a b s t r a c t

Objective: Guidewire-induced arrhythmias that occur during central venous catheterization can progress to ma- lignant arrhythmias in rare cases. This study compared the incidence of arrhythmia during central venous cath- eterization using three different depths of guidewire insertion into the right internal jugular vein.

Methods: Sixty-nine patients undergoing elective surgery requiring central venous catheterization through the right internal jugular vein were enrolled in this double-blind, prospective, randomized, and controlled study. Pa- tients were randomly allocated to receive guidewire insertions to 15 cm, 17.5 cm, or 20 cm before tissue dilation. Arrhythmic episodes were then monitored during dilation of the soft tissue.

Results: A total of 29 patients (42%) experienced arrhythmic episodes during tissue dilation. The guidewire- induced arrhythmia rates of the 15 cm group, 17.5 cm group, and 20 cm group were 0.26 (95% confidence interval [CI] = 0.10, 0.48), 0.35 (95% CI = 0.16, 0.57), and 0.65 (95% CI = 0.43, 0.84), respectively. The incidence of ar- rhythmic episodes was higher in the 20 cm group than in the 15 cm (odds ratio [OR] = 5.31; 95% CI = 1.50, 18.84) and 17.5 cm (OR =3.52; 95% CI = 1.05, 11.83) groups. There was no significant difference in arrhythmia rates between the 15 cm group and 17.5 cm group (p = 0.542).

Conclusions: During central venous catheterization through the right internal jugular vein, inserting guidewires to depths of 15 or 17.5 cm before tissue dilation reduced the incidence of arrhythmic episodes compared to a depth of 20 cm.

(C) 2017

Introduction

Central venous catheterization is widely performed in emergency departments, Operating rooms, and intensive care units for various pur- poses. The three routes for central venous catheterization are through the internal jugular vein, the subclavian vein, and the femoral vein. In addition, each route can be accessed from the right or left side of the pa- tient. There are advantages and disadvantages associated with each route [1,2]. Catheterization through the right internal jugular vein is most commonly performed. Transient arrhythmias are frequently ob- served during the procedure, and most arrhythmias result from me- chanical irritation by the guidewire inserted to an excessive depth [3, 4]. In these cases, withdrawal of the guidewire to an adequate depth

* Corresponding author at: Department of Anesthesiology and pain medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Sindaebang 2-dong 425, Dongjak-gu, Seoul 07061, Republic of Korea.

E-mail address: [email protected] (S.-W. Min).

or even in the absence of any further treatment, most arrhythmias gen- erally disappear readily and rapidly. However, malignant arrhythmias such as ventricular fibrillation or ventricular tachycardia can occur dur- ing the process of central venous catheterization and these cannot easily resolve with withdrawal of the guidewire. Although malignant arrhyth- mias are rare during central venous catheterization (Our hospital had 2 malignant guidewire-induced arrhythmia cases following 1512 central venous catheterizations (0.13%) over a 29-month period (unpublished data)), they can be fatal and require specific treatment such as an anti-arrhythmic agent or direct current cardioversion [5-9].

A previous study suggested that guidewires should not be inserted to depths N 20 cm [10] and most physicians tried to limit insertion of guidewires to depths beyond 20 cm. However, many physicians may habitually insert guidewires to depths of 20 cm rather than shallower depth such as 15 cm. The purpose this study was to evaluate whether the length of guidewire inserted during catheterization affects the inci- dence of arrhythmias. We investigated guidewires insertion depths of 15, 17.5, and 20 cm.

http://dx.doi.org/10.1016/j.ajem.2017.01.016

0735-6757/(C) 2017

Methods

This prospective, randomized, controlled study was approved by the Institutional Review Board of the Seoul Metropolitan Government-Seoul National University Boramae Medical Center (16-2015-105) and was reg- istered in ClinicalTrials.gov (NCT02711761). Written informed consent was obtained from each patient. Our institute, a training hospital, has nearly 800 beds and over 600 central venous catheterizations through right internal jugular veins are performed in the operating theater annually.

