The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study.

BACKGROUND: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. METHODS: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. CONCLUSIONS: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Impact of Lower Tidal Volumes During One-Lung Ventilation: A 2022 Update of the Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: To clarify the influence of lower tidal volume (4-7 mL/kg) compared with higher tidal volume (8-15 mL/kg) during one-lung ventilation (OLV) on gas exchange and postoperative clinical outcome. DESIGN: Meta-analysis of randomized trials. SETTING: Thoracic surgery. PARTICIPANTS: Patients receiving OLV. INTERVENTIONS: Lower tidal volume during OLV. MEASUREMENTS AND MAIN RESULTS: Primary outcome was PaO2-to-the oxygen fraction (PaO2/FIO2) ratio at the end of the surgery, after the reinstitution of two-lung ventilation. Secondary endpoints included perioperative changes in PaO2/FIO2 ratio and carbon dioxide (PaCO2) tension, airway pressure, the incidence of postoperative pulmonary complications, arrhythmia, and length of hospital stay. Seventeen randomized controlled trials (1,463 patients) were selected. Overall analysis showed that the use of low tidal volume during OLV was associated with a significantly higher PaO2/FIO2 ratio 15 minutes after the start of OLV and at the end of surgery (mean difference 33.7 mmHg [p = 0.02] and mean difference 18.59 mmHg [p < 0.001], respectively). The low tidal volume also was associated with higher PaCO2 values 15 minutes and 60 minutes after the start of OLV and with lower airway pressure, which was maintained during two-lung ventilation after surgery. Moreover, the application of lower tidal volume was associated with fewer postoperative pulmonary complications (odds ratio 0.50; p < 0.001) and arrhythmias (odds ratio 0.58; p = 0.009), with no difference in length of hospital stay. CONCLUSIONS: The use of lower tidal volume, a component of protective OLV, increases the PaO2/FIO2 ratio, reduces the incidence of postoperative pulmonary complications, and should be considered strongly in daily practice.

Propofol and survival: an updated meta-analysis of randomized clinical trials.

BACKGROUND: Propofol is one of the most widely used hypnotic agents in the world. Nonetheless, propofol might have detrimental effects on clinically relevant outcomes, possibly due to inhibition of other interventions' organ protective properties. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate if propofol reduced survival compared to any other hypnotic agent in any clinical setting. METHODS: We searched eligible studies in PubMed, Google Scholar, and the Cochrane Register of Clinical Trials. The following inclusion criteria were used: random treatment allocation and comparison between propofol and any comparator in any clinical setting. The primary outcome was mortality at the longest follow-up available. We conducted a fixed-effects meta-analysis for the risk ratio (RR). Using this RR and 95% confidence interval, we estimated the probability of any harm (RR > 1) through Bayesian statistics. We registered this systematic review and meta-analysis in PROSPERO International Prospective Register of Systematic Reviews (CRD42022323143). RESULTS: We identified 252 randomized trials comprising 30,757 patients. Mortality was higher in the propofol group than in the comparator group (760/14,754 [5.2%] vs. 682/16,003 [4.3%]; RR = 1.10; 95% confidence interval, 1.01-1.20; p = 0.03; I2 = 0%; number needed to harm = 235), corresponding to a 98.4% probability of any increase in mortality. A statistically significant mortality increase in the propofol group was confirmed in subgroups of cardiac surgery, adult patients, volatile agent as comparator, large studies, and studies with low mortality in the comparator arm. CONCLUSIONS: Propofol may reduce survival in perioperative and critically ill patients. This needs careful assessment of the risk versus benefit of propofol compared to other agents while planning for large, pragmatic multicentric randomized controlled trials to provide a definitive answer.

Meta-Analysis of Glucocorticoids for Covid-19 Patients Not Receiving Oxygen.

Glucocorticoids for Covid-19 Patients Not on OxygenGlucocorticoids reduce mortality in hospitalized patients with severe and critical Covid-19. Covello et al. performed a meta-analysis to test the hypothesis that glucocorticoids could be detrimental in patients not on oxygen therapy.

Outcomes of COVID-19 Patients with Severe Hypoxemic Acute Respiratory Failure: Non-Invasive Ventilation vs. Straight Intubation-A Propensity Score-Matched Multicenter Cohort Study.

