Tetanus Immunoglobulin Dosing for Generalized Tetanus Without Prior Vaccination
For generalized tetanus in an unvaccinated patient, administer 3,000–6,000 units of human tetanus immunoglobulin (TIG) intramuscularly as soon as possible after diagnosis. 1
Therapeutic Dose for Active Tetanus Disease
The Centers for Disease Control and Prevention recommends a standard therapeutic dose of 3,000–6,000 units of tetanus immunoglobulin for active tetanus cases, which is dramatically higher than the 250-unit prophylactic dose used in wound management. 1
This high-dose regimen is necessary because TIG works by neutralizing circulating tetanus toxin but cannot neutralize toxin already bound to nerve endings—early administration is therefore critical. 1
Administration Protocol
TIG must be administered at a different anatomic site than any tetanus toxoid-containing vaccine using separate syringes to prevent interference with the immune response. 1
Concurrent administration of tetanus toxoid vaccine (Tdap preferred) should be initiated at a separate site to begin active immunization, as passive immunization with TIG does not confer long-term immunity. 1, 2
The patient must subsequently complete a full 3-dose primary tetanus vaccination series for long-term protection: second dose ≥4 weeks after the first, and third dose 6–12 months after the second. 2
Evidence Comparing Human vs. Equine Antitoxin
A 2022 randomized controlled trial of 272 adults with generalized tetanus found no clinical advantage of human TIG (3,000 IU) over equine antitoxin (21,000 U) for the primary outcome of mechanical ventilation requirement (45% vs. 44%, RR 1.01,95% CI 0.75–1.36, p=0.95). 3
Despite equivalent efficacy, human TIG remains preferred over equine antitoxin because it provides longer protection and causes fewer adverse reactions, according to CDC guidelines. 2
Intrathecal Administration: Not Recommended
The same 2022 trial evaluated intrathecal TIG (500 IU) versus sham procedure and found no overall benefit—mechanical ventilation was required in 43% of the intrathecal group versus 50% of the sham group (RR 0.87,95% CI 0.66–1.13, p=0.29). 3
While intrathecal administration was safe and showed promise in a small 1980 study (250 IU intrathecal resulted in only 1 death among 49 patients versus 10 deaths among 48 receiving 1,000 IU intramuscularly), the larger modern trial does not support routine intrathecal use. 3, 4
Critical Clinical Pearls
Administer TIG as soon as possible after diagnosis—delay reduces efficacy since the toxin progressively binds to nerve endings where it becomes inaccessible to neutralization. 1
Despite proper treatment with high-dose TIG and supportive care, tetanus still carries significant mortality risk, emphasizing the critical importance of prevention through proper immunization. 1
Patients with unknown or uncertain vaccination histories should be treated as having zero previous doses and require both therapeutic TIG and initiation of the primary vaccination series. 2