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Despite the low risk of peripherally inserted central catheter (PICC) insertion-related bleeding, the practice of administering prophylactic platelets varies greatly. Limiting unnecessary blood product transfusions reduces transfusion-related adverse events, financial cost, and delays in care. We assessed the impact of lowering prophylactic platelet administration threshold on blood product utilization patterns and bleeding events. This quasi-experimental study was conducted in an urban academic tertiary medical center. The study population included patients with platelet counts ≥ 10,000/µL and 50,000/µL undergoing PICC placement in 2018 and 2019 when the minimum platelet thresholds were 50,000/µL and 10,000/µL, respectively. The primary outcome was blood product utilization and the secondary outcome was PICC insertion-related bleeding complications. Thirty-five patients using the 10,000/µL (10 K) platelet threshold and 46 patients using the 50,000/µL (50 K) platelet threshold were enrolled. The 50 K group received more platelets before PICC insertion (0.870 ± 0.885 and 0.143 ± 0.430 pools of platelets-per-person, p 0.001). No patients experienced clinically significant bleeding. Immediately following PICC insertion, minor bleeding occurred in five patients (two [4.3%] and three [8.6%] in the 50 K and 10 K groups, respectively). Bleeding rates between the two cohorts did not differ (p = 0.647). Lowering the minimum platelet threshold from 50,000/µL to 10,000/µL resulted in less prophylactic platelet and total blood product administration with no appreciable difference in PICC insertion-related bleeding.

Purpose Hydroxocobalamin has been observed to cause transient hypertension in healthy subjects, but rigorous studies examining its efficacy are lacking. Materials and methods Adults in shock who received hydroxocobalamin from 2017 to 2021 were analyzed retrospectively. Hourly hemodynamics from 24 h before and after treatment were collected, and the difference and hourly change of mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and norepinephrine-equivalent dose (NED) were examined in mixed-effects models. Results This study included 3992 hemodynamic data points from 35 patients and is the largest case series to date. In the mixed effects model, there was no difference in MAP 24-h after hydroxocobalamin administration (estimated fixed effect [EFE] −0.2 mmHg, p = 0.89). A two-piecewise mixed model found that the hourly change in MAP was not different from zero in either the pre-administration (EFE 0.0 mmHg/h, p = 0.80) or post-administration segments (EFE 0.0 mmHg/h, p = 0.55). Analysis of the SBP, DBP, and NED also found similar insignificant results. Conclusions Although hydroxocobalamin has been observed to cause hypertension in healthy subjects, our results suggest that in patients with shock, hydroxocobalamin may not be effective in improving hemodynamics at 24 h after administration.

Compared with conventional coagulation tests and factor-specific assays, viscoelastic hemostatic assays (VHAs) can provide a more thorough evaluation of clot formation and lysis but have several limitations including clot deformation. In this proof-of-concept study, we test a noncontact technique, termed resonant acoustic rheometry (RAR), for measuring the kinetics of human plasma coagulation. Specifically, RAR utilizes a dual-mode ultrasound technique to induce and detect surface oscillation of blood samples without direct physical contact and measures the resonant frequency of the surface oscillation over time, which is reflective of the viscoelasticity of the sample. Analysis of RAR results of normal plasma allowed defining a set of parameters for quantifying coagulation. RAR detected a flat-line tracing of resonant frequency in hemophilia A plasma that was corrected with the addition of tissue factor. Our RAR results captured the kinetics of plasma coagulation and the newly defined RAR parameters correlated with increasing tissue factor concentration in both healthy and hemophilia A plasma. These findings demonstrate the feasibility of RAR as a novel approach for VHA, providing the foundation for future studies to compare RAR parameters to conventional coagulation tests, factor-specific assays, and VHA parameters.

