The use of angiotensin II for the management of distributive shock: expert consensus statements.

BACKGROUND: Despite the growing body of evidence supporting the use of angiotensin II (ATII) in distributive shock, its integration into existing treatment algorithms requires careful consideration of factors related to patient comorbidities, hemodynamic parameters, cost-effectiveness, and risk-benefit balance. Moreover, several questions regarding its use in clinical practice warrant further investigations. To address these challenges, a group of Italian intensive care specialists (the panel) developed a consensus process using a modified Delphi technique. METHODS: The panel defined five clinical questions during an online scoping workshop and then provided a short list of statements related to each clinical question based on literature review and clinical experience. A total of 20 statements were collected. Two coordinators screened and selected the final list of statements to be included in the online survey, which consisted of 17 statements. The consensus was reached when ≥ 75% of respondents assigned a score within the 3-point range of 1-3 (disagreement) or 7-9 (agreement). RESULTS: Overall, a consensus on agreement was reached on 13 statements defining the existing gaps in scientific evidence, the possibility of evaluating the addition of drugs with different mechanisms of action for the treatment of refractory shock, the utility of ATII in reducing the catecholamine requirements in the treatment of vasopressor-resistant septic shock, and the effectiveness of ATII in treating patients in whom angiotensin-converting enzyme activity is reduced or pharmacologically blocked. It was widely shared that renin concentration can be used to identify patients who most likely benefit from ATII to restore vascular tone. Thus, the patients who might benefit most from using ATII were defined. Lastly, some potential barriers to the use of ATII were described. CONCLUSIONS: ATII was recognized as a useful treatment to reduce catecholamine requirements in treating vasopressor-resistant septic shock. At the same time, the need for additional clinical trials to further elucidate the efficacy and safety of ATII, as well as investigations into potential mechanisms of action and optimization of treatment protocols in patients with refractory distributive shock, emerged.

Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

A Multi-Country Survey on the Availability of Intraoperative Use of Echocardiography for Noncardiac Surgery.

BACKGROUND: This survey aimed to explore the availability and accessibility of echocardiography during noncardiac surgery worldwide. METHODS: An internet-based 45-item survey was sent, followed by reminders from August 30, 2021, to August 20, 2022. RESULTS: 1189 responses were received from 62 countries. Nearly seventy-one percent of respondents had intraoperatively used transesophageal or transthoracic echocardiography (TEE and TTE, respectively) for monitoring or examination. The unavailability of echocardiography machines (30.3%), lack of trained personnel (30.2%), and absence of clinical indications (22.6%) were the top 3 reasons for not using intraoperative echocardiography in noncardiac surgery. About 61.5% of participants had access to at least one echocardiography machine. About 41% had access to at least 1 TEE probe, and 62.2% had access to at least 1 TTE probe. Seventy-four percent of centers had a procedure to request intraoperative echocardiography if needed for noncardiac cases. Intraoperative echocardiography service was immediately available in 58% of centers. CONCLUSIONS: Echocardiography machines and skilled echocardiographers are still unavailable at many centers worldwide. National societies should aim to train a critical mass of certified TEE/TTE anesthesiologists and provide all anesthesiologists access to perioperative TEE/TTE machines in anesthesiology departments, considering the increasing number of older and sicker surgical patients scheduled for noncardiac surgery.

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.).

Sequential Normothermic Regional Perfusion and End-ischemic Ex Situ Machine Perfusion Allow the Safe Use of Very Old DCD Donors in Liver Transplantation.

BACKGROUND: In Italy, 20 min of continuous, flat-line electrocardiogram are required for death declaration. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death (cDCD) liver transplantation by combining normothermic regional and end-ischemic machine perfusion (MP). The aim of this study was to evaluate the safety and feasibility of the use of septuagenarian and octogenarian cDCD donors with this approach. METHODS: All cDCD older than 70 y were evaluated during normothermic regional perfusion and then randomly assigned to dual hypothermic or normothermic MP. RESULTS: In the period from April 2021 to December 2022, 17 cDCD older than 70 y were considered. In 6 cases (35%), the graft was not considered suitable for liver transplantation, whereas 11 (65%) were evaluated and eventually transplanted. The median donor age was 82 y, being 8 (73%) older than 80. Median functional warm ischemia and no-flow time were 36 and 28 min, respectively. Grafts were randomly assigned to ex situ dual hypothermic oxygenated MP in 6 cases (55%) and normothermic MP in 5 (45%). None was discarded during MP. There were no cases of primary nonfunction, 1 case of postreperfusion syndrome (9%) and 2 cases (18%) of early allograft dysfunction. At a median follow-up of 8 mo, no vascular complications or ischemic cholangiopathy were reported. No major differences were found in terms of postoperative hospitalization or complications based on the type of MP. CONCLUSIONS: The implementation of sequential normothermic regional and end-ischemic MP allows the safe use of very old donation after circulatory death donors.

