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. 2024 May 6;19(5):e0300425. doi: 10.1371/journal.pone.0300425

Risk of deep venous thrombosis associated with peripherally inserted central catheter: A retrospective cohort study of 11.588 catheters in Brazil

Telma Christina do Campo Silva 1,*, Luciene Muniz Braga 2, Jose Mauro Vieira Junior 3
Editor: Eyüp Serhat Çalık4
PMCID: PMC11073680  PMID: 38709807

Abstract

Introduction

Deep Venous Thrombosis (DVT) due to Peripherally Inserted Central Catheter (PICC) is one of the most threatening complications after device insertion.

Objective

To assess the rate of PICC-associated DVT and analyze the risk factors associated with this event in cancer and critically ill patients.

Methods

We conducted a descriptive, retrospective cohort study with 11,588 PICCs from December 2014 to December 2019. Patients ≥ 18 years receiving a PICC were included. Pre-and post-puncture variables were collected and a logistic regression was used to identify the independent factors associated with the risk of DVT.

Results

The DVT prevalence was 1.8% (n = 213). The median length of PICC use was 15.3 days. The median age was 75 years (18; 107) and 52% were men, 53.5% were critically ill and 29.1% oncological patients. The most common indications for PICC’s were intravenous antibiotics (79.1%). Notably, 91.5% of PICC showed a catheter-to-vein ratio of no more than 33%. The tip location method with intracavitary electrocardiogram was used in 43%. Most catheters (67.9%) were electively removed at the end of intravenous therapy. After adjusting for cancer profile ou chemotherapy, regression anaysis revealed that age (OR 1.011; 95% CI 1.002–1.020), previous DVT (OR 1.96; 95% CI 1.12–3.44) and obstruction of the device (OR 1.60; 95% CI 1.05–2.42) were independent factors associated with PICC-associated DVT, whereas the use of an anticoagulant regimen was a protective variable (OR 0.73; 95% CI 0.54–0.99).

Conclusion

PICC is a safe and suitable intravenous device for medium and long-term therapy, with low rates of DVT even in a cohort of critically ill and cancer patients.

Introduction

There have been several advancements available for patients needing prolonged intravenous therapy, from which the peripherally inserted central catheter (PICC) is highlighted for having advantages over other devices, including a reduced risk of complications related to insertion, such as pneumothorax, easy maintenance and dehospitalization of patients undergoing antibiotic therapy or chemotherapy [14].

The main indications for PICC are intravenous therapy for ≥14 days, intravenous therapy with incompatibility for peripheral venous access, critically-ill patients with bleeding disorders, the continuous use of vesicant infusions, such as parenteral nutrition or irritant solutions, cyclic chemotherapy treatment, and patients under palliative care [5].

In order to obtain good results with PICC use, the Infusion Nurses Society (INS) guidelines recommend vessel occupancy ≤ 45%, and insertion of the catheter in ideal sites using the zone insertion method (ZIM). Technologies related to PICC insertion, device characteristics, employing the best practices, as the use of ultrasound to ensure puncture in the ideal zone, calculation of vessel occupancy according to the catheter used, and the advent of vascular access teams have improved the results of these catheters [1,69].

However, PICC use is still associated with risks such as infection and deep venous thrombosis (DVT). Catheter-related DVT is a serious vascular access complication that can lead to the development of pulmonary thromboembolism (PTE), infection, access dysfunction, and post-thrombotic syndrome. These complications can not only interrupt the treatment, but also in addition increase costs, morbidity, and mortality [8,10].

The worldwide use of PICC is growing and services experiences with its employement have been described. Here, our objective is to describe the actual rate and risk factors associated with symptomatic DVT in PICC patients, in a tertiary brazilian hospital, particularly in a scenario of cancer and critically-ill patients.

Materials and methods

Study design and recruitment criteria

This study was a descriptive and retrospective cohort study involving all adult patients at the Sírio Libanês Hospital (HSL), a tertiary, high acuity, JCI-accredited hospital in São Paulo, Brazil, undergoing PICC insertion from December 2014 to December 2019.

The Research Electronic Data Capture (REDCap) was used for data collection. The patients with PICC-associated DVT diagnosis were compared to the rest of the database. Inpatients and outpatients with PICCs dwell time ≥3 days were included [11]. (Fig 1)

Fig 1. Data collection flowchart.

Fig 1

Venous Doppler was performed only in patients with symptoms, such as pain, increased arm circumference, pain in the axillary region, and edema of the extremities. An active ultrasound-armed surveillance search for PICC-associated DVT was not routinely performed.

Inclusion and exclusion criteria

Inclusion Criteria: Adult in and outpatients, undergoing PICC insertion using the modified Seldinger technique by the exclusive dedicated vascular access nurses team at the HSL.

Exclusion criteria: Patients with a catheterization duration of ≤ 3 days; < 18 years-old.

Study variables

The variables analyzed were age, sex, reason and site of admission, severity of the disease, oncological or surgical patient profile, previous DVT, use of oral or parenteral anticoagulants, number of vein puncture attempts, punctured limb, puncture area, chosen venous access, vessel occupancy, type of PICC, catheter tip location at the end of the procedure.

