Faculty Profiles - KOSAKA Junko

Papers - KOSAKA Junko

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Clinical predictors of extubation failure in postoperative critically ill patients: a post-hoc analysis of a multicenter prospective observational study. International journal

Jun Hattori, Aiko Tanaka, Junko Kosaka, Osamu Hirao, Nana Furushima, Yuichi Maki, Daijiro Kabata, Akinori Uchiyama, Moritoki Egi, Hiroshi Morimatsu, Satoshi Mizobuchi, Yoshifumi Kotake, Ayumi Shintani, Yukiko Koyama, Takeshi Yoshida, Yuji Fujino

BMC anesthesiology 25 ( 1 ) 127 - 127 2025.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Postoperative patients constitute majority of critically ill patients, although factors predicting extubation failure in this group of patients remain unidentified. Aiming to propose clinical predictors of reintubation in postoperative patients, we conducted a post-hoc analysis of a multicenter prospective observational study. METHODS: This study included postoperative critically ill patients who underwent mechanical ventilation for > 24 h and were extubated after a successful 30-min spontaneous breathing trial. The primary outcome was reintubation within 48 h after extubation, and clinical predictors for reintubation were investigated using logistic regression analyses. RESULTS: Among the 355 included patients, 10.7% required reintubation. Multivariable logistic regression identified that the number of endotracheal suctioning episodes during the 24 h before extubation and underlying respiratory disease or pneumonia occurrence were significantly associated with reintubation (adjusted odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.18, p < 0.001; adjusted OR 2.58, 95%CI 1.30-5.13, p = 0.007). The probability of reintubation was increased significantly with the higher frequency of endotracheal suctioning, as indicated by restricted cubic splines. Subgroup analysis showed that these predictors were consistently associated with reintubation regardless of the use of noninvasive respiratory support after extubation. CONCLUSIONS: Endotracheal suctioning frequency and respiratory complications were identified as independent predictors of reintubation. These readily obtainable predictors may aid in decision-making regarding the extubation of postoperative patients.

DOI： 10.1186/s12871-025-02996-1

Early Fluid Balance Is Associated with 90-Day Mortality in Patients Receiving Continuous Renal Replacement Therapy. Reviewed

Yusheng Guo, Junko Kosaka, Hiroshi Morimatsu

Acta medica Okayama 77 ( 3 ) 263 - 272 2023.6

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Continuous renal replacement therapy (CRRT) is widely used to control fluid balance, but the optimal fluid balance to improve the prognosis of patients remains debated. Appropriate fluid management may depend on hemodynamic status. We investigated the association between 90-day mortality and fluid balance/mean arterial pressure (MAP) in patients receiving CRRT. This single-center retrospective study was conducted between May 2018 and March 2021. Based on the cumulative fluid balance at 72 h after initiation of CRRT, the cases were divided into negative (< 0 mL) and positive (> 0 mL) fluid balance groups. Ninety-day mortality was higher in the positive fluid balance group (p=0.009). At 4 h before and after CRRT initiation, the mean MAP was lower in the positive fluid balance group (p<0.05). After multivariate cox adjustment, 72-h positive fluid balance was independently associated with 90-day mortality (p=0.004). In addition, the cumulative fluid balance was associated with 90-day mortality (p<0.05) in cases without shock, high APACHE II score, sepsis, dialysis dependence, or vasopressor use. A 72-h positive fluid balance was associated with 90-day mortality in patients receiving CRRT.

DOI： 10.18926/AMO/65491

Impact of Different KDIGO Criteria on Clinical Outcomes for Early Identification of Acute Kidney Injury after Non-Cardiac Surgery. Reviewed International journal

Jingwen Fu, Junko Kosaka, Hiroshi Morimatsu

Journal of clinical medicine 11 ( 19 ) 2022.9

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

The Kidney Disease Improving Global Outcomes (KDIGO) guidelines are currently used in acute kidney injury (AKI) diagnosis and include both serum creatinine (SCR) and urine output (UO) criteria. Currently, many AKI-related studies have inconsistently defined AKI, which possibly affects the comparison of their results. Therefore, we hypothesized that the different criteria in the KDIGO guidelines vary in measuring the incidence of AKI and its association with clinical outcomes. We retrospectively analyzed that data of patients admitted to the intensive care unit after non-cardiac surgery in 2019. Three different criteria used to define AKI were included: UOmean, mean UO < 0.5 mL/kg/h over time; UOcont, hourly UO < 0.5 mL/kg/h over time; or SCR, KDIGO guidelines SCR criteria. A total of 777 patients were included, and the incidence of UOmean-AKI was 33.1%, the incidence of UOcont-AKI was 7.9%, and the incidence of SCR-AKI was 2.0%. There were differences in the length of ICU stay and hospital stay between AKI and non-AKI patients under different criteria. We found differences in the incidence and clinical outcomes of AKI after non-cardiac surgery when using different KDIGO criteria.

