Ultrasound Imaging Reduces Failure
Rates of Percutaneous Central Venous
Catheterization in Children
Nobuaki Shime, MD, PhD1; Koji Hosokawa, MD, PhD2; Graeme MacLaren, MBBS, FCCM3,4
Objective: Ultrasound imaging has been shown to be beneficial for
percutaneous central venous cannulation in systematic reviews of
randomized controlled trials in adult patients, but not in pediatrics.
The aim of this updated review was to determine whether percu-
taneous central venous catheterization with the aid of ultrasound
reduces cannulation failure in children.
Data Sources: PubMed was searched using the terms: ultrasound,
catheterization, central vein (including internal jugular and femoral
veins), and pediatrics.
Study Selection: Both nonrandomized comparative studies and
randomized controlled trials were eligible for inclusion if they
assessed the rate of cannulation failure using real-time, dynamic
ultrasound guidance, ultrasound-assisted vein prelocation, and/or
anatomic landmark technique.
Data Extraction: Five nonrandomized studies and nine random-
ized controlled trials were included. The rates of cannulation fail-
ure and arterial puncture were retrieved.
Data Synthesis: Random-effects meta-analysis was applied.
Conclusions: The meta-analysis of five nonrandomized stud-
ies showed that the rate of cannulation failure was signifi-
cantly lower with real-time ultrasound guidance than anatomic
landmark technique (odds ratio, 0.44 [95% CI, 0.27–0.72];
1
Emergency and Critical Care Medicine, National Hospital Organization
Kyoto Medical Center, Kyoto, Japan.
2
Department of Intensive Care, Erasme University Hospital, Université
Libre de Bruxelles, Brussels, Belgium.
3
Cardiothoracic ICU, National University Health System, Singapore.
4
Paediatric ICU, Department of Paediatrics, The Royal Children’s Hospital,
University of Melbourne, Melbourne, VIC, Australia.
Drs. Shime and Hosokawa contributed equally to this work.
Supplemental digital content is available for this article. Direct URL cita-
tions appear in the printed text and are provided in the HTML and PDF
versions of this article on the journal’s website (http://journals.lww.com/
pccmjournal).
The authors have disclosed that they do not have any potential conflicts
of interest.
For information regarding this article, E-mail: shime@koto.kpu-m.ac.jp
Copyright © 2015 by the Society of Critical Care Medicine and the World
Federation of Pediatric Intensive and Critical Care Societies
DOI: 10.1097/PCC.0000000000000470
Pediatric Critical Care Medicine
Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
p = 0.001). The combination of nine randomized controlled tri-
als also showed lower failure rates with either the real-time ultra-
sound guidance or the prelocation technique over the landmark
technique (odds ratio, 0.22 [95% CI, 0.07–0.69]; p = 0.0003)
and fewer arterial punctures in the ultrasound group (odds ratio,
0.31 [95% CI, 0.09–1.08]; p = 0.07). However, seven out of
nine studies were assessed as having high risk of bias. Since
the lower cannulation failure and less frequent chance of arterial
puncture with ultrasound were predominantly shown in studies
at high risk of bias, further definitive and adequately powered
studies with clear outcomes are needed. (Pediatr Crit Care
Med 2015; XX:00–00)
Key Words: anatomic landmark; central venous catheterization;
pediatrics; real time; systematic review; ultrasound
U
ltrasound imaging has been recommended in practice
guidelines and evidence-based consensus statements
to assist percutaneous central venous (CV) cannula-
tion in both adults and children (1–4). Although this technol-
ogy can be used in infants and children (5, 6), two systematic
reviews of randomized controlled trials (RCTs) did not show
significantly more successful cannulation using real-time
ultrasound compared with the anatomic landmark technique
(7, 8). The quality of these analyses, however, was limited by
the small number of studies included in them.
In an effort to reexamine this issue, we conducted an
updated meta-analysis including studies published since the
last systematic review (7) as well as incorporating nonran-
domized studies. Although the latter increases bias, it may
also partially compensate for the paucity of RCTs and still
provide useful data.
The aim of this study was to systematically review nonran-
domized studies and RCTs to determine whether real-time
ultrasound guidance or ultrasound-assisted vein preloca-
tion might reduce the occurrence rate of cannulation failure
in pediatric percutaneous CV catheterization compared with
anatomic landmark techniques. Additionally, the time to suc-
cessful venipuncture, the number of puncture attempts, and
the rates of arterial puncture were assessed.
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 Shime et al
METHODS
The authors of this review were guided by the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) Statement (9, 10) and Cochrane Handbook (11).
PubMed was searched using the technical terms: ultrasound,
