J Vasc Access 2014 ; 15 ( 4): 241- 248 REVIEW

DOI: 10.5301/jva.5000225

Flushing the central venous catheter: is heparin necessary?

Alberto Dal Molin1, Elias Allara2, Doriana Montani3, Simona Milani4, Cristina Frassati4, Simonetta Cossu4,
Simone Tonella4, Dania Brioschi4, Laura Rasero5
1
School of Nursing, Biella Hospital, Avogadro University, Biella - Italy
2
Department of Translational Medicine, Avogadro University, Novara - Italy
3
School of Nursing, Novara Hospital, Avogadro University, Novara - Italy
4
Biella Hospital, Biella - Italy
5
Florence University, Florence - Italy

ABSTRACT
Purpose: The aim of this systematic review was to assess the efficacy of heparin flushing in the lock of central venous
catheters.
Methods: We searched MEDLINE and CINAHL databases. Eligible studies were randomized controlled trials evaluating the
use of heparin versus normal saline or other solution in the flushing of central catheter among adult patients. No language re-
strictions were applied. Two reviewers independently screened titles and abstracts in order to identify relevant publications.
The same two reviewers retrieved and evaluated full texts. Parameter estimates regarding catheter occlusion were pooled
using network meta-analysis with Bayesian hierarchical modeling.
Results: We identified 462 references. Eight studies were included. There was no evidence that heparin was more effective
than normal saline in reducing occlusions. It was unclear whether urokinase and lepirudin were more effective than heparin
in reducing occlusions. Vitamin C solution does not appear to prolong catheter patency.
Conclusions: There is no evidence of a different effectiveness between heparin flushing and normal saline or other solutions
in reducing catheter occlusions. Due to the little and inconclusive evidence available in this field, further studies might be
necessary.

Key words: Central venous catheter, Flushing, Heparin, Saline

Accepted: February 12, 2014

INTRODUCTION for lock of catheter must be used (9). Flushing protocols

In order to prevent some complications such as ob-
struction, adequate flushing of central venous catheter is
necessary (1, 2). The device must be flushed before and
after drug administration or transfusion of blood compo-
nents, after obtaining blood specimens and for device
maintenance when not in use (3). Most manufacturers
indicate that flushing must be performed every 4 weeks
when the device is not in use (4). However, some stud-
ies suggest that less frequent flushing could be safe and
feasible (5-8).
The aim of flushing is to clear the infused medica-
tion and to prevent contact between other drugs; the final
flush solution is thought to be important to decrease the
risk of occlusion (2, 9). The nurse must flush the catheter
using a pulsated push-pause technique that creates turbu-
lence within the device lumen allowing removal of debris.
In order to prevent reflux of blood, the positive pressure
vary by facility and type of vascular catheter, but in most
cases it is performed with 10 to 20 mL of normal saline,
followed by 5 mL of heparin solution (3). However, the
effectiveness of heparin is unproven (10) and diversity of
practice was documented by some surveys (11, 12). In
particular, Sona et al (12) reported that in most cases the
nurses use only physiological saline to flush central cath-
eters and maintain patency. The authors concluded that a
randomized controlled trial (RCT) was necessary to deter-
mine the adequate flushing solution.
Some adverse effects are associated with heparin use,
such as autoimmune-mediated heparin-induced thrombo-
cytopenia, allergic reactions and the potential for bleeding
complications following multiple, unmonitored heparin
flushes (10, 13, 14).
The use of normal saline instead of heparin in the
lock of catheter is reported in some studies (15-17), and
systematic reviews agree that in the peripheral venous

