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Arterial Blood Pressure and Neurological Outcome
After Resuscitation From Cardiac Arrest
J. Hope Kilgannon, MD1; Brian W. Roberts, MD1; Alan E. Jones, MD2; Neil Mittal, MD1;
Evan Cohen, MD1; Jessica Mitchell, MD1,3; Michael E. Chansky, MD1; Stephen Trzeciak, MD, MPH1,3
Objectives: Guidelines for post–cardiac arrest care recommend
blood pressure optimization as one component of neuroprotection. Although some retrospective clinical studies suggest that
postresuscitation hypotension may be harmful, and laboratory
studies suggest that a postresuscitation hypertensive surge may
be protective, empirical data are few. In this study, we prospectively measured blood pressure over time during the postresuscitation period and tested its association with neurological outcome.
Design: Single center, prospective observational study from 2009
to 2012.
Patients: Inclusion criteria were age 18 years old or older, prearrest independent functional status, resuscitation from cardiac
arrest, and comatose immediately after resuscitation.
Measurements and Main Results: Our research protocol measured blood pressure noninvasively every 15 minutes for the first
6 hours after resuscitation. We calculated the 0- to 6-hour timeweighted average mean arterial pressure and used multivariable
logistic regression to test the association between increasing
time-weighted average mean arterial pressures and good neurological outcome, defined as Cerebral Performance Category 1
or 2 at hospital discharge. Among 151 patients, 44 (29%) experienced good neurological outcome. The association between
blood pressure and outcome appears to have a threshold effect
at time-weighted average mean arterial pressure value of 70 mm
Department of Emergency Medicine, Cooper University Hospital,
Camden, NJ.
2
Department of Emergency Medicine, The University of Mississippi Medical Center, Jackson, MS.
3
Division of Critical Care Medicine, Department of Medicine, Cooper University Hospital, Camden, NJ.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF
versions of this article on the journal’s website (http://journals.lww.com/
ccmjournal).
Dr. Kilgannon’s work was supported by a Career Development Grant from
the Emergency Medicine Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: [email protected]
Copyright © 2014 by the Society of Critical Care Medicine and Lippincott
Williams & Wilkins
DOI: 10.1097/CCM.0000000000000406
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Hg. This threshold (mean arterial pressure > 70 mm Hg) had
the strongest association with good neurological outcome (odds
ratio, 4.11; 95% CI, 1.34–12.66; p = 0.014). A sustained intrinsic hypertensive surge was relatively uncommon and was not
associated with neurological outcome.
Conclusions: We found that time-weighted average mean arterial
pressure was associated with good neurological outcome at a
threshold of mean arterial pressure greater than 70 mm Hg. (Crit
Care Med 2014; XX:00–00)
Key Words: brain injury; cardiopulmonary resuscitation; ischemiareperfusion injury; return of spontaneous circulation
T
he post–cardiac arrest syndrome is a state of severe,
global ischemia/reperfusion injury with potentially
devastating consequences (1, 2). The mortality associated with this condition is extremely high, and among those
that survive, many are left with permanent, disabling neurological injury. The discovery that controlling body temperature
after return of spontaneous circulation (ROSC) may improve
neurological function (3–5) provides hope that additional
postresuscitation interventions may be found to reduce the
degree of brain injury and further improve clinical outcomes.
Patients with post–cardiac arrest syndrome experience
ongoing oxidant damage (6, 7), profound systemic inflammation (8–10), myocardial stunning (11, 12), and adrenal axis
suppression (13, 14), which commonly result in major hemodynamic instability (15–18). Given that the injured brain commonly has dysfunctional autoregulation of the cerebral blood
flow, including brain injury secondary to cardiac arrest (19,
20), it is possible that post-ROSC blood pressure alterations
may be a factor in ongoing cerebral injury and eventual neurological outcome. With disruption of normal cerebrovascular autoregulation, cerebral blood flow may become directly
related to cerebral perfusion pressure (20), which is dependent
on mean arterial pressure (MAP).