central vein, and pediatrics on June 15, 2014 (Appendix 1). In
the citation database, the authors included both nonrandom-
ized comparative studies and RCTs that assessed the rate of CV
(internal jugular vein [IJV] and femoral vein) cannulation fail-
ure between the various cannulation techniques, specifically
real-time ultrasound guidance, ultrasound-assisted vein pre-
location, and the anatomic landmark technique. References on
related scientific literature were also reviewed. Noncomparative
studies, articles evaluating Doppler guidance technique, and
investigations for open cut-down technique were excluded.
The selection process was displayed using a PRISMA flowchart
(9, 10) (Fig. 1).
The included studies were used to extract the methodology,
number of participants, comparison of technique, description
of ultrasound technique, position of patients, operators’ pro-
files, mean or median body weight, place of practice, the site of
CV access, and the rate of failure of CV cannulation, time to
success, success rate within first to third attempts, and the rates
of arterial puncture. They were also reviewed to assess their
risks of bias.
The risks of bias in the included studies were assessed by
answering six different items with three scores (low, unclear,
and high) by two authors (N.S., K.H.) according to the
Cochrane Handbook (11) and plotting the evaluation on
Review Manager (Version 5.3., 2014, The Nordic Cochrane
Centre, The Cochrane Collaboration, Copenhagen) (Fig. 2).
Figure 1. Preferred Reporting Items for Systematic Reviews and
­Meta-Analyses flow diagram of selection process. *One randomized
controlled trial (21) assessing real-time ultrasound (US) guidance v­ ersus
­US-assisted vein prelocation was excluded from the meta-analysis.
LM = anatomical landmark technique.
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Meta-analysis was undertaken on the group of nonrandomized
studies and RCTs separately. Random-effects meta-analysis,
using the inverse variance method, was conducted on the same
software to estimate odds ratio (OR), 95% CI, and p value and
calculate Tau2 and I2 for assessment of heterogeneity. Funnel
plots were also examined to select studies that potentially cause
high heterogeneity. A p value of less than 0.05 was considered
as a significant difference between groups.
Secondary analysis was undertaken on 1) a subgroup of dif-
ferent venous sites (IJV and femoral vein) and 2) a subgroup of
real-time ultrasound versus landmark and prelocation versus
landmark studies.
RESULTS
In the citation database (1,059 from PubMed; two additional
citation from references), 15 articles including 1,543 patients
met the criteria (Fig. 1 and Table 1). We finally included five
nonrandomized studies (two prospective studies [12, 13],
three retrospective observational studies [14–16]) and nine
RCTs (17–20, 22–26) consisting of 1,503 pediatric patients
for the meta-analysis, after excluding one RCT perform-
ing a comparison among the ultrasound techniques (21).
The mean body weight of participants ranged from 3.1 to
32.0 kg. In the nine RCTs, real-time ultrasound guidance over
the landmark technique was evaluated in six RCTs and prelo-
cation over landmark in three RCTs (Table 1). Vascular access
was achieved by cannulating the IJV in nine studies, femoral
vein in three studies, IJV and subclavian vein in one study,
and not assigned in one study.
Most studies did not describe the technique or patient posi-
tion sufficiently to evaluate the impact of those interventions
on the risk of failure (Table 1). The majority of operators of
CV cannulation were fellows in four RCTs (17–19, 21) and
attending physicians in two studies (16, 25). The failure rate in
landmark methods varied among reports (4–38%). One obser-
vational study reported similarly low failure rates with real-
time ultrasound guidance among the four different levels of
trainees but observed longer times to successful CV cannula-
tion and a greater number of attempts with landmark methods
in the resident group and more inadvertent artery punctures in
the fellow group (13).
Cannulation Failure
Data from five nonrandomized studies (12–16) were com-
bined using random-effects meta-analysis and showed a signif-
icant reduction of the risk of cannulation failure in ultrasound
assistance compared with the landmark technique (11% vs
23%; OR, 0.44 [95% CI, 0.27–0.72]; p = 0.001; heterogeneity:
Tau2 = 0.06; p = 0.29) (Fig. 2). These studies were conducted
in different situations. Of note, Alten et al (16) reported a high
success rate with real-time ultrasound (95% vs 80%; p = 0.02),
where procedures in 150 neonates in the PICU and the opera-
tion theater were assessed by a third-party team.
Nine RCTs had wide variability in their study settings
(Table 1). Meta-analysis of RCTs (n = 9) (17–20, 22–26),
however, showed a significant reduction of failure by using
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 Feature Review Article

