Thrombosis Risk With PICC in Critically Ill Children

Alexander M. Castellino, PhD

December 08, 2016

SAN DIEGO — The dramatic increase in venous thromboembolism (VTE) seen in children's hospitals in the United States may be associated with not just the use of central venous catheters (CVC) but also where they are placed.

Preliminary results from an analysis of 1096 children show that the incidence of CVC-associated VTE was 5.7% across all the children, but 85% of the events were in children with peripherally inserted central catheters (PICCs).

The new finding comes from the CIRCLE (Clot Incidence Rates in Central Lines) study presented here at the American Society of Hematology (ASH) 2016 Annual Meeting (Abstract 419).

The results of our study are cause to pause. Dr Julie Jaffray

"We are putting a lot more central lines in children, and most of them are receiving PICCs. The results of our study are cause to pause," presenter Julie Jaffray, MD, from the Children's Hospital of Los Angeles and The University of Southern California, told Medscape Medical News.

"An overwhelming number of blood clots happen in patients with PICCs placed when compared to tunneled lines," Dr Jaffray said in an ASH press release. "We know children with cancer or who are in the pediatric intensive care unit will need a central line placed. But these lines aren't perfect. The important question is: are we choosing the right line for them or are we just putting in the line that's easier to place?"

"PICCs do not require scheduling a surgery and can typically be placed by a specialized nurse. These conveniences are perhaps the main reasons why PICCs are the choice of CVCs in most practices," she told Medscape Medical News. "But they also may be the biggest reason why VTE rates are going up in children," she said.

Largest Study to Date

Dr Jaffray explained that when the study was planned, special care was taken to see that a sufficient number of children with centrally inserted tunneled lines (TLs) was enrolled so that a comparison was possible.

"This is the largest prospective, observational study to determine VTE rates and risk factors in children," Dr Jaffray said. The final analysis will include 2000 children.

"This study needed to be done," Nicole Kucine, MD, MS, pediatric hematologist-oncologist at Weill Cornell Medicine and New York-Presbyterian, New York City, told Medscape Medical News. "It is a prospective study and was done across diverse major institutions, which provided the large numbers that a trial such as this needed," she said. 

This sentiment was also echoed by Mary Cushman, MD, MSc, from the University of Vermont Medical Center in Burlington. "This is an interesting and an important study," she said. "We use CVCs quite a lot and it is important to know risk factors associated with CVC-related VTEs," she added.

According to Dr Kucine, this study brings to light an important point: "If VTE is higher with PICC lines than with tunneled catheters, are there patient populations where we should consider tunnel catheters over PICCs?"

CIRCLE Study Results

The CIRCLE study is a prospective, multicenter, observational study, enrolling children from four children's hospitals in the United States: Children's Hospital Los Angeles, Children's Hospital of Philadelphia, Texas Children's Hospital, and Nationwide Children's Hospital.

The interim analysis presented at the meeting is based on 1096 children, aged between 6 months and 18 years, who had newly placed PICCs or TLs.

Of 1233 CVCs, 827 (67%) were PICCs and 406 (33%) were tunnel catheters, which included ports, pheresis catheters, Hickman catheters, and Broviac catheters.

Electronic medical records were reviewed from the time of CVC insertion until removal of CVC, death, or transfer 6 months after a diagnosis of VTE or 6 months after CVC placement if no VTE was reported.

"A distinctive feature of our study was that there was no screening for VTE and all VTE cases required diagnostic imaging," Dr Jaffray said.

Most of the previous studies on CVC-related VTE either were retrospective, limited, and specific to patient populations or required radiologic screening for VTE, she explained.

In this interim analysis, children enrolled in the study had a history of cancer (40%), congenital heart disease (9%), previous CVC (28%), infections (20%), or surgery in the last 30 days (18%) and were dependent on total parental nutrition (18%).

Reasons for CVC were varied and included chemotherapy delivery (31%), total parenteral nutrition (21%), medication use (50%), use of blood products or draws (42%), and difficult venous access (30%).

