Cancer, HPN, and chemotherapy are recognized risk factors for the development of severe complications (i.e., CRBSI and thrombosis) and mechanical complications (i.e., lumen occlusion, dislocation) in patients with a central VAD [1, 6, 7, 31–33]. The main finding of this study was that, if inserted and managed according to proper evidence-based protocols, PICCs can be safely used in cancer patients receiving chemotherapy and/or HPN, with a low incidence of CRBSI, thrombosis, and mechanical complications; a long catheter life span; and a low probability of catheter removal because of complications.
Based on a large and growing clinical experience, PICCs started to be used frequently in cancer patients [3, 15, 17, 18, 23, 31, 34–39]. However, conflicting evidences on the rate of PICC-related complications were reported in literature in oncology settings. Walshe et al. in 2002 documented an overall complication rate of 10.9 per 1,000 catheter days in 351 patients (58 % outpatients) with 366 PICCs used for multiple purposes (10,562 catheter days) [17], but argued for continued PICC use in the cancer population. Cheong et al. in 2004, in a small-size retrospective study (17 patients, 27 PICCs used for chemotherapy), found an overall complication rate of 40.7 % catheter days [23]. Actually, at the same institution 2 years after the introduction of proper strategies to reduce PICC complications, Yap et al. described in 73 similar patients with 88 PICCs a reduced overall complication rate of 15.9 % or 2 per 1,000 catheter days (P = 0.006) [18]. Worth et al. in 2009 described a CRBSI rate of 6.6 and a thrombosis rate of 7.7 per 1,000 catheter days in oncohematological patients with 75 PICCs [36]. Differently, in a 2011 study regarding 807 PICCs used for chemotherapy or autologous stem cell procedures in 727 patients with solid and hematogenous tumors, Mollee et al. reported a rate of BSI (1.81 per 1,000 catheter days over 41,876 catheter days) and concluded suggesting the use of PICCs in such population [38]. In our study, the overall complication rate was 17.5 %, but just 0.85 per 1,000 catheter days due to the long median PICC duration (about 6 months); moreover, PICCs were removed because of complications only in 7 % of cases.
The rate of central catheter-related complications has changed: CRBSIs, thrombosis, and mechanical complications are lower than those reported in the last 20 years. Nowadays, the goal of “near zero” CRBSI—the most feared complication—is no longer a dream [40, 41]. In recent years, several technological novelties have considerably improved the safety of PICCs (i.e., ultrasound-guided venipuncture of the upper midarm, novel materials, sutureless devices for catheter securement), whereas new policies have successfully decreased the overall risk of complications (well-defined “bundles” of evidence-based interventions, strict policies on hand washing, proper skin antisepsis, training of healthcare professionals, etc.) [14, 18, 37]. In oncology patients, Tian et al. reported that after helpful interventions in reducing complications, the overall PICC complication rate has decreased from 30 to 11 % (P = 0.0004) [37]. Harnage in a medical center—adopting the multimodality “bundle” for infection prevention—has reported for a huge number of PICCs (i.e., 12,577) an incidence of zero BSI per 1,000 catheter days for a period of 7 years [14]. Recently, a prospective study—with a large proportion of oncologic patients enrolled—has reported zero CRBSI and zero thrombosis in HPN patients with 48 PICCs [15]. Similarly, a prospective study at our institution with a small number of PICCs and a limited follow-up (65 PICCs and 18 months, respectively) reported the same results in cancer patients [31].
A critical issue is the scenario where the PICC is used because the in-hospital setting is markedly different from the out-hospital one. Chopra et al. clearly demonstrated that PICCs are associated with a lower risk of BSI (0.5 %) than central venous catheters (2.1 %) in outpatients [42]. Conversely, contradictory data on the rate of PICC-related BSI were described for inpatients (mainly, intensive care unit patients) [16]. In this study, a low incidence of CRBSI was reported (0.05 per 1,000 catheter/days) in non-hospitalized cancer patients. The following key components of our PICC management may as well have been the reason for this result: (a) the consistent use of ultrasound guidance and sutureless devices [31], (b) the exclusive use of single-lumen PICCs [16], and (c) the consistent use of maximal barrier precautions and skin antisepsis with 2 % chlorhexidine [30, 37].
