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Journal of Parenteral and Enteral Nutrition
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Presentations

Treatment of Catheter Occlusion in Pediatric Patients

John A. Kerner, Jr, MD*,{dagger}, Manuel G. Garcia-Careaga, MD*,{dagger}, Amy A. Fisher, MS, RN, CNSN{dagger} and Robert L. Poole, PharmD{dagger}

From the * Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Stanford University Medical Center, Stanford, California; and the{dagger} Department of Pharmacy, Lucile Packard Children's Hospital, Palo Alto, California

Correspondence: John A. Kerner, Jr, MD, Division of Pediatric Gastroenterology, 750 Welch Road, Suite 116, Palo Alto, CA 94304. Electronic mail may be sent to jkerner{at}stanfordmed.org.

A proper initial assessment of catheter occlusion is the key to successful management. The assessment screens are for both thrombotic and nonthrombotic causes (including mechanical occlusion). If mechanical occlusion is excluded, thrombotic occlusion is treated with alteplase. Nonthrombotic occlusions are treated according to their primary etiologies: lipid occlusion is treated with 70% ethanol, mineral precipitates are treated with 0.1-N hydrochloric acid (HCl), drug precipitates are treated according to their pH—acidic drugs can be cleared with 0.1-N HCl, basic medications can be cleared with sodium bicarbonate or 0.1-N sodium hydroxide (NaOH). Prevention of occlusion of central venous access devices is also critical. To date, no data conclusively show heparin flushes to be superior to saline flushes. No prophylactic regimen, including low-dose warfarin, low-molecular-weight heparin, or 1 unit heparin/mL of parenteral nutrition has been endorsed by any major medical, nursing, or pharmacy group due to lack of scientific evidence. The most encouraging information on decreasing occlusion rate comes from experience with positive-pressure devices that attach to the hub of most catheter lumens and prevent retrograde blood flow and, consequently, decrease the risk of thrombus formation in the catheter lumen.

It is estimated that >5 million central venous access devices (CVADs) are inserted in patients in the United States each year and that up to 25% of these catheters will develop problems with occlusion.1 Catheter occlusion occurs at a rate of 0.071 episodes per catheter-year in home parenteral nutrition (HPN) patients.2 An analysis of >50,000 CVADs used in home care patients revealed that approximately 5% of the devices experienced a loss of patency.3 Gorski4 found occlusion rates of 6.5% in peripherally inserted central catheters (PICCs) and 1.8% in non-PICC CVADs in a 4-year analysis of CVAD-related outcomes for 1 home care agency.


   Catheter Occlusion: Definition
Top
 Catheter Occlusion: Definition
Primary Assessment of Catheter...
 Thrombotic Catheter Occlusion
 Nonthrombotic Catheter Occlusion
 Prevention of Catheter Occlusion
 Warfarin
 Conclusions
 
Catheter occlusion is defined as a partial or complete obstruction of the CVAD that limits or prevents the ability to withdraw blood, flush the catheter, or administer parenteral solutions or medications. Catheter occlusion is a significant complication because infusion therapy may be delayed or interrupted. In many cases, catheter occlusion can be treated, avoiding the trauma and cost of catheter removal and replacement.4


   Primary Assessment of Catheter Occlusion
Top
 Catheter Occlusion: Definition
 Primary Assessment of Catheter...
Thrombotic Catheter Occlusion
 Nonthrombotic Catheter Occlusion
 Prevention of Catheter Occlusion
 Warfarin
 Conclusions
 
The proper assessment of catheter occlusions is key to successful management. The primary assessment should include screening for both thrombotic and nonthrombotic occlusions (Table I).


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  		TABLE I Causes of catheter occlusion

 

The following steps are suggested: (a) screen for extrinsic compression from clamps, sutures, and kinked catheter tubing; (b) check catheter function in terms of infusion and blood aspiration; (c) assess whether the occlusion is relieved by postural changes such as raising the ipsilateral arm and shrugging the shoulders forward; (d) take a careful history of what was recently infused through the catheter (eg, medications, blood products); (e) perform a careful physical examination, looking for signs of edema, redness, pain, or dilated vessels.

