Neck circumference as reliable predictor of mechanical ventilation support in adult inpatients with COVID-19: A multicentric prospective evaluation.

AIMS: COVID-19 is especially severe for elderly subjects with cardiometabolic and respiratory comorbidities. Neck circumference (NC) has been shown to be strongly related to cardiometabolic and respiratory illnesses even after adjustment for body mass index (BMI). We performed a prospective study to investigate the potential of NC to predict the need for invasive mechanical ventilation (IMV) in adult COVID-19 inpatients. MATERIALS AND METHODS: We prospectively and consecutively enrolled COVID-19 adult patients admitted to dedicated medical wards of two Italian hospitals from 25 March to 7 April 2020. On admission, clinical, biochemical and anthropometric data, including BMI and NC were collected. As primary outcome measure, the maximum respiratory support received was evaluated. Follow-up time was 30 days from hospital admission. RESULTS: We enrolled 132 subjects (55.0-75.8 years, 32% female). During the study period, 26 (19.7%) patients underwent IMV. In multivariable logistic regression analyses, after adjusting for age, sex, diabetes, hypertension and COPD, NC resulted independently and significantly associated with IMV risk (adjusted OR 1.260-per 1 cm increase 95% CI:1.120-1.417; P < .001), with a stronger association in the subgroup with BMI ≤30 Kg/m2 (adjusted OR 1.526; 95% CI:1.243-1.874; P < .001). NC showed a good discrimination power in predicting patients requiring IMV (AUC 0.783; 95% CI:0.684-0.882; P < .001). In particular, NC > 40.5 cm (>37.5 for females and >42.5 for males) showed a higher and earlier IMV risk compared to subjects with lower NC (Log-rank test: P < .001). CONCLUSIONS: NC is an easy to measure parameter able to predict the need for IMV in adult COVID-19 inpatients.

Coupled Plasma Filtration Adsorption for Treatment of Capillary Leak Syndrome Superimposed to Acute Generalized Exanthematous Pustolosis: A Case Report.

Coupled plasma filtration adsorption (CPFA) is an extracorporeal supportive therapy based on nonspecific adsorption of pro- and anti-inflammatory mediators combined with continuous renal replacement therapy. The main field of CPFA application is septic shock, and there are limited data about its efficacy in the treatment of other acute conditions characterized by a dysregulation in immune homeostasis. Capillary leak syndrome (CLS) defines a life-threatening condition sustained by hypercytokinemia and characterized by abrupt onset of increased capillary permeability leading to severe generalized edema and hypovolemic shock refractory to fluid administration. Therapy for CLS is not specific and, at present time, it consists in the use of steroids or intravenous immunoglobulins. We present the case of a 34-year-old woman who developed CLS superimposed to acute generalized exanthematous pustulosis after initiating therapy with hydroxychloroquine for undifferentiated connective tissue disease. CLS did not respond to steroids and intravenous immunoglobulins, while it was successfully treated with CPFA. This observation supports the possible role of CPFA in restoring a proper immunologic homeostasis not only in sepsis but also in other devastating conditions sustained by hypercytokinemia.

A Position Paper on IgM-Enriched Intravenous Immunoglobulin Adjunctive Therapy in Severe Acute Bacterial Infections: The TO-PIRO SCORE Proposal.

IgM-enriched immunoglobulins (e-IgM) may be useful in patients with severe acute bacterial infections. The evidence for the administration of e-IgM is not extensive and a definitive consensus has never been reached on its best use in patients with acute infections as well as in critically ill patients. However, the official indication in several countries, including Italy, is quite wide and mainly refers to supportive treatment of patients with acute severe bacterial infections. A multidisciplinary meeting of Italian Experts in Infectious Diseases, Anesthesia and Critical Care, Pneumology, Microbiology and Oncohaematology aimed to produce a statement on the best practical methodological score that could improve the use of e-IgM in patients with different infections, variable severity of disease and etiology. The Expert Panel reviewed the literature and the available guidelines, discussed the experience and eventually proposed to adapt the PIRO score to the practical methodological needs of a simple tool that could guide the administration of e-IgM.

