What Italian PICU Healthcare Providers Think About Donation After Cardiocirculatory Determination of Death: A National Survey.

BACKGROUND: Italy presently does not have a pediatric organ donation program after cardiocirculatory determination of death (pDCDD). Before implementing a pDCDD program, many centers globally have conducted studies on the attitudes of pediatric intensive care unit (PICU) staff. This research aims to minimize potential adverse reactions and evaluate the acceptance of the novel donation practice. METHODS: We conducted an electronic and anonymous survey on attitudes toward pDCDD among healthcare professionals (HCPs) working at eight Italian PICUs. The survey had three parts: (I) questions about general demographic data; (II) 18 statements about personal wishes to donate, experience of discussing donation, and knowledge about donation; (III) attitudinal statements regarding two pediatric Maastricht III scenarios of organ donation. RESULTS: The response rate was 54.4%, and the majority of respondents were nurses. Of those who responded, 45.3% worked in the Center, 40.8% in the North, and 12.8% in the South of Italy. In total, 93.9% supported pediatric organ and tissue donation, 90.3% supported donation after neurological determination of death (DNDD), 78.2% supported pDCDD, and 69.7% felt comfortable about the idea of participating in pDCDD on Type III patients, with a higher percentage of supportive responses in the Center (77.2%) than in the North (65.1%) and South (54.5%) of Italy (p-value < 0.004). Concerning scenarios, 79.3% of participants believed that organ retrieval took place in a patient who was already deceased. Overall, 27.3% considered their knowledge about DCDD to be adequate. CONCLUSIONS: Our study provides insight into the attitudes and knowledge of PICU staff members regarding pDCDD in Italy. Despite a general lack of knowledge on the subject, respondents showed positive attitudes toward pDCDD and a strong consensus that the Italian legislation protocol for determining death based on cardiocirculatory criteria respects the "dead donor rule." There were several distinctions among the northern, central, and southern regions of Italy, and in our view, these disparities can be attributed to the varying practices of commemorating the deceased. In order to assess how practice and training influence the attitude of PICU staff members, it would be interesting to repeat the survey after the implementation of a program.

Peri-partum respiratory management of pregnant women with neuro-muscular disorders: a prospective observational study (IT-NEUMA-Pregn study).

BACKGROUND: Pregnant women with neuromuscular diseases (NMDs) often display respiratory muscle impairment which increases the risk for pulmonary complications (PCs). The aim of this study was to identify pregnant NMDs patients with pulmonary risk factors and to apply in these women non-invasive ventilation (NIV) combined with mechanical insufflation-exsufflation (MI-E) in the peri-partum period. METHODS: We conducted a multicenter observational study on women with NMDs undergoing cesarean section or spontaneous labor in a network of 7 national hospitals. In these subjects we applied a protocol for screening and preventing PCs, and we evaluated PCs rate, maternal and neonatal outcome. RESULTS: Twenty-four patients out of the 94 enrolled pregnant women were at risk for PCs and were trained or retrained to use NIV and/or MI-E before delivery. After delivery, 17 patients required NIV with or without MI-E. Despite nine out of the 24 women at pulmonary risk developed postpartum PCs, none of them needed reintubation nor tracheostomy. In addition, the average birth weight and Apgar score were normal. Only one patient without pulmonary risk factors developed postpartum PCs. CONCLUSION: This study showed the feasibility of applying a protocol for screening and treating pregnant NMDs women with pulmonary risk. Despite a PCs rate of 37% was observed in these patients, maternal and neonatal outcome were favorable.

Effects of pneumoperitoneum on hemodynamics evaluated by continuous noninvasive arterial pressure monitoring. A single-center observational study.