Figure 2. Meta-analysis of the risk of cannulation failure between ultrasound (US) assistance versus anatomic landmark techniques. Separately
conducted random-effects meta-analysis on five nonrandomized studies and nine randomized controlled trials (RCTs) showed a significant reduction of
failure of cannulation in the US assistance compared with the anatomic landmark technique. The two studies assessed as having low risk of bias (Bruzoni
et al [24] and Aouad et al [25]) were not combined in the subtotal but included in the meta-analysis. Each study was cited by the name of first author
and published year. Risk of bias: A, Random sequence generation (selection bias); B, Allocation concealment (selection bias); C, Blinding of participants
and personnel (performance bias); D, Blinding of outcome assessment (detection bias); E, Incomplete outcome data (attrition bias); F, Selective reporting
(reporting bias); G, Other bias. The risks in each question are represented as low (+), unclear (?), and high (−). IV = inverse variance.

ultrasound (7% vs 24%; OR, 0.20 [0.07–0.60]; p = 0.004; het-
erogeneity: Tau2 = 0.77; p = 0.0005) (Fig. 2). Only two RCTs
(24, 25) were evaluated as being at low risk of bias (Fig. 2). The
combined data from these two RCTs weighed up to 25% in
the meta-analysis. From asymmetry of a funnel plot (data not
shown), high heterogeneity among nine RCTs was caused by
the study by Grebenik et al (22), which showed higher failure
rate in real-time ultrasound guidance than anatomic landmark
technique.
A subgroup analysis of the seven RCTs limited to IJV can-
nulation (17–20, 22, 23, 26) showed a significant reduction
of failure (OR, 0.18 [0.04–0.70]; p = 0.01; Supplemental
Fig. 1, Supplemental Digital Content 1, http://links.lww.com/
PCC/A173). Meta-analysis on data from femoral vein inser-
tion was not conducted due to small numbers of studies. In
another subgroup of real-time ultrasound versus landmark
RCTs (n = 6) (17, 18, 20, 22, 24, 25), the failure rate tended
to be lower with real-time ultrasound guidance than the ana-
tomic landmark technique (8% vs 24%; OR, 0.31 [0.08–1.15];
p = 0.08). A comparison of prelocation and anatomic land-
mark techniques, reported in three RCTs (19, 23, 26), showed
significantly lower rates of cannulation failure with preloca-
tion (1% vs 27%; OR, 0.06 [0.01–0.28]; p = 0.0003). Finally,
one RCT showed a significant reduction of cannulation failure
in real-time ultrasound guidance over prelocation (21).
Other Outcomes
The time to success was reported in nine studies (13, 14, 17,
18, 20, 22, 24–26) (Supplemental Table 1, Supplemental Digi-
tal Content 2, http://links.lww.com/PCC/A174). Although the
definition differed between studies, the reduction in time to
success was generally seen in the ultrasound groups: time to
blood flashback (0.4–0.6 vs 0.7–0.9 min), time to guidewire
insertion (0.8–1.9 vs 1–6.8 min), or time to successful cannula-
tion (4.2–4.5 vs 6.6–14 min). The rate of successful puncture
at first attempt increased in the ultrasound group over the
landmark group (65–82% vs 31–45%). Finally, arterial punc-
ture tended to occur less frequently in the ultrasound group yr