CVADs can migrate at any time.5 Radiographic studies to confirm CVAD placement or device patency should be performed. Another potential mechanical problem is "pinch-off syndrome." Blood return is only obtained when the patient's arm, on the same side as the catheter insertion site, is raised parallel to the shoulder. This maneuver indicates the catheter is compressed between the clavicle and the first rib. Pinch-off syndrome can lead to catheter fracture and embolism. Removal of the catheter and placement of a new catheter lateral to the midclavicular line is recommended.6,7 Suspect malpositioning if you have difficulty aspirating fluid from the catheter and that difficulty resolves after the patient coughs, performs a Valsalva maneuver, or changes his body position. If these actions solve the problem only temporarily, the physician may need to partially withdraw the catheter or reposition it using fluoroscopy.7


   Thrombotic Catheter Occlusion
Top
 Catheter Occlusion: Definition
 Primary Assessment of Catheter...
 Thrombotic Catheter Occlusion
Nonthrombotic Catheter Occlusion
 Prevention of Catheter Occlusion
 Warfarin
 Conclusions
 
Thrombotic catheter occlusions account for approximately 60% of all catheter occlusions1 (Table I). They occur when deposits of fibrin and blood components within and around CVADs impede or disrupt flow through the catheter.4 PICC lines may be more prone to thrombotic occlusion due to their longer length and smaller diameter.8 Thrombotic occlusions may slowly develop over time or occur suddenly.4 There are 4 main types of thrombotic occlusions (Table II). These 4 types have been well described previously.4,9,10 Thrombotic occlusions may contribute to the development of CVAD-related infection because the blood clot serves as a rich culture medium for bacterial growth.11 Clinicians should be aware that when a patient has a multilumen CVAD, it is not acceptable practice to leave an occluded lumen untreated just because another lumen is functional.


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  		TABLE II Types of thrombotic catheter occlusions

 

In the past, urokinase (Abbokinase, Abbott Laboratories, Abbott Park, IL) was the drug of choice for treating thrombotic CVAD occlusions. The US Food and Drug Administration (FDA) halted the shipment of urokinase in 1999, citing manufacturing deficiencies, specifically having concerns of transmission of infectious agents. Streptokinase, a thrombolytic agent derived from group C β-hemolytic streptococci, was not considered an optimal alternative due to FDA warnings regarding the risk of life-threatening anaphylaxis.12

Clinicians began to evaluate alteplase (t-PA) as an alternative declotting agent. In 1994, when urokinase was still the standard for catheter declotting, it was demonstrated that a low dose of t-PA was actually more successful than urokinase in restoring catheter function.13 This randomized trial compared use of a 2-mg dose of t-PA to a 10,000-unit dose of urokinase (twice the normal dosage) in occluded catheters as confirmed by a radiographic dye study. Return of catheter function occurred in 89% of t-PA-treated catheters vs 59% in the urokinase-treated catheters (p = .013). In both groups, up to 2 doses of drug were administered.

t-PA is genetically engineered human tissue–plasminogen activase. It works by acting on fibrin-bound plasminogen (clot), producing plasmin at the surface of the clot, which works from the outside in to cause lysis of the clot.

Two major phase III trials were initiated in July 1999 to evaluate t-PA as a possible alternative to urokinase in clearing occluded catheters without x-ray verification. The first trial (Cardiovascular thrombolytic to Open Occluded Lines; COOL-1) was a double-blind, randomized, prospective study comparing t-PA (2 mg/2 mL) to placebo in 149 patients.14 Function was restored in 74% of catheters treated with a single dose of t-PA vs 17% for placebo (p < .0001). Cumulative efficacy after up to 2 doses was 90%, with no reported drug-related adverse events. The second trial (COOL-2) was an open-label, single-arm study in nearly 1000 patients with dysfunctional CVADs. The COOL-2 study enrolled 995 patients between the ages of 2 and 91 years and demonstrated that t-PA treatment was highly effective in restoring catheter function (88%) with minimal adverse events.15 The doses of t-PA in COOL-1 and COOL-2 were:

