Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported. METHODS: We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM-related side effects, ECMO weaning, and mortality. RESULTS: The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM-related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%-18% in patients anticoagulated with NM. Weaning and survival varied across studies. CONCLUSION: Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high-risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO.

Full and simplified assessment of left ventricular diastolic function in covid-19 patients admitted to ICU: Feasibility, incidence, and association with mortality.

PURPOSE: Left ventricular diastolic dysfunction (LVDD) is associated with poor outcomes in the intensive care unit (ICU). Nonetheless, precise reporting of LVDD in COVID-19 patients is currently lacking and assessment could be challenging. METHODS: We performed an echocardiography study in COVID-19 patients admitted to ICU with the aim to describe the feasibility of full or simplified LVDD assessment and its incidence. We also evaluated the association of LVDD or of single echocardiographic parameters with hospital mortality. RESULTS: Between 06.10.2020 and 18.02.2021, full diastolic assessment was feasible in 74% (n = 26/35) of patients receiving a full echocardiogram study. LVDD incidence was 46% (n = 12/26), while the simplified assessment produced different results (incidence 81%, n = 21/26). Nine patients with normal function on full assessment had LVDD with simplified criteria (grade I = 2; grade II = 3; grade III = 4). Nine patients were hospital-survivors (39%); the incidence of LVDD (full assessment) was not different between survivors (n = 2/9, 22%) and non-survivors (n = 10/17, 59%; p = .11). The E/e' ratio lateral was lower in survivors (7.4 [3.6] vs. non-survivors 10.5 [6.3], p = .03). We also found that s' wave was higher in survivors (average, p = .01). CONCLUSION: In a small single-center study, assessment of LVDD according to the latest guidelines was feasible in three quarters of COVID-19 patients. Non-survivors showed a trend toward greater LVDD incidence; moreover, they had significantly worse s' values (all) and higher E/e' ratio (lateral).

Implementation of video-calls between patients admitted to intensive care unit during the COVID-19 pandemic and their families: a pilot study of psychological effects

Background The coronavirus disease 2019 (COVID-19) pandemic has caused over 530 million infections to date (June 2022), with a high percentage of intensive care unit (ICU) admissions. In this context, relatives have been restricted from visiting their loved ones admitted to hospital. This situation has led to an inevitable separation between patients and their families. Video communication could reduce the negative effects of such phenomenon, but the impact of this strategy on levels of anxiety, depression, and PTSD disorder in caregivers is not well-known. Methods We conducted a prospective study (6 October 2020–18 February 2022) at the Policlinico University Hospital in Catania, including caregivers of both COVID-19 and non-COVID-19 ICU patients admitted during the second wave of the pandemic. Video-calls were implemented twice a week. Assessment of anxiety, depression, and PTSD was performed at 1-week distance (before the first, T1, and before the third, video-call, T2) using the following validated questionnaires: Impact of Event Scale (Revised IES-R), Center for Epidemiologic Studies Depression Scale (CES-D), and Hospital Anxiety and Depression Scale (HADS). Results Twenty caregivers of 17 patients completed the study (T1 + T2). Eleven patients survived (n = 9/11 in the COVID-19 and n = 2/6 in the “non-COVID” group). The average results of the questionnaires completed by caregivers between T1 and T2 showed no significant difference in terms of CES-D (T1 = 19.6 ± 10, T2 = 22 ± 9.6;p = 0.17), HADS depression (T1 = 9.5 ± 1.6, T2 = 9 ± 3.9;p = 0.59), HADS anxiety (T1 = 8.7 ± 2.4, T2 = 8.4 ± 3.8;p = 0.67), and IES-R (T1 = 20.9 ± 10.8, T2 = 23.1 ± 12;p = 0.19). Similar nonsignificant results were observed in the two subgroups of caregivers (COVID-19 and “non-COVID”). However, at T1 and T2, caregivers of “non-COVID” patients had higher scores of CES-D (p = 0.01 and p = 0.04, respectively) and IES-R (p = 0.049 and p = 0.02, respectively), while HADS depression was higher only at T2 (p = 0.02). At T1, caregivers of non-survivors had higher scores of CES-D (27.6 ± 10.6 vs 15.3 ± 6.7, p = 0.005) and IES-R (27.7 ± 10.0 vs 17.2 ± 9.6, p = 0.03). We also found a significant increase in CES-D at T2 in ICU-survivors (p = 0.04). Conclusions Our preliminary results showed that a video-call implementation strategy between caregivers and patients admitted to the ICU is feasible. However, this strategy did not show an improvement in terms of the risk of depression, anxiety, and PTSD among caregivers. Our pilot study remains exploratory and limited to a small sample. Supplementary Information The online version contains supplementary material available at 10.1186/s44158-022-00067-2.

