Efficacy of pulsed radiofrequency on the suprascapular and axillary-circumflex nerve for shoulder pain: A randomised controlled trial.

Background and Aims: Painful shoulder is one of the most frequent consultation causes. Multiple treatments have been described to relieve pain, restore range of motion and improve functionality. Methods: This randomised clinical trial was conducted in 60 patients. The treatment group received combined pulsed radiofrequency (PRF) on suprascapular nerve (SN) and axillary-circumflex nerve (ACN). The control group received PRF on SN only. The primary outcome was pain intensity measured by the Numerical Rating Scale (NRS). The secondary outcomes were the Shoulder Pain and Disability Index (SPADI), the Constant-Murley range of motion scale and Disability of the Arm, Shoulder and Hand (DASH) scale. The patients were monitored at the baseline visit and at 1, 3, 6 and 9 months. A mixed ordinal regression model was estimated to evaluate the association between the study group and pain measured with NRS. Results: A global decrease in pain at the end of the study was noted. The global baseline NRS was 8.4, and the global final NRS at 9 months of follow-up was 6.2. Combined PRF on SN and ACN was not associated with lower NRS pain scores compared to single SN PRF [odds ratio (OR) =1.04, 95% confidence interval (CI) 0.91-1.20, P = 0.507]. Secondary outcomes showed no significant differences: SPADI (OR = 1.04, 95% CI 0.92-1.18), Constant-Murley (OR = 1.01, 95% CI 0.90-1.14), DASH (OR = 1.04, 95% CI 0.92-1.17). Conclusion: Combined PRF applied to SN and ACN was not superior to PRF applied to SN alone.

Underneath Images and Robots, Looking Deeper into the Pneumoperitoneum: A Narrative Review.

Laparoscopy offers numerous advantages over open procedures, minimizing trauma, reducing pain, accelerating recovery, and shortening hospital stays. Despite other technical advancements, pneumoperitoneum insufflation has received little attention, barely evolving since its inception. We explore the impact of pneumoperitoneum on patient outcomes and advocate for a minimally invasive approach that prioritizes peritoneal homeostasis. The nonlinear relationship between intra-abdominal pressure (IAP) and intra-abdominal volume (IAV) is discussed, emphasizing IAP titration to balance physiological effects and surgical workspace. Maintaining IAP below 10 mmHg is generally recommended, but factors such as patient positioning and surgical complexity must be considered. The depth of neuromuscular blockade (NMB) is explored as another variable affecting laparoscopic conditions. While deep NMB appears favorable for surgical stillness, achieving a balance between IAP and NMB depth is crucial. Temperature and humidity management during pneumoperitoneum are crucial for patient safety and optical field quality. Despite the debate over the significance of temperature drop, humidification and the warming of insufflated gas offer benefits in peritoneal homeostasis and visual clarity. In conclusion, there is potential for a paradigm shift in pneumoperitoneum management, with dynamic IAP adjustments and careful control of insufflated gas temperature and humidity to preserve peritoneal homeostasis and improve patient outcomes in minimally invasive surgery.

Low intra-abdominal pressure in laparoscopic surgery: a systematic review and meta-analysis.

BACKGROUND: Guidelines do not provide clear recommendations with regard to the use of low intra-abdominal pressure (IAP) during laparoscopic surgery. The aim of this meta-analysis is to assess the influence of low versus standard IAP during laparoscopic surgery on the key-outcomes in perioperative medicine as defined by the StEP-COMPAC consensus group. MATERIALS AND METHODS: We searched the Cochrane Library, PubMed, and EMBASE for randomized controlled trials comparing low IAP (<10 mmHg) with standard IAP (10 mmHg or higher) during laparoscopic surgery without time, language, or blinding restrictions. According to the PRISMA guidelines, two review authors independently identified trials and extracted data. Risk ratio (RR), and mean difference (MD), with 95% CIs were calculated using random-effects models with RevMan5. Main outcomes were based on StEP-COMPAC recommendations, and included postoperative complications, postoperative pain, postoperative nausea and vomiting (PONV) scores, and length of hospital stay. RESULTS: Eighty-five studies in a wide range of laparoscopic procedures (7349 patients) were included in this meta-analysis. The available evidence indicates that the use of low IAP (<10 mmHg) leads to a lower incidence of mild (Clavien-Dindo grade 1-2) postoperative complications (RR=0.68, 95% CI: 0.53-0.86), lower pain scores (MD=-0.68, 95% CI: -0.82 to 0.54) and PONV incidence (RR=0.67, 95% CI: 0.51-0.88), and a reduced length of hospital stay (MD=-0.29, 95% CI: -0.46 to 0.11). Low IAP did not increase the risk of intraoperative complications (RR=1.15, 95% CI: 0.77-1.73). CONCLUSIONS: Given the established safety and the reduced incidence of mild postoperative complications, lower pain scores, reduced incidence of PONV, and shorter length of stay, the available evidence supports a moderate to strong recommendation (1a level of evidence) in favor of low IAP during laparoscopic surgery.