Earlier studies have reported risks of symptomatic catheter-related thrombosis as high as 28 %, but more recent studies suggest a much lower incidence at 5 % or less [17, 43, 44]. Lee et al. reported in a prospective study over 76,713 patient days (500 cancer patients, 444 VADs with 65 % PICCs) that the incidence of symptomatic catheter-related thrombosis was 4.3 % or 0.3 per 1,000 catheter days [44]. Chopra et al. have recently reported in a meta-analysis that PICCs were associated with a higher risk of deep vein thrombosis in cancer patients [45]. Nevertheless, Tian et al. in a study on cancer patients with 267 PICCs reported that the incidence of thrombosis has decreased from 2.9 to 0.61 % using relatively simple and inexpensive interventions [37].
In this study, a low incidence of symptomatic PICC-related thrombosis was reported (1.1 %; 0.05 per 1,000 catheter days). This result was probably due to several factors: (a) the consistent use of ultrasound guidance for PICC placement, (b) the consistent choice of deep veins of the upper midarm (mainly, the basilic vein), (c) the systematic choice of a vein with an appropriate ratio between catheter diameter and vein diameter (i.e., 1:3 ratio), (d) the consistent use of single-lumen PICCs, (e) the consistent use of sutureless devices, (f) the prevalent use of a PICC of relatively small diameter (i.e., 4 Fr), and (g) the consistent control of the position of the catheter tip, with reposition of the catheter if the tip of the PICC was not at the appropriate location. Indeed, data from literature demonstrated that the risk of thrombosis decreased when PICCs were placed according to this decision-making [31, 43, 45]. Moreover, our study was not designed to investigate the incidence of asymptomatic thrombosis; thus, the incidence most likely would have been higher if our patients systematically had been explored using ultrasound.
On the whole, the reasons for discrepancies between reported rates of PICC-related complications are not clearly known, but may include advances in catheter materials, securement devices, and insertion technique; differences in patient populations (e.g., non- and cancer patients, in- and outpatients); and design (e.g., retrospective vs. prospective) and methodological limitations of some of the studies (e.g., earlier experiences, small-size samples, different definitions of complications).
Anecdotally, in this paper was reported a case series of seven patients with a PICC in site for more than 2 years, with two PICCs lasting more than 3 years. Although these PICCs were used also in the hospital setting—with a higher risk of complications than the home setting [42]—as well as for HPN, chemotherapy, and drawing blood, no infectious complications or thrombosis occurred and the PICCs were not removed because of complications. Despite the very small number of cases, it seems that PICCs, when optimally managed, can be even successfully used for very long periods in cancer patients requiring a long-term vascular access.
In summary, we believe that three key elements played a pivotal role to reduce the overall rate of complications and prolong the PICC life span in our patient population: (a) the availability of a knowledgeable and experienced central venous access team; (b) the use of ultrasound-guided venipuncture; and (c) a proper patients’ education and a specific caregivers’ training, along with close monitoring by trained nurses at home.
Strengths and limitations of the study
To the best of our knowledge, this is the largest study reporting catheter-related complications in a case series of non-hospitalized cancer patients with 269 PICCs used for chemotherapy and/or HPN for a long period (5 years and over 55,000 catheter days). If compared with previous studies in this field, our study has some relevant and original features: (1) data were collected through a clinical study and not from a database, registry, or questionnaire; (2) it was a prospective study; (3) only cancer patients were enrolled; (4) only outpatients were enrolled; (5) most of the enrolled patients (71 %) were receiving chemotherapy during the course of the study; (6) all PICCs were inserted with the same evidence-based protocol and all patients received the same evidence-based protocol of maintenance/care at home; (7) the median dwell time for PICCs was very long (more than 6 months); and (8) no patient was lost at follow-up.
Our study presented several limitations. First, this was a single-center study carried out by teams with a well-established experience in PICC placement and home management, as well as a well-defined collaboration with the oncologists. Second, in this study, almost all patients with solid tumors were enrolled; therefore, our results may not be extended to all cancer patients (e.g., hematological malignancies). Third, only non-hospitalized cancer patients receiving chemotherapy and/or HPN—always assisted at home by trained caregivers and specifically trained nurses—were included. Therefore, because this is a small subset of cancer patients, our results may not be generalizable to inpatient populations or different outpatient settings (e.g., patients receiving chemotherapy alone). Fourth, patient-related factors, such as impingement on quality of life and cost of VAD maintenance, have not been explored in this study. Finally, this was an observational study, and a trial comparing PICCs with well-defined long-term VADs (i.e., tunneled catheters and ports) needs to be carried out to recommend the use of PICCs as long-term VADs in non-hospitalized cancer patients.
Despite several limitations, our study suggests that PICCs can be successfully utilized as safe and long-lasting VADs in non-hospitalized cancer patients recording a low and acceptable incidence of overall complications.