Acute kidney injury associated with nephrotoxic drugs in critically ill patients: a multicenter cohort study using electronic health record data.

Background: Nephrotoxic drugs frequently cause acute kidney injury (AKI) in adult intensive care unit (ICU) patients. However, there is a lack of large pharmaco-epidemiological studies investigating the associations between drugs and AKI. Importantly, AKI risk factors may also be indications or contraindications for drugs and thereby confound the associations. Here, we aimed to estimate the associations between commonly administered (potentially) nephrotoxic drug groups and AKI in adult ICU patients whilst adjusting for confounding. Methods: In this multicenter retrospective observational study, we included adult ICU admissions to 13 Dutch ICUs. We measured exposure to 44 predefined (potentially) nephrotoxic drug groups. The outcome was AKI during ICU admission. The association between each drug group and AKI was estimated using etiological cause-specific Cox proportional hazard models and adjusted for confounding. To facilitate an (independent) informed assessment of residual confounding, we manually identified drug group-specific confounders using a large drug knowledge database and existing literature. Results: We included 92 616 ICU admissions, of which 13 492 developed AKI (15%). We found 14 drug groups to be associated with a higher hazard of AKI after adjustment for confounding. These groups included established (e.g. aminoglycosides), less well established (e.g. opioids) and controversial (e.g. sympathomimetics with α- and ß-effect) drugs. Conclusions: The results confirm existing insights and provide new ones regarding drug associated AKI in adult ICU patients. These insights warrant caution and extra monitoring when prescribing nephrotoxic drugs in the ICU and indicate which drug groups require further investigation.

Incidence, risk factors and pre-emptive screening for COVID-19 associated pulmonary aspergillosis in an era of immunomodulant therapy.

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment. MATERIALS AND METHODS: A retrospective, observational, multicentre study was performed from September 2020-April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria. RESULTS: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy. CONCLUSIONS: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation.

Mini-Bronchoalveolar Lavage for Diagnosing Coronavirus Disease 2019-Associated Invasive Pulmonary Aspergillosis.

To evaluate the yield of mini-bronchoalveolar lavage compared with that of directed bronchoalveolar lavage in critically ill patients with suspected coronavirus disease 2019-associated pulmonary aspergillosis. DESIGN: A retrospective cohort study. SETTING: The ICU of the Amsterdam University Medical Centers. PATIENTS: Patients with confirmed coronavirus disease 2019 screened for coronavirus disease 2019-associated pulmonary aspergillosis. INTERVENTIONS: Mini-bronchoalveolar lavage and/or directed bronchoalveolar lavage. MEASUREMENTS AND MAIN RESULTS: In total, 76 patients were included, 20 of whom underwent bronchoalveolar lavage, 40 mini-bronchoalveolar lavage, and 16 both mini-bronchoalveolar lavage and bronchoalveolar lavage. The percentage of samples with one or more positive Aspergillus detecting test (galactomannan, culture, polymerase chain reaction) did not differ significantly between bronchoalveolar lavage and mini-bronchoalveolar lavage (16.7% vs 21.4%). However, in mini-bronchoalveolar lavage samples, this was more frequently driven by a positive polymerase chain reaction than in bronchoalveolar lavage samples (17.9% vs 2.8%; p = 0.030). In 81% of patients (13/16) with both mini-bronchoalveolar lavage and bronchoalveolar lavage, the test results were in agreement. In 11 of 12 patients (92%) with first a negative mini-bronchoalveolar lavage, the subsequent bronchoalveolar lavage sample was also negative. CONCLUSIONS: We found a similar percentage of positive test results in mini-bronchoalveolar lavage and bronchoalveolar lavage samples in patients with suspected coronavirus disease 2019-associated pulmonary aspergillosis. Our findings indicate that mini-bronchoalveolar lavage could be a useful tool for coronavirus disease 2019-associated pulmonary aspergillosis screening in ICU patients.

Multinational Observational Cohort Study of COVID-19-Associated Pulmonary Aspergillosis1.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.

Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy. METHODS: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course. FINDINGS: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78). Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.. INTERPRETATION: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19. FUNDING: Amsterdam UMC Corona Research Fund.

Incidence of venous thromboembolism in hospitalized patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications. OBJECTIVES: To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID-19. METHODS: Single-center cohort study of 198 hospitalized patients with COVID-19. RESULTS: Seventy-five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow-up of 7 days (IQR, 3-13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10-22), 33% (95% CI, 23-43) and 42% (95% CI 30-54) respectively. For symptomatic VTE, these were 10% (95% CI, 5.8-16), 21% (95% CI, 14-30) and 25% (95% CI 16-36). VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02-5.5). The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17-37), 47% (95% CI, 34-58), and 59% (95% CI, 42-72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4-15), 9.2% (95% CI, 2.6-21), and 9.2% (2.6-21) at 7, 14, and 21 days). CONCLUSIONS: The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Early versus delayed initiation of renal replacement therapy for acute kidney injury: an updated systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials. / Início precoce em comparação ao início tardio da terapia de substituição renal para lesão renal aguda: revisão sistemática atualizada, metanálise, metarregressão e análise sequencial de ensaios clínicos randomizados e controlados.

OBJECTIVE: To evaluate whether early initiation of renal replacement therapy is associated with lower mortality in patients with acute kidney injury compared to delayed initiation. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials comparing early versus delayed initiation of renal replacement therapy in patients with acute kidney injury without the life-threatening acute kidney injury-related symptoms of fluid overload or metabolic disorders. Two investigators extracted the data from the selected studies. The Cochrane Risk of Bias Tool was used to assess the quality of the studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to test the overall quality of the evidence. RESULTS: Six randomized controlled trials (1,292 patients) were included. There was no statistically significant difference between early and delayed initiation of renal replacement therapy regarding the primary outcome (OR 0.82; 95%CI, 0.48 - 1.42; p = 0.488), but there was an increased risk of catheter-related bloodstream infection when renal replacement therapy was initiated early (OR 1.77; 95%CI, 1.01 - 3.11; p = 0.047). The quality of evidence generated by our meta-analysis for the primary outcome was considered low due to the risk of bias of the included studies and the heterogeneity among them. CONCLUSION: Early initiation of renal replacement therapy is not associated with improved survival. However, the quality of the current evidence is low, and the criteria used for -early- and -delayed- initiation of renal replacement therapy are too heterogeneous among studies.

OBJETIVO: Avaliar se, em comparação ao início tardio, o início precoce da terapia de substituição renal se associa com menor mortalidade em pacientes com lesão renal aguda. MÉTODOS: Conduzimos uma revisão sistemática e metanálise de ensaios clínicos randomizados e controlados, que compararam terapia de substituição renal com início precoce àquela com início tardio em pacientes com lesão renal aguda, sem sintomas relacionados à insuficiência renal aguda que oferecessem risco à vida, como sobrecarga hídrica ou distúrbios metabólicos. Dois investigadores extraíram os dados a partir de estudos selecionados. Utilizaram-se a ferramenta Cochrane Risk of Bias, para avaliar a qualidade dos estudos, e a abordagem Grading of Recommendations Assessment, Development and Evaluation (GRADE), para testar a qualidade geral da evidência. RESULTADOS: Incluíram-se seis estudos clínicos randomizados e controlados (1.292 pacientes). Não houve diferença estatisticamente significante entre o início precoce e tardio da terapia de substituição renal, no que se referiu ao desfecho primário (OR 0,82; IC95% 0,48 - 1,42; p = 0,488). Foi maior o risco de infecção da corrente sanguínea relacionada ao cateter quando a terapia de substituição renal foi iniciada precocemente (OR 1,77; IC95% 1,01 - 3,11; p = 0,047). A qualidade da evidência gerada por nossa metanálise para o desfecho primário foi considerada baixa, em razão do risco de viés dos estudos incluídos e da heterogeneidade entre eles. CONCLUSÃO: O início precoce da terapia de substituição renal não se associou com melhora da sobrevivência. Entretanto, a qualidade da evidência atual é baixa, e os critérios utilizados para início precoce e tardio da terapia de substituição renal foram demasiadamente heterogêneos entre os estudos.

