eMedicine Specialties > Emergency Medicine > Infectious Diseases

Thrombophlebitis, Septic

Author: Christian Theodosis, MD, MPH, Resident Physician, Section of Emergency Medicine, Yale School of Medicine
Coauthor(s): Craig Feied, MD, FACEP, FAAEM, FACPh, Professor of Emergency Medicine, Georgetown University; Director, National Institute for Medical Informatics; Director, Federal Project ER One; Director, National Center for Emergency Medicine Informatics; Jonathan A Handler, MD, Director of Informatics, Assistant Professor, Department of Emergency Medicine, Northwestern Memorial Hospital
Contributor Information and Disclosures

Updated: Sep 8, 2006

Introduction

Background

The clinical course and severity of septic thrombophlebitis are quite variable. Many cases present as benign localized lesions that require minimal intervention after which complete recovery is expected. Some cases present as severe systemic infections culminating in profound shock, refractory even to aggressive management, including operative intervention and appropriate treatment in the intensive care unit.

The approach to septic phlebitis depends on which veins are involved, the underlying etiology of the phlebitis, which organisms are involved, and the patient's underlying physiology.

Peripheral septic thrombophlebitis is a common problem that can develop spontaneously but more often is associated with breaks in the skin. Peripheral septic phlebitis is most commonly caused by intravenous catheters, venipuncture for phlebotomy, or intravenous injection. Septic phlebitis may produce septic emboli, which can seed distant sites. Extensive showering of septic emboli may initiate a systemic inflammatory response, culminating in septic shock, which has a poor prognosis even when managed ideally.

Catheter-related septic phlebitis is one of the most common causes of fever after the third postoperative day. Catheter-associated phlebitis may develop at any site but is most frequent after cannulation of lower limb veins and veins at the groin. Catheter-related phlebitis also can result from chemical or mechanical irritation without infection, but infection must be strongly suspected in any patient with catheter-related phlebitis. Sterile superficial phlebitis should be evaluated and managed as discussed in Thrombophlebitis, Superficial.

Septic phlebitis of a superficial vein without frank purulence is known as simple phlebitis. Simple phlebitis can be benign, but when progressive, it may cause serious complications including death.

Suppurative superficial thrombophlebitis, in which actual purulent material can be expressed from a vein, portends a much poorer prognosis. Such cases are often associated with frank sepsis and therefore confer a substantial risk of mortality even when treated aggressively. Patients with this condition are likely to appear toxic (eg, high fevers, rigors, sweats, chills, altered sensorium, poor urine output).

Septic phlebitis of the deep veins is a life-threatening emergency that may fail to respond to even the most aggressive therapy. Septic pelvic thrombophlebitis and septic ovarian vein thrombophlebitis are seen principally as complications of puerperal infection and septic abortion. Occasionally, septic pelvic phlebitis may be secondary to pelvic inflammatory disease or progressive infection of the urinary tract. In diverticulitis, infection may spread to cause septic phlebitis of the portal venous system (pylephlebitis).

Lemierre syndrome is an anaerobic suppurative thrombophlebitis of the internal jugular vein, most commonly as a complication of pharyngeal, dental, or mastoidal infection. Lemierre syndrome is much more common than generally appreciated, and it may be complicated by septic emboli. Septic emboli can lodge in the lungs (septic pulmonary emboli). Less commonly, septic emboli may traverse a patent foramen ovale resulting in distant metastatic infections. Secondary infections may include septic arthritis, paravertebral abscess, cutaneous abscess, periorbital cellulitis, meningitis, and osteomyelitis.

Thrombophlebitis of the intracranial venous sinuses is a particularly serious problem. Infection of the medial third of the face is associated with cavernous sinus thrombophlebitis. Mastoiditis is associated with septic phlebitis involving the lateral sinuses. Cases of intracranial septic thrombophlebitis are fatal in more than a third of cases.

