Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force.

OBJECTIVES: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. DESIGN: Review and task force position statements with necessary guidance. SETTING: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. SUBJECTS: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. INTERVENTIONS: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. MEASUREMENTS AND MAIN RESULTS: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. CONCLUSIONS: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

Temporary Mechanical Circulatory Support in Sepsis-Associated Cardiogenic Shock With and Without Acute Myocardial Infarction.

OBJECTIVES: To describe the current use and outcomes of temporary mechanical circulatory support (MCS) in patients with sepsis-associated cardiogenic shocks with and without acute myocardial infarction (AMI) in the United States. DESIGN: Retrospective cohort study. SETTING: The National Inpatient Sample database from 2017 to 2019. PARTICIPANTS: Adult patients with sepsis-associated cardiogenic shock with and without AMI. INTERVENTIONS: Temporary MCSs, including intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD), and extracorporeal membrane oxygenation (ECMO). MEASUREMENTS AND MAIN RESULTS: Multivariate logistic regression analyses adjusting for patient characteristics, organ failures, and socioeconomic status. Although the uses of IABP and pLVAD were associated with significantly lower odds of in-hospital mortality in patients with sepsis-associated cardiogenic shock (IABP: adjusted odds ratio [aOR] 0.57, 95% CI 0.44-0.73, p < .001; pLVAD: aOR 0.66, 95% CI 0.45-0.98, p = .037), ECMO was not (aOR 1.51, 95% CI 0.93-2.45, p = 0.096). In the subgroup with AMI, temporary MCSs were not associated with significantly lower or higher odds of in-hospital mortality. In the subgroup without AMI, IABP was associated with significantly lower odds of in-hospital mortality (aOR 0.43, 95% CI 0.28-0.65, p < 0.001). CONCLUSIONS: Although temporary MCS is deemed to be a feasible option in sepsis-associated cardiogenic shock, the selection of the right patients whose shock is driven mainly by cardiogenic shock rather than septic shock, as represented by low cardiac output and high systemic vascular resistance, plays a critical role in the feasibility of this approach in the absence of clinical trials.

Lung Ultrasonographic Signs in Pulmonary Disease - A Video Review.

Lung ultrasound (US) is a well-established imaging tool in the inpatient and critical care setting. It has proven its worth in the rapid bedside diagnosis of a variety of conditions pertaining to the lungs and the thorax. Lung US was initially introduced as a bedside imaging tool to evaluate the size and characteristics of pleural effusion. Over the years, the field of lung ultrasonography has rapidly expanded introducing nuances in image interpretation. Numerous primary and secondary signs have been described in the literature to identify both normal and abnormal findings. The primary signs can help narrow the list of differential diagnoses, whereas the addition of secondary signs help create an imaging pattern facilitating the confirmation of diagnosis or recognition of the underlying disease process. These wide variety of signs and patterns can present a challenge to the learning of lung ultrasonography, particularly to a novice user. We sought to compile a comprehensive list of these findings to serve as a useful resource to aid effortless adoption of lung ultrasonography in clinical practice. In this review, we narrate the evolution of lung US, describe common protocols applied in performance of the lung US, and illustrate a comprehensive list of common lung US signs and patterns along with their differential diagnosis and clinical utility.

Prevalence and Prognosis of Sepsis-Induced Cardiomyopathy: A Systematic Review and Meta-Analysis.

Purpose: The prevalence and its impact on mortality of sepsis-induced cardiomyopathy (SICM) remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and prognosis of SICM. Materials and Methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Titles and abstracts were evaluated based on the following criteria: (1) published in English, (2) randomized controlled trials, cohort studies, or cross-sectional studies, (3) ≥ 18 years with sepsis, (4) reporting the prevalence and/or comparison of short-term mortality between those with and without SICM, defined as the new-onset reduction in left ventricular ejection fraction (LVEF) within 72 h on admission or from the diagnosis of sepsis. The random-effect model was used for all analyses. This meta-analysis was registered at PROSPERO (CDR42022332896). Results: Sixteen studies reported the prevalence of SICM and the pooled prevalence of SICM was 20% (95% confidence interval [CI], 16-25%; I2 = 89.9%, P < 0.01). Eleven studies reported short-term mortality and SICM was associated with significantly higher short-term mortality (The pooled odds ratio: 2.30, 95% CI, 1.43-3.69; I2 = 0%, P = 0.001). Conclusion: The prevalence of SICM was 20% in patients with sepsis, and the occurrence of SICM was associated with significantly higher short-term mortality.