Início precoce em comparação ao início tardio da terapia de substituição renal para lesão renal aguda: revisão sistemática atualizada, metanálise, metarregressão e análise sequencial de ensaios clínicos randomizados e controlados / Early versus delayed initiation of renal replacement therapy for acute kidney injury: an updated systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials

RESUMO Objetivo: Avaliar se, em comparação ao início tardio, o início precoce da terapia de substituição renal se associa com menor mortalidade em pacientes com lesão renal aguda. Métodos: Conduzimos uma revisão sistemática e metanálise de ensaios clínicos randomizados e controlados, que compararam terapia de substituição renal com início precoce àquela com início tardio em pacientes com lesão renal aguda, sem sintomas relacionados à insuficiência renal aguda que oferecessem risco à vida, como sobrecarga hídrica ou distúrbios metabólicos. Dois investigadores extraíram os dados a partir de estudos selecionados. Utilizaram-se a ferramenta Cochrane Risk of Bias, para avaliar a qualidade dos estudos, e a abordagem Grading of Recommendations Assessment, Development and Evaluation (GRADE), para testar a qualidade geral da evidência. Resultados: Incluíram-se seis estudos clínicos randomizados e controlados (1.292 pacientes). Não houve diferença estatisticamente significante entre o início precoce e tardio da terapia de substituição renal, no que se referiu ao desfecho primário (OR 0,82; IC95% 0,48 - 1,42; p = 0,488). Foi maior o risco de infecção da corrente sanguínea relacionada ao cateter quando a terapia de substituição renal foi iniciada precocemente (OR 1,77; IC95% 1,01 - 3,11; p = 0,047). A qualidade da evidência gerada por nossa metanálise para o desfecho primário foi considerada baixa, em razão do risco de viés dos estudos incluídos e da heterogeneidade entre eles. Conclusão: O início precoce da terapia de substituição renal não se associou com melhora da sobrevivência. Entretanto, a qualidade da evidência atual é baixa, e os critérios utilizados para início precoce e tardio da terapia de substituição renal foram demasiadamente heterogêneos entre os estudos.

ABSTRACT Objective: To evaluate whether early initiation of renal replacement therapy is associated with lower mortality in patients with acute kidney injury compared to delayed initiation. Methods: We performed a systematic review and meta-analysis of randomized controlled trials comparing early versus delayed initiation of renal replacement therapy in patients with acute kidney injury without the life-threatening acute kidney injury-related symptoms of fluid overload or metabolic disorders. Two investigators extracted the data from the selected studies. The Cochrane Risk of Bias Tool was used to assess the quality of the studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to test the overall quality of the evidence. Results: Six randomized controlled trials (1,292 patients) were included. There was no statistically significant difference between early and delayed initiation of renal replacement therapy regarding the primary outcome (OR 0.82; 95%CI, 0.48 - 1.42; p = 0.488), but there was an increased risk of catheter-related bloodstream infection when renal replacement therapy was initiated early (OR 1.77; 95%CI, 1.01 - 3.11; p = 0.047). The quality of evidence generated by our meta-analysis for the primary outcome was considered low due to the risk of bias of the included studies and the heterogeneity among them. Conclusion: Early initiation of renal replacement therapy is not associated with improved survival. However, the quality of the current evidence is low, and the criteria used for -early- and -delayed- initiation of renal replacement therapy are too heterogeneous among studies.

Renal replacement therapy intensity for acute kidney injury and recovery to dialysis independence: a systematic review and individual patient data meta-analysis.

