Ultrasound-guided Axillary Artery Catheter Placement and Associated Complications in Critically Ill Patients.

BACKGROUND: Arterial catheter placement for hemodynamic monitoring is commonly performed in critically ill patients. The radial and femoral arteries are the two sites most frequently used; there is limited data on the use of the axillary artery for this purpose. The aim of this study was to investigate the rate of complications from ultrasound-guided axillary artery catheter placement in critically ill patients. METHODS: A retrospective study at a tertiary care center of patients admitted to an intensive care unit who had ultrasound-guided axillary artery catheter placement during admission. Primary outcome of interest was catheter related complications, including bleeding, vascular complications, compartment syndrome, stroke or air embolism, catheter malfunction, and need for surgical intervention. RESULTS: This study identified 88 patients who had an ultrasound-guided axillary artery catheter placed during their admission. Of these 88, nine patients required multiple catheters placed, for a total of 99 axillary artery catheter placement events. The median age was 64 [IQR 48, 71], 41 (47%) were female, and median body mass index (BMI) was 26 [IQR 22, 30]. The most common complication was minor bleeding (11%), followed by catheter malfunction (2%), and vascular complications (2%). Univariate analyses did not show any association between demographics and clinical variables, and complications related to axillary arterial catheter. CONCLUSION: The most common complication found with ultrasound-guided axillary artery catheter placement was minor bleeding, followed by catheter malfunction, and vascular complications. Ultrasound-guided axillary arterial catheters are an alternative in patients in whom radial or femoral arterial access is difficult or not possible to achieve.

Prevalence of peri-intubation major adverse events among critically ill patients: A systematic review and meta analysis.

BACKGROUND: Peri-intubation major adverse events (MAEs) are potentially preventable and associated with poor patient outcomes. Critically ill patients intubated in Emergency Departments, Intensive Care Units or medical wards are at particularly high risk for MAEs. Understanding the prevalence and risk factors for MAEs can help physicians anticipate and prepare for the physiologically difficult airway. METHODS: We searched PubMed, Scopus, and Embase for prospective and retrospective observational studies and randomized control trials (RCTs) reporting peri-intubation MAEs in intubations occurring outside the operating room (OR) or post-anesthesia care unit (PACU). Our primary outcome was any peri-intubation MAE, defined as any hypoxia, hypotension/cardiovascular collapse, or cardiac arrest. Esophageal intubation and failure to achieve first-pass success were not considered MAEs. Secondary outcomes were prevalence of hypoxia, cardiac arrest, and cardiovascular collapse. We performed random-effects meta-analysis to identify the prevalence of each outcome and moderator analyses and meta-regressions to identify risk factors. We assessed studies' quality using the Cochrane Risk of Bias 2 tool and the Newcastle-Ottawa Scale. RESULTS: We included 44 articles and 34,357 intubations. Peri-intubation MAEs were identified in 30.5% of intubations (95% CI 25-37%). MAEs were more common in the intensive care unit (ICU; 41%, 95% CI 33-49%) than the Emergency Department (ED; 17%, 95% CI 12-24%). Intubation for hemodynamic instability was associated with higher rates of MAEs, while intubation for airway protection was associated with lower rates of MAEs. Fifteen percent (15%, 95% CI 11.5-19%) of intubations were complicated by hypoxia, 2% (95% CI 1-3.5%) by cardiac arrest, and 18% (95% CI 13-23%) by cardiovascular collapse. CONCLUSIONS: Almost one in three patients intubated outside the OR and PACU experience a peri-intubation MAE. Patients intubated in the ICU and those with pre-existing hemodynamic compromise are at highest risk. Resuscitation should be considered an integral part of all intubations, particularly in high-risk patients.

Venoarterial Extracorporeal Membrane Oxygenation With or Without Advanced Intervention for Massive Pulmonary Embolism.

