A Prospective Comparison of Standard Technique, Doppler Ultrasonography, and Pressure Waveform Analysis for Confirming Intraosseous Catheter Placement.

Purpose: Intraosseous (IO) catheters allow healthcare workers to rapidly administer fluids and medications to critically ill patients when intravenous access is inadequate or unable to be obtained. An improperly placed IO catheter can lead to delays in care, as well as serious complications such as limb necrosis. Methods: In this single-center, prospective, observational study, we compared 2 established methods of confirming proper IO catheter placement to a novel pressure waveform analysis technique in which the IO catheter is attached to a standard pressure transducer. Attaching a pressure transducer to a properly placed IO catheter produces a pulsatile waveform. Misplacement of the IO catheter produces a flatline waveform. Results: Of 42 IO catheters, 8 (19%) were incorrectly placed per the waveform analysis technique. Compared to the pressure waveform analysis technique, the standard method and the power Doppler method incorrectly classified 4/8 (50%) and 5/8 (62.5%) of the misplaced catheters, respectively. The standard method had a higher positive predictive value for detecting incorrectly placed IO catheters than the power Doppler method (100% vs 63%, respectively). Blinded reviewers demonstrated better agreement using the pressure waveform analysis technique than using power Doppler (k = 0.77 vs k = 0.58, respectively). Conclusion: The standard and power Doppler ultrasonography techniques identify incorrectly placed IO catheters sub-optimally. The pressure waveform analysis technique is more accurate than the standard of care and has superior interrater agreement compared to the ultrasound method of confirmation. With more than 500 000 IO catheters placed in the United States each year, this novel technique may improve overall IO safety. Trial Registration Number: NCT03908879.

Symptoms and Impaired Quality of Life After COVID-19 Hospitalization: Effect of Therapeutic Heparin in Non-ICU Patients in the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 Acute Trial: Effect on 3-Month Symptoms and Quality of Life.

BACKGROUND: Therapeutic-dose heparin decreased days requiring organ support in noncritically ill patients hospitalized for COVID-19, but its impact on persistent symptoms or quality of life (QOL) is unclear. RESEARCH QUESTION: In the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE (ACTIV-4a) trial, was randomization of patients hospitalized for COVID-19 illness to therapeutic-dose vs prophylactic heparin associated with fewer symptoms and better QOL at 90 days? STUDY DESIGN AND METHODS: This was an open-label randomized controlled trial at 34 hospitals in the United States and Spain. A total of 727 noncritically ill patients hospitalized for COVID-19 from September 2020 to June 2021 were randomized to therapeutic-dose vs prophylactic heparin. Only patients with 90-day data on symptoms and QOL were analyzed. We ascertained symptoms and QOL by the EQ-5D-5L at 90-day follow-up in a preplanned analysis for the ACTIV-4a trial. Individual domains assessed by the EQ-5D-5L included mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Univariate and multivariate analyses were performed. RESULTS: Among 571 patients, 288 (50.4%) reported at least one symptom. Among 410 patients, 148 (36.1%) reported moderate to severe impairment in one or more domains of the EQ-5D-5L. The presence of 90-day symptoms was associated with moderate-severe impairment in the EQ-5D-5L domains of mobility (adjusted OR [aOR], 2.37; 95% CI, 1.22-4.59), usual activities (aOR, 3.66; 95% CI, 1.75-7.65), pain (aOR, 2.43; 95% CI, 1.43-4.12), and anxiety (aOR, 4.32; 95% CI, 2.06-9.02), compared with patients reporting no symptoms There were no differences in symptoms or in the overall EQ-5D-5L index score between treatment groups. Therapeutic-dose heparin was associated with less moderate-severe impairment in all physical functioning domains (mobility, self-care, usual activities) but was independently significant only in the self-care domain (aOR, 0.32; 95% CI, 0.11-0.96). INTERPRETATION: In a randomized controlled trial of hospitalized noncritically ill patients with COVID-19, therapeutic-dose heparin was associated with less severe impairment in the self-care domain of EQ-5D-5L. However, this type of impairment was uncommon, affecting 23 individuals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04505774; URL: www. CLINICALTRIALS: gov.

Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial.

