SARS-CoV-2 pneumonia succesfully treated with cpap and cycles of tripod position: a case report.

BACKGROUND: Pneumonia induced by 2019 Coronavirus (COVID-19) is characterized by hypoxemic respiratory failure that may present with a broad spectrum of clinical phenotypes. At the beginning, patients may have normal lung compliance and be responsive to noninvasive ventilatory support, such as CPAP. However, the transition to more severe respiratory failure - Severe Acute Respiratory Syndrome (SARS-CoV-2), necessitating invasive ventilation is often abrupt and characterized by a severe V/Q mismatch that require cycles of prone positioning. The aim of this case is to report the effect on gas exchange, respiratory mechanics and hemodynamics of tripod (or orthopneic sitting position) used as an alternative to prone position in a patient with mild SARS-CoV-2 pneumonia ventilated with helmet CPAP. CASE PRESENTATION: A 77-year-old awake and collaborating male patient with mild SARS-CoV-2 pneumonia and ventilated with Helmet CPAP, showed sudden worsening of gas exchange without dyspnea. After an unsuccessful attempt of prone positioning, we alternated three-hours cycles of semi-recumbent and tripod position, still keeping him in CPAP. Arterial blood gases (PaO2/FiO2, PaO2, SaO2, PaCO2 and A/a gradient), respiratory (VE, VT, RR) and hemodynamic parameters (HR, MAP) were collected in the supine and tripod position. Cycles of tripod position were continued for 3 days. The patient had a clinically important improvement in arterial blood gases and respiratory parameters, with stable hemodynamic and was successfully weaned and discharged to ward 10 days after pneumonia onset. CONCLUSIONS: Tripod position during Helmet CPAP can be applied safely in patients with mild SARS-CoV-2 pneumonia, with improvement of oxygenation and V/Q matching, thus reducing the need for intubation.

Validation of PLASMIC score and follow-up data in a cohort of patients with suspected microangiopathies from Southern Italy.

Severe ADAMTS13 deficiency (activity < 10%) is pathognomonic of thrombotic thrombocytopenic purpura. ADAMTS13 testing is time-consuming and unavailable in many hospitals. Recently, a seven-variables score named PLASMIC score, has been developed to stratify acute patients, based on their risk of having a severe ADAMTS13 deficiency. We present the application of this score in a cohort of patients referred to our Center. From 2012 to 2017, 42 patients with suspected thrombotic microangiopathies from 6 Centers were referred to Hemostasis and Thrombosis Center of "Casa Sollievo della Sofferenza" Hospital/Research Institute for ADAMTS13 testing. For all patients, relevant medical and laboratory information were collected. To obtain the statistical measure of the discriminatory power of PLASMIC scoring system, the Area Under the Curve Receiver Operating Characteristic (AUC ROC) was calculated. We were able to calculate the PLASMIC score in 27 out of 42 patients; we found a good discrimination performance of the score with a resulting AUC value of 0.86 (95% CI 0.71-1.0; p = 0.015). All patients but one with a high risk PLASMIC score (6-7) showed a severe deficiency. Among patients belonging to the intermediate risk (PLASMIC score 5) group, 2 showed normal ADAMTS13 activity and 2 levels below 10%. In none of the patients in the low risk group (PLASMIC score 0-4), a severe ADAMTS13 deficiency was found. Present results confirm and extend previous data regarding the predictive value of the PLASMIC score. Indeed, it shows a good diagnostic performance and can be useful for decision makers to properly and promptly define the better therapeutic approach.

Peep titration based on the open lung approach during one lung ventilation in thoracic surgery: a physiological study.

