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ABSTRACT: PURPOSE: Detailed procedures for optimal therapeutic hypothermia (TH) have yet to be established. We examined how duration of well-controlled core temperature within the first 24 hours after cardiac arrests (CA) correlated with neurological outcomes of successfully resuscitated out-of-hospital CA (OHCA) patients. METHODS: OHCA patients who survived over 24 hours and treated with TH were included. Core temperature was measured every hour. Physicians intended to maintain temperature at 33°C ± 1°C for 24 hours. Cerebral performance categories (CPC) of patients at 6 months were recorded and patients were retrospectively divided into favorable (CPC1,2) and poor (CPC3-5) neurological outcome groups. Total time while the core temperature reached to 33°C ± 1°C within the first 24 hours after CA was measured and this duration was defined that of well-controlled temperature. receiver-operating characteristic analysis was performed on duration of well-controlled temperature to select the optimal cutoff value. Neurological outcome predictors were investigated by logistic regression analysis. RESULTS: Fifty-six patients were included. Optimal cutoff value of duration of well-controlled temperature was 18 hours. Ratio of male sex, witnessed by emergency medical service (EMS) personnel, first electrocardiogram as shockable, and duration of well-controlled core temperature ≥18 h of favorable neurological outcome group (n = 21) were significantly larger than that of poor neurological outcome group (n = 35). Logistic regression analysis identified "witnessed by EMS", "performed bystander CPR," and "the duration ≥18 h" as independent predictors of favorable neurological outcome. CONCLUSION: TH maintained at target temperature of 33°C ± 1°C over 18 hours independently correlated with favorable neurological outcome. Therefore, stable core temperature control may improve neurological outcome of successfully resuscitated OHCA.
The American journal of emergency medicine 07/2012; · 1.54 Impact Factor
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ABSTRACT: Various approaches such as ventilator management involving lung-protective ventilation, corticosteroids, prone positioning, and nitric oxide have failed to maintain sufficient lung oxygenation or appropriate ventilation competence in very severe acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) has been aggressively introduced for such patients, although in only a few institutions. The clinical usefulness of ECMO in a large-scale multicenter study (CESAR trial, 2009) and continued development/improvement of ECMO devices have facilitated performance of ECMO, with further increase in the number of institutions adopting ECMO therapy. Clinical usefulness of ECMO was documented in many cases of severe ARDS secondary to influenza A (H1N1) 2009 infection. ECMO requires establishment of an appropriate management system to minimize fatal complications (e.g., hemorrhage), which requires a multidisciplinary team. This, in combination with a new technique, interventional lung assist, will further extend the indications for ECMO. ECMO can be expected to gain importance as a respiratory support technique.
General Thoracic and Cardiovascular Surgery 04/2012; 60(4):192-201.
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Yosuke Matsumura,
Shigeto Oda,
Tomohito Sadahiro,
Masataka Nakamura,
Yo Hirayama,
Eizo Watanabe,
Ryuzo Abe,
Taka-Aki Nakada,
Yoshihisa Tateishi,
Taku Oshima, Koichiro Shinozaki,
Hiroyuki Hirasawa
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ABSTRACT: Cytokines play pivotal roles in the pathophysiology of severe sepsis/septic shock, and continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) removes cytokines efficiently and continuously, mainly through adsorption to a hemofilter membrane. The aim of this study was to investigate the clinical efficacy of enhanced intensity PMMA-CHDF in treating refractory septic shock.
Seventy-two septic shock patients admitted to the intensive care unit (ICU) underwent critical care including PMMA-CHDF. We employed enhanced intensity PMMA-CHDF to improve the cytokine removal rate by increasing the hemofilter membrane area in 10 refractory septic shock patients (enhanced intensity group, EI group; 2 extracorporeal CHDF circuits using the hemofilter with a larger membrane area of 2.1 m2). Other patients undergoing conventional PMMA-CHDF and matched for severity with the EI group, comprised a matched conventional group (MC group; using a PMMA membrane hemofilter with a membrane area of 1.0 m2; n=15). The case-control comparison was performed between the 2 groups.