Mechanisms of Acute Right Ventricular Injury in Cardiothoracic Surgical and Critical Care Settings: Part 2.

The right ventricle (RV) is intricately linked in the clinical presentation of critical illness; however, the basis of this is not well-understood and has not been studied as extensively as the left ventricle. There has been an increased awareness of the need to understand how the RV is affected in different critical illness states. In addition, the increased use of point-of-care echocardiography in the critical care setting has allowed for earlier identification and monitoring of the RV in a patient who is critically ill. The first part of this review describes and characterizes the RV in different perioperative states. This second part of the review discusses and analyzes the complex pathophysiologic relationships between the RV and different critical care states. There is a lack of a universal RV injury definition because it represents a range of abnormal RV biomechanics and phenotypes. The term "RV injury" (RVI) has been used to describe a spectrum of presentations, which includes diastolic dysfunction (early injury), when the RV retains the ability to compensate, to RV failure (late or advanced injury). Understanding the mechanisms leading to functional 'uncoupling' between the RV and the pulmonary circulation may enable perioperative physicians, intensivists, and researchers to identify clinical phenotypes of RVI. This, consequently, may provide the opportunity to test RV-centric hypotheses and potentially individualize therapies.

IDSA made 4 strong recommendations for preventing COVID-19 infection in health care personnel.

SOURCE CITATION: Lynch JB, Davitkov P, Anderson DJ, et al. Infectious Diseases Society of America guidelines on infection prevention for health care personnel caring for patients with suspected or known COVID-19. Clin Infect Dis. 2020. [Epub ahead of print.] 32716496.

Effect of IV High-Dose Vitamin C on Mortality in Patients With Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials to investigate whether IV high-dose vitamin C improves the short-term mortality of patients with sepsis. DESIGN: This study is a systematic review and meta-analysis of randomized controlled trials. We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for randomized controlled trials that met inclusion criteria. The protocol was registered at the University hospital Medical Information Network Clinical Trials Registry (UMIN000040528). All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as 28-day, 30-day, or in-hospital mortality. PATIENTS: Two authors independently evaluated the following eligibility criteria: 1) randomized controlled trial, 2) patients with sepsis aged ≥18 years, and 3) received intravenous high-dose vitamin C in addition to standard of care, or standard of care alone. Then, two authors independently extracted the selected patient and study characteristics and outcomes from studies that met above eligibility criteria. MEASUREMENTS AND MAIN RESULTS: Eleven randomized controlled trials (n = 1,737 patients) were included in this meta-analysis. High-dose IV vitamin C was not associated with a significantly lower short-term mortality (risk ratio, 0.88; 95% CI, 0.73-1.06; p = 0.18; I2 = 29%) but was associated with a significantly shorter duration of vasopressor use (standardized mean difference, -0.35; 95% CI, -0.63 to -0.07; p < 0.01; I2 = 80%) and a significantly greater decline in the Sequential Organ Failure Assessment score at 72-96 hours (standardized mean difference, -0.20; 95% CI, -0.32 to -0.08; p < 0.01; I2 = 16%). One study reported significant association with hypernatremia, but adverse effects were rare, and high-dose vitamin C is deemed relatively safe. CONCLUSIONS: In this meta-analysis, the use of IV high-dose vitamin C in patients with sepsis was not associated with lower short-term mortality although it was associated with significantly shorter duration of vasopressor use and greater decline in the Sequential Organ Failure Assessment score at 72-96 hours.