Although some retrospective clinical studies suggest that
postresuscitation hypotension is associated with lower survival (16–18, 21), and laboratory studies suggest that inducing a postresuscitation hypertensive surge may confer
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Kilgannon et al
neuroprotection (22, 23), there remains a paucity of data on
the relationship between post-ROSC blood pressure and neurological outcome. The 2010 American Heart Association
Guidelines for Cardiopulmonary Resuscitation (CPR) and
Emergency Cardiovascular Care recommend post-ROSC
goal-directed hemodynamic support including blood pressure
optimization with IV fluids and vasopressors to achieve a target MAP greater than or equal to 65 mm Hg (24). However,
the relationship between post-ROSC MAP and neurological
outcome remains incompletely understood. Specifically, it is
unclear if there is an association between MAP and neurological outcome, and if they are associated, it is unknown if it is
a threshold effect at a specific low MAP value versus a linear
relationship in which hypertension is protective.
In this prospective observational study of adult patients
resuscitated from cardiac arrest, our objectives were to measure
blood pressure over time in the immediate postresuscitation
period and to test the association between postresuscitation
blood pressure and neurological outcome at hospital discharge.
We hypothesized that higher post-ROSC blood pressures
would be independently associated with good neurological
outcome.
METHODS
Setting
This was a prospective observational study conducted at a
single urban academic medical center, Cooper University Hospital in Camden, New Jersey. Subjects were enrolled in the
emergency department (ED) and ICU from 2009 to 2012. The
institutional review board approved this study with a waiver of
written informed consent.
Participants
We enrolled in- and out-of-hospital adult post–cardiac arrest
patients who were comatose immediately after ROSC. The
inclusion criteria were 1) age 18 years old or older; 2) independent functional status prior to cardiac arrest; 3) cardiac arrest,
defined as a documented absence of pulse and CPR initiated;
4) ROSC; and 5) inability to follow commands immediately
after ROSC. We excluded patients with cardiac arrest related to
trauma. We also excluded patients if, for any reason, post-ROSC
blood pressure recordings were not captured per protocol (see
detail described below). Figure 1 displays our screening process.
Patient Identification
We used the following methodology previously described for
real-time, prospective identification of post–cardiac arrest
patients (25). This included a 24-hour per day, 7-day per week
paging system activated in one of two ways: 1) a hospital-wide
“code blue” activation anytime a cardiac arrest occurred in the
hospital; 2) ED unit secretaries were trained to activate a page
when an out-of-hospital cardiac arrest arrived in the ED (or
a cardiac arrest occurred in the ED). An investigator received
the page and responded to the cardiac arrest event to begin
data capture.
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Figure 1. Patient screening and inclusion flow diagram.
Post–Cardiac Arrest Care
Our institution uses state-of-the-art postresuscitation care for
post–cardiac arrest patients and a previously published standard
operating procedure, by our group, including all of the following
elements recommended for regional cardiac arrest centers: 1)
immediate evaluation for percutaneous coronary intervention
(if needed); 2) immediate evaluation for therapeutic hypothermia; 3) evaluation and management by an in-house critical care
physician; and 4) evidence-based timing and methods of neurological prognostication (26, 27). Our institution uses a standardized order set for treatment with therapeutic hypothermia, using
a surface cooling system (Arctic Sun, Medivance, Louisville, CO),
and our clinicians have demonstrated proficiency in achieving
and maintaining target temperature (33–34°C) in 96% of cases,
within a median time of 4.4 hours from ROSC (28). The decision on whether or not to initiate therapeutic hypothermia was
made by the treating physicians and was not part of the study
protocol. In general, our clinicians use therapeutic hypothermia
for out-of-hospital cardiac arrest due to ventricular fibrillation
(VF) and pulseless ventricular tachycardia (VT) (i.e., level 1
recommendation in the current guidelines) (24), and its use in
other patients (e.g., nonshockable initial rhythm or in-hospital
cardiac arrest) is at the discretion of the treating physician.
Data Collection
We collected basic demographics as well as the data and outcome variables consistent with the Utstein style for reporting
cardiac arrest research, including the post-ROSC variables recommended for postresuscitation research (29, 30). For measuring the exposure of interest (arterial blood pressure over time),
our research protocol cycled a noninvasive blood pressure cuff
every 15 minutes for the first 6 hours after ROSC and recorded
all blood pressure measurements. We entered the data into a
dedicated Access database (Microsoft Corporation, Redmond,
WA) and exported to StatPlus:mac version 2009 (AnalystSoft,
Alexandria, VA) for analysis.