BACKGROUND AND OBJECTIVES: The induction of pneumoperitoneum (PP) during laparoscopy may cause hemodynamic alterations, especially in patients with unknown cardiovascular diseases. While invasive arterial monitoring could be considered excessive, continuous noninvasive arterial pressure (CNAP) monitoring may allow careful evaluation of hemodynamic variations during laparoscopy. MATERIALS AND METHODS: The objective of this single center observational study was to evaluate hemodynamic changes after insufflation and after deflation of PP with CNAP monitoring. Patients included where adults undergoing elective laparoscopic cholecystectomy (American Society of Anesthesiologists physical status classification II and III). The Hemodynamic data (blood-pressure, cardiac-index, heart-rate, stroke-volume index, stoke-volume variation and arterialelastance) were collected 30 seconds before pneumoperitoneum (t1), and compared to values at 2 (t2), 10 (t3) and 20 (t4) minutes after pneumoperitoneum insufflation. We also compared data 30 seconds before and 2 minutes after release of pneumoperitoneum. RESULTS: 65 patients were included. Compared with reference values at t1, blood-pressure values increased at all timepoints (t2-t3-t4); cardiac-index augmented at t3 and t4 (p<0.05); heart-rate increased at t3 (p<0.005); stroke-volume index decreased at t2 (p<0.005) and was higher at t4 (p<0.005). While stoke-volume variation remained always stable after pneumoperitoneum induction, arterial-elastance increased significantly at all time-points (t2-t3-t4). The only difference at pneumoperitoneum deflation was a reduction in stoke-volume variation (p<0.05). CONCLUSIONS: In patients undergoing elective cholecystectomy, CNAP monitoring showed significant hemodynamic changes that would have been underappreciated with standard non-invasive monitoring with increase in arterial elastance under stable preload conditions. Whether this effect is due to unknown cardiovascular diseases facilitating ventriculo-arterial decoupling remains to be determined. KEY WORDS: Arterial Elastance, Cardiac Outp, Pneumoperitoneum, Stroke Volume, Stroke Volume Variation.

Italian pediatric intensive care units admitting critically ill cancer children: results from a national survey.

BACKGROUND: Pediatric patients affected by oncologic disease have a significant risk of clinical deterioration that requires admission to the intensive care unit. This study reported the results of a national survey describing the characteristics of Italian onco-hematological units (OHUs) and pediatric intensive care units (PICUs) that admit pediatric patients, focusing on the high-complexity treatments available before PICU admission, and evaluating the approach to the end-of-life (EOL) when cared in a PICU setting. METHODS: A web-based electronic survey has been performed in April 2021, involving all Italian PICUs admitting pediatric patients with cancer participating in the study. RESULTS: Eighteen PICUs participated, with a median number of admissions per year of 350 (IQR 248-495). Availability of Extracorporeal Membrane Oxygenation therapy and the presence of intermediate care unit are the only statistically different characteristics between large or small PICUs. Different high-level treatments and protocols are performed in OHUs, non depending on the volume of PICU. Palliative sedation is mainly performed in the OHUs (78%), however, in 72% it is also performed in the PICU. In most centers protocols that address EOL comfort care and treatment algorithms are missing, non depending on PICU or OHU volume. CONCLUSIONS: A non-homogeneous availability of high-level treatments and in OHUs is described. Moreover, protocols addressing EOL comfort care and treatment algorithms in palliative care are lacking in many centers.

Assessment of the inferior vena cava collapsibility from subcostal and trans-hepatic imaging using both M-mode or artificial intelligence: a prospective study on healthy volunteers.

PURPOSE: Assessment of the inferior vena cava (IVC) respiratory variation may be clinically useful for the estimation of fluid-responsiveness and venous congestion; however, imaging from subcostal (SC, sagittal) region is not always feasible. It is unclear if coronal trans-hepatic (TH) IVC imaging provides interchangeable results. The use of artificial intelligence (AI) with automated border tracking may be helpful as part of point-of-care ultrasound but it needs validation. METHODS: Prospective observational study conducted in spontaneously breathing healthy volunteers with assessment of IVC collapsibility (IVCc) in SC and TH imaging, with measures taken in M-mode or with AI software. We calculated mean bias and limits of agreement (LoA), and the intra-class correlation (ICC) coefficient with their 95% confidence intervals. RESULTS: Sixty volunteers were included; IVC was not visualized in five of them (n = 2, both SC and TH windows, 3.3%; n = 3 in TH approach, 5%). Compared with M-mode, AI showed good accuracy both for SC (IVCc: bias - 0.7%, LoA [- 24.9; 23.6]) and TH approach (IVCc: bias 3.7%, LoA [- 14.9; 22.3]). The ICC coefficients showed moderate reliability: 0.57 [0.36; 0.73] in SC, and 0.72 [0.55; 0.83] in TH. Comparing anatomical sites (SC vs TH), results produced by M-mode were not interchangeable (IVCc: bias 13.9%, LoA [- 18.1; 45.8]). When this evaluation was performed with AI, such difference became smaller: IVCc bias 7.7%, LoA [- 19.2; 34.6]. The correlation between SC and TH assessments was poor for M-mode (ICC = 0.08 [- 0.18; 0.34]) while moderate for AI (ICC = 0.69 [0.52; 0.81]). CONCLUSIONS: The use of AI shows good accuracy when compared with the traditional M-mode IVC assessment, both for SC and TH imaging. Although AI reduces differences between sagittal and coronal IVC measurements, results from these sites are not interchangeable.

