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Introduction A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).Methods A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to

Abstract Background The pupillary dilation reflex (PDR) is an objective indicator of analgesic levels in anesthetized patients. Through measurement of the PDR during increasing tetanic stimulation (10–60 mA), it is possible to obtain the pupillary pain index (PPI), a score that assesses the level of analgesia. Objectives The depth of analgesia during opioid-sparing anesthesia (OSA) with continuous infusion of dexmedetomidine in addition to general anesthesia was assessed. Design Observational prospective feasibility pilot study Setting This study was performed in the operating rooms of the Spedali Civili University-affiliated hospital of Brescia, Italy. Patients Forty-five adults who underwent elective open (5-cm incision) surgery under general anesthesia (78% inhalation anesthesia), from Feb. 18th to Aug. 1st, 2019, were enrolled. Exclusion criteria were as follows: implanted pacemaker or ICD, ophthalmological comorbidities, chronic opioid use, peripheral neuropathy, other adjuvant drugs, epidural analgesia, or locoregional block. Main outcome measures The first aim was to verify the feasibility of applying a study protocol to evaluate the depth of analgesia during intraoperative dexmedetomidine administration using an instrumental pupillary evaluation. The secondary outcome was to evaluate appropriate analgesia, drug dosage, anesthesia depth, heart rate, blood pressure, transient side effects, postoperative nausea and vomiting (PONV), and pain numerical rating scale (NRS) score. Results Thirty out of 50 patients (60%) treated with dexmedetomidine during the study period were included in the DEX group (8 males, age 42 ± 13 years, BMI 45 ± 8), and 15 other patients were included in the N-DEX group (8 males, age 62 ± 13 years, BMI 26 ± 6). Patients who underwent bariatric, abdominal, or plastic surgery were enrolled. At least 3 pupillary evaluations were taken for each patient. PPI ≤ 3 was observed in 97% of patients in the DEX group and 53% in the N-DEX group. Additionally, the DEX group received less than half the remifentanil dose than the N-DEX group (0.13 ± 0.07 vs 0.3 ± 0.11 mcg kg−1 min−1). The average dose of dexmedetomidine administered was 0.17 ± 0.08 mcg kg−1 h−1. Conclusion The feasibility of applying the protocol was verified. An OSA strategy involving dexmedetomidine may be associated with improved analgesic stability: a randomized controlled trial is necessary to verify this hypothesis. Trial registration Trial.gov registration number: NCT05785273

IntroductionLong-term weakness is common in survivors of COVID-19-associated acute respiratory distress syndrome (CARDS). We longitudinally assessed the predictors of muscle weakness in patients evaluated 6 and 12 months after intensive care unit discharge with in-person visits.MethodsMuscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, the compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), a 6-min walk test, severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength and Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for their essential role in ankle control.ResultsMVC improved at 12 months compared with 6 months. CMAP-TA-S100 (P = 0.016) and the presence of severe fatigue (P = 0.036) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT.DiscussionElectrical neuromuscular abnormalities and severe fatigue are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.

In this paper we present experimental results obtained by applying a Model Predictive Control strategy for the control of Depth of Hypnosis in general anesthesia. In particular, the Bispectral Index Scale is employed as the controlled variable and the administration of the hypnotic drug propofol is determined by applying a Generalized Predictive Control algorithm, which considers a process model that is linearized by means of an external predictor. The results of four patients who underwent elective plastic surgeries are analyzed and discussed, showing the feasibility of the approach in a practical context.

Take home message Future randomized trials are required to adopt EEG monitoring during CPR, also considering its possible role in a multiparametric assessment of cerebral function and perfusion.

