Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Objective:To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU.Design:Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups g

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Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Fifteen recommendations and a therapeutic algorithm regarding the management of acute respiratory distress syndrome (ARDS) at the early phase in adults are proposed. The Grade of Recommendation Assessment, Development and Evaluation (GRADE) methodology has been followed. Four recommendations (low tidal volume, plateau pressure limitation, no oscillatory ventilation, and prone position) had a high level of proof (GRADE 1 + or 1 −); four (high positive end-expiratory pressure [PEEP] in moderate and severe ARDS, muscle relaxants, recruitment maneuvers, and venovenous extracorporeal membrane oxygenation [ECMO]) a low level of proof (GRADE 2 + or 2 −); seven (surveillance, tidal volume for non ARDS mechanically ventilated patients, tidal volume limitation in the presence of low plateau pressure, PEEP > 5 cmH2O, high PEEP in the absence of deleterious effect, pressure mode allowing spontaneous ventilation after the acute phase, and nitric oxide) corresponded to a level of proof that did not allow use of the GRADE classification and were expert opinions. Lastly, for three aspects of ARDS management (driving pressure, early spontaneous ventilation, and extracorporeal carbon dioxide removal), the experts concluded that no sound recommendation was possible given current knowledge. The recommendations and the therapeutic algorithm were approved by the experts with strong agreement.

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Formal guidelines: management of acute respiratory distress syndrome

Author(s): Devlin, John W; Skrobik, Yoanna; Gelinas, Celine; Needham, Dale M; Slooter, Arjen JC; Pandharipande, Pratik P; Watson, Paula L; Weinhouse, Gerald L; Nunnally, Mark E; Rochwerg, Bram; Balas, Michele C; van den Boogaard, Mark; Bosma, Karen J; Brummel, Nathaniel E; Chanques, Gerald; Denehy, Linda; Drouot, Xavier; Fraser, Gilles L; Harris, Jocelyn E; Joffe, Aaron M; Kho, Michelle E; Kress, John P; Lanphere, Julie A; McKinley, Sharon; Neufeld, Karin J; Pisani, Margaret A; Payen, Jean-Francois; Pun, Brenda T; Puntillo, Kathleen A; Riker, Richard R; Robinson, Bryce RH; Shehabi, Yahya; Szumita, Paul M; Winkelman, Chris; Centofanti, John E; Price, Carrie; Nikayin, Sina; Misak, Cheryl J; Flood, Pamela D; Kiedrowski, Ken; Alhazzani, Waleed

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Executive Summary : Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Importance Daily spontaneous breathing trials (SBTs) are the best approach to determine whether patients are ready for disconnection from mechanical ventilation, but mode and duration of SBT remain controversial. Objective To evaluate the effect of an SBT consisting of 30 minutes of pressure support ventilation (an approach that is less demanding for patients) vs an SBT consisting of 2 hours of T-piece ventilation (an approach that is more demanding for patients) on rates of successful extubation. Design, Setting, and Participants Randomized clinical trial conducted from January 2016 to April 2017 among 1153 adults deemed ready for weaning after at least 24 hours of mechanical ventilation at 18 intensive care units in Spain. Follow-up ended in July 2017. Interventions Patients were randomized to undergo a 2-hour T-piece SBT (n = 578) or a 30-minute SBT with 8-cm H2O pressure support ventilation (n = 557). Main Outcome and Measures The primary outcome was successful extubation (remaining free of mechanical ventilation 72 hours after first SBT). Secondary outcomes were reintubation among patients extubated after SBT; intensive care unit and hospital lengths of stay; and hospital and 90-day mortality. Results Among 1153 patients who were randomized (mean age, 62.2 [SD, 15.7] years; 428 [37.1%] women), 1018 (88.3%) completed the trial. Successful extubation occurred in 473 patients (82.3%) in the pressure support ventilation group and 428 patients (74.0%) in the T-piece group (difference, 8.2%; 95% CI, 3.4%-13.0%;P = .001). Among secondary outcomes, for the pressure support ventilation group vs the T-piece group, respectively, reintubation was 11.1% vs 11.9% (difference, −0.8%; 95% CI, −4.8% to 3.1%;P = .63), median intensive care unit length of stay was 9 days vs 10 days (mean difference, −0.3 days; 95% CI, −1.7 to 1.1 days;P = .69), median hospital length of stay was 24 days vs 24 days (mean difference, 1.3 days; 95% CI, −2.2 to 4.9 days;P = .45), hospital mortality was 10.4% vs 14.9% (difference, −4.4%; 95% CI, −8.3% to −0.6%;P = .02), and 90-day mortality was 13.2% vs 17.3% (difference, −4.1% [95% CI, −8.2% to 0.01%;P = .04]; hazard ratio, 0.74 [95% CI, 0.55-0.99]). Conclusions and Relevance Among patients receiving mechanical ventilation, a spontaneous breathing trial consisting of 30 minutes of pressure support ventilation, compared with 2 hours of T-piece ventilation, led to significantly higher rates of successful extubation. These findings support the use of a shorter, less demanding ventilation strategy for spontaneous breathing trials. Trial Registration ClinicalTrials.gov Identifier:NCT02620358

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Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV). A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10–14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP–FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes. Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8–22] vs. 2 (IQR 0–15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance). Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.