The best timing for endotracheal intubation in patients with coronavirus disease 2019 (COVID-19) hypoxemic acute respiratory failure (hARF) remains debated. Aim of this study is to compare the outcomes of COVID-19 patients with hARF receiving either a trial of non-invasive ventilation (NIV) or intubated with no prior attempt of NIV ("straight intubation"). All consecutive patients admitted to the 25 participating ICUs were included and divided in two groups: the "straight intubation" group and the "NIV" group. A propensity score matching was performed to correct for biases associated with the choice of the respiratory support. Primary outcome was in-hospital mortality. Secondary outcomes were length of mechanical ventilation, hospital stay and reintubation rate. A total of 704 COVID-19 patients were admitted to ICUs during the study period. After matching, 141 patients were included in each group. No clinically relevant difference at ICU admission was found between groups. In-hospital mortality was significantly lower in the NIV group (22.0% vs. 36.2%), with no significant difference in secondary endpoints. There was no significant mortality difference between patients who received straight intubation and those intubated after NIV failure. In COVID-19 patients with hARF it is worth and safe attempting a trial of NIV prior to intubation.

Angiotensin II - A Brief Review and Role in Severe SARS-COV-2 Sepsis.

The renin-angiotensin-aldosterone system (RAAS), whose major vasopressor effector is angiotensin II (ATII), has multiple activities and regulates sodium-water homeostasis and fluid and blood pressure homeostasis. RAAS plays a crucial role in cardiocirculatory shock because it counteracts hypotension and hypovolemia by activating different physiologic responses. Based on the encouraging results of the ATHOS-3 trial, the US Food and Drug Administration and the European Medicines Agency approved the use of ATII for catecholamine-resistant vasodilatory shock. More recently, ATII was used for the compassionate treatment of critically ill patients with COVID-19. Beyond its vasopressor properties, ATII was hypothesized to have antiviral activity because it induces internalization and degradation of angiotensin-converting enzyme 2 receptors used by SARS-Cov-2 to infect cells. Overall, the use of ATII in patients with COVID-19 showed promising results because its administration was associated with the achievement and maintenance of target mean arterial pressure, increased PaO2/FIO2 ratio, and decreased FIO2. The aim of this narrative review is to summarize the available knowledge on the use of ATII in patients with COVID-19.

Single-injection regional analgesia techniques for mastectomy surgery: A network meta-analysis.

BACKGROUND: Patients undergoing mastectomy surgery experience severe postoperative pain. Several regional techniques have been developed to reduce pain intensity but it is unclear, which of these techniques is most effective. OBJECTIVES: To synthesise direct and indirect comparisons for the relative efficacy of different regional and local analgesia techniques in the setting of unilateral mastectomy. Postoperative opioid consumption at 24 h, postoperative pain at extubation, 1, 12 and 24 h, postoperative nausea and vomiting were collected. DESIGN: Systematic review with network meta-analysis (PROSPERO:CRD42021250651). DATA SOURCE: PubMed, Scopus, the Cochrane Central Register of Controlled Trials (from inception until 7 July 2021). ELIGIBILITY CRITERIA: All randomised controlled trials investigating single-injection regional and local analgesia techniques in adult patients undergoing unilateral mastectomy were included in our study without any language or publication date restriction. RESULTS: Sixty-two included studies randomising 4074 patients and investigating nine techniques entered the analysis. All techniques were associated with less opioid consumption compared with controls The greatest mean difference [95% confidence interval (CI)] was associated with deep serratus anterior plane block: mean difference -16.1 mg (95% CI, -20.7 to -11.6). The greatest reduction in pain score was associated with the interpectoral-pecto-serratus plane block (mean difference -1.3, 95% CI, -1.6 to - 1) at 12 h postoperatively, and with superficial serratus anterior plane block (mean difference -1.4, 95% CI, -2.4 to -0.5) at 24 h. Interpectoral-pectoserratus plane block resulted in the greatest statistically significant reduction in postoperative nausea/vomiting when compared with placebo/no intervention with an OR of 0.23 (95% CI, 0.13 to 0.40). CONCLUSION: All techniques were associated with superior analgesia and less opioid consumption compared with controls. No single technique was identified as superior to others. In comparison, local anaesthetic infiltration does not offer advantages over multimodal analgesia alone. TRIAL REGISTRATION: PROSPERO (CRD4202125065).

Chest X-ray Does Not Predict the Risk of Endotracheal Intubation and Escalation of Treatment in COVID-19 Patients Requiring Noninvasive Respiratory Support.

