Effects of Peripherally inserted Central Catheter (PICC) materials and designs on reduction of PICC‐related complications: A systematic review and meta‐analysis

Abstract

Studies showed that integrating coating or valve into Peripherally Inserted Central (PICC) can prevent related complications. However, data regarding efficiency were controversial. Therefore, a systematic review was needed to analyse the effect of PICC materials and designs on reduction of PICC‐related complications. We searched PubMed, Cochrane library, EMbase, grey literature and referent literature from inception to 5 August 2022. Randomized controlled trials (RCTs) and case–control study were included. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook for Systematic Reviews (V5.1.0), case–control study was assessed by the Newcastle‐Ottawa Scale. Data were analysed using Review Manager (v5.3.0). A total of 10 RCTs and one case–control study were included. Meta‐analysis results showed that PICC designs reduce the incidence of obstruction, and at the critical value of PICC‐associated bloodstream infection, but may have no effects on other complications. Based on the literature reviewed, we can only say PICC new materials did not reflect significant reduction on complications, what's more, the result needs more multicentre, large RCTs to support. We suggested clinicians combine descriptive research and cost‐effect analysis to select appropriate PICC materials and designs for patients.

1. BACKGROUND

Peripherally Inserted Central Catheter (PICC) refers to the catheterization of the catheter through the patient's peripheral venous puncture, so that the tip of the catheter reaches the lower 1/3 of the superior vena cava, or the central venous catheter where the superior vena cava joins the right atrium. PICCs are used for intravenous fluids, medications, blood products and for blood sampling to prevent frequent venipuncture, which can enable treatment in inpatient, outpatient and community‐based. ¹ The study showed that about one‐third of PICCs failed prior to completion of treatment, due to infections, blockage, dislodgement, vein thrombosis, occlusion and so on. ² The United States National Healthcare Safety Network reported that Catheter‐Related Blood Stream Infection (CRBSI) rates up to 3.5%, ³ another study which included France, Germany, Italy and the United Kingdom estimated that CRBSI was associated with costs of between EUR 35.9 and EUR 163.9 million per year in these countries. ⁴ It reported that symptomatic thrombosis incidence rate can be up to 3%–20%, ⁵ , ⁶ , ⁷ , ⁸ , ⁹ asymptomatic thrombosis can be 61.9%, ¹⁰ and 25%–30% ¹¹ of catheters were occluded.

Integrating antithrombotic and anti‐infective technologies into the PICC materials are potential innovations to prevent complications. There are four common antithrombotic materials, which include hydrophilic surfaces, hydrophobic surfaces, biological surfaces and added drugs. ¹² Cochrane review ¹³ which included 57 studies concluded that impregnation, coating or bonding central venous catheters (CVCs) significantly reduced catheter‐associated blood stream Infection (CABSI) risk. An animal experiment ¹⁴ demonstrated that Chlorhexidine gluconate (CHG) coating controlled the fibrin sheath development after 30 days in situ, compared with uncoated catheters. Also, a study ¹⁵ showed that heparin coating was thought to reduce bacterial growth via a prevention of fibrin deposition and thrombus formation in the catheters. Ullman AJ ¹⁶ team conducted a protocol of a multicentre, parallel group, superiority randomized controlled trial, and compared the effect of hydrophobic PICC (with pressure activated valve), chlorhexidine gluconate‐impregnated PICC (with external clamp) and conventional polyurethane PICC (with external clamp) on reduction of infections and clots. An evidence‐based study ¹⁷ which was published in 2016 suggested that antimicrobial PICCs may reduce CLABSI. However, the team of Ullman AJ conducted ¹⁸ an analysis of 42 562 hospitalized patients and concluded that antimicrobial and antithrombogenic PICCs were not associated with a reduction in major catheter complications.

PICC design included valves built into the device to reduce occlusion. It prevents reflux of blood from catheter tip to the distal end of the catheter. One research ¹⁹ showed that proximal valve polyurethane PICCs were more durable than distal valve silicone PICCs. However, a randomized controlled trial (RCT) concluded that no differences in device longevity or occlusion rates were observed when three different valve types were compared head to head. ²⁰ So, the effects of PICC designs on complications remained elusive.

Overall, Since 2016 several new studies to compare the effect of coating PICC were published, there were also necessary to know the effects of PICC valve design. Therefore, we would update the systematic review of PICC materials published in 2016, and conduct a new systematic review to compare the effect of PICC valve design, to provide evidence for clinical practice.

