Masanori Takinami

Validation of the Kidney Disease Improving Global Outcomes Criteria for AKI and Comparison of Three Criteria in Hospitalized Patients

BACKGROUND AND OBJECTIVES AKI is a major clinical problem and predictor of outcome in hospitalized patients. In 2013, the Kidney Disease: Improving Global Outcomes (KDIGO) group published the third consensus AKI definition and classification system after the Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease (RIFLE) and the Acute Kidney Injury Network (AKIN) working group systems. It is unclear which system achieves optimal prognostication in hospital patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective observational study using hospital laboratory, admission, and discharge databases was performed that included adult patients admitted to a teaching hospital in Tokyo, Japan between April 1, 2008, and October 31, 2011. AKI occurring during each hospital stay was identified, and discriminative ability of each AKI classification system based on serum creatinine for the prediction of hospital mortality was assessed. The receiver operating characteristic curve, a graphical measure of test performance, and the area under the curve were used to evaluate how classifications preformed on the study population. RESULTS In total, 49,518 admissions were studied, of which 11.0% were diagnosed with RIFLE criteria and 11.6% were diagnosed with KDIGO criteria, but only 4.8% were diagnosed with AKIN criteria. Overall hospital mortality was 3.0%. AKI staging and hospital mortality were closely correlated in all systems. Discrimination for hospital mortality was similar for RIFLE and KDIGO criteria (area under the curve=0.77 versus 0.78; P=0.02), whereas AKIN discrimination was inferior (area under the curve=0.69 versus RIFLE [P<0.001] versus KDIGO [P<0.001]). CONCLUSION Among hospital patients, KDIGO and RIFLE criteria achieved similar discrimination, but the discrimination of AKIN was inferior.

Anesthetic management of high-risk cardiac patients undergoing noncardiac surgery under the support of intraaortic balloon pump

Patients with severely impaired left ventricular function, an uncorrectable coronary artery disease, and a recent myocardial infarction are at high risk of cardiac complications after major noncardiac surgery. We present two patients with extensive three-vessel coronary artery disease who underwent intraperitoneal surgery under the support of intraaortic balloon pump (IABP). In one patient, the IABP was inserted urgently because of the development of chest pain with significant ST depression on arrival in the operating room, and the other patient was managed with prophylactic IABP. There were no intraoperative or postoperative cardiac events in either patient. Thus, IABP should be considered in the perioperative management of patients with severe cardiac diseases.

Removal of 2-Arachidonylglycerol by Direct Hemoperfusion Therapy With Polymyxin B Immobilized Fibers Benefits Patients With Septic Shock

Arachidonylethanolamide (AEA) and 2‐arachidonylglycerol (2‐AG) are endocannabinoids involved in septic shock, and 8‐epi prostaglandin F2α (F2‐isoprostane) is a biomarker of oxidative stress in biological systems. Because the antibiotic polymyxin B absorbs endocannabinoids as well as endotoxins, direct hemoperfusion therapy with polymyxin B‐immobilized fibers (PMX‐DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and determine the proper use of PMX‐DHP, we measured the changes in levels of endocannabinoids and F2‐isoprostane in patients with septic shock. Twenty‐six patients with septic shock, including those with septic shock induced by peritonitis, underwent laparotomy for drainage. Endocannabinoids absorption with PMX‐DHP was examined in two groups of patients: patients whose mean arterial blood pressure (mABP) had increased more than 20 mm Hg (responder group; N = 13); and patients iwhose mABP did not increase or had increased no more than 20 mm Hg (non‐responder group; N = 13). Levels of AEA did not change after PMX‐DHP in either the non‐responder or responder groups, whereas levels of 2‐AG decreased significantly after PMX‐DHP in the responder group, but not in the non‐responder group. F2‐isoprostane gradually increased after PMX‐DHP treatment; on the other hand, levels of F2‐isoprostane remained constant in the responder group. Patients with septic shock are under considerable oxidative stress, and 2‐AG plays an important role in the cardiovascular status of these patients. The removal of 2‐AG by PMX‐DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long‐term oxidative stress.