Data collection and quality assurance

All patients used catheters from a single brand, chosen by the institution (Becton Dickinson—BD®). The device materials were polyurethane and silicone. Open-tip and valved catheters (anti-reflux, Groshong®) were used.

The ideal zone in the green area was the first choice for PICC insertion. All catheters were inserted by a team of ten fully trainned and dedicated nurses, using the ultrasound-guided at the bedside or in the operating room, with maximum barrier protection [7].

In relation to TIP location assessing method, the first choice as October 2016 was intracavitary ECG and in cases of impossibility of using this technology, the navigation resource with confirmation through chest x-ray or scopy was used.

In cases where the x-ray was used, the tip location was defined according Sweet-spot. The technique was created to reduce complications caused by vascular access. A rectangular template is superimposed on a frontal radiograph whose internal margins are acceptable for the catheter tip position. It has fixed portions called A, B and C. Measurement of catheter occupancy in relation to vein size was collected directly by Site-Rite 5® or Site-Rite 8® ultrasound equipment [6,12].

The current Infusion Nurses Society guidelines, recommend the use of PICC`s with a catheter-to-vein ratio of no more than 45% prior to insertion of a vascular access device in the upper extremity, and we follow this guideline [6].

The precautions recommended for PICC maintenance bundle were performed first by dressing with gauze and sterile transparent film, and eventually changed to a medicated transparent film after 24 h, and a fixation device without suture (Statlock®) was used in all devices in order to avoid dislodgement.

Statistical methods

The continuous variables were analyzed for distribution parametric versus nonparametric and were presented as median and interquartil interval (IQ) for nonparametric and mean ± standard deviation (SD) for continuous parametric variables. Groups (PICC-related DVT and the controls) were compared using the Student’s t-test or the Mann-Whitney test, when applicable. The categorical variables were described using absolute and relative frequencies; additionally, the difference was verified with the chi-square or exact tests (Fisher’s exact test or likelihood ratio test).

The odds ratio (OR) of each variable evaluated were estimated for the occurrence of DVT with the respective 95% confidence intervals (CI) using unadjusted and adjusted logistic regression. A joint model was built to explain the occurrence of DVT using multiple logistic regression. A significance level of 5% was set for the tests.

Ethics statement

The data were collected after research project approval by the HSL Institutional Review Board (IRB) (approval number CAAE 99329118.6.0000.5461). The requirement for informed consent from participants was waived owing to the retrospective characteristics of the study, based on data collection in the REDCap system.

Results

From December 2014 to December 2019, a total of 12,292 patients underwent PICC insertion. Of these, 595 patients were excluded due to age <18 years and 109 patients were excluded with PICCs dwell time ≤ 3 days. In total, 11,588 procedures were included. Regarding the type of care, 11,009 patients (95%) were inpatients whereas only 574 (5%) were outpatients.

The overall DVT prevalence rate in the period considered for the study was 1.8% (n = 213), from which 201 occurred in inpatients (94.4%) and 12 (5.6%) in outpatients.

General characteristics of the cohort

The population consisted of 52% male (n = 6,021). The mean age was 70.6 ± 18.2 years. The mean duration of PICC placement was 15.3 ± 19.3 days. Among the participants, 53.5% (n = 6,156) were critically ill, and 29.1% (n = 3,334) were cancer patients. Concerning intravenous therapy, most patients underwent PICC insertion for antibiotic administration 79.1%, (n = 9,149). As for anticoagulant therapy, 43.3% (n = 4.912) of the patients used anticoagulants during the use of PICC for either prophylactic or therapeutic indications. Low molecular weight heparin was used in 56.1% (n = 2,731) (Table 1).

Table 1. General characteristics (n = 11,588).

Category/Variable n %
Sex
Men 6021 52
Women 5567 48
Age (years)
Mean ± SD* 70.6 ± 18.2
Median (min, max) 75 (18, 107)
PICC usage time (days)
Mean ± SD*

Mean ± SD* 15.3 ± 19.3
Mean ± SD*
Median (min, max) 11 (0, 395)
Patient characterization
Critical 6156 53.5
Oncological 3334 29.1
Surgical 3080 26.9
Active cancer 2375 72.7
Previous DVT* 422 3.8
Indication for PICC insertion
Antibiotic 9149 79.1
Irritating or vesicant drugs
(pH <5 or >9)
5149 44.5
Damaged peripheral venous system 4455 38.6
Hypertonic solutions 3077 26.6
Vasoactive drugs 1761 15.2
Chemotherapy 998 8.6
Parenteral nutrition 542 4.7
Transfusion 270 2.4
Anticoagulant therapy 4912 43.3
Low molecular weight heparin 2731 56.1
Unfractionated heparin 1624 33.3
Rivaroxaban 271 5.6
Warfarin 125 2.5
Apixaban 103 2.1
Dabigratan etexilate 13 0.3
Fondaparinux sodium 3 0.1

*DVT—Deep Venous Thrombosis; SD—Standard Deviation.