Forms of noninvasive respiratory support (NIRS) have been widely used to avoid endotracheal intubation in patients with coronavirus disease-19 (COVID-19). However, inappropriate prolongation of NIRS may delay endotracheal intubation and worsen patient outcomes. The aim of this retrospective study was to assess whether the CARE score, a chest X-ray score previously validated in COVID-19 patients, may predict the need for endotracheal intubation and escalation of respiratory support in COVID-19 patients requiring NIRS. From December 2020 to May 2021, we included 142 patients receiving NIRS who had a first chest X-ray available at NIRS initiation and a second one after 48-72 h. In 94 (66%) patients, the level of respiratory support was increased, while endotracheal intubation was required in 83 (58%) patients. The CARE score at NIRS initiation was not predictive of the need for endotracheal intubation (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.96-1.06) or escalation of treatment (OR 1.01, 95% CI 0.96-1.07). In conclusion, chest X-ray severity, as assessed by the CARE score, did not allow predicting endotracheal intubation or escalation of respiratory support in COVID-19 patients undergoing NIRS.

Preoperative dexmedetomidine and intraoperative bradycardia in laparoscopic cholecystectomy: a meta-analysis with trial sequential analysis.

BACKGROUND: While laparoscopic surgical procedures have various advantages over traditional open techniques, artificial pneumoperitoneum is associated with severe bradycardia and cardiac arrest. Dexmedetomidine, an imidazole derivative that selectively binds to α2-receptors and has sedative and analgesic properties, can cause hypotension and bradycardia. Our primary aim was to assess the association between dexmedetomidine use and intraoperative bradycardia during laparoscopic cholecystectomy. METHODS: We performed a systematic review with a meta-analysis and trial sequential analysis using the following PICOS: adult patients undergoing endotracheal intubation for laparoscopic cholecystectomy (P); intravenous dexmedetomidine before tracheal intubation (I); no intervention or placebo administration (C); intraoperative bradycardia (primary outcome), intraoperative hypotension, hemodynamics at intubation (systolic blood pressure, mean arterial pressure, heart rate), dose needed for induction of anesthesia, total anesthesia requirements (both hypnotics and opioids) throughout the procedure, and percentage of patients requiring postoperative analgesics and experiencing postoperative nausea and vomiting and/or shivering (O); randomized controlled trials (S). RESULTS: Fifteen studies were included in the meta-analysis (980 patients). Compared to patients that did not receive dexmedetomidine, those who did had a higher risk of developing intraoperative bradycardia (RR: 2.81, 95% CI [1.34, 5.91]) and hypotension (1.66 [0.92,2.98]); however, they required a lower dose of intraoperative anesthetics and had a lower incidence of postoperative nausea and vomiting. In the trial sequential analysis for bradycardia, the cumulative z-score crossed the monitoring boundary for harm at the tenth trial. CONCLUSIONS: Patients undergoing laparoscopic cholecystectomy who receive dexmedetomidine during tracheal intubation are more likely to develop intraoperative bradycardia and hypotension.

High-Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in Patients with COVID-19.

Rationale: The "Berlin definition" of acute respiratory distress syndrome (ARDS) does not allow inclusion of patients receiving high-flow nasal oxygen (HFNO). However, several articles have proposed that criteria for defining ARDS should be broadened to allow inclusion of patients receiving HFNO. Objectives: To compare the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to invasive mechanical ventilation (IMV). Methods: From previously published studies, we analyzed patients with coronavirus disease (COVID-19) who had PaO2/FiO2 of ⩽300 while treated with ⩾40 L/min HFNO, or noninvasive ventilation (NIV) with positive end-expiratory pressure of ⩾5 cm H2O (comparator). In patients transitioned from HFNO/NIV to invasive mechanical ventilation (IMV), we compared ARDS severity during HFNO/NIV and soon after IMV. We compared 28-day mortality in patients treated exclusively with HFNO/NIV versus patients transitioned to IMV. Measurements and Main Results: We analyzed 184 and 131 patients receiving HFNO or NIV, respectively. A total of 112 HFNO and 69 NIV patients transitioned to IMV. Of those, 104 (92.9%) patients on HFNO and 66 (95.7%) on NIV continued to have PaO2/FiO2 ⩽300 under IMV. Twenty-eight-day mortality in patients who remained on HFNO was 4.2% (3/72), whereas in patients transitioned from HFNO to IMV, it was 28.6% (32/112) (P < 0.001). Twenty-eight-day mortality in patients who remained on NIV was 1.6% (1/62), whereas in patients who transitioned from NIV to IMV, it was 44.9% (31/69) (P < 0.001). Overall mortality was 19.0% (35/184) and 24.4% (32/131) for HFNO and NIV, respectively (P = 0.2479). Conclusions: Broadening the ARDS definition to include patients on HFNO with PaO2/FiO2 ⩽300 may identify patients at earlier stages of disease but with lower mortality.

