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Nursing Interventions to Reduce Peripherally Inserted Central Catheter Occlusion for Cancer Patients

A Systematic Review of Literature

Pan, Mengting RN; Meng, Aifeng RN; Yin, Rong PhD; Zhi, Xiaoxu RN; Du, Shizheng RN; Shi, Ruchu RN; Zhu, Ping RN; Cheng, Fang RN; Sun, Mengqing RN; Li, Cheng RN; Fang, Hong RN

Author Information
doi: 10.1097/NCC.0000000000000664
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In recent years, cancer has become the leading threat to human life and health.1 According to the International Agency for Research on Cancer, 14.1 million new cancer cases were diagnosed, and 8.2 million cancer-related deaths occurred in 2012.2 Cancer treatments include surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, and endocrine therapy. Among them, chemotherapy is the most common, and its main infusion is through peripherally inserted central catheters (PICCs).3 Peripherally inserted central catheters can be inserted by specialists or doctors through peripheral veins (such as the basilica, cephalic, or brachial veins) of the upper extremities under the guidance of ultrasound. General anesthetics, sedation, or surgical procedures are not needed. An x-ray examination is performed to ensure that the tips have reached the lower third of the superior vena cava.4,5 Groshong and power-injectable PICCs generally consist of a wire inside a tube with a length of 50 to 60 cm and material around the wire made of silicone or polyurethane.6,7 Peripherally inserted central catheters typically have a single lumen or 2 lumens with a classification of 1F, 2F, 3F, 4F, and 5F for the diameter of each lumen. 4F and 5F are usually used for adults, whereas 1F is used for infants. At present, PICCs have become increasingly popular because they can be retained for almost a year and avoid the pain of repeated punctures, thereby protecting the superficial vein network in patients’ upper limbs. Peripherally inserted central catheters can be easily repaired and managed by nurses. Moreover, PICC maintenance is relatively easy, considerably reducing medical expenses.8 These characteristics suggest that PICCs can be ideal lines for cancer patients.9

Although PICCs have been widely used clinically, they can have complications, such as upper extremity venous thromboembolism, catheter line-associated bloodstream infection, and occlusion,10,11 the latter being the most common complication.12 Grau et al13 reported a high incidence of occlusion with catheter removal resulting in all cases. Gonsalves et al14 documented that patients with PICCs have a 7% risk of developing occlusion and that the risk of occlusion becomes higher as the number of days of catheter retention increases. When occlusion occurs, the venous pressure of the upper limb increases, resulting in varicosity, which in turn leads to the lymphedema of the limb.15 Occlusion requires catheter removal, which interrupts the treatment and thus aggravates the clinical work, and intensifies the pain and financial burden of the patients.16 Patients who undergo unplanned catheter removal during treatment experience pain, anxiety, helplessness, and fear of a next catheter injection. This negative experience may influence the consideration other patients give to having a PICC.17 A catheter can be easily withdrawn from a patient’s vein without a guidewire; however, reinsertion is likely difficult or even impossible in some situations. Therefore, preventing and treating PICC line occlusion are important clinical care practices. Patients with PICCs must visit a hospital for maintenance at most every 7 days, during which 2% chlorhexidine solution tends to be used for skin antisepsis.18 A nursing care maintenance procedure is used if the PICC is not to be used for a long time.19 Catheter pressure can be monitored to detect occlusion, and a pump can be used for continuous intravenous infusion to maintain the catheter patency.20,21 However, these practices have not been widely applied. In general, in cases of PICC occlusion, thrombolytic therapy is considered a safe and effective strategy for addressing catheter thrombosis. Plasminogen activators, such as urokinase, are commonly used, and 1 mL (urokinase 5000 U) of urokinase solution is typically injected into the catheter for a 30-minute recanalization. If the first attempt fails, the urokinase is typically readministered.22–24 The catheter is removed after 2 failed attempts. Tissue plasminogen activators, such as alteplase, can also be applied in 2-mg/mL doses to manage the occlusion.25

Cancer patients are considered at risk of catheter occlusion and its consequences.26–28 Malignant tumor cells contain cancerous coagulants, which change the blood composition and cause high blood viscosity. In addition, the PICC catheter can remain in the blood vessel for up to 1 year. The long-term floatation of the catheter in the blood vessels affects blood circulation, and blood impinges on the head, consequently deforming the vortex and causing microvascular thrombosis at the tip of the catheter. At the same time, a number of tumor cells can secrete certain tissue factors and mucin, which can damage vascular endothelial cells, induce X-factor activator formation, increase the activity of coagulation factors, and considerably increase the number of fibrinogens.

