Among intravital imaging instruments, the intravital two-photon fluorescence excitation microscope has the advantage of enabling real-time 3D fluorescence imaging deep into cells and tissues, with reduced photobleaching and photodamage compared with conventional intravital confocal microscopes. However, excessive motion of organs due to involuntary movement such as breathing may result in out-of-focus images and severe fluorescence intensity fluctuations, which hinder meaningful imaging and analysis. The clinically approved alpha-2 adrenergic receptor agonist dexmedetomidine was administered to mice during two-photon fluorescence intravital imaging to alleviate this problem. As dexmedetomidine blocks the release of the neurotransmitter norepinephrine, pain is suppressed, blood pressure is reduced, and a sedation effect is observed. By tracking the quality of focus and stability of detected fluorescence in two-photon fluorescence images of fluorescein isothiocyanate-sensitized liver vasculature in vivo, we demonstrated that intravascular dexmedetomidine can reduce fluorescence fluctuations caused by respiration on a timescale of minutes in mice, improving image quality and resolution. The results indicate that short-term dexmedetomidine treatment is suitable for reducing involuntary motion in preclinical intravital imaging studies. This method may be applicable to other animal models.

Introduction: Determining fluid status prior to resuscitation provides a more accurate guide for appropriate fluid administration in the setting of undifferentiated hypotension. Emergency Department (ED) point of care ultrasound (PoCUS) has been proposed as a potential non-invasive, rapid, repeatable investigation to ascertain inferior vena cava (IVC) characteristics. Our goal was to determine the feasibility of using PoCUS to measure IVC size and collapsibility. Methods: This was a planned secondary analysis of data from a prospective multicentre international study investigating PoCUS in ED patients with undifferentiated hypotension. We prospectively collected data on IVC size and collapsibility using a standard data collection form in 6 centres. The primary outcome was the proportion of patients with a clinically useful (determinate) scan defined as a clearly visible intrahepatic IVC, measurable for size and collapse. Descriptive statistics are provided. Results: A total of 138 scans were attempted on 138 patients; 45.7% were women and the median age was 58 years old. Overall, one hundred twenty-nine scans (93.5%; 95% CI 87.9 to 96.7%) were determinate. 131 (94.9%; 89.7 to 97.7%) were determinate for IVC size, and 131 (94.9%; 89.7 to 97.7%) were determinate for collapsibility. Conclusion: In this analysis of 138 ED patients with undifferentiated hypotension, the vast majority of PoCUS scans to investigate IVC characteristics were determinate. Future work should include analysis of the value of IVC size and collapsibility in determining fluid status in this group.

Introduction: Patients presenting to the emergency department (ED) with hypotension have a high mortality rate and require careful yet rapid resuscitation. The use of cardiac point of care ultrasound (PoCUS) in the ED has progressed beyond the basic indications of detecting pericardial fluid and activity in cardiac arrest. We examine if finding left ventricular dysfunction (LVD) on emergency physician performed PoCUS reliably predicts the presence of cardiogenic shock in hypotensive ED patients. Methods: We prospectively collected PoCUS findings performed in 135 ED patients with undifferentiated hypotension as part of an international study. Patients with clearly identified etiologies for hypotension were excluded, along with other specific presumptive diagnoses. LVD was defined as identification of a generally hypodynamic LV in the setting of shock. PoCUS findings were collected using a standardized protocol and data collection form. All scans were performed by PoCUS-trained emergency physicians. Final shock type was defined as cardiogenic or non-cardiogenic by independent specialist blinded chart review. Results: All 135 patients had complete follow up. Median age was 56 years, 53% of patients were male. Disease prevalence for cardiogenic shock was 12% and the mortality rate was 24%. The presence of LVD on PoCUS had a sensitivity of 62.50% (95%CI 35.43% to 84.80%), specificity of 94.12% (88.26% to 97.60%), positive-LR 10.62 (4.71 to 23.95), negative-LR 0.40 (0.21 to 0.75) and accuracy of 90.37% (84.10% to 94.77%) for detecting cardiogenic shock. Conclusion: Detecting left ventricular dysfunction on PoCUS in the ED may be useful in confirming the underlying shock type as cardiogenic in otherwise undifferentiated hypotensive patients.