Importance: Platelet activation is a potential therapeutic target in patients with COVID-19. Objective: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients. Intervention: Participants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis. Results: At the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77). Conclusions and Relevance: In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

Point-of-Care Ultrasound in the Intensive Care Unit: Applications, Limitations, and the Evolution of Clinical Practice.

The use of point-of-care ultrasonography in the intensive care unit has been rapidly advancing over the past 20 years. This review will provide a broad overview of the discipline spanning lung ultrasonography to advanced critical care echocardiography. It will highlight new research that questions the utility of the inferior vena cava for determining volume responsiveness and will introduce the reader to cutting-edge technology including artificial intelligence, which is likely to revolutionize ultrasound teaching and image interpretation, increasing the reach of this modality for the frontline clinician.

Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

Medical Education During the COVID-19 Pandemic.

All aspects of medical education were affected by the COVID-19 pandemic. Several challenges were experienced by trainees and programs alike, including economic repercussions of the pandemic; social distancing affecting the delivery of medical education, testing, and interviewing; the surge of patients affecting redeployment of personnel and potential compromises in core training; and the overall impact on the wellness and mental health of trainees and educators. The ability of medical teams and researchers to peer review, conduct clinical research, and keep up with literature was similarly challenged by the rapid growth in peer-reviewed and preprint literature. This article reviews these challenges and shares strategies that institutions, educators, and learners adopted, adapted, and developed to provide quality education during these unprecedented times.

Ultrasonography in the Critical Care Unit.

PURPOSE OF REVIEW: This article summarizes the utility and evidence supporting the use of ultrasound exams in the intensive care unit. RECENT FINDINGS: Point-of-care ultrasonography (POCUS) is widely used by intensivists managing critically ill patients whereby they can accurately and rapidly assess for many pathologies such as pneumothorax, pulmonary edema, hydronephrosis, hemoperitoneum, and deep vein thrombosis among others. Basic and advanced critical care echocardiography, including transesophageal echocardiography, are routinely performed to determine the etiology of hemodynamic instability in undifferentiated shock and to guide subsequent therapy. The use of POCUS in the assessment of volume status is controversial with studies demonstrating that respiratory variation of the IVC is not reliable and with analysis of aortic blood flow velocity after passive leg raising maneuvers being the most promising. Point-of-care ultrasonography allows frontline clinicians to make real-time diagnoses and treatment decisions. This article will provide the reader with a broad overview of this important topic.

Primary cardiac angiosarcoma: a rare cause of diffuse alveolar haemorrhage.

Primary cardiac angiosarcoma is a rare disease with a dismal prognosis. We report a case of a 50-year-old man who presented with haemoptysis, cough and worsening dyspnoea. An intracardiac mass was visualised on echocardiogram. He was treated for diffuse alveolar haemorrhage and acute respiratory distress syndrome but died from refractory hypoxaemic respiratory failure leading to cardiac arrest. The diagnosis of primary cardiac angiosarcoma with haemorrhagic pulmonary metastases leading to diffuse alveolar damage was confirmed on autopsy.

Evaluation of Left Ventricular Diastolic Function by the Intensivist.

The assessment of left ventricular diastolic function is an important element of advanced critical care echocardiography. Standard methods of evaluating diastolic function that are routinely performed on an elective basis in the cardiology echocardiography laboratory may be difficult to apply in the critical care unit. In this article, we review methods of measuring diastolic function with echocardiography that are of relevance to the intensivist and present two options for measurement: the standard cardiology method and a simplified approach.

Defining a Ventilation Strategy for Flexible Bronchoscopy on Mechanically Ventilated Patients in the Medical Intensive Care Unit.

BACKGROUND: Flexible bronchoscopy (FB) in intubated patients on mechanical ventilation increases airway resistance. During FB, two ventilatory strategies are possible: maintaining tidal volume (VT) while maintaining baseline CO2 or allowing reduction of VT. The former strategy carries risk of hyperinflation due to expiratory flow limitation with FB. The aim of the authors was too study end expiratory lung volume (EELV) during FB of intubated subjects while limiting VT. METHODS: We studied 16 subjects who were intubated on mechanical ventilation and required FB. Changes in EELV were measured by respiratory inductance plethysmography. Ventilator mechanics, EELV, and arterial blood gases, were measured. RESULTS: FB insertions decreased EELV in 64% of cases (-325±371 mL) and increased it in 32% of cases (65±59 mL). Suctioning decreased EELV in 76% of cases (-120±104 mL) and increased it in 16% of cases (29±33 mL). Respiratory mechanics were unchanged. Pre-FB and post-FB, PaO2 decreased by 61±96 mm Hg and PaCO2 increased by 15±7 mm Hg. CONCLUSIONS: There was no clinically significant increase in EELV in any subject during FB. Decreases in EELV coincided with FB-suctioning maneuvers. Peak pressure limiting ventilation protected the subject against hyperinflation with a consequent, well-tolerated reduction in VT, and hypercapnea. Suctioning should be limited, especially in patients vulnerable to derecruitment effect.

