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Pain, Inflammation and a Nodule After IV Medication

Vol. 13 •Issue 7 • Page 21
Pain, Inflammation and a Nodule After IV Medication

Elizabeth, a 20-year-old college student, presented to the student health center where I work in January 2005. She reported having a painful vein on her right forearm since an intravenous medication injection a month prior. She had gone home over the Christmas break, become ill with gastroenteritis and sought medical treatment in the emergency department of a large teaching hospital near her home.

She received intravenous promethazine (Phenergan) and recalled that it burned considerably as it was administered. Elizabeth said that when she mentioned this to the staff member giving her the medication, the person told her she was "fine" and that she should apply warm compresses to the area if her discomfort persisted.

By the time she presented to the student health center, Elizabeth had been following this regimen for a month without relief and still had a tender, hard area on the vein above her right wrist. Her pain was constant and moderate in severity, made worse by contact and only slightly better with the warm compresses. She said she recently noticed a "knot" on her right arm just below her elbow.

Elizabeth had no fever, chills, shortness of breath, chest pain or cough. She reported no injury to the area. Her past medical history was unremarkable; she took no medications other than oral contraceptives and had no drug allergies. She was a nonsmoker.

Exam and Diagnostic Tests

On exam, Elizabeth was alert, afebrile and in no distress. On the dorsal aspect of her distal right forearm were two swollen, tender, inflamed areas along the track of her basilic vein. One area was approximately 4 cm long and just proximal to her right wrist. The other was approximately 1 cm long and just proximal to the first inflamed segment. I palpated a 0.5-cm, somewhat firm nodule on the dorsal proximal right forearm about 2 cm distal to the medial condyle. This appeared similar to the epitrochlear node but was not in the classic position for it.

I diagnosed Elizabeth with superficial phlebitis. Since she reported no history of gastrointestinal bleeding or ulcers, I prescribed oral naproxen sodium (Naprosyn) 500 mg every 12 hours with food. I also instructed her to take one 81-mg enteric-coated aspirin daily for its antiplatelet properties and wrote a referral for venous Doppler study to rule out thrombophlebitis. I instructed her to continue the warm compresses 4 to 6 times daily and to elevate her arm as much as possible. I further instructed her to report to the emergency department should she develop any shortness of breath, chest pain or hemoptysis. She was discharged home with further follow-up to be determined once the Doppler study results were in.

Elizabeth had her Doppler study a week later, and the results indicated a localized venous thrombosis in the right basilic vein just distal to the elbow. The radiologist noted that a superficial vein on the dorsum of the right hand demonstrated marked wall thickening but had good flow and compressibility, probably due to chronic thrombophlebitis. Based on these results, I referred Elizabeth to a local surgeon who evaluated her and instructed her to return for local excision in 2 months if the clot did not resolve.


Superficial thrombophlebitis occurs frequently, yet it does not get much attention in the literature.1 This lack of attention is probably because the condition is often relatively mild and self-limiting. The list of risk factors is long (Table 1).

In contrast to deep vein thrombosis (DVT), which may result from hereditary blood disorders or chronic illness, superficial thrombophlebitis is typically the result of trauma (e.g., IV insertion and infusion of irritating medicines) or infection.1,2 This condition is common, occurs most frequently in young to middle-aged adults, and is slightly more frequent in women.1

Superficial thrombophlebitis does not typically cause significant morbidity or mortality unless the condition extends to the deep venous system. When this occurs, it can be the source of a pulmonary embolus (PE). Superficial thrombophlebitis is an acute inflammatory condition. Unlike DVT (which is typically not associated with inflammation), superficial thrombi adhere firmly to the inside of vessel walls and generally do not form emboli.3,4

Patients with thrombophlebitis frequently have alterations in one or more components of Virchow's Triad: damage to the intimal wall of the vessel, venous stasis and altered coagulation.4 In this case, Elizabeth probably developed intimal damage as a result of the peripheral intravenous catheter. She had also received intravenous promethazine, and this nausea medication can induce the formation of antiphospholipid antibodies, another risk factor for thrombophlebitis.5

Differential Diagnosis

Signs and symptoms of superficial thrombophlebitis include tenderness, warmth and heat along the course of the affected vein, along with swelling in the affected extremity.1,3,5 The vein may have a palpable cord or knot. Table 2 lists differential diagnoses.

Examination should include the affected area, the regional lymph nodes and a cardiovascular exam if you suspect PE. Measurement of extremity circumference will objectively quantify any limb swelling. Measure at the same point on both extremities. I typically choose a bony landmark and measure from that landmark to the area of greatest circumference. I make sure that I measure from that same point on the other extremity. For example: "Arm circumference was 20 cm on the left and 18 cm on the right, measured 10 cm distal to the lateral condyles."

