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Importance: Meropenem is a widely prescribed β-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.

Background and Aim of the Work: Healthcare workers are often exposed to secondary traumatic stress. The SARS-CoV-2 outbreak caused intense psychological pressure in various healthcare professionals, with increased risk of post-traumatic stress disorder. Objective of our study was to evaluate the incidence of post-traumatic stress disorder in italian residents in Intensive Care and Emergency Departments facing COVID-19 emergency., Methods: We developed a short, anonymous web-questionnaire to obtain data regarding sociodemographic, professional characteristics, history of psychological trauma, psychotherapy, use of psychiatric medications and the presence of symptoms of post-traumatic stress disorder. Primary outcome was the incidence of post-traumatic stress disorder. Secondary endpoint was to identify possible risk factors associated with the development of post-traumatic stress disorder.  Post-traumatic stress disorder symptoms were assessed by the Impact of Event Scale-Revised.  A cut-off of 33 identified a probable diagnosis of post-traumatic stress disorder while a cut-off of 22 identified subclinical post-traumatic stress disorder., Results: 503 residents completed the questionnaire. Among residents who were directly involved in the clinical assistance of COVID-19 patients, 34.3% presented a probable diagnosis of post-traumatic stress disorder, while 21.5% presented subclinical post-traumatic stress disorder. Female gender and history of psychological trauma were significantly associated with the development of post-traumatic stress symptoms., Conclusions: Our data suggest a high incidence of post-traumatic stress disorder in Italian residents working in Intensive Care Units and Emergency Departments during the SARS-CoV-2 outbreak. This finding supports the importance of promptly implementing any strategy that might preserve staff mental health.

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., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Carotid endarterectomy remains the most effective surgical treatment for reducing the risk of stroke in patients with significant carotid stenosis. In fact, endovascular approach is associated with a higher incidence of perioperative and long-term minor stroke when compared to carotid endarterectomy although long-term functional outcome and risk of major stroke are similar. However, advanced age resulted to be associated with an increased risk of complications after carotid endarterectomy. Therefore, we decided to evaluate the outcome of carotid endarterectomy in octogenarians in our high-volume center., Methods: Data of all patients who underwent CEA between June 2009 and December 2014 were retrospectively recorded. Patients were categorized as aged <80 or ≥80 years. Propensity score matching based on baseline clinical variables was performed to correct for any bias. Primary outcome was the difference in combined stroke and death. Secondary outcomes included incidence of myocardial infarction, surgical reintervention, unplanned intensive care unit admission and length of hospital stay., Results: A total of 2463 carotid endarterectomies were performed, including 439 patients aged ≥80 years. After propensity score adjustment all octogenarians were matched one-to-one to younger patients. No differences in combined stroke and death were found (1.10% in octogenarians vs. 0.46% in younger patients; P=0.45). Octogenarians had an increased length of hospital stay when compared to younger patients (3.1±0.7 vs. 3.4±1.3 days; P=0.0001). No differences in other secondary outcomes were found., Conclusions: Age ≥80 years does not entail an increased perioperative risk after carotid endarterectomy. Hence, surgical carotid revascularization in octogenarians can be regarded as a safe and viable alternative to best medical therapy alone when performed in high-volume centers.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Background and Aim of the Work: electroconvulsive therapy is a psychiatric procedure requiring general anesthesia. The choice of the hypnotic agent is important because the success of the intervention is associated to the occurrence and duration of motor convulsion. However, all available anesthetic agents have anti-convulsant activity. We compared the effect of thiopental and propofol on seizures., Methods: We designed a retrospective study at Mood Disorders Unit of a teaching Hospital. Fifty-six consecutive patients undergoing electroconvulsive therapy were enrolled. Patients received fentanyl followed by either thiopental or propofol. We evaluated the incidence and the duration of seizure after electric stimulus at the first session of electroconvulsive therapy for each patient. Adverse perioperative effects were recorded., Results: Patients were 60±12.1 years old and 64% was female. There was a statistically significant higher number of patients who had motor convulsion activity in the thiopental group when compared to the propofol group (25 vs 13, p=0.023). Seizure duration was statistically significant longer in the thiopental group than in the propofol group (35 sec vs 11 sec, p=0.046). No hemodynamic instability, oxygen desaturation episodes, prolonged recovery time from anesthesia and adverse effects related to anesthesia were recorded., Conclusions: Thiopental induction has a favourable effect on seizure when compared to propofol in patients undergoing electroconvulsive therapy.