Outcome Measures
The primary outcome was good neurological function at hospital discharge, defined as a Cerebral Performance Category
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(CPC) 1 or 2, which is the most commonly used outcome
measure in clinical trials of post–cardiac arrest interventions
(31). The CPC is a validated five-point scale of neurological
disability (1: good cerebral performance, 2: moderate cerebral
disability, 3: severe cerebral disability, 4: coma/vegetative state,
and 5: death) (29, 32, 33). Patients with a CPC of 1 or 2 had
sufficient cerebral function at discharge to live independently.
Data Analysis
We began our analysis with descriptive statistics. We described
continuous data as mean values and sd or median values and
interquartile range (IQR), based on distribution of data, and
displayed categorical data as counts and proportions.
Quantifying the Exposure. For each post–cardiac arrest
patient, we calculated the time-weighted average mean arterial pressure (TWA-MAP) for the first 6 hours after ROSC. We
calculated the TWA-MAP for each patient in a manner consistent with previously published methods of calculating exposures over time in epidemiological research (34–36). For each
patient, we multiplied the length of time that the patient spent
at a specific MAP value by that MAP value, added all these values together, and then divided by the total length of postresuscitation observation time. Thus, we used the equation:
[(MAPa × Time a)
+ (MAPb × Time b)
+ … (MAPz × Time z)]
TWA-MAP =
(Time a + Time b + … Time z )
For example, if a patient had the following exposures—
MAP 70 mm Hg for 30 minutes, MAP 72 mm Hg for 15 minutes, MAP 74 mm Hg for 60 minutes, MAP 77 mm Hg for 45
minutes, MAP 80 mm Hg for 60 minutes, MAP 82 mm Hg for
45 minutes, MAP 85 mm Hg for 60 minutes, and MAP 87 mm
Hg for 45 minutes, the TWA-MAP for the 6-hour postresuscitation period would be: (2,100 mm Hg × min + 1,080 mm
Hg × min + 4,440 mm Hg × min + 3,465 mm Hg × min +
4,800 mm Hg × min + 3,690 mm Hg × min + 5,100 mm Hg ×
min + 3,915 mm Hg × min)/360 min = 79 mm Hg. Thus, this
value, 79 mmHg, would be the time-weighted average value for
the MAP over the duration of the 6-hour period.
We calculated odds ratios (ORs) using multivariate logistic
regression to determine if the TWA-MAP was independently
associated with neurological function at hospital discharge. To
test if the TWA-MAP had a linear association with neurological
outcome, we entered TWA-MAP into the model as a continuous variable. To test if the association was a threshold effect
at a specific arterial blood pressure, we performed additional
multivariate logistic regression analyses, each with TWA-MAP
at different binary cutoffs (5 mm Hg increments from MAP >
65 mm Hg to MAP > 90 mm Hg). We selected the following
candidate variables for the regression models on the grounds
that they were previously demonstrated to predict outcome in
post–cardiac arrest patients: 1) age (decile), 2) initial cardiac
rhythm (i.e., VF/VT vs asystole or pulseless electrical activity
Critical Care Medicine
[PEA]), and 3) prearrest comorbidities (i.e., Charlson comorbidities index) (24, 37–39).
Sample Size Calculation. To ensure adequate power to test
these four covariates in a multivariate model, we estimated
the necessary sample size, based on the following assumptions: 1) a predicted survival with good neurological function
rate of 28% (40); and 2) an estimated event (survival with
good neurological function) per covariate ratio of 10:1 necessary for multivariate modeling (41, 42). In order to accrue
the necessary 40 survivors with good neurological function,
we estimated that a minimum of 143 total subjects would be
necessary.
RESULTS
One hundred fifty-one patients met all inclusion and no exclusion criteria and were enrolled. Table 1 displays baseline characteristics. The mean (sd) age of subjects was 63 (± 16) years.
Sixty-four (42%) were women. The majority of the subjects in
the cohort had an in-hospital arrest, and most had an initial
recorded rhythm of PEA or asystole. Eighty-six of the subjects
(57%) required a continuous infusion of vasopressor agents in
the first 6 hours after ROSC.
Therapeutic hypothermia was used in 16 of 23 patients
(70%) with out-of-hospital arrest, and 52 of 151 of all patients
(34%). In the treated population, target temperature was
achieved in 46 of 52 patients (88%), with a median (IQR)
time to target temperature of 3.9 hours (2.8–4.9 hr). Good
neurological outcome occurred in 26% of those treated versus 31% of patients not treated with therapeutic hypothermia (p = 0.578, using Fisher exact test). The majority of those
treated with therapeutic hypothermia (42 of 54 [78%]) had
PEA/asystole as initial rhythm.