An educational intervention to reduce the incidence of postoperative residual curarisation: a cluster randomised crossover trial in patients undergoing general anaesthesia.

BACKGROUND: The incidence of postoperative residual curarisation remains unacceptably high. We assessed whether an educational intervention on perioperative neuromuscular block management can reduce it. METHODS: In this multicentre, cluster randomised crossover trial, centres were allocated to receive an educational intervention either in a first or a second period. The educational intervention consisted of a lecture about neuromuscular management key points, including quantitative neuromuscular monitoring and use of reversal agents. The lecture was streamed to allow repetition. Additionally, memory cards were distributed in each operating theatre. The primary outcome was postoperative residual curarisation in the PACU. Secondary outcomes were frequency of quantitative neuromuscular monitoring, use of reversal agents, and incidence of postoperative pulmonary complications during hospital stay. Measurements were performed before randomisation and after the first and the second period. The effect of the educational intervention was estimated using multivariable mixed effects logistic regression models. RESULTS: We included 2314 subjects in 34 Spanish centres. Postoperative residual curarisation incidence was not affected by the educational intervention (odds ratio [OR] 0.90 [95% confidence interval {CI}: 0.51-1.58]; P=0.717 and 1.30 [0.73-2.30]; P=0.371] for first and second time-period interaction). The educational intervention increased the quantitative neuromuscular monitor usage (OR 2.04 [95% CI: 1.31-3.19]; P=0.002), the use of reversal agents was unchanged (OR 0.79 [95% CI: 0.50-1.26]; P=0.322), and the incidence of postoperative pulmonary complications decreased (OR 0.19 [95% CI: 0.10-0.35]; P<0.001). CONCLUSIONS: An educational intervention on perioperative neuromuscular block management did not reduce the incidence of postoperative residual curarisation nor increase reversal, despite increased quantitative neuromuscular monitoring. Sugammadex reversal was associated with reduced postoperative residual curarisation. The educational intervention was associated with a decrease in postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03128151.

An Individualized Low-Pneumoperitoneum-Pressure Strategy May Prevent a Reduction in Liver Perfusion during Colorectal Laparoscopic Surgery.

High intra-abdominal pressure (IAP) during laparoscopic surgery is associated with reduced splanchnic blood flow. It is uncertain whether a low IAP prevents this reduction. We assessed the effect of an individualized low-pneumoperitoneum-pressure strategy on liver perfusion. This was a single-center substudy of the multicenter 'Individualized Pneumoperitoneum Pressure in Colorectal Laparoscopic Surgery versus Standard Therapy II study' (IPPCollapse-II), a randomized clinical trial in which patients received an individualized low-pneumoperitoneum strategy (IPP) or a standard pneumoperitoneum strategy (SPP). Liver perfusion was indirectly assessed by the indocyanine green plasma disappearance rate (ICG-PDR) and the secondary endpoint was ICG retention rate after 15 min (R15) using pulse spectrophotometry. Multivariable beta regression was used to assess the association between group assignment and ICG-PDR and ICG-R15. All 29 patients from the participating center were included. Median IAP was 8 (25th-75th percentile: 8-10) versus 12 (12,12) mmHg, in IPP and SPP patients, respectively (p < 0.001). ICG-PDR was higher (OR 1.42, 95%-CI 1.10-1.82; p = 0.006) and PDR-R15 was lower in IPP patients compared with SPP patients (OR 0.46, 95%-CI 0.29-0.73; p = 0.001). During laparoscopic colorectal surgery, an individualized low pneumoperitoneum may prevent a reduction in liver perfusion.

