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Prone positioning is a well-established treatment in mechanically ventilated patients with acute respiratory distress syndrome. Although recommended by guidelines, limited evidence exists on the benefits of prone positioning in awake Corona Virus Disease 2019 (COVID-19) patients. Aim of our systematic review was to provide an overview of all published evidence on this intervention in the setting of COVID-19. Moreover, we aimed to investigate feasibility, efficacy and safety of awake prone positioning in COVID-19 patients with acute respiratory failure. Inclusion criteria were: adult hospitalized, awake, COVID-19 patients, lying in the prone position for respiratory failure. All kind of studies were included without language restriction. Eighty manuscripts involving 3226 patients were included. Need for mechanical ventilation was reported in 26.8% of patients. No periprocedural death or severe adverse events were reported. During prone positioning, a significant improvement in peripheral capillary oxygen saturation (SpO2) and ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) was obtained, together with a reduction in respiratory rate. These improvements persisted after resupination. Awake prone positioning in non-intubated COVID-19 patients is safe and improves oxygenation both during and after the end of proning cycles. Large, high-quality, randomized clinical trials are warranted to determine the impact of prone positioning on survival. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Severe cases of COVID-19 are characterized by massive hyper-inflammatory host response. • Anakinra is a recombinant form of IL-1 receptor antagonist. • Several studies on anakinra in COVID-19 reported positive effects on mortality. • Our meta-analyses included four observational studies involving 184 patients. • Anakinra was associated with reduction in mortality and mechanical ventilation. Severe COVID-19 cases have a detrimental hyper-inflammatory host response and different cytokine-blocking biologic agents were explored to improve outcomes. Anakinra blocks the activity of both IL-1α and IL‑1β and is approved for different autoinflammatory disorders, but it is used off-label for conditions characterized by an excess of cytokine production. Several studies on anakinra in COVID-19 patients reported positive effects. We performed a meta-analysis of all published evidence on the use of anakinra in COVID19 to investigate its effect on survival and need for mechanical ventilation. We searched for any study performed on adult patients with acute hypoxemic failure related to 2019-nCoV infection, receiving anakinra versus any comparator. Primary endpoint was mortality at the longest available follow-up. Adverse effects, need for mechanical ventilation and discharge at home with no limitations were also analysed. Four observational studies involving 184 patients were included. Overall mortality of patients treated with anakinra was significantly lower than mortality in the control group (95% CI 0.14-0.48, p<0.0001). Moreover, patients treated with anakinra had a significantly lower risk of need for mechanical ventilation than controls (95% CI 0.250.74, p=0.002). No difference in adverse events and discharge at home with no limitations was observed. The Trial Sequential Analysis z-cumulative line reached the monitoring boundary for benefit and the required sample size. Administration of anakinra in COVID-19 patients was safe and might be associated with reductions in both mortality and need for mechanical ventilation. Randomized clinical trials are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Aims: To determine if percutaneous tracheostomy is safe in critically ill patients treated with anticoagulant therapies. Settings and Design: Single-center retrospective study including all the patients who underwent percutaneous dilatational tracheostomy (PDT) placement over a 1-year period in a 14-bed, cardiothoracic and vascular Intensive Care Unit (ICU). Materials and Methods: Patients demographics and characteristics, anticoagulant and antiplatelet therapies, coagulation profile, performed technique and use of bronchoscopic guidance were retrieved. Results: Thirty-six patients (2.7% of the overall ICU population) underwent PDT over the study period. Twenty-six (72%) patients were on anticoagulation therapy, 1 patient was on antiplatelet therapy and 2 further patients received prophylactic doses of low molecular weight heparin. Only 4 patients had normal coagulation profile and were not receiving anticoagulant or antiplatelet therapies. Overall, bleeding of any severity complicated 19% of PDT. No procedure-related deaths occurred. Conclusions: PDT was proved to be safe even in critically ill-patients treated with anticoagulant therapies. Larger prospective studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Introduction The preoperative period is a stressing occurrence for most people undergoing surgery, in particular children. Approximately 50–75% of children undergoing surgery develop anxiety which is associated with distress on emergence from anesthesia and with later postoperative behavioral problems. Premedication, commonly performed with benzodiazepines, reduces preoperative anxiety, facilitates separation from parents, and promotes acceptance of mask induction. Dexmedetomidine is a highly selective α2-agonist with sedative and analgesic properties. A meta-analysis of all randomized controlled trials (RCTs) on dexmedetomidine versus midazolam was performed to evaluate its efficacy in improving perioperative sedation and analgesia, and in reducing postoperative agitation when used as a preanesthetic medication in children. Methods Studies were independently searched in PubMed, BioMedCentral, Embase, and the Cochrane Central Register of clinical trials and updated on August 15th, 2014. Primary outcomes were represented by improved sedation at separation from parents, at induction of anesthesia, and reduction in postoperative agitation. Secondary outcomes were reduction in rescue analgesic drugs, and duration of surgery and anesthesia. Inclusion criteria were random allocation to treatment and comparison between dexmedetomidine and midazolam. Exclusion criteria were adult studies, duplicate publications, intravenous administration, and no data on main outcomes. Results Data from 1033 children in 13 randomized trials were analyzed. Overall, in the dexmedetomidine group there was a higher incidence of satisfactory sedation at separation from parents (314 of 424 [74%] in the dexmedetomidine group vs 196 of 391 [50%] in the midazolam group, RR = 1.30 [1.05–1.62], P = 0.02), a reduced incidence of postoperative agitation (14 of 140 [10%] vs 56 of 141 [40%], RR = 0.31 [0.13–0.73], P = 0.008), and a significant reduction in the rescue doses of analgesic drugs (49 of 241 [20%] vs 95 of 243 [39%], RR = 0.52 [0.39–0.70], P < 0.001). There was no evidence of a higher incidence of satisfactory sedation at anesthesia induction or any reduction of duration of surgery and anesthesia. Conclusions Dexmedetomidine is effective in decreasing anxiety upon separation from parents, decreasing postoperative agitation, and providing more effective postoperative analgesia when compared with midazolam. [ABSTRACT FROM AUTHOR]

