壊死性 enterocolitis における遠隔虚血性コンディショニング：フェーズI安全性延長試験

Remote ischemic conditioning (RIC) potentially is an innovative therapeutic strategy for preterm infants with necrotizing enterocolitis (NEC). RIC appears safe in human premature neonates with NEC, as demonstrated by no adverse effects or complications due to RIC in our previous trial. The aim of the current study is to further assess the safety of RIC during its extended application in preterm infants with NEC.

A single center phase I non-randomized trial was conducted. Preterm (< 36 weeks gestational age at birth) infants with confirmed NEC were recruited and received RIC intervention. RIC consisted of four cycles of limb ischemia (5-min via cuff inflation) followed by reperfusion (5-min via cuff deflation), repeated on two consecutive days post enrollment. Demographic and clinical data were collected at enrollment. The primary endpoint of this study was safety defined as perfusion returning to baseline within 5 min after cuff deflation. Secondary endpoints included cutaneous injury and pain (measured by PIPP scores).

A total of 6 neonates were recruited. All neonates were preterm with a birth weight ranging from 450 to 3150 g. NEC was diagnosed between 7 and 30 days and weight at RIC ranged from 780 to 3040 g. Two (33.3%) patients had medical NEC. Four (66.7%) patients underwent RIC postoperatively. RIC was completed in all neonates. Arterial flow and limb perfusion returned to baseline within 5 min in all patients. All patients had a normal grasp reflex both before and after RIC. No new-onset skin lesions were observed. There was no significant difference in PIPP score before and after RIC.

RIC intervention with 5-min ischemia-reperfusion cycles is safe. RIC is also safe when extended to extremely preterm neonates with confirmed medical or surgical NEC.