Midline Catheter Tip Position and Catheter-Related Complications in Antimicrobial Therapy- A Multi-centre Randomized Controlled Trial
Phase: NA
Conditions: Infection
Sponsor: Sir Run Run Shaw Hospital

Midline Catheter Tip Positioning and Catheter-Related Complications during
Antimicrobial Therapy: A Multicenter Randomized Controlled Trial
NCT04601597
January 30, 2021

Method
2.1 Study Design
This was a researcher-initiated, multicenter, randomized controlled trial conducted in
six first-class general hospitals in China's Zhejiang, Fujian, Jiangsu, and Liaoning
provinces.
Twelve
IV
nurse
specialists
were
involved
in
performing
the
catheterizations. The research protocol was based on assigning patients to three
different catheter tip placement groups and observing the relationship between tip
placement
and
catheter-related
complications.
The
institutional
review
board
approved the research protocol of each participating hospital according to the Helsinki
Declaration that respects individuals and recognizes vulnerable groups. All the
participants had the right to make informed decisions. (IRB:20200107-11). Patients
who underwent MC placement in all six hospitals were enrolled, and the study was
conducted between September 2020 and January 2021.
2.2 Participants
A fixed-point continuous convenience sampling method was adopted to enroll
330 participants. The participants who met the clinical criteria for this study were
informed about the study and written informed consent was obtained from each
participant. Consent may also have been obtained from legally authorized persons.
The inclusion criteria were as follows ①estimated time of intravenous infusion ≥1
week before catheterization; ②age: ≥18 years; ③antimicrobial therapy was only
used for treatment during hospitalization, with a pH value of 5–9 and osmotic
pressure< 900 mOsm/L; and ④patients were conscious and able to communicate
normally. ⑤The catheter-to-vessel ratio is less than 45%. The exclusion criteria were
as follows: ①a history of radiotherapy, thrombosis, and trauma at the catheterization
site and ②plans to discharge with a catheter during the study duration. Withdrawal
criteria were as follows: ①active discharge from the hospital during indwelling of
the catheter; ②failure to be followed-up after catheterization due to disease; and ③a
change in health status during antimicrobial therapy treatment, requiring other drugs
to be infused treatment through the MC.
2.3 Sampling
A general formula-based sample estimation method using the data on the
relationship between MC tip position and catheter-related complications was used to
calculate the sample size (Wu et al., 2020). Based on the selected reference, the
incidence of complications at the tip of the MC at the thoracic wall of the axillary vein
was 32.5% (Wu et al., 2020), while the incidence of complications in the subclavian
vein was 12.5% (Wu et al., 2020). A power analysis was performed to calculate the
effect size. Efficacy was set at 0.8 (with an 80% probability of finding a difference
between populations) and 0.05 (5% of Type I error). Considering external factors that
may have caused loss and withdrawal, each group was increased in size by 20%, to 65
patients per group.
2.4 Randomization and Grouping
There were 428 eligible patients, and 330 consented to participating in this study.
A random sequence was generated after participants were recruited, and participants
were randomized into three groups using a computerized random number generation

technique. Then, a proportional allocation of treatment methods was adopted to
equalize the participants in all groups. Microsoft Excel generated 1000 random
integers and 330 corresponding numbers were drawn. The 330 corresponding
numbers were arranged into opaque and sequentially numbered envelopes. Then, the
envelopes were sorted by random sequence and evenly distributed among the six
selected hospitals. Three different study groups with equal numbers of participants
(n=110) were established using this non-stratified random allocations.
2.4.1 Study Groups
1. Experimental Group 1 contained patients assigned with the numbers obtained
after dividing the computer-generated random numbers by three, with a
remainder of one.
2. Experimental Group 2 contained patients assigned with numbers obtained
after dividing computer-generated random numbers by three, with a remainder
of two.
3. The control group included patients assigned numbers obtained when the
random numbers were divisible by three.
2.5 Intervention
Detailed history-taking, including medical history, and clinical exams were
provided to all participants were, and written informed consent was obtained. A
single-blind design was adopted, in which the participants did not know their
inclusion status, or whether they were in the control or experimental groups. Double
blinding was avoided due to ethical concerns and the questionable efficacy of the
experiment. After obtaining informed consent from the patients, the project
coordinators of each hospital opened the envelopes according to their serial number.
They informed the catheterization nurse about the patient’s inclusion status.
2.5.1 Catheter Pre-Placement Length Measurement and Evaluation of Tip Position
The measurement of catheter pre-placement length and the determination method
of catheter tip position were formulated based on the Consensus (Bai & Guo, 2019),
expert opinions on vascular anatomy, and relevant literature (Huang et al., 2018;
Pathak et al., 2015; Sun et al., 2014). An intravenous therapy (IV) specialist nurse
confirmed catheter tip positioning by ultrasound during catheterization, and the
position of the catheter tip was adjusted according to ultrasound imaging. X-ray
imaging was performed after catheterization to confirm the position of the catheter tip.
The measurement methods for the tip position and pre-placement insertion length of
the different groups of catheters were as follows:
(1) Experimental Group 1: The catheter tip was placed in the subclavian vein. The
pre-placement catheter length measured through the body surface was greater than the
actual length. Therefore, 2 cm was subtracted from the pre-puncture point to the
ipsilateral sternoclavicular joint to calculate the effective catheter pre-placement
length.
(2) Experiment Group 2: The tip of the catheter was placed in the axillary vein of the
chest wall. The pre-placement length of the catheter was measured by subtracting 3–4
cm from the distance between the puncture point and ipsilateral midclavicular line.