Diagnostic tests distinguish thrombophlebitis from phlebitis and rule out thrombi of the deep venous system. Additional tests may be needed to evaluate for pulmonary embolism if DVT is present or you suspect PE. Several tests are available:2

Compression ultrasonography. This is the noninvasive test of choice; it uses sound waves to generate pictures inside an extremity and can identify superficial and deep thrombi. The patient in this case had this test.

Contrast venography. Although venogram is the gold standard, this is no longer the initial study of choice because of its invasive nature. The test involves threading a catheter into the affected vein and injecting contrast dye, which enables veins (and clots) to show up on x-ray.

Magnetic resonance imaging. Although not as widely used as venography and ultrasound, this may be useful when the patient cannot tolerate intravenous dye (e.g., dye allergy, pregnancy, renal failure).

While blood tests for coagulation disorders and blood dyscrasias are indicated in cases of DVT, my review of the literature did not find a similar recommendation for cases of uncomplicated superficial thrombophlebitis.

When PE is a concern, relevant diagnostic tests include ventilation or perfusion lung scanning, spiral CT of the chest and serum d-dimer level.


Most cases of superficial thrombophlebitis are self-limiting and respond to conservative measures. Warm compresses and nonsteroidal anti-inflammatory drugs (NSAIDs) are mainstays of therapy.

While aspirin may be of benefit as an NSAID, its use as an antiplatelet agent is of little benefit because superficial thrombophlebitis is due to inflammation and fibrin clot, not platelet aggregation.1

Anticoagulants (e.g., heparin), while useful in the management of DVT, are not typically used in superficial cases of thrombophlebitis. Removal of an offending intravenous catheter and initiation of antibiotics are indicated in cases of thrombophlebitis caused by infection. Culture the catheter tip to identify the specific bacteria involved.

Follow-Up and Referral

Symptoms that do not resolve after 4 weeks require follow-up. In such cases, refer the patient to a general or vascular surgeon for excision of the clot under local anesthesia. Patients also should return if their symptoms worsen or if additional thrombi form, and they should seek emergency care for any signs or symptoms of pulmonary embolus (chest pain, shortness of breath, tachypnea, cough or hemoptysis).


1. Johnson G Jr. Superficial thrombophlebitis. eMedicine 2005. Available at:

2. Lip GY, Pineo GF, Bauer KA. Patient information: venous thrombosis. UpToDate 2005. Available with subscription at:

3. Beers MH (ed.) Superficial thrombophlebitis. In The Merck Manual of Medical Information Online (2nd ed.) 2004. Available at:

4. McMorran J, Crowther DC, McMorran S, et al. Superficial vein thrombosis. GPnotebook 2005. Available at:

5. Bauer KA, Lip GY. Evaluation of the patient with established venous thrombosis. UpToDate 2005. Available with subscription at:

Andrew Craig, NP, is a family nurse practitioner at The University of North Carolina-Charlotte's Student Health Center and an NP in the U.S. Naval Reserve. He is also a member of the ADVANCE for Nurse Practitioners editorial advisory board and is the journal's technology consultant.

Table 1: Risk Factors for Thrombophlebitis1,2,4

• Previous surgery

• Pregnancy

• Obesity

• Age older than 60 years

• Use of oral contraceptives, hormone replacement therapy or tamoxifen

• Immobilization, extended travel ("economy class syndrome")

• Smoking

• Presence of an intravenous catheter

• Injection of caustic or irritating substances

• Previous thromboembolism

• Chronic medical conditions such as heart failure, renal disease or cancer

• Blood disorders such as polycythemia vera

• Elevated blood homocysteine; positive antiphospholipid antibodies

Table 2: Differential Diagnosis1

• Cellulitis

• Suppurative thrombophlebitis, a serious condition associated with intravenous infection and septicemia, manifested by purulence in the affected vein

• Migratory thrombophlebitis, recurrent, progressive thrombi along the course of a vein, usually in the lower extremities, associated with carcinoma


