909024

research-article2020
JVA0010.1177/1129729820909024The Journal of Vascular AccessElli et al.

Original research article

JVA The Journal of
Vascular Access

The Journal of Vascular Access

Changing the syringe pump: A challenging

1­–7
© The Author(s) 2020
Article reuse guidelines:
procedure in critically ill patients sagepub.com/journals-permissions
https://doi.org/10.1177/1129729820909024
DOI: 10.1177/1129729820909024
journals.sagepub.com/home/jva

Stefano Elli1 , Elisa Mattiussi2, Stefano Bambi3 ,

Serena Tupputi1, Salvatore San Fratello4, Angela De Nunzio4,
Salvatore D’Auria5, Roberto Rona1, Roberto Fumagalli6
and Alberto Lucchini1

Abstract
Introduction: In the literature, the change of a syringe pump is described as a dangerous situation, especially in the
case of vasoactive drug administration.
Methods: Different variables have been studied (central venous pressure, pump displacement in relation to the patient
position, utilization of a stopcock, or a neutral displacement needle-free connector between the syringe and the infusion
tubing) to understand their influence on medication administration in terms of backflow or bolus creation when changing
the syringe.
Results: We performed 576 measurements with different combinations. With respect to all the observations, in
comparison with “time zero,” we found the following differences expressed in microliters: 0 (±1) at the plunger opening;
0 (±3) at the syringe extraction from the pump; 0 (±7) at the syringe disconnection from the infusion tubing; 0 (±11)
at the syringe reconnection to the infusion tubing; 1 (±7) at the syringe insertion in the pump; 3 (±23) at the plunger
closing; 8 (±33) at the stabilization at the maneuver end.
Conclusion: The syringe change can be a very critical moment given different influencing variables. Syringe pump
position, displaced higher than the patient level, always generates a medication bolus that is higher at the lowering of
the central venous pressure value. The presence of a neutral displacement needle-free connector reduces the incidence
of boluses. When the pump is placed at the patient level, the presence of neutral displacement needle-free connector
reduces the establishment of boluses, even in a central venous pressure of −5 mmHg simulations.

Keywords
Backflow, bolus, changeover, infusion, inotrope infusion, needle-free connector, syringe pump vasoactive drug
pumping, vasoactive drug administration