Abstract Adult and pediatric palliative care (PC) share common aims and ethical principles but differ in many organizational and practical aspects. The aim of this narrative review is to analyze these differences and focus on which key aspects of pediatric palliative care could integrate adult services for a better care of suffering patients. Interventions which are peculiar of pediatric PC respect to adult PC include: an earlier referral to the PC service to identify the needs and plan the interventions at an earlier stage of the disease; consequently, a more systematic cooperation with the disease-specific physicians to reduce the burden of treatments; a better integration with the community and the social surroundings of the patients, to prevent social isolation and preserve their social role; a more dynamic organization of the PC services, to give patients the chance of being stabilized at in-hospital or residential settings and subsequently discharged and cared at home whenever possible and desired; the implementation of respite care for adults, to help the families coping with the burden of the disease of their beloved and promote the home-based PC. This review underlines the relevance of some key-aspects of pediatric PC that can be beneficial also within PC of adults. Its findings give the chance for a more dynamic and modern organization of adult PC services and may serve as a basis of future research for new interventions.

Abstract Background The current organizational structure of the Italian healthcare system does not include the institutionalization of clinical ethics services. To describe the need for structured clinical ethics consultation services for ICU staff members in the intensive care unit (ICU), a monocentric observational survey study was performed utilizing a paper-based questionnaire. Results A total of 73 healthcare professionals (HCPs) responded out of a team of 84 people (87%). The results showed that the need for ethics consultation in the ICU is urgent, the institutionalization of the clinical ethics service is perceived as useful and should be a priority, and the issues on which the HCPs would like ethics consultation to focus are various and belong to “end of life” topics. Conclusions HCPs believe that the clinical ethicist should become an integral part of ICU healthcare teams, offering consultations similar to the other specialistic consultations carried out in hospitals.

IntroductionPatients admitted to the intensive care unit (ICU) following severe acute respiratory syndrome 2 (SARS-CoV-2) infection may have muscle weakness up to 1 year or more following ICU discharge. However, females show greater muscle weakness than males, indicating greater neuromuscular impairment. The objective of this work was to assess sex differences in longitudinal physical functioning following ICU discharge for SARS-CoV-2 infection.MethodsWe performed longitudinal assessment of physical functioning in two groups: 14 participants (7 males, 7 females) in the 3-to-6 month and 28 participants (14 males, 14 females) in the 6-to-12 month group following ICU discharge and assessed differences between the sexes. We examined self-reported fatigue, physical functioning, compound muscle action potential (CMAP) amplitude, maximal strength, and the neural drive to the tibialis anterior muscle.ResultsWe found no sex differences in the assessed parameters in the 3-to-6-month follow-up, indicating significant weakness in both sexes.Sex differences emerged in the 6-to-12-month follow-up. Specifically, females exhibited greater impairments in physical functioning, including lower strength, walking lower distances, and high neural input even 1 year following ICU-discharge.DiscussionFemales infected by SARS-CoV-2 display significant impairments in functional recovery up to 1 year following ICU discharge. The effects of sex should be considered in post-COVID neurorehabilitation.

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

Abstract Background Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. Methods This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. Results Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6–40.5%), and Bland–Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7–92.6%) and a specificity of 72% (95% CI 51.9–94.0%) with an AUC of 76% (95% CI 65.6–85.5%). Conclusions and relevance ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. Trial registration: NCT02322970 .

Introduction: Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. Methods: Narrative review based on a literature search through PubMed and Cochrane using the following keywords: “multi-drug resistant (MDR)”, “extensively drug resistant (XDR)”, “pan-drug-resistant (PDR)”, “difficult-to-treat (DTR) Gram-negative infection,” “antibiotic duration therapy”, “antibiotic combination therapy” “antibiotic monotherapy” “Gram-negative bacteremia”, “Gram-negative pneumonia”, and “Gram-negative intra-abdominal infection”. Results: Current literature data suggest adopting longer (≥10–14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45–50%), MDR (35%), XDR (15–20%), PDR (5.9–6.2%), and carbapenemases (CP)/metallo-β-lactamases (MBL)-producing (12.5–20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (≤5–7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum β-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum β-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. Conclusions: Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.