Provider, device and insertion characteristics

Table 2 shows that 51.2% (n = 5,914) of the PICC were inserted in the right upper limb (RUL). Notably, 88.4% (n = 10,176) of insertions were performed in the first puncture attempt. The basilic vein was the first choice in 61% (n = 7,011), 78% (n = 9,001) being inserted in the green zone. Regarding vessel occupancy, in the period that Site-Rite 5 was used, 94.6% (n = 4,280) procedures had a vessel occupancy ≤ 33% (the Site-Rite 5 does not have the resource for measuring the vessel in a three dimensional way), and with Site-Rite 8 usage, most procedures 54.8% (n = 3,630) had a vessel occupancy of 11–20%. The first catheter choice was the 5 Fr DL (double-lumen French) open-tip polyurethane in 43.3% (n = 5,015), and 70% of all devices were 5Fr or smaller (Table 2).

Table 2. Device characteristics.

Variables N %
Member
RUL* 5914 51.2
LUL* 5633 48.8
Missing data: 41
Number of puncture attempts
1 10176 88.4
2 870 7.6
3 324 2.8
4 136 1.2
Missing data: 82
Chosen venous access
Basilic 7011 61
Brachial 4362 38
Cephalic 110 1
Middle cubital 8 0.1
Saphena 1 0
Axillary 1 0
Missing data: 95
Venipuncture area
Green zone 9045 78
Ideal zone 2192 19
Yellow zone 267 2.3
Red zone 84 0.7
Equipment used
Site-Rite 5 4719 40.7
Site-Rite 8 6869 59.3
Site-Rite 5 vessel occupancy
≤33% 4280 94.6
≥33% 246 5.4
Site-Rite 8 vessel occupancy
1–10% 1495
22.6
11–20%
3630
54.8
21–30%
1197 18.1
31–40%
295 4.5
41–50%
10 0.2
>51%
Missing data: 434
1
0
Type of catheter
4 Fr* ML* open-tip polyurethane 1965 17
5 Fr ML open-tip polyurethane 1194 10
5 Fr DL* open-tip polyurethane 5015 43.3
5 Fr TL* polyurethane 3 0
6 Fr DL open-tip polyurethane 2995 25.9
6 Fr TL open-tip polyurethane 409 3.2
4 Fr ML Groshong valve silicone 7 0.1
Radiography/Navigation/Scopy
(Proper positioning)
5759 57
Zone A (atrium-Cava junction) 3851 66.9
Zone B (superior vena cava) 1379 23.9
Zone C (brachycephalic vein) 529 9.2
Intracavitary ECG* 4976 43
Missing data: 853

*RUL–a; *LUL–Left upper limb; *Fr–French; *ML—Mono lumen; *DL—Double lumen; *TL–Triple lumen; *ECG–electrocardiogram.

About tip location, radiography/navigation scopy was used in 57% (n = 5,759) of the procedures, and in these procedures PICC tip final position was located in zone A in 66.9% (n = 3,851). Proper tip location was verified by intracavitary ECG in 43% of the procedures (n = 4,976).

Device complications and outcomes

Symptomatic DVT was the most prevalent complication, ocurring in 1.8% (n = 213) of PICCs. In 80% of cases associated with PICC, DVT occurred before 20 days of PICC placement. Confirmed CLABSI occurred in 0.9% (n = 107) patients, but suspected CLABSI was noted in 14.1% (n = 1,183) patients, which led to cathether removal. In relation to minor complications, reversible catheter oclusion occurred in 8.7% (n = 1011) and acidental dislodgment in 2.6% (n = 218). The most common reasons for removing the catheter was the conclusion of infusion therapy, 67.9% (n = 5711). Eleven percent of patients died during follow-up, due to their underlying conditions.

The results of the unadjusted analyses of the pre-puncture characteristics. Only the indication for use of chemotherapy, the characterization of the cancer patient profile, and previous DVT showed a statistically significant association with the occurrence of PICC-associated DVT (p = 0.002, p = 0.041, and p = 0.024, respectively) Table 3.

Table 3. Description of DVT occurrence by pre-puncture characteristics and unadjusted analysis results.

