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Naoki Aikawa

Publications and source records attributed to Naoki Aikawa.

At least 19 recordsLinked to original sources

The role of the surgeon as intensivist: an international perspective.

PURPOSE OF REVIEW: Critical care is a young specialty. It emerged less than 50 years ago in response to new technologies that could prolong the survival of patients who previously would have died. The diseases that posed this threat to life were varied and the original practitioners of critical care came from a variety of medical backgrounds, and created a multidisciplinary specialty. As it continues to evolve, however, the participation and influence of surgeons is waning. CONTENT: We have sought the perspectives of an international group of intensivists on the role of surgeons in the future of critical care. These perspectives are varied. Surgeons play the largest role in North American critical care, although even here that role is diminishing, and new models of practice are needed. Surgical involvement is even less in Japan, Europe, and South America. The important role of the surgical perspective in differentiating heroic from futile intervention is underlined by Alsanea from Saudi Arabia. CONCLUSIONS: Surgical involvement in the practice of critical care is declining around the world. The reasons are complex, and include competing clinical imperatives, economics, and the demands of training programs. New models are needed to revitalize critical care as a multidisciplinary specialty.

Argentina↗

Population pharmacokinetics of Arbekacin in patients infected with methicillin-resistant Staphylococcus aureus.

Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). The population pharmacokinetics of arbekacin was investigated in the Japanese, using 353 patients infected with MRSA and 50 healthy or renally impaired volunteers. The age of the study population ranged from 8 to 95 years, and weight ranged from 10.8 to 107 kg. In total, 1,581 serum arbekacin concentrations were measured (primarily from routine patient care) and used to perform the present pharmacokinetic analysis. Drug concentration-time data were well described by a two-compartment open model. Factors influencing arbekacin pharmacokinetics were investigated using a nonlinear mixed-effect model analysis. The best-developed model showed that drug clearance (CL) was related to creatinine clearance (CL(CR)), age, and body weight (WT), as expressed by CL (liter/h) = 0.0319CL(CR) + (26.5/age) (CL(CR) < 80 ml/min) and CL (liter/h) = 0.0130 CL(CR) + 0.0342WT + (26.5/age) (CL(CR) >/= 80 ml/min). The volume of distribution for the central and peripheral compartments was different in healthy subjects and infected patients, and this difference was more pronounced among disease types. The elderly subjects (aged 80 years or over) exhibited, on average, a 19% greater volume for the central compartment. The volumes for the peripheral compartment were 50.6 liters in patients with pneumonia and 24.3 liters in patients with sepsis. The population pharmacokinetic parameters of arbekacin obtained here are useful for optimal use of this aminoglycoside in the treatment of MRSA-infected patients.

Adolescent↗

Pharmacokinetic-pharmacodynamic relationship of arbekacin for treatment of patients infected with methicillin-resistant Staphylococcus aureus.

Arbekacin is widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have determined the optimal concentration targets of arbekacin for both efficacy and safety. A pharmacokinetic-pharmacodynamic analysis was performed to relate exposure to the drug and clinical cure/improvement or nephrotoxicity. Since we have reported the population pharmacokinetic parameters for arbekacin in the preceding paper (Y. Tanigawara, R. Sato, K. Morita, M. Kaku, N. Aikawa, and K. Shimizu, Antimicrob. Agents Chemother. 50:3754-3762, 2006), individual exposure parameters, such as area under the concentration-time curve (AUC), peak concentration (C(max)), AUC/MIC, C(max)/MIC, and trough concentration (C(min)) were estimated by the Bayesian method. Logistic regression was used to describe the relationship between exposure to the drug and the probability of clinical cure/improvement or nephrotoxicity. For the clinical efficacy analysis, 174 patients confirmed to have an MRSA infection were evaluated. The C(max), C(min), and AUC of arbekacin were associated with the probability of clinical cure/improvement during monotherapy. It was shown that the probability of cure/improvement rose when the C(max) of arbekacin was increased, with an odds ratio of 6.7 for a change in C(max) from 7.9 to 12.5 microg/ml (P = 0.037). For the nephrotoxic risk analysis, 333 patients were included, regardless of whether a pathogen was identified. Logistic regression analysis revealed C(min) and AUC as risk factors of nephrotoxicity (P < 0.005). The estimated probabilities of arbekacin-induced nephrotoxicity were 2.5, 5.2, and 13.1% when the C(min) values were 1, 2, and 5 microg/ml, respectively. The present findings are useful for optimizing the individual dose of arbekacin for the treatment of MRSA-infected patients.