DOI： 10.3390/jcm11195589

Prediction Model of Extubation Outcomes in Critically Ill Patients: A Multicenter Prospective Cohort Study. Reviewed International journal

Aiko Tanaka, Daijiro Kabata, Osamu Hirao, Junko Kosaka, Nana Furushima, Yuichi Maki, Akinori Uchiyama, Moritoki Egi, Ayumi Shintani, Hiroshi Morimatsu, Satoshi Mizobuchi, Yoshifumi Kotake, Yuji Fujino

Journal of clinical medicine 11 ( 9 ) 2022.4

Language：English Publishing type：Research paper (scientific journal)

Liberation from mechanical ventilation is of great importance owing to related complications from extended ventilation time. In this prospective multicenter study, we aimed to construct a versatile model for predicting extubation outcomes in critical care settings using obtainable physiological predictors. The study included patients who had been extubated after a successful 30 min spontaneous breathing trial (SBT). A multivariable logistic regression model was constructed to predict extubation outcomes (successful extubation without reintubation and uneventful extubation without reintubation or noninvasive respiratory support) using eight parameters: age, heart failure, respiratory disease, rapid shallow breathing index (RSBI), PaO2/FIO2, Glasgow Coma Scale score, fluid balance, and endotracheal suctioning episodes. Of 499 patients, 453 (90.8%) and 328 (65.7%) achieved successful and uneventful extubation, respectively. The areas under the curve for successful and uneventful extubation in the novel prediction model were 0.69 (95% confidence interval (CI), 0.62-0.77) and 0.70 (95% CI, 0.65-0.74), respectively, which were significantly higher than those in the conventional model solely using RSBI (0.58 (95% CI, 0.50-0.66) and 0.54 (95% CI, 0.49-0.60), p = 0.004 and <0.001, respectively). The model was validated using a bootstrap method, and an online application was developed for automatic calculation. Our model, which is based on a combination of generally obtainable parameters, established an accessible method for predicting extubation outcomes after a successful SBT.

DOI： 10.3390/jcm11092520

Renal, Cardiac, and Autonomic Effects of Catheter-Based Renal Denervation in Ovine Heart Failure. Reviewed International journal

Lindsea C Booth, R Anethra U de Silva, Roberto B Pontes, Song T Yao, Sally G Hood, Yugeesh R Lankadeva, Junko Kosaka, Nina Eikelis, Gavin W Lambert, Markus P Schlaich, Clive N May

Hypertension (Dallas, Tex. : 1979) 78 ( 3 ) 706 - 715 2021.9

Systemic haemodynamic, renal perfusion and renal oxygenation responses to changes in inspired oxygen fraction during total intravenous or volatile anaesthesia. Reviewed International journal

Naoya Iguchi, Junko Kosaka, Yoko Iguchi, Roger G Evans, Rinaldo Bellomo, Clive N May, Yugeesh R Lankadeva

British journal of anaesthesia 125 ( 2 ) 192 - 200 2020.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Anaesthesia-induced changes in renal perfusion are dependent on the choice of anaesthetic agent. However, the effects of varying inspired oxygen fraction (FiO2) on renal perfusion and oxygenation during TIVA (propofol + fentanyl) or volatile anaesthesia (VA; isoflurane) are unknown. METHODS: In 16 Merino ewes, we surgically implanted a renal artery flow probe and laser-Doppler and oxygen-sensing probes in the renal medulla and cortex. We compared the systemic and renal effects of graded alterations in FiO2 (0.21, 0.40, 0.60, and 1.0) during TIVA or VA and compared the changes with those in the non-anaesthetised state. RESULTS: Compared with the non-anaesthetised state, TIVA and VA decreased renal blood flow (-50% vs -75%), renal oxygen delivery (-50% vs -80%), and renal cortical (-40% vs -60%) and medullary perfusion (-50% vs -75%). At an FiO2 of 0.21, both anaesthetic regimens induced similar reductions in cortical (-58 vs -65%) and medullary (-37% vs -38%) oxygenation. At higher concentrations of FiO2, renal blood flow and renal tissue perfusion were not changed, but intrarenal oxygenation improved similarly under TIVA and VA. In particular, at an FiO2 of ≥0.40 and ≤0.60, cortical and medullary oxygen tension were similar to the non-anaesthetised state. CONCLUSIONS: Irrespective of FiO2, TIVA decreased renal and intrarenal perfusion less than VA, but at low FiO2 concentrations both led to equivalent reductions in renal cortical and medullary oxygenation. However, with FiO2 between 0.40 and 0.60 during TIVA or VA, both cortical and medullary oxygenation was maintained at normal physiological levels.