Variable Thrombosis (PICC) OR 95% CI p
No Yes Inferior Superior
Sex, n (%)           0.230
Men 5919 (98.3) 102 (1.7) 1.00      
Women 5456 (98) 111 (2) 1.18 0.90 1.55  
Age (years)     1.005 0.997 1.013 0.215**
Mean ± SD 70.6 ± 18.2 72.1 ± 18.2        
Median (min, max) 75 (18, 107) 77 (21, 102)        
Antibiotic, n (%)           0.351
No 2367 (97.9) 50 (2.1) 1.00      
Yes 8986 (98.2) 163 (1.8) 0.86 0.62 1.18  
DVA, n (%)           0.146
No 9624 (98.2) 173 (1.8) 1.00      
Yes 1721 (97.7) 40 (2.3) 1.29 0.91 1.83  
Irritating or vesicant drugs, n (%)         0.322
No 6299 (98.3) 111 (1.7) 1.00      
Yes 5047 (98) 102 (2) 1.15 0.87 1.50  
Hypertonic solutions, n (%)         0.094
No 8316 (98) 167 (2) 1.00      
Yes 3031 (98.5) 46 (1.5) 0.76 0.54 1.05  
Parenteral nutrition, n (%)           0.741
No 10811 (98.2) 202 (1.8) 1.00      
Yes 531 (98) 11 (2) 1.11 0.60 2.05  
Damaged peripheral venous system, n (%)         0.917
No 6970 (98.2) 131 (1.8) 1.00      
Yes 4374 (98.2) 81 (1.8) 0.99 0.75 1.30  
Chemotherapy, n (%)           0.002
No 10373 (98.3) 182 (1.7) 1.00      
Yes 967 (96.9) 31 (3.1) 1.83 1.24 2.69  
Transfusion, n (%)           0.643*
No 10938 (98.2) 205 (1.8) 1.00      
Yes 264 (97.8) 6 (2.2) 1.21 0.53 2.76  
Critical, n (%)           0.741
No 5254 (98.1) 101 (1.9) 1.00      
Yes 6045 (98.2) 111 (1.8) 0.96 0.73 1.25  
Oncological, n (%)           0.041
No 7995 (98.3) 137 (1.7) 1.00      
Yes 3259 (97.8) 75 (2.2) 1.34 1.01 1.79  
Surgical, n (%)           0.750
No 8230 (98.2) 153 (1.8) 1.00      
Yes 3021 (98.1) 59 (1.9) 1.05 0.78 1.42  
Previous thrombosis, n (%)           0.024
No 10571 (98.2) 194 (1.8) 1.00      
Yes 408 (96.7) 14 (3.3) 1.87 1.08 3.25  
Active cancer           0.670
No 873 (97.7) 21 (2.3) 1.00      
Yes 2325 (97.9) 50 (2.1) 0.89 0.53 1.50  
Anticoagulants, n (%)           0.069
No 6299 (98) 129 (2) 1.00      
Yes 4836 (98.5) 76 (1.5) 0.77 0.58 1.02  
Number of puncture attempts, n (%)         0.490#
1 9994 (98.2) 182 (1.8) 1.00      
2 849 (97.6) 21 (2.4) 1.36 0.86 2.15  
3 320 (98.8) 4 (1.2) 0.69 0.25 1.86  
4 133 (97.8) 3 (2.2) 1.24 0.39 3.93  
Punctured limb, n (%)         0.183
LUL 5520 (98) 113 (2) 1.00      
RUL/RLL 5817 (98.3) 99 (1.7) 0.83 0.63 1.09  

Chi-square test

# Likelihood ratio test

** Student’s t-test.

DVA: Vasoactive drug.

The next table shows the results of unadjusted analyses of the post-puncture characteristics. We found that the application of a high pressure saline flush in cases in which PICC repositioning was necessary statistically associated with a decrease in the occurrence of PICC-associated DVT (p = 0.030). Additionally, reversible catheter oclusion as an adverse event showed a statistically significant association with the occurrence of PICC-related thrombosis (p = 0.039). None of the technical aspects of the insertion, such as choice of the site, type and size of the cathether, vessel occupancy ratio or cathether tip location had association with the risk of PICC-related thrombosis (Table 4).

Table 4. Description of DVT occurrence by post-puncture characteristics and unadjusted analysis results.

Variable Thrombosis (PICC) OR 95% CI p
No Yes Inferior Superior
Vessel occupancy 33%, n (%)         0.771
No 10526 (98.2) 195 (1.8) 1.00      
Yes 542 (98) 11 (2) 1.10 0.59 2.02  
Venipuncture area, n (%)           0.112#
Green area 8828 (98.1) 173 (1.9) 1.14 0.80 1.63  
Yellow area 265 (99.3) 2 (0.7) 0.44 0.11 1.83  
Red area 84 (100) 0 (0) &      
Ideal zone 2155 (98.3) 37 (1.7) 1.00      
Chosen venous access, n (%)         0.329#
Basilic 6874 (98) 137 (2) 1.00      
Brachial 4290 (98.3) 72 (1.7) 0.84 0.63 1.12  
Others 119 (99.2) 1 (0.8) 0.42 0.06 3.04  
Type of catheter, n (%)           0.161#
3 Fr Mono 65 (97) 2 (3) 1.00      
4 Fr Mono 1949 (98.8) 23 (1.2) 0.38 0.09 1.66  
5 Fr Mono 1132 (98.2) 21 (1.8) 0.60 0.14 2.63  
4 Fr Double/5 Fr Double 4925 (98.1) 95 (1.9) 0.63 0.15 2.60  
6 Fr Double 2932 (97.9) 63 (2.1) 0.70 0.17 2.92  
5 Fr Triple/6 Fr Triple 363 (97.6) 9 (2.4) 0.81 0.17 3.81  
Central tip location, n (%)           0.128#
No 849 (97) 26 (3) 1.00      
Yes 5733 (98.1) 110 (1.9) 0.63 0.41 0.97  
Yes, with fold in the tip 60 (98.4) 1 (1.6) 0.54 0.07 4.08  
Vena cava, n (%)           0.429#
Superior vena cava 5668 (98.1) 109 (1.9) 1.00      
Anomalous vena cava 31 (100) 0 (0) &      
Inferior vena cava 14 (100) 0 (0) &      
Vena cava zone, n (%)           0.477
Zone A 3784 (98.3) 67 (1.7) 1.00      
Zone B 1349 (97.8) 30 (2.2) 1.26 0.81 1.94  
Zone C 517 (97.7) 12 (2.3) 1.31 0.70 2.44  
Other veins, n (%)           0.160#
Axillary 31 (96.9) 1 (3.1) 1.00      
Subclavian 251 (96.2) 10 (3.8) 1.24 0.15 9.98  
Jugular 106 (94.6) 6 (5.4) 1.76 0.20 15.13  
Atrium 449 (98.2) 8 (1.8) 0.55 0.07 4.56  
High pressure saline flush successfully performed, n (%)       0.030 *
No 118 (93.7) 8 (6.3) 1.00      
Yes 266 (98.2) 5 (1.8) 0.28 0.09 0.87  
Tip confirmation method, n (%)         0.079
Radiography/Navigation/Scopy 6464 (98) 134 (2) 1.00      
ECG 4897 (98.4) 79 (1.6) 0.78 0.59 1.03  
Reversible catheter oclusion, n (%)           0.039
No 10391 (98.2) 186 (1.8) 1.00      
Yes 984 (97.3) 27 (2.7) 1.53 1.02 2.31  
Tip repositioning, n (%)         >0.999*
No 11348 (98.2) 213 (1.8) 1.00      
Yes 27 (100) 0 (0) &      

