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Importance Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). Objective To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. Design, Setting, and Participants This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase–polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. Exposures Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. Main Outcomes and Measures Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. Results Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). Conclusions and Relevance In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.

Question What are the baseline characteristics and outcomes of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to intensive care units (ICUs) in Lombardy, Italy? Findings In this retrospective case series that involved 1591 critically ill patients admitted from February 20 to March 18, 2020, 99% (1287 of 1300 patients) required respiratory support, including endotracheal intubation in 88% and noninvasive ventilation in 11%; ICU mortality was 26%. Meaning In this case series of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed coronavirus disease 2019 (COVID-19), a high proportion required mechanical ventilation and ICU mortality was 26% as of March 25, 2020.Importance In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio(2) was greater than 50% in 89% of patients. The median Pao(2)/Fio(2) was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged = 64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio(2) was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao(2)/Fio(2) was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao(2)/Fio(2) (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age >= 64 years) had higher mortality than younger patients (n = 795; age

Anesthetic management of patients undergoing endovascular procedures for treating intracranial aneurysms or cerebrovascular malformations must consider a number of specific challenges, in addition to those associated with anesthesia for other specialties. In addition to maintenance of physiological stability, manipulation of systemic and cerebral hemodynamic parameters may be required to treat any sudden unexpected catastrophic neurological events. A multidisciplinary group including neuro- and pediatric anesthesiologists, interventional neuroradiologists, neurosurgeons, and a clinical methodologist contributed to this document. This consensus working group from 21 Italian institutions identified open questions regarding the best practices for management of anesthesia during endovascular neuroradiological procedures for intracranial aneurysms and cerebrovascular malformations, and addressed these by formulating practical consensus statements. At the first meeting in November 2015, nine key areas were identified regarding choice of anesthetic, patient monitoring, hemodynamic targets, postoperative care, and the management of neuromuscular blockade, anticoagulant and/or antiplatelet therapy, and special considerations for pediatric patients. Nine subgroups were established and a medical librarian performed literature searches in the Cochrane and MEDLINE/PubMed databases for each group. Groups drafted literature summaries and provisional responses in the form of candidate consensus statements based on evidence, when possible, and clinical experience, when this was lacking. Final wording was agreed at a meeting in April 2016 and where possible evidence was graded using United States Preventive Services Task Force criteria. Consensus (defined as >90% agreement) was based on evidence, clinical experience, clinician preference, feasibility in the Italian healthcare system, and cost/benefit considerations.

The Pringle maneuver, which is performed during liver surgery to reduce blood loss, may result in liver ischemia/reperfusion injury resulting in metabolic, immunological, and microvascular changes, which may lead to hepatocellular damage. The aim of this study was the investigation of the effects of N-acetylcysteine (NAC) and methylprednisolone (MET) in the modulation of liver warm ischemia during hepatic resection. Forty-eight patients were enrolled in a pilot double-blind, randomized clinical trial. The patients received either NAC, MET, or placebo. The primary endpoint was the reduction in postoperative alanine aminotransferase and bilirubin. The secondary endpoint was the difference in morbidity and mortality. All the 48 patients had liver resection with no mortality. Morbidity was observed in 8 (16 %) patients equally distributed among the groups. There was a significant favorable recovery of liver function tests in patients treated with NAC or MET compared with the placebo when the Pringle maneuver exceeded 70 min. The administration of NAC or MET prior to the Pringle maneuver during hepatic resection is associated with lower postoperative aberration in liver function tests compared with placebo when the Pringle maneuver exceeded 70 min. Larger studies are required to validate our findings and to investigate the specific role of NAC and MET in liver surgery.

Objective: Isoflurane is a volatile anesthetic that has a vasodilating effect on cerebral vessels producing a cerebral blood flow increase. Furthermore, it has been shown in animal studies that isoflurane, when used as a preconditioning agent, has neuroprotective properties, inducing tolerance to ischemia. However, it is not routinely used in neurointensive care because of the potential increase in intracranial pressure caused by the rise in cerebral blood flow. Nevertheless, subarachnoid hemorrhage patients who are at risk for vasospasm may benefit from an increase in cerebral blood flow. We measured regional cerebral blood flow during intravenous sedation with propofol and during sedation with isoflurane in patients with severe subarachnoid hemorrhage not having intracranial hypertension. Design: The study is a crossover, open clinical trial (NCT00830843). Setting: Neurointensive care unit of an academic hospital. Patients: Thirteen patients with severe subarachnoid hemorrhage , (median Fisher scale 4), monitored on clinical indication with intracranial pressure device and a thermal diffusion probe for the assessment of regional cerebral blood flow. An intracranial pressure >18 mm Hg was an exclusion criterion. Interventions: Cerebral and hemodynamic variables were assessed at three steps. Step 1: sedation with propofol 3–4 mg/ kg/hr; step 2: after 1 hr of propofol discontinuation and isoflurane 0.8%; step 3: after 1 hr of propofol at the same previous infusion rate. Cerebral perfusion pressure and arterial Pco 2 were maintained constant. Mean cerebral artery flow velocity and jugular vein oxygen saturation were measured at the end of each step. Measurements and Main Results: Regional cerebral blood flow increased significantly during step 2 (39.3 ± 29 mL/100 hg/min) compared to step 1 (20.8 ± 10.7) and step 3 (24.7 ± 8). There was no difference in regional cerebral blood flow comparing step 1 vs. step 3. No significant difference in intracranial pressure, mean cerebral artery transcranial Doppler velocity, PaCO 2 , cerebral perfusion pressure between the different steps. Conclusions: Isoflurane increases regional cerebral blood flow in comparison to propofol. Intracranial pressure did not change significantly in the population not affected by intracranial hypertension. (Crit Care Med 2012; 40:2797–2804)