Nafamostat mesilate as an anticoagulant during continuous veno-venous hemodialysis: A three-year retrospective cohort study

Introduction Although nafamostat mesilate, a synthetic serine protease inhibitor, has been commonly used in Japan as an anticoagulant during continuous renal replacement therapy (CRRT), its clinical utility has not been well determined. The aim of this study was to evaluate the efficacy (filter survival) and safety (bleeding complications) of nafamostat mesilate in CRRT for acute kidney injury (AKI) among critically ill patients. Methods We retrospectively studied consecutive patients with AKI treated with continuous veno-venous hemodialysis and nafamostat mesilate from April 2005 to March 2008. Demographic, clinical and laboratory data were extracted from the clinical chart. Results Fifty-eight patients were enrolled in this study (45 males with an average age of 66±15 years). The median filter survival was 21.8 h (range: 2.8–55.5 h), and the mean was 20.8±8.4 h. Only 38 out of 181 filters (21%) were interrupted because of filter failure within 24 hours and 89 filters (49%) were electively renewed within 24 hours. Activated partial thromboplastin time was elevated especially during the first 24 hours (46.7±13.1 s at baseline versus 73.9±24.3 s at day 1; ANOVA p<0.01). Hematocrit level was kept around 30% and did not change significantly (ANOVA p=0.69). No patients experienced major bleeding while treated with CRRT. Conclusions Nafamostat mesilate provided sufficient filter survival without causing major bleeding complications despite the prolongation of APTT.

Intraoperative hydroxyethyl starch 70/0.5 is not related to acute kidney injury in surgical patients: retrospective cohort study.

BACKGROUND: Although high-molecular-weight hydroxyethyl starch (HES) has been reported to cause acute kidney injury (AKI), it is not clear whether low-molecular-weight HES (6% HES 70/0.5) can be a risk for AKI or not. We hypothesized that intraoperative 6% HES 70/0.5 administration is not related to postoperative AKI. METHODS: A retrospective chart review was conducted to identify adult surgical patients with intraoperative blood loss of ≥1000 mL at a university hospital. AKI was defined as >50% increase in serum creatinine from the preoperative value within 7 days after the operation according to the RIFLE (Risk, Injury, Failure, Loss, or End-stage kidney disease) criteria. We compared the incidence of AKI between patients with and without intraoperative HES administration. Multivariate logistic regression analysis and propensity score matching were also conducted to elucidate the impact of HES on postoperative AKI. RESULTS: Among 14,332 surgical cases, 846 patients met the inclusion criteria. In patients given HES (a median dose of 1000 mL, n = 635), 12.9% developed AKI, compared with 16.6% (−3.7%, −1.7% to 9.1%) in patients without HES (n = 211). Multivariate logistic regression analysis showed that HES was not an independent risk factor for postoperative AKI (odds ratio: 0.76, 0.48–1.21). Using the propensity score, 179 pairs were matched. In patients with HES, 12.3% developed AKI, compared with 14.5% in patients without HES (−2.2%, −4.9% to 9.3%). CONCLUSION: In this uncontrolled retrospective chart review, intraoperative 6% HES 70/0.5 in a low dose was not related to postoperative AKI in patients with major intraoperative blood loss. Randomized controlled trials are warranted to further evaluate the safety and efficacy of low-molecular-weight HES.

Epidemiology, prevention, and treatment of new-onset atrial fibrillation in critically ill: a systematic review

BackgroundAtrial fibrillation (AF) is a common arrhythmia in the ICU. The aim of this review is to summarize relevant information on new-onset AF in non-cardiac critical illness with respect to epidemiology, prevention, and treatment.MethodsWe conducted a PubMed search in June 2014 and included studies describing the epidemiology, prevention, and treatment of new-onset AF and atrial flutter during ICU stay in non-cardiac adult patients. Selected studies were divided into the three categories according to the extracted information. The methodological quality of selected studies was described according to the Grading of Recommendations Assessment, Development and Evaluation system.ResultsWe identified 1,132 citations, and after full-text-level selection, we included 10 studies on etiology/outcome and five studies on treatment. There was no study related to prevention. Overall quality of evidence was mostly low or very low due to their observational study designs, small sample sizes, flawed diagnosis of new-onset AF, and the absence of mortality evaluation. The incidence of new-onset AF varied from 4.5% to 15.0%, excluding exceptional cases (e.g., septic shock). Severity scores of patients with new-onset AF were higher than those without new-onset AF in eight studies, in four of which the difference was statistically significant. Five studies reported risk factors for new-onset AF, all of which used multivariate analyses to extract risk factors. Multiple risk factors are reported, e.g., advanced age, the white race, severity scores, organ failures, and sepsis. Hospital mortality in new-onset AF patients was higher than that of patients without AF in all studies, four of which found statistical significance. Among the five studies on treatment, only one study was randomized controlled, and various interventions were studied.ConclusionsNew-onset AF occurred in 5%–15% of the non-cardiac critically ill patients. Patients with new-onset AF had poor outcomes compared with those without AF. Despite the high incidence of new-onset AF in the general ICU population, currently available information for AF, especially for management (prevention, treatment, and anticoagulation), is quite limited. Further research is needed to improve our understanding of new-onset AF in critically ill patients.