Date received: 1 July 2019; accepted: 25 January 2020

Introduction
Background and rationale
Intensive care unit (ICU) patients often require adminis-
tration of intravenous therapies. A concentrated continu-
ous infusion of medications, rather than a diluted
concentration, is frequently used because of fluid restric-
tions in critically ill patients.1 In particular, vasoactive
drugs are the mainstay of hemodynamic management of
critically ill patients.2,3 Medical devices, such as syringe
pumps, are commonly used for the continuous infusion of
highly concentrated drugs. The syringe pumps, thanks to
technological innovation, are able to deliver very precise
drug doses, in the order of 0.1 mL/h. However, the current
1
 eneral Intensive Care Unit, Emergency Department – ASST Monza,
G
San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
2
School of Nursing, Department of Medical and Biological Sciences,
Udine University, Udine, Italy
3
Medical & Surgical Intensive Care Unit, Careggi University Hospital,
Florence, Italy
4
General Intensive Care Unit, Azienda Ospedaliera Universitaria di
Parma, Parma, Italy
5
General Intensive Care Unit, Istituto Auxologico, Milano, Italy
6
Department of Anesthesia and Intensive Care Medicine, Niguarda Ca’
Granda, University Hospital of Milano-Bicocca, Milano, Italy
Corresponding author:
Alberto Lucchini, General Intensive Care Unit, Emergency Department
– ASST Monza, San Gerardo Hospital, University of Milano-Bicocca, Via
Pergolesi 33, 20900 Monza, Italy.
Emails: a.lucchini@asst-monza.it; alberto.lucchini@unimib.it
2 The Journal of Vascular Access 00(0)
Figure 1.  Change of syringe in a patient with continuous norepinephrine infusion.
sAP: systolic arterial blood pressure; mAP: mean arterial blood pressure; dAP: diastolic arterial blood pressure.
literature identifies several factors that can contribute to
reducing the stability of the administration: device’s tech-
nical features, catheter patency, start-up delay, mechani-
cal occlusion of the infusion tubing, siphoning, users’
knowledge, and so on.1 These factors are capable of modi-
fying the stability of the infusion and determining hemo-
dynamic imbalances. Various precautions are suggested to
avoid changes in the current flow during infusion: avoid
vertical displacements of the pump, use of needle-free
connectors (NFC), use of two parallel pumps, and avoid
infusion of different drugs in the same tubing.1,4,5 The
greatest risk of altering the stability of the infusion arises
from the replacement of syringe. In every ICU, syringe
replacement is a common practice performed by many
people. The risk of hemodynamic imbalances or other
problems is always present.6,7 During the change, the con-
tinuity and integrity of infusion tubing and protection
against the interactions between blood pressure and tub-
ing pressure are lost. Figure 1 shows a modification
induced by syringe replacing in a patient with norepineph-
rine infusion. In this case, the infusion of 0.10 µg/kg/min
(infusion rate of 5 mL/h) of norepinephrine required 8 min
to recover the previous arterial pressure values.
We can call “blood pressure” the pressure of the blood-
stream at the tip of the catheter, which causes resistance to
infusion. We can call “tubing pressure” the pressure
induced by the height of the liquid column in the infusion
tubing in relation to the patient. In ICU wards, drugs are
generally administrated via a central venous catheter, so the
“blood pressure” is generally similar to central venous
pressure (CVP). CVP values can vary considerably depend-
ing on the type of ventilation, blood volume, and many
other factors; differences of 10–15 mmHg (15–20 cmH2O)
can be found between a patient in mechanical ventilation
and one in spontaneous breathing with severe respiratory
distress.8,9 If the pressure of the infusion tubing is higher
than the “blood pressure,” the solution in the tubing will be
pushed toward the patient, thus causing a bolus of the medi-
cation with an immediate overdose. If the pressure in the
infusion tubing is lower than the “blood pressure,” blood
will flow back into the infusion tubing, thus stopping the
infusion of the medication and, perhaps, a delay in stabiliz-