Chi-square test

* Fisher’s exact test; # Likelihood ratio test

** Student’s t-test; & Unable to estimate.

The result of the model adjusted for patients using chemotherapy and cancer patients. Overall, the chance of PICC-related DVT increased with each year of increasing age (OR, 1.011; 95% CI, 1.002–1.020), patients with previous DVT were more likely to have PICC-related DVT (OR, 1.96; 95% CI, 1.12–3.44), the use of anticoagulants reduced the chance of PICC-related DVT (OR, 0.73; 95% CI, 0.54–0.99), and the occurrence of obstruction increased the chance of PICC-related thrombosis (OR, 1.60; 95% CI, 1.05–2.42) (Table 5).

Table 5. Adjusted model results to explain the occurrence of DVT due to PICC.

Variable OR 95% CI p
Inferior Superior
Sex (Women) 1.18 0.89 1.57 0.241
Age (years) 1.011 1.002 1.020 0.013
DVA 1.36 0.94 1.96 0.099
Chemotherapy 1.53 0.94 2.50 0.090
Oncological 1.28 0.91 1.80 0.162
Previous thrombosis 1.96 1.12 3.44 0.018
Anticoagulant 0.73 0.54 0.99 0.040
Punctured limb, n (%) 0.85 0.64 1.13 0.261
Venipuncture area        
Green area 1.00      
Yellow area 0.41 0.10 1.65 0.209
Red area &     0.997
Ideal zone 0.89 0.61 1.30 0.553
Tip confirmation method (ECG) 0.80 0.59 1.08 0.148
Obstruction 1.60 1.05 2.42 0.028

Multiple logistic regression; & Unable to estimate.

PICC-related DVT

In the period determined for the study, 11,588 procedures were included. Symptomatic PICC-related DVT was identified in 1.8% (n = 213) of the cases. Kaplan-Meier analysis demonstrated that approximately 80% of the cases of PICC-associated DVT occurred within 20 days of catheter insertion (Fig 2).

Fig 2. DVT probability with the duration of PICC use (n = 213).

Fig 2

Discussion

This is a descriptive and retrospective cohort study with patients conducted in Brazil, with a robust sample of adult patients (11,588) with PICC inserted by a dedicated team of nurses with expertise in vascular access. We provide insights about indications of PICC use, insertion techniques and outcomes.

The rate of PICC-associated DVT was 1.8% in this study. We understand that this is a very low rate, considering the characteristics of the population studied. Previously, a systematic review and meta-analysis found a DVT rate of 1–3% in non-cancer patients and rate of 5–6% in cancer patients. Balsonaro et al, in a meta-analysis that included only studies in which catheter insertion had been performed according to good clinical practices, PICC-related DVT was 2.4% in non-cancer patients, 2.2% in cancer patients and 5.9% in hematologic patients. Recently, Bahl and colleagues, in another systematic review, found DVT rates ranging from 0.9 to 10%, depending on the catheter diameter, and likewise they did not find higher risk in oncological patients. Our results are in agreement with that study, since for PICC devices not larger than 5 Fr, the DVT rate stays very low. In another multicenter study, data from 16 brazilian hospitals including 12,725 patients, catheter-related DVT rate was 1.0% and reversible catheter oclusion was 2.5% [1316].

Regarding critically ill patients, a large study demonstrated a large variation in PICC use practices in ICU setting, DVT incidence could reach more than 10%, and a multivariate analysis showed that PICC in ICU had almost double risk of PICC-associated DVT, compared to ward patients. Our study did not find any independent further risk for DVT in critically ill patients. Nonetheless, further studies should confirm effectiveness and safety of PICC in ICU scenario. The present study adds to field in a way that we sought to identify, in a population with a high risk of thrombosis, which were the potential risk factors associated with PICC-associated DVT. For this purpose we were able to collect a vast array of variables related to either characteristics of the patients, devices and the insertion technique. Interestingly, the only independent variables associated to DVT were non-modifiable, intrinsic characteristics, such as age and history of previous DVT, and two potentially modifiable variables. The presence of obstruction associated with a higher risk, and anticoagulant use conferred protection. Both variables might be subjected to future interventions in order to decrease risk [17,18].