Objectives: The link between ventilation strategies and perioperative outcomes remains one of the fundamental paradigms of thoracic anaesthesia. During one-lung ventilation (OLV), one lung is excluded from gas exchange and ventilation is directed at the dependent lung. The authors hypothesised that the use of low tidal volumes (V T ) during OLV provides adequate gas exchange and improves postoperative outcome., Design: Meta-analysis of randomized clinical trials., Setting: Thoracic surgery., Participants: Patients undergoing OLV., Interventions: None., Measurements and Main Results: The authors performed a meta-analysis of all randomized trials on low versus high V T during OLV in patients undergoing thoracic surgery. Outcomes of the study were gas exchange and airway pressures during and after OLV, postoperative pulmonary complications (PPCs), and hospital stay (HLOS). Fourteen randomized trials were selected, but only a few of them contained one outcome of interest. Low V T was associated with lower arterial oxygen tension, lower airway pressures, and higher arterial carbon dioxide tension at specific time points during OLV. Low V T was associated with preserved gas exchange after OLV, lower incidence of pulmonary infiltrations, and acute respiratory distress syndrome. Incidences of PPCs and HLOS were similar., Conclusions: The use of low V T reduces airway pressure but worsens gas exchange during OLV. Preservation of postoperative oxygenation and reduction in infiltrates suggest a lung-protective modality with no demonstrable impact on PPCs and HLOS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Of the 230 million patients undergoing major surgical procedures every year, more than 1 million will die within 30 days. Thus, any nonsurgical interventions that help reduce perioperative mortality might save thousands of lives. The authors have updated a previous consensus process to identify all the nonsurgical interventions, supported by randomized evidence, that may help reduce perioperative mortality., Design and Setting: A web-based international consensus conference., Participants: The study comprised 500 clinicians from 61 countries., Interventions: A systematic literature search was performed to identify published literature about nonsurgical interventions, supported by randomized evidence, showing a statistically significant impact on mortality. A consensus conference of experts discussed eligible papers. The interventions identified by the conference then were submitted to colleagues worldwide through a web-based survey., Measurements and Main Results: The authors identified 11 interventions contributing to increased survival (perioperative hemodynamic optimization, neuraxial anesthesia, noninvasive ventilation, tranexamic acid, selective decontamination of the gastrointestinal tract, insulin for tight glycemic control, preoperative intra-aortic balloon pump, leuko-depleted red blood cells transfusion, levosimendan, volatile agents, and remote ischemic preconditioning) and 2 interventions showing increased mortality (beta-blocker therapy and aprotinin). Interventions then were voted on by participating clinicians. Percentages of agreement among clinicians in different countries differed significantly for 6 interventions, and a variable gap between evidence and clinical practice was noted., Conclusions: The authors identified 13 nonsurgical interventions that may decrease or increase perioperative mortality, with variable agreement by clinicians. Such interventions may be optimal candidates for investigation in high-quality trials and discussion in international guidelines to reduce perioperative mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Postoperative pulmonary complications (PPC) are among the most common complications after noncardiac surgery. Men, smokers, and elderly patients with chronic obstructive pulmonary disease or heart failure are more likely to experience PPC. The majority of patients undergoing vascular surgery belong in these categories and are at higher risk of developing PPC. Moreover, the surgical site is one of the most important risk factors associated with PPC, and aortic surgery carries the highest risk. The aim of this systematic review was to obtain an additional understanding of the real incidence of PPC after open abdominal aortic surgery and the impact of PPC on survival., Design: Systematic review and meta-analysis., Setting: Hospitals PARTICIPANTS: Patients who underwent open abdominal aortic surgery., Interventions: None., Measurements and Main Results: A literature search was performed on BioMedCentral, PubMed, Embase, and the Cochrane Register of clinical trials. All prospective or retrospective studies reporting data on PPC after open abdominal aortic surgery were included. Co-primary endpoints were the PPC rate and the correlation between PPC and perioperative mortality. The secondary endpoint was the difference in the PPC rate and mortality between elective and urgent surgery. Data on 269,637 patients from 213 studies were analyzed. The overall median incidence of PPC was 10.3% (interquartile range 5.55%-19.1%). Pneumonia, respiratory insufficiency, prolonged mechanical ventilation, need for unplanned mechanical ventilation, atelectasis, acute respiratory distress syndrome, pulmonary edema, and pleural effusions were the most common PPC reported in the literature. Occurrence of PPC was associated with postoperative mortality (r = 0.65, p<0.01) and was significantly