Search

Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach is required and that integrated biologic and physiologic data identify reproducible subpopulations that may respond differently to treatment. This article reviews the current state of the field and considers how to successfully transition to a precision medicine approach. To impact clinical care, identification of subpopulations must do more than differentiate prognosis. It must differentiate response to treatment, ideally by defining subgroups with distinct functional or pathobiological mechanisms (endotypes). There are now multiple examples of reproducible subpopulations of sepsis, acute respiratory distress syndrome, and acute kidney or brain injury described using clinical, physiological, and/or biological data. Many of these subpopulations have demonstrated the potential to define differential treatment response, largely in retrospective studies, and that the same treatment-responsive subpopulations may cross multiple clinical syndromes (treatable traits). To bring about a change in clinical practice, a precision medicine approach must be evaluated in prospective clinical studies requiring novel adaptive trial designs. Several such studies are underway, but there are multiple challenges to be tackled. Such subpopulations must be readily identifiable and be applicable to all critically ill populations around the world. Subdividing clinical syndromes into subpopulations will require large patient numbers. Global collaboration of investigators, clinicians, industry, and patients over many years will therefore be required to transition to a precision medicine approach and ultimately realize treatment advances seen in other medical fields. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) survivors are at an increased risk of chronic kidney disease, end-stage kidney disease, and mortality. Little is known about the effect of erythropoietin (EPO), a kidney-producing hormone, in post-AKI setting. We aimed to investigate the role of EPO as a predictor of long-term outcomes in post-severe AKI survivors. Methods: We performed a retrospective analysis of post-AKI cohort conducted between August 2018 and December 2021. Adults who survived severe AKI stages 2–3 were enrolled. Serum EPO was obtained at 1 month after hospital discharge. We explored whether EPO level could predict long-term kidney outcomes at 12 months including mortality, kidney replacement therapy, doubling serum creatinine, and major adverse kidney events at 365 days. Results: One hundred and twelve patients were enrolled. Median EPO level was significantly higher in non-survivors than survivors (28.9 [interquartile range: 16.2–50.7] versus 11.6 mU/mL [7.5–22.3], p = 0.003). The best EPO level cut-off was 16.2 mU/mL (sensitivity 77.8%, specificity 62.1%). Serum EPO predicted 12-month mortality with an area under the curve (AUC) of 0.69. Combining clinical model using age, baseline, and discharge kidney function with serum EPO improved prediction with AUC of 0.74. Multivariable analysis demonstrated that high-level of EPO group had significantly higher mortality compared with low-level EPO group (15.2% vs. 3.0%, p = 0.020). Hematocrit was significantly lower in high-level EPO group compared with low-level EPO group at 12 months (33.4 ± 1.1% vs. 36.0 ± 0.9%, p = 0.038). Conclusions: Plasma EPO appears to be a useful marker for predicting long-term outcome in post-severe AKI survivors. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend monitoring of post-filter ionized calcium (pfCa) when using regional citrate anticoagulation during continuous renal replacement therapy (RCA-CRRT) to determine citrate efficiency for the prevention of filter clotting. However, the reliability of pfCa raises the question of whether routine monitoring is required. Reducing the frequency of pfCa monitoring could potentially reduce costs and workload. Our objective was to test the efficacy and safety of no pfCa monitoring among critically ill patients receiving RCA-CRRT. Methods This study was a non-inferiority randomized controlled trial conducted between January 2021 and October 2021 at King Chulalongkorn Memorial Hospital, Thailand. Critically ill patients who were treated with RCA-CRRT were randomized to receive either standard pfCa monitoring (aiming pfCa level of 0.25–0.35 mmol/L), or no pfCa monitoring, in which a constant rate of citrate infusion was maintained at pre-determined citrate concentrations of 4 mmol/L with blinding of pfCa levels to treating clinicians. The primary outcome was the filter lifespan. Non-inferiority would be demonstrated if the upper limit of the 95% confidence interval (CI) for the difference in filter lifespan between the groups was less than 20 h. Results Fifty patients were randomized to the standard pfCa monitoring group (n  = 25) or no pfCa monitoring group (n  = 25). The mean filter lifespan was 54 ± 20 h in the standard pfCa monitoring group and 47 ± 23 h in the no pfCa monitoring group (absolute difference 7.1 h; 95% CI –5.3, 19.5, P  = .25). When restricting the analysis to circuits reaching the maximum duration of circuit lifespan at 72 h and clotted filters, the filter lifespan was 61 ± 17 h in the standard pfCa group vs 60 ± 19 h in the no pfCa monitoring group (absolute difference 0.9 h; 95% CI –11.5, 13.4, P  = .88). Compared with the no pfCa monitoring group, the standard pfCa monitoring group had a significantly higher mean citrate concentrations (4.43 ± 0.32 vs 4 mmol/L, P  < .001) and a higher rate of severe hypocalcemia (44% vs 20%, P  = .13). No statistical differences were found in filter clotting, citrate accumulation, citrate overload and mortality between the two groups. Conclusions Among critically ill patients receiving RCA-CRRT, no pfCa monitoring by maintaining the citrate concentrations of 4 mmol/L is feasible. Larger randomized controlled trials should be conducted to ensure the efficacy, safety and cost-effectiveness of this strategy. Trial registration ClinicalTrials.gov : NCT04792424 (registered 11 March 2021) [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to explore the changes in AKI epidemiology between the first and the second COVID wave in the United Kingdom (UK). Methods: This was an observational study of critically ill adult patients with COVID-19 in an expanded tertiary care intensive care unit (ICU) in London, UK. Baseline characteristics, organ support, COVID-19 treatments, and patient and kidney outcomes up to 90 days after discharge from hospital were compared. Results: A total of 772 patients were included in the final analysis (68% male, mean age 56 ± 13.6). Compared with wave 1, patients in wave 2 were older, had higher body mass index and clinical frailty score, but lower baseline serum creatinine and C-reactive protein (CRP). The proportion of patients receiving invasive mechanical ventilation (MV) on ICU admission was lower in wave 2 (61% vs 80%; p < 0.001). AKI incidence within 14 days of ICU admission was 76% in wave 1 and 51% in wave 2 (p < 0.001); in wave 1, 32% received KRT compared with 13% in wave 2 (p < 0.001). Patients in wave 2 had significantly lower daily cumulative fluid balance (FB) than in wave 1. Fewer patients were dialysis dependent at 90 days in wave 2 (1% vs. 4%; p < 0.001). Conclusions: In critically ill adult patients admitted to ICU with COVID-19, the risk of AKI and receipt of KRT significantly declined in the second wave. The trend was associated with less MV, lower PEEP and lower cumulative FB. Trial registration: NCT04445259. [ABSTRACT FROM AUTHOR]

