Neurologic Critical Care
Arterial Blood Pressure and Neurologic 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 postcardiac arrest care recommend
blood pressure optimization as one component of neuroprotec-
tion. 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 prospec-
tively measured blood pressure over time during the postresusci-
tation period and tested its association with neurologic outcome.
Design: Single center, prospective observational study from 2009
to 2012.
Patients: Inclusion criteria were age 18 years old or older, pre-
arrest independent functional status, resuscitation from cardiac
arrest, and comatose immediately after resuscitation.
Measurements and Main Results: Our research protocol mea-
sured blood pressure noninvasively every 15 minutes for the first
6 hours after resuscitation. We calculated the 0- to 6-hour time-
weighted average mean arterial pressure and used multivariable
logistic regression to test the association between increasing
time-weighted average mean arterial pressures and good neu-
rologic outcome, defined as Cerebral Performance Category 1
or 2 at hospital discharge. Among 151 patients, 44 (29%) expe-
rienced good neurologic outcome. The association between
blood pressure and outcome appears to have a threshold
*See also p. 2145.
1
Department of Emergency Medicine, Cooper University Hospital,
Camden, NJ.
2
Department of Emergency Medicine, The University of Mississippi Medi-
cal Center, Jackson, MS.
3
Division of Critical Care Medicine, Department of Medicine, Cooper Uni-
versity Hospital, Camden, NJ.
Supplemental digital content is available for this article. Direct URL cita-
tions appear in the printed text and are provided in the HTML and PDF
versions of this article on the journals website (http://journals.lww.com/
ccmjournal).
Dr. Kilgannons work was supported by a Career Development Grant from
the Emergency Medicine Foundation. The remaining authors have dis-
closed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: kilgannon-hope@cooper-
health.edu
Copyright 2014 by the Society of Critical Care Medicine and Lippincott
Williams & Wilkins
DOI: 10.1097/CCM.0000000000000406
Critical Care Medicine
effect at time-weighted average mean arterial pressure value of
70 mm Hg. This threshold (mean arterial pressure > 70 mm Hg)
had the strongest association with good neurologic outcome
(odds ratio, 4.11; 95% CI, 1.3412.66; p = 0.014). A sustained
intrinsic hypertensive surge was relatively uncommon and was
not associated with neurologic outcome.
Conclusions: We found that time-weighted average mean arte-
rial pressure was associated with good neurologic outcome at a
threshold of mean arterial pressure greater than 70 mm Hg. (Crit
Care Med 2014; 42:20832091)
Key Words: brain injury; cardiopulmonary resuscitation; ischemia-
reperfusion injury; return of spontaneous circulation
T
he postcardiac arrest syndrome is a state of severe,
global ischemia/reperfusion injury with potentially
devastating consequences (1, 2). The mortality associ-
ated with this condition is extremely high, and among those
that survive, many are left with permanent, disabling neuro-
logic injury. The discovery that controlling body temperature
after return of spontaneous circulation (ROSC) may improve
neurologic function (35) provides hope that additional
postresuscitation interventions may be found to reduce the
degree of brain injury and further improve clinical outcomes.
Patients with postcardiac arrest syndrome experience ongo-
ing oxidant damage (6, 7), profound systemic inflammation
(810), myocardial stunning (11, 12), and adrenal axis suppres-
sion (13, 14), which commonly result in major hemodynamic
instability (1518). 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 ongo-
ing cerebral injury and eventual neurologic outcome. With dis-
ruption 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 sur-
vival (1618, 21), and laboratory studies suggest that induc-
ing 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
neurologic 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 tar-
get MAP greater than or equal to 65 mm Hg (24). However,
the relationship between post-ROSC MAP and neurologic
outcome remains incompletely understood. Specifically, it is
unclear if there is an association between MAP and neuro-
logic 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 neurologic outcome at hospital discharge.
We hypothesized that higher post-ROSC blood pressures
would be independently associated with good neurologic
outcome.
METHODS
Setting
This was a prospective observational study conducted at a
single urban academic medical center, Cooper University Hos-
pital 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 postcardiac arrest
patients who were comatose immediately after ROSC. The
inclusion criteria were 1) age 18 years old or older; 2) indepen-
dent 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 postcardiac 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.
PostCardiac Arrest Care
Our institution uses state-of-the-art postresuscitation care for
postcardiac 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 hypother-
mia; 3) evaluation and management by an in-house critical care
physician; and 4) evidence-based timing and methods of neuro-
logic prognostication (26, 27). Our institution uses a standard-
ized 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 (3334C) in 96% of cases,
within a median time of 4.4 hours from ROSC (28). The deci-
sion 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 out-
come variables consistent with the Utstein style for reporting
cardiac arrest research, including the post-ROSC variables rec-
ommended for postresuscitation research (29, 30). For measur-
ing 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 neurologic function at hos-
pital discharge, defined as a Cerebral Performance Category
3EPTEMBERs6OLUMEs.UMBER