Abstract Backgrounds The COVID-19 pandemic drastically strained the health systems worldwide, obligating the reassessment of how healthcare is delivered. In Lombardia, Italy, a Regional Emergency Committee (REC) was established and the regional health system reorganized, with only three hospitals designated as hubs for trauma care. The aim of this study was to evaluate the effects of this reorganization of regional care, comparing the distribution of patients before and during the COVID-19 outbreak and to describe changes in the epidemiology of severe trauma among the two periods. Methods A cohort study was conducted using retrospectively collected data from the Regional Trauma Registry of Lombardia (LTR). We compared the data of trauma patients admitted to three hub hospitals before the COVID-19 outbreak (September 1 to November 19, 2019) with those recorded during the pandemic (February 21 to May 10, 2020) in the same hospitals. Demographic data, level of pre-hospital care (Advanced Life Support-ALS, Basic Life Support-BLS), type of transportation, mechanism of injury (MOI), abbreviated injury score (AIS, 1998 version), injury severity score (ISS), revised trauma score (RTS), and ICU admission and survival outcome of all the patients admitted to the three trauma centers designed as hubs, were reviewed. Screening for COVID-19 was performed with nasopharyngeal swabs, chest ultrasound, and/or computed tomography. Results During the COVID-19 pandemic, trauma patients admitted to the hubs increased (46.4% vs 28.3%, p < 0.001) with an increase in pre-hospital time (71.8 vs 61.3 min, p < 0.01), while observed in hospital mortality was unaffected. TRISS, ISS, AIS, and ICU admission were similar in both periods. During the COVID-19 outbreak, we observed substantial changes in MOI of severe trauma patients admitted to three hubs, with increases of unintentional (31.9% vs 18.5%, p < 0.05) and intentional falls (8.4% vs 1.2%, p < 0.05), whereas the pandemic restrictions reduced road- related injuries (35.6% vs 60%, p < 0.05). Deaths on scene were significantly increased (17.7% vs 6.8%, p < 0.001). Conclusions The COVID-19 outbreak affected the epidemiology of severe trauma patients. An increase in trauma patient admissions to a few designated facilities with high level of care obtained satisfactory results, while COVID-19 patients overwhelmed resources of most other hospitals.

PurposeLimb intensive care unit (ICU)-acquired weakness (ICUAW) and ICU acquired diaphragm weakness (DW) occur frequently in mechanically ventilated (MV) patients; their coexistence in cooperative and uncooperative patients is unknown. This study was designed to (1) describe the co-occurrence of the two conditions (2) evaluate the impact of ICUAW and DW on the ventilator-free days (VFDs) at 28 days and weaning success, and (3) assess the correlation between maximal inspiratory pressure (MIP) and thickening fraction (TFdi) in patients with DW.MethodsThis prospective pilot study was conducted in a single-center on 73 critically ill MV patients. Muscle weakness was defined as a Medical Research Council score < 48 in cooperative patients or a bilateral mean simplified peroneal nerve test < 5.26 mV in uncooperative patients. Diaphragm dysfunction was defined as MIP < 30 cm H2O or as a TFdi < 29%. Weaning success was defined according to weaning according to a new definition (WIND).ResultsFifty-seven patients (78%) had ICUAW and 59 (81%) had DW. The coexistence of the two conditions occurred in 48 patients (65%), without association (χ2 = 1.06, p = 0.304). In the adjusted analysis, ICUAW was independently related to VFDs at 28-days (estimate difference 6 days, p = 0.016), and WIND (OR of 3.62 for having WIND different than short weaning), whereas DW was not. The linear mixed model showed a significant but weak correlation between MIP and TFdi (p < 0.001).ConclusionThis pilot study is the first to explore the coexistence of ICUAW and DW in both cooperative and uncooperative patients; a lack of association was found between DW and ICUAW when considering both cooperative and uncooperative patients. We found a strong correlation between ICUAW but not DW with the VFDs at 28 days and weaning success. A future larger study is warranted in order to confirm our results, and should also investigate the use of transdiaphragmatic twitch pressure measurement during bilateral anterior magnetic phrenic nerve stimulation for the diagnosis of DW.

