Impact of peripherally inserted central venous catheter‐associated phlebitis in neonate guided by intracavitary electrocardiogram: A systematic review and meta‐analysis of randomised controlled trials

Abstract

Because the application of intracavitary electrocardiogram (IC‐ECG)‐guided peripherally inserted central catheter (PICC) in the treatment of neonates is controversial in terms of phlebitis reduction compared with traditional X‐ray positioning technique, a systematical evaluation is needed on the impact of IC‐ECG on this common complication following PICC. Literature retrieval was conducted on large databases including PubMed, Google Scholar, Cochrane library, and CNKI. Randomised controlled trials (RTCs) of intracavitary electrocardiogram‐guided peripherally inserted central catheter tip placement in the treatment of neonates up to July 7, 2022, were collected. Then indicators of included studies were compared and analysed by two researchers. Meta‐analysis was performed on the STATA 17.0 software. After excluding invalid trials, 11 out of 316 randomised controlled trials were included for further analysis. Meta‐analysis results showed that compared with the control group, IC‐ECG‐guided PICC could decrease the incidence of phlebitis (I ² = 0.00%, P = 0.76, OR = 0.33, 95% CI 0.19–0.56) and that no significant difference was observed between preterm neonates and term neonates (P = 0.74). Meanwhile, total complications were decreased in neonates (I ² = 0.00%, P = 0.00 OR = 0.23, 95% CI 0.16–0.33). IC‐ECG‐guided PICC could also improve the accuracy of optimal tip location (I ² = 0.00%, P = 0.53, OR = 5.37, 95% CI 3.80–7.59). IC‐ECG‐guided PICC could achieve reduced phlebitis incidence and total complications in the treatment of neonates, as well as increased accuracy of optimal tip location, no matter if those neonates were preterm or not. This study was registered in inplasy.com with No. INPLASY202280012 (DOI: 10.37766/inplasy2022.8.0012).

1. BACKGROUND

Phlebitis as a common complication associated with PICC lines and the inflammation of the tunica intima of the vein may lead to further consequences, such as discomfort, damage of affected veins, missed medication doses, significant morbidity or mortality, and a subsequent longer hospital stay with increased treatment costs. ¹ PICC is a highly recommended venous infusion technique which provides long‐term intravenous medication and nutrition to critically ill newborns in neonatal intensive care units (NICU). ² , ³ Proper placement of the catheter tip plays a crucial role in ensuring the effectiveness of PICC. The optimal location of a central venous catheter tip is the cavoatrial junction (CAJ) and other acceptable locations include lower third of superior vena cava (SVC) and upper part of the right atrium (RA). ⁴ Although chest radiography has long been a standard approach to verifying the correct tip location after catheterization, ⁵ IC‐ECG has been developed for real‐time monitoring and verification of PICC tip placement. ⁶ , ⁷ Nevertheless, it's noteworthy that it is more difficult to place the tip in a correct location in neonates because of the uncertainty in estimating the depth from the puncture site to the CAJ. ⁴ Furthermore, repeated peripheral venipuncture may cause pain and hinder the neurodevelopment in neonates. Therefore, reposition more complications may occur with neonatal PICC replacement and repositions are needed. ​In clinical studies, incorrect tip placement is accompanied by the risk of phlebitis. ⁸ , ⁹ , ¹⁰ As phlebitis is irreversible, early diagnosis and treatment are particularly important for neonates with PICC. ¹¹ , ¹² , ¹³