Moral Distress in Healthcare Providers Who Take Care of Critical Pediatric Patients throughout Italy-Cultural Adaptation and Validation of the Italian Pediatric Instrument.

BACKGROUND: Although Moral Distress (MD) is a matter of concern within the Pediatric Intensive Care Unit (PICU), there is no validated Italian instrument for measuring the phenomenon in nurses and physicians who care for pediatric patients in Intensive Care. The authors of the Italian Moral Distress Scale-Revised (Italian MDS-R), validated for the adult setting, in 2017, invited further research to evaluate the generalizability of the scale to clinicians working in other fields. Our study aims to reduce this knowledge gap by developing and validating the pediatric version of the Italian MDS-R. METHODS: We evaluated the new instrument for construct validity, then we administered it in a multicenter, web-based survey that involved healthcare providers of three PICUs and three adult ICUs admitting children in northern, central, and southern Italy. Finally, we tested it for internal consistency, confirmatory factorial validity, convergent validity, and differences between groups analysis. RESULTS: The 14-item, three-factor model best fit the data. The scale showed good reliability (a = 0.87). Still, it did not correlate with the Emotional Exhaustion and Depersonalization sub-scales of the Maslach Burnout Inventory (MBI) or with the 2-item Connor-Davidson Resilience Scale (CD-RISC 2) or the Satisfaction with Life Scale (SWLS). A mild correlation was found between the Italian Pediatric MDS-R score and intention to resign from the job. No correlation was found between MD and years of experience. Females, nurses, and clinicians who cared for COVID-19 patients had a higher MD score. CONCLUSIONS: The Italian Pediatric MDS-R is a valid and reliable instrument for measuring MD among Italian health workers who care for critically ill children. Further research would be helpful in better investigating its applicability to the heterogeneous scenario of Italian Pediatric Critical Care Medicine.

Hemoperfusion and blood purification strategies in patients with COVID-19: A systematic review.

BACKGROUND: Coronavirus disease-19 (COVID-19) ranges from asymptomatic infection to severe cases requiring admission to the intensive care unit. Together with supportive therapies (ventilation in particular), the suppression of the pro-inflammatory state has been a hypothesized target. Pharmacological therapies with corticosteroids and interleukin-6 (IL-6) receptor antagonists have reduced mortality. The use of extracorporeal cytokine removal, also known as hemoperfusion (HP), could be a promising non-pharmacological approach to decrease the pro-inflammatory state in COVID-19. METHODS: We conducted a systematic review of PubMed and EMBASE databases in order to summarize the evidence regarding HP therapy in COVID-19. We included original studies and case series enrolling at least five patients. RESULTS: We included 11 articles and describe the characteristics of the populations studied from both clinical and biological perspectives. The methodological quality of the included studies was generally low. Only two studies had a control group, one of which included 101 patients in total. The remaining studies had a range between 10 and 50 patients included. There was large variability in the HP techniques implemented and in clinical and biological outcomes reported. Most studies described decreasing levels of IL-6 after HP treatment. CONCLUSION: Our review does not support strong conclusions regarding the role of HP in COVID-19. Considering the very low level of clinical evidence detected, starting HP therapies in COVID-19 patients does not seem supported outside of clinical trials. Prospective randomized data are needed.

Tracheal intubation while wearing personal protective equipment in simulation studies: a systematic review and meta-analysis with trial-sequential analysis.