ing the infusion. It would be desirable to reduce these risks
with an optimal use of the available technology and the use
of standardized change procedures.
Objective
The purpose of this experimental study is to analyze the
effects of syringe replacement on the continuity of drug
infusion, based on the absence/presence of different
syringe infusion set-ups.
Methods
Study design and setting
We conducted an “in vitro experimental study” during
August/September 2017 in a laboratory of an ICU in a
North Italian University Hospital. We assembled a
Elli et al. 3
Figure 2.  Experimental set-up.
simulation system for measuring fluid displacement into
the infusion tubing during syringe replacement. The simu-
lation system was assembled with the following devices:
two different types of syringe pump (Pilot A2®; Fresenius
Kabi AG, Bad Homburg, Germany; Injectomat Agilia®,
Fresenius Kabi AG), a 50-mL syringe (BD Perfusion 50 mL
Syringe; Becton Dickinson, Franklin Lakes, NJ, USA), a
250-cm-long infusion tubing (ICU Medical, San Clemente,
CA, USA), three-way stopcock (Bicakcilar, Istanbul,
Turkey), hemodynamic pressure transducer (TruWave;
Edwards Lifesciences, Irvine CA, USA), multiparametric
monitor (Draeger SC 9000; Draeger Medical, Telford,
Pennsylvania USA), two different types of neutral dis-
placement NFC (Neutraclear®; Becton Dickinson,
Bionecteur®; Vygon, Ecouen, France) with different perfor-
mances,10,11 and 500 mL of colored normal saline connected
to an Infusion Set (Rays SpA, Osimo, Italy). Variables stud-
ied were the following: type of pump used, pump highness
in relation to the simulated patient,12,13 three different CVP
simulated values,8,9 connection between the syringe and
the infusion tubing, and operator. The pump positions
considered in relation to the patient were 50 cm above the
position of the heart, patient in supine position (heart level)
and 32 cm below the patient, with respect to heart level.
Simulated CVP values analyzed were +15, 0, and
−5 mmHg. How the simulation system was assembled and
the variables studied are explained in Figure 2. An air bub-
ble was inserted in the tubing at the “displacement measur-
ing area” and used as reference for measurements10. The
displacement of the air bubble was measured during each
of the six steps of the syringe change after stopping of infu-
sion: plunger opening (S0), syringe extraction from the
pump (S1), disconnection from infusion tubing (S2), recon-
nection to the infusion tubing (S3), syringe insertion in the
pump (S4), plunger closing (S5), and stabilization at the
end of maneuver (S6). Four different operators (nurses with
up to 5 years of experience in ICU) carried out the “six
steps” of standardized change procedure in all possible
combinations of the studied variables. During each step, the
movements of the air bubble in the “displacement measur-
ing area” were manually noted, as reported in Figure 3. The
measures, expressed in centimeters, were then converted
into milliliter of fluid displacement in the infusion tubing.
A positive displacement was identified as “bolus” and a
negative displacement was identified as “backflow” (reflux
of blood into the catheter).
Statistical analysis
Statistical analysis was performed using Statistical
Package for the Social Sciences, version 22.0, (SPSS Inc.,
Chicago, IL, USA). Continuous variables were expressed
4 The Journal of Vascular Access 00(0)
Figure 3.  Displacement measuring area.
as mean ± SD or median (interquartile range). One-way
repeated-measures analysis of variance (rmANOVA) was
used to evaluate the differences at the six steps of the
syringe change (plunger opening, syringe extraction from
the pump, disconnection from infusion tubing, reconnec-
tion to the infusion tubing, syringe insertion in the pump,
plunger closing, and stabilization at the end of maneuver),
with only possible combinations of the six variables inves-
tigated (NFC, CVP values, syringe pump position, opera-
tor, type of syringe pump). A value of p < 0.05 was
considered statistically significant.
Results
We performed 576 measurements with different combina-
tions of the investigated variables. With respect to all the
observations, in comparison with “time zero,” we found