Patient selection and randomization

A total of 69 adult patients were enrolled in this study between Sep- tember 2015 and March 2016. They were in sinus rhythm, had American Society of Anesthesiologists physical statuses of I or II, and were undergoing elective surgeries requiring central venous catheteri- zation through the right internal jugular vein. Patients were excluded for arrhythmias detected prior to anesthesia, abnormal electrolyte levels, insufficient neck length to perform catheterization by a senior su- pervisor anesthesiologist’s judgement, suspected infections on the right side of the neck, and ventriculo-peritoneal shunts or chemo-ports in the right side of the chest that were too close to the operating site. A nurse enrolled all patients. And, we planned that the senior supervisor anes- thesiologist would exclude a patient with insufficient neck length in the operating theater.

After enrolment, patients were randomly assigned, with 1:1:1 ratio, to one of three different groups that would undergo insertion of a guidewire to depths of 15, 17.5, or 20 cm group before a dilator would be used to facilitate central catheter placement into the internal jugular vein. An investigator, who did not clinically participate in this study, generated the random allocation sequence by computer-generated allo- cation numbering (www.radomizer.org) using random sequence of 3- sized blocks including letters of A, B and C. Each letter was concealed in a sequentially numbered envelope in order of the generated random allocation sequence. Enrolled patients were allocated to assigned groups depending on the letter (A, B or C) inside the concealed envelope that was opened in the order of sequentially number on the envelope by an anesthesia nurse who was unaware of the study on the day of oper- ation. The nurse showed the letter to only one senior investigator who adjusted the insertion depth of guidewire before a care provider per- formed tissue dilation, and then assessed whether guidewire-induced arrhythmia developed or not. Patients were blinded to their group as- signment. Catheterization was performed by physicians with a rage of experience, from first-year anesthesiology residents to attending anes- thesiology physicians. All practitioners were blinded to the depth of in- sertion and all had already performed N 50 central venous catheterizations through right internal jugular vein before initiation of the study.

Anesthesia and study protocol

All procedures utilized a two-lumen ARROWg + ardBlue(R) Catheter set (Arrow International Inc., Reading, PA, USA) consisting of a 7French (Fr), 20 cm catheter and a 60-cm J-shaped spring-wire guide. Each pa- tient was admitted into the operating room without premedication. Electrocardiograms, as well as blood pressure, and peripheral capillary oxygen saturation measurements were obtained before induction of an- esthesia. Anesthesia was induced with 2 mg/kg of propofol and 100 ug of fentanyl, and 0.6 mg/kg of rocuronium was administrated for Muscle relaxation. After intubation, mechanical ventilation was initiated with a tidal volume of 8 ml/kg, a respiratory rate of 10-12/min, and an F_IO₂ of

0.5. Anesthesia was maintained with sevoflurane through surgery. Arte- rial catheterization was also performed to monitor blood pressure con- tinuously. The operating table was tilted ~ 15? Trendelenburg head down and the patients’ heads were rotated ~ 30? to the left. Angular

measurements were made using a digital BevelBox (L.V. Level Co, Jiang- su, China) protractor as reported previously [11].

After sterile preparation, central venous catheterization through the right jugular vein was performed using the modified Seldinger tech- nique under ultrasound guidance. The insertion point for the needle was at the level of the crease of the cricoid cartilage. A guidewire was inserted through the needle after checking that dark red blood could be freely aspirated. For this process, the guidewire was inserted only to 15 cm. The needle used to introduce the guidewire was then removed on maintaining the position of the guidewire and preventing movement of it. Depending on the group assignment for each patient, the guidewire was advanced to the appropriate depth (15, 17.5, or 20 cm) by one sterile-gowned senior investigator who was not performing the central venous catheterization. During this adjustment, the practi- tioner performing the catheterization was ordered to close their eyes to remain blinded to group assignments and study protocols. The senior investigator, who only known an assigned group to the lying patient, then applied the tissue dilator mounting on the inserted guidewire until the tip of dilator contacted the skin of the patient. At this point, the practitioner opened their eyes and dilated the patient’s tissue. In the meantime, the senior investigator checked whether arrhythmias oc- curred or not. After checking for arrhythmias, the practitioner inserted the central venous catheter according to the modified Seldinger technique.