DOI： 10.1016/j.bja.2020.03.033

Carotid artery and cerebral blood flow during experimental cardiopulmonary resuscitation: A systematic review of the literature. Reviewed International journal

Luca Lucchetta, Timothy N Kwan, Junko Kosaka, Aiko Tanaka, Glenn M Eastwood, Matthew Chan, Johan Martensson, Clive N May, Rinaldo Bellomo

Resuscitation 138 46 - 52 2019.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The carotid artery blood flow (CABF) or cerebral blood flow (CBF) achieved with current techniques of cardiac compression in humans are unknown. Animal experiments may provide useful information on such flows and on possible techniques to optimize them. OBJECTIVES: To obtain an estimate of carotid and cerebral blood flows during cardiac compression with different techniques. METHODS: We performed a systematic review of all studies in the English literature that measured the CABF and/or CBF during cardiac compression in experimental models of cardiac arrest, expressed as a percentage of baseline (pre-arrest) values. We compared the effect of vasopressor use, thoracic compression technique, pre-arrest infusion and animal model on maximum blood flows using standard statistical methodologies. RESULTS: Overall, 133 studies were reviewed. Of these, 45 studies provided information only on CABF; 77 only on CBF, and 11 studies on both flows. The overall weighted mean (±SD) CABF was 35.2 ± 27.7% of baseline. Porcine studies showed lower CABF when vasopressors were used (p = 0.0002). Studies of CBF reported a weighted mean value of 66.5 ± 48.5% of baseline. Adjunctive vasopressor therapy significantly increased CBF (p = 0.007), as did fluid administration (P = 0.049). In studies reporting both CABF and CBF, the median CABF/CBF ratio was 0.67 (range 0.21-1.96). CONCLUSIONS: During experimental cardiac compression, compared to baseline, CABF appears to decrease much more than CBF. However results should be regarded with caution. They are affected by ancillary interventions and measurement methods, variability is marked and, in experiments measuring CABF and CBF simultaneously, their ratios range well outside physiologically plausible values.

DOI： 10.1016/j.resuscitation.2019.02.016

Renal perfusion, oxygenation, and sympathetic nerve activity during volatile or intravenous general anaesthesia in sheep. Reviewed International journal

Naoya Iguchi, Junko Kosaka, Lindsea C Booth, Yoko Iguchi, Roger G Evans, Rinaldo Bellomo, Clive N May, Yugeesh R Lankadeva

British journal of anaesthesia 122 ( 3 ) 342 - 349 2019.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Global and intra-renal perfusion and oxygenation may be affected by the choice of anaesthetic. We compared the effects of isoflurane with those of propofol and fentanyl on renal blood flow (RBF) and intra-renal perfusion and oxygenation, and assessed how these were associated with renal sympathetic nerve activity (RSNA). METHODS: A renal artery flow probe and laser Doppler and oxygen-sensing probes were surgically implanted in the renal medulla and cortex in 20 Merino ewes. RSNA was measured in 12 additional ewes. We compared the effects of volatile or i.v. anaesthesia on global RBF, renal oxygen delivery (RDO2), intra-renal perfusion, and RSNA with the non-anaesthetised state on postoperative day 3 as control reference. RESULTS: Compared with a non-anaesthetised state, volatile anaesthesia reduced global RBF [-76 (82-68)%], RDO2 [-76 (83-71)%], and cortical [-68 (74-54)%] and medullary [-76 (84-72)%] perfusion. I.V. anaesthesia reduced RBF [-55 (67-38)%], RDO2 [-55 (65-44)%], and cortical [-27 (45-6)%] and medullary [-35 (48-30)%] perfusion, but to a lesser extent than volatile anaesthesia. Renal PO2 was not influenced by anaesthesia, whilst RSNA was elevated during volatile, but not during i.v. anaesthesia. CONCLUSIONS: Volatile and i.v. general anaesthesia markedly reduced global RBF, RDO2, and regional kidney perfusion. These effects were greater with volatile anaesthesia, and were paralleled by an increase in RSNA. Our findings suggest a neurogenic modulatory effect of anaesthetics on renal perfusion and oxygenation.

