BACKGROUND: The objective of this study was to establish the efficacy and safety of procalcitonin (PCT)-guided antibiotic discontinuation in critically ill patients with sepsis in a country with a high prevalence of antimicrobial resistance and a national health insurance system. METHODS: In a multi-center randomized controlled trial, patients were randomly assigned to a PCT group (stopping antibiotics based on a predefined cut-off range of PCT) or a control group. The primary end-point was antibiotic duration. We also performed a cost-minimization analysis of PCT-guided antibiotic discontinuation. RESULTS: The two groups (23 in the PCT group and 29 in the control group) had similar demographic and clinical characteristics except for need for renal replacement therapy on ICU admission (46% vs. 14%; P = 0.010). In the per-protocol analysis, the median duration of antibiotic treatment for sepsis was 4 days shorter in the PCT group than the control group (8 days; interquartile range [IQR], 6–10 days vs. 14 days; IQR, 12–21 days; P = 0.001). However, main secondary outcomes, such as clinical cure, 28-day mortality, hospital mortality, and ICU and hospital stays were not different between the two groups. In cost evaluation, PCT-guided therapy decreased antibiotic costs by USD 30 (USD 241 in the PCT group vs. USD 270 in the control group). The results of the intention-to-treat analysis were similar to those obtained for the per-protocol analysis. CONCLUSION: PCT-guided antibiotic discontinuation in critically ill patients with sepsis could reduce the duration of antibiotic use and its costs with no apparent adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02202941
Anti-Bacterial Agents ; Biomarkers ; Calcitonin ; Costs and Cost Analysis ; Critical Illness ; Hospital Mortality ; Humans ; Intensive Care Units ; Length of Stay ; Mortality ; National Health Programs ; Prevalence ; Renal Replacement Therapy ; Sepsis

BACKGROUND: Admission blood glucose (BG) level is a predictor of mortality in critically ill patients with various conditions. However, limited data are available regarding this relationship in critically ill patients with cardiovascular diseases according to diabetic status. METHODS: A total of 1,780 patients (595 with diabetes) who were admitted to cardiac intensive care unit (CICU) were enrolled from a single center registry. Admission BG level was defined as maximal serum glucose level within 24 hours of admission. Patients were divided by admission BG level: group 1 (< 7.8 mmol/L), group 2 (7.8–10.9 mmol/L), group 3 (11.0–16.5 mmol/L), and group 4 (≥ 16.6 mmol/L). RESULTS: A total of 105 patients died in CICU (62 non-diabetic patients [5.2%] and 43 diabetic patients [7.9%]; P = 0.105). The CICU mortality rate increased with admission BG level (1.7%, 4.8%, 10.3%, and 18.8% from group 1 to group 4, respectively; P < 0.001). On multivariable analysis, hypertension, mechanical ventilator, continuous renal replacement therapy, acute physiology and chronic health evaluation II (APACHE II) score, and admission BG level significantly influenced CICU mortality in non-diabetic patients (group 1 vs. group 3: hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.47–7.44; P = 0.004; group 1 vs. group 4: HR, 6.56; 95% CI, 2.76–15.58; P < 0.001). However, in diabetic patients, continuous renal replacement therapy and APACHE II score influenced CICU mortality but not admission BG level. CONCLUSION: Admission BG level was associated with increased CICU mortality in critically ill, non-diabetic patients admitted to CICU but not in diabetic patients.
APACHE ; Blood Glucose ; Cardiovascular Diseases ; Critical Care ; Critical Illness ; Diabetes Mellitus ; Humans ; Hypertension ; Intensive Care Units ; Mortality ; Prognosis ; Renal Replacement Therapy ; Ventilators, Mechanical

