Intensive Care Med (2011) 37:284–289 DOI 10.1007/s00134-010-2043-x
ORIGINAL
Manuela Bonizzoli Stefano Batacchi Giovanni Cianchi Giovanni Zagli Francesco Lapi Valentina Tucci Giacomo Martini Simona Di Valvasone Adriano Peris
Peripherally inserted central venous catheters and central venous catheters related thrombosis in post-critical patients
Received: 31 January 2010 Accepted: 29 July 2010 Published online: 21 September 2010 Ó Copyright jointly held by Springer and ESICM 2010
Abstract Background: Peripherally inserted central venous catheters (PICC) have been proposed as an alternative to central venous catheters (CVC). The aim of this study was to determine the thrombosis rate in relation to PICC placement in patients discharged from the intensive care unit (ICU). Methods: Data of patients admitted to the ICU (Careggi Teaching Hospital, Florence, Italy; January–August 2008) and discharged with a central venous device were sequentially studied. During the first 4 months, CVCs were used (CVC group), whereas during the last 4 months, PICCs were used (PICC group). Demographic/clinical and catheter-related data were collected. Intensivists performed Doppler examination at ICU discharge and 7, 15, and 30 days after placement. Results: Data of 239 patients were analyzed (125 of CVC group, 114 of PICC group). A total of 2,747 CVCdays and 4,024 PICC-days of observation were included. Patient characteristics were comparable between groups. Patients with PICC had a significantly higher incidence
M. Bonizzoli S. Batacchi G. Cianchi G. Zagli ()) V. Tucci G. Martini A. Peris Anesthesia and Intensive Care Unit of Emergency Department, Careggi Teaching Hospital, Viale Morgagni 85, 50134 Florence, Italy e-mail:
[email protected] Tel.: ?39-05-57947473 Fax: ?39-05-57947821 F. Lapi Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy F. Lapi Epidemiology Unit, Regional Agency for Health Care Services of Tuscany, Florence, Italy S. Di Valvasone Postgraduate School of Anesthesia and Intensive Care, Faculty of Medicine, University of Florence, Florence, Italy
Introduction Peripherally inserted central venous catheters (PICC) are nontunnelled, medium-term vascular access devices inserted through a peripheral vein of the arm. PICCs have been proposed in outpatients as an alternative to central
rate of deep venous thrombosis (DVT) than patients with CVC (27.2 vs. 9.6%, P = 0.0012). The rate of DVT/1,000 catheter days was 4.4 for CVCs and 7.7 for PICCs. Eighty percent of DVTs occurred within 2 weeks after insertion. Binary logistic analysis showed a two-fold increased risk for women and a threefold increased risk when using the left basilic vein in the PICC group. Conclusions: In our post-critically ill population, PICCs were associated with a higher rate of DVT complications than CVCs. Routine ultrasound surveillance for the first 2 weeks after patient discharge from the ICU with a PICC and preferential use of CVC for these patients may be warranted. Keywords Peripherally inserted central venous catheters Central venous catheters Critically ill patients Deep venous thrombosis Post-intensive ward
venous catheters (CVC), mainly for longer in situ duration and because they can be inserted bedside by nurses [1]. PICCs have also been proposed for inpatients, particularly critically ill patients discharged from the intensive care unit (ICU) to the post-intensive ward [2–5]. Despite widespread use, there is a lack of data on significant
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advantages or disadvantages of PICCs over CVCs in hospitalized patients [5]. The aim of this study was to determine the rate of deep venous thrombosis (DVT) related to PICC and CVC placement before ICU discharge in critically ill patients discharged to post-intensive wards.
