Full text of DOI:10.1080/10903120090940967

ORIGINAL ARTICLES
EFFECTS OF PREHOSPITAL NITROGLYCERIN
ON HEMODYNAMICS AND CHEST PAIN INTENSITY
Steven Engelberg, RPA-C, Adam J. Singer, MD, Janice Moldashel, MD,
Joseph Sciammarella, MD, Henry C. Thode, PhD, Mark Henry, MD
ABSTRACT
in the prehospital setting. Conclusions. Use of prehospital
NTG appears safe. While NTG reduces CP, most patients
have residual pain. Key words: organic nitrates; nitroglyc-
erin; chest pain; prehospital; EMS.
Objective. To assess the effects of prehospital nitroglycerin
(NTG) on vital signs and chest pain intensity. Methods. A
retrospective review of advanced life support (ALS) run
sheets was performed in a suburban volunteer emergency
medical services (EMS) system receiving 8,000 annual ALS
calls. All consecutive patients who were administered NTG
by EMS were included. Standardized forms were used to
collect data on patient demographics, history, and physical
exam. Patients assessed their chest pain (CP) before and
after NTG on a verbal numeric scale of 0–10 from least to
most severe. The presence of syncope, dysrhythmias, or pro-
found hypotension [loss of peripheral pulses, a systolic
blood pressure (SBP) of <90 mm Hg after NTG, or a drop of
>100 mm Hg in BP] was noted. Results. One thousand six
hundred sixty-two patients received NTG over 18 months,
their mean age was 66 years, and 48% were female.
Indications for NTG included CP (83%), dyspnea (45%), and
congestive heart failure (20%). After NTG administration,
the CP score decreased from 6.9 to 4.4 (mean difference =
2.6; 95% CI = 2.4 to 2.8). The CP completely resolved in 10%
of the patients. Mean decreases in SBPs and diastolic BPs
were 11.8 mm Hg (95% CI = 10.7 to 13.0) and 4.0 mm Hg
(95% CI = 2.9 to 5.1). The mean pulse rate increased by 2.7
beats/min (95% CI = 0.6 to 4.9). There were 12 patients with
adverse events [0.7% (95% CI = 0.4% to 1.3%)], including
profound bradycardia and hypotension (1), transient drop
in SBP of 100 mm Hg responding to fluids (6), post-NTG
SBP <90 mm Hg (4), and syncope (1). There were no deaths
PREHOSPITAL EMERGENCY CARE 2000;4:290–293
Nitroglycerin (NTG) is one of the most important
medications used to treat ischemic heart disease in
both the prehospital and inpatient settings.1,2 Initially
described in 1879,3 its vasodilatory effects were first
noted by Sir Thomas Lewis in 1933.1
Since administration of NTG may be associated with
a decrease in blood pressure, many prehospital sys-
tems (as well as emergency departments) have proto-
cols requiring the insertion of an intravenous (IV)
catheter prior to the administration of NTG. For exam-
ple, New York State Emergency Medical Services
(EMS) protocols,4 New York City protocols,5 and
Suffolk County protocols6 all require establishment of
IV access prior to administration of NTG. In addition,
NTG is usually contraindicated in the presence of a
low systolic blood pressure (SBP), usually defined as
an SBP of less than 100–120 mm Hg.7
Other common adverse effects associated with the
administration of sublingual NTG include nausea,
headache, vomiting, lightheadedness, flushing, palpi-
tations, and reflex tachycardia.8 Syncope, hypotension
with bradyarrhythmias, and even asystole have been
less frequently described.9 Despite these potential
adverse events, many patients self-administer NTG on
a daily basis without the need for IV access. As a
result, we questioned the need for establishing IV
access in all patients prior to administering NTG in the
prehospital setting.
The objectives of the current study were to assess
the incidence of adverse events associated with use of
sublingual NTG in the prehospital setting and to eval-
uate the effectiveness of NTG in reducing the intensi-
ty of chest pain (CP).
Received November 12, 1999, from the Department of Emergency
Medicine, State University of New York at Stony Brook, Stony
Brook, New York (SE, AJS, JM, JS, HCT, MH). Revision received
March 21, 2000; accepted for publication March 27, 2000.
Presented at the Society for Academic Emergency Medicine annual
meeting, Boston, Massachusetts, May 1999.
