Caring for acute coronary syndrome and other time-sensitive medical emergencies during the coronavirus disease 2019 pandemic in Northern Italy: report from a hub center.

BACKGROUND: The Lombardy region, in Northern Italy, suffered a major outbreak of Coronavirus disease 2019 (COVID-19) at the end of February 2020. The health system was rapidly overwhelmed by the pandemic. It became evident that patients suffering from time-sensitive medical emergencies like stroke, cerebral hemorrhage, trauma and acute myocardial infarction required timely, effective and safe pathways to be treated. The problem was addressed by a regional decree that created a hub-and-spoke system for time-sensitive medical emergencies. METHODS: We report the re-organizational changes adopted at a hub hospital (despite having already destined to COVID-19 patients most resources), and the number of emergent procedures for medical emergencies on the first 30-day of activity. These data were compared with the hospital activity in the same period of the previous year. RESULTS: Organizational changes were implemented in few hours. Dedicated pathways for non-COVID-19 patients affected by a medical emergency were set up in the emergency department, in the labs and in the operating theater. Ten intensive beds were implemented from a high-dependency unit; two operating rooms were reserved 24 h/day to neurosurgical or trauma emergencies. The number of emergent procedures was not different from that of the previous year, no admission refusal, no treatment delay and no viral transmission to the treated patients were recorded. No viral transmission to health care workers was observed. CONCLUSIONS: Re-organization of a hospital in order to adopt a hub-and-spoke model resulted feasible and allowed to face acute coronary syndrome and other time-sensitive medical emergencies timely and safely.

Immunosuppressive strategies in invasively ventilated ARDS COVID-19 patients.

BACKGROUND: COVID-19 is associated with elevated levels of inflammatory cytokines. We present the characteristics and outcomes of patients treated in the Intensive Care Unit (ICU) with immunosuppressive drugs, either tocilizumab or anakinra compared with controls. METHODS: A single-center observational prospective study on ICU invasively ventilated COVID-19 patients. The primary outcome was the clinical improvement at day 28. A Bayesian framework was employed, and all analyses were adjusted for confounders. RESULTS: Sixty-one consecutive invasively ventilated patients were included, nine (14.7%) received tocilizumab and 15 (24.6%) received anakinra. Over the first seven days, tocilizumab was associated with a greater decrease in C-reactive protein (P<0.001). After adjusting for confounders, the probability of clinical improvement at day 28 compared to control was 7∙6% (OR=0.36 [95% CrI: 0.09-1.46]) for tocilizumab and 40.9% (OR=0.89 [95% CrI: 0.32-2.43]) for anakinra. At day 28, the probability of being in a better clinical category was 2.5% (OR=2.98 [95% CrI: 1.00-8.88]) for tocilizumab, and 49.5% (OR=1.00 [95% CrI: 0.42-2.42]) for anakinra. CONCLUSIONS: In invasively ventilated COVID-19 patients, treatment with anakinra was associated with a higher probability of clinical improvement compared to tocilizumab; however, treatment with either drug did not result in clinically meaningful improvements compared with controls.

Novel Coronavirus Disease (COVID-19) in Italian Patients: Gender Differences in Presentation and Severity.

BACKGROUND: In the first wave of the novel coronavirus (severe acute respiratory syndrome coronavirus 2) infections, Italy experienced a heavy burden of hospital admissions for acute respiratory distress syndromes associated with the novel coronavirus disease (COVID-19). Early evidence suggested that females are less affected than males. OBJECTIVE: This study aimed to assess the gender-related differences in presentation and severity among COVID-19 patients admitted to IRCCS San Raffaele Hospital, Milan, Italy. MATERIALS AND METHODS: This prospective observational study included all patients admitted to the hospital between February 25 and April 19, 2020, with a positive real-time reverse-transcriptase polymerase chain reaction for COVID-19. The following data were collected: date of admission, gender, age and details of intensive care unit admission and outcomes. RESULTS: A total of 901 patients with COVID-19 were admitted to the hospital and provided consent for the study. Of these, 284 were female (31.5%). The percentage of admitted female patients significantly increased over time (25.9% of all admissions in the first half of the study period vs. 37.1% in the second half; P < 0.001). Females accounted for 14.4% of all COVID-19 intensive care unit admissions. There was no gender-based difference in the overall hospital mortality: 20.1% for females and 19.2% for males (P = 0.8). CONCLUSIONS: In our hospital, which was in the epicenter of the first wave of COVID-19 pandemic in Italy, female patients were few, presented late and were less critical than male patients.

Angiotensin II infusion and markers of organ function in invasively ventilated COVID-19 patients.

Objective: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. Design: Prospective observational study. Setting: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. Participants: Adult patients receiving mechanical ventilation due to COVID-19. Interventions: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. Main outcome measures: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. Results: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg; 95% CI, 1.87-16.22; P = 0.013) and the PaO2/FiO2 ratio (median difference, 23.17; 95% CI, 3.46-42.88; P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32; 95% CI, 0.09-0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). Conclusions: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and PaO2/FiO2 ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only. Trial registration:ClinicalTrials.gov NCT04318366.

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.

Effect of Continuous Epinephrine Infusion on Survival in Critically Ill Patients: A Meta-Analysis of Randomized Trials.

OBJECTIVES: Epinephrine is frequently used as an inotropic and vasopressor agent in critically ill patients requiring hemodynamic support. Data from observational trials suggested that epinephrine use is associated with a worse outcome as compared with other adrenergic and nonadrenergic vasoactive drugs. We performed a systematic review and meta-analysis of randomized controlled trials to investigate the effect of epinephrine administration on outcome of critically ill patients. DATA SOURCES: PubMed, EMBASE, and Cochrane central register were searched by two independent investigators up to March 2019. STUDY SELECTION: Inclusion criteria were: administration of epinephrine as IV continuous infusion, patients admitted to an ICU or undergoing major surgery, and randomized controlled trials. Studies on epinephrine administration as bolus (e.g., during cardiopulmonary resuscitation), were excluded. The primary outcome was mortality at the longest follow-up available. DATA EXTRACTION: Two independent investigators examined and extracted data from eligible trials. DATA SYNTHESIS: A total of 5,249 studies were assessed, with a total of 12 studies (1,227 patients) finally included in the meta-analysis. The majority of the trials were performed in the setting of septic shock, and the most frequent comparator was a combination of norepinephrine plus dobutamine. We found no difference in all-cause mortality at the longest follow-up available (197/579 [34.0%] in the epinephrine group vs 219/648 [33.8%] in the control group; risk ratio = 0.95; 95% CI, 0.82-1.10; p = 0.49; I = 0%). No differences in the need for renal replacement therapy, occurrence rate of myocardial ischemia, occurrence rate of arrhythmias, and length of ICU stay were observed. CONCLUSIONS: Current randomized evidence showed that continuous IV administration of epinephrine as inotropic/vasopressor agent is not associated with a worse outcome in critically ill patients.