Background: There is little known about the contribution of microRNAs (miRNAs) in the recovery from acute kidney injury (AKI). This study aimed to discover and validate miRNA profiles for predicting renal recovery from severe AKI. Patients and methods: A prospective observational study was conducted between June 2020 and January 2021. Urine and serum samples of participants with AKI stage 3 were collected from two groups: renal recovery and renal non-recovery. Transcriptomic analysis was performed using nCounter miRNA Expression Assay. Expression levels of candidate miRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: The discovery phase identified 18 and 11 differentially expressed miRNAs that were statistically significant between the two groups in urine and serum specimens, respectively. Top candidate miRNAs selected included miR-556-3p, miR-1915-3p, miR-4284, miR-32-5p, miR-96-5p, and miR-556-5p in urine, and miR-499b-5p, miR-30a-3p, miR-92b-3p and miR-770-5p in serum. This study enrolled 110 participants in the validation phase. The qRT-PCR analysis indicated that urine miR-556-3p was significantly higher in the renal recovery group than in the renal non-recovery group. Urine miR-556-3p alone predicted renal recovery with an area under the curve (AUC) of 0.64 (95%CI 0.52–0.75, p = 0.03). Combining the clinical model with urine miR-556-3p predicted renal recovery with an AUC of 0.83 (95%CI 0.75–0.92, p < 0.01). Conclusion: This data provides evidence that microtranscriptome profiles of severe AKI patients with renal recovery differed from the non-recovery group. Urine miR-556-3p had the potential to improve the prediction of renal recovery from severe AKI. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a frequent complication in patients with severe respiratory failure receiving extracorporeal membrane oxygenation (ECMO). However, little is known of long-term kidney function in ECMO survivors. We aimed to assess the long-term mortality and kidney outcomes in adult patients treated with veno-venous ECMO (VV-ECMO). Methods: This was a single-centre retrospective study of adult patients (≥ 18 years old) who were treated with VV-ECMO at a commissioned ECMO centre in the UK between 1st September 2010, and 30th November 2016. AKI was defined and staged using the serum creatinine and urine output criteria of the Kidney Diseases: Improving Global Outcomes (KDIGO) classification. The primary outcome was 1-year mortality. Secondary outcomes were long-term mortality (up to March 2020), 1-year incidence of end-stage kidney disease (ESKD) or chronic kidney disease (CKD) among AKI patients who received renal replacement therapy (AKI-RRT), AKI patients who did not receive RRT (AKI-no RRT) and patients without AKI (non-AKI). Results: A total of 300 patients [57% male; median age 44.5; interquartile range (IQR) 34–54] were included in the final analysis. Past medical histories included diabetes (12%), hypertension (17%), and CKD (2.3%). The main cause of severe respiratory failure was pulmonary infection (72%). AKI occurred in 230 patients (76.7%) and 59.3% received renal replacement therapy (RRT). One-year mortality was 32% in AKI-RRT patients vs. 21.4% in non-AKI patients (p = 0.014). The median follow-up time was 4.35 years. Patients who received RRT had a higher risk of 1-year mortality than those who did not receive RRT (adjusted HR 1.80, 95% CI 1.06, 3.06; p = 0.029). ESKD occurred in 3 patients, all of whom were in the AKI-RRT group. At 1-year, 41.2% of survivors had serum creatinine results available. Among these, CKD was prevalent in 33.3% of AKI-RRT patients vs. 4.3% in non-AKI patients (p = 0.004). Conclusions: VV-EMCO patients with AKI-RRT had high long-term mortality. Monitoring of kidney function after hospital discharge was poor. In patients with follow-up creatinine results available, the CKD prevalence was high at 1 year, especially in AKI-RRT patients. More awareness about this serious long-term complication and appropriate follow-up interventions are required. [ABSTRACT FROM AUTHOR]