© 2014 Wichtig Publishing - ISSN 1129-7298 241

Heparin in catheter flushing

catheter, heparin intermittent flushing is no more effective
than flushing with normal saline alone (18-20).
AIM
The aim of this study was to compare the effectiveness
of heparin over other solutions in catheter flushing among
adult patients with central venous catheter.
METHODS
Search strategy
We identified relevant primary studies by searching
the MEDLINE and CINAHL databases.
We defined the clinical question by using the PICO
framework (21) (Tab. I). We used the following keywords:
“Heparin,” “Catheterization, central venous,” “Catheter
Irrigation, vascular” (Tab. II).
Eligible studies were RCTs evaluating the use of hepa-
rin versus normal saline or other solution in the flushing of
central catheter in adult patients. No language restrictions
were applied.
TABLE I - PICO FRAMEWORK
Population Patients using central venous catheter
Intervention Use of heparin solution in the catheter flushing
Observational studies, reviews or studies conducted in
pediatrics patients or in patients with hemodialysis cath-
eters or with peripheral venous catheter were excluded.
Additional primary studies were identified by the first
author of reference list in published reviews.
Two reviewers (SM and CF) independently screened ti-
tles and abstracts in order to identify relevant publications.
Full texts were retrieved and evaluated by the same two
reviewers. Discrepancies were resolved by discussion with
first author (ADM) and final decision was made by him.
The concordance of their revision was assessed using
Cohen Kappa: if K <0.20 the correlation was poor; fair if
between 0.21 and 0.40; moderate if between 0.41 and
0.60; good if between 0.61 and 0.80 and very good if
≥0.81 (22).
Data extraction
For each included study, the following data were
extracted:
-  First author, name of journal and year of publication
-  Number of patients included in the study
- Characteristics of patients included in the study (mean
age, sex)
- Intervention
-  Principal results
Data were extracted by three independent review-
ers (ST, SC and DM). Discrepancies were resolved by
discussion.

Comparison Other substances/solutions (such as normal saline) Quality assessment of primary studies

Outcome Obstructions, infections, venous thrombosis, heparin- The quality of the included studies was assessed with
induced thrombocytopenia, other complications Critical Appraisal Skills Programme (CASP) for RCTs (23).
related to the management of central venous catheter
This appraisal tool was structured by ten questions.

Outcomes of interest
TABLE II - SEARCH STRATEGY
Primary outcome of interest was occlusion. Secondary
Database Keywords Limits Abstracts outcomes were venous thromboembolism, catheter-related
bloodstream infection and heparin-induced thrombocyto-
PubMed “Heparin” [Mesh] AND No 326
“Catheterization, central venous” penia (HIT). Studies without at least one of these outcomes
[Mesh] were excluded from the analysis.

CINAHL “Heparin” [Mesh] AND No 53

“Catheterization, central venous”
[Mesh]
CINAHL “Catheter Irrigation, vascular”
[Mesh] AND “Catheterization,
central venous” [Mesh]
CINAHL “Catheter Irrigation, vascular”
[Mesh] AND “Heparin” [Mesh]
Additional study found in review bibliography
Data synthesis
Parameter estimates of included studies were pooled
No 10 for the primary endpoint, that is, occlusion of cathe-
ter, which was measured in all of the included studies.
Estimates for secondary endpoints were summarized nar-
No 72 ratively due to the small number of studies available for
each comparison.
Due to the presence of multiple interventions (hepa-
1
rin, sodium chloride, urokinase, lepirudin, and vitamin C),