Background: There is no consensus whether higher intensity dose renal replacement therapy (RRT) compared with standard intensity RRT has survival benefit and achieves better renal recovery in acute kidney injury (AKI). Methods: In an individual patient data meta-analysis, we merged individual patient data from randomized controlled trials (RCTs) comparing high with standard intensity RRT in intensive care unit patients with severe AKI. The primary outcome was all-cause mortality. The secondary outcome was renal recovery assessed as the proportion of patients who were RRT dependent at key trial endpoints and by time to the end of RRT dependence. Results: Of the eight prospective RCTs assessing different RRT intensities, seven contributed individual patient data (n = 3682) to the analysis. Mortality was similar between the two groups at 28 days [769/1884 (40.8%) and 744/1798 (41.4%), respectively; P = 0.40] after randomization. However, more participants assigned to higher intensity therapy remained RRT dependent at the most common key study point of 28 days [e.g. 292/983 (29.7%) versus 235/943 (24.9%); relative risk 1.15 (95% confidence interval 1.00-1.33); P = 0.05]. Time to cessation of RRT through 28 days was longer in patients receiving higher intensity RRT (log-rank test P = 0.02) and when continuous renal replacement therapy was used as the initial modality of RRT (log-rank test P = 0.03). Conclusions: In severe AKI patients, higher intensity RRT does not affect mortality but appears to delay renal recovery. Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) identifier ACTRN12615000394549 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615000394549).

Determinants of gentamicin concentrations in critically ill patients: a population pharmacokinetic analysis.

When treating critically ill patients with gentamicin for severe infection, peak concentrations (Cmax) determine clinical efficacy and trough concentrations (Cmin) determine toxicity. Despite administration of body weight-standardised starting doses, a wide range of Cmax is generally observed. Furthermore, in therapeutic drug monitoring, several measures of renal function are used to predict appropriate Cmin and gentamicin dosing intervals, but the most accurate predictor is not known. This study aimed to quantify the impact of several patient parameters on gentamicin Cmax values and to determine which measure of renal function best predicts gentamicin clearance (CL). Clinical data and serum gentamicin levels were retrospectively collected from all critically ill patients treated with gentamicin at our intensive care unit between 1 January and 30 June 2011. Data were analysed using non-linear mixed-effects modelling (NONMEM v.7.1.2). A two-compartmental model was developed based on 303 gentamicin concentration-time data from 44 critically ill patients. Serum albumin levels explained 25% of interindividual variability in the volume of distribution (Vd). Creatinine clearance calculated from the creatinine concentration in a 6-h urine portion (CalcCLCr) resulted in acceptable estimation of gentamicin CL, whilst serum creatinine (SCr) and creatinine clearance estimated by the Cockcroft-Gault formula (CGCLCr) overestimated gentamicin CL and therefore underestimated Cmin. In conclusion, low albumin concentrations resulted in a larger Vd and lower Cmax of gentamicin. These results suggest that use of a higher gentamicin starting dose in critically ill patients with hypoalbuminaemia may prevent underdosing. Urinary CalcCLCr is a better predictor of Cmin than SCr or CGCLCr.

Acute kidney injury defined according to the 'Risk,' 'Injury,' 'Failure,' 'Loss,' and 'End-stage' (RIFLE) criteria after repair for a ruptured abdominal aortic aneurysm.

