Cases & Commentaries

Central Line Clot

Spotlight Case
Commentary By Adrienne G. Randolph, MD, MSc

Case Objectives

  • List the complications of central line
    manipulation
  • Appreciate the limitations of diagnostic
    studies for PE in children
  • Describe modalities for prevention of
    catheter-related venous thrombosis

Case & Commentary: Part 1

An 8-month-old girl had been in the intensive
care unit for 6 days for treatment of septic shock secondary to
meningococcemia, and was ready to be transferred to a general
pediatrics ward. In preparation for transfer, the nurse flushed the
patient’s central venous catheter with heparin and
“hep-locked” the line. Within minutes, the infant
became cyanotic and apneic. A full code ensued and after a brief
time, the patient was stabilized with a blood pressure of 95/55,
heart rate of 120, a RR of 35, and an O2 sat of 90% on 100%
non-rebreather.

Manipulation of central venous catheters can lead
to arrhythmias, venous air embolism, and thromboembolism.(1) If the tip
of the catheter is in the heart, irritation of the cardiac
conducting system by the catheter can cause premature atrial and
ventricular contractions and arrhythmias. Although rhythm
disturbances can lead to cardiac arrest requiring resuscitation,
this usually occurs in children with depressed cardiac function
and/or abnormal electrolytes.

For the infant in this case, the acute onset of a
high O2 requirement raises the suspicion of sudden embolism of air
or clot. Immediate aspiration of the central venous catheter,
ideally with the patient positioned with the right side up, can
help diagnose and treat venous air embolism. This maneuver would be
less effective if performed after CPR, such as in this patient,
because it is likely that any air would be dislodged by the chest
compressions. In this patient, venous thromboembolism must be
strongly suspected because she is recovering from a hypercoagulable
state; meningococcemia is associated with acquired deficiency of
Protein C.(2)

Pulmonary thromboembolism is reported much less
frequently in infants and children than in adult patients, with
scattered case reports and autopsy studies in the
literature.(3) It is not
clear if this is due to a true lower incidence or underdiagnosis.
Radiographic studies for pulmonary embolism are not always readily
available in children’s hospitals. Thus, therapeutic
anticoagulation is not recommended without very high suspicion of
or confirmation of a clot or pulmonary embolism. In this patient,
the suspicion of pulmonary embolism is high, and starting
anticoagulation with unfractionated heparin while further studies
are pending would be acceptable but not mandatory. If this infant
did not regain hemodynamic stability, it would be prudent to obtain
an emergent echocardiogram to evaluate the function of the right
ventricle, looking for evidence of septal deviation and pulmonary
hypertension. This would be evidence of submassive pulmonary
embolism that may require thrombolytic therapy after
confirmation.(4)

The gold standard test for diagnosing pulmonary
embolism is a pulmonary angiogram.(Figure 1)
Alternative tests are spiral computed tomography (CT) (Figure 2) and
ventilation-perfusion (VQ) scan.(5) (Figure 3) In
adults, spiral CT has been shown to have good sensitivity for
diagnosing large, centrally located pulmonary emboli and good
specificity when read by experienced radiologists.(6) Because
pulmonary embolism is rarely reported in infants and children, many
pediatric radiologists do not have experience interpreting spiral
CT scans. No studies have been done to evaluate the performance of
spiral CT in infants and children for diagnosing pulmonary
embolism. Ventilation-perfusion scans can be useful if the patient
has relatively normal lungs. Areas of atelectasis or infiltrate can
hinder accurate interpretation as blood flow to those areas may be
constricted due to decreased ventilation. Because pediatric
angiograms are rarely performed, they are not always readily
available. Therefore, despite the limitations of spiral CT and VQ
scan, these are often the first-line diagnostic studies. A readily
available study that may rule out the diagnosis of pulmonary
embolism in low-risk patients is a negative D-dimer test.(7) However,
this test has not been validated in children, and due to poor
specificity, the test cannot be used to confirm pulmonary embolism.
In this case, the patient may have a positive D-dimer because of
her meningococcemia, and therefore the D-dimer result may not help
diagnostically.

Case & Commentary: Part 2

A spiral CT revealed multiple pulmonary
emboli. Anticoagulation therapy was started. The patient improved
and was discharged home several days later without sequelae from
this event.

The coagulation system of prepubertal children is
different from that of adults, making spontaneous clots less
likely.(8) The
incidence of DVT and pulmonary embolism is not well studied in
children. One prospective study of 59 hospitalized children with
two or more risk factors identified only one patient with a
DVT.(9) A
retrospective study of pediatric trauma patients identified three
cases of DVT in 2,746 admissions.(3) The
incidence in the critically ill pediatric population is not known.
Almost all deep venous clots in neonates, and one-third in infants
and young children, are related to central venous access
devices.(10)
Catheter-related DVTs are reported in 8% to 25% of infants and
children in the ICU, as detected by ultrasound.(11,12) Even
more may be seen by venography, a more sensitive test for detecting
DVT. However, other factors also put children at risk including
congenital or acquired abnormalities of anticoagulant factors
including Protein C, Protein S, antithrombin III deficiency, Factor
V Leiden mutation, and other medical comorbidities.(Table 1) This
patient had at least two risk factors, including acquired
hypercoagulability from meningococcemia and a central venous
catheter.