Introduction: The effect of dexmedetomidine on length of intensive care unit (ICU) stay and time to extubation is still unclear. Materials and Methods: Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials (updated February first 2013). Randomized studies (dexmedetomidine versus any comparator) were included if including patients mechanically ventilated in an intensive care unit (ICU). Co-primary endpoints were the length of ICU stay (days) and time to extubation (hours). Secondary endpoint was mortality rate at the longest follow-up available. Results: The 27 included manuscripts (28 trials) randomized 3,648 patients (1,870 to dexmedetomidine and 1,778 to control). Overall analysis showed that the use of dexmedetomidine was associated with a significant reduction in length of ICU stay (weighted mean difference (WMD) = −0.79 [−1.17 to −0.40] days, p for effect <0.001) and of time to extubation (WMD = −2.74 [−3.80 to −1.65] hours, p for effect <0.001). Mortality was not different between dexmedetomidine and controls (risk ratio = 1.00 [0.84 to 1.21], p for effect = 0.9). High heterogeneity between included studies was found. Conclusions: This meta-analysis of randomized controlled studies suggests that dexmedetomidine could help to reduce ICU stay and time to extubation, in critically ill patients even if high heterogeneity between studies might confound the interpretation of these results. [ABSTRACT FROM AUTHOR]

Objective: Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay. Data sources and study selection: Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients. Data extraction and synthesis: Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found. Conclusions: Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients," by D. Heyland, J. Muscedere, P. E. Wischmeyer and colleagues in the April 18, 2013 issue.

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. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is strongly associated with high morbidity and mortality of critically ill patients. In the last years several different biological markers with higher sensitivity and specificity for the occurrence of renal impairment have been developed in order to promptly recognize and treat AKI. Nonetheless, their potential role in improving patients' outcome remains unclear since the effectiveness of an "earlier" initiation of renal replacement therapy (RRT) is still debated. Since one large, high-quality randomized clinical trial has been recently pubblished, we decided to perform a meta-analysis of all the RCTs ever performed on "earlier" initiation of RRT versus standard RRT in critically ill patients with AKI to evaluate its effect on major outcomes. Methods: Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and Cochrane Central Register of clinical trials. The following inclusion criteria were used: random allocation to treatment ("earlier" initiation of RRT versus later/standard initiation); critically ill patients. Results: Ten trials randomizing 2214 patients, 1073 to earlier initiation of RRT and 1141 to later initiation were included. No difference in mortality (43.3% (465 of 1073) for those receiving early RRT and 40.8% (466 of 1141) for controls, p = 0.97) and survival without dependence on RRT (3.6% (34 of 931) for those receiving early RRT and 4.2% (40 of 939) for controls, p = 0.51) were observed in the overall population. On the contrary, early initiation of RRT was associated with a significant reduction in hospital length of stay. No differences in occurrence of adverse events were observed. Conclusions: Our study suggests that early initiation of RRT in critically ill patients with AKI does not provide a clinically relevant advantage when compared with standard/late initiation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Initiation strategies for renal-replacement therapy in the intensive care unit" by S. Gaudry and colleagues in the July 14, 2016 issue.