Enhanced intensity PMMA-CHDF significantly increased mean arterial pressure by 23.8% in 1 hour (p=0.037), decreased the blood lactate level by 28.6% in 12 hours (p=0.006), and reduced blood IL-6 level in 24 hours (p=0.005). The ICU survival rate in the EI group was significantly better than that in the MC group (60% vs. 13.3%, p=0.028).
Enhanced intensity PMMA-CHDF may improve hemodynamics and survival rate in patients with refractory septic shock.
The International journal of artificial organs 01/2012; 35(1):3-14. · 1.86 Impact Factor
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ABSTRACT: In general, a prediction of neurologic outcome with respect to the resuscitated cardiac arrest patients has been performed by the auditory brainstem response and somatic evoked potential. The auditory brainstem response and somatic evoked potential are known as the predictors that correspond to neurologically poor outcome. None of the methods have been established to access neurologically good outcome. Because the hippocampal CA3 pyramidal cells have been widely used for pathophysiologic analyses concerning the hypoxic-ischemic encephalopathy and also the source of P50 components of the auditory evoked potential has been considered to be the hippocampal CA3 pyramidal cells, the authors assume that it might be possible that neurologic outcome in resuscitated cardiac arrest patients would be predicted by evaluating the P50 components. The purpose was to examine the P50 as a predictor of neurologic outcome in resuscitated cardiac arrest patients at the early stage from the onset. The P50 components of the auditory evoked potential are recorded in a conditioning-testing paradigm, that is, EEG responses to a pair of auditory stimuli with 500-millisecond interclick interval. In this study, subjects are 10 out-of-hospital cardiac arrest patients, 8 men and 2 women with a mean age of 54.8 years, who were admitted to the intensive care unit after the return of spontaneous circulation, with the presence of both the auditory brainstem response wave V and the somatic evoked potential wave N20 between the period from June 2008 to July 2009. It was found that the presence of the P50 at the early stage from the onset (days 5 ± 1.20) indicates good neurologic outcome, while the absence of the P50 implies poor prognosis. As to the auditory sensory gating of the P50, almost no reduction response to the second stimulus was observed. As a consequence, the evaluation of the P50 in resuscitated cardiac arrest patients would have a possibility to predict neurologically good outcome.
Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 06/2011; 28(3):302-7. · 1.47 Impact Factor
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Koichiro Shinozaki,
Shigeto Oda,
Tomohito Sadahiro,
Masataka Nakamura,
Yo Hirayama,
Eizo Watanabe,
Yoshihisa Tateishi,
Kazuya Nakanishi,
Nobuya Kitamura,
Yasunori Sato,
Hiroyuki Hirasawa
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ABSTRACT: No reliable predictor for the prognosis of out-of-hospital cardiac arrest (OHCA) on arrival at hospital has been identified so far. We speculate that ammonia and lactate may predict patient outcome.
This is a prospective observational study. Non-traumatic OHCA patients who gained sustained return of spontaneous circulation and were admitted to acute care unit were included. Blood ammonia and lactate levels were measured on arrival at hospital. The patients were classified into two groups: 'favourable outcome' group (Cerebral Performance Category CPC1-2 at 6-months' follow-up) and 'poor outcome' group (CPC3-5). Basal characteristics obtained from the Utstein template and biomarker levels were compared between these two outcome groups. Independent predictors were selected from all candidates using logistic regression analysis.
A total of 98 patients were included. Ammonia and lactate levels in the favourable outcome group (n=10) were significantly lower than those in poor outcome group (n=88) (p<0.05, respectively). On receiver operating characteristic analysis, the optimal cut-off value for predicting favourable outcome was determined as 170 μg dl(-1) of ammonia and 12.0 mmol l(-1) of lactate (area under the curve; 0.714 and 0.735, respectively). Logistic regression analysis identified ammonia (≤170 μg dl(-1)), therapeutic hypothermia and witnessed by emergency medical service personnel as independent predictors of favourable outcome. When both these biomarker levels were over threshold, positive predictive value (PPV) for poor outcome was calculated as 100%.
Blood ammonia and lactate levels on arrival are independent prognostic factors for OHCA. PPV with the combination of these biomarkers predicting poor outcome is high enough to be useful in clinical settings.