2. METHODS

2.1. Search strategy

PubMed, Cochrane library, Embase, grey literature and referent literature were searched from inception to 5 August 2022. The search strategies were (‘PICC’ OR ‘peripheral catheterization*’ OR ‘peripherally inserted central catheter*’ OR ‘peripheral arterial catheterization*’ OR ‘peripheral venous catheterization*’) AND (‘Chlorhexidine’ OR ‘Antithrombogenic’ OR ‘Antimicrobial’ OR ‘hydrophobic’ OR ‘polyurethane’ OR ‘fluorinated’ OR ‘Anti‐infective’ OR ‘minocycline‐rifampicin’ OR ‘chlorhexidine gluconate’ OR ‘CHG’ OR ‘Distal Valve’ OR ‘Proximal Valve’ OR ‘external clamp’ OR ‘internal valve’). An experienced expert was invited to review the selected search strategy. In addition, we manually searched for the unpublished literature and also tried to contact the authors via email to obtain unreliable literature.

2.2. Eligibility criteria

2.2.1. Types of participants

Patients with PICC were included. We did not limit the age, type of diseases, inpatient or outpatient.

2.2.2. Types of intervention

We considered intervention as any PICC with new materials or designs, included antimicrobial impregnated PICC, hydrophobic PICC, antibiotic impregnated PICC, proximal valved PICC, solo valved PICC, pressure activated safety valved PICC and Groshong valved PICC. Also, both simple intervention and multiple interventions were included.

2.2.3. Comparators

The control group was the control group set in each study was unified into the traditional PICC.

2.2.4. Outcome measures

The outcomes were PICC‐associated BSI, thrombosis, occlusion and dislodgement.

2.2.5. Types of study

RCTs and case–control study were included. Conference presentations, thesis and abstracts were excluded.

2.3. Study selection

All studies were selected in the EndNote X8 which was a literature management software. Two authors independently reviewed the titles and abstracts to screen studies, then reviewed the full‐text to include studies for quantitative analysis. A third reviewer would be invited when there were differences between the two authors.

2.4. Data extraction

Two authors independently extracted data according to a predesigned form, which included study characteristics (first author, year, country, study type), patient characteristics (sample type, sample size, male/female, age, interventions and controls) and outcomes (incidence of CRSBI, thrombus, occlusion and dislodgement).

2.5. Quality assessment

Two reviewers independently assessed the risk of bias of RCT using the Cochrane Handbook for Systematic Reviews (V5.1.0), ²¹ which included random sequence generation, allocation concealment, participants/personnel blinding, outcome assessor blinding, incomplete outcome data, selective reporting and other bias. Case–control study was assessed by the Newcastle‐Ottawa Scale (NOS), ²² which includes ‘the selection of the study groups’, ‘the comparability of the groups’ and ‘the ascertainment of either the exposure or outcome of interest for case‐control or cohort studies, respectively’. A third reviewer would be invited when there were differences between the two authors.

2.6. Data synthesis and statistical methods

We performed meta‐analysis of the included trials with Review Manager 5.3 (Revman 5.3). For dichotomous outcomes, we used the OR and 95% CIs to measure treatment effects. For the heterogeneity test, if p ≥ 0.1, I ² < 50%, the fixed effects model was used for analysis; otherwise, we will consider there is a large heterogeneity between the studies and sensitivity analysis and subgroup analysis will be performed to find the source of heterogeneity. If data cannot be combined quantitatively, we will perform qualitative analysis.

PROSPERO registration number: CRD42022356087.

3. RESULTS

3.1. Study inclusion

The initial literature search retrieved 1680 potentially eligible studies. After screening titles, abstracts and full‐text review, 11 studies were included in review, two studies included three comparisons of interventions and split into four studies, so, 13 studies were analysed. The study flow diagram is shown in Figure 1. Among the 11 studies with 2346 patients, 10 studies were RCT, one study was case–control study, one study was from Asia, 10 studies were from Europe; the details are shown in Table 1.

FIGURE 1.

Study flow diagram. CVC, Central venous catheter; PICC, Peripherally Inserted Central Catheter.

TABLE 1.

Characteristics of studies included in the meta‐analysis.