BACKGROUND: During thoracic surgery in lateral decubitus, one lung ventilation (OLV) may impair respiratory mechanics and gas exchange. We tested a strategy based on an open lung approach (OLA) consisting in lung recruitment immediately followed by a decremental positive-end expiratory pressure (PEEP) titration to the best respiratory system compliance (CRS) and separately quantified the elastic properties of the lung and the chest wall. Our hypothesis was that this approach would improve gas exchange. Further, we were interested in documenting the impact of the OLA on partitioned respiratory system mechanics. METHODS: In thirteen patients undergoing upper left lobectomy we studied lung and chest wall mechanics, transpulmonary pressure (PL), respiratory system and transpulmonary driving pressure (ΔPRS and ΔPL), gas exchange and hemodynamics at two time-points (a) during OLV at zero end-expiratory pressure (OLVpre-OLA) and (b) after the application of the open-lung strategy (OLVpost-OLA). RESULTS: The external PEEP selected through the OLA was 6 ± 0.8 cmH2O. As compared to OLVpre-OLA, the PaO2/FiO2 ratio went from 205 ± 73 to 313 ± 86 (p = .05) and CL increased from 56 ± 18 ml/cmH2O to 71 ± 12 ml/cmH2O (p = .0013), without changes in CCW. Both ΔPRS and ΔPL decreased from 9.2 ± 0.4 cmH2O to 6.8 ± 0.6 cmH2O and from 8.1 ± 0.5 cmH2O to 5.7 ± 0.5 cmH2O, (p = .001 and p = .015 vs OLVpre-OLA), respectively. Hemodynamic parameters remained stable throughout the study period. CONCLUSIONS: In our patients, the OLA strategy performed during OLV improved oxygenation and increased CL and had no clinically significant hemodynamic effects. Although our study was not specifically designed to study ΔPRS and ΔPL, we observed a parallel reduction of both after the OLA. TRIAL REGISTRATION: TRN: ClinicalTrials.gov , NCT03435523 , retrospectively registered, Feb 14 2018.

Electrical Impedance Tomography during Abdominal Laparoscopic Surgery: A Physiological Pilot Study.

BACKGROUND: Both general anesthesia and pneumoperitoneum insufflation during abdominal laparoscopic surgery can lead to atelectasis and impairment in oxygenation. Setting an appropriate level of external PEEP could reduce the occurrence of atelectasis and induce an improvement in gas exchange. However, in clinical practice, it is common to use a fixed PEEP level (i.e., 5 cmH2O), irrespective of the dynamic respiratory mechanics. We hypothesized setting a PEEP level guided by EIT in order to obtain an improvement in oxygenation and respiratory system compliance in lung-healthy patients than can benefit a personalized approach. METHODS: Twelve consecutive patients scheduled for abdominal laparoscopic surgery were enrolled in this prospective study. The EIT Timpel Enlight 1800 was applied to each patient and a dedicated pneumotachograph and a spirometer flow sensor, integrated with EIT, constantly recorded respiratory mechanics. Gas exchange, respiratory mechanics and hemodynamics were recorded at five time points: T0, baseline; T1, after induction; T2, after pneumoperitoneum insufflation; T3, after a recruitment maneuver; and T4, at the end of surgery after desufflation. RESULTS: A titrated mean PEEP of 8 cmH2O applied after a recruitment maneuver was successfully associated with the "best" compliance (58.4 ± 5.43 mL/cmH2O), with a low percentage of collapse (10%), an acceptable level of hyperdistention (0.02%). Pneumoperitoneum insufflation worsened respiratory system compliance, plateau pressure, and driving pressure, which significantly improved after the application of the recruitment maneuver and appropriate PEEP. PaO2 increased from 78.1 ± 9.49 mmHg at T0 to 188 ± 66.7 mmHg at T4 (p < 0.01). Other respiratory parameters remained stable after abdominal desufflation. Hemodynamic parameters remained unchanged throughout the study. CONCLUSIONS: EIT, used as a non-invasive intra-operative monitor, enables the rapid assessment of lung volume and regional ventilation changes in patients undergoing laparoscopic surgery and helps to identify the "optimal" PEEP level in the operating theatre, improving ventilation strategies.

Immunological effects of glutamine supplementation in polytrauma patients in intensive care unit.

