Repeated vital sign measurements in the emergency department predict patient deterioration within 72 hours: a prospective observational study

More than one in five patients presenting to the emergency department (ED) with (suspected) infection or sepsis deteriorate within 72 h from admission, despite treatment [1]. Recent advances in research have improved our understanding of the pathophysiology of sepsis [2]. The adoption of surviving sepsis campaign (SSC) guidelines, increased awareness and early goal-directed therapy dramatically reduced sepsis-related mortality over the past two decades [3, 4]. However, one of the main challenges for the physician in the ED remains to determine the risk of deterioration for the individual patient [2]. The numerous sepsis-related biomarkers lack sensitivity and specificity for deterioration and are not readily available in the ED [5‐7]. Despite the relative ease of measurement, surprisingly little is known about vital signs in relation to clinical outcomes, especially in the ED setting [8‐11]. There is limited evidence that oxygen saturation and consciousness level at ED arrival are associated with mortality, and that heart rate and Glasgow coma scale (GCS) are associated with intensive care unit (ICU) admission [9, 11]. For all other vital signs, insufficient evidence is available [9, 11]. The few available studies mostly studied vital signs used in triage systems or vital signs obtained at the time of ED admission [9, 12]. Almost one third of the medical patients who arrive at the ED with normal vital signs show signs of deterioration in vital signs within 24 h [13]. Our pilot study in the ED showed that vital signs change significantly during the patient’s stay in the ED [7]. However, surprisingly little is known on how to monitor and identify deteriorating patients in the emergency department [13]. The latest SSC guidelines recommend a thorough re-evaluation of routinely measured vital signs as parameter for response to treatment [4]. Therefore, the aim of the current study was to determine whether repeated vital sign measurements during the patient’s stay in the ED can distinguish between patients who will deteriorate within 72 h from admission and patients who will not.

The aim of our study was to determine whether repeated vital sign measurements in the ED can identify patients with sepsis or infection that will deteriorate within 72 h. We found an increase in MAP over time was associated with a lower risk of deterioration, and a higher variability of the MAP or increase in respiratory rate over time, in combination with their respective values at ED admission, were associated with patient deterioration. Inclusion of repeated MAP measurements resulted in the largest AUC (.800), whereas repeated respiratory rate measurements only slightly improved the predictive capabilities of the logistic regression model over the base model. Repeated measurements of heart rate and body temperature were not associated with patient deterioration.

Our results indicate that changes and variability of the MAP are associated with patient deterioration in ED patients with infection or sepsis. This suggests that keeping a close eye on the MAP during the patients stay in the ED is important. Our study shows that this not only applies to patients with septic shock (only 1.9% of our population), as recommended by the surviving sepsis campaign (SSC) guidelines, but for all patients with sepsis or infection [4].

Apart from our earlier pilot study, little is known about repeated vital sign measurements in patients with infection or sepsis during their stay in the ED in relation to clinical outcomes, patient deterioration and (early) signs of organ failure. Our pilot study showed that vital signs changed significantly during the patient’s stay in the ED, but did not analyse patient deterioration [7]. Henriksen et al... retrospectively found a deterioration of vital signs from the normal to abnormal range within 4–13 h after arrival in 31% of patients in the general ED population, leading to a four times higher 30-day mortality risk [13]. The available studies on vital signs in the ED mostly use only single measurements, mainly at triage [9, 12]. Furthermore, these were often retrospective studies in contrast to our study. Finally, they often included the general ED population and thus a more heterogeneous population. The endpoints and cut-off values differ from study to study, most studies used mortality endpoints, several studies had ICU admission as an endpoint and only a few studies included organ failure [8, 11, 13, 19‐22]. The single measurements, heterogeneous patient populations and different endpoints make a direct comparison of those results with our study’s results impossible. Coslovsky et al aimed to develop a prediction model for in-hospital mortality using a model with age, prolonged capillary refill, blood pressure, mechanical ventilation, oxygen saturation index, GSC and the APACHEII diagnostic category in a cohort that contained 15% patients with infection among which 7.3% with sepsis. Their model had an AUC of 0.92, although, it should be noted that their model was based on a heterogeneous patient population, single measurements and a combination of multiple vital signs [23]. Yamamoto et al. found an association between low body temperature (< 36 °C) at ED admission and higher 30 day in-hospital mortality risk in patients with suspected sepsis [24]. In our study, we did not find an association between body temperature and deterioration. Furthermore, it should be noted that the in-hospital mortality in our study (3.3%) is much lower than in the study of Yamamoto (9.6%). In summary, available studies did not specifically investigate ED patients with infection or sepsis, mostly used single vital sign measurements (at triage) and primarily had mortality or ICU admission endpoints.