Address correspondence and reprint requests to: Adam J. Singer,
MD, Department of Emergency Medicine, University Medical
Center, L4-515, Stony Brook, NY 11794-7400. e-mail: <asinger@
epo.som.sunysb.edu>.
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Engelberg et al. NITROGLYCERIN EFFECTS ON CHEST PAIN INTENSITY
291
Measurements
METHODS
A structured closed-question data instrument was
used to collect demographic and clinical data for all
patients. Data collection was performed by certified
medical control operators specifically trained in the
use of the Suffolk County EMS ALS run sheet. Data
collected included chief complaint, past medical histo-
ry, medication and allergy history (including prior use
of NTG and self-administration of NTG prior to EMS
arrival), vital signs, and physical examination find-
ings. Repeated measurements of vital signs and phys-
ical findings were performed approximately every 3–5
minutes. Patients assessed their CP intensity before
and after NTG using a verbal numeric scale of 0–10
from least to most severe10 and this information was
recorded on the run sheet. Complete relief of pain was
considered to be present if the post-NTG pain score
was 0. The presence of syncope, dysrhythmias, or pro-
found hypotension (arbitrarily defined as a loss of
peripheral pulses, a drop of >100 mm Hg in SBP, or a
post-NTG SBP of less than 90 mm Hg) was noted.
Study Design
A retrospective review of advanced life support (ALS)
run sheets was performed to assess the incidence of
adverse events associated with administration of NTG
in the prehospital setting. In our EMS system, ALS run
sheets are completed on all ALS calls to medical con-
trol and entered daily into a computerized database.
The study was approved by the University Hospital
and Medical Center at Stony Brook Institutional
Review Board.
Study Setting
The study was conducted within the Suffolk County
EMS System, which is a multi-tiered system, and
included patients transported to any one of 12 hospitals
by an ALS ambulance. Suffolk County, New York, is a
suburban/rural county on eastern Long Island. The
county covers 932 square miles and has a population of
1.5 million. The Suffolk County Department of Health
Services administers the EMS system, which provides
both basic and ALS care. Fire, rescue, and emergency
medical services throughout the region are provided on
an all-volunteer basis by 111 fire departments (of whom
63 provide ambulance service) and 31 volunteer ambu-
lance corps. Seventy-five of these services provide ALS-
level care to all or part of their service areas. Advanced
life support crews consist of at least one critical care
emergency medical technician (EMT) or paramedic.
The emergency ambulance services in the county
respond to more than 80,000 calls each year, of which
approximately 8,000 involve ALS care.
Data Analysis
Data were entered into Access 97 (Microsoft, Inc.,
Redmond, WA) and imported into SPSS 8.0 for
Windows (SPSS Inc., Chicago, IL) for statistical analy-
sis. The incidence of adverse events is presented as
frequency of occurrence with 95% confidence inter-
vals (CIs). The effect of NTG on the intensity of CP
was assessed by subtracting the post-NTG verbal
numeric score from the pre-NTG score. Descriptive
statistics were used to analyze blood pressures and
heart rates before and after administration of NTG.
The Department of Emergency Medicine of the
University Medical Center at Stony Brook serves as
the sole online medical control facility for all 12 ambu-
lance-receiving hospitals in Suffolk County. Providers
performing ALS services must contact medical con-
trol, where care is directed by one of 19 emergency
physicians certified as base-station medical control
physicians. The ALS protocols for all services are
reviewed and approved by the county EMS medical
director.
All patients who were administered NTG by pre-
hospital providers in the Suffolk County EMS system
between January 1993 and June 1994 were included in
the study. All patients received a single dose of 0.4 mg
sublingual NTG. During the study period all patients
were routinely transported to one of 12 receiving hos-
pitals in the county for continuing treatment.
Indications for administering NTG in the prehospital
setting include the presence of CP of suspected cardiac
origin and/or the presence of signs or symptoms con-
sistent with congestive heart failure (CHF). Morphine
sulfate is not routinely administered to patients with
CP or CHF.