Effectiveness of a Critical Care Ultrasonography Course.

BACKGROUND: Widespread use of critical care ultrasonography (CCUS) for the management of patients in the ICU requires an effective training program. The effectiveness of national and regional CCUS training courses is not known. This study describes a national-level, simulation-based, 3-day CCUS training program and evaluates its effectiveness. METHODS: Five consecutive CCUS courses, with a total of 363 people, were studied. The 3-day CCUS training program consisted of didactic lectures, ultrasonography interpretation sessions, and hands-on modules with live models. Thoracic, vascular, and abdominal ultrasonography were taught in addition to goal-directed echocardiography. Learners rotated between hands-on training and interpretation sessions. The teacher-to-learner ratio was 1:3 during hands-on training. Interpretation sessions were composed of interactive small groups that reviewed normal and abnormal ultrasonography images. Learners completed a video-based examination before and after completion of the courses. Hands-on image acquisition skills were tested at the completion of the course. RESULTS: Average scores on the pretest and posttest were 57% and 90%, respectively (P < .001). The average score on the hands-on test was 86%. Learners aged 20 to 39 years compared with learners ≥ 40 years old scored better on the pretest (64% vs 51%; P < 0.001), posttest (91% vs 88%; P < .010), and hands-on test (90% vs 82%; P < .001). CONCLUSIONS: Learners demonstrated a significant improvement in written test scores that assessed cognitive and image interpretation abilities. In addition, they demonstrated acquisition of practical skills as evidenced by high scores during hands-on testing. Further studies are needed to determine if a simulation-based CCUS course will translate into effective clinical practice and to measure the durability of training. This 3-day course is an effective method to train large groups of critical care clinicians in the skills requisite for CCUS (image acquisition and image interpretation).

A Serious Adult Intraosseous Catheter Complication and Review of the Literature.

OBJECTIVE: Current guidelines recommend the use of intraosseous access when IV access is not readily attainable. The pediatric literature reports an excellent safety profile, whereas only small prospective studies exist in the adult literature. We report a case of vasopressor extravasation and threatened limb perfusion related to intraosseous access use and our management of the complication. We further report our subsequent systematic review of intraosseous access in the adult population. DATA SOURCES: Ovid Medline was searched from 1946 to January 2015. STUDY SELECTION: Articles pertaining to intraosseous access in the adult population (age greater than or equal to 14 years) were selected. Search terms were "infusion, intraosseous" (all subfields included), and intraosseous access" as key words. DATA EXTRACTION: One author conducted the initial literature review. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. DATA SYNTHESIS: The case of vasopressor extravasation was successfully treated with pharmacologic interventions, which reversed the effects of the extravasated vasopressors: intraosseous phentolamine, topical nitroglycerin ointment, and intraarterial verapamil and nitroglycerin. Our systematic review of the adult literature found 2,332 instances of intraosseous insertion. A total of 2,106 intraosseous insertion attempts were made into either the tibia or the humerus; 192 were unsuccessful, with an overall success rate of 91%. Five insertions were associated with serious complications. A total of 226 insertion attempts were made into the sternum; 54 were unsuccessful, with an overall success rate of 76%. CONCLUSIONS: Intraosseous catheter insertion provides a means for rapid delivery of medications to the vascular compartment with a favorable safety profile. Our systematic literature review of adult intraosseous access demonstrates an excellent safety profile with serious complications occurring in 0.3% of attempts. We report an event of vasopressor extravasation that was potentially limb threatening. Therapy included local treatment and injection of intraarterial vasodilators. Intraosseous access complications should continue to be reported, so that the medical community will be better equipped to treat them as they arise.