Summary Background & aims Survivors of critical illness requiring prolonged mechanical ventilation (PMV) are predisposed to malnutrition, muscle wasting, and weakness. There is a lack of data regarding nutrition adequacy among these patients, and although nitrogen balance has been studied as a marker of adequate protein intake in healthy individuals and acutely critically ill patients, it has not been well studied in critically ill patients with PMV. The purpose of this study was to determine if patients requiring PMV admitted to a long-term acute care hospital (LTACH) achieved registered dietitian (RD) recommended goals for energy and protein intake and if the recommendations were adequate to avoid negative nitrogen balance. Methods Using a retrospective, cohort study design, patients requiring PMV who had orders for 24-h urine collections for urea nitrogen (24hrUUN) were included. Energy and protein intake was calculated from chart documentation of dietary intake for the 24-h period during which patients underwent a 24hrUUN. Nitrogen intake was estimated from protein intake. Dietary intake was compared to RD-recommendations to determine the percentage of RD-recommendations achieved. Nitrogen balance was calculated as nitrogen intake minus nitrogen loss, with negative balance categorized as less than −1. Results Subjects (n = 16) were 38% male and 75% African American (mean age 61.5 ± 3.2 years; mean BMI 27.5 ± 2.5 kg/m2). Duration of LTACH hospitalization was 26.5 (6–221) days. Mean energy and protein intake was 21.7 ± 2.9 kcal/kg/d and 1.1 ± 0.1 g/kg/d, respectively, which corresponded to 86% of both RD energy and protein recommendations. Ten patients achieved a positive nitrogen balance (mean 0.9 ± 1.1 g). In addition, there was a positive linear relationship between protein intake and nitrogen balance (r = 0.59, p = 0.016). Conclusion Survivors of critical illness requiring PMV achieved a high percentage of RD-recommended protein and calories, and prevented a negative nitrogen balance in a majority of patients. Increasing protein intake can prevent a negative nitrogen balance. Future studies should evaluate whether these patients are able to maintain a steady state of nitrogen intake and excretion over time and how this affects time to and/or success of weaning.

Background: Invasive procedures are a core aspect of pulmonary and critical care practice. Procedures performed in the intensive care unit can be divided into high-risk, low-volume (HRLV) procedures and low-risk, high-volume (LRHV) procedures. HRLV procedures include cricothyroidotomy, pericardiocentesis, Blakemore tube placement, and bronchial blocker placement. LRHV procedures include arterial line placement, central venous catheter placement, thoracentesis, and flexible bronchoscopy. Despite the frequency and importance of procedures in critical care medicine, little is known about the similarities and differences in procedural training between different Pulmonary and Critical Care Medicine (PCCM) and Critical Care Medicine (CCM) training programs. Furthermore, differences in procedural training practices for HRLV and LRHV procedures have not previously been described. Objective: To assess procedural training practices in PCCM and CCM fellowship programs in the United States, and compare differences in training between HRLV and LRHV procedures. Methods: A novel survey instrument was developed and disseminated to PCCM and CCM program directors and associate program directors at PCCM and CCM fellowship programs in the United States to assess procedural teaching practices for HRLV and LRHV procedures. Results: The survey was sent to 221 fellowship programs, 168 PCCM and 34 CCM, with 70 unique respondents (31.7% response rate). Of the procedural educational strategies assessed, each strategy was used significantly more frequently for LRHV versus HRLV procedures. The majority of respondents (51.1%) report having no dedicated training for HRLV procedures versus 6.9% reporting no dedicated training for any LRHV procedure (P

Background: Management of mechanical ventilation (MV) is a curricular milestone for trainees in pulmonary critical care medicine (PCCM) and critical care medicine (CCM) fellowships. Though recognition of ventilator waveform abnormalities that could result in patient complications is an important part of management, it is unclear how well fellows recognize these abnormalities. Objective: To study proficiency of ventilator waveform analysis among first-year fellows enrolled in a MV course compared with that of traditionally trained fellows. Methods: The study took place from July 2016 to January 2019, with 93 fellows from 10 fellowship programs completing the waveform examination. Seventy-three fellows participated in a course during their first year of fellowship, with part I occurring at the beginning of fellowship in July and part II occurring after 6 months of clinical work. These fellows were given a five-question ventilator waveform examination at multiple time points throughout the two-part course. Twenty fellows from three other fellowship programs who were in their first, second, or third year of fellowship and who did not participate in this course served as the control group. These fellows took the waveform examination a single time, at a median of 23 months into their training. Results: Before the course, scores were low but improved after 3 days of education at the beginning of the fellowship (18.0 ± 1.6 vs. 45.6 ± 3.0; P