Introduction: Endotracheal intubation (EI) is frequently performed in the emergency department (ED). Although this procedure is generally life-saving, EI is also known to cause adverse effects, such as hemodynamic alterations. A systolic blood pressure <90 mmHg is the most commonly accepted definition of hypotension; however systolic blood pressure naturally increases with age. The National Trauma Triage Protocol now states that this threshold could be raised to 110 mmHg in older patients. Objective: to determine the impact of increasing the post-intubation hypotension (PIH) threshold to 110 mmHg on hospital length of stay and mortality in older patients. Methods: Design: A historical cohort of patients admitted in a level-1 trauma center ED between 06/2011 and 05/2016 was constituted. Population: Patients were included if pre-EI vital signs were available, their intubation was performed in the resuscitation room, were aged ≥65, if no surgical access was needed and if EI was performed in ≤3 attempts. Measures: All clinical data including vitals were prospectively recorded using the software ReaScribe. Main outcome was in-hospital mortality. Analyses: Univariate and multivariate analyses assessed the relation between PHI and outcomes. Results: A total of 181 patients were included. When using the 90-mmHg threshold, 92 patients suffered from PIH. Mean length of stay for these PIH patients was 18.9 days, compared to 12.0 days for non-hypotensive patients (P = 0.06). Mortality rate at 24 hours was 9.78% and 15.83% for PIH and non PIH patients, respectively (p = 0.2). The 110-mmHg threshold identified 33 additional PIH patients (n = 125) and their mean length of stay was 17.8 compared to 10.2 days for non PIH patients (P = 0.02). Mortality rate at 24 hours was 9.90% for PIH patients and 21.43% for non PIH patients (p = 0.02). Conclusion: PIH was associated with a significant increase in LOS when the PIH threshold is set at 110. Mortality rate is high in the intubated ED older patient and that increasing hypotension threshold for older patient seem to have no impact on patient mortality at 24 hours. Since our sample is limited, more research is needed to confirm these results.

Introduction: Undifferentiated hypotension remains one of the most life-threatening presentations to emergency departments (ED) around the world. An accurate and rapid initial assessment is essential, as shock carries a high mortality with multiple unique etiologies and management plans. Point of care ultrasound (PoCUS) has emerged as a promising tool to improve these diagnostic and management challenges, yet its reliability in this setting remains unclear. Methods: We performed a systematic review of Medline, EMBASE, CINAHL, Cochrane, and clinicaltrials.gov databases from inception to June 8, 2018. Databases were reviewed by two independent researchers and all languages were included. The methodological quality of included studies were evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Our primary outcome was diagnostic accuracy of PoCUS in hypotension, with secondary outcomes including patient outcomes and changes to management. Results: Our literature search revealed 5345 articles after duplicates were removed, leaving 235 articles for full article review. Following full article review, 9 studies remained and were included in the systematic review. There were 2 randomized control trials, 6 prospective cohort trials, and 1 retrospective cohort trial. For our primary outcome of diagnostic accuracy, eight studies were included; we extracted Kappa values ranging from 0.70 to 0.971, pooled sensitivity ranging from 69% to 88%, and pooled specificity ranging from 88% to 96%. Four studies reported on management change including results reporting shorter time to disposition, change in diagnostic test ordering (18% to 31%), change in consultation (13.6%), change in admission location (12%) and change in management plan (25% to 40%). Only one study reported on patient outcomes, which revealed no survival or length of stay benefit. Conclusion: When assessing for the diagnostic accuracy of PoCUS in the setting of undifferentiated hypotension presenting to the emergency department, we found fair consistency between PoCUS and final diagnosis with high Kappa values, fair to good pooled sensitivities, and good to excellent specificities. There was no strong evidence indicating improved outcomes. However, the large amount of heterogeneity amongst studies has limited our ability to make a strong conclusion except that future research should focus on a uniform study design and patient focused outcomes.

