the handy aspect of this technique. While some authors recommend that PDT should only be performed by surgically trained individuals, others have reported that successful PDT can be performed with no association between physician specialty and complication rate as long as patient selection and bronchoscopic assistance are performed properly. Considering the present situation surrounding PDT, now may be the time to promote the collaborative multidisciplinary team approach to perform successful PDT utilizing the specialty of each participant and the benefit of this technique itself. Recent reports advocate the implementation of PDT teams consisting of otolaryngologists and either intensivists or pulmonary/critical care specialists and suggest the potential benefits of such team approaches. OurPDTteam consists of anesthesiologists and otolaryngologists, and to date the system runs smoothly. Future assessments and improvements of these approaches are warranted. © 2012 Japanese Society of Anesthesiologists.