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy used in critically ill patients with severe cardiopulmonary dysfunction. Continuous renal replacement therapy (CRRT) is supplemented to treat fluid overload, acute kidney injury, and electrolyte disturbances during ECMO. However, the best time to initiate CRRT is not well-defined. We performed this study to identify the optimal timing of CRRT for ECMO. METHODS: We conducted a multicenter retrospective cohort study of 296 patients over 12 years. Patients received CRRT during ECMO at Seoul National University Hospital, Seoul National University Bundang Hospital, or Yonsei University Hospital. We assigned patients to an early or late CRRT group depending on the CRRT initiation time. We considered early CRRT to be CRRT instituted within 72 hours of ECMO initiation. RESULTS: Among 296 patients, 212 patients (71.6%) received early CRRT. After using a propensity score matching method, 47 patients were included in each group. The time from ECMO initiation to CRRT initiation was 1.1 ± 0.9 days in the early CRRT group and 14.6 ± 18.6 days in the late CRRT group. No difference in patients’ mortality (P = 0.834) or hospital stay (P = 0.627) between the early and late CRRT groups was found. After adjusting all covariables, there was no significant difference in mortality between the early and late CRRT groups (hazard ratio, 0.697; 95% confidence interval, 0.410–1.184; P = 0.182). CONCLUSION: This study showed that early CRRT may not be superior to late CRRT in ECMO patients. Further clinical trials are warranted.
Acute Kidney Injury ; Cohort Studies ; Critical Illness ; Extracorporeal Membrane Oxygenation* ; Humans ; Length of Stay ; Methods ; Mortality ; Propensity Score ; Renal Replacement Therapy* ; Retrospective Studies ; Seoul ; Time-to-Treatment

Acute kidney injury (AKI) is characterized by abrupt deterioration of renal function, and its diagnosis relies on creatinine measurements and urine output. AKI is associated with higher morbidity and mortality, and is a risk factor for development of chronic kidney disease. There is no proven medication for AKI. Therefore, prevention and early detection are important. Physicians should be aware of the risk factors for AKI and should monitor renal function in high-risk patients. Management of AKI includes optimization of volume status and renal perfusion, avoidance of nephrotoxic agents, and sufficient nutritional support. Continuous renal replacement therapy is widely available for critically ill children, and this review provides basic information regarding this therapy. Long-term follow-up of patients with AKI for renal function, blood pressure, and proteinuria is recommended.
Acute Kidney Injury* ; Blood Pressure ; Child* ; Creatinine ; Critical Illness ; Diagnosis ; Follow-Up Studies ; Humans ; Mortality ; Nutritional Support ; Perfusion ; Proteinuria ; Renal Insufficiency, Chronic ; Renal Replacement Therapy* ; Risk Factors

BACKGROUND: The purpose of this study was to assess the role of hypophosphatemia in major clinical outcomes of patients treated with low- or high-intensity continuous renal replacement therapy (CRRT). METHODS: We performed a retrospective analysis of data collected from 492 patients. We divided patients into two CRRT groups based on treatment intensity (greater than or equal to or less than 40 mL/kg/hour of effluent generation) and measured serum phosphate level daily during CRRT. RESULTS: We obtained a total of 1,440 phosphate measurements on days 0, 1, and 2 and identified 39 patients (7.9%), 74 patients (15.0%), and 114 patients (23.1%) with hypophosphatemia on each of these respective days. In patients treated with low-intensity CRRT, there were 23 episodes of hypophosphatemia/1,000 patient days, compared with 83 episodes/1,000 patient days in patients who received high-intensity CRRT (P < 0.01). Multiple Cox proportional hazards analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) III score, utilization of vasoactive drugs, and arterial pH on the second day of CRRT were significant predictors of mortality, while serum phosphate level was not a significant contributor to mortality. CONCLUSION: APACHE score, use of vasoactive drugs, and arterial pH on the second CRRT day were identified as significant predictors of mortality. Hypophosphatemia might not be a major risk factor of increased mortality in patients treated with CRRT.
Acute Kidney Injury* ; APACHE ; Critical Illness* ; Humans ; Hydrogen-Ion Concentration ; Hypophosphatemia* ; Mortality ; Renal Replacement Therapy* ; Retrospective Studies ; Risk Factors

