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 .
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
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.
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.
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.
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.
NCT03231748, registered on 27th July 2017.
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.
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.
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.
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).
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.
clinicaltrials.gov, NCT02730117 . Registered 6 April 2016.
Abstract
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.
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.
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.
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 (UF
) prescription in hemodynamically stable patients were 149 mL/hr. (IQR 100-200) and 300 mL/hr. (IQR 201-352), respectively, compared to a median UF
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.
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.
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 intervalCI 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.
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.
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.
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.
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.
ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.
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