DOI： 10.1016/j.bja.2018.11.018

Effects of Fluid Bolus Therapy on Renal Perfusion, Oxygenation, and Function in Early Experimental Septic Kidney Injury. Reviewed International journal

Yugeesh R Lankadeva, Junko Kosaka, Naoya Iguchi, Roger G Evans, Lindsea C Booth, Rinaldo Bellomo, Clive N May

Critical care medicine 47 ( 1 ) e36-e43 2019.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To examine the effects of fluid bolus therapy on systemic hemodynamics, renal blood flow, intrarenal perfusion and oxygenation, PO2, renal function, and fluid balance in experimental early septic acute kidney injury. DESIGN: Interventional study. SETTING: Research institute. SUBJECTS: Adult Merino ewes. INTERVENTIONS: Implantation of flow probes on the pulmonary and renal arteries and laser Doppler oxygen-sensing probes in the renal cortex, medulla, and within a bladder catheter in sheep. Infusion of Escherichia coli to induce septic acute kidney injury (n = 8). After 24, 25, and 26 hours of sepsis, fluid bolus therapy (500 mL of Hartmann's solution over 15 min) was administered. MEASUREMENTS AND MAIN RESULTS: In conscious sheep, infusion of Escherichia coli decreased creatinine clearance and increased plasma creatinine, renal blood flow (+46% ± 6%) and cortical perfusion (+25% ± 4%), but medullary perfusion (-48% ± 5%), medullary PO2 (-56% ± 4%), and urinary PO2 (-54% ± 3%) decreased (p < 0.01). The first fluid bolus therapy increased blood pressure (+6% ± 1%), central venous pressure (+245% ± 65%), cardiac output (+11% ± 2%), medullary PO2 (+280% ± 90%), urinary PO2 (+164% ± 80%), and creatinine clearance (+120% ± 65%) at 30 minutes. The following two boluses had no beneficial effects on creatinine clearance. The improvement in medullary oxygenation dissipated following the third fluid bolus therapy. Study animals retained 69% of the total volume and 80% of sodium infused. Throughout the study, urinary PO2 correlated significantly with medullary PO2. CONCLUSIONS: In early experimental septic acute kidney injury, fluid bolus therapy transiently improved renal function and medullary PO2, as also reflected by increased urinary PO2. These initial effects of fluid bolus therapy dissipated within 4 hours, despite two additional fluid boluses, and resulted in significant volume retention.

DOI： 10.1097/CCM.0000000000003507

Alterations in regional kidney oxygenation during expansion of extracellular fluid volume in conscious healthy sheep. Reviewed International journal

Yugeesh R Lankadeva, Roger G Evans, Junko Kosaka, Lindsea C Booth, Naoya Iguchi, Rinaldo Bellomo, Clive N May

American journal of physiology. Regulatory, integrative and comparative physiology 315 ( 6 ) R1242-R1250 2018.12

Language：English Publishing type：Research paper (scientific journal)

Expansion of extracellular fluid volume with crystalloid solutions is a common medical intervention, but its effects on renal cortical and medullary oxygenation are poorly understood. Therefore, we instrumented sheep under general anesthesia to enable continuous measurement of systemic and renal hemodynamics, global renal oxygen delivery and consumption, and intrarenal tissue perfusion and oxygen tension (Po2) in conscious animals ( n = 7). The effects of three sequential intermittent infusions of 500 ml of compound sodium lactate solution, administered at hourly intervals, were determined. Volume expansion induced transient increases in mean arterial pressure (+7 ± 2%), central venous pressure (+50 ± 19%), and cardiac output (+15 ± 3%). There were sustained increases in renal medullary tissue Po2 (+35 ± 10%) despite increases in global renal oxygen consumption (+66 ± 18%) and renal oxygen extraction (+64 ± 8%). Volume expansion did not significantly alter renal blood flow, renal oxygen delivery, or medullary perfusion. The sustained increase in medullary Po2 was paralleled by increased bladder urine Po2 (34 ± 4%). Cortical perfusion and Po2 did not change significantly. Our findings indicate that extracellular fluid volume expansion can increase renal medullary oxygenation, providing a potential mechanistic basis for its use as prophylaxis against iatrogenic acute kidney injury. They also indicate that continuous measurement of bladder urine Po2 could be used to monitor the effects of volume expansion on medullary oxygenation. However, the mechanisms mediating increased medullary oxygenation during volume expansion remain to be determined.

DOI： 10.1152/ajpregu.00247.2018

Differential effects of isotonic and hypotonic 4% albumin solution on intracranial pressure and renal perfusion and function. Reviewed International journal

Naoya Iguchi, Junko Kosaka, Joseph Bertolini, Clive N May, Yugeesh R Lankadeva, Rinaldo Bellomo

Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine 20 ( 1 ) 48 - 53 2018.3

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Albumin is used to resuscitate trauma patients but may increase intracranial pressure (ICP). Its effects on renal blood flow and function are unknown. Our aim was to examine the effects of hypertonic albumin on ICP and renal function, and if any effects are due to the hypotonicity of the solution containing albumin or to albumin itself. DESIGN, SETTING AND SUBJECTS: Cross-over, randomised controlled experimental study of six adult Merino ewes in the animal facility of a research institute. METHOD: Sheep were implanted with flow probes around the pulmonary and renal arteries and an ICP monitoring catheter in a lateral cerebral ventricle. Conscious sheep received normal saline, commercially available hypotonic 4% albumin solution (4% Albumex [278 mOsm/kg]) or a novel isotonic 4% albumin solution (288 mOsm/kg), with at least 48 hours between each intervention. RESULTS: Commercial hypotonic albumin solution increased ICP (by 8.5 mmHg [SEM, 2.1 mmHg]; P < 0.01), but neither isotonic albumin solution nor saline significantly changed ICP. The increase in ICP with hypotonic albumin solution was associated with an increase in central venous pressure (CVP) (by 5.4 mmHg [SEM, 0.6 mmHg]; P < 0.001), but no significant changes in cardiac output or stroke volume. None of the infusions changed renal blood flow, plasma creatinine level, creatinine clearance or plasma or urinary electrolyte levels. CONCLUSION: Compared with saline or isotonic albumin solution, hypotonic albumin solution increased ICP and CVP, but did not alter arterial pressure, cardiac output renal blood flow or renal function. Our findings support the view that the tonicity of the albumin solution, rather than the albumin itself, is responsible for increasing ICP.

Urinary Oxygenation as a Surrogate Measure of Medullary Oxygenation During Angiotensin II Therapy in Septic Acute Kidney Injury. Reviewed International journal

Yugeesh R Lankadeva, Junko Kosaka, Roger G Evans, Rinaldo Bellomo, Clive N May

Critical care medicine 46 ( 1 ) e41-e48 2018.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Angiotensin II is an emerging therapy for septic acute kidney injury, but it is unknown if its vasoconstrictor action induces renal hypoxia. We therefore examined the effects of angiotensin II on intrarenal PO2 in ovine sepsis. We also assessed the validity of urinary PO2 as a surrogate measure of medullary PO2. DESIGN: Interventional study. SETTING: Research Institute. SUBJECTS: Sixteen adult Merino ewes (n = 8/group). INTERVENTIONS: Sheep were instrumented with fiber-optic probes in the renal cortex, medulla, and within a bladder catheter to measure PO2. Conscious sheep were infused with Escherichia coli for 32 hours. At 24-30 hours, angiotensin II (0.5-33.0 ng/kg/min) or saline vehicle was infused. MEASUREMENTS AND MAIN RESULTS: Septic acute kidney injury was characterized by hypotension and a 60% ± 6% decrease in creatinine clearance. During sepsis, medullary PO2 decreased from 36 ± 1 to 30 ± 3 mm Hg after 1 hour and to 20 ± 2 mm Hg after 24 hours; at these times, urinary PO2 was 42 ± 2, 34 ± 2, and 23 ± 2 mm Hg. Increases in urinary neutrophil gelatinase-associated lipocalin (12% ± 3%) and serum creatinine (60% ± 23%) were only detected at 8 and 24 hours, respectively. IV infusion of angiotensin II, at 24 hours of sepsis, restored arterial pressure and improved creatinine clearance, while not exacerbating medullary or urinary hypoxia. CONCLUSIONS: In septic acute kidney injury, renal medullary and urinary hypoxia developed several hours before increases in currently used biomarkers. Angiotensin II transiently improved renal function without worsening medullary hypoxia. In septic acute kidney injury, angiotensin II appears to be a safe, effective therapy, and urinary PO2 may be used to detect medullary hypoxia.

DOI： 10.1097/CCM.0000000000002797

An Ovine Model for Studying the Pathophysiology of Septic Acute Kidney Injury. International journal

Yugeesh R Lankadeva, Junko Kosaka, Roger G Evans, Clive N May

Methods in molecular biology (Clifton, N.J.) 1717 207 - 218 2018

Language：English Publishing type：Research paper (scientific journal)

The development of acute kidney injury (AKI) is both a significant and independent prognostic factor of mortality in patients with sepsis, but its pathophysiology remains unclear. Herein, we describe an ovine model of sepsis evoked by the administration of live Escherichia coli in which there is hypotension, peripheral vasodilatation with a large increase in cardiac output; a similar hyperdynamic state to that commonly reported in humans. Interestingly, in this sheep model of sepsis, despite an increase in global kidney blood flow, there is a progressive reduction in renal function. Although renal hyperperfusion develops, renal tissue hypoxia due to redistribution of intrarenal blood flow may contribute to the pathogenesis of septic AKI. We have, therefore, developed a novel methodology to chronically implant combination probes to monitor intrarenal tissue perfusion and oxygen tension during the development of septic AKI in conscious sheep with hyperdynamic sepsis.

