Intravenous immunoglobulin in pediatric critical care: Bridging evidence gaps and guiding rational use

Table 1 Clinical decision guidance for intravenous immunoglobulin use in pediatric intensive care unit

Indication	Approval status	Level of evidence	Typical IVIG dose	Clinical message
KD[4,21]	FDA and EMA approved	I-A	2 g/kg single dose + aspirin	Use
Primary immunodeficiency (CVID, XLA, SCID)[18]	FDA and EMA approved	I-A	0.4-0.6 g/kg every 3-4 weeks (replacement)	Use
CIDP[4]	FDA and EMA approved	I-A	2 g/kg induction; 1 g/kg maintenance	Use
ITP[4]	FDA approved	I-A	0.8-1 g/kg single dose	Use
Guillain-Barré syndrome[4,22]	EMA approved; not FDA approved	I-A	2 g/kg over 5 days	Use
MIS-C[4]	Guideline-recommended (AAP, WHO)	I-B (cohort data, expert consensus)	2 g/kg single dose	Use with adjunct therapy
Autoimmune encephalitis (anti-NMDAR)[17]	Off-label	II-B (cohort studies, case series)	1-2 g/kg	Consider with caution
ADEM[15]	Off-label	II-B (cohort studies)	1-2 g/kg	Consider with caution
FIRES[18]	Off-label	III-C (case series, expert opinion)	1-2 g/kg	Consider with caution
Refractory myasthenia gravis[17]	Off-label in children	II-B (small studies)	1-2 g/kg	Consider with caution
Acute myocarditis[4,23]	Off-label (AAAAI: “may provide benefit”)	III-C (small studies, expert opinion)	2 g/kg	Selective use only
Juvenile dermatomyositis[1]	Off-label	II-B (cohort, open-label trials)	1-2 g/kg monthly	Consider with caution
Secondary HLH (non-KD)[18,24]	Off-label	III-C (case series)	1-2 g/kg	Cautious use
Septic shock (without defined immune defect)[1,25]	Off-label	I-D (RCT data: Inconsistent; no survival benefit in meta-analyses)	Not defined	Not routinely recommended
Neonatal sepsis[26]	Off-label	I-D (Cochrane review showed no mortality benefit)	Not defined	Not Recommended
Rh/ABO hemolytic disease of the newborn[27]	Off-label (previously used)	I-D (latest guidelines do not recommend routine use)	Not defined	Not routinely recommended
Viral encephalitis/dengue[28]	Off-label	I-D (RCT data: Inconsistent; no survival benefit in meta-analyses)	Not defined	Not recommended for outside rescue use

AAAAI: American Academy of Allergy, Asthma, and Immunology; AAP: American Academy of Pediatrics; ADEM: Acute disseminated encephalomyelitis; CIDP: Chronic inflammatory demyelinating polyradiculoneuropathy; CVID: Common variable immunodeficiency; EMA: European Medicines Agency; FDA: Food and Drug Administration; FIRES: Febrile infection-related epilepsy syndrome; HLH: Hemophagocytic lymphohistiocytosis; ITP: Immune thrombocytopenia; IVIG: Intravenous immunoglobulin; KD: Kawasaki disease; MIS-C: Multisystem inflammatory syndrome in children; NMDAR: N-methyl-D-aspartate receptor; RCT: Randomized clinical trial; SCID: Severe combined immunodeficiency; WHO: World health organization; XLA: X-linked agammaglobulinemia.