Background: In July of 2013, the University of Maryland launched MarylandCCProject.com. This free-access educational website delivers asynchronous high-quality multidisciplinary critical care education targeted at critical care trainees. The lectures, presented in real time on-site, are recorded and available on the website or as a podcast on iTunes or Android. Thus, the curriculum can be easily accessed around the world. Objective: We sought to identify the impact this website has on current and former University of Maryland critical care trainees. Methods: A 32-question survey was generated using a standard survey generation tool. The survey was e-mailed in the fall of 2019 to the University of Maryland Multi-Departmental Critical Care current and graduated trainees from the prior 7 years. Survey data were collected through December 2019. The questions focused on user demographics, overall experience with the website, scope of website use, and clinical application of the content. Anonymous responses were electronically gathered. Results: A total of 186 current trainees and graduates were surveyed, with a 39% (n = 72) response rate. Of responders, 76% (55) use the website for ongoing medical education. The majority use the website at least monthly. Most users (63%, n = 35) access the lectures directly through the website. All 55 current users agree that the website has improved their medical knowledge and is a useful education resource. Platform use has increased and includes users from around the world. Conclusion: Based on our current data, the MarylandCCProject remains a valuable and highly used educational resource, impacting patient care both during and after critical care fellowship training.

The globalization of medical research and global health's increasing popularity worldwide have resulted in greater geographic, ethnic, and socioeconomic diversity of studies published in the scientific literature. Yet the geographic distribution, authorship representation, and subject trends among Low-/Low-Middle-Income Country (LIC/LMIC)-based scientific publications remain largely unknown. This analysis assesses these gaps in knowledge. We performed a comprehensive bibliometric analysis of all scientific articles published between January 2014 and June 2016 in the four most prominent general medicine and five most prominent general global health journals based on impact factor. The African region, containing 24% of the global LIC/LMIC population, accounted for 49.9% of all publications. Corresponding authors with either exclusive or joint appointment to a LIC/LMIC institution were present in 26.2% of all included articles. Over one-quarter (28.8%) of all publications did not list a local author. Nearly two-thirds (62.1%) of articles published in global health journals and roughly half (52.4%) in general medicine journals involved infectious diseases. Non-HIV infectious disease studies were by far the most frequent subject areas across all journals. The trends identified in this study may help to inform the evolution and prioritization of future research efforts, thereby allowing global health to remain truly global.

Endothelial dysfunction is common in septic shock and has been shown to impair angiotensin converting enzyme and the renin-angiotensin-aldosterone system (RAAS). Dysregulation of this pathway, which can be measured with plasma renin activity (PRA), is important not only because RAAS dysfunction is associated with increased mortality but also because treatment with angiotensin II (Ang-2) has been shown to decrease mortality. In this case series of 2 patients, serial PRA levels identified septic shock patients with RAAS dysfunction. The patients were treated with Ang-2, an angiotensin type 1 receptor agonist, which resulted in significant improvements in hemodynamics and PRA levels during treatment.

Introduction An airway exchange catheter is a hollow-lumen tube able to deliver oxygen and maintain access to a difficult endotracheal airway. This case report demonstrates an undocumented complication associated with an airway exchange catheter and jet ventilation, particularly in a patient with reduced airway diameter due to thick endotracheal secretions. Due to the frequent use of airway exchange catheters in the intensive care unit, this report highlights an adverse event of bilateral pneumothoraces that can be encountered by clinicians. Case Presentation This case report describes a 24-year-old female with severe adult respiratory distress syndrome and thick endotra-cheal secretions whose hospital course was complicated by bilateral pneumothoraces resulting from the use of an airway exchange catheter connected to jet ventilation. During the exchange, the catheter occluded the narrowed endotracheal tube to create a one-way valve that led to excessive lung inflation. Conclusion Airway exchange catheters used with jet ventilation in a patient with a narrowed endotracheal tube and reduced lung compliance have the potential risk of causing a pneumothorax. Clinicians should avoid temporary concomitant oxygenation via jet ventilation in patients with these findings and reserve the use of airway exchange catheters for difficult airways.