To expand our understanding of the role of angiotensin II (ANGII) in coronavirus infectious disease 2019 (COVID‐19), we conducted an international, multicenter registry study to assess the use of ANGII in patients with COVID‐19 compared to patients not receiving ANGII. Critically ill adult patients who were diagnosed with COVID‐19 and received ANGII were matched with COVID‐19 patients not receiving ANGII according to age, respiratory support, history of hypertension, use of angiotensin‐converting enzyme inhibitors and/or ANGII receptor blocker, and date of admission. All outcomes were exploratory in nature and included improvement in oxygenation, duration of organ support, and mortality. In one year, 132 patients were included (65 in the ANGII group and 67 in the control group), and patients were comparable in baseline characteristics. During the first 12 h of infusion, patients in the ANGII had a faster decrease in FiO2 and maintained similar mean arterial pressure levels. Hospital mortality was not statistically significantly different between the groups (53.8% vs. 40.3%; p = 0.226). Within the limitations of such a study design, our findings confirm previous observations of a potentially positive effect of ANGII on blood pressure and FiO2 but no effect on patient‐centered outcomes. Highlights: In patients with coronavirus infectious disease 2019, the physiological effect of angiotensin II (ANGII) on oxygenation was recently assessed in an uncontrolled case series.During the first 12 h of infusion, patients in the ANGII had a faster decrease in FiO2 and maintained similar mean arterial pressure levels.Hospital mortality was not statistically significantly different between the groups. [ABSTRACT FROM AUTHOR]

Background: Regional citrate anticoagulation (RCA) is recommended for continuous renal replacement therapy (CRRT). However, filter life varies and premature filter clotting can occur. The aims of this explorative prospective study were to investigate the effects of RCA on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving CRRT, to compare clotting parameters between systemic and intra-circuit blood samples, and to screen participants for coagulation disorders. We recruited critically ill adult patients admitted to a 30-bedded Intensive care unit in a tertiary care hospital who required CRRT with RCA for acute kidney injury (AKI). Patients with pre-existing thrombotic, bleeding tendencies or a CRRT duration less than 48 h were excluded. We measured coagulation and thrombophilia parameters at baseline. Thrombin generation, D-dimer and platelet function were measured pre-CRRT and at 12, 24, 36, 48 and 72 h after commencing CRRT using blood samples taken from the arterial line and the circuit. Results: At baseline, all eleven patients (mean age 62.4 years, 82% male) had Factor VIII and von Willebrand Factor concentrations above reference range and significantly increased peak thrombin generation. During CRRT, there were no significant changes in systemic maximum peak thrombin generation, time to peak thrombin generation, fibrinogen, D-dimer and platelet function analysis. We observed no significant difference between paired samples taken from the patient's arterial line and the circuit. Conclusions: Critically ill patients with AKI requiring CRRT are hypercoagulable. Citrate used for anticoagulation during CRRT does not affect thrombin generation, D-dimer or platelet function. Systemic clotting parameters reflect intra-circuit results. Trial registration: ClinicalTrials.gov Identifier: NCT02486614. Registered 01 July 2015—Registered after recruitment of first patient. https://clinicaltrials.gov/ct2/show/NCT02486614 [ABSTRACT FROM AUTHOR]