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Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome.

Midazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients. A total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events. The incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P 0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01). Sequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical effectiveness and better cost-benefit ratio than midazolam or propofol used alone, for long-term sedation of critically ill mechanically ventilated patients. Current Controlled Trials ISRCTN01173443
 . Registered 25 February 2014.

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Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study.

The mechanisms of lung injury in acute respiratory distress syndrome (ARDS) are not well understood.Piezo1 was recently identified as a mechanotransduction protein. The present study found the expression of Piezo1 in type II pneumocytes and investigated its role in mediating ARDS-related lung injury. Sprague-Dawley rats were used to establish an ARDS model, the expression of Piezo1,lung injuries, apoptosis as well as calcium influx were assessed. Piezo1 was expressed in type II pneumocytes as shown by immunofluorescence staining and expression was increased in the ARDS model. Knockdown of Piezo1 reduced apoptosis which was related to the elevation of Bcl-2.Calcium influx played a vital role in Piezo1-induced apoptosis. Piezo1 was expressed in type II pneumocytes. Mechanical stretch of alveoli during ARDS induced activation of the Piezo1 channel,which resulted in calcium influx. The increased intracellular Ca2+ induced the apoptosis of type II pneumocytes, which may be related to the Bcl-2 pathway.

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Piezo1 induced apoptosis of type II pneumocytes during ARDS.

BACKGROUND: The objective of this work was to identify the unique characteristics of patients who experienced success in a 30-min spontaneous breathing trial (SBT) but failed at 120 min METHODS: Patients who had received mechanical ventilation for >24 h were eligible for inclusion in this study The SBT was performed by 7 cm H2O of pressure support with zero PEEP After a successful 120-min SBT, weaning from mechanical ventilation was performed Data were collected at 30 and 120 min or at the failure of the SBT All patients who successfully completed a 30-min SBT were enrolled RESULTS: We enrolled 352 subjects in this study Of these, 311 subjects (884%) directly completed a 120-min SBT (success group), and 41 subjects (116%) passed the test for at least 30 min but failed before 120 min (failure group) In data collected before the SBT, presence of chronic cardiopulmonary disease, number of previous SBT attempts before 30-min SBT success, age, and PaCO2 were independently associated with 120-min SBT failure A scale was developed that used these 4 variables The failure rate was low in subjects with ≤2 points (3%) but significantly higher in subjects with >2 points (46%) In data collected at the 30-min SBT, PaCO2, rapid shallow breathing index, ΔPaO2/FIO2, Δbreathing frequency, and ΔpH were independently associated with 120-min SBT failure These 5 variables were then used to develop another scale to predict SBT success Similar to the previous score, the failure rate was low in subjects with ≤2 points (1%) and significantly higher in subjects with >2 points (55%) CONCLUSIONS: This study highlights differences between subjects who completed a 120-min SBT and those who succeeded at 30 min but failed by 120 min In subjects with a score >2 points, reflecting a greater risk of SBT failure, a 120-min SBT may be required

http://rc.rcjournal.com/content/respcare/63/4/388.full.pdf

Characteristics of Subjects Who Failed a 120-Minute Spontaneous Breathing Trial.

Background Although neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in several diseases, its role in pediatric sepsis remains unclear. Our study aimed to assess the predictive significance of NLR for severe pediatric sepsis in the pediatric intensive care unit (PICU). Methods We retrospectively recruited critically ill children in the PICU with severe pediatric sepsis from January 2019 to January 2020 in West China Hospital of Sichuan University. Univariate and multivariable logistic regression analysis was used to assess the risk factors of severe pediatric sepsis. Receiver operating characteristic (ROC) curves were plotted for the comparison of the prediction significance of NLR. Results Overall, 202 patients (severe sepsis 45; non-severe sepsis 157) were included. In the severe sepsis group, the levels of NLR (P<0.001), procalcitonin (PCT; P<0.001), and the Pediatric Risk of Mortality score (PRISM III) were higher than those in the nonsevere sepsis group (P<0.001). The PICU stay time (P<0.001), mechanical ventilation length (P=0.004), and hospital stay time (P<0.001) in the severe sepsis patients were noticeably more extended than those in the control patients. The area under the ROC curve (AUC) of NLR was 0.715 (P<0.001), which was higher than that of the PRISM III score (AUC =0.651, P<0.001) and PCT (AUC =0.647, P<0.001). Furthermore, the constructed predictive model of NLR + PCT + PRISM III showed a better prediction significance than they alone (AUC =0.888, P<0.001). Conclusions Results indicated that the initial NLR value was a significant biomarker for predicting severe pediatric sepsis. The combined NLR and PCT improved the evaluation for further early identification of severe sepsis in children.

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Guopeng Liang

Papers

Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome.

Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study.

Piezo1 induced apoptosis of type II pneumocytes during ARDS.

Characteristics of Subjects Who Failed a 120-Minute Spontaneous Breathing Trial.

Neutrophil-to-lymphocyte ratio as a predictive marker for severe pediatric sepsis.