Factors improving mortality in critically ill patients with liver failure - A systematic review.

Background: Acute and chronic hepatic failure can lead to increased mortality in critically ill and perioperative patients. Understanding the pathophysiological principles of these conditions in critically ill patients is of great importance to reduce mortality. The aim of our systematic literature review was to identify all randomized controlled trials on any intervention that had a statistically significant documented reduction in mortality in patients with hepatic failure. Methods: We searched PubMed, Scopus and Embase databases for pertinent studies on January 1st 2021. The following studies were included: randomized controlled trials; studies investigating adult critically ill or perioperative patient populations with any form of hepatic failure; mortality as primary or secondary outcome; and statistically significant differences in mortality between the examined groups. Results: We finally found nine trials in our systematic review on the effect of antibiotic administration and infectious diseases among patients with cirrhosis (three studies); immune modulation after liver transplantation (one study); administration of colloids in cirrhotic patients (one study); the effect of high-volume plasma exchange in acute liver failure (one study); administration of N-acetylcysteine in acute liver failure (one study); and treatment with terlipressin (two studies). Conclusion: In the present review we found only nine randomized studies with a documented survival benefit in patients with liver failure. Strategies that most improved mortality were associated with the outcome of sepsis and renal function.

Dexmedetomidine versus remifentanil for sedation under monitored anesthetic care in complex endovascular aortic aneurysm repair: a single center experience with mid-term follow-up.

BACKGROUND: Sedation protocols in patients undergoing complex endovascular aortic aneurysm repair are not fully investigated. The aim of this study was to compare a dexmedetomidine (DEX) based sedation protocol with a remifentanil-based sedation protocol. METHODS: Seventy-nine consecutive patients undergoing complex endovascular aortic repair were enrolled and retrospectively analyzed. Forty-two received 0.03 mg/kg midazolam intravenous bolus with remifentanil (0.075-0.1 µg/kg/min for 10 minutes followed by continuous infusion 0.050-0.25 µg/kg/min) and 37 DEX (1 µg/kg over 10 minutes and continuous infusion 0.50-0.75 µg/kg/hour) to achieve an Observer Assessment of Alertness/Sedation Scale (OAAS) ≤4, a Richmond Agitation/Sedation Scale (RASS) ≤-2 and a Visual Analogic Scale (VAS) <4. The primary endpoint was patients' satisfaction. Secondary endpoints included assessment of sedation and pain, the incidence of perioperative hemodynamic or gas exchange imbalance, and 36 month-mortality. RESULTS: Remifentanil group showed a higher satisfaction rate than DEX (P<0.001). Patients on DEX were more sedated than remifentanil according to OAAS (3 [2-3] vs. 4 [3-4]; P=0.001) and RASS (-2[-3/-2] vs. -2[-2/-2]; P=0.001) with no difference in VAS (2 [1-3] vs. 2 [1-3]; P=0.41). DEX provides reliable sedation with lower patient's satisfaction. A higher number of patients were discharged from the recovery room on vasopressors in the DEX group compare with the remifentanil group (5 vs. 0; P=0.045, respectively). The two groups showed a non-significant difference in the survival rate at 36-month (DEX 67% vs. remifentanil 73%; (P=0.90). CONCLUSIONS: In this setting remifentanil provides reliable sedation with higher patient's satisfaction and less hemodynamic effect than DEX.

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.

Procedural sedation and analgesia for percutaneous high-tech cardiac procedures.

The interest in percutaneous high-tech cardiac procedures has increased in recent years together with its safety and efficacy. In fragile patients, procedural sedation and analgesia are used to perform most of the procedures. General anesthesia remains the technique of choice during the team learning curve and might be required in selected patients or in emergent situations. Despite the high costs of percutaneous high-tech cardiac procedures, the decrease in length of hospital stays, rate of intensive care admission and complications, balance the increase in devices costs. In fragile patients who undergo percutaneous high tech cardiac procedures, the primary role of the anesthesiologist is to prevent the need for postprocedural intensive care unit and complications rate. Starting from the experience of a large university third level hospital we identified the eight most commonly performed contemporary percutaneous high tech cardiac procedures (ventricular tachycardia and atrial fibrillation ablation, protected percutaneous coronary intervention, transcatheter aortic valve implantation, MitraClip® (Abbott Laboratories; Abbott Park, IL, USA), percutaneous patent foramen ovale closure, left atrial appendage closure, and dysfunctional lead extraction), discuss the role of procedural sedation and analgesia in this setting, and explore future perspectives.

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.