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 Shime et al

Table 1. Summary of Included Studies

Reference Study na Comparisona Description of Position of Patients and Ultrasound-Guided Approaches

Nonrandomized studies, all of them as real-time ultrasound guidance vs anatomic landmark

 Alten et al Ret 76 vs 39 RT vs LM Patients are flat and supine with leg abduction at ~60°; a small (2.3 cm)
(16) roll placed under lumbosacrum region to extend hips; after the vessels
are identified, probe is moved to obtain long-axis view of FV; once
needle and vein are in view, needle is advanced “in-plane” until tip first
indents and then punctures through anterior wall of vein

 Yoshida et al Ret 101 vs 55 RT vs LM Skin surface marking of IJV under ultrasound image; cannulation guided
(14) using real-time ultrasound image on the marking
 Froehlich Pro 119 vs 93 RT vs LM One-person technique (one hand to hold ultrasound probe, the other to
et al (13) place catheter) or a two-person technique (one operator to hold the
ultrasound probe and one operator to place the catheter); vessels
located in transverse plane with probe perpendicular to skin

 Iwashima Pro 43 vs 44 RT vs LM Two operators (assistant maintained the transducer)

et al (12)
 Leyvi et al Ret 47 vs 102 RT vs LM Spot where artery and vein maximally separated, or where vein had the
(15) largest size, was located
RCTs
 Real-time ultrasound guidance vs anatomic landmark
  Bruzoni RCT 66 vs 84 RT vs LM Trendelenburg position; head positioned away from insertion side;
et al (24) ultrasound probe placed at apex of triangle formed between two heads
of sternocleidomastoid muscle and clavicle; IJV and common carotid
artery were visualized, with vein identified by its larger size, relative
anatomic position, and compressibility
  Aouad RCT 24 vs 24 RT vs LM Legs were revolved externally and bent at the knees (frog position); out-
et al (25) of-plane technique; probe was held in left hand and cannulation was
done by right hand

  Ovezov RCT 107 vs 102 RT vs LM Cross-scanning

et al (20)
  Grebenik RCT 59 vs 65 RT vs LM Head-down position and hepatic compression; ultrasound probe with
et al (22) attached needle guide

  Verghese RCT 16 vs 16 RT vs LM Trendelenburg (10° ± 15°) with towels placed under shoulder; head
et al (17) placed in midline position; probe placed perpendicular to the vessels;
needle aligned with center of transducer or passed through a needle
guide and advanced into vein directed by ultrasound visualization
  Verghese RCT 43 vs 52 RT vs LM Trendelenburg position (15°) with the head in the midline; probe placed
et al (18) perpendicular to vessels by operator’s left hand; needle could be seen
to dimple the vein and indent the overlying skin when needle point
positioned correctly
(Continued)

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 Feature Review Article

Body Vascular Failure

Description of Operators Weight (kg)b Place Access Ratea

Ultrasound-guided CVC cannulation, in both cardiac ICU and OR, was 3.1 OR, PICU FV 5% vs 21%
performed by two PICU physicians, having 4–6 yr of ultrasound-
guided venous access experience, or by fellowship trainees under
direct supervision (n = 9); LM technique CVC insertion was performed
in the OR by four senior pediatric cardiac anesthesiologists or one
senior surgical assistant, each with at least 10 yr of CVC experience
NM 9.3 OR IJV 10% vs 24%