Abstract Background The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient’s inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation. Methods Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume. Results Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p

This paper investigates the performance achievable with a fractional-order PID regulator controlling the Depth of Hypnosis (measured via the Bispectral Index Scale) through the administration of propofol during the maintenance phase of total intravenous anesthesia. In particular, two different methodologies were applied to tune the controller: in the first case, genetic algorithms (GAs) were used to minimize the integrated absolute error, while in the second case, the isodamping approach—a method that targets phase margin invariance with respect to the process dc gain—was employed. In both cases, the performance was extensively analyzed and compared with that of a standard PID controller by simulating multiple patients through a Monte Carlo method. The results demonstrate that a fractional-order PID controller can be effectively used to control the Depth of Hypnosis, but the improvement with respect to a standard PID controller is marginal.

Abstract Intensive care survivors often experience post-intensive care sequelae, which are frequently gathered together under the term “post-intensive care syndrome” (PICS). The consequences of PICS on quality of life, health-related costs and hospital readmissions are real public health problems. In the present Viewpoint, we summarize current knowledge and gaps in our understanding of PICS and approaches to management.

Abstract Background COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. Methods We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. Results Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. Conclusions Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease (COVID-19), is a major pandemic challenging health care systems around the world. The optimal management of patients infected with COVID-19 is still unclear, although the consensus is moving toward the need of a biphasic approach. During the first phase of the disease (from onset of the symptoms up to 7–10 days) viral-induced effects are prominent, with the opportunity to institute antiviral therapy. In the second inflammatory phase of the disease, immunosuppressive strategies (for example with glucocorticoids or anticytokine drugs) may be considered. This latter stage is characterized by the development of progressive lung involvement with increasing oxygen requirements and occasionally signs of the hemophagocytic syndrome. The management of the disease in patients with kidney disease is even more challenging, especially in those who are immunosuppressed or with severe comorbidities. Here we present the therapeutic approach used in Brescia (Italy) for managing patients infected with COVID-19 who underwent kidney transplantation and are receiving hemodialysis. Furthermore, we provide some clinical and physiopathological background, as well as preliminary outcome data of our cohort, to better clarify the pathogenesis of the disease and clinical management. Key Words: COVID-19, dialysis, kidneys, management, patients, SARS-CoV-2, transplant

Abstract Background Post-traumatic cerebral infarction (PTCI) is common after traumatic brain injury (TBI). It is unclear what the occurrence of a PTCI is, how it impacts the long-term outcome, and whether it adds incremental prognostic value to established outcome predictors. Methods This was a prospective multicenter cohort study of moderate and severe TBI patients. The primary objective was to evaluate if PTCI was an independent risk factor for the 6-month outcome assessed with the Glasgow Outcome Scale (GOS). We also assessed the PTCI occurrence and if it adds incremental value to the International Mission for Prognosis and Clinical Trial design in TBI (IMPACT) core and extended models. Results We enrolled 143 patients, of whom 47 (32.9%) developed a PTCI. In the multiple ordered logistic regression, PTCI was retained in both the core and extended IMPACT models as an independent predictor of the GOS. The predictive performances increased significantly when PTCI was added to the IMPACT core model (AUC = 0.73, 95% C.I. 0.66–0.82; increased to AUC = 0.79, 95% CI 0.71–0.83, p = 0.0007) and extended model (AUC = 0.74, 95% C.I. 0.65–0.81 increased to AUC = 0.80, 95% C.I. 0.69–0.85; p = 0.00008). Patients with PTCI showed higher ICU mortality and 6-month mortality, whereas hospital mortality did not differ between the two groups. Conclusions PTCI is a common complication in patients suffering from a moderate or severe TBI and is an independent risk factor for long-term disability. The addition of PTCI to the IMPACT core and extended predictive models significantly increased their performance in predicting the GOS. Trial registration The present study was registered in ClinicalTrial.gov with the ID number NCT02430324.

