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1. Serial Urinary C-C Motif Chemokine Ligand 14 and Risk of Persistent Severe Acute Kidney Injury

Author: Prowle, JR, Artigas, A, Bagshaw, SM, Forni, LG, Heung, M, Hoste, Eric, Marlies, O, Koyner, JL, Chawla, L, Kampf, JP, Kwan, T, McPherson, P, and Kellum, JA
Subjects: Medicine and Health Sciences, Critical illness, Prognosis, Biomarkers, C-C motif chemokine ligand 14, Acute kidney injury
Abstract: Retrospective observational study. Data derived from two multinational ICU studies (Ruby and Sapphire). Critically ill patients with early stage 2-3 AKI. None. We analyzed three consecutive uCCL14 measurements at 12-hour intervals after diagnosis of stage 2-3 AKI by Kidney Disease Improving Global Outcomes criteria. Primary outcome was persistent severe AKI, defined as 72 consecutive hours of stage 3 AKI, death, or receipt of dialysis prior to 72 hours. uCCL14 was measured using the NEPHROCLEAR uCCL14 Test on the Astute 140 Meter (Astute Medical, San Diego, CA). Based on predefined, validated cutoffs, we categorized uCCL14 as: low (≤ 1.3 ng/mL), medium (> 1.3 to ≤ 13 ng/mL), or high (> 13 ng/mL). Seventy-five of 417 patients with three consecutive uCCL14 measurements developed persistent severe AKI. Initial uCCL14 category strongly correlated with primary endpoint and, in most cases (66%), uCCL14 category was unchanged over the first 24 hours. Compared with no change and accounting for baseline category, decrease in category was associated with decreased odds of persistent severe AKI (odds ratio [OR], 0.20; 95% CI, 0.08-0.45; p < 0.001) and an increase in category with increased odds (OR, 4.04; 95% CI, 1.75-9.46; p = 0.001). In one-third of patients with moderate to severe AKI uCCL14 risk category altered over three serial measurements and such changes were associated with altered risk for persistent severe AKI. Serial CCL-14 measurement may detect progression or resolution of underlying kidney pathology and help refine AKI prognosis.
Published: 2023

2. Bioimpedance as a measure of fluid overload in patients recently admitted to intensive care

Author: O'Connor, M, Galtrey, E, Kirwan, CJ, and Prowle, JR
Published: 2015
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3. Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom

Author: Patel, BV, Haar, S, Handslip, R, Lee, TM-L, Patel, S, Harston, JA, Hosking-Jervis, F, Kelly, D, Sanderson, B, Bogatta, B, Tatham, K, Welters, I, Camporota, L, Gordon, AC, Komorowski, M, Antcliffe, D, Prowle, JR, Puthucheary, Z, and Faisal, AA
Abstract: Background To date the description of mechanically ventilated patients with Coronavirus Disease 2019 (COVID-19) has focussed on admission characteristics with no consideration of the dynamic course of the disease. Here, we present a data-driven analysis of granular, daily data from a representative proportion of patients undergoing invasive mechanical ventilation (IMV) within the United Kingdom (UK) to evaluate the complete natural history of COVID-19. Methods We included adult patients undergoing IMV within 48 hours of ICU admission with complete clinical data until death or ICU discharge. We examined factors and trajectories that determined disease progression and responsiveness to ARDS interventions. Our data visualisation tool is available as a web-based widget (https://www.CovidUK.ICU). Findings Data for 623 adults with COVID-19 who were mechanically ventilated between 01 March 2020 and 31 August 2020 were analysed. Mortality, intensity of mechanical ventilation and severity of organ injury increased with severity of hypoxaemia. Median tidal volume per kg across all mandatory breaths was 5.6 [IQR 4.7-6.6] mL/kg based on reported body weight, but 7.0 [IQR 6.0-8.4] mL/kg based on calculated ideal body weight. Non-resolution of hypoxaemia over the first week of IMV was associated with higher ICU mortality (59.4% versus 16.3%; P
Published: 2020

4. Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference

Author: Ostermann, M, Bellomo, R, Burdmann, EA, Doi, K, Endre, ZH, Goldstein, SL, Kane-Gill, SL, Liu, KD, Prowle, JR, Shaw, AD, Srisawat, N, Cheung, M, Jadoul, M, Winkelmayer, WC, Kellum, JA, Ostermann, M, Bellomo, R, Burdmann, EA, Doi, K, Endre, ZH, Goldstein, SL, Kane-Gill, SL, Liu, KD, Prowle, JR, Shaw, AD, Srisawat, N, Cheung, M, Jadoul, M, Winkelmayer, WC, and Kellum, JA
Abstract: In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). The guideline was derived from evidence available through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing AKI. In April of 2019, KDIGO held a controversies conference entitled Acute Kidney Injury with the following goals: determine best practices and areas of uncertainty in treating AKI; review key relevant literature published since the 2012 KDIGO AKI guideline; address ongoing controversial issues; identify new topics or issues to be revisited for the next iteration of the KDIGO AKI guideline; and outline research needed to improve AKI management. Here, we present the findings of this conference and describe key areas that future guidelines may address.
Published: 2020

5. Acute kidney injury of all severity is associated with extended hospitalization after critical illness

Author: Prowle, JR, Kolic, I, Purdell-Lewis, J, and Kirwan, CJ
Published: 2014
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6. Perioperative fluid balance and postoperative changes in serum creatinine in patients admitted to critical care after elective major surgery

Author: Rajendram, R and Prowle, JR
Published: 2014
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7. Survivors of acute kidney injury requiring renal replacement therapy rarely receive follow-up: identification of an unmet need

Author: Kirwan, CJ, Taylor, R, and Prowle, JR
Published: 2013
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8. Estimated glomerular filtration rate based on hospital discharge creatinine may significantly overestimate renal function and underestimate chronic kidney disease in survivors of critical illness

Author: Kolic, I, Purdell-Lewis, J, Kirwan, CJ, and Prowle, JR
Published: 2013
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9. Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study (vol 9, 99, 2019)

Author: Harrois, A, Anstey, JR, Taccone, FS, Udy, AA, Citerio, G, Duranteau, J, Ichai, C, Badenes, R, Prowle, JR, Ercole, A, Oddo, M, Schneider, A, van der Jagt, M, Wolf, S, Helbok, R, Nelson, DW, Skrifvars, MB, Cooper, DJ, Bellomo, R, Long, K, Rodrigues, A, Lozano, A, Saxby, E, Vargiolu, A, Quintard, H, Robba, C, Sisson, A, Allen, G, Baro, N, Kofler, M, Harrois, A, Anstey, JR, Taccone, FS, Udy, AA, Citerio, G, Duranteau, J, Ichai, C, Badenes, R, Prowle, JR, Ercole, A, Oddo, M, Schneider, A, van der Jagt, M, Wolf, S, Helbok, R, Nelson, DW, Skrifvars, MB, Cooper, DJ, Bellomo, R, Long, K, Rodrigues, A, Lozano, A, Saxby, E, Vargiolu, A, Quintard, H, Robba, C, Sisson, A, Allen, G, Baro, N, and Kofler, M
Abstract: Following publication of the original article [1], we were notified that the collaborators' names part of the "The TBI Collaborative" group has not been indexed in Pubmed. Below the collaborators names full list.
Published: 2019

10. Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study

Author: Harrois, A, Anstey, JR, Taccone, FS, Udy, AA, Citerio, G, Duranteau, J, Ichai, C, Badenes, R, Prowle, JR, Ercole, A, Oddo, M, Schneider, A, van Der Jagt, M, Wolf, S, Helbok, R, Nelson, DW, Skrifvars, MB, Cooper, DJ, Bellomo, R, Long, K, Rodrigues, A, Lozano, A, Saxby, E, Vargiolu, A, Quintard, H, Robba, C, Sisson, A, Allen, G, Baro, N, Kofler, M, Harrois, A, Anstey, JR, Taccone, FS, Udy, AA, Citerio, G, Duranteau, J, Ichai, C, Badenes, R, Prowle, JR, Ercole, A, Oddo, M, Schneider, A, van Der Jagt, M, Wolf, S, Helbok, R, Nelson, DW, Skrifvars, MB, Cooper, DJ, Bellomo, R, Long, K, Rodrigues, A, Lozano, A, Saxby, E, Vargiolu, A, Quintard, H, Robba, C, Sisson, A, Allen, G, Baro, N, and Kofler, M
Abstract: BACKGROUND: In traumatic brain injury (TBI) patients desmopressin administration may induce rapid decreases in serum sodium and increase intracranial pressure (ICP). AIM: In an international multi-centre study, we aimed to report changes in serum sodium and ICP after desmopressin administration in TBI patients. METHODS: We obtained data from 14 neurotrauma ICUs in Europe, Australia and UK for severe TBI patients (GCS ≤ 8) requiring ICP monitoring. We identified patients who received any desmopressin and recorded daily dose, 6-hourly serum sodium, and 6-hourly ICP. RESULTS: We studied 262 severe TBI patients. Of these, 39 patients (14.9%) received desmopressin. Median length of treatment with desmopressin was 1 [1-3] day and daily intravenous dose varied between centres from 0.125 to 10 mcg. The median hourly rate of decrease in serum sodium was low (- 0.1 [- 0.2 to 0.0] mmol/L/h) with a median period of decrease of 36 h. The proportion of 6-h periods in which the rate of natremia correction exceeded 0.5 mmol/L/h or 1 mmol/L/h was low, at 8% and 3%, respectively, and ICPs remained stable. After adjusting for IMPACT score and injury severity score, desmopressin administration was independently associated with increased 60-day mortality [HR of 1.83 (1.05-3.24) (p = 0.03)]. CONCLUSIONS: In severe TBI, desmopressin administration, potentially representing instances of diabetes insipidus is common and is independently associated with increased mortality. Desmopressin doses vary markedly among ICUs; however, the associated decrease in natremia rarely exceeds recommended rates and median ICP values remain unchanged. These findings support the notion that desmopressin therapy is safe.
Published: 2019

11. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II

Author: Tumlin, JA, Murugan, R, Deane, AM, Ostermann, M, Busse, LW, Ham, KR, Kashani, K, Szerlip, HM, Prowle, JR, Bihorac, A, Finkel, KW, Zarbock, A, Forni, LG, Lynch, SJ, Jensen, J, Kroll, S, Chawla, LS, Tidmarsh, GF, Bellomo, R, Tumlin, JA, Murugan, R, Deane, AM, Ostermann, M, Busse, LW, Ham, KR, Kashani, K, Szerlip, HM, Prowle, JR, Bihorac, A, Finkel, KW, Zarbock, A, Forni, LG, Lynch, SJ, Jensen, J, Kroll, S, Chawla, LS, Tidmarsh, GF, and Bellomo, R
Abstract: OBJECTIVE: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. DESIGN: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. SETTING: ICUs. PATIENTS: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). INTERVENTIONS: IV angiotensin II or placebo. MEASUREMENTS AND MAIN RESULTS: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. CONCLUSIONS: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.
Published: 2018

12. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial

Author: Gordon, AC, Mason, AJ, Thirunavukkarasu, N, Perkins, GD, Cecconi, M, Cepkova, M, Pogson, DG, Aya, HD, Anjum, A, Frazier, GJ, Santhakumaran, S, Ashby, D, Brett, SJ, VANISH Investigators, COLLABORATORS, Warwick, J, Griffiths, S, Cross, M, Mason, A, Frazier, G, Das, N, Bellingan, G, Gordon, A, Brett, S, Perkins, G, Beale, R, Banks, F, Watts, T, Andrews, P, McAuley, D, Collier, T, Templeton, M, Errington, E, Gladas, K, Banach, D, Kitson, D, Matthew-Thomas, R, Hauer, V, Ochelli-Okpue, A, Stotz, M, Ostermann, M, Lei, K, Chan, K, Smith, J, Shankar-Hari, M, Carungcong, J, Handy, J, Hopkins, P, Harris, CL, Wade-Smith, F, Birch, S, Hurst, T, Mellinghoff, J, Di Tomasso, N, Ebm, C, Iannucceli, F, Kirwan, CJ, Creary, T, Correia, C, Prowle, JR, Jaques, N, Brown, A, Walden, A, Joscak, J, Bangalan, J, Tamm, T, Snow, L, Stapleton, C, Pahary, SM, Gould, T, Bewley, J, Sweet, K, Grimmer, L, Shah, S, Williams, S, Pulletz, M, Golder, K, Bolger, C, Salmon, K, Skinner, B, Vickers, E, Scott, M, Rose, S, Lamb, N, Mouland, J, Pogson, D, Bullock, L, Bland, M, Harrison-Briggs, D, Wilkinson, K, Krige, A, Ward, G, Ting, J, and Bassford, C
Abstract: Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. clinicaltrials.gov Identifier: ISRCTN 20769191.
Published: 2016

13. Renal replacement therapy in acute kidney injury: controversy and consensus

Author: Ronco, C, Ricci, Z, De Backer, D, Kellum, JA, Taccone, FS, Joannidis, M, Pickkers, P, Cantaluppi, V, Turani, F, Saudan, P, Bellomo, R, Joannes-Boyau, O, Antonelli, M, Payen, D, Prowle, JR, Vincent, J-L, Ronco, C, Ricci, Z, De Backer, D, Kellum, JA, Taccone, FS, Joannidis, M, Pickkers, P, Cantaluppi, V, Turani, F, Saudan, P, Bellomo, R, Joannes-Boyau, O, Antonelli, M, Payen, D, Prowle, JR, and Vincent, J-L
Abstract: Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future.
Published: 2015

