877323

research-article2019
JVA0010.1177/1129729819877323The Journal of Vascular AccessLv and Zhang

Original research article

JVA The Journal of
Vascular Access

The Journal of Vascular Access

The incidence and risk of infusion

1­–8
© The Author(s) 2019
Article reuse guidelines:
phlebitis with peripheral intravenous sagepub.com/journals-permissions
https://doi.org/10.1177/1129729819877323
DOI: 10.1177/1129729819877323

catheters: A meta-analysis journals.sagepub.com/home/jva

Luyu Lv1 and Jiaqian Zhang2

Abstract
Introduction: Phlebitis is a common complication associated with the use of peripheral intravenous catheters. The
aim of this study was to estimate the incidence of phlebitis with peripheral intravenous catheter use and to identify risk
factors for phlebitis development.
Method: Literature survey was conducted in electronic databases (CINAHL, Embase, Google Scholar, Ovid, and
PubMed), and studies were included if they used peripheral intravenous catheter for therapeutic or volumetric infusion
and reported phlebitis incidence rates. Random effects meta-analyses were performed to obtain overall and subgroup
phlebitis incidence rates and odds ratio between males and females in phlebitis incidence.
Results: Thirty-five studies were included (20,697 catheters used for 15,791 patients; age 57.1 years (95% confidence
interval: 55.0, 59.2); 53.9% males (95% confidence interval: 42.3, 65.5)). Incidence of phlebitis was 30.7 per 100 catheters
(95% confidence interval: 27.2, 34.2). Incidence of severe phlebitis was 3.6% (95% confidence interval: 2.7%, 4.6%).
Incidence of phlebitis was higher in non-intervened (30% (95% confidence interval: 27%, 33%)) than in intervened (21%
(95% confidence interval: 15%, 27%)) groups, and with Teflon (33% (95% confidence interval: 25%, 41%)) than Vialon
(27% (95% confidence interval: 21%, 32%)) cannula use. Odds of developing phlebitis was significantly higher in females
(odds ratio = 1.42 (95% confidence interval: 1.05, 1.93); p = 0.02). Longer dwelling time, antibiotics infusion, female
gender, forearm insertion, infectious disease, and Teflon catheter are important risk factors for phlebitis development
identified by the included studies.
Conclusion: Incidence of phlebitis with the use of peripheral intravenous catheters during infusion is 31%. Severe
phlebitis develops in 4% of all patients. Risk of phlebitis development can be reduced by adapting appropriate interventions.