higher in urgent procedures (p<0.001)., Conclusions: Incidence of PPC after open abdominal aortic surgery is high and is associated with increased postoperative morbidity and mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Bispectral Index Scale (BIS)-guided closed-loop delivery of anesthetics has been extensively studied. We performed a meta-analysis of all the randomized clinical trials comparing efficacy and performance between BIS-guided closed-loop delivery and manually controlled administration of total IV anesthesia. Scopus, PubMed, EMBASE, and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and closed-loop delivery systems versus manually controlled administration of total IV anesthesia in any surgical setting. Exclusion criteria were duplicate publications and nonadult studies. Twelve studies were included, randomly allocating 1284 patients. Use of closed-loop anesthetic delivery systems was associated with a significant reduction in the dose of propofol administered for induction of anesthesia (mean difference [MD] = 0.37 [0.17-0.57], P for effect <0.00001, P for heterogeneity = 0.001, I = 74%) and a significant reduction in recovery time (MD = 1.62 [0.60-2.64], P for effect <0.0001, P for heterogeneity = 0.06, I = 47%). The target depth of anesthesia was preserved more frequently with closed-loop anesthetic delivery than with manual control (MD = -15.17 [-23.11 to -7.24], P for effect <0.00001, P for heterogeneity <0.00001, I = 83%). There were no differences in the time required to induce anesthesia and the total propofol dose. Closed-loop anesthetic delivery performed better than manual-control delivery. Both median absolute performance error and wobble index were significantly lower in closed-loop anesthetic delivery systems group (MD = 5.82 [3.17-8.46], P for effect <0.00001, P for heterogeneity <0.00001, I = 90% and MD = 0.92 [0.13-1.72], P for effect = 0.003, P for heterogeneity = 0.07, I = 45%). When compared with manual control, BIS-guided anesthetic delivery of total IV anesthesia reduces propofol requirements during induction, better maintains a target depth of anesthesia, and reduces recovery time.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To comprehensively assess published randomized peer-reviewed studies related to volatile agents used for sedation in intensive care unit (ICU) settings, with the hypothesis that volatile agents could reduce time to extubation in adult patients., Design: Systematic review and meta-analysis of randomized trials., Setting: Intensive care units., Participants: Critically ill patients., Interventions: None., Measurements and Main Results: The BioMedCentral, PubMed, Embase, and Cochrane Central Register databases of clinical trials were searched systematically for studies on volatile agents used in the ICU setting. Articles were assessed by trained investigators, and divergences were resolved by consensus. Inclusion criteria included random allocation to treatment (volatile agents versus any intravenous comparator, with no restriction on dose or time of administration) in patients requiring mechanical ventilation in the ICU. Twelve studies with 934 patients were included in the meta-analysis. The use of halogenated agents reduced the time to extubation (standardized mean difference = -0.78 [-1.01 to -0.55] hours; p for effect<0.00001; p for heterogeneity = 0.18; I(2) = 32% in 7 studies with 503 patients). Results for time to extubation were confirmed in all subanalyses (eg, medical and surgical patients) and sensitivity analyses. No differences in length of hospital stay, ICU stay, and mortality were recorded., Conclusions: In this meta-analysis of randomized trials, volatile anesthetics reduced time to extubation in medical and surgical ICU patients. The results of this study should be confirmed by large and high-quality randomized controlled studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Methylene blue commonly is used as a dye or an antidote, but also can be used off label as a vasopressor. Serotonin toxicity is a potentially lethal and often misdiagnosed condition that can result from drug interaction. Mild serotonin toxicity previously was reported in settings in which methylene blue was used as a dye. The authors report 3 cases of life-threatening serotonin toxicity in patients undergoing chronic selective serotonin reuptake inhibitor (SSRI) therapy who also underwent cardiac surgery and received methylene blue to treat vasoplegic syndrome., Design: An observational study., Setting: A cardiothoracic intensive care unit (ICU) in a teaching hospital., Participants: Three patients who received methylene blue after cardiac surgery, later discovered to be undergoing chronic SSRI therapy., Interventions: None., Measurements and Main Results: All 3 patients received high doses of fentanyl during general anesthesia. They all developed vasoplegic syndrome and consequently were given methylene blue in the ICU. All 3 patients developed serotonin toxicity, including coma, after this administration and diagnostic tests were negative for acute intracranial pathology. Coma lasted between 1 and 5 days. Two patients were discharged from the ICU shortly after awakening, whereas the third patient experienced a complicated postoperative course for concomitant refractory low-cardiac-output syndrome., Conclusions: Patients undergoing chronic SSRI therapy should not be administered methylene blue to treat vasoplegic syndrome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Delirium