The Burden of Carbapenem-Resistant Acinetobacter baumannii in ICU COVID-19 Patients: A Regional Experience.

Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (n = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, p = 0.006 and 9.5 ± 3.6, p < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, p = 0.03), septic shock (61; 35%, p < 0.001), and in elders (66 ± 10, p < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (p = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (p < 0.001). Being colonized by CR-Ab was associated with a higher risk of developing invasive infections (p < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028−1.115) p = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572−18.988, p = 0.008). Constant infection-control measures are necessary to stop the spread of A. baumannii in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team.

Normothermic Regional Perfusion and Hypothermic Oxygenated Machine Perfusion for Livers Donated After Controlled Circulatory Death With Prolonged Warm Ischemia Time: A Matched Comparison With Livers From Brain-Dead Donors.

Prolonged warm ischemia time (WIT) has a negative prognostic value in liver transplantation (LT) using grafts procured after circulatory death (DCD). To assess the value of abdominal normothermic regional perfusion (A-NRP) associated with dual hypothermic oxygenated machine perfusion (D-HOPE) in controlled DCD LT, prospectively collected data on LTs performed between January 2016 and July 2021 were analyzed. Outcome of controlled DCD LTs performed using A-NRP + D-HOPE (n = 20) were compared to those performed with grafts procured after brain death (DBD) (n = 40), selected using propensity-score matching. DCD utilization rate was 59.5%. In the DCD group, median functional WIT, A-NRP and D-HOPE time was 43, 246, and 205 min, respectively. Early outcomes of DCD grafts recipients were comparable to those of matched DBD LTs. In DCD and DBD group, incidence of anastomotic biliary complications and ischemic cholangiopathy was 15% versus 22% (p = 0.73) and 5% versus 2% (p = 1), respectively. One-year patient and graft survival was 100% versus 95% (p = 0.18) and 90% versus 95% (p = 0.82). In conclusion, the association of A-NRP + D-HOPE in DCD LT with prolonged WIT allows achieving comparable outcomes to DBD LT.

Massive cerebral venous sinus thrombosis in vaccine-induced immune thrombotic thrombocytopenia after ChAdOx1 nCoV-19 serum: case report of a successful multidisciplinary approach.

We report a case of massive cerebral venous sinus thrombosis in the contest of vaccine-induced immune thrombotic thrombocytopenia that required the rapid coordination of many specialists from different departments, notably emergency, neurology, neuroradiology, hematology, and neurosurgery. The patient was rapidly treated with steroids, immunoglobulin, and fondaparinux. She underwent within 6 h after hospital admission a mechanical thrombectomy in order to allow flow restoration in cerebral venous systems. Neuroendovascular treatment in cerebral venous thrombosis related to VITT has never been described before. It can represent a complementary tool along with the other therapies and a multidisciplinary approach.

Comparison of ECMO vs ECpella in Patients With Non-Post-Pericardiotomy Cardiogenic Shock: An Updated Meta-Analysis.

INTRODUCTION: The impact of Impella and ECMO (ECPELLA) in cardiogenic shock (CS) remains to be defined. The aim of this meta-analysis is to evaluate the benefit of ECPELLA compared to VA-ECMO in patients with non post-pericardiotomy CS. METHODS: All studies reporting short term outcomes of ECpella or VA ECMO in non post-pericardiotomy CS were included. The primary endpoint was 30-day mortality. Vascular and bleeding complications and LVAD implantation/heart transplant within 30-days were assessed as secondary outcomes. RESULTS: Of 407 studies identified, 13 observational studies (13,682 patients, 13,270 with ECMO and 412 with ECpella) were included in this analysis. 30-day mortality was 55.8% (51.6-59.9) in the VA-ECMO group and 58.3% (53.5-63.0) in the ECpella group. At meta-regression analysis the implantation of IABP did not affect mortality in the ECMO group. The rate of major bleeding in patients on VA-ECMO and ECpella support were 21.3% (16.9-26.5) and 33.1% (25.9-41.2) respectively, while the rates of the composite outcome of LVAD implantation and heart transplantation within 30-days in patients on VA-ECMO and ECpella support were 14.4% (9.0-22.2) and 10.8%. When directly compared in 3 studies, ECpella showed a positive effect on 30-day mortality compared to ECMO (OR: 1.81: 1.039-3.159). CONCLUSION: Our data suggest that ECpella may reduce 30-day mortality and increase left ventricle recovery, despite increased of bleeding rates.