Resuscitation 01/2011; 82(4):404-9. · 3.60 Impact Factor
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ABSTRACT: Bacteremia is recognized as a critical condition that influences the outcome of sepsis. Although large-scale surveillance studies of bacterial species causing bacteremia have been published, the pathophysiological differences in bacteremias with different causative bacterial species remain unclear. The objective of the present study is to investigate the differences in pathophysiology and the clinical course of bacteremia caused by different bacterial species.
We reviewed the medical records of all consecutive patients admitted to the general intensive care unit (ICU) of a university teaching hospital during the eight-year period since introduction of a rapid assay for interleukin (IL)-6 blood level to routine ICU practice in May 2000. White blood cell count, C-reactive protein (CRP), IL-6 blood level, and clinical course were compared among different pathogenic bacterial species.
The 259 eligible patients, as well as 515 eligible culture-positive blood samples collected from them, were included in this study. CRP, IL-6 blood level, and mortality were significantly higher in the septic shock group (n = 57) than in the sepsis group (n = 127) (P < 0.001). The 515 eligible culture-positive blood samples harbored a total of 593 isolates of microorganisms (Gram-positive, 407; Gram-negative, 176; fungi, 10). The incidence of Gram-negative bacteremia was significantly higher in the septic shock group than in the sepsis group (P < 0.001) and in the severe sepsis group (n = 75, P < 0.01). CRP and IL-6 blood level were significantly higher in Gram-negative bacteremia (n = 176) than in Gram-positive bacteremia (n = 407) (P < 0.001, <0.0005, respectively).
The incidence of Gram-negative bacteremia was significantly higher in bacteremic ICU patients with septic shock than in those with sepsis or severe sepsis. Furthermore, CRP and IL-6 levels were significantly higher in Gram-negative bacteremia than in Gram-positive bacteremia. These findings suggest that differences in host responses and virulence mechanisms of different pathogenic microorganisms should be considered in treatment of bacteremic patients, and that new countermeasures beyond conventional antimicrobial medications are urgently needed.
Critical care (London, England) 03/2010; 14(2):R27. · 4.61 Impact Factor
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ABSTRACT: It has been reported that hypercytokinemia plays a pivotal role in the pathophysiology of severe acute pancreatitis (SAP). In our previous reports, continuous hemodiafiltration (CHDF) using a polymethyl methacrylate (PMMA) membrane hemofilter (PMMA-CHDF) was found to be capable of efficiently removing various cytokines from circulating blood. The present study was undertaken to evaluate the efficacy of PMMA-CHDF aimed at cytokine removal in the treatment of SAP. Patients with blood IL-6 level > or =400 pg/ml were considered indicated for initiation of PMMA-CHDF based on our previous data. Among the patients enrolled in the present study, there were significant differences in APACHE II sore, JMHLW (Japanese Ministry of Health, Labour, and Welfare) severity score, Ranson score, blood lactate level on ICU admission, and length of ICU stay between patients with blood IL-6 levels > or =400 pg/ml and patients with levels < 400 pg/ml. Using this PMMA-CHDF initiation criterion, PMMA-CHDF was performed on 82 SAP patients. Mean blood IL-6 level, which was 998 pg/ml on admission to the ICU, was significantly lower (335 pg/ml) after 3 days treatment of PMMA-CHDF (p < 0.01). In addition, heart rate, blood lactate level, and intra-abdominal pressure also decreased significantly (p < 0.01). At the time of weaning from PMMA-CHDF, blood IL-6 level had decreased to 99 pg/ml. The mortality rate among patients who received PMMA-CHDF was 6.1%, and significantly lower than that of patients before the introduction of PMMA-CHDF under non-renal indication (25.0%). These findings suggest that PMMA-CHDF is effective for treatment of SAP and that it can be expected to contribute to improving the outcome of SAP patients.