OBJECTIVE: Acute kidney injury (AKI) is a serious complication after repair of a ruptured abdominal aortic aneurysm (RAAA). In the present Society for Vascular Surgery (SVS)/International Society for CardioVascular Surgery (ISCVS) reporting standards patients are classified as no dialysis (grade I), as temporary dialysis (grade II), and as permanent dialysis or fatal outcome (grade III). However, AKI is a broad clinical syndrome including more than the requirement for renal replacement therapy. The recently introduced 'Risk,' 'Injury,' 'Failure,' 'Loss,' and 'End-stage' (RIFLE) classification for AKI comprises three severity categories based on serum creatinine and urine output ('Risk,' 'Injury,' and 'Failure'). The objective of the present study was to assess the incidence of AKI using the RIFLE criteria (AKIRIFLE). Secondary objectives were to assess the incidence of AKI as defined using the SVS/ISCVS reporting standards (AKISVS/ISCVS) and the association between AKIRIFLE and death. METHODS: This was an observational cohort study in 362 consecutive patients with an RAAA in three hospitals in Amsterdam (The Netherlands) between 2004 and 2011. The end points were the incidence of AKIRIFLE, of AKISVS/ISCVS, and the combined 30-day or in-hospital death rate. A multivariable logistic regression model was made to assess the association between AKIRIFLE and death after adjustment for preoperative shock profile (Glasgow Aneurysm Score) and postoperative shock profile (Acute Physiology and Chronic Health Evaluation [APACHE] II score, use of vasopressors, and fluid balance during the first 24 hours after intervention). RESULTS: AKIRIFLE occurred in 74% (267/362; 95% confidence interval [CI], 69%-78%), with 27% of these patients categorized as 'Risk' (71/267; 95% CI, 22%-32%), 39% categorized as 'Injury' (104/267, 95% CI, 33%-45%), and 34% categorized as 'Failure' (92/267; 95% CI, 29%-40%). AKISVS/ISCVS occurred in 48% (175/362; 95% CI, 43%-53%), with 53% of these categorized as 'grade I' (92/175; 95% CI, 45%-60%), 19% as 'grade II' (34/175; 95% CI, 14%-26%), and 28% as 'grade III' (49/175; 95% CI, 22%-35%). After multivariable adjustment for shock profiles the risk of dying in patients categorized as AKIRIFLE 'Failure' was greater than in patients without AKIRIFLE (adjusted odds ratio, 6.360; 95% CI, 2.231-18.130). CONCLUSIONS: The incidence of AKI defined according to the RIFLE criteria (74%) was greater than defined using the SVS/ISCVS reporting standards (48%) and patients categorized as 'Failure' using the RIFLE criteria had a greater risk of dying than patients without AKI. These results indicate that the problem of AKI is much bigger than previously anticipated and that minimizing injury to the kidney could be an important focus of future research on reducing the death rate after RAAA repair.

Association between renal replacement therapy in critically ill patients with severe acute kidney injury and mortality.

PURPOSE: To evaluate the characteristics and outcomes of critically ill patients with severe acute kidney injury (AKI) treated and not treated with renal replacement therapy (RRT). METHODS: Secondary analysis of a multi-centre cohort study. Primary exposure was RRT. Primary outcome was propensity and multi-variable adjusted-hospital mortality. RESULTS: We studied 1250 patients (71.3%) who received and 502 (28.7%) who did not receive RRT. Reasons for not starting RRT (not mutually exclusive) were limitations of support (33.6%, n = 169), adequate urine output (46.2%; n = 232), plan to observe (56.4%; n = 283), and advanced age (12.6%; n = 63). Mortality was higher in those not receiving RRT due to limitations and advanced age but lower for adequate urine output and plan to observe. Propensity and multi-variable adjusted analysis showed no statistical difference in hospital mortality (adj-OR 1.47; 95% CI, 0.93-2.24) in patients receiving RRT. Results were similar in a sensitivity analysis restricted to patients fulfilling risk, injury, failure, loss, end-stage kidney disease-FAILURE criteria (37.0%; n = 446) (adj-OR 1.36; 95% CI, 0.70-2.66). CONCLUSION: In this cohort, reasons for not starting RRT included limitations of support and perception of impending renal recovery. Despite similar risk of mortality after adjusting for selection bias and confounders, RRT-treated patients were fundamentally different from non-treated patients across a spectrum of variables that precludes valid comparison in observational data.

[Necrotising soft-tissue infections: diagnostics and treatment]. / Necrotiserende wekedeleninfecties: diagnostiek en behandeling.