14. ESICM LIVES 2016: part two : Milan, Italy. 1-5 October 2016

Author: Sivakumar, S, Taccone, FS, Desai, KA, Lazaridis, C, Skarzynski, M, Sekhon, M, Henderson, W, Griesdale, D, Chapple, L, Deane, A, Williams, L, Ilia, S, Henderson, A, Hugill, K, Howard, P, Roy, A, Bonner, S, Monteiro, E, Baudouin, S, Ramírez, CS, Escalada, SH, Banaszewski, M, Sertedaki, A, Kaymak, Ç, Viera, MA, Santana, MC, Balcázar, LC, Monroy, NS, Campelo, FA, Vázquez, CF, Santana, PS, Cerejo, A, Santana, SR, Charmadari, E, Carteron, L, Kovach, L, Patet, C, Quintard, H, Solari, D, Bouzat, P, Oddo, M, Wollersheim, T, Malleike, J, Haas, K, Stratakis, CA, Rocha, AP, Carbon, N, Şencan, I, Schneider, J, Birchmeier, C, Fielitz, J, Spuler, S, Weber-Carstens, S, Enseñat, L, Pérez-Madrigal, A, Briassouli, E, Saludes, P, Proença, L, Elsayed, AA, Meço, B, Gruartmoner, G, Espinal, C, Mesquida, J, Huber, W, Eckmann, M, Elkmann, F, Goukos, D, Gruber, A, Lahmer, T, Mayr, U, Herner, A, Özçelik, M, Abougabal, AM, Schellnegger, R, Schmid, RM, Ayoub, W, Psarra, K, Samy, W, Esmat, A, Battah, A, Mukhtar, S, Mongkolpun, W, Ünal, N, Cortés, DO, Beshey, BN, Cordeiro, CP, Vincent, JL, Leite, MA, Creteur, J, Funcke, S, Groesdonk, H, Saugel, B, Wagenpfeil, G, Wagenpfeil, S, Reuter, DA, Fernandez, MM, Alzahaby, KM, Botoula, E, Fernandez, R, Magret, M, González-Castro, A, Bouza, MT, Ibañez, M, García, C, Balerdi, B, Jenni-Moser, B, Mas, A, Arauzo, V, Tsagarakis, S, Añón, JM, Pozzebon, S, Ruiz, F, Ferreres, J, Tomás, R, Alabert, M, Tizón, AI, Altaba, S, Jeitziner, MM, Llamas, N, Haroon, BA, Edul, VS, Goligher, EC, Fan, E, Herridge, M, Ortiz, AB, Vorona, S, Sklar, M, Dres, M, Rittayamai, N, Lanys, A, Schreiber, J, Mageira, E, Urrea, C, Tomlinson, G, Reid, WD, Rubenfeld, GD, Kavanagh, BP, Cristallini, S, Brochard, LJ, Ferguson, ND, Neto, AS, De Abreu, MG, Routsi, C, Imiela, J, Galassi, MS, Pelosi, P, Schultz, MJ, PRoVENT investigators and the PROVE Network, Guérin, C, Papazian, L, Reignier, J, Lheureux, O, Ayzac, L, Nanas, S, Loundou, A, Forel, JM, Sales, FL, Rolland-Debord, C, Bureau, C, Poitou, T, Clavel, M, Perbet, S, Terzi, N, Kouatchet, A, Briassoulis, G, Brasseur, A, Similowski, T, Demoule, A, De Moraes, KC, Hunfeld, N, Trogrlic, Z, Ladage, S, Osse, RJ, Koch, B, Rietdijk, W, Boscolo, A, Devlin, J, Van der Jagt, M, Picetti, E, Batista, CL, Ceccarelli, P, Mensi, F, Malchiodi, L, Risolo, S, Rossi, I, Bertini, D, Antonini, MV, Servadei, F, Caspani, ML, Roquilly, A, Júnior, JA, Lasocki, S, Seguin, P, Geeraerts, T, Perrigault, PF, Campello, E, Dahyot-Fizelier, C, Paugam-Burtz, C, Cook, F, Cinotti, R, Dit Latte, DD, Mahe, PJ, Marcari, TB, Fortuit, C, Feuillet, F, Lucchetta, V, Asehnoune, K, Marzorati, C, Spina, S, Scaravilli, V, Vargiolu, A, Riva, M, Giussani, C, Lobato, R, Sganzerla, E, Hravnak, M, Osaku, EF, Citerio, G, Barbadillo, S, De Molina, FJ, Álvarez-Lerma, F, Rodríguez, A, SEMICYUC/GETGAG Working Group, Zakharkina, T, Martin-Loeches, I, Castro, CS, Matamoros, S, Fuhrmann, V, Piasentini, E, Povoa, P, Yousef, K, Torres, A, Kastelijn, J, Hofstra, JJ, De Jong, M, Schultz, M, Sterk, P, Artigas, A, De Souza, LM, Aktepe, O, Bos, LJ, Moreau, AS, Chang, Y, Salluh, J, Rodriguez, A, Nseir, S, TAVeM study group, De Jong, E, Fildisis, G, Rodrigues, FF, Van Oers, JA, Beishuizen, A, Girbes, AR, Nijsten, MW, Crago, E, De Lange, DW, Bonvicini, D, Labate, D, Benacchio, L, Radu, CM, Olivieri, A, Stepinska, J, Wruck, ML, Pizzirani, E, Lopez-Delgado, JC, Gonzalez-Romero, M, Fuentes-Mila, V, Berbel-Franco, D, Friedlander, RM, Romera-Peregrina, I, Manesso, L, Martinez-Pascual, A, Perez-Sanchez, J, Abellan-Lencina, R, Correa, NG, Ávila-Espinoza, RE, Moreno-Gonzalez, G, Sbraga, F, Griffiths, S, Grocott, MP, Creagh-Brown, B, Simioni, P, Abdelmonem, SA, POPC-CB investigators, Doyle, J, Wilkerson, P, Pelegrini, AM, Soon, Y, Huddart, S, Dickinson, M, Riga, A, Zuleika, A, Ori, C, Miyamoto, K, Kawazoe, Y, Tahon, SA, Morimoto, T, Yamamoto, T, Eid, RA, Fuke, A, Hashimoto, A, Koami, H, Beppu, S, Su, H, Katayama, Y, Ito, M, Ohta, Y, Yamamura, H, Helmy, TA, DESIRE (DExmedetomidine for Sepsis in ICU Randomized Evaluation) Trial Investigators, Timenetsky, KT, Rygård, SL, Holst, LB, Wetterslev, J, Lam, YM, Johansson, PI, Perner, A, Soliman, IW, Van Dijk, D, Van Delden, JJ, Meligy, HS, Cazati, D, Cremer, OL, Slooter, AJ, Willis, K, Peelen, LM, McWilliams, D, Snelson, C, Neves, AD, Loudet, CI, Busico, M, Vazquez, D, Villalba, D, Lobato, M, Puig, F, Kott, M, Pullar, V, Veronesi, M, Lischinsky, A, López, FJ, Mori, LB, Plotnikow, G, Díaz, A, Giannasi, S, Hernandez, R, Krzisnik, L, Diniz, PS, Hubner, RP, Cecotti, C, Dunn-Siegrist, I, Viola, L, Lopez, R, Sottile, JP, Benavent, G, Estenssoro, E, Chen, CM, Lai, CC, Cheng, KC, Costa, CR, Rocha, LL, Chou, W, Chan, KS, Pugin, J, Roeker, LE, Horkan, CM, Gibbons, FK, Christopher, KB, Weijs, PJ, Mogensen, KM, Furche, M, Rawn, JD, Cavalheiro, AM, Robinson, MK, Tang, Z, Gupta, S, Qiu, C, Ouyang, B, Cai, C, Guan, X, Tsang, JL, Regueira, T, Cea, L, Topeli, A, Lucinio, NM, Carlos, SJ, Elisa, B, Puebla, C, Vargas, A, Govil, D, Poulsen, MK, De Guadiana-Romualdo, LG, Thomsen, LP, Kjærgaard, S, Rees, SE, Karbing, DS, Schwedhelm, E, Frank, S, Müller, MC, Carbon, NM, Skrypnikov, V, Rebollo-Acebes, S, Srinivasan, S, Pickerodt, PA, Falk, R, Mahlau, A, Santos, ER, Lee, A, Inglis, R, Morgan, R, Barker, G, Esteban-Torrella, P, Kamata, K, Abe, T, Patel, SJ, Saitoh, D, Tokuda, Y, Green, RS, Norrenberg, M, Butler, MB, Erdogan, M, Hwa, HT, Jiménez-Sánchez, R, Gil, LJ, Vaquero, RH, Rodriguez-Ruiz, E, Lago, AL, N, JK, Allut, JL, Gestal, AE, Gleize, A, Gonzalez, MA, Thomas-Rüddel, DO, Jiménez-Santos, E, Schwarzkopf, D, Fleischmann, C, Reinhart, K, Suwanpasu, S, Sattayasomboon, Y, Filho, NM, Gupta, A, Oliveira, JC, Preiser, JC, Ballalai, CS, Zitta, K, Ortín-Freire, A, De Lucia, CV, Araponga, GP, Veiga, LN, Silva, CS, Garrido, ME, Ramos, BB, Ricaldi, EF, Gomes, SS, Tomar, DS, Simón, IF, Hernando-Holgado, A, GEMINI, Gemmell, L, MacKay, A, Wright, C, Docking, RI, Doherty, P, Black, E, Stenhouse, P, Plummer, MP, Finnis, ME, Albaladejo-Otón, MD, Carmona, SA, Shafi, M, Phillips, LK, Kar, P, Bihari, S, Biradar, V, Moodie, S, Horowitz, M, Shaw, JE, Deane, AM, Coelho, L, Yatabe, T, Valhonrat, IL, Inoue, S, Harne, R, Sakaguchi, M, Egi, M, Abdelhamid, YA, Motta, MF, Domínguez, JP, Arora, DP, Hokka, M, Pattinson, KT, Mizobuchi, S, Pérez, AG, Abellán, AN, Plummer, M, Giersch, E, Talwar, N, Summers, M, Pelenz, M, Hatzinikolas, S, Heller, S, Chapman, M, Jones, K, Almudévar, PM, Schweizer, R, Jacquet-Lagreze, M, Portran, P, Rabello, L, Mazumdar, S, Junot, S, Allaouchiche, B, Fellahi, JL, Guerci, P, Ergin, B, Lange, K, Kapucu, A, Ince, C, Cioccari, L, Luethi, N, Crisman, M, Papakrivou, EE, Bellomo, R, Mårtensson, J, Shinotsuka, CR, Fagnoul, D, Kluge, S, Orbegozo, D, Makris, D, Thooft, A, Brimioulle, S, Dávila, F, Iwasaka, H, Brandt, B, Tahara, S, Nagamine, M, Ichigatani, A, Cabrera, AR, Zepeda, EM, Granillo, JF, Manoulakas, E, Sánchez, JS, Montoya, AA, Rubio, JJ, Montenegro, AP, Blanco, GA, Robles, CM, Drolz, A, Horvatits, T, Roedl, K, Rutter, K, Tsolaki, B, Funk, GC, Póvoa, P, Ramos, AJ, Schneeweiss, B, Sabetian, G, Pooresmaeel, F, Zand, F, Ghaffaripour, S, Farbod, A, Tabei, H, Taheri, L, TAVeM study Group, Karadodas, B, Reina, Á, Anandanadesan, R, Metaxa, V, Teixeira, C, Pereira, SM, Hernández-Marrero, P, Carvalho, AS, Beckmann, M, Hartog, CS, Varis, E, Raadts, A, López, NP, Zakynthinos, E, Robertsen, A, Førde, R, Skaga, NO, Helseth, E, Honeybul, S, Ho, K, Vazquez, AR, Lopez, PM, Gonzalez, MN, Ortega, PN, Pérez, MA, Sola, EC, Garcia, IP, Spasova, T, De la Torre-Prados, MV, Kopecky, O, Rusinova, K, Pettilä, V, Waldauf, P, Cepeplikova, Z, Balik, M, Ordoñez, PF, Apolo, DX, Almudevar, PM, Martin, AD, Muñoz, JJ, Poukkanen, M, Castañeda, DP, Villamizar, PR, Ramos, JV, Pérez, LP, Lucendo, AP, Villén, LM, Ejarque, MC, Estella, A, Camps, VL, Neitzke, NM, Encinares, VS, Martín, MC, Masnou, N, Bioethics work group of SEMICYUC, Barbosa, S, Varela, A, Palma, I, López, FM, Cristina, L, Nunes, E, Jacob, S, Pereira, I, Campello, G, Ibañez, MP, Granja, C, Pande, R, Pandey, M, Varghese, S, Chanu, M, García, IP, Van Dam, MJ, Schildhauer, C, Karlsson, S, Ter Braak, EW, Gracia, M, Viciana, R, Montero, JG, Recuerda, M, Fontaiña, LP, Tharmalingam, B, Kovari, F, Zöllner, C, Rose, L, Mcginlay, M, Amin, R, Burns, K, Connolly, B, Hart, N, Labrador, G, Jouvet, P, Katz, S, Leasa, D, Takala, J, Izurieta, JR, Mawdsley, C, Mcauley, D, Blackwood, B, Denham, S, Worrall, R, Arshad, M, Cangueiro, TC, Isherwood, P, Wilkman, E, Khadjibaev, A, Guerrero, JJ, Sabirov, D, Rosstalnaya, A, Parpibaev, F, Sharipova, V, Guzman, CI, FINNAKI Study Group, Poulose, V, Renal Transplantation HUVR, Lundberg, OH, Koh, J, Calvert, S, Cha, YS, Lee, SJ, Tyagi, N, Rajput, RK, Birri, PN, Taneja, S, Singh, VK, Sharma, SC, Mittal, S, Quint, M, Kam, JW, Rao, BK, Ayachi, J, Fraj, N, Romdhani, S, Bergenzaun, L, Khedher, A, Meddeb, K, Sma, N, Azouzi, A, Bouneb, R, Giribet, A, Adeniji, K, Chouchene, I, Yeter, H, El Ghardallou, M, Rydén, J, Boussarsar, M, Jennings, R, Walter, E, Ribeiro, JM, Moniz, I, Marçal, R, Santos, AC, Young, R, Candeias, C, E Silva, ZC, Rosenqvist, M, Kara, A, Gomez, SE, Nieto, OR, Gonzalez, JA, Cuellar, AI, Mildh, H, Korhonen, AM, Shevill, DD, Elke, G, Moraes, MM, Ala-Kokko, T, Reinikainen, M, Robertson, E, Garside, P, Tavladaki, T, Isotti, P, De Vecchi, MM, Perduca, AE, Cuervo, MA, Melander, O, Negro, A, Villa, G, Manara, DF, Cabrini, L, Zangrillo, A, Frencken, JF, Spanaki, AM, Van Baal, L, Donker, DW, Chew, MS, Cuervo, RA, Horn, J, Van der Poll, T, Van Klei, WA, Bonten, MJ, Menard, CE, Kumar, A, Dimitriou, H, Rimmer, E, Doucette, S, Esteban, MA, Turgeon, AF, Houston, BL, Houston, DS, Zarychanski, R, Pinto, BB, Carrara, M, Ferrario, M, Bendjelid, K, Kondili, E, Nunes, J, Fraile, LI, Diaz, P, Silva, G, Escórcio, S, Chaves, S, Jardim, M, Fernandes, N, Câmara, M, Duarte, R, Pereira, CA, Choulaki, C, Mittelbrum, CP, Vieira, J, Nóbrega, JJ, De Oca-Sandoval, MA, Sánchez-Rodríguez, A, Joya-Galeana, JG, Correa-Morales, A, Camarena-Alejo, G, Aguirre-Sánchez, J, Franco-Granillo, J, Albaiceta, GM, Meleti, E, Soliman, M, Al Azab, A, El Hossainy, R, Nagy, H, Nirmalan, M, Crippa, IA, Cavicchi, FZ, Koeze, J, Kafetzopoulos, D, Chaari, A, Hakim, KA, Hassanein, H, Etman, M, El Bahr, M, Bousselmi, K, Khalil, ES, Kauts, V, Tsolakoglou, I, Casey, WF, Imahase, H, Georgopoulos, D, Sakamoto, Y, Yamada, KC, Miike, T, Nagashima, F, Iwamura, T, Keus, F, Hummitzsch, L, Kishihara, Y, Heyland, D, Spiezia, L, Dieperink, W, Souza, RB, Yasuda, H, Martins, AM, Liberatore, AM, Kang, YR, Nakamae, MN, La Torre, AG, Vieira, JC, Koh, IH, Hanslin, K, Wilske, F, Van der Horst, IC, Jaskowiak, JL, Skorup, P, Sjölin, J, Lipcsey, M, Long, WJ, Zhen, CE, Vakalos, A, Avramidis, V, Wu, SH, Shyu, LJ, Rebollo, S, Van Meurs, M, Li, CH, Yu, CH, Chen, HC, Wang, CH, Lin, KH, Aray, ZE, Gómez, CF, Tsvetanova-Spasova, T, Tejero, AP, Monge, DD, Zijlstra, JG, Losada, VM, Tarancón, CM, Cortés, SD, Gutiérrez, AM, Álvarez, TP, Rouze, A, Jaffal, K, Six, S, Jimenez, R, Nuevo-Ortega, P, Stolz, K, Roberts, S, Cattoen, V, Arnal, JM, Saoli, M, Novotni, D, Garnero, A, Becher, T, Torrella, PE, Buchholz, V, Schädler, D, Rueda-Molina, C, Caballero, CH, Frerichs, I, Weiler, N, Eronia, N, Mauri, T, Gatti, S, Maffezzini, E, Fernandez, A, Bronco, A, Alban, L, Sasso, T, Marenghi, C, Isgro, G, Fernández-Porcel, A, Grasselli, G, Pesenti, A, Bellani, G, Al-Fares, A, Dubin, A, Del Sorbo, L, Anwar, S, Facchin, F, Azad, S, Zamel, R, Hall, D, Ferguson, N, Camara-Sola, E, Cypel, M, Keshavjee, S, Sanchez, S, Durlinger, E, Spoelstra-de Man, A, Smit, B, De Grooth, HJ, Girbes, A, Beitland, S, Straaten, HO, Smulders, Y, Salido-Díaz, L, Ortin, A, Alfaro, MA, Parrilla, F, Meli, A, Pellegrini, M, Rodriguez, N, Goyeneche, JM, Morán, I, Intas, G, Aguirre, H, Mancebo, J, Bassi, GL, Heines, SJ, García-Alcántara, A, Strauch, U, Bergmans, DC, Blankman, P, Shono, A, Hasan, D, Gommers, D, Trøseid, AM, Chung, WY, Prats, RG, Lee, KS, Jung, YJ, Park, JH, Sheen, SS, Park, KJ, Worral, R, Brusletto, BS, Larraza, S, Dey, N, Spadaro, S, Brohus, JB, Winding, RW, Volta, CA, Silva, MM, Waldum-Grevbo, BE, Ampatzidou, F, Vlachou, A, Kehagioglou, G, Karaiskos, T, Madesis, A, Mauromanolis, C, Michail, N, Drossos, G, Aguilera, E, Saraj, N, Berg, JP, Rijkenberg, S, Feijen, HM, Endeman, H, Donnelly, AA, Morgan, E, Garrard, H, Buckley, H, Russell, L, Marti, D, Haase, N, Sunde, K, Goh, C, Mouyis, K, Woodward, CL, Halliday, J, Encina, GB, Ros, J, Ranzani, OT, Lagunes, L, Tabernero, J, Huertas, DG, Bosch, F, Rello, J, Manzano, F, Morente-Constantin, E, Rivera-Ginés, B, Rigol, M, Colmenero-Ruiz, M, Meleti, DE, Sanz, JG, Dogliotti, A, Simon, IF, Valbuena, BL, Pais, M, Ramalingam, S, Quintana, MM, Díaz, C, Fox, L, Santafe, M, Fernandez, L, Barba, P, García, M, Leal, S, Pérez, M, Pérez, ML, Osuna, A, Ferrer, M, Veganzones, J, Martínez, N, Santiago-Ruiz, F, Moors, I, Mokart, D, Pène, F, Lambert, J, Mayaux, J, Vincent, F, Nyunga, M, Bruneel, F, Stergiannis, P, Laisne, L, Rabbat, A, Lebert, C, Perez, P, Suberviola, B, Chaize, M, Renault, A, Meert, AP, Hamidfar, R, Jourdain, M, Rodríguez-Mejías, C, Lanziotti, VS, Darmon, M, Schlemmer, B, Chevret, S, Lemiale, V, Azoulay, E, Rowland, MJ, Riera, J, Benoit, D, Martins-Branco, D, Sousa, M, Wangensteen, R, Marum, S, Bouw, MJ, Galstyan, G, Makarova, P, Parovichnikova, E, Kuzmina, L, Troitskaya, V, Rellan, L, Drize, N, Zaponi, RS, Gemdzhian, E, Jamaati, HR, Savchenko, V, Chao, HC, Kılıc, E, Demiriz, B, Uygur, ML, Sürücü, M, Cınar, K, Yıldırım, AE, Pulcheri, L, Sanchez, M, Kiss, K, Masjedi, M, Köves, B, Csernus, V, Molnár, Z, Ntantana, A, Matamis, D, Savvidou, S, Giannakou, M, Ribeiro, MO, Gouva, M, Nakos, G, Robles, JC, Koulouras, V, Gaffney, S, Docking, R, Judge, C, Drew, T, Barbosa, AP, Misran, H, Munshi, R, McGovern, L, Coyle, M, Hashemian, SM, Lopez, E, Dunne, L, Deasy, E, Lavin, P, Fahy, A, Antoniades, CA, Ramos, A, Darcy, DM, Donnelly, M, Ismail, NH, Hall, T, Wykes, K, Jack, J, Vicente, R, Ngu, WC, Morgan, P, E Silva, JR, Ruiz-Ramos, J, Ramirez, P, Gordon, M, Villarreal, E, Frasquet, J, Poveda-Andrés, JL, Abbasi, G, Castellanos, A, Ijssennagger, CE, Miñambres, E, Soares, M, Ten Hoorn, S, Van Wijk, A, Van den Broek, JM, Tuinman, PR, Elmenshawy, AM, Hammond, BD, Gibbon, G, Khaloo, V, Belcham, T, Burton, K, Salluh, JI, Taniguchi, LU, Santibañez, M, Ramos, FJ, Momma, AK, Martins-Filho, AP, Bartocci, JJ, Lopes, MF, Sad, MH, Tabei, SH, Rodrigues, CM, Pires, EM, Vieira, JM, Le Guen, M, Murbach, LD, Barreto, J, Duarte, ST, Taba, S, Kolaros, AA, Miglioranza, D, Gund, DP, Lordani, CF, Ogasawara, SM, Moore, J, Jorge, AC, Duarte, PA, Capuzzo, M, Marqués, MG, Kafilzadeh, A, Corte, FD, Terranova, S, Scaramuzzo, G, Fogagnolo, A, Bertacchini, S, Bellonzi, A, Garry, P, Mason, N, Ragazzi, R, Moreno, AP, Bakhodaei, HH, Cruz, C, Nunes, A, Pereira, FS, Aragão, I, Cardoso, AF, Santos, C, Malheiro, MJ, Castro, H, Abentroth, LR, Windpassinger, M, Cardoso, T, Diaz, JA, Paratz, J, Kenardy, J, Comans, 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JR, Simon, MG, Thiébaut, PA, Arizmendi, AM, Carratalá, A, Sánchez, RDEP, El Maraghi, S, Yehia, A, Bakry, M, Shoman, A, Backes, FN, Bianchin, MM, Vieira, SR, Maupoint, J, De Souza, A, Lucas, JH, Backes, AN, Klein, C, García-Guillen, FJ, Arunkumar, AS, Lozano, A, Mulder, P, Gallaher, C, Cattlin, S, Ñamendys-Silva, SA, Gordon, S, Picard, J, Fontana, V, Bond, O, Coquerel, D, Nobile, L, Mrozek, S, Delamarre, L, Maghsoudi, B, Capilla, F, Al-Saati, T, Fourcade, O, Renet, S, Dominguez-Berrot, AM, Gonzalez-Vaquero, M, Vallejo-Pascual, ME, Gupta, D, Ivory, BD, Chopra, M, Emami, M, Khaliq, W, McCarthy, J, Felderhof, CL, Do Rego, JC, MacNeil, C, Maggiorini, M, Duska, F, Department of Professional Development, ESICM, Fumis, RR, Junior, JM, Khosravi, MB, Amarante, G, Rieusset, J, Skorko, A, Sanders, S, Aron, J, Kroll, RJ, Redfearn, C, Harish, MM, Krishnan, P, Khalil, JE, Kongpolprom, N, Richard, V, Gulia, V, Lourenço, E, Duro, C, Baptista, G, Alves, A, Arminda, B, Rodrigues, M, Tamion, F, Tabatabaie, HR, Hayward, J, Baldwin, F, Gray, R, Katinakis, PA, Stijf, M, Ten Kleij, M, Jansen-Frederiks, M, Broek, R, De Bruijne, M, Mengelle, C, Spronk, PE, Sinha, K, Luney, M, Palmer, K, Keating, L, Abu-Habsa, M, Bahl, R, Baskaralingam, N, Ahmad, A, Kanapeckaite, L, Bhatti, P, Strong, AJ, Sabetiyan, G, Glace, S, Jeyabraba, S, Lewis, HF, Kostopoulos, A, Raja, M, West, A, Ely, A, Turkoglu, LM, Zolfaghari, P, Baptista, JP, Mokri, A, Marques, MP, Martins, P, Pimentel, J, Su, YC, Singer, M, Villacres, S, Stone, ME, Parsikia, A, Medar, S, O'Dea, KP, Nurses of the Central and General ICUs of Shiraz Namazi Hospital, Porter, J, Tirlapur, N, Jonathan, JM, Singh, S, Takata, M, Critical Care Research Group, McWhirter, E, Lyon, R, Troubleyn, J, Hariz, ML, Ferlitsch, A, Azmi, E, Alkhan, J, Smulders, YM, Movsisyan, V, Petrikov, S, Marutyan, Z, Aliev, I, Evdokimov, A, Antonucci, E, Diltoer, M, Merz, T, Hartmann, C, De Waard, MC, Calzia, E, Radermacher, P, Nußbaum, B, Huber-Lang, M, Fauler, G, Gröger, M, Jacobs, R, Zaleska-Kociecka, M, Van Straaten, HM, Trauner, M, Svoren-Jabalera, E, Davenport, EE, Humburg, P, Nguyen, DN, Knight, J, Hinds, CJ, Jun, IJ, Prabu, NR, Kim, WJ, Lee, EH, Besch, G, Perrotti, A, Puyraveau, M, Baltres, M, Eringa, EC, De Waele, E, Samain, E, Chocron, S, Pili-Floury, S, Plata-Menchaca, EP, Sabater-Riera, J, Estruch, M, Boza, E, Toscana-Fernández, J, Man, AM, Bruguera-Pellicer, E, De Regt, J, Ordoñez-Llanos, J, Pérez-Fernández, XL, SIRAKI group, Cavaleiro, P, Tralhão, A, Arrigo, M, Lopes, JP, Lebrun, M, Favier, B, Pischke, S, Cholley, B, PerezVela, JL, Honoré, PM, MarinMateos, H, Rivera, JJ, Llorente, MA, De Marcos, BG, Fernandez, FJ, Laborda, CG, Zamora, DF, Fischer, L, Alegría, L, Grupo ESBAGA, Delgado, JC, Imperiali, C, Myers, RB, Van Gorp, V, Dastis, M, Thaiss, F, Soto, D, Górka, J, Spapen, HD, Górka, K, Iwaniec, T, Koch, M, Frołow, M, Polok, K, Luengo, C, Fronczek, J, Kózka, M, Musiał, J, Szczeklik, W, Contreras, RS, Bangert, K, Gomez, J, Sileli, M, Havaldar, AA, Toapanta, ND, Jarufe, N, Moursia, C, Maleoglou, H, Leleki, K, Uz, Z, Ince, Y, Papatella, R, Bulent, E, Moreno, G, Grabowski, M, Bruhn, A, De Mol, B, Vicka, V, Gineityte, D, Ringaitiene, D, Norkiene, I, Sipylaite, J, Möller, C, Sabater, J, Castro, R, Thomas-Rueddel, DO, Vlasakov, V, Lohse, AW, Rochwerg, B, Theurer, P, Al Sibai, JZ, Camblor, PM, Kattan, E, Torrado, H, Siddiqui, S, Fernandez, PA, Gala, JM, Guisasola, JS, Tamura, T, Miyajima, I, Yamashita, K, Yokoyama, M, Tapia, P, Nashan, B, Gonzalez, M, Dalampini, E, Nastou, M, Baddour, A, Ignatiadis, A, Asteri, T, Hathorn, KE, Sterneck, M, Rebolledo, R, Purtle, SW, Marin, M, Viana, MV, Tonietto, TA, Gross, LA, Costa, VL, Faenza, S, Tavares, AL, Payen, D, Lisboa, BO, Moraes, RB, Farigola, E, Viana, LV, Azevedo, MJ, Ceniccola, GD, Pequeno, RS, Siniscalchi, A, Holanda, TP, Mendonça, VS, Achurra, P, Araújo, WM, Carvalho, LS, Segaran, E, Vickers, L, Gonzalez, A, Brinchmann, K, Pierucci, E, Wignall, I, De Brito-Ashurst, I, Ospina-Tascón, G, Del Olmo, R, Esteban, MJ, Vaquerizo, C, Carreño, R, Gálvez, V, Kaminsky, G, Mancini, E, Fernandez, J, Nieto, B, Fuentes, M, De la Torre, MA, Bakker, J, Torres, E, Alonso, A, Velayos, C, Saldaña, T, Escribá, A, Krishna, B, Grip, J, Kölegård, R, Vera, A, Sundblad, P, Rooyackers, O, Hernández, G, Naser, B, Jaziri, F, Jazia, AB, Barghouth, M, Ricci, D, Hentati, O, Skouri, W, El Euch, M, Mahfoudhi, M, Gisbert, X, Turki, S, Dąbrowski, M, Bertini, P, Abdelghni, KB, Abdallah, B, Gemelli, C, Maha, BN, Cánovas, J, Sotos, F, López, A, Lorente, M, Burruezo, A, Torres, D, Juliá, C, Guarracino, F, Cuoghi, A, Włudarczyk, A, Hałek, A, Bargouth, M, Bennasr, M, Baldassarri, R, Magnani, S, Uya, J, Abdelghani, KB, Abdallah, TB, Geenen, IL, Parienti, JJ, Straaten, HM, Shum, HP, King, HS, Kulkarni, AP, Pinsky, MR, Chan, KC, Corral, L, Yan, WW, Londoño, JG, Cardenas, CL, Pedrosa, MM, Gubianas, CM, Bertolin, CF, Batllori, NV, Atti, M, Sirvent, JM, Sedation an Delirium Group Hospital Universitari de Bellvitge, Mukhopadhyay, A, Chan, HY, Kowitlawakul, Y, Remani, D, Leong, CS, Henry, CJ, Vera, M, Puthucheary, ZA, Mendsaikhan, N, Begzjav, T, Elias-Jones, I, Lundeg, G, Dünser, M, Espinoza, ED, Welsh, SP, Guerra, E, Poppe, A, Zerpa, MC, Zechner, F, Berdaguer, F, Risso-Vazquez, A, Masevicius, FD, Greaney, D, Dreyse, J, Magee, A, Fitzpatrick, G, Lugo-Cob, RG, Jermaine, CM, Tejeda-Huezo, BC, Cano-Oviedo, AA, Carpio, D, Aydogan, MS, Togal, T, Taha, A, Chai, HZ, Sriram, S, Kam, C, Razali, SS, Sivasamy, V, Randall, D, Kuan, LY, Henriquez, C, Morales, MA, Pires, T, Adwaney, A, Wozniak, S, Gajardo, D, Herrera-Gutierrez, ME, Azevedo, LC, Blunden, M, Prowle, JR, Kirwan, CJ, Thomas, N, Martin, A, Owen, H, Darwin, L, Robertson, CS, Bravo, S, Barrueco-Francioni, J, Conway, D, Atkinson, D, Sharman, M, Barbanti, C, Amour, J, Gaudard, P, Rozec, B, Mauriat, P, M'rini, M, Arias-Verdú, D, Rusin, CG, Leger, PL, Cambonie, G, Liet, JM, Girard, C, Laroche, S, Damas, P, Assaf, Z, Loron, G, Lozano-Saez, R, Lecourt, L, Pouard, P, Hofmeijer, J, Kim, SH, Divatia, JV, Na, S, Kim, J, Jung, CW, Sondag, L, Yoo, SH, Min, SH, Chung, EJ, Quesada-Garcia, G, Lee, NJ, Lee, KW, Suh, KS, Ryu, HG, Marshall, DC, Goodson, RJ, Tjepkema-Cloostermans, MC, Salciccioli, JD, Shalhoub, J, Seller-Pérez, G, Potter, EK, Kirk-Bayley, J, Karanjia, ND, Forni, LG, Kim, S, Creagh-Brown, BC, Bossy, M, Nyman, M, Tailor, A, Figueiredo, A, SPACeR group (Surrey Peri-operative, Anaesthesia and Critical Care Collaborative Research Group), D'Antini, D, Valentino, F, Winkler, MS, Sollitto, F, Cinnella, G, Mirabella, L, Anzola, Y, Bosch, FH, Baladron, V, Villajero, P, Lee, M, Redondo, J, Liu, J, Shen, F, Teboul, JL, Anguel, N, Van Putten, MJ, Beurton, A, Bezaz, N, Richard, C, Park, SY, Monnet, X, Fossali, T, Pereira, R, Colombo, R, Ottolina, D, Rossetti, M, Mazzucco, C, Marchi, A, Porta, A, Catena, E, Piotrowska, K, So, S, Bento, L, Tollisen, KH, Andersen, G, Heyerdahl, F, Jacobsen, D, Van IJzendoorn, MC, Buter, H, Kingma, WP, Navis, GJ, Boerma, EC, Rulisek, J, Zacharov, S, Kim, HS, Jeon, SJ, Namgung, H, Lee, E, Lai, M, Kačar, MB, Cho, YJ, Lee, YJ, Huang, A, Deiana, M, Forsberg, M, Edman, G, Kačar, SM, Höjer, J, Forsberg, S, Freile, MT, Hidalgo, FN, Molina, JA, Lecumberri, R, Rosselló, AF, Travieso, PM, Leon, GT, Uddin, I, Sanchez, JG, Ali, MA, Frias, LS, Rosello, DB, Verdejo, JA, Serrano, JA, Winterwerp, D, Van Galen, T, Vazin, A, Karimzade, I, Belhaj, AM, Zand, A, Ozen, E, Ekemen, S, Akcan, A, Sen, E, Yelken, BB, Kureshi, N, Fenerty, L, Thibault-Halman, G, Aydın, MA, Walling, S, Almeida, R, Seller-Perez, G, Clarke, DB, Briassoulis, P, Kalimeris, K, Ntzouvani, A, Nomikos, T, Papaparaskeva, K, Avsec, D, Politi, E, Kostopanagiotou, G, Crewdson, K, Vardas, K, Rehn, M, Vaz-Ferreira, A, Weaver, A, Brohi, K, Lockey, D, Wright, S, Thomas, K, Mudersbach, E, Baker, C, Mansfield, L, Pozo, MO, Stafford, V, Wade, C, Watson, G, Silva, J, Bryant, A, Chadwick, T, Shen, J, Wilkinson, J, Kapuağası, A, Furneval, J, and Clinical Neurophysiology
Subjects: Queen Square Neuroanaesthesia and Neurocritical Care Resreach Group, TAVeM study Group, Renal Transplantation HUVR, Flow (psychology), lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Critical Care and Intensive Care Medicine, Grupo ESBAGA, GEMINI, 03 medical and health sciences, chemistry.chemical_compound, SPACeR group (Surrey Peri-operative, Anaesthesia and Critical Care Collaborative Research Group), 0302 clinical medicine, Critical Care Research Group, Journal Article, PRoVENT investigators and the PROVE Network, Medicine, Sedation an Delirium Group Hospital Universitari de Bellvitge, 030212 general & internal medicine, Bioethics work group of SEMICYUC, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), SEMICYUC/GETGAG Working Group, FINNAKI Study Group, POPC-CB investigators, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], SIRAKI group, 030208 emergency & critical care medicine, EDISVAL Group, PLUG Working group, DESIRE (DExmedetomidine for Sepsis in ICU Randomized Evaluation) Trial Investigators, chemistry, Anesthesia, Carbon dioxide, Breathing, Department of Professional Development, ESICM, business, Nurses of the Central and General ICUs of Shiraz Namazi Hospital
Abstract: Contains fulltext : 172382.pdf (Publisher’s version ) (Open Access)
Published: 2016