the following differences expressed in microliters: 0 (±1)
at the plunger opening; 0 (±3) at the syringe extraction
from the pump; 0 (±7) at the syringe disconnection from
the infusion tubing; 0 (±11) at the syringe reconnection to
the infusion tubing; 1 (±7) at the syringe insertion in the
pump; 3 (±23) at the plunger closing; 8 (±33) at the stabi-
lization at the maneuver end. All these maneuvers sum-
marize all the modifications given by the 576 analyzed
variables. If data are analyzed considering the simulated
values of CVP, the absence/presence of a stopcock between
the syringe and the infusion tubing, and the vertical posi-
tion of the pump, they can demonstrate the influence of
each single variable in determining boluses or backflow. In
Table 1, data are represented in relation to the seven inves-
tigated phases combined with the previous considered
variables. In Figure 4, the average value at the end of
maneuver is graphically represented, in relation to the dif-
ferent devices and the different experimental set-ups. It is
appreciable how a position of the pump, displaced higher
than the patient level, always generates a medication bolus
that is higher at the lowering of the CVP value. In this
situation, the presence of a neutral connector (Bionecteur)
reduces the incidence of boluses. When the pump is dis-
placed at the patient level, the presence of neutral displace-
ment NFC reduces the establishment of boluses, even in
simulations considering a CVP of −5 mmHg. Finally, if the
pump is displaced lower than the patient level, a backflow
is established, within average volumes of 50 µL in the
absence of a stopcock or a neutral displacement NFC and
with a CVP value of 10 mmHg. In this case, the device
that mainly reduces the occurrence of backflow is the
stopcock. The influence given by the variable “operator”
results in statistical significance only at the reconnection to
the infusion tubing (p = 0.044) and at the plunger closing
(p = 0.034). In Figure 5, it is possible to appreciate that the
average backflow never results in statistical significance in
relation to the pump used, even if there are different values
for each step.
Discussion
In the past research, intravascular drug administration
focused mainly on medication concentration and methods
of administration. In the literature, the major data concern
the administration of vasoactive drugs.3,4 However, there is
a scarce discussion about syringe exchange events and the
subsequent effects on patient’s vital signs. In effect, many
intensive care practitioners have experienced the storm that
can develop following the procedure.14,15 The main results
of our study emphasize that exchange of the syringe in the
pump, especially during vasoactive drug handling, can be
dangerous for the stability of patients’ vital signs. Nurses
should always consider the existing correlation between the
patient’s CVP and the vertical displacement of the pump to
choose the better pump position, when deciding definite
pump displacement. The side effects due to the association
of the two considered variables are maximized when any
dispositive is placed between the infusive pump and the
infusion tubing. Our data suggest that, without a disposi-
tive, a maximal backflow can occur in the intraluminal
catheter tract (thus not visible for the operator) when we
consider a high CVP, and the pump is lower than the patient
position. The registered backflow can vary between
−54 ± 82 µL. This situation can be represented by the fol-
lowing clinical scenario: an ambulance transfer of an 80-kg
patient, the trunk of whom is mobilized at 30° with the
syringe pumps displaced at the leg level; continuous nor-
epinephrine infusion within a dilution of 4 mg in 50 mL for
a 4 mL/h speed (0.004 µg/kg/min). In the case of a −54 µL
backflow, a 7-min time is necessary for the infusion to
“wash” the backflow until the medication administration is
restored. Alternatively, a manual bolus equal to 0.028 µg
(0.004 µg/kg/min × 7 min) is necessary to restore the medi-
cation administration. If we still consider any dispositive
between the syringe and the infusion tubing, an opposite
situation can happen in the considered patient with a low
Elli et al. 5