The outcome for critically ill patients is burdened by a double mortality rate and a longer hospital stay in the case of sepsis or septic shock. The adequate use of antibiotics may impact on the outcome since they may affect the pharmacokinetics (Pk) and pharmacodynamics (Pd) of antibiotics in such patients. Acute renal failure (ARF) occurs in about 50% of septic patients, and the consequent need for continuous renal replacement therapy (CRRT) makes the renal elimination rate of most antibiotics highly variable. Antibiotics doses should be reduced in patients experiencing ARF, in accordance with the glomerular filtration rate (GFR), whereas posology should be increased in the case of CRRT. Since different settings of CRRT may be used, identifying a standard dosage of antibiotics is very difficult, because there is a risk of both oversimplification and failing the therapeutic efficacy. Indeed, it has been seen that, in over 25% of cases, the antibiotic therapy does not reach the necessary concentration target mainly due to lack of the proper minimal inhibitory concentration (MIC) achievement. The aim of this narrative review is to clarify whether shared algorithms exist, allowing them to inform the daily practice in the proper antibiotics posology for critically ill patients undergoing CRRT.

Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedation—in terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortality—between COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p < 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p < 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16–27) vs. 14 (10.5–19.5) days (p < 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.

OBJECTIVES:. To describe the epidemiology of superinfections (occurring > 48 hr after hospital admission) and their impact on the ICU and 28-day mortality in patients with coronavirus disease 2019 with acute respiratory distress syndrome, requiring mechanical ventilation. DESIGN:. Retrospective analysis of prospectively collected observational data. SETTING:. University-affiliated adult ICU. PATIENTS:. Ninety-two coronavirus disease 2019 patients admitted to the ICU from February 21, 2020, to May 6, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The prevalence of superinfection at ICU admission was 21.7%, and 53 patients (57.6%) had at least one superinfection during ICU stay, with a total of 75 (82%) ventilator-associated pneumonia and 57 (62%) systemic infections. The most common pathogens responsible for ventilator-associated pneumonia were Pseudomonas aeruginosa (n = 26, 34.7%) and Stenotrophomonas maltophilia (n = 14, 18.7%). Bloodstream infection occurred in 16 cases, including methicillin-resistant Staphylococcus epidermidis (n = 8, 14.0%), Enterococcus species (n = 6, 10.5%), and Streptococcus species (n = 2, 3.5%). Fungal infections occurred in 41 cases, including 36 probable (30 by Candida albicans, six by C. nonalbicans) and five proven invasive candidiasis (three C. albicans, two C. nonalbicans). Presence of bacterial infections (odds ratio, 10.53; 95% CI, 2.31–63.42; p = 0.005), age (odds ratio, 1.17; 95% CI, 1.07–1.31; p = 0.001), and the highest Sequential Organ Failure Assessment score (odds ratio, 1.27; 95% CI, 1.06–1.63; p = 0.032) were independently associated with ICU or 28-day mortality. CONCLUSIONS:. Prevalence of superinfections in coronavirus disease 2019 patients requiring mechanical ventilation was high in this series, and bacterial superinfections were independently associated with ICU or 28-day mortality (whichever comes first).

Background and Objective: Cerebral microdialysis (CMD) enables monitoring brain tissue metabolism and risk factors for secondary brain injury such as an imbalance of consumption, altered utilization, and delivery of oxygen and glucose, frequently present following spontaneous intracerebral hemorrhage (SICH). The aim of this study was to evaluate the relationship between lactate/pyruvate ratio (LPR) with hemodynamic variables [mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebrovascular pressure reactivity (PRx)] and metabolic variables (glutamate, glucose, and glycerol), within the cerebral peri-hemorrhagic region, with the hypothesis that there may be an association between these variables, leading to a worsening of outcome in comatose SICH patients.Methods: This is an international multicenter cohort study regarding a retrospective dataset analysis of non-consecutive comatose patients with supratentorial SICH undergoing invasive multimodality neuromonitoring admitted to neurocritical care units pertaining to three different centers. Patients with SICH were included if they had an indication for invasive ICP and CMD monitoring, were >18 years of age, and had a Glasgow Coma Scale (GCS) score of ≤8.Results: Twenty-two patients were included in the analysis. A total monitoring time of 1,558 h was analyzed, with a mean (SD) monitoring time of 70.72 h (66.25) per patient. Moreover, 21 out of the 22 patients (95%) had disturbed cerebrovascular autoregulation during the observation period. When considering a dichotomized LPR for a threshold level of 25 or 40, there was a statistically significant difference in all the measured variables (PRx, glucose, glutamate), but not glycerol. When dichotomized PRx was considered as the dependent variable, only LPR was related to autoregulation. A lower PRx was associated with a higher survival [27.9% (23.1%) vs. 56.0% (31.3%), p = 0.03].Conclusions: According to our results, disturbed autoregulation in comatose SICH patients is common. It is correlated to deranged metabolites within the peri-hemorrhagic region of the clot and is also associated with poor outcome.