15. Fluid Management in Septic Acute Kidney Injury and Cardiorenal Syndromes

Author: Bellomo, R, Prowle, Jr, Echeverri, Je, Ligabo, V, and Ronco, C
Published: 2010

16. Clinical review: Volume of fluid resuscitation and the incidence of acute kidney injury - a systematic review

Author: Prowle, JR, Chua, H-R, Bagshaw, SM, Bellomo, R, Prowle, JR, Chua, H-R, Bagshaw, SM, and Bellomo, R
Abstract: Intravenous fluids are widely administered to maintain renal perfusion and prevent acute kidney injury (AKI). However, fluid overload is of concern during AKI. Using the Pubmed database (up to October 2011) we identified all randomised controlled studies of goal-directed therapy (GDT)-based fluid resuscitation (FR) reporting renal outcomes and documenting fluid given during perioperative care. In 24 perioperative studies, GDT was associated with decreased risk of postoperative AKI (odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.39 to 0.89) but additional fluid given was limited (median: 555 ml). Moreover, the decrease in AKI was greatest (OR = 0.47, 95% CI = 0.29 to 0.76) in the 10 studies where FR was the same between GDT and control groups. Inotropic drug use in GDT patients was associated with decreased AKI (OR = 0.52, 95% CI = 0.34 to 0.80, P = 0.003), whereas studies not involving inotropic drugs found no effect (OR = 0.75, 95% CI = 0.37 to 1.53, P = 0.43). The greatest protection from AKI occurred in patients with no difference in total fluid delivery and use of inotropes (OR = 0.46, 95% CI = 0.27 to 0.76, P = 0.0036). GDT-based FR may decrease AKI in surgical patients; however, this effect requires little overall FR and appears most effective when supported by inotropic drugs.
Published: 2012

17. Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury

Author: Prowle, JR, Schneider, A, Bellomo, R, Prowle, JR, Schneider, A, and Bellomo, R
Abstract: Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.
Published: 2011

18. Oliguria as predictive biomarker of acute kidney injury in critically ill patients

Author: Prowle, JR, Liu, Y-L, Licari, E, Bagshaw, SM, Egi, M, Haase, M, Haase-Fielitz, A, Kellum, JA, Cruz, D, Ronco, C, Tsutsui, K, Uchino, S, Bellomo, R, Prowle, JR, Liu, Y-L, Licari, E, Bagshaw, SM, Egi, M, Haase, M, Haase-Fielitz, A, Kellum, JA, Cruz, D, Ronco, C, Tsutsui, K, Uchino, S, and Bellomo, R
Abstract: INTRODUCTION: During critical illness, oliguria is often used as a biomarker of acute kidney injury (AKI). However, its relationship with the subsequent development of AKI has not been prospectively evaluated. METHODS: We documented urine output and daily serum creatinine concentration in patients admitted for more than 24 hours in seven intensive care units (ICUs) from six countries over a period of two to four weeks. Oliguria was defined by a urine output < 0.5 ml/kg/hr. Data were collected until the occurrence of creatinine-defined AKI (AKI-Cr), designated by RIFLE-Injury class or greater using creatinine criteria (RIFLE-I[Cr]), or until ICU discharge. Episodes of oliguria were classified by longest duration of consecutive oliguria during each day were correlated with new AKI-Cr the next day, examining cut-offs for oliguria of greater than 1,2,3,4,5,6, or 12 hr duration, RESULTS: We studied 239 patients during 723 days. Overall, 32 patients had AKI on ICU admission, while in 23, AKI-Cr developed in ICU. Oliguria of greater than one hour was significantly associated with AKI-Cr the next day. On receiver-operator characteristic area under the curve (ROCAUC) analysis, oliguria showed fair predictive ability for AKI-Cr (ROCAUC = 0.75; CI:0.64-0.85). The presence of 4 hrs or more oliguria provided the best discrimination (sensitivity 52% (0.31-0.73%), specificity 86% (0.84-0.89%), positive likelihood ratio 3.8 (2.2-5.6), P < 0.0001) with negative predictive value of 98% (0.97-0.99). Oliguria preceding AKI-Cr was more likely to be associated with lower blood pressure, higher heart rate and use of vasopressors or inotropes and was more likely to prompt clinical intervention. However, only 30 of 487 individual episodes of oliguria preceded the new occurrence of AKI-Cr the next day. CONCLUSIONS: Oliguria was significantly associated with the occurrence of new AKI-Cr, however oliguria occurred frequently compared to the small number of patients (~10%) developing AKI-Cr in
Published: 2011

19. Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality

Author: Prowle, JR, Echeverri, JE, Ligabo, EV, Sherry, N, Taori, GC, Crozier, TM, Hart, GK, Korman, TM, Mayall, BC, Johnson, PDR, Bellomo, R, Prowle, JR, Echeverri, JE, Ligabo, EV, Sherry, N, Taori, GC, Crozier, TM, Hart, GK, Korman, TM, Mayall, BC, Johnson, PDR, and Bellomo, R
Abstract: INTRODUCTION: To estimate the incidence of intensive care unit (ICU)-acquired bloodstream infection (BSI) and its independent effect on hospital mortality. METHODS: We retrospectively studied acquisition of BSI during admissions of >72 hours to adult ICUs from two university-affiliated hospitals. We obtained demographics, illness severity and co-morbidity data from ICU databases and microbiological diagnoses from departmental electronic records. We assessed survival at hospital discharge or at 90 days if still hospitalized. RESULTS: We identified 6339 ICU admissions, 330 of which were complicated by BSI (5.2%). Median time to first positive culture was 7 days (IQR 5-12). Overall mortality was 23.5%, 41.2% in patients with BSI and 22.5% in those without. Patients who developed BSI had higher illness severity at ICU admission (median APACHE III score: 79 vs. 68, P < 0.001). After controlling for illness severity and baseline demographics by Cox proportional-hazard model, BSI remained independently associated with risk of death (hazard ratio from diagnosis 2.89; 95% confidence interval 2.41-3.46; P < 0.001). However, only 5% of the deaths in this model could be attributed to acquired-BSI, equivalent to an absolute decrease in survival of 1% of the total population. When analyzed by microbiological classification, Candida, Staphylococcus aureus and gram-negative bacilli infections were independently associated with increased risk of death. In a sub-group analysis intravascular catheter associated BSI remained associated with significant risk of death (hazard ratio 2.64; 95% confidence interval 1.44-4.83; P = 0.002). CONCLUSIONS: ICU-acquired BSI is associated with greater in-hospital mortality, but complicates only 5% of ICU admissions and its absolute effect on population mortality is limited. These findings have implications for the design and interpretation of clinical trials.
Published: 2011

20. Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study

Author: Haase-Fielitz, A, Mertens, PR, Plass, M, Kuppe, H, Hetzer, R, Westerman, M, Ostland, V, Prowle, JR, Bellomo, R, Haase, M, Haase-Fielitz, A, Mertens, PR, Plass, M, Kuppe, H, Hetzer, R, Westerman, M, Ostland, V, Prowle, JR, Bellomo, R, and Haase, M
Abstract: INTRODUCTION: Conventional markers of acute kidney injury (AKI) lack diagnostic accuracy and are expressed only late after cardiac surgery with cardiopulmonary bypass (CPB). Recently, interest has focused on hepcidin, a regulator of iron homeostasis, as a unique renal biomarker. METHODS: We studied 100 adult patients in the control arm of a randomized, controlled trial http://www.clinicaltrials.gov/NCT00672334 who were identified as being at increased risk of AKI after cardiac surgery with CPB. AKI was defined according to the Risk, Injury, Failure, Loss, End-stage renal disease classification of AKI classification stage. Samples of plasma and urine were obtained simultaneously (1) before CPB (2) six hours after the start of CPB and (3) twenty-four hours after CPB. Plasma and urine hepcidin 25-isoforms were quantified by competitive enzyme-linked immunoassay. RESULTS: In AKI-free patients (N = 91), urine hepcidin concentrations had largely increased at six and twenty-four hours after CPB, and they were three to seven times higher compared to patients with subsequent AKI (N = 9) in whom postoperative urine hepcidin remained at preoperative levels (P = 0.004, P = 0.002). Furthermore, higher urine hepcidin and, even more so, urine hepcidin adjusted to urine creatinine at six hours after CPB discriminated patients who did not develop AKI (area under the curve (AUC) receiver operating characteristic curve 0.80 [95% confidence interval (95% CI) 0.71 to 0.87] and 0.88 [95% CI 0.78 to 0.97]) or did not need renal replacement therapy initiation (AUC 0.81 [95% CI 0.72 to 0.88] 0.88 [95% CI 0.70 to 0.99]) from those who did. At six hours, urine hepcidin adjusted to urine creatinine was an independent predictor of ruling out AKI (P = 0.011). Plasma hepcidin did not predict no development of AKI. The study findings remained essentially unchanged after excluding patients with preoperative chronic kidney disease. CONCLUSIONS: Our findings suggest that urine hepcidin is an early pr
Published: 2011

21. Measurement of renal blood flow by phase-contrast magnetic resonance imaging during septic acute kidney injury: A pilot investigation*.

Author: Prowle JR, Molan MP, Hornsey E, and Bellomo R
Abstract: OBJECTIVE: : In septic patients, decreased renal perfusion is considered to play a major role in the pathogenesis of acute kidney injury. However, the accurate measurement of renal blood flow in such patients is problematic and invasive. We sought to overcome such obstacles by measuring renal blood flow in septic patients with acute kidney injury using cine phase-contrast magnetic resonance imaging. DESIGN: : Pilot observational study. SETTING: : University-affiliated general adult intensive care unit. PATIENTS: : Ten adult patients with established septic acute kidney injury and 11 normal volunteers. INTERVENTIONS: : Cine phase-contrast magnetic resonance imaging measurement of renal blood flow and cardiac output. MEASUREMENTS AND MAIN RESULTS: : The median age of the study patients was 62.5 yrs and eight were male. At the time of magnetic resonance imaging, eight patients were mechanically ventilated, nine were on continuous hemofiltration, and five required vasopressors. Cine phase-contrast magnetic resonance imaging examinations were carried out without complication. Median renal blood flow was 482 mL/min (range 335-1137) in septic acute kidney injury and 1260 mL/min (range 791-1750) in healthy controls (p = .003). Renal blood flow indexed to body surface area was 244 mL/min/m (range 165-662) in septic acute kidney injury and 525 mL/min/m(range 438-869) in controls (p = .004). In patients with septic acute kidney injury, median cardiac index was 3.5 L/min/m (range 1.6-8.7), and median renal fraction of cardiac output was only 7.1% (range 4.4-10.8). There was no rank correlation between renal blood flow index and creatinine clearance in patients with septic acute kidney injury (r = .26, p = .45). CONCLUSIONS: : Cine phase-contrast magnetic resonance imaging can be used to noninvasively and safely assess renal perfusion during critical illness in man. Near-simultaneous accurate measurement of cardiac output enables organ blood flow to be assessed in the context of the global circulation. Renal blood flow seems consistently reduced as a fraction of cardiac output in established septic acute kidney injury. Cine phase-contrast magnetic resonance imaging may be a valuable tool to further investigate renal blood flow and the effects of therapies on renal blood flow in critical illness. [ABSTRACT FROM AUTHOR]
Published: 2012
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22. ESICM LIVES 2016: part three : Milan, Italy. 1-5 October 2016