Necrotising soft-tissue infections occur in the soft tissue compartment consisting of the dermis, subcutaneous tissue, superficial fascia (fascia of Scarpa), deep fascia and muscle. Although this severe and acutely life-threatening infection has a low incidence, both GPs and specialists will see a necrotizing soft-tissue infection more than once during their career. The mortality related to necrotising soft-tissue infections has been halved during the past 15 years from nearly 40 to 20% due to adequate treatment. Laboratory examination and X-ray findings could be of added value, but the gold standard remains biopsy of the fascia and Gram staining. Treatment consists of prompt volume resuscitation in case of sepsis, administration of broad spectrum antibiotics and surgical debridement; this debridement should be as skin-sparing as possible. The use of hyperbaric oxygen therapy has remained a controversial issue, unless a patient has gas gangrene, caused by Clostridium species. A multidisciplinary treatment and admission to a tertiary intensive care unit are indispensable for the treatment of a septic patient with necrotizing soft-tissue infection.

Systemic and urinary neutrophil gelatinase-associated lipocalins are poor predictors of acute kidney injury in unselected critically ill patients.

Background. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine have been suggested as potential early predictive biological markers of acute kidney injury (AKI) in selected critically ill patients. Methods. We performed a secondary analysis of a multicenter prospective observational cohort study of unselected critically ill patients. Results. The analysis included 140 patients, including 57 patients who did not develop AKI, 31 patients who developed AKI, and 52 patients with AKI on admission to the ICU. Levels of sNGAL and uNGAL on non-AKI days were significantly lower compared to levels of sNGAL on RIFLE(RISK) days, RIFLE(INJURY) days, and RIFLE(FAILURE) days. The AUC of sNGAL for predicting AKI was low: 0.45 (95% confidence interval (CI) 0.27-0.63) and 0.53 (CI 0.38-0.67), 2 days and 1 day before development of AKI, respectively. The AUC of uNGAL for predicting AKI was also low: 0.48 (CI 0.33-0.62) and 0.48 (CI 0.33-0.62), 2 days and 1 day before development of AKI, respectively. AUC of sNGAL and uNGAL for the prediction of renal replacement therapy requirement was 0.47 (CI 0.37-0.58) and 0.26 (CI 0.03-0.50). Conclusions. In unselected critically ill patients, sNGAL and uNGAL are poor predictors of AKI or RRT.

A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ill patients.

INTRODUCTION: The Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) is a consensus-based classification system for diagnosing acute kidney insufficiency (AKI), based on serum creatinine (SCr) and urine output criteria (RIFLESCr+UO). The urine output criteria, however, are frequently discarded and many studies in the literature applied only the SCr criteria (RIFLESCr). We diagnosed AKI using both RIFLE methods and compared the effects on time to AKI diagnosis, AKI incidence and AKI severity. METHODS: This was a prospective observational cohort study during four months in adult critically ill patients admitted to the ICU for at least 48 hours. During the first week patients were scored daily for AKI according to RIFLESCr+UO and RIFLESCr. We assessed urine output hourly and fluid balance daily. The baseline SCr was estimated if a recent pre-ICU admission SCr was unknown. Based on the two RIFLE methods for each patient we determined time to AKI diagnosis (AKI-0) and maximum RIFLE grade. RESULTS: We studied 260 patients. A pre-ICU admission SCr was available in 101 (39%) patients. The two RIFLE methods resulted in statistically significantly different outcomes for incidence of AKI, diagnosis of AKI for individual patients, distribution of AKI-0 and distribution of the maximum RIFLE grade. Discarding the RIFLE urine criteria for AKI diagnosis significantly underestimated the presence and grade of AKI on admission and during the first ICU week (P < 0,001) and significantly delayed the diagnosis of AKI (P < 0.001). Based on RIFLESCr 45 patients had no AKI on admission but subsequently developed AKI. In 24 of these patients (53%) AKI would have been diagnosed at least one day earlier if the RIFLE urine criteria had been applied. Mortality rate in the AKI population was 38% based on RIFLESCr and 24% based on RIFLESCr+UO (P = 0.02). CONCLUSIONS: The use of RIFLE without the urine criteria significantly underscores the incidence and grade of AKI, significantly delays the diagnosis of AKI and is associated with higher mortality.

Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation.

INTRODUCTION: Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. OBJECTIVE: To determine whether ventilator settings in critically ill patients without acute lung injury (ALI) at onset of mechanical ventilation affect the development of AKI. DESIGN, SETTING, AND PATIENTS: Secondary analysis of a randomized controlled trial (N = 150), comparing conventional tidal volume (V(T), 10 mL/kg) with low tidal volume (V(T), 6 mL/kg) mechanical ventilation in critically ill patients without ALI at randomization. During the first 5 days of mechanical ventilation, the RIFLE class was determined daily, whereas neutrophil gelatinase-associated lipocalin and cystatin C levels were measured in plasma collected on days 0, 2, and 4. RESULTS: Eighty-six patients had no AKI at inclusion, and 18 patients (21%) subsequently developed AKI, but without significant difference between ventilation strategies. (Cumulative hazard, 0.26 vs 0.23; P = .88.) The courses of neutrophil gelatinase-associated lipocalin and cystatin C plasma levels did not differ significantly between randomization groups. CONCLUSION: In the present study in critically patients without ALI at onset of mechanical ventilation, lower tidal volume ventilation did not reduce the development or worsening of AKI compared with conventional tidal volume ventilation.

Cooling the crisis: therapeutic hypothermia after sickle cardiac arrest.

OBJECTIVE: The management of patients with sickle-cell disease and cardiac arrest presents special challenges. Mild therapeutic hypothermia may improve survival and neurologic outcome after cardiac arrest, however, it may also precipitate sickling in patients with sickle-cell disease. Rigorous exchange transfusion may enable mild therapeutic hypothermia after cardiac arrest in patients with sickle-cell disease. DESIGN: Case report. SETTING: A 28-bed closed format intensive care unit in a university hospital. PATIENT: A 41-yr-old man with a double-heterozygous sickle-cell ß-0 thalassemia was admitted to the internal ward for acute chest syndrome. On the third day he developed cardiac arrest. Return of spontaneous circulation was achieved after 45 mins of full cardiopulmonary resuscitation. INTERVENTIONS: Postcardiac arrest rigorous exchange transfusion and mild therapeutic hypothermia were applied. MEASUREMENT AND MAIN RESULT: Erythrocytapheresis lowered the content of hemoglobin S to 5.6%, and therapeutic hypothermia was successfully maintained for 24 hrs without adverse events. After 2 critical weeks, the patient regained full consciousness. CONCLUSION: Therapeutic hypothermia after cardiac arrest is feasible following rigorous exchange transfusion in patients with sickle-cell disease.

Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy.

PURPOSE: To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). METHODS: Multicenter prospective observational cohort study in patients ≥18 years old and with expected ICU stay ≥72 h. The RIFLE class for AKI was calculated daily, while sCyC and uCyC were determined on days 0, 1, and alternate days until ICU discharge. Test characteristics were calculated to assess the diagnostic performance of CyC. RESULTS: One hundred fifty-one patients were studied, and three groups were defined: group 0 (N = 60), non-AKI; group 1 (N = 35), AKI after admission; and group 2 (N = 56), AKI at admission. We compared the two days prior to developing AKI from group 1 with the first two study days from group 0. On Day -2, median sCyC was significantly higher (0.93 versus 0.80 mg/L, P = 0.01), but not on Day -1 (0.98 versus 0.86 mg/L, P = 0.08). The diagnostic performance for sCyC was fair on Day -2 [area under the curve (AUC) 0.72] and poor on Day -1 (AUC 0.62). Urinary CyC had no diagnostic value on either of the two days prior to AKI (AUC <0.50). RRT was started in 14 patients with AKI; sCyC and uCyC determined on Day 0 were poor predictors for the need for RRT (AUC ≤0.66). CONCLUSIONS: In this study, sCyC and uCyC were poor biomarkers for prediction of AKI and the need for RRT.