Beyond the Surviving Sepsis Campaign Guidelines: a systematic review of interventions affecting mortality in sepsis.

INTRODUCTION: Sepsis-related mortality is decreasing over time after the introduction of "Surviving Sepsis Campaign" Guidelines in 2004. The last Guidelines version collects 93 recommendations, but several interventions supported by randomized evidence of mortality reduction are not included. EVIDENCE ACQUISITION: We performed a systematic review of all randomized controlled trials reporting a statistically significant mortality reduction in septic patients and compared the identified studies to the Surviving Sepsis Campaign Guidelines 2021 to highlight discrepancies. EVIDENCE SYNTHESIS: We identified 83 randomized controlled trials (58 interventions) influencing mortality in sepsis. Only 9/58 of these interventions were included in the Guidelines: lactate measurement and lactate-guided hemodynamic management, procalcitonin-guided antibiotics discontinuation, balanced crystalloids as first choice fluids, albumin infusion, avoidance of starches, noradrenaline as first line vasopressor, vasopressin as an adjunctive vasopressor to noradrenaline, neuromuscular blocking agents in moderate-severe sepsis-associated acute respiratory distress syndrome, and corticosteroids use. Only 11/93 Guidelines recommendations were supported by randomized evidence with mortality difference. Five of the interventions with survival benefit in literature (vitamin C, terlipressin, polymyxin B, liberal transfusion strategy and immunoglobulins) were recommended to avoid in the Guidelines, while 44 interventions were not mentioned, including three interventions (esmolol, omega 3, and external warming) with at least two randomized controlled trials with a documented survival benefit. CONCLUSIONS: Several discrepancies exist between the randomized controlled trials with mortality difference in septic patients and the latest Surviving Sepsis Campaign Guidelines. This systematic review can be of help for improving future guidelines and may guide research on specific promising topics.

Interventions reducing mortality in COVID-19 patients: a systematic review of randomized evidence.

INTRODUCTION: COVID-19 pandemic changed the way medical research is published, possibly forever. As the need for rapidity led to the rise of preprint servers, the undeniable drop in the overall quality of scientific publications requires an in-depth review of all available evidence. The present manuscript aims to identify and summarize all treatments which have been reported to reduce mortality in randomized trials in hospitalized COVID-19 patients. EVIDENCE ACQUISITION: Independent investigators searched MEDLINE/PubMed, Scopus, and Embase databases to identify all randomized trials of any intervention influencing mortality in hospitalized COVID-19 patients up to August 18th, 2022. Articles were selected only when they fulfilled all the following: randomized trial design; dealing with any kind of interventions in adult hospitalized COVID-19 patients; and statistically significant reduction in mortality. EVIDENCE SYNTHESIS: We identified 28 interventions (42 manuscripts) reducing mortality in hospitalized COVID-19 patients. About 60% of the studies (26/42) were multicentric, for a total of 1140 centers involved worldwide. Several of these studies were published in high-ranked, peer-reviewed journals. Interventions with randomized evidence of mortality reduction in hospitalized COVID-19 patients belonged to 5 domains: corticosteroids, immunomodulators, antimicrobials, supportive therapies, and other drugs. CONCLUSIONS: Many interventions have the potential to reduce mortality in COVID-19 hospitalized patients. The correct treatment of future pandemics relies on large, multicentric randomized clinical trials for further evaluation of these promising strategies.

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.

Gender-gap in randomized clinical trials reporting mortality in the perioperative setting and critical care: 20 years behind the scenes.

Background: Women researchers might experience obstacles in academic environments and might be underrepresented in the authorship of articles published in peer-reviewed journals. Material and Methods: This is a cross-sectional analysis of female-led RCTs describing all interventions reducing mortality in critically ill and perioperative patients from 1981 to December 31, 2020. We searched PubMed/MEDLINE and EMBASE with the keywords RCTs and mortality. The gender of the first author was extracted and descriptive analysis was performed including the year of publication, impact factor, country of the first author, and methodological aspects. Results: We analyzed 340 RCTs, of which 42 (12%) were led by female researchers. The presence of women increased from 8% (14/172) until 2010 up to 17% (28/168) in 2010 and beyond. The United States, the United Kingdom, and Brazil were the main countries of origin of female researchers. Women authors conducted mainly single-center and single-nation studies as compared to male authors. The median impact factor of the target journal was 6 (3-27) in women vs. 7 (3-28) in men, with a p-value of 0.67; Critical Care Medicine, JAMA, and The New England Journal of Medicine were the most frequent target journals for both women and men. Conclusion: In the last 40 years, only one out of eight RCTs had a woman as the first author but the presence of women increased up to 17% by 2010 and beyond. The impact factor of publication target journals was high and not different between genders.

Is Gastrointestinal Bleeding a Problem for COVID-19 Intensive Care Unit Patients?

