With the advent of advanced therapies for acute pulmonary embolism (PE), the necessity
for risk stratification has become more pronounced. There is a growing interest in
establishing dedicated Pulmonary Embolism Response Teams (PERT), which help in rapid
identification of intermediate to high-risk cases, and determine the need for advanced
interventions.[1]
[2]
[3] Multiple scoring systems have been described in the literature, which help in risk
stratification of patients in an evidenced-based fashion.[4]
[5]
[6]
[7] The simplified pulmonary embolism severity index (SPESI) is a well-validated and
simple to use scoring system to predict 30-day mortality in acute PE.[4]
[5] Cleveland Clinic was one of the early adopters of a multidisciplinary PERT, which
was established in October 2014. Our experience over the past 3 years has led us to
recognize the difficulty in risk stratification of patients using evidence-based methods
like the SPESI score. Three of 6 points of the SPESI score are attributed to vital
signs, including systolic blood pressure, heart rate, and oxygen saturation. Typically,
there are multiple vital signs charted during evaluation of a patient with suspected
acute PE in the initial 6 hours. Vital signs may fluctuate after initial stabilization
with fluids, supplemental oxygen, and anticoagulation. Optimal timing of vital signs
to calculate a SPESI score has never been addressed in the literature, and this question
has come up at multiple occasions during PERT meetings at our institution.
Our objective was to study the variability in SPESI score in patients with acute PE,
when multiple vital signs were available from the initial encounter up to the first
6 hours from acute presentation. We sought to identify the optimal timing of vitals
used to calculate a SPESI score which best predicts 30-day all-cause mortality.
This is a retrospective review of the PERT registry at the Cleveland Clinic, a large
tertiary care referral center. The study protocol was approved by the Cleveland Clinic
Institutional Review Board (Study Number 16–547). All patients presenting to our health
system with a confirmed diagnosis of acute PE for which PERT was activated between
October 2014 and August 2016 were initially reviewed (n = 111). Sixty-six patients were excluded as the initial vital signs were not available
in the 0- to 6-hour window. Thus, 45 patients were included for further analysis ([Fig. 1]). We included PERT activations from emergency department (ED) (n = 36) and inpatient settings (n = 9). We hypothesized four ways of collecting vital signs in 0 to 6 hours of initial
presentation to calculate four possible SPESI scores for every patient:
Fig. 1 Subject disposition.
-
The first set of vital signs upon initial presentation to the ED (0 hour vitals),
or upon onset of symptoms or signs leading to the diagnosis of acute PE in inpatient
setting. SPESI calculated from this vital sign was called “SPESI at 0 hour.”
-
Vital signs taken 2 hours after the 0 hour vitals (2 hour vitals). These were hypothesized
to be the poststabilization vitals after initial resuscitation. SPESI calculated from
this set of vital signs was called “SPESI at 2 hours.”
-
Combination of vitals in the 0- to 6-hour window leading to the highest possible SPESI
score (we refer to them as the “sickest vitals” for the purpose of discussion). The
respective score was called the “highest SPESI.”
-
Opposite to above, a combination of vitals in the 0- to 6-hour window leading to the
lowest possible SPESI score (referred to as “healthiest vitals”). The respective score
was called the “lowest SPESI.”
The primary outcome was 30-day mortality from all causes. The mean SPESI scores at
four time points were compared using Kruskal–Wallis rank test. SPESI calculated from
the four hypothesized time points were used to predict the primary outcome of 30-day
mortality from all causes, and C-statistic was used to compare the area under receiver
operator curve (AUROC) for the predictive models. Data analysis was performed using
STATA/IC 14.1 for Mac (64-bit Intel, Revision July 6, 2016).
The demographics, interventions, and outcomes are described in [Table 1]. The descriptive statistics for the SPESI scores calculated at the four hypothesized
time points are listed in [Table 2]. The healthiest vitals led to the lowest SPESI score whereas the sickest vitals
led to the highest SPESI score. There was a significant difference between the four
groups of SPESI scores calculated from various time points (p-value of 0.0002). Comparison of C-statistic for SPESI scores at four hypothesized
time points to predict a 30-day mortality outcome is illustrated in [Fig. 2]. The “SPESI at 0 hour” was the best predictor of a 30-day mortality with an AUROC
of 0.756, followed by “highest SPESI” with an AUROC of 0.753. “Lowest SPESI” is the
poorest predictor of 30-day mortality with an AUROC of 0.533. The AUROC for “SPESI
at 2 hours” is 0.689. There was a statistically significant difference between AUROCs
of all four groups (p = 0.0002).
Fig. 2 Comparison of C-statistics for SPESI scores calculated from four hypothesized time
points. Values in brackets represent the respective AUROCs. Abbreviations: AUROC,
area under the received operator curve; SPESI, simplified pulmonary embolism severity
index.