INTRODUCTION: Massive pulmonary embolism (MPE) is a rare but highly fatal condition. Our study's objective was to evaluate the association between advanced interventions and survival among patients with MPE treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: This is a retrospective review of the Extracorporeal Life Support Organization (ELSO) registry data. We included adult patients with MPE who were treated with VA-ECMO during 2010-2020. Our Primary outcome was survival to hospital discharge; secondary outcomes were ECMO duration among survivors and rates of ECMO-related complications. Clinical variables were compared using the Pearson chi-square and Kruskal-Wallis H tests. RESULTS: We included 802 patients; 80 (10%) received SPE and 18 (2%) received CDT. Overall, 426 (53%) survived to discharge; survival was not significantly different among those treated with SPE or CDT on VA-ECMO (70%) versus VA-ECMO alone (52%) or SPE or CDT before VA-ECMO (52%). Multivariable regression found a trend towards increased survival among those treated with SPE or CDT while on ECMO (AOR 1.8, 95% CI 0.9-3.6), but no significant correlation. There was no association between advanced interventions and ECMO duration among survivors, or rates of ECMO-related complications. CONCLUSION: Our study found no difference in survival in patients with MPE who received advanced interventions prior to ECMO, and a slight non-significant benefit in those who received advanced interventions while on ECMO.

Intracranial and Blood Pressure Variability and In-Hospital Outcomes in Intracranial Device-Monitored Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is a major health concern and has high mortality rates up to 52%. Despite a decrease in its incidence, fatality rates remain unchanged; understanding and preventing of factors associated with mortality and treatments for these are needed. Blood pressure variability (BPV) has been shown to be a potential modifiable factor associated with clinical outcomes in patients with traumatic intracerebral hemorrhage and sICH. Few data are available on the effect of intracranial pressure (ICP) variability (ICPV) and outcomes in patients with sICH. The goal of our study was to investigate the association between ICPV and BPV during the first 24 h of intensive care unit (ICU) admission and external ventricular drain (EVD) placement, and mortality in patients with sICH who were monitored with an EVD. METHODS: We conducted a single-center retrospective study of adult patients admitted to an ICU with a diagnosis of sICH who required EVD placement during hospitalization. We excluded patients with ICH secondary to other pathological conditions such as trauma, underlying malignancy, or arteriovenous malformation. Blood pressure and ICP measurements were collected and recorded hourly during the first 24 h of ICU admission and EVD placement, respectively. Measures of variability used were standard deviation (SD) and successive variation (SV). Primary outcome of interest was in-hospital mortality, and secondary outcomes were hematoma expansion and discharge home (a surrogate for good functional outcome at discharge). Descriptive statistics and multivariable logistic regressions were performed. RESULTS: We identified 179 patients with sICH who required EVD placement. Of these, 52 (29%) patients died, 121 (68%) patients had hematoma expansion, and 12 (7%) patients were discharged home. Patient's mean age (± SD) was 56 (± 14), and 87 (49%) were women. The mean opening ICP (± SD) was 21 (± 8) and median ICH score (interquartile range) was 2 (2-3). Multivariable logistic regression found an association between ICP-SV and ICP-SD and hematoma expansion (odds ratio 1.6 [1.03-2.30], p = 0.035 and odds ratio 0.77 [0.63-0.93] p = 0.009, respectively). CONCLUSIONS: Our study found an association between ICPV and hematoma expansion in patients with sICH monitored with an EVD. Measures of ICPV relating to rapid changes in ICP (ICP-SV) were associated with a higher odds of hematoma expansion, whereas measures relating to tight control of ICP (ICP-SD) were associated with a lower odds of hematoma expansion. One measure of BPV, sytolic blood pressure maximum-minimum (SBP max-min), was found to be weakly associated with discharge home (a surrogate for good functional outcome at hospital discharge). More research is needed to support these findings.

Blood Pressure Variability and Outcome in Traumatic Brain Injury: A Propensity Score Matching Study.

INTRODUCTION: Patients with tIPH (used here to refer to traumatic intraparenchymal hemorrhagic contusion) or intraparenchymal hemorrhage face high rates of mortality and persistent functional deficits. Prior studies have found an association between blood pressure variability (BPV) and neurologic outcomes in patients with spontaneous IPH. Our study investigated the association between BPV and discharge destination (a proxy for functional outcome) in patients with tIPH. METHODS: We retrospectively reviewed the charts of patients admitted to a Level I trauma center for ≥ 24 hours with tIPH. We examined variability in hourly BP measurements over the first 24 hours of hospitalization. Our outcome of interest was discharge destination (home vs facility). We performed 1:1 propensity score matching and multivariate regressions to identify demographic and clinical factors predictive of discharge home. RESULTS: We included 354 patients; 91 were discharged home and 263 to a location other than home. The mean age was 56 (SD 21), 260 (73%) were male, 22 (6%) were on anticoagulation, and 54 (15%) on antiplatelet therapy. Our propensity-matched cohorts included 76 patients who were discharged home and 76 who were discharged to a location other than home. One measure of BPV (successive variation in systolic BP) was identified as an independent predictor of discharge location in our propensity-matched cohorts (odds ratio 0.89, 95% confidence interval 0.8-0.98; P = 0.02). Our model demonstrated good goodness of fit (P-value for Hosmer-Lemeshow test = 0.88) and very good discriminatory capability (AUROC = 0.81). High Glasgow Coma Scale score at 24 hours and treatment with fresh frozen plasma were also associated with discharge home. CONCLUSION: Our study suggests that increased BPV is associated with lower rates of discharge home after initial hospitalization among patients with tIPH. Additional research is needed to evaluate the impact of BP control on patient outcomes.

