External Validation for Acute Kidney Injury Severity Scores: A Multicenter Retrospective Study in 14 Japanese ICUs.

BACKGROUND/AIMS: Acute kidney injury (AKI) is associated with high mortality. Multiple AKI severity scores have been derived to predict patient outcome. We externally validated new AKI severity scores using the Japanese Society for Physicians and Trainees in Intensive Care (JSEPTIC) database. METHODS: New AKI severity scores published in the 21st century (Mehta, Stuivenberg Hospital Acute Renal Failure (SHARF) II, Program to Improve Care in Acute Renal Disease (PICARD), Vellore and Demirjian), Liano, Simplified Acute Physiology Score (SAPS) II and lactate were compared using the JSEPTIC database that collected retrospectively 343 patients with AKI who required continuous renal replacement therapy (CRRT) in 14 intensive care units. Accuracy of the severity scores was assessed by the area under the receiver-operator characteristic curve (AUROC, discrimination) and Hosmer-Lemeshow test (H-L test, calibration). RESULTS: The median age was 69 years and 65.8% were male. The median SAPS II score was 53 and the hospital mortality was 58.6%. The AUROC curves revealed low discrimination ability of the new AKI severity scores (Mehta 0.65, SHARF II 0.64, PICARD 0.64, Vellore 0.64, Demirjian 0.69), similar to Liano 0.67, SAPS II 0.67 and lactate 0.64. The H-L test also demonstrated that all assessed scores except for Liano had significantly low calibration ability. CONCLUSIONS: Using a multicenter database of AKI patients requiring CRRT, this study externally validated new AKI severity scores. While the Demirjian's score and Liano's score showed a better performance, further research will be required to confirm these findings.

The lower limit of intensity to control uremia during continuous renal replacement therapy.

INTRODUCTION: The recommended lower limit of intensity during continuous renal replacement therapy (CRRT) is 20 or 25 mL/kg/h. However, limited information is available to support this threshold. We aimed to evaluate the impact of different intensities of CRRT on the clearance of creatinine and urea in critically ill patients with severe acute kidney injury (AKI). METHODS: This is a multicenter retrospective study conducted in 14 Japanese ICUs in 12 centers. All patients older than 18 years and treated with CRRT due to AKI were eligible. We evaluated the effect of CRRT intensity by two different definitions: daily intensity (the mean intensity over each 24-h period) and average intensity (the mean of daily intensity during the period while CRRT was performed). To study the effect of different CRRT intensity on clearance of urea and creatinine, all patients/daily observations were arbitrarily allocated to one of 4 groups based on the average intensity and daily intensity: <10, 10-15, 15-20, and >20 mL/kg/h. RESULTS: Total 316 patients were included and divided into the four groups according to average CRRT intensity. The groups comprised 64 (20.3%), 138 (43.7%), 68 (21.5%), and 46 patients (14.6%), respectively. Decreases in creatinine and urea increased as the average intensity increased over the first 7 days of CRRT. The relative changes of serum creatinine and urea levels remained close to 1 over the 7 days in the "<10" group. Total 1,101 daily observations were included and divided into the four groups according to daily CRRT intensity. The groups comprised 254 (23.1%), 470 (42.7%), 239 (21.7%), and 138 observations (12.5%), respectively. Creatinine and urea increased (negative daily change) only in the "<10" group and decreased with the increasing daily intensity in the other groups. CONCLUSIONS: The lower limit of delivered intensity to control uremia during CRRT was approximately between 10 and 15 mL/kg/h in our cohort. A prescribed intensity of approximately 15 mL/kg/h might be adequate to control uremia for patients with severe AKI in the ICU. However, considering the limitations due to the retrospective nature of this study, prospective studies are required to confirm our findings.

Validity of low-intensity continuous renal replacement therapy*.