frequently is observed in critically ill patients in the intensive care unit (ICU) and is associated strongly with a poor outcome. Dexmedetomidine seems to reduce time to extubation and ICU stay without detrimental effects on mortality. The objective of the authors' study was to evaluate the effect of this drug on delirium, agitation, and confusion in the ICU setting., Design: Meta-analysis of all the randomized clinical trials ever performed on dexmedetomidine versus any comparator in the ICU setting., Setting: Intensive care units., Participants: Critically ill patients., Interventions: None, Measurements and Main Results: Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials. Primary endpoint was the rate of delirium, including the adverse events, agitation and confusion. The 13 included manuscripts (14 trials) randomized 3,029 patients. Overall analysis showed that the use of dexmedetomidine was associated with significant reductions in the incidence of delirium, agitation and confusion (298/1,565 [19%] in the dexmedetomidine group v 337/1,464 [23%] in the control group, RR = 0.68 [0.49 to 0.96], p = 0.03). Results were confirmed in subanalyses performed on patients undergoing noninvasive ventilation (1/53 [2%] in the dexmedetomidine group v 7/49 [14%] in the control group, RR=0.18 [0.03 to 1.01], p = 0.05), receiving midazolam as a comparator (268/1,164 [23%] in the dexmedetomidine group v 277/1,025 [27%] in the control group, RR = 0.68 [0.47 to 1.00], p = 0.05) and in general ICU setting patients (204/688 [30%] in the dexmedetomidine group v 204/560 [36%] in the control group, RR = 0.68 [0.45 to 0.81], p < 0.01)., Conclusions: This meta-analysis of randomized controlled studies suggests that dexmedetomidine could help to reduce delirium in critically ill patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate the role of intrathecal lactate as an early predictor of spinal cord injury during thoracoabdominal aortic aneurysmectomy., Design: Observational study., Setting: University hospital., Participants: Forty-four consecutive patients scheduled to undergo thoracoabdominal aortic aneurysmectomy. Two patients had a type-B dissecting aneurysm while the other 42 patients suffered from degenerative aneurysm., Interventions: None., Methods: During surgery, samples of cerebrospinal fluid and arterial blood were withdrawn simultaneously to evaluate lactate concentration. Samples were collected at 4 fixed times during and after surgery: T1 (beginning of the intervention), T2 (15 minutes after aortic cross-clamping), T3 (just before unclamping), T4 (end of surgery)., Measurements and Main Results: Mean lactate levels in cerebrospinal fluid rose consistently and steadily from the beginning of the intervention until after surgery (T1 = 1.83 mmol/L), T2 = 2.10 mmol/L, T3 = 2.72 mmol/L, T4 = 3.70 mmol/L). Seven patients developed spinal cord injury; two of them had delayed injury occurring 24 hours after the end of surgery; the remaining 5 had early onset. In this group of 5 patients, preoperative cerebrospinal fluid lactate levels were significantly (p = 0.04) higher than those of the other 37 patients preoperatively (2.12 ± 0.35 v 1.79 ± 0.29 mmol/L)., Conclusions: Preoperative cerebrospinal lactate concentration is elevated in patients who will develop early-onset spinal cord injury after thoracoabdominal aortic aneurysmectomy. This may allow a better stratification of these patients, suggesting a more aggressive strategy of spinal cord function preservation, such as systematic reimplanting of intercostal arteries, and possibly obtaining a better outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Perioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin (and possibly clonidine) may reduce the risk of postoperative acute kidney injury (AKI)., Methods and Analysis: After receipt of grant funding, serial postoperative serum creatinine measurements began to be recorded in consecutive patients enrolled at substudy participating centres. With respect to the study schedule, the last of over 6500 substudy patients from 82 centres in 21 countries were randomised in December 2013. The authors will use logistic regression to estimate the adjusted OR of AKI following surgery (compared with the preoperative serum creatinine value, a postoperative increase ≥26.5 μmol/L in the 2 days following surgery or an increase of ≥50% in the 7 days following surgery) comparing each intervention to placebo, and will report the adjusted relative risk reduction. Alternate definitions of AKI will also be considered, as will the outcome of AKI in subgroups defined by the presence of preoperative chronic kidney disease and preoperative chronic aspirin use. At the time of randomisation, a subpopulation agreed to a single measurement of serum creatinine between 3 and 12 months after surgery, and the authors will examine intervention effects on this outcome., Ethics and Dissemination: The authors were competitively awarded a grant from the Canadian Institutes of Health Research for this POISE-2 AKI substudy. Ethics approval was obtained for additional kidney data collection in consecutive patients enrolled at participating centres, which first began for patients enrolled after January 2011. In patients who provided consent, the remaining longer term serum creatinine data will be collected throughout 2014. The results of this study will be reported no later than 2015., Clinical Trial Registration Number: NCT01082874.