Adolescent↗

Orthostatic decrease in cardiac chaos during the head-up tilt test in patients with vasovagal syncope.

BACKGROUND: Autonomic dysfunction contributes to orthostatic intolerance in vasovagal syncope (VVS), but as it has not been identified by spectral analysis of heart rate variability (HRV) in previous studies, the present hypothesis was that nonlinear analysis of HRV would identify the orthostatic intolerance in VVS. METHODS AND RESULTS: Twenty-six patients with VVS and 14 matched controls were subjected to 80-degree head-up tilt test (positive: 13 patients; negative: 13 patients and 14 controls). There were no differences in the orthostatic changes in the indices of spectral analyses of HRV among the 3 groups. The Lyapunov exponent (LE) was calculated from 200 consecutive RR-intervals to investigate chaotic behavior, and cardiac chaos was defined as the incidence of the presence of a positive finite LE. Orthostatic decreases in cardiac chaos were observed in the VVS patients (both the positive and negative groups), although there was no orthostatic decrease in the control group (ANOVA: p = 0.008). The receiver-operator characteristic curve indicated that cardiac chaos during the tilt identified VVS regardless of the results of the tilt (p < 0.001, sensitivity: 85.7%, specificity: 96.2%). CONCLUSIONS: The decrease in cardiac chaos during the tilt test was specific to patients with VVS, even if their response to the test was negative.

Adult↗

[Efficacy of micafungin sodium on fungal infection in critical care].

The clinical effects and tolerability of micafungin sodium in daily practice for the treatment of fungal infection in critically ill patients were evaluated in an open-labeled, non-comparative, observational study. All patients admitted to intensive care units (ICUs) of 3 hospitals in Chiba prefecture between June 2003 and March 2005, who were treated with micafungin because of known or suspected fungal infection, were included in the study. A total of 34 patients received micafungin and 29 cases of them were subjected to analysis. Fungal infections were classified as "proven" in 3 patients (10.3%) and "possible" in 26 (89.7%). Candida was detected in 16 patients, most of them were Candida albicans and 4 cases were non-albicans Candida. Clinical effects of micafungin were "cured" and "improved" in 20 patients (77%), "failure" in 6 (23%), and "undetermined" in 3 cases. Adverse events were reported in 10 patients, but there was no significant event. In conclusion, micafungin was effective in 77% of proven or suspected fungal infections in critically ill patients admitted to the ICU. The drug was well tolerated and discontinuation of its treatment due to adverse events was not experienced during the study period.

Antifungal Agents↗

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2003 and March 2004].

Tendency of isolated bacteria from infections in general surgery during the period from April 2004 to March 2005 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 645 strains including 17 strains of Candida spp. were isolated from 226 (79.0%) of 286 patients with surgical infections. Three hundred and seventeen strains were isolated from primary infections, and 345 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria and anaerobic Gram-negative bacteria were predominant, while aerobic Gram-positive bacteria were predominant from postoperative infections. The isolation rate of aerobic Gram-positive bacteria, such as Enterococcus spp. and Staphylococcus aureus were higher from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Citrobacter freundii in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by E. coli, E. cloacae, and K. pneumoniae. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both primary infections followed by Bilophila wadsworthia. While the isolation rate of B. fragilis group was also the highest from postoperative infections, the following bacteria were Bacteroides thetaiotaomicron and B. wadsworthia in this order. In this series, we noticed no vancomycin-resistant Gram-positive cocci, but a few strains of moderately arbekacin-resistant MRSA. Carbapenem-resistant P. aeruginosa but not multidrug-resistant was seen in 13.3 per cents. Also cefazolin-resistant E. coli probably producing extended spectrum beta-lactamase was seen in 7.0 per cents. We should be carefully followed up the facts that an increasing isolation rates of B. fragilis group and B. wadsworthia which were resistant to both penicillins and cephems.

Anti-Bacterial Agents↗

Prognostic implications of inhalation injury in burn patients in Tokyo.