Keywords
Phlebitis, thrombophlebitis, catheter, intravenous infusion, incidence

Date received: 26 November 2018; accepted: 22 August 2019

Introduction systemic complications is rare with the use of PIVCs but

The use of peripheral intravenous catheters (PIVCs) is
essential for the intravenous infusion of medication and
blood components and in maintaining required body fluid
compositions in hospitalized patients.1 Indications for
intravenous infusion may include hemodynamic monitor-
ing, fluid maintenance or replacement, medication, blood
or blood product administration, nutritional administra-
tion, and other entities such as contrast agent administra-
tion in radiological imaging.2
Generally, PIVCs are inserted into superficial veins of the
lower arm to infuse non-irritating, isotonic solutions. Risk of
chances for phlebitis and catheter-related infections and
obstructions are substantial3,4 and their proper management
1Venous Blood Collection Room, Changchun Children’s Hospital,
Changchun, China
2Department of Cardiology, Sino-Japanese Friendship Hospital, Jilin
University, Changchun, China
Corresponding author:
Jiaqian Zhang, Department of Cardiology, Sino-Japanese Friendship
Hospital, Jilin University, No. 126, Xiantai Street, Erdao District,
Changchun 130033, Jilin, China.
Email: jqzhang_med@126.com
2 The Journal of Vascular Access 00(0)
remains an important task for healthcare professionals, espe-
cially for nurses, as the parenteral administration is an inte-
gral part of nursing practice.5 Phlebitis, the inflammation of
the tunica intima of the vein, may cause discomfort, damage
of affected veins, significant morbidity or mortality, missed
medication doses, and a subsequent longer duration of hospi-
tal stay with increased treatment costs.6 Phlebitis is usually
associated with swelling, pain, erythema, and thrombosis of
the vein, which determine the severity of this condition.7
The nature of the causative agents may be chemical
such as drugs or infusates; mechanical such as size, loca-
tion, and material of PIVC; biological such as infections;
or patient-related factors such as age and gender.8 In the
literature, many studies have reported the incidence and
risk factors for the development of phlebitis, but outcomes
vary greatly across these studies and there appears to be a
list of risk factors associated with the development of phle-
bitis. The aim of this study was to perform a meta-analysis
of phlebitis incidence rate by pooling the estimates
reported in individual studies and to synthesize knowledge
of the risk factors identified in these studies.
Method
Eligibility criteria
Studies were included if PIVCs were used for therapeutic or
volumetric infusion in medical/surgical ward or intensive/
critical care unit and the incidence rate of phlebitis was
reported. Studies were excluded if they reported (a) other
related endpoints such as PIVC failure, occlusion, infiltration,
and accidental dislodgement but not phlebitis; (b) measures
other than incidence rates such as correlation or regression
coefficients; (c) incidence of phlebitis in experimental healthy
individuals; (d) only abstracts that were published but not the
article; (e) the opinions of healthcare staff regarding the inci-
dence of phlebitis; (f) a case report.
Literature search
We searched CINAHL, Embase, Google Scholar, Ovid, and
PubMed from database inception through October 2018 for
studies fulfilling the abovementioned eligibility criteria.
Search terms used were phlebitis, thrombophlebitis, inci-
dence, visual scale, infusion, peripheral, intravenous, cath-
eter, cannula, dressing, hand, wrist, forearm, antecubital,
cubital, Teflon, Vialon, polyurethane, gauze, tape, failure,
infection, occlusion, dislodgement, removal, and complica-
tions. Search also encompassed screening of the references
list of important research and review articles.
Data and analyses
From the selected research articles of respective studies, the
following data were extracted and organized in datasheets:
study size, design, and time-period; main inclusion/exclusion
criteria of study; patients’ demographics and clinical charac-
teristics; catheterization characteristics; study outcome meas-
ures, analytical tools, and study outcomes. For obtaining the
effect sizes of phlebitis incidence rate, random effects meta-
analyses were carried out with Stata software (version 12;
Stata Corporation, Texas, USA) by pooling the incidence
rates of individual studies, which yielded inverse variance
weighted overall and subgroup effect sizes. To evaluate the
significance of difference in the incidence of phlebitis
between male and female patients, a meta-analysis of odds
ratio (OR) was performed under random effects model with
RevMan software (version 5.3; Cochrane Collaboration).
Metaregression analyses were performed to examine the
effect of age, gender, smoking, diabetes mellitus, and publica-
tion period on the incidence of phlebitis. Statistical heteroge-
neity (between-study inconsistency in outcomes) was
quantified by the I2 index.
Results
Thirty-five studies9–43 were included in the meta-analy-
sis (Figure 1): 9 were randomized controlled trials
(RCTs), 24 were non-randomized prospective studies,
and 2 were retrospective analyses. In these studies,
20,697 PIVCs were used for 15,791 patients.
Characteristics of the included studies are presented in
Table 1. The age of the participants (weighted average
with 95% confidence interval (CI)) was 57.1 years
(55.0, 59.2), and 54% (95% CI: 42%, 66%) of these
patients were male. The prevalence of diabetes in this
patient population was 24% (95% CI: 21%, 27%).
Placement of catheter was 50% (95% CI: 39%, 60%) in
forearm, 21% (95% CI: 19%, 24%) in wrist, 17% (95%
CI: 12%, 21%) antecubital/cubital, and 16% (95% CI:
12%, 19%) in hand.
Incidence of phlebitis was 30.7 per 100 catheters (95%
CI: 27.2, 34.2) (Figure 2) or 27.2 per 100 patients (95% CI:
18.3, 36.1). However, the incidence of severe phlebitis was
3.63% (95% CI: 2.65%, 4.62%) (Figure 3). Risk of the