Continuous vs intermittent Non-Invasive blood pressure MONitoring in preventing postoperative organ failure (niMON): study protocol for an open-label, multicenter randomized trial.

BACKGROUND: Blood pressure has become one of the most important vital signs to monitor in the perioperative setting. Recently, the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) recommended, with low level of evidence, continuous monitoring of blood pressure during the intraoperative period. Continuous monitoring allows for early detection of hypotension, which may potentially lead to a timely treatment. Whether the ability to detect more hypotension events by continuous noninvasive blood pressure (C-NiBP) monitoring can improve patient outcomes is still unclear. Here, we report the rationale, study design, and statistical analysis plan of the niMON trial, which aims to evaluate the effect of intraoperative C-NiBP compared with intermittent (I-NiBP) monitoring on postoperative myocardial and renal injury. METHODS: The niMon trial is an investigator-initiated, multicenter, international, open-label, parallel-group, randomized clinical trial. Eligible patients will be randomized in a 1:1 ratio to receive C-NiBP or I-NiBP as an intraoperative monitoring strategy. The proportion of patients who develop myocardial injury in the first postoperative week is the primary outcome; the secondary outcomes are the proportions of patients who develop postoperative AKI, in-hospital mortality rate, and 30 and 90 postoperative days events. A sample size of 1265 patients will provide a power of 80% to detect a 4% absolute reduction in the rate of the primary outcome. CONCLUSIONS: The niMON data will provide evidence to guide the choice of the most appropriate intraoperative blood pressure monitoring strategy. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration: NCT05496322, registered on the 5th of August 2023.

The role of beta-blocker drugs in critically ill patients: a SIAARTI expert consensus statement.

BACKGROUND: The role of ß-blockers in the critically ill has been studied, and data on the protective effects of these drugs on critically ill patients have been repeatedly reported in the literature over the last two decades. However, consensus and guidelines by scientific societies on the use of ß-blockers in critically ill patients are still lacking. The purpose of this document is to support the clinical decision-making process regarding the use of ß-blockers in critically ill patients. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient's care process. METHODS: The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects underlying the use of ß-blockers in critically ill adult patients. The methodology followed by the experts during this process was in line with principles of modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales in the form of informative text. The overall list of statements was subjected to blind votes for consensus. RESULTS: The literature search suggests that adrenergic stress and increased heart rate in critically ill patients are associated with organ dysfunction and increased mortality. Heart rate control thus seems to be critical in the management of the critically ill patient, requiring careful clinical evaluation aimed at both the differential diagnosis to treat secondary tachycardia and the treatment of rhythm disturbance. In addition, the use of ß-blockers for the treatment of persistent tachycardia may be considered in patients with septic shock once hypovolemia has been ruled out. Intravenous application should be the preferred route of administration. CONCLUSION: ß-blockers protective effects in critically ill patients have been repeatedly reported in the literature. Their use in the acute treatment of increased heart rate requires understanding of the pathophysiology and careful differential diagnosis, as all causes of tachycardia should be ruled out and addressed first.

[Tracheal rupture treated with robotic surgery: the importance of evidence-based practice in nursing management. A case report]. / Rottura tracheale trattata con chirurgia robotica: l'importanza dell'evidence-based practice nella gestione infermieristica. Un caso clinico.

. Tracheal rupture treated with robotic surgery: the importance of evidence-based practice in nursing management. A case report. Tracheal rupture is a very rare condition with high morbidity and mortality. While it has a multifactorial etiology, however it occurs most frequently after orotracheal intubation. The case of a 76-year-old woman who underwent out-of-hospital orotracheal intubation for severe respiratory failure due to a state of coma is described. The patient suddenly developed a subcutaneous emphysema extending from the chest to the skull due to tracheal laceration. The management of the case is described with special focus on nursing goals to prevent ventilator associated pneumonia and mediastinitis, avoid the endotracheal tube dislocation and further tracheal injuries. The case presented underlines the importance of a systematic recourse to evidence-based practice (EBP), which allowed to effectively manage a complex situation.

