A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Revisiting the Classification of Neuromuscular Blockade, Aligning Clinical Practice and Research.

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A multifaceted individualized pneumoperitoneum strategy for laparoscopic colorectal surgery: a multicenter observational feasibility study

BACKGROUND: While guidelines for laparoscopic abdominal surgery advise using the lowest possible intra-abdominal pressure, commonly a standard pressure is used. We evaluated the feasibility of a predefined multifaceted individualized pneumoperitoneum strategy aiming at the lowest possible intra-abdominal pressure during laparoscopic colorectal surgery. METHODS: Multicenter prospective study in patients scheduled for laparoscopic colorectal surgery. The strategy consisted of ventilation with low tidal volume, a modified lithotomy position, deep neuromuscular blockade, pre-stretching of the abdominal wall, and individualized intra-abdominal pressure titration; the effect was blindly evaluated by the surgeon. The primary endpoint was the proportion of surgical procedures completed at each individualized intra-abdominal pressure level. Secondary endpoints were the respiratory system driving pressure, and the estimated volume of insufflated CO2 gas needed to perform the surgical procedure. RESULTS: Ninety-two patients were enrolled in the study. Fourteen cases were converted to open surgery for reasons not related to the strategy. The intervention was feasible in all patients and well-accepted by all surgeons. In 61 out of 78 patients (78%), surgery was performed and completed at the lowest possible IAP, 8 mmHg. In 17 patients, IAP was raised up to 12 mmHg. The relationship between IAP and driving pressure was almost linear. The mean estimated intra-abdominal CO2 volume at which surgery was performed was 3.2 L. CONCLUSION: A multifaceted individualized pneumoperitoneum strategy during laparoscopic colorectal surgery was feasible and resulted in an adequate working space in most patients at lower intra-abdominal pressure and lower respiratory driving pressure. ClinicalTrials.gov (Trial Identifier: NCT03000465)

Quality of Recovery and Innate Immune Homeostasis in Patients Undergoing Low-pressure Versus Standard-pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery (RECOVER): A Randomized Controlled Trial

OBJECTIVE: To study the effects of intra-abdominal pressure on the quality of recovery and innate cytokine production capacity after laparoscopic colorectal surgery within the enhanced recovery after surgery program. BACKGROUND: There is increasing evidence for the safety and advantages of low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade (NMB). Nonetheless, there is a weak understanding of the relationship between clinical outcomes, surgical injury, postoperative immune dysfunction, and infectious complications. METHODS: Randomized controlled trial of 178 patients treated at standard-pressure pneumoperitoneum (12 mm Hg) with moderate NMB (train-of-four 1-2) or low pressure (8 mm Hg) facilitated by deep NMB (posttetanic count 1-2). The primary outcome was the quality of recovery (Quality of Recovery 40 questionnaire) on a postoperative day 1 (POD1). The primary outcome of the immune substudy (n=100) was ex vivo tumor necrosis factor α production capacity upon endotoxin stimulation on POD1. RESULTS: Quality of Recovery 40 score on POD1 was significantly higher at 167 versus 159 [mean difference (MD): 8.3 points; 95% confidence interval (CI): 2.5, 14.1; P =0.005] and the decline in cytokine production capacity was significantly less for tumor necrosis factor α and interleukin-6 (MD: -172 pg/mL; 95% CI: -316, -27; P =0.021 and MD: -1282 pg/mL; 95% CI: -2505, -59; P =0.040, respectively) for patients operated at low pressure. Low pressure was associated with reduced surgical site hypoxia and inflammation markers and circulating damage-associated molecular patterns, with a less impaired early postoperative ex vivo cytokine production capacity. At low pressure, patients reported lower acute pain scores and developed significantly less 30-day infectious complications. CONCLUSIONS: Low intra-abdominal pressure during laparoscopic colorectal surgery is safe, improves the postoperative quality of recovery and preserves innate immune homeostasis, and forms a valuable addition to future enhanced recovery after surgery programs

Correction to: An individualised versus a conventional pneumoperitoneum pressure strategy during colorectal laparoscopic surgery: Rationale and study protocol for a multicentre randomised clinical study (Trials DOI: 10.1186/s13063-019-3255-1)

After publication of our article [1] the authors have notified us that there are changes in the primary outcome and the statistical analysis plan of the study. These changes were made after the recruitment of participants and after approval by the Institutional Review Board, and registration at clinicaltrials.gov (study identifier), but before cleaning and closing of the database. The Postoperative Quality of Recovery Scale (PQRS), an outcome used in the IPPCollapse II study, is a five– dimensional ordinal scale designed to estimate patients' recovery in the postoperative period [2]. Each patient is scored at predefined time points and is classified as either 'recovered' if the score reaches at least the predetermined baseline score or 'not recovered' if otherwise. The five dimensions are then combined in an 'overall score' – a patient is classified as 'overall recovered' if 'recovered' in every domain and as 'overall not recovered' if 'not recovered' in any of the five domains. Outcome variables that are repeatedly assessed over time in the same study patients are to be treated as 'repeated measures' or 'longitudinal data' [3]. Common statistical techniques applied on cross-sectional data assume independence between observations [4]. This crucial assumption is not fulfilled by 'repeated measures' or 'longitudinal data'. Ignoring this correlation can lead to biased estimates, invalid P values and confidence intervals, as well as loss of statistical power [5, 6]. We incorrectly detailed how the PQRS score was to be analysed. We suggested to treat the scores at the four different time points as individual outcomes. From hindsight we feel that this approach does not consider the conceptual underlying model (i.e., between patients' variability) and the temporal design. Furthermore, we also imperfectly reported our primary outcome since we did not specified which domain of the scale was analyzed as primary endpoint although we did report which one we used (i.e. physiologic score) in the sample size calculation. We therefore changed the primary and secondary outcomes as follows: 1. The primary outcome of the IPPCollapse II study is the recovery of the 'physiologic' component of the PQRS score over the assessed time points; 2. The other domains, i.e., the 'nociceptive', 'emotional', 'cognitive', and 'functional' components, as well as the 'overall score' are used as secondary outcomes; 3. Association between group assignment and recovery of PQRS score in each domain is assessed by a mixed logistic regression, introducing patients as random factors, and age, weight, BMI and sex as covariables; 4. The originally reported analysis (i.e. ordinal regression) is still carried out, however only as a sensitivity analysis