The use of CVC has become part of the routine management of hospitalized patients for chemotherapy, antibiotic therapy, and parenteral nutrition. In this cohort study, PICC insertion was exclusively performed by a team of dedicated nurses, with a success rate in the procedure between 95 to 99% and accomplished in the first attempt in 88.4%. Besides that, the adequate choice of the cathether size, the use of ultrasound guide and the help of devices that increase the chance of the proper location of the cathether tip might have contributed to the our results. Indeed, catheter-to-vein ratio in 91.5% procedures was < 33%, along with the majority being 5Fr or smaller, which must have contibuted to low rates of DVT [19].

As for the choice of limb, 51.2% of the procedures were in RUL. In a randomized clinical trial, the overall incidence of right-sided complications was 23% versus 34% on the left, confirming the hypothesis that right-sided insertions lead to fewer complications (p = 0.046) regardless of hand dominance, however, in another retrospective study the laterality of PICC insertion was not significantly associated with major complications [7,20,21].

In the present study, 61% of the procedures were performed in the basilic vein, and the site of punction did not associate with DVT risk. A retrospective study by Liem et al. demonstrated a DVT rate was 3.1% in the basilic vein and 2.2% in the brachial vein [22].

With regard to minor complication, catheter obstruction occurred in 8.7% and remained as an independent variable associated with PICC-related DVT. Obstruction is the most common PICC-related adverse event, and good device maintenance and management practices can reduce this adverse event. The PICC must be washed before and after the administration of medications using a pulsatile technique to reduce the risk of intraluminal occlusion, but there must have been other non modifiable factors related to patient [23].

In this study, the reason for the removal of PICC was the end of therapy in 67.9%, and a suspected CLABSI was noted in 14% of the cases. The implementation of protocols with a clinically valid indication for device insertion and removal must be implemented, avoiding overuse in indication and mantainance. The low duration of the PICC in our cohort, based on the awareness for the prompt removal when possible, might have helped with our results.

The incidence of DVT, which is a threatening complication with this catheter, is current low, provided all the best technologies and practices in insertion and maintenance are employed. There has been a growth of PICC usage even in a middle-income countries as an effective alternative to other central venous lines, even in a scenario of high risk of DVT. We corroborate the increasing knowledge that even ICU and cancer patients, those with the highest risk for DVT might safely benefit with the use of PICC.

Conclusion

This study indicates that PICC is a safe and suitable intravenous device for medium- and long-term intravenous therapy. Using PICC in a service with bundles and a specialized, fully trainned and dedicated vascular access nurse team evidenced a low incidence of DVT despite a high prevalence of patients with critical and oncological profiles in the sample.

Study limitations

This study has some limitations. The first one is the single center and its retrospective aspect, although our sample is quite robust to allow interpretation and the collection of the data was performed prospectively. Secondly, we have an issue related to the reason for the use of anticoagulants. Our database did not allow us to separate between the use of prophylactic and therapeutic anticoagulants, although based on our hospital historical epidemiologic data, it is highly suggested that most of the anticoagulants were prophylactic (either low molecular weight or unfractioned heparin, based on a JCI approved institution-based DVT prophylaxis guideline), with a very low number of the patients receiving oral anticoagulants.

Another limitation is related to systemic infections or systemic inflammatory response syndrome evaluation regarding the risk of DVT, since most patients underwent the placement of the catheter for this reason, and we did not collect any biomarker for infection/inflammation that coud help predict DVT risk.

Supporting information

S1 File

(XLSX)

pone.0300425.s001.xlsx (20.7KB, xlsx)

Acknowledgments

Professor Eneida Rabelo Rejane da Silva, for her collaboration in this study.

Data Availability

All relevant data is in the manuscript and its supporting information files.

Funding Statement

The author didn't receive specific funding for this work.

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Decision Letter 0

Eyüp Serhat Çalık

20 Nov 2023

PONE-D-23-26732RISK OF DEEP VENOUS THROMBOSIS ASSOCIATED WITH PERIPHERALLY INSERTED CENTRAL CATHETER: A RETROSPECTIVE COHORT STUDY OF 11,588 CATHETERS IN BRAZILPLOS ONE

Dear Dr. MAZZETTO,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Academic Editor

PLOS ONE

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Additional Editor Comments:

I congratulate the authors for this valuable work.

The prevalence of DVT associated with PICC and its successful implementation deserves appreciation. The manuscript was reviewed by three peer reviewers, their comments are below. A recent meta-analysis (https://doi.org/10.1177/10760296221144041) found that the prevalence of PICC-related DVT increased significantly with increasing catheter diameters. Do you have a method to determine the size of catheter to be used? Do you determine the catheter size based on the patient's BMI or venous diameter? Please specify.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: N/A

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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Reviewer #2: No

Reviewer #3: Yes

**********

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Reviewer #1: Nice and sincere efforts spent to collet these large number of cases. The draft give important idea about PICC and DVT relation. Its considered as relevant and worth data that we could depend on its results.

Reviewer #2: The authors tried to demonstrate safety and feasibility of PICC therapy introduced by a specialized team. Although it might be an interesting report, there are several issues to be revised.

1) What is the main objective in this study? To analyze the risk factors for DVT or to check the competency of the special team? The conclusion does not correspond to the objective in the abstract and the manuscript as well.