OBJECTIVE: To study the hospital mortality of patients with severe acute kidney injury treated with low-intensity continuous renal replacement therapy. DESIGN: Multicenter retrospective observational study (Japanese Society for Physicians and Trainees in Intensive Care), combined with previously conducted multinational prospective observational study (Beginning and Ending Supportive Therapy). SETTING: Fourteen Japanese ICUs in 12 tertiary hospitals (Japanese Society for Physicians and Trainees in Intensive Care) and 54 ICUs in 23 countries (Beginning and Ending Supportive Therapy). PATIENTS: Consecutive adult patients with severe acute kidney injury requiring continuous renal replacement therapy admitted to the participating ICUs in 2010 (Japanese Society for Physicians and Trainees in Intensive Care, n = 343) and 2001 (Beginning and Ending Supportive Therapy Beginning and Ending Supportive Therapy, n = 1,006). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, variables at continuous renal replacement therapy initiation, continuous renal replacement therapy settings, and outcomes (ICU and hospital mortality and renal replacement therapy requirement at hospital discharge) were collected. Continuous renal replacement therapy intensity was arbitrarily classified into seven subclasses: less than 10, 10-15, 15-20, 20-25, 25-30, 30-35, and more than 35 mL/kg/hr. Multivariable logistic regression analysis was conducted to investigate risk factors for hospital mortality. The continuous renal replacement therapy dose in the Japanese Society for Physicians and Trainees in Intensive Care database was less than half of the Beginning and Ending Supportive Therapy database (800 mL/hr vs 2,000 mL/hr, p < 0.001). Even after adjusting for the body weight and dilution factor, continuous renal replacement therapy intensity was statistically different (14.3 mL/kg/hr vs 20.4 mL/kg/hr, p < 0.001). Patients in the Japanese Society for Physicians and Trainees in Intensive Care database had a lower ICU mortality (46.1% vs 55.3%, p = 0.003) and hospital mortality (58.6% vs 64.2%, p = 0.070) compared with patients in the Beginning and Ending Supportive Therapy database. In multivariable regression analysis after combining the two databases, no continuous renal replacement therapy intensity subclasses were found to be statistically different from the reference intensity (20-25 mL/kg/hr). Several sensitivity analyses (patients with sepsis, patients from Western countries in the Beginning and Ending Supportive Therapy database) confirmed no intensity-outcome relationship. CONCLUSIONS: Continuous renal replacement therapy at a mean intensity of 14.3 mL/kg/hr did not have worse outcome compared with 20-25 mL/kg/hr of continuous renal replacement therapy, currently considered the standard intensity. However, our study is insufficient to support the use of low-intensity continuous renal replacement therapy, and more studies are needed to confirm our findings.

[Perioperative fibrinogen concentrations in cardiac surgery with cardiopulmonary bypass].

BACKGROUND: Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) need many blood products due to deficiency of coagulation factors. Blood transfusion therapy in patients with excessive bleeding after CPB is generally empiric. We checked and studied the fibrinogen concentration and transfusion, as well as bleeding amount in the perioperative period. METHODS: The study was approved by our institutional ethics committee. Thirty patients were studied. Blood samples were obtained at the induction of anesthesia (before CPB), at the end of CPB, at the end of operation, and on the next morning, or before the patient was given fresh frozen plasma in the intensive care unit. RESULTS: For all cases, fibrinogen concentration and platelet concentration were lowest at the end of CPB. Fibrinogen concentration rose up to before CPB level on the next morning. The group in which fibrinogen concentration was less than 150 mg x dl(-1) at the end of CPB consumed more blood products than the group with fibrinogen concentration of over 150 mg x dl(-1). CONCLUSIONS: Blood transfusion therapy based on fibrinogen concentration is needed to maintain adequacy of the perioperative blood transfusion and blood conservation in cardiac surgery.

[Use of landiolol hydrochloride for the prevention of atrial fibrillation after lung resection].

BACKGROUND: We examined the effect of landiolol hydrochloride, a selective beta1-adrenoreceptor antagonist, on the incidence of atrial fibrillation(AF). METHODS: The incidence of AF after lung resection was evaluated retrospectively in patients with intraoperative treatment with landiolol hydrochloride or those without it. Landiolol hydrochloride (5 microg x kg(-1) x min(-1)) was administered intravenously from the beginning of anesthesia induction to the end of operation. RESULTS: In non-treatment group with landiolol hydrochloride (224 patients), the incidence of AF after surgery was 14.2%, peaking on postoperative day 2, and the average peak day was day 3.5. Older age, removal of the lymph nodes, lengthy surgery, and ischemic heart failure were risk factors. In treatment group with landiolol hydrochloride (77 patients), the incidence of AF after surgery was 5.2%, which was significantly lower than that in non-treatment group. Increased numbers of risk factors led to the high incidence of AF. But the administration of landiolol hydrochloride suppressed the incidence of AF. CONCLUSIONS: Landiolol hydrochloride is effective for the preventionof AF and it is safe without causing a severe decrease in blood pressure and bradycardia in high risk patients.

[A case of deep vein thrombosis in spite of using an intermittent pneumatic compression device].

A 69-year-old male patient underwent subtotal esophagectomy for esophageal cancer under sevoflurane anesthesia combined with epidural analgesia. According to the protocol for the prevention of deep vein thrombosis (DVT) in our hospital, only an intermittent pneumatic compression device (IPC) and elastic stockings were perioperatively used for prophylaxis of DVT although D-dimer level was slightly increased to 1.2 microg x ml(-1). On the 2nd post-operative day, a venous ultrasound examination was performed, because D-dimer level was suddenly increased up to 41.5 microg x ml(-1) without any signs of thrombus in the atrium and pleural cavity. Since DVT was detected with the right lower limb, the use of an IPC was stopped and an inferior vena cava filter was inserted through the right jugular vein with a continuous administration of heparin. An aggressive search should be performed if DVT is suspected by any clinical signs including an increase in D-dimer level. We should also keep in mind the possibility of DVT even if an IPC and elastic stockings are perioperatively used.