Subacute kidney injury in hospitalized patients.

BACKGROUND AND OBJECTIVES The epidemiology of AKI and CKD has been described. However, the epidemiology of progressively worsening kidney function (subacute kidney injury [s-AKI]) developing over a longer time frame than defined for AKI (7 days), but shorter than defined for CKD (90 days), is completely unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This retrospective study used a hospital laboratory and admission database. Adult patients admitted to a teaching hospital in Tokyo, Japan, between April 1, 2008, and October 31, 2011, were included. s-AKI was classified into three grades of severity (mild, moderate, severe) in accordance with the Risk, Injury, and Failure categories of the Risk, Injury, Failure, Risk, Loss, and ESRD classification, but did not use its time frame. Kidney injury (AKI and s-AKI) occurring during each hospital stay was identified, and logistic regression analysis was performed to assess their effect on hospital mortality. RESULTS Of 56,567 patients admitted to the hospital during the study period, 49,518 were included. Of these, 87.8% had no evidence of kidney dysfunction, 11.0% had AKI, and 1.1% had s-AKI. Patients with s-AKI had mild renal dysfunction in 82.7% of cases, moderate in 12.1%, and severe in 5.0%. Worsening s-AKI category was linearly correlated with hospital mortality, as previously described for AKI (no injury: 1.2%, mild: 6.5%, moderate: 12.9%, severe: 20.7%). Although mortality (8.0% versus 17.5%) and need for renal replacement therapy (0.2% versus 2.2%) were lower in patients with s-AKI than in those with AKI, multivariable regression analysis confirmed that s-AKI was an independent risk factor for hospital mortality (odds ratio (OR), 5.44; 95% confidence interval [95% CI], 3.89 to 7.44); the OR with AKI was 14.8 (95% CI, 13.2 to 16.7). CONCLUSIONS Close to 1% of hospitalized patients develop s-AKI. This condition is independently associated with increased hospital mortality, and the risk for death increases with s-AKI severity. Patients with s-AKI had a better outcome and were less likely to require renal replacement therapy than patients with AKI.

Prospective external validation of the new scoring system for disseminated intravascular coagulation by Japanese Association for Acute Medicine (JAAM).

INTRODUCTION A new disseminated intravascular coagulation (DIC) scoring system was recently announced by Japanese Association for Acute Medicine (JAAM). We have conducted a prospective external validation study to assess the accuracy of this scoring system. MATERIALS AND METHODS All patients admitted to the ICU in a tertiary academic hospital in 2007 were prospectively observed. All patients younger than 15 years of age, those who stayed in the ICU for less than 24 hours, had cardiac surgery, hematological diseases, recent chemotherapy or radiotherapy or liver cirrhosis were excluded. The remaining patients were then screened using the JAAM DIC scoring system. RESULTS DIC was diagnosed by the JAAM DIC scoring system in 45 of the 242 patients screened (18.6%). The DIC patients were older, had a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and stayed in the ICU longer in comparison to the non-DIC patients. However, hospital mortality was similar between the two groups (p=0.98). There was no difference in the JAAM DIC score between the surviving and non-surviving DIC patients (p=0.40). A multivariate logistic regression analysis revealed the DIC diagnosed by JAAM to have a non-significant low odds ratio for hospital mortality (OR 0.29, 95%CI 0.08-1.08, p=0.066). CONCLUSION We have reported an external validation study of the JAAM DIC scoring system, which was conducted outside of the centers where data for developing the score were collected. DIC diagnosed by this scoring system was not related to hospital mortality.