RESULTS
During the study period there were 8,255 patients
treated in the Suffolk County EMS system, of whom
1,662 (20%) received sublingual NTG. The mean age of
the patients who were administered NTG was 66 15
years (range = 16–99 years); 48% were female. The
indications for administering NTG in the prehospital
setting were CP (901), respiratory distress consistent
with CHF (251), or a combination of CP and respirato-
ry distress (510). Of all patients, 265 (16%) had self-
administered NTG immediately prior to ALS arrival
and administration of NTG by an ALS provider.
The mean pre-NTG SBP and diastolic blood pres-
sure (DBP) were 157.6 mm Hg (95% CI = 155.2 to
158.9) and 90.0 mm Hg (95% CI = 88.8 to 91.3), respec-
tively. The mean pre-NTG heart rate was 93.2
beats/min (95% CI = 90.9 to 91.6). After administering
NTG, the mean decrease in SBP was 11.8 mm Hg (95%
CI = 10.7 to 13.0). The mean decrease in DBP was 4.0
mm Hg (95% CI = 2.9 to 5.1). The mean increase in
heart rate was 2.7 beats/min (95% CI = 0.6 to 4.9).

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There were 12 adverse events associated with pre-
series of 815 patients who received prehospital NTG,
Brice et al. noted hypotension (SBP < 100 mm Hg) in
only 37 patients (3.6%) with very few other adverse
events.13 While relatively safe, use of NTG has been
associated with significant adverse events such as
bradycardia, hypotension, and even asystole.9
Nemerovski and Shaw reviewed 17 cases of patients
who developed hypotensive bradycardia after admin-
istration of sublingual NTG. Unfortunately, they were
unable to identify any clinical factors that would allow
physicians to predict which patients would develop a
hypotensive bradycardic reaction after NTG.14
Ferguson et al. found that hypotension after NTG was
more frequent in patients who subsequently were
diagnosed as having right ventricular myocardial
infarctions.15 However, they were unable to identify
any other risk factor for adverse events after NTG
administration. Finally, Cheng found that hypoten-
sive bradycardia developed in 5% of 3,000 patients
undergoing cardiac catheterization who also received
sublingual NTG.16 Whether these results can be gener-
alized to the prehospital setting is questionable. While
we recognize the potential for serious adverse events
after NTG, the rarity of such events should not pre-
vent administration of NTG to patients in the prehos-
pital setting in whom IV establishment is delayed or
not possible. Furthermore, since nitrates have been
shown to reduce the odds of death after acute myocar-
dial infarction (AMI),11 withholding such therapy may
be detrimental. Finally, the American College of
Cardiology and the American Heart Association rec-
ommend sublingual NTG every 5 minutes at home,
where IV access is almost never established.3
Therefore, withholding such therapy in an ambulance
does not make sense.
Few studies have addressed the effect of NTG on CP
intensity. In a study comparing sublingual nifedipine
and NTG in 13 patients who developed CP during
diagnostic exercise stress testing, complete pain relief
was noted in five of seven patients (71%) who received
NTG.17 In a study evaluating the effectiveness of IV
boluses of NTG in emergency department patients
who failed to experience pain relief after one to two
sublingual doses, Nashed et al. noted complete relief
in two of five patients with AMI and nine of 11
patients with unstable angina.18 Previous reports
examining continuous IV NTG infusions in patients
with unstable angina have yielded rates of complete
pain relief ranging from 0% to 81%.19–22 We are
unaware of any prior studies that specifically evaluat-
ed the changes in CP intensity after administration of
a single dose of sublingual NTG in the prehospital or
hospital setting. In the current study prehospital
administration of a single dose of NTG resulted in a
mean decrease of 2.6 units on the verbal numeric pain
score (or a relative reduction of approximately 40%)
hospital NTG administration, including profound
bradycardia and hypotension (1), a transient drop in
SBP of 100 mm Hg responding to IV fluids or leg ele-
vation (6), a post-NTG SBP of less than 90 mm Hg (4),
and syncope (1). All patients in whom the SBP
dropped at least 100 mm Hg had an SBP greater than
210 mm Hg prior to administration of NTG. There
were no deaths reported. Thus, the estimated inci-
dence of adverse events was 0.7% (95% CI = 0.4% to
1.3%). None of the adverse events noted above
occurred in patients who had self-administered NTG
prior to receiving NTG from an ALS provider.
