Hemorrhage Volume Drives Early Brain Injury and Outcome in Poor-Grade Aneurysmal SAH.

BACKGROUND AND PURPOSE: Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV-V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome. MATERIALS AND METHODS: Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3-4), in-hospital mortality (mRS 6), and functional independence (mRS 0-2) at follow-up. RESULTS: Among 400 patients (median global intracranial hemorrhage volume of 91 mL; interquartile range, 59-128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0-2 at a median of 13 (interquartile range, 3-26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004-1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001-1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98-0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50-70, older than 70 year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome. CONCLUSIONS: Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema.

COVID-19 second wave: appropriateness of admissions to the Emergency Department of a main metropolitan hospital in Milan.

BACKGROUND: In Europe, Italy and Lombardy, in autumn 2020, there was a steep increase in reported cases due to the second epidemic wave of SARS-Cov-2 infection. We aimed to evaluate the appropriateness of COVID-19 patients' admissions to the ED of the San Raffaele Hospital. METHODS: We compared data between the inter-wave period (IWP, from 1st to 30th September) and the second wave period (WP, 1st October to 15th November) focusing on the ED presentation, discharge priority colour code and outcomes. RESULTS: Out of 977 admissions with a SARS-Cov-2 positive swab, 6% were in the IWP and 94% in the WP. Red, yellow and white code increased (these latter from 1.8% to 5.4%) as well as self-presented in yellow and white code. Discharges home increased from 1.8% to 5.4%, while hospitalizations decreased from 63% to 51%. DISCUSSION: We found a rise in white codes (among self-presented patients), indicating inappropriateness of admissions. The increase in discharges suggests that several patients did not require hospitalization. CONCLUSIONS: The pandemic brought out the fundamental role of primary care to manage patients with low-intensity needs. The important increase in ED admissions of COVID-19 patients caused a reduction of NO-COVID-19 patients, with possible inadequate treatment.

Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy.

BACKGROUND: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. OBJECTIVE: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. METHODS: Observational study in a tertiary care hospital in Milan, Italy. RESULTS: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. CONCLUSIONS: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy.

OBJECTIVE: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). DESIGN: Case series of 73 patients. SETTING: Large tertiary hospital in Milan. PARTICIPANTS: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. MAIN OUTCOME MEASURES: Demographic and daily clinical data were collected to identify predictors of early mortality. RESULTS: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3; IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL; IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 µg/m; IQR, 5.0-23.8 µg/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12; 95% CI, 1.04-1.22; P = 0.004) and hypertension (OR, 6.15; 95% CI, 1.75-29.11; P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). CONCLUSIONS: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04318366.

Fast reshaping of intensive care unit facilities in a large metropolitan hospital in Milan, Italy: facing the COVID-19 pandemic emergency

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was Lombardy, with the first reported case on 20 February 2020. San Raffaele Scientific Institute ­ a large tertiary hospital and research centre in Milan, Italy ­ was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy. In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces. All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs. Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.

Randomized Evidence for Reduction of Perioperative Mortality: An Updated Consensus Process.

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.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A National Analysis of Data from 10-Year Post-marketing Surveillance.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, severe and potentially fatal cutaneous adverse drug reaction (the mortality rate is up to 10 %) associated with numerous and apparently heterogeneous drugs. The aetiology is unknown. OBJECTIVE: To report Italian cases of DRESS over a 10-year period. METHODS: We searched the National Pharmacovigilance Network (NPN) for the term 'drug reaction with eosinophilia and systemic symptoms' from 1 January 2004 to 1 January 2014, to identify all reports of DRESS. Each case was checked to avoid duplication. RESULTS: In the NPN, we identified 91 serious cases of DRESS: 68 were spontaneous, still-unpublished reports, while 23 additional cases were derived from screening of the scientific literature, performed by marketing authorization holders. Notably, the single common element linking all cases of DRESS was intake of a drug containing an aromatic ring. CONCLUSION: Thanks to the largest national DRESS case series ever reported, we were able to hypothesize, for the first time, that there is an association between use of drugs containing an aromatic ring in their chemical structure and DRESS. This might aid understanding of the aetiology of DRESS and facilitate diagnosis.

Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: The first double blind randomized controlled trial.

