Effects of CPAP and FiO2 on respiratory effort and lung stress in early COVID-19 pneumonia: a randomized, crossover study.

BACKGROUND: in COVID-19 acute respiratory failure, the effects of CPAP and FiO2 on respiratory effort and lung stress are unclear. We hypothesize that, in the compliant lungs of early Sars-CoV-2 pneumonia, the application of positive pressure through Helmet-CPAP may not decrease respiratory effort, and rather worsen lung stress and oxygenation when compared to higher FiO2 delivered via oxygen masks. METHODS: In this single-center (S.Luigi Gonzaga University-Hospital, Turin, Italy), randomized, crossover study, we included patients receiving Helmet-CPAP for early (< 48 h) COVID-19 pneumonia without additional cardiac or respiratory disease. Healthy subjects were included as controls. Participants were equipped with an esophageal catheter, a non-invasive cardiac output monitor, and an arterial catheter. The protocol consisted of a random sequence of non-rebreather mask (NRB), Helmet-CPAP (with variable positive pressure and FiO2) and Venturi mask (FiO2 0.5), each delivered for 20 min. Study outcomes were changes in respiratory effort (esophageal swing), total lung stress (dynamic + static transpulmonary pressure), gas-exchange and hemodynamics. RESULTS: We enrolled 28 COVID-19 patients and 7 healthy controls. In all patients, respiratory effort increased from NRB to Helmet-CPAP (5.0 ± 3.7 vs 8.3 ± 3.9 cmH2O, p < 0.01). However, Helmet's pressure decreased by a comparable amount during inspiration (- 3.1 ± 1.0 cmH2O, p = 0.16), therefore dynamic stress remained stable (p = 0.97). Changes in static and total lung stress from NRB to Helmet-CPAP were overall not significant (p = 0.07 and p = 0.09, respectively), but showed high interpatient variability, ranging from - 4.5 to + 6.1 cmH2O, and from - 5.8 to + 5.7 cmH2O, respectively. All findings were confirmed in healthy subjects, except for an increase in dynamic stress (p < 0.01). PaO2 decreased from NRB to Helmet-CPAP with FiO2 0.5 (107 ± 55 vs 86 ± 30 mmHg, p < 0.01), irrespective of positive pressure levels (p = 0.64). Conversely, with Helmet's FiO2 0.9, PaO2 increased (p < 0.01), but oxygen delivery remained stable (p = 0.48) as cardiac output decreased (p = 0.02). When PaO2 fell below 60 mmHg with VM, respiratory effort increased proportionally (p < 0.01, r = 0.81). CONCLUSIONS: In early COVID-19 pneumonia, Helmet-CPAP increases respiratory effort without altering dynamic stress, while the effects upon static and total stress are variable, requiring individual assessment. Oxygen masks with higher FiO2 provide better oxygenation with lower respiratory effort. Trial registration Retrospectively registered (13-May-2021): clinicaltrials.gov (NCT04885517), https://clinicaltrials.gov/ct2/show/NCT04885517 .

Efficacy and adverse events profile of videolaryngoscopy in critically ill patients: subanalysis of the INTUBE study.

BACKGROUND: Tracheal intubation is a high-risk procedure in the critically ill, with increased intubation failure rates and a high risk of other adverse events. Videolaryngoscopy might improve intubation outcomes in this population, but evidence remains conflicting, and its impact on adverse event rates is debated. METHODS: This is a subanalysis of a large international prospective cohort of critically ill patients (INTUBE Study) performed from 1 October 2018 to 31 July 2019 and involving 197 sites from 29 countries across five continents. Our primary aim was to determine the first-pass intubation success rates of videolaryngoscopy. Secondary aims were characterising (a) videolaryngoscopy use in the critically ill patient population and (b) the incidence of severe adverse effects compared with direct laryngoscopy. RESULTS: Of 2916 patients, videolaryngoscopy was used in 500 patients (17.2%) and direct laryngoscopy in 2416 (82.8%). First-pass intubation success was higher with videolaryngoscopy compared with direct laryngoscopy (84% vs 79%, P=0.02). Patients undergoing videolaryngoscopy had a higher frequency of difficult airway predictors (60% vs 40%, P<0.001). In adjusted analyses, videolaryngoscopy increased the probability of first-pass intubation success, with an OR of 1.40 (95% confidence interval [CI] 1.05-1.87). Videolaryngoscopy was not significantly associated with risk of major adverse events (odds ratio 1.24, 95% CI 0.95-1.62) or cardiovascular events (odds ratio 0.78, 95% CI 0.60-1.02). CONCLUSIONS: In critically ill patients, videolaryngoscopy was associated with higher first-pass intubation success rates, despite being used in a population at higher risk of difficult airway management. Videolaryngoscopy was not associated with overall risk of major adverse events. CLINICAL TRIAL REGISTRATION: NCT03616054.