Abstract Background Weaning protocols expedite extubation in mechanically ventilated patients, yet the literature investigating the application in tracheostomized patients remains scarce. The primary objective of this parallel randomized controlled pilot trial (RCT) was to assess the feasibility and safety of a nurse-led weaning protocol (protocol) compared to weaning based on physician’s clinical judgment (control) in tracheostomized critically ill patients. Results We enrolled 65 patients, 27 were in the protocol group and 38 in the control group. Of 27 patients in the protocol group, 1 (3.7%) died in the ICU, 24 (88.9%) were successfully weaned from tracheostomy, and 2 (7.4%) were transferred still on the ventilator. Of 38 patients in the control group, 2 (5.3%) died in the ICU, 22 (57.9%) were successfully weaned from tracheostomy, and 14 were transferred still on the ventilator (36.8%). Risk of being discharged from the ICU on the ventilator was higher in the control group (relative risk: 1.5, IC 95% 1.14–2.01). Concerning safety and feasibility, no patients were excluded after randomization. There was no crossover between the two study arms nor missing data, and no severe adverse event related to the study protocol application was recorded by the staff. Weaning time and rate of successful weaning were not different in the protocol group compared to the control group (long-rank test, p = 0.31 for MV duration, p = 0.45 for weaning time). Based on our results and assuming a 30% reduction of the weaning time for the protocol group, 280 patients would be needed for a RCT to establish efficacy. Conclusions In this pilot RCT we demonstrated that a nurse-led weaning protocol from tracheostomy was feasible and safe. A larger RCT is justified to assess efficacy.

Abstract In this review, we seek to highlight how critical illness and critical care affect longer-term outcomes, to underline the contribution of ICU delirium to cognitive dysfunction several months after ICU discharge, to give new insights into ICU acquired weakness, to emphasize the importance of value-based healthcare, and to delineate the elements of family-centered care. This consensus of 29 also provides a perspective and a research agenda about post-ICU recovery.

Capnocytophaga canimorsus infection was recently recognized as a zoonosis. We report the first case of fulminant septic shock in Italy caused by this pathogen. The patient, with a history of splenectomy, died at the main hospital in Brescia with a presumptive diagnosis of sepsis. PCR and sequencing on post mortem samples confirmed C. canimorsus as a causative organism. Our purpose is to alert medical professionals to the virulence of C. canimorsus in asplenic and immunocompromised patients. Keywords: Capnocytophaga canimorsus, septic shock, PCR, sequencing

We report a case of a 41-year-old man, victim of accidental avalanche burial, who donated his organs for transplantation after prolonged cardiopulmonary resuscitation and extracorporeal membrane oxygenation.

Intensive care unit–acquired weakness (ICU-AW) is the most common neuromuscular impairment in critically ill patients. We discuss critical aspects of ICU-AW that have not been completely defined or that are still under discussion. Critical illness polyneuropathy, myopathy, and muscle atrophy contribute in various proportions to ICU-AW. Diagnosis of ICU-AW is clinical and is based on Medical Research Council sum score and handgrip dynamometry for limb weakness and recognition of a patient’s ventilator dependency or difficult weaning from artificial ventilation for diaphragmatic weakness (DW). ICU-AW can be caused by a critical illness polyneuropathy, a critical illness myopathy, or muscle disuse atrophy, alone or in combination. Its diagnosis requires both clinical assessment of muscle strength and complete electrophysiological evaluation of peripheral nerves and muscles. The peroneal nerve test (PENT) is a quick simplified electrophysiological test with high sensitivity and good specificity that can be used instead of complete electrophysiological evaluation as a screening test in non-cooperative patients. DW, assessed by bilateral phrenic nerve magnetic stimulation or diaphragm ultrasound, can be an isolated event without concurrent limb muscle involvement. Therefore, it remains uncertain whether DW and limb weakness are different manifestations of the same syndrome or are two distinct entities. Delirium is often associated with ICU-AW but a clear correlation between these two entities requires further studies. Artificial nutrition may have an impact on ICU-AW, but no study has assessed the impact of nutrition on ICU-AW as the primary outcome. Early mobilization improves activity limitation at hospital discharge if it is started early in the ICU, but beneficial long-term effects are not established. Determinants of ICU-AW can be many and can interact with each other. Therefore, future studies assessing early mobilization should consider a holistic patient approach with consideration of all components that may lead to muscle weakness.