  • Patients ≥30 kg received 2 mg in 2 mL to fill the lumen of the catheter.
  • Patients <30 kg received a dose equal to 110% of the internal catheter volume.
  • Dysfunctional catheters were defined by the inability to withdraw 3 mL of blood. Patients were excluded from the study if it was not possible to infuse the necessary volume of study drug into the CVAD. In both COOL-1 and COOL-2, the primary safety end-point was intracranial hemorrhage (ICH) within 5 days; combining the patients from the 2 studies (n = 1064 patients),16 there were no incidences of ICH and no embolic events within 30 days of treatment. Other side effects included gastrointestinal bleeding (0.3%), thrombosis (0.3%), and sepsis (0.4%). One event (fever) was attributed to the study drug.16 Due to the rare adverse reactions of sepsis, gastrointestinal bleeding, and deep-vein thrombosis (DVT), it is recommended that t-PA be used with caution if there is known or suspected catheter-related infection and in patients with bleeding disorders or who are at risk for bleeding.4,16
  • In unpublished observations, we evaluated the results of the pediatric patients ages 2–17 in COOL-1 (n = 12) and COOL-2 (n = 117). In COOL-1, there was restoration of function in 5 of 6 (83.3%) catheters in the t-PA arm vs 1 of 6 (16.7%) catheters in the placebo arm. In COOL-2, 100/114 (87.7%) had catheter function restored after 2 doses of t-PA. Shen and coworkers17 did a pediatric subgroup analysis of subjects 2 through 18 years of age in COOL-2. Restoration of function of the catheters occurred in 87% who received up to 2 doses of t-PA.17 T-PA (Cathflo Activase, Genentech, South San Francisco, CA) was approved for catheter clearance in adults in September 2001; the FDA requested additional data in the pediatric population. In March 2002, the phase IIIB, multicenter, prospective, single-arm, open-label, FDA study began in the pediatric population—Cathflo Activase in Pediatrics Study (CAPS). The study, not yet published, has been completed in 310 children: 55 <2 years and 255 ≥2 years. Preliminary data from the Investigator Close-out meeting, October 2003, Orlando, Florida, show that Cathflo Activase is safe in both patients <2 years of age and the general pediatric population <17 years of age. No ICH, major hemorrhage, thrombosis, or embolic events occurred. Incidence of protocol-defined sepsis was similar to that seen in COOL-2. The high rate of efficacy in restoring catheter function was similar to that seen in COOL-1 and COOL-2.
  • Several recent studies in pediatric patients have shown similar efficacy with minimal side effects. Jacobs et al18 reported the use of t-PA in managing occluded catheters in 228 children. The overall efficacy rate was 91%, with no adverse events attributed to t-PA treatment. Fisher et al19 cleared 95% of occluded catheters in 21 pediatric patients. Choi et al20 restored catheter patency in 85% of catheters in 25 children. Chesler et al21 demonstrated a complete response to treatment in 37 of 42 pediatric patients (88% success rate). Our protocol for the use of t-PA in pediatric patients is shown in Figure 1.
  • Recently, Svoboda and colleagues22 have studied recombinant urokinase (r-UK). Pediatric and adult patients with any type of CVAD occlusion of any duration were entered in this multicenter, open-label study to test the hypothesis that a new r-UK is safe and effective in reestablishing patency in a large unselected cohort of occluded CVADs. All were treated with 5000 IU/mL intracatheter r-UK. r-UK instillations totaling 903 in 878 patients (ages 16 days to 96 years) resulted in restoring patency to at least 1 occluded lumen in 79% of devices (712 of 902). Patency was restored equally in catheters with total occlusion (76%) as in patients with only "withdrawal occlusion" (75%). Median time to patency was 15 ± 26.8 minutes (range, 5–203 minutes). One-third of the catheters in the study were totally occluded. The drug proved to be both safe and effective. Haire et al23 performed a phase III multicenter double-blinded study of r-UK (5000 IU r-UK vs placebo). If there was no response after 30 minutes, a second dose was given. If there was no response after 1 hour, 2 open-label r-UK doses were given. Haire and colleagues studied 180 patients (20% were ≤18 years of age). R-UK was significantly better than placebo: 54% vs 30% for restoring catheter function. There was no difference in the side effects in the 2 groups. In the accompanying editorial to Dr Svoboda's work, Horne24 pointed out that r-UK is currently not marketed and that previous work suggests that t-PA will perform better than r-UK.13 Horne suggested that t-PA could achieve the same success rates in totally obstructed catheters using the technique used by Dr Svoboda and colleagues, using a 3-way stopcock. In this method, a syringe containing the medication, an empty 12-mL syringe, and the catheter lumen are each attached to one part of the stopcock. First, the empty syringe and catheter lumen are opened and the syringe is pulled back to the 10-mL marking and then closed. This creates negative pressure within the catheter. Opening the stopcock to the medication allows it to be pulled into the catheter. This method reduces the risk of catheter rupture as the pharmacologic agents are not instilled under positive pressure.
  • Reteplase (Retavase, Centocor, Inc, Malvern, PA) is a new recombinant tissue plasminogen activator similar to t-PA but is missing several structural domains. Fibrinolysis with t-PA proceeds from the outer surface of the thrombus to the inner mesh. Reteplase, due to its unique structure, may result in increased thrombus penetration and allow fibrinolysis to occur throughout the thrombus.
  • A retrospective analysis of a single 0.4-unit dose of reteplase in adults with occluded catheters was shown to restore patency to 74% of the CVADs, with dwell times of 30 minutes.25 Reteplase was given to 15 clotted CVCs in children with cancer.26 The study was a dose escalation trial, initiated at 0.1 units and increased by increments of 0.1 units to a maximum dose of 0.4 units. Twelve of the 15 catheters cleared, with an average dwell time of 38 minutes (time to patency did not correlate with the dose). No adverse events were reported. Reteplase appears to have a comparable efficacy with t-PA, but reteplase may require shorter dwell times. In adults, an open-label single-arm prospective trial was performed to evaluate the safety and efficacy of reteplase.27 Reteplase (0.4 units) was installed into each catheter lumen, with a dwell time of 30 minutes in patients with cancer and a dysfunctional CVAD. If the first dose failed, 30 extra minutes of dwell time were given; if there was no function at 1 hour, a second dose was instilled for 60 more minutes (120 minutes with up to 2 doses). One hundred thirty-nine patients were studied. By 30 minutes, 66.9% of catheters cleared; success rates were 88.5%, 94.7%, and 94.7% at 60 minutes, 90 minutes, and 120 minutes, respectively. There were no adverse effects. A prospective, randomized, clinical trial is warranted to compare safety and efficacy of t-PA vs reteplase.