Physical and Quality of Life Changes in Elderly Patients after Laparoscopic Surgery for Colorectal Cancer-A Prospective Cohort Study.

Background-The incidence of colorectal cancer is increasing among elderly people, where postoperative complications are frequent. Methods-We evaluated postoperative physical and quality of life changes in elderly patients undergoing laparoscopic surgery for colorectal cancer. A prospective cohort study was performed in 31 colorectal cancer patients ≥60 years who were scheduled for laparoscopic surgery due to colorectal cancer. Outcomes were measured one month preoperative (T1), three days postoperative (T2) and one month postoperative (T3). Results-The largest early postoperative (from T1 to T2) declines were observed for isometric knee extension strength (33.1%), 30 s Chair Stand Test (27.9%) and handgrip strength (16.9%). Significant reductions in quality of life measured with the QLQ-C30 summary score and the EQ 5D index score were found between T1-T3 and T1-T2, respectively. Conclusions-A decline in isometric knee extension strength, 30 s Chair Stand Test, handgrip strength and quality of life is evident in elderly patients in the days following laparoscopic surgery for colorectal cancer. Preoperative values are recovered one month after surgery for all the outcomes, except for isometric knee extension, which should receive especial attention.

The RALE Score Versus the CT Severity Score in Invasively Ventilated COVID-19 Patients-A Retrospective Study Comparing Their Prognostic Capacities.

BACKGROUND: Quantitative radiological scores for the extent and severity of pulmonary infiltrates based on chest radiography (CXR) and computed tomography (CT) scan are increasingly used in critically ill invasively ventilated patients. This study aimed to determine and compare the prognostic capacity of the Radiographic Assessment of Lung Edema (RALE) score and the chest CT Severity Score (CTSS) in a cohort of invasively ventilated patients with acute respiratory distress syndrome (ARDS) due to COVID-19. METHODS: Two-center retrospective observational study, including consecutive invasively ventilated COVID-19 patients. Trained scorers calculated the RALE score of first available CXR and the CTSS of the first available CT scan. The primary outcome was ICU mortality; secondary outcomes were duration of ventilation in survivors, length of stay in ICU, and hospital-, 28-, and 90-day mortality. Prognostic accuracy for ICU death was expressed using odds ratios and Area Under the Receiver Operating Characteristic curves (AUROC). RESULTS: A total of 82 patients were enrolled. The median RALE score (22 [15-37] vs. 26 [20-39]; p = 0.34) and the median CTSS (18 [16-21] vs. 21 [18-23]; p = 0.022) were both lower in ICU survivors compared to ICU non-survivors, although only the difference in CTSS reached statistical significance. While no association was observed between ICU mortality and RALE score (OR 1.35 [95%CI 0.64-2.84]; p = 0.417; AUC 0.50 [0.44-0.56], this was noticed with the CTSS (OR, 2.31 [1.22-4.38]; p = 0.010) although with poor prognostic capacity (AUC 0.64 [0.57-0.69]). The correlation between the RALE score and CTSS was weak (r2 = 0.075; p = 0.012). CONCLUSIONS: Despite poor prognostic capacity, only CTSS was associated with ICU mortality in our cohort of COVID-19 patients.

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.

Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

PURPOSE OF REVIEW: Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action. RECENT FINDINGS: We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects.

Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials.

BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).

Opioid Receptor Expression in Colorectal Cancer: A Nested Matched Case-Control Study.

