Version May 2024
INTRODUCTION — Owing to ease of insertion through peripheral veins of the upper extremity, peripherally inserted central catheter (PICC) use has become increasingly popular. Although the insertion route of PICCs avoids complications such as pneumothorax or injury to the vessels of the neck and chest, PICCs are associated with important complications [1]. Principal among these is an increased risk of deep vein thrombosis (DVT) [2,3]. Some estimates suggest that PICCs are responsible for over one-third of all upper extremity DVTs [4], suggesting that the arm veins are perhaps the most thrombotic sites in which a central venous catheter can be placed [5].
Upper extremity venous thrombosis related to PICCs is reviewed here. An overview of upper extremity catheter-related venous thrombosis is provided separately. (See "Catheter-related upper extremity venous thrombosis in adults".)
INCIDENCE AND RISK FACTORS — Even when used for short-term (days) or medium-term (weeks) treatment, PICCs carry a substantial risk of thrombosis that should be carefully considered prior to use [6-8]. PICCs appear to be associated with a greater risk for venous thrombosis overall (superficial and deep thrombosis) compared with centrally inserted catheters (CICCs; including ports), particularly in those who are critically ill or who have malignancy [4,7-18]. The incidence of deep vein thrombosis (DVT) for PICCs is between 5 and 15 percent for hospitalized patients and 2 and 5 percent for ambulatory patients [12,19,20]. Studies that screen for PICC-related DVT using weekly surveillance, regardless of the presence of symptoms, report rates of DVT as high as 33 percent [14].
A systematic review that included 64 studies found that PICCs were associated with a stepwise increase in the prevalence of DVT based on patient population [14]. As an example, the prevalence of PICC-related DVT in studies including hospitalized patients was 3 percent and was 6 percent in patients with cancer. Studies of critically ill patients with PICCs had the highest risk of PICC-related DVT, with a prevalence of 13 percent. Among 12 studies that directly compared risk of thrombosis of PICCs with central venous catheters (CVCs) placed in the internal jugular and subclavian vein, PICCs were associated with a 2.5-fold greater risk of thrombosis.
The Medical Inpatients and Thrombosis (MITH) Study was a case-cohort study in which all cases of venous thromboembolism at a single institution from 2000 to 2009 were matched 1:2 with patients who did not have venous thromboembolism [8]. In this study, central catheter use was associated with a 14-fold increased risk for upper extremity DVT, without a significantly increased risk for pulmonary embolism. PICCs were associated with a higher risk compared with CICCs. The cumulative incidences for upper extremity DVTs were 0.2, 4.8, and 8.1 per 1000 admissions for no central venous catheters, CICCs, and PICCs, respectively.
Later studies examining PICC insertion using "modern" insertion techniques such as ultrasound-guided insertion, micro-introducers, and ECG guidance suggest that when these are used, the risk of PICC-related DVT may be lower than previously reported. In a systematic review of 15 studies published after 2010, the overall rate of PICC-related DVT was 2.4 percent (95% CI 1.5 to 3.3 percent) [21]. However, the incidence remained high in studies of hematology and oncology patients at 5.9 percent (95% CI 1.2 to 10.0 percent). Importantly, there was considerable heterogeneity of the included populations (I2 = 75 percent), and bias related to loss to follow-up among the included studies was reported.
Risk factors — Risk factors associated with PICC thrombosis can be categorized as patient-, provider-, and device-related factors [22]. The best way to prevent DVT is to avoid a device unless absolutely necessary. Choosing an appropriate device is therefore paramount in preventing PICC-related thrombosis. (See 'Prevention' below and "Central venous access: Device and site selection in adults".)
Patient factors — Among patient factors, prior history of DVT (especially if such an event occurred within 30 days), obesity, hematological malignancies, critical illness, and comorbidities such as diabetes and obstructive lung disease have been linked to PICC-related DVT [9,10,23-29]. Cancer, in particular, remains an important patient subset in which use of PICCs is associated with significant risk of DVT [30-32]. As an example, in a review of over 3000 patients with solid cancers, catheter occlusion occurred in 10 percent of patients, and DVT occurred in 3.6 percent. (See "Overview of the causes of venous thrombosis" and "Overview of thoracic central venous obstruction".)