It is unclear how many catheter-related thrombi
result in pulmonary emboli in children. This is partly because no
prospective studies have been done performing spiral CT, VQ, or
angiogram in pediatric populations with documented DVT. A more
commonly detected problem is thrombus propagation from the tip of
the catheter, ultimately resulting in inferior vena cava or
subclavian vein occlusion.(13) Clinically,
this can lead to swelling and discoloration of the extremity for
femoral catheters or swelling of the head or arm for subclavian or
internal jugular catheters. For most otherwise healthy children,
catheter removal and anticoagulation results in recannulation of
the vessel and/or good collateral blood flow over time. However,
clotting of the major vessels is a serious problem for chronically
ill children who require repeated central venous access, and
postphlebitic syndrome can develop.(13) Registries
of serious thrombotic complications in infants and children have
been developed in Canada and the Netherlands.(10,13,14) These
registries show that DVT in infants and children can have very
serious morbidity. Although registry data has serious limitations
in assessing actual incidence of these severe complications,
pediatric intensivists are now becoming more concerned about
catheter-related thrombosis and are looking at ways to prevent
it.

To date, the best evidence for preventing
catheter-related thrombosis in children supports use of
heparin-bonded central venous lines.(11,12) A
single-center randomized controlled clinical trial and a
before-after trial have shown that heparin-bonded catheters not
only markedly decrease the incidence of thrombus formation but also
decrease the incidence of catheter-related infection.(11,12) Low-dose
heparin flushes (10 u/ml) through the catheter are not beneficial
for adults and probably would not be for children.(15,16) Higher
doses may be effective but could result in systemic anticoagulation
in children. Dosing of low molecular weight heparin (LMWH) in
children is similar to the adult population.(17,18) However,
there have been no clinical trials evaluating LMWH for DVT
prophylaxis in this population. Since other measures to prevent DVT
such as pneumatic compression boots and compression stockings are
available only in adult size, these measures are unsuitable for
neonates and children.

In conclusion, lack of strong evidence (Table 2) makes
it difficult to write practice recommendations for prevention of
DVT in prepubertal children. There is not enough data, even in
adult patients, to determine whether thrombus associated with
central venous catheters is preventable with heparin. A multicenter
randomized clinical trial is needed to confirm whether
heparin-bonded catheters or heparin in the infusate should become
standard of care to prevent DVT. Until adequate data is available,
it would be risky to write practice recommendations, as heparin is
not without side effects. For adolescents, evidence-based
recommendations for prophylaxis, diagnosis, and management that are
available for adult patients can be applied. Once DVT or pulmonary
embolism is recognized in a young child, anticoagulation and close
follow-up are required.

Take-Home Points

  • Complications of central line
    manipulation include arrhythmias, thrombosis, and
    embolism.
  • The
    incidence of DVT/pulmonary embolism in infants and children is
    thought to be much lower than in adults; however, sub-optimal
    diagnostic modalities in this population may result in
    underestimation of these events.
  • The majority of
    thrombotic episodes in the pediatric population occur as a
    complication of central venous catheters.
  • Central line thromboses can result in serious
    morbidity, including emboli, SVC syndrome, and iliofemoral and IVC
    clots.
  • Heparin-bonded
    catheters may be an effective modality for prevention of central
    venous catheter-related
    thrombosis.

Adrienne G.
Randolph, MD, MSc
Senior Associate in Critical Care, Children's Hospital, Boston,
Massachusetts
Assistant Professor of Pediatrics (Anaesthesia), Harvard Medical
School
Chair, Pediatric Acute Lung Injury and Sepsis Investigator's
(PALISI) Network

Faculty
Disclosure: Dr. Randolph has declared that neither she, nor
any immediate member of her family, has a financial arrangement or
other relationship with the manufacturers of any commercial
products discussed in this continuing medical education activity.
In addition, her commentary does not include information regarding
investigational or off-label use of pharmaceutical products or
medical devices.

References

1. Polderman KH,
Girbes AJ. Central venous catheter use. Part 1: mechanical
complications. Intensive Care Med. 2002;28:1-17.[ go to PubMed
]

2. Faust SN, Levin M,
Harrison OB, et al. Dysfunction of endothelial protein C activation
in severe meningococcal sepsis. N Engl J Med. 2001;345:408-16.[ go to PubMed
]

3. Grandas OH, Klar
M, Goldman MH, Filston HC. Deep venous thrombosis in the pediatric
trauma population: an unusual event: report of three cases. Am
Surg. 2000:66:273-276.[ go to PubMed
]

