Analysis of Peripherally Inserted Central Catheter-Related Complications and Causes: a Retrospective Study of 2974 Children Blood Disease Patients in Single Center in China

Background: The peripherally inserted central catheter (PICC) has been widely used. However, there is still a lack of large sample size-based relevant risk factor investigation in children with blood diseases in china. Methods: We performed a retrospective, the single-center cohort study of child blood disease patients with PICC insertion. Totally, 2974 patients were enrolled for our study. Results: B-ultrasound plus Seldinger technology signicantly improved the success rate of PICC insertion. The most common non-infectious complications were rash, followed by catheter blockage, mechanical phlebitis, and catheter broke. the male, 1-3 years old, Power PICC solo catheter and spring are risk factors for the rash. The power PICC solo catheter was the most important risk factor for catheter blockage. Insertion site under the elbow was the most important risk factor for phlebitis and catheter damage. Conclusion: Our nding rst shed new light on the risk factors associated with PICC complications for Chinese blood disease children. PICC, odds ratios; Cis, APL, HAL, Acute MDS: Myelodysplastic syndrome; HPS, Haemophilic cell syndrome; Juvenile chronic granular SAA, Sever aplastic HA, Hemolytic IST,


Background
The peripherally inserted central catheter (PICC) signi cantly reduces the number of venipunctures in children with chemotherapy or long-term treatment, and the damage to blood vessels caused by chemotherapy drugs, which drastically relieve the pain of children during treatment. Although the PICC has been widely used in the clinic, however, the success rate of related operations and complications, such as phlebitis, rash, and catheter broken after PICC implantation still occur. PICC catheterization has been widely used in clinical practice with a history of more than 80 years. In the late 1990s, PICC was introduced into China and developed rapidly, widely used in tumor chemotherapy, nutritional pathway establishment of premature infants, and tumor chemotherapy for children [1]. It is widely used in children with blood diseases that require long-term chemotherapy and special immunosuppressive agents, but there is still no large number of cases reported in China. So the analysis of the related risk factors of complications is essential. Herein, we, through analyzing different operation methods, the factors affecting the success rate of PICC implantation were summarized. Combined with catheter material, puncture method, insertion site, gender, age, season, and the possible risk factors of different postoperative complications were analyzed.

Methods
Patients A retrospective, the single-center, cohort study of child blood disease patients with PICC insertion was performed to determine the incidence and risk factors associated with PICC complications and the rate of PICC insertion success. 2,974 patients with hematological diseases who underwent PICC placement in Chinese academy of medical sciences blood disease hospital children's blood disease diagnosis and treatment center during 2004.3-2018.12. We tried to nd the critical factor for the successful PICC operation and the risk factors for postoperative complications; we comprehensively analyzed the success rate of PICC operation, the occurrence and type of complications after PICC placement, the development status of PICC approaches or materials in our center.

PICC operating procedures and principles
Catheters were inserted using the sterile technique at the bedside or operating room by quali ed PICC nurses. Before placing the tube, the puncture arm should be thoroughly cleaned with chlorhexidine disinfectant. PICC catheter types of technology as the technology advances, catheter method including the Non-assistive technique (blind insertion) (550 cases), ultrasound (48 cases) and plug technology (1067), plug dingle + ultrasound-guided puncture technology (1309), we will compare the success rate of catheter methods for clinical provide a higher success rate of catheter method; The puncture position of the catheter is under the elbow and above the elbow. The types of catheters include Groshong®NXT ClearVue TM Catheter 4F (4F), Groshong® Catheter 3F (3F), and Power PICC SOLO 2TM catheter (Power PICC SOLO). Generally, the catheter type is selected according to the principle that the ratio of the catheter to vessel diameter(A/B) is < 45% (Fig. S1). There are two kinds of catheter materials, silicone material (3F and 4F) and polyurethane material (Power PICC solo). We will provide a data basis for the clinical selection of catheter types and materials by analyzing the differences between different insertion sites, catheter materials, and the incidence of later complications. The length of the external catheter is generally 4-5cm, of which 2cm is in the decompression sleeve. All PICCs were routinely maintained weekly by PICC nurses using sterile technique. The catheters were ushed with 10 mL normal saline and then sealed with 2 mL heparin saline (50-100 IU) according to institutional maintenance protocol. In the case of contamination, lm crimping, and loosening, the catheter can be nursed at any time.