2) Why could the authors conclude that “using PICC in a service with bundles and a specialized team evidenced a low incidence of DVT”? To which factors listed in the Table 3 and 4 did the team contribute or correlate?

3) There is little consistency and profound discussion in the Discussion section. Most paragraphs only demonstrate the data from the references. What are the new findings in this study? How do they differ from the previous studies? What is the clinical implication of the study?

4) There were too many errors of English grammar and word spelling. The Conclusion section should be written in English in the 1st page. The authors should get English proofreading again for the manuscript.

5) Moreover, the authors should check “Submission Guidelines” of this Journal again. The title page is necessary and References should be listed according to the PLOSONE guidelines.

Reviewer #3: I think the analysis results based on the large number of cases are excellent in this paper. This paper is worthy of publication. I would like to ask you a few questions below.

1. What kind of treatment is positive pressure (flush) successfully performed?

2. Depending on the guidelines, patients with a history of thrombosis may be given anticoagulants, which may be beneficial in preventing thrombosis. How often do they experience bleeding?

3. If PICC is indicated for a patient with cancer and a history of thrombosis, anticoagulants will eventually be indicated. It was important to take into account which anticoagulants were indicated or PICC were introduced, these treatments were depended on the degree of progression of the cancer. Medical systems differ in many countries, which do you prefer anticoagulants or use of PICC in your country?

4. This underlined part, death 11.4%) in the results of abstract, is incorrect.

**********

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Reviewer #1: Yes: Aram Baram

Reviewer #2: Yes: Hiroki Hata

Reviewer #3: No

**********

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PLoS One. 2024 May 6;19(5):e0300425. doi: 10.1371/journal.pone.0300425.r002

Author response to Decision Letter 0


18 Feb 2024

Response to Editor and reviewers:

I congratulate the authors for this valuable work. The prevalence of DVT associated with PICC and its successful implementation deserves appreciation.

We deeply thank to the Editor for the appreciation of our study and the opportunity given in order to improve the manuscript. You will be able to see that we made modifications based on the commentaries/suggestions received, and we reviewed the format and references altogether.

The manuscript was reviewed by three peer reviewers, their comments are below. A recent meta-analysis (https://doi.org/10.1177/10760296221144041) found that the prevalence of PICC-related DVT increased significantly with increasing catheter diameters.

Thank you for the commentaries. We have now added this recent, important paper to the references list. And we incorporated to the manuscript (results and discussion), the aspect of the size of the device. We made it clearer that most of our PICC inserted were 5F or smaller, which might have contributed to our good results.

Do you have a method to determine the size of catheter to be used? Do you determine the catheter size based on the patient's BMI or venous diameter? Please specify.

We appreciate your comments. Yes, we do have a method for determining the size of vein, based on ultrasound measurements, and therefore catheter to be used. First, we define the number of lumen`s catheter according to the patient’s diagnosis, comorbidities, intravenous therapy and time of hospital stay. And employing an ultrasound we then estimate vein diameter in order to choose a cathether that would end up respecting the suggested ratio (The current Infusion Nurses Society guidelines 2021 recommend the use of PICC`s with a catheter-to-vein ratio of no more than 45% prior to insertion of a vascular access device in the upper extremity, and we follow this guideline).

More specifically, during the data collection period, two equipments were used. The Site Rite 5 (BD), was used from February 2012 to January 2017, which gives us a more limited view. Thereafter, the site rite 8 (BD) started to be used from February 2017 until nowadays. This equipment provides a more accurate catheter-to-vein ratio, in three-dimensional way. We do not consider BMI in our decision-making process.

______________________________________________________________________

Reviewer #1: Nice and sincere efforts spent to collet these large number of cases. The draft give important idea about PICC and DVT relation. Its considered as relevant and worth data that we could depend on its results.

We appreciate your comments. We used the RedCap to collect the number of cases. We did this in a retrospective way and now we made it clearer in the manuscript.

______________________________________________________________________

Reviewer #2: The authors tried to demonstrate safety and feasibility of PICC therapy introduced by a specialized team. Although it might be an interesting report, there are several issues to be revised.

We are deeply grateful for your insightful commentaries and suggestions, that will definitely improve our manuscript. We hope we now comply to your requests (see below).

1) What is the main objective in this study? To analyze the risk factors for DVT or to check the competency of the special team? The conclusion does not correspond to the objective in the abstract and the manuscript as well.

Thanks for the precise notation. Our main objective is to describe the actual rate and risk factors for DVT in PICC patients in a cohort of a tertiary hospital in a Middle income country, particularly in scenario of cancer and critically-ill patients, which we understand could contribute and predispose to this complication. We hope we now made it more clear in the current version of the manuscript. Nevertheless, since these data we obtained might not necessarily apply to other Middle incomes countries services, we tried to ensure that those data might have resulted from some features. For instance, our hospital is accredited by Joint Commission International (JCI) and we have a service with bundles and a specialized nurses fully trainned and dedicated to the purpose of the PICC insertion and maintainnance, which may not be the case in other services. Yet, we appreciate the comment about conclusion, and we have rewritten this topic.

2) Why could the authors conclude that “using PICC in a service with bundles and a specialized team evidenced a low incidence of DVT”? To which factors listed in the Table 3 and 4 did the team contribute or correlate?