Table 1
Demographic, interventions, and outcomes from the pulmonary embolism response team
cohort
|
Demographics[a]
|
N = 45
|
|
Age, y, mean (SD)
|
59.5 (13.7)
|
|
Female sex
|
19 (42.2%)
|
|
Cancer
|
13 (28.9%)
|
|
Diabetes mellitus
|
13 (28.9%)
|
|
Hypertension
|
20 (44.4%)
|
|
Previous pulmonary embolism
|
5 (11.1%)
|
|
Chronic obstructive pulmonary disease
|
7 (15.6%)
|
|
Location of pulmonary embolism
|
|
Saddle
|
14 (31.1)
|
|
Main pulmonary artery
|
20 (44.4%)
|
|
Lobar
|
35 (77.8%)
|
|
Segmental
|
32 (71.1%)
|
|
Risk level
|
|
Massive
|
7 (15.5%)
|
|
Submassive
|
28 (62.2%)
|
|
Low risk
|
10 (22.2%)
|
|
Interventions
|
|
tPA administered
|
13 (28.9%)
|
|
Catheter directed tPA
|
5
|
|
Full dose systemic tPA
|
1
|
|
Half dose systemic tPA
|
7
|
|
Outcomes
|
|
30-day mortality
|
4 (8.9%)
|
|
Hospital mortality
|
2 (4.4%)
|
|
Intracranial bleeding
|
1
|
|
Length of stay, d, mean (SD)
|
12.6 (7.6)
|
|
Length of ICU stay, d, mean (SD)
|
5.1 (6.1)
|
Abbreviations: ICU, intensive care unit; SD, standard deviation; tPA, tissue plasminogen
activator.
a Results are provided as n (%) unless otherwise stated.
Table 2
Descriptive statistics and SPESI scores from the four hypothesized time points
|
Timing of vitals
|
SPESI score
|
|
Mean (SD)
|
Median (IQR)
|
Minimum
|
Maximum
|
|
0 h
|
1.20 (1.05)
|
1 (0–2)
|
0
|
4
|
|
2 h
|
1.22 (1.16)
|
1 (0–2)
|
0
|
5
|
|
Sickest vitals (0–6 h)
|
1.88 (1.26)
|
2 (1–3)
|
0
|
6
|
|
Healthiest vitals (0–6 h)
|
0.77 (0.84)
|
1 (0–1)
|
0
|
3
|
|
p-Value (Kruskal–Wallis)
|
0.0002
|
|
|
|
Abbreviations: IQR, interquartile range; SD, standard deviation; SPESI, simplified
pulmonary embolism severity index.
To the best of our knowledge, this is the first study to address the issue of timing
of vital signs and its effect of risk stratification in acute PE. This study adds
to the literature that timing of vitals significantly affects the risk prediction
in acute PE, and the “first vitals” (SPESI at 0 hour) or the “sickest vitals” (highest
SPESI) are the best predictors of a 30-day mortality outcome. Results from the study
suggests that PERT should utilize the initial vital signs to risk stratify the patient
in a more evidence-based way, and is applicable to both ED and inpatient settings.
This also emphasizes the necessity of accurate documentation of the initial and the
sickest vital signs.
Accurate risk stratification is crucial to determine which therapeutic approach is
indicated for any given acute PE patient.[8] In high-risk PE, defined as circulatory shock, there is wide agreement that early
reperfusion therapy is indicated. In normotensive PE patients, risk stratification
starts with the calculation of the PE severity index. Of all the risk prediction models,
we chose the SPESI score for this study, because it is easy to calculate and is noninferior
to the more exhaustive PESI score. During PERT calls at our institution, we struggled
with the SPESI estimation in terms of timing of the vital signs for optimal predictive
value. Although we have a prospective PERT registry at our institution, the specific
research question we had was best addressed by a retrospective review. Our hypothesis
necessitated the vitals to be collected in the 0- to 6-hour window of acute presentation.
A prospective study where a patient is enrolled after a diagnosis of acute PE is confirmed
and PERT is activated, would have failed to capture vitals in the first 6 hours. Overall,
our results are consistent with the original study in which the SPESI score was first
described. Jiménez et al calculated a mortality rate of 8.9% for high-risk SPESI score
(≥1), and an AUROC of 0.75[4] to predict mortality, which are both very similar to our findings. We recognize
the limitation that this is a single-center study and 45 out of 111 patients were
analyzed, and very few of those were inpatients. Being a major tertiary care referral
center, our hospital receives a large number of patients from outside hospitals as
transfers and direct admits. We did not have access to the initial vital signs in
case of any of these patients (n = 66). Thus, all the aforementioned patients were excluded. The study answers a very
practical clinical question and we believe the results would directly impact clinical
practice.
We conclude that timing of vitals significantly affects risk stratification in acute
PE. SPESI score calculated using the “first vitals” or the “sickest vitals” in the
initial 6 hours are best predictors of a 30-day mortality outcome. Evidence from this
study can help PERT teams to risk stratify patients in the ED.