Background: Regional citrate anticoagulation (RCA) is recommended for continuous renal replacement therapy (CRRT). However, filter life varies and premature filter clotting can occur. The aims of this explorative prospective study were to investigate the effects of RCA on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving CRRT, to compare clotting parameters between systemic and intra-circuit blood samples, and to screen participants for coagulation disorders. We recruited critically ill adult patients admitted to a 30-bedded Intensive care unit in a tertiary care hospital who required CRRT with RCA for acute kidney injury (AKI). Patients with pre-existing thrombotic, bleeding tendencies or a CRRT duration less than 48 h were excluded. We measured coagulation and thrombophilia parameters at baseline. Thrombin generation, D-dimer and platelet function were measured pre-CRRT and at 12, 24, 36, 48 and 72 h after commencing CRRT using blood samples taken from the arterial line and the circuit. Results: At baseline, all eleven patients (mean age 62.4 years, 82% male) had Factor VIII and von Willebrand Factor concentrations above reference range and significantly increased peak thrombin generation. During CRRT, there were no significant changes in systemic maximum peak thrombin generation, time to peak thrombin generation, fibrinogen, D-dimer and platelet function analysis. We observed no significant difference between paired samples taken from the patient's arterial line and the circuit. Conclusions: Critically ill patients with AKI requiring CRRT are hypercoagulable. Citrate used for anticoagulation during CRRT does not affect thrombin generation, D-dimer or platelet function. Systemic clotting parameters reflect intra-circuit results. Trial registration: ClinicalTrials.gov Identifier: NCT02486614. Registered 01 July 2015—Registered after recruitment of first patient. https://clinicaltrials.gov/ct2/show/NCT02486614 [ABSTRACT FROM AUTHOR]

Citrate has been proposed as anticoagulation of choice in continuous renal replacement therapy (CRRT). However, little is known about the pharmacokinetics (PK) and metabolism of citrate in liver failure patients who require CRRT with regional citrate anticoagulation (RCA). This prospective clinical PK study was conducted at King Chulalongkorn Memorial Hospital between July 2019 to April 2021, evaluating seven acute liver failure (ALF) and seven acute-on-chronic liver failure (ACLF) patients who received CRRT support utilizing RCA as an anticoagulant at a citrate dose of 3 mmol/L. For evaluation of the citrate PK, we delivered citrate for 120 min and then stopped for a further 120 min. Total body clearance of citrate was 152.5 ± 50.9 and 195.6 ± 174.3 mL/min in ALF and ACLF, respectively. The ionized calcium, ionized magnesium, and pH slightly decreased after starting citrate infusion and gradually increased to baseline after stopping citrate infusion. Two of the ACLF patients displayed citrate toxicity during citrate infusion, while, no ALF patient had citrate toxicity. In summary, citrate clearance was significantly decreased in critically ill ALF and ACLF patients receiving CRRT. Citrate use as an anticoagulation in these patients is of concern for the risk of citrate toxicity. [ABSTRACT FROM AUTHOR]

Malnutrition is highly prevalent in patients with acute kidney injury, especially in those receiving renal replacement therapy (RRT). For the assessment of nutritional status, a combination of screening tools, anthropometry, and laboratory parameters is recommended rather than a single test. To avoid underfeeding and overfeeding during RRT, energy expenditure should be measured by indirect calorimetry or calculated using predictive equations. Nitrogen balance should be periodically measured to assess the degree of catabolism and to evaluate protein intake. However, there is limited data for nutritional targets specifically for patients on RRT, such as protein intake. The composition of commercial solutions for continuous renal replacement therapy (CRRT) varies. CRRT itself can be associated with both, nutrient losses into the effluent fluid and caloric gain from dextrose, lactate, and citrate. The role of micronutrient supplementation, and potential use of micronutrient enriched CRRT solutions in this setting is unknown, too. This review provides an overview of existing knowledge and uncertainties related to nutritional aspects in patients on CRRT and emphasizes the need for more research in this area. [ABSTRACT FROM AUTHOR]

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 . [ABSTRACT FROM AUTHOR]

Background: There are limited data on acute kidney injury (AKI) progression and long-term outcomes in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to describe the prevalence and risk factors for development of AKI, its subsequent clinical course and AKI progression, as well as renal recovery or dialysis dependence and survival in this group of patients. Methods: This was a retrospective observational study in an expanded tertiary care intensive care unit in London, United Kingdom. Critically ill patients admitted to ICU between 1st March 2020 and 31st July 2020 with confirmed SARS-COV2 infection were included. Analysis of baseline characteristics, organ support, COVID-19 associated therapies and their association with mortality and outcomes at 90 days was performed. Results: Of 313 patients (70% male, mean age 54.5 ± 13.9 years), 240 (76.7%) developed AKI within 14 days after ICU admission: 63 (20.1%) stage 1, 41 (13.1%) stage 2, 136 (43.5%) stage 3. 113 (36.1%) patients presented with AKI on ICU admission. Progression to AKI stage 2/3 occurred in 36%. Risk factors for AKI progression were mechanical ventilation [HR (hazard ratio) 4.11; 95% confidence interval (CI) 1.61–10.49] and positive fluid balance [HR 1.21 (95% CI 1.11–1.31)], while steroid therapy was associated with a reduction in AKI progression (HR 0.73 [95% CI 0.55–0.97]). Kidney replacement therapy (KRT) was initiated in 31.9%. AKI patients had a higher 90-day mortality than non-AKI patients (34% vs. 14%; p < 0.001). Dialysis dependence was 5% at hospital discharge and 4% at 90 days. Renal recovery was identified in 81.6% of survivors at discharge and in 90.9% at 90 days. At 3 months, 16% of all AKI survivors had chronic kidney disease (CKD); among those without renal recovery, the CKD incidence was 44%. Conclusions: During the first COVID-19 wave, AKI was highly prevalent among severely ill COVID-19 patients with a third progressing to severe AKI requiring KRT. The risk of developing CKD was high. This study identifies factors modifying AKI progression, including a potentially protective effect of steroid therapy. Recognition of risk factors and monitoring of renal function post-discharge might help guide future practice and follow-up management strategies. Trial registration NCT04445259 [ABSTRACT FROM AUTHOR]