Aim. To evaluate the conditioning capabilities of the DAR™ Hygrobac™ S, a Heat and Moisture Exchanger (HME), using a new device to measure the temperature (T) and the absolute humidity (AH) of the ventilated gases in vivo during mechanical ventilation in Intensive Care Unit (ICU) patients. Materials and Methods. In 49 mechanically ventilated ICU patients, we evaluated T and AH, indicating the HME efficacy, during the inspiratory phase upstream and downstream the HME and the ratio of inspired AH to expired AH and the difference between expired T and inspired T indicated the HME efficiency. Efficacy and efficiency were assessed at three time points: at baseline (t0, HME positioning time), at 12 hours (t1), and at 24 hours (t2) using a dedicated, ad hoc built wireless device. Differences over time were evaluated using one-way ANOVA for repeated measures, whereas differences between in vivo and laboratory values (declared by the manufacturer according to UNI® EN ISO 9360 international standard) were evaluated using one-sample Student t-test. Results. 49 HMEs were analysed in vivo during mechanical ventilation. T and AH means (SD) of the inspired gas (the efficacy) were 31.5°C (1.54) and 32.3 mg/l (2.60) at t0, 31.1°C (1.34) and 31.7 mg/l (2.26) at t1, and 31°C (1.29) and 31.4 mg/l (2.27) at t2. Both efficiency parameters were constant over time (inspired AH/expired AH=89%, p=0.24; and expired T–inspired T = 2.2°C, p=0.81). Compared with laboratory values, in vivo T and AH indicating efficacy were significantly lower (p

Objectives: To evaluate the accuracy of the peroneal nerve test (PENT) in the diagnosis of critical illness polyneuropathy (CIP) and myopathy (CIM) in the intensive care unit (ICU). We hypothesised that abnormal reduction of peroneal compound muscle action potential (CMAP) amplitude predicts CIP/CIM diagnosed using a complete nerve conduction study and electromyography (NCS-EMG) as a reference diagnostic standard. Design: prospective observational study. Setting: Nine Italian ICUs. Patients: One-hundred and twenty-one adult (≥18 years) neurologic (106) and non-neurologic (15) critically ill patients with an ICU stay of at least 3 days. Interventions: None. Measurements and main results: Patients underwent PENT and NCS-EMG testing on the same day conducted by two independent clinicians who were blind to the results of the other test. Cases were considered as true negative if both NCS-EMG and PENT measurements were normal. Cases were considered as true positive if the PENT result was abnormal and NCS-EMG showed symmetric abnormal findings, independently from the specific diagnosis by NCS-EMG (CIP, CIM, or combined CIP and CIM). All data were centrally reviewed and diagnoses were evaluated for consistency with predefined electrophysiological diagnostic criteria for CIP/CIM. During the study period, 342 patients were evaluated, 124 (36.3%) were enrolled and 121 individuals with no protocol violation were studied. Sensitivity and specificity of PENT were 100% (95% CI 96.1-100.0) and 85.2% (95% CI 66.3-95.8). Of 23 patients with normal results, all presented normal values on both tests with no false negative results. Of 97 patients with abnormal results, 93 had abnormal values on both tests (true positive), whereas four with abnormal findings with PENT had only single peroneal nerve neuropathy at complete NCS-EMG (false positive). Conclusions: PENT has 100% sensitivity and high specificity, and can be used as a screening test to diagnose CIP/CIM in the ICU.