Background: There is growing interest in the possible effect of perioperative anesthetic management on the growth and spread of cancer. The impact of perioperative use of opioids on cancer recurrence remains controversial and an assessment cannot yet be established based on current publications. This study aimed to assess the differential expression of opioid receptors between healthy and tumor tissues in patients with stage II and III colorectal cancer undergoing elective surgery by immunohistochemistry (IHC). Methods: Propensity-score matched case-control study nested in a retrospective cohort of patients with stage II or III colorectal. The primary endpoint was the difference in µ-opioid receptor (MOR) expression measured by IHC between tumor and healthy tissue in subject with or without recurrence. Secondary endpoints were to evaluate the differences in Opioid Growth Factor Receptor (OGFR), cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) in the matched sample and from a from samples of colorectal cancer stored in the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression Project (GTEx). Results: There was a significant difference in MOR receptor (median 3 [intequartile range IQR: 1-3] and 0 [IQR: 0-2], P<0.001) and OGFR receptor (median 6 [IQR: 5-6] and 2 [IQR: 1-2], P<0.001) in tumor and control tissue respectively. However, there were no significant differences in cAMP nor PKA expression between both types of tissues and in expression in any of the analyzed variables by recurrence status. The MOR and OGFR expression data from TCGA database were similar to our sample size data with lower expression of MOR and higher expression of OGFR in tumoural samples with a skewed distribution for MOR expression in tumor tissue both in patients with and without recurrence. Conclusion: In patients with stage II and III colorectal cancer, overall expression of MOR and OGFR was significantly increased but was not different between previously matched patients with or without recurrence. No differences were found in the analyzed metabolic pathway of cAMP-PKA: These results were confirmed by an in silico analysis of samples from the TCGA-GTEx database.

Associations of dynamic driving pressure and mechanical power with postoperative pulmonary complications-posthoc analysis of two randomised clinical trials in open abdominal surgery.

Background: While an association of the intraoperative driving pressure with postoperative pulmonary complications has been described before, it is uncertain whether the intraoperative mechanical power is associated with postoperative pulmonary complications. Methods: Posthoc analysis of two international, multicentre randomised clinical trials (ISRCTN70332574 and NCT02148692) conducted between 2011-2013 and 2014-2018, in patients undergoing open abdominal surgery comparing the effect of two different positive end-expiratory pressure (PEEP) levels on postoperative pulmonary complications. Time-weighted average dynamic driving pressure and mechanical power were calculated for individual patients. A multivariable logistic regression model adjusted for confounders was used to assess the independent associations of driving pressure and mechanical power with the occurrence of a composite of postoperative pulmonary complications, the primary endpoint of this posthoc analysis. Findings: In 1191 patients included, postoperative pulmonary complications occurrence was 35.9%. Median time-weighted average driving pressure and mechanical power were 14·0 [11·0-17·0] cmH2O, and 7·6 [5·1-10·0] J/min, respectively. While driving pressure was not independently associated with postoperative pulmonary complications (odds ratio, 1·06 [95% CI 0·88-1·28]; p=0.534), the mechanical power had an independent association with the occurrence of postoperative pulmonary complications (odds ratio, 1·28 [95% CI 1·05-1·57]; p=0.016). These findings were independent of body mass index or the level of PEEP used, i.e., independent of the randomisation arm. Interpretation: In this merged cohort of surgery patients, higher intraoperative mechanical power was independently associated with postoperative pulmonary complications. Mechanical power could serve as a summary ventilatory biomarker for the risk for postoperative pulmonary complications in these patients, but our findings need confirmation in other, preferably prospective studies. Funding: The two original studies were supported by unrestricted grants from the European Society of Anaesthesiology and the Amsterdam University Medical Centers, Location AMC. For this current analysis, no additional funding was requested. The funding sources had neither a role in the design, collection of data, statistical analysis, interpretation of data, writing of the report, nor in the decision to submit the paper for publication.

Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project.

Background: Opioid receptors are expressed not only by neural cells in the central nervous system, but also by many solid tumor cancer cells. Whether perioperative opioids given for analgesia after tumor resection surgery might inadvertently activate tumor cells, promoting recurrence or metastasis, remains controversial. We analysed large public gene repositories of solid tumors to investigate differences in opioid receptor expression between normal and tumor tissues and their association with long-term oncologic outcomes. Methods: We investigated the normalized gene expression of µ, κ, δ opioid receptors (MOR, KOR, DOR), Opioid Growth Factor (OGFR), and Toll-Like 4 (TLR4) receptors in normal and tumor samples from twelve solid tumor types. We carried out mixed multivariable logistic and Cox regression analysis on whether there was an association between these receptors' gene expression and the tissue where found, i.e., tumor or normal tissue. We also evaluated the association between tumor opioid receptor gene expression and patient disease-free interval (DFI) and overall survival (OS). Results: We retrieved 8,780 tissue samples, 5,852 from tumor and 2,928 from normal tissue, of which 2,252 were from the Genotype Tissue Expression Project (GTEx) and 672 from the Cancer Genome Atlas (TCGA) repository. The Odds Ratio (OR) [95%CI] for gene expression of the specific opioid receptors in the examined tumors varied: MOR: 0.74 [0.63-0.87], KOR: 1.27 [1.17-1.37], DOR: 1.66 [1.48-1.87], TLR4: 0.29 [0.26-0.32], OGFR: 2.39 [2.05-2.78]. After controlling all confounding variables, including age and cancer stage, there was no association between tumor opioid receptor expression and long-term oncologic outcomes. Conclusion: Opioid receptor gene expression varies between different solid tumor types. There was no association between tumor opioid receptor expression and recurrence. Understanding the significance of opioid receptor expression on tumor cells remains elusive.