Device factors — The device factors most associated with PICC-related DVT include the size of the catheter, which, in turn, is related to the number of catheter lumens, and catheter tip location. As with centrally inserted catheters, the incidence of PICC-related DVT increases with increasing number of lumens [10,15,24] and for left-sided catheters [33]. Another risk factor is exchange of PICCs over a guidewire, which may be done if a PICC tip has been malpositioned or if the catheter becomes dislodged [34].
PICCs traverse a greater length of vein, and, although the catheter is small relative to the central veins, the catheter may occupy the entire internal diameter of the peripheral vein into which it is inserted [9]. The increase in thrombogenicity of PICCs is explained, in part, by their insertion route; PICCs are placed into the smaller, peripheral veins of the upper extremity, typically in the arm (eg, brachial vein, basilic vein), where they occupy a greater fraction of the cross-sectional area of the vein. This property (termed the catheter-to-vein ratio) is a key factor associated with PICC-related DVT [14]. Add to this the endothelial injury associated with PICC insertion and the hypercoagulable profile of hospitalized patients who often receive this device, and PICCs easily satisfy Virchow's triad. A prospective cohort study suggested that the optimal catheter-to-vein ratio is <45 percent; that is, the catheter should not occupy more than 45 percent of the vessel diameter; PICCs that did not respect this rule were associated with a 13-fold greater risk of thrombosis [35]. Later studies suggest that in certain patient groups, ensuring a smaller catheter-to-vein ratio by using the smallest caliber catheter possible for the visualized vein diameter may be more important [36]. Thus, observance of the catheter-to-vein ratio is an important provider-dependent factor associated with thrombosis [37]. The brachial and basilic veins provide a large cross-sectional area for placing a PICC [38]. Alternatively, puncture of veins that are more proximal (eg, the axillary vein in the deltopectoral groove) provides access to larger-caliber vessels and results in lower rates of DVT [39].
In general, the greater the number of PICC lumens, the greater the size of the catheter and resultant vein size that is necessary. The larger diameter of double- or triple-lumen catheters occupies a greater cross-sectional area of the smaller peripheral (compared with axillosubclavian) vein, leading to more stasis. A prospective study evaluating outcomes for triple-lumen PICCs was terminated prematurely after venous thrombosis was identified in 58 percent of the patients. Only 20 percent of these patients were symptomatic, and 10 percent involved the deep veins [40]. In another prospective study evaluating 2014 PICC placements, the incidence of symptomatic DVT was 3 percent [10].
Using the least number of lumens and catheter size to meet clinical needs is thus advised by most guidelines [41,42] and has been shown to prevent complications in a number of clinical settings [43-46]. In response to this issue, manufacturers are designing newer-generation PICCs that provide more lumens with less cross-sectional diameter.
Provider factors — Appropriate patient selection, proper placement, and positioning are key provider components that contribute to the incidence of PICC-related DVT. The use of ultrasound for PICC placement, a practice that is associated with fewer attempts to placement, is associated with lower rates of PICC-related DVT, lower rates of phlebitis, and lower rates of thrombosis [47,48]. (See "Basic principles of ultrasound-guided venous access" and "Central venous access in adults: General principles", section on 'Use of ultrasound'.)
Catheter tip location is another important device factor. PICC tips should reside at the cavoatrial junction (CAJ) or the right atrium (RA), where blood flow is greatest and risk of DVT is lowest [49,50]. PICCs that do not terminate in this location (ie, those in the middle to proximal third of the superior vena cava) are associated with sevenfold greater rates of DVT [51]. Similarly, power injection of contrast dye may promulgate tip malposition, which is important to consider when using PICCs for radiographic studies [52,53]. Placement methods that ensure proper PICC tip positioning may reduce the incidence of DVT. (See "Central venous access in adults: General principles", section on 'Confirming catheter tip position'.)