Complication de nition
Complications were monitored and treated by clinicians and PICC nurses. The common complications in our center included phlebitis, catheter occlusion, accidental withdrawal, breakage, and skin allergy. Rash, Catheter occlusion, breakage, or phlebitis was de ned according to Infusion Nursing Standards of Practice [2].

Statistical analysis
The date was analyzed using the chi-square test and multivariable logistic regression models. These results were presented as adjusted odds ratios (ORs) with 95% con dence intervals (CIs). All statistical tests were two-sided, and p values <0.05 were considered statistically signi cant. Statistical analysis was performed with SPSS software (IBM SPSS statistics 20).

B-ultrasound plus Seldinger technology can signi cantly improve the success rate of PICC insertion
The success rate of four different operation techniques was analyzed, including no assistive technology (A), simple B-ultrasound (B), simple Seldinger technology (C), and B-ultrasound plus Seldinger technology (D). As shown in Table 1, The success rate of group D (99.7%) and C (98.9%) are higher than in other groups, with signi cant statistical difference compared with group A (p=0.00). The success rate of group D is the highest.

Analysis of risk factors of common complications
The common complications in our center included rash (453 cases,15.2%), catheter blockage (433 cases, 14.6%), phlebitis (282 cases, 9.5%), and PICC catheter broken (164 cases, 5.5%). Rare complications included total catheter detachment (34 cases,1.1%), catheter rupture (intravascular 2 cases, 0.06%; Extravascular 9 cases, 0.3%). The speci c values and annual incidence trends are shown in Fig. 1. Here, we mainly analyzed the risk factors of common complications such as rash, catheter blockage, phlebitis, and PICC catheter broken in our center. Phlebitis and catheter broken peak occurred mainly in 2004 to 2013, decreased signi cantly after 2014 ( Fig. 1), considering that the biggest technical change of PICC catheterization in our center since 2014 is that the insertion site is mainly changed from the lower elbow joint to the upper elbow joint, it is preliminarily estimated that may be phlebitis and catheter broken related to the position of catheterization. Fig. 1 shows that the peak of catheter blockage and rash occurred in 2014, and the peak value was in 2015 and 2016, respectively. Considering that the Power PICC solo catheter was used in our center at that time, the possible reason was related to the type of catheter. Therefore, in this paper, we combined the gender, age, puncture location, PICC type, and season to conduct a comprehensive analysis, looking for relevant risk factors of common complications.

1) Analysis of risk factors for rash:
Chi-square test (Table S1) and logistic analysis ( Table 2) showed that males were more likely to have rash than females, and the incidence of rash in children aged 1-3 was highest than other groups, and the incidence of rash was signi cantly different from that in children aged 7-18, with a statistically signi cant difference. The incidence of Power PICC (30.7%) was the highest, followed by 3F (18.4%) and 4F (9.6%). The most rashes occurred in spring (28.5%), followed by summer(27.8%), autumn(23%) and winter(20.8%). The incidence of rashes in spring was statistically different from that in winter. In the chisquare test, the insertion site under the elbow is more likely to have a rash than above the elbow. However, the removal of other factors in logistic analysis suggests that the placement of the catheter is not a risk factor for skin rash. The results suggested that male, 1-3 years old, Power PICC solo catheter and spring were risk factors for the rash occurrence, among which Power PICC solo catheter was the most important risk factor for rash (OR 3.235, 95% CI: 2.255-4.642).

2) Risk factors associated with PICC catheter blockage
Catheter blockage occurred in 433 cases. Chi-square analysis (Table S2) showed that age, insertion site, and catheter type were related to catheter occlusion, and the rate of catheter occlusion was the highest in children aged 11-18 years old(19.6%), followed by 1-3 years old (15.1%), 7-10 years old (14%), and 4-6 years old (12.1%). Power PICC solo catheters have the highest catheter blockage rate (47.7%), with the statistical signi cance of other PICC types. The results of the Logistic regression analysis (Table 3) indicated that the Power PICC solo catheter was the most important risk factor for catheter blockage (OR 4.982, 95% CI: 3.817-6.504).