High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial.

PURPOSE: This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock. METHODS: Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care. RESULTS: Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010). CONCLUSION: The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.

How to communicate with families living in complete isolation.

IMPORTANCE: During the SARS-CoV-2 pandemic, a complete physical isolation has been worldwide introduced. The impossibility of visiting their loved ones during the hospital stay causes additional distress for families: in addition to the worries about clinical recovery, they may feel exclusion and powerlessness, anxiety, depression, mistrust in the care team and post-traumatic stress disorder. The impossibility of conducting the daily meetings with families poses a challenge for healthcare professionals. OBJECTIVE: This paper aims to delineate and share consensus statements in order to enable healthcare team to provide by telephone or video calls an optimal level of communication with patient's relatives under circumstances of complete isolation. EVIDENCE REVIEW: PubMed, Cochrane Database of Systematic Reviews, Database of Abstracts and Reviews of Effectiveness and the AHCPR Clinical Guidelines and Evidence Reports were explored from 1999 to 2019. Exclusion criteria were: poor or absent relevance regarding the aim of the consensus statements, studies prior to 1999, non-English language. Since the present pandemic context is completely new, unexpected and unexplored, there are not randomised controlled trials regarding clinical communication in a setting of complete isolation. Thus, a multiprofessional taskforce of physicians, nurses, psychologists and legal experts, together with some family members and former intensive care unit patients was established by four Italian national scientific societies. Using an e-Delphi methodology, general and specific questions were posed, relevant topics were argumented, until arriving to delineate position statements and practical checklist, which were set and evaluated through an evidence-based consensus procedure. FINDINGS: Ten statements and two practical checklists for phone or video calls were drafted and evaluated; they are related to who, when, why and how family members must be given clinical information under circumstances of complete isolation. CONCLUSIONS AND RELEVANCE: The statements and the checklists offer a structured methodology in order to ensure a good-quality communication between healthcare team and family members even in isolation, confirming that time dedicated to communication has to be intended as a time of care.

Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19.

OBJECTIVES: No agent has yet been proven to be effective for the treatment of patients with severe COVID-19. METHODS: We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6±12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to-severe adverse events attributable to TCZ were recorded. RESULTS: We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa02) to the fraction of inspired oxygen (Fi02) improved (mean±SD Pa02/Fi02 at admission: 152±53; at day 7: 283.73±115.9, at day 14: 302.2±126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). CONCLUSIONS: In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.

[Clinical ethics recommendations for the allocation of intensive care treatments, in exceptional, resource-limited circumstances.] / Raccomandazioni di etica clinica per l'ammissione a trattamenti intensivi e per la loro sospensione, in condizioni eccezionali di squilibrio tra necessità e risorse disponibili.

On February 21st, 2020 the first case of severe acute respiratory syndrome due to the coronavirus 2 (SARS-CoV-2) causing the CoViD-19 disease, was identified in Italy. In the following days, despite the restrictive public health measures aimed to avoid the infection's spread, the number of cases increased. As of March 8th, 2020, Italy is the 2nd most affected country in the world. As of March 6th, 2020, the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) published operational recommendations and ethical considerations to support the clinicians involved in the care of critically-ill CoViD-19 patients, in regard a probable scenario where an imbalance between supply and demand of ICU beds, is put in place by a steadily rising number of these patients.

Pulse wave velocity and short-term outcome in patients requiring intravascular volume expansion: a pilot study.

