The Journal of Emergency Medicine, Vol. -, No. -, pp.

1–7, 2017
Ó 2017 Published by Elsevier Inc.
0736-4679/$ - see front matter

https://doi.org/10.1016/j.jemermed.2017.09.007

Brief
Report

COMPLICATIONS FROM ADMINISTRATION OF VASOPRESSORS THROUGH

PERIPHERAL VENOUS CATHETERS: AN OBSERVATIONAL STUDY

Kamal Medlej, MD,* Amin Antoine Kazzi, MD,† Ahel El Hajj Chehade, MD,† Mothana Saad Eldine, MD,†
Ali Chami, MD,† Rana Bachir, MPH,† Dina Zebian, PHD,† and Gilbert Abou Dagher, MD†
*Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts and †Department of Emergency Medicine,
American University of Beirut Medical Center, Beirut, Lebanon
Reprint Address: Gilbert Abou Dagher, MD, Department of Emergency Medicine, American University of Beirut Medical Center,
P.O. Box 11-0236, Riad El Solh 110 72020, Beirut, Lebanon

, Abstract—Background: The placement of a central
venous catheter for the administration of vasopressors is still
recommended and required by many institutions because of
concern about complications associated with peripheral
administration of vasopressors. Objective: Our aim was to
determine the incidence of complications from the adminis-
tration of vasopressors through peripheral venous catheters
(PVC) in patients with circulatory shock, and to identify the
factors associated with these complications. Methods: This
was a prospective, observational study conducted in the
emergency department (ED) of a tertiary care medical cen-
ter. Patients presenting to the ED with circulatory shock and
in whom a vasopressor was started through a PVC were
included. Research fellows examined the i.v. access site for
complications twice daily during the period of peripheral
vasopressor administration, then daily up to 48 h after treat-
ment discontinuation or until the patient expired. Results:
Of the 55 patients that were recruited, 3 (5.45% overall,
6% of patients receiving norepinephrine) developed compli-
cations; none were major. Two developed local extravasation
and one developed local thrombophlebitis. All three compli-
cations occurred during the vasopressor infusion, none in
the 48 h after discontinuation, and none required any med-
ical or surgical intervention. Two of the three complications
occurred in the hand, and all occurred in patients receiving
norepinephrine and with 20-gauge catheters. Conclusions:
The incidence of complications from the administration of
vasopressors through a PVC is small and did not result in
significant morbidity in this study. Larger prospective
studies are needed to better determine the factors that
are associated with these complications, and identify
patients in whom this practice is safe. Ó 2017 Published
by Elsevier Inc.
, Keywords—complications; critical care; peripheral
venous catheters; sepsis; septic shock; vasopressors
INTRODUCTION
Circulatory shock is frequently encountered in the emer-
gency department (ED) and is a life-threatening condition
if not addressed promptly (1). The early initiation of vaso-
active agents in certain distributive shock states like septic
shock has been associated with improved survival (2–4).
The early goal-directed therapy (EGDT) trial by Rivers
et al. emphasized early aggressive i.v. fluid administra-
tion, vasopressor initiation in cases of refractory hypoten-
sion, and placement of a central venous catheter (CVC) to
measure central venous pressure (CVP) and central
venous oxygen saturation (ScvO2) (5,6). Since the
introduction of EGDT, the need for placement of a CVC
in sepsis has come under increasing scrutiny. Alternative
means of monitoring fluid responsiveness and adequacy
of resuscitation that do not rely on central venous access

RECEIVED: 19 May 2017; FINAL SUBMISSION RECEIVED: 22 August 2017;

