A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Repeated Levosimendan Infusions in the Management of Advanced Heart Failure: Review of the Evidence and Meta-analysis of the Effect on Mortality.

ABSTRACT: In the latest years, several studies described the impact of repetitive/intermittent i.v. levosimendan treatment in the management of advanced heart failure. For this updated review, we systematically searched the literature for clinical trials, registries , and real-world data and identified 31 studies that we commented in a narrative review: 3814 patients were described, of whom 1744 were treated repetitively with levosimendan. On the basis of the nature of the study protocols and of the end points, out of those studies, we further selected 9 that had characteristics, making them suitable for a meta-analysis on mortality. This short list describes data from 680 patients (of whom 399 received repeated doses of levosimendan) and 110 death events (of which 50 occurred in the levosimendan cohort). In the meta-analysis, repetitive/intermittent therapy with i.v. levosimendan was associated with a significant reduction in mortality at the longest time point available: 50 of 399 (12.5%) versus 60 of 281 (21.4%) in the control arms, with a risk ratio of 0.62 (95% confidence interval, 0.42-0.90; P < 0.01). In a sensitivity analysis, removing each trial and reanalyzing the remaining data set did not change the trend, magnitude, or significance of the results. A visual inspection of the funnel plot did not suggest publication bias. The results provide a very strong rationale for continuing to investigate the repetitive use of levosimendan in patients with advanced heart failure by properly powered regulatory clinical trials. Meanwhile, it seems that the use of repetitive/intermittent i.v. levosimendan infusions has become one of the few effective options for preserving the hemodynamic and symptomatic balance in such patients.

Safety of Levosimendan in Pediatric Patients: An Up-to-Date Systematic Review.

BACKGROUND: The potential risks associated with the use of levosimendan in the pediatric population has not been systematically evaluated. This study aimed to review the available evidence regarding the safety of this treatment. METHODS: Bio Med Central, PubMed, Embase, and the Cochrane Central Register of clinical trials were searched for studies describing levosimendan administration in the pediatric population in any setting. Relevant studies were independently screened, selected, and their data extracted by two investigators. The authors excluded: reviews, meta-analyses, as well as basic research and trials involving patients >18 years old. The primary outcome was the number and the type of adverse side effects reported during levosimendan administration. RESULTS: The updated systematic review included 48 studies, enrolling a total of 1,271 pediatric patients who received levosimendan as treatment (790 patients in the 11 studies that reported side effects). The primary adverse effects of levosimendan administration were hypotension and cardiac arrhythmias, particularly tachycardia. Hypotension occurred in approximately 28.9% of patients, while arrhythmia occurred in about 12.3% of patients. Meta analysis of RCTs revealed a rate of all-cause mortality of 2.0% (8 out of 385) in the levosimendan group compared to 3.9% (15 out of 378) in the control group (dobutamine, milrinone or placebo) (risk ratio [RR] = 0.55; 95% confidence interval [CI] = 0.25-1.21; P = 0.14; I2 = 0%) CONCLUSIONS: Hypotension and cardiac arrhythmia are the most reported side effects of levosimendan in pediatric patients. However, adverse events remain underreported, especially in randomized trials.

The Use of Pulmonary Artery Catheters and Echocardiography in the Cardiac Surgery Setting: A Nationwide Italian Survey.