Author: Velasquez, T., Mackey, G., Lusk, J., Kyle, Ug, Fontenot, T., Marshall, P., Shekerdemian, Ls, Coss-Bu, Ja, Nishigaki, A., Yatabe, T., Tamura, T., Yamashita, K., Yokoyama, M., Ruiz-Rodriguez, Jc, Encina, B., Belmonte, R., Troncoso, I., Tormos, P., Riveiro, M., Baena, J., Sanchez, A., Bañeras, J., Cordón, J., Duran, N., Ruiz, A., Caballero, J., Nuvials, X., Riera, J., Serra, J., Rutten, Am, Ieperen, Sn, Kinderen, Ep, Logten, T., Kovacikova, L., Skrak, P., Zahorec, M., Akcan-Arikan, A., Silva, Jc, Goldsworthy, M., Wood, D., Harrison, D., Parslow, R., Davis, P., Pappachan, J., Goodwin, S., Ramnarayan, P., Chernyshuk, S., Yemets, H., Zhovnir, V., Pulitano, Sm, Rosa, S., Mancino, A., Villa, G., Tosi, F., Franchi, P., Conti, G., Patel, B., Khine, H., Shah, A., Sung, D., Singer, L., Haghbin, S., Inaloo, S., Serati, Z., Idei, M., Nomura, T., Yamamoto, N., Sakai, Y., Yoshida, T., Matsuda, Y., Yamaguchi, Y., Takaki, S., Yamaguchi, O., Goto, T., Longani, N., Medar, S., Abdel-Aal, Ir, El Adawy, As, Mohammed, Hm, Mohamed, An, Parry, Sm, Knight, Ld, Denehy, L., Morton, N., Baldwin, Ce, Sani, D., Kayambu, G., Da Silva, Vz, Phongpagdi, P., Puthucheary, Za, Granger, Cl, Rydingsward, Je, Horkan, Cm, Christopher, Kb, Mcwilliams, D., Jones, C., Reeves, E., Atkins, G., Snelson, C., Aitken, Lm, Rattray, J., Kenardy, J., Hull, Am, Ullman, A., Le Brocque, R., Mitchell, M., Davis, C., Macfarlane, B., Azevedo, Jc, Rocha, Ll, Freitas, Ff, Cavalheiro, Am, Lucinio, Nm, Lobato, Ms, Ebeling, G., Kraegpoeth, A., Laerkner, E., Brito-Ashurst, I., White, C., Gregory, S., Forni, Lg, Flowers, E., Curtis, A., Wood, Ca, Siu, K., Venkatesan, K., Muhammad, Jb, Ng, L., Seet, E., Baptista, N., Escoval, A., Tomas, E., Agrawal, R., Mathew, R., Varma, A., Dima, E., Charitidou, E., Perivolioti, E., Pratikaki, M., Vrettou, C., Giannopoulos, A., Zakynthinos, S., Routsi, C., Atchade, E., Houzé, S., Jean-Baptiste, S., Thabut, G., Genève, C., Tanaka, S., Lortat-Jacob, B., Augustin, P., Desmard, M., Montravers, P., Molina, Fj, Barbadillo, S., Alejandro, R., Álvarez-Lerma, F., Vallés, J., Catalán, Rm, Palencia, E., Jareño, A., Granada, Rm, Ignacio, Ml, Getgag, Working Group, Cui, N., Liu, D., Wang, H., Su, L., Qiu, H., Li, R., Jaffal, K., Rouzé, A., Poissy, J., Sendid, B., Nseir, S., Paramythiotou, E., Rizos, M., Frantzeskaki, F., Antoniadou, A., Vourli, S., Zerva, L., Armaganidis, A., Gottlieb, J., Greer, M., Wiesner, O., Martínez, M., Acuña, M., Rello, J., Welte, T., Mignot, T., Soussi, S., Dudoignon, E., Ferry, A., Chaussard, M., Benyamina, M., Alanio, A., Touratier, S., Chaouat, M., Lafaurie, M., Mimoun, M., Mebazaa, A., Legrand, M., Sheils, Ma, Patel, C., Mohankumar, L., Akhtar, N., Noriega, Sk, Aldana, Nn, León, Jl, Baquero, Jd, Bernal, Ff, Ahmadnia, E., Hadley, Js, Millar, M., Hall, D., Hewitt, H., Yasuda, H., Sanui, M., Komuro, T., Kawano, S., Andoh, K., Yamamoto, H., Noda, E., Hatakeyama, J., Saitou, N., Okamoto, H., Kobayashi, A., Takei, T., Matsukubo, S., Jseptic, Clinical Trial Group, Rotzel, Hb, Lázaro, As, Prada, Da, Gimillo, MR, Barinas, Od, Cortes, Ml, Franco, Jf, Roca, Jm, Carratalá, A., Gonçalves, B., Turon, R., Mendes, A., Miranda, F., Mata, Pj, Cavalcanti, D., Melo, N., Lacerda, P., Kurtz, P., Righy, C., Rosario, Le, Lesmes, Sp, Romero, Jc, Herrera, An, Pertuz, Ed, Sánchez, Mj, Sanz, Er, Hualde, Jb, Hernández, Aa, Irazabal, Jm, Spatenkova, V., Bradac, O., Suchomel, P., Urli, T., Lazzeri, Eh, Aspide, R., Zanello, M., Perez-Borrero, L., Garcia-Alvarez, Jm, Arias-Verdu, Md, Aguilar-Alonso, E., Rivera-Fernandez, R., Mora-Ordoñez, J., La Fuente-Martos, C., Castillo-Lorente, E., Guerrero-Lopez, F., Ramírez, Jr, León, Jp, Navarro-Guillamón, L., Cordovilla-Guardia, S., Iglesias-Santiago, A., Guerrero-López, F., Fernández-Mondéjar, E., Vidal, A., Perez, M., Juez, A., Arias, N., Colino, L., Perez, Jl, Pérez, H., Calpe, P., Alcala, Ma, Robaglia, D., Perez, C., Lan, Sk, Cunha, Mm, Moreira, T., Santos, F., Lafuente, E., Fernandes, Mj, Silva, Jg, Echeverría, Jg, Podlepich, V., Sokolova, E., Alexandrova, E., Lapteva, K., Shuinotsuka, C., Rabello, L., Vianna, G., Reis, A., Cairus, C., Salluh, J., Bozza, F., Torres, Jc, Araujo, Nj, García-Olivares, P., Keough, E., Dalorzo, M., Tang, Lk, Sousa, I., Díaz, M., Marcos-Zambrano, Lj, Guerrero, Je, Gomez, Se, Lopez, Gd, Cuellar, Ai, Nieto, Or, Gonzalez, Ja, Bhasin, D., Rai, S., Singh, H., Gupta, O., Bhattal, Mk, Sampley, S., Sekhri, K., Nandha, R., Aliaga, Fa, Olivares, F., Appiani, F., Farias, P., Alberto, F., Hernández, A., Pons, S., Sonneville, R., Bouadma, L., Neuville, M., Mariotte, E., Radjou, A., Lebut, J., Chemam, S., Voiriot, G., Dilly, Mp, Mourvillier, B., Dorent, R., Nataf, P., Wolff, M., Timsit, Jf, Ediboglu, O., Ataman, S., Ozkarakas, H., Kirakli, C., Vakalos, A., Avramidis, V., Obukhova, O., Kurmukov, Ia, Kashiya, S., Golovnya, E., Baikova, Vn, Ageeva, T., Haritydi, T., Kulaga, Ev, Rios-Toro, Jj, Lopez-Caler, C., Rodriguez-Fernandez, S., Sanchez-Orézzoli, Mg, Martin-Gallardo, F., Nikhilesh, J., Joshi, V., Villarreal, E., Ruiz, J., Gordon, M., Quinza, A., Gimenez, J., Piñol, M., Castellanos, A., Ramirez, P., Jeon, Yd, Jeong, Wy, Kim, Mh, Jeong, Iy, Ahn, My, Ahn, Jy, Han, Sh, Choi, Jy, Song, Yg, Kim, Jm, Ku, Ns, Shah, H., Kellner, F., Rezai, F., Mistry, N., Yodice, P., Ovnanian, V., Fless, K., Handler, E., Alejos, Rm, Romeu, Jd, Antón, Dg, Quinart, A., Martí, At, Laura Navarro Guillamon, Lobo-Civico, A., Ventura-Rosado, A., Piñol-Tena, A., Pi-Guerrero, M., Paños-Espinosa, C., Peralvo-Bernat, M., Marine-Vidal, J., Gonzalez-Engroba, R., Montesinos-Cerro, N., Treso-Geira, M., Valeiras-Valero, A., Martinez-Reyes, L., Sandiumenge, A., Jimenez-Herrera, Mf, Capcri, Study, Helyar, S., Riozzi, P., Noon, A., Hallows, G., Cotton, H., Keep, J., Hopkins, Pa, Taggu, A., Renuka, S., Sampath, S., Rood, Pj, Frenzel, T., Verhage, R., Bonn, M., Pickkers, P., Hoeven, Jg, Den Boogaard, M., Corradi, F., Melnyk, L., Moggia, F., Pienovi, R., Adriano, G., Brusasco, C., Mariotti, L., Lattuada, M., Bloomer, Mj, Coombs, M., Ranse, K., Endacott, R., Maertens, B., Blot, K., Blot, S., Amerongen, Mp, Heiden, Es, Twisk, Jw, Girbes, Ar, Spijkstra, Jj, Bell, C., Peters, K., Feehan, A., Churchill, K., Hawkins, K., Brook, R., Paver, N., Maistry, N., Wijk, A., Rouw, N., Galen, T., Evelein-Brugman, S., Krishna, B., Putzu, A., Fang, M., Berto, Mb, Belletti, A., Cassina, T., Cabrini, L., Mistry, M., Alhamdi, Y., Welters, I., Abrams, St, Toh, Ch, Han, Hs, Gil, Em, Lee, Ds, Park, Cm, Winder-Rhodes, S., Lotay, R., Doyle, J., Ke, Mw, Huang, Wc, Chiang, Ch, Hung, Wt, Cheng, Cc, Lin, Kc, Lin, Sc, Chiou, Kr, Wann, Sr, Shu, Cw, Kang, Pl, Mar, Gy, Liu, Cp, Dubó, S., Aquevedo, A., Jibaja, M., Berrutti, D., Labra, C., Lagos, R., García, Mf, Ramirez, V., Tobar, M., Picoita, F., Peláez, C., Carpio, D., Alegría, L., Hidalgo, C., Godoy, K., Bakker, J., Hernández, G., Sadamoto, Y., Katabami, K., Wada, T., Ono, Y., Maekawa, K., Hayakawa, M., Sawamura, A., Gando, S., Marin-Mateos, H., Perez-Vela, Jl, Garcia-Gigorro, R., Peiretti, Ma, Lopez-Gude, Mj, Chacon-Alves, S., Renes-Carreño, E., Montejo-González, Jc, Parlevliet, Kl, Touw, Hr, Beerepoot, M., Boer, C., Elbers, Pw, Tuinman, Pr, Abdelmonem, Sa, Helmy, Ta, El Sayed, I., Ghazal, S., Akhlagh, Sh, Masjedi, M., Hozhabri, K., Kamali, E., Zýková, I., Paldusová, B., Sedlák, P., Morman, D., Youn, Am, Ohta, Y., Sakuma, M., Bates, D., Morimoto, T., Su, Pl, Chang, Wy, Lin, Wc, Chen, Cw, Facchin, F., Zarantonello, F., Panciera, G., Cassai, A., Venrdramin, A., Ballin, A., Tonetti, T., Persona, P., Ori, C., Del Sorbo, L., Rossi, S., Vergani, G., Cressoni, M., Chiumello, D., Chiurazzi, C., Brioni, M., Algieri, I., Guanziroli, M., Colombo, A., Tomic, I., Crimella, F., Carlesso, E., Gasparovic, V., Gattinoni, L., Neto, As, Schmidt, M., Pham, T., Combes, A., Abreu, Mg, Pelosi, P., Schultz, Mj, Prove, Reva Research Network And The Network Investigators, Katira, Bh, Engelberts, D., Giesinger, Re, Ackerley, C., Zabini, D., Otulakowski, G., Post, M., Kuebler, Wm, Mcnamara, Pj, Kavanagh, Bp, Pirracchio, R., Rigon, MR, Carone, M., Chevret, S., Annane, D., Eladawy, S., El-Hamamsy, M., Bazan, N., Elgendy, M., Pascale, G., Vallecoccia, Ms, Cutuli, Sl, Di Gravio, V., Pennisi, Ma, Antonelli, M., Andreis, Dt, Khaliq, W., Singer, M., Hartmann, J., Harm, S., Carmona, Sa, Almudevar, Pm, Abellán, An, Ramos, Jv, Pérez, Lp, Valbuena, Bl, Sanz, Nm, Simón, If, Arrigo, M., Feliot, E., Deye, N., Cariou, A., Guidet, B., Jaber, S., Leone, M., Resche-Rigon, M., Baron, Av, Gayat, E., Frog Icu, Investigators, Balik, M., Kolnikova, I., Maly, M., Waldauf, P., Tavazzi, G., Kristof, J., Herpain, A., Su, F., Post, E., Taccone, F., Vincent, Jl, Creteur, J., Lee, C., Hatib, F., Jian, Z., Buddi, S., Cannesson, M., Fileković, S., Turel, M., Knafelj, R., Gorjup, V., Stanić, R., Gradišek, P., Cerović, O., Mirković, T., Noč, M., Tirkkonen, J., Hellevuo, H., Olkkola, Kt, Hoppu, S., Chiang, Cc, Juan, Wc, Lin, Ph, Fong, Ky, Hou, Ds, Chen, Ys, Paul, M., Bougouin, W., Geri, G., Dumas, F., Champigneulle, B., Legriel, S., Charpentier, J., Mira, Jp, Sandroni, C., Zimmerman, J., Sullivan, E., Noursadeghi, M., Fox, B., Sampson, D., Mchugh, L., Yager, T., Cermelli, S., Seldon, T., Bhide, S., Brandon, Ra, Brandon, Rb, Zwaag, J., Beunders, R., Kox, M., Gul, F., Arslantas, Mk, Genc, D., Zibandah, N., Topcu, L., Akkoc, T., Cinel, I., Greco, E., Lauretta, Mp, Garcia, Ip, Cordero, M., Martin, Ad, Pallás, Ta, Montero, Jg, Rey, Jr, Malo, Lr, Montoya, Aa, Martinez, Ad, Ayala, Ly, Zepeda, Em, Granillo, Jf, Sanchez, Ja, Alejo, Gc, Cabrera, Ar, Montenegro, Ap, Beduneau, G., Schortgen, F., Piquilloud, L., Zogheib, E., Jonas, M., Grelon, F., Runge, I., Terzi, N., Grangé, S., Barberet, G., Guitard, Pg, Frat, Jp, Constan, A., Chrétien, Jm, Mancebo, J., Mercat, A., Richard, Jc, Brochard, L., Wind, Study Group, Soilemezi, E., Koco, E., Savvidou, S., Nouris, C., Matamis, D., Plug Working Group, Di Mussi, R., Spadaro, S., Volta, Ca, Mariani, M., Colaprico, A., Antonio, C., Bruno, F., Grasso, S., Rodriguez, A., Martín-Loeches, I., Díaz, E., Masclans, Jr, Gordo, F., Solé-Violán, J., Bodí, M., Avilés-Jurado, Fx, Trefler, S., Magret, M., Reyes, Lf, Marín-Corral, J., Yebenes, Jc, Esteban, A., Anzueto, A., Aliberti, S., Restrepo, Mi, GETGAG/SEMICYUC, Larsson, Js, Redfors, B., Ricksten, Se, Haines, R., Powell-Tuck, J., Leonard, H., Ostermann, M., Berthelsen, Re, Itenov, Ts, Perner, A., Jensen, Ju, Ibsen, M., Jensen, Ae, Bestle, Mh, Bucknall, T., Dixon, J., Boa, F., Macphee, I., Philips, Bj, Aki, Research Group, St George’s University of London, Saadat, F., Samuels, T., Huddart, S., Mccormick, B., Debrunnar, R., Preece, J., Swart, M., Peden, C., Richardson, S., Forni, L., Kalfon, P., Baumstarck, K., Estagnasie, P., Geantot, Ma, Berric, A., Simon, G., Floccard, B., Signouret, T., Boucekine, M., Fromentin, M., Nyunga, M., Sossou, A., Venot, M., Robert, R., Follin, A., Renault, A., Garrouste, M., Collange, O., Levrat, Q., Villard, I., Thévenin, D., Pottecher, J., Patrigeon, Rg, Revel, N., Vigne, C., Mimoz, O., Auquier, P., Iprea, Study Group, Pawar, S., Jacques, T., Deshpande, K., Pusapati, R., Wood, B., Pulham, Ra, Wray, J., Brown, K., Pierce, C., Nadel, S., Azevedo, Jr, Montenegro, Ws, Rodrigues, Dp, Sousa, Sc, Araujo, Vf, Leitao, Al, Prazeres, Ph, Mendonca, Av, Paula, Mp, Das Neves, A., Loudet, Ci, Busico, M., Vazquez, D., Villalba, D., Lischinsky, A., Veronesi, M., Emmerich, M., Descotte, E., Juliarena, A., Bisso, Mc, Grando, M., Tapia, A., Camargo, M., Ulla, Dv, Corzo, L., Dos Santos, Hp, Ramos, A., Doglia, Ja, Estenssoro, E., Carbonara, M., Magnoni, S., Donald, Cl, Shimony, Js, Conte, V., Triulzi, F., Stretti, F., Macrì, M., Snyder, Az, Stocchetti, N., Brody, Dl, Shimanskiy, V., Savin, I., Chumaev, A., Tjepkema-Cloostermans, Mc, Hofmeijer, J., Beishuizen, A., Hom, H., Blans, Mj, Putten, Mj, Longhi, L., Frigeni, B., Curinga, M., Mingone, D., Beretta, S., Patruno, A., Gandini, L., Vargiolu, A., Ferri, F., Ceriani, R., Rottoli, MR, Lorini, L., Citerio, G., Pifferi, S., Battistini, M., Cordolcini, V., Agarossi, A., Di Rosso, R., Ortolano, F., Lourido, Cm, Cabrera, Jl, Santana, Jd, Alzola, Lm, Del Rosario, Cg, Pérez, Hr, Torrent, Rl, Eslami, S., Dalhuisen, A., Fiks, T., Hanna, Aa, Spronk, Pe, Wood, M., Maslove, D., Muscedere, J., Scott, Sh, Saha, T., Hamilton, A., Petsikas, D., Payne, D., Boyd, Jg, Mcnelly, As, Rawal, J., Connolly, B., Mcphail, Mj, Sidhu, P., Rowlerson, A., Moxham, J., Harridge, Sd, Hart, N., Montgomery, He, Jovaisa, T., Thomas, B., Gupta, D., Wijayatilake, Ds, Shum, Hp, King, Hs, Chan, Kc, Tang, Kb, Yan, Ww, Arias, Cc, Latorre, J., La Rica, As, Garrido, Em, Feijoo, Am, Gancedo, Ch, Tofiño, Al, Rodríguez, Fg, Gemmell, Lk, Campbell, R., Doherty, P., Mackay, A., Singh, N., Vitaller, S., Nagib, H., Prieto, J., Del Arco, A., Zayas, B., Gomez, C., Tirumala, S., Pasha, Sa, Kumari, Bk, Martinez-Lopez, P., Puerto-Morlán, A., Nuevo-Ortega, P., Pujol, Lm, Dolset, Ra, González, Bs, Riera, Sq, Álvarez, Jt, Quintana, S., Martínez, L., Algarte, R., Sánchez, B., Trenado, J., Brock, N., Viegas, E., Filipe, E., Cottle, D., Traynor, T., Martínez, Mv, Márquez, Mp, Gómez, Lc, Martínez, Na, Muñoz, Jm, Bellver, Bq, Varea, Mm, Llorente, Má, Calvo, Cp, Hillier, Sd, Faulds, Mc, Hendra, H., Lawrence, N., Kodate, A., Tominaga, N., Mizugaki, A., Murakami, H., Silva, S., Kerhuel, L., Malagurski, B., Chabanne, R., Laureys, S., Puybasset, L., Nobile, L., Pognuz, Er, Rossetti, Ao, Verginella, F., Gaspard, N., Ben-Hamouda, N., Oddo, M., Taccone, Fs, Iijima, H., Andersen, Lw, Raymond, T., Berg, R., Nadkarni, V., Grossestreuer, A., Kurth, T., Donnino, M., Krüger, A., Ostadal, P., Janotka, M., Vondrakova, D., Kongpolprom, N., Cholkraisuwat, J., Pekkarinen, Pt, Ristagno, G., Masson, S., Latini, R., Bendel, S., Ala-Kokko, T., Varpula, T., Vaahersalo, J., Tiainen, M., Mion, Mm, Plebani, M., Pettilä, V., Skrifvars, Mb, Finnresusci, Study Group, Son, Y., Kim, Ks, Suh, Gj, Kwon, Wy, Ko, Ji, Park, Mj, Cavicchi, Fz, Iesu, E., Tanaka, H., Otani, N., Ode, S., Ishimatsu, S., Romero, I., Martínez, F., Kruger, A., Malek, F., Neuzil, P., Yeh, Yc, Wang, Ch, Huang, Ch, Chao, A., Lee, Ct, Lai, Ch, Chan, Ws, Cheng, Yj, Sun, Wz, Kaese, S., Horstmann, C., Lebiedz, P., Mourad, M., Gaudard, P., Eliet, J., Zeroual, N., Colson, P., Mlcek, M., Hrachovina, M., Mates, M., Hala, P., Kittnar, O., Jacky, A., Rudiger, A., Spahn, Dr, Bettex, Da, Kara, A., Akin, S., Dos Reis Miranda, D., Struijs, A., Caliskan, K., Thiel, Rj, Dubois, Ea, Wilde, W., Zijlstra, F., Gommers, D., Ince, C., Marca, L., Xini, A., Mongkolpun, W., Cordeiro, Cp, Leite, Rt, Lheureux, O., Bader, A., Rincon, L., Santacruz, C., Preiser, Jc, Chao, As, Kim, W., Ahn, C., Cho, Y., Lim, Th, Oh, J., Choi, Ks, Jang, Bh, Ha, Jk, Mecklenburg, A., Stamm, J., Soeffker, G., Kubik, M., Sydow, K., Reichenspurner, H., Kluge, S., Braune, S., Bergantino, B., Ruberto, F., Magnanimi, E., Privato, E., Zullino, V., Bruno, K., Pugliese, F., Sales, G., Girotto, V., Vittone, F., Brazzi, L., Fritz, C., Kimmoun, A., Vanhuyse, F., Trifan, B., Orlowski, S., Albuisson, E., Tran, N., Levy, B., Chhor, V., Joachim, J., Chatelon, J., Fave, G., Mantz, J., Diaz, Dd, Villanova, M., Aguirregabyria, M., Andrade, G., López, L., John, G., Cowan, R., Hart, R., Lake, K., Litchfield, K., Song, Jw, Lee, Yj, Cho, Yj, Choi, S., Vermeir, P., Vandijck, D., Mariman, A., Verhaeghe, R., Deveugele, M., Vogelaers, D., Chok, L., Bachli, Eb, Bettex, D., Cottini, Sr, Keller, E., Maggiorini, M., Schuepbach, R., Stiphout, C., Grevelink, M., Vaneker, I., Ruijter, A., Buise, M., Tena, Sa, Barrachina, Lg, Portillo, Jh, Aznar, Gp, Campos, Lm, Sellés, Md, Tomás, Ma, Muncharaz, Ab, Skinner, L., Monsalvo, S., Olavarria, E., Stümpfle, R., Na, Sj, Park, J., Chung, Cr, Suh, Gy, Yang, Jh, Witter, T., Brousseau, C., Butler, Mb, Erdogan, M., Dougall, Pc, Green, Rs, Abbott, Te, Torrance, Hd, Cron, N., 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Garcia, Pk, Contreras, Km, Rodriguez, P., and Echeverri, Je

23. Clinician assessment of kidney function from plasma creatinine values during critical illness: A scenario-based international multi-professional survey.