(CPC) 1 or 2, which is the most commonly used outcome mea-
sure in clinical trials of postcardiac arrest interventions (31).
The CPC is a validated five-point scale of neurologic disability
(1: good cerebral performance, 2: moderate cerebral disabil-
ity, 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 postcardiac arrest
patient, we calculated the time-weighted average mean arte-
rial pressure (TWA-MAP) for the first 6 hours after ROSC. We
calculated the TWA-MAP for each patient in a manner consis-
tent with previously published methods of calculating expo-
sures over time in epidemiological research (3436). 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 val-
ues together, and then divided by the total length of postresus-
citation observation time. Thus, we used the equation:
[(MAPa Time a)
+ (MAPb Time b)
+ (MAPz Time z)]
TWA-MAP =
( T ime 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 min-
utes, 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 postresus-
citation 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 neurologic function at hospital discharge. To
test if the TWA-MAP had a linear association with neurologic
outcome, we entered TWA-MAP into the model as a continu-
ous 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
postcardiac arrest patients: 1) age (decile), 2) initial cardiac
rhythm (i.e., VF/VT vs asystole or pulseless electrical activity
Critical Care Medicine
Neurologic Critical Care
[PEA]), and 3) prearrest comorbidities (i.e., Charlson comor-
bidities index) (24, 3739).
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 assump-
tions: 1) a predicted survival with good neurologic function
rate of 28% (40); and 2) an estimated event (survival with
good neurologic function) per covariate ratio of 10:1 neces-
sary for multivariate modeling (41, 42). In order to accrue
the necessary 40 survivors with good neurologic function,
we estimated that a minimum of 143 total subjects would be
necessary.
RESULTS
One hundred fifty-one patients met all inclusion and no exclu-
sion criteria and were enrolled. Table 1 displays baseline char-
acteristics. 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 (2.84.9 hr). Good neuro-
logic 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, TWA-
MAP 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 neurologic function at
hospital discharge. Fourteen (32%) of those who met the pri-
mary outcome had initial rhythm of VF/VT. Twenty-nine per-
cent (14 of 49) of those with an initial rhythm of VT/VF had
a good neurologic outcome and likewise 29% (30 of 102) of
those with an initial rhythm of PEA/asystole had a good neu-
rologic outcome.
The mean (SD) TWA-MAP among patients with good neu-
rologic fnction and poor neurologic function at hospital dis-
charge was 83 ( 13) and 77 ( 18), respectively (p = 0.042).
Figure 3 displays the good neurologic function at hospital dis-
charge in relation to the TWA-MAP value for the first 6 hours
after ROSC.
Table 2 displays the results of the multivariate logistic regres-
sion model with TWA-MAP as a continuous independent vari-
able and good neurologic function at hospital discharge as the
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Kilgannon et al