We figured that if the technical aspects of insertion had varied regarding choice of the site, type and syze of the catheter, catheter-to-vein ratio and tip location, those could have been independent contributing variables to DVT. However, data in table ensure that the there was an overall compliance to best practices. We now state in the manuscript that inference. Yet, the team had 88.4% the puncture in the first attemp, 91,5% occupancy < 33% and 98,3% of procedures in the ideal zone, 98.1% tip location in the superior vena cava. Data could have been different in case of a distinct organization and with inferior quality indicators.

3) There is little consistency and profound discussion in the Discussion section. Most paragraphs only demonstrate the data from the references. What are the new findings in this study? How do they differ from the previous studies? What is the clinical implication of the study?

We thank you for the comments about the topic discussion. As we can see in the new discussion section, we sought to follow the topics we pointed. In summary: our study adds to field in a way that we sought to identify, in a population with a high risk of thrombosis, which were the potential risk factors for PICC-associated DVT. The incidence of DVT, which is a threatening complication with this catheter, is current low, provided all the best technologies and practices in insertion and maintenance are employed. And yet, the study shows a regression analysis finding independent variables associated with the DVT risk, which might shed light to future studies. We corroborate to the increasing knowledge that even ICU and cancer patients, those with the highest risk for DVT might safely benefit with the use of PICC. We included some data on ICU patients from the literature.

4) There were too many errors of English grammar and word spelling. The Conclusion section should be written in English in the 1st page. The authors should get English proofreading again for the manuscript.

We apologize for the typos and errors of English grammar. We have now thoroughfully revised the manuscript.

5) Moreover, the authors should check “Submission Guidelines” of this Journal again. The title page is necessary and References should be listed according to the PLOSONE guidelines. Reviewer #2: The authors tried to demonstrate safety and feasibility of PICC therapy introduced by a specialized team. Although it might be an interesting report, there are several issues to be revised.

We attached the tittle page, and we adjusted the references according to the PLOS ONE.

______________________________________________________________________

Reviewer #3: I think the analysis results based on the large number of cases are excellent in this paper. This paper is worthy of publication. I would like to ask you a few questions below.

1) What kind of treatment is positive pressure (flush) successfully performed?

We appreciate your relevant questions. We use positive pressure in polyurethane catheters. This catheter has greater rigidity, low thrombogenicity and thermosensitive, which allows us sometimes to reposition the device. For instance, when we observed after insertion that it was positioned in the subclavian vein, and even when it migrated to an innapropriate position, in these cases we use/apply positive pressure with saline solution to reposition the catheter in the vena cava superior.

2) Depending on the guidelines, patients with a history of thrombosis may be given anticoagulants, which may be beneficial in preventing thrombosis. How often do they experiencie bleeding?

That is an interesting question. Unfortunately our database did not allow us to separate between the use of prophylactic and therapeutic anticoagulants, although based on our hospital historical epidemiologic data, it is highly suggested that most of the anticoagulants in our cohort were prophylactic (we now made it more clear in the manuscript and table). Besides that, the kit to insert the guidewire and thereafter the catheter is based on a small needle micropuncture, and bleeding is not an expected complication. Last, bleedings related to the insertion on maintenance of a PICC device would be reported as an adverse event in our electronic medical record-based reporting database, and we could not find adverse events related to bleeding, though.

3) If PICC is indicated for a patient with cancer and a history of thrombosis, anticoagulants will eventually be indicated. It was important to take into account which anticoagulants were indicated or PICC were introduced, these treatments were depended on the degree of progression of the cancer. Medical systems differ in many countries, which do you prefer anticoagulants or use of PICC in your country?

Our database did not allow us to separate between the use of prophylactic and therapeutic anticoagulants, although based on our hospital historical epidemiologic data, it is highly suggested that most of the anticoagulants were prophylactic (either low molecular weight or unfractioned heparin) based on a JCI approved institution-based DVT prophylaxis guideline, with a very low number of the patients receiving oral anticoagulants. As mentioned above, we now made it more clear in the manuscript and we now depicted these data in table (we now can see clearly that most of the patients were under low weight or unfractioned heparin, with smaller portion of the cohort receiving either warfarin or new antithrombotic drugs).

4) This underlined part, death 11.4% in the results of abstract, is incorrect.

Thank you for the important observation. It was a lapse, and now we correctly mention the mortality rate of the cohort in the proper place in the manuscript. As we can also see, the abstract was rewritten not to adjust for the lenght, but also to comply with the most important informations of the study.

Attachment

Submitted filename: Response to Reviewers.docx

pone.0300425.s002.docx (28.5KB, docx)

Decision Letter 1

Eyüp Serhat Çalık

28 Feb 2024

Risk of Deep Venous Thrombosis associated with Peripherally Inserted Central Catheter: a retrospective cohort study of 11.588 catheters in Brazil

PONE-D-23-26732R1

Dear Dr. Mazzetto,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Eyüp Serhat Çalık

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 File

    (XLSX)

    pone.0300425.s001.xlsx (20.7KB, xlsx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    pone.0300425.s002.docx (28.5KB, docx)

    Data Availability Statement

    All relevant data is in the manuscript and its supporting information files.


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