Introduction About one-third of critically ill patients with acute kidney injury (AKI) develop persistently decreased kidney function, known as acute kidney disease (AKD), which may progress to chronic kidney disease (CKD). Although sepsis is the most common cause of AKI, little is known about sepsis-associated AKD. Methods Using data from a large randomized trial including 1341 patients with septic shock, we studied patients with stage 2 or 3 AKI on day 1 of hospitalization. We defined AKD as a persistently reduced glomerular filtration rate for >7 days. In addition to clinical data, we measured several urinary biomarkers (tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2∗IGFBP7], neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], liver-type fatty acid binding protein, and type 4 collagen) at 0, 6, and 24 hours, to predict AKD. Results Of 598 patients, 119 (19.9%) died within 7 days, 318 (53.2%) had early reversal of AKI within the first 7 days, whereas 161 (26.9%) developed AKD. In patients with early reversal, 45 (14.2%) had relapsed AKI after early reversal, and only about one-third of these recovered. Among patients developing AKD, only 15 (9.3%) recovered renal function prior to discharge. Male sex, African American race, and underlying CKD were more predominant in patients developing AKD. None of the biomarkers tested performed well for prediction of AKD, although NGAL modestly increased the performance of a clinical model. Conclusions AKD is common in patients with septic shock, especially among African American males and those with underlying CKD. Existing AKI biomarkers have limited utility for predicting AKD but might be useful together with clinical variables. Novel predictive biomarkers for renal recovery are needed., Graphical abstract

Whole blood (WB) has been used for more than a century for far-forward combat resuscitation. Following the Iraq/Afghanistan combat, maritime, and austere environment use of WB for the resuscitation of severely hemorrhaging patients, there has been an increasing use of WB for the civilian urban resuscitation environment population. The impetus for this was not just improved outcomes in far-forward hospitals, which had different populations and different needs than the civilian urban population, but also an application of the lessons suggested by recent 1:1:1 plasma:platelets:packed red cells fixed-ratio studies for patients with massive transfusion needs. Mechanistic, logistic, and standardization concerns have been addressed and are evolving as the WB project advances. A small number of studies have been published on WB in the civilian urban trauma population. In addition, European experience with viscoelastic testing and resuscitation with fibrinogen and prothrombin complex concentrate has provided another viewpoint regarding the choice of resuscitation strategies for severely bleeding trauma patients in urban civilian environments. There are randomized controlled trials in process, which are testing the hypothesis that WB may be beneficial for the civilian urban population. Whether WB will improve mortality significantly is now a matter of intense study, and this commentary reviews the history, mechanistic foundations, and logistical aspects for the use of WB in the civilian trauma population.