TABLE 1. Baseline Characteristics of All Subjects

All Subjects Subjects With Subjects With
Patient Characteristics (n = 151) TWA-MAP 70a (n = 36) TWA-MAP > 70a (n = 115)

Age, yr (SD) 63 ( 16) 66 ( 13) 62 ( 17)

Female gender, n (%) 64 (42) 14 (39) 50 (43)
Preexisting comorbidities, n (%)
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)
Charlson comorbidity score (39), 2 (14) 3 (15) 2 (04)
median (interquartile range)
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)
Floor/unmonitored bed 2 (1) 0 2 (2)
Other 15 (10) 1 (3) 14 (12)
Initial arrest rhythm, n (%)
Pulseless electrical activity/asystole 119 (79) 32 (89) 87 (76)
Ventricular fibrillation/ventricular 32 (21) 4 (11) 28 (24)
tachycardia
Estimated downtime > 10 min, n (%) 50 (33) 13 (38) 37 (33)
TWA-MAP = time-weighted average mean arterial pressure.
a
Measured in mm Hg.

dependent variable (OR, 1.02; 95% CI, 1.001.02; 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 inde-
pendently 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 indepen-
dent 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 neurologic function at hospital discharge among
all binary thresholds tested, OR 4.11 (95% CI, 1.3412.66,
p = 0.014). On further sensitivity analysis, TWA-MAP greater
than 70 mm Hg remained the MAP threshold with the stron-
gest association with good neurologic outcome after adjusting
for duration of CPR or downtime longer than 10 minutes,
OR 5.25 (95% CI, 1.7315.98, p = 0.003) (details of the models
are displayed in the supplemental data, Supplemental Digital
Content 1, http://links.lww.com/CCM/A971). Table 4 reports
neurologic outcome as it relates to vasopressor use in the first
6 hours after ROSC.
DISCUSSION
In this prospective observational study, we tested the relation-
ship between arterial blood pressure after resuscitation from
cardiac arrest and neurologic outcome. We sought to test this
relationship because the injured brain may be especially vul-
nerable to blood pressure alterations after ROSC due to a loss
of normal cerebral autoregulation and disruption of micro-
vascular 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 neuropro-
tection. To date, there has been little empirical data on this
topic in human subjects, limited only to retrospective analyses
(1618) and one recent pilot study (43); thus, we felt that a
rigorous prospective study with dense data capture of blood

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 Neurologic Critical Care

resuscitated from cardiac

arrest (40). We found that arte-
rial 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 neurologic out-
come. This association appears
to be driven by the strong asso-
ciation between hypotension
and poor neurologic outcome,
as opposed to an association
between intrinsic hyperten-
sion and better neurologic
outcome. In our analysis, there
was a threshold effect with a
TWA-MAP greater than 70
mm Hg having the greatest
association with good neuro-
Figure 2. Distribution of the time-weighted average mean arterial blood pressure values in the first 6 hr after logic function, and we did not
cardiac arrest.
find higher MAP thresholds
pressure recordings over time in the immediate postresuscita- (> 75, > 80, > 85 mm Hg, etc.) to be associated with favorable
tion period was needed. neurologic outcome.
We found that of the 151 patients enrolled, 29% (44 of In contrast to some prior studies, a major strength of the
151) met our primary outcome of good neurologic 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 quanti-
fying the exposure; the unique-
ness of the results is that they
provide more granular data on
the relationship between blood
pressure and neurologic out-
come 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 car-
diac arrest is a leading cause of
death and neurologic devasta-
tion among adults (4446).
Furthermore, the postcardiac
arrest syndrome is typically
Figure 3. Good neurologic function at hospital discharge in relation to the time-weighted average mean
arterial pressure (TWA-MAP) value for the first 6 hr after return of spontaneous circulation. There was a characterized with marked
statistically significant difference in the proportion of patients with good neurologic outcome between the swings in blood pressure due
TWA-MAP 70 and TWA-MAP 7180 groups, 11% versus 37% (p = 0.009 by Fisher exact test). There to fluctuating hemodynamic
was no difference between the TWA-MAP 7180 and TWA-MAP 8190 groups, 37% versus 36% (p = 1
by Fisher exact test) or between TWA-MAP 8190 and TWA-MAP > 90 groups, 36% versus 32% perturbations after reperfu-
(p = 0.804 by Fisher exact test). sion (2, 1518). Therefore, this