Protocol	Author/year	Study type	Country	Sample type	Age		Male/Female		Interventions		Outcomes
					Intervention group	Control group	Intervention group	Control group	Intervention group	Control group
PICC new materials	Nicole C. Gavin 2020	RCT	Australia	Adult	59 ± 15	62 ± 16	28/56	24/53	Hydrophobic polyurethane PICC with a proximal valve	Traditional PICC	1, 2, 3, 4
	M. Klemme 2019	RCT	Germany，Italy	Neonates	NA	NA	17/37	18/34	Antibiotic‐impregnated PICC	Traditional PICC	2, 4
	Susan Storey 2016	RCT	USA	Adult	62	64	NA	NA	Chlorhexidine PICC	Traditional PICC	2, 4
	Evgenia Kagan 2018	Case–control study	USA	Adult	59	55	49/93	117/263	Antimicrobial PICC	Traditional PICC	2
	Hiromichi Miyagaki 2012	RCT	Japan	Adult	64.5 (56 ~ 80)	67 (58 ~ 80)	13/14	11/11	Polyurethane catheter with open‐end tip	Traditional PICC	1, 2, 4
	Ruth Gilbert 2019	RCT	England	Neonatal	NA	NA	214/430	225/431	Antimicrobial impregnated PICC	Traditional PICC	2
PICC new designs	Cheng K 2010	RCT	\	Adult	49.0 ± 15.8	51.9 ± 17.9	119/198	128/194	Proximal valve polyurethane PICCs	Traditional PICC	1, 2, 3
	Mauro Pittiruti 2014	RCT	Italy	Adult	64 ± 12.1	62 ± 14.5	22/61	19/59	Solo valve	Traditional PICC	4
	Mauro Pittiruti 2014 2	RCT	Italy	Adult	61 ± 10.1	62 ± 14.5	22/60	19/59	Pressure activated safety valve	Traditional PICC	4
	Tricia Kleidon 2017	RCT	Australia	Paediatric	7.1 ± 5.1	7.5 ± 4.9	45/75	41/75	PICC with internal valve	Traditional PICC	1, 2, 3, 4
	Eric K 2001	RCT	USA	Adult	47.5 (18 ~ 85)	52.1 (18 ~ 89)	35/52	31/48	Proximal valve	Traditional PICC	1, 2, 3
	Andrew J. Johnston 2012	RCT	UK	Adult	53.7 ± 18.7	60.7 ± 14.9	20/34	12/34	Groshong valve	Traditional PICC	1
	Andrew J. Johnston 2012 2	RCT	UK	Adult	58.5 ± 16.1	60.7 ± 14.9	22/33	12/34	PICC with pressure activated safety valve	Traditional PICC	1

Note: Outcome 1: Occlusion; outcome 2: PICC‐associated BSI; outcome 3: Dislodgement; outcome 4: PICC‐associated thrombosis.

Abbreviations: NA, Not available; PICC, Peripherally inserted central catheters; RCTs, Randomized controlled trials.

3.2. Quality of inclusion study

Ten studies were RCT, the risk of bias assessed by Cochrane Handbook for Systematic Reviews (V5.1.0), the red, yellow and green represented high, unclear and low risk of bias, one study reported no participants and personnel blinding, which was high‐risk bias, other studies reported unclear or blind for participants and personnel. One case–control study was included, and was evaluated by NOS. The study population were patients with CLABSI, the origin of infection was PICC, and the diagnosis were made by microbiological laboratory, and data were collected continuously for 4 years, the control group consisted of patients without PICC CLABSI. Also, the study analysed potential risk factors, and the data can be found in the hospital charts, the exposure factors are the same, the quality score was 5 points, the quality of study was medium. Details are shown in Figure 2 and Table 2.

FIGURE 2.

Risk of bias.

TABLE 2.

Risk of bias of included case–control studies.

Study	Representativeness of the exposed cohort	Selection of the non‐exposed cohort	Ascertainment of exposure	Demonstration that outcome of interest was not present at the start of study	Comparability of cohorts on the basis of the design or analysis	Assessment of outcome	Was followed‐up long enough for outcomes to occur	Adequacy of follow‐up of cohorts	Quality score
Evgenia Kagan 2018	*	*	/	*	*	*	/	/	5

3.3. Synthesized outcomes

3.3.1. Occlusion

Seven studies (five studies were new design, two studies were new materials) were included in these outcomes. There was no significant heterogeneity among the studies of new design (I ² = 11%, p = 0.34) and new materials (I ² = 0%, p = 0.49), so we chose the fixed effects model. The results revealed that PICC new designs may reduce incidence of occlusion (p = 0.02), but the evidence of new materials was poor (p = 0.25). For details see Figure 3.

FIGURE 3.

Forest of occlusion.

3.3.2. Peripherally inserted central catheter‐associated bloodstream infection

PICC‐associated BSI included nine studies (three studies were new design, six studies were new materials), we selected the fixed effects model because the heterogeneity were not significant of new design (I ² = 0%, p = 0.37) and new materials (I ² = 50%, p = 0.07). The results did not demonstrate reduction of PICC‐associated BSI of new designs (p = 0.05) and materials (p = 0.26), but new designs were at the critical value, which may be small sample size and sample inadequately powered to measure BSIs. For details see Figure 4.

FIGURE 4.

Forest of Peripherally Inserted Central Catheter‐associated bloodstream infection.

3.3.3. Dislodgement

Four studies (three studies were new design, one study was new material) were included in dislodgement. There was no significant heterogeneity among the studies of new design (I ² = 0%, p = 0.92), we selected the fixed effects model. The included studies did not fully demonstrate the effectiveness of new materials and designs on dislodgement, which may be due to the small number of included studies. For details see Figure 5.