Materials and methods Study design and data collection Data of patients admitted to the ICU of a referral trauma center (Careggi Teaching Hospital, Florence, Italy) from January 2008 to August 2008 were prospectively studied. During the first 4 months (January–April 2008), patients were discharged from ICU with CVCs (CVC group), whereas during the last 4 months of the study period (May–August 2008), PICCs were used (PICC group). All catheters were inserted within 3 days before discharge. In those patients with no venous access acceptable for PICC positioning, a CVC was used. Patients’ data were collected from the institutional ICU database (software: FileMaker Pro 5.5 v. 2, FileMaker, USA). For the purpose of the study, enrollment was limited to patients discharged to post-intensive wards with an anticipation of prolonged intravenous therapy. Patients younger than 18 years of age were excluded. The following information was collected for all patients: demographic and clinical data, admission diagnosis, simplified acute physiology score (SAPS) II, injury severity score (ISS), length of stay (LOS) in ICU, catheter-related DVT in post-intensive ward, and catheter duration. Before ICU discharge, all patients were screened to exclude the presence of thrombosis. This study followed the principles of the Helsinki declaration and was approved by the Internal Review Board. Informed consent for procedures and data publication was obtained. Catheter insertion procedure and post-intensive ward follow-up All CVCs and PICCs were positioned bedside by trained anesthetists within 3 days before ICU discharge. The following devices were implanted during this study: (1) Groshong-valved bi-lumen PICC 5 Fr, BARD Access Systems, Salt Lake City, UT, USA; (2) nonvalved bi-lumen PICC 5 Fr, Vygon, Germany; (3) tri-lumen 7 Fr CVC, Arrows International, USA. Implantations in the internal jugular vein (CVC) and upper arm vein (PICC) were conducted under ultrasonographic examination with portable device (Site-Rite,
Bard, Pittsburgh, PA, USA), whereas for CVC positioning in subclavian vein, the classic landmark technique was used. Venous districts were previously checked with ultrasound to exclude pre-existing thrombosis. Procedures were performed in full aseptic conditions according to routine operating-room protocols, and asepsis was obtained with 2% chlorhexidine. The ultrasound probe was covered by a sterile latex-free ultrasound-transducer cover kit. Patients were continuously monitored (ECG monitor, pulse oximetry, noninvasive blood pressure). In keeping with infection control guidelines [6–8], patients did not received antibiotic prophylaxis routinely. Local anesthesia was achieved by site infiltration with 2% lidocaine. A post-procedure chest X-ray was performed within 6 h in all patients to confirm the tip location (lower superior vena cava/atriocaval junction) and to exclude complications. Low-molecular-weight heparin was administered in all patients as thrombo-prophylaxis (dalteparin, 5,000 IU/day). The post-ICU ward staff was trained to manage the central venous device correctly at periodic intra-hospital refresher courses (Critical Setting Course). Following institutional protocols, an ICU physician performed a level I vascular ultrasound examination (MyLab 30, ESAOTE, Genoa, Italy) at 7, 15, and 30 days after catheter placement. The level I vascular ultrasound in the examination consisted of the evaluation of lumen, and complete compressibility of the vein compression. Patients with extended thrombosis or difficult diagnosis were checked with level II ultrasound by a specialist.
Statistical analysis Statistical analyses were carried out with PASW Statistics 18 (SPSS, Chicago, IL, USA). Continuous variables [means ± standard error of mean (SEM)] were analyzed with two-tail Student’s t-test, whereas categorical variables were examined using v2-test. Continuous variables are expressed as means ± SEM. A P value below 0.05 was considered an index of statistical significance. Univariate comparisons were reported as relative risks with 95% confidence intervals (CI). Furthermore, a logistic regression model was adopted to investigate the predictors of thrombosis among patients exposed to PICC and CVC procedures, taken separately. Each predictor likely to be related to the outcome was evaluated on statistical and clinical bases. Any covariate that was associated with the response variables (P \ 0.05) in univariate analysis, as well as those that could have a clinical meaning based on the medical literature, was retained in the final model. Herein, multivariate logistic regression included age, gender, BMI, SAPS II, ICU admission pathology, insertion site, indwelling days, and ICU length of stay (LOS).