3) Results of risk factors for phlebitis
There were 283 cases of phlebitis, including 51 cases of grade I, 45 cases of grade II, and 177 cases of grade III. Chi-square and Logistic analysis results showed that (Table S3, Table 4 Table S4, the main factors in uencing the catheter broken include 3F catheters (8.7%), insertion site under the elbow position (8.3%), 1-3 years (7.7%) and autumn (7.1%). Logistic results ( Table 5) also indicated that the insertion site under the elbow position, autumn, spring, 3F catheters were risk factors for catheter damage. The insertion site under the elbow position was the most important risk factor for catheter damage(OR 3.304, 95% CI: 2.237-4.878).

6) Analysis of other postoperative complications:
We preliminarily analyzed the characteristics of 32 cases of accidental catheter detachment, 23 was male and 9 was female, including 27 cases of self-removal, 1 case of dressing change, 4 cases of self-removal due to rash and itching. 2 cases of internal rupture of the catheter, one of which occurred after the catheter was blocked, and the other were found at the nal extubation. All the 9 cases of in vitro rupture of catheters were disconnected near the Luhe joint, among which 6 cases were male, 3 cases were female, 8 cases were 3F catheter, 1 case was 4F catheter, and no rupture was found in the Power PICC SOLO catheter.

Discussion
We summarized 2974 cases of children with catheterization in our center and analyzed PICC catheterization technology and complications after catheterization. According to the development of technology, PICC insertion technology experienced Non-assistive technique (blind insertion), insertion uses ultrasound, plug technology, plug + ultrasound-guided insertion technology, and we compared the success rate of four technicals, results show that the plug + B ultrasonic technology is the best method of PICC insertion.
Skin rash is the most common postoperative complication in our center. The results show that the incidence of skin rash is highest in spring, male children, children aged 1-3 years, and children carried Power PICC SOLO catheters. The analysis reason is that spring is the season prone to allergic diseases; male children aged 1-3 years have high activity and sweat easily under the membrane. The results showed that the incidence of Power PICC SOLO rash was more common than other catheters, which was related to polyurethane material. These results suggest that local care should be strengthened to effectively reduce the occurrence of rashes for young male children who carried Power PICC SOLO catheters.
Catheter blockage is also one of the common complications. A total of 433 cases occurred in our center, with an incidence rate of 14.6%. Combined with the chi-square test and logistic regression analysis, it was found that Power PICC SOLO catheters had the highest rate of catheter blockage and were statistically signi cant. This is related to the fact that there is no three-way valve in front of the Power PICC SOLO catheter, and blood ow is easy to ow back into the catheter, which is also consistent with literature reports [8]. Therefore, for patients who carried Power PICC SOLO catheters, appropriately increasing the number of ushing is the main method to reduce catheter blockage.
There were 283 cases of phlebitis (14.6%), which was higher than that reported in the literature [8]. Our results showed that the main factors affecting the occurrence of phlebitis were related to age, insertion site, and type of catheter. Children aged 7-18 years old with under the elbow insertion site are more prone to phlebitis. Consider that the diameter of the 4F catheter selected for children aged 7-18 years is larger, and under the elbow, insertion site increases the frequency of catheter wear on the vein, it is more likely to have phlebitis. Therefore, avoid placing catheters in areas of exion is very important to reduce phlebitis [9].
There were 164 cases of catheter broken, including 8 cases of in vivo broken and 156 cases of extracorporeal broken. The analysis results showed that: 1-6 years old, puncture under the elbow, 3F catheter was the main cause of catheter damage. This is related to a large amount of activity in children 1-6 years old, the puncture under the elbow joint is affected by the activity of the elbow joint, and the silicone material is related to the literature reports [8]. Joint movement, extracorporeal catheters are easy to be broken and damaged, suggesting that you should also avoid puncture at the joint site.
We preliminary analyzed the characteristics of the cases of accidental catheter detachment and rupture, and the results showed that children younger than three years old are prone to catheter prolapse, and power PICC solo catheter is not prone to rupture.

Conclusion
In summary, 1) B-ultrasound plus Seldinger technology can signi cantly improve the success rate of PICC insertion. 2) The most common non-infectious complications of PICC catheter implantation in children with blood diseases were rash, followed by catheter blockage, mechanical phlebitis, and catheter broke.
3) Male, 1-3 years old, Power PICC solo catheter and spring were risk factors for the rash occurrence, among which Power PICC solo catheter was the most important risk factor for rash. 4) Power PICC solo catheter was the most important risk factor for catheter blockage, followed by the age of 7-11 years old. 5) The insertion site under the elbow was the most important risk factor for phlebitis and catheter damage.