BACKGROUND: Fluid therapy has a pivotal role in the management of acutely ill patients. However, whether or not a patient can tolerate additional intravascular volume is controversial and optimal strategy is unknown. Carotid femoral pulse wave velocity (cfPWV) evaluates arterial stiffness. OBJECTIVE: To determine whether cfPWV can predict the ability of patients to tolerate clinically indicated acute fluid expansion. METHODS: 50 consecutive patients requiring intravascular volume expansion were prospectively recruited in intensive care units. All subjects underwent transthoracic echocardiography, pulmonary ultrasound assessment, and a cfPWV study (S. Giovanni Bosco Hospital in Turin, Italy, between 2015 and 2016) at baseline and after 24 hours. Acute outcomes were registered at 24 hours ("soft" end points) and 30 days ('hard' end points: death, acute myocardial infarction, stroke, occurrence of atrial fibrillation, need for dialysis) after initial fluid therapy. Multivariate logistic regression was used to assess association of the initial cfPWV with outcomes. RESULTS: cfPWV was significantly higher (10.6±3.6 vs 7.4±2.2 m/s, P<0.0001) in subjects who met the prespecified combined endpoints (hard or soft) than in those who did not. After adjustment for confounding factors, initial cfPWV was significantly and independently associated with the occurrence of hard events (OR=2.8 (95% CI 1.36 to 5.97), P=0.005; area under the receiver operating characteristic curve 84%). cfPWV of <9 m/s had a negative predictive value of 93%, excluding hard events associated with fluid expansion. CONCLUSION: cfPWV appears to reflect the ability of the patient to tolerate an intravascular fluid expansion when clinically indicated. Increased cfPWV could help to identify subjects at greater risk of developing signs and symptoms of fluid overload.

[Extracorporeal therapy in sepsis].

Acute renal injury (AKI) occurs in 19% of patients with sepsis, 23% of those with severe sepsis and up to 50% of patients with septic shock. AKI represents an independent prognostic factor of mortality (about 45%); epidemiological studies have pointed out that the onset of AKI in sepsis (S-AKI) correlates with an unfavourable outcome, reaching a mortality of 75%. Over the years, efforts have been made to prevent and treat "low flow" hemodynamic damage resulting from shock by increasing renal blood flow, improving cardiac output and perfusion pressure. New experimental studies in S-AKI have shown that renal blood flow is maintained, and indeed increases, in the course of septic shock. Recently, a "single theory" has been proposed that defines acute renal injury as the final result of the interaction between inflammation, oxidative stress, apoptosis, microcirculatory dysfunction and the adaptive response of tubular epithelial cells to the septic insult. The type of treatment, the dose and the starting time of RRT are of strategic importance in the recovery of AKI in septic patients. The use of new anticoagulation strategies in critically ill patients with S-AKI has allowed treatments to be carried out for enough time to reach the correct dose of purification prescribed, minimizing down-time and bleeding risk. The availability of new technologies allows to customize treatments more and more; the collaboration between nephrologists and intensivists must always increase in order to implement modern precision medicine in critical care.

Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia.

PURPOSE: The lateral Trendelenburg position (LTP) may hinder the primary pathophysiologic mechanism of ventilator-associated pneumonia (VAP). We investigated whether placing patients in the LTP would reduce the incidence of VAP in comparison with the semirecumbent position (SRP). METHODS: This was a randomized, multicenter, controlled study in invasively ventilated critically ill patients. Two preplanned interim analyses were performed. Patients were randomized to be placed in the LTP or the SRP. The primary outcome, assessed by intention-to-treat analysis, was incidence of microbiologically confirmed VAP. Major secondary outcomes included mortality, duration of mechanical ventilation, and intensive care unit length of stay. RESULTS: At the second interim analysis, the trial was stopped because of low incidence of VAP, lack of benefit in secondary outcomes, and occurrence of adverse events. A total of 194 patients in the LTP group and 201 in the SRP group were included in the final intention-to-treat analysis. The incidence of microbiologically confirmed VAP was 0.5% (1/194) and 4.0% (8/201) in LTP and SRP patients, respectively (relative risk 0.13, 95% CI 0.02-1.03, p = 0.04). The 28-day mortality was 30.9% (60/194) and 26.4% (53/201) in LTP and SRP patients, respectively (relative risk 1.17, 95% CI 0.86-1.60, p = 0.32). Likewise, no differences were found in other secondary outcomes. Six serious adverse events were described in LTP patients (p = 0.01 vs. SRP). CONCLUSIONS: The LTP slightly decreased the incidence of microbiologically confirmed VAP. Nevertheless, given the early termination of the trial, the low incidence of VAP, and the adverse events associated with the LTP, the study failed to prove any significant benefit. Further clinical investigation is strongly warranted; however, at this time, the LTP cannot be recommended as a VAP preventive measure. CLINICALTRIALS. GOV IDENTIFIER: NCT01138540.