Figure 1
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  		FIGURE 1. Pediatric order form for the use of alteplase. Reprinted with permission from the Lucile Packard Children's Hospital at Stanford.

 

   Nonthrombotic Catheter Occlusion
Top
 Catheter Occlusion: Definition
 Primary Assessment of Catheter...
 Thrombotic Catheter Occlusion
 Nonthrombotic Catheter Occlusion
Prevention of Catheter Occlusion
 Warfarin
 Conclusions
 
Once the mechanical causes of catheter occlusion have been excluded by careful assessment, nonthrombotic occlusion causes should be considered, and should include drug or mineral precipitates and lipid residue.

Fat Deposition. Pennington and Pithie28 observed increased resistance when flushing the catheter for several days before the catheter completely occludes with lipid sludge. Five patients had received "all-inone" PN with lipid occlusions. Four out of 5 catheters cleared after 3 mL of 70% ethanol was left in situ for 1 hour; then the catheter was flushed with saline and heparinized.

Pennington,29 in a subsequent letter to the editor, stated that if urokinase was given first in a lipid occlusion, complete occlusion would occur. Further, he recommended that patients successfully treated with ethanol should replace their saline flush with a flush of 10 mL of 20% ethanol; he believed that such ethanol flushes led to a reduction in incidence of occlusion.