incidence of phlebitis was found to be modifiable as in
non-intervened groups, it was 30% (95% CI: 27%, 33%),
whereas it was 21% (95% CI: 15%, 27%) in the intervened
group. Odds of developing phlebitis was significantly
higher in females (OR = 1.42 (95% CI: 1.05, 1.93); p =
0.02; I2 = 58%; Figure 4).
Incidence of phlebitis was found to be lower with the use
of visual infusion phlebitis (VIP) scale (25.9% (95% CI:
19.6%, 32.1%)) than with investigators’ developed scale
(37.8% (95% CI: 28.1%, 47.6%)). Difference in phlebitis
incidence was also evident in the types of cannula use
(Teflon 33% (95% CI: 25%, 41%) vs Vialon 26.5% (95%
CI: 21%, 32%)). There were no meaningful differences in
the outcomes with regard to the study design: RCTs (31.5%
(95% CI: 26%, 37%)), and non-randomized prospective
studies (28% (95% CI: 24%, 32%)). There were also no dif-
ferences in the outcomes with regard to the time-period of
Lv and Zhang 3
Figure 1.  A flowchart of study screening and selection
process. *Reasons for exclusion included study reported
combined incidence of phlebitis with other complications;
study reported phlebitis scale score but not incidence; study
reported other related endpoints such as PIVC failure,
occlusion, infiltration, accidental dislodgement but not phlebitis;
study reported measures other than incidence rates such as
correlation or regression coefficients; study reported incidence
of phlebitis in healthy individuals; study authors published only
abstract but not research article; study reported the opinions
of healthcare staff regarding the incidence of phlebitis; or was a
case report.
study publication: before 2010 (29.3% (95% CI: 24.2%,
34.3%)) and after 2009 (30.7% (95% CI: 25.6%, 35.6%)).
In metaregression analyses, age was inversely (metar-
egression coefficient (MC): –0.899 (–1.719, –0.0803); p
= 0.032) associated but percentage of females in a study
was positively (MC = 0.339 (0.009, 0.667); p = 0.044)
associated with the incidence of phlebitis. Percentage of
diabetic patients in a study (MC = 0.354 (–0.861, 1.570);
p = 0.538) or year of study publication (MC = –0.314
(–1.114, 0.485); p = 0.434) was not significantly associ-
ated with the incidence of phlebitis.
A number of risk factors for the development of phle-
bitis were identified by the individual studies. Among
these, risk factors identified by at least three studies
included longer dwelling time,13,16,17,27,28,34,36,41 antibiotics
infusion,25,27,30,34,38 female gender,9,14,27,30,32 forearm inser-
tion,9,30,38,39 infectious disease,18,32,34 and Teflon catheter
use.23,27,40 Risk factors identified by two studies were dia-
betes mellitus17,32 and drug infusion.9,39 Risk factors that
were identified by a single study were insertion near
elbow,42 no splint use,10 hand insertion,14 cannula size
16–20,14 no change of cannula in 2 days,11 intermittent
infusion,42 pain,28 chronic disease,18 later age,25 Vialon
catheter use,21 no hand wash,33 male gender,25 potassium
chloride infusion,38 small catheter size, and blood product
infusion.39
Discussion
In this meta-analysis, we have found that the incidence of
severe phlebitis is approximately 4% in patients who
received infusion through a peripheral catheter. Phlebitis
of any grade was much higher (approximately 31%). Risk
of phlebitis incidence was lower in intervened than in non-
intervened patients (21% vs 30%). There was also higher
incidence of phlebitis with the use of Teflon cannula than
with Vialon cannula (33% vs 27%). Risk of phlebitis
development was significantly higher in females.
Phlebitis is a common complication associated with the
use of PIVCs, which demands for the removal of catheter
and insertion of a new catheter at a different place. If it
happens repeatedly, it can cause difficulties in venous
access and use of more invasive procedures. Infusion
Nurses Society (INS) recommends that phlebitis rate
should be less than 5%44 and phlebitis of grade above 2
will need intervention.45 Our estimates are much above
INS’s recommendations and even the incidence of severe
phlebitis is found to be approximately 4%.
This study confirms that longer dwelling time, antibi-
otics infusion, female gender, forearm insertion, infec-
tious disease, and use of Teflon cannula are more
important risk factors for phlebitis development. In this
study, four of the included studies reported female gen-
der as a risk factor for the development of phlebitis and
a meta-analysis of 10 studies found significantly higher
odds of developing phlebitis by the female patients.
Among the included studies, only Lanbeck et al.25 have
reported male gender as a risk factor for phlebitis grade
2–3 incidence (OR = 1.35 (95% CI: 1.01, 1.80)), but
they could not find this relationship in the multivariate
analysis. Washington and Barrett43 noticed that female
patients who received more medication doses through
PIVCs of longer duration and who experience unin-
tended weight loss had higher phlebitis rates. It has also
been suggested that hormonal differences may have a
role in phlebitis development in females.32
Two studies identified diabetes mellitus as a risk factor
for developing phlebitis,17,32 but two others could not find
a significant association between diabetes and phlebitis
risk.24,31 Cicolini et al.24 and Singh et al.39 have noticed that
diameter of cannula may also affect phlebitis rate. Size and
physicochemical properties of the cannula may also affect
the development of phlebitis.14,39,46 A smaller diameter
cannula that can reconcile patient’s veins with prescribed
therapy can minimize the risk of phlebitis.47,48
The incidence of infection with PIVC is reported to be
low but variable ranging from 0.06 bacteremias/1000
PIVC-days,49 0.9% blood stream infections; 264 events
from 28,987 PIVCs50 and 0.2 to 0.7 bacteremias/1000
PIVC-days3 to 2.3%; 9 from 390 PIVCs.51 However, it is
suggested that not all infectious events may end in clear
signs, and short dwell times and early discharge of patients
may affect the actual incidence rates, which stresses for a
 4