Agreement between Capillary Refill Time measured at Finger and Earlobe sites in different positions: a pilot prospective study on healthy volunteers.

BACKGROUND: Capillary Refill Time (CRT) is a marker of peripheral perfusion usually performed at fingertip; however, its evaluation at other sites/position may be advantageous. Moreover, arm position during CRT assessment has not been fully standardized. METHODS: We performed a pilot prospective observational study in 82 healthy volunteers. CRT was assessed: a) in standard position with participants in semi-recumbent position; b) at 30° forearm elevation, c and d) at earlobe site in semi-recumbent and supine position. Bland-Altman analysis was performed to calculate bias and limits of agreement (LoA). Correlation was investigated with Pearson test. RESULTS: Standard finger CRT values (1.04 s [0.80;1.39]) were similar to the earlobe semi-recumbent ones (1.10 s [0.90;1.26]; p = 0.52), with Bias 0.02 ± 0.18 s (LoA -0.33;0.37); correlation was weak but significant (r = 0.28 [0.7;0.47]; p = 0.01). Conversely, standard finger CRT was significantly longer than earlobe supine CRT (0.88 s [0.75;1.06]; p < 0.001) with Bias 0.22 ± 0.4 s (LoA -0.56;1.0), and no correlation (r = 0,12 [-0,09;0,33]; p = 0.27]. As compared with standard finger CRT, measurement with 30° forearm elevation was significantly longer (1.17 s [0.93;1.41] p = 0.03), with Bias -0.07 ± 0.3 s (LoA -0.61;0.47) and with a significant correlation of moderate degree (r = 0.67 [0.53;0.77]; p < 0.001). CONCLUSIONS: In healthy volunteers, the elevation of the forearm significantly prolongs CRT values. CRT measured at the earlobe in semi-recumbent position may represent a valid surrogate when access to the finger is not feasible, whilst earlobe CRT measured in supine position yields different results. Research is needed in critically ill patients to evaluate accuracy and precision at different sites/positions.

α-2 agonists vs. fentanyl as adjuvants for spinal anesthesia in elective cesarean section: a meta-analysis.

INTRODUCTION: Elective cesarean section (CS) is usually performed using spinal anesthesia (SA), which requires the use of local anesthetic (LA) agents, commonly combined with adjuvant drugs. We performed a systematic review and meta-analysis aimed at studying the advantages of α-2 agonists as compared to fentanyl during SA for CS. EVIDENCE ACQUISITION: We screened PubMed and EMBASE for randomized controlled trials (RCTs). We calculated the mean difference (MD) for continuous outcomes, and the relative risk for dichotomous outcomes, using a random-effect model with 95% confidence interval (CI). We performed a Trial Sequential Analysis (TSA) assuming an alpha risk of 5%. The primary outcome was the time to first rescue analgesia. EVIDENCE SYNTHESIS: Eight RCTs were included. Time to first rescue analgesia was significantly longer when the α-2 agonists were used (MD 85.9 min [95% CI: 23.8, 147.9]; P=0.007). Duration of sensory block was also longer in the α-2 group (MD 40.5 [95% CI: 20.21,60.7]; P<0.0001), while no differences were found for onset of sensory block and onset and duration of motor block. Rates of shivering and nausea or vomiting were significantly lower in the α-2 agonist group, while risk of hypotension or respiratory depression were not different. The TSA on the primary outcome suggests the need of further research before drawing conclusions. CONCLUSIONS: α2-agonists seem to increase the time to first rescue analgesia and to prolong the duration of sensory block when used as adjuvants to LA in CS patients compared to fentanyl. Also, α2-agonists may reduce the incidence of shivering and nausea or vomiting.