Erdman et al30 showed in a pediatric study of 15 cases that lipid buildup was less likely with 3-in-1 solutions used within 28 hours (in inpatients) vs longer storage periods (up to 7 days) in the home setting. Their group showed that separate (SPLIT) infusions of IV fat and glucose/amino acid solutions (ie, separate infusions of the IV fat and of the glucose amino acid, with the IV fat infusion "Y'd" in just above the entry to the vein) decrease the incidence of occlusion. Line life in the SPLIT group was 290 days (n = 7); in the 3-in-1 group, line life was only 70 days (n = 8).

In pediatric patients, Werlin et al31 identified 10 of 26 occlusions associated with lipid administration. His group used 0.55 mL/kg 70% ethanol (to a maximum of 3 mL). In adult patients, ter Borg et al32 showed that slow infusion of 10–20 mL of 0.1 mmol/mL NaOH successfully improved occlusion from 3-in-1 solutions in 13 adults. They postulated the catheter occlusion etiology was lipid-fibrin occlusions. Interestingly, we reported a case of a pediatric patient with an occlusion caused by fibrofatty tissue, a combination of fibrin and fat.33 We cleared the occlusion after multiple treatments with urokinase and ethanol. An ethanol installation finally cleared the catheter.

An ethanol lock has recently been shown to aid in the treatment of bloodstream infections in pediatric oncology patients with Broviac catheters.34 Eighteen patients had the ethanol-lock technique and IV antibiotics; 13 patients had IV antibiotics alone. Within 4 weeks of treatment, no relapse of any kind occurred in 67% of those treated with the ethanol-lock and 47% treated only with antibiotics.34 A 31-year-old patient with recurrent catheter-related sepsis had 22 admissions for catheter-related infection from 1993 to 2000 and no infections after using an ethanol lock daily from 2001 through 2003.35

Calcium Phosphate Precipitates. Hydrochloric acid has been used to dissolve calcium phosphate precipitates that occluded catheters as a result of PN solutions containing high concentrations of calcium and phosphorus.36–39 The solubility of calcium phosphate decreases with increased pH, increased concentrations of calcium and phosphorus, elevated temperature (common in neonatal ICU hotbeds), and time since preparation. Infants have increased daily requirements of calcium and phosphorus, and if they are critically ill, fluid restriction may be necessary. These 2 factors may increase the risk of calcium phosphate precipitation, resulting in catheter occlusion.38

Holcombe and colleagues40 inject a volume of up to 1 mL of 0.1-N HCl into the CVAD to restore patency. This small amount is unlikely to cause a metabolic acidosis.36 Breaux et al37 reported that 42% of patients who received 0.1-N HCl irrigations into their CVADs had a febrile reaction. Duffy et al38 reported no adverse reactions because the HCl was aspirated from the catheter rather than infused. Werlin et al31 infused up to 3 mL of 0.1-N HCl (up to 1 mL in infants between 1 and 3 kg). A 1-mL syringe containing 0.5 mL of the solution is connected to the catheter hub and a gentle push-pull motion applied to the syringe plunger. If the catheter did not clear, treatment remains in the line up to 1 hour; then it is aspirated. Werlin et al31 demonstrated 3 mineral precipitates in their series. Shulman et al36 gave 0.2–1.0 mL 0.1-N HCl and cleared 2 of 2 calcium-phosphate precipitates.

Of further interest is a fascinating study from Canada. In a retrospective review, 42 pediatric oncology patients at the Children's Hospital at Westmead, Canada, received IV antibiotics and 2-M HCl between 1994 and 2000.41 These patients had persistent positive blood cultures after 48 hours of IV antibiotic treatment. HCl installation was then added to the regimen. Sixty-seven percent of the infection episodes were eradicated. The above treatment enabled both (1) catheter salvage and (2) eradication of antibiotic-refractory catheter-related infection.41

Drug Precipitates. The administration of medications that have low solubility is often incompatible with PN solutions or is incompatible with other drugs and can result in a precipitate that occludes the CVAD. These occlusions are usually sudden and occur with infusion of a drug or heparin. They are often the result of inadequate flushing techniques between drug administration or between drug and PN administration.42