ACCEPTED: 14 September 2017

1
2 K. Medlej et al.
have been described (7–14). The placement of a CVC has
also been identified as a barrier to the implementation of
EGDT, as it is a time-consuming procedure that cannot
always be easily or safely performed in the ED
(15,16). However, the placement of a CVC for the
administration of vasopressors is still recommended and
required by many institutions, given the concern for
complications associated with peripheral administration
of vasopressors. A literature search for the nature
and incidence of complications associated with
administration of vasopressors through a PVC yielded a
number of case series and case reports describing
skin necrosis after the administration of norepinephrine
(17–19). One study dating back to 1956 described two
cases of tissue necrosis in 55 patients who received the
drug (3.6% complication rate) (19). These complications
were also described with vasopressin and dopamine
(20–23). It must be noted, however, that the placement
of a CVC can have complication rates as high as 22%
(24–28).
While administration of vasopressors through a PVC
is usually avoided, it is difficult to properly assess the
risk of such practice without further studies. We are
unaware of any large prospective studies looking at the
incidence of complications from the peripheral adminis-
tration of vasopressors. The rate of extravasation, rate of
complications, infusion sites most likely to lead to com-
plications, and concentrations of vasopressors most likely
to lead to complications remain unknown.
This prospective observational study was conducted in
the ED of a tertiary care academic center that routinely
administers vasopressors through a PVC. We hope it
will help determine the true incidence of complications
associated with peripheral administrations of vasopres-
sors, as well as identify factors associated with complica-
tions, and situations in which this practice may be safe.
MATERIALS AND METHODS
This study was submitted to and approved by the Institu-
tional Review Board (IRB). Between May 2013 and April
2015, we identified all patients presenting to the ED of a
tertiary care academic center who were started on vaso-
pressors through a PVC (of note, infusion of vasopressors
through ultrasound-guided peripheral lines is infrequent,
but not expressly forbidden at our institution). The pa-
tients, or their next of kin if the patients did not have ca-
pacity to understand or sign the consent forms, were
approached by research fellows and the purpose of the
study was explained. Fifty-five patients were enrolled in
the study after signing an informed consent form that
was approved by the IRB. Of note, prospective research
in the emergency setting in our patient population is, un-
fortunately, not common, and potential subjects are
sometimes reluctant to enroll in academic studies, given
the high-pressure context. In our study, 13 patients
refused to sign consent and could not be recruited.
Once enrolled, patients were followed by research fel-
lows (recently graduated MDs choosing to work as post-
doctoral research fellows for 1–2 years before starting
their residency) who physically examined the i.v. access
sites twice daily during the period of peripheral vaso-
pressor administration, then daily up to 48 h after treat-
ment discontinuation, or until the patient expired. The
period of 48 h was chosen because some studies have re-
ported a delayed presentation of complications up to 48 h
after the discontinuation of the peripheral infusion of va-
sopressors (17,19). The different types of circulatory
shock were prospectively assessed for each patient by
the research fellows in consultation with the principal
investigator. The research fellows were physicians that
had been educated to identify the complications of
interest, which were divided into minor complications
(drug extravasation, thrombophlebitis, and localized
cellulitis) and major complications (tissue necrosis and
limb ischemia). The role of the research fellows was
entirely observational and they did not influence
decisions made by the medical teams caring for the
patients.
Data on the duration of peripheral vasopressor treat-
ment, type of vasopressor used, dilution of the vaso-
pressor, maximal infusion rate (norepinephrine i.v.
infusion is dosed in mg/min and dopamine infusion is
dosed in mg/kg/min), and PVC location were collected.
In addition, we also recorded the gauge of the catheter
used; reason for treatment discontinuation; duration of
vasopressor use through the peripheral line post recogni-
tion of a complication; and complication type, site, and
timing (complications were prospectively classified as
major and minor, with major complications defined as re-
sulting in long-term morbidity and mortality). We further
documented the location of inpatient transfer (regular
floor or intensive care unit [ICU]), the duration of hospital
stay, and the date the patient expired, when applicable.
Categorical variables were tabulated and analyzed us-
ing frequency and percentage, whereas the continuous