Life-threatening complications after postoperative intermediate care unit discharge: A retrospective, observational study.

BACKGROUND Postoperative patients who require intensive monitoring, intervention with an arterial line, vasoactive drugs and prolonged ventilator weaning are admitted to the postoperative intermediate care unit (IMCU). OBJECTIVES The aim of this study was to estimate the prevalence of life-threatening complications within 7 days after IMCU discharge. Furthermore, we searched for associations between perioperative risk factors and these life-threatening complications. DESIGN A retrospective observational study. SETTING The postoperative IMCU of a university hospital in Tokyo, Japan, between 2010 and 2012. PATIENTS All adult patients who stayed in the postoperative IMCU and who were discharged to general wards without being transferred to the ICU were included. MAIN OUTCOME MEASURES A composite outcome of life-threatening complications needing unplanned ICU admission within 7 days after IMCU stay, or death within 7 days after IMCU stay. RESULTS Forty out of 3093 patients (1.3%) presented a life-threatening complication; all had an unplanned ICU admission, and none died. Patients with life-threatening complications had a longer length of hospital stay [median 38.0 (interquartile range, IQR 21.3 to 56.8) days vs. 12.0 (IQR 8.0 to 23.0), P < 0.001] and a higher in-hospital mortality (12.5 vs. 0.7%, P < 0.001). Independent risk factors were an emergency operation before IMCU admission [vs. elective; odds ratio (OR) 20.5; 95% confidence interval (95% CI) 12.2 to 36.0, P < 0.001], higher cumulative perioperative fluid load during the surgical operation and IMCU stay (3000 to 4999 vs. <1000 ml; OR 5.7; 95% CI 1.6 to 23.7, P = 0.009; ≥5000 vs. <1000 ml; OR 7.2; 95% CI 1.3 to 39.6, P = 0.021), mechanical ventilation during IMCU stay less than 6 h (vs. no use; OR 3.6; 95% CI 1.4 to 9.2, P = 0.007). CONCLUSION More than 1% of patients had a life-threatening complication within 7 days after IMCU discharge, but with no deaths. Risk factors were an emergency operation before IMCU admission, higher cumulative perioperative fluid load and a short period of mechanical ventilation during the IMCU stay.

The Impact of Ventilator-Associated Events in Critically Ill Subjects With Prolonged Mechanical Ventilation

BACKGROUND: The Centers for Disease Control and Prevention recently released a surveillance definition for respiratory complications in ventilated patients, ventilator-associated events (VAEs), to replace ventilator-associated pneumonia (VAP). VAEs consist of ventilator-associated conditions (VAC), infection-related ventilator-associated complications (IVAC), and possible VAP. A duration of mechanical ventilation of at least 4 d is required to diagnose VAE. However, the observed duration of mechanical ventilation was < 4 d in many previous studies. We evaluated the impact of VAEs on clinical outcomes in critically ill subjects who required mechanical ventilation for ≥ 4 d. METHODS: This single-center retrospective cohort study was conducted in the general ICU of an academic hospital. We included 407 adult subjects who were admitted to the ICU and required mechanical ventilation for at least 4 d. VAC and IVAC were identified from the electronic medical records. VAP was defined according to the Centers for Disease Control and Prevention 2008 criteria and was identified from the surveillance data of the infection control team of our hospital. Clinical outcomes were studied in the VAC, IVAC, and VAP groups. Possible VAP was not investigated. RESULTS: Higher mortality was seen in VAC and IVAC subjects, but not in VAP subjects, compared with those without VAEs and VAP. By multivariable hazard analysis for hospital mortality, IVAC was independently associated with hospital mortality (hazard ratio 2.42, 95% CI 1.39–4.20, P = .002). VAC also tended to show a similar association with hospital mortality (hazard ratio 1.45, 95% CI 0.97–2.18, P = .07). On the other hand, VAP did not increase a hazard of hospital death (hazard ratio 1.08, 95% CI 0.44–2.66, P = .87). CONCLUSIONS: We found that a VAE was related to hospital mortality in critically ill subjects with prolonged mechanical ventilation, and that VAP was not.