The method for clearing those precipitates depends on the pH of the drug. Acidic drugs such as vancomycin and etoposide can be cleared using 0.1-N hydrochloric acid (0.1-N HCl)39; 0.1-N HCl was also used to clear a catheter occlusion secondary to the sequential administration of amikacin, piperacillin, vancomycin, and heparin.36 When the occlusion is suspected to be the result of basic medications (eg, ticarcillin, oxacillin, heparin, phenytoin, imipenem) it can be cleared with sodium bicarbonate (1 mL of 1 mEq/mL)40 or 0.1-N NaOH.42 Shulman et al36 cleared 2 pediatric drug precipitates with 0.1-N HCl. Werlin et al31 cleared 13 pediatric drug precipitates with 0.1-N HCl.


   Prevention of Catheter Occlusion
Top
 Catheter Occlusion: Definition
 Primary Assessment of Catheter...
 Thrombotic Catheter Occlusion
 Nonthrombotic Catheter Occlusion
 Prevention of Catheter Occlusion
Warfarin
 Conclusions
 
Nursing Interventions. Using a normal saline flush before and after administration of blood, blood products, and medications; before and after blood sampling; and at each IV tubing change is recommended to minimize the number of occlusions.43 When flushing the catheter, it is recommended to use the "push-stop-push-stop" technique to create turbulent flow and reduce the buildup of residue on the inner surface of the catheter.4 When administering medications, we recommend using the SASH (saline-administer drug-saline-heparin) procedure. Using a positive-end pressure technique while flushing, such as clamping the CVAD while maintaining syringe pressure, minimizes blood reflux and is an Infusion Nursing Society (INS) standard of practice.44

A positive-pressure device can be attached to the hubs of most CVAD lumens. These devices maintain positive pressure within the lumen when syringes and IV tubing are disconnected from the catheter, preventing backflow of blood that can result in occlusion. Examples of such devices include the CLC2000 adapter valve (ICU Medical, San Clemente, CA) and the PASV valve (Boston Scientific Corporation, Natick, MA) and the MaxPlus positive flow needleless connector (Maximus Medical Products, Inc, Ontario, CA). Rummel et al45 have recently shown that the use of a positive pressure device (the CLC2000) in 10 patients on an oncology inpatient unit decreased the incidence of catheter-related thrombus (CRT) and CRT-related costs. We have found a decreased incidence in catheter occlusion since our hospital began to use such positive-pressure devices.

Heparin. The addition of heparin (1000 units/L) to the PN solution to prevent thrombosis is controversial; no randomized, controlled studies have demonstrated benefit. Heparin administration can result in heparin induced thrombocytopenia (HIT) and loss of bone mineral.2

FLUSHES. Several recent studies have shown no benefit from heparin flushes of catheters compared with saline flushes in preventing catheter occlusion.46,47

ADDING HEPARIN TO PN. A randomized controlled trial of heparin for prevention of catheter occlusions in PICC lines showed no difference in infants receiving PN with 1 unit/mL of heparin vs those with no heparin.48

META-ANALYSIS. Randolf et al49 performed an elegant meta-analysis on the benefit of heparin in central venous and pulmonary artery catheters. Twelve separate trials were included in their analysis. For catheter thrombus or fibrin sheath, there was a trend for heparin to be beneficial in preventing catheter thrombi or fibrin sleeves; however, this finding did not reach statistical significance.

In contrast, heparin effectively reduced catheter-related venous thrombosis by 57%. Heparin also significantly decreased the bacterial colonization of the catheter, and there was a strong reduction in catheter-related bacteremia.