BackgroundDegeneration of intraepidermal nerve fibers (IENF) is a hallmark of small fiber neuropathy of different etiology, whose clinical picture is dominated by neuropathic pain. It is unknown if critical illness can affect IENF.MethodsWe enrolled 14 adult neurocritical care patients with prolonged intensive care unit (ICU) stay and artificial ventilation (≥ 3 days), and no previous history or risk factors for neuromuscular disease. All patients underwent neurological examination including evaluation of consciousness, sensory functions, muscle strength, nerve conduction study and needle electromyography, autonomic dysfunction using the finger wrinkling test, and skin biopsy for quantification of IENF and sweat gland innervation density during ICU stay and at follow-up visit. Development of infection, sepsis and multiple organ failure was recorded throughout the ICU stay.ResultsOf the 14 patients recruited, 13 (93%) had infections, sepsis or multiple organ failure. All had severe and non-length dependent loss of IENF. Sweat gland innervation was reduced in all except one patient. Of the 7 patients available for follow-up visit, three complained of diffuse sensory loss and burning pain, and another three showed clinical dysautonomia.ConclusionsSmall fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in neurocritical care survivors. Its impact on long term disability warrants further studies involving also non-neurologic critical care patients.

BackgroundMedia coverage of the vegetative state (VS) includes refutations of the VS diagnosis and describes behaviors inconsistent with VS. We used a quality score to assess the reporting in articles describing the medical characteristics of VS in Italian newspapers.Methodology/principal findingsOur search covered a 7-month period from July 1, 2008, to February 28, 2009, using the online searchable databases of four major Italian newspapers: Corriere della Sera, La Repubblica, La Stampa, and Avvenire. Medical reporting was judged as complete if three core VS characteristics were described: patient unawareness of self and the environment, preserved wakefulness (eyes open), and spontaneous respiration (artificial ventilator not needed). We retrieved 2,099 articles, and 967 were dedicated to VS. Of these, 853 (88.2%) were non-medical and mainly focused on describing the political, legal, and ethical aspects of VS. Of the 114 (11.8%) medical articles, 53 (5.5%) discussed other medical problems such as death by dehydration, artificial nutrition, neuroimaging, brain death, or uterine hemorrhage, and 61 (6.3%) described VS. Of these 61, only 18 (1.9%) reported all three CORE characteristics and were judged complete. We found no differences among the four investigated newspapers (Fisher's exact = 0.798), and incomplete articles were equally distributed between journalistic pieces and expert opinions (χ(2) = 1.8854, P = 0.170). Incorrect descriptions of VS were significantly more common among incomplete articles (13 of 43 vs. 1 of 18; Fisher's exact P = 0.047).Conclusions/significanceCore VS characteristics are rarely reported in Italian newspaper articles, which can alter adequate comprehension of new developments and (mis)inform political, legal, and ethical decisions.

Background Lockdown measures during the recent pandemic, due to the novel COVID-19, affected several other aspects of lifestyle, but little is known about their long-term impact, especially among adolescents. Our study aimed to assess the long-term consequences of changes in diet, exercise and screen activity levels, sleep quality, smoke, smartphone addiction and emotional distress among a sample of Italian adolescents, 2 years after the beginning of the pandemic.Methods We submitted an online survey to high-school students in the province of Brescia, a city in Northern Italy, investigating changes in food consumption and in physical and screen activities, cooking skills, sleep duration and quality, emotional distress, smartphone addiction and nutrition knowledge. We assigned an Eating Habit Index (EHI) score from 0 to 54, reflecting a current worsening (lower score) or improvement (higher score) in overall diet quality, compared with the pre-pandemic period. The χ2 test or Fisher’s exact probability test and Mann-Whitney test were used as appropriate; a binary logistic regression model was carried out, with EHI score≥33 as the dependent variable.Results We collected 1686 questionnaires. Consumption of healthy foods increased, as it was for ultraprocessed foods (UPFs). EHI score>33 (75° percentile value) was associated with female gender (OR 1.81, p