Inhalation injury has recently emerged as the major cause of mortality in burn patients. However, the prognostic value of inhalation injury has not been thoroughly assessed in Japanese burn facilities. The aim of the present study was to evaluate the impact of inhalation injury on burn patients' mortality in Tokyo. Of 6416 patients admitted to 13 burn facilities of the Tokyo Burn Unit Association between 1984 and 2002; the 5560 eligible patients were included in this study (mean age, 40+/-20 years; male, 61.6%; mean partial- and full-thickness burn size, 10.7+/-13.0% and 9.6+/-20.5%). Of the 5560 patients, 1690 patients (30.4%) had experienced inhalation injury. The overall in-hospital mortality rate of the patients with inhalation injury was higher than that of those without inhalation injury (33.6% versus 8.1%, odds ratio, 5.72 [95% CI, 4.91-6.67]). The results of the multivariate analysis indicated that inhalation injury; full- and partial-thickness burn size, and age were independent predictors of outcome (relative risk, 2.58 [2.03-3.29], 1.10 [1.09-1.11], 1.06 [1.06-1.07], 1.05 [1.05-1.06], respectively). In conclusion, inhalation injury was the most important predictor of overall mortality among burned patients in Tokyo.

Adult↗

Multicenter prospective study of procalcitonin as an indicator of sepsis.

The clinical significance of serum procalcitonin (PCT) for discriminating between bacterial infectious disease and nonbacterial infectious disease (such as systemic inflammatory response syndrome (SIRS)), was compared with the significance of endotoxin, beta-D: -glucan, interleukin (IL)-6, and C-reactive protein (CRP) in a multicenter prospective study. The concentrations of PCT in patients with systemic bacterial infection and those with localized bacterial infection were significantly higher than the concentrations in patients with nonbacterial infection or noninfectious diseases. In addition, PCT, endotoxin, IL-6, and CRP concentrations were significantly higher in patients with bacterial infectious disease than in those with nonbacterial infectious disease (P<0.001, P<0.005, P<0.001, and P<0.001, respectively). The cutoff value of PCT for the discrimination of bacterial and nonbacterial infectious diseases was determined to be 0.5 ng/ml, which was associated with a sensitivity of 64.4% and specificity of 86.0%. Areas under the receiver operating characteristic curves (POCs) were 0.84 for PCT, 0.60 for endotoxin, 0.77 for IL-6, and 0.78 for CRP in the combined group of patients with bacterial infectious disease and those with nonbacterial infectious disease, and the area under the ROC for PCT was significantly higher than that for endotoxin (P<0.001). In patients diagnosed with bacteremia based on clinical findings, the positive rate of diagnosis with PCT was 70.2%, while that of blood culture was 42.6%. PCT is thus essential for discriminating bacterial infection from SIRS, and is superior in this respect to conventional serum markers and blood culture.

Biomarkers↗

Current status of diagnosis and treatment of invasive fungal infections in Japan: the influence of the new Japanese guidelines.

One year after the release of the Japanese "Guidelines for the Diagnosis and Treatment of Deep-Seated Mycosis" we conducted a survey of clinicians to determine the extent to which the new guidelines had penetrated clinical practice, and compared these results with those of a previous survey. The responses to the current survey regarding the diagnosis and treatment had changed from those of the previous survey to reflect the new recommendations, showing that the guidelines have had an effect on clinical practice. However, the current survey highlights a need to provide more practical information in the guidelines for use in the clinical settings. In particular, physicians expect the guidelines to proactively provide more information about the features of both current and new drugs. In addition, an effective drug against the genus Aspergillus is eagerly awaited. However, because it is difficult to differentiate among filamentous fungi, there is a need for a drug with broad-spectrum coverage against filamentous fungi. Investigation of combination therapy consequently becomes necessary. Definitive diagnoses of invasive fungal infection are too scarce at the national level. The cooperation of clinicians for organizing more definitive diagnoses would be appreciated when the guidelines are revised.

Antifungal Agents↗

Emergency medical services in Japan: an opportunity for the rational development of pre-hospital care and research.

Japan is at a crossroads in the development of its Emergency Medical Services (EMS). At present, Japan has an essentially pure scoop-and-run, defibrillation system. However, there is a strong movement toward expanding the scope of paramedic practice to include more complex, Advanced Life Support (ALS) and trauma protocols to its nationally standardized pre-hospital protocols. The implications of introducing complex pre-hospital protocols guided by the use of existing scientific evidence to support such action is discussed in the context of Japan's unique opportunity to test many fundamental questions in pre-hospital medical care and the public's understanding and acceptance of these practices. Japan, a technologically advanced country that is not encumbered by entrenched "standards of care," has the opportunity to develop an efficient and rational EMS system.

Ambulances↗

Flow-independent myocardial ischemia induced by endothelin-1: an NADH fluorescence analysis.