The impact of right ventricular injury on the mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Previous studies have found various incidences of right ventricular (RV) injury and its association with clinical outcome in patients with acute respiratory distress syndrome (ARDS). In this systematic review and meta-analysis, we aimed to investigate the impact of the presence of RV injury on mortality in patients with ARDS. METHOD: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies investigating the association between RV injury and mortality. Two authors independently evaluated whether studies meet eligibility criteria and extracted the selected patients' and studies' characteristics and outcomes. RV injury was diagnosed by trans-thoracic echocardiogram (TTE), trans-esophageal echocardiogram (TEE) and PAC (pulmonary artery catheter) in the included studies. The primary outcome was the association between mortality and the presence of RV injury in patients with ARDS. The overall reported mortality was defined as either the intensive care unit (ICU) mortality, in-hospital mortality, or mortality within 90 days, and short-term mortality was defined as ICU-mortality, in-hospital mortality, or mortality within 30 days. RESULTS: We included 9 studies (N = 1861 patients) in this meta-analysis. RV injury that included RV dysfunction, RV dysfunction with hemodynamic compromise, RV failure, or acute cor-pulmonale was present in 21.0% (391/1,861). In the pooled meta-analysis, the presence of RV injury in patients with ARDS was associated with significantly higher overall mortality (OR 1.45, 95% CI 1.13-1.86, p-value = 0.003, I2 = 0%), as well as short-term mortality (OR 1.48, 95% CI 1.14-1.93, p-value = 0.003, I2 = 0%). CONCLUSION: In this systematic review and meta-analysis including 1861 patients with ARDS, the presence of RV injury was significantly associated with increased overall and short-term mortality. TRIAL REGISTRATION: The protocol was registered at PROSPERO (CRD42020206521).

Transthoracic Right Heart Echocardiography for the Intensivist.

BACKGROUND: The impact of critical illness on the right ventricle (RV) can be profound and RV dysfunction is associated with mortality. Intensivists are becoming more facile with bedside echocardiography, however, pedagogy has largely focused on left ventricular function. Here we review measurements of right heart function by way of echocardiographic modalities and list clinical scenarios where the RV dysfunction is a salient feature. MAIN: RV dysfunction is heterogeneously defined across many domains and its diagnosis is not always clinically apparent. The RV is affected by conditions commonly seen in the ICU such as acute respiratory distress syndrome, pulmonary embolism, RV ischemia, and pulmonary hypertension. Basic ultrasonographic modalities such as 2D imaging, M-mode, tissue Doppler, pulsed-wave Doppler, and continuous Doppler provide clinicians with metrics to assess RV function and response to therapy. CONCLUSION: The right ventricle is impacted by various critical illnesses with substantial mortality and mortality. Focused bedside echocardiographic exams with attention to the right heart may provide intensivists insight into RV function and provide guidance for patient management.

Best practice statements and recommendations for caring for critically ill patients with COVID-19.

SOURCE CITATION: Alhazzani W, Møller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48:e440-69. 32224769.

Prevalence and prognosis of hyperdynamic left ventricular systolic function in septic patients: a systematic review and meta-analysis.

PURPOSE: The prevalence of hyperdynamic left ventricular (LV) systolic function in septic patients and its impact on mortality remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and association of hyperdynamic LV systolic function with mortality in patients with sepsis. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Primary outcomes were the prevalence of hyperdynamic LV systolic function in adult septic patients and the associated short-term mortality as compared to normal LV systolic function. Hyperdynamic LV systolic function was defined using LV ejection fraction (LVEF) of 70% as cutoff. Secondary outcomes were heart rate, LV end-diastolic diameter (LVEDD), and E/e' ratio. RESULTS: Four studies were included, and the pooled prevalence of hyperdynamic LV systolic function was 18.2% ([95% confidence interval (CI) 12.5, 25.8]; I2 = 7.0%, P < 0.0001). Hyperdynamic LV systolic function was associated with higher mortality: odds ratio of 2.37 [95%CI 1.47, 3.80]; I2 = 79%, P < 0.01. No difference was found in E/e' (P = 0.43) between normal and hyperdynamic LV systolic function, while higher values of heart rate (mean difference: 6.14 beats/min [95%CI 3.59, 8.69]; I2 = 51%, P < 0.0001) and LVEDD (mean difference: - 0.21 cm [95%CI - 0.33, - 0.09]; I2 = 73%, P < 0.001) were detected in patients with hyperdynamic LV systolic function. CONCLUSION: The prevalence of hyperdynamic LV systolic function is not negligible in septic patients. Such a finding is associated with significantly higher short-term mortality as compared to normal LV systolic function.

INVASIVE HEMODYNAMIC MONITORING WITH PULMONARY ARTERY CATHETER IN SEPSIS-ASSOCIATED CARDIOGENIC SHOCK.