Background: Bleeding and transfusions affect mortality in aortic surgery. Although tranexamic acid significantly reduced bleeding in multiple settings, its role in major vascular surgery was never studied. The aim of this study was to determine if tranexamic acid reduces blood loss in open abdominal aortic aneurysm (AAA) surgery.Methods: A total of 100 patients undergoing elective open AAA repair were randomised to receive tranexamic acid (a loading dose of 500 mg and a continuous infusion of 250 mg h-1) or placebo. The primary outcome was intraoperative blood loss, and the secondary outcomes were the number of patients receiving red blood cells, occurrence of thromboembolic events, and mortality. Data were analysed using the intention-to-treat principle.Results: Fifty patients were randomised into each group. Median (inter-quartile range) intraoperative blood loss was 400 (300-1050) ml in the tranexamic acid group vs 500 (360-1000) ml in the placebo group (P=0.44). Transfusion rate was seven/50 (14%) in the tranexamic group vs 12/50 (24%) in the placebo group (P=0.20). No thrombosis was recorded. In a post hoc analysis, postoperative blood loss was reduced in the tranexamic group both at 4 h (60 [40-80] ml vs 100 [60-140] ml, P<0.001) and 24 h (180 [120-275] vs 275 [190-395] ml, P=0.003) after surgery. At 1 yr, three patients were dead, all in the placebo group (P=0.24) and all after 28 days.Conclusions: Tranexamic acid did not reduce intraoperative blood loss or blood transfusions in open AAA repair, although it may reduce postoperative blood loss without increasing adverse effects.Clinical Trial Registration: NCT02335359. [ABSTRACT FROM AUTHOR]

Severe COVID-19 patients can develop a maladaptive immune response with hyperproduction of cytokines and chemokines which lead to alveolar damage, endothelial activation, coagulopathy and thromboembolic events. We performed a meta-analysis which included any study performed on COVID-19 patients with respiratory hypoxemic failure who received anakinra versus any comparator. Primary endpoint was mortality. Secondary endpoints were intubation rate, superinfection and thromboembolic events. Subgroups analyses included patients in general ward, with hyperinflammation and/or baseline ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) >200. Twenty-four studies were included. Mortality in anakinra patients was significantly lower than mortality of controls (19% vs. 28%; p < 0.0001). Anakinra patients had significantly lower risk of intubation (16% vs. 33%; p < 0.001). Mortality reduction was confirmed in general ward settings, in patients with hyperinflammation and with PaO2/FiO2 >200, but not when selecting randomized studies only. A trend towards increased mortality in more severe patients was observed. [ABSTRACT FROM AUTHOR]

Septic shock survival rate and host immune response are intimately interlaced. In the last years, biological and pre-clinical studies demonstrated sex-specific differences in the immune response to infection. In the hypothesis that survival rate is related to the hormonal framework, the aim of the present study was to observe sex-specific differences in 28-day mortality rate between women of childbearing potential and same-age men. This multicenter study was conducted in six Italian intensive care units (ICUs). We enrolled consecutive patients ≤ 55 years old admitted to the Intensive Care Unit from January 2011 to January 2020, who were diagnosed with septic shock at the time of ICU admission or during the ICU stay. We gathered baseline characteristics and outcomes. The primary outcome was 28-day mortality; secondary outcomes included ICU mortality, in-hospital mortality and length of stay in the ICU and in the hospital. Moreover, data from >55 years old patients were collected and analyzed. We enrolled 361 young patients with septic shock: 215 were males (60%) and 146 females (40%). While baseline and ICU characteristics were similar between the two groups, males had a higher 28-day mortality rate (39.5% vs. 29%, p = 0.035), ICU mortality rate (49% vs. 38%, p = 0.040) and hospital mortality rate (61% vs. 50%, p = 0.040) as compared to females. Findings were confirmed in patients with septic shock at ICU admission. Young adult females developed septic shock less frequently than young males, displaying a reduced mortality rate as compared to that of their same-age male counterpart. These findings may stimulate future research and therapies. [ABSTRACT FROM AUTHOR]