Outcomes and data acquisition

The primary outcome of this study was the occurrence of guidewire- induced arrhythmias during central venous catheterization. Both the in- cidence and type of arrhythmia were recorded. For each patient, gender, height, weight, and histories of hypertension, diabetes mellitus, or chronic kidney disease were recorded. Preoperative levels of Blood urea nitrogen , serum creatinine (SCr) and potassium were also obtained.

Sample size calculation and statistical analyses

In a simple pilot observation involving 31 patients, the incidence of arrhythmia during central venous catheterization through the right in- ternal jugular vein was: 1/10 for patients receiving guidewire insertion to ~ 15 cm, 4/10 for insertion between 17 and 18 cm, and 7/11 for inser- tion to ~ 20 cm. To adequately test our hypothesis, a total of 69 patients (n = 23/group) was needed to achieve an alpha-level of 0.05 and a beta-level of 0.10.

Quantitative variables of patient characteristics and outcome measures are presented as mean +- standard deviation (SD). Num- bers and percentages are presented for categorical variables. Com- parisons between groups were performed using ?² tests or Fisher’s exact tests, depending on the variables being examined. P-values b 0.05 were considered statistically significant. SPSS Statistics

21.0 software (IBM Corporation, USA) was used for all statistical

analyses.

Results

Patient screening, enrollment, randomization, and analysis are shown in the CONSORT flow diagram in Fig. 1. A total of 69 patients were monitored for guidewire-induced arrhythmia following insertion of guidewires to depths of 15, 17.5, or 20 cm. None of the guidewires were accidently dislodged or pulled during any procedures. The preva- lence of chronic kidney disease, BUN, and SCr values were different be- tween the three study groups (Table 1).

Arrhythmic episodes were observed in 29 out of 69 (42%) patients. Arrhythmias were observed in 6 out of 23 (26.1%; 95% confidence inter- val [CI] = 10.2-48.4%) at 15 cm, 8 out of 23 (34.8%; 95% CI = 16.4-

57.3%) at 17.5 cm, and 15 out of 23 (65.2%; 95% CI = 42.7-83.6%) at

Fig. 1. CONSORT flow diagram.

20 cm. Specifically, premature atrial contractions (n = 17), premature ventricular contractions (n = 7), loss of one beat (n = 1), and sinus tachycardia of 144 bpm (n = 1) occurred (Table 2). As shown in the Table 2, premature atrial contraction and premature ventricular con- traction were the primary guidewire-induced arrhythmias that were observed. All but one incidence of arrhythmias resolved spontaneously

with guidewires still in place, or soon after withdrawal. One patient ex- perienced tachyarrhythmia at 144 beats per minute that lasted

~ 1.5 min. This patient’s heart rate was 77 bpm prior to the procedure. Upon detection of tachyarrhythmia, the guidewire was immediately withdrawn and then the patient’s heart rate returned to normal without any additional treatment.

Table 1

Patient characteristics.

Patient characteristics	15 cm group	17.5 cm group	20 cm group
	(n = 23)	(n = 23)	(n = 23)
Gender (M/F)	10/13	9/14	11/12
Age	61.1 +- 13.9	62.5 +- 13.4	57.8 +- 13.9
Height	161.3 +- 7.7	164.2 +- 8.7	160.7 +- 7.6
Weight	62.4 +- 11.2	63.9 +- 8.0	65.2 +- 17.4
BMI	23.9 +- 3.1	23.7 +- 2.8	25.2 +- 6.7
practitioner experience?	(10/13)	(9/14)	(12/11)
(1st year resident/N1 year)
HTN	9	11	8
DM	5	6	3
CKD	0	5	0
BUN	12.4 +- 4.5	22.0 +- 20.5	12.5 +- 3.8
Cr	0.74(0.45, 1.17)	0.91(0.54, 8.81)	0.77(0.47, 1.15)
K+ 4.3 +- 0.4		4.3 +- 0.4	4.2 +- 0.4

Data except SCr were presented by mean +- standard deviation. SCr was presented by me- dian (range).