Chemotherapy often induces nausea and vomiting, resulting in increased chest pressure. It can cause appetite loss and water intake reduction, contributing to increased blood viscosity. In addition, chemotherapy induces fatigue, leading to reduced spontaneous activity of the PICC limb, slowed blood flow, agglutination of red blood cells and platelets, and ultimately catheter occlusion.29,30 Catheter occlusion can negatively impact patients’ mood, decreasing quality of life and possibly delaying treatment. Therefore, nursing interventions that effectively prevent or reduce PICC line occlusion are important.


Basing on a systematic review of the literature, we aimed to evaluate nursing interventions that could decrease PICC occlusion and reduce pain for cancer patients during treatment.


Literature Search

Searches were performed in both English and Chinese databases, including PubMed, Web of Science, Science Direct (Elsevier), EMBASE, Cochrane Library, CNKI, and Wanfang, for relevant articles from their inception up to January 2017. For the English databases, the following medical subject heading terms and text words were used: (“peripheral inserted central catheter” OR “PICC”) AND (“occlusion” OR “catheter blockage” OR “catheter obstruction”). For the Chinese databases, the literature resource “English” was added to the search strategy.

Eligibility Criteria

The literature selection in this present study was based on the following inclusion criteria: patients were of 18 years or older; the catheter must be a PICC line inserted in the upper limbs with the tip position in the superior vena cava regardless of the material (polyurethane or silicon), number of lumens, insertion technique (percutaneous with or without fluoroscopy or ultrasound guidance), thickness, and tip appearance (valued or not valued); prevention data regarding PICC occlusion must be the results section; catheter occlusion or slow infusion occurrence was reported; and articles were available electronically.

Study Procedure

First, the search strategy was performed in the 5 English and 2 Chinese databases to extract the relevant titles and abstracts. Duplicate studies were removed. Then, 2 independent authors (M.P. and X.Z.) reviewed the literature in accordance with the study inclusion criteria. The titles and abstracts were reviewed, and the unrelated studies were excluded. Full texts were evaluated after the primary screening to obtain the final literature. If a conflict occurred between the 2 authors, a third author (C.L.) was designated to decide the outcome.

Data Extraction

The following data were extracted from the selected literature: authors and year of the study, country where the study was performed, subjects, study design, intervention, measurements in the control groups, and the final results.

Quality Critical Appraisal

Two authors (M.P. and X.Z.) independently evaluated each literature’s quality using the Cochrane criteria. The criteria have standards for randomized controlled trials (RCTs) and quasi-experimental studies. Randomized controlled trials included 6 items: randomized method, allocation concealment, blinding of outcome reporting, incomplete data outcomes, intentional analysis, and baseline comparability. The same criteria were applied to the quasi-experimental studies but without the randomized method. Each item can be rated as “yes,” “unclear,” or “no.” Subsequently, all studies can be assigned a quality grade. A quality grade of A implied that the evidence was of high quality and highly recommended to all clinical staff. A grade of B indicated that the evidence was of moderate quality and was applicable to a certain extent. A grade of C meant that the evidence was of low quality and should be used cautiously.

Data Analysis

The extracted data were analyzed by meta-analysis with the RevMan 5.3 software provided by Cochrane. Narrative analysis was used where data were not reported or did not report sufficient information. Meta-analysis was performed using the RevMan 5.3 software. The continuous variable was analyzed to derive the mean and SDs, and a rank variable was converted into a dichotomous variable to obtain percentages. A χ2 test was used to analyze the heterogeneity of the results; results with good heterogeneity would be those with P > .10, I2 < 50%. Then, a fixed-effects model (FEM) was used; if results were heterogeneous (I2 ≥ 50%), a random-effects model was used for further analyses. The weighted mean difference method was applied when the measurement standard was consistent for the continuous variable. Conversely, the standardized mean differences method was used for an inconsistent measurement standard. Relative risk (RR) with 95% confidence interval (CI) was calculated for all analyses.