Author: Azzopardi G, Mekhaimar A, Haines RW, Stephens TJ, Puthucheary Z, and Prowle JR
Abstract: Purpose: During critical illness interpretation of serum creatinine is affected by non-steady state conditions, reduced creatinine generation, and altered distribution. We evaluated healthcare professionals' ability to adjudicate underlying kidney function, based on simulated creatinine values., Methods: We developed an online survey, incorporating 12 scenarios with simulated trajectories of creatinine based on profiles of muscle mass, GFR and fluid balance using bespoke kinetic modelling. Participants predicted true underlying GFR (<5, 5-14, 15-29, 30-44, 45-59, 60-90, >90 ml.min -1 .1.73 m -2 ) and AKI stage (stages 1-3, defined as 33 %, 50 %, 66 % decrease in GFR from baseline) during the first 7-days and at ICU discharge., Results: 100 of 103 respondents from 16 countries, 94 completed 1 or more scenarios. 43(43 %) were senior physicians, 74(74 %) critical care and 31(31 %) nephrology physicians. Over the first 7-days, true GFR was correctly estimated 43 % of the time and underlying AKI stage in 57 % of patient days. At ICU discharge GFR was predicted 35 % of the time. At all timepoints, over and under-estimation of GFR was observed., Conclusion: Participants displayed marked variation in estimation of kidney function, suggesting difficulty in accounting for multiple confounders. There is need for alternative, unbiased measures of kidney function in critical illness to avoid misclassifying kidney disease., Competing Interests: Declaration of competing interest Dr. Prowle has recent consultancy agreements with Jaffron Biomedical Co Ltd., Paion Ltd., Nephrolyx GmbH, Mission Therapeutics, Vantive Inc. and Nikkiso Europe GmbH. Dr. Prowle has received speaker's fees and hospitality from Vantive Inc., BBraun and Nikkiso Europe. Dr. Prowle has received research support from Astute Medical a Biomerieux company and Jaffron Biomedical Co Ltd. Dr. Prowle serves on a DMSB for Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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24. The effect of high protein dosing in critically ill patients: an exploratory, secondary Bayesian analyses of the EFFORT Protein trial.

Author: Haines RW, Granholm A, Puthucheary Z, Day AG, Bear DE, Prowle JR, and Heyland DK
Subjects: Humans, Male, Middle Aged, Female, Aged, Acute Kidney Injury chemically induced, Adult, Creatinine blood, Intensive Care Units, Dietary Proteins administration & dosage, Treatment Outcome, Organ Dysfunction Scores, Bayes Theorem, Critical Illness
Abstract: Background: The EFFORT Protein trial assessed the effect of high vs usual dosing of protein in adult ICU patients with organ failure. This study provides a probabilistic interpretation and evaluates heterogeneity in treatment effects (HTE)., Methods: We analysed 60-day all-cause mortality and time to discharge alive from hospital using Bayesian models with weakly informative priors. HTE on mortality was assessed according to disease severity (Sequential Organ Failure Assessment [SOFA] score), acute kidney injury, and serum creatinine values at baseline., Results: The absolute difference in mortality was 2.5% points (95% credible interval -6.9 to 12.4), with a 72% posterior probability of harm associated with high protein treatment. For time to discharge alive from hospital, the hazard ratio was 0.91 (95% credible interval 0.80 to 1.04) with a 92% probability of harm for the high-dose protein group compared with the usual-dose protein group. There were 97% and 95% probabilities of positive interactions between the high protein intervention and serum creatinine and SOFA score at randomisation, respectively. Specifically, there was a potentially relatively higher mortality of high protein doses with higher baseline serum creatinine or SOFA scores., Conclusions: We found moderate to high probabilities of harm with high protein doses compared with usual protein in ICU patients for the primary and secondary outcomes. We found suggestions of heterogeneity in treatment effects with worse outcomes in participants randomised to high protein doses with renal dysfunction or acute kidney injury and greater illness severity at baseline., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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25. Assessing the role of Chemokine (C-C motif) ligand 14 in AKI: a European consensus meeting.

Author: Koyner JL, Arndt C, Baldira Martinez de Irujo J, Coelho S, Garcia-Montesinos de la Peña M, di Girolamo L, Joannidis M, Jorge-Monjas P, Koch C, Lobaz S, Meyer A, Ostermann M, Pertica N, Prowle JR, Silversides J, Zarbock A, Echeverri J, Harenski K, and Forni LG
Subjects: Humans, Consensus, Chemokines, CC urine, Europe, Acute Kidney Injury urine, Acute Kidney Injury therapy, Acute Kidney Injury diagnosis, Biomarkers urine, Delphi Technique, Renal Replacement Therapy
Abstract: Background: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions., Methods: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale)., Results: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan ( p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences., Conclusion: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.
Published: 2024
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26. Dynamic dosing for continuous renal replacement therapy: Service evaluation of the safety and effectiveness of titrating dose to biochemistry.

Author: Eldridge JC, Bhardwaj Shah A, Lucena-Amaro S, Kirwan CJ, Prowle JR, and Wan YI
Abstract: Introduction: Continuous renal replacement therapy (CRRT) dose is usually fixed and primarily weight-based. Whilst this is safe, theoretically, underdosing or overdosing may occur in those requiring acute versus maintenance CRRT respectively. We have developed a dynamic dosing protocol for CRRT which individualises and updates dosing according to biochemistry. Here we describe the protocol and compare it to a fixed dose protocol to evaluate its safety and effectiveness., Methods: We conducted a service evaluation of this novel protocol using data from consecutive non-COVID-19 admissions receiving CRRT within Barts Health NHS trust, United Kingdom (UK). Fifty admissions using the dynamic protocol were compared to historically collected data from 108 admissions who used the fixed protocol. Acute and maintenance CRRT subgroups were analysed., Results: For the dynamic protocol 49 patients were treated with 135 CRRT circuits. One patient had two admissions. Protocol compliance (compared in one ICU) was 76% (dynamic) vs 61% (fixed) ( p < 0.05). For the dynamic versus fixed protocol, median CRRT lifespan censored for reasons other than clotting was: 56 h vs 58 h RCA (ns), 27 h versus 20 h heparin (ns) and 79 h versus 22 h no anticoagulation ( p < 0.05). The dynamic vs fixed protocol average CRRT dose was: 30 ml/kg/h (14-57) vs 26 ml/kg/h (20-62) ( p < 0.05). The dynamic protocol generated a similar rate of increase of bicarbonate in an acute phase (RCA: 0.2 mmol/l/h vs 0.21 mmol/l/h, ns) and maintained a more stable level in a maintenance phase (RCA: -0.01 mmol/l/h vs 0.07 mmol/l/h, p < 0.05)., Discussion: Dynamic dosing for CRRT in this institution was safe and may lead to more tailored maintenance of biochemical homoeostasis., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Jack Eldridge, Aroon Bhardwaj Shah, Yize Wan and Susana Lucena-Amaro have no conflicts of interest to declare. Christopher Kirwan has received speaker fees from Baxter Inc, B. Braun Medical Ltd, Fresenius Medical Care and Nikkiso. He has received an unrestricted educational grant from Nikkiso and consultancy fees from Nikkiso and B. Braun Medical Ltd. John Prowle has received hospitality from B. Braun Medical Ltd. and speakers fees from Fresenius Medical Care, Nikkiso Europe GmbH and Baxter Inc. He has performed paid consultancy for Nikkiso Europe GmbH, Baxter Inc and Jafron Biomedical Co Ltd and has received an unrestricted research grant from Jafron Biomedical Co Ltd., (© The Intensive Care Society 2023.)
Published: 2024
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27. Cystatin C or creatinine for pre-operative assessment of kidney function and risk of post-operative acute kidney injury: a secondary analysis of the METS cohort study.

Author: Prowle JR, Croal B, Abbott TEF, Cuthbertson BH, and Wijeysundera DN
Abstract: Background: Post-operative acute kidney injury (PO-AKI) is a common surgical complication consistently associated with subsequent morbidity and mortality. Prior kidney dysfunction is a major risk factor for PO-AKI, however it is unclear whether serum creatinine, the conventional kidney function marker, is optimal in this population. Serum cystatin C is a kidney function marker less affected by body composition and might provide better prognostic information in surgical patients., Methods: This was a pre-defined, secondary analysis of a multi-centre prospective cohort study of pre-operative functional capacity. Participants were aged ≥40 years, undergoing non-cardiac surgery. We assessed the association of pre-operative estimated glomerular filtration rate (eGFR) calculated using both serum creatinine and serum cystatin C with PO-AKI within 3 days after surgery, defined by KDIGO creatinine changes. The adjusted analysis accounted for established AKI risk factors., Results: A total of 1347 participants were included (median age 65 years, interquartile range 56-71), of whom 775 (58%) were male. A total of 82/1347 (6%) patients developed PO-AKI. These patients were older, had higher prevalence of cardiovascular disease and related medication, were more likely to have intra-abdominal procedures, had more intraoperative transfusion, and were more likely to be dead at 1 year after surgery 6/82 (7.3%) vs 33/1265 (2.7%) ( P = .038). Pre-operative eGFR was lower in AKI than non-AKI patients using both creatinine and cystatin C. When both measurements were considered in a single age- and sex-adjusted model, eGFR-Cysc was strongly associated with PO-AKI, with increasing risk of AKI as eGFR-Cysc decreased below 90, while eGFR-Cr was no longer significantly associated., Conclusions: Data from over 1000 prospectively recruited surgical patients confirms pre-operative kidney function as major risk factor for PO-AKI. Of the kidney function markers available, compared with creatinine, cystatin C had greater strength of association with PO-AKI and merits further assessment in pre-operative assessment of surgical risk., Competing Interests: J.R.P. has received honoraria from Paion Ltd, Baxter Inc., Biomerieux SA and Nikkiso Europe GmbH; he is a scientific advisor for Mission Therapeutics Ltd, Jafron Biomedical Co. Ltd and Nephrolyx GmbH, and serves on a Data Monitoring and Safety Board for Novartis Inc.; he is a specialty editor for the Clinical Kidney Journal and Blood Purification. B.H.C. and D.N.W. are supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto. D.N.W. is supported in part by the Endowed Chair in Translational Anesthesiology Research at St Michael's Hospital and the University of Toronto. D.N.W. has received honoraria from Edwards Lifesciences within the last 5 years and is a member of the Scientific Advisory Board for Surgical Safety Technologies Inc. T.E.F.A. is an NIHR Clinical Lecturer, an editor of the British Journal of Anaesthesia, has received research funding from the Medical Research Council, the National Institute of Academic Anaesthesia and Barts Charity, and has received consultancy fees from MSD and Edwards Life Sciences unrelated to this work. All other authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)
Published: 2024
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28. Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT).

Author: Haines RW, Prowle JR, Day A, Bear DE, Heyland DK, and Puthucheary Z
Subjects: Adult, Humans, Urea, Bayes Theorem, Renal Replacement Therapy, Critical Illness therapy, Continuous Renal Replacement Therapy
Abstract: Background: Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein., Methods: We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses., Results: Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time., Conclusions: The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients., Clinicaltrials: gov Identifier: NCT03160547 (2017-05-17)., (© 2024. The Author(s).)
Published: 2024
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29. Tackling sepsis-associated AKI: are there any chances of REVIVAL with new approaches?

Author: Prowle JR, Bagshaw SM, and Forni LG
Subjects: Humans, Acute Kidney Injury therapy, Acute Kidney Injury complications, Sepsis complications
Published: 2024
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30. Health Resource Utilisation and Disparities: an Ecological Study of Admission Patterns Across Ethnicity in England Between 2017 and 2020.

Author: Toal CM, Fowler AJ, Pearse RM, Puthucheary Z, Prowle JR, and Wan YI
Subjects: Humans, Minority Groups, England epidemiology, Health Resources, Ethnicity, Pandemics
Abstract: Background and Aim: The COVID-19 pandemic highlighted adverse outcomes in Asian, Black, and ethnic minority groups. More research is required to explore underlying ethnic health inequalities. In this study, we aim to examine pre-COVID ethnic inequalities more generally through healthcare utilisation to contextualise underlying inequalities that were present before the pandemic., Design: This was an ecological study exploring all admissions to NHS hospitals in England from 2017 to 2020., Methods: The primary outcomes were admission rates within ethnic groups. Secondary outcomes included age-specific and age-standardised admission rates. Sub-analysis of admission rates across an index of multiple deprivation (IMD) deciles was also performed to contextualise the impact of socioeconomic differences amongst ethnic categories. Results were presented as a relative ratio (RR) with 95% confidence intervals., Results: Age-standardised admission rates were higher in Asian (RR 1.40 [1.38-1.41] in 2019) and Black (RR 1.37 [1.37-1.38]) and lower in Mixed groups (RR 0.91 [0.90-0.91]) relative to White. There was significant missingness or misassignment of ethnicity in NHS admissions: with 11.7% of admissions having an unknown/not-stated ethnicity assignment and 'other' ethnicity being significantly over-represented. Admission rates did not mirror the degree of deprivation across all ethnic categories., Conclusions: This study shows Black and Asian ethnic groups have higher admission rates compared to White across all age groups and when standardised for age. There is evidence of incomplete and misidentification of ethnicity assignment in NHS admission records, which may introduce bias to work on these datasets. Differences in admission rates across individual ethnic categories cannot solely be explained by socioeconomic status. Further work is needed to identify ethnicity-specific factors of these inequalities to allow targeted interventions at the local level., (© 2022. The Author(s).)
Published: 2023
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31. Hypoxemia Trajectory of Non-COVID-19 Acute Respiratory Distress Syndrome Patients. An Observational Study Focusing on Hypoxemia Resolver Status.

Author: Toal CM, Fowler AJ, Patel BV, Puthucheary Z, and Prowle JR
Abstract: Importance: Most studies on acute respiratory distress syndrome (ARDS) group patients by severity based on their initial degree of hypoxemia. However, this grouping has limitations, including inconsistent hypoxemia trajectories and outcomes., Objectives: This study explores the benefits of grouping patients by resolver status based on their hypoxemia progression over the first 7 days., Design Setting and Participants: This is an observational study from a large single-center database. Medical Information Mart for Intensive Care (MIMIC)-IV and MIMIC Chest X-ray JPEG databases were used. Mechanically ventilated patients that met the Berlin ARDS criteria were included., Main Outcomes and Measures: The primary outcome was the proportion of hypoxemia resolvers vs. nonresolvers in non-COVID-19 ARDS patients. Nonresolvers were defined as those whose hypoxemia worsened or remained moderate or severe over the first 7 days. Secondary outcomes included baseline admission characteristics, initial blood gases and ventilation settings, length of invasive mechanical ventilation, length of ICU stay, and ICU survival rates across resolver groups., Results: A total of 894 ICU admissions were included in the study. Of these, 33.9% were hypoxemia nonresolvers. The resolver groups showed no significant difference in age, body mass index, comorbidities, or Charlson score. There was no significant difference in the percentage of those with initial severe hypoxemia between the two groups (8.1% vs. 9.2%; p = 0.126). The initial Pao 2 /Fio 2 ratio did not significantly increase the odds ratio (OR) of being a nonresolver (OR, 0.84; 95% CI, 0.65-1.10). Nonresolver mortality was 61.4%, comparable to the survival rates seen in nonresolvers in a previous large COVID-19 ARDS study., Conclusions and Relevance: Our study shows that resolver status is a valuable grouping in ARDS. It has significant advantages over grouping by initial degree of hypoxemia, including better mapping of trajectory and comparable outcomes across other studies. While it may offer insights into disease-specific associations, future studies should include resolver status analysis for more definitive conclusions., Competing Interests: Dr. Fowler reports grants from the National Institutes of Health Research and Barts Charity. Dr. Patel reports consulting fees from GlaxoSmithKline and Faraday Health, he received grants from Mermaid Care A/C, he received grants from European Society of Intensive Care Medicine, he received grants from Royal Brompton & Harefield Charity, he received grants from European Commission, he grants from Academy of Medical Sciences, and he received grants from Imperial College London Covid Fund. Dr. Puthucheary reports honoraria for consultancy from GlaxoSmithKline, Lyric Pharmaceuticals, Faraday Pharmaceuticals, and Fresenius Kabi; he received speaker fees from Orion, Baxter, Nutricia, and Nestle; and he received educational grants from Baxter and VitaFlo. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)
Published: 2023
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32. Characterising biological mechanisms underlying ethnicity-associated outcomes in COVID-19 through biomarker trajectories: a multicentre registry analysis.

Author: Wan YI, Puthucheary ZA, Pearse RM, and Prowle JR
Subjects: Humans, Ethnicity, SARS-CoV-2, C-Reactive Protein, Biomarkers, Registries, COVID-19
Abstract: Background: Differences in routinely collected biomarkers between ethnic groups could reflect dysregulated host responses to disease and to treatments, and be associated with excess morbidity and mortality in COVID-19., Methods: A multicentre registry analysis from patients aged ≥16 yr with SARS-CoV-2 infection and emergency admission to Barts Health NHS Trust hospitals during January 1, 2020 to May 13, 2020 (wave 1) and September 1, 2020 to February 17, 2021 (wave 2) was subjected to unsupervised longitudinal clustering techniques to identify distinct phenotypic patient clusters based on trajectories of routine blood results over the first 15 days of hospital admission. Distribution of trajectory clusters across ethnic categories was determined, and associations between ethnicity, trajectory clusters, and 30-day survival were assessed using multivariable Cox proportional hazards modelling. Secondary outcomes were ICU admission, survival to hospital discharge, and long-term survival to 640 days., Results: We included 3237 patients with hospital length of stay ≥7 days. In patients who died, there was greater representation of Black and Asian ethnicity in trajectory clusters for C-reactive protein and urea-to-creatinine ratio associated with increased risk of death. Inclusion of trajectory clusters in survival analyses attenuated or abrogated the higher risk of death in Asian and Black patients. Inclusion of C-reactive protein went from hazard ratio (HR) 1.36 [0.95-1.94] to HR 0.97 [0.59-1.59] (wave 1), and from HR 1.42 [1.15-1.75]) to HR 1.04 [0.78-1.39] (wave 2) in Asian patients. Trajectory clusters associated with reduced 30-day survival were similarly associated with worse secondary outcomes., Conclusions: Clinical biochemical monitoring of COVID-19 and progression and treatment response in SARS-CoV-2 infection should be interpreted in the context of ethnic background., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2023
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33. Long-term disease interactions amongst surgical patients: a population cohort study.