Risk Factors for General Anesthesia Conversion in Anterior Circulation Stroke Patients Undergoing Endovascular Treatment.

BACKGROUND AND PURPOSE: No current consensus exists on the best anesthetic management of ischemic stroke patients undergoing mechanical thrombectomy. Both conscious sedation (CS) and general anesthesia (GA) are currently considered valid anesthetic strategies, yet patients managed under CS may require emergent conversion to GA, which has been associated with worse outcomes. The aim of this study was to analyze the conversion rate and potential risk factors for GA conversion during mechanical thrombectomy. METHODS: Two-hundred and twenty-seven patients with consecutive acute anterior circulation ischemic stroke treated with mechanical thrombectomy and initiated under CS or local anesthesia were included in this retrospective analysis. Conversion rate to GA was calculated, while univariate and multivariate analysis were used to identify risk factors. RESULTS: Twenty patients (8.8%) were switched to GA. Multivariate analysis identified procedure duration (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.00-1.02, p value 0.028), tandem stroke (OR 8.57, 95% CI 2.06-35.7, p value 0.003), Sequential Organ Failure Assessment (SOFA) (OR 1.76, 95% CI 1.19-2.61, p value 0.005), and number of pharmacological agents used (OR 5.76, 95% CI 2.49-13.3, p value <0.001) as independently associated with conversion to GA. CONCLUSION: In our study, tandem occlusion, longer endovascular procedures, SOFA, and number of pharmacological agents used predicted the risk of emergent conversion to GA in stroke patients undergoing endovascular treatment. Prospective studies investigating optimal CS strategies are deemed necessary.

Safety in training for ultrasound guided internal jugular vein CVC placement: a propensity score analysis.

BACKGROUND: Central venous catheter (CVC) placement is a routine procedure but is potentially associated with severe complications. Relatively small studies investigated if the use of ultrasound is effective in bridging the skill gap between proficient and not proficient operators, while patient safety during training remains a controversial topic. The first aim of this study was to evaluate if resident proficiency affects the failure rate in CVC positioning under ultrasound guidance. In addition, it aimed to investigate the different rate of complications between proficient and non proficient residents. METHODS: We conducted a cohort study including CVC placed by residents at the University Hospital of Padova, from November 1, 2012 to July 9, 2020 comparing proficient and non proficient residents. To avoid bias the two cohorts were matched using propensity score. RESULTS: A total of 356 residents positioned 2310 CVC during the 8 year study period. Among them, two groups of 1060 CVCs each were matched with a propensity score analysis. There was no difference in the failure rate among the groups (2.8 vs 2.7%, p-value 0.895). Moreover, cohorts had the same rate of hematomas, catheter tip malposition, arterial puncture and pneumothorax. No cases of hemothorax were reported. CONCLUSIONS: We found the same rate of success and incidence of adverse complications among cohorts, meaning that the process of skill acquisition is safe as long as appropriate training and direct supervision by a senior consultant are available.

Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study.

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A "training sample" (March-June 2020) and a "testing sample" (September 2020-January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). "Training" and "testing" samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.

Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study.

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06-4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04-1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.

Electrical impedance tomography: A compass for the safe route to optimal PEEP.

Setting the proper level of positive end-expiratory pressure (PEEP) is a cornerstone of lung protective ventilation. PEEP keeps the alveoli open at the end of expiration, thus reducing atelectrauma and shunt. However, excessive PEEP may contribute to alveolar overdistension. Electrical impedance tomography (EIT) is a non-invasive bedside tool that monitors in real-time ventilation distribution. Aim of this narrative review is summarizing the techniques for EIT-guided PEEP titration, while providing useful insights to enhance comprehension on advantages and limits of EIT for current and future users. EIT detects thoracic impedance to alternating electrical currents between pairs of electrodes and, through the analysis of its temporal and spatial variation, reconstructs a two-dimensional slice image of the lung depicting regional variation of ventilation and perfusion. Several EIT-based methods have been proposed for PEEP titration. The first described technique estimates the variations of regional lung compliance during a decremental PEEP trial, after lung recruitment. The optimal PEEP value is represented by the best compromise between lung collapse and overdistension. Later on, a second technique assessing alveolar recruitment by variation of the end-expiratory lung impedance was validated. Finally, the global inhomogeneity index and the regional ventilation delay, two EIT-derived parameters, showed promising results selecting the optimal PEEP value as the one that presents the lowest global inhomogeneity index or the lowest regional ventilation delay. In conclusion EIT represents a promising technique to individualize PEEP in mechanically ventilated patients. Whether EIT is the best technique for this purpose and the overall influence of personalizing PEEP on clinical outcome remains to be determined.