High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.

BACKGROUND: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. METHODS: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. DISCUSSION: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.

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.

An extensive evaluation of hepatic markers of damage and regeneration in controlled and uncontrolled donation after circulatory death.

Livers from donations after circulatory death (DCDs) are very sensitive to ischemia/reperfusion injury and thus need careful reconditioning, such as normothermic regional perfusion (NRP). So far, its impact on DCDs has not been thoroughly investigated. This pilot cohort study aimed to explore the NRP impact on liver function by evaluating dynamic changes of circulating markers and hepatic gene expression in 9 uncontrolled DCDs (uDCDs) and 10 controlled DCDs. At NRP start, controlled DCDs had lower plasma levels of inflammatory and liver damage markers, including α-glutathione s-transferase, sorbitol-dehydrogenase, malate dehydrogenase 1, liver-type arginase-1, and keratin-18, but higher levels of osteopontin, sFas, flavin mononucleotide, and succinate than uDCDs. During 4-hour NRP, some damage and inflammatory markers increased in both groups, while IL-6, HGF, and osteopontin increased only in uDCDs. At the NRP end, the tissue expression of early transcriptional regulators, apoptosis, and autophagy mediators was higher in uDCDs than in controlled DCDs. In conclusion, despite initial differences in liver damage biomarkers, the uDCD group was characterized by a major gene expression of regenerative and repair factors after the NRP procedure. Correlative analysis among circulating/tissue biomarkers and the tissue congestion/necrosis degree revealed new potential candidate biomarkers.

Early versus late tracheostomy for traumatic brain injury: a systematic review and meta-analysis.

INTRODUCTION: Tracheostomy is the most frequent bedside surgical procedure performed on patients with traumatic brain injury who require mechanical ventilation. To compare the effects of early tracheostomy vs. late tracheostomy on the duration of mechanical ventilation in patients with traumatic brain injury, we carried out a systematic review and meta-analysis. EVIDENCE ACQUISITION: MEDLINE, Scopus, Web of Science, and Cochrane were searched from inception to 17th October 2022. Eligible clinical trials and observational studies reporting early versus late tracheostomy in TBI were searched. Two reviewers extracted data and independently assessed the risk of bias. The duration of mechanical ventilation was the primary outcome. EVIDENCE SYNTHESIS: We pooled standardized mean differences and risk differences for random effects model. A total of 368 studies were retrieved and screened. Nineteen studies were selected, including 6253 patients. Mean time for early tracheostomy and late tracheostomy procedures was 6±2.9 days and 17±10.7 days, respectively. Early tracheostomy was associated with shorter mechanical ventilation duration (SMD=-1.79, 95% CI -2.71; -0.88) and fewer ventilator associated pneumonia (RD=-0.11, 95% CI -0.16; -0.06) when compared with late tracheostomy. Moreover, intensive care unit (ICU) (SMD=-1.64, 95% CI -2.44; -0.84) and hospital (SMD=-1.26, 95% CI -1.97; -0.56) length of stay were shorter when compared with late tracheostomy. CONCLUSIONS: The findings from this meta-analysis suggest that early tracheostomy in severe TBI patients contributes to a lower exposure to secondary insults and nosocomial adverse events, increasing the opportunity of patient's early rehabilitation and discharge.