C-Reactive protein kinetics after cardiac surgery: A retrospective multicenter study.

Background: Recognition of postoperative infection after cardiac surgery is challenging. Biomarkers may be very useful to recognize infection at early stage, but the literature is controversial. Methods: We conducted a retrospective study at two large University Hospitals, including adult patients undergoing cardiac surgery (excluding those with preoperative infections, cirrhotic or immunocompromised). We evaluated the kinetics of C-Reactive Protein (CRP) and White Cell Count (WCC) during the first postoperative week. Primary outcomes were CRP and WCC changes according to the development of postoperative infection. In order to evaluate the influence of cardiopulmonary bypass on biomarker kinetics, we also studied CRP and WCC changes in patients without postoperative infection and undergoing on- vs off-pump coronary-artery bypass grafting. Results: Among 429 included, 45 patients (10.5%) had evidence of postoperative infection. Patients with postoperative infection had higher CRP and WCC values than those without infection, with between-groups difference becoming significant from postoperative day 2 for CRP (120.6 ± 3.6 vs. 134.6 ± 7.9, P < 0.01), and from postoperative day 3 for WCC (10.5 ± 0.5 vs. 9.9 ± 0.2, P = 0.02). Over the postoperative period, CRP and WCC showed significant within-group changes regardless of development of postoperative infection (P < 0.001 for both). We found no differences in CRP and WCC kinetics between patients undergoing on- vs off-pump procedure. Conclusions: During the first week after cardiac surgery, CRP increases one day earlier than WCC in patients developing postoperative infections, with such difference becoming significant on the second postoperative day. In not infected patients, use of cardiopulmonary bypass does not influence CRP and WCC kinetics.

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).

Propofol and α2-Agonists Attenuate Microglia Activation and Restore Mitochondrial Function in an In Vitro Model of Microglia Hypoxia/Reoxygenation.

Cerebrovascular ischemia is a common clinical disease encompassing a series of complex pathophysiological processes in which oxidative stress plays a major role. The present study aimed to evaluate the effects of Dexmedetomidine, Clonidine, and Propofol in a model of hypoxia/reoxygenation injury. Microglial cells were exposed to 1%hypoxia for 3 h and reoxygenated for 3 h, and oxidative stress was measured by ROS formation and the expression of inflammatory process genes. Mitochondrial dysfunction was assessed by membrane potential maintenance and the levels of various metabolites involved in energetic metabolism. The results showed that Propofol and α2-agonists attenuate the formation of ROS during hypoxia and after reoxygenation. Furthermore, the α2-agonists treatment restored membrane potential to values comparable to the normoxic control and were both more effective than Propofol. At the same time, Propofol, but not α2-agonists, reduces proliferation (Untreated Hypoxia = 1.16 ± 0.2, Untreated 3 h Reoxygenation = 1.28 ± 0.01 vs. Propofol hypoxia = 1.01 ± 0.01 vs. Propofol 3 h Reoxygenation = 1.12 ± 0.03) and microglial migration. Interestingly, all of the treatments reduced inflammatory gene and protein expressions and restored energy metabolism following hypoxia/reoxygenation (ATP content in hypoxia/reoxygenation 3 h: Untreated = 3.11 ± 0.8 vs. Propofol = 7.03 ± 0.4 vs. Dexmedetomidine = 5.44 ± 0.8 vs. Clonidine = 7.70 ± 0.1), showing that the drugs resulted in a different neuroprotective profile. In conclusion, our results may provide clinically relevant insights for neuroprotective strategies in intensive care units.

The influence of policies limiting author self-citations on journals impact factor and self-citation rate in respiratory system.