Search Process

Screening the titles and the abstracts yielded 583 potentially relevant articles (518 and 65 articles in English and Chinese, respectively). After 228 duplicates were excluded, 255 articles were evaluated further, of which 133 full-text articles were requested. Of these, 13 articles satisfied the predefined inclusion criteria for analysis (Figure 1).

Figure 1:
Flowchart of selection process.

Characteristics of Eligible Articles

The details of the 13 articles are in Table 1. These studies originated from China33,35–37,40 (n = 5), the United States31,32,34,41 (n = 4), Italy42,43 (n = 2), Canada38 (n = 1), and Japan39 (n = 1). A total of 3061 patients were included. Nine of the studies were RCTs,31,33–35,38–42 and 4 were quasi-experimental studies.32,36,37,43

Table 1:
Characteristics of Included Studies

Quality Critical Appraisal

Tables 2 and 3 present the quality evaluations of the RCTs and the quasi-experimental studies, respectively. Of the 9 RCTs, 3 studies34,35,39 used randomized methods and explained the implementation of these methods; only 1 of these 3 studies34 described the details of concealment. Blinding of participants or outcome reporting was performed in all 9 studies. One article earned a quality grade of A, and the other 8 received a B. All 4 quasi-experimental studies did not address the allocation concealment and were thus assigned a quality grade of B.

Table 2:
Quality Evaluation on Randomized Controlled Trials

Interventions to Improve Occlusion


Among the 13 studies, 3 evaluated the effect of education on nurses’ knowledge and skills to reduce occlusion.32,36,37 These studies suggested various strategies, such as developing vascular access update classes and implementing the intervention for over 1 year to enhance the knowledge, self-efficacy, and skills of nurses on PICCs. All nurses of the PICC and intravenous teams were requested to participate in a mandatory education program that taught the correct practices to prevent catheter complications. The programs were generally based on a multidisciplinary task force, including lectures about care after PICC insertion and the methods to recognize PICC location via chest x-ray. Other important lessons of the education programs were strategies addressing correct ways of managing catheter complications.

Table 3:
Quality Evaluation on Quasi-experimental Studies


Six studies31,33,38,39,42,43 discussed issues related to types of PICCs, namely, valved and nonvalved catheters. When valved catheters were subjected to a normal central venous pressure, the valves remained closed. However, the valves opened under a positive pressure inside the catheter for the infusion. By contrast, the valves remained open to allow “aspiration” into the catheter under a negative pressure.44,45 Nonvalved catheters do not prevent blood from refluxing, resulting in higher risks of catheter occlusion.


Three studies34,35,41 discussed flushing solutions, including using heparin to flush the catheters, using only normal saline by a fast-slow-fast method every 4 hours, and using both saline and heparin for PICC flushing. Peripherally inserted central catheters in the control groups were flushed with 0.9% sodium chloride in 2 studies, and catheters were flushed every 6 to 8 hours with normal saline.


Only 1 study40 considered the influence of PICC insertion techniques, which were described as the modified Seldinger technique (MST) of insertion with ultrasound guidance in the experimental group and the conventional insertion technique (traditional or blind insertion) in the control group.

Outcome Analysis

The catheters can partly or completely block blood vessels, interfering in the transport of liquids or drugs. This interference can be considered a PICC occlusion. All 13 studies reported catheter occlusion occurrence as complete occlusion (no infusion, no withdrawal), partial occlusion (difficult infusion or withdrawal), partial withdrawal occlusion (infusion but no withdrawal), occlusion solved by flushing or pharmacological action (urokinase), and PICC removal because of irreversible occlusion.