Association between resuscitation in the critical care resuscitation unit and in-hospital mortality.

INTRODUCTION: Patients who present in shock have high expected mortality and early resuscitation is crucial to improve their outcomes. The Critical Care Resuscitation Unit (CCRU) is a specialized unit at the University of Maryland Medical Center (UMMC) that prioritizes early resuscitation of critically ill patients. We hypothesized that lactate clearance and reduction of Sequential Organ Failure Assessment (SOFA) score during CCRU stay would be associated with lower in-hospital mortality. METHODS: We performed a retrospective analysis of adult patients who were admitted to the CCRU between 01/01/2018-12/31/2018 and had a diagnosis of severe shock, determined by serum lactate ≥4 mmol/L. We excluded patients who died during CCRU stay. We used multivariable logistic regression to evaluate the association between lactate clearance and reduction in SOFA scores during CCRU stay and in-hospital mortality. RESULTS: Out of 1740 patients admitted to the CCRU in 2018, 172 (10%) had serum lactate ≥4 mmol/L. Twenty-two (13%) patients died during their CCRU stay. Our primary analysis included 129 patients with lactate clearance data and 136 patients with SOFA data. Average patients' age was 54 years, and median length of stay in the CCRU was 6 h 55 min. The average lactate and SOFA score on admission were 7.4 (3.8) mmol/L and 8.3 (4.7), respectively. Average lactate clearance was 1.9 (3.1) and average SOFA score reduction was 0.2 (2.9). In multivariable logistic regressions evaluating SOFA score and lactate separately, SOFA score reduction during CCRU stay was associated with lower in-hospital mortality (OR 0.83, 95% CI: 0.70-0.97) but lactate clearance was not (OR 0.90, 95% CI 0.78-1.03). In forward stepwise multivariable analysis containing both SOFA score and lactate values, SOFA score clearance during CCRU stay was still associated with decreased in-hospital mortality (OR 0.84, 95% CI 0.72-0.98). CONCLUSIONS: Care in the CCRU is more effective at reducing lactate than SOFA scores in patients with severe shock. However, SOFA score reduction in the resuscitation phase during the CCRU stay was associated with decreased odds of in-hospital mortality in this group of patients. Further studies are necessary to confirm our observations.

Endothelial-specific loss of Krüppel-Like Factor 4 triggers complement-mediated endothelial injury.

Thrombotic microangiopathy (TMA) in the kidney represents the most severe manifestation of kidney microvascular endothelial injury. Despite the source of the inciting event, the diverse clinical forms of kidney TMA share dysregulation of endothelial cell transcripts and complement activation. Here, we show that endothelial-specific knockdown of Krüppel-Like Factor 4 (Klf4)ΔEC, an anti-inflammatory and antithrombotic zinc-finger transcription factor, increases the susceptibility to glomerular endothelial injury and microangiopathy in two genetic murine models that included endothelial nitric oxide synthase knockout mice and aged mice (52 weeks), as well as in a pharmacologic model of TMA using Shiga-toxin 2. In all models, Klf4ΔEC mice exhibit increased pro-thrombotic and pro-inflammatory transcripts, as well as increased complement factors C3 and C5b-9 deposition and histologic features consistent with subacute TMA. Interestingly, complement activation in Klf4ΔEC mice was accompanied by reduced expression of a key KLF4 transcriptional target and membrane bound complement regulatory gene, Cd55. To assess a potential mechanism by which KLF4 might regulate CD55 expression, we performed in silico chromatin immunoprecipitation enrichment analysis of the CD55 promotor and found KLF4 binding sites upstream from the CD55 transcription start site. Using patient-derived kidney biopsy specimens, we found glomerular expression of KLF4 and CD55 was reduced in patients with TMA as compared to control biopsies of the unaffected pole of patient kidneys removed due to kidney cancer. Thus, our data support that endothelial Klf4 is necessary for maintenance of a quiescent glomerular endothelial phenotype and its loss increases susceptibility to complement activation and induction of prothrombotic and pro-inflammatory pathways.