The mean (sd) TWA-MAP for the entire cohort was 79 (± 17).
Figure 2 displays the distribution of TWA-MAP values and
shows that sustained low arterial pressure, for example, TWAMAP less than or equal to 70 mm Hg, was relatively common
(25% of patients), whereas an intrinsic sustained hypertensive
surge, for example, TWA-MAP greater than 100 mm Hg, was
relatively uncommon (< 10% of patients).
Twenty-nine percent (44 of 151) of all patients were found
to have the primary outcome of good neurological function at
hospital discharge. Fourteen (32%) of those who met the primary outcome had initial rhythm of VF/VT. Twenty-nine percent (14 of 49) of those with an initial rhythm of VT/VF had
a good neurological outcome and likewise 29% (30 of 102) of
those with an initial rhythm of PEA/asystole had a good neurological outcome.
The mean (sd) TWA-MAP among patients with good neurological function and poor neurological function at hospital
discharge was 83 (± 13) and 77 (± 18), respectively (p = 0.042).
Figure 3 displays the good neurological function at hospital
discharge in relation to the TWA-MAP value for the first 6
hours after ROSC.
Table 2 displays the results of the multivariate logistic regression model with TWA-MAP as a continuous independent variable and good neurological function at hospital discharge as the
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Kilgannon et al
Table 1.
Baseline Characteristics of All Subjects
Patient Characteristics
All Subjects
(n = 151)
Subjects With
TWA-MAP ≤ 70a (n = 36)
Subjects With
TWA-MAP > 70a (n = 115)
Age, yr (sd)
63 (± 16)
66 (± 13)
62 (± 17)
Female gender, n (%)
64 (42)
14 (39)
50 (43)
Diabetes
55 (36)
14 (39)
41 (36)
Known coronary artery disease
34 (23)
9 (25)
25 (22)
Hypertension
79 (52)
23 (64)
56 (47)
Malignancy
30 (20)
10 (28)
20 (17)
Renal insufficiency
32 (21)
12 (33)
20 (17)
Pulmonary disease
32 (32)
6 (17)
26 (23)
Congestive heart failure
29 (19)
7 (19)
22 (19)
Preexisting comorbidities, n (%)
Charlson comorbidity score (39),
median (interquartile range)
2 (1–4)
3 (1–5)
2 (0–4)
Arrest location, n (%)
Out-of-hospital/emergency department
41 (27)
11 (31)
30 (26)
ICU
74 (49)
19 (53)
55 (48)
Floor/monitored bed
19 (13)
5 (14)
14 (12)
2 (1)
0
2 (2)
Floor/unmonitored bed
Other
15 (10)
1 (3)
14 (12)
119 (79)
32 (89)
87 (76)
Ventricular fibrillation/ventricular
tachycardia
32 (21)
4 (11)
28 (24)
Estimated downtime > 10 min, n (%)
50 (33)
13 (38)
37 (33)
Initial arrest rhythm, n (%)
Pulseless electrical activity/asystole
TWA-MAP = time-weighted average mean arterial pressure.
a
Measured in mm Hg.
dependent variable (OR, 1.02; 95% CI, 1.00–1.02; p = 0.086).
Table 3 displays additional multivariate logistic regression
models with TWA-MAP at different binary thresholds. There
appears to be a threshold effect at a TWA-MAP greater than
70 mm Hg. We found that a TWA-MAP greater than 70 mm
Hg was the highest blood pressure threshold that was independently associated with the outcome. That is, in starting at a
MAP of 90 mm Hg and decreasing the binary cutoff by 5 mm
Hg increments, TWA-MAP first becomes an independent predictor of outcome at a threshold greater than 70 mm Hg. A
TWA-MAP greater than 70 mm Hg also had the highest OR
for good neurological function at hospital discharge among
all binary thresholds tested, OR 4.11 (95% CI, 1.34–12.66,
p = 0.014). On further sensitivity analysis, TWA-MAP greater
than 70 mm Hg remained the MAP threshold with the strongest association with good neurological outcome after adjusting for duration of CPR or “downtime” longer than 10 minutes,
OR 5.25 (95% CI, 1.73–15.98, p = 0.003) (details of the models
are displayed in the supplemental data, Supplemental Digital
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Content 1, http://links.lww.com/CCM/A971). Table 4 reports
neurological outcome as it relates to vasopressor use in the first
6 hours after ROSC.