ABSTRACT: Background: Both sepsis-induced cardiomyopathy and worsening of preexisting cardiac disease can contribute to circulatory shock in septic patients. The early use of pulmonary artery catheter (PAC) could play a pivotal role in the management of sepsis-associated cardiogenic shock. In this study, we aimed to evaluate the impact of early invasive hemodynamic monitoring with PAC in patients with sepsis-associated cardiogenic shock. Method: We performed a retrospective study using the National Inpatient Sample data from January 2017 to December 2019. The early use of PAC was defined as the use of PAC within 2 days from the admission. We performed the multivariable logistic regression analysis to investigate the association between the early use of PAC and in-hospital mortality in patients with sepsis-associated cardiogenic shock and sepsis without cardiogenic shock, respectively. Results: There was no difference in in-hospital mortality between PAC and no PAC groups in sepsis without cardiogenic shock (adjusted odds ratio [aOR] = 1.05, 95% confidence interval [CI] = 0.82-1.35, P = 691). On the other hand, the early use of PAC was independently associated with lower in-hospital mortality in patients with sepsis-associated cardiogenic shock (aOR = 0.58, 95% confidence interval [CI] = 0.46-0.72, P < 0.001). The use of PAC was also associated with increased use of mechanical circulatory support in those with sepsis-associated cardiogenic shock (aOR = 12.26, 95% CI = 9.37-16.03, P < 0.001). For patients with sepsis-associated cardiogenic shock, the use of PAC after 2 days of admission was associated with significantly higher in-hospital mortality and decreased use of mechanical circulatory support. Conclusion: The use of pulmonary artery catheters in sepsis-associated cardiogenic shock was associated with significantly lower in-hospital mortality and increased use of mechanical circulatory supports in patients with sepsis-associated cardiogenic shock.

Hospital-Onset Sepsis Warrants Expanded Investigation and Consideration as a Unique Clinical Entity.

Sepsis causes more than a quarter million deaths among hospitalized adults in the United States each year. Although most cases of sepsis are present on admission, up to one-quarter of patients with sepsis develop this highly morbid and mortal condition while hospitalized. Compared with patients with community-onset sepsis (COS), patients with hospital-onset sepsis (HOS) are twice as likely to require mechanical ventilation and ICU admission, have more than two times longer ICU and hospital length of stay, accrue five times higher hospital costs, and are twice as likely to die. Patients with HOS differ from those with COS with respect to underlying comorbidities, admitting diagnosis, clinical manifestations of infection, and severity of illness. Despite the differences between these patient populations, patients with HOS sepsis are understudied and warrant expanded investigation. Here, we outline important knowledge gaps in the recognition and management of HOS in adults and propose associated research priorities for investigators. Of particular importance are questions regarding standardization of research and clinical case identification, understanding of clinical heterogeneity among patients with HOS, development of tailored management recommendations, identification of impactful prevention strategies, optimization of care delivery and quality metrics, identification and correction of disparities in care and outcomes, and how to ensure goal-concordant care for patients with HOS.

Validity of International Classification of Diseases, Tenth Revision, codes for atrial fibrillation/flutter in critically ill patients with sepsis.

BACKGROUND: Atrial fibrillation (AF) and atrial flutter (AFL) are frequently seen in critically ill sepsis patients and are associated with poor outcomes. There is a need for further research, however, studies are limited due to challenges in identifying patient cohorts. Administrative data using the International Classification of Diseases, Tenth Revision (ICD-10) are routinely used for identifying disease cohorts in large datasets. However, the validity of ICD-10 for AF/AFL remains unexplored in these populations. METHODS: This validation study included 6554 adults with sepsis and septic shock admitted to the intensive care unit. We sought to determine whether ICD-10 coding could accurately identify patients with and without AF/AFL compared to manual chart review. We also evaluated whether the date of ICD-10 code entry could distinguish prevalent from incident AF/AFL, presuming codes dated during the index admission to be incident AF/AFL. A manual chart review was performed on 400 randomly selected patients for confirmation of AF/AFL, and validity was measured using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Among the 400 randomly selected patients, 293 lacked ICD-10 codes for AF/AFL. The manual chart review confirmed the absence of AF/AFL in 286 patients (NPV 97.3%, specificity 99.7%). Among the 107 patients with ICD-10 codes for AF/AFL, 106 were confirmed to have AF/AFL by manual chart review (PPV 99.1%, sensitivity 93.0%). Out of the 114 patients with confirmed AF/AFL, 44 had ICD-10 codes dated during the index admission. All 44 were confirmed to have AF/AFL, however, 18 patients had prior documentation of AF/AFL (incident AF/AFL: PPV 59.1%). Specificity for incident (95.1%) and prevalent (99.7%) AF/AFL were high; however, sensitivity was 76.5% and 77.5%, respectively. DISCUSSION/CONCLUSION: ICD-10 codes perform well in identifying clinical AF/AFL in critically ill sepsis. However, their temporal specificity in distinguishing incidents from prevalent AF/AFL is limited.