Table 1.  Characteristics of the included studies.

Study nCat. nPt. Design Age Males (%) T2DM (%) Ward Catheter location (%) Catheter use Scale
(years) (days)

  Cubital Forearm Hand Wrist  

Abolfotouh et al.9 842 359 PROSP 57 MED/SURG/INF VIP

Ayat-Isfahani et al.10 60 60 RCT 65 ± 15 74 27 Cardiology 25 17 29 IDS
Barker et al. 11 84 47 RCT 62 ± 17 64 MED/SURG 3.81 ± 1.6 Other
Bregenzer et al.12 665 451 PROSP 64 ± 16 55 ICU/MED 70.2 18.35 4.3 ± 3.8 Other
Catney et al.13 411 411 PROSP 65 ± 14 100 MED/SURG IDS
Cicolini et al.14 427 427 PROSP 48 ± 22 33 MED/SURG 47 43 10 IDS
Cornely et al.15 319 175 PROSP 48 ± 18 65 HEMA/ONCOL/INF 77.4 2.821 24.45 4.2 ± 2.7 Maki
do Rego Furtado16 186 186 RETRO SURG 21.5 25.3 17.2 32.3 VIP
do Rego Furtado17 286 171 PROSP 45 21.05 SURG 25.2 32 22 17.8 VIP
Enes et al.18 122 122 PROSP 46 ± 18 50 MED 2.85 ± 1.9 VIP
Gallant and Schultz19 851 509 PROSP 65 ± 13 65 SURG 30 39 17 14 VIP
Grüne et al.20 2495 1582 PROSP 54 ± 16 25 MED/SURG 2 ± 1.35 CDC
Gupta et al.21 70 70 RCT 58 ± 11 91 45.71 SURG Dinley
Johann et al.22 169 169 RCT 55 ± 18 52 MED/SURG 12 ± 8.6 VIP
Karadag and Görgülü23 255 255 RCT  
Karadeniz et al.24 58 58 PROSP 53 33 41 41 33 IDS
Lanbeck et al.25 1386 550 PROSP 45 15 INF IDS
Lundgren et al.26 60 60 PROSP 61 ± 17 63 MED/SURG IDS
Maki and Ringer27 1054 714 RCT 52 ± 16 57 25.4 MED/SURG 2.5 ± .5 Maki
Malach et al.28 578 578 PROSP MED/SURG CDC
Mestre Roca et al.30 1201 967 PROSP 55 ± 20 46 MED/SURG/ED 35.1 16.57 16.57 1.5 ± 2.7 VIP
Monreal et al.31 766 766 PROSP 55 ± 23 71 16.5 MED 5 ± 5.4 IDS
Nassaji-Zavareh and 300 300 PROSP 52 ± 223 52 37 MED/SURG IDS
Ghorbani32
Neopane33 100 100 PROSP 48 ± 21 44 22 MED IDS
Osei-Tutu et al.34 224 224 PROSP 43 ± 19 54 MED/SURG 16 39 30 16 3.94 ± 2.6 VIP
Panadero et al.35 60 60 RCT 45 ± 12 37 SURG Baxter
Powell et al.36 679 679 RETRO MED/SURG 1.9 ± 1.4 VIP
Rickard et al.37 1709 1709 RCT 60 ± 7 59 MED/SURG 5 66 7 12 2.2 ± 0.67 Other
Salgueiro-Oliveria et al.38 1244 987 PROSP 76 ± 15 51 MED/SURG 9.6 26 36 15 3.88 ± Other
Singh et al.39 230 230 PROSP 24 MED/SURG/ICU 46.1 27.83 2.8 ± IDS
Tanabe et al.40 407 307 PROSP 69 ± 13 61 MED 94 2 2.2 ± 2.5 VIP
Urbanetto et al.41 361 171 PROSP 57 ± 19 52 MED/SURG 1.9 25.2 27.8 3.37 ± 1.1 VIP
Uslusoy and Mete42 586 355 PROSP 46 SURG VIP
Washington and Barrett43 188 169 PROSP 63 ± 16 50 MED/SURG 2.73 ± VIP