DOI： 10.1007/978-1-4939-7526-6_16

Direct cerebral perfusion and cooling in experimental cardiac arrest. Reviewed International journal

Rinaldo Bellomo, Bruno Marino, Peter Angelopoulos, Scott Carson, Glenn Eastwood, Junko Kosaka, Naoya Iguchi, Andrew Hilton, Clive May

Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine 18 ( 4 ) 255 - 260 2016.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cerebral protection is a key priority during cardiac arrest (CA). However, current approaches are suboptimal. OBJECTIVE: To test whether direct perfusion and cooling of the anterior cerebral circulation by means of cerebral vessel cannulation and extracorporeal membrane oxygenation (ECMO) increases cerebral oxygenation and induces cerebral hypothermia during CA. METHODS: We performed proof-of-concept animal experiments in sheep. We cannulated the carotid artery (for antegrade perfusion) or the jugular vein (for retrograde perfusion) for direct perfusion and cooling, and the jugular vein on the opposite side for drainage. We connected these cannulae to an ECMO circuit. We induced CA and, after 10 minutes, and during open-chest cardiac massage, we provided ECMO-based perfusion and cooling. We measured cerebral tissue oxygen saturation (SctO2) by near infrared spectroscopy (NIRS) and cerebral temperature by means of invasively inserted tissue temperature probes. RESULTS: In the antegrade perfusion experiments (n = 2), CA markedly decreased the SctO2 to below 40% over 10 minutes, despite open-chest cardiac massage. ECMO-based cerebral perfusion and cooling increased SctO2 levels to 60% and lowered cerebral temperature to 25°C within about 3 minutes. With retrograde perfusion (n = 2), ECMObased cerebral perfusion and cooling was less effective; ECMO increased SctO2 levels slowly and to a much lesser extent and similarly decreased cerebral temperature slowly and to a lesser extent. CONCLUSIONS: During experimental CA, cerebral perfusion and cooling are possible by means of an ECMO circuit connected to the anterior cerebral circulation. Antegrade perfusion appears to be superior. Further investigations of the antegrade perfusion technique appear justified.

Histopathology of Septic Acute Kidney Injury: A Systematic Review of Experimental Data. Reviewed International journal

Junko Kosaka, Yugeesh R Lankadeva, Clive N May, Rinaldo Bellomo

Critical care medicine 44 ( 9 ) e897-903 2016.9

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The histopathologic changes associated with septic acute kidney injury are poorly understood, in part, because of the lack of biopsy data in humans. Animal models of septic acute kidney injury may help define such changes. Therefore, we performed a systematic review of the histopathologic changes found in modern experimental septic acute kidney injury models. DATA SOURCES: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and PubMed (from January 2007 to February 2015). STUDY SELECTION: We reviewed experimental studies reporting findings on the histopathology of contemporary experimental septic acute kidney injury. DATA EXTRACTION: We focused on the presence or the absence of acute tubular necrosis, tubular cell apoptosis, and other nonspecific findings. DATA SYNTHESIS: We identified 102 studies in 1,059 animals. Among the 1,059 animals, 53 (5.0%) did not have any renal histopathologic changes, but acute tubular necrosis was found in 184 (17.4%). The prevalence of acute tubular necrosis was not related to animal size or model of sepsis and was only found in models with low cardiac output and decreased renal blood flow (p < 0.0001). Only 21 studies (170 animals) assessed the prevalence of tubular cell apoptosis, which was reported in 158 animals (92.9%). The prevalence of tubular cell apoptosis was significantly higher in studies using small animals (p < 0.0001) and in peritonitis models (p < 0.0001). Simultaneous acute tubular necrosis and tubular cell apoptosis was rare (55 animals [32.4%]) and only seen with decreased cardiac output and renal blood flow. Nonspecific changes (vacuolization of tubular cells, loss of brush border, and tubular cell swelling) were each observed in 423 (39.9%), 250 (23.6%) and 243 (22.9%) animals, respectively. CONCLUSIONS: In models of experimental septic acute kidney injury in contemporary articles, acute tubular necrosis was relatively uncommon and, when present, reflected the presence of an associated low cardiac output or low renal blood flow syndrome. Tubular cell apoptosis seemed frequent in the few studies in which it was investigated. Nonspecific morphologic changes, however, were the most common histopathologic findings.