OBJECTIVE: Wide variations exist in the use of pulmonary artery catheters (PACs) and echocardiography in the field of cardiac surgery. DESIGN: A national survey promoted by the Italian Association of Cardio-Thoracic Anesthesiologists and Intensive Care was conducted. SETTING: The study occurred in Italian cardiac surgery centers (n = 71). PARTICIPANTS: Anesthesiologists-intensivists were enrolled. INTERVENTIONS: Anonymous questionnaires were used to investigate the use of PACs and echocardiography in the operating room (OR) and intensive care unit (ICU). MEASUREMENTS AND MAIN RESULTS: A total of 257 respondents (32.2% response rate) from 59 centers (83.1% response rate) participated. Use of PACs seems less common in ORs (median insertion in 20% [5-70] of patients), with slightly higher use in ICUs; in about half of cases, it was the continuous cardiac output monitoring system of choice. Almost two-thirds of respondents recently inserted at least one PAC within a few hours of ICU admission, despite its need being largely preoperatively predictable. Protocols regulating PAC insertion were reported by 25.3% and 28% of respondents (OR and ICU, respectively). Transesophageal echocardiography (TEE) was performed intraoperatively in >75% of patients by 86.4% of respondents; only 23.7% stated that intraoperative TEE relied on anesthesiologists. Tissue Doppler and/or 3D imaging were widely available (87.4% and 82%, respectively), but only 37.8% and 24.3% of respondents self-declared skills in these modalities, respectively; 77.1% of respondents had no echocardiography certification, nor were pursuing certification (various reasons); 40.9% had not attended recent echocardiography courses. Lower PAC use was associated with university hospitals (OR: p = 0.014, ICU: p = 0.032) and with lower interventions/year (OR: p = 0.023). Higher independence in performing TEE was reported in university hospitals (OR: p < 0.001; ICU: p = 0.006), centers with higher interventions/year (OR: p = 0.019), and by respondents with less experience in cardiology (ICU: p = 0.046). CONCLUSION: Variability in the use of PACs and echocardiography was found. Protocols regulating the use of PACs seem infrequent. University centers use PACs less and have greater skills in TEE. Training and certifications in echocardiography should be encouraged.

Effect of Levosimendan Treatment in Pediatric Patients With Cardiac Dysfunction: An Update of a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Levosimendan increasingly has been used to treat heart failure and cardiac dysfunction in pediatric patients. Currently, there is only limited evidence that this drug positively affects outcomes. The authors' aim was to investigate the effects of levosimendan on hemodynamic parameters and outcomes in pediatric patients in all clinical settings. The study design was a systematic review of randomized and nonrandomized studies. Randomized clinical trials (RCTs) were included in a meta-analysis. The primary outcome of the meta-analysis was the effect of levosimendan on central venous oxygen saturation (ScvO2) and lactate values as surrogate markers of low-cardiac-output syndrome. The study setting was any acute care setting. Study participants were pediatric patients (age <18 years) receiving levosimendan, and the intervention was levosimendan versus any control treatment. The authors identified 44 studies published from 2004 to 2020, including a total of 1,131 pediatric patients. Nine studies (enrolling 547 patients) were RCTs, all performed in a pediatric cardiac surgery setting. Three RCTs were judged to carry a low risk of bias. In the RCTs, levosimendan administration was associated with a significant improvement of ScvO2 (p = 0.03) and a trend toward lower postoperative lactate levels (p = 0.08). No differences could be found for secondary outcomes. Levosimendan use in pediatric patients is not associated with major side effects and may lead to hemodynamic improvement after cardiac surgery. However, its impact on major clinical outcomes remains to be determined. Overall, the quality of evidence for levosimendan use in pediatric patients is low, and further high-quality RCTs are needed.

Procalcitonin and Early Postoperative Infection After Pediatric Cardiopulmonary Bypass Surgery.

OBJECTIVES: Systemic inflammation and bacterial infections are critical occurrences after pediatric cardiac surgery. Elevated white blood cell count and C-reactive protein cannot discriminate between these two conditions in the early postoperative period. The aim of this study was to understand whether procalcitonin (PCT) values within 48 hours of surgery could be a useful marker of postoperative infection. DESIGN: Retrospective observational study. SETTING: The study was performed in a teaching hospital. PARTICIPANTS: All patients ≤six years of age. INTERVENTIONS: Cardiac surgery on cardiopulmonary bypass from January 1, 2017 to January 1, 2020. MEASUREMENT AND MAIN RESULTS: PCT, white blood cell count, and C-reactive protein values were measured at intensive care unit admission and at 24 and 48 hours after surgery. All positive cultures in the first seven days after surgery were recorded. Out of 177 consecutive patients, 22 (12%) developed infections. PCT at 48 hours after surgery was the only laboratory predictor of infections in the first seven days after surgery (p = 0.02). Receiver operating curve analyses on PCT values at 48 hours identified an optimal cut-off value of 1.85 ng/mL in the overall population. Area under the curve was 0.63, sensitivity 63%, and specificity 69%. CONCLUSIONS: In light of this preliminary result, the clinical relevance and predictive accuracy of PCT are promising in patients with increasing values of PCT but need to be confirmed in a larger sample.

Antibiotic Management for Delayed Sternal Closure Following Pediatric Cardiac Surgery: A Systematic Review of Recent Literature.