BACKGROUND: Fluid overload prior to continuous renal replacement therapy (CRRT) is an important prognostic factor. Thus, precise evaluation of fluid status is necessary to treat such patients. In this study, we investigated whether fluid assessment using bioelectrical impedance analysis (BIA) can predict outcomes in critically ill patients requiring CRRT. METHODS: A prospective observational study was performed in patients who were admitted to the intensive care unit and who required CRRT. BIA was conducted before CRRT; then, the ratio of extracellular water to total body water (ECW/TBW) was derived to estimate volume status. RESULTS: A total of 31 patients treated with CRRT were included. There were 18 men (58.1%), and the median age was 67 years (interquartile range, 51 to 78 years). Fourteen patients (45.2%) died within 28 days after CRRT initiation. Patients were divided into 16 with ECW/TBW ≥0.41 and 15 with ECW/TBW <0.41. Survival rate within 28 days was different between the two groups (P = 0.044). Cox regression analysis revealed a relationship between ECW/TBW ≥0.41 and 28-day mortality, but it was not statistically significant (hazard ratio, 3.0; 95% confidence interval, 0.9 to 9.8; P = 0.061). Lastly, the area under the curve of ECW/TBW for 28-day mortality was analyzed. The area under the curve of ECW/TBW was 0.73 (95% confidence interval, 0.54 to 0.92), and this was significant (P = 0.037). CONCLUSIONS: Fluid status can be assessed using BIA in critically ill patients requiring CRRT, and BIA can predict mortality. Further large trials are needed to confirm the usefulness of BIA in critically ill patients.
Body Water ; Critical Illness* ; Electric Impedance* ; Humans ; Intensive Care Units ; Male ; Mortality ; Observational Study* ; Prospective Studies* ; Renal Replacement Therapy* ; Survival Rate ; Water

BACKGROUND: Fluid overload prior to continuous renal replacement therapy (CRRT) is an important prognostic factor. Thus, precise evaluation of fluid status is necessary to treat such patients. In this study, we investigated whether fluid assessment using bioelectrical impedance analysis (BIA) can predict outcomes in critically ill patients requiring CRRT. METHODS: A prospective observational study was performed in patients who were admitted to the intensive care unit and who required CRRT. BIA was conducted before CRRT; then, the ratio of extracellular water to total body water (ECW/TBW) was derived to estimate volume status. RESULTS: A total of 31 patients treated with CRRT were included. There were 18 men (58.1%), and the median age was 67 years (interquartile range, 51 to 78 years). Fourteen patients (45.2%) died within 28 days after CRRT initiation. Patients were divided into 16 with ECW/TBW ≥0.41 and 15 with ECW/TBW <0.41. Survival rate within 28 days was different between the two groups (P = 0.044). Cox regression analysis revealed a relationship between ECW/TBW ≥0.41 and 28-day mortality, but it was not statistically significant (hazard ratio, 3.0; 95% confidence interval, 0.9 to 9.8; P = 0.061). Lastly, the area under the curve of ECW/TBW for 28-day mortality was analyzed. The area under the curve of ECW/TBW was 0.73 (95% confidence interval, 0.54 to 0.92), and this was significant (P = 0.037). CONCLUSIONS: Fluid status can be assessed using BIA in critically ill patients requiring CRRT, and BIA can predict mortality. Further large trials are needed to confirm the usefulness of BIA in critically ill patients.
Body Water ; Critical Illness ; Electric Impedance ; Humans ; Intensive Care Units ; Male ; Mortality ; Observational Study ; Prospective Studies ; Renal Replacement Therapy ; Survival Rate ; Water

Positive fluid balance is a risk factor for mortality in critically ill patients, especially those requiring continuous renal replacement therapy (CRRT). However, the association between daily fluid balance and various organ impairments remains unclear. This study investigated the impacts of daily fluid balance prior to CRRT on organ dysfunction, as well as mortality in critically ill patients. We identified daily fluid balance between intensive care unit (ICU) admission and CRRT initiation. According to daily fluid balance, the time to CRRT initiation and the rate of organ failure based on the sequential organ failure assessment (SOFA) score were assessed. We recruited 100 patients who experienced CRRT for acute kidney injury. CRRT was initiated within 2 [0, 4] days. The time to CRRT initiation was shortened in proportion to daily fluid balance, even after the adjustment for the renal SOFA score at ICU admission (HR 1.14, P = 0.007). Based on the SOFA score, positive daily fluid balance was associated with respiratory, cardiovascular, nervous, and coagulation failure, independent of each initial SOFA score at ICU admission (HR 1.36, 1.26, 1.24 and 2.26, all P < 0.05). Ultimately, we found that positive fluid balance was related with an increase in the rate of 28-day mortality (HR 1.14, P = 0.012). Positive daily fluid balance may accelerate the requirement for CRRT, moreover, it can be associated with an increased risk of multiple organ failure in critically ill patients.
Acute Kidney Injury/*diagnosis/mortality/therapy ; Aged ; Critical Illness/*mortality ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Organ Dysfunction Scores ; *Renal Replacement Therapy ; Retrospective Studies ; Risk Factors ; Survival Rate ; Water-Electrolyte Balance/*physiology