Resident (n = 35), fellow (n = 147), attending (n = 14), pediatric 16.1 PICU NM 9% vs 12%
nurse practitioner (n = 16); neither the time nor the attempts
were different in CVCs placed by attendings or nurse practitioners
between RT vs LM; shorter time of successful CVC, smaller number
of attempts in RT with resident group; less inadvertent artery
punctures occurred with fellow group
NM 10 OR FV 33% vs 41%

NM 17.6 OR IJV 9% vs 27%

Attending pediatric surgeons or pediatric surgery fellows; all surgeons 32.0 OR IJV (for RT 5% vs 26%c
completed the American College of Surgeons online course on and LM),
surgical ultrasound and were proctored for at least 20 procedures subclavian
with the ultrasound-guided technique vein (for LM)

Attending cardiac anesthesiologist localized and marked the femoral 12.7 OR FV 4% vs 4%

artery in the LM group and scanned the inguinal area in the ultrasound
group; a CA-3–level anesthesia resident with no experience in
ultrasound guidance and minimal experience with CVC using the LM
under the supervision of a cardiac anesthesiologist; residents were
instructed about the use of ultrasound guidance for femoral catheter
insertion by watching three cases before the beginning of the study
NM 15.7 NM IJV 7% vs 35%

One of three consultant pediatric cardiac anesthesiologists, whom 8.7 OR IJV 22% vs 11%
had some experience of using the ultrasound probe. The amount of
previous experience varied, but the least experienced operator had
performed five CVCs with ultrasound before the start of the study
Pediatric anesthesia fellows under the supervision of a pediatric cardiac 6.2 OR IJV 6% vs 19%
anesthesiologist. Their general experience with CVC in older children
by using the LM technique was similar. All were trained in the use of
LM as well as ultrasound techniques in five nonstudy cases
Fellows who were trained in LM and ultrasound techniques using five 5.9 OR IJV 0% vs 23%
patients not included in the protocol

(Continued)

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 Shime et al

Table 1. (Continued). Summary of Included Studies

Reference Study na Comparisona Description of Position of Patients and Ultrasound-Guided Approaches

 Real-time ultrasound guidance vs ultrasound-assisted vein prelocation

  Hosokawa RCT 33 vs 27 RT vs PL Application of 5 cm H2O positive end-expiratory pressure; in 30°
et al (21) Trendelenburg position, a shoulder roll was placed to extend the
neck; bed also rotated to allow horizontal access to IJV; for RT, CVC
assisted by 2D ultrasound imaging and probe handled by assistant;
for PL, location of IJV was marked as line on skin with assistance of
ultrasound; operator performed CVC along the marking
 Ultrasound-assisted vein prelocation vs anatomic landmark
  Chuan RCT 32 vs 30 PL vs LM A shallow pillow under the shoulders, head was lowered by 15° and
et al (23) turned to left by 45°; transesophageal echography intraoperative
probe; several lines drawn on skin by ultrasound; midaxis of probe
placed longitudinal to IJV; needle was advanced along the skin
marking
  Shime RCT 30 vs 34 PL vs LM Head slightly turned to opposite side; a mark made along IJV; operator
et al (19) made punctures using the lined
  Alderson RCT 20 vs 20 PL vs LM Rolled towel was placed under shoulders, head turned to the opposite
et al (26) side and table tilted head-down by 15°; using ultrasound, projection
of IJV was marked on overlying skin; line then served as a guide for
cannulation
Ret = retrospective observational study, RT = real-time ultrasound guidance, LM = anatomical landmark technique, FV = femoral vein,
CVC = central venous catheterization, OR = operating room, IJV = internal jugular vein, Pro = prospective observational study,
CA = clinical anesthesia training, NM = not mentioned, RCT = randomized controlled trial, PL = ultrasound-assisted vein prelocation.
Presented as intervention (RT or PL) versus control (PL or LM).
a

b
Values are shown in mean, except those of Ovezov et al (20), Froehlich et al (13), and Iwashima et al (12) in median.
c
More than four attempts of puncture trial.
d
Translated from the original article in Japanese.