BACKGROUND: In polytrauma intensive care unit (ICU) patients, glutamine (GLN) becomes a "conditionally essential" amino acid; its role has been extensively studied in numerous clinical trials but their results are inconclusive. We evaluated the IgA-mediated humoral immunity after GLN supplementation in polytrauma ICU patients. METHODS: All consecutive patients with polytrauma who required mechanical ventilation and enteral nutrition (EN) provided within 24 h since the admission in ICU at the University Hospital of Foggia from September 2016 to February 2017 were included. Thereafter, two groups were identified: patients treated by conventional EN (25 kcal/kg/die) and patients who have received conventional EN enriched with 50 mg/kg/ideal body weight of alanyl-GLN 20% intravenously. We analysed the plasmatic concentration of IgA, CD3+/CD4+ T helper lymphocytes, CD3+/CD8+ T suppressor lymphocytes, CD3+/CD19+ B lymphocytes, IL-4 and IL-2 at admission and at 4 and 8 days. RESULTS: We identified 30 patients, with 15 subjects per group. IgA levels increased significantly in GLN vs the control group at T0, T4 and T8. CD3+/CD4+ T helper lymphocyte and CD3+/CD8+ T suppressor lymphocyte levels significantly increased in GLN vs the control group at T4 and T8. CD3+/CD19+ B lymphocyte levels increased significantly in GLN vs the control group only at T8. IL-2 and IL-4 levels showed no significant differences when comparing GLN with the control group. CONCLUSIONS: Our study showed that there was an improvement in humoral and cell-mediated immunity with GLN supplementation in polytrauma ICU patients using recommended doses.

Machine learning and predictive models: 2 years of Sars-CoV-2 pandemic in a single-center retrospective analysis.

BACKGROUND: Since January 2020, coronavirus disease 19 (COVID-19) has rapidly spread all over the world. An early assessment of illness severity is crucial for the stratification of patients in order to address them to the right intensity path of care. We performed an analysis on a large cohort of COVID-19 patients (n=581) hospitalized between March 2020 and May 2021 in our intensive care unit (ICU) at Policlinico Riuniti di Foggia hospital. Through an integration of the scores, demographic data, clinical history, laboratory findings, respiratory parameters, a correlation analysis, and the use of machine learning our study aimed to develop a model to predict the main outcome. METHODS: We deemed eligible for analysis all adult patients (age >18 years old) admitted to our department. We excluded all the patients with an ICU length of stay inferior to 24 h and the ones that declined to participate in our data collection. We collected demographic data, medical history, D-dimers, NEWS2, and MEWS scores on ICU admission and on ED admission, PaO2/FiO2 ratio on ICU admission, and the respiratory support modalities before the orotracheal intubation and the intubation timing (early vs late with a 48-h hospital length of stay cutoff). We further collected the ICU and hospital lengths of stay expressed in days of hospitalization, hospital location (high dependency unit, HDU, ED), and length of stay before and after ICU admission; the in-hospital mortality; and the in-ICU mortality. We performed univariate, bivariate, and multivariate statistical analyses. RESULTS: SARS-CoV-2 mortality was positively correlated to age, length of stay in HDU, MEWS, and NEWS2 on ICU admission, D-dimer value on ICU admission, early orotracheal intubation, and late orotracheal intubation. We found a negative correlation between the PaO2/FiO2 ratio on ICU admission and NIV. No significant correlations with sex, obesity, arterial hypertension, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, diabetes mellitus, dyslipidemia, and neither MEWS nor NEWS on ED admission were observed. Considering all the pre-ICU variables, none of the machine learning algorithms performed well in developing a prediction model accurate enough to predict the outcome although a secondary multivariate analysis focused on the ventilation modalities and the main outcome confirmed how the choice of the right ventilatory support with the right timing is crucial. CONCLUSION: In our cohort of COVID patients, the choice of the right ventilatory support at the right time has been crucial, severity scores, and clinical judgment gave support in identifying patients at risk of developing a severe disease, comorbidities showed a lower weight than expected considering the main outcome, and machine learning method integration could be a fundamental statistical tool in the comprehensive evaluation of such complex diseases.

A Pilot Study on Electrical Impedance Tomography During CPAP Trial in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: The Bright Side of Non-invasive Ventilation.