Pathophysiology

Septic phlebitis can develop spontaneously or as a result of a break in the skin through which offending organisms are introduced. Septic phlebitis most commonly occurs in association with protracted use of intravenous cannulas for administration of fluids or medications.

Prolonged catheterization, use of semipermeable transparent dressings, and a jugular insertion site are independent risk factors for developing septic phlebitis. Septic phlebitis often complicates other illnesses that depress the immune response, including malnutrition, diabetes, liver disease, and malignancy, and in patients taking immunosuppressant agents.

Catheter-associated septic thrombophlebitis often progresses to involve the deep veins; nearly one fourth of long-term central venous catheters result in septic phlebitis in deep veins.

Deep or superficial septic phlebitis also can occur by direct invasion from adjacent nonvascular infections. Endometritis or urinary tract infections, for example, may spread to cause septic pelvic thrombophlebitis or septic ovarian vein thrombophlebitis. Pylephlebitis (septic thrombophlebitis of the portal vein) usually occurs as a complication of diverticulitis or another infection in the region drained by the portal venous system.

Systemic effects can be due to bacteremia per se or may be related to bacterial endotoxin production. Streptococcal toxic shock syndrome has been reported in association with pediatric peripheral septic thrombophlebitis.

Regardless of the original etiology or site of infection, septic thrombophlebitis may produce secondary endocarditis, arteritis, or pneumonia due to septic thromboemboli. Embolic pneumonias have a high incidence of abscess formation and cavitation (empyema). Peripheral septic metastases are seen in patients who develop left-sided endocarditis and in those with right-sided endocarditis who also have a patent foramen ovale.

The etiologic agent of septic or suppurative phlebitis usually can be cultured both from blood and from metastatic sites of infection. Septic phlebitis can be caused by gram-positive or gram-negative organisms or by candidal or mycobacterial species. Staphylococcus epidermidis, group A streptococci, and Klebsiella and Enterobacter species are common causes of phlebitis. The most severe cases are seen in patients with phlebitis due to Candida species, Pseudomonas aeruginosa, or Staphylococcus aureus.

The offending organism often can be predicted by the site of infection. Peripheral bacterial phlebitis virtually always is caused by aerobic organisms, while septic pelvic thrombophlebitis and septic internal jugular phlebitis (Lemierre syndrome) usually are caused by anaerobic pathogens. The organism most frequently associated with Lemierre syndrome is Fusobacterium necrophorum, an endotoxin-producing gram-negative obligate anaerobe found in the upper respiratory, gastrointestinal, and genitourinary tracts. Other organisms that may cause Lemierre syndrome include Bacteroides melaninogenicus, Eikenella corrodens, and non-group A streptococci. The bacteremia of pylephlebitis is often polymicrobial, reflecting the underlying diverticular source, but the most common blood isolate is Bacteroides fragilis. Septic cavernous sinus thrombophlebitis most often is caused by S aureus.

Frequency

United States

The annual incidence is unknown, but septic phlebitis due to intravenous catheters is one of the most common causes of fever after the third postoperative day, occurring in at least 12% of patients who have undergone surgery. Patients in the intensive care unit (ICU) are at particularly high risk: 24% of ICU patients with central venous catheters and 9% of those with peripheral catheters develop fever and bacteremia and have positive results on culture of the venous catheter tip.

International

Incidence in developing countries is thus far unstudied and therefore unknown. In resource-poor settings, a definitive diagnosis is often impossible. Patients in whom the diagnosis is strongly suspected should certainly receive empiric antibiotic therapy. The decision to anticoagulate must be carefully weighed against local capacity to manage potential complications.

Mortality/Morbidity

Major complications occur in one third of all episodes of peripheral septic phlebitis caused by percutaneously inserted catheters.