Purpose The primary objective was to evaluate the impact of an analgosedation protocol in a cardiac intensive care unit (CICU) on daily doses and costs of analgesic, sedative, and antipsychotic medications. Methods We conducted a single-center quasi-experimental study in 363 mechanically ventilated patients admitted to our CICU from March 1, 2011, to April 13, 2013. On March 1, 2012, an analgosedation protocol was implemented. Patients in the pre-implementation group were managed at the cardiologist’s discretion, which consisted of a continuous sedative-hypnotic approach and opioids as needed. Patients in the implementation group were managed using this protocol. Results The mean ± S.D. per-patient doses (mg/day) of propofol, lorazepam, and clonazepam decreased with the use of an analgosedation protocol (propofol 132,265.7 ± 12,951 versus 87,980.5 ± 10,564 [p = 0.03]; lorazepam 10.5 ± 7.3 versus 3.3 ± 4.0 [p < 0.001]; clonazepam 9.9 ± 8.3 versus 1.1 ± 0.5 [p = 0.03]). The mean daily cost of propofol and lorazepam also significantly decreased (33.5% reduction in propofol cost [p = 0.03]; 69.0% reduction in lorazepam cost [p < 0.001]). The per-patient dose and cost of fentanyl (mcg/day) declined with analgosedation protocol use (fentanyl 2,274.2 ± 2317.4 versus 1,026.7 ± 981.4 [p < 0.001]; 54.8% decrease in fentanyl cost [p < 0.001]). Conclusion The implementation of an analgosedation protocol significantly decreased both the use and cost of propofol, lorazepam, and fentanyl. Further investigation of the clinical impact and cost-effectiveness of a critical care consultation service with implementation of an analgosedation protocol is warranted in the CICU.

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction

Background: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. Methods: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables. Results: Among all 79 patients, 12 (15.2%) had bleeding events, and 20 (25.3%) had thrombosis. Multivariate logistic regression analysis identified a prediction model for bleeding (adjusted R2 = 0.787, p &lt, 0.001) comprised of increased reaction time (p = 0.016), decreased fibrinogen (p = 0.006), decreased D-dimer (p = 0.063), and increased activated partial thromboplastin time (p = 0.084). Multivariate analysis of thrombosis identified a weak prediction model (adjusted R2 = 0.348, p &lt, 0.001) comprised of increased D-dimer (p &lt, 0.001), decreased reaction time (p = 0.002), increased maximum amplitude (p &lt, 0.001), and decreased alpha angle (p = 0.014). Adjunctive thromboelastography decreased the use of packed red cells (p = 0.031) and fresh frozen plasma (p &lt, 0.001). Conclusions: Significantly, this study demonstrates the need for a precision-based titration strategy of anticoagulation for hospitalized COVID-19 patients. Since severely ill COVID-19 patients may switch between thrombotic or hemorrhagic phenotypes or express both simultaneously, institutions may reduce these complications by developing their own titration strategy using daily conventional coagulation tests with adjunctive thromboelastography.

Objectives Whole blood lactate concentration is widely used in shock states to assess perfusion. We aimed to determine if the change in plasma renin concentration over time would be superior to the change in lactate concentration for predicting in-hospital mortality in hypotensive patients on vasopressors. Design Prospective, observational cohort study. Setting Tertiary academic ICU. Patients Adult patients on vasopressors for greater than 6 hours to maintain a mean arterial pressure greater than or equal to 65 mm Hg during January 2020. Interventions Plasma renin concentrations were measured at enrollment and at 24, 48, and 72 hours. Whole blood lactate measurements were performed according to normal standard of care. Logistic regression was performed to evaluate whether the change in renin or lactate concentration could predict in-hospital mortality. Generalized estimating equations were used to analyze the association between renin and lactate concentration and in-hospital mortality. The area under the receiver operating characteristics curve was performed to measure the discriminative ability of initial and peak renin and lactate concentration to predict mortality. The association between renin and lactate concentration above the upper limit of normal at each timepoint with in-hospital mortality was also examined. Measurements and main results The study included 197 renin and 148 lactate samples obtained from 53 patients. The slope of the natural log (ln) of renin concentration was independently associated with mortality (adjusted odds ratio, 10.35; 95% CI, 1.40-76.34; p = 0.022), but the slope of ln-lactate concentration was not (adjusted odds ratio, 4.78; 95% CI, 0.03-772.64; p = 0.55). The generalized estimating equation models found that both ln-renin (adjusted odds ratio, 1.18; 95% CI, 1.02-1.37; p = 0.025) and ln-lactate (adjusted odds ratio, 2.38; 95% CI, 1.05-5.37; p = 0.037) were associated with mortality. Area under the receiver operating characteristics curve analysis demonstrated that initial renin could predict in-hospital mortality with fair discrimination (area under the receiver operating characteristics curve, 0.682; 95% CI, 0.503-0.836; p = 0.05), but initial lactate could not (area under the receiver operating characteristics curve, 0.615; 95% CI, 0.413-0.803; p = 0.27). Peak renin (area under the receiver operating characteristics curve, 0.728; 95% CI, 0.547-0.888; p = 0.01) and peak lactate (area under the receiver operating characteristics curve, 0.746; 95% CI, 0.584-0.876; p = 0.01) demonstrated moderate discrimination. There was no significant difference in discriminative ability between initial or peak renin and lactate concentration. At each study time point, a higher proportion of renin values exceeded the threshold of normal (40 pg/mL) in nonsurvivors than in survivors, but this association was not significant for lactate. Conclusions Although there was no significant difference in the performance of renin and lactate when examining the absolute values of each laboratory, a positive rate of change in renin concentration, but not lactate concentration, over 72 hours was associated with in-hospital mortality. For each one-unit increase in the slope of ln-renin, the odds of mortality increased 10-fold. Renin levels greater than 40 pg/mL, but not lactate levels greater than 2 mmol/L, were associated with in-hospital mortality. These findings suggest that plasma renin kinetics may be superior to lactate kinetics in predicting mortality of hypotensive, critically ill patients.