Contributions to nephrology 01/2010; 166:54-63. · 1.49 Impact Factor
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ABSTRACT: Fulminant hepatic failure (FHF) can be described as a potentially fatal condition presenting with hepatic encephalopathy (HE) and coagulopathy associated with acute hepatic dysfunction, regardless of its etiology. Blood purification (BP) is expected to be effective against HE and coagulopathy in FHF. In this paper, we outline the objectives and methods of BP in the treatments of cases with FHF and indicate a concrete method for and outcomes of BP at our facility. In high-flow dialysate continuous hemodiafiltration (HFCHDF), the conventional CHDF bedside console is connected to a personal dialysis console to induce a high flow rate of dialysate. With this method, the dialysate flow rate is about 500 ml/min at maximum, equivalent to about 50 times the dialysate flow rate during ordinary CHDF. The role of plasma exchange (PE) is considered a means of replacing useful substances, such as clotting factors in fresh frozen plasma rather than a means of removing pathogenic substances. As needed, slow PE (SPE) can be incorporated by connection in series. Analysis of data from 90 patients with FHF who underwent BP at our facility after 1990 revealed that restoration of consciousness was achieved in 33 (70.2%) of 47 cases when treated with HFCHDF. This survival in the HFCHDF group was significantly higher than that in the CHDF group. Analysis of data from cases in which ammonia could be measured continuously revealed that blood ammonia level decreased over time following HFCHDF. We also revealed that HFCHDF was useful for preventing the side effects of PE, such as hypernatremia, metabolic alkalosis, and sharp decrease in colloid osmotic pressure. It is concluded that HFCHDF is useful in the treatment of HE and for preventing the side effects of PE. Therefore, we suggested that HFCHDF + SPE should be standardized for the treatment of FHF.
Contributions to nephrology 01/2010; 166:64-72. · 1.49 Impact Factor
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ABSTRACT: Neurological prognostic factors after cardiopulmonary resuscitation (CPR) in patients with cardiac arrest (CA) as early and accurately as possible are urgently needed to determine therapeutic strategies after successful CPR. In particular, serum levels of protein neuron-specific enolase (NSE) and S-100B are considered promising candidates for neurological predictors, and many investigations on the clinical usefulness of these markers have been published. However, the design adopted varied from study to study, making a systematic literature review extremely difficult. The present review focuses on the following three respects for the study design: definitions of outcome, value of specificity and time points of blood sampling.
A Medline search of literature published before August 2008 was performed using the following search terms: "NSE vs CA or CPR", "S100 vs CA or CPR". Publications examining the clinical usefulness of NSE or S-100B as a prognostic predictor in two outcome groups were reviewed. All publications met with inclusion criteria were classified into three groups with respect to the definitions of outcome; "dead or alive", "regained consciousness or remained comatose", and "return to independent daily life or not". The significance of differences between two outcome groups, cutoff values and predictive accuracy on each time points of blood sampling were investigated.
A total of 54 papers were retrieved by the initial text search, and 24 were finally selected. In the three classified groups, most of the studies showed the significance of differences and concluded these biomarkers were useful for neurological predictor. However, in view of blood sampling points, the significance was not always detected. Nevertheless, only five studies involved uniform application of a blood sampling schedule with sampling intervals specified based on a set starting point. Specificity was not always set to 100%, therefore it is difficult to indiscriminately assess the cut-off values and its predictive accuracy of these biomarkers in this meta analysis.
In such circumstances, the findings of the present study should aid future investigators in examining the clinical usefulness of these markers and determination of cut-off values.
Critical care (London, England) 08/2009; 13(4):R121. · 4.61 Impact Factor
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ABSTRACT: Most patients with cardiac arrest (CA) admitted to hospitals after successful cardiopulmonary resuscitation (CPR) are discharged with various degree of neurological deficits. To determine predictor of neurological outcome early and accurately, and to determine cutoff values, serum levels of protein S-100B and neuron-specific enolase (NSE) within 24h after CA were assessed.
A multicenter prospective observational study was conducted between May 2007 and April 2008 at three medical institutions in Japan on 107 consecutive non-traumatic CA patients with return of spontaneous circulation after CPR. Based on "best-ever achieved" Glasgow-Pittsburgh cerebral performance categories (CPC) score within 6 months after CA, patients were classified into a "poor neurological outcome" group (CPC3 to CPC5) (n=67) and "favorable neurological outcome" group (CPC1 and CPC2) (n=13). Blood was sampled on admission, at 6 and 24h after CA. Serum S-100B and NSE in "poor outcome" group were higher than those in "favorable outcome" group (P<0.01). On ROC analysis, area under the curve of S-100B was 0.85, 0.94 and 1.0, respectively. These were greater than those of NSE at all sampling points. The "100%-specific" cutoff values of S-100B predictive of poor neurological outcome were 1.41, 0.21, and 0.05ng/mL, respectively. These values corresponded to sensitivities of 20.9%, 62.8%, and 100%, respectively, each of which was higher than those of NSE.