Placement of PICCs using electrocardiographic technology (a technique that localizes the PICC tip to the sinoatrial node that resides close to the CAJ/RA) is an advance that helps assure optimal tip position [54,55]. In a secondary analysis of a prospective registry, the overall incidence of DVT among 42,687 patients with PICCs was 1.3 percent [56]. About half of PICCs were confirmed radiographically, and the other half were confirmed using electrocardiography. Following adjustment for other DVT risk factors (eg, larger catheter size, history of DVT, cancer), electrocardiographic guidance was associated with a lower risk of PICC-related DVT compared with radiographic imaging (odds ratio 0.74, 95% CI, 0.58-0.93). These findings suggest that electrocardiographic guidance may not only provide benefits related to radiographic exposure, but also safety with respect to thrombosis.
Risk prediction — Several investigators have sought to predict and stratify risk of upper extremity DVT associated with central venous catheters, and PICCs specifically.
●One tool to predict the risk of upper extremity DVT assigns points to each of the following risk factors: presence of any intravenous device, localized pain, unilateral edema, or alternative plausible cause for symptoms [57]. Although useful, this tool was not PICC specific and often placed patients in an intermediate risk category.
●Another model to predict DVT was developed using available data on patient, provider, and device factors from 1728 patients who received PICCs [10]. The best-performing model for DVT (area under the curve, 0.83) included prior DVT (odds ratio [OR] 9.92, 95% CI 5.08-21.25), use of double-lumen 5-French (Fr; OR 7.54, 95% CI 1.61-100+) or triple-lumen 6-Fr (OR 19.50, 95% CI 3.54-100+) PICCs, and surgery lasting >60 minutes while the PICC was in place (OR 1.66, 95% CI 0.91-3.01).
●The Michigan Risk Score (MRS (calculator 1)) is a model based on data from over 20,000 patients. Risk factors associated with PICC-related DVT included history of previous DVT, placement of a multilumen PICC, active cancer, presence of another central venous catheter when the PICC was placed, and white blood cell count greater than 12,000 [24]. Four risk classes were created based on thrombosis risk. Thrombosis rates were 0.9 percent for class I, 1.6 percent for class II, 2.7 percent for class III, and 4.7 percent for class IV. Validation studies of the MRS suggest that its performance may vary across patient populations [58,59].
CLINICAL FEATURES AND DIAGNOSIS — Most events occur within the first 7 to 14 days of catheter insertion (ie, dwell time) and accumulate as catheter dwell times increases [27]. Catheter-related thromboses (PICCs and centrally inserted venous catheters alike) typically remain clinically silent [60]. It is estimated that only 3 to 10 percent of patients with PICC-related deep vein thrombosis (DVT) exhibit symptoms. Thus, a diagnosis of PICC-related thrombosis should be guided by clinical suspicion, which in turn may be assessed through risk prediction models. (See 'Risk prediction' above.).
Most PICC-related DVT does not occur at the site of insertion but in the deep veins of the upper extremity, typically at the junction of the axillary and subclavian veins. When symptomatic, the patient often complains of arm or forearm pain or swelling [12]. Measurement of limb circumference (which should be documented at baseline when a PICC is placed) is an objective and helpful way to assess an increase in girth [61]. As thrombosis progresses, dilation of the veins of the upper extremity, chest, and neck may result as collaterals develop to bypass the obstruction. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Clinical presentation' and "Clinical features, diagnosis, and classification of thoracic central venous obstruction".)
Superficial vein thrombosis (redness, pain, and swelling over the site of skin puncture and catheter entry) was a common occurrence among older-generation PICCs that were made of silicone [62,63] and inserted without ultrasound guidance. It is less common with newer polyurethane devices placed using ultrasound guidance.
Pulmonary embolism (PE) is rare with PICC-related DVT. However, PICC use has been linked to development of lower extremity thrombosis and may increase the risk of PE from this location [18]. The precise mechanism by how PICCs are linked to lower extremity DVT is unclear, but the fact that lower extremity clots are more often symptomatic and easier to detect (ie, ascertainment bias) may play a role.
