eMedicine Specialties > Emergency Medicine > Infectious Diseases

Thrombophlebitis, Septic

Christian Theodosis, MD, MPH, Resident Physician, Section of Emergency Medicine, Yale School of Medicine
Craig F Feied, MD, FACEP, FAAEM, FACPh, Professor of Emergency Medicine, Georgetown University School of Medicine; General Manager, Microsoft Enterprise Health Solutions Group; Jonathan A Handler, MD, Director of Informatics, Assistant Professor, Department of Emergency Medicine, Northwestern Memorial Hospital

Updated: Jul 24, 2009

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.^1,2 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,³ 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 herpes zoster
• Insect bites
• Intravenous drug abuse
• Local trauma (eg, lacerations, abrasions, "bites")
• Oropharyngitis
• Puncture wounds
• Salpingitis
• Varicose veins
• Venipuncture
• Venography
• Venous infusion catheters

Differential Diagnoses

Other Problems to Be Considered

Lymphangitis

Workup

Laboratory Studies

• When catheter-related sepsis is suspected, blood cultures should be drawn through the line.
  • If imaging studies show thrombus or a fibrin sheath attached to the catheter, fibrinolysis should be performed prior to catheter removal in order to avoid embolization of large clumps of infected material. Once the risk of septic embolization is eliminated, the catheter should be removed in a sterile procedure and the tip should be cut off and sent for culture.
  • When suppurative phlebitis is present, the purulent material that is expressed from the vessel should be sent for Gram stain and cultures to identify the causative organism.
• Fever, signs of sepsis, and persistent candidemia are characteristic of peripheral septic thrombophlebitis caused by Candida species. Candidal thrombophlebitis of the great vessels is uncommon, but it should be suspected when candidemia persists after removal of a central venous catheter and endocarditis is not believed to be present.
• White blood cell (WBC) counts are of little value in patients with septic phlebitis, because WBC counts often do not reflect the seriousness of disease and because the WBC may be elevated markedly in patients with thrombophlebitis even in the absence of infection.

Imaging Studies

• Imaging studies are useful to rule out thrombosis of deep system vessels, but they cannot distinguish between septic phlebitis and nonseptic thrombophlebitis.
• The injection of contrast material into a central catheter often permits visualization of catheter-associated thrombus or of an extensive fibrin sheath that extends, cloudlike, away from the catheter. When present, a fibrin sheath is an ideal medium for infection.
• Contrast-enhanced CT or magnetic resonance imaging (MRI) is essential when pursuing the possible diagnosis of internal jugular vein thrombophlebitis. Both CT scan and MRI can identify the extent of thrombus, the local anatomy of the affected tissues, and any pockets of purulent material that may require drainage. Other modalities that can help to make the diagnosis of Lemierre syndrome include gallium scanning, retrograde venography, and duplex ultrasonography.

Treatment

Prehospital Care

• Septic phlebitis does not require any prehospital intervention.

Emergency Department Care

• Uncomplicated superficial septic phlebitis due to a peripheral IV catheter often responds to systemic antibiotics and removal of the cannula.
  • Peripheral intravenous catheters should be removed at the first sign of erythema, induration, or edema.
  • The temptation to try to preserve a peripheral intravenous catheter must be resisted, because the morbidity and mortality rates associated with septic phlebitis are substantial and increase dramatically over time if the catheter is left in place.
• Once phlebitis has become suppurative, simply removing the cannula is no longer sufficient. Suppurative superficial veins must be removed surgically as soon as possible.
  • Immediate excision of the involved purulent vein dramatically reduces the likelihood of spread into the deep system and of septic metastasis.
  • In many cases, the best method of removal is to perform percutaneous phlebectomy using Ramelet or Mueller hooks (or other similar phlebectomy hooks) to extract the vein through a series of needle punctures or tiny stab incisions. If necessary, suppurative veins may be removed by cutdown, but the results are less cosmetically pleasing.
  • Some authors believe that a fully open approach to phlebectomy is always best because it allows the wounds to be packed open to prevent re-accumulation of pus in the subcutaneous tissues.
  • Some authors believe that the presence of bacteremia in a patient with superficial septic phlebitis is an indication for immediate phlebectomy even in the absence of any demonstrable purulent material.
• In contrast to peripheral catheters, infected central venous catheters should not be removed precipitously. Infected central catheters often have an extensive infected free-floating fibrin sheath, and a large mass of septic thrombus may be attached to the catheter. If the catheter is withdrawn precipitously, this septic material may embolize to cause septic pulmonary emboli or septic distant metastases.
  • Before an infected central catheter is removed, contrast venography should be performed through the catheter to identify any fibrin sheath or thrombus. If thrombus or a sheath is present, removal should be delayed until antibiotic levels are therapeutic and until the infected thrombus or sheath can be dissolved by local fibrinolysis.
  • Fibrinolysis in this setting is very easy and effective because the catheter tip usually is positioned perfectly to permit delivery of lytic agents directly into the fibrin sheath and thrombus. In most cases, complete dissolution of the local thrombus is possible using low doses of lytic agents without producing a systemic lytic state. Block et al describe safe removal of a catheter by thrombolysis using local urokinase infusion for catheter-related C albicans thrombophlebitis.⁴
  • Dissolving a large mass of septic thrombus rather than letting it embolize as a whole is worth the effort. This transcatheter procedure is performed routinely by interventional radiologists, but it may be carried out easily in the ED if assistance from interventional radiology is not immediately available.