variables were summarized as mean 6 standard devia-
tion. All analyses were conducted using the Statistical
Package for Social Science, version 22.0.
RESULTS
Patient Demographics
Fifty-five patients were enrolled in this study, 34 (61.8%)
males and 21 (38.2%) females, with a combined mean
age of 70 years. Two-thirds of the patients had a history
of hypertension (67.3%) and about half had diabetes
Administration of Vasopressors Through PVCs
mellitus (47.3%). More than one-third had coronary ar-
tery disease (40%) and about one-third had a malignancy
(34.5%) (Table 1).
Septic shock was the most prevalent type of shock
(83.6%), followed by cardiogenic shock (10.9%) and
hemorrhagic/hypovolemic shock (5.5%) (Table 2).
Treatment-Related Variables
All 55 patients received vasopressor therapy through pe-
ripheral infusion, with norepinephrine being the most
common agent (50 patients [90.9%]). Dopamine was
used in 5 patients (9.1%). Three of the 55 patients
required a second peripheral vasopressor to maintain
adequate perfusion. The same PVC was used for admin-
istration of the second vasopressor (2 patients received
dopamine, 1 patient received epinephrine). None of the
patients who received two vasopressors through periph-
eral infusion experienced complications. The maximum
infusion rate of norepinephrine (at the standard concen-
tration of 8 mg in 250 mL of 5% dextrose in water
[D5W]) was 30 mg/min, with a duration median of
13 h, an interquartile range of 6.5–31.5 h, and a treatment
duration range of 2–146 h. The maximum infusion rate of
dopamine was 15 mg/kg/min, with a duration median of
53 h and an interquartile range of 15.5–113 h. In 37 pa-
tients, the peripheral vasopressor infusion was discontin-
ued because it was no longer required. In 13 patients,
peripheral treatment was stopped because a CVC was in-
serted and used for vasopressor administration. In 5 pa-
tients, therapy was discontinued because the patient
expired. The antecubital fossa was the most common
i.v. access site (40%), followed by the dorsum of the
hand (36.4%) and the forearm flexor surface veins
(18.2%). Most of the catheters used were 20-gauge
(50.9%) and 18-gauge (36.4%) (Table 3).
Course of Hospitalization
Thirty-six patients were admitted to the ICU (65.5%), 16
were admitted to regular floor beds (29.1%), and 3
Table 1. Characteristics of Patients at Baseline
Characteristic n (%)
Sex
Female 21 (38.2)
Male 34 (61.8)
Comorbid conditions
Hypertension 37 (65.5)
Diabetes mellitus 27 (49.1)
Coronary artery disease 23 (41.8)
Cancer 19 (34.5)
Dyslipidemia 16 (29)
Congestive heart failure 14 (25.5)
3
Table 2. Types of Shock
Type of Shock n (%)
Septic 46 (83.6)
Cardiogenic 6 (10.9)
Hypovolemic/hemorrhagic 3 (5.5)
expired in the ED (5.5%). The in-hospital mortality rate
was 32.1%. All patients with ongoing vasopressor admin-
istration were admitted to the ICU.
Complications
In this prospective observational study on the peripheral
administration of vasopressors, we found that administra-
tion of norepinephrine resulted in a low rate (5.5%) of mi-
nor complications, and none (0%) of the three
complications that occurred were serious or required
any interventions. The three complications were two
cases of extravasations with local erythema and one
case of local thrombophlebitis. In the 5 patients who
expired while receiving peripheral vasopressor therapy,
it was not believed that the deaths were related to the
vasopressor. All three complications occurred during
the vasopressor infusion and none in the 48 h after discon-
tinuation.
The first complication was local thrombophlebitis of
the right hand. It occurred in a 58-year-old female pre-
senting with septic shock who received norepinephrine
(8 mg in 250 mL D5W) through a 20-gauge catheter in
her right hand. The norepinephrine was infused for a total
period of 40 h and the maximal infusion rate was 7 mg/
min. Therapy was discontinued around 3.3 h post recog-
nition of the complication, not due to this complication
but because she was weaned off vasopressors. No inter-
vention was required. She survived the admission and
was discharged from the hospital.
The second complication was extravasation of norepi-
nephrine in the left hand causing skin pallor. It occurred
in a 57-year-old male presenting with septic shock who
received norepinephrine (8 mg in 250 mL D5W) through
a 20-gauge catheter in his left hand. The norepinephrine
was infused for 11 h and the maximal infusion rate was
7 mg/min. Therapy was discontinued around 1.9 h post
recognition of the complication, not due to this complica-
tion but because he was weaned off vasopressors. No
intervention was required. He survived the admission
and was discharged from the hospital.
The third complication was extravasation causing non-
blanching skin erythema of the right antecubital area. It
occurred in a 42-year-old female presenting with septic
shock and receiving norepinephrine (8 mg in 250 mL
D5W) through a 20-gauge catheter in the right antecubital
fossa. The norepinephrine was infused for 28 h and the
4 K. Medlej et al.