Complete or partial occlusion or difficulty infusing or aspirating from the PICC may be associated with but is not necessarily a sign of PICC-related venous thrombosis. Intraluminal precipitation of drugs or minerals, blood products, or kinking of the catheter from extraluminal causes can create this clinical picture. Furthermore, formation of fibrin tails or sheaths (thin, slender structures that wrap around the catheter or the distal end of the device) can also lead to catheter dysfunction. The term catheter-related venous thrombosis should be reserved for radiographic evidence of thrombosis involving the vein in which a catheter resides.
Diagnosis — As is the case with most DVT, diagnosis of PICC-related DVT is best made by compression ultrasonography or duplex- or Doppler-enhanced ultrasound for upper extremity thromboses [64]. Visible thrombus in the vein in which a catheter resides, absence of compressibility, or reversal of blood flow are commonly reported radiographic findings in the setting of PICC-related DVT. A systematic review of 793 patients reported a sensitivity and specificity of compression ultrasound of 97 and 96 percent, respectively [65]. However, the performance drops significantly for central thromboses involving the subclavian or chest veins when anatomic structures and vessel depth limit compression and visualization. If suspicion for DVT remains high in spite of negative ultrasound, additional testing is recommended using venography (computed tomography, catheter based) with or without use of highly sensitive D-dimer [64]. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Diagnostic evaluation' and "Clinical features, diagnosis, and classification of thoracic central venous obstruction".)
TREATMENT — Treatment of PICC-related thrombosis includes symptomatic care, anticoagulation, and possibly thrombolysis. Symptomatic care includes extremity elevation, warm or cold compresses, and oral nonsteroidal anti-inflammatory agents (NSAIDs). Whether to remove the catheter depends upon whether it is functional and necessary. Replacement of the PICC must weigh the increased risk for venous thrombosis at the site of the newly placed catheter [24,27]. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Superficial vein thrombosis and phlebitis'.)
Anticoagulation — Guidelines for the treatment of venous thromboembolism disease recommend at least three months of uninterrupted systemic anticoagulation for catheter-related upper extremity DVT (including PICC-related DVT) involving deep veins of the upper extremity (eg, brachial veins, axillary veins) or chest (eg, subclavian vein, other great vessels) [66-68]. The type and intensity of anticoagulant therapy with catheter-related upper extremity DVT is similar to that given to prevent embolization from lower extremity DVT. While both warfarin and low-molecular-weight heparin (LMWH) may be used, LMWH is preferred in patients with catheter-related DVT who are pregnant or those with cancer [69]. Alternative agents may be needed in those who cannot take heparin. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Anticoagulation' and "Overview of thoracic central venous obstruction", section on 'Anticoagulation'.)
Although there are no specific recommendations regarding direct oral anticoagulants (DOACs) for catheter-related upper extremity DVT, one study reported faster resolution of PICC-related DVT with low rates of bleeding in those treated with rivaroxaban compared with traditional agents [70]. Several studies are ongoing examining the role of DOACs in catheter-related DVT [31]. In addition, cancer-related guidelines and recommendations are evolving to more frequently recommend DOACs in patients with malignancy-related thrombosis [67,68,71-73].
Anticoagulation should be continued for as long as the PICC remains in place [67,68,74,75]. However, data supporting this recommendation are scant and largely extrapolated from retrospective cohort studies and trials involving lower extremity DVT. (See 'Handling the catheter' below.)
Thrombolysis — Interventional techniques may also be used to treat PICC-related DVT, especially if the burden of thrombosis is large or if there is concern for phlegmasia. Thrombolysis can be considered for patients who meet the following criteria: severe symptoms that do not improve with anticoagulation, thrombosis spanning both the subclavian and axillary veins, good performance status, symptoms <14 days, life expectancy >1 year, and low risk for bleeding [67]. Although phlegmasia involving the upper extremities is rare, a case series and report of 37 patients found that it commonly occurred in the setting of indwelling vascular catheters; concomitant lower extremity thrombosis was associated with worse outcomes [76]. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Deep vein thrombolysis' and "Overview of thoracic central venous obstruction", section on 'Endovenous intervention'.)