Influence of Timing of Initiation and Volume of Processed Plasma on the Outcome of Septic Shock Patients Treated with Coupled Plasma Filtration and Adsorption.

BACKGROUND: The extracorporeal removal of mediators is a rescue strategy for septic shock patients, which is still under investigation. Several techniques are available: coupled plasma filtration and adsorption (CPFA) combines plasma processing with renal replacement therapy. METHODS: The study aimed to elucidate the role of both timing of initiation and intensity of treatment on the outcome, for which we retrospectively studied 52 patients. We collected the overall pre-CPFA time interval, starting from the first episode of hypotension in the wards and the volume of processed plasma (Vp), which we used as a proxy for intensity of treatment. RESULTS: Timing of initiation did not significantly differ between survivors and non-survivors (25 vs. 27 h), while the Vp did (0.25 vs. 0.17 L/kg/session, p < 0.05). The significance of Vp was confirmed by a multiple logistic regression model. CONCLUSION: Our study confirms that intensity of CPFA, but not its timing of initiation, correlates with survival of septic shock patients.

Effects of the volume of processed plasma on the outcome, arterial pressure and blood procalcitonin levels in patients with severe sepsis and septic shock treated with coupled plasma filtration and adsorption.

AIMS: To understand how coupled plasma filtration and adsorption (CPFA) could influence the time course of the advanced stages of sepsis, mean arterial pressure (MAP) and norepinephrine dosage. METHODS: Patients with severe sepsis and septic shock with ≥2 organ failures not responding to volume resuscitation and vasopressor infusion were treated with CPFA within 8 h of admission to the intensive care unit. RESULTS: Thirty-nine patients were treated (median age: 63 years, median SAPS II score: 45) and 28 survived advanced sepsis. In the latter, the median MAP increased and the norepinephrine dosage decreased significantly after CPFA, whereas in the nonsurvivors these values did not change significantly. The volume of treated plasma was significantly higher in survivors than nonsurvivors. CONCLUSION: These results suggest a possible existence of a dose-response effect for CPFA. Future studies are therefore recommended to evaluate the efficacy of this treatment and to determine its best timing and intensity.

End-tidal versus manually-controlled low-flow anaesthesia.

During low-flow manually-controlled anaesthesia (MCA) the anaesthetist needs constantly adjust end-tidal oxygen (EtO2) and anaesthetic concentrations (EtAA) to assure an adequate and safe anaesthesia. Recently introduced anaesthetic machines can automatically maintain those variables at target values, avoiding the burden on the anaesthetist. End-tidal-controlled anaesthesia (EtCA) and MCA provided by the same anaesthetic machine under the same fresh gas flow were compared. Eighty patients were prospectively observed: in MCA group (n = 40) target end-tidal sevoflurane (1%) and EtO2 concentrations (≥ 35%) were manually controlled by the anaesthetist. In EtCA group (n = 40) the same anaesthetic machine with an additional end-tidal control feature was used to reach the same targets, rendering automatic the achievement and maintenance of those targets. Anaesthetic machine characteristics, amount of consumed gases, oxygen and sevoflurane efficiencies, and the amount of interventions by the anaesthetist were recorded. In EtCA group EtAA was achieved later (145 s) than in MCA (71 s) and remained controlled thereafter. Even though the target expired gas fractions were achieved faster in MCA, manual adjustments were required throughout anaesthesia for both oxygen and sevoflurane. In MCA patients the number of manual adjustments to stabilize EtAA and EtO2 were 137 and 107, respectively; no adjustment was required in EtCA. Low-flow anaesthesia delivered with an anaesthetic machine able to automatically control EtAA and EtO2 provided the same clinical stability and avoided the continuous manual adjustment of delivered sevoflurane and oxygen concentrations. Hence, the anaesthetist could dedicate more time to the patient and operating room activities.