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Results In total, 239 patients were enrolled. Among them, 125 were discharged from the ICU with a CVC (CVC group), and 114 with a PICC (PICC group). During the study period, ten patients did not have vascular access appropriate for PICC insertion at ultrasound examination; in these cases, a CVC was positioned, and the patients were then assigned to the CVC group. As summarized in Table 1, the groups showed similar demographic and clinical characteristics, ICU LOS, and post-ICU ward allocations. Admission diagnoses were also comparable among groups, with a prevalence of trauma patients (with or without brain injury), followed by medical admission (sepsis, respiratory/cardiac/renal failure), and post-surgical complications (Table 1). A total of 2,747 CVC-days and 4,024 PICC-days of observation were included in the study. Valved and nonvalved PICCs were used in 62 (54.4%) and 52 (45.6%) patients, respectively. As expected based on the different catheters, mean PICC duration was significantly longer than CVC (35.3 vs. 25.5 days, P = 0.0001). Table 1 Characteristics of patients and catheter-related thrombotic complication PICC group (N = 114)
58.8 ± 1.5 79 (63.2%) 26.5 ± 0.4 46.5 ± 1.2 28.7 ± 2.1
54.3 ± 1.8 65 (57%) 25.6 ± 0.5 46.2 ± 1.3 29.3 ± 1.9
34 (27.2%) 22 (17.6%) 43 (34.4%) 26 (20.8%) 16.4 ± 0.6
24 (21.1%) 20 (17.5%) 46 (40.3%) 24 (21.1%) 17.6 ± 0.8
58 (46.4%) 67 (53.6%) 2,747 22.5 ± 0.5 12 (9.6%) 4.4
60 (52.6%) 54 (47.4%) 4,024 35.3 ± 0.9§ 31 (27.2%) 7.7
42 26 26 31
18 16
(33.6%) (20.8%) (20.8%) (24.8%) 60 (52.6%) 54 (47.4%)
CVC PICC
14
Patients (N)
Age (years) Male sex, N (%) BMI SAPS II ISS (trauma patients) Admission diagnosis, N (%) Polytrauma with brain injury Polytrauma without brain injury Medical Post-surgical ICU LOS (days) Post-intensive ward, N (%) Medical Surgical Total catheter days Catheter days (mean) DVT, N (%) DVT rate per 1,000 catheter days Insertion site, N (%) Right internal jugular vein Left internal jugular vein Right subclavian vein Left subclavian vein Right basilic vein Left basilic vein
CVC group (N = 125)
Patients with PICC had a significantly higher incidence of DVT than patients with CVC (27.2 vs. 9.6%, respectively, P = 0.0007) (Table 1). The rate of DVT/1,000 catheter days was 4.4 for CVCs and 7.7 for PICCs. At ultrasound examination, thrombi were found to be adherent to the catheter body, asymptomatic in all patients, and in no case was the vein lumen totally occluded. Among the possible sites for PICC access, the left basilic vein was associated with DVT onset significantly more often than the right basilic vein (37.1 vs. 18.3%, respectively, P = 0.0347). Thrombosis started from the basilic vein in 19 cases (61.3%), involving the axillary and subclavian veins in 6 and 3 cases, respectively. In 12 patients (38.7%), thrombosis initiated far from the catheter’s access site, starting from the axillary veins and arriving at the subclavian vein in 8 cases. The analysis of the time course of DVT onset showed that most of the cases of thrombosis occurred during the second week after insertion, both in the PICC and the CVC group (Fig. 1). As shown in Table 2, no significant differences in demographic and clinical characteristics were found among patients with or without DVT in the overall population and subgroups. No cases of pulmonary embolism occurred in patients with DVT. The relative risk analysis (Table 3) showed a three-fold higher risk for DVT in medical patients who underwent CVC positioning (P = 0.0223), and a two-fold higher risk for DVT in the PICC group if the left basilic vein access was used (P = 0.0199). The binary logistic regression model (adjusted for age, gender, BMI, SAPS II, admission diagnosis, indwelling days, ICU LOS, site access) showed a significant additional risk of DVT development in the PICC group for women (OR 2.403; 95% CI 0.944–6.118; P = 0.044) and confirmed the higher risk of using the left basilic vein (OR 3.280; 95% CI 1.259–8.544; P = 0.015), whereas no significant risk factors were found in the CVC group using the binary logistic regression model.