S-100B is more reliable as an early predictor of poor neurological outcome within 24h after CA than NSE and can be applied clinically.
Resuscitation 06/2009; 80(8):870-5. · 3.60 Impact Factor
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Noriyuki Hattori,
Shigeto Oda,
Tomohito Sadahiro,
Masataka Nakamura,
Ryuzo Abe, Koichiro Shinozaki,
Fumio Nomura,
Takeshi Tomonaga,
Kazuyuki Matsushita,
Yoshio Kodera,
Kazuyuki Sogawa,
Mamoru Satoh,
Hiroyuki Hirasawa
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ABSTRACT: To investigate changes in protein expression by proteomic analysis in the sera of patients with sepsis and to identify new biomarkers of sepsis. A total of 45 consecutive patients with severe sepsis or septic shock (sepsis group), 22 healthy volunteers, and 23 patients undergoing off-pump coronary artery bypass grafting (control group). Serum samples from eight patients of each group underwent proteomic analysis involving removal of 12 major proteins and subsequent reversed-phase high-performance liquid chromatography fractionation and one-dimensional electrophoresis. The intensity of 41 bands (with 12 proteins identified) increased and that of 42 bands (with 22 proteins identified) decreased in the sepsis group. Results of proteomic analysis successfully validated by Western blotting and/or enzyme-linked immunosorbent assay for three proteins (YKL-40, lipocalin 2, and S100A9) increased in the sepsis group as well as two proteins (retinol-binding protein, vitamin D-binding protein) decreased. Serum YKL-40 levels (sYKL-40) on intensive care unit (ICU) admission were assessed by enzyme-linked immunosorbent assay between the two groups; resulting YKL-40 was significantly higher in the sepsis group (P < 0.001). Furthermore, sYKL-40 on ICU admission was significantly higher in patients with positive blood culture (P < 0.005), patients with septic shock (P < 0.05), and patients requiring continuous hemodiafiltration (P < 0.05) or hydrocortisone replacement therapy (P < 0.005) during subsequent treatment. A positive correlation between sYKL-40 and blood IL-6 level on ICU admission was noted in the sepsis group (r = 0.465, P < 0.01). YKL-40 identified by proteomic analysis is considered as a biomarker of sepsis. However, further investigation is needed to clarify its roles and clinical usefulness as a biomarker.
Shock (Augusta, Ga.) 02/2009; 32(4):393-400. · 2.87 Impact Factor
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ABSTRACT: Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system associated with significant morbidity and mortality. High-dose corticosteroid administration has been considered the mainstay of treatment for ADEM; however, some patients with ADEM are refractory to steroid therapy. We report a case of a 17-year-old man suffering from ADEM who did not respond to corticosteroid therapy, but who exhibited a dramatic recovery with plasmapheresis. He became comatose, requiring ventilatory support, and exhibited abnormalities of some brainstem reflexes prior to treatment. He underwent sequential courses of plasma exchange therapy for three days. Plasma exchanges were carried out with concomitant continuous hemodiafiltration (CHDF) to control intracranial pressure by stabilizing pH, plasma Na+ concentration, and colloid osmotic pressure. After plasma exchanges, his reflexes and level of consciousness gradually improved. Eleven months after this treatment, he had only minimal neurological deficit that did not interfere with any of his activities of daily living. The efficacy of plasmapheresis for ADEM has not yet been established. Plasmapheresis may be indicated for ADEM, not only for patients with severe disease in whom high-dose corticosteroid treatment has failed, but also as first-line treatment for ADEM. Early initiation of plasmapheresis appears to be associated with moderate to marked improvement. Early recognition and early treatment of ADEM are thus of paramount importance.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 11/2008; 12(5):401-5. · 1.39 Impact Factor