Both pre- and post-NTG verbal numeric rating pain
scores were available for 779 patients (47%). The mean
pre-NTG pain score was 6.9 (95% CI = 6.8 to 7.1). The
mean decrease in pain scores after administration of
NTG was 2.6 (95% CI = 2.4 to 2.8). After administra-
tion of NTG, the CP completely resolved in only 80
patients (10%).
DISCUSSION
The results of the current study indicate that the over-
all rate of serious adverse events associated with pre-
hospital administration of NTG is small, with an
upper 95% CI of less than 1.5%. Also, the occurrence of
adverse events was not associated with self-adminis-
tration of NTG immediately prior to receiving NTG
from ALS providers. Importantly, no deaths were
associated with use of prehospital NTG. Thus, our
results (as well as common sense) suggest that use of
prehospital NTG is safe and may not necessitate the
establishment of IV access prior to administration.
However, since all patients in our study had IV access,
it is unclear what if any consequences these adverse
events would have had without such access. For
example, several patients who developed a 100-mm
Hg decline in the SBP were successfully treated with
IV fluid. We can only speculate on what the outcome
may have been had these patients not received imme-
diate fluid resuscitation if IV access could not have
been established.
Requiring routine establishment of IV access in all
patients prior to administering NTG could potentially
prolong the time spent at the scene by prehospital
providers, delaying patient transport to the hospital
for definitive care. Furthermore, establishment of IV
access (especially during transport) may be difficult or
impossible, which would delay or prevent patients
with ischemia or CHF from receiving NTG in the pre-
hospital setting, denying them the clinical benefits of
nitrates.11
Our results are in agreement with those of prior
reports. For example, Wuerz et al. found that of 300
patients receiving NTG in the prehospital setting, only
four (1.3%) developed adverse effects.12 Similarly, in a

Engelberg et al. NITROGLYCERIN EFFECTS ON CHEST PAIN INTENSITY
293
from 6.9 to 4.4. While a difference in visual analog
scale (VAS) pain scores of this magnitude is consid-
ered to be of clinical significance,23 pain relief was
complete in only 10% of patients. Thus, most patients
continued to experience pain in the ambulance. While
prior studies indicate that most patients get relief from
NTG, in many of these studies patients received more
than one dose of NTG. Furthermore, in many such
studies, relief of CP was defined as complete or partial
relief of pain. In contrast, we defined pain relief as a
post-NTG pain score of 0. Finally, many of our
patients may not have had ischemic heart disease as
the cause of their pain, limiting extrapolation of our
results to patients with ischemic heart disease who
develop chest pain.
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LIMITATIONS AND FUTURE QUESTIONS
Our study has several limitations that merit further
discussion. The first and foremost limitation of this
study was that we did not obtain any information
regarding final diagnoses. Thus, we cannot comment
on the safety and effectiveness of sublingual NTG
specifically for patients with ischemic heart disease.
Similarly, without a final diagnosis, we cannot com-
ment on the safety of NTG for subsets of ischemic
heart disease, such as right-sided myocardial infarc-
tions, in which one would expect a higher rate of
adverse events after administration of NTG. However,
in reality, rarely can this determination be made in the
prehospital setting. Second, complete data collection
was not available in all patients. This may have led to
either underestimation or overestimation of NTG’s
safety and effectiveness.
CONCLUSIONS
The results of our study indicate that administration
of sublingual NTG to patients presenting with CP of
suspected cardiac origin or CHF in the prehospital set-
ting is safe. Although rapid establishment of IV access
is recommended in all patients with suspected chest
pain of ischemic origin or CHF, we do not feel that
withholding sublingual NTG in patients without IV
access is justified. While significantly reducing pain, a
single dose of sublingual NTG does not result in com-
plete CP relief in most patients in the prehospital set-
ting.
21. DePace NL, Herling IM, Kotler MN, et al. Intravenous nitro-
glycerin for rest angina. Arch Intern Med. 1982;142:1806–9.
22. Mikolich JR, Nicoloff NB, Robinson PH, et al. Relief of refracto-
ry angina with continuous intravenous infusion of nitroglyc-
erin. Chest. 1980;77:375–9.
23. Todd KH, Funk KG, Funk JP. Clinical significance of reported
changes in pain severity. Ann Emerg Med. 1996;27:485–9.