242 © 2014 Wichtig Publishing - ISSN 1129-7298

Dal Molin et al

a network meta-analysis was performed to allow head-

to-head comparisons for all the treatments considered
in this review—even when a direct comparison was not
available.
A Bayesian hierarchical modeling approach was cho-
sen for its flexibility in accounting for the inherent correla-
tion in multiarm trials and for using the exact likelihood
of the data (e.g., Binomial or Poisson) rather than approxi-
mation to Normal (24). Parsimoniously, a random effects
model with logit link was fitted. The posterior distribution
was generated using the JAGS Monte Carlo Markov Chain
sampler. We specified 500,000 iterations, 5,000 adapta-
tion iterations and a thinning of 10 for each chain. Con-
vergence to the target distribution was assessed via visual
inspection of the sample plots, which revealed consis-
tent trajectory of the chains over time. Due to a minimal
asymmetry of the posterior distributions, median log odds
ratios (ORs) were preferred over the empirical mean log
ORs. The lower bound of each credible interval was ob-
tained from the 2.5th percentile and the upper bound from
the 97.5th percentile. Both point estimates and bounds of
credible intervals were exponentiated to allow interpreta- Fig. 1 - Structure of the network of included studies. Clockwise: L = Lepi-
tion as ORs and their 95% credible intervals. The gemtc rudin; H = Heparin; VitC = Vitamin C; UK = Urokinase; NaCl = Sodium
R package was used for such analyses and for generating chloride.
diagnostic plots.
Main issues of network meta-analyses are loop incon-
sistency and design inconsistency (25, 26). Loop incon- with traditional and network meta-analysis were very
sistency, that is, the lack of agreement between direct and similar, only the latter were shown.
indirect comparisons, was not a problem in this review
because all comparisons were either purely direct or pure-
ly indirect (Fig. 1). Design inconsistency, that is, lack of RESULTS
agreement between pair-wise estimates stratified by study
design, could have been an issue for the heparin vs. sodi- We identified 462 references by the search strategy,
um chloride comparison due to the presence of one study conducted on January 20, 2014; 400 were excluded af-
with three arms (heparin, vitamin C and sodium chloride) ter title/abstract review. A very good correlation was ob-
while all other studies had two arms. Thus, an inconsis- served between the two reviewers (Cohen’s K 0.898; 95%
tency model including a design-by-treatment interaction confidence interval [CI] 0.836 to 0.960). Discrepancies
term was tested against a consistency model without such were resolved by the first author. Of the remaining 62
interaction term (25). The chi-squared test showed no evi- studies, 54 were excluded after a full-text evaluation. In
dence (p=0.274) of a difference in the effect of heparin vs. this phase, we assessed a good correlation between two
sodium chloride in the two-arm trial and in the three-arm reviewers (Cohen’s K 0.780; 95% CI 0.576 to 0.983).
trial. At the time of writing, the gemtc R package did not Thus, eight studies were eligible for inclusion (Tab. III).
provide a stable function for the analysis of heterogeneity. Occlusion of catheter was measured in seven two-
Thus, both consistency and inconsistency models were fit- arm studies (17, 28-33) and in one three-arm study (34).
ted by using mvmeta, a Stata macro that performs random Direct comparisons were feasible for heparin vs. sodium
effects multivariate meta-regression (27). chloride, heparin vs. urokinase and heparin vs. vitamin C.
Since network meta-analysis is a relatively recent and Results of pooled analyses are shown in Table IV. There
nonfully consolidated methodology, direct comparisons was no evidence of superiority of any of the treatments over
were also analyzed with traditional meta-analysis. Hetero- the others, either in the direct or indirect comparisons.
geneity of intervention effects was assessed with Cochran’s
Q tests. A random effects model was fitted and forest plots Heparin vs. normal saline
were generated for each direct comparison (heparin vs. so-
dium chloride, heparin vs. urokinase, heparin vs. lepirudin Five studies (17, 28-30, 34) compared heparin and
and heparin vs. vitamin C). The metaphor R package was normal saline for flushing to maintain patency of central
used. Since the point estimates and inferences obtained venous catheters.

© 2014 Wichtig Publishing - ISSN 1129-7298 243

Heparin in catheter flushing

TABLE III - PRIMARY STUDIES

Author Study design Patients Interventions Main Results

Ray et al RCT n=105 Twice-daily heparin flushing Occlusions:

(1999) Male = 65 with heparin (10 IU/mL) Twice-daily heparin flushing with
Female = 40 versus heparin = 8 (16%)
Heparin = 52 (49.5%) Twice-daily heparin flushing twice-daily heparin flushing with once-
Heparin and urokinase = 53 with once-weekly urokinase weekly urokinase instillation = 2 (4%)
(50.5%) instillation (9000 U/1.8 mL) P<0.05
≥18 years of age Infections and occlusions
Cancer patients with Twice-daily heparin flushing with
Hickwmann catheter heparin = 11 (21%)
twice-daily heparin flushing with once-
weekly urokinase instillation = 3 (6%)
P=0.02
Venous thrombosis
Twice-daily heparin flushing with
heparin = 5 (10%)
twice-daily heparin flushing with once-
weekly urokinase instillation = 6 (11%)
P=ns

Solomon RCT open label n=100 Twice-weekly flushes of Occlusions

et al (2001) Conducted in Male = 33 heparin (50 IU/5 mL) Heparin group: 30/48
two centers Female = 67 versus Urokinase group: 30/52
>16 years p=0.681
Twice-weekly flushes of
Oncology patients with urokinase (5000 IU/2 mL) Catheter-related septicemia
double-lumen Hickmann Heparin group = 9/48
catheter Urokinase group = 8/52
Heparin flushing = 48 (48%) p=0.50
Urokinase flushing = 52 (52%) Exit site infections
Heparin group = 28/48
Urokinase group = 27/52
p=0.122
Venous thromboembolism
Heparin group = 6/48
Urokinase group = 8/52
p=0.726