Author: Fowler AJ, Wahedally MAH, Abbott TEF, Prowle JR, Cromwell DA, and Pearse RM
Subjects: Adult, Humans, Cohort Studies, Elective Surgical Procedures, Logistic Models, Seizures, Risk Factors, Retrospective Studies, State Medicine, Postoperative Complications epidemiology
Abstract: Background: The average age of the surgical population continues to increase, as does prevalence of long-term diseases. However, outcomes amongst multi-morbid surgical patients are not well described., Methods: We included adults undergoing non-obstetric surgical procedures in the English National Health Service between January 2010 and December 2015. Patients could be included multiple times in sequential 90-day procedure spells. Multi-morbidity was defined as presence of two or more long-term diseases identified using a modified Charlson comorbidity index. The primary outcome was 90-day postoperative death. Secondary outcomes included emergency hospital readmission within 90 days. We calculated age- and sex-adjusted odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. We compared the outcomes associated with different disease combinations., Results: We identified 20 193 659 procedure spells among 13 062 715 individuals aged 57 (standard deviation 19) yr. Multi-morbidity was present among 2 577 049 (12.8%) spells with 195 965 deaths (7.6%), compared with 17 616 610 (88.2%) spells without multi-morbidity with 163 529 deaths (0.9%). Multi-morbidity was present in 1 902 859/16 946 808 (11.2%) elective spells, with 57 663 deaths (2.7%, OR 4.9 [95% CI: 4.9-4.9]), and 674 190/3 246 851 (20.7%) non-elective spells, with 138 302 deaths (20.5%, OR 3.0 [95% CI: 3.0-3.1]). Emergency readmission followed 547 399 (22.0%) spells with multi-morbidity compared with 1 255 526 (7.2%) without. Multi-morbid patients accounted for 57 663/114 783 (50.2%) deaths after elective spells, and 138 302/244 711 (56.5%) after non-elective spells. The rate of death varied five-fold from lowest to highest risk disease pairs., Conclusion: One in eight patients undergoing surgery have multi-morbidity, accounting for more than half of all postoperative deaths. Disease interactions amongst multi-morbid patients is an important determinant of patient outcome., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2023
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34. Comparison of Cystatin C and Creatinine in the Assessment of Measured Kidney Function during Critical Illness.

Author: Haines RW, Fowler AJ, Liang K, Pearse RM, Larsson AO, Puthucheary Z, and Prowle JR
Subjects: Humans, Bayes Theorem, Creatinine, Critical Illness, Glomerular Filtration Rate physiology, Kidney diagnostic imaging, Kidney physiology, Cystatin C, Iohexol
Abstract: Background: Incomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded by muscle loss and may improve identification of persistent kidney dysfunction., Methods: To assess kidney function during prolonged critical illness, we enrolled 38 mechanically ventilated patients with an expected length of stay of >72 hours near admission to intensive care unit (ICU) in a single academic medical center. We assessed sequential kidney function using creatinine, cystatin C, and iohexol clearance measurements. The primary outcome was difference between eGFR creatinine and eGFR cystatin C at ICU discharge using Bayesian regression modeling. We simultaneously measured muscle mass by ultrasound of the rectus femoris to assess the confounding effect on serum creatinine generation., Results: Longer length of ICU stay was associated with greater difference between eGFR creatinine and eGFR cystatin C at a predicted rate of 2 ml/min per 1.73 m 2 per day (95% confidence interval [CI], 1 to 2). By ICU discharge, the posterior mean difference between creatinine and cystatin C eGFR was 33 ml/min per 1.73 m 2 (95% credible interval [CrI], 24 to 42). In 27 patients with iohexol clearance measured close to ICU discharge, eGFR creatinine was on average two-fold greater than the iohexol gold standard, and posterior mean difference was 59 ml/min per 1.73 m 2 (95% CrI, 49 to 69). The posterior mean for eGFR cystatin C suggested a 22 ml/min per 1.73 m 2 (95% CrI, 13 to 31) overestimation of measured GFR. Each day in ICU resulted in a predicted 2% (95% CI, 1% to 3%) decrease in muscle area. Change in creatinine-to-cystatin C ratio showed good longitudinal, repeated measures correlation with muscle loss, R =0.61 (95% CI, 0.50 to 0.72)., Conclusions: eGFR creatinine systematically overestimated kidney function after prolonged critical illness. Cystatin C better estimated true kidney function because it seemed unaffected by the muscle loss from prolonged critical illness., Clinical Trial Registry Name and Registration Number: Skeletal Muscle Wasting and Renal Dysfunction After Critical Illness Trauma - Outcomes Study (KRATOS), NCT03736005 ., (Copyright © 2023 by the American Society of Nephrology.)
Published: 2023
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35. Long-term healthcare use after postoperative complications: an analysis of linked primary and secondary care routine data.

Author: Fowler AJ, Brayne AB, Pearse RM, and Prowle JR
Abstract: Background: Postoperative complications are associated with reduced long-term survival. We characterise healthcare use changes after sentinel postoperative complications., Methods: We linked primary and secondary care records of patients undergoing elective surgery at four East London hospitals (2012-7) with at least 90 days follow-up. Complication codes (wound infection, urinary tract infection, pneumonia, new stroke, and new myocardial infarction) recorded within 90 days of surgery were identified from primary or secondary care. Outcomes were change in healthcare contact days in the 2 yr before and after surgery, and 2 yr mortality. We report rate ratios (RaR) with 95% confidence intervals and adjusted for baseline healthcare use and confounders using negative binomial regression., Results: We included 49 913 patients (median age 49 yr [inter-quartile range {IQR}: 34-64]), 27 958 (56.0%) were female. Amongst 3883 (7.8%) patients with complications (median age 58 [IQR: 43-72]), there were 18.4 days per year in contact with healthcare before surgery and 25.3 days after surgery (RaR: 1.38 [1.37-1.39]). Patients without complications (median age 48 [IQR: 33-63]) had 12.3 days per year in contact with healthcare before surgery and 14.0 days after surgery (RaR: 1.14 [1.14-1.15]). The adjusted incidence rate ratio of days in contact with healthcare associated with complications was 1.67 (1.49-1.87). More patients (391; 10.1%) with complications died within 2 yr than those without (1428; 3.1%)., Conclusions: Patients with postoperative complications are older with greater healthcare use before surgery. However, their absolute and relative increases in healthcare use after surgery are greater than patients without complications., (© 2023 Published by Elsevier Ltd on behalf of British Journal of Anaesthesia.)
Published: 2023
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36. Serial Urinary C-C Motif Chemokine Ligand 14 and Risk of Persistent Severe Acute Kidney Injury.

Author: Prowle JR, Artigas A, Bagshaw SM, Forni LG, Heung M, Hoste E, Marlies O, Koyner JL, Chawla L, Kampf JP, Kwan T, McPherson P, and Kellum JA
Abstract: To assess the added prognostic value of serial monitoring of urinary C-C motif chemokine ligand 14 (uCCL14) over that of single measurements, which have been shown to be prognostic for development of persistent severe acute kidney injury (AKI) in critically ill patients., Design: Retrospective observational study., Setting: Data derived from two multinational ICU studies (Ruby and Sapphire)., Patients: Critically ill patients with early stage 2-3 AKI., Interventions: None., Measurements and Main Results: We analyzed three consecutive uCCL14 measurements at 12-hour intervals after diagnosis of stage 2-3 AKI by Kidney Disease Improving Global Outcomes criteria. Primary outcome was persistent severe AKI, defined as 72 consecutive hours of stage 3 AKI, death, or receipt of dialysis prior to 72 hours. uCCL14 was measured using the NEPHROCLEAR uCCL14 Test on the Astute 140 Meter (Astute Medical, San Diego, CA). Based on predefined, validated cutoffs, we categorized uCCL14 as: low (≤ 1.3 ng/mL), medium (> 1.3 to ≤ 13 ng/mL), or high (> 13 ng/mL). Seventy-five of 417 patients with three consecutive uCCL14 measurements developed persistent severe AKI. Initial uCCL14 category strongly correlated with primary endpoint and, in most cases (66%), uCCL14 category was unchanged over the first 24 hours. Compared with no change and accounting for baseline category, decrease in category was associated with decreased odds of persistent severe AKI (odds ratio [OR], 0.20; 95% CI, 0.08-0.45; p < 0.001) and an increase in category with increased odds (OR, 4.04; 95% CI, 1.75-9.46; p = 0.001)., Conclusions: In one-third of patients with moderate to severe AKI uCCL14 risk category altered over three serial measurements and such changes were associated with altered risk for persistent severe AKI. Serial CCL-14 measurement may detect progression or resolution of underlying kidney pathology and help refine AKI prognosis., Competing Interests: Drs. Kampf, Kwan, and McPherson are employees of Astute Medical. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)
Published: 2023
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37. Hemoperfusion in Trauma.

Author: Eldridge JC, Wan YI, and Prowle JR
Subjects: Humans, Multiple Organ Failure etiology, Multiple Organ Failure prevention & control, Hemorrhage etiology, Hemorrhage therapy, Hemoperfusion, Multiple Trauma therapy
Abstract: Major trauma care has seen significant improvements in early mortality, reflecting improvements in prehospital techniques for hemorrhage control and speed of access to specialized trauma centers. However, many patients then go on to die in the intensive care unit (ICU), and improvements in immediate trauma care are presenting intensivists with greater numbers of severely injured patients who might previously have died shortly after injury. It is theorized that, despite initial survival, these patients deteriorate due to massive release of damage associated molecular patterns (DAMPs) after traumatic and ischemic tissue injury. These trigger a vicious cycle of overactive pro- and anti-inflammatory pathways, leading to organ dysfunction and immunoparesis. Extracorporeal hemoperfusion, with its ability to adsorb both DAMPs and inflammatory mediators from the bloodstream, has the potential to break this cycle and could, in theory, then prevent early death or organ dysfunction in the ICU. However, currently, there has been little research around the indications for, and efficacy of, this therapy in the setting of polytrauma. Here we outline potential molecular targets, summarize existing exploratory studies, and suggest areas for future research required to establish the benefits of hemoperfusion as an adjunct therapy in major polytrauma., (© 2023 S. Karger AG, Basel.)
Published: 2023
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38. COVID-19-associated AKI.

Author: Matsumoto K and Prowle JR
Subjects: Humans, Renal Replacement Therapy, Intensive Care Units, Glomerular Filtration Rate, Risk Factors, Retrospective Studies, COVID-19 complications, Acute Kidney Injury epidemiology, Acute Kidney Injury etiology, Acute Kidney Injury therapy
Abstract: Purpose of Review: While it is now widely established acute kidney injury (AKI) is a common and important complication of coronavirus disease (COVID-19) disease, there is marked variability in its reported incidence and outcomes. This narrative review provides a mid-2022 summary of the latest epidemiological evidence on AKI in COVID-19., Recent Findings: Large observational studies and meta-analyses report an AKI incidence of 28-34% in all inpatients and 46-77% in intensive care unit (ICU). The incidence of more severe AKI requiring renal replacement therapy (RRT) in ICU appears to have declined over time, in data from England and Wales RRT use declined from 26% at the start of the pandemic to 14% in 2022. The majority of survivors apparently recover their kidney function by hospital discharge; however, these individuals appear to remain at increased risk of future AKI, estimated glomerular filtration rate (eGFR) decline and chronic kidney disease. Importantly even in the absence of overt AKI a significant proportion of survivors of COVID-19 hospitalisation had reduced eGFR on follow-up., Summary: This review summarises the epidemiology, risk factors, outcomes and treatment of COVID-19-associated AKI across the global pandemic. In particular the long-term impact of COVID-19 disease on kidney health is uncertain and requires further characterisation., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2022
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39. Long-term mortality following complications after elective surgery: a secondary analysis of pooled data from two prospective cohort studies.

Author: Fowler AJ, Wan YI, Prowle JR, Chew M, Campbell D, Cuthbertson B, Wijeysundera DN, Pearse R, and Abbott T
Subjects: Cohort Studies, Female, Humans, Male, Middle Aged, Postoperative Complications etiology, Prospective Studies, Elective Surgical Procedures adverse effects, Quality of Life
Abstract: Background: Complications after surgery affect survival and quality of life. We aimed to confirm the relationship between postoperative complications and death within 1 yr after surgery., Methods: We conducted a secondary analysis of pooled data from two prospective cohort studies of patients undergoing surgery in five high-income countries between 2012 and 2014. Exposure was any complication within 30 days after surgery. Primary outcome was death within 1 yr after surgery, ascertained by direct follow-up or linkage to national registers. We adjusted for clinically important covariates using a mixed-effect multivariable Cox proportional hazards regression model. We conducted a planned subgroup analysis by type of complication. Data are presented as mean with standard deviation (sd), n (%), and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs)., Results: The pooled cohort included 10 132 patients. After excluding 399 (3.9%) patients with missing data or incomplete follow-up, 9733 patients were analysed. The mean age was 59 [sd 16.8] yr, and 5362 (55.1%) were female. Of 9733 patients, 1841 (18.9%) had complications within 30 days after surgery, and 319 (3.3%) died within 1 yr after surgery. Of 1841 patients with complications, 138 (7.5%) died within 1 yr after surgery compared with 181 (2.3%) of 7892 patients without complications (aHR 1.94 [95% CI: 1.53-2.46]). Respiratory failure was associated with the highest risk of death, resulting in six deaths amongst 28 patients (21.4%)., Conclusions: Postoperative complications are associated with increased mortality at 1 yr. Further research is needed to identify patients at risk of complications and to reduce mortality., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2022
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40. Postoperative Acute Kidney Injury.

Author: Boyer N, Eldridge J, Prowle JR, and Forni LG
Subjects: Humans, Risk Factors, Postoperative Complications diagnosis, Postoperative Complications etiology, Postoperative Complications therapy, Creatinine, Biomarkers, Acute Kidney Injury diagnosis, Acute Kidney Injury etiology, Acute Kidney Injury therapy
Abstract: Postoperative AKI is a common complication of major surgery and is associated with significant morbidity and mortality. The Kidney Disease Improving Global Outcomes AKI definition allows consensus classification and identification of postoperative AKI through changes in serum creatinine and/or urine output. However, such conventional diagnostic criteria may be inaccurate in the postoperative period, suggesting a potential to refine diagnosis by application of novel diagnostic biomarkers. Risk factors for the development of postoperative AKI can be thought of in terms of preoperative, intraoperative, and postoperative factors and, as such, represent areas that may be targeted perioperatively to minimize the risk of AKI. The treatment of postoperative AKI remains predominantly supportive, although application of management bundles may translate into improved outcomes., (Copyright © 2022 by the American Society of Nephrology.)
Published: 2022
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41. Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) Trial.

Author: Haines RW, Fowler AJ, Wan YI, Flower L, Heyland DK, Day A, Pearse RM, Prowle JR, and Puthucheary Z
Subjects: Bayes Theorem, Creatinine, Humans, Oxidative Stress, Urea, Critical Illness therapy, Glutamine
Abstract: Objectives: Ongoing risk of death and poor functional outcomes are important consequences of prolonged critical illness. Characterizing the catabolic phenotype of prolonged critical illness could illuminate biological processes and inform strategies to attenuate catabolism. We aimed to examine if urea-to-creatinine ratio, a catabolic signature of prolonged critical illness, was associated with mortality after the first week of ICU stay., Design: Reanalysis of multicenter randomized trial of glutamine supplementation in critical illness (REducing Deaths due to OXidative Stress [REDOXS])., Setting: Multiple adult ICUs., Patients: Adult patients admitted to ICU with two or more organ failures related to their acute illness and surviving to day 7., Interventions: None., Measurements and Main Results: The association between time-varying urea-to-creatinine ratio and 30-day mortality was tested using Bayesian joint models adjusted for prespecified-covariates (age, kidney replacement therapy, baseline Sequential Organ Failure Assessment, dietary protein [g/kg/d], kidney dysfunction, and glutamine-randomization). From 1,021 patients surviving to day 7, 166 (16.3%) died by day 30. After adjustment in a joint model, a higher time-varying urea-to-creatinine ratio was associated with increased mortality (hazard ratio [HR], 2.15; 95% credible interval, 1.66-2.82, for a two-fold greater urea-to-creatinine ratio). This association persisted throughout the 30-day follow-up. Mediation analysis was performed to explore urea-to-creatinine ratio as a mediator-variable for the increased risk of death reported in REDOXS when randomized to glutamine, an exogenous nitrogen load. Urea-to-creatinine ratio closest to day 7 was estimated to mediate the risk of death associated with randomization to glutamine supplementation (HR, 1.20; 95% CI, 1.04-1.38; p = 0.014), with no evidence of a direct effect of glutamine (HR, 0.90; 95% CI, 0.62-1.30; p = 0.566)., Conclusions: The catabolic phenotype measured by increased urea-to-creatinine ratio is associated with increased risk of death during prolonged ICU stay and signals the deleterious effects of glutamine administration in the REDOXS study. Urea-to-creatinine ratio is a promising catabolic signature and potential interventional target., Competing Interests: Dr. Pearse’s institution received funding from Intersurgical and Edwards Lifesciences; he received funding from GlaxoSmithKline. Dr. Prowle received funding from Fresenius Kabi, Baxter, Nikkiso Europe GmbH Consultancy, Jafron Biomedical, Mission Therapeutics, Quark Pharma, Medibeacon, and Biomerieux. Dr. Puthucheary received funding from Nestle, Fresenius Kabi, Nutricia, Faraday Pharmaceuticals, and Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)
Published: 2022
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42. Effect of intermittent or continuous feeding and amino acid concentration on urea-to-creatinine ratio in critical illness.