Peri-intubation Cardiovascular Collapse in Patients Who Are Critically Ill: Insights from the INTUBE Study.

Rationale: Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. Objectives: To identify potentially modifiable variables associated with peri-intubation cardiovascular instability/collapse (i.e., systolic arterial pressure <65 mm Hg [once] or <90 mm Hg for >30 minutes; new/increased vasopressor requirement; fluid bolus >15 ml/kg, or cardiac arrest). Methods: INTUBE (International Observational Study to Understand the Impact and Best Practices of Airway Management In Critically Ill Patients) was a multicenter prospective cohort study of patients who were critically ill and undergoing tracheal intubation in a convenience sample of 197 sites from 29 countries across five continents from October 1, 2018, to July 31, 2019. Measurements and Main Results: A total of 2,760 patients were included in this analysis. Peri-intubation cardiovascular instability/collapse occurred in 1,199 out of 2,760 patients (43.4%). Variables associated with this event were older age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02-1.03), higher heart rate (OR, 1.008; 95% CI, 1.004-1.012), lower systolic blood pressure (OR, 0.98; 95% CI, 0.98-0.99), lower oxygen saturation as measured by pulse oximetry/FiO2 before induction (OR, 0.998; 95% CI, 0.997-0.999), and the use of propofol as an induction agent (OR, 1.28; 95% CI, 1.05-1.57). Patients with peri-intubation cardiovascular instability/collapse were at a higher risk of ICU mortality with an adjusted OR of 2.47 (95% CI, 1.72-3.55), P < 0.001. The inverse probability of treatment weighting method identified the use of propofol as the only factor independently associated with cardiovascular instability/collapse (OR, 1.23; 95% CI, 1.02-1.49). When administered before induction, vasopressors (OR, 1.33; 95% CI, 0.84-2.11) or fluid boluses (OR, 1.17; 95% CI, 0.96-1.44) did not reduce the incidence of cardiovascular instability/collapse. Conclusions: Peri-intubation cardiovascular instability/collapse was associated with an increased risk of both ICU and 28-day mortality. The use of propofol for induction was identified as a modifiable intervention significantly associated with cardiovascular instability/collapse.Clinical trial registered with clinicaltrials.gov (NCT03616054).

Challenges and outcomes in airway management outside the operating room.

PURPOSE OF REVIEW: Airway management outside the operating room poses unique challenges that every clinician should recognize. These include anatomic, physiologic, and logistic challenges, each of which can contribute to complications and lead to poor outcomes. Recognizing these challenges and highlighting known outcome data may better prepare the team, making this otherwise daunting procedure safer and potentially improving patient outcomes. RECENT FINDINGS: Newer intubating techniques and devices have made navigating anatomic airway challenges easier. However, physiological challenges during emergency airway management remain a cause of poor patient outcomes. Hemodynamic collapse has been identified as the most common peri-intubation adverse event and a leading cause of morbidity and mortality associated with the procedure. SUMMARY: Emergency airway management outside the operating room remains a high-risk procedure, associated with poor outcomes. Pre-intubation hemodynamic optimization may mitigate some of the risks, and future research should focus on identification of best strategies for hemodynamic optimization prior to and during this procedure.

Tracheal intubation in the critically ill patient.

Tracheal intubation is among the most commonly performed and high-risk procedures in critical care. Indeed, 45% of patients undergoing intubation experience at least one major peri-intubation adverse event, with cardiovascular instability being the most common event reported in 43%, followed by severe hypoxemia in 9% and cardiac arrest in 3% of cases. These peri-intubation adverse events may expose patients to a higher risk of 28-day mortality, and they are more frequently observed with an increasing number of attempts to secure the airway. The higher risk of peri-intubation complications in critically ill patients, compared with the anaesthesia setting, is the consequence of their deranged physiology (e.g. underlying respiratory failure, shock and/or acidosis) and, in this regard, airway management in critical care has been defined as "physiologically difficult". In recent years, several randomised studies have investigated the most effective preoxy-genation strategies, and evidence for the use of positive pressure ventilation in moderate-to-severe hypoxemic patients is established. On the other hand, evidence on interventions to mitigate haemodynamic collapse after intubation has been elusive. Airway management in COVID-19 patients is even more challenging because of the additional risk of infection for healthcare workers, which has influenced clinical choices in this patient group. The aim of this review is to provide an update of the evidence for intubation in critically ill patients with a focus on understanding peri-intubation risks and evaluating interventions to prevent or mitigate adverse events.