Chronic cerebrospinal venous insufficiency (CCSVI), or the pathological restriction of venous vessel discharge from the CNS has been proposed by Zamboni, et al, as having a correlative relationship to Multiple Sclerosis. From a clinical perspective, it has been demonstrated that the narrowed jugular veins in an MS patient, once widened, do affect the presenting symptoms of MS and the overall health of the patient. It has also been noted that these same veins once treated, restenose after a time in the majority of cases. Why the veins restenose is speculative. One insight, developed through practical observation, suggests that there are gaps in the therapy protocol as it is currently practiced. In general, CCSVI therapy has focused on directly treating the venous system and the stenosed veins. Several other factors that would naturally affect vein recovery have received much less consideration. As to treatment for CCSVI, it should be noted that no meaningful aftercare protocol based on evidence has been considered by the main proponents of the ‘liberation’ therapy (neck venoplasty). In fact, in all of the clinics or hospitals examined for this study, patients weren’t required to stay in the clinical setting any longer than a few hours post-procedure in most cases. Even though it has been observed to be therapeutically useful by some of the main early practitioners of the ‘liberation’ therapy, follow-up, supportive care for recovering patients post-operatively has not seriously been considered to be part of the treatment protocol. To date, follow-up care has primarily centered on when vein re-imaging should be done post-venoplasty. The fact is, by that time, most patients have restenosed (or partially restenosed) and the follow-up Doppler testing is simply detecting restenosis and retrograde flow in veins that are very much deteriorated due to scarring left by the initial procedure. This article discusses a variable approach as to a combination of safe and effective interventional therapies that have been observed to result in enduring venous drainage of the CNS to offset the destructive effects of inflammation and neurodegeneration, and to regenerate disease damaged tissue.
As stated, it has been observed that a number of presenting symptoms of MS almost completely vanish as soon as the jugulars are widened and the flows equalize in most MS patients. Where a small number of MS patients have received no immediate benefit from the ‘liberation’ procedure, flows in subject samples have been shown not to have equalized post-procedure in these patients and therefore even a very small retrograde blood flow back to the CNS can offset the therapeutic benefits. Furthermore once the obstructed veins are further examined for hemodynamic obstruction and widened at the point of occlusion in those patients to allow full drainage, the presenting symptoms of MS retreat. This noted observation along with the large number of MS patients who have CCSVI establish a clear association of vein disease with MS, although it is clearly not the disease ‘trigger’.For more information please visit

Leo  July 25, 2012

Stem cells are “non-specialized” cells that have the potential to form into other types of specific cells, such as blood, muscles or nerves. They are unlike "differentiated" cells which have already become whatever organ or structure they are in the body. Stem cells are present throughout our body, but more abundant in a fetus.
Medical researchers and scientists believe that stem cell therapy will, in the near future, advance medicine dramatically and change the course of disease treatment. This is because stem cells have the ability to grow into any kind of cell and, if transplanted into the body, will relocate to the damaged tissue, replacing it. For example, neural cells in the spinal cord, brain, optic nerves, or other parts of the central nervous system that have been injured can be replaced by injected stem cells. Various stem cell therapies are already practiced, a popular one being bone marrow transplants that are used to treat leukemia. In theory and in fact, lifeless cells anywhere in the body, no matter what the cause of the disease or injury, can be replaced with vigorous new cells because of the remarkable plasticity of stem cells. Biomed companies predict that with all of the research activity in stem cell therapy currently being directed toward the technology, a wider range of disease types including cancer, diabetes, spinal cord injury, and even multiple sclerosis will be effectively treated in the future. Recently announced trials are now underway to study both safety and efficacy of autologous stem cell transplantation in MS patients because of promising early results from previous trials.
Research into stem cells grew out of the findings of two Canadian researchers, Dr’s James Till and Ernest McCulloch at the University of Toronto in 1961. They were the first to publish their experimental results into the existence of stem cells in a scientific journal. Till and McCulloch documented the way in which embryonic stem cells differentiate themselves to become mature cell tissue. Their discovery opened the door for others to develop the first medical use of stem cells in bone marrow transplantation for leukemia. Over the next 50 years their early work has led to our current state of medical practice where modern science believes that new treatments for chronic diseases including MS, diabetes, spinal cord injuries and many more disease conditions are just around the corner.
There are a number of sources of stem cells, namely, adult cells generally extracted from bone marrow, cord cells, extracted during pregnancy and cryogenically stored, and embryonic cells, extracted from an embryo before the cells start to differentiate. As to source and method of acquiring stem cells, harvesting autologous adult cells entails the least risk and controversy.
Autologous stem cells are obtained from the patient’s own body; and since they are the patient’s own, autologous cells are better than both cord and embryonic sources as they perfectly match the patient’s own DNA, meaning that they will never be rejected by the patient’s immune system. Autologous transplantation is now happening therapeutically at several major sites world-wide and more studies on both safety and efficacy are finally being announced. With so many unrealized expectations of stem cell therapy, results to date have been both significant and hopeful, if taking longer than anticipated.
What’s been the Holdup?
Up until recently, there have been intense ethical debates about stem cells and even the studies that researchers have been allowed to do. This is because research methodology was primarily concerned with embryonic stem cells, which until recently required an aborted fetus as a source of stem cells. The topic became very much a moral dilemma and research was held up for many years in the US and Canada while political debates turned into restrictive legislation. Other countries were not as inflexible and many important research studies have been taking place elsewhere. Thankfully embryonic stem cells no longer have to be used as much more advanced and preferred methods have superseded the older technologies. While the length of time that promising research has been on hold has led many to wonder if stem cell therapy will ever be a reality for many disease types, the disputes have led to a number of important improvements in the medical technology that in the end, have satisfied both sides of the ethical issue.
CCSVI Clinic
CCSVI Clinic has been on the leading edge of MS treatment for the past several years. We are the only group facilitating the treatment of MS patients requiring a 10-day patient aftercare protocol following neck venous angioplasty that includes daily ultrasonography and other significant therapeutic features for the period including follow-up surgeries if indicated. There is a strict safety protocol, the results of which are the subject of an approved IRB study. The goal is to derive best practice standards from the data. With the addition of ASC transplantation, our research group has now preparing application for member status in International Cellular Medicine Society (ICMS), the globally-active non-profit organization dedicated to the improvement of cell-based medical therapies through education of physicians and researchers, patient safety, and creating universal standards. For more information please visit