The endothelin-1 (ET-1) is known to cause myocardial ischemia; however, whether this effect is entirely dependent on vasoconstriction is uncertain. The aim of this study was to characterize the myocardial ischemia after the intracoronary administration of endothelin-1, and compare it with that induced by coronary stenosis. In the left anterior descending coronary artery of 15 dogs, a mild inflow reduction (30%) was produced for 10 minutes using intracoronary endothelin-1 (46 +/- 33 pmol/min) or coronary stenosis. The hearts were rapidly cross-sectioned at short axial plane and freeze-clamped within 120 milliseconds using a specially developed device to visualize and quantify the area of ischemia (%IA) with NADH fluorescence photography. The %IA was larger in the endothelin-1 group than in the stenosis group (66 +/- 23 versus 18 +/- 18, P = 0.0005); furthermore, the ischemia was transmural in the ET-1 group, but limited to subendocardium in the stenosis group. ET-1 increased the coronary arterial resistance especially in subepicardial region and produced smaller ischemic foci in microcirculation. The mechanism of larger ischemia produced by ET-1 might depend on pro-ischemic effects on myocytes and vasoconstriction of the coronary microcirculation, predominantly in the subepicardium in vivo.

Animals↗

Heat stroke with multiple organ failure treated with cold hemodialysis and cold continuous hemodiafiltration: a case report.

A 23-year-old comatose man was presented in the emergency room. He had been working inside a building under construction on a hot summer's day. His core body temperature was 42.1 degrees C and he was diagnosed with heat stroke. Urgent cooling procedures, including applying cold vapor to the patient's skin, a gastric lavage with cold water and an intravenous cold saline infusion, were not completely successful and his body temperature remained above 40 degrees C. Because his high temperature was refractory to conventional cooling procedures and we suspected that acute renal failure (ARF) by rhabdomyolysis would develop, we applied hemodialysis (HD) using cold dialysate (initially 30 degrees C and later 35 degrees C), followed by continuous hemodiafiltration (CHDF) with cold dialysate (35 degrees C) at a high flow rate of 18,000 mL per hour. The patient's body temperature fell below 38.0 degrees C within 3 h and was kept below 38.0 degrees C. Continuous hemodiafiltration was continued for one week. During the first week, the patient suffered from multiple organ failure (MOF) involving renal failure, as well as the failure of heart, liver, lung, and central nervous systems. Disseminated intravascular coagulation also developed. However, by virtue of cold CHDF, he almost recovered 3 weeks after the onset, except for remaining mild liver and renal dysfunction. In severe heat stroke, cold HD and high flow, cold CHDF should be a therapeutic choice for cooling and treatment of MOF. Considering mild liver and renal dysfunction still remained, this case suggested these procedures should be initiated at the very beginning of the treatment of severe heat stroke.

Adult↗

A case of severe heat stroke with abnormal cardiac findings.

We document serial changes in the electrocardiogram (ECG) and myocardial markers in a case of severe heat stroke treated with cooling procedures. A 23-year-old comatose male with heat stroke was presented in the emergency room. The condition of the patient was complicated by hepatic failure, rhabdomyolysis, acute renal failure, and cardiac abnormalities. ECG revealed diffuse ST-T elevation; serum levels of myocardial markers were remarkably high and diffuse hypokinesis was observed on the echocardiogram. Cooling procedures, including applying cold vapor to the patient's skin, a gastric lavage with cold water, and an intravenous cold fluid infusion were not successful. Since multiple organ damage (heart, liver, central nervous system, and kidney) was evident, we utilized continuous hemodialysis and hemofiltration, using cold dialysate for efficient cooling. The patient recovered from the multiple organ damage and was removed from the intensive care unit 14 days after the onset. The cardiac abnormalities had normalized within several days without any damage to the myocardium. Q waves were not detected in any lead in the ECG. When interpreting ST-T elevation in the ECG of a heat stroke patient, caution should be used so as to not misdiagnose it as an acute myocardial infarction.

Adult↗

Cost-minimisation analysis of sivelestat for acute lung injury associated with systemic inflammatory response syndrome.