Short and long-term complications due to standard and extended prone position cycles in CoViD-19 patients.

OBJECTIVE: To investigate short and long-term complications due to standard (≤24 hours) and extended (>24 hours) prone position in COVID-19 patients. METHODS: Retrospective cohort study conducted in an Italian general intensive care unit. We enrolled patients on invasive mechanical ventilation and treated with prone positioning. We recorded short term complications from the data chart and long-term complications from the scheduled follow-up visit, three months after intensive care discharge. RESULTS: A total of 96 patients were included in the study. Median time for each prone positioning cycle (302 cycles) was equal to 18 (16-32) hours. In 37 (38%) patients at least one cycle of extended pronation was implemented. Patients with at least one pressure sore due to prone position were 38 (40%). Patients with pressure sores showed a statistically significative difference in intensive care length of stay, mechanical ventilation days, numbers of prone position cycles, total time spent in prone position and the use of extended prone position, compared to patients without pressure sores. All lesions were low grade. Cheekbones (18%) and chin (10%) were the most affected sites. Follow-up visit, scheduled three months after intensive care discharge, was possible in 58 patients. All patients were able to have all 12 muscle groups examined using theMedical Research Council scale examination. No patient reported sensory loss or presence of neuropathic pain for upper limbs. CONCLUSIONS: Extended prone position is feasible and might reduce the workload on healthcare workers without significant increase of major prone position related complications.

Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac?

BACKGROUND: Cytokine release syndrome (CRS) is a major complication after chimeric-antigen receptor T-cell treatment, characterized by an uncontrolled systemic inflammatory reaction. We investigated the potential role of diclofenac in the management of CRS in five pediatric patients treated for relapsed/refractory B-lineage acute lymphoblastic leukemia. METHODS: In case of persistent fever with fever-free intervals shorter than 3 hours, diclofenac continuous infusion was initiated, at the starting dose of 0.5 mg/Kg/day, the lowest effective pediatric dose in our experience, possibly escalated up to 1 mg/Kg/day, as per institutional guidelines. RESULTS: CRS occurred at a median of 20 hours (range 8-27) after tisagenlecleucel infusion. Diclofenac was started at a median of 20 hours (range 13-33) after fever onset. A mean of 3.07 febrile peaks without diclofenac and 0.95 with diclofenac were reported (p = 0.02). Clinical benefit was achieved by hampering the progression of tachypnea and tachycardia. Despite fever control, CRS progressed in four of the five patients, and hypotension requiring vasopressors and fluid retention, as well as hypoxia, occurred. Vasopressors were followed by 1-2 doses of tocilizumab (one in patient 2 and two in patients 3, 4, and 5), plus steroids in patients 4 and 5. CONCLUSION: Based on a limited number of patients, diclofenac leads to better fever control, which translates into symptom relief and improvement of tachycardia, but could not prevent the progression of CRS.

Capnography use in the critical care setting: why do clinicians fail to implement this safety measure?

Tracheal intubation is among the most frequently performed manoeuvres in the critical care setting, and can be life-saving in critical illness, though also associated with serious adverse events such as oesophageal intubation or tracheal tube obstruction, displacement, or disconnection from the ventilator. A key finding of the 4th National Audit Project (NAP4) was identification of waveform capnography as the single intervention with the highest potential for reducing morbidity and mortality during tracheal intubation and maintenance of an artificial airway. In the INTUBE study, penetration of capnography into ICUs was low, and was not in use in 70% of the episodes of oesophageal intubation. To reduce harm and avoidable death, there is a need for a global initiative to increase access to and use of capnography in ICUs.

Helmet and face mask for non-invasive respiratory support in patients with acute hypoxemic respiratory failure: A retrospective study.