* Practitioner experience was described as (the number of 1st-year residents/the number

of anesthesiology attending physicians trained N 1 year) in each group. BMI: body mass index; HTN: hypertension; DM: diabetes mellitus; CKD: chronic kidney disease; BUN: blood urea nitrogen; SCr: serum creatinine; K⁺: serum potassium.

The incidence of guidewire-induced arrhythmias differed between the three groups (p = 0.019). Arrhythmias were more frequent in the 20-cm group than the 15-cm group (odds ratio [OR] = 5.31; 95% CI = 1.50, 18.84) and the 17.5-cm group (OR = 3.52; 95% CI = 1.05,

11.83) (Fig. 2). However, there was no significant difference in the inci- dence of arrhythmia between the 15- and 17.5-cm groups (p = 0.542), or between other variables and arrhythmia rates (Table 3). A total of 6 first-year anesthesiology residents participated in the study with a me- dian of 4.5 (range 2-10) patients. A total of 18 anesthesiologists with N 1 year experience participated in the study with a median of 1.5 (range 1-7) patients. When physicians were classified as either first- year anesthesiology residents or others who had more experience, there was no difference in arrhythmia rates between physicians with different levels of experience (p = 0.788) (Table 3).

The height of all patients was mean 162.1 cm +- standard deviation (SD) 8.1 cm in our study population. When sub-grouping patient’s height to ‘short patients group’ (b 158 cm [about mean of total 69 pa- tients’ height - SD/2]) and ‘tall patients group’ (>= 166 cm [about mean + SD/2]) in each study group, shorter individuals was prone to ar- rhythmias at 20 cm group than taller individuals (Fig. 3, Table 4).

Discussion

A higher incidence of guidewire-induced arrhythmias was observed when guidewires were inserted to 20 cm compared to 15 or 17.5 cm. These results are consistent with our hypothesis that 15 cm would have the lowest incidence of guidewire-induced arrhythmia. However, the incidences of arrhythmia were not different at 15 and 17.5 cm, sug- gesting that both depths are equally safe in terms of inducing arrhyth- mias. Our findings are consistent with a previous study which inserted

guidewires to 18 cm for central venous catheterization through the

Fig. 2. Distribution of patients who experienced arrhythmia during central venous catheterization in each group. The incidence of guidewire-induced arrhythmia was higher in the 20-cm group than in the 15-cm *(odds ratio [OR] = 5.31; 95% confidence interval [CI] = 1.50, 18.84) and 17.5-cm +(OR = 3.52; 95% CI = 1.05, 11.83) groups.

right internal jugular vein [12]. Depths of 15 or 17.5 cm were not asso- ciated with accidental unthreading of the guidewire from the internal jugular vein.

There are two reasons to insert guidewires beyond a minimum depth. First, additional depth prevents accidental unthreading of guidewires from an internal jugular vein. Second, additional depth may prevent perforation by the catheter itself. It is currently considered to insert a guidewire 2-3 cm longer than insertion depth of the catheter [13]. However, evidence for this being safe is weak. Furthermore, using the distance from the round terminal of the ‘J’ shape as the point to mea- sure insertion depth may not allow the catheter tip to perforate the atri- um or vessel wall, even if the guidewire insertion depth is the same as the intended length of catheter insertion (13-15 cm depending on pa- tient height).

Many studies investigated the optimal depth to insert central venous catheters into the right internal jugular vein. Specific catheter lengths of 16.5, 15, and 12.5 cm, or equations based on patient height have been studied. While there is not a strong consensus or any particular length, recent studies support shortening insertion depth of catheter from older guidelines [14-20]. Recently, a study reported that a topographic

Table 3

Correlation between guidewire-induced arrhythmias and patient’s characteristics.