Comparison of Central and Peripheral Arterial Blood Pressure Gradients in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic circulation. We aimed to perform a systematic review and meta-analysis on blood pressure differences between central and peripheral arterial cannulation in critically ill patients. DATA SOURCES: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase from inception to December 26, 2023, using Medical Subject Headings (MeSH) terms and keywords. STUDY SELECTION: Observation study of adult patients in ICUs and operating rooms who underwent simultaneous central (femoral, axillary, or subclavian artery) and peripheral (radial, brachial, or dorsalis pedis artery) arterial catheter placement in ICUs and operating rooms. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool. DATA SYNTHESIS: Twenty-four studies that enrolled 1598 patients in total were included. Central pressures (mean arterial pressure [MAP] and systolic blood pressure [SBP]) were found to be significantly higher than their peripheral counterparts, with mean gradients of 3.5 and 8.0 mm Hg, respectively. However, there was no statistically significant difference in central or peripheral diastolic blood pressure (DBP). Subgroup analysis further highlighted a higher MAP gradient during the on-cardiopulmonary bypass stage of cardiac surgery, reperfusion stage of liver transplant, and in nonsurgical critically ill patients. SBP or DBP gradient did not demonstrate any subgroup specific changes. CONCLUSIONS: SBP and MAP obtained by central arterial cannulation were higher than peripheral arterial cannulation; however, clinical implication of a difference of 8.0 mm Hg in SBP and 3.5 mm Hg in MAP remains unclear. Our current clinical practices preferring peripheral arterial lines need not change.

Peripheral Administration of Norepinephrine: A Prospective Observational Study.

BACKGROUND: Historically, norepinephrine has been administered through a central venous catheter (CVC) because of concerns about the risk of ischemic tissue injury if extravasation from a peripheral IV catheter (PIVC) occurs. Recently, several reports have suggested that peripheral administration of norepinephrine may be safe. RESEARCH QUESTION: Can a protocol for peripheral norepinephrine administration safely reduce the number of days a CVC is in use and frequency of CVC placement? STUDY DESIGN AND METHODS: This was a prospective observational cohort study conducted in the medical ICU at a quaternary care academic medical center. A protocol for peripheral norepinephrine administration was developed and implemented in the medical ICU at the study site. The protocol was recommended for use in patients who met prespecified criteria, but was used at the treating clinician's discretion. All adult patients admitted to the medical ICU receiving norepinephrine through a PIVC from February 2019 through June 2021 were included. RESULTS: The primary outcome was the number of days of CVC use that were avoided per patient, and the secondary safety outcomes included the incidence of extravasation events. Six hundred thirty-five patients received peripherally administered norepinephrine. The median number of CVC days avoided per patient was 1 (interquartile range, 0-2 days per patient). Of the 603 patients who received norepinephrine peripherally as the first norepinephrine exposure, 311 patients (51.6%) never required CVC insertion. Extravasation of norepinephrine occurred in 35 patients (75.8 events/1,000 d of PIVC infusion [95% CI, 52.8-105.4 events/1,000 d of PIVC infusion]). Most extravasations caused no or minimal tissue injury. No patient required surgical intervention. INTERPRETATION: This study suggests that implementing a protocol for peripheral administration of norepinephrine safely can avoid 1 CVC day in the average patient, with 51.6% of patients not requiring CVC insertion. No patient experienced significant ischemic tissue injury with the protocol used. These data support performance of a randomized, prospective, multicenter study to characterize the net benefits of peripheral norepinephrine administration compared with norepinephrine administration through a CVC.