Delayed sternal closure after pediatric cardiac surgery is a management option for the treatment of patients with severely impaired heart function. The optimal antimicrobial treatment strategy for this condition is unknown. The aim of this systematic review was to evaluate the current antibiotic administration attitudes in pediatric cardiac surgery patients needing an open chest in terms of infection with a focus on surgical site infection rate. The authors performed a systematic review and meta-analysis of all articles, which described the antibiotic administration strategy and surgical site infection rate in pediatric patients with an open chest after cardiac surgery. The authors performed a subgroup analysis on "standard" versus "non-standard" (defined as any antimicrobial drugs different from the adult guidelines recommendations) therapy for one-proportion meta-analysis with a random effect model. The authors identified 12 studies published from January 1, 2000 to July 1, 2019 including a total of 2,203 patients requiring an open chest after cardiac surgery, 350 of whom (15.9%) developed infections and 182 (8.3%) developed a surgical site infection. The surgical site infection rate in patients with "non-standard" strategy was higher than in patients with "standard" strategy: 8.8% (140 reported infections/1,582 patients) versus 6.8% (42 reported infections/621 patients), p = 0.001. The "standard" antibiotic management proposed by guidelines for adult cardiac surgery patients could be used an acceptable strategy to treat pediatric patients with an open chest after cardiac surgery.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality.

OBJECTIVE: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: Two hundred fifty-one physicians from 46 countries. INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality.

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.

Fibrinogen levels and postoperative chest drain blood loss in low-weight (<10 kg) children undergoing cardiac surgery.

INTRODUCTION: Low-weight (<10 kg) children undergoing cardiac surgery with cardiopulmonary bypass are prone to dilution and consumption of soluble coagulation factors and fibrinogen. Low levels of fibrinogen may represent a possible cause of severe postoperative chest drain blood loss. The present study investigates the association between post-cardiopulmonary bypass fibrinogen levels and postoperative chest drain blood loss and severe bleeding, aiming to identify possible cut-off values to trigger specific interventions. METHODS: Prospective cohort study on 77 patients weighing <10 kg undergoing cardiac surgery with cardiopulmonary bypass. Haemostasis and coagulation data were collected before surgery (standard tests and thromboelastometry), after protamine (thromboelastometry) and at the arrival in the intensive care unit (standard tests). The primary outcome variable was severe bleeding (chest drain blood loss >30 ml kg-1/24h). RESULTS: Factors being independently associated with severe bleeding were the international normalized ratio and the fibrinogen levels at the arrival in the intensive care unit. Once corrected for other confounders, fibrinogen levels had an odds ratio of 0.2 (95% confidence interval = 0.011-0.54) per 1 gL-1 for severe bleeding. The discrimination power was fair (area under the curve = 0.770). The best cut-off value was identified at a fibrinogen level of 150 mg dL-1, with a sensitivity of 52%, a specificity of 85% and a positive predictive value of 60% for severe bleeding. CONCLUSION: Both a prolonged international normalized ratio and low fibrinogen levels were predictive for severe bleeding, underscoring the role of coagulation factors dilution and consumption in this specific patient population.

The Brachiocephalic Vein as a Safe and Viable Alternative to Internal Jugular Vein for Central Venous Cannulation.

BACKGROUND: Although many studies have compared success and complication rates for central line insertion sites with and without ultrasound, few have examined the use of the brachiocephalic vein for central venous access. The aim of this study was to describe the brachiocephalic vein as an alternative site for elective ultrasound vascular cannulation in adults, and to compare it with the more commonly used internal jugular vein site in terms of procedural difficulties, first pass failure rate, overall failure rate, and safety. METHODS: In this single-center, retrospective cohort study, clinical data from consecutive adult patients undergoing elective ultrasound-guided central venous catheterization of upper body were retrieved from the department database. All of these central venous catheters were requested by department team, none was positioned for surgery. Seven hundred nine patients underwent central venous catheterization via the internal jugular approach and 285 patients via the brachiocephalic route. Patients catheterized via the brachiocephalic vein approach were then compared with those catheterized via the internal jugular vein in terms of ease of catheterization, success rate, and complications. Differences between approaches were assessed by univariate analyses and multivariable analysis. RESULTS: Overall, 994 patients underwent central venous catheterization. A total of 87% had a successful catheter implantation at the first attempt, 6.7% of insertions were difficult, 5.7% were complicated, and 3.4% failed. Procedural difficulty was more frequent with the internal jugular than with the brachiocephalic approach (odds ratio, 0.38; 95% confidence interval, 0.19-0.76; P = .007) after correction for potential confounders. Differences between groups in complication rate (6.3% vs 4.1%) or failure rate (3.4% vs 3.5%) were not significant. CONCLUSIONS: Brachiocephalic cannulation is a reasonable alternative to ultrasound-guided internal jugular vein catheterization.