Rabe et al RCT blinding n=99 Sodium chloride 0.9% solution Occlusions

(2002) Male = 42
Female = 57
≥18 years of age
Patients, with three-lumen
CVC, admitted on a bed
medical Intensive care unit
Sodium chloride = 33 (33%)
Heparin = 33 (33%)
Vitamin C = 33 (33%)
Sodium chloride group = 9 (2.97%)
versus
Heparin group = 2 (0.66%)
heparin solutions 5000 IU/mL Vitamin C group = 12 occlusions (3.96%)
p<0.03
versus
Vitamin C 200 mg/mL

Horne et al RCT, double n=49 3 mL heparin 100 IU/mL Withdrawal occlusions

(2006) blinded Male = 33 Heparin group = 3 (12.5%)
versus
Female = 16 Lepirudin group = 5 (20%)
≥ 18 years of age 3 mL lepirudin 100 μg/mL RR 1.6; 95% CI 0.40-13.86; p=0.70
Cancer patients with an open-
ended, double or triple lumen,
subcutaneously tunneled central
venous access device
Heparin group = 24 (49%)
Lepirudin group = 25 (51%)
To be continued

244 © 2014 Wichtig Publishing - ISSN 1129-7298

Dal Molin et al

TABLE III - continued

Author Study design Patients Interventions Main Results

Bowers et al RCT open n=102 0.9% sodium chloride i Occlusions

(2008) label Male = 51 njections Normal saline group = 3 (6%)
Female = 51 versus Heparin = 0 (0%)
≥18 years of age Heparin lock flush 100 U/mL Average number of days (mean, SD)
Peripherally inserted central Normal saline group: 2.1 (4.0)
catheters (PICC) Heparin group: 2.9 (5.7)
p=ns
Normal saline group = 50 (49%)
Heparin group = 52 (51%)
Fuentes i RCT, double Phase 1 Phase 1 Occlusions
Pumarola blinded n = 128 Heparin 500 IU/5 mL Phase 1
et al (2007) Heparin 500 IU/5 mL=49 (38.3%) versus Heparin 500 IU/5 mL: 2 (4.9%)
Heparin 100 IU/5 mL=79 (61.7%) Heparin 100 IU/5 mL Heparin 100 IU/5 mL: 3 (4.5%)
Phase 2 Phase 2 p=0.937
n=95 Normal saline Phase 2
Normal saline = 57 (60%) versus Normal saline = 0
Heparin = 38 (40%) Heparin 100 IU/5 mL Heparin 100 IU/5 mL = 0
≥18 years of age p=ns
Patients admitted to critical care
unit three-lumen CVC
Schallom RCT open n=341 patients randomized 0.9% sodium chloride Occlusions
et al (2012) label n=295 patients included in the versus 0.9% sodium chloride = 25 (6.3%)
analysis Heparin 10 U/mL Heparin 10 U/mL = 12 (3.8%)
Male = 151 RR 1.66, 95% CI 0.86-3.22; p=0.136
Female =144 Catheter-related bloodstream infection
0.9% sodium chloride = 150 0.9% sodium chloride = 3.1 per 1,000
Heparin = 145 catheter days
Heparin 10 U/mL = 0 per 1,000 catheter
≥18 years of age days,
Patients admitted to critical p=0.125
care unit
Multilumen CVC Average number of days (mean, SD):
0.9% sodium chloride: 7.6 (4.3)
Heparin 10 U/mL: 8.0 (4)
Goossens RCT open n=802 patients randomized Normal saline Easy injection, impossible aspiration
et al (2013) label n=765 patients included in the versus RR=0.94%(95% CI 0.67-1.32%)
analysis Heparin (300 U/3 mL) Catheter-related bloodstream infection
Normal saline = 382 Normal saline group = 0.03 per 1,000
Heparin = 383 catheter days
≥18 years of age Heparin group = 0.10 per 1,000 catheter
Patients with port access days

CI = confidence interval; CVC = central venous catheter; RCT = randomized controlled trial; RR = risk ratio.