DISCUSSION
In this prospective observational study, we tested the relationship between arterial blood pressure after resuscitation from
cardiac arrest and neurological outcome. We sought to test this
relationship because the injured brain may be especially vulnerable to blood pressure alterations after ROSC due to a loss
of normal cerebral autoregulation and disruption of microvascular perfusion (19, 20), and thus maintaining an adequate
MAP (or raising the MAP) in the postresuscitation period may
help ensure adequate cerebral perfusion and confer neuroprotection. To date, there has been little empirical data on this
topic in human subjects, limited only to retrospective analyses
(16–18) and one recent pilot study (43); thus, we felt that a
rigorous prospective study with dense data capture of blood
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resuscitated from cardiac
arrest (40). We found that arterial hypotension was common
while relatively fewer patients
had an intrinsic hypertensive
surge. On multivariate logistic
regression analyses, we found
that TWA-MAP was associated with good neurological
outcome. This association
appears to be driven by the
strong association between
hypotension and poor neurological outcome, as opposed to
an association between intrinsic hypertension and better
neurological outcome. In our
analysis, there was a threshold effect with a TWA-MAP
greater than 70 mm Hg having
the greatest association with
Figure 2. Distribution of the time-weighted average mean arterial blood pressure values in the first 6 hr after
good neurological function,
cardiac arrest.
and we did not find higher
pressure recordings over time in the immediate postresuscita- MAP thresholds (> 75, > 80, > 85 mm Hg, etc.) to be associated with favorable neurological outcome.
tion period was needed.
In contrast to some prior studies, a major strength of the
We found that of the 151 patients enrolled, 29% (44 of
151) met our primary outcome of good neurological outcome current study is the prospective, dense data capture of blood
at hospital discharge; this is consistent with the outcomes pressure recordings over the early postresuscitation period to
in previously published large series of patients successfully allow rigorous measurement of the true “exposure” and using
TWA as mechanism of quantifying the exposure; the uniqueness of the results is that they
provide more granular data on
the relationship between blood
pressure and neurological outcome by identifying a numeric
threshold of potential harm. In
2008, the International Liaison
Committee on Resuscitation
identified that determining
the optimal target range for
MAP after cardiac arrest was a
critical knowledge gap in post–
cardiac arrest care (2). This is
an important area of clinical
investigation, as sudden cardiac arrest is a leading cause of
death and neurological devastation among adults (44–46).
Furthermore, the post–cardiac
arrest syndrome is typically
Figure 3. Good neurological function at hospital discharge in relation to the time-weighted average mean
characterized with marked
arterial pressure (TWA-MAP) value for the first 6 hr after return of spontaneous circulation. There was a
swings in blood pressure due
statistically significant difference in the proportion of patients with good neurological outcome between the
TWA-MAP ≤ 70 and TWA-MAP 71–80 groups, 11% versus 37% (p = 0.009 by Fisher exact test). There
to fluctuating hemodynamic
was no difference between the TWA-MAP 71–80 and TWA-MAP 81–90 groups, 37% versus 36% (p = 1 by
perturbations after reperfuFisher exact test) or between TWA-MAP 81–90 and TWA-MAP > 90 groups, 36% versus 32% (p = 0.804 by
Fisher exact test).
sion (2, 15–18). Therefore, this
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Kilgannon et al
Table 2. Multivariate Logistic Regression Model of the Association Between TimeWeighted Average Mean Arterial Pressure During the First 6 Hours After Return of
Spontaneous Circulation and Good Neurological Outcome (Defined as Cerebral
Performance Category 1 or 2) at Hospital Discharge
OR
95% Lower CI
95% Upper CI
p
Mean arterial pressure
1.02
1.00
1.04
0.086
Age
0.93
0.75
1.15
0.490
Pulseless electrical activity/asystole initial rhythm
0.45
0.20
1.05
0.064
Charlson comorbidity index
0.88
0.62
1.25
0.474
Variable
OR = odds ratio.
Time-weighted average mean arterial pressure is entered into the model as a continuous variable.
study addresses a clinical scenario that is relatively common
and represents a critical phase in the trajectory of the eventual
outcome following cardiac arrest.