Table 3. Treatment-Related Variables ischemia. Second, these agents usually require the
placement of a CVC, a procedure that is time consuming
Variable Data
and can be difficult to perform in places with limited
Site of PVC, n (%) resources (15,16). The insertion of a CVC is associated
External jugular 2 (3.6) with many complications, including pneumothorax,
Upper arm 1 (1.8)
Antecubital fossa 22 (40) arterial puncture, thrombosis, air embolism,
Forearm 10 (18.2) dysrhythmia, hemothorax, and death. A number of
Hand 20 (36.4) factors can affect the rate of complications, but it has
Catheter gauge, n (%)
16 6 (10.9) been reported to be as high as 22% according to some
18 20 (36.4) studies, even though not all reported complications lead
20 28 (50.9) to significant morbidity or mortality (24–28).
22 1 (1.8)
First vasopressor, n (%) Most accounts of complications from the peripheral
Norepinephrine 50 (90.9) administration of vasopressors, such as norepinephrine,
Dopamine 5 (9.1) epinephrine, dopamine, phenylephrine, and vasopressin,
Maximal infusion rate of vasopressor, n (%)
#5 mg/min 10 (18.2) were published in the form of case report or case series
6 to #10 mg/min 22 (40.0) (17–23). Few recent studies have prospectively
11 to #15 mg/min 14 (25.5) attempted to determine the rate of complications
16 to #20 mg/min 6 (10.9)
21 to #30 mg/min 3 (5.5) associated with the peripheral administration of
Duration of vasopressor infusion, h, median (IQR) vasopressors. A retrospective study in neonates that
Norepinephrine or dopamine 14 (7–40) received vasopressors through a PVC did not show any
Norepinephrine 13 (6.5–31.5)
Dopamine 53 (15.5–113) complications, even with extravasation of the agent in
Reason for treatment discontinuation, n (%) 11 cases (29). Because the population of septic patients
Infusion changed to CVC from PVC 13 (23.6) is usually older and has more comorbidities leading to
Vasopressor no longer required 37 (67.3)
Patient expired 5 (9.1) poor peripheral circulation, such as diabetes or peripheral
vascular disease, it is possible that these findings may not
CVC = central venous catheter; IQR = interquartile range; apply to the adult and geriatric population.
PVC = peripheral venous catheter.
In a recent prospective randomized parallel-group
study comparing complications from the insertion of pe-
ripheral vs. central catheter insertion in an adult popula-
maximal infusion rate was 19 mg/min. Therapy was dis- tion of ICU patients, 19 cases of extravasation were
continued around 2.5 h post recognition of the complica- reported (30). The overall complication rate was very
tion, not due to this complication but because she was high for peripheral catheter insertion, significantly higher
weaned off vasopressors. No intervention was required, than the present standard of care, which raises the possi-
and the patient was admitted to the ICU, but expired dur- bility that the extravasation rate was likely much higher
ing the hospital admission. than average. Despite this fact, none of the 19 cases re-
sulted in any long-term morbidity or mortality.
DISCUSSION A single hospital chart review from 1952 reported two
cases of limb ischemia in 55 patients who received pe-
Patients with severe sepsis and septic shock are managed ripheral norepinephrine administration, for a complica-
with several interventions, including antibiotics, aggres- tion rate of 3.6% (19). None of the patients followed in
sive fluid resuscitation, and the initiation of vasopressors the current study developed limb ischemia, a serious
in cases of refractory hypotension. The delay in initiation complication that might require medical or surgical inter-
of vasopressors in patients that are no longer fluid respon- vention. More recently, a systematic review of 85 articles
sive has been shown to be associated with increased mor- with 270 patients reported 325 separate cases of local tis-
tality. For every 1-h delay in norepinephrine initiation sue injury and extravasations, with 318 events resulting
within 6 h after the onset of septic shock, mortality was from peripheral vasopressor administration (97.8%) and
shown to increase by 5.3% (2,3). Early norepinephrine 7 events resulting from central administration (2.3%).
infusion in septic shock has also been shown to lead to In 85.3% of the reported complications, the infusion
a significant increase in cardiac preload, cardiac output, site was distal to the antecubital fossa. Because most of
and contractility (4). These delays in vasopressor initia- the data were retrieved from case reports and case series,
tion can usually be attributed to two factors. First, physi- complication rates cannot be derived and are influenced
cians and nurses are reluctant to initiate vasopressors by selection bias (31). Two of the three complications
through a PVC, given the reported risk of potentially se- encountered in our study resulted from administration