Background: Different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia phenotypes were described that match with different lung compliance and level of oxygenation, thus requiring a personalized ventilator setting. The burden of so many patients and the lack of intensive care unit (ICU) beds often force physicians to choose non-invasive ventilation (NIV) as the first approach, even if no consent has still been reached to discriminate whether it is safer to choose straightforward intubation, paralysis, and protective ventilation. Under such conditions, electrical impedance tomography (EIT), a non-invasive bedside tool to monitor lung ventilation and perfusion defects, could be useful to assess the response of patients to NIV and choose rapidly the right ventilatory strategy. Objective: The rationale behind this study is that derecruitment is a more efficient measure of positive end expiratory pressure (PEEP)-dependency of patients than recruitment. We hypothesized that patients who derecruit significantly when PEEP is reduced are the ones that do not need early intubation while small end-expiratory lung volume (ΔEELV) variations after a single step of PEEP de-escalation could be predictive of NIV failure. Materials and Methods: Consecutive patients admitted to ICU with confirmed SARS-CoV-2 pneumonia ventilated in NIV were enrolled. Exclusion criteria were former intubation or NIV lasting > 72 h. A trial of continuos positive airway pressure (CPAP) 12 was applied in every patient for at least 15 min, followed by the second period of CPAP 6, either in the supine or prone position. Besides standard monitoring, ventilation of patients was assessed by EIT, and end-expiratory lung impedance (ΔEELI) (%) was calculated as the difference in EELI between CPAP12 and CPAP6. Tidal volume (Vt), Ve, respiratory rate (RR), and FiO2 were recorded, and ABGs were measured. Data were analyzed offline using the dedicated software. The decision to intubate or continue NIV was in charge of treating physicians, independently from study results. Outcomes of patients in terms of intubation rate and ICU mortality were recorded. Results: We enrolled 10 male patients, with a mean age of 67 years. Six patients (60%) were successfully treated by NIV until ICU discharge (Group S), and four patients failed NIV and were intubated and switched to MV (Group F). All these patients died in ICU. During the supine CPAP decremental trial, all patients experienced an increase in RR and Ve. ΔEELI was < 40% in Group F and > 50% in Group S. In the prone trial, ΔEELI was > 50% in all patients, while RR decreased in Group S and remained unchanged in Group F. Conclusion: ΔEELI < 40% after a single PEEP de-escalation step in supine position seems to be a good predictor of poor recruitment and CPAP failure.

Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial).

INTRODUCTION: In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250 mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose. METHODS AND ANALYSIS: The study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60 mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100 mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250 mg/kg. The primary endpoint will be all-cause mortality at 28 days. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell'Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences. TRIAL REGISTRATION DETAILS: The trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019.

Patient-Ventilator Asynchronies: Clinical Implications and Practical Solutions.

Mechanical ventilation is a supportive treatment commonly applied in critically ill patients. Whenever the patient is spontaneously breathing, the pressure applied to the respiratory system depends on the sum of the pressure generated by the respiratory muscles and the pressure generated by the ventilator. Patient-ventilator interaction is of utmost importance in spontaneously breathing patients, and thus the ventilator should be able to adapt to patient's changes in ventilatory demand and respiratory mechanics. Nevertheless, a lack of coordination between patient and ventilator due to a mismatch between neural and ventilator timing throughout the respiratory cycle may make weaning difficult and lead to prolonged mechanical ventilation. Therefore, appropriate monitoring of asynchronies is mandatory to improve the applied strategies and thus improve patient-ventilator interaction. We conducted a literature review regarding patient-ventilator interaction with a focus on the different kinds of inspiratory and expiratory asynchronies, their monitoring, clinical implications, possible prevention, and treatment. We believe that monitoring patient-ventilator interaction is mandatory in spontaneously breathing patients to understand, by using the available technologies, the type of asynchrony and consequently improve the adaptation of the ventilator to the patient's needs. Asynchronies are relatively frequent during mechanical ventilation in critically ill patients, and they are associated with poor outcomes. This review summarizes the different types of asynchronies and their mechanisms, consequences, and potential management. The development and understanding of monitoring tools are necessary to allow a better appraisal of this area, which may lead to better outcomes for patients.

Intra-abdominal hypertension and acute renal failure in critically ill patients.