The authors combined all trials using various prophylactic doses of heparin. Trials using heparin at doses of 3 units/mL in PN, 5000 units every 6 or every 12 hours, or 2500 units of subcutaneous low-molecular-weight heparin every day decreased the risk of major vessel thrombosis; they concluded that lower doses may not be effective.49

HEPARIN-BONDED CATHETERS. A series of 50 pediatric intensive care unit patients prospectively received either a heparin-bonded (n = 25) or standard femoral venous catheter (n = 25). Patients were followed with weekly ultrasonography. Thrombotic complications occurred in 44% of the standard catheter group vs 8% in the heparin-bonded catheter group. Positive catheter blood cultures were obtained in 24% of the standard catheter group vs 0% in the heparin-bonded catheter group.50 Heparin-bonded catheters are not without complications; their use has been associated with heparin-associated antiplatelet antibodies and thrombocytopenia in adults.51


   Warfarin
Top
 Catheter Occlusion: Definition
 Primary Assessment of Catheter...
 Thrombotic Catheter Occlusion
 Nonthrombotic Catheter Occlusion
 Prevention of Catheter Occlusion
 Warfarin
Conclusions
 
Very low doses of warfarin have been shown to be effective in reducing CRT. Bern et al52 randomized 82 patients with solid tumors to receive or not receive 1 mg of warfarin beginning 3 days before catheter insertion and continuing for 90 days. The rates of venogram-proven thrombosis were 4 of 42 in the treatment group vs 15 of 40 in the control group. Unfortunately, warfarin had to be discontinued in 10% of the patients due to prolongation in the prothrombin time.52 Yet, low-dose anticoagulant therapy (eg, 1 mg/d of warfarin) is cited as an evidence-based practice guideline for preventing catheter-related thrombosis in patients who have cancer.53 Andrew et al54 effectively treated 5 children with warfarin (0.12–0.28 mg/kg/d). These children had extensive evidence of DVT. Andrew and coworkers54 achieved an INR of 1.4–1.8. Neither bleeding nor further central venous line–related DVT occurred subsequently.

We have found absorption rates of oral warfarin to be quite variable in our short bowel patients, making this group difficult to adequately control on warfarin. Recent studies of low-dose warfarin do not support its use in prophylaxis of catheter occlusion.55 Prophylactic flushes with unfiltered heparin or saline are the standard of care to maintain CVAD patency but are inadequate to prevent blood-vessel thrombosis. The benefit of systemic prophylaxis with low-molecular-weight heparin or warfarin has not been well established. Although larger placebo-controlled studies of low-dose warfarin may be warranted, it might be more fruitful to use newer factor Xa inhibitors, such as pentasaccharide, or direct thrombin inhibitors, such as ximelagatran.55


   Conclusions
Top
 Catheter Occlusion: Definition
 Primary Assessment of Catheter...
 Thrombotic Catheter Occlusion
 Nonthrombotic Catheter Occlusion
 Prevention of Catheter Occlusion
 Warfarin
 Conclusions
 
A proper initial assessment of catheter occlusions is the key to successful management. The assessment screens are for both thrombotic and nonthrombotic causes (including mechanical occlusion). Highlights of that assessment and of the symptoms, treatment, and pediatric dosage guidelines for each type of occlusion are depicted in Table III. To help decide the order of agents to infuse into occluded catheters, a number of algorithms have been published. We have found the 2 most helpful algorithms are from Holcombe et al40 and from Jacobs.56


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  		TABLE III Diagnosis and treatment of catheter occlusions

 

Prevention of occlusion of CVADs is also critical. Specific flushing guidelines have been discussed in detail in this manuscript. To date, no data conclusively show heparin flushes to be superior to saline flushes; saline flushes are less expensive and avoid potential toxicities of heparin flushes, HIT and loss of bone mineral. No prophylactic regimen, including low-dose warfarin, low-molecular-weight heparin, 1 unit heparin/mL of PN, has been endorsed by any major medical, nursing, or pharmacy group due to lack of solid scientific evidence. The most encouraging information on decreasing occlusion comes from experience with positive-pressure devices that attach to the hub of most catheter lumens, prevent retrograde blood flow, and consequently decrease the risk of thrombus formation in the catheter lumen.4,45 These devices need to be flushed only with saline, which leads to a significant cost savings as well.45

The work was supported in part by the Carl and Patricia Dierkes Endowed Fund for Nutrition and Home Care.

Received for publication April 14, 2005. Accepted for publication October 3, 2005.

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Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 1 suppl, S73-S81 (2006)
DOI: 10.1177/01486071060300S1S73
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