Hemoperfusion with high-affinity polyethylene microbeads (Seraph-100®) for the removal of pathogens in chronic critically ill patients: Clinical experience.

Critically ill septic patients present variable clinical trajectories, with some succumbing to hyperinflammatory responses while others develop a chronic critical illness, characterized by a prolonged low-grade inflammation, muscle atrophy, and mechanical ventilation dependency and often develop secondary infections often caused by from low-virulence microorganisms or reactivated latent viruses. The Seraph-100® hemoperfusion cartridge takes advantage from heparin-coated ultra-high molecular weight polyethylene microbeads mimicking pathogen-binding cell receptors and can adsorb both pathogens and damage-associated molecular patterns released by injured tissues. We describe two chronic critically ill patients who developed secondary viral bloodstream infections successfully treated with this device.

Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23.

BACKGROUND: In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. METHODS: A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. RESULTS: The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. CONCLUSIONS: Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.

The Techniques of Blood Purification in the Treatment of Sepsis and Other Hyperinflammatory Conditions.

Even in the absence of strong indications deriving from clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Despite the different underlying mechanisms of action, they are collectively indicated as blood purification techniques. Their main categories include blood- and plasma processing procedures, which can run in a stand-alone mode or, more commonly, in association with a renal replacement treatment. The different techniques and principles of function, the clinical evidence derived from multiple clinical investigations, and the possible side effects are reviewed and discussed along with the persisting uncertainties about their precise role in the therapeutic armamentarium of these syndromes.

The Role of the Intravenous IgA and IgM-Enriched Immunoglobulin Preparation in the Treatment of Sepsis and Septic Shock.

Polyclonal Intravenous Immunoglobulins (IvIg) are often administered to critically ill patients more as an act of faith than on the basis of relevant clinical studies. This particularly applies to the treatment of sepsis and septic shock because the current guidelines recommend against their use despite many investigations that have demonstrated their beneficial effects in different subsets of patients. The biology, mechanisms of action, and clinical experience related to the administration of IvIg are reviewed, which aim to give a more in-depth understanding of their properties in order to clarify their possible indications in sepsis and septic shock patients.

Waterhouse-Friderichsen syndrome following a dog bite in an asplenic patient: case report and review of the literature.

The Waterhouse-Friderichsen syndrome represents a critical condition characterized by a septic shock associated with a disseminated intravascular coagulation causing the plugging of the microvascular network virtually all organs and systems, including the skin, the kidneys, the liver, and adrenal glands; the mortality rate is elevated, and survivors often must undergo multiple limb amputations. Here, we describe the uncommon case of an asplenic patient who developed this syndrome after a superficial wound caused by a dog bite causing an initial infection due to Capnocytophaga canimorsus that is part of the normal oral microbiome of pets. The clinical and pathological findings and the current and future therapeutic options are reviewed and discussed.

Early short-term application of high-frequency percussive ventilation improves gas exchange in hypoxemic patients.

BACKGROUND: Hypoxemia in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients represents a common finding in the intensive care unit (ICU) and frequently does not respond to standard ventilatory techniques. OBJECTIVE: To study whether the early short-term application of high-frequency percussive ventilation (HFPV) can improve gas exchange in hypoxemic patients with ALI/ARDS or many other conditions in comparison to conventional ventilation (CV) using the same mean airway pressure (P(aw)), representing the main determinant of oxygenation and hemodynamics, irrespective of the mode of ventilation. METHODS: Thirty-five patients not responding to CV were studied. During the first 12 h after admission to the ICU the patients underwent CV. Thereafter HFPV was applied for 12 h with P(aw) kept constant. They were then returned to CV. Gas exchange was measured at: 12 h after admission, every 4 h during the HFPV trial, 1 h after the end of HFPV, and 12 h after HFPV. Thirty-five matched patients ventilated with CV served as the control group (CTRL). RESULTS: PaO(2)/FiO(2) and the arterial alveolar ratio (a/A PO(2)) increased during HFPV treatment and a PaO(2)/FiO(2) steady state was reached during the last 12 h of CV, whereas both did not change in CTRL. PaCO(2) decreased during the first 4 h of HFPV, but thereafter it remained unaltered; PaCO(2) did not vary in CTRL. Respiratory system compliance increased after HFPV. CONCLUSIONS: HFPV improved gas exchange in patients who did not respond to conventional treatment. This improvement remained unaltered until 12 h after the end of HFPV.