OBJECTIVE: To investigate the relationship between intra-abdominal hypertension (IAH) and acute renal failure (ARF) in critically ill patients. DESIGN AND SETTING: Prospective, observational study in a general intensive care unit. PATIENTS: Patients consecutively admitted for >24 h during a 6-month period. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Intra-abdominal pressure (IAP) was measured through the urinary bladder pressure measurement method. The IAH was defined as a IAP > or =12 mmHg in at least two consecutive measurements performed at 24-h intervals. The ARF was defined as the failure class of the RIFLE classification. Of 123 patients, 37 (30.1%) developed IAH. Twenty-three patients developed ARF (with an overall incidence of 19%), 16 (43.2%) in IAH and 7 (8.1%) in non-IAH group (p<0.05). Shock (p<0.001), IAH (p=0.002) and low abdominal perfusion pressure (APP; p=0.046) resulted as the best predictive factors for ARF. The optimum cut-off point of IAP for ARF development was 12 mmHg, with a sensitivity of 91.3% and a specificity of 67%. The best cut-off values of APP and filtration gradient (FG) for ARF development were 52 and 38 mmHg, respectively. Age(p=0.002), cumulative fluid balance (p=0.002) and shock (p=0.006) were independent predictive factors of IAH. Raw hospital mortality rate was significantly higher in patients with IAH; however, risk-adjusted and O/E ratio mortality rates were not different between groups. CONCLUSIONS: In critically ill patients IAH is an independent predictive factor of ARF at IAP levels as low as 12 mmHg, although the contribution of impaired systemic haemodynamics should also be considered.

Reference values for coagulation assessment in full-term newborns.

BACKGROUND: Most data in the literature report reduced coagulation activities in the first few days of life with respect to adults and the effects of these differences must be considered when diagnosing and treating hemostatic disorders. The management of pediatric population is further complicated by the lack of age-related reference values and by the unreliability of currently-used hemostatic tests, while an accurate interpretation of results is required to reduce the cases of inappropriate investigation. Thromboelastography (TEG®) is a point-of-care test that provides an efficient analysis of the dynamic viscoelastic properties of whole blood that may provide superior evaluation and management of coagulopathies in newborn. This study was designed to determine reference values for kaolin-activated TEG in full-term healthy newborn by taking small blood samples from the umbilical cord and facilitate accurate interpretation of neonatal TEG results. METHODS: Kaolin-activated TEG was performed in 85 full-term healthy newborn and 40 healthy adults. TEG data analyzed were: reaction time, clot formation time, α-angle, maximum amplitude, clot lysis at 30 minutes, Functional Fibrinogen and coagulation index. RESULTS: Reference values for kaolin-activated TEG in healthy full-term newborn are presented, despite a large variability in reaction time, clot formation time and in coagulation index, not significant impact on range values was evident and no significant differences between neonates and adults were observed. CONCLUSIONS: Neonatal coagulation tests are closer to adult standards and although significant age-related differences in kaolin-activated TEG variables do not appear to be present, the usefulness of TEG for pediatric population is an open field that needs to be further evaluated, the results of this study can be used to interpret the data for newborn.

Transesophageal echocardiography for diagnosis of traumatic aortic injury: an appraisal of the evidence.

BACKGROUND: An overview of the validity of transesophageal echocardiography (TEE) in patients suspected to have traumatic aortic injury (TAI). METHODS: Computerized bibliographic search of trials from 1994 to 2002 evaluating the use of TEE to confirm the diagnosis of TAI. Seven relevant studies out of 204 were identified, involving 758 patients. The accuracy of TEE was analyzed by constructing summary receiver-operating characteristic (sROC) curves and computing areas under the sROC curve. RESULTS: No prospective randomized trial was found. Although accuracy varied greatly, summary ROC curve found that TEE enjoyed a high diagnostic performance. Some study characteristics can affect accuracy. CONCLUSIONS: Our findings seems to indicate that TEE is a valuable tool for diagnosing TAI, and its use as first-line evaluation of such patients can be supported; however, given the lack of randomized trials, no standard of care can be drawn from the present overview: future studies should look at this problem more carefully, and should be methodologically rigorous.