This adjustment was intended to prevent the catheter tip from entering the subclavian
vein.
(3) The control group: the catheter tip was located distal to the axillary vein. The
measurement method of catheter pre-placement length was as follows: in cases where
the catheter was punctured from the basilic and brachial veins, the distance from the
pre-puncture point to the intermuscular sulcus of the ipsilateral deltoid muscle and
pectoralis major muscle was measured (not surpassing the intermuscular sulcus and
not reaching the axilla); however, the distance from the pre-puncture point to the
ipsilateral sub shoulder or axilla was measured.
2.5.2 Catheter Insertion Procedure
A fixed routine for pre-insertion cleaning and equipment was followed, including
hand washing, placing the patient in the supine position, skin antisepsis, and
preparation of the sterile field. Catheter insertion was performed by senior nurses in
the intravenous treatment room, which was a standardized setting for venipuncture.
Conventional catheter placement and maintenance methods were adopted as follows:
①evaluation: physicians confirmed the condition of the pre-puncture intima through
ultrasound before catheterization. If ultrasound imaging did not show endothelium
abnormalities, such as rough intima, it was noted as a smooth standard. Subsequently,
12 catheterization nurses selected the puncture site guided by ultrasound. Nurses took
1/3 of the middle part of the patient's upper arm as the best puncture area and used
ultrasound to measure the diameter of the vessel (Chen et al., 2018). ②
Catheterization: each hospital assigned two senior IV nurses for MC puncture and
measured the catheter pre-placement length according to the measurement method of
different groups, and the catheter was placed using ultrasound-guided and modified
Seldinger techniques. After confirming the position of the tip, the catheter was
trimmed, and the extension sets was connected, with the length of the external
catheter were3
cm. ③Maintenance: 24 IV specialist nurses were trained to monitor
and evaluate catheter functioning weekly, and clinical nurses conducted routine
maintenance until study completion. Daily data were recorded and updated to
computerized data records.
2.5.3 Catheter Maintenance
As suggested by the relevant literature, members of the research group designed
the first draft of the MC tip positioning complication observation table. The
observation table was later improved after modification by the IV specialist nurse of
each hospital, and a third-party Statistics agent designed the electronic database for
research. The collected data included the following two categories: ①baseline data of
participants: age, sex, educational background, height, weight, diagnosis, history of
thrombosis, surgical trauma, and chronic diseases, hemoglobin concentration, platelet
count, white blood cell count, prothrombin time, activated partial thrombin time,
history of CVC, PICC, and MC; ②Data on catheterization conditions: number of
catheterizations, placement site, placement vein, and successful catheterization with
the first attempt; ③Data on the use and maintenance of catheters: daily catheter
function evaluation, assessment of complications, and the time and reason of removal
IV lines, and the types of antibiotics used in antimicrobial therapy.

2.6 Evaluation Indicators and Judgment Criteria
2.6.1 Incidence of Catheter-Related Complications
First, the catheter-related complications were assessed. The complications
studied included phlebitis, catheter-related thrombosis, catheter occlusion, catheter
dislodgement, bleeding, catheter-related infections, and infiltration. In this assessment,
the incidence of each complication (i.e., number of patients with these complications)
was divided by the total number of cases. Then, the total number of incidences of
catheter-related complications was taken as the main outcome index (i.e., the number
of patients with complications/the total number of patients). One patient with one or
multiple complications was counted as one case in total.
The judgment criteria for each complication were as follows: ①phlebitis: the
relevant contents in the Standard (Gorski et al., 2021) were considered; ②
catheter-related thrombosis, also referred to as symptomatic thrombosis, was observed
and reported either by patients or bedside nurses. Edema the limbs, neck, shoulder,
chest, and/or face on the side of catheterization was observed for and reported to
physicians, in order to perform an ultrasound for venous thrombosis detection; ③
catheter-related
infections
included local
infection
at the
puncture
site
and
catheter-related bloodstream infection, which were evaluated according to the
corresponding diagnostic criteria in the Standard (Gorski et al., 2021); ④catheter
occlusion, inability to withdraw blood or sluggish blood return, sluggish flow;
resistance or inability to flush lumen, inability to infuse fluid, Frequent occlusion
alarms on electronic infusion pump. ⑤catheter dislodgement included dislodgement
of more than 3 cm; ⑥infiltration was noted when the puncture site had liquid
exudation; and ⑦bleeding referred to the blood exudation at the puncture site 48 h
after catheterization.
2.6.2 Indwelling Catheter Duration
Indwelling catheter duration referred to the number of days between the date of
catheter placement and removal.
2.7 Data Collection
Catheterization nurses recorded baseline data prior to catheterization, and only the
most recent results were recorded one week prior to catheterization, when multiple
laboratory results were available. Catheterization site evaluations were recorded after
placement, and patients were followed up for 48 h after catheterization as well as
every 7th day by IV specialist nurses to review and record the progress of
antimicrobial therapy. The last follow-up was conducted at the time of removal,
where the reason for removal was also recorded. In addition, bedside nurses evaluated
and recorded catheter functioning and complications daily.
2.8 Quality Control
Quality standards and controls were maintained throughout the study. All
hospitals included in this study used the same brand and batch number of
silicone-valved catheters, with a total length of 30 cm. Catheters could be trimmed to
ensure a consistent length of the external catheter and a unified catheter placement
and maintenance process. The same criteria were used to appoint IV specialized
nurses in each hospital. Only those who had more than three years of PICC or MC

placement experience and more than 200 cases of catheterization were assigned. After
catheterization, the evaluation video for catheter-related complications was sent to the
nurse managers of the department in which the participants were located. Bedside
nurses were trained and assessed by a nurse manager in the department. Researchers
with unified training collected the relevant data, followed up, and stored the data in a
dedicated electronic database. One researcher was assigned to check the data entries
from each hospital, and a third-party statistics agent rechecked all entries. In case of
extreme or missing values, the data were rechecked by the project coordinator of each
hospital.