FIGURE 5.

Forest of dislodgement.

3.3.4. PICC‐associated thrombosis

Six studies (three studies were new design, three studies were new materials) reported PICC‐associated thrombosis, no statistical heterogeneity was observed among the studies of new deigns (I ² = 11%, p = 0.33) and new materials (I ² = 0%, p = 0.75). There were no statistical differences of the results of both designs and materials. For details see Figure 6.

FIGURE 6.

Forest of Peripherally Inserted Central Catheter‐associated thrombosis.

3.3.5. Sensitivity analysis

We performed sensitivity analysis by sequential culling to test stability. For every outcome, one study was excluded in turn, and the remaining studies were meta‐analysed and merged, We found the models of the four outcomes were stable.

4. DISCUSSION

The result of our meta‐analysis showed that new designs of PICC can reduce incidence of occlusion, but it was not statistically significant for other complications, while the new PICC material had no effect on all complications, but the effect of infection was at the cut‐off value of statistical variability. Seven studies reported randomized method, four studies did not mention. Five studies reported allocation concealment and is low‐risk bias, one study reported no participants and personnel blinding, which were high‐risk bias, other studies were unclear or report blind. The quality of the case–control study was medium. Overall, the quality of included studies was reliable, but more studies with large samples are needed to verify.

4.1. The effect of new materials on PICC‐related complications

Fibrin sheath was triggered by the vessel injury during catheter implantation, and covered the entire catheter within a few days. ²³ Fibrin sheath was associated with CLABSI pathogens, which enter the bloodstream through both extraluminal and inner luminal wall of implanted catheter, seeding of bacterial pathogens from bioflm also induces CLABSI. ²⁴ Bio‐passive surface coated to target both thrombosis and infection gradually was a successful approach for medical devices and implants. Gavin et al. ²⁵ showed the effectiveness of PICC new materials (hydrophobic polyurethane PICC) in an adult population, not only in‐patients, but also patients discharged from hospital. A systematic review ¹⁷ suggested that antimicrobial PICCs may reduce CLABSI for the high‐risk population. Takezawa et al. ²⁶ showed that synthetic polymer‐coated PICC is safe and has less catheter complications. However, a prospective cohort study involving 52 hospitals showed that antimicrobial and antithrombogenic PICCs cannot reduce catheter complications, and proposed more attention to balance benefits against cost. ¹⁶ Also, antibiotic coated CVCs have limited clinical success in resisting bloodstream infection and may increase the risk of emerging antibiotic resistant strains, and is not widely recommended, except in high‐risk patient populations, for example, surgical patients with cancer or infection, immunocompromised, adult burn patients or infants. ¹⁷ Therefore, the effect of PICC new materials on complications was still unclear, and need more trials to innovate new materials.

4.2. The effect of new designs on PICC‐related complications

PICC valves designed can reduce reflux of blood from the catheter tip back into the lumen as a means to prevent occlusion. Significantly lower incidence of complications was found when compared with the open‐ended catheters, ²⁷ and a study showed that proximal valve polyurethane PICCs ¹⁹ were more durable than traditional PICCs. However, Pittiruti et al. ²⁸ showed no clinical advantages of valved versus non‐valved PICCs, also, another study ²⁰ showed that valved PICCs do not appear to influence PICC occlusion rates. Our study showed that valved PICC may reduce complications, the reasons may be the control group included were not only valved PICC, but also mixed interventions of different PICC materials.

4.3. Limitations

This study has several limitations. Firstly, limited number of studies were included, and only one study was from Asia, study representation may not be strong. Secondly, because too few studies were included, we did not limit the population characteristics of the included studies, and clinical heterogeneity may be observed. Thirdly, the control group was not uniform and may have an impact on heterogeneity. Fourthly, studies did not have cost–benefit analyses, could not inform clinicians to choose better. Finally, the quality of the included study was not high, more multicentre, large‐sample RCTs are needed.

5. CONCLUSION

We concluded that PICC new designs may reduce the incidence of catheter obstruction and PICC‐associated BSI. The impact of PICC new materials was inconclusive and may not demonstrate a reduction on complications based on the literature reviewed. We suggested that the clinicians should consider cost‐effect analysis to select appropriate PICC materials and designs for patients.

CONFLICT OF INTEREST STATEMENT

All authors disclosed no relevant relationships.

Supporting information

Data S1. Supporting information.

Ding N, Peng H, Zhao W, et al. Effects of Peripherally inserted Central Catheter (PICC) materials and designs on reduction of PICC‐related complications: A systematic review and meta‐analysis. Int Wound J. 2024;21(3):e14468. doi: 10.1111/iwj.14468

DATA AVAILABILITY STATEMENT

The data that supports the findings of this study are available in the supplementary material of this article