Objective: The authors measured cardiac index in unstable patients after cardiac surgery with the Pressure Recording Analytic Method (PRAM) and compared it with the reference method of thermodilution (ThD) with the pulmonary artery catheter; using the hypothesis that there were no significant differences between the 2 methods., Design: A prospective study., Setting: Cardiac surgery intensive care unit in a teaching hospital., Participants: Ninety-four measurements from 59 patients with ongoing high doses of inotropic drugs and/or an intra-aortic balloon pump for low-cardiac-output syndrome after cardiac surgery were studied., Interventions: The pulmonary artery catheter and the radial or femoral arterial catheter for measuring blood pressure were already in place for standard hemodynamic monitoring., Measurements and Main Results: The mean of the total CI measurements was 2.94 ± 0.67 L/min/m(2) with PRAM and 2.95 ± 0.63 L/min/m(2) with ThD, with no significant difference according to the linear mixed models analysis. The PRAM and ThD techniques were similar in unstable patients without atrial fibrillation (mean bias 0.047 ± 0.395 L/min/m(2) and a percentage error of 29%), while no agreement between PRAM and ThD was found in unstable patients with atrial fibrillation (mean bias 0.195 ± 0.885 L/min/m(2) and a percentage error of 69%)., Conclusion: Cardiac index measurements after cardiac surgery performed with PRAM and with ThD showed a good agreement in hemodynamically unstable patients given high doses of inotropes and/or an IABP in patients in sinus rhythm, but not in those with atrial fibrillation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting., Design and Setting: Systematic literature review and international web-based survey., Participants: More than 300 physicians from 62 countries., Interventions: Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality., Measurements and Main Results: Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions., Conclusion: The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of methylene blue in raising mean arterial pressure in hypotensive patients., Design: A meta-analysis of randomised controlled trials., Data Sources: We searched BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials., Data Extraction: Inclusion criteria were random allocation to treatment and comparison of methylene blue versus any comparator. Exclusion criteria were duplicate publications, non-adult studies and no data on main outcomes. The primary end point was mean arterial blood pressure value 1 hour after the study drug administration; the secondary end points were mortality at the longest follow-up available, and cardiac index., Data Synthesis: Data from 174 patients in five randomised controlled studies were analysed. Mean arterial pressure rose in patients receiving methylene blue (weighted mean difference = 6.93 mmHg; 95% CI, 1.67 to 12.18; P for effect = 0.01; P for heterogeneity = 0.17; I2 = 41%). Only two studies reported the values of cardiac index with a non-statistically significant improvement in the methylene blue group (mean difference = 0.76 L/min/m2; 95% CI, ? 0.32 to 1.84; P for effect = 0.2). The overall mortality rate was 16% (14/88) among methylene blue treated patients and 23% (20/86) in the control group (odds ratio = 0.65; 95% CI, 0.21 to 2.08; P for effect = 0.5)., Conclusions: Methylene blue increases arterial blood pressure and systemic vascular resistances in vasoplegic patients without a detrimental effect on survival.

Objective: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence., Design and Setting: A web-based international consensus conference., Participants: More than 1,000 physicians from 77 countries participated in this web-based consensus conference., Interventions: Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials., Measurements and Main Results: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality., Conclusions: Future research and health care funding should be directed toward studying and evaluating these interventions., (Copyright © 2012 Elsevier Inc. All rights reserved.)