TABLE IV - RANDOM EFFECTS NETWORK META-ANALYSIS FOR OCCLUSION OF CATHETER

Heparin vs. sodium chloride 5 (1) 110/800 vs. 136/885 0.55 (0.12 to 1.37)
Heparin vs. urokinase 2 (0) 38/100 vs. 32/105 1.99 (0.44 to 12.48)
Heparin vs. lepirudin 1 (0) 3/24 vs. 5/25 0.54 (0.04 to 7.09)
Heparin vs. vitamin C 1 (1) 25/33 vs. 31/33 0.22 (0.01 to 2.16)
Urokinase vs. sodium chloride None – 0.27 (0.02 to 1.39)
Urokinase vs. lepirudin None – 0.27 (0.01 to 5.05)
Urokinase vs. vitamin C None – 0.10 (0.00 to 1.60)
Lepirudin vs. sodium chloride None – 0.98 (0.04 to 14.59)
Lepirudin vs. vitamin C None – 0.39 (0.01 to 12.75)
Vitamin C vs. sodium chloride None – 2.44 (0.19 to 33.35)

© 2014 Wichtig Publishing - ISSN 1129-7298 245

Heparin in catheter flushing
Rabe et al randomized 99 patients with three-lumen
central venous catheters, in three treatment groups: sodium
chloride 0.9%, vitamin C (200 mg/mL) and heparin (5,000 IU/
mL). They found significant differences in catheter patency
among the groups (p<0.03, long-rank test). In particular,
catheter survival was higher in the catheter group flushing
with heparin than the group flushing with sodium chloride
0.9% (p<0.04, long-rank test). No statistical difference in
catheter patency was found comparing sodium chloride
and vitamin C flushing (p<0.56, long-rank test) (34).
Fuentes i Pumarola et al have structured a blind RCT
in two phases. In the first phase they compared flushing
with sodium heparin 100 IU and sodium heparin 500 IU,
while in the second phase they randomized catheters in
two groups: heparin and saline flushing. They found no
statistically significant differences in catheter patency be-
tween groups. This study was characterized by high attri-
tion rate: in the first phase only 128 of 291 catheters were
analyzed (49 in 500 IU heparin group and 79 in 100 IU
heparin group), while in the second phase only 95 out
of 250 were analyzed (38 heparin flushing and 57 saline
flushing) (28).
Similar results were highlighted in the randomized open
label trial by Schallom et al where they randomized patients,
with multilumen central venous catheters, in heparin flush-
ing versus saline 0.9% sodium chloride group. The occlu-
sion rate was higher in the NaCl group, but this difference
was not statistically significant (6.3 vs. 3.8; risk ratio [RR]
1.66; 95% CI 0.86 to 3.22, p=0.136). Four catheter-related
bloodstream infections developed in the saline group
(3.1 per 1,000 catheter day vs. 0 per 1,000 catheter days,
p=0.125). The authors suggested that the 0.9% sodium chlo-
ride might be used in catheter flushing for short term (17).
Bowers et al structured a nonblinded RCT in which
they randomized 102 patients with peripherally inserted
central catheters (PICCs) in two groups: 0.9% sodium
chloride injections and heparin 100 U/mL lock flush.
Significant differences were present in patient character-
istics between the groups. The no-patency rate was higher
in the saline group (6% vs. 0%), but this difference was
not statistically significant. The average duration of PICC
was 2.1 in the normal saline group and 2.9 in the heparin
group (p=ns) (29).
In a recent noninferiority open trial 802 cancer pa-
tients were randomized to heparin lock or to normal sa-
line lock. The incidence rate of easy injection, impossible
aspiration was 3.70% in the sodium chloride group and
3.92% in heparin group. The relative risk was 0.94% (95%
CI 0.67-1.32%) (30).
Heparin vs. other solutions
In four studies (31-34) included in the review, the
interventions were heparin vs. urokinase or vitamin C or
lepirudin.
246 © 2014 Wichtig Publishing - ISSN 1129-7298
Ray et al designed a prospective, controlled, random-
ized study in which 105 patients with Hickmann catheter
were allocated to two groups: heparin flushing or heparin
flushing and urokinase flushing. The results of their study
indicate that the use of urokinase reduces catheter-relat-
ed complications. In particular, the infections and fibrin
sheath formed was higher in the heparin group than in
the group where catheters were flushed with heparin and
urokinase (31).
Solomon et al also compared heparin flush to a uroki-
nase flush in another RCT open-label study, but they con-
cluded that urokinase was not reducing the frequency of
Hickmann complications. An elevated drop-out rate was