Patient characteristics Arrhythmia P-value No Yes

Group 15 cm group (n = 23) 17 (73.9%) 6 (26.1%) 0.019

17.5 cm group (n = 23) 15 (65.2%) 8 (34.8%)

20 cm group (n = 23) 8 (34.8%) 15 (65.2%)

Sex Female 16 (53.3%) 14 (46.7%) 0.494

Male 24 (61.5%) 15 (38.5%)

Practitioner 1st year resident 18 (56.2%) 14 (43.8%) 0.788

*

experience N 1 year 22 (59.5%) 15 (40.5%)

HTN No 27 (65.9%) 14 (34.1%) 0.108

Yes 13 (46.4%) 15 (53.6%)

Table 2	DM	No	35 (63.6%)	20 (36.4%)	0.059
Types of guidewire-induced arrhythmias in three groups.		Yes	5 (35.7%)	9 (64.3%)

Type of arrhythmias 15 cm group

(n = 23)

17.5 cm group

(n = 23)

20 cm group

(n = 23)

P-value

Age 60.0 +- 13.3 61.1 +- 14.3 0.730

PAC 4 (17.4%) 5 (21.7%) 11 (47.8%) 0.048

CKD	No	37 (57.8%)	27 (42.2%)	1.000
	Yes	3 (60.0%)	2 (40.0%)

PVC 1 (4.3%) 2 (8.7%) 4 (17.4%) 0.484

Loss of 1 beat 0 (0%) 1 (4.3%) 0 (0%) 1.000

Sinus tachycardia? 1 (4.3%) 0 (0%) 0 (0%) 1.000

Total 6 (26.1%) 8 (34.8%) 15 (65.2%) 0.019

PAC: premature atrial contracture; PVC: premature ventricular contracture.

* One patient of 15-cm group experienced sinus tachycardia with heart rate of 144 beats per minute.

Height 163.5 +- 7.4 160.1 +- 8.7 0.089

BUN 14.4 +- 7.0 17.3 +- 18.2 0.346

SCr 1.0 +- 1.0 1.3 +- 2.0 0.347

K⁺ 4.2 +- 0.4 4.4 +- 0.4 0.086

* The practitioner experience compared is for the incidence of arrhythmia for cases involving 1st year residents vs. anesthesiology attendings trained N 1 year. BMI: body mass index; HTN: hypertension; DM: diabetes mellitus; CKD: chronic kidney disease; BUN: blood urea nitrogen; SCr: serum creatinine; K⁺: serum potassium.

Fig. 3. Incidence of guidewire-induced arrhythmia of subgroups composed of short or tall patients in each study groups. *represented that short patients (b158 cm [= mean of total 69 patients’ height - SD/2]) were prone to arrhythmias at guidewire insertion depth of 20 cm (p = 0.031). Error bars represents 95% confidence interval.

approach was superior to a fixed depth of 15 cm for central venous cath- eterization through the right internal jugular vein. The insertion depths in the topographic group ranged from 9 to 12.5 cm [18]. These could imply that shallower depths of guidewire insertion may be sufficient.

It has been suggested that guidewire depths should be b 20 cm in a previous study [10]. However, the authors of that previous study did not directly compare insertion depths in a randomized controlled man- ner. Furthermore, they found the incidence of arrhythmia was actually higher when the insertion depth between 16 and 19 cm compared to 20 cm. These results might arise from the primary focus of that study, which was to compare the incidence of arrhythmia according to inser- tion depths of guidewires between using marked guidewires and un- marked guidewires. Another previous study suggested that guidewires should be inserted b 18 cm on the basis of the distances from access site for central venous catheterization to the cava-atrial junction mea- sured using fluoroscopic imaging [12]. However, this depth of 18 cm was determined from a mean value of distances from the internal jugu- lar veins and subclavian veins and authors did not investigate the inci- dence of arrhythmias at the recommended insertion depth.

Our study revealed no significant difference in the incidences of ar- rhythmias between 15 cm and17.5 cm. However, the incidences of ar- rhythmias were approximately 30% rather than near to zero in both two groups. Considering both depths were sufficiently shallow to prevent ar- rhythmias, we hypothesized that the force of tissue dilation caused tran- sient migration of guidewire and compressed the advancing site of the tissue dilator. Both of these could cause arrhythmias. It also supports our hypothesis that vagal stimulation can cause arrhythmia [21,22].