Higher versus lower positive end-expiratory pressure in patients without acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

BACKGROUND: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the association of higher positive end-expiratory pressure (PEEP), as opposed to lower PEEP, with hospital mortality in adult intensive care unit (ICU) patients undergoing invasive mechanical ventilation for reasons other than acute respiratory distress syndrome (ARDS). METHODS: We performed an electronic search of MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science from inception until June 16, 2021 with no language restrictions. In addition, a research-in-progress database and grey literature were searched. RESULTS: We identified 22 RCTs (2225 patients) comparing higher PEEP (1007 patients) with lower PEEP (991 patients). No statistically significant association between higher PEEP and hospital mortality was observed (risk ratio 1.02, 95% confidence interval 0.89-1.16; I2 = 0%, p = 0.62; low certainty of evidence). Among secondary outcomes, higher PEEP was associated with better oxygenation, higher respiratory system compliance, and lower risk of hypoxemia and ARDS occurrence. Furthermore, barotrauma, hypotension, duration of ventilation, lengths of stay, and ICU mortality were similar between the two groups. CONCLUSIONS: In our meta-analysis of RCTs, higher PEEP, compared with lower PEEP, was not associated with mortality in patients without ARDS receiving invasive mechanical ventilation. Further large high-quality RCTs are required to confirm these findings.

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS.

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

Intraoperative protective ventilation in patients undergoing major neurosurgical interventions: a randomized clinical trial.

BACKGROUND: Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. METHODS: This single-centre, pilot randomized clinical trial was conducted at the University Hospital "Maggiore della Carità" (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6-8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. RESULTS: A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. CONCLUSIONS: LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. TRIAL REGISTRATION: registered on the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ), registration number ACTRN12615000707561.

Effect of dexmedetomidine on hemodynamic responses to tracheal intubation: A meta-analysis with meta-regression and trial sequential analysis.

STUDY OBJECTIVE: An uncontrolled adrenergic response during tracheal intubation may lead to life-threatening complications. Dexmedetomidine binds to α2-receptors and may attenuate this response. The primary aim of our meta-analysis is to investigate dexmedetomidine efficacy in attenuating sympathetic response to tracheal intubation, compared with placebo or no dexmedetomidine, in terms of heart rate and blood pressure at intubation. DESIGN: Meta-analysis with meta-regression and trial sequential analysis. SETTING: Systematic search from inception until December 1, 2020 in the following databases: Pubmed, Scopus, the Cochrane Central Register of Controlled Trials, EMBASE and Google Scholar. INTERVENTIONS: All randomized controlled trials investigating intravenous dexmedetomidine as premedication in adult patients undergoing tracheal intubation were included in our study. Studies were included without any language or publication date restriction. A trial sequential analysis and a post-hoc meta-regression were performed on the main outcomes. MEASUREMENTS: Hemodynamic parameters and heart rate at tracheal intubation, dose of anesthetic needed for induction of anesthesia, total anesthetic requirement throughout the operative procedure, postoperative pain and percentage of patients requiring analgesics at 24 postoperative hours, postoperative nausea and vomiting, intraoperative and postoperative bradycardia, hypotension, dizziness, shivering and/or respiratory depression. MAIN RESULTS: Ninety-nine included studies randomized 6833 patients. During laryngoscopy, all hemodynamic parameters were significantly greater in the no dexmedetomidine group. In particular, in the dexmedetomidine group, systolic blood pressure differed by -21.8 mm Hg (95% CI -26.6 to -17.1, p-value < 0.001, I2 97%), mean arterial pressure by -12.8 mm Hg (95% CI -15.6 to -10.0, p-value < 0.001, I2 98%), and heart rate by -16.9 bpm (95% CI -19.8 to -13.9, p-value < 0.001, I2 98%). CONCLUSIONS: Patients receiving premedication with dexmedetomidine for tracheal intubation, compared with no dexmedetomidine, have a lower blood pressure and heart rate, however, the risk of bradycardia and hypotension is relevant and its use during daily practice should be cautiously evaluated for each patient.