Prognostication using SpO2/FiO2 in invasively ventilated ICU patients with ARDS due to COVID-19 - Insights from the PRoVENT-COVID study.

BACKGROUND: The SpO2/FiO2 is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO2/FiO2 for mortality in patients with ARDS due to COVID-19. METHODS: This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID-19. The primary endpoint was 28-day mortality. RESULTS: In 869 invasively ventilated patients, 28-day mortality was 30.1%. The SpO2/FiO2 on day 1 had no prognostic value. The SpO2/FiO2 on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO2/FiO2 on day 2 (OR, 0.66 [95%-CI 0.46-0.96]) and on day 3 (OR, 0.70 [95%-CI 0.51-0.96]) were associated with 28-day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76-0.79]). The measured PaO2/FiO2 and the PaO2/FiO2 calculated from SpO2/FiO2 were strongly correlated (Spearman's r = 0.79). CONCLUSIONS: In this cohort of patients with ARDS due to COVID-19, the SpO2/FiO2 on day 2 and day 3 are independently associated with and have prognostic capacity for 28-day mortality. The SpO2/FiO2 is a useful metric for risk stratification in invasively ventilated COVID-19 patients.

Effect of intraoperative PEEP with recruitment maneuvers on the occurrence of postoperative pulmonary complications during general anesthesia--protocol for Bayesian analysis of three randomized clinical trials of intraoperative ventilation.

Background: Using the frequentist approach, a recent meta-analysis of three randomized clinical trials in patients undergoing intraoperative ventilation during general anesthesia for major surgery failed to show the benefit of ventilation that uses high positive end-expiratory pressure with recruitment maneuvers when compared to ventilation that uses low positive end-expiratory pressure without recruitment maneuvers. Methods: We designed a protocol for a Bayesian analysis using the pooled dataset. The multilevel Bayesian logistic model will use the individual patient data. Prior distributions will be prespecified to represent a varying level of skepticism for the effect estimate. The primary endpoint will be a composite of postoperative pulmonary complications (PPC) within the first seven postoperative days, which reflects the primary endpoint of the original studies. We preset a range of practical equivalence to assess the futility of the intervention with an interval of odds ratio (OR) between 0.9 and 1.1 and assess how much of the 95% of highest density interval (HDI) falls between the region of practical equivalence. Ethics and dissemination: The used data derive from approved studies that were published in recent years. The findings of this current analysis will be reported in a new manuscript, drafted by the writing committee on behalf of the three research groups. All investigators listed in the original trials will serve as collaborative authors.

Association of Time-Varying Intensity of Ventilation With Mortality in Patients With COVID-19 ARDS: Secondary Analysis of the PRoVENT-COVID Study.