Introduction: Hypotension is known to be associated with increased mortality in severe traumatic brain injury (TBI) patients. Systolic blood pressure (SBP) of <90 mmHg is the threshold for hypotension in consensus TBI treatment guidelines; however, evidence suggests hypotension should be defined at higher levels for these patients. Our objective was to determine the influence of hypotension on mortality in TBI patients requiring ICU admission using different thresholds of SBP on arrival at the emergency department (ED). Methods: Retrospective cohort study of patients with severe TBI (Abbreviated Injury Scale Head score ≥3) admitted to ICU at the QEII Health Sciences Centre (Halifax, Canada) between 2002 and 2013. Patients were grouped by SBP on ED arrival ( <90 mmHg, <100 mmHg, <110 mmHg). We performed multiple logistic regression analysis with mortality as the dependent variable. Models were adjusted for confounders including age, gender, Injury Severity Score (ISS), injury mechanism, and trauma team activation (TTA). Results: A total of 1233 patients sustained a severe TBI and were admitted to the ICU during the study period. The mean age was 43.4 ± 23.9 years and most patients were male (919/1233; 74.5%). The most common mechanism of injury was motor vehicle collision (491/1233; 41.2%) followed by falls (427/1233; 35.8%). Mean length of stay in the ICU was 6.1 ± 6.4 days, and the overall mortality rate was 22.7%. SBP on arrival was available for 1182 patients. The <90 mmHg group had 4.6% (54/1182) of these patients; mean ISS was 20.6 ± 7.8 and mortality was 40.7% (22/54). The <100 mmHg had 9.3% (110/1182) of patients; mean ISS was 19.3 ± 7.9 and mortality was 34.5% (38/110). The <110 mmHg group had 16.8% (198/1182) of patients; mean ISS was 17.9 ± 8.0 and mortality was 28.8% (57/198). After adjusting for confounders, the association between hypotension and mortality was 2.22 (95% CI 1.19-4.16) using a <90 mmHg cutoff, 1.79 (95% CI 1.12-2.86) using a <100 mmHg cutoff, and 1.50 (95% CI 1.02-2.21) using a <110 mmHg cutoff. Conclusion: While we found that TBI patients with a SBP <90 mmHg were over 2 times more likely to die, patients with an SBP <110 mmHg on ED arrival were still 1.5 times more likely to die from their injuries compared to patients without hypotension. These results suggest that establishing a higher threshold for clinically meaningful hypotension in TBI patients is warranted.

Introduction: Although use of point of care ultrasound (PoCUS) protocols for patients with undifferentiated hypotension in the Emergency Department (ED) is widespread, our previously reported SHoC-ED study showed no clear survival or length of stay benefit for patients assessed with PoCUS. In this analysis, we examine if the use of PoCUS changed fluid administration and rates of other emergency interventions between patients with different shock types. The primary comparison was between cardiogenic and non-cardiogenic shock types. Methods: A post-hoc analysis was completed on the database from an RCT of 273 patients who presented to the ED with undifferentiated hypotension (SBP <100 or shock index > 1) and who had been randomized to receive standard care with or without PoCUS in 6 centres in Canada and South Africa. PoCUS-trained physicians performed scans after initial assessment. Shock categories and diagnoses recorded at 60 minutes after ED presentation, were used to allocate patients into subcategories of shock for analysis of treatment. We analyzed actual care delivered including initial IV fluid bolus volumes (mL), rates of inotrope use and major procedures. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: Although there were expected differences in the mean fluid bolus volume between patients with non-cardiogenic and cardiogenic shock, there was no difference in fluid bolus volume between the control and PoCUS groups (non-cardiogenic control 1878 mL (95% CI 1550 – 2206 mL) vs. non-cardiogenic PoCUS 1687 mL (1458 – 1916 mL); and cardiogenic control 768 mL (194 – 1341 mL) vs. cardiogenic PoCUS 981 mL (341 – 1620 mL). Likewise there were no differences in rates of inotrope administration, or major procedures for any of the subcategories of shock between the control group and PoCUS group patients. The most common subcategory of shock was distributive. Conclusion: Despite differences in care delivered by subcategory of shock, we did not find any significant difference in actual care delivered between patients who were examined using PoCUS and those who were not. This may help to explain the previously reported lack of outcome difference between groups.