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Kilgannon et al
TABLE 2. Multivariate Logistic Regression Model of the Association Between Time-
Weighted Average Mean Arterial Pressure During the First 6 Hours After Return
of Spontaneous Circulation and Good Neurologic Outcome (Defined as Cerebral
Performance Category 1 or 2) at Hospital Discharge
Variable
Mean arterial pressure
Age
Pulseless electrical activity/asystole initial rhythm
Charlson comorbidity index
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
postcardiac arrest care recommended post-ROSC goal-
directed hemodynamic optimization; however, the guide-
lines 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 optimiza-
tion, including MAP targets, for patients with other etiolo-
gies of critical illness (4749), it is also, in theory, possible
that blood pressure optimization could improve neurologic
outcome among patients with postcardiac arrest syndrome.
However, this hypothesis has not yet been tested in a clini-
cal 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 neurologic outcome compared
with patients who achieved a TWA-MAP greater than 70
with vasopressor administration, 48% versus 24%, respec-
tively (p = 0.01). We were unable to show a statistically sig-
nificant difference in good neurologic 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 bodys intrinsic ability to
maintain adequate perfusion pressure without vasopressors
after ROSC is a predictor of eventual good neurologic out-
come 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 report-
ing that an induced hypertensive surge for cerebral blood
flow promotion can attenuate brain injury and improve out-
come (22, 23, 50, 51). Our study design did not test a vaso-
pressor 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 associa-
tion between TWA-MAPs greater than 90 mm Hg and good
outcome, OR 1.12 (95% CI, 0.482.60, p = 0.794). We found
only one clinical study that tested this induced hypertensive
2088 www.ccmjournal.org
OR 95% Lower CI 95% Upper CI p
1.02 1.00 1.04 0.086
0.93 0.75 1.15 0.490
0.45 0.20 1.05 0.064
0.88 0.62 1.25 0.474
surge hypothesis, a recently published pilot interventional
trial of induced hypertension after cardiac arrest, which
reported that supranormal MAP did not affect cerebral tis-
sue 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 isch-
emic 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 isch-
emic penumbra and protect the injured brain from further
insult (5263). 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 with 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 Time-

Weighted Average of Mean Arterial Pressure at Different Binary Thresholds During
the First 6 Hr After Return of Spontaneous Circulation and Good Neurologic Function
(Defined as Cerebral Performance Category 1 or 2) at Hospital Discharge
Variable 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
Variable 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
Variable 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
Variable OR 95% LCI 95% UCI p

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
Variable OR 95% LCI 95% UCI p

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
Variable OR 95% LCI 95% UCI p

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
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 neurologic 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
70 mm Hg for a good neurologic outcome (OR, 4.11; 95% CI,
1.3412.66), 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 Neurologic Outcome Stratified by Time-Weighted Average Mean Arterial

Pressure (mm Hg) and Vasopressor Use
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

Good neurologic outcome (%) 26 (48) 14 (24) 1 (10) 3 (11)

TWA-Cumulative Vasopressor Index, 0 4 (35) 0 6 (312)
median (interquartile range)
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 postcardiac arrest patients
treated according to consensus recommendations, we found
that arterial pressure over the first 6 hours following resusci-
tation was associated with neurologic outcome. Specifically,
we found a threshold effect with a TWA-MAP greater than
70 mm Hg being associated with good neurologic function.
Further investigation is warranted to determine if interven-
tions to support blood pressure and promote cerebral blood
flow would improve neurologic outcome after cardiac arrest.
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