The prognostic importance of chronic end-stage diseases in geriatric patients admitted to 163 Italian ICUs.

BACKGROUND: The number of elderly patients undergoing major surgical interventions and then needing admission to intensive care unit (ICU) grows steadily. We investigated this issue in a cohort of 232,278 patients admitted in five years (2011-2015) to 163 Italian general ICUs. METHODS: Surgical patients older than 75 registered in the GiViTI MargheritaPROSAFE project were analyzed. The impact on hospital mortality of important chronic conditions (severe COPD, NYHA class IV, dementia, end-stage renal disease, cirrhosis with portal hypertension) was investigated with two prognostic models developed yearly on patients staying in the ICU less or more than 24 hours. RESULTS: 44,551 elderly patients (19.2%) underwent emergency (47.3%) or elective surgery (52.7%). At least one severe comorbidity was present in 14.6% of them, yielding a higher hospital mortality (32.4%, vs. 21.1% without severe comorbidity). In the models for patients staying in the ICU 24 hours or more, cirrhosis, NYHA class IV, and severe COPD were constant independent predictors of death (adjusted odds ratios [ORs] range 1.67-1.97, 1.54-1.91, and 1.34-1.50, respectively), while dementia was statistically significant in four out of five models (adjusted ORs 1.23-1.28). End-stage renal disease, instead, never resulted to be an independent prognostic factor. For patients staying in the ICU less than 24 hours, chronic comorbidities were only occasionally independent predictors of death. CONCLUSIONS: Our study confirms that elderly surgical patients represent a relevant part of all ICUs admissions. About one of seven bear at least one severe chronic comorbidity, that, excluding end-stage renal disease, are all strong independent predictors of hospital death.

Making a case for controlled organ donation after cardiac death: the story of Italy's first experience.

Donation after circulatory death (DCD) is a valuable option for the procurement of organs for transplantation. In Italy, organ procurement after controlled DCD is legally and ethically conceivable within the current legislative framework. However, although formal impediments do not exist, the health care team is faced with many obstacles that may hinder the implementation of such programs. We report the case of Italy's first controlled DCD, specifically discussing the role of the patient's family in the shared decision-making process. In our case, the death of the patient subsequent to the withdrawal of life-sustaining therapies was consistent with the patient's wishes, showing respect for his dignity and honoring his autonomy, as expressed to his family previously. By making donation possible, the medical team was able to fulfill the family's last request on behalf of the patient. This case should stimulate deliberation regarding the potential to shorten the 20-minute no-touch period currently in place in Italy. Such an action would not have injured this patient and would certainly have increased the quality of the procured organs.

Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial.