DOI： 10.1097/CCM.0000000000001735

Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury. Reviewed International journal

Yugeesh R Lankadeva, Junko Kosaka, Roger G Evans, Simon R Bailey, Rinaldo Bellomo, Clive N May

Kidney international 90 ( 1 ) 100 - 8 2016.7

Language：English Publishing type：Research paper (scientific journal)

Norepinephrine is the principal vasopressor used to restore blood pressure in sepsis, but its effects on intrarenal oxygenation are unknown. To clarify this, we examined renal cortical, medullary, and urinary oxygenation in ovine septic acute kidney injury and the response to resuscitation with norepinephrine. A renal artery flow probe and fiberoptic probes were placed in the cortex and medulla of sheep to measure tissue perfusion and oxygenation. A probe in the bladder catheter measured urinary oxygenation. Sepsis was induced in conscious sheep by infusion of Escherichia coli for 32 hours. At 24 to 30 hours of sepsis, either norepinephrine, to restore mean arterial pressure to preseptic levels or vehicle-saline was infused (8 sheep per group). Septic acute kidney injury was characterized by a reduction in blood pressure of ∼12 mm Hg, renal hyperperfusion, and oliguria. Sepsis reduced medullary perfusion (from an average of 1289 to 628 blood perfusion units), medullary oxygenation (from 32 to 16 mm Hg), and urinary oxygenation (from 36 to 24 mm Hg). Restoring blood pressure with norepinephrine further reduced medullary perfusion to an average of 331 blood perfusion units, medullary oxygenation to 8 mm Hg and urinary oxygenation to 18 mm Hg. Cortical perfusion and oxygenation were preserved. Thus, renal medullary hypoxia caused by intrarenal blood flow redistribution may contribute to the development of septic acute kidney injury, and resuscitation of blood pressure with norepinephrine exacerbates medullary hypoxia. The parallel changes in medullary and urinary oxygenation suggest that urinary oxygenation may be a useful real-time biomarker for risk of acute kidney injury.

DOI： 10.1016/j.kint.2016.02.017

Clonidine Restores Pressor Responsiveness to Phenylephrine and Angiotensin II in Ovine Sepsis. Reviewed International journal

Yugeesh R Lankadeva, Lindsea C Booth, Junko Kosaka, Roger G Evans, Luc Quintin, Rinaldo Bellomo, Clive N May

Critical care medicine 43 ( 7 ) e221-9 2015.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: In sepsis, prolonged, sympathetic overstimulation may lead to vasopressor-refractory hypotension. We therefore examined the effects of the α2-adrenergic agonist clonidine on mean arterial pressure, renal sympathetic nerve activity, and pressor responsiveness to phenylephrine and angiotensin II during hypotensive sepsis in conscious sheep. DESIGN: Interventional study. SETTING: Research institute. SUBJECTS: Twelve adult Merino ewes (n = 6 per group). INTERVENTIONS: Sepsis was induced by IV infusion of Escherichia coli for 32 hours. Pressor responses to increasing doses of phenylephrine and angiotensin II were measured at baseline and at 24, 28, and 32 hours of sepsis. Sheep were treated with clonidine (1 μg/kg/hr) or saline-vehicle from 24 to 32 hours of sepsis. MEASUREMENTS AND MAIN RESULTS: Sepsis was characterized by hypotension (~12 mm Hg), increased heart rate (~80 beats/min), increased renal sympathetic nerve activity (~70%), and blunted pressor responses to phenylephrine and angiotensin II. In vehicle-treated sheep, mean arterial pressure progressively declined from 25 to 32 hours of sepsis (73 ± 3 to 66 ± 3 mm Hg; p = 0.013) while the elevations in heart rate and renal sympathetic nerve activity and reduced pressor responsiveness to vasopressors persisted. Clonidine treatment prevented the further decline in mean arterial pressure, substantially reduced heart rate and renal sympathetic nerve activity and restored pressor responsiveness to both phenylephrine and angiotensin II toward preseptic levels. CONCLUSIONS: Administration of clonidine during hypotensive sepsis reduced renal sympathetic nerve activity, restored vascular sensitivity to both phenylephrine and angiotensin II, and resulted in better preservation of arterial pressure. Considering these findings, a clinical trial for the use of clonidine in the treatment of persistent vasopressor-refractory hypotension in patients with septic shock would be worthwhile.

DOI： 10.1097/CCM.0000000000000963

Effects of biliverdin administration on acute lung injury induced by hemorrhagic shock and resuscitation in rats. Reviewed International journal

Junko Kosaka, Hiroshi Morimatsu, Toru Takahashi, Hiroko Shimizu, Susumu Kawanishi, Emiko Omori, Yasumasa Endo, Naofumi Tamaki, Manabu Morita, Kiyoshi Morita

PloS one 8 ( 5 ) e63606 2013

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-α and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the control animals. We also confirmed that biliverdin administration after hemorrhagic shock and resuscitation had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

DOI： 10.1371/journal.pone.0063606

[Successful anesthetic management of a patient with thyroid storm using landiolol]. Reviewed

Tomihiro Fukushima, Hiroaki Tokioka, Fumiko Ishii, Takeshi Mikane, Satoru Oku, Hiromi Fujii, Daisuke Katayama, Susumu Kawanishi, Junko Kosaka, Yuri Nagano