present (32).
In another study (33) 49 adults undergoing bone mar-
row transplantation for hematologic malignancies or met-
astatic solid tumors were randomized to lepirudin flushes
or heparin flushes. The authors concluded that lepirudin
was not more effective than heparin to reduce withdrawal
occlusion (RR 1.6; 95% CI 0.40 to 13.86; p=0.70).
Rabe et al have structured a RCT in which patients
were randomized to three intervention groups and con-
clude that vitamin C solution does not prolong catheter
patency (34).
One study compared different dosages of heparin for
flushing the central venous catheter. Fuentes i Pumarola
et al indicate that the occlusion rate is not different if
flushing is performed with heparin 500 IU/5 mL or with
heparin 100 IU/5 mL (4.9% vs. 4.5%; p=0.937) (28).
Quality assessment of RCT studies
In all trials the focus of the study was clearly defined
and the RCT was appropriately carried out. The methods
of randomization and allocation have not always been
clearly described and one study (Bowers et al) showed
a statistically significant difference (gender) between the
groups. Many studies were conducted in a open-label or
single-blind fashion, thus determining the possibility of
the presence of some bias, while in some other studies
there has been an important dropout of patients (such as
Fuentes i Pumarola et al). In some cases the sample of
study was small. Calculations for sample power calcula-
tions were not always being shown.
DISCUSSION
The central venous catheter is widely used in clinical
practice, but not without complications (6, 35). Nursing is
important in order to reduce complications. Flushing is re-
quired for assuring the function of the catheter and it must
be performed using turbulent flush technique and posi-
tive-pressure locking techniques (9, 36). Heparin flushes
are normally used to prevent thrombus formation and to
Dal Molin et al
reduce occlusion of catheter. However, there is still no
consensus about this practice, and the use of heparin can
be associated with complications such as autoimmune-
mediated HIT, allergic reactions and the potential for
bleeding complications following multiple, unmonitored
heparin flushes (10).
The aim of this systematic review of RCTs was to de-
termine the efficacy of heparin flushing in the central ve-
nous catheter. In our review we did not include studies
conducted in pediatric patients and in patients with he-
modialysis catheters.
Our results, in accordance with other reviews (37, 38),
indicate that there is insufficient evidence to conclude
whether heparin flushing is more effective than NaCl 0.9%
solution.
One retrospective observational cohort study con-
ducted in 610 patients with totally implantable long-term
central vascular access shows no statistically significant
differences for occlusive events between the group where
the catheter was flushed with heparin solution and that of
normal saline (39).
The use of heparin is not risk free. Garajová et al re-
ported one case of heparin-induced delayed hypersen-
sitivity after Port-a-Cath heparinization in a 79-year-old
female patient, for whom heparin flushing (50 IU/5 mL)
was performed every 30-40 days to prevent clotting. This
reaction was developed after 52 months of Port-a-Cath
maintenance (14).
The heparin concentration documented in the trials
was wide. In accordance with the International Infusion
Nursing Society heparin lock solution 10 units/mL is the
preferred lock solution after each intermittent use. In order
to reduce the risk of HIT, all patients must be monitored
and heparin should be discontinued immediately if signs
or symptoms of HIT appear (2).
Another not completely resolved issue is whether the
use of urokinase is effective for patency. One study (31)
suggests that twice-daily heparin flushing with once-week-
ly urokinase instillation is more effective than twice-daily
heparin flushing with heparin. However, another study
REFERENCES
1. Gillanders L, Angstmann K, Ball P, et al; Australasian Society
of Parenteral and Enteral Nutrition. AuSPEN clinical practice
guideline for home parenteral nutrition patients in Australia
and New Zealand. Nutrition. 2008;24(10):998-1012.
2. INS Standards—Intravenous Nurses Society. Infusion nurs-