12 10 8 6 4 2
Continuous data are expressed as means ± standard error of mean 0 (SEM). Percent data reflect the total population of each group. 7 days 8-15 days 16-30 days Statistical analysis: Student’s t test, v2 test; § P \ 0.0001, Time from insertion to DVT ultrasound diagnosis P = 0.0007 BMI Body mass index, CVC central venous catheter, DVT deep venous thrombosis, ISS injury severity score, LOS length Fig. 1 Time distribution of deep venous thrombosis occurrences of stay, PICC peripherally inserted central venous catheters, SAPS after catheter insertion (CVC central venous catheter, PICC simplified acute physiology score peripherally inserted central venous catheters)
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Table 2 Comparison of baseline and clinical characteristics between patients with and without DVT Overall
Number Age (years) Male sex, N (%) BMI SAPS II ISS (trauma patients) Admission diagnosis Medical, N (%) Polytrauma with brain injury, N (%) Polytrauma without brain injury, N (%) Post-surgical, N (%) Catheter days (mean) Medical Polytrauma with brain injury Polytrauma without brain injury Post-surgical ICU LOS (days)
CVC group
PICC group
No DVT
DVT
No DVT
DVT
No DVT
DVT
196 57.1 ± 1.3 121 (61.7%) 26 ± 0.4 46.2 ± 1 29.1 ± 1.6
43 54.8 ± 3.6 23 (53.5%) 26.2 ± 0.9 47.1 ± 2.4 28.9 ± 2.8
113 59.2 ± 1.6 71 (62.8%) 26.4 ± 0.5 46.3 ± 1.3 28.9 ± 2.2
12 56.2 ± 6.5 8 (66.7%) 27 ± 1.7 48.4 ± 5.3 28.3 ± 4.3
83 54.3 ± 2.1 50 (60.2%) 25.4 ± 0.6 46.1 ± 1.6 29.4 ± 2.6
31 53.3 ± 3.7 15 (48.4%) 25.9 ± 1.1 46.8 ± 2.7 29.1 ± 3.9
68 48 35 45
21 (48.8%) 10 (23.2%) 6 (14%) 6 (14%)
35 31 21 26
8 (66.7%) 3 (25%) 1 (8.3%) –
33 17 14 19
13 (41.9%) 7 (22.6%) 5 (16.1%) 6 (19.4%)
29.7 31.8 38.3 29.9 18.8
24.6 22.3 22.4 19.9 16.1
16.6 ± 9 23 ± 8.9 28 – 19.6 ± 2.5
36.8 36.7 35.7 32.9 17.2
(34.7%) (24.5%) (17.9%) (22.9%)
30.5 27.4 27.7 25.4 16.6
± ± ± ± ±
9.5 9.9 10.3 10.4 0.5
± ± ± ± ±
Continuous data are expressed as means ± standard error of mean (SEM). Percent data reflect the total population of each subgroup. Statistical analysis: Student’s t-test, v2-test. There were no significant differences between groups
7.7 10.8 6.9 8.9 1.2
(31%) (27.4%) (18.6%) (23%) ± ± ± ± ±
3.5 5.4 4.5 5-6 0.6
(39.8%) (20.4) (16.9%) (22.9%) ± ± ± ± ±
9.9 9.6 11.5 10.9 0.9
32.8 ± 6.3 35.6 ± 9.6 40 ± 5.7 29 ± 8.9 18.6 ± 1.5
BMI Body mass index, CVC central venous catheter, DVT deep venous thrombosis, ISS injury severity score, LOS length of stay, PICC peripherally inserted central venous catheters, SAPS simplified acute physiology score
Table 3 Relative risk of deep vein thrombosis development
Relative risk CVC group Female sex Admission diagnosis Medical Polytrauma with brain injury Polytrauma without brain injury Site access Right internal jugular vein Left internal jugular vein Right subclavian vein Left subclavian vein PICC group Female sex Admission diagnosis Medical Polytrauma with brain injury Polytrauma without brain injury Post-surgical Site access Left basilic vein Nonvalved PICC
95% CI
P
0.4861
0.7773–2.576
0.2326
3.814* 0.8922 0.4256
1.217–11.95 0.2566–3.102 0.05788–3.130
0.0223 0.9987 0.6906
0.6587 0.9103 1.269 1.011
0.1881–2.306 0.2668–3.106 0.3697–4.358 0.2918–3.501
0.7494 0.9989 0.7126 0.9881
1.415
0.1778–1.329
0.2917
1.068 1.094 0.9615 0.8544
0.5815–1.960 0.5369–2.228 0.4231–2.185 0.3945–1.851
0.8337 0.8006 0.9997 0.8022
2.182* 1.544
1.122–4.244 0.4677–3.521
0.0199 0.3417
Statistical analysis: v2-test, * P \0.05 CVC Central venous catheter, PICC peripherally inserted central venous catheters
Discussion The main finding of our study was the evidence of a higher DVT incidence using PICCs rather than CVCs. In particular, the higher risk of DVT development was found to be related to gender (female) and site access (left
basilic vein). The incidence of DVT by insertion site reported by Allen and colleagues in a retrospective study of 354 PICCs placed in 119 patients was cephalic 57%, basilic 14%, and brachial 10% [9]. In our sample, we observed a higher rate in the basilic vein than Allen and co-workers, with a twofold increased risk using the left
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basilic vein. However, in a more recent article, an incidence rate of up to 37.5% was observed, decreasing to 22.9% in patients under anticoagulant therapy [10]. However, our population was different from the cited studies, since hospitalized patients (in particular critically ill patients) present additional risk factors for thrombus formation, despite anticoagulant prophylaxis. To our knowledge, gender has not previously been reported to be a specific risk factor for DVT development when using PICC. Due to the limited sample size of our subgroups, no definitive conclusions can be made, but a direct genderbased and site access-based surveillance might be advisable. The observed higher incidence of DVT with