Leptospirosis can cause a high mortality rate, especially in severe cases. This multicenter cross-sectional study aimed to examine both host and pathogen factors that might contribute to the disease severity. A total of 217 leptospirosis patients were recruited and divided into two groups of non-severe and severe. Severe leptospirosis was defined by a modified sequential organ failure assessment (mSOFA) score of more than two or needed for mechanical ventilation support or had pulmonary hemorrhage or death. We found that leptospiremia, plasma neutrophil gelatinase-associated lipocalin (pNGAL), and interleukin 6 (IL-6) at the first day of enrollment (day 1) and microscopic agglutination test (MAT) titer at 7 days after enrollment (days 7) were significantly higher in the severe group than in the non-severe group. After adjustment for age, gender, and the days of fever, there were statistically significant associations of baseline leptospiremia level (OR 1.70, 95% CI 1.23–2.34, p = 0.001), pNGAL (OR 9.46, 95% CI 4.20–21.33, p < 0.001), and IL-6 (OR 2.82, 95% CI 1.96–4.07, p < 0.001) with the severity. In conclusion, a high leptospiremia, pNGAL, and IL-6 level at baseline were associated with severe leptospirosis. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic tests (RDTs) have become widely used in low-resource settings for leptospirosis diagnostic. This study aims to evaluate the diagnostic performance of the five commercially available RDTs to detect human IgM against Leptospira spp. in Thai population. Methodology/Principal findings: Ninety-nine serum samples from Leptospirosis suspicious patients were tested with five RDTs, including Medical Science Public Health, Leptocheck-WB, SD bioline, TRUSTline, and J.Mitra. The case definition was based on MAT, qPCR, and culture results. Diagnostic accuracy was determined based on the first day of enrollment in an overall analysis and stratified according to days post-onset of fever. The five RDTs had overall sensitivity ranging from 1.8% to 75% and specificity ranging from 52.3% to 97.7%. Leptocheck-WB had high sensitivity of 75.0%. The sensitivity of five RDTs increased on days 4–6 post-onset of fever, while the specificity of all tests remained relatively stable at different days post-onset of fever. Conclusions/Significance: The tested RDTs showed low sensitivity. Therefore, based on the present study, five commercially available RDTs might not be an appropriate test for acute leptospirosis screening in the Thai population. Author summary: Leptospirosis is an important zoonosis, especially in the tropics. Rapid diagnostic tests (RDTs) have become widely used in low-resource settings for leptospirosis diagnostics. In this study, we evaluated the diagnostic performance of five commercially available RDTs in Thai population. The overall sensitivity ranged from 1.8% to 75%, and specificity was 52.3% to 97.7%. Leptocheck-WB had the highest sensitivity of 75.0%. The sensitivity of five RDTs increased on days 4–6 post onset of fever, while the specificity of all tests remained relatively stable at different days post onset of fever. Based on these results, RDTs showed low sensitivity and might not be an appropriate test for acute leptospirosis screening in the Thai population. [ABSTRACT FROM AUTHOR]

The authors discuss a study by S. Demirjian et al on the performance of new prediction models in adult patients undergoing coronary artery bypass graft, valve, or aorta surgery. Topics include basis of the diagnosis of acute kidney injury (AKI), strengths and limitation of the study, and argument on hemodynamic optimization and avoidance of nephrotoxic drugs.

Background: The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.Methods: This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations.Results: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period.Conclusion: EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.Trial Registration: NCT03231748, registered on 27th July 2017. [ABSTRACT FROM AUTHOR]

Shock is an acute condition of circulatory failure resulting in life-threatening organ dysfunction, high morbidity and high mortality. Current management includes fluid and catecholamine therapy to maintain adequate mean arterial pressure and organ perfusion. Norepinephrine is recommended as first-line vasopressor, but other agents are available. Angiotensin II is an alternative potent vasoconstrictor without chronotropic or inotropic properties. Several studies, including a large randomized controlled trial have demonstrated its ability to increase blood pressure with catecholamine-sparing effects. Angiotensin II was consequently approved by the US FDA in 2017 and the EU in 2019 as an add-on vasopressor in vasodilatory shock. This review aims to discuss its basic pharmacology, clinical efficacy, safety and future perspectives. [ABSTRACT FROM AUTHOR]