Dr Jaffray explained that if a CVC was placed in a particular limb, then only a VTE in the same side of the body was considered CVC related. Cumulative incidence of CVC-related VTEs were 2% and 7.5% in children receiving TLs and PICCs, respectively — translating to 85% of VTEs occurring in children with PICCs.

Dr Cushman pointed out that results from the CIRCLE study are similar to those reported from her group in hospitalized adult patients. In that study, the use of CVC was associated with a 14-fold increased risk for upper-extremity deep-vein thrombosis and PICCs were associated with significantly higher odds for thrombosis compared with centrally inserted catheters (J Thromb Haemost. 2015;13:2155-2160).

Dr Jaffray also reported on the rates of central line–associated bloodstream infection (CLABSI) — 12% in the total population; however, this time the rates were higher in children receiving TLs (9% vs 16% for PICCs).

"Bloodstream infection was significantly more likely in children receiving TLs over PICCs," Dr Jaffray said.

For Dr Kucine, the CLABSI data were intriguing. "In children, I would expect PICC lines would get more easily contaminated than Mediports," she said.

Dr Jaffray explained to Medscape Medical News that this was a surprising finding and may be due to the fact that tunnel catheters remain inserted for longer time intervals, even for years, compared with PICCs, which typically remain inserted for a few weeks.

"We still have to take a deeper look at catheter-days in patients," she said.

Additionally, children with cancer, especially leukemia, and those with congenital heart disease are at increased risk for VTE. Use of multiple-lumen CVCs was also a risk factor for VTE in children.

Clinical Implications

"VTE has become a huge problem in children in the past 15 years and there is a 70% increase in VTE rates in children of all ages, which is associated with increased mortality and increased hospital stays," Dr Jaffray told Medscape Medical News.

"Our sick children are living longer and we are doing a better job caring for them; we are also taking better care of our children with congenital heart disease, also a risk factor for VTE," she explained.

"Perhaps we are also seeing an increase in VTE because our imaging techniques are now more advanced and we are thinking of clots a lot more," she added.

"But when high-risk children, such as those with leukemia and congenital heart disease, require a CVC, the dramatic increase in PICC-related VTE should provide cause for concern and make clinicians think a little more in what lines to place," Dr Jaffray said.

She is optimistic that the results of their study should help guide clinical decision making. Currently, there are no guidelines for CVC use, Dr Jaffray said. However, the Children's Hospitals' Solutions for Patient Safety — a network of 100 children's hospitals — is attempting to decrease the rates of hospital-acquired problems and VTE is one of them, Dr Jaffray pointed out. As a committee member on the VTE panel, she hopes that this study will provide the basis to create guidelines for CVC insertion regarding catheter type, insertion technique, and need for prophylaxis.

"In clinical practice, anticoagulant therapy is offered on the basis of an overt medical observation suggestive of a clot involvement," Dr Jaffray said. "Thromboses which are diagnosed incidentally, without any clinical symptoms, usually do not receive anticoagulant therapy," she said.

Medscape Medical News asked Dr Kucine what she does in her own clinical practice. "I frequently use PICC lines in oncology patients for specific reasons, including ease of placement and ease of removal in emergency settings such as sepsis," she said.

Children with leukemias often get a PICC line during induction because risk for infection is high; TLs are then used later, starting with consolidation therapy, Dr Kucine explained.

"If the higher CLABSI rates are found to occur after months or years of placement, then the decreased rates of thrombosis might still make TL a more desirable line," Dr Kucine said. "However, because of findings of the increased rates of CLABSI, TLs may be less appealing in certain patient populations, such as a child with [acute lymphocytic leukemia] during induction," Dr Kucine explained.

Dr Jaffray has disclosed no relevant financial relationships.

American Society of Hematology (ASH) 2016 Annual Meeting. Presented December 4, 2016. Abstract. 419

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