Recent advances in device technology and image analysis software used to assess the sublingual microcirculation have expanded clinicians' understanding of hemodynamics beyond assessments of blood pressure and end-organ function to provide unique insight into blood flow at the tissue level. Similarly, significant advances in virtual education and telemedicine have transpired recently, especially during the coronavirus disease (COVID-19) pandemic. However, the training of clinicians to acquire microcirculation images continues to rely on in-person instruction, which can be limited by available local expertise and resources, as well as geographic access to instructors.Our project aimed to test the feasibility of deploying an online curriculum in combination with tele-guidance versus an in-person guided approach to instruct novices to understand basic principle of microcirculatory function and to acquire sublingual microcirculatory images.After participating in brief didactics, 14 participants were divided into two groups to acquire microcirculatory images on a healthy volunteer. Each participant eitherParticipants' image quality scores (14.7 vs. 23.6,This feasibility study provides a novel framework for how to successfully deploy asynchronous education and telemedicine to direct novices to acquire sublingual microcirculatory images. Using technological advances to teach microcirculation may enhance wide-scale adoption of a promising clinical monitoring tool for critically ill patients.

Handheld vital microscopy (HVM) can deepen our understanding of hematologic diseases and therapeutics. However, limited reports have assessed human microcirculation during profound anemia, and response to hemoglobin-based oxygen carriers (HBOCs). A 58-year-old woman presented with constitutional symptoms and was diagnosed with acute myeloblastic leukemia. Subsequently, the patient clinically decompensated and was found to have a hemoglobin of 1.9 g/dL. Human blood product administration was not consistent with her beliefs, and she received supportive care with HBOC-201. Concomitantly, her sublingual microcirculation revealed a markedly low microvascular flow index (2.59±0.26), proportion perfused vessels (66.8±18.8%), perfused vessel density (4.41±0.56 mm/mm2), and total vessel density (6.93±1.91 mm/mm2). HVM imaging is a promising point-of-care device for various hematologic conditions, with the potential to understand tissue-level perfusion in novel clinical scenarios, including profound anemia and HBOC administration, as illustrated in this case report.

Background Nurses and other non-physician providers have demonstrated proficiency at obtaining images in the tele-ultrasound system. However, use of this skill requires comfort with the procedure and willingness to incorporate it into practice. Objectives To assess 1) level of comfort of non-physician providers performing tele-ultrasound before and after brief training and 2) feasibility of implementing an educational programme that improves level of comfort. Methods Feasibility study including a brief training session followed by hands-on tele-ultrasound. The pilot cohort performed tele-ultrasound on a healthy volunteer. The clinical cohort performed tele-ultrasound on criticalli ill patients with shock or respiratory failure. Remote intensivists provided real-time guidance via tele-medicine technology. Each participant completed a survey assessing training experience and level of comfort before and after training. Results Sixteen non-physician providers participated. All participants agreed that the training session prepared them for image acquisition and that the training experience was positive. The number of participants comfortable with ultrasound improved significantly (before vs. after training: 5/16 [31%] vs. 16/16 [100%], mean Likert score 2.7 vs. 4.8, p = 0.001). Conclusions After brief training, participants could comfortably perform tele-ultrasound and were more willing to incorporate it into tele-ICU-directed care. Results support conducting a larger-scale trial of tele-US to assess clinical utility.