The objective of this study was to describe the COVID-19 intensive care unit population and analyze the characteristics and outcomes of gastrointestinal bleeding patients. An observational prospective study design was used following the STROBE checklist. All patients admitted between February and April 2020 to the intensive care unit were included. Main outcome measures were first bleeding event timing, sociodemographic and clinical data before admission, and gastrointestinal symptoms. A total of 116 COVID-19 patients were included; 16 (13.8%) developed gastrointestinal bleeding, 15 were males (93.7%), and the median age was 65.64 ± 7.33 years. All 16 patients were mechanically ventilated, one (6.3%) already had gastrointestinal symptoms, 13 (81.3%) had at least one concomitant disease, and six (37.5%) died. Bleeding episodes occurred on a mean of 16.9 ± 9.5 days after admission. Nine cases (56.3%) had effects on their hemodynamics, hemoglobin levels, or transfusion requirements; six (37.5%) required diagnostic imaging; and two (12.5%) underwent endoscopy procedures. The Mann-Whitney test showed statistically significant differences between the two groups of patients concerning comorbidities. Gastrointestinal bleeding can occur in critically ill patients with COVID-19. Having a solid tumor or chronic liver disease seems to increase that risk. Nurses caring for COVID-19 patients are urged to individualize patients at higher risk in order to improve safety.

Effects on health-related quality of life of interventions affecting survival in critically ill patients: a systematic review.

Survival has been considered the cornerstone for clinical outcome evaluation in critically ill patients admitted to intensive care unit (ICU). There is evidence that ICU survivors commonly show impairments in long-term outcomes such as quality of life (QoL) considering them as the most relevant ones. In the last years, the concept of patient-important outcomes has been introduced and increasingly reported in peer-reviewed publications. In the present systematic review, we evaluated how many randomized controlled trials (RCTs) were conducted on critically ill patients and reporting a benefit on survival reported also data on QoL. All RCTs investigating nonsurgical interventions that significantly reduced mortality in critically ill patients were searched on MEDLINE/PubMed, Scopus and Embase from inception until August 2021. In a second stage, for all the included studies, the outcome QoL was investigated. The primary outcome was to evaluate how many RCTs analyzing interventions reducing mortality reported also data on QoL. The secondary endpoint was to investigate if QoL resulted improved, worsened or not modified. Data on QoL were reported as evaluated outcome in 7 of the 239 studies (2.9%). The tools to evaluate QoL and QoL time points were heterogeneous. Four interventions showed a significant impact on QoL: Two interventions improved survival and QoL (pravastatin in subarachnoid hemorrhage, dexmedetomidine in elderly patients after noncardiac surgery), while two interventions reduced mortality but negatively influenced QoL (caloric restriction in patients with refeeding syndrome and systematic ICU admission in elderly patients). In conclusion, only a minority of RCTs in which an intervention demonstrated to affect mortality in critically ill patients reported also data on QoL. Future research in critical care should include patient-important outcomes like QoL besides mortality. Data on this topic should be collected in conformity with PROs statement and core outcome sets to guarantee quality and comparability of results.

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.

Predictors of Pneumothorax/Pneumomediastinum in Mechanically Ventilated COVID-19 Patients.

OBJECTIVE: To determine the incidence, predictors, and outcome of pneumothorax (PNX)/pneumomediastinum (PMD) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). DESIGN: Observational study. SETTING: Tertiary-care university hospital. PARTICIPANTS: One hundred sixteen consecutive critically ill, invasively ventilated patients with COVID-19 ARDS. INTERVENTIONS: The authors collected demographic, mechanical ventilation, imaging, laboratory, and outcome data. Primary outcome was the incidence of PNX/PMD. Multiple logistic regression analyses were performed to identify predictors of PNX/PMD. MEASUREMENTS AND MAIN RESULTS: PNX/PMD occurred in a total of 28 patients (24.1%), with 22 patients developing PNX (19.0%) and 13 developing PMD (11.2%). Mean time to development of PNX/PMD was 14 ± 11 days from intubation. The authors found no significant difference in mechanical ventilation parameters between patients who developed PNX/PMD and those who did not. Mechanical ventilation parameters were within recommended limits for protective ventilation in both groups. Ninety-five percent of patients with PNX/PMD had the Macklin effect (linear collections of air contiguous to the bronchovascular sheaths) on a baseline computed tomography scan, and tended to have a higher lung involvement at intensive care unit (ICU) admission (Radiographic Assessment of Lung Edema score 32.2 ± 13.4 v 18.7 ± 9.8 in patients without PNX/PMD, p = 0.08). Time from symptom onset to intubation and time from total bilirubin on day two after ICU admission were the only independent predictors of PNX/PMD. Mortality was 60.7% in patients who developed PNX/PMD versus 38.6% in those who did not (p = 0.04). CONCLUSION: PNX/PMD occurs frequently in COVID-19 patients with ARDS requiring mechanical ventilation, and is associated with increased mortality. Development of PNX/PMD seems to occur despite use of protective mechanical ventilation and has a radiologic predictor sign.

Why are Asian countries outperforming the Western world in controlling COVID-19 pandemic?

COVID-19 already caused more than 1,260,000 deaths around the world. However, mortality rates are not equal amongst the different countries. Mortality rates are ranging from less than 1 death per million in Taiwan, Vietnam and Thailand to 1,112 deaths per million in Belgium. In the present article, we report a striking difference in mean per million mortality between Asian and European countries (2.7 vs 197 deaths per million population, p < 0.001). In addition, we confirmed that the later a specific country was hit by the epidemic, the milder the impact on mortality during the first 50 days was. We analyzed several factors that may have contributed to this discrepancy including population age, previous experience of epidemics in the modern era, social acceptance of physical distancing and face masks, percentage of active smokers and lastly genetic prothrombotic mutations.