The effect of education for nurses about occlusion was evaluated in the 3 studies.32,36,37 These data were used in the present analysis, with results (I2 = 0% and P = .86) indicating nonsignificant statistical heterogeneity across the 3 studies. Therefore, an FEM was utilized for meta-analysis, and the results revealed that education for nurses to improve their knowledge and skills significantly reduced the incidence of occlusion in experimental groups compared with control groups (RR, 0.31; 95% CI, 0.19–0.51; P < .00001) (Figure 2).

Figure 2:
Effect of education for nurses on occlusion.


In the 6 studies (5 RCTs31,33,38,39,42 and 1 quasi-experimental43), the effect of PICC types on occlusion was evaluated in the experimental group. The data from 5 studies were used for this analysis. The results showed a small statistical heterogeneity with I2 = 0% and P = .44. As shown in Figure 3, meta-analysis based on the FEM model confirmed that the incidence of occlusion was not reduced by the valved PICCs in the experimental group (RR, 0.60; 95% CI, 0.32–1.15; P = .12). Only the quasi-experimental studies demonstrated that the valved PICCs can significantly decrease the incidence of occlusion as compared with nonvalved PICCs (based on calculating the RR value of 0.36).

Figure 3:
Effect of the peripherally inserted central catheter type.


Three studies34,35,41 investigated the effect of flushing solution for catheters but applied different measurements. Thus, the data from these 3 studies cannot be analyzed together. Descriptive analysis was used to assess whether the different flushing solutions can influence the incidence of occlusion. The results implied that the occlusion can be reduced by using heparin or both heparin and saline to flush PICC as compared with using only sodium for flushing. Furthermore, flushing with a fast-slow-fast method every 4 hours was more effective than flushing with normal saline every 6 to 8 hours.


Only 1 study40 reported the effect of PICC insertion techniques on occlusion. The MST insertion technique with ultrasound guidance had no obvious advantages over the conventional insertion technique (traditional, blind insertion).


The toxicities of cancer treatment, the pain of adverse reactions from repeated therapy, and the fear of cancer recurrence seriously adversely influence the quality of life of cancer patients. Peripherally inserted central catheter is the main method of intravenous treatment for cancer patients. If occlusion occurs during therapy on patients with PICCs, patients’ quality of life could decrease even further. Peripherally inserted central catheter occlusion can be prevented through proper interventions.46 The present study aimed to determine appropriate clinical nursing measures that can reduce the adverse effect of occlusion and improve the quality of life of cancer patients with PICCs. A systematic and critical review was performed on the literature about the interventions for reducing the incidence of PICC occlusion.

Education for Nurses

This study showed that the incidence of occlusion can be reduced by education of nurses. Nurses may not be knowledgeable about PICCs. Most oncology nurses have insufficient knowledge about the standardized maintenance measures for a PICC, and irregular maintenance could result in catheter obstruction.47 Furthermore, nurses may not have knowledge regarding how to manage complete occlusion, such as suctioning through a syringe or using urokinase for thrombolytic therapy.48 In the absence of obvious improvements secondary to attempts to remove the occlusion, the catheter will be removed. If a partial occlusion occurs, the liquid would usually be difficult to push when the catheter is flushed; however, this situation may be ignored.49,50 Complete occlusion occurs gradually because of the accumulation from a partial occlusion. Nurses who have placed PICCs as part of their jobs may still have unanswered questions regarding PICCs.51 Oncology nurses themselves believe that such knowledge is necessary and important.50,52,53 Classes or lectures on the manifestations of occlusion, treatments, and practical operation during the therapy of patients receiving cancer treatment through PICCs can be offered to reduce the incidence of occlusion and consequently improve the quality of life of the patients.