Objective: To report the first performance of simultaneous bilateral percutaneous nephrolithotomy and flexible ureteroscopy carried out in tandem by 2 different surgeons in a patient with bilateral medium-sized renal calculi, describing step-by-step details of the surgical technique.Materials and Methods: A 46-year-old man, affected with hyperparathyroidism, was diagnosed with asymptomatic bilateral medium-sized renal stones. An abdominal noncontrast computed tomography scan revealed a left single kidney stone with a maximum diameter of 16 mm and 2 right renal stones located in the pelvis and in the lower calyx, of 21 and 19 mm in maximum diameter, respectively. A bilateral simultaneous percutaneous nephrolithotomy on the right side and flexible ureteroscopy on the left side were therefore carried out.Results: The total operative time was 80 minutes. No intra- or postoperative complications were experienced. On postoperative day 1, the creatinine serum level was stable (0.7 mg/dL); he was discharged home 48 hours later. Ureteral stents were removed 7 days after the procedure. At 2 weeks follow-up, an abdominal noncontrast computed tomography scan showed a stone-free status and no changes in renal function were detected.Conclusion: A simultaneous bilateral endoscopic manipulation is feasible and safe and it can be offered in the presence of medium-sized bilateral renal stones in high-volume centers by experienced surgeons. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Intra-aortic balloon pump (IABP) is an established tool in the management of cardiac dysfunction in cardiac surgery. The best timing for IABP weaning is unknown and varies greatly among cardiac centers. The authors investigated the differences in IABP management among 66 cardiac surgery centers performing 40,675 cardiac surgery procedures in the 12-month study period. The centers were contacted through email, telephone, or in person interview. IABP management was very heterogeneous in this survey: In 43% centers it was routinely removed on the first postoperative day, and in 34% on the second postoperative day. In 50% centers, it was routinely removed after extubation of the patients whereas in 15% centers it was removed while the patients were sedated and mechanically ventilated. In 66% centers, patients were routinely receiving pharmacological inotropic support at the time of removal of IABP. The practice of decreasing IABP support was also heterogeneous: 57% centers weaned by reducing the ratio of beat assistance whereas 34% centers weaned by reducing balloon volume. We conclude that the management of IABP is heterogeneous and there is a need for large prospective studies on the management of IABP in cardiac surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pediatric patients are particularly prone to cardiopulmonary bypass (CPB)‐induced coagulopathy mainly due to hemodilution, consumption of coagulation factors and hypothermia. The aim of the present study was to examine the possible role of platelet count and function as it relates to the bleeding risk after CPB in the pediatric population. All consecutive patients (age <13 years) scheduled for elective cardiac surgery between January 2019 and November 2019 were retrospectively considered for the study. We gathered demographic characteristics, perioperative laboratory data (mainly platelet count and function), transfusion requirements, and blood loss for each patient. Patients with a chest tube output during the first 24 hours after surgery >75th percentile were bleeders (cases). Controls were nonbleeders. A total of 31 patients were enrolled [median age 17 (4‐57) months]. A significant postoperative reduction in platelet count (P <.001) and function either in ADP‐test (P <.001), TRAP‐test (P <.001) and ASPI‐test (P <.001) was found, with positive correlations between chest tube output within the first 24 hours after surgery and postoperative impairment of platelet count (R = 0.553, P =.001), ADP‐test (R = 0.543, P =.001), TRAP‐test (R = 0.627, P <.001) and ASPI‐test (R = 0.436, P =.014). Eight children (26%) experienced major postoperative bleeding. Bleeders were significantly younger (P =.015) and underwent longer CPB duration (P =.015). Despite no significant differences in postoperative platelet count and function between cases and controls, the postoperative reduction (Δ) in platelet count (P =.002) and function in ADP‐test (P =.007), TRAP‐test (P =.020) and ASPI‐test (P =.042) was significantly greater in bleeders vs. nonbleeders. A ΔPLT >262 500 ×109/L, a ΔADP‐test >29 U, a ΔTRAP‐test >44 U and a ΔASPI‐test >26 U showed to be predictive of major postoperative bleeding. Postoperative bleeding in children undergoing cardiac surgery with CPB was linked to younger age, longer CPB duration, and significant postoperative reduction in platelet count and function. Larger studies are needed to confirm our results and define strategies to reduce postoperative bleeding in these patients. [ABSTRACT FROM AUTHOR]