Catheter-directed thrombolysis with infusion of tissue plasminogen activator (tPA) over a 12- to 24-hour period has been used to manage such cases with reasonable success (50 to 90 percent clot lysis) but with an increased risk of bleeding (10 percent) [77-79]. In addition, pharmacomechanical thrombolysis with tPA infusion with or without angioplasty or stent placement of the affected vessel has been attempted for severe cases of central venous outflow obstruction [80,81]. (See "Endovenous intervention for thoracic central venous obstruction".)
Percutaneous intervention followed by anticoagulation is associated with improved patency and a lowered incidence of post-thrombotic syndrome among patients with lower extremity DVT [82], but data regarding clinical outcomes in patients treated with this approach for PICC-related DVT do not exist.
Handling the catheter — As with other central venous catheters, routine PICC removal in the setting of DVT is not recommended. Rather, several factors should be considered in this respect, including:
●Is the catheter clinically necessary?
●Is the PICC functional (that is, does it aspirate or infuse to achieve the intended clinical purpose)?
●Is the PICC tip centrally located? PICC tips that do not terminate at the cavoatrial junction or right atrium should be repositioned to ensure that the device is located in the ideal position.
●Is there a concern for infection associated with the catheter?
Resolution of thrombosis may be faster if the PICC is removed while anticoagulation is instituted; however, any desire to remove and reinsert the PICC in the contralateral upper extremity needs to weighed against the known high risk of recurrent thrombosis at the new site [24,27]. The risk of embolization of thrombus during catheter removal has not been well studied, but clinical practice suggests that overt embolization is low. An important exception is if the PICC is nonfunctional, as removal may help resolution of thrombosis and avoid complications such as bacteremia that may occur in the setting of thrombus [83,84]. Removal of the PICC should be considered if symptoms persist despite systemic anticoagulation or if thrombosis is associated with bacteremia [67,85,86].
COMPLICATIONS — Complications of PICC-related deep vein thrombosis (DVT) can be classified as local versus systemic.
Local complications include phlebitis and inflammation of the affected vein ultimately leading to scarring and venous stenosis [87,88]. These changes have important implications for patients, especially those with chronic kidney disease; prior PICC placement is among the most important predictors of arteriovenous graft or fistula failure and threatens the success of dialysis in these individuals [89,90]. (See "Overview of thoracic central venous obstruction", section on 'Etiologies' and "Central vein obstruction associated with upper extremity hemodialysis access", section on 'Mechanisms of obstruction'.)
Although less frequent than in the lower extremities, pulmonary embolism may also occur with PICC-related DVT. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Embolization'.)
Post-thrombotic syndrome, while infrequent, has also been described with PICC-related DVT and may lead to chronic pain, swelling, and/or extremity discoloration [91]. (See "Post-thrombotic (postphlebitic) syndrome".)
PREVENTION — Like treatment, prevention of PICC-related deep vein thrombosis (DVT) includes the following:
●Avoiding use of the PICC unless it is clinically appropriate or substituting a device associated with lower risk of thrombosis is a key strategy to prevent PICC-related DVT, especially given concerns for overuse of this device. Using published appropriateness criteria can assist with such decision making prior to PICC insertion [92]. Prospective studies examining implementation of appropriate use criteria across 50 Michigan hospitals demonstrated a reduction in PICC DVT with their use [93]. (See "Central venous access: Device and site selection in adults", section on 'Michigan Appropriateness Guide for Intravenous Catheters (MAGIC)'.)
●When the use of PICC is deemed appropriate, sizing the catheter properly relative to the target vein diameter and ensuring appropriate catheter tip location are important to minimize stasis vein and endothelial injury. (See 'Device factors' above and 'Provider factors' above.)