The Effects of Hemoadsorption on the Kinetics of Antibacterial and Antifungal Agents.

The extracorporeal elimination of a pathogen or damage-associated molecular pattern via blood purification techniques is increasingly being used in patients with septic shock and other clinical conditions characterized by a life-threatening inflammatory response. The removal of these substances can be accomoplished by means of ultrafiltration or hemoadsorption. Independently from the blood putification technique used, they could also affect the clearance of antibacterial and antifungal agents with a potentially significant clinical impact. In our review, we describe the basic principles of ultrafiltration and hemoadsorption, the available devices for this latter and the existing experimental and clinical studies; the final paragraph is dedicated to practical considerations that can help clinicians to consider the clearance of antibiotics and antifungals attributable to these techniques to minimize the risk of a iatrogenic underdosage.

Widespread Arterial Thrombosis after ChAdOx1 nCov-19 Vaccination.

Vaccine-induced thrombotic thrombocytopenia is an uncommon complication of COVID-19 vaccines using adenovirus mRNA carriers and has been associated with thrombosis of the cerebral venous sinuses and portal system. We report a case of a 69-year-old woman admitted to the intensive care unit due to stroke caused by thrombosis of the right carotid artery 9 days after receiving the ChAdOx1 nCov-19 vaccine. Further investigations demonstrated multiple thrombi in the arterial tree in the absence of any venous involvement. The clinical course and the treatment are described and discussed.

Effects of the timing and intensity of treatment on septic shock patients treated with CytoSorb®: Clinical experience.

INTRODUCTION: A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb® interval and its intensity on the outcome. METHODS: The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA. RESULTS: Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59-76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS. CONCLUSIONS: In this group of septic shock patients, the earlier initiation of Cytosorb®, its longer duration and the higher volume of blood processed were associated with a better survival.

Effects of tocilizumab versus hemoadsorption combined with tocilizumab in patients with SARS-CoV-2 pneumonia: Preliminary results.

OBJECTIVE: To assess the variations of Interleukin-6 (IL-6) in patients with SARS-CoV-2 infection treated with Tocilizumab (TCZ) alone or in association with hemoadsorption (HA). DESIGN: Retrospective. SETTING: An Intensive Care Unit (ICU) admitting mechanically ventilated patients with SARS-CoV-2 pneumonia. PATIENTS: Four adult patients. INTERVENTIONS: We compared the blood values of IL-6, C-reactive protein (CRP) and of other biochemical variables including the PaO2/FiO2 in two patients who received TCZ alone and in other 2 in whom it was associated with the HA (TCZ-HA) due to the presence of impending or established organ failures other than the lung. All variables were measured before, during and after the treatment. MAIN RESULTS: In all patients, the IL-6 increased during the treatment; after its termination, its values sharply decreased only in those treated also with HA; conversely, the CRP decreased in all patients; the PaO2/FiO2 increased in three patients and remained stable in the remaining one. Both the TCZ and the HA were well tolerated; all patients were weaned from the mechanical ventilation and discharged from the hospital. LIMITATIONS: Although the limited number of patients does not allow to draw firm conclusions, the increase of the IL-6 of can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ-HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with the SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators.

Multimodal Long-Term Predictors of Outcome in Out of Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management at 36 °C.