Background: Tracheal intubation in patients at risk for secondary spinal cord injury is potentially difficult and risky.Objectives: To compare tracheal intubation techniques in adult patients at risk for secondary cervical spinal cord injury undergoing surgery. Primary outcome was first-attempt failure rate. Secondary outcomes were time to successful intubation and procedure complications.Design: Systematic review and meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA).Data Sources: Databases searched up to July 2019.Eligibility: Randomized controlled trials comparing different intubation techniques.Results: We included 18 trials enrolling 1972 patients. Four studies used the "awake" approach, but no study compared awake versus non-awake techniques. In remaining 14 RCTs, intubation was performed under general anesthesia. First-attempt failure rate was similar when comparing direct laryngoscopy or fiberoptic bronchoscopy versus other techniques. A better first-attempt failure rate was found with videolaryngoscopy and when pooling all the fiberoptic techniques together. All these results appeared not significant at TSA, suggesting inconclusive evidence. Intubating lighted stylet allowed faster intubation. Postoperative neurological complications were 0.34% (no significant difference among techniques). No life-threatening adverse event was reported; mild local complications were common (19.5%). The certainty of evidence was low to very low mainly due to high imprecision and indirectness.Conclusions: Videolaryngoscopy and fiberoptic-assisted techniques might be associated with higher first-attempt failure rate over controls. However, low to very low certainty of evidence does not allow firm conclusions on the best tracheal intubation in patients at risk for cervical spinal cord injury. [ABSTRACT FROM AUTHOR]

Objective: Noninvasive ventilation is a life-saving technique increasingly used to treat acute respiratory failure. Noninvasive ventilation has been applied mostly in ICUs, but several reasons brought to an increasing application of noninvasive ventilation in ordinary wards. Few articles evaluated the outcomes of patients receiving noninvasive ventilation including long-term follow-up. The aim of the present study was to assess 1-year survival rate of patients treated with noninvasive ventilation outside the ICU for acute respiratory failure of heterogeneous causes and to identify the predictors of long-term mortality.Design: Prospective, observational, pragmatic study.Setting: Ordinary wards of a teaching hospital.Patients: Consecutive patients treated with noninvasive ventilation for acute respiratory failure.Interventions: None.Measurements and Main Results: Two-hundred and twenty-patients were enrolled. Mortality rates at 30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding patients with "do-not-resuscitate" status, mortality rates were 13%, 19%, and 28%. The multivariate analyses identified solid cancer, pneumonia in hematologic patients, and do-not-resuscitate status as independent predictors of mortality with postoperative acute respiratory failure associated with improved survival. The same predictors were confirmed when excluding do-not-resuscitate patients from the analyses.Conclusions: Noninvasive ventilation applied in ordinary wards was effective, with long-term outcomes not different from those reported for ICU settings. Solid cancer, pneumonia in hematologic malignancies, and do-not-resuscitate status predicted mortality, whereas patients with postoperative acute respiratory failure had the best survival rate. Additional studies are required to evaluate noninvasive ventilation efficacy in the wards compared with ICU. [ABSTRACT FROM AUTHOR]