The 2010 American Heart Association guidelines for
post–cardiac arrest care recommended post-ROSC goaldirected hemodynamic optimization; however, the guidelines acknowledged the lack of high-quality evidence to
support a specific target for MAP after ROSC (24). As there
is proven benefit of goal-directed hemodynamic optimization, including MAP targets, for patients with other etiologies of critical illness (47–49), it is also, in theory, possible
that blood pressure optimization could improve neurological outcome among patients with post–cardiac arrest syndrome. However, this hypothesis has not yet been tested in
a clinical trial. In a subanalysis of our study population, we
found that patients who were able to maintain a TWA-MAP
greater than 70 mm Hg without vasopressor administration had a higher proportion of good neurological outcome
compared with patients who achieved a TWA-MAP greater
than 70 with vasopressor administration, 48% versus 24%,
respectively (p = 0.01). We were unable to show a statistically significant difference in good neurological outcome for
patients administered vasopressors to maintain TWA-MAP
greater than 70 mm Hg compared with patients with a TWAMAP less than or equal to 70 who did not receive vasopressors, 24% versus 10%, respectively (Table 4). One possibility
to explain these findings is that the body’s intrinsic ability to
maintain adequate perfusion pressure without vasopressors
after ROSC is a predictor of eventual good neurological outcome and that supporting the MAP with the application of
vasopressor agents may not confer benefit. However, animal
models have shown evidence to the contrary, in fact reporting that an induced hypertensive surge for cerebral blood
flow promotion can attenuate brain injury and improve outcome (22, 23, 50, 51). Our study design did not test a vasopressor therapeutic approach, and we found fewer patients
with sustained intrinsic hypertension than expected (12 of
151 had TWA-MAP > 100 mm Hg) with no clear association between TWA-MAPs greater than 90 mm Hg and good
outcome, OR 1.12 (95% CI, 0.48–2.60, p = 0.794). We found
only one clinical study that tested this induced hypertensive
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surge hypothesis, a recently published pilot interventional
trial of induced hypertension after cardiac arrest, which
reported that supranormal MAP did not affect cerebral tissue oxygenation (43).
Regarding blood pressure support after cardiac arrest
and outcome, there may be important parallels between the
global cerebral ischemia/reperfusion injury of cardiac arrest
and the regional ischemia/reperfusion injury of acute ischemic stroke (AIS). In patients with AIS, it is widely accepted
that arterial hypotension is associated with worse outcomes
because it exacerbates cerebral ischemia, and permissive
hypertension could preserve cerebral perfusion in the ischemic penumbra and protect the injured brain from further
insult (52–63). Although ideal target blood pressure after
cardiac arrest remains unknown, enough evidence exists to
compel clinicians at the bedside pay close attention to blood
pressure, specifically avoiding hypotension after resuscitation
from cardiac arrest.
Limitations
We acknowledge that our data have important limitations
to consider. Most notably, this was an observational study.
Although many patients in the study received vasoactive agents,
this was not an interventional protocol with a predefined MAP
goal. Thus, we can only report associations in this study rather
than infer causation.
By study design, we did not require invasive blood pressure
monitoring nor could we control for the effects on outcome
created by having various clinicians involved in patient care.