In the present study, 5 patients had chronic kidney disease and all were randomly assigned to the 17.5 cm group. Arrhythmias developed in 2 patients of them. Of remained 18 patients in the 17.5 cm group, 4 patients experienced arrhythmia. In a previous report, a lethal cardiac arrhythmia occurred during central venous catheterization of a uremic patient [9]. The results of another study suggested that arrhythmias dur- ing central catheterization occurred more frequently in patients with higher BUN and SCr levels [23]. While this differs from our findings, our sample size was inadequate and a larger sample size might reveal a correlation.

Table 4

Incidence of guidewire-induced arrhythmia of subgroups of patients by height in each study groups.

Insertion depth of guidewire Incidence of arrhythmia in patients P-value

	b158 cm	158-166 cm >= 166 cm
15 cm	2/7 (28.6%)	3/9 (33.3%) 1/7 (14.3%)	0.843
17.5 cm	3/7 (42.9%)	1/5 (20.0%) 4/11 (36.4%)	0.859
20 cm	6/6 (100%)	7/11 (63.6%) 2/6 (33.3%)	0.061

It has been suggested that the use of marked guidewires could pre- vent excessive insertion [10], and many common central venous cathe- ter lacked guidewire markings [13]. The guidewires used in our study had three markings at 10 cm intervals from the J-tip and a wide marking at 35 cm from the J-tip. A previous study using Schon Duo-Flow guidewires (Angiodynamics, Queensbury, NY, USA) reported they had six markings at 2-cm intervals starting 14 cm from the J-tip [13]. Mark- ing guidewires at 15 cm or every 2 cm between 10 cm and 20 cm could help reduce inadvertent arrhythmic episodes.

There were limitations associated with our study. First, arrhythmia incidence did not significantly correlate with the clinician experience. We hypothesized that procedures performed by first-year residents would result in more guidewire-induced arrhythmias than more senior residents or post-residency clinicians even if the same insertion depth of guidewire, because we thought that the more experienced clinicians could more gently and more proficiently dilate the soft tissue. In this study, first-year residents already participated in N 50 cases before the start of this trial. Consequently, a correlation between clinicians’ experi- ence and arrhythmias could not be correctly investigated in our study. Future studies should investigate practitioners with less experience, as well as a larger sample size. Second, our study was not designed to de- termine adequate guidewire insertion depth based on patient height. Therefore, this study did not have sufficient sample size for analysis with subgroup of patients according to height, which could be a con- founding factor. It may be reasonable that height would be a significant confounding factor to find ideal guidewire insertion depth. We random- ized the guidewire insertion depth to simple lengths (15 vs 17.5 vs 20 cm) in the present study. For patients over 180 cm, the insertion depth of 20 cm of guidewire could rarely cause guidewire-induced ar- rhythmia. Although sample size of our study was small and any patient over 180 cm was not enrolled in this study, the shorter individuals were more prone to arrhythmias in the 20 cm group. However, insertion of 20 cm of guidewire will not be necessary for insertion depth of central venous catheter shallower than 15 cm. That is, 15 cm or 17.5 cm could be sufficient for the majority of patients including those N 180 cm based on our results and the previous studies about the optimal inser- tion depth of central venous catheter [17-19,24,25]. Also, numerous dif- ferent insertion depths of guidewire according to patient height would not be a simple guideline for physicians to accept in clinical setting.

In conclusion, our study demonstrate that during central venous catheterization through the right internal jugular vein, guidewire inser- tion depths of 15 cm and 17.5 cm results in fewer guidewire-induced ar- rhythmias compared with a depth of 20 cm.

Details of authors’ contributions

Jung-Man Lee, M.D.

Role: This author helped design the study, conducted the study, an- alyzed the data, obtained the informed consent from patients, and wrote the manuscript.

Jiwon Lee, M.D.

Role: This author helped design the study, analyzed the data, and wrote the manuscript.

Jin-Young Hwang

Role: This author conducted the study.

Jee-Eun Chang

Role: This author conducted the study.

Heyrim Kim

Role: This author conducted the study.

Sohee Oh

Role: This author helped design the study, analyzed the data.

Eun-Ah Oh

Role: This author conducted the study.

Seong-Won Min

Role: This author helped design the study, conducted the study.

Conflicts of interest

Authors declare that they have no conflicts of interest or financial ties.

Funding

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

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