Masui. The Japanese journal of anesthesiology 56 ( 2 ) 193 - 5 2007.2

Language：Japanese Publishing type：Research paper (scientific journal)

We report successful anesthetic management of a 38-year-old man with thyroid storm using an ultra-short acting beta blocker, landiolol. The patient was admitted to the hospital for severe abdominal pain. An emergency laparotomy was scheduled for perforated gastric ulcer under a condition of uncontrolled thyrotoxicosis. On arriving the operating room, he showed tachycardia of 140 beats x min(-1) and blood pressure of 140/75 mmHg and high fever of 39 degrees C with tremor, sweating and diarrhea. He was anesthetized with oxygen, nitrous oxide, sevoflurane and fentanyl. Heart rate was around 130 beats x min(-1), and the landiolol was given continuously at a rate of 0.02-0.04 microg x kg(-1) x min(-1). Heart rate was controlled bellow 120 beats x min(-1) without hypotension during anesthesia. Thiamazole and inorganic iodine were given through an enterostomy tube postoperatively, and heart rate decreased gradually. He was extubated on the third postoperative day without any sequelae.

[Perioperative management of abdominal operation in three patients with pulmonary emphysema associated with pulmonary hypertension]. Reviewed

Ken Takata, Junko Kamitani, Daisuke Katayama, Hiromi Fujii, Satoru Oku, Hiroaki Tokioka

Masui. The Japanese journal of anesthesiology 55 ( 9 ) 1158 - 60 2006.9

Language：Japanese Publishing type：Research paper (scientific journal)

Anesthesia for abdominal operation in patients with emphysema is accompanied with a high risk of respiratory insufficiency requiring postoperative artificial ventilation. Furthermore, in patients whose pulmonary emphysema progresses and leads to pulmonary hypertension, there is the risk of developing right heart failure with postoperative respiratory insufficiency. Because perioperative circulatory drifting is massive in abdominal operation, they develop right heart failure easily during the postoperative refilling phase. Therefore, it is important to avoid right heart failure during the postoperative period in these patients. We estimate pulmonary artery pressure using echocardiography at bedside and give dopamine for diuresis during the postoperative period. We succeeded in perioperative management of abdominal operation in three patients with pulmonary emphysema associated with pulmonary hypertension.

[A case of general anesthesia combined with epidural anesthesia in a pregnant woman undergoing laparoscopic cholecystectomy]. Reviewed

Junko Kamitani, Yoko Monobe, Hiromi Fujii, Satoru Oku, Takeshi Mikane, Tomihiro Fukushima, Yutaka Shimoda, Fumiko Ishii, Hiroaki Tokioka

Masui. The Japanese journal of anesthesiology 55 ( 4 ) 457 - 9 2006.4

Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal)

We report a case of general anesthesia for laparoscopic cholecystectomy at 12 weeks of gestation. A 20-year-old woman weighing 123 kg was admitted with epigastralgia. She was diagnosed as pregnancy of 6 weeks of gestation and acute cholecystitis. Percutaneous trans-gallbladder drainage was performed to delay operation until 12 weeks of gestation. Laparoscopic cholecystectomy was performed uneventfully under general anesthesia combined with epidural anesthesia. There were no clinical signs of fetal distress during the perioperative period.

[General anesthesia outside the operating room in patients with Pierre-Robin syndrome]. Reviewed

Junko Kamitani, Yuichiro Toda, Hideki Nakatsuka, Kenji Sato, Hiroshi Morimatsu, Naoyuki Taga, Mamoru Takeuchi, Kiyoshi Morita

Masui. The Japanese journal of anesthesiology 54 ( 6 ) 687 - 9 2005.6

Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal)

Anesthesiologists are increasingly asked to involve in administering general anesthesia outside the operating room for such procedures as computed tomography, magnetic resonance imaging or angiography. Especially, pediatric patients require some kind of sedation or general anesthesia during these procedures. We report general anesthesia outside the operating room in patients with Pierre-Robin syndrome, who are expected to have possible difficult airway. A one-year-old girl and a 16-year-old boy were anesthetized for cardiac catheterization. General anesthesia was given at the angiography room which was located outside the operating room. Anesthesia was induced with oxygen, nitrous oxide and sevoflurane while portable storage unit for difficult airway was prepared including various types and size of laryngoscopes, laryngeal mask airway, fiberoptic intubation equipment and surgical airway access. Fortunately, tracheas were successfully intubated without using special devices, although cautious care during induction was taken. According to development of medical and surgical procedures, it is readily presumed that anesthesiologists will be more often involved in the sedation or anesthesia conducted outside the operating room in future. Anesthesiologists should always ensure enough staffing, proper monitoring and equipment when sedation or anesthesia is conducted outside the operating room, particularly if patients have anesthetic risks.

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