Sensitivity analyses also showed that cohort 2 had higher mortality compared with cohort 1. Supplementary Figure 1 (Supplemental Digital Content 2, http://links.lww.com/CCX/A49; legend, Supplemental Digital Content 4, http://links.lww.com/CCX/A51) shows a forest plot comparing the odds ratio for death across all primary and secondary analyses as well as the difference in mortality between cohorts 2 and 1. The crude odds ratio for death was the highest (1.43 [1.19–1.73]), whereas the IPWRA analysis using multiple imputation showed the lowest (1.20 [1.001–1.41]). Similarly, the difference (treatment effect) in mortality between cohort 1 and cohort 2 (mortality of cohort 2–mortality of cohort 1) was similarly highest for the crude analysis (mean difference in absolute mortality, 0.068; 95% CI, 0.03–0.11) and lowest for the IPWRA analysis using multiple imputation (difference, 0.032; 95% CI, 0.001–0.066). Odds ratios and absolute mean differences were in between these values for the IPWRA and propensity score-matched analysis (complete case analysis), as well as the adjusted analysis and the propensity score-matched analysis using multiple imputation. Covariates were adequately balanced between the two groups (cohorts 1 and 2) for the IPWRA and propensity-matched analyses based on visual inspection of distributions for each covariate (data not shown), distributions for the propensity scores (Supplementary Fig. 2, Supplemental Digital Content 3, http://links.lww.com/CCX/A50; legend, Supplemental Digital Content 4, http://links.lww.com/CCX/A51) and the overidentification test for covariate balance for the IPWRA analysis(p = 0.42). A sensitivity analysis focused only upon those receiving vasopressors demonstrated that while unadjusted mortality differences remained, adjusted mortality differences are not significant between groups. (Table 3).
Finally, we also stratified cases based on the quintiles of the propensity scores calculated for the above analyses and calculated stratum-specific odds ratios for mortality before hospital discharge for cohort 2 (POCUS before) versus cohort 1 (no POCUS) as well as a pooled estimate. The test for homogeneity (p = 0.35) suggests that ORs are homogenous across the five strata (quintiles) of propensity scores. Odds ratios ranged from 2.6 (quintile 1) to 1.2 (quintile 5), with a Mantel-Haenszel pooled estimate of 1.32 (95% CI, 1.07–1.63). We also repeated the adjusted analysis using only individuals with a propensity score greater than 0.1 and less than 0.9. The aOR for death comparing cohort 2 to cohort 1 was 1.29 (95% CI, 1.004–1.658).
In this study, we explored the impact of POCUS performed in the ED on the outcomes in critically ill patients in our two large academic EDs. We found critically ill patients that had POCUS performed prior to an intervention (cohort 2) had a higher in-hospital mortality. Although a recent prospective clinical trial suggests the ED POCUS has no impact on clinical outcomes (43) in patients with undifferentiated shock patients, ours is the first to suggest an association with potentially adverse outcomes of ED POCUS in critically ill patients.
A key question that needs exploration is: Why POCUS in the ED would result in higher in-hospital mortality? In this cohort study, ED patients that had POCUS prior to intervention had less aggressive treatment interventions in the ED when measured by both the volumes and timing of IV fluid and rates of intubation. These findings suggest POCUS influenced the aggressiveness of the immediate resuscitation in the ED.
Potentially, POCUS results in significant delays in treatment in the ED enough to adversely affect outcomes. Another potential explanation is that there is a group of patients with diagnostic uncertainty that POCUS identified ED patients who otherwise would not have been considered critically ill. Specifically, the etiology of shock upon initial evaluation in the ED is inherently challenging. There are not established characteristics of nontraumatic hypotension and shock in the ED (1). Thus, there may be differences in the role of POCUS in ED patients with undifferentiated shock versus those with obvious etiologies. There also may be differences in the use of POCUS for diagnosis and categorization than for therapy titration. Clearly, POCUS has been proposed not only for diagnostic purposes in shock but also to determine central venous pressure (44) and to guide fluid resuscitation (45).
There may also be a difference in the impact of POCUS between fluids and vasopressors. A sensitivity analysis focused only upon those receiving vasopressors demonstrated that while unadjusted mortality differences remained, adjusted mortality differences are not significant between groups. Yet looking at only patients receiving vasopressors is a limitation. Fluids and vasopressors are the two main interventions available in the ED for a hemodynamically unstable patient. ED POCUS has been widely touted to distinguish the fluid status these patients (hypovolemic, euvolemic, hypervolemic) and whether contractility is compromised. Thus, the purpose of POCUS in the ED is to guide whether to give more fluids, less fluids, or start a vasopressor/inotrope. It is not the ultrasound that changes the outcomes; it is the treatment decisions that come from doing the ultrasound (fluids or vasopressors).
POCUS in critically ill patients has widespread enthusiasm given the potential for rapid, noninvasive, and easily repeatable assessments of hemodynamics. In the ICU setting, there is evidence that POCUS can positively impact care outcomes. In a recent study by Kanji, a hemodynamic-guided echocardiogram was performed in patients admitted to the ICU with undifferentiated shock at a median time of 11 hours from admission. They found an improvement in mortality, which appears due to a reduction in total fluids in day 1 (44). A recent analysis of the Medical Information Mart for Intensive Care-III database showed reduced odds of mortality in patients that received formal echocardiography, interpreted by a cardiologist, in the ICU (45).