Introduction: Hypotensive state is frequently observed in several critical conditions. If an adequate mean arterial pressure is not promptly restored, insufficient tissue perfusion and organ dysfunction may develop. Fluids and catecholamines are the cornerstone of critical hypotensive states management. Catecholamines side effects such as increased myocardial oxygen consumption and development of arrhythmias are well known. Thus, in recent years, interest in catecholamine-sparing agents such as vasopressin, terlipressin and methylene blue has increased; however, few randomized trials, mostly with small sample sizes, have been performed. We therefore conducted a meta-analysis of randomized trials to investigate the effect of non-catecholaminergic vasopressors on mortality. Methods: PubMed, BioMed Central and Embase were searched (update December 31st, 2014) by two independent investigators. Inclusion criteria were: random allocation to treatment, at least one group receiving a non-catecholaminergic vasopressor, patients with or at risk for vasodilatory shock. Exclusion criteria were: crossover studies, pediatric population, non-human studies, studies published as abstract only, lack of data on mortality. Studied drugs were vasopressin, terlipressin and methylene blue. Primary endpoint was mortality at the longest follow-up available. Results: A total of 1,608 patients from 20 studies were included in our analysis. The studied settings were sepsis (10/20 studies [50%]), cardiac surgery (7/20 [35%]), vasodilatory shock due to any cause (2/20 [19%]), and acute traumatic injury (1/20 [5%]). Overall, pooled estimates showed that treatment with non-catecholaminergic agents improves survival (278/810 [34.3%] versus 309/798 [38.7%], risk ratio = 0.88, 95% confidence interval = 0.79 to 0.98, p = 0.02). None of the drugs was associated with significant reduction in mortality when analyzed independently. Results were not confirmed when analyzing studies with a low risk of bias. Conclusions: Catecholamine-sparing agents in patients with or at risk for vasodilatory shock may improve survival. Further researches on this topic are needed to confirm the finding. [ABSTRACT FROM AUTHOR]

Objective: Noninvasive ventilation is increasingly applied to prevent or treat acute respiratory failure, but its benefit on survival is still controversial for many indications. We performed a metaanalysis of randomized controlled trials focused on the effect of noninvasive ventilation on mortality. Data Sources: BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials (updated December 31, 2013) were searched. Study Selection: We included all the randomized controlled trials published in the last 20 years performed in adults, reporting mortality, comparing noninvasive ventilation to any other treatment for prevention or treatment of acute respiratory failure or as a tool allowing an earlier extubation. Studies with unclear methodology, comparing two noninvasive ventilation modalities, or in palliative settings were excluded. Data Extraction: We extracted data on mortality, study design, population, clinical setting, comparator, and follow-up duration. Data Synthesis: Seventy-eight studies were analyzed. Noninvasive ventilation was associated with a reduction in mortality (12.6% in the noninvasive ventilation group vs 17.8% in the control arm; risk ratio = 0.73 [0.66-0.81]; p < 0.001; number needed to treat = 19 with 7,365 patients included) at the longest available followup. Mortality was reduced when noninvasive ventilation was used to treat (14.2% vs 20.6%; risk ratio = 0.72; p < 0.001; number needed to treat = 16, with survival improved in pulmonary edema, chronic obstructive pulmonary disease exacerbation, acute respiratory failure of mixed etiologies, and postoperative acute respiratory failure) or to prevent acute respiratory failure (5.3% vs 8.3%; risk ratio = 0.64 [0.46-0.90]; number needed to treat = 34, with survival improved in postextubation ICU patients), but not when used to facilitate an earlier extubation. Overall results were confirmed for hospital mortality. Patients randomized to noninvasive ventilation maintained the survival benefit even in studies allowing crossover of controls to noninvasive ventilation as rescue treatment. Conclusions: This comprehensive metaanalysis suggests that noninvasive ventilation improves survival in acute care settings. The benefit could be lost in some subgroups of patients if noninvasive ventilation is applied late as a rescue treatment. Whenever noninvasive ventilation is indicated, an early adoption should be promoted. [ABSTRACT FROM AUTHOR]