A Comparison between Conventional and Extracorporeal Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.

There is limited evidence comparing the use of extracorporeal cardiopulmonary resuscitation (ECPR) to CPR in the management of refractory out-of-hospital cardiac arrest (OHCA). We conducted a systematic review and meta-analysis to compare survival and neurologic outcomes associated with ECPR versus CPR in the management of OHCA. We searched PubMed, EMBASE, and Scopus to identify observational studies and randomized controlled trials comparing ECPR and CPR. We used the Newcastle−Ottawa Scale and Cochrane's risk-of-bias tool to assess studies' quality. We used random-effects models to compare outcomes between the pooled populations and moderator analysis to identify sources of heterogeneity and perform subgroup analysis. We identified 2088 articles and included 13, with 18,620 patients with OHCA. A total of 16,701 received CPR and 1919 received ECPR. Compared with CPR, ECPR was associated with higher odds of achieving favorable neurologic outcomes at 3 (OR 5, 95% CI 1.90−13.1, p < 0.01) and 6 months (OR 4.44, 95% CI 2.3−8.5, p < 0.01). We did not find a significant survival benefit or impact on neurologic outcomes at hospital discharge or 1 month following arrest. ECPR is a promising but resource-intensive intervention with the potential to improve long-term outcomes among patients with OHCA.

How effective is extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest? A systematic review and meta-analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has gained increasing as a promising but resource-intensive intervention for out-of-hospital cardiac arrest (OHCA). There is little data to quantify the impact of this intervention and the patients likely to benefit from its use. We conducted a meta-analysis of the literature to assess the survival benefit associated with ECPR for OHCA. METHODS: We searched PubMed, Embase, and Scopus databases to identify relevant observational studies and randomized control trials. We used the Newcastle-Ottawa Scale and Cochrane risk-of-bias tool to assess studies' quality. We performed random-effects meta-analysis for the primary outcome of survival to hospital discharge and used meta-regressions to assess heterogeneity. RESULTS: We identified 1287 articles, reviewed the full text of 209 and included 44 in our meta-analysis. Our analysis included 3097 patients with OHCA. Patients' mean age was 52, 79% were male, and 60% had primary ventricular fibrillation/ventricular tachycardia arrest. We identified a survival-to-discharge rate of 24%; 18% survived with favorable neurologic function. 30- and 90-days survival rates were both around 18%. The majority of included articles were high quality studies. CONCLUSIONS: Extracorporeal cardiopulmonary resuscitation is a promising but resource-intensive intervention that may increase rates of survival to hospital discharge among patients who experience OHCA.

Perceptions and Patterns of Cigarette and E-Cigarette Use among Hispanics: A Heterogeneity Analysis of the 2017-2019 Health Information National Trends Survey.

There are documented disparities in smoking behaviors among Hispanic adults in the U.S., but little is known about patterns of e-cigarette use. Using data from the HINTS 5 cycle 1-3, we examined cigarette and e-cigarette history and current use, as well as perceptions of the dangers of e-cigarette use relative to cigarette use. Primary predictors were Hispanic ethnic group, gender, age, education, income, and English language proficiency. Binary outcomes were modeled using the logit link, and multinomial outcome variables were modeled using generalized logit model. Fifty-three percent of participants were Mexican, 8% Puerto Rican, 4% were Cuban, and 35% identified as other Hispanics. Of the 1618 respondents, 23% were former cigarette smokers and 10% were current cigarette smokers. Twenty percent reported history of electronic cigarettes and 4% reported current use. In multivariable models, Hispanic women were significantly less likely to report ever being smokers compared to Hispanic men (aOR = 0.61, 95% CI = 0.42, 0.88). Puerto Ricans were 2.4 times as likely to report being current smokers (95% CI = 1.11, 5.11) compared to Mexicans. Among Hispanics, significant differences in e-cigarette and cigarette use behaviors emerged by gender, age, ethnicity, and cancer history, with implications for tailoring smoking prevention and cessation messages.

Predictors of intubation in COVID-19 patients undergoing awake proning in the emergency department.