Extrapolation of these findings with POCUS in the ICU setting to the ED setting has been acceptable in our institutions given that POCUS allows for earlier diagnosis and treatment, improves confidence in the diagnosis (29–354346), and leads to changes in resuscitation strategy 25–30% of the time (35). Indeed, this has led to general recommendations and endorsements for POCUS to be performed in critically ill patients, including in the ED (4647). Furthermore, recent literature has shown that a positive fluid balance, generally considered as “over-resuscitation,” is associated with a higher mortality in shock (457810). An extension of this logic is that patients at risk of fluid overload, such as those with heart failure or renal failure, will be at greater risk of fluid overload. The best estimates of the prevalence of comorbid heart failure and renal failure are 20% and 10%, respectively (8911). Additionally, the utility of the fluid bolus has recently come under scrutiny as large database analyses are conflicting over the contribution of the fluid bolus to the mortality reduction seen with early resuscitation in septic shock (9–11). For these reasons, we hypothesized that POCUS prior to any intervention in the ED should reduce mortality.
Yet, what is less clear is the accuracy of the diagnoses or the impact of the resulting therapeutic interventions. Sekiguchi et al (35) performed focused cardiac ultrasounds on septic patients presenting to their medical ICU. The therapeutic plan was changed in 27%, and confidence in the diagnosis was enhanced in 37%. However, on independent review, providers incorrectly classified left ventricular (LV) function in 40% and right ventricular function in 50%; and no mortality data were reported. In another recent study by Hu et al (48), there is only moderate agreement between physician sonographers in the interpretation of cardiac standstill. In light of our results, this raises the question if physicians are making incorrect decisions based on what they think they see with POCUS? If LV function is impaired, which can be accurately estimated by emergency physicians (49), what is the threshold for using an inotrope in contrast to vasopressors or fluids? A possible explanation for our findings is inaccurate interpretation of POCUS images, and the therapeutic decisions based on those images. Thus, POCUS-related changes in fluid administration and vasoactive agents due to incorrect interpretation could have contributed to the differences in mortality. Perhaps it is not the first POCUS study that matters, but the one that comes after an initial period of resuscitation.
There are several limitations to our study, and these results must be interpreted with caution. We developed our registry to prospectively follow the care and outcomes of all critically ill patients admitted to the ICU from our EDs. Yet there are inherent limitations in these types of registries, including the dependence upon available clinical data rather than standardized research data obtained in an investigator controlled study. We used our formal ED ultrasound program to assure compliance with training and competence of providers performing POCUS and certification of the quality of ultrasound images. Yet, we did not review each individual study for formal cardiac functional measurements. Our methods were designed to reduce bias, however even though our sensitivity analyses retained the significant association with mortality in the POCUS group, the effect sizes were smaller and may be a result of other unmeasured confounders. Our registry also does not include patients that were resuscitated in the ED and avoided ICU admission, which could potentially bias against POCUS. The care the patients received after ICU admission could have been different between the groups as well and could have affected our results.
Furthermore, there are limitations in the analysis of observational studies that require special attention (50) including: 1) Causal inference requires careful consideration of confounding, 2) Interpretation of results should not rely on the magnitude of p values, and 3) Results should be presented in a granular and transparent fashion. We do not assert in this report that POCUS is causal. We merely suggest that the impact of POCUS on care processes and outcomes needs to be further interrogated. Our methods were designed to address known confounders and reduce bias, however even though our sensitivity analyses retained the significant association with mortality in the POCUS group, the effect sizes were smaller and may be a result of other unmeasured confounders.
There may be unknown clinical and system confounders in this retrospective cohort analysis. We attempted to control for potential confounders with our IPWRA, which maintained an increase in probability of mortality with POCUS before any intervention. Yet the resulting study data are counter to our original hypothesis that the POCUS-guided resuscitation would improve outcomes. A key known confounder is severity of illness. We used the Emergency Severity Index (ESI) as a measure of severity of illness as the ESI is a good predictor of critical care outcomes (51). ESI has the advantages of reflecting the patient at the time of the initial encounter in the ED (before interventions, including POCUS), being available on all patients (not just a subset) and being uniformly applied across this all-inclusive patient registry of critically ill patients in the ED. With the exception of ESI, all severity of illness scales are calculated by the worst value for each variable in a 24-hour period. When studying an intervention such as POCUS, separating if any difference in severity of illness is a potential confounder or if it is a result of the intervention will be impossible.
Further explorations of the impact on patient outcomes and the optimal role of POCUS in the ED appear warranted despite the widespread adoption of POCUS. Previous technologies that were widely adopted by providers as valuable clinical aids, including MAST trousers, pulmonary arterial catheters, and mixed venous oxygen saturation monitors were eventually found not to impact patient outcomes and even to be harmful (52). Given that a recent randomized controlled trial found no improvement in mortality in undifferentiated shock patients with POCUS use in the ED (52), we propose a larger prospective investigation to define the optimal role and impact of POCUS in the ED resuscitation of critically ill patients
POCUS in the ED has been widely adopted by the providers in our academic hospital EDs. Contrary to our hypothesis, POCUS prior to a key intervention in the ED appears to be associated with a higher mortality in critically ill patients with hemodynamic instability. Key questions that need further exploration include how POCUS in the ED may impact resuscitation strategies, treatment times, and patient outcomes through larger prospective studies.
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