Types of PICC

Different types of PICCs have different incidences of occlusion. Catheter occlusion typically results from clotted blood or drug precipitate. A clot is formed at the distal catheter tip if blood reflux occurs or if the infusion pressure becomes equalized, thereby allowing blood retrograde into the catheter. Intraluminal drug precipitation is due to the simultaneous infusion of noncompatible drugs, inadequate flushing in between different infusions, or the infusion of large molecules and highly sticky substances, such as blood products, albumin, and certain nutrients. Infusion speed gradually slows after the use of these drugs as they attach to the catheter wall, ultimately leading to partial or complete occlusion. In most cases, the primary strategy to prevent the accumulation of blood or drugs is flushing the catheter. The presence of valves, regardless of position, can avoid blood reflux when the catheter is disconnected, thereby decreasing the occurrence of occlusion.54,55 Only 1 study38 among the 6 studies did not indicate the advantages of valved PICCs. The total number of indwelling catheter days for the 25 patients with valved PICCs was 898, which is much longer than those for the 28 patients with nonvalved PICCs (658). A longer catheter retention time corresponds to a greater possibility of complications.56,57 Therefore, the incidence of occlusion for valved PICCs is higher than that of nonvalved ones.

Flushing Solution of PICC

A correct flushing procedure can decrease the incidence of occlusion. Three studies introduced different flushing solutions with various liquids and flushing techniques. The results indicated that heparin plays an important role in preventing catheter blockage to maintain catheter patency.58,59 Heparin, generated from mastocytes and basophilic granulocytes in animal bodies, is a mucopolysaccharide ester consisting of glucosamine and glucuronic acid. Heparin cannot directly inactivate blood coagulation factors, although its anticoagulant activity can combine with antithrombin III to implement anticoagulant effects at the pentose active center. Heparin then combines with the lysine of antithrombin III, resulting in changes of the arginine reaction center conformation of antithrombin and producing anticoagulant effects. Another mechanism is that heparin can activate heparin cofactor II to inactivate blood coagulation factor IIa. This mechanism relies not on the electric charge but on the pentose structure.60–62 In general, 10 U/mL heparin is used to lock the catheter in accordance with the “Infusion Therapy Standards of Practice.”63 Pulse flushing of fast-slow-fast may create a vortex in the catheter that helps to remove the clot or drugs on the catheter wall, thereby reducing the incidence of catheter blockage.

PICC Insertion Techniques

Venous access of the percutaneous procedure with ultrasound guidance can provide operators with a general understanding of the upper limb venous network and determine the existence of venous anatomic variants; therefore, this strategy should be considered the criterion standard.64,65 Modified Seldinger technique insertion with ultrasound guidance can improve the insertion success rate in patients. Given that the status of vessels and the appropriate vein for puncture are easier to determine directly with ultrasound guidance, this method can effectively reduce bleeding at the puncture site and decrease catheter blockage significantly.66,67 In this way, the catheter tip can be placed in the right location, and patients can feel more comfortable.68 However, the included study was inconsistent with this conclusion. There were only 4.09% of the patients with good vascular access in the ultrasound-guided MST group, whereas 67.26% of the patients who had poor vascular status were those in whom PICC catheters were placed, the vascular endothelium was easily damaged, and platelet accumulation and PICC occlusion eventually occurred.40


This study has 4 limitations. First, only 1 study was of high quality. Additional high-quality trials are required to advance the science in this field. Second, only 1 study explored flushing solutions and insertion techniques. Therefore, more studies will be required to confirm these findings. Last but not least, other nursing interventions, such as maintenance time of the catheters and the dressing effectiveness, may also affect occlusion occurrence.69–72 Exploration of the effects of these interventions was beyond the scope of the current review.


Effective reduction of the incidence of PICC occlusions can improve patients’ quality of life and reduce unnecessary costs. This systematic literature review found that PICC occlusions were significantly associated with nurses’ knowledge and skills, flushing solution and method, and insertion techniques. We did not find an association between catheter type and PICC occlusion. To reduce occlusion, educational programs focusing on PICC-related knowledge and skills for oncology nurses, MST insertion with ultrasound guidance, using heparin as the flush, and applying the fast-slow-fast flushing method should be encouraged. These measures will very likely lead to prevention or reduction PICC occlusions. At present, nursing interventions are available to resolve a PICC occlusion; however, some of these measures are not yet evidence based. This systematic review provides important information for clinical practice. For hospitals, particularly cancer centers, these conclusions can be used to develop suitable and targeted clinical practices. Nurses can knowledgeably manage occlusion.


The authors thank the project team who supported this study and 3 reviewers for their valuable comments.


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Clinic practice; Meta-analysis; Occlusion; PICC

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