Nonsurgical Strategies to Reduce Mortality in Patients Undergoing Cardiac Surgery: An Updated Consensus Process.

OBJECTIVE: A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: More than 400 physicians from 52 countries participated in this web-based consensus conference. INTERVENTIONS: The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide. MEASUREMENTS AND MAIN RESULTS: Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions. CONCLUSIONS: This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field.

Hemodilution on Cardiopulmonary Bypass: Thromboelastography Patterns and Coagulation-Related Outcomes.

OBJECTIVE: Hemodilution has been associated with both hypocoagulability and hypercoagulability in studies based on thromboelastography (TEG). Severe hemodilution during cardiopulmonary bypass (CPB) is a risk factor for morbidity in cardiac surgery. This study investigated the effects of different degrees of hemodilution with CPB on post-CPB TEG parameters and coagulation-related outcomes. DESIGN: Retrospective cohort study. SETTING: University research hospital. PARTICIPANTS: The study comprised 793 cardiac surgery patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The patient population was divided into low (LH), moderate (MH), and severe (SH) hemodilution groups based on the hemodilution degree on CPB. Differences in TEG parameters and coagulation-related outcomes were assessed. Patients with SH experienced significantly (p = 0.019) prolonged clotting times (median r-time 6.1 min, interquartile range 5.1-7.4 min) with respect to patients with MH (median r-time 5.8 min, interquartile range 4.8-7 min) and LH (median r-time 5.9 min, interquartile range 4.8-7.2 min). Clot firmness was significantly (p = 0.001) lower in patients with SH (median maximum amplitude 63 mm, interquartile range 57-68 mm) compared with patients with MH (median maximum amplitude 65 mm, interquartile range 61-71 mm) and LH (median maximum amplitude 67 mm, interquartile range 62-74 mm). Patients with SH had higher chest drain blood loss and required more fresh frozen plasma and platelet concentrate transfusions than did patients with MH or LH. Postoperative thromboembolic complications were significantly (p = 0.006) more common in patients with SH (2.6%) than in patients with MH (0%) or LH (0.4%). CONCLUSIONS: SH on CPB is associated with hypocoagulation, bleeding, and thrombosis-associated worse outcomes.

Preoperative colonization in pediatric cardiac surgery and its impact on postoperative infections.

BACKGROUND: Patients with congenital heart defects are frequently hospitalized before surgery. This exposes them to a high risk for pathogen colonization. There are limited data on colonization prevalence in the pediatric cardiac population, and limited data concerning its potential role in the risk of developing infections after cardiac surgery. AIM: This study aimed to verify the impact of preoperative colonization on postoperative infections in a population of pediatric cardiac surgery patients coming from Italy and developing countries. METHODS: This was a retrospective study conducted in all the patients aged ≤18 years who underwent pediatric open-heart surgery in the year 2015. Clinical data were retrieved from the institutional database for cardiac surgery patients. Data on swab cultures were retrieved from the laboratory database. Swab colonization was tested for association with infection and other outcomes. RESULTS: Among 169 children who performed the screening for pathogen colonization, 50% had at least one positive swab. Italian patients were (P=.001) less likely to be colonized with respect to foreign patients (relative risk 0.17, 95% CI 0.09-0.35). Postoperative infections in colonized patients occurred at a similar rate as in noncolonized patients (relative risk 1.24, 95% CI 0.64-2.39; P=.532). Colonized patients had a preoperative stay (P=.021) longer than noncolonized patients (mean difference 2 days, 95% CI 0.3-3.8 days). CONCLUSION: The results of our study suggest that the impact of preoperative colonization on outcome and postoperative infections may be negligible; larger series are required to clearly define this issue.