BACKGROUND: Target Controlled Infusion is a sophisticated tool for providing optimal sedation regimen avoiding under or oversedation in gastrointestinal endoscopy. AIMS: To compare standard moderate sedation vs. non-anaesthesiologist-administered propofol sedation during gastrointestinal endoscopy. METHODS: Randomized controlled trial of 70 consecutive colonoscopies and 70 consecutive esophagogastroduodenoscopies (EGD). Standard group (n=70), received fentanyl (1 µg/kg)+midazolam (0.03-0.04 mg/kg) or midazolam only; propofol group (n=70), received fentanyl (1 µg/kg)+propofol Target Controlled Infusion (1.2-1.6 µg/ml) or propofol Target Controlled Infusion only. Discharge time, endoscopist satisfaction and patient satisfaction were recorded in all endoscopies. RESULTS: Colonoscopy: discharge time was significantly shorter in the propofol than the standard group (1.1 ± 0.3 vs. 5 ± 10.2 min, respectively; P=0.03). Endoscopist satisfaction was significantly higher (98.3 ± 11.4/100 vs. 87.2±12/100; P=0.001); patient satisfaction was significantly higher (95 ± 9.3/100 vs. 85.5 ± 14.4/100; P=0.002) in the propofol compared to the standard group. EGD: discharge time was not significantly different in the propofol and standard groups (1.1 ± 0.7 vs. 3.9 ± 9.2 min, respectively; P=0.146). Endoscopist satisfaction was significantly higher (92.7 ± 14.3/100 vs. 82.8 ± 21.2/100; P=0.03); patient satisfaction was significantly higher (93.8 ± 18.2/100 vs. 76.5 ± 25.2/100; P=0.003). In the propofol group 94.3% of patients vs. 71.4% of patients in standard group asked to receive the same sedation in the future (P=0.021). CONCLUSION: Target Controlled Infusion is a promising method for non-anaesthesiologist-administered propofol sedation.

A systematic review on levosimendan in paediatric patients.

Levosimendan is a calcium-sensitizing agent that improves cardiac function, hemodynamic performance, and survival in critically ill adult patient. Few data exist on its off-label use in paediatric patients. We therefore performed a systematic review updated in September 2013 of all the published articles describing the use of levosimendan in paediatric patients. We identified 24 studies published in the period 2004-2013 that included a total of 623 patients, the largest one being a case series of 293 patients. Most of the patients underwent cardiac surgery, other settings consisting of chronic heart failure, primary congenital heart diseases and sepsis and cancer-associated cardiac dysfunction. Most studies reported improvement in ventricular function, central venous oxygen saturation, serum lactate levels or cardiac index. The 5 randomized studies published so far have all been performed in cardiac surgery and suggest a beneficial effect on hemodynamic data with no effect on intensive care unit stay, hospital stay or survival. Side effects (e.g. hypotension) were reported. This inodilator merits to be investigated with further randomized trials focusing on clinically relevant outcomes.

Two dosages of remifentanil for patient-controlled analgesia vs. meperidine during colonoscopy: a prospective randomized controlled trial.

UNLABELLED: BACKGROUND AND STUDY: Combined use of opiates and benzodiazepines often results in delayed discharge after colonoscopy. AIMS: To compare sedation quality of two dosages of patient controlled analgesia remifentanil with one another and with that of a midazolam-meperidine association during colonoscopy. METHODS: Ninety patients undergoing colonoscopy were randomly assigned to three groups. Group M received a meperidine bolus (0.7 mg/kg) and sham patient controlled analgesia. Group R1 received remifentanil 0.5 µg/kg and group R2 remifentanil 0.8 µg/kg together with a patient-controlled analgesia pump injecting further boluses (2-min lock-out). Technical difficulties of the examination, gastroenterologist's and patient's satisfaction with sedoanalgesia were evaluated after colonoscopy on a 100 mm Visual Analogue Scale. Patient's satisfaction was assessed 24 h later. RESULTS: Group M had more adverse events (p = 0.044), required more rescue boluses (p = 0.0010), had lower Observer's Assessment of Alertness and Sedation Scale score at the end of the procedure (p = 0.0016) and longer discharge time (p = 0.0001). Groups R1 and R2 did not differ with respect to these variables. Patient's degree of pain and satisfaction with sedo-analgesia, endoscopist's technical difficulty and satisfaction were not different among groups. CONCLUSIONS: Remifentanil patient controlled analgesia is a safe approach to sedation for colonoscopy.