Early warning scores (EWS), like the national early warning score (NEWS) and many variants and related scores, are increasingly being used throughout healthcare. These EWS commonly contain a combination of various vital sign parameters, supplemented with laboratory values or other items, where each item is scored at certain thresholds. Early warning scores are mostly used as ‘track-and-trigger’ systems to trigger the nurse to call the physician or a rapid response team, or to predict a high risk of mortality or ICU admission [25, 26]. The many different EWS and patient populations, in which they have been validated, make it difficult to compare their performance. However, a recent review by Nannan Panday et al. showed that the NEWS score was the best to predict mortality or ICU admission in the general ED population and the modified early warning score was the best in patients with suspected infection or sepsis [25]. Their performance (AUC) was in the same range as we found for our repeated blood pressure measurements (MAP). However, it should be noted that we used only a single vital sign repeated measurement and had a composite outcome of patient deterioration, which included signs of organ dysfunction. Another recent study by Kivipuro et al. showed that the NEWS score was significantly higher before ICU admission when a patient was transferred from the ward to the ICU, compared to the NEWS score of the same patient at the ED [27]. In our hospital, modified early warning scores (MEWS) are taken at admission to the ward and thereafter three times per day. Deterioration of the MEWS score triggers an early response team. Further research is needed to clarify whether repeated vital sign measurements in combination with repeated early warning scores are useful in the detection of patient deterioration in patients with sepsis or infection.

We have shown that almost 30% of the patients presenting to the ED with suspected infection or sepsis deteriorated within 72 h of admission and over 28% of the patients showed signs of (multiple) organ failure despite treatment. Our results show that 18.3% of the patients with infection, 32.9% of the patients with sepsis and in total 29.5% of the patients deteriorated within 72 h (Table 4). Glickman et al. showed that almost 23% of patients with uncomplicated sepsis progress to severe sepsis or septic shock within 72 h from admission [1]. Although a direct comparison cannot be made because of a different population and different endpoints, these results clearly show that a large part of the patients with infection deteriorate in the first days in the hospital and develop (severe) sepsis. Therefore, we question whether the introduction of the recent Sepsis-3 definitions, in which infection or uncomplicated sepsis are no longer part of the sepsis severity spectrum, will lead to better patient care [28]. We would like to emphasise that it is important to properly monitor and treat all patients with infection or sepsis in the ED. Since sepsis-related mortality has dramatically reduced over the past two decades, we believe that early detection or prevention of organ failure is where the future focus of infection/sepsis research should be, since there is a lot to gain [29].

The 30-min measurement interval in the current study was arbitrarily chosen, since there is no standard on how often vital signs should be measured in the ED and only little research has been conducted on this topic. Descriptive studies in the general ED population have shown that the time between two measurements is between 67 and 130 min and that a higher illness severity results in more frequent measurements [10, 30]. We believe that these measurement intervals are not representative for patients with infection or sepsis, however, there are no specific guidelines on how often vital signs should be measured in these patients [13]. The 30-min measurement interval in our study was much more frequent than the median intervals reported by Johnson and Lambe [10, 30]. A higher measurement frequency might provide even more information about deterioration, although this might lead to a higher burden on the patient and staff. Therefore, we recommend continuous measurement of vital signs on a beat-to-beat level, preferably automated with the use of bed-side patients monitors or wearable devices [3]. Our next step, as a follow-up of this study, is to shorten the measurement interval to a beat-to-beat interval with heart rate variability (HRV) measured using bed-side patient monitors in the SepsiVit study [3]. As we have shown, a substantial number of patients deteriorate in the first days from admission. In the currently running SepsiVit study, we will extend the measurements beyond the boundaries of the ED towards the nursing wards during the first 48 h of hospitalization. During this period, we will investigate whether the combination of HRV with monitoring on the nursing wards can provide an early warning of patient deterioration. Such an early warning could provide a possible opportunity for intervention in the future.

Repeated measurement of vital signs in the ED are better at identifying patients at risk for deterioration within 72 h from admission than single vital sign measurements at ED admission. Repeated measurements of MAP and respiratory rate are associated with patient deterioration. Since almost one third of patients presenting with infection or sepsis to the ED deteriorate within 72 h, repeated vital sign measurements may be an important way to guarantee early identification of deterioration.