The traditional evaluation standard of the positioning accuracy of PICC catheter tip is X‐ray chest examination, ¹⁴ which then was replaced by the “IC‐ECG.” Recently, the IC‐ECG‐guided PICC insertion to support accurate tip placement is available in NICU settings. The IC‐ECG monitor is connected to the neonate via 3 ECG pads and the ECG waveform is observed when the PICC is correctly placed. When the catheter reaches the superior vena cava, the P wave is elevated or amplified. As the catheter continues to reach the junction of the superior vena cava and the right atrium, the P‐wave amplitude increases to a peak. ¹⁵ Variations in P‐wave amplitude are used to adjust the real‐time PICC tip position. ¹⁶ This IC‐ECG‐guided PICC tip positioning technique helps nurses and physicians identify the PICC tip position in real time. ¹⁷ , ¹⁸ This improved approach is expected to help reduce the incidence of phlebitis and is recommended by domestic and foreign guidelines for the treatment of PICC. ¹⁹ , ²⁰ , ²¹ However, several studies have reported the incidence of phlebitis. Huang et al ²² indicated that incidence rate of phlebitis within a week post‐PICC guided by IC‐ECG was not lower than that positioned by traditional measurement of body surface. Jiang et al and Yang et al also reported that nearly 3% patients received the treatment of IC‐ECG‐guided PICC had phlebitis. ²³ , ²⁴ The current limited clinical application report data of IC‐ECG‐guided PICC in neonate and the inconsistent results of related studies for technical limitations of randomised controlled trials might limit the application of that in clinical practice. Therefore, our current study conducted a meta‐analysis of phlebitis prevalence by pooling estimations from individual studies, which hopefully provides evidence for the PICC treatment.

2. METHODS

The meta‐analysis is conducted in accordance with the Preferred Reporting Items for Systematic Evaluation and Meta‐Analysis (PRISMA). ²⁵ As personal data of the participants were not included in this analysis, ethical approval was not required.

2.1. Search strategy

Two researchers (Gan and Hu) searched relevant papers about RCTs of IC‐ECG‐guided PICC tip placement in neonates that were published before 7 July 2022 in PubMed, Google Scholar, Cochrane library and CNKI by using the key words of (“PICC” OR “peripherally inserted central venous catheter” AND “IC‐ECG” OR “intracavitary electrocardiogram” OR “tip placement” AND “phlebitis” AND “neonate” AND “RCT” OR “randomized controlled trial” [MeSH]). No limitation of language was conducted in included study.

2.2. Literature inclusion and exclusion criteria

The following inclusion criteria were implemented: (1) RCTs of intracavitary electrocardiogram‐guided PICC tip placement in the treatment of neonates less than a month of birth; (2) all patients were diagnosed with PICC. The experimental group received treatment with intracavitary electrocardiogram while the control group received the conventional X‐ray chest examination. Other clinical treatments were the same on the two groups. (3) The indicators for phlebitis estimation were reported. The exclusion criteria included (1) duplicate publications; (2) studies whose data were unusable or missing; and (3) reviews, letters, meta‐analysis, and cases.

2.3. Data extraction

Two researchers independently screened and cross‐checked the literature we retrieved against the inclusion and exclusion criteria. In case of disagreement, they discussed or consulted a third party to assist in the verdict. Information including authors, year of publication, basic information about the study population, sample size, treatment regimen, outcome indicators, and other important data were extracted by the two researchers according to the designed data extraction form. If there was not enough relevant outcome data, we would contact the authors whenever possible.

2.4. Quality evaluation

The second version of the Cochrane risk of bias toll (RoB 2.0) ²⁶ was used to evaluate the methodological quality and risk of bias of included RCTs, and any disagreement concerning the quality evaluation was resolved by discussion and consensus. The Cochrane risk of bias tool includes five specific domains: randomization process, deviations from the intended interventions, missing outcome data, measurement of the outcome, and selection of the reported results. ²⁷ The tool provides an overall rating of a study, and the measured results can be classified into low‐risk bias, high‐risk bias, or unclear risk of bias according to specific judging criteria.

2.5. Statistical analysis

The STATA 17.0 software (Stata Corp LLC, Texas) was adopted in this study to perform a meta‐analysis of the included literature. Odds ratio (OR) was used to describe dichotomous variables, mean difference (MD) was used to describe continuity variables, and all effect sizes were expressed as 95% confidence interval (CI). P < 0.05 suggests that the difference between groups was statistically significant. Concerning the clinical and methodological heterogeneity of the included studies, the DerSimonian & Laird method, a random‐effect model, was selected for meta‐analysis in this study. ²⁸ I ² value from 0 to 25% was considered as mild heterogeneity, between 50% and 75% was corresponded to moderate heterogeneity, and between 75% and 100% was an indicator of high heterogeneity. Funnel plot and Egger's test were conducted to determine whether there was a publication bias reflected by the results of meta‐analysis. ²⁹ If a publication bias was identified, the shear and complement method would be used to further evaluate the stability and reliability of the meta‐analysis results. In addition, sensitivity analysis was performed to assess the robustness of the meta‐analysis results.