Leo VoiseyMarch 29, 2012
Pune, AL

“Unnecessary risks are being taken by patients seeking the liberation treatment.” says Dr. Avneesh Gupte of the CCSVI Clinic. “It has been our contention since we started doing minimally invasive venous angioplasties nearly 6 years ago that discharging patients who have had neck vein surgery on an outpatient basis is contra-indicated. We have been keeping patients hospitalized for a week to 10 days as a matter of safety and monitoring them for symptoms. Nobody who has the liberation therapy gets discharged earlier than that. During that time we do daily Doppler Ultrasounds, blood work and blood pressure monitoring among other testing. This has been the safe practice standard that we have adopted and this post-procedure monitoring over 10 days is the subject of our recent study as it relates to CCSVI for MS patients.”

Although the venous angioplasty therapy on neck veins has been done for MS patients at CCSVI Clinic only for the last 18 months it has been performed on narrow or occluded neck veins for other reasons for many years. “Where we encounter blocked neck veins resulting in a reflux of blood to the brain, we treat it as a disease,” says Gupte. “It’s not normal pathology and we have seen improved health outcomes for patients where we have relieved the condition with minimal occurrences of re-stenosis long-term. We believe that our record of safety and success is due to our post-procedure protocol because we have had to take patients back to the OR to re-treat them in that 10-day period. Otherwise some people could have run into trouble, no question.”

Calgary MS patient Maralyn Clarke died recently after being treated for CCSVI at Synergy Health Concepts of Newport Beach, California on an outpatient basis. Synergy Health Concepts discharges patients as a rule without in-clinic provisions for follow up and aftercare. Post-procedure, Mrs. Clarke was discharged, checked into a hotel, and suffered a massive bleed in the brain only hours after the procedure. Dr. Joseph Hewett of Synergy Health recently made a cross-Canada tour promoting his clinic for safe, effective treatment of CCSVI for MS patients at public forums in major Canadian cities including Calgary.

“That just couldn’t happen here, but the sooner we develop written standards and best practices for the liberation procedure and observe them in practice, the safer the MS community will be”, says Dr. Gupte. “The way it is now is just madness. Everyone seems to be taking shortcuts. We know that it is expensive to keep patients in a clinical setting over a single night much less 10 days, but it’s quite absurd to release them the same day they have the procedure. We have always believed it to be unsafe and now it has proven to be unsafe. The thing is, are Synergy Health Concepts and other clinics doing the Liberation Treatment going to be changing their aftercare methods even though they know it is unsafe to release a patient on the same day? The answer is no, even after Mrs. Clarke’s unfortunate and unnecessary death. Therefore, they are not focused on patient safety…it’s become about money only and lives are being put at risk as a result.”

Joanne Warkentin of Morden Manitoba, an MS patient who recently had both the liberation therapy and stem cell therapy at CCSVI Clinic agrees with Dr. Gupte. “Discharging patients on the same day as the procedure is ridiculous. I was in the hospital being monitored for 12 days before we flew back. People looking for a place to have the therapy must do their homework to find better options. We found CCSVI Clinic and there’s no place on earth that’s better to go for Liberation Therapy at the moment. I have given my complete medical file from CCSVI Clinic over to my Canadian physician for review.” For more information Log on to OR Call on Toll Free: 888-419-6855.

robert taylorJuly 25, 2011


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