Consultations

• Well-localized superficial phlebitis, even if suppurative, does not require any consultation provided the emergency physician is capable of performing the indicated superficial phlebectomy. Patients with widespread suppurative phlebitis or suppurative phlebitis threatening the deep venous system, however, benefit from consultation with a vascular surgeon.
• Infected central lines with an extensive fibrin sheath or with associated thrombus benefit from fibrinolysis and antibiotics prior to removal of the catheter. If the emergency physician cannot carry out this fibrinolysis, an interventional radiologist should be consulted prior to removing the catheter.
• The mortality and morbidity rates of septic phlebitis are so high that antibiotic choice and dosing always should be guided by current recommendations from an expert in infectious diseases.

Medication

To be effective, treatment of progressive septic phlebitis (at any location) must include both antibiotics and heparin.

Whenever possible, the choice of initial antibiotics should be based upon the Gram stain and the results of bacterial culture. When Gram stain is not possible, empiric therapy must take into consideration the location of the septic thrombus, the underlying etiology, and the condition of the host. No matter what the organism, extended high-dose antimicrobial therapy is recommended because of the high risk of endocarditis or of septic emboli.

Heparin is essential because infected thrombus provides a dangerous nidus for infection that is refractory to treatment with antibiotics. Heparin halts the progression of septic thrombophlebitis and eliminates an ongoing source of septic emboli.

Because heparin alone cannot dissolve existing infected clot, septic thrombophlebitis of the deep veins is an indication for local-regional treatment with fibrinolytic agents along with antibiotics and heparin. Fibrinolysis also is indicated when septic phlebitis involves a dialysis graft, when septic phlebitis is resistant to antibiotics and heparin, and when catheter-associated thrombus and fibrin sheaths cause sequestration of infection and make it resistant to treatment. Because removal of an infected indwelling catheter often causes septic emboli, fibrinolytic agents also are used before removing an infected central catheter that has an extensive fibrin sheath and thrombus associated with it.

Fibrinolytics (thrombolytics)

The goal of fibrinolytic therapy is to dissolve an infected fibrin sheath or an infected thrombus that can serve as a nidus for resistant infection and as a source of septic emboli.

Catheter-directed local infusions of fibrinolytic agents are safer than systemic fibrinolytic regimens because they use a low dose of the drug and usually do not produce a systemic lytic state. Several fibrinolytic agents currently are available for local-regional lysis of infected thrombus.

Reteplase is a second-generation recombinant tissue-type plasminogen activator that seems to work more quickly and to have a lower bleeding risk than the first-generation agent (alteplase).

Alteplase is the first-generation recombinant tissue-type plasminogen activator. It is the fibrinolytic agent most familiar to EDs and the one most often used for the treatment of coronary artery thrombosis, pulmonary embolism, and acute stroke.

Urokinase is the fibrinolytic agent most familiar to interventional radiologists and the one that has been used most often for septic phlebitis. At the time of this writing, urokinase is not available from the manufacturer. The future availability of urokinase is not known. In the meantime, the US Food and Drug Administration (FDA) has encouraged the off-label use of reteplase and alteplase for local-regional lysis of venous and arterial thrombus at any location.

Streptokinase is a less-expensive alternative that unfortunately is highly antigenic and produces a high incidence of untoward reactions. This drawback limits the usefulness of streptokinase in the clinical setting.

Reteplase (Retavase)

Second-generation recombinant tissue-type plasminogen activator. As fibrinolytic agent, seems to work faster than its forerunner, alteplase, and also may be more effective in patients with larger clot burden. Also has been reported to be more effective than other agents in lysis of older clot. In patients being treated for peripheral vascular disease, has been reported to cause fewer bleeding complications than alteplase.
Contrast venography used to guide duration and intensity of therapy.
For local lysis of arterial thrombosis (with or without associated infection), suggested dose is lower (0.5 U/h infusion).