PURPOSE: Non-invasive respiratory support could reduce the incidence of intubation in patients with Acute Hypoxemic Respiratory Failure (AHRF). The optimal interface or modality of non-invasive respiratory support is debated. We sought to evaluate the differences between patients who succeeded or failed non-invasive respiratory support, with a specific focus on the type of non-invasive respiratory support (i.e. helmet CPAP versus face mask NIV). MATERIALS AND METHODS: In a single-center observational retrospective study, we investigated baseline, clinical characteristics and AHRF management by non-invasive respiratory support between January 2015 to December 2016. Data on gas exchange and respiratory mechanics, non-invasive respiratory support duration, ICU length of stay and mortality were collected. RESULTS: 110 patients with AHRF were included of which 41 patients (37%) were intubated. The use of helmet CPAP (p = 0.016) and a lower fluid balance (p = 0.038) were independently associated with a decreased rate of intubation after adjustment for confounders. Face mask NIV patients trended to a higher respiratory frequency at 1 h after treatment [28 (22-36) versus 24 (18-29) hours, p = 0.067], and showed a longer ICU stay (p = 0.009) compared to patients treated with helmet CPAP. CONCLUSIONS: Helmet CPAP and a lower fluid balance were independent predictors of a lower intubation rate in AHRF patients in ICU. Prospective studies aimed at identifying the optimal interface and modality of non-invasive respiratory support in AHRF patients are needed.

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events-in particular cardiovascular instability-were observed frequently.

Thromboelastometry, Thromboelastography, and Conventional Tests to Assess Anticoagulation During Extracorporeal Support: A Prospective Observational Study.

Optimal anticoagulation monitoring in patients with extracorporeal membrane oxygenation (ECMO) is fundamental to avoid hemorrhagic and thromboembolic complications. Besides conventional coagulation tests, there is growing interest in the use of viscoelastic hemostatic assays (VHA), in particular of tromboelastography (TEG). Evidence on the use of rotational thromboelastometry (ROTEM) is lacking in this setting. The aim of the study was to evaluate ROTEM as a tool for assessing hemostasis during ECMO, by comparing it to TEG and conventional coagulation assays. We conducted a prospective, observational, single-center study on adult patients on ECMO support anticoagulated with unfractioned heparin (UFH). Kaolin reaction time (R, min) for TEG and INTEM clotting time (CT, sec) for ROTEM were analyzed and compared with conventional coagulation tests. In the study period, we included 25 patients on ECMO support (14 V-A and 11 V-V); 84 data points were available for the analysis. Median UFH infusion rate was 15 [11-18] IU/min/kg. Median values for activated partial thromboplastin time (aPTT) ratio, Kaolin TEG R time, and INTEM CT were 1.44 [1.21-1.7], 22 [13-40] min, and 201 [183-225] sec, respectively. INTEM CT (ROTEM) showed a moderate correlation with standard coagulation tests (R2 = 0.34 and 0.3 for aPTT and activated clotting time (ACT), respectively, p < 0.001). No significant correlation was found between INTEM CT and Kaolin R time (R2 = 0.01). Further studies are needed to identify an appropriate anticoagulation target for ROTEM during ECMO.

Management of critically ill patients with COVID-19: suggestions and instructions from the coordination of intensive care units of Lombardy.

With 63,098 confirmed cases on 17 April 2020 and 11,384 deaths, Lombardy has been the most affected region in Italy by coronavirus disease 2019 (COVID-19). To cope with this emergency, the COVID-19 Lombardy intensive care units (ICU) network was created. The network identified the need of defining a list of clinical recommendations to standardize treatment of patients with COVID-19 admitted to Intensive Care Unit (ICU). Three core topics were identified: 1) rational use of intensive care resources; 2) ventilation strategies; 3) non-ventilatory interventions. Identification of patients who may benefit from ICU treatment is challenging. Clinicians should consider baseline performance and frailty status and they should adopt disease-specific staging tools. Continuous positive airway pressure, mainly delivered through a helmet as elective method, should be considered as initial treatment for all patients with respiratory failure associated with COVID-19. In case of persisting dyspnea and/or desaturation despite 4-6 hours of noninvasive ventilation, endotracheal intubation and invasive mechanical ventilation should be considered. In the early phase, muscle relaxant use and volume-controlled ventilation is recommended. Prone position should be performed in patients with PaO2/FiO2≤100 mmHg. For patients admitted to ICU with COVID-19 interstitial pneumonia, we do not recommend empiric antibiotic therapy for community-acquired pneumonia. Consultation of an infectious disease specialist is suggested before start of any antiviral therapy. In conclusion, the COVID-19 Lombardy ICU Network identified a list of best practice statements supported by the available evidence and clinical experience or identified as panel members expert opinions for the management of critically ill patients with COVID-19.