Introduction: Early prediction of long-term outcomes in patients resuscitated after cardiac arrest (CA) is still challenging. Guidelines suggested a multimodal approach combining multiple predictors. We evaluated whether the combination of the electroencephalography (EEG) reactivity, somatosensory evoked potentials (SSEPs) cortical complex and Gray to White matter ratio (GWR) on brain computed tomography (CT) at different temperatures could predict survival and good outcome at hospital discharge and six months after the event. Methods: We performed a retrospective cohort study including consecutive adult, non-traumatic patients resuscitated from out-of-hospital CA who remained comatose on admission to our intensive care unit from 2013 to 2017. We acquired SSEPs and EEGs during the treatment at 36 °C and after rewarming at 37 °C, Gray to white matter ratio (GWR) was calculated on the brain computed tomography scan performed within six hours of the hospital admission. We primarily hypothesized that SSEP was associated with favor-able functional outcome at distance and secondarily that SSEP provides independent information from EEG and CT. Outcomes were evaluated using the Cerebral Performance Category (CPC) scale at six months from discharge. Results: Of 171 resuscitated patients, 75 were excluded due to missing data or uninterpretable neurophysiological findings. EEG reactivity at 37 °C has been shown the best single predictor of good out-come (AUC 0.803) while N20P25 was the best single predictor for survival at each time point. (AUC 0.775 at discharge and AUC 0.747 at six months follow up). The predictive value of a model including EEG reactivity, average GWR, and SSEP N20P25 amplitude was superior (AUC 0.841 for survival and 0.920 for good out-come) to any combination of two tests or any single test. Conclusions: Our study, in which life-sustaining treatments were never suspended, suggests SSEP cortical complex N20P25, after normothermia and off sedation, is a reliable predictor for survival at any time. When SSEP cortical complex N20P25 is added into a model with GWR average and EEG reactivity, the predictivity for good outcome and survival at distance is superior than each single test alone.

Radiological-pathological signatures of patients with COVID-19-related pneumomediastinum: is there a role for the Sonic hedgehog and Wnt5a pathways?

Pneumomediastinum is a rare complication of ARDS but is more common during #COVID19. The fibrous hyaline degeneration of the tracheal rings seen in this autoptic series is an original observation that has not been previously described in COVID-19 patients. https://bit.ly/3vxTQde.

Rationale for Polyclonal Intravenous Immunoglobulin Adjunctive Therapy in COVID-19 Patients: Report of a Structured Multidisciplinary Consensus.

INTRODUCTION: Adjunctive therapy with polyclonal intravenous immunoglobins (IVIg) is currently used for preventing or managing infections and sepsis, especially in immunocompromised patients. The pathobiology of COVID-19 and the mechanisms of action of Ig led to the consideration of this adjunctive therapy, including in patients with respiratory failure due to the SARS-CoV-2 infection. This manuscript reports the rationale, the available data and the results of a structured consensus on intravenous Ig therapy in patients with severe COVID-19. METHODS: A panel of multidisciplinary experts defined the clinical phenotypes of COVID-19 patients with severe respiratory failure and, after literature review, voted for the agreement on the rationale and the potential role of IVIg therapy for each phenotype. Due to the scarce evidence available, a modified RAND/UCLA appropriateness method was used. RESULTS: Three different phenotypes of COVID-19 patients with severe respiratory failure were identified: patients with an abrupt and dysregulated hyperinflammatory response (early phase), patients with suspected immune paralysis (late phase) and patients with sepsis due to a hospital-acquired superinfection (sepsis by bacterial superinfection). The rationale for intravenous Ig therapy in the early phase was considered uncertain whereas the panelists considered its use in the late phase and patients with sepsis/septic shock by bacterial superinfection appropriate. CONCLUSION: As with other immunotherapies, IVIg adjunctive therapy may have a potential role in the management of COVID-19 patients. The ongoing trials will clarify the appropriate target population and the true effectiveness.