Table 1.  Fluid displacement with different devices and set-up combinations.

Syringe pump Simulated Connector/ S0 S1 S2 S3 S4 S5 S6

position CVP, mmHg stopcock
High (+50 cm 10 No 0 ± 1 1 ± 2 1 ± 2 3 ± 4 14 ± 10 20 ± 15 26 ± 20
up to Neutraclear 0 ± 0 0 ± 2 0 ± 2 3 ± 3 8 ± 4 14 ± 9 21 ± 17
simulated Bionecteur 0 ± 0 0 ± 1 0 ± 1 0 ± 1 0 ± 1 1 ± 2 2 ± 4
patient) Stopcock 0 ± 0 1 ± 2 1 ± 2 1 ± 2 1 ± 2 4 ± 8 33 ± 24
0 No 0 ± 0 1 ± 1 1 ± 2 2 ± 4 14 ± 14 27 ± 31 33 ± 34
Neutraclear 0 ± 1 1 ± 2 0 ± 3 7 ± 4 17 ± 8 28 ± 13 42 ± 28
Bionecteur 0 ± 1 1 ± 1 1 ± 2 3 ± 4 6 ± 7 11 ± 15 16 ± 27
Stopcock 0 ± 2 2 ± 3 2 ± 3 2 ± 3 2 ± 3 4 ± 7 28 ± 22
–5 No 0 ± 1 3 ± 5 4 ± 7 7 ± 10 19 ± 14 32 ± 22 56 ± 37
Neutraclear 0 ± 0 1 ± 1 1 ± 2 6 ± 10 14 ± 17 22 ± 22 29 ± 24
Bionecteur 0 ± 0 2 ± 2 2 ± 3 5 ± 4 10 ± 8 17 ± 14 23 ± 18
Stopcock 1 ± 1 1 ± 1 1 ± 2 1 ± 2 2 ± 2 4 ± 6 31 ± 22
Equal (some 10 No 0 ± 0 0 ± 0 0 ± 1 1 ± 2 2 ± 3 6 ± 6 9 ± 10
level to Neutraclear 0 ± 1 –1 ± 1 –1 ± 2 –1 ± 1 –1 ± 3 0 ± 4 2 ± 7
simulated Bionecteur 0 ± 0 0 ± 0 0 ± 1 0 ± 0 0 ± 1 0 ± 1 1 ± 3
patient) Stopcock 0 ± 0 0 ± 1 1 ± 1 1 ± 1 1 ± 1 1 ± 1 3 ± 7
0 No 0 ± 0 0 ± 1 0 ± 1 1 ± 3 5 ± 6 10 ± 18 13 ± 21
Neutraclear 0 ± 0 1 ± 1 0 ± 1 1 ± 4 1 ± 4 3 ± 9 9 ± 19
Bionecteur 0 ± 0 0 ± 0 1 ± 2 2 ± 3 2 ± 2 3 ± 4 9 ± 23
Stopcock 0 ± 0 0 ± 1 1 ± 2 1 ± 2 1 ± 2 2 ± 2 6 ± 9
–5 No 0 ± 0 0 ± 1 1 ± 2 3 ± 4 6 ± 5 9 ± 9 13 ± 12
Neutraclear 0 ± 0 0 ± 3 0 ± 5 10 ± 10 13 ± 9 21 ± 11 34 ± 16
Bionecteur 0 ± 0 1 ± 3 2 ± 2 5 ± 6 6 ± 6 9 ± 10 21 ± 21
Stopcock 0 ± 0 1 ± 1 1 ± 2 1 ± 2 1 ± 2 3 ± 6 17 ± 19
Lower 10 No 0 ± 0 –4 ± –4 –12 ± 22 –27 ± 50 –40 ± 65 –46 ± 72 –54 ± 82
(−32 cm down Neutraclear 0 ± 0 –4 ± 7 –7 ± 9 –10 ± 9 –19 ± 20 –23 ± 25 –31 ± 38
to simulated Bionecteur 0 ± 0 –3 ± 3 –4 ± 5 –6 ± 6 –16 ± 17 –21 ± 20 –22 ± 20
patient) Stopcock 0 ± 0 0 ± 1 1 ± 1 1 ± 2 1 ± 2 1 ± 2 –2 ± 7
0 No 0 ± 0 –1 ± 3 –2 ± 4 –3 ± 6 –5 ± 8 –6 ± 9 –10 ± 15
Neutraclear 0 ± 0 –1 ± 2 –2 ± 4 –1 ± 4 –3 ± 4 –4 ± 5 –8 ± 13
Bionecteur 0 ± 0 –2 ± 3 –3 ± 4 –5 ± 7 –13 ± 15 –14 ± 17 –20 ± 32
Stopcock 0 ± 0 1 ± 2 1 ± 2 1 ± 2 1 ± 2 1 ± 2 –1 ± 14
–5 No 0 ± 0 0 ± 1 –1 ± 2 –1 ± 2 –1 ± 3 –1 ± 4 0 ± 7
Neutraclear 0 ± 0 0 ± 1 –1 ± 1 –1 ± 1 –1 ± 2 –2 ± 4 –3 ± 8
Bionecteur 0 ± 0 –4 ± 9 –5 ± 11 –8 ± 14 –15 ± 20 –17 ± 25 –28 ± 47
Stopcock 0 ± 1 1 ± 1 1 ± 1 1 ± 2 1 ± 2 1 ± 2 4 ± 11

CVP: central venous pressure; S0: plunger opening; S1: syringe extraction from the pump; S2: disconnection from infusion line; S3: reconnection to
the infusion line; S4: syringe insertion in the pump; S5: plunger closing; S6: stabilization at the end of maneuver.
All results are expressed in microliters.