OBJECTIVES: Coupled plasma filtration adsorption (CPFA, Bellco, Italy), to remove inflammatory mediators from blood, has been proposed as a novel treatment for septic shock. This multicenter, randomised, non-blinded trial compared CPFA with standard care in the treatment of critically ill patients with septic shock. DESIGN: Prospective, multicenter, randomised, open-label, two parallel group and superiority clinical trial. SETTING: 18 Italian adult, general, intensive care units (ICUs). PARTICIPANTS: Of the planned 330 adult patients with septic shock, 192 were randomised to either have CPFA added to the standard care, or not. The external monitoring committee excluded eight ineligible patients who were erroneously included. INTERVENTIONS: CPFA was to be performed daily for 5 days, lasting at least 10 h/day. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was mortality at discharge from the hospital at which the patient last stayed. Secondary endpoints were: 90-day mortality, new organ failures and ICU-free days within 30 days. RESULTS: There was no statistical difference in hospital mortality (47.3% controls, 45.1% CPFA; p=0.76), nor in secondary endpoints, namely the occurrence of new organ failures (55.9% vs 56.0%; p=0.99) or free-ICU days during the first 30 days (6.8 vs 7.5; p=0.35). The study was terminated on the grounds of futility. Several patients randomised to CPFA were subsequently found to be undertreated. An a priori planned subgroup analysis showed those receiving a CPFA dose >0.18 L/kg/day had a lower mortality compared with controls (OR 0.36, 95% CI 0.13 to 0.99). CONCLUSIONS: CPFA did not reduce mortality in patients with septic shock, nor did it positively affect other important clinical outcomes. A subgroup analysis suggested that CPFA could reduce mortality, when a high volume of plasma is treated. Owing to the inherent potential biases of such a subgroup analysis, this result can only be viewed as a hypothesis generator and should be confirmed in future studies. CLINICALTRIALSGOV: NCT00332371; ISRCTN24534559.

The influence of gender on the epidemiology of and outcome from severe sepsis.

INTRODUCTION: The impact of gender on outcome in critically ill patients is unclear. We investigated the influence of gender on the epidemiology of severe sepsis and associated morbidity and mortality in a large cohort of ICU patients in the region of Piedmont in Italy. METHODS: This was a post-hoc analysis of data from a prospective, multicenter, observational study in which all patients admitted to one of 24 participating medical and/or surgical ICUs between 3 April 2006 and 29 September 2006 were included. RESULTS: Of the 3,902 patients included in the study, 63.5% were male. Female patients were significantly older than male patients (66±16 years vs. 63±16 years, P<0.001). Female patients were less likely to have severe sepsis and septic shock on admission to the ICU and to develop these syndromes during the ICU stay. ICU mortality was similar in men and women in the whole cohort (20.1% vs. 19.8%, P=0.834), but in patients with severe sepsis was significantly greater in women than in men (63.5% vs. 46.4%, P=0.007). In multivariate logistic regression analysis with ICU outcome as the dependent variable, female gender was independently associated with a higher risk of ICU death in patients with severe sepsis (odds ratio=2.33, 95% confidence interval=1.23 to 4.39, P=0.009) but not in the whole cohort (odds ratio=1.07, 95% confidence interval=0.87 to 1.34). CONCLUSION: In this large regional Italian cohort of ICU patients, there were more male than female admissions. The prevalence of severe sepsis was lower in women than in men, but female gender was independently associated with a higher risk of death in the ICU for patients with severe sepsis.

A narrative-based study on communication by family members in intensive care unit.

PURPOSE: This study investigates how informative stories are, as written by patients' families in an intensive care unit (ICU) guest book, in terms of families' emotional responses, needs, perceptions, and satisfaction with the quality of care supplied. MATERIALS AND METHODS: Design was retrospective observational. Spontaneously written stories (440), gathered between 2009 and 2011, described experiences of 332 family members and 258 patients. Multivariate information from stories was analyzed using cluster analysis. RESULTS: Most frequently, stories were written in the form of letters addressed to patients (38%, 168 stories). Family members wrote mainly to give encouragement and to motivate patients to live (34%, 150 stories), expressing love or affection (56%, 245 stories). Feedback to ICU staff was provided in 65 stories, and competence was the most relevant skill recognized (31%, 20 stories). Cluster analysis highlighted links between positive feedback and families' positive emotional responses. CONCLUSIONS: The study suggests that ICU guest books can be an effective and simple means of communication between the family, the patient, and the ICU staff. Families shared thoughts, feelings, or opinions, which were meant to be supportive for the patients or rewarding for the staff.