Sepsis management demands early diagnosis and timely treatment that includes source control, antimicrobial therapy, and resuscitation. Currently employed diagnostic tools are ill-equipped to rapidly diagnose sepsis and isolate the offending pathogen, which limits the ability to offer targeted and lowest-toxicity treatment. Cutting edge diagnostics and therapeutics in development may improve time to diagnosis and address two broad management principles: (1) source control by removing the molecular infectious stimulus of sepsis, and (2) attenuation of the pathological immune response allowing the body to heal. This review addresses novel diagnostics and therapeutics and their role in the management of sepsis.

Background Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Methods Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p Results Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Conclusion Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Critically ill patients can present at any time and location, and they demand high quality care. Historical experiences from military, wilderness, and disaster medicine settings have helped shape the modern concept of caring for the most severely ill with limited available resources. We introduce a method to help design a successful critical care medical support endeavor, which includes properly defining components of Navigation, Environment, Resupply, Energy, Unconventional problems, and Support (NEREUS). Additionally, we provide recommendations for optimal team personnel composition, including utilization of paramedics, critical care providers, nurses, and respiratory therapists across the spectrum of care provided at point of injury, en route to definitive care, and definitive care. A review of critical care principles relevant to the austere setting proceeds with a systematic organization according to airway, breathing, circulation, and neurologic management. Lastly, we employ our proposed method of organizing a critical care medical support endeavor to a post-hurricane scenario. In summary, this review provides the historical background, modern definition, and practical framework for successfully administering critical care in scenarios with limited available resources. We emphasize the need to appropriately adapt critical care concepts to meet the unique demands of a specific scenario.

Introduction: Angiotensin II (Ang-2) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptor. Its utility as a vasopressor and a catecholamine-sparing agent was demonstrated in the pivotal ATHOS-3 trial, and numerous post-hoc analyses have shown reduced mortality in certain subsets of the population. Methods: Consecutive adult patients at 5 centers who received Ang-2 from 2017-2020 were included in this multicenter, retrospective observational cohort study. Patient demographics, hemodynamics, and adverse events were collected. The primary outcomes of the study were the mean difference in MAP and norepinephrine (NEpi)-equivalent dose at hours 0 and 3 following initiation of Ang-2 therapy. Results: One hundred and sixty-two patients were included in this study. The primary outcomes of an increase in MAP (mean difference 9.3 mmHg, 95% CI 6.4-12.1, p < 0.001) and a reduction in NEpi equivalent dose (mean difference 0.16 µg/kg/min, 95% CI 0.10-0.22, p < 0.001) between hours 0 and 3 were statistically significant. The median time to reach a MAP ≥65 was 16 minutes (IQR 5-60 min). After stratifying patients by the NED dose and number of vasopressors administered prior to the initiation of Ang-2, those with a NED dose < 0.2 µg/kg/min, NED dose < 0.3 µg/kg/min, or those on ≤ 3 vasopressors had a significantly greater reduction in NED by hour 3 than those patients above these thresholds. Conclusion: Ang-2 is an effective vasopressor and reduces catecholamine dose significantly. Its effect is rapid, with target MAP obtained within 30 minutes in most patients. Given the critical importance of adequate blood pressure to organ perfusion, Ang-2 should be considered when target MAP cannot be achieved with conventional vasopressors. Ang-2 should be utilized early in the course of shock, before the NED dose exceeds 0.2-0.3 µg/kg/min and before the initiation of the fourth-line vasopressor.