What is the correct method for administering vitamin K (phytonadione), including dose, route, and technique, for newborn prophylaxis and for rapid warfarin reversal in adults?

Vitamin K Injection Administration Method

For warfarin reversal in adults with major bleeding, administer vitamin K 10 mg by slow intravenous infusion (diluted in 25-50 mL normal saline over 15-30 minutes), not exceeding 1 mg per minute, combined with 4-factor prothrombin complex concentrate (4F-PCC). 1

Warfarin Reversal in Adults

Route Selection and Technique

• Intravenous administration is preferred for rapid warfarin reversal because it produces a more predictable and rapid reduction in INR (4-6 hours) compared to oral (18-24 hours) or subcutaneous (unpredictable and not recommended) routes. 1

• Dilute phytonadione in 25-50 mL normal saline and infuse slowly over 15-30 minutes, never exceeding 1 mg per minute to minimize risk of adverse reactions. 1, 2

• Subcutaneous administration results in unpredictable response and is not recommended for urgent reversal situations. 1, 3

• Anaphylactic reactions previously reported with IV administration are not encountered with current preparations when administered slowly. 1

Dosing Algorithm for Adults

For elevated INR with major bleeding:

• Administer vitamin K 5-10 mg IV by slow infusion 1, 3
• Must be combined with 4F-PCC (dosed based on INR: 25 U/kg for INR 2-<4,35 U/kg for INR 4-6,50 U/kg for INR >6; max 5,000 units) 1
• Vitamin K alone does not result in immediate correction of coagulopathy 1

For elevated INR (>6) without bleeding:

• Omit next 1-2 warfarin doses 3
• Administer vitamin K 1-2.5 mg orally, especially if bleeding risk factors present 3
• Monitor INR within 24 hours 3

For INR 4-10 without bleeding:

• Oral vitamin K 1-2.5 mg is sufficient 3
• Oral route is preferred over IV when bleeding is not present due to lower risk of anaphylactoid reactions 3

Critical Pitfalls to Avoid

• Do not use subcutaneous route for urgent reversal - absorption is unpredictable and unreliable. 1, 3

• Do not administer IV vitamin K rapidly - must not exceed 1 mg per minute to prevent anaphylactoid reactions. 2

• Do not give vitamin K alone for major bleeding - it takes 4-6 hours to work; must combine with 4F-PCC for immediate factor repletion. 1

• Avoid excessive vitamin K doses (>10 mg) as this can cause warfarin resistance. 3

Newborn Prophylaxis

Standard Prophylaxis Protocol

For all healthy term newborns, administer vitamin K 0.5-1 mg intramuscularly within one hour of birth. 2, 4, 5

• Intramuscular route is the preferred and most reliable method for newborn prophylaxis, providing superior protection against late vitamin K deficiency bleeding (VKDB) compared to oral administration. 4, 5

• A single IM dose effectively prevents all forms of VKDB (early, classic, and late). 4, 5

Alternative Oral Regimen (When IM Declined)

If parents decline IM administration:

• Give 2 mg oral vitamin K at birth, repeated at 2-4 days and 6-8 weeks 5
• Alternative: 2 mg at birth, then 1 mg weekly for 3 months 4
• Document parental refusal of IM route due to increased risk of late VKDB 4
• If infant vomits within 1 hour, repeat the oral dose 4

High-Risk Newborns

For premature infants or those at high risk of hemorrhage (birth asphyxia, difficult delivery, maternal anticoagulant use), the first dose must be administered IM or slow IV route, with repeated doses as needed. 6

• Oral route is not appropriate for preterm infants, those with cholestasis, impaired intestinal absorption, or infants too unwell to take oral medication 4

Treatment of Hemorrhagic Disease of Newborn

• Administer phytonadione 1 mg subcutaneously or intramuscularly 2
• Higher doses may be necessary if mother received oral anticoagulants 2
• Expect prompt response (shortened prothrombin time in 2-4 hours); failure to respond indicates another diagnosis 2

Preparation and Storage

• Protect from light at all times during storage and administration 2

• For dilution, use preservative-free 0.9% sodium chloride, 5% dextrose, or 5% dextrose and sodium chloride injection (benzyl alcohol preservatives are toxic to newborns) 2

• Administer immediately after dilution and discard unused portions 2

• Inspect visually for particulate matter and discoloration before administration 2

Special Populations

Maternal prophylaxis for mothers on vitamin K-inhibiting drugs:

• Give 10-20 mg/day orally for 15-30 days before delivery to prevent early VKDB 6
• Newborn still requires standard prophylaxis with repeated doses as clinically indicated 6

Formula-fed infants:

• Single 2 mg oral dose at birth plus second 2 mg dose at days 2-7 is sufficient 6

Exclusively breastfed infants:

• Require extended prophylaxis: weekly 2 mg oral doses (or 25 mcg/day) until completion of breastfeeding after initial two doses 6