Two Different Endoscopic Procedures Made Feasible by the Janus Mask in a High-Risk Patient.

The Janus mask is a full face mask designed for providing noninvasive ventilation (NIV) during any kind of upper endoscopies (e.g., fiber-optic bronchoscopy, gastrointestinal endoscopy, and transesophageal echocardiography). Due to its unique conformation, its use can be considered for both elective and urgent endoscopic procedures in high-risk patients. In this case report, we present a patient with acute respiratory failure who underwent two consecutive different endoscopic procedures (fiber-optic bronchoscopy and gastrointestinal endoscopy) during continuous positive airway pressure support by means of this novel NIV mask, thus avoiding tracheal intubation and at the same time, improving his respiratory condition.

Worldwide Opinion on Multicenter Randomized Interventions Showing Mortality Reduction in Critically Ill Patients: A Democracy-Based Medicine Approach.

OBJECTIVES: Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. DESIGN AND SETTING: A systematic review of literature followed by web-based voting on findings of a consensus conference. PARTICIPANTS: A total of 555 clinicians from 61 countries. INTERVENTIONS: The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents' agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians' approach to interventions also were investigated. MEASUREMENTS AND MAIN RESULTS: According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians' agreement. CONCLUSIONS: Physicians' clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences.

Mortality in Multicenter Critical Care Trials: An Analysis of Interventions With a Significant Effect.

OBJECTIVES: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. DATA SOURCES: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. STUDY SELECTION: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. DATA EXTRACTION: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. DATA SYNTHESIS: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. CONCLUSIONS: We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.

Do we need heparin coating for extracorporeal membrane oxygenation? New concepts and controversial positions about coating surfaces of extracorporeal circuits.

Blood contact with surfaces of the extracorporeal circuit provokes the activation of the coagulation system. To improve biocompatibility of the extracorporeal circuit without increasing the risk of bleeding, coatings of artificial surfaces were designed; many of them involve the use of heparin. Data in the literature show that heparin-induced thrombocytopenia is a major issue in the extracorporeal membrane oxygenation scenario, and no relevant benefits have been shown comparing heparin and no-heparin coating.

Preoperative urinary neutrophil gelatinase-associated lipocalin and outcome in high-risk heart failure patients undergoing cardiac surgery.

OBJECTIVE: To investigate the ability of early urinary neutrophil gelatinase-associated lipocalin to predict postoperative complications in adult patients with ventricular dysfunction undergoing cardiac surgery. DESIGN: Prospective observational study. SETTING: Single-center study, university hospital. PARTICIPANTS: Fifty-six adult high-risk cardiac surgical patients with preoperative cardiac failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics were obtained, and neutrophil gelatinase-associated lipocalin was measured at baseline and at several time points after surgery. Patient characteristics and neutrophil gelatinase-associated lipocalin levels were related to renal and patient outcome. On multivariate analyses, preoperative urinary neutrophil gelatinase-associated lipocalin was an independent predictor of length of intensive care stay (p = 0.004) and in-hospital stay (p = 0.04), but not of acute kidney injury or renal replacement therapy and was not associated with baseline renal function. CONCLUSIONS: In a cohort of high-risk cardiac surgery patients, preoperative urinary neutrophil gelatinase-associated lipocalin value provided prognostic information that was independent of the onset of acute kidney injury or of preoperative renal function.

Fascial plane blocks for cardiothoracic surgery: a narrative review.

In recent years, there has been a growing awareness of the limitations and risks associated with the overreliance on opioids in various surgical procedures, including cardiothoracic surgery.This shift on pain management toward reducing reliance on opioids, together with need to improve patient outcomes, alleviate suffering, gain early mobilization after surgery, reduce hospital stay, and improve patient satisfaction and functional recovery, has led to the development and widespread implementation of enhanced recovery after surgery (ERAS) protocols.In this context, fascial plane blocks are emerging as part of a multimodal analgesic in cardiac surgery and as alternatives to conventional neuraxial blocks for thoracic surgery, and there is a growing body of evidence suggesting their effectiveness and safety in providing pain relief for these procedures. In this review, we discuss the most common fascial plane block techniques used in the field of cardiothoracic surgery, offering a comprehensive overview of regional anesthesia techniques and presenting the latest evidence on the use of chest wall plane blocks specifically in this surgical setting.