vere complications, such as skin necrosis and limb of norepinephrine in the hand. This is consistent with
Administration of Vasopressors Through PVCs
prior literature showing a higher incidence of complica-
tions when vasopressors are administered in the hands
and feet (17–23,31). This is likely multifactorial and a
reflection of smaller and more fragile veins that can
burst and result in infiltration of vasopressors.
A review of the literature on the complication rates
associated with the infusion of vasopressors through a
CVC did not yield any significant results. In a large multi-
center, randomized trial comparing dopamine and norepi-
nephrine for the treatment of shock, 79 (9.2%) such
complications in the dopamine group and 54 (6.5%) in
the norepinephrine group were reported. The study,
however, did not specify whether these occurred while
the vasopressors were administered through a PVC or a
CVC (32).
Limitations
A major limitation to this study is the small sample size of
55 patients. While all patients started on peripheral vaso-
pressors in the ED were identified and approached by our
research fellows, a number of patients, or family mem-
bers, did not consent to their enrollment in the study.
We did not keep a tally of patients who declined partici-
pation in the study.
Also, this is a single-center study at an institution that
has extensive experience with infusion of vasopressors
through PVCs. While the institution does not have a pro-
tocol for the initiation and monitoring of vasopressor
infusion through peripheral lines, nurses are usually
mindful of the risk of infiltration of the vasopressors
and use only well-secured catheters with good flow.
Even though most patients were in septic shock
(83.6%), we see no reason why these results could not
be generalized to patient populations suffering for other
types of shock.
Norepinephrine was by far the most commonly used
vasopressor (90.9%). Even though we cannot make reli-
able conclusions concerning the safety of administering
dopamine through a PVC, norepinephrine is the vaso-
pressor of choice in a number of conditions, including
septic and cardiogenic shock (6,32,33). While several
institutions allow for the temporary administration of
dopamine through a PVC, this study has shown that
administering norepinephrine could be as safe and
might therefore be preferred in septic patients.
All three complications occurred in patients with 20-
gauge catheters. Because the number of complications
was small overall, it is difficult to come to a reliable
conclusion that this catheter size should not be used. Prior
studies have concluded that catheters that completely
occluded the vein in which they were placed in (i.e.,
only vasopressor circulating in the vein) resulted in a
higher incidence of skin necrosis (17,18). It could very
5
well be that the size of the catheter was a reflection of a
vein that was too small and therefore at a higher risk
for extravasation of the drug.
CONCLUSIONS
In this prospective observational study of 55 patients
receiving vasopressors through a PVC, the rate of compli-
cations was very low and did not result in significant
morbidity. Because the delay in vasopressor administra-
tion in septic patients has been associated with increased
mortality, this study offers evidence that initiation of va-
sopressors can be done easily and safely through a PVC
and should not be delayed until a CVC is placed. While
the risk for significant complications from this practice
is small, evidence of safety is still lacking and larger pro-
spective studies are needed.
Acknowledgments—The authors would like to thank the nurses
of the emergency department of the American University of
Beirut Medical Center for their assistance in identifying patients
that were potential candidates for this study.
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Administration of Vasopressors Through PVCs 7

ARTICLE SUMMARY
1. Why is this topic important?
This topic is important to emergency and critical care
physicians who may face reluctance to start vasopressors
through a peripheral i.v. catheter.
2. What does this study attempt to show?
This study attempts to show that the administration of
vasopressors through a peripheral i.v. line is safe and
does not result in significant morbidity.
3. What are the key findings?
Out of the total study population, 5.45% developed one
of the prespecified complications, none of which required
any medical or surgical intervention. Two of the three
complications occurred in the hand, and all occurred in
patients receiving norepinephrine and with 20-gauge
catheters.
4. How is patient care impacted?
Patients in shock and in need of vasopressors can
benefit from prompt and safe administration of vasopres-
sors through a peripheral i.v. line before central venous
catheter placement.