Background: High intensity of ventilation has an association with mortality in patients with acute respiratory failure. It is uncertain whether similar associations exist in patients with acute respiratory distress syndrome (ARDS) patients due to coronavirus disease 2019 (COVID-19). We investigated the association of exposure to different levels of driving pressure (ΔP) and mechanical power (MP) with mortality in these patients. Methods: PRoVENT-COVID is a national, retrospective observational study, performed at 22 ICUs in the Netherlands, including COVID-19 patients under invasive ventilation for ARDS. Dynamic ΔP and MP were calculated at fixed time points during the first 4 calendar days of ventilation. The primary endpoint was 28-day mortality. To assess the effects of time-varying exposure, Bayesian joint models adjusted for confounders were used. Results: Of 1,122 patients included in the PRoVENT-COVID study, 734 were eligible for this analysis. In the first 28 days, 29.2% of patients died. A significant increase in the hazard of death was found to be associated with each increment in ΔP (HR 1.04, 95% CrI 1.01-1.07) and in MP (HR 1.12, 95% CrI 1.01-1.36). In sensitivity analyses, cumulative exposure to higher levels of ΔP or MP resulted in increased risks for 28-day mortality. Conclusion: Cumulative exposure to higher intensities of ventilation in COVID-19 patients with ARDS have an association with increased risk of 28-day mortality. Limiting exposure to high ΔP or MP has the potential to improve survival in these patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04346342.

Practice of adjunctive treatments in critically ill COVID-19 patients-rational for the multicenter observational PRoAcT-COVID study in The Netherlands.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) may need hospitalization for supplemental oxygen, and some need intensive care unit (ICU) admission for escalation of care. Practice of adjunctive and supportive treatments remain uncertain and may vary widely between countries, within countries between hospitals, and possibly even within ICUs. We aim to investigate practice of adjunctive and supportive treatments, and their associations with outcome, in critically ill COVID-19 patients. METHODS: The 'PRactice of Adjunctive Treatments in Intensive Care Unit Patients with Coronavirus Disease 2019' (PRoAcT-COVID) study is a national, observational study to be undertaken in a large set of ICUs in The Netherlands. The PRoAcT-COVID includes consecutive ICU patients, admitted because of COVID-19 to one of the participating ICUs during a 3-month period. Daily follow-up lasts 28 days. The primary endpoint is a combination of adjunctive treatments, including types of oxygen support, ventilation, rescue therapies for hypoxemia refractory to supplementary oxygen or during invasive ventilation, other adjunctive and supportive treatments, and experimental therapies. We will also collect tracheostomy rate, duration of invasive ventilation and ventilator-free days and alive at day 28 (VFD-28), ICU and hospital length of stay, and the mortality rates in the ICU, hospital and at day 90. DISCUSSION: The PRoAcT-COVID study is an observational study combining high density treatment data with relevant clinical outcomes. Information on treatment practices, and their associations with outcomes in COVID-19 patients in highly and urgently needed. The results of the PRoAcT-COVID study will be rapidly available, and circulated through online presentations, such as webinars and electronic conferences, and publications in peer-reviewed journals-findings will also be presented at a dedicated website. At request, and after agreement of the PRoAcT-COVID steering committee, source data will be made available through local, regional and national anonymized datasets. TRIAL REGISTRATION: The PRoAcT-COVID study is registered at clinicaltrials.gov (study identifier NCT04719182).

Combined Noninvasive Respiratory Support Therapies to Treat COVID-19.

BACKGROUND: The roles of high-flow nasal cannula (HFNC) and CPAP in coronavirus disease 2019 (COVID-19) are controversial. The objective of the study was to evaluate the impact of the application of a noninvasive respiratory support algorithm on clinical outcomes in subjects with COVID-19 and with acute respiratory failure. METHODS: We performed a single-center prospective observational study of subjects with respiratory failure from COVID-19 managed with HFNC and with CPAP plus HFNC (combined therapy). The main outcome was the intubation rate, which defined failure of therapy. We also analyzed the role of the ROX index ([[Formula: see text]/[Formula: see text]]/breathing frequency) to predict the need for intubation. RESULTS: From June to December 2020, 113 subjects with COVID-19 respiratory failure were admitted to our respiratory intermediate care unit. HFNC was applied in 65 subjects (57.52%) and combined therapy in 48 subjects (42.47%). A total of 83 subjects (73.45%) were successfully treated with noninvasive respiratory support. The intubation rate was 26.54%, and the overall mortality rate was 14.15%. The mortality rate in subjects who were intubated was 55.2%. An ROX index of 6.28 at 12 h predicted noninvasive respiratory support failure, with 97.6% sensitivity and 51.8% specificity. CONCLUSIONS: Data from our cohort managed in a respiratory intermediate care unit showed that combined noninvasive respiratory support was feasible, with favorable outcomes. Further prospective studies are required.