Our study does, however, reflect real clinical practice and a
readily available marker of inadequate perfusion (cuff blood
pressure). Although our institution used a standardized order
set for therapeutic hypothermia (28), and our clinicians have
previously demonstrated a median time to achieving target
temperature that was less than 4 hours (compared to 8 hr in the
Hypothermia After Cardiac Arrest trial) (5), there was likely
some degree of heterogeneity in the selection of patients for
therapeutic hypothermia. As expected, the majority of cardiac
arrest cases were in-hospital, nonshockable initial rhythms—
a population where the efficacy of hypothermia is not clearly
established (class IIb evidence)—and thus the practice at our
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Table 3. Multivariate Logistic Regression Models of the Association Between TimeWeighted Average of Mean Arterial Pressure at Different Binary Thresholds During the
First 6 Hours After Return of Spontaneous Circulation and Good Neurological Function
(Defined as Cerebral Performance Category 1 or 2) at Hospital Discharge
OR
95% LCI
95% UCI
p
TWA-MAP > 65 mm Hg
4.04
1.13
14.42
0.031
Age
0.94
0.76
1.17
0.597
PEA/asystole initial rhythm
0.47
0.21
1.09
0.080
Charlson comorbidity index
0.90
0.63
1.28
0.565
OR
95% LCI
95% UCI
p
TWA-MAP > 70 mm Hg
4.11
1.34
12.66
0.014
Age
0.94
0.76
1.16
0.547
PEA/asystole initial rhythm
0.49
0.21
1.13
0.093
Charlson comorbidity index
0.92
0.64
1.32
0.656
OR
95% LCI
95% UCI
p
TWA-MAP > 75 mm Hg
1.22
0.58
2.57
0.594
Age
0.91
0.74
1.13
0.401
PEA/asystole initial rhythm
0.46
0.20
1.04
0.063
Charlson comorbidity index
0.86
0.61
1.22
0.407
OR
95% LCI
TWA-MAP > 80 mm Hg
1.44
0.70
2.98
0.321
Age
0.92
0.74
1.14
0.443
PEA/asystole initial rhythm
0.46
0.20
1.04
0.063
Charlson comorbidity index
0.87
0.62
1.24
0.442
OR
95% LCI
TWA-MAP > 85 mm Hg
1.48
0.70
3.14
0.310
Age
0.92
0.74
1.14
0.432
PEA/asystole initial rhythm
0.45
0.20
1.02
0.056
Charlson comorbidity index
0.86
0.61
1.22
0.396
OR
95% LCI
TWA-MAP > 90 mm Hg
1.12
0.48
2.60
0.794
Age
0.91
0.74
1.13
0.398
PEA/asystole initial rhythm
0.45
0.20
1.02
0.056
Charlson comorbidity index
0.86
0.61
1.21
0.381
Variable
Variable
Variable
Variable
Variable
Variable
95% UCI
95% UCI
95% UCI
p
p
p
OR = odds ratio, LCI = lower CI, UCI = upper CI, TWA-MAP = time-weighted average mean arterial pressure, PEA = pulseless electrical activity.
There appears to be a threshold effect at a TWA-MAP > 70 mm Hg. A TWA-MAP > 70 mm Hg is the highest blood pressure value that is independently
associated with good outcome. As the binary cutoff decreases by 5 mm Hg increments, TWA-MAP first becomes an independent predictor of outcome at 70 mm
Hg. A TWA-MAP > 70 mm Hg also has the highest odds ratio for good neurological outcome at hospital discharge among all thresholds tested.
institution is to leave the decision on whether or not to treat
with hypothermia up to the treating clinician.
This study was limited to a single medical center, and thus,
the sample size led to the wide CIs for the adjusted ORs on
the multivariable logistic regression model (Table 3). Although
the CIs are wide for the threshold cutoff of MAP greater than
Critical Care Medicine
70 mm Hg for a good neurological outcome (OR, 4.11; 95% CI,
1.34–12.66), they remain significant (p = 0.014).
Lastly, although we used multivariable logistic regression
analyses to adjust for cardiac arrest characteristics known to
predict poor outcomes, there always exists the potential of
unmeasured confounders with an observational design.
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Kilgannon et al
Table 4. Good Neurological Outcome Stratified by Time-Weighted Average Mean Arterial
Pressure (mm Hg) and Vasopressor Use
Good neurological outcome (%)
TWA-Cumulative Vasopressor Index,
median (interquartile range)
TWA-MAP > 70
TWA-MAP > 70
TWA-MAP < 70
TWA-MAP < 70
No Vasopressors
Vasopressors
No Vasopressors
Vasopressors
n = 54
n = 59
n = 10
n = 28
26 (48)
0
14 (24)
4 (3–5)
1 (10)
0
3 (11)
6 (3–12)
TWA-MAP = time-weighted average mean arterial pressure.
Column 2 versus column 3, 48% versus 24% (p = 0.010 by Fisher exact test).
Column 3 versus column 4, 24% versus 10% (p = 0.442 by Fisher exact test).
Column 3 versus column 5, 24% versus 11% (p = 0.247 by Fisher exact test).
CONCLUSIONS
In this prospective study of post–cardiac arrest patients
treated according to consensus recommendations, we found
that arterial pressure over the first 6 hours following resuscitation was associated with neurological outcome. Specifically,
we found a threshold effect with a TWA-MAP greater than
70 mm Hg being associated with good neurological function.
Further investigation is warranted to determine if interventions to support blood pressure and promote cerebral blood
flow would improve neurological outcome after cardiac arrest.
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