PICC use in our population is a confirmation of what was reported in a recent review, which shows that PICCs often need removal sooner despite their expected longer catheter life [5]. Notably, all the thrombotic events in our study were asymptomatic. The strict ultrasound follow-up provided by the internal protocol might have permitted the diagnosis before the clinical manifestation. In accordance with literature data [5], we saw a higher incidence of DVT diagnosis early on (highest during the second week after insertion), with 80% of overall DVTs occurring in the first 14 days (Fig. 1). In this regard, a study designed to determine the optimal timing of Doppler follow-up might be advisable. The absence of clinical signs might even be related to the administration of low-molecular-weight heparin as prophylactic therapy, which could have avoided the total occlusion of the vein lumen, even if no definitive evidence is available to support the indication for anticoagulation for catheter-related thrombosis prevention in acute care setting [5]. A post-thrombotic syndrome defined as edema, the development of brawny, tender induration of the subcutaneous tissues of the arm, can complicate a catheterrelated DVT, even if this syndrome has been more frequently described in lower limbs [11]. The postthrombotic syndrome can be directly related to vein stenosis (even without previous diagnosis of DVT) following upper extremity PICC placement. In 2003, Gonsalves and co-workers [12] showed that patients who underwent the placement of a PICC in the upper arm had a 7% risk of developing central vein stenosis or occlusion; the risk was unrelated to catheter caliber. A phone interview conducted on DVT patients still alive (9 patients in the CVC group and 24 patients in the PICC group) at 17 months after DVT diagnosis revealed post-thrombotic syndrome symptoms in 1 CVC patient (11%) and in 6 PICC patients (25%). This finding on such a limited sample cannot demonstrate a higher incidence of postthrombotic syndrome using PICC instead of CVC and should be considered as an observation to be clarified with future studies.
Blood flow through the brachial vein is less than that through the other central veins such as the subclavian or internal jugular. This feature, also in view of the smaller size of the vessel, and therefore the relatively larger intraluminal occupation, should be considered the main predisposing factor for PICC-related thrombosis. Moreover, the longer body of PICC with respect to a CVC might represent an important difference. This consideration is reinforced by the observation that the left basilic vein was associated with a higher DVT rate (Table 3), suggesting that the longer vessel exposure to a foreign object might represent another risk factor. As the PICC insertion procedure is usually more difficult than CVC positioning (with regard to the smaller diameter of the vein), the thrombosis rate could be related to the primary endothelial lesion due to repeated venipuncture attempts. However, the observation that most DVTs occurred during the second week after insertion (Fig. 1) makes this hypothesis less probable. This factor remains to be clarified. Limitations of the present results need to be mentioned. The nonrandomized design of the study limits the reliability of the results. Even if groups were homogeneous, the lack of randomization could have influenced the results. The sensitivity of ultrasound inspection of the subclavian vein could be lower than the basilic/axillary vein due to its lesser compressibility. Nevertheless, the reported sensitivity of venous Doppler ultrasound for upper limb thrombosis diagnosis ranges from 78 to 100% and its specificity ranges from 82 to 100% [13]. Even if the presence of false-negative patients in the CVC group cannot be excluded, the absence of clots at catheter removal confirmed the high sensitivity of level I Doppler ultrasound, if the operators are properly skilled. As mentioned above, the subgroup analysis is limited by the relatively small sample size, thus, the magnitude of the significant risk factor (and even the nonsignificant ones) could have been influenced. Finally, the use of two different PICCs might have created a potential confounding factor in data elaboration, even if the PICCs had the same diameter (5 Fr), and the presence of the valve was taken into account in the statistical analysis.
Conclusions A revision of PICC use in post-critical patients might be helpful. Until further studies are done, our data indicate that PICCs are associated with a higher rate of DVT complications than CVCs in post-critically ill patients. A routine ultrasound surveillance protocol is advisable, especially during the first 2 weeks after central line placement, to permit early diagnosis and treatment.
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