3. RESULTS

3.1. Study inclusion

As shown in Figure 1, a total of 316 literature entries were obtained from PubMed, Google Scholar, Cochrane library, Embase and CNKI, among which 11 RCTs were selected for further analysis and quantitative synthesis. ³ , ¹⁹ , ²² , ²³ , ²⁴ , ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ Table 1 shows the characteristics of the included studies.

FIGURE 1.

PRISMA flow diagram

TABLE 1.

Characteristics of included studies

Study ID	Total Patients	Phlebitis events(n)				PICC tip verified?	Approach	Catheters	Preterm neonates reported?
		IC⁃ECG group		Comparison group
		Yes	No	Yes	No
Xiao et al, 2019	161	2	76	7	76	Yes	superior vena cava	1.9Fr Medcomp	Yes
Ling et al, 2019	160	1	79	7	73	Yes	superior vena cava	1.9Fr Medcomp	Yes
Huang Y et al, 2020	144	2	70	5	67	Yes	lower limb veins	1.9Fr	Yes
Huang T et al, 2020	62	0	31	2	29	NR	superior vena cava	NR	No
Tang et al, 2021	210	2	103	9	96	Yes	superior vena cava	1.9Fr PRODIMED	Yes
Yu et al, 2021	130	1	54	10	65	Yes	superior vena cava	1.9Fr	No
Yang L et al, 2021	400	6	194	7	193	Yes	superior vena cava	1.9Fr, Medcomp	No
Jiang et al, 2021	172	3	83	6	80	Yes	superior vena cava	1.9Fr UNI	Yes
Yang C et al, 2021	180	0	90	4	86	Yes	lower limb veins	NR	No
Zhang, 2021	142	0	71	5	66	NR	superior vena cava	1.9Fr UNI	No
Zhang et al, 2022	200	1	99	3	97	Yes	superior vena cava	NR	No

3.2. Quality of included studies

The bias risk assessment tool was adopted for quality evaluation. ³⁶ As can be seen in Figure S1 and Figure 2, nine RCTs were confirmed with a low risk of bias, while the remaining two RCTs were classified with some concerns. The domain which was highly rated with some‐concerns was randomization process, in which two RCTs with unknown randomization scheme had clear randomization schemes, and the patients were randomised using a random number table or the computer randomization method.

FIGURE 2.

Risk of bias summary

3.3. Synthesised outcomes

3.3.1. Phlebitis

The eleven studies reported the probability of phlebitis caused by IC‐ECG‐guided PICC tip placement in neonates. Compared with the control group, IC‐ECG‐guided PICC placement in the treatment of neonates significantly reduced the risk of phlebitis. (OR = 0.33, 95% CI 0.19–0.56, P < 0.001, in Figure 3). Moreover, five studies reported the probability of phlebitis caused by IC‐ECG‐guided PICC tip placement in preterm neonates and six studies in term neonates. Subgroup analysis suggested that there was no significant difference of results between the preterm and term group (P = 0.74) (Figure 4).

FIGURE 3.

Forest plots of phlebitis with neonates

FIGURE 4.

Forest plots of phlebitis with preterm neonates and term neonates

3.3.2. Optimal tip location

Ten studies reported the optimal tip location of IC‐ECG‐guided PICC tip placement in neonates. Meta‐analysis results indicated that there was no heterogeneity between studies (I ² = 0.00%, P = 0.53), and a fixed‐effects model was selected. Compared with the control group, IC‐ECG increased the accuracy of optimal tip location in the treatment of neonates (OR = 5.37, 95% CI 3.80–7.59, P < 0.001, in Figure. 5).

FIGURE 5.