Regional Cerebral Oxygen Saturation to Predict Favorable Outcome in Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to investigate the role of regional cerebral oxygen saturation (rSO2) in predicting survival and neurologic outcomes after extracorporeal cardiopulmonary resuscitation (ECPR). DESIGN: The study authors performed a systematic review and meta-analysis of all available literature. SETTING: The authors searched relevant databases (Pubmed, Medline, Embase) for studies measuring precannulation rSO2 in patients undergoing ECPR and reporting mortality and/or neurologic outcomes. PARTICIPANTS: The authors included both in-hospital and out-of-hospital cardiac arrest patients receiving ECPR. They identified 3 observational studies, including 245 adult patients. INTERVENTIONS: The authors compared patients with a low precannulation rSO2 (≤15% or 16%) versus patients with a high (>15% or 16%) precannulation rSO2. In addition, the authors carried out subgroup analyses on out-of-hospital cardiac arrest (OHCA) patients. MEASUREMENTS AND MAIN RESULTS: A high precannulation rSO2 was associated with an overall reduced risk of mortality in ECPR recipients (98 out of 151 patients [64.9%] in the high rSO2 group, v 87 out of 94 patients [92.5%] in the low rSO2 group, risk differences [RD] -0.30; 95% CI -0.47 to -0.14), and in OHCA (78 out of 121 patients [64.5%] v 82 out of 89 patients [92.1%], RD 0.30; 95% CI -0.48 to -0.12). A high precannulation rSO2 also was associated with a significantly better neurologic outcome in the overall population (42 out of 151 patients [27.8%] v 2 out of 94 patients [2.12%], RD 0.22; 95% CI 0.13-0.31), and in OHCA patients (33 out of 121 patients [27.3%] v 2 out of 89 patients [2.25%] RD 0.21; 95% CI 0.11-0.30). CONCLUSIONS: A low rSO2 before starting ECPR could be a predictor of mortality and survival with poor neurologic outcomes.

Beneficial effects of levosimendan to wean patients from VA-ECMO: a systematic review and meta-analysis.

INTRODUCTION: Patients with refractory cardiogenic shock can benefit from veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The use of levosimendan in VA-ECMO patients may facilitate weaning and enhance survival. EVIDENCE ACQUISITION: MEDLINE, Scopus, Web of Science, and Cochrane were searched from inception to October 10th, 2021. Eligible clinical trials and observational studies reporting the use of levosimendan in VA-ECMO were searched. Two reviewers extracted data and independently assessed the risk of bias. To integrate the data, a random-effect model was applied. The success of weaning from VA-ECMO was the primary outcome. EVIDENCE SYNTHESIS: Ten observational studies, including a total of 987 patients, were identified. Levosimendan was associated with successful weaning (362/448) compared with controls (328/539) (OR 2.37, 95% CI 1.71-3.28; P=0.01) and reduced mortality (144/433 vs. 258/507) (nine studies, OR 0.53, 95% CI 0.36-0.78; P=0.01) compared with control. CONCLUSIONS: Levosimendan was associated with successful weaning and increased survival in VA-ECMO patients. Randomized trials should confirm these findings.

Transcatheter aortic valve replacement with or without anesthesiologist: results from a high-volume single center.

AIMS: Local instead of general anesthesia has become the standard approach in many centers for transfemoral transcatheter aortic valve replacement (TAVR). New generation devices and an increase in operator skills had led to a drastic reduction in periprocedural complications, bringing in the adoption of a minimalist approach. In our study, we aimed to compare patients treated with TAVR under local anesthesia with or without the presence of an anesthesiologist on site (AOS). METHODS: We compare procedural aspects and results of patients treated with TAVR with an AOS against patients treated with TAVR with an anesthesiologist on call (AOC). From January 2019 to December 2020, all consecutive patients undergoing transfemoral TAVR with either the self-expandable Evolut (Medtronic, MN, USA) or balloon-expandable SAPIEN 3 (Edwards Lifesciences, CA, USA) were collected. RESULTS: Of 332 patients collected, 96 (29%) were treated with TAVR with AOS, while 236 (71%) were treated with TAVR with AOC. No differences in procedural time, fluoroscopy time and amount of contrast medium were observed. No procedural death and conversion to open-chest surgery was reported. The rate of stroke/transient ischemic attacks and major vascular complications was similar in the two groups. No patients in both groups required conversion to general anesthesia. Two patients (0.8%) in the AOC group required urgent intervention of the anesthesiologist. In the AOC group, there was a greater use of morphine (55.9% vs. 33.3%, P  = 0.008), but with a lower dose for each patient (2.0 vs. 2.8 mg, P  = 0.006). On the other hand, there was a lower use of other painkiller drugs (3.4% vs. 20.8%, P  = 0.001). No difference in inotropic drugs use was observed. CONCLUSION: In patients at low or intermediate risk undergoing transfemoral TAVR, a safe procedure can be performed under local anesthesia without the presence of an anesthesiologist in the catheterization laboratory.