Objective: Sepsis is a complex inflammatory disease, rising in response to infection. Drotrecogin alfa, approved in 2001 for severe sepsis, has been withdrawn from the market. The aim of this study was to assess if drotrecogin alfa-activated can reduce mortality in the more severe septic patients. Methods: We searched PubMed, Embase, Scopus, BioMedCentral, and in Clinicaltrials. gov databases to identify every randomized study performed on drotrecogin alfa-activated in any clinical setting in humans, without restrictions on dose or time of administration. Our primary end-point was mortality rate in high risk patients. Secondary endpoints were mortality in all patients, in patients with an Acute Physiology and Chronic Health Evaluation (APACHE) 2 score > 25 and in those with an APACHE 2 score ≤25. Results: Five trials were identified and included in the analysis. They randomized 3196 patients to drotrecogin alfa and 3111 to the control group. Drotrecogin alfa was associated with a reduction in mortality (99/263 [37.6%] vs 115/244 [47.1%], risk ratios (RR) = 0.80[0.65; 0.98], p = 0.03) in patients with multiple organ failure and a mortality risk in the control group of >40%, but not in the overall population or in lower risk populations. Conclusions: In high risk populations of patients with multiple organ failure and a mortality of >40% in the control group, Drotrecogin alfa may still have a role as a lifesaving treatment. No beneficial effect in low risk patients was found. An indivi-dual patient meta-analysis including all randomized controlled trial on sepsis is warranted, along with new studies on similar drugs such as protein C zymogen. [ABSTRACT FROM AUTHOR]

Objective. The latest European guidelines for the management of hemorrhagic shock suggest the use of vasopressors (nore-pinephrine) in order to restore an adequate mean arterial pressure when fluid resuscitation therapy fails to restore blood pressure. The administration of arginine vasopressin (AVP), or its analogue terlipressin, has been proposed as an alternative treatment in the early stages of hypovolemic shock. Design. A meta-analysis of randomized controlled animal trials. Participants. A total of 433 animals from 15 studies were included. Interventions. The ability of AVP and terlipressin to reduce mortality when compared with fluid resuscitation therapy, other vasopressors (norepinephrine or epinephrine), or placebo was investigated. Measurements and Main Results. Pooled estimates showed that AVP and terlipressin consistently and significantly improve survival in hemorrhagic shock (mortality: 26/174 (15%) in the AVP group versus 164/259 (63%) in the control arms; OR = 0.09; 95% CI 0.05 to 0.15; P for effect < 0.001; P for heterogeneity = 0.30; I2 = 14%). Conclusions. Results suggest that AVP and terlipressin improve survival in the early phases of animal models of hemorrhagic shock. Vasopressin seems to be more effective than all other treatments, including other vasopressor drugs. These results need to be confirmed by human clinical trials. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Vertebral lumbar surgery can be performed under both general anesthesia (GA) and spinal anesthesia. A clear benefit from spinal anesthesia (SA) remains unproven. The aim of our meta-analysis was to compare the early analgesic efficacy and recovery after SA and GA in adult patients undergoing vertebral lumbar surgery. A systematic investigation with the following criteria was performed: adult patients undergoing vertebral lumbar surgery (P); single-shot SA (I); GA care with or without wound infiltration (C); analgesic efficacy measured as postoperative pain, intraoperative hypotension, bradycardia, length of surgery, blood loss, postoperative side effects (such as postoperative nausea/vomiting and urinary retention), overall patient and surgeon satisfaction, and length of hospital stay (O); and randomized controlled trials (S). The search was performed in Pubmed, the Cochrane Central Register of Controlled Trials, and Google Scholar up to 1 November 2020. Eleven studies were found upon this search. SA in vertebral lumbar surgery decreases postoperative pain and the analgesic requirement in the post anesthesia care unit. It is associated with a reduced incidence of postoperative nausea and vomiting and a higher patient satisfaction. It has no effect on urinary retention, intraoperative bradycardia, or hypotension. SA should be considered as a viable and efficient anesthetic technique in vertebral lumbar surgery. [ABSTRACT FROM AUTHOR]

The growth in popularity of flying ultralight aircraft and paragliding has been associated with an increased involvement of Emergency Medical Services because of various types of trauma suffered from both inexperienced and skilled individuals. This case presentation reports on a paraglider pilot, who was seen spinning 'unusually' rapidly toward the ground, without visible attempts to regain control of the aircraft. Besides the bilateral mydriasis and the absence of any ECG activity, there was a significant swelling of face, lips, neck, and tongue. Upon opening the mouth, a dead bee was found over the tongue, underneath the palate. A fatal anaphylactic shock was the likely cause of death of the pilot while still 'in mid-air.' This case is certainly different from the commonly reported accidents during paragliding. An updated review of the medical literature shows no reported cases of fatal anaphylactic shock during the practice of paragliding. [ABSTRACT FROM AUTHOR]