Positive fluid balance is a risk factor for mortality in critically ill patients, especially those requiring continuous renal replacement therapy (CRRT). However, the association between daily fluid balance and various organ impairments remains unclear. This study investigated the impacts of daily fluid balance prior to CRRT on organ dysfunction, as well as mortality in critically ill patients. We identified daily fluid balance between intensive care unit (ICU) admission and CRRT initiation. According to daily fluid balance, the time to CRRT initiation and the rate of organ failure based on the sequential organ failure assessment (SOFA) score were assessed. We recruited 100 patients who experienced CRRT for acute kidney injury. CRRT was initiated within 2 [0, 4] days. The time to CRRT initiation was shortened in proportion to daily fluid balance, even after the adjustment for the renal SOFA score at ICU admission (HR 1.14, P = 0.007). Based on the SOFA score, positive daily fluid balance was associated with respiratory, cardiovascular, nervous, and coagulation failure, independent of each initial SOFA score at ICU admission (HR 1.36, 1.26, 1.24 and 2.26, all P < 0.05). Ultimately, we found that positive fluid balance was related with an increase in the rate of 28-day mortality (HR 1.14, P = 0.012). Positive daily fluid balance may accelerate the requirement for CRRT, moreover, it can be associated with an increased risk of multiple organ failure in critically ill patients.
Acute Kidney Injury/*diagnosis/mortality/therapy ; Aged ; Critical Illness/*mortality ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Organ Dysfunction Scores ; *Renal Replacement Therapy ; Retrospective Studies ; Risk Factors ; Survival Rate ; Water-Electrolyte Balance/*physiology

PURPOSE: This study was designed to investigate whether nutritional supply influences biochemical markers and clinical outcomes in patients who received continuous renal replacement therapy (CRRT) by evaluating adequacy of nutritional supply for patients. METHODS: From January 2012 to December 2013, 239 adult patients who received CRRT in the intensive care unit for more than 3 days were included. General information from electronic medical records and nutritional status related biochemical data and clinical outcomes on the first day of CRRT and 2 weeks after CRRT were collected. RESULTS: The rate of delivered energy and protein was 68.06% and 43.13% which was much lower than energy and protein supply based on their requirement. When the patients were divided into two groups according to 70% of energy received rate and 50% of protein received rate, the group with more than 70% of energy received rate showed significant decrease of length of hospital stay (p = 0.007), length of stay in intensive care unit (ICU) (p = 0.008), duration of CRRT (p < 0.001), and APACHE II score (p < 0.001) compared to less than 70% of energy received rate after adjusting for age. In addition, the group with more than 50% of protein received rate showed decreased mortality (p = 0.031), length of hospital stay (p = 0.008), length of ICU stay (p = 0.035), duration of CRRT (p < 0.001), and APACHE II score (p < 0.001) after adjusting for age. We found that the level of hematocrit (p = 0.006) was significantly improved in the group with more than 70% of energy received rate, and the level of TLC (p = 0.049), hematocrit (p = 0.041) was significantly improved in the group with more than 50% of protein received rate. We also found that energy delivery was negatively correlated with length of stay in ICU (p = 0.049) and positively correlated with level of calcium (p = 0.037). In addition, protein delivery was correlated with the levels of serum total protein (p = 0.021), serum albumin (p = 0.048), hematocrit (p = 0.009), and total cholesterol (p = 0.021) when dead patients were included, but was correlated with the levels of hematocrit (p = 0.034) and calcium (p = 0.024) when dead patients were excluded. CONCLUSION: Proper nutritional delivery may help patients' clinical outcomes for patients receiving CRRT. However, their actual intakes of energy and protein were not adequate for their requirements. Identification of patients with malnutrition is necessary and a multidisciplinary approach for systemic management is also required.
Adult ; APACHE ; Biomarkers ; Calcium ; Cholesterol ; Critical Illness* ; Electronic Health Records ; Hematocrit ; Humans ; Intensive Care Units ; Length of Stay ; Malnutrition ; Mortality ; Nutritional Status* ; Renal Replacement Therapy* ; Serum Albumin