OBJECTIVES: To conduct a cost-minimisation analysis of sivelestat sodium hydrate treatment for patients in the intensive care unit (ICU) with acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS) caused by infection. DESIGN: The analysis was performed based on data from a phase III randomised, multicentre, double-blind, controlled clinical study of up to 14 days treatment with sivelestat, in which the effect of intravenous sivelestat at a high dose (0.20 mg/kg/h; the sivelestat group) was compared with that at a low dose (0.004 mg/kg/h, effectively a placebo; the control group). PATIENTS: Patients with ALI associated with SIRS caused by infection, who began their treatment under mechanical ventilation management in the ICU. METHODS: A four-stage Markov model was constructed to represent the possible conditions of an ALI patient: ICU plus intubated mechanical ventilation; ICU plus weaned from a mechanical ventilator; admission to the general ward; and death. The base-case analysis used a mechanical ventilator weaning daily rate of 2.9% for the control group and 4.0% for the sivelestat group, and the same mortality (1.2%) for both groups at all stages of the Markov model. Medical costs were estimated from standard fees and Japanese National Health Insurance drug prices included fees for hospitalisation within the ICU and general wards, mechanical ventilation, examinations and drug expenditure. Costs were in 2001 values. Sensitivity analyses were performed by varying the weaning rate, mortality, time between weaning and discharge to the general ward, and drug costs. PERSPECTIVE: Payers of healthcare costs. MAIN OUTCOMES: The expected 30-day medical costs per patient in the control and sivelestat groups were Japanese yen (yen) 4,144,887 and 3,975,451 yen, respectively; a difference of 169,436 yen. Drug expenditure accounted for more than half of the medical costs for each group. The periods under mechanical ventilation management and in the ICU for the sivelestat group were shorter than those for the control group by 2 and 1.8 days, respectively. This was of significance in the reduction of the medical costs. A sensitivity analysis suggested that the expected costs for the sivelestat group exceeded those for the control group when the daily weaning rate for the sivelestat group was <3.5%, and also when mortality rates were set at 0.9% in the sivelestat group and 1.4% in the control group. CONCLUSIONS: This analysis suggests that from the Japanese healthcare payer perspective, treatment with sivelestat may reduce medical costs compared with standard care for patients with ALI associated with SIRS caused by infection.

Adolescent↗

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2003 and March 2004].

Tendency of isolated bacteria from infections in general surgery during the period from April 2003 to March 2004 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 455 strains including 14 strains of Candida spp. were isolated from 191(75.2%) of 254 patients with surgical infections. Two hundred and thirty-nine strains were isolated from primary infections, and 216 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria and aerobic Gram-negative bacteria were predominant, while aerobic Gram-positive bacteria were predominant from postoperative infections. The isolation rate of aerobic Gram-positive bacteria, such as Enterococcus spp. and Staphylococcus aureus were higher from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa in this order, and from postoperative infections, E. coli was the most predominantly isolated, followed by P. aeruginosa, E. cloacae, and K. pneumoniae. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. The isolation rate of anaerobic Gram-positive bacteria from primary infections and that of aerobic Gram-positive bacteria from postoperative infections were high in the last several years. In this series, we noticed no vancomycin-resistant Gram-positive cocci, but a few strains of moderately arbekacin-resistant MRSA. Carbapenm-resistant P. aeruginosa was seen in less than 10 per cents. Last year we noticed that there were cefazolin-resistant E. coli producing extended spectrum beta-lactamase, but there was no highly cefazolin-resistant E. coli in this year. In the next series, increase of both anaerobic bacteria and Enterococcus spp. should be carefully followed up.

Anti-Bacterial Agents↗

Plasma hepatocyte growth factor is increased in early-phase sepsis.

To elucidate the involvement of hepatocyte growth factor (HGF) in systemic inflammatory response syndrome (SIRS) and sepsis, we investigated the plasma levels of HGF, as well as those of various proinflammatory and anti-inflammatory cytokines, in 50 patients who visited our emergency department (ED). The patients were divided into four groups, depending on the existence of SIRS and infection: group 1 (G1), no infection and no SIRS; group 2 (G2), infection and no SIRS; group 3 (G3), no infection and SIRS; and group 4 (G4), infection and SIRS (e.g., sepsis). We found that plasma HGF levels in G4 were significantly higher than those in the groups without infection (G1 and G3). However, the correlations between HGF and other cytokines were comparatively low compared with those between any other pairs of cytokines, suggesting independent regulation of HGF production in vivo. High plasma HGF was significantly correlated with the presence of infection and with serum total bilirubin (TB) level on multivariate logistic regression analysis. Considering HGF's known functions, we speculated that high plasma HGF levels may indicate the occurrence or necessity for tissue protection and regeneration after acute systemic insults in sepsis.

Adult↗