An individualised versus a conventional pneumoperitoneum pressure strategy during colorectal laparoscopic surgery: rationale and study protocol for a multicentre randomised clinical study

Abstract Background A recent study shows that a multifaceted strategy using an individualised intra-abdominal pressure titration strategy during colorectal laparoscopic surgery results in an acceptable workspace at low intra-abdominal pressure in most patients. The multifaceted strategy, focused on lower to individualised intra-abdominal pressures, includes prestretching the abdominal wall during initial insufflation, deep neuromuscular blockade, low tidal volume ventilation settings and a modified lithotomy position. The study presented here tests the hypothesis that this strategy improves outcomes of patients scheduled for colorectal laparoscopic surgery. Methods The Individualized Pneumoperitoneum Pressure in Colorectal Laparoscopic Surgery versus Standard Therapy (IPPCollapse-II) study is a multicentre, two-arm, parallel-group, single-blinded randomised 1:1 clinical study that runs in four academic hospitals in Spain. Patients scheduled for colorectal laparoscopic surgery with American Society of Anesthesiologists classification I to III who are aged > 18 years and are without cognitive deficits are randomised to an individualised pneumoperitoneum pressure strategy (the intervention group) or to a conventional pneumoperitoneum pressure strategy (the control group). The primary outcome is recovery assessed with the Post-operative Quality of Recovery Scale (PQRS) at postoperative day 1. Secondary outcomes include PQRS score in the post anaesthesia care unit and at postoperative day 3, postoperative complications until postoperative day 28, hospital length of stay and process-related outcomes. Discussion The IPPCollapse-II study will be the first randomised clinical study that assesses the impact of an individualised pneumoperitoneum pressure strategy focused on working with the lowest intra-abdominal pressure during colorectal laparoscopic surgery on relevant patient-centred outcomes. The results of this large study, to be disseminated through conference presentations and publications in international peer-reviewed journals, are of ultimate importance for optimising the care and safety of laparoscopic abdominal surgery. Selection of patient-reported outcomes as the primary outcome of this study facilitates the translation into clinical practice. Access to source data will be made available through anonymised datasets upon request and after agreement of the Steering Committee of the IPPCollapse-II study. Trial registration ClinicalTrials.gov, NCT02773173. Registered on 16 May 2016. EudraCT, 2016-001693-15. Registered on 8 August 2016

Pre-clinical validation of a turbine-based ventilator for invasive ventilation–The ACUTE-19 ventilator

Background: The severe acute respiratory syndrome-coronavirus 2 pandemic pressure on healthcare systems can exhaust ventilator resources, especially where resources are restricted. Our objective was a rapid preclinical evaluation of a newly developed turbine-based ventilator, named the ACUTE-19, for invasive ventilation. Methods: Validation consisted of (a) testing tidal volume delivery in 11 simulated models, with various resistances and compliances; (b) comparison with a commercial ventilator (VIVO-50) adapting the United Kingdom Medicines and Healthcare products Regulatory Agency-recommendations for rapidly manufactured ventilators; and (c) in vivo testing in a sheep before and after inducing acute respiratory distress syndrome by saline lavage. Results: Differences in tidal volume in the simulated models were marginally different (largest difference 33 ml [95% CI 31 to 36]; P < .001). Plateau pressure was not different (−0.3 cmH2O [95% CI −0.9 to 0.3]; P = .409), and positive end-expiratory pressure was marginally different (0.3 cmH2O [95% CI 0.2 to 0.3]; P < .001) between the ACUTE-19 and the commercial ventilator. Bland-Altman analyses showed good agreement (mean bias −0.29 [limits of agreement 0.82 to −1.42], and mean bias 0.56 [limits of agreement 1.94 to −0.81], at a plateau pressure of 15 and 30 cmH2O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after acute respiratory distress syndrome induction. Conclusions: The ACUTE-19 performed accurately in simulated and animal models yielding a comparable performance with a VIVO-50 commercial device. The ACUTE-19 can provide the basis for the development of a future affordable commercial ventilator

Adenovirus Entry From the Apical Surface of Polarized Epithelia Is Facilitated by the Host Innate Immune Response

Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAREx8 may be to facilitate host innate immunity. We show that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAREx8 via activation of AKT/S6K and inhibition of GSK3β. Apical CAREx8 tethers infiltrating neutrophils at the apical surface of a polarized epithelium. Moreover, neutrophils present on the apicalepithelial surface enhance adenovirus entry into the epithelium. These findings suggest that adenovirus evolved to co-opt an innate immune response pathway that stimulates the expression of its primary receptor, apical CAREx8, to allow the initial infection the intact epithelium. In addition, CAREx8 is a new target for the development of novel therapeutics for both respiratory inflammatory disease and adenoviral infection