Background Etiologies for acute kidney injury (AKI) vary by geographic region and socioeconomic status. While considerable information is now available on AKI in the Americas, Europe and China, large comprehensive epidemiologic studies of AKI from Southeast Asia (SEA) are still lacking. The aim of this study was to investigate the rates and characteristics of AKI among intensive care unit (ICU) patients in Thailand. Methods We conducted the largest prospective observational study of AKI in SEA. The data were serially collected on the first 28 days of ICU admission by registration in electronic web-based format. AKI status was defined by full Kidney Disease: Improving Global Outcome criteria. We used AKI occurrence as the clinical outcome and explored the impact of modifiable and non-modifiable risk factors on the development and progression of AKI. Results We enrolled 5476 patients from 17 ICU centres across Thailand from February 2013 to July 2015. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 2471 of 4668 patients (52.9%). Overall, the maximum AKI stage was Stage 1 in 7.5%, Stage 2 in 16.5% and Stage 3 in 28.9%. In the multivariable adjusted model, we found that older age, female sex, admission to a regional hospital, medical ICU, high body mass index, primary diagnosis of cardiovascular-related disease and infectious disease, higher Acute Physiology and Chronic Health Evaluation II, non-renal Sequential Organ Failure Assessment scores, underlying anemia and use of vasopressors were all independent risk factors for AKI development. Conclusions In Thai ICUs, AKI is very common. Identification of risk factors of AKI development will help in the development of a prognostic scoring model for this population and should help in decision making for timely intervention, ultimately leading to better clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) has become a global health issue. Little is known about the disease burden in Laos. We aimed to evaluate the burden and outcomes of AKI as well as assess the availability of AKI treatment in Laos.Methods: We performed a multicentric prospective observational study in adult patients who had been admitted to 5 intensive care units (ICU) in Laos. The data was serially collected on the first 28 days of ICU admission. Patients were diagnosed by the KDIGO 2012 criteria for AKI. We used AKI occurrence as the primary outcome and explored risk factors on the development and outcomes of AKI.Results: We enrolled 1480 patients from 5 ICU centers across Laos from January to December 2016. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 508 of the 1460 enrolled patients (34.8%). Overall, the rates of maximum AKI staging were 4% for stage 1, 10.3% for stage 2, and 20.5% for stage 3. Risk factors for AKI were older age, obesity, cardiovascular diseases, respiratory diseases, renal diseases, oncologic diseases, and chronic kidney diseases. Only 1.8% of all participants received RRT. The mortality rate was 28.4% in non-AKI patients compared to 44.5% in AKI patients, which increased according to the stage of AKI (stage 1, 4.9%; stage 2, 28.3%; stage 3 66.8%; P < 0.001). There were 13.6% who were discharged against medical advice.Conclusions: AKI is a huge burden in Laos with under-recognition and poor outcomes. [ABSTRACT FROM AUTHOR]