BACKGROUND: Tracheal intubation in patients with coronavirus disease-19 is a high-risk procedure that should be performed with personal protective equipment (PPE). The influence of PPE on operator's performance during tracheal intubation remains unclear. METHODS: We conducted a systematic review and meta-analysis of simulation studies to evaluate the influence of wearing PPE as compared to standard uniform regarding time-to-intubation (TTI) and success rate. Subgroup analyses were conducted according to device used and operator's experience. RESULTS: The TTI was prolonged when wearing PPE (eight studies): Standard Mean Difference (SMD) -0.54, 95% Confidence Interval [-0.75, -0.34], p <  0.0001. Subgroup analyses according to device used showed similar findings (direct laryngoscopy, SMD -0.63 [-0.88, -0.38], p < 0.0001; videolaryngoscopy, SMD -0.39 [-0.75, -0.02], p =  0.04). Considering the operator's experience, non-anesthesiologists had prolonged TTI (SMD -0.75 [-0.98, -0.52], p < 0.0001) while the analysis on anesthesiologists did not show significant differences (SMD -0.25 [-0.51, 0.01], p = 0.06). The success rate of tracheal intubation was not influenced by PPE: Risk Ratio (RR) 1.02 [1.00, 1.04]; p = 0.12). Subgroup analyses according to device demonstrated similar results (direct laryngoscopy, RR 1.03 [0.99, 1.07], p = 0.15, videolaryngoscopy, RR 1.01 [0.98, 1.04], p =  0.52). Wearing PPE had a trend towards negative influence on success rate in non-anesthesiologists (RR 1.05 [1.00, 1.10], p = 0.05), but not in anesthesiologists (RR 1.00 [0.98, 1.03], p = 0.84). Trial-sequential analyses for TTI and success rate indicated robustness of both results. CONCLUSIONS: Under simulated conditions, wearing PPE delays the TTI as compared to dressing standard uniform, with no influence on the success rate. However, certainty of evidence is very low. Performing tracheal intubation with direct laryngoscopy seems influenced to a greater extent as compared to videolaryngoscopy. Similarly, wearing PPE affects more the non-anesthesiologists subgroup as compared to anesthesiologists.

COVID-19-related echocardiographic patterns of cardiovascular dysfunction in critically ill patients: A systematic review of the current literature.

PURPOSE: Coronavirus disease 2019 (COVID-19) infection may trigger a multi-systemic disease involving different organs. There has been growing interest regarding the harmful effects of COVID-19 on the cardiovascular system. This systematic review aims to systematically analyze papers reporting echocardiographic findings in hospitalized COVID-19 subjects. MATERIALS AND METHODS: We included prospective and retrospective studies reporting echocardiography data in >10 hospitalized adult subjects with COVID-19; from 1st February 2020 to 15th January 2021. RESULTS: The primary electronic search identified 1120 articles. Twenty-nine studies were finally included, enrolling 3944 subjects. Overall the studies included a median of 68.0% (45.5-100.0) of patients admitted to ICU. Ten studies (34.4%) were retrospective, and 20 (68.9%) single-centred. Overall enrolling 1367 subjects, three studies reported normal echocardiographic findings in 49 ± 18% of cases. Seven studies (24.1%) analyzed the association between echocardiographic findings and mortality, mostly related to right ventricular (RV) dysfunction. CONCLUSIONS: Data regarding the use of echocardiography on hospitalized, predominantly ICU, COVID-19 patients were retrieved from studies with heterogeneous designs, variable sample sizes, and severity scores. Normal echocardiographic findings were reported in about 50% of subjects, with LVEF usually not affected. Overall, RV dysfunction seems more likely associated with increased mortality. TRIAL REGISTRATION: CRD42020218439.

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study.

INTRODUCTION: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. METHODS: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. CONCLUSION: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Fatal VAP-related pulmonary aspergillosis by Aspergillus niger in a positive COVID-19 patient.

Invasive pulmonary aspergillosis, known as a complication in patients with severe respiratory syndromes, recently showed a correlation with COVID-19 pneumonia, and the clinical characteristics of COVID-19 associated pulmonary aspergillosis (CAPA) have been described. Unfortunately, infections by the Aspergillus genus are often diagnosed in post-mortem time, because of diagnostic delays and a rapid worsening of respiratory conditions. Literature data document, in fact, only few cases of COVID-19 Aspergillus niger coinfection. The aim of this study was to describe a case of a VAP-related probable pulmonary aspergillosis by Aspergillus niger in a COVID-19 patient. Despite the definition of fungal etiology and the rapid administration of antifungal therapy, the patient died while on ventilator support because of severe respiratory impairment.