Dosing

Adult

For venous thrombus: 1 U/h local/regional IV infusion for 18-36 h
For infected catheter thrombus or fibrin sleeve: 1 U/h IV for 3 h
For thrombosed dialysis grafts: 5-10 U/h IV bolus by pulse-spray delivery

Pediatric

Not established

Interactions

May increase effects of warfarin, heparin, and aspirin

Contraindications

Documented hypersensitivity; uncontrolled hypertension; recent intracranial surgery; arteriovenous malformation or aneurysm; bleeding diathesis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular arrhythmias, hypotension, and perfusion arrhythmias; when used as infusion for local or regional fibrinolysis, some monitor fibrinogen levels at 6 h intervals; if systemic fibrinogen levels drop below 100 U, infusion rate reduced by half

Alteplase (Activase)

First recombinant tissue plasminogen activator to be released for clinical use, and agent with which EDs are most familiar.
Although best known as fibrinolytic agent used for coronary artery occlusion and for PE, also widely used for catheter-directed lysis of DVT, for dissolution of catheter-related thrombus, and for re-opening of occluded central lines and thrombosed dialysis grafts.
Contrast venography used to guide duration and intensity of therapy.

Dosing

Adult

For catheter-directed treatment of DVT: 5 mg IV bolus and 1 mg/h IV infusion for 12-24 h
For infected catheter thrombus or fibrin sleeve: 1 mg/h for 3 h
For occluded dialysis grafts: 10 mg IV bolus delivered into graft site, repeated q2h for 4 doses prn

Pediatric

Administer as in adults

Interactions

Drugs that alter platelet function (eg, aspirin, dipyridamole, abciximab) may increase risk of bleeding prior to, during, or after therapy; may give heparin with and after alteplase infusions to reduce risk of rethrombosis—either heparin or alteplase may cause bleeding complications

Contraindications

Documented hypersensitivity; active internal bleeding; cerebrovascular accident or stroke within last 2 mo; intracranial or intraspinal surgery or trauma; intracranial hemorrhage on pretreatment evaluation; suspicion of subarachnoid hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm; bleeding diathesis; severe uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor for bleeding, especially at arterial puncture sites, with coadministration of vitamin K antagonists; control and monitor BP frequently during and following administration (when managing acute ischemic stroke); do not use >0.9 mg/kg to manage acute ischemic stroke; doses >0.9 mg/kg may cause ICH

Anticoagulants

Anticoagulation with some form of heparin is essential in patients with septic phlebitis, but anticoagulation alone does not guarantee a successful outcome. Progression of the disease may occur despite full and effective heparin anticoagulation.

Heparin works by activating antithrombin III to slow or prevent the progression of venous thrombosis. Heparin does not dissolve existing clot.

When low-molecular-weight heparin (LMWH) is used, checking the aPTT has no utility, because aPTT does not correlate with therapeutic effect or with bleeding risk in patients receiving LMWH.

When unfractionated heparin is used, an aPTT of at least 1.5 times the control value is necessary for a therapeutic effect. To achieve this, unfractionated heparin must be given IV in adequate doses. Low-dose subcutaneous unfractionated heparin should not be used, as it is neither an effective therapy for septic phlebitis nor an effective prophylaxis against progression of the disease.

Warfarin should not be used in the acute treatment of septic phlebitis, because the early risk of increased thrombogenesis outweighs any convenience of oral therapy.

Heparin

Initial bolus used for patients with inflammatory and septic thrombosis is lower than that needed for spontaneous DVT and PE, because most patients with inflammatory or septic thrombophlebitis do not have underlying hypercoagulability. Patients with DVT or PE require more aggressive therapy because DVT is manifestation of active hypercoagulable state.
Do not check aPTT until 6 h after initial bolus of unfractionated heparin, as extremely high or low value during this time should not provoke any action.