CDC: Centers for Disease Control and Prevention; ED: emergency department; HEMA: hematology; ICU: intensive care unit; IDS: investigator developed scale; INF: infectious diseases; MED: medical; nCat.: number of catheters;
nPt.: number of patients; ONCOL: oncology; PROSP: prospective; RETRO: retrospective; RCT: randomized controlled trial; SURG: surgery; T2DM: type 2 diabetes mellitus; VIP: visual infusion phlebitis.
The Journal of Vascular Access 00(0)
Lv and Zhang 5

Figure 2.  A forest graph showing the pooled incidence of phlebitis with overall effect size and subgroup effect sizes with regard to
the use of phlebitis measuring tools. cat: catheter; FEP: tetrafluoroethylene-hexafluoropropylene; PEU: polyetherurethane without
leachable additives; PU: polyetherurethane.

need to have more in-depth studies of the pathophysiology
of phlebitis.52
Other factors such as the use of poor aseptic technique
for insertion, lack of stabilization, and inconsistencies with
dressings may promote the incidence of phlebitis. Poor
adherence to standard aseptic precautions has been reported
to double the incidence of thrombophlebitis.53 Proper stabi-
lization and securement of catheter is very important. Good
stabilization of catheter can reduce the risk of phlebitis and
other phlebitis-related complications.54 Medication pH and
blood tonicity should be adjusted optimally to reduce
chances of phlebitis development. Noting date and time of
insertion can help in determining about possibilities and
feasibilities of site changes. Attendant staff should also
monitor nutritional schedule and adequacy. A consideration
of PVC replacement every 72–96 h may be fruitful.55,56
6 The Journal of Vascular Access 00(0)

Figure 3.  A forest graph showing the pooled incidence of severe phlebitis.

Figure 4.  A forest graph showing the outcomes of a meta-analysis of odds ratios between females and males in developing
phlebitis.

However, practical difficulties do exist. A wide gap has
been found between the current standards of infusion ther-
apy and the nurses’ knowledge about risk factors for phle-
bitis in a study appraising nurses for their perceptions
regarding the risk factors for phlebitis development.57
Moreover, because several risk factors are identified by
researchers and, for many, there is still no consensus based
on available data, it is therefore necessary to evaluate pos-
sible risk factors in future randomized trials.
High statistical heterogeneity observed in the inci-
dence rate in this study is an important consideration.
Several factors affecting the incidence of phlebitis were
identified by the individual studies; therefore, it can be
conceived that such factors could be the source of high
Lv and Zhang 7
statistical heterogeneity in the overall effect size. Our
data were derived from the study reports published dur-
ing 1991 and 2018, which is a long period, and methodo-
logical features have advanced in more recent years,
which could also affect the outcomes to some extent. A
metaregression analysis to test such an effect could not
find any significant association, but the overall relation-
ship between the incidence of phlebitis and publication
year was inverse.
An important limitation of this study is the use of sev-
eral scales for the measurement of phlebitis by the indi-
vidual studies, which has an impact on overall outcomes.
Placement of catheter was also at four different sites in
the overall population, and because at least four studies
have identified forearm insertion as a risk factor for phle-
bitis development, variance related to anatomical site in
present study data could have also influenced the overall
outcomes. Twenty-four percent population of this study
was diabetic, which may have also contributed to the het-
erogeneity to some extent.
Conclusion
Phlebitis incidence is considerably high (approximately
31%) with the use of PIVCs, and the incidence of severe
phlebitis is approximately 4%. Risk of phlebitis incidence
is found to be modifiable as the incidence rate was lower in
intervened groups (21%) than in non-intervened patients
(30%). Incidence of phlebitis has also been found to be
higher with the use of Teflon cannula (33%) than with
Vialon cannula (27%). Longer dwelling time, antibiotics
infusion, female gender, forearm insertion, patient’s infec-
tious disease, and use of Teflon cannula are more important
risk factors for phlebitis development.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Ethical statement
All analyses were based on previous published studies;
therefore, no ethical approval and patient consent were
required.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Jiaqian Zhang https://orcid.org/0000-0003-4696-4211
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