BACKGROUND: Awake prone positioning (PP) has been used to avoid intubations in hypoxic COVID-19 patients, but there is limited evidence regarding its efficacy. Moreover, clinicians have little information to identify patients at high risk of intubation despite awake PP. We sought to assess the intubation rate among patients treated with awake PP in our Emergency Department (ED) and identify predictors of need for intubation. METHODS: We conducted a multicenter retrospective cohort study of adult patients admitted for known or suspected COVID-19 who were treated with awake PP in the ED. We excluded patients intubated in the ED. Our primary outcome was prevalence of intubation during initial hospitalization. Other outcomes were intubation within 48 h of admission and mortality. We performed classification and regression tree analysis to identify the variables most likely to predict the need for intubation. RESULTS: We included 97 patients; 44% required intubation and 21% were intubated within 48 h of admission. Respiratory oxygenation (ROX) index and P/F (partial pressure of oxygen / fraction of inspired oxygen) ratio measured 24 h after admission were the variables most likely to predict need for intubation (area under the receiver operating characteristic curve = 0.82). CONCLUSIONS: Among COVID-19 patients treated with awake PP in the ED prior to admission, ROX index and P/F ratio, particularly 24 h after admission, may be useful tools in identifying patients at high risk of intubation.

Intubation rate of patients with hypoxia due to COVID-19 treated with awake proning: A meta-analysis.

BACKGROUND: Awake prone positioning (PP), or proning, is used to avoid intubations in hypoxic patients with COVID-19, but because of the disease's novelty and constant evolution of treatment strategies, the efficacy of awake PP is unclear. We conducted a meta-analysis of the literature to assess the intubation rate among patients with COVID-19 requiring oxygen or noninvasive ventilatory support who underwent awake PP. METHODS: We searched PubMed, Embase, and Scopus databases through August 15, 2020 to identify relevant randomized control trials, observational studies, and case series. We performed random-effects meta-analyses for the primary outcome of intubation rate. We used moderator analysis and meta-regressions to assess sources of heterogeneity. We used the standard and modified Newcastle-Ottawa Scales (NOS) to assess studies' quality. RESULTS: Our search identified 1043 articles. We included 16 studies from the original search and 2 in-press as of October 2020 in our analysis. All were observational studies. Our analysis included 364 patients; mean age was 56.8 (SD 7.12) years, and 68% were men. The intubation rate was 28% (95% CI 20%-38%, I2 = 63%). The mortality rate among patients who underwent awake PP was 14% (95% CI 7.4%-24.4%). Potential sources of heterogeneity were study design and setting (practice and geographic). CONCLUSIONS: Our study demonstrated an intubation rate of 28% among hypoxic patients with COVID-19 who underwent awake PP. Awake PP in COVID-19 is feasible and practical, and more rigorous research is needed to confirm this promising intervention.

Krüppel-like factor 4 is a negative regulator of STAT3-induced glomerular epithelial cell proliferation.

Pathologic glomerular epithelial cell (GEC) hyperplasia is characteristic of both rapidly progressive glomerulonephritis (RPGN) and subtypes of focal segmental glomerulosclerosis (FSGS). Although initial podocyte injury resulting in activation of STAT3 signals GEC proliferation in both diseases, mechanisms regulating this are unknown. Here, we show that the loss of Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, enhances GEC proliferation in both RPGN and FSGS due to dysregulated STAT3 signaling. We observed that podocyte-specific knockdown of Klf4 (C57BL/6J) increased STAT3 signaling and exacerbated crescent formation after nephrotoxic serum treatment. Interestingly, podocyte-specific knockdown of Klf4 in the FVB/N background alone was sufficient to activate STAT3 signaling, resulting in FSGS with extracapillary proliferation, as well as renal failure and reduced survival. In cultured podocytes, loss of KLF4 resulted in STAT3 activation and cell-cycle reentry, leading to mitotic catastrophe. This triggered IL-6 release into the supernatant, which activated STAT3 signaling in parietal epithelial cells. Conversely, either restoration of KLF4 expression or inhibition of STAT3 signaling improved survival in KLF4-knockdown podocytes. Finally, human kidney biopsy specimens with RPGN exhibited reduced KLF4 expression with a concomitant increase in phospho-STAT3 expression as compared with controls. Collectively, these results suggest the essential role of KLF4/STAT3 signaling in podocyte injury and its regulation of aberrant GEC proliferation.