• Complications include septic shock, sustained or refractory sepsis, suppurative thrombophlebitis, metastatic infection, endocarditis, and arteritis. Patients may die because of sepsis, and hospital stay is prolonged in the majority of cases.
• In critically ill patients, intravenous lines are responsible for about one quarter of the cases of nosocomial bloodstream infection, which has a mortality rate of 25% and costs $29,000 per survivor.
• Lemierre syndrome and intracranial septic thromboses are of special concern because the mortality rate is high even when appropriate treatment is initiated early. Of patients with Lemierre phlebitis, 20% eventually die despite prolonged intravenous antibiotic therapy. The mortality rate is even higher for patients with septic cavernous sinus or lateral sinus phlebitis.

Age

• Vulnerability to vascular infection is increased in neonates because of their undeveloped host defenses.
• Vulnerability is increased in elderly patients because of concomitant illnesses and a nonspecific age-related decline in immunopotency.

Clinical

History

• Superficial septic phlebitis most often begins with a localized break in the skin, such as an intravenous catheter, a puncture wound, an insect bite, a phlebotomy attempt, or an intravenous injection. The initial site of infection often is apparent as an initially well-localized area of tenderness and erythema. The original portal of entry may become less obvious over time, as pain, tenderness, swelling, and redness spread along the entire course of the infected vessel.
  • Intravenous drug abusers often have localized areas of cellulitis or even frank abscesses at the sites of injection.
  • Local pain, swelling, and redness are apparent from the onset of infection, but systemic signs, such as fever and chills, occur only after the superficial phlebitis is well established.
• Septic phlebitis in the deep veins generally presents with systemic symptoms alone. Patients with catheter-associated deep system phlebitis often have no symptoms of pain or swelling at the site of a central venous catheter.
• Septic pelvic thrombophlebitis usually presents as a late complication of a recognized puerperal infection, such as postpartum endometritis, while puerperal ovarian vein thrombophlebitis presents in the first week of the puerperium, usually as lower quadrant pain that may masquerade as appendicitis and be identified correctly only at laparotomy.

Physical

• Local signs of phlebitis include the traditional cardinal signs of inflammation: calor, dolor, rubor, and tumor (heat, pain, redness, and swelling).
• Septic phlebitis sometimes can be confused with superficial thrombophlebitis that is not infected. Septic phlebitis must be assumed when a patient has cellulitis, abscess, a break in the skin, or fever and chills.
• Suppurative phlebitis is recognized when any amount of purulent material can be expressed from within or around the lumen of a vessel.
• Infection at a peripheral intravenous site usually is obvious because it presents as localized cellulitis with inflammation along the course of the vein, often with associated lymphangitis and regional lymphadenopathy.
• The inflamed superficial vein usually is identifiable and palpable as a red, tender cord.
• In contrast, central line septic phlebitis often is clinically occult because the infected thrombus is located in the region of the catheter tip and usually does not involve the site of skin puncture.
• If deep system blood flow is obstructed, extremity pain and edema are present, but, in most cases, the patient has only fever, chills, and positive blood culture results.
• The diagnosis of catheter-associated deep septic phlebitis usually is made by culturing the tip of the catheter itself. If the catheter cannot be withdrawn, cultures of blood taken from peripheral sites may be compared with cultures of blood drawn from the suspect catheter.
• Septic pelvic thrombophlebitis and ovarian vein phlebitis are difficult to diagnose on the basis of the history and physical findings, because most patients who develop septic pelvic or ovarian phlebitis already have a diagnosis of endometritis or salpingitis.

Causes

Any event producing cutaneous discontinuity (break in skin) predisposes the human organism to soft-tissue infections that may result in septic phlebitis.

• Abscesses
• Cellulitis
• Diverticulitis
• Endometritis
• Herpes simplex or zoster
• Insect bites
• Intravenous drug abuse
• Local trauma (eg, lacerations, abrasions, "bites")
• Oropharyngitis
• Puncture wounds
• Salpingitis
• Varicose veins
• Venipuncture
• Venography
• Venous infusion catheters

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