To assess the presence of journal policies discouraging inappropriate author's self-citation (A-SC) in "Respiratory System" journals, we evaluated submission guidelines of "Respiratory System" journals included in Journal-Citation Reports 2020 (Clarivate Analytics®) for the presence of policies on A-SC and its impact on journals' self-citation (J-SC) rate and impact factor (IF). We found that 14.3% of journals (n=8/56) reported policies on inappropriate A-SC. The median IF was not different in "Respiratory System" journals with (3.6; IQR:2.3) vs without A-SC policies (3.1; IQR:3.0; p=0.41). The J-SC rate was not influenced by the presence of A-SC policies (p=0.83). Fully open-access (n=14) and traditional (n=42) journals had no differences in IF (3.3; IQR:1.5 vs 3.1; IQR:3.4, respectively; p=0.77) and J-SC rate (4.5%; IQR:5.6 vs 6.2%; IQR:8.4, respectively; p=0.38). The majority of "Respiratory System" journals do not have policies discouraging A-SC. The presence of such policies is not associated with changes in IF or J-SC rates.

Use of ketamine in patients with refractory severe asthma exacerbations: systematic review of prospective studies.

PURPOSE: Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring emergency department visits. In addition to conventional strategies for SAEs (inhaled ß-agonists, anticholinergics, and systemic corticosteroids), another pharmacological option is represented by ketamine. We performed a systematic review to explore the role of ketamine in refractory SAEs. METHODS: We performed a systematic search on PubMed and EMBASE up to August 12th, 2021. We selected prospective studies only, and outcomes of interest were oxygenation/respiratory parameters, clinical status, need for invasive ventilation and effects on weaning. RESULTS: We included a total of seven studies, five being randomized controlled trials (RCTs, population range 44-92 patients). The two small prospective studies (n = 10 and n = 11) did not have a control group. Four studies focused on adults, and three enrolled a pediatric population. We found a large heterogeneity regarding sample size, age and gender distribution, inclusion criteria (different severity scores, if any) and ketamine dosing (bolus and/or continuous infusion). Of the five RCTs, three compared ketamine to placebo, while one used fentanyl and the other aminophylline. The outcomes evaluated by the included studies were highly variable. Despite paucity of data and large heterogeneity, an overview of the included studies suggests absence of clear benefit produced by ketamine in patients with refractory SAE, and some signals towards side effects. CONCLUSION: Our systematic review does not support the use of ketamine in refractory SAE. A limited number of prospective studies with large heterogeneity was found. Well-designed multicenter RCTs are desirable.

Agreement between subcostal and transhepatic longitudinal imaging of the inferior vena cava for the evaluation of fluid responsiveness: A systematic review.

PURPOSE: Assessment of fluid-responsiveness is a key aspect of daily management in critically ill patients. Non-invasive evaluation of the variation of inferior vena cava (IVC) diameter during ventilation may provide useful information. However, a standard sagittal IVC visualization from the subcostal (SC) region is not always feasible. An alternative method to visualize the IVC is a coronal trans-hepatic (TH) approach. MATERIALS AND METHODS: We performed a systematic search to explore the interchangeability of IVC evaluation with SC and TH views. We searched Medline and EMBASE to identify prospective studies. We did not consider the relationship between axial and sagittal visualization of the IVC. RESULTS: We included seven studies reporting data on IVC evaluation with both SC and TH IVC views. Four studies were conducted on spontaneously breathing patients/volunteers, two on fully mechanically ventilated patients, and one in a mixed population, with large heterogeneity regarding the analyses reported. Limits of agreement between SC and TH were large. Concordance of the IVC collapsibility/distensibility indices are not interchangeable between SC and TH view. Correlation between diameters measured with SC and TH approach and intra/inter-observer correlation produced variable results. CONCLUSIONS: An overview of the included studies suggests that longitudinal TH and SC assessment of IVC size and respiratory variation are not interchangeable. New studies with accurate data reporting and appropriate statistical analysis are needed to define proper cut-offs for fluid responsiveness when using TH approach for IVC visualization.

Caution Is Warranted When Assessing Diastolic Function Using Transesophageal Echocardiography. Comment on Kyle et al. Consensus Defined Diastolic Dysfunction and Cardiac Postoperative Morbidity Score: A Prospective Observational Study. J. Clin. Med. 2021, 10, 5198.

Kyle et al. [...].

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.