ing standard of practice. Journal of Intravenous Nursing.
2011;34(1S):S96.
3. Gallieni M, Pittiruti M, Biffi R. Vascular access in oncology
patients. CA Cancer J Clin. 2008;58(6):323-346.
© 2014 Wichtig Publishing - ISSN 1129-7298
(32) in which patients were randomized to twice-weekly
flushes of heparin or to twice-weekly flushes of urokinase
indicates that there is no evidence of a difference in rates
of occlusions, infections and venous thrombosis. These
results suggest the possibility that the catheter complica-
tions may be reduced with the associated use of heparin
and urokinase. However, further randomized controlled
studies should be conducted to confirm this possibility.
Occlusion rate is higher in patients for whom flushing
is performed with vitamin C rather than heparin. No dif-
ferent rate of occlusion was identified between lepirudin
and heparin.
This review has some limitations. We searched only
MEDLINE and CINAHL, without searching for gray litera-
ture. However, those are the major medical/nursing data-
bases and we did not set any language constraints. Thus,
we feel that our search provides an acceptable overview
of the studies which are currently in the public domain.
In conclusion, our data suggest that heparin can be
used in the clinical practice for flushing the catheter when
indicated by the manufacturer. Nevertheless, further stud-
ies may be necessary in this field to clarify whether saline
solution may be a viable and cheaper alternative to hepa-
rin. However, to this day there is not enough evidence
supporting the use of saline solution in catheter flushing.
ACKNOWLEDGMENTS
The authors wish to thank Mauro Pittiruti for his advice in re-
viewing the manuscript.
Financial support: None.
Conflict of interest: None.
Address for correspondence:
Alberto Dal Molin
Corso Pella 10
Biella, Italy
alberto.dalmolin@gmail.com
4. Vescia S, Baumgärtner AK, Jacobs VR, et al. Management
of venous port systems in oncology: a review of current
evidence. Ann Oncol. 2008;19(1):9-15.
5. Kuo YS, Schwartz B, Santiago J, Anderson PS, Fields AL,
Goldberg GL. How often should a port-A-cath be flushed?
Cancer Invest. 2005;23(7):582-585.
6. Dal Molin A, Rasero L, Guerretta L, Perfetti E, Clerico M.
The late complications of totally implantable central venous
access ports: the results from an Italian multicenter pro-
spective observation study. Eur J Oncol Nurs. 2011;15(5):
377-381.
247
Heparin in catheter flushing
7. Kefeli U, Dane F, Yumuk PF, et al. Prolonged interval in
prophylactic heparin flushing for maintenance of subcuta-
neous implanted port care in patients with cancer. Eur J
Cancer Care (Engl). 2009;18(2):191-194.
8. Ignatov A, Ignatov T, Taran A, Smith B, Costa SD, Bischoff J.
Interval between port catheter flushing can be extended to
four months. Gynecol Obstet Invest. 2010;70(2):91-94.
9. RCN Standards—Royal College of Nurses. Standards for
infusion therapy, 2010.
10. Pratt RJ, Pellowe CM, Wilson JA, et al. epic2: national ev-
idence-based guidelines for preventing healthcare-associ-
ated infections in NHS hospitals in England. J Hosp Infect.
2007;65(Suppl 1):S1-S64.
11. Clemence MA, Walker D, Farr BM. Central venous cath-
eter practices: results of a survey. Am J Infect Control.
1995;23(1):5-12.
12. Sona C, Prentice D, Schallom L. National survey of central
venous catheter flushing in the intensive care unit. Crit Care
Nurs. 2012;32(1):e12-e19.
13. Passannante A, Macik BG. The heparin flush syn-
drome: a cause of iatrogenic hemorrhage. Am J Med Sci.
1988;296(1):71-73.
14. Garajová I, Nepoti G, Paragona M, Brandi G, Biasco G.
Port-a-Cath-related complications in 252 patients with sol-
id tissue tumours and the first report of heparin-induced
delayed hypersensitivity after Port-a-Cath heparinisation.
Eur J Cancer Care (Engl). 2013;22(1):125-132.
15. Milani A. Positive pressure and normal saline instead of hep-
arinized solution when washing indwelling ports in patients
with cancer. Presented at the 2005 ECCO Congress, Paris.
16. Da Ros L, Ponzo C, Storto S, Ciuffreda L. Assessment of
the use of heparinated solution for clamping medium/
long term CVC after 8 hours. Ann Oncol. 2008;19(Supp 9):
x112-ix117.
17. Schallom ME, Prentice D, Sona C, Micek ST, Skrupky LP.
Heparin or 0.9% sodium chloride to maintain central ve-