Dosing

Adult

60 U/kg (max 4000 U) IV bolus, followed by a 12 U/kg/h (max 1000 U/h) maintenance infusion
After bolus, check aPTT every 6 h until stable, and adjust dosing as follows:
If aPTT is low (<1.5 times control value), rebolus with 4000 U and increase drip by 10%
If aPTT is high (>2.5 times control value), decrease drip 10%
If aPTT is extremely high (>100 sec), hold heparin drip for 1 h and decrease drip 10%

Pediatric

Administer as in adults

Interactions

Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity

Contraindications

Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Thromboembolism may occur if dosing inadequate; may cause hemorrhagic complications and can trigger immune thrombotic thrombocytopenia 1-2 wk after beginning treatment; platelet-consuming disseminated thrombosis refractory to traditional treatment can be fatal if not recognized quickly and managed appropriately; if significant bleeding develops, 15 mg of protamine (infused over 3 min) usually reverses anticoagulant effect; in neonates, preservative-free heparin recommended to avoid possible toxicity (ie, gasping syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and shock

Enoxaparin (Lovenox)

First LMWH released in US. Only LMWH now approved by FDA for both treatment and prophylaxis of DVT. Widely used in pregnancy, although clinical trials not yet available to demonstrate that it is as safe as unfractionated heparin. No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect).

Dosing

Adult

Thrombosis: 1 mg/kg SC q12h
Prophylaxis: 30 mg SC q12h

Pediatric

Not established; suggested dose 1.6 mg/kg SC bid if aged <2 months and 1 mg/kg/dose SC bid if >2 months

Interactions

Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding

Contraindications

Documented hypersensitivity; major bleeding; thrombocytopenia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

If thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminases may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated LMWH; 1 mg of protamine sulfate reverses effect of approximately 1 mg of enoxaparin if significant bleeding complications develop

Antibiotics

Choice of antibiotic depends upon results of blood cultures or Gram stain and culture of material taken from the suppurative vessel or from a metastatic septic focus.

For superficial phlebitis, aerobic coverage is sufficient.

Anaerobic coverage is required for patients with abscess formation, those with pelvic or ovarian vein phlebitis, and those with Lemierre syndrome of internal jugular phlebitis (often due to F necrophorum).

Candidal phlebitis is treated with amphotericin B.

Penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Aqueous penicillin G is first choice for treatment of susceptible infections because of its rapid onset of action.
Useful in infections of the head and neck due to Streptococcus, Clostridium, Actinomycosis, Listeria, Erysipelothrix, and Pasteurella species as well as fusospirochetal infections.

Dosing

Adult

3-4 million U IV q4h

Pediatric

30,000-40,000 U/kg IV q4h

Interactions

Probenecid can increase effects; tetracyclines can decrease effects; ethacrynic acid, aspirin, indomethacin, and furosemide may compete for renal tubular secretion, resulting in increase in penicillin serum concentrations

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft-tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Dosing

Adult

150-300 mg IV q6h

Pediatric

2-4 mg/kg IV q6h
Severe infections: 5 mg/kg IV q6h

Interactions

Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption

Contraindications

Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).

Dosing

Adult

Initial dose: 15 mg/kg IV over 1 h
Subsequent doses: 7.5 mg/kg over 1 h q6-8h; not to exceed 4 g in 24 h

Pediatric

5-10 mg/kg IV q 8 h; not to exceed 500 mg/dose

Interactions

Cimetidine may increase toxicity; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Chloramphenicol (Chloromycetin)

Binds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.

Dosing

Adult

12-25 mg/kg IV q6h; not to exceed 4 g/d

Pediatric

12-20 mg/kg IV q6h

Interactions

Barbiturates may decrease serum levels while barbiturate levels may increase, causing toxicity; sulfonylureas may cause manifestations of hypoglycemia; rifampin may reduce serum levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity and increasing or decreasing chloramphenicol levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use only for indicated infections, or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur—evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)

Amphotericin B (AmBisome)

Produced by strain of Streptomyces nodosus. Can be fungistatic or fungicidal (effective against candidal phlebitis). Binds to sterols, such as ergosterol, in fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Dosing

Adult

3 mg/kg IV qd administered over 2 h

Pediatric

Administer as in adults

Interactions

Antineoplastic agents may enhance potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; cyclosporine increases risk of renal toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Monitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) if interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)

Follow-up

Further Outpatient Care

• Because septic phlebitis is associated with a high incidence of secondary endocarditis and other secondary endovascular infection, high-dose antibiotics are continued for at least 6 weeks after blood cultures become negative.

Deterrence/Prevention

• True prevention
  • As is the case for most clinically apparent illnesses, many cases of septic thrombophlebitis could be prevented. A substantial body of evidence exists mandating early removal and replacement of central and peripheral catheters. A similar body of knowledge underlies the importance of sterile technique, which should always be used when physicians perform procedures that involve disruption of the patient's skin.
  • This being said, studies suggest that deviation from standard best practices is common. It cannot be overemphasized that meticulous attention to sterile technique and early replacement of access devices are key strategies the physician must use in order to manage this problem successfully.
• Mitigation
  • Peripheral septic phlebitis occurs more frequently after cannulation of lower limb veins. Therefore, this route should be used only when upper extremity veins are unavailable. Meticulously aseptic technique should be used for all intravenous cannulae.
  • Central lines (especially femoral lines) are associated with deep vein thrombosis and central venous septic thrombophlebitis. Central lines should be avoided in favor of peripheral lines whenever possible.