4. Konstantinides S,
Geibel A, Heusel G, Heinrich F, Kasper W. Management strategies and
prognosis of pulmonary embolism-3 trial investigators. Heparin plus
alteplase compared with heparin alone in patients with submassive
pulmonary embolism. N Engl J Med. 2002;347:1143-50.[ go to PubMed
]

5. Velmahos GC,
Vassiliu P, Wilcox A, et al. Spiral computed tomography for the
diagnosis of pulmonary embolism in critically ill surgical
patients: a comparison with pulmonary angiography. Arch Surg.
2001;136:505-11.[ go to PubMed
]

6. Baile EM, King GG,
Muller NL, et al. Spiral computed tomography is comparable to
angiography for the diagnosis of pulmonary embolism. Am J Respir
Crit Care Med. 2000;161:1010-5.[ go to PubMed
]

7. Kelly J, Rudd A,
Lewis RR, Hunt BJ. Plasma D-dimers in the diagnosis of venous
thromboembolism. Arch Intern Med. 2002;162:747-756.[ go to PubMed
]

8. Chan AK, Berry LR,
Monagle PT, Andrew M. Decreased concentrations of heparinoids are
required to inhibit thrombin generation in plasma from newborns and
children compared to plasma from adults due to reduced thrombin
potential. Thromb Haemost. 2002;87:606-13.[ go to PubMed
]

9. Rohrer MJ, Cutler
BS, MacDougall E, Herrmann JB, Anderson FA Jr, Wheeler HB. A
prospective study of the incidence of deep venous thrombosis in
hospitalized children. J Vasc Surg. 1996;24:46-9.[ go to PubMed
]

10. van Ommen CH,
Heijboer H, Buller HR, Hirasing RA, Heijmans HS, Peters M. Venous
thromboembolism in childhood: a prospective two-year registry in
the Netherlands. J Pediatr. 2001:139:676-81.[ go to PubMed
]

11. Pierce CM, Wade
A, Mok Q. Heparin-bonded central venous lines reduce thrombotic and
infective complications in critically ill children. Intensive Care
Med. 2000;26:967-72.[ go to PubMed
]

12. Krafte-Jacobs B,
Sivit CJ, Mejia R, Pollack MM. Catheter-related thrombosis in
critically ill children: comparison of catheters with and without
heparin bonding. J Pediatr. 1995;126:50-4.[ go to PubMed
]

13. Monagle P, Adams
M, Mahoney M, et al. Outcome of pediatric thromboembolic disease: a
report from the Canadian Childhood Thrombophilia Registry. Pediatr
Res. 2000;47:763-6.[ go to PubMed
]

14. Andrew M, David
M, Adams M, et al. Venous thromboembolic complications (VTE) in
children: first analyses of the Canadian Registry of VTE. Blood.
1994;83:1251-7.[ go to PubMed
]

15. Randolph AG, Cook
DJ, Gonzales CA, Andrew M. Benefit of heparin use in central venous
and pulmonary artery catheters: a meta-analysis of randomized
controlled trials. Chest. 1998;113:165-71.[ go to PubMed
]

16. Smith S, Dawson
S, Hennessey R, Andrew M. Maintenance of the patency of indwelling
central venous catheters: is heparin necessary? Am J Pediatr
Hematol Oncol. 1991;13:141-3.[ go to PubMed
]

17. Albisetti M,
Andrew M. Low molecular weight heparin in children. Eur J Pediatr.
2002:161;71-7.[ go to PubMed
]

18. Massicotte P,
Adams M, Marzinotto V, Brooker LA, Andrew M. Low-molecular-weight
heparin in pediatric patients with thrombotic disease: a dose
finding study. J Pediatr. 1996;128:313-8.[ go to PubMed
]

Tables

Table 1. Risk
Factors for DVT in Infants and
Children

Central venous catheter

Sepsis and other acute states with
disseminated intravascular coagulation

Hereditary or acquired abnormalities of
anticoagulant factors

Immobility

Cancer

Nephrotic syndrome

Moderate to severe dehydration

Greater than 150% ideal body weight

Use of oral contraceptives

History of DVT or pulmonary embolism in
the past

Table 2. Possible
Interventions to Prevent Catheter-Related Thrombosis in
Children

Intervention

Supportive Evidence in
Children

Heparin infusate

Ineffective at low doses (15,16)
May be dangerous in small children at high doses due to amount of
heparin exposure

LMWH prophylaxis

No data on efficacy in children

Heparin-bonded catheters

One RCT in 228 patients showed markedly
decreased thrombosis (ARR 8%, 95% CI 2.6% to 13%) and infection
(ARR 88%, 95% CI 67% to 95%).(11) A smaller
before-and-after prospective study also showed decreased thrombosis
and infection.(12)

Figures

Figure 1.
Pulmonary angiogram in a patient with PE. The clot appears as a
filling defect (arrow).


Figure 2. Spiral
CT in a patient with PE. The clot appears as a filling defect
(arrow).


Figure 3.
Ventilation-Perfusion (VQ) Scan. Clots appear as perfusion defects,
without corresponding defects on the ventilation scan ('mismatched
defects').