Intravenous heparin in combination with antibiotics for the treatment of deep vein septic thrombophlebitis: A systematic review

Abstract

Antibiotics, heparin, and several surgical interventions have been used in various combinations for the treatment of septic thrombophlebitis, but the optimal management remains unclear. There are limited data from comparative trials studying this issue. Specifically, only one randomized controlled trial was conducted, while the rest of the evidence comes from case series and case reports. The results of this systematic review of septic thrombophlebitis suggest that the use of heparin in combination with antibiotics is associated with low mortality in patients with this serious type of infection. In addition, adverse effects related to heparin were limited in the reported literature. Although data from comparative trials are required to draw definitive conclusions, the available evidence suggests that the administration of heparin should be considered early in the management of patients with septic thrombophlebitis.

Introduction

Septic thrombophlebitis is a life-threatening complication of infections and/or venous thrombosis at various body sites. The most common forms of septic thrombophlebitis are manifested in pelvic veins (usually as a result of cesarean section or vaginal delivery), internal jugular vein (following infections of the head and neck — Lemierre's syndrome), portal vein (resulting from intra-abdominal infections such as appendicitis and diverticulitis), veins of the upper trunk and veins of the limbs (after intravenous injection of drugs or insertion of central venous catheters). Its diagnosis is based on clinical suspicion, and it is verified by the isolation of bacteria in blood cultures and imaging techniques like computed tomography (CT) scan and ultrasound testing. However, verification is not always possible (e.g. septic thrombophlebitis of small veins may not be visualized with the use of CT scan) and in these cases the diagnosis is based on medical history and persistent spiking fever (enigmatic fever) (Collins et al., 1951, Collins, 1970, Twickler et al., 1991, Woo et al., 1993).

Surgical intervention is an option in the treatment of patients with septic thrombophlebitis. Nowadays, surgery is used for cases of superficial vein septic thrombophlebitis and cases of deep vein septic thrombophlebitis refractory to medical treatment (Sitzmann et al., 1985, Stein and Pruitt, 1970). Therefore, the treatment of septic thrombophlebitis is based on monotherapy of broad-spectrum antibiotics or a combination of antibiotics (e.g. clindamycin, ampicillin and gentamicin).

Frequently, heparin is added to the antimicrobial regimen, either immediately after a strong clinical suspicion of septic thrombophlebitis or a few days later, when the administration of antibiotics alone does not lead to the desirable effect. However, the usefulness of heparin therapy in this population is debated over decades (Plemmons et al., 1995, Sinave et al., 1989). In this systematic review of case series and comparative trials we sought to explore the usefulness of heparin in the treatment of patients with deep vein septic thrombophlebitis.