nous catheter patency: a randomized trial. Crit Care Med.
2012;40(6):1820-1826.
18. Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit
of heparin in peripheral venous and arterial catheters: sys-
tematic review and meta-analysis of randomised controlled
trials. BMJ. 1998;28(316):969-975.
19. Goode CJ, Titler M, Rakel B, et al. A meta-analysis of effects
of heparin flush and saline flush: quality and cost implica-
tions. Nurs Res. 1991;40(6):324-330.
20. Peterson FY, Kirchhoff KT. Analysis of the research about
heparinized versus nonheparinized intravascular lines.
Heart Lung. 1991;20(6):631-640.
21. Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The
well-built clinical question: a key to evidence-based deci-
sions. ACP J Club. 1995;123(3):A12-A13.
22. Altman DG. Practical Statistics for Medical Research.
London: Chapman & Hall; 1992.
23. Guyatt GH, Sackett DL, Cook DJ. Users’ guides to the medical
literature. II. How to use an article about therapy or preven-
tion. JAMA. 1993;270:2598-2601 and 1994;271(1):59-63.
24. Chaimani A, Salanti G. Background document. Proceedings
on the “Statistical issues in NMA” CMIMG Meeting. 2013. Avail-
able from: http://cmimg.cochrane.org/sites/cmimg.cochrane.
248 © 2014 Wichtig Publishing - ISSN 1129-7298
org/files/uploads/CMIMG%20Stream%202%20document%
202013%2010%2001.pdf. Accessed 30 January, 2014.
25. Higgins JPT, Jackson D, Barrett JK, Lu G, Ades AE, White
IT. Consistency and inconsistency in network meta-analy-
sis: concepts and models for multi-arm studies. Res Synth
Methods 2012:3(2):98-110.
26. Mills EJ, Thorlund K, Ioannidis JPA. Demystifying trial net-
works and network meta-analysis. BMJ. 2013;346(May14):
f2914.
27. White I. Multivariate random-effects meta-analysis. Stata J.
2009;9:40-56.
28. i Pumarola CF, Mercader RC, Plana MC, et al. Comparative
study of maintenance of patency of triple-lumen central
venous catheter. Enferm Intensiva. 2007;1(18):25-35.
29. Bowers L, Speroni KG, Jones L, Atherton M. Comparison of
occlusion rates by flushing solutions for peripherally insert-
ed central catheters with positive pressure Luer-activated
devices. J Infus Nurs. 2008;31(1):22-27.
30. Goossens GA, Jérôme M, Janssens C, et al. Comparing
normal saline versus diluted heparin to lock non-valved
totally implantable venous access devices in cancer pa-
tients: a randomised, non-inferiority, open trial. Ann Oncol.
2013;24(7):1892-1899.
31. Ray CE Jr, Shenoy SS, McCarthy PL, Broderick KA, Kaufman
JA. Weekly prophylactic urokinase instillation in tun-
neled central venous access devices. J Vasc Interv Radiol.
1999;10(10):1330-1334.
32. Solomon B, Moore J, Arthur C, Prince HM. Lack of efficacy
of twice-weekly urokinase in the prevention of complica-
tions associated with Hickman catheters: a multicentre
randomised comparison of urokinase versus heparin. Eur J
Cancer. 2001;37(18):2379-2384.
33. Horne MK III, McCloskey DJ, Calis K, Wesley R, Childs R,
Kasten-Sportes C. Use of heparin versus lepirudin flushes
to prevent withdrawal occlusion of central venous access
devices. Pharmacotherapy. 2006;26(9):1262-1267.
34. Rabe C, Gramann T, Sons X, et al. Keeping central venous
lines open: a prospective comparison of heparin, vitamin C
and sodium chloride sealing solutions in medical patients.
Intensive Care Med. 2002;28(8):1172-1176.
35. Dal Molin A, Di Massimo DS, Braggion C, et al. Totally im-
plantable central venous access ports in patients with cys-
tic fibrosis: a multicenter prospective cohort study. J Vasc
Access. 2012;13(3):290-295.
36. Registered Nurses Association of Ontario (RNAO). Care
and maintenance to reduce vascular access complication.
Nursing Best Practice Guideline. 2008.
37. Mitchell MD, Anderson BJ, Williams K, Umscheid CA.
Heparin flushing and other interventions to maintain pa-
tency of central venous catheters: a systematic review. J
Adv Nurs. 2009;65(10):2007-2021.
38. López-Briz E, Ruiz-García V. [Effectiveness of heparin
versus NaCl 0.9% in central venous catheter flushing. A
systematic review]. Farm Hosp. 2005;29(4):258-264.
39. Bertoglio S, Solari N, Meszaros P, et al. Efficacy of nor-
mal saline versus heparinized saline solution for locking
catheters of totally implantable long-term central vascu-
lar access devices in adult cancer patients. Cancer Nurs.
2012;35(4):E35-E42.