●Removing devices promptly when they are no longer necessary is another important recommendation as most events occur within the first 7 to 14 days of dwell and accumulate over catheter dwell times [27]. Ensuring appropriate catheter tip location and sizing of catheter to veins to prevent stasis are also key prevention strategies.
Systemic use of venous thromboembolism prophylaxis (eg, subcutaneous heparin or low-molecular-weight heparin) is not associated with reduction in the risk of either centrally inserted venous catheter (CICC)- or PICC-related DVT. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Prophylactic anticoagulation'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism" and "Society guideline links: Venous access".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)" and "Patient education: Warfarin (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Peripherally inserted central catheters – Peripherally inserted central catheter (PICC) use has become increasingly popular, but PICCs are associated with a greater risk for venous thrombosis (superficial and deep veins) compared with centrally inserted catheters. Some estimates suggest that PICCs are responsible for over one-third of all upper extremity deep vein thromboses (DVTs). (See 'Incidence and risk factors' above.)
●Risk for PICC-related DVT – Risk factors for DVT associated with PICC placement include prior DVT, obesity, recent surgery, malignancy, critical illness, presence of certain comorbidities (eg, diabetes, obstructive lung disease, obesity), use of multilumen catheters, lack of ultrasound use for PICC placement, malpositioned PICCs and guidewire exchange of PICCs. (See 'Risk factors' above.)
●Symptoms of thrombosis – Most catheter-related thromboses are clinically silent and usually occur in the first 7 to 14 days from the time of catheter placement. When symptoms do occur, patients typically complain of arm or forearm pain or swelling. The chest/upper extremity veins may dilate as collaterals develop to bypass the obstruction. (See 'Clinical features and diagnosis' above.)
●Diagnosis – The diagnosis of PICC-related DVT may be suspected clinically but must be confirmed with imaging that demonstrates venous thrombosis, typically using compression or duplex ultrasonography. Most PICC-related DVT occurs at the junction of the axillary and subclavian veins, but some also occur in isolated fashion in the vessels of the arm. Venography (computed tomography, catheter based) may be indicated if the diagnosis remains in question and clinical suspicion remains high. (See 'Clinical features and diagnosis' above.)
●Treatment – The treatment of PICC-related DVT is similar to that of other catheter-related DVT and consists of symptomatic care (extremity elevation, nonsteroidal anti-inflammatory drugs [NSAIDs]) and anticoagulation for a minimum of three months or longer if the catheter remains in place or if irreversible risk factors exist (eg, cancer).
•The type and intensity of anticoagulation for catheter-related upper extremity DVT is similar to that given to prevent embolization from lower extremity DVT. (See 'Anticoagulation' above.)
•Thrombolysis can be considered for selected patients (low risk, adequate life expectancy) with PICC-related DVT who have severe symptoms (<14 days) that do not improve with anticoagulation and thrombosis spanning both the subclavian and axillary veins. (See 'Thrombolysis' above.)
•Nonfunctional PICCs and those that are no longer clinically necessary should be removed, which may help resolution of thrombosis and avoid complications that may occur in the setting of thrombus (eg, bacteremia). (See 'Handling the catheter' above.)
•For functioning PICCs that remain clinically necessary, routine removal in the setting of DVT is not recommended since reinsertion of a catheter in the contralateral upper extremity is associated with high risk of thrombosis. (See 'Handling the catheter' above.)
●Complications – Phlebitis and inflammation of the affected upper extremity veins ultimately leads to scarring and venous stenosis. Such changes have important implications, particularly for patients with chronic kidney disease. Prior PICC placement is among the most important risk factors for hemodialysis arteriovenous vascular access failure, threatening the success of dialysis in these individuals. (See 'Complications' above.)
●Prevention – Prevention of PICC-related DVT includes (see 'Prevention' above):
•Avoiding use of the PICC unless it is clinically appropriate
•Ensuring appropriate catheter tip location
•Sizing of the catheter properly relative to the target vein diameter
•Removing devices promptly when they are no longer necessary
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