Patient Education

• For excellent patient education resources, visit eMedicine's Circulatory Problems Center. Also, see eMedicine's patient education articles Phlebitis and Blood Clot in the Legs.

Miscellaneous

Medicolegal Pitfalls

• Failure to diagnose and treat thrombophlebitis in a rapid and appropriate manner leads to poor patient outcomes and to substantial legal liability. Most allegations of mismanagement fall into one of a small number of categories.
  • Failure to suspect the diagnosis when a reasonable physician would have suspected it
  • Considering the diagnosis but failing to pursue the diagnostic workup despite the fact that clinical diagnosis alone is known to be inadequate
  • Beginning a diagnostic workup but failing to pursue the workup to completion (Once a workup has been initiated, abandoning the workup without a definitive diagnosis is not acceptable.)
  • Making the diagnosis but failing to institute appropriate treatment in a timely manner
  • Failing to recognize that a patient is getting worse instead of better, especially when the patient has returned for a second or even a third visit

Special Concerns

• Recent case reports and controversies
  • Recent case reports - Amiodarone, propofol
    • Amiodarone: Long-standing controversies exist over whether or not various medicines may cause phlebitis when infused, particularly when infused into small peripheral veins. General consensus has been that amiodarone is one such medicine. A case report by Aljitawi et al (2005) again documented a case of superficial phlebitis related to amiodarone administered peripherally.⁵ Whether or not amiodarone is the culprit remains controversial, but the preponderance of evidence suggests that the clinician should opt for the PO route when possible or for the central venous route when PO is not clinically appropriate.
    • Propofol: Propofol is a medicine that has historically been formulated in a lipid-based diluent. Last year, an alternate formulation of propofol was available in some markets in aqueous diluent. A case report by Dubey and Kumar (2005) reported a case of acute phlebitis that may have been related to this new formulation.⁶ No definitive studies on the matter are available, but the clinician should be aware that acute phlebitis may occur and one's index of suspicion must be high, particularly when administering new formulations of medicines.
  • A case of cryptogenic septic shock
    • It is understood that surgical debridement and excision may be indicated for clinically apparent and surgically amenable cases of superficial thrombophlebitis. A case report by Katz et al (2005) described a case in which a multiply injured trauma patient was found to have prolonged and unexplained shock.⁷ The treating physicians ultimately determined it had been caused by a superficial septic thrombophlebitis that had not been detected early. They reported that excision produced a prompt improvement in the patient's clinical condition.
    • This case raises the importance not only of appropriate management for clinically apparent illness but also emphasizes that efforts should be made to rule out septic thrombophlebitis in patients who are at risk.

References

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Keywords

septic phlebitis, septic thrombophlebitis, septic emboli, septic shock, catheter-related septic phlebitis, suppurative superficial thrombophlebitis, septic pelvic thrombophlebitis, septic ovarian vein thrombophlebitis, septic pelvic phlebitis, Lemierre syndrome

Contributor Information and Disclosures

Author

Christian Theodosis, MD, MPH, Resident Physician, Section of Emergency Medicine, Yale School of Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Craig F Feied, MD, FACEP, FAAEM, FACPh, Professor of Emergency Medicine, Georgetown University School of Medicine; General Manager, Microsoft Enterprise Health Solutions Group
Craig F Feied, MD, FACEP, FAAEM, FACPh is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Phlebology, American College of Physicians, American Medical Association, American Medical Informatics Association, American Venous Forum, Medical Society of the District of Columbia, Society for Academic Emergency Medicine, and Undersea and Hyperbaric Medical Society
Disclosure: Nothing to disclose.

Jonathan A Handler, MD, Director of Informatics, Assistant Professor, Department of Emergency Medicine, Northwestern Memorial Hospital
Jonathan A Handler, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Richard S Krause, MD, Senior Faculty, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine
Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eddy Lang, MDCM, CCFP (EM), CSPQ, Assistant Professor, Department of Family Medicine, McGill University; Consulting Staff, Department of Emergency Medicine, The Sir Mortimer B Davis-Jewish General Hospital
Eddy Lang, MDCM, CCFP (EM), CSPQ is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

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