Forest plots of optimal tip location

3.3.3. Total complications

Eleven RCTs reported implications associated with IC‐ECG‐guided PICC tip placement in neonates. The results of meta‐analysis identified no heterogeneity among the eleven studies (I ² = 0.00%, P = 0.00), and a fixed‐effects model was selected. Compared with the control group, IC‐ECG‐guided PICC tip placement significantly reduces the occurrence of total complications (OR = 0.23, 95% CI 0.16–0.33, P < 0.001, in Figure S2) in neonates.

3.3.4. Catheter dwell time

Two studies reported reduced catheter dwell time of IC‐ECG‐guided PICC tip placement in neonates (MD = −5.86, 95% CI −16.36 to 4.65, P = 0.00). The results of meta‐analysis identified considerable heterogeneity between studies (I ² = 99.64%) (Figure S3).

3.4. Sensitivity analysis

Sensitivity analysis presented that the studies led to none of significant change in the primary data, suggesting the stability and reliance.

3.5. Publications of bias

Publication bias was assessed by funnel plot and egger's test. As shown by the results in Figure 6, Figures S4 and S5, the shear and complement method present stable result although there is publication bias (P = 0.0019).

FIGURE 6.

Funnel plot of included studies

4. DISCUSSION

Our study set out to systematically compare the incidence of phlebitis in PICC‐treated neonates between IC‐ECG and traditional X‐ray method through a meta‐analysis. Our synthesised data suggested that the incidence of phlebitis was lower in neonates treated with IC‐ECG‐guided PICC tip placement compared with that of X‐ray control. The main strength of this meta‐analysis is that all trials were conducted prospectively to be similar with each other in design. As a result, related heterogeneity across the trials was low.

Phlebitis is known as inflammation and a common complication of PICC, which can bring mechanical risk factors, such as catheter material, size, site and duration, to vein. ³⁷ , ³⁸ This means that different methods of catheter placement led to varying catheter tip positioning accuracy, which may increase the risk of complications, especially in neonates because of significant individual differences in the vascular conditions of them. Among these determinants, accuracy of location was in our study proved to be increased if IC‐ECG could be used as the positioning technique rather than conventional method in PICC. This was in line with previous systematic review reported by Liu et al that the success rate of IC‐ECG‐guided PICC tip position was greater than conventional x‐ray methods in adult patients. ³⁹ Also, Chen et al conducted a meta‐analysis suggested that ECG applied in PICC tip positioning helps improve the accuracy of catheter tip positioning while reducing the incidence of related complications, including phlebitis, which further supported our conclusions despite of a limited sample size. ⁴⁰

Apart from these, characteristics of the X‐ray technique, including weakness of real‐time monitoring, increasing operating time, and radiological damage, may cause the minimised efficiency and accuracy during PICC procedure. ¹⁶ , ⁴¹ In contrast, advantages of IC‐ECG‐guided PICC catheter tip positioning such as early detection of ectopic PICC tip location, simple operation at the bedside which was time‐consuming and reduced physical radiation might also be underlying mechanisms of our conclusion. ⁴² , ⁴³

However, this meta‐analysis also has some limitations. First, participants included in our study were relatively small, partly because of low patient compliance and follow‐up losses. Second, up‐to‐date academic conference literature or unpublished data were not included in our analysis. A larger sample size and more reliable data should be incorporated in future studies to further examine the role of IC‐ECG‐guided PICC placement in phlebitis incidence reduction and placement success improvement.

In summary, IC‐ECG as a technique with high accuracy and feasibility, could guide the PICC tip placement in neonates, and reduce phlebitis rates and total complications with great safety and effectiveness, as well as increase accuracy of optimal tip location, no matter if those neonates were preterm or not. As such, the IC‐ECG‐guided PICC placement could be recommended for the clinical treatment of neonatal diseases.

Supporting information

Figure S1. Risk of bias graph

Figure S2. Forest plots of complications

Figure S3. Forest plots of catheter dwell time

Figure S4. Egger's test of included studies

Figure S5. Shear and complement results

Gan W, Hu L, Luo Y, Tang M. Impact of peripherally inserted central venous catheter‐associated phlebitis in neonate guided by intracavitary electrocardiogram: A systematic review and meta‐analysis of randomised controlled trials. Int Wound J. 2023;20(4):1130‐1138. doi: 10.1111/iwj.13971

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.