Sepsis may not be a risk factor for mortality in patients with acute kidney injury treated with continuous renal replacement therapy.

PURPOSE: We aimed to study the clinical characteristics, courses, and outcomes of critically ill patients with septic acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) in comparison with nonseptic AKI treated with CRRT. METHODS: This is a multicenter retrospective observational study conducted in 14 Japanese intensive care units in 2010. All adult patients with severe AKI treated with CRRT were eligible (n = 343), and information on patient characteristics, variables at CRRT initiation, CRRT settings, and outcomes was collected. Patients were categorized into the septic AKI group and the nonseptic AKI group according to contributing factors to AKI. RESULTS: Approximately half of study patients (48.7%) had sepsis/septic shock as a contributing factor to AKI, and patients with septic AKI treated with CRRT had more serious clinical conditions than patients with nonseptic AKI. However, no significant difference was observed in intensive care unit mortality (48.5% vs 43.8%; P = .44) and hospital mortality (61.1% vs 56.3%; P = .42) between patients with septic and nonseptic AKIs treated with CRRT. Furthermore, sepsis was associated with lower hospital mortality (odds ratio, 0.378; P = .012) in multivariable regression analysis. CONCLUSION: Sepsis may not be a risk factor for mortality in patients with AKI whose condition has become severe enough to require CRRT.

[Effects of low dose colforsin daropate hydrochloride in patients undergoing off-pump coronary artery bypass grafting].

BACKGROUND: We evaluated retrospectively the effectiveness of low dose colforsin daropate hydrochloride (CDH) in 12 patients undergoing off-pump coronary artery bypass grafting (CABG). METHODS: Low dose CDH was administered intravenously at a rate of 0.05-0.1 microg x kg(-1) x min(-1) from sternotomy to the end of coronary artery anastomosis. Hemodynamic measurements were made before infusion of CDH, and before, during, and after coronary artery anastomosis. RESULTS: Heart rate was significantly higher before, during and after the anastomosis compared with the value before the infusion of CDH. Heart rate was also significantly higher after the anastomosis compared with the value before the anastomosis. Systolic blood pressure, mean pulmonary pressure, right atrial pressure and pulmonary artery wedge pressure showed no significant changes after the start of infusion of CDH. Cardiac output was significantly higher before, during and after the anastomosis compared with the value before the infusion of CDH. Systemic vascular resistance was significantly lower before and during anastomosis compared with the value before the infusion of CDH. CONCLUSIONS: Infusion of low dose CDH prevents the elevations of mean pulmonary artery pressure, right atrial pressure and pulmonary artery wedge pressure without reducing systolic bood pressure during coronary artery anastomosis. Cardiac output was significantly increased, and SVR as well as PVR were significantly decreased after the infusion of CDH. In patients undergoing off-pump CABG, we recommend infusion of low dose colforsin daropate hydrochloride from sternotomy to the end of coronary artery anastomosis.

Who may not benefit from continuous renal replacement therapy in acute kidney injury?

This study aimed to identify factors that may predict early kidney recovery (less than 48 hours) or early death (within 48 hours) after initiating continuous renal replacement therapy (CRRT) in acute kidney injury (AKI) patients. This is a multicenter retrospective observational study of 14 Japanese Intensive care units (ICUs) in 12 tertiary hospitals. Consecutive adult patients with severe AKI requiring CRRT admitted to the participating ICUs in 2010 (n=343) were included. Patient characteristics, variables at CRRT initiation, settings, and outcomes were collected. Patients were grouped into early kidney recovery group (CRRT discontinuation within 48 hours after initiation, n=52), early death group (death within 48 hours after CRRT initiation, n=52), and the rest as the control group (n=239). The mean duration of CRRT in the early kidney recovery group and early death group was 1.3 and 0.9 days, respectively. In multivariable regression analysis, in comparison with the control group, urine output (mL/h) (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03), duration between ICU admission to CRRT initiation (days) (OR: 0.65, 95% CI: 0.43-0.87), and the sepsis-related organ failure assessment score (OR: 0.87, 95% CI; 0.78-0.96) were related to early kidney recovery. Serum lactate (mmol/L) (OR: 1.19, 95% CI: 1.11-1.28), albumin (g/dL) (OR: 0.52, 95% CI: 0.28-0.92), vasopressor use (OR: 3.68, 95% CI: 1.37-12.16), and neurological disease (OR: 9.64, 96% CI: 1.22-92.95) were related to early death. Identifying AKI patients who do not benefit from CRRT and differentiating such patients from the study cohort may allow previous and future studies to effectively evaluate the indication and role of CRRT.