than the anatomic landmark group, as shown by the combi-
nation of four nonrandomized studies (7% vs 16%; OR, 0.32
[0.15–0.68]; p = 0.003) and nine RCTs (4% vs 15%; OR, 0.31
[0.09–1.08]; p = 0.07) (Supplemental Fig. 2, Supplemental
Digital Content 3, http://links.lww.com/PCC/A175).
DISCUSSION
This meta-analysis showed that the use of ultrasound-guided
techniques, whether real-time ultrasound guidance or ultra-
sound-assisted prelocation, significantly reduced the failure
rate of percutaneous CV cannulation in the pediatric popu-
lation. Discrepancy between our results and previous reviews
was mainly due to our inclusion of a wider range of studies:
nonrandomized trials and studies of ultrasound-guided CV
cannulation, which included both real-time ultrasound guid-
ance and ultrasound-assisted prelocation. The latter technique
was not included in one of the prior systematic reviews (7).
While including a broader range of studies resulted in a loss of
specificity and carried the risk of including low-quality studies,
it allowed us to perform extensive subgroup analyses based on
study methodology, different types of ultrasound use, or rank-
ing of the risk of bias.
The high risk of bias among the collected RCTs might call
into question the accuracy of the estimation. In general, inves-
tigations into this topic inherently carry bias owing to the
unmasked nature of the intervention and the methods used
to assess outcome. As a result, only two RCTs (24, 25) were
assessed as having relatively low risk of bias. Even in these
two RCTs, bias was generated from a different intervention
between groups (24) and small numbers of enrolled patients
(25). Consequently, including high-quality nonrandomized
studies, such as those in which the outcome was assessed by a
third-party quality assessment team (16), would appear to be
valid if separate meta-analyses on nonrandomized studies and
RCTs were conducted.
The degree to which operator experience influences the
success of catheterization is still a subject of debate (27). In
the study by Froehlich et al (13), a significant reduction in
the number of attempts or arterial punctures by ultrasound
was noted only in the resident or fellow groups, but not in the
attending physician group. Two RCTs in which the operators
were either experienced in landmark methods or under expert
supervision showed low failure rates in the landmark method
(4% and 11%) (22, 25). One of them showed comparably
low failure rates with ultrasound guidance, whereas another
showed a significant increase in failure rates and arterial punc-
tures with real-time ultrasound guidance (22).
Unfortunately, because of the limited number of reports,
there was less evidence about other outcome measures, such as
time to cannulation, number of attempts for successful cannu-
lation, and complications (28). Similarly, no firm conclusions
could be made regarding the different types of puncture site,

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 Feature Review Article

Body Vascular Failure

Description of Operators Weight (kg)b Place Access Ratea

Fellows of anesthesia department (n = 10) with 3–6 yr of training 4.8 OR IJV 0% vs 26%c
in clinical anesthesia and formal training in adult CVC, without
special training in pediatric CVC. They were assisted by one of two
experienced pediatric cardiac anesthesiologists, who manipulated
the ultrasound probe

Not mentioned 8.8 OR IJV 0% vs 20%

Fellows of anesthesia department, who had had > 3 yr of training in 7.6 OR IJV 3% vs
clinical anesthesiad 38%
Not mentioned 6.7 OR IJV 0% vs
20%

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Appendix 1. Search Formula on PubMed
Interface
#1 echo OR ultrasound OR “Ultrasonography”[Mesh]:
468,727 citations.
#2 (jugular vein) OR (groin vein) OR (femoral vein) OR
(central venous) OR “Catheterization, Central Venous”[Mesh]:
66,117 citations.
#3 neonates OR neonate OR infants OR infant OR children
OR child OR pediatrics OR pediatric OR “Pediatrics”[Mesh]:
2,484,018 citations.
#4 #1 AND #2 AND #3 AND: 1,059 citations.
8 www.pccmjournal.org
Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Unauthorized reproduction of this article is prohibited
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