We aimed to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) can accurately predict persistent AKI, major adverse kidney events at 30 days (MAKE30) and 365 days (MAKE365) in hospitalized AKI patients. This is a retrospective study of adult patients who were admitted at King Chulalongkorn Memorial Hospital. We performed multivariable logistic regression for persistent AKI, MAKE30, and MAKE365. We developed equations for predicting MAKE30 and MAKE365 and divided the dataset into derivation and validation cohorts. uNGAL performance and predictive models were assessed using the area under the receiver operating characteristic curve (AROC). Among 1,322 patients with AKI, 76.9%, 45.1%, and 61.7% had persistent AKI, MAKE30, and MAKE365. The AROC were 0.75 (95% confidence interval[CI] 0.70–0.80), 0.66 (95%CI 0.61–0.71), and 0.64 (95%CI 0.59–0.70) for prediction of persistent AKI, MAKE30, and MAKE365 by uNGAL. The AROC in the validation dataset combining uNGAL with clinical covariates were 0.74 (95%CI 0.69–0.79) and 0.72 (95%CI 0.67–0.77) for MAKE30 and MAKE365. We demonstrated an association between uNGAL and persistent AKI, MAKE30, and MAKE365. Prediction models combining uNGAL can modestly predict MAKE30 and MAKE365. Therefore, uNGAL is a useful tool for improving AKI risk stratification. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common problem in critically ill patients and associated with high rates of morbidity and mortality. Recently, Major Adverse Kidney Events (MAKE) were introduced as important kidney endpoints. If these endpoints can be predicted, then it may help the physicians to identify high-risk patients and provide the opportunity to have targeted preventive therapy. The objective of this study was to create a simplified scoring system to predict MAKE within 28 days among AKI patients in ICU. Methods: This is a prospective web-based multicenter cohort study that was conducted in adults who were admitted to the ICU in 17 centers across Thailand from 2013 to 2015. A predicting score was derived from the regression equation with Receiver Operating Characteristic (ROC) analysis to evaluate the diagnostic test and produce predictive models. Internal validation was obtained using the bootstrapping method. Results: From 5071 cases, 2856 (56%) had AKI. Among those with AKI, 1749 (61%) had MAKE. Among those that have MAKE, there were 1175 (41.4%) deaths, 414 (14.4%) were on dialysis and 1154 (40.7%) had non-recovery renal function. The simplified score points of low Glasgow coma scale was 3, tachypnea was 1, vasopressor use was 1, on mechanical ventilation was 2, oliguria was 2, serum creatinine rising ≥ 3 times was 5, high blood urea nitrogen was 3, low hematocrit was 2, and thrombocytopenia was 1. The area under ROC curve for optimism corrected performance was 0.80 (0.78, 0.81). When the cut-off value was 7, the sensitivity, specificity, positive likelihood ratio, and positive predictive values were 0.75, 0.76, 3.10, and 0.84, respectively. When the scoring system was calibrated, the α intercept and β slope were 1.001 and 0, respectively. Conclusions: SEA-MAKE scoring system is a new simplified clinical tool that can be used to predict major adverse kidney events in AKI patients. The simplicity of the scoring system is highly likely to be used in resource-limited settings. However, external validation is necessary before widespread use. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is one of the most important zoonosis in the tropics. Currently, specific laboratory diagnostic test for leptospirosis such as polymerase chain reaction (PCR) or direct culture cannot be applied at the primary care setting especially in the resource- limited countries. Therefore, clinical presentation and laboratory examination are still the primary diagnostic tools for leptospirosis. Objectives: To detect clinical factors for predicting leptospirosis in suspected cases, and to create a clinical prediction score (THAI-LEPTO) that is practical and easy to use in general practice while awaiting laboratory results. Materials & methods: We performed a prospective multicenter study with a development and a validation cohort of patients presenting with clinical suspicion of leptospirosis as per the WHO clinical criteria. The development cohort was conducted at 11 centers in 8 provinces around Thailand. The validation cohort was conducted at 4 centers in 1 province from the Northeastern part of Thailand. Leptospirosis confirmed cases were defined if any one of the tests were positive: microscopic agglutination test, direct culture, or PCR technique. Multivariable logistic regression was used to identify predictors of leptospirosis. The clinical prediction score was derived from the regression coefficients (original) or from the odds ratio values (simplified). We used receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic ability of our score and to find the optimal cutoff values of the score. We used a validation cohort to evaluate the accuracy of our methods. Results: In the development cohort, we enrolled 221 leptospirosis suspected cases and analyzed 211. Among those, 105 (50%) were leptospirosis confirmed cases. In logistic regression adjusted for age, gender, day of fever, and one clinical factor at a time, leptospirosis group had more hypotension OR = 2.76 (95% CI 1.07–7.10), jaundice OR = 3.40 (95%CI 1.48–8.44), muscle pain OR = 2.12 (95%CI 1.06–4.26), acute kidney injury (AKI) OR = 2.90 (95%CI 1.31–6.15), low hemoglobin OR = 3.48 (95%CI 1.72–7.04), and hypokalemia with hyponatremia OR = 3.56 (95%CI 1.17–10.84) than non-leptospirosis group. The abovementioned factors along with neutrophilia and pulmonary opacity were used in the development of the score. The simplified score with 7 variables was the summation of the odds ratio values as follows: hypotension 3, jaundice 2, muscle pain 2, AKI 1.5, low hemoglobin 3, hypokalemia with hyponatremia 3, and neutrophilia 1. The score showed the highest discriminatory power with area under the curve (AUC) 0.82 (95%CI 0.67–0.97) on fever day 3–4. In the validation cohort we enrolled 96 leptospirosis suspected cases and analyzed 92. Of those, 69 (75%) were leptospirosis confirmed cases. The performance of the simplified score with 7 variables at a cutoff of 4 was AUC 0.78 (95%CI 0.68–0.89); sensitivity 73.5; specificity 73.7; positive predictive value 87.8; negative predictive value 58.3. Conclusions: THAI-LEPTO score is a newly developed diagnostic tool for early presumptive diagnosis of leptospirosis in patients presenting with severe clinical suspicion of the disease. The score can easily be applied at the point of care while awaiting confirmatory laboratory results. Each predictor used has been supported by evidence of clinical and pathophysiological correlation. [ABSTRACT FROM AUTHOR]