CVP (–5 mmHg—example: a patient with adult respiratory
distress syndrome undergoing non-invasive ventilation)16
and a displacement of the pump higher than the patient
level. In this case, there will be a bolus of the medication
equal to 56 ± 37 µL corresponding to a 0.028-µg infusion.
The air enters into the administration set when in the dis-
connection no occlusive system is applied, excluding the
manual procedure done by the operator. Air entrance will
further determine a stop in the medication infusion when
the air will reach the catheter tip. All of these varying situ-
ations can be limited, as observed in our study, when a
device such as a stopcock or a neutral displacement NFC is
placed between the syringe and the administration set. In
our study, we tested two different devices of neutral pres-
sure with different performances. In two recent reports,10,11
the Bionecteur demonstrated high performances in main-
taining a neutral pressure in the intravascular tubing,
achieving similar performances to those created for periph-
erally inserted central venous catheters (PICC). The appli-
cation of the device reduces in an important way all the
situations of bolus or backflow in all the different situations
tested. The other tested device, the Neutraclear, given the
lower performances compared to the Bionecteur, reduces
the complications in a limited way. The use of neutral dis-
placement NFC reduces the backflow or the bolus compli-
cations especially when the CVP is higher than 0 mmHg
6 The Journal of Vascular Access 00(0)
Figure 4.  Mean value of bolus/backflow, step: stabilization at the end of maneuver.
Figure 5.  Difference in the six investigated steps between
two different syringe pumps investigated.
and when the syringe pumps are displaced matching to the
patient level or higher. When the syringe pumps are dis-
placed lower than the patient level, the use of a stopcock
between the syringe and the administration set seems to
represent the preferable solution to reduce the backflow
events. The application of a stopcock is simple, but can
generate a stop of the medication’s administration if inac-
curately left closed until the pressure alarm of the pump
rings.17 Applying a neutral displacement NFC with high
performances represents the easiest and safer implementing
solution.10,11 From the results of our study, we can limit all
the possible complications given by the change of syringe
pumps with the application of simple nursing interventions
as the following:
Utilization of neutral displacement NFC to limit bolus
and backflow events;
Displacement of the pumps infusing vasoactive drugs
higher than the patient level (always considering the
entry point of the catheter if the patient is not in supine
position);
Reduce the medication concentration to diminish the
total amount of medication eventually contained in the
bolus or in the backflow.
Study limitations
This is a single-center study. The results are achieved by
the utilization of only two NFC whose performances can
differ from other available devices. The two NFC used
were purchased by our hospital at the time of the study.
Furthermore, we did not experiment the use of the new-
generation NFC designed for PICC,10,11 given their high
cost and the presence of a double valve system. When con-
sidering the CVP system, it was unable to reproduce dif-
ferent CVP values or physiological fluctuation produced
Elli et al. 7
in humans by heart and lung interactions. This CVP fluc-
tuation could be very pronounced, especially when consid-
ering a patient with spontaneous breathing due to acute or
chronic respiratory insufficiency, thus influencing the
achieved results, and all data were simulated considering a
patient in supine position.
Finally, we did not address the problem related to sur-
face disinfection of the NFC. In clinical practice, the disin-
fection of NFC could increase the problems related to the
interruption of the infusion, amplifying the results high-
lighted in our study. Moreover, in our study, when discon-
nected, the NFC would remain exposed to air for a few
seconds, reducing the need for disinfection. The manufac-
turers recommend the devices to be replaced after about
350 connections and/or 7 days of use. This would mean a
daily average of connections equal to 50. When syringe
changes become frequent, nurses usually increase the drug
concentration. It is unlikely that NFC, used on pump
syringes, will reach 50 connections/day.
Conclusion
The syringe change can be a very critical moment given
different influencing variables. Syringe pump position,
displaced higher than the patient level, always generates a
medication bolus that is higher at the lowering of the CVP
value. In this situation, the presence of a neutral displace-
ment NFC reduces the incidence of boluses. When the
pump is displaced at the patient level, the presence of a
neutral displacement NFC reduces the establishment of
boluses, even in simulations considering a CVP of
−5 mmHg. A low CVP, or a negative one, can increase the
risks. Bolus or backflow is not completely preventable but
can be limited and controlled. More studies are awaited to
investigate the problem.
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.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iDs
Stefano Elli https://orcid.org/0000-0002-8785-824X
Stefano Bambi https://orcid.org/0000-0002-0360-4470
Alberto Lucchini https://orcid.org/0000-0002-7475-277X
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