Author: Flower L, Haines RW, McNelly A, Bear DE, Koelfat K, Damink SO, Hart N, Montgomery H, Prowle JR, and Puthucheary Z
Subjects: Amino Acids, Essential, Creatinine, Critical Care, Humans, Urea, Amino Acids, Critical Illness therapy
Abstract: Background: We sought to determine whether peaks in essential amino acid (EAA) concentration associated with intermittent feeding may provide anabolic advantages when compared with continuous feeding regimens in critical care., Methods: We performed a secondary analysis of data from a multicenter trial of UK intensive care patients randomly assigned to intermittent or continuous feeding. A linear mixed-effects model was developed to assess differences in urea-creatinine ratio (raised values of which can be a marker of muscle wasting) between arms. To investigate metabolic phenotypes, we performed k-means urea-to-creatinine ratio trajectory clustering. Amino acid concentrations were also modeled against urea-to-creatinine ratio from day 1 to day 7. The main outcome measure was serum urea-to-creatinine ratio (millimole per millimole) from day 0 to the end of the 10-day study period., Results: Urea-to-creatinine ratio trajectory differed between feeding regimens (coefficient -.245; P = .002). Patients receiving intermittent feeding demonstrated a flatter urea-to-creatinine ratio trajectory. With k-means analysis, the cluster with the largest proportion of continuously fed patients demonstrated the steepest rise in urea-to-creatinine ratio. Neither protein intake per se nor serum concentrations of EAA concentrations were correlated with urea-to-creatinine ratio (coefficient = .088 [P = .506] and coefficient <.001 [P = .122], respectively)., Conclusion: Intermittent feeding can mitigate the rise in urea-to-creatinine ratio otherwise seen in those continuously fed, suggesting that catabolism may have been, to some degree, prevented., (© 2021 American Society for Parenteral and Enteral Nutrition.)
Published: 2022
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43. Ethnic disparities in hospitalisation and hospital-outcomes during the second wave of COVID-19 infection in east London.

Author: Wan YI, Apea VJ, Dhairyawan R, Puthucheary ZA, Pearse RM, Orkin CM, and Prowle JR
Subjects: Adult, Aged, Asian People, Black People, COVID-19 ethnology, COVID-19 therapy, COVID-19 virology, Female, Hospitals, Humans, Intensive Care Units, London, Male, Middle Aged, Proportional Hazards Models, Risk Factors, SARS-CoV-2 isolation & purification, Survival Analysis, White People, COVID-19 mortality, Ethnicity, Hospitalization statistics & numerical data
Abstract: It is unclear if changes in public behaviours, developments in COVID-19 treatments, improved patient care, and directed policy initiatives have altered outcomes for minority ethnic groups in the second pandemic wave. This was a prospective analysis of patients aged ≥ 16 years having an emergency admission with SARS-CoV-2 infection between 01/09/2020 and 17/02/2021 to acute NHS hospitals in east London. Multivariable survival analysis was used to assess associations between ethnicity and mortality accounting for predefined risk factors. Age-standardised rates of hospital admission relative to the local population were compared between ethnic groups. Of 5533 patients, the ethnic distribution was White (n = 1805, 32.6%), Asian/Asian British (n = 1983, 35.8%), Black/Black British (n = 634, 11.4%), Mixed/Other (n = 433, 7.8%), and unknown (n = 678, 12.2%). Excluding 678 patients with missing data, 4855 were included in multivariable analysis. Relative to the White population, Asian and Black populations experienced 4.1 times (3.77-4.39) and 2.1 times (1.88-2.33) higher rates of age-standardised hospital admission. After adjustment for various patient risk factors including age, sex, and socioeconomic deprivation, Asian patients were at significantly higher risk of death within 30 days (HR 1.47 [1.24-1.73]). No association with increased risk of death in hospitalised patients was observed for Black or Mixed/Other ethnicity. Asian and Black ethnic groups continue to experience poor outcomes following COVID-19. Despite higher-than-expected rates of hospital admission, Black and Asian patients also experienced similar or greater risk of death in hospital since the start of the pandemic, implying a higher overall risk of COVID-19 associated death in these communities., (© 2022. The Author(s).)
Published: 2022
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44. Death after surgery among patients with chronic disease: prospective study of routinely collected data in the English NHS.

Author: Fowler AJ, Wahedally MAH, Abbott TEF, Smuk M, Prowle JR, Pearse RM, and Cromwell DA
Subjects: Adult, Aged, Chronic Disease, Elective Surgical Procedures mortality, Elective Surgical Procedures statistics & numerical data, England, Female, Humans, Male, Middle Aged, Postoperative Complications epidemiology, Prospective Studies, Risk Factors, Routinely Collected Health Data, State Medicine, Surgical Procedures, Operative statistics & numerical data, Survival Rate, Postoperative Complications mortality, Surgical Procedures, Operative mortality
Abstract: Background: Five million surgeries take place in the NHS each year. Little is known about the prevalence of chronic diseases among these patients, and the association with postoperative outcomes., Methods: Analysis of routine data from all NHS hospitals in England including patients aged ≥18 yr undergoing non-obstetric surgery between January 1, 2010 and December 31, 2015. The primary outcome was death within 90 days after surgery. For each chronic disease, we adjusted for age, sex, presence of other diseases, emergency surgery, and year using logistic regression models. We defined high-risk diseases as those with an adjusted odds ratio (OR) for death ≥2 and report associated 2-yr survival., Results: We included 8 624 611 patients (median age, 53 [36-68] yr), of whom 6 913 451 (80.2%) underwent elective surgery and 1 711 160 (19.8%) emergency surgery. Overall, 2 311 600 (26.8%) patients had a chronic disease, of whom 109 686 (4.7%) died within 90 days compared with 24 136 (0.4%) of 6 313 011 without chronic disease. Respiratory disease (1 002 281 [11.6%]), diabetes mellitus (662 706 [7.7%]), and cancer (310 363; 3.6%) were the most common. Four chronic diseases accounted for 7.7% of patients but 59.0% of deaths: cancer (37 693 deaths [12.1%]; OR=8.3 [8.2-8.5]), liver disease (8638 deaths [10.3%]; OR=4.5 [4.4-4.7]), cardiac failure (26 604 deaths [12.6%]; OR=2.4 [2.4-2.5]), and dementia (19 912 deaths [17.9%]; OR=2.0 [1.9-2.0]). Two-year survival was 67.7% among patients with high-risk chronic disease, compared with 97.1% without., Conclusion: One in four surgical patients has a chronic disease with an associated 10-fold increase in risk of postoperative death. Two-thirds of all deaths after surgery occur among patients with high-risk diseases (cancer, cardiac failure, liver disease, dementia)., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)
Published: 2022
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45. Characteristics and Outcomes of Patients With Frailty Admitted to ICU With Coronavirus Disease 2019: An Individual Patient Data Meta-Analysis.

Author: Subramaniam A, Anstey C, Curtis JR, Ashwin S, Ponnapa Reddy M, Aliberti MJR, Avelino-Silva TJ, Welch C, Koduri G, Prowle JR, Wan YI, Laurent MR, Marengoni A, Lim JP, Pilcher D, and Shekar K
Abstract: Frailty is often used in clinical decision-making for patients with coronavirus disease 2019, yet studies have found a variable influence of frailty on outcomes in those admitted to the ICU. In this individual patient data meta-analysis, we evaluated the characteristics and outcomes across the range of frailty in patients admitted to ICU with coronavirus disease 2019., Data Sources: We contacted the corresponding authors of 16 eligible studies published between December 1, 2019, and February 28, 2021, reporting on patients with confirmed coronavirus disease 2019 admitted to ICU with a documented Clinical Frailty Scale., Study Selection: Individual patient data were obtained from seven studies with documented Clinical Frailty Scale were included. We classified patients as nonfrail (Clinical Frailty Scale = 1-4) or frail (Clinical Frailty Scale = 5-8)., Data Extraction: We collected patient demographics, Clinical Frailty Scale score, ICU organ supports, and clinically relevant outcomes (ICU and hospital mortality, ICU and hospital length of stays, and discharge destination). The primary outcome was hospital mortality., Data Synthesis: Of the 2,001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and Sequential Organ Failure Assessment score, Clinical Frailty Scale score greater than or equal to 4, use of mechanical ventilation, vasopressors, renal replacement therapy, and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in patients with frailty (65.2% vs 41.8%; p < 0.001), with adjusted mortality increasing with a rising Clinical Frailty Scale score beyond 3. Younger and nonfrail patients were more likely to receive mechanical ventilation. Patients with frailty spent less time on mechanical ventilation (median days [interquartile range], 9 [5-16] vs 11 d [6-18 d]; p = 0.012) and accounted for only 12.3% of total ICU bed days., Conclusions: Patients with frailty with coronavirus disease 2019 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with nonfrail patients. Patients with frailty receiving mechanical ventilation were at greater risk of death than patients without frailty., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)
Published: 2022
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46. Admission serum myoglobin and the development of acute kidney injury after major trauma.

Author: Tarazona V, Figueiredo S, Hamada S, Pochard J, Haines RW, Prowle JR, Duranteau J, Vigué B, and Harrois A
Abstract: Background: Myoglobin and creatine kinase (CK) are both established markers of muscle injury but their hospital admission values have never been compared to predict post-traumatic acute kidney injury (AKI)., Methods: An observational registry study of consecutive trauma patients admitted to a major regional trauma centre. The primary outcome was stage 1 or more AKI in the first 7 days after trauma. We assessed the association of hospital admission myoglobin or CK with development of AKI both alone and when added to two existing risk prediction models for post traumatic AKI., Results: Of the 857 trauma patients (median age 36 [25-52], 96% blunt trauma, median ISS of 20 [12-47]) included, 102 (12%) developed AKI. Admission myoglobin performed better than CK to predict AKI any stage with an AUC-ROC of 0.74 (95% CI 0.68-0.79) and 0.63 (95% CI 0.57-0.69), respectively (p < 0.001). Admission myoglobin also performed better than CK to predict AKI stage 2 or 3 [AUC-ROC of 0.79 (95% CI 0.74-0.84) and 0.74 (95% CI 0.69-0.79), respectively (p < 0.001)] with a best cutoff value of 1217 µg/L (sensitivity 74%, specificity 77%). Admission myoglobin added predictive value to two established models of AKI prediction and showed significant ability to reclassify subjects regarding AKI status, while admission CK did not. Decision curve analysis also revealed that myoglobin added net benefit to established predictive models. Admission myoglobin was better than CK at predicting development of significant rhabdomyolysis., Conclusions: Admission myoglobin better predicts the development of AKI and severe rhabdomyolysis after major trauma. Admission myoglobin should be added in established predictive models of post-traumatic AKI to early identify high-risk patients., (© 2021. The Author(s).)
Published: 2021
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47. Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative.

Author: Prowle JR, Forni LG, Bell M, Chew MS, Edwards M, Grams ME, Grocott MPW, Liu KD, McIlroy D, Murray PT, Ostermann M, Zarbock A, Bagshaw SM, Bartz R, Bell S, Bihorac A, Gan TJ, Hobson CE, Joannidis M, Koyner JL, Levett DZH, Mehta RL, Miller TE, Mythen MG, Nadim MK, Pearse RM, Rimmele T, Ronco C, Shaw AD, and Kellum JA
Subjects: Acute Kidney Injury physiopathology, Acute Kidney Injury prevention & control, Humans, Kidney physiopathology, Postoperative Complications physiopathology, Postoperative Complications prevention & control, Risk Factors, Acute Kidney Injury etiology, Postoperative Complications etiology
Abstract: Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research., (© 2021. The Author(s).)
Published: 2021
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48. Fluid balance-adjusted creatinine in diagnosing acute kidney injury in the critically ill.

Author: Törnblom S, Wiersema R, Prowle JR, Haapio M, Pettilä V, and Vaara ST
Subjects: Creatinine, Humans, Prospective Studies, Water-Electrolyte Balance, Acute Kidney Injury diagnosis, Critical Illness
Abstract: Background: Acute kidney injury (AKI) is often diagnosed based on plasma creatinine (Cr) only. Adjustment of Cr for cumulative fluid balance due to potential dilution of Cr and subsequently missed Cr-based diagnosis of AKI has been suggested, albeit the physiological rationale for these adjustments is questionable. Furthermore, whether these adjustments lead to a different incidence of AKI when used in conjunction with urine output (UO) criteria is unknown., Methods: This was a post hoc analysis of the Finnish Acute Kidney Injury study. Hourly UO and daily plasma Cr were measured during the first 5 days of intensive care unit admission. Cr values were adjusted following the previously used formula and combined with the UO criteria. Resulting incidences and mortality rates were compared with the results based on unadjusted values., Results: In total, 2044 critically ill patients were analyzed. The mean difference between the adjusted and unadjusted Cr of all 7279 observations was 5 (±15) µmol/L. Using adjusted Cr in combination with UO and renal replacement therapy criteria resulted in the diagnosis of 19 (1%) additional AKI patients. The absolute difference in the incidence was 0.9% (95% confidence interval [CI]: 0.3%-1.6%). Mortality rates were not significantly different between the reclassified AKI patients using the full set of Kidney Disease: Improving Global Outcomes criteria., Conclusion: Fluid balance-adjusted Cr resulted in little change in AKI incidence, and only minor differences in mortality between patients who changed category after adjustment and those who did not. Using adjusted Cr values to diagnose AKI does not seem worthwhile in critically ill patients., (© 2021 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)
Published: 2021
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49. Ethnicity and acute hospital admissions: Multi-center analysis of routine hospital data.

Author: Wan YI, Robbins AJ, Apea VJ, Orkin CM, Pearse RM, Puthucheary ZA, and Prowle JR
Abstract: Background: The effects of ethnic and social inequalities on patient outcomes in acute healthcare remain poorly understood. Methods: Prospectively-defined analysis of registry data from four acute NHS hospitals in east London including all patients ≥ 18 years with a first emergency admission between 1st January 2013 and 31st December 2018. We calculated adjusted one-year mortality risk using logistic regression. Results are presented as n (%), median (IQR), and odds ratios (OR) with 95% confidence intervals. Findings: We included 203,182 patients. 43,101 (21%) patients described themselves as Asian, 21,388 (10.5%) Black, 2,982 (1.4%) Mixed, 13,946 (6.8%) Other ethnicity, and 100,065 (49%) White. We excluded 21,700 (10.7%) patients with undisclosed ethnicity. 16,054 (7.9%) patients died within one year. Non-white patients were younger (Asian: 43 [31-62] years; Black: 48 [33-63] years; Mixed 36 [26-52] years) than White patients (55 [35-75] years), with a higher incidence of comorbid disease. In each age-group, non-white patients were more likely to be admitted to hospital. This effect was greatest in the ≥ 80 years age-group (32% non-white admitted to hospital versus 23% non-white in community population). Deprivation was associated with increased mortality in all ethnic groups (OR 1.41 [1.33-1.50]; p < 0.001). However, when adjusted for age, Asian (0.69 [0.66-0.73], p < 0.0001) and Black patients (0.79 [0.74-0.85]; p < 0.0001) experienced a lower mortality risk than White patients. Interpretation: Ethnic and social disparities are associated with important differences in acute health outcomes. However, these differences are masked by statistical adjustment because patients from ethnic minorities present at a younger age. Funding: None., Competing Interests: All authors declare no other competing interests., (© 2021 The Author(s).)
Published: 2021
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50. Acute kidney injury in the critically ill: an updated review on pathophysiology and management.

Author: Pickkers P, Darmon M, Hoste E, Joannidis M, Legrand M, Ostermann M, Prowle JR, Schneider A, and Schetz M
Subjects: Biomarkers, Humans, Kidney, Prognosis, Acute Kidney Injury diagnosis, Acute Kidney Injury etiology, Acute Kidney Injury therapy, Critical Illness
Abstract: Acute kidney injury (AKI) is now recognized as a heterogeneous syndrome that not only affects acute morbidity and mortality, but also a patient's long-term prognosis. In this narrative review, an update on various aspects of AKI in critically ill patients will be provided. Focus will be on prediction and early detection of AKI (e.g., the role of biomarkers to identify high-risk patients and the use of machine learning to predict AKI), aspects of pathophysiology and progress in the recognition of different phenotypes of AKI, as well as an update on nephrotoxicity and organ cross-talk. In addition, prevention of AKI (focusing on fluid management, kidney perfusion pressure, and the choice of vasopressor) and supportive treatment of AKI is discussed. Finally, post-AKI risk of long-term sequelae including incident or progression of chronic kidney disease, cardiovascular events and mortality, will be addressed., (© 2021. The Author(s).)
Published: 2021
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