Background: Using movies has been accepted worldwide as a tool to help students learn medical professionalism. In the second year, a group of medical students conducted the “Cinemeducation” project to promote professionalism in the “Medical Ethics and Critical Thinking” course. Method: Five movies with professionalism issues were screened with 20-30 students attending each session. After the show, participants then were asked to reflect on what they had learned in terms of professionalism. Two students led group discussion emphasizing questioning and argumentation for 60 min. Additional learning issues emerging from each session were also explored in more depth and arranged into a report. Results: In the Cinemeducation Project, medical students have learned five main ethical issues in each film, which were the doctor-patient relationship, informed consent and clinical trials in patients, management of genetic disorders, patient management, and brain death and organ transplantation. In addition to issues of professionalism, they also developed critical thinking and moral reasoning skills. Conclusion: Using a case-based scenario in movies has proven to be an effective and entertaining method of facilitating students with learning on professionalism. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common after cardiac surgery. To date, there are no specific pharmacological therapies. In this review, we summarise the existing evidence for prevention and management of cardiac surgery-associated AKI and outline areas for future research. Preoperatively, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be withheld and nephrotoxins should be avoided to reduce the risk. Intraoperative strategies include goal-directed therapy with individualised blood pressure management and administration of balanced fluids, the use of circuits with biocompatible coatings, application of minimally invasive extracorporeal circulation, and lung protective ventilation. Postoperative management should be in accordance with current KDIGO AKI recommendations. [ABSTRACT FROM AUTHOR]

Background: Currently, there is a lack of evidence to guide optimal care for acute kidney injury (AKI) survivors. Therefore, post-discharge care by a multidisciplinary care team (MDCT) may improve these outcomes. This study aimed to demonstrate the outcomes of implementing comprehensive care by a MDCT in severe AKI survivors.Methods: This study was a randomized controlled trial conducted between August 2018 to January 2021. Patients who survived severe AKI stage 2-3 were enrolled and randomized to be followed up with either comprehensive or standard care for 12 months. The comprehensive post-AKI care involved an MDCT (nephrologists, nurses, nutritionists, and pharmacists). The primary outcome was the feasibility outcomes; comprising of the rates of loss to follow up, 3-d dietary record, drug reconciliation, and drug alert rates at 12 months. Secondary outcomes included major adverse kidney events, estimated glomerular filtration rate (eGFR), and the amount of albuminuria at 12 months.Results: Ninety-eight AKI stage 3 survivors were enrolled and randomized into comprehensive care and standard care groups (49 patients in each group). Compared to the standard care group, the comprehensive care group had significantly better feasibility outcomes; 3-d dietary record, drug reconciliation, and drug alerts (p < 0.001). The mean eGFR at 12 months were comparable between the two groups (66.74 vs. 61.12 mL/min/1.73 m2, p = 0.54). The urine albumin: creatinine ratio (UACR) was significantly lower in the comprehensive care group (36.83 vs. 177.70 mg/g, p = 0.036), while the blood pressure control was also better in the comprehensive care group (87.9% vs. 57.5%, p = 0.006). There were no differences in the other renal outcomes between the two groups.Conclusions: Comprehensive care by an MDCT is feasible and could be implemented for severe AKI survivors. MDCT involvement also yields better reduction of the UACR and better blood pressure control. Trial registration Clinicaltrial.gov: NCT04012008 (First registered July 9, 2019). [ABSTRACT FROM AUTHOR]

Background: Fluid overload is common in patients in the intensive care unit (ICU) and ultrafiltration (UF) is frequently required. There is lack of guidance on optimal UF practice. We aimed to explore patterns of UF practice, barriers to achieving UF targets, and concerns related to UF practice among practitioners working in Europe.Methods: This was a sub-study of an international open survey with focus on adult intensivists and nephrologists, advanced practice providers, and ICU and dialysis nurses working in Europe.Results: Four hundred eighty-five practitioners (75% intensivists) from 31 countries completed the survey. The most common criteria for UF initiation was persistent oliguria/anuria (45.6%), followed by pulmonary edema (16.7%). Continuous renal replacement therapy was the preferred initial modality (90.0%). The median initial and maximal rate of net ultrafiltration (UFNET) prescription in hemodynamically stable patients were 149 mL/hr. (IQR 100-200) and 300 mL/hr. (IQR 201-352), respectively, compared to a median UFNET rate of 98 mL/hr. (IQR 51-108) in hemodynamically unstable patients and varied significantly between countries. Two-thirds of nurses and 15.5% of physicians reported assessing fluid balance hourly. When hemodynamic instability occurred, 70.1% of practitioners reported decreasing the rate of fluid removal, followed by starting or increasing the dose of a vasopressor (51.3%). Most respondents (90.7%) believed in early fluid removal and expressed willingness to participate in a study comparing protocol-based fluid removal versus usual care.Conclusions: There was a significant variation in UF practice and perception among practitioners in Europe. Future research should focus on identifying the best strategies of prescribing and managing ultrafiltration in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells.Methods: We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28.Results: Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups.Conclusion: PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression.Trial Registration: ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015. [ABSTRACT FROM AUTHOR]

Background: The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT.Methods: FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT.Results: FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P <  0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002).Conclusion: The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation.Trial Registration: clinicaltrials.gov, NCT02730117 . Registered 6 April 2016. [ABSTRACT FROM AUTHOR]

A letter to the editor and a response to the article "Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier," by Ashish Upadhyay and Katrin Uhlig in the 2011 issue is presented.