Remote ischaemic conditioning in necrotising enterocolitis: a phase I feasibility and safety study

Abstract

ObjectiveRemote ischaemic conditioning (RIC) improves the outcome of experimental necrotising enterocolitis (NEC) by preserving intestinal microcirculation. The feasibility and safety of RIC in preterm infants with NEC are unknown. The study aimed to assess the feasibility and safety of RIC in preterm infants with suspected or confirmed NEC.DesignPhase I non-randomised pilot study conducted in three steps: step A to determine the safe duration of limb ischaemia (up to 4 min); step B to assess the safety of 4 repeated cycles of ischaemia-reperfusion at the maximum tolerated duration of ischaemia determined in step A; step C to assess the safety of applying 4 cycles of ischaemia-reperfusion on two consecutive days.SettingLevel III neonatal intensive care unit, The Hospital for Sick Children (Toronto, Canada).PatientsFifteen preterm infants born between 22 and 33 weeks gestational age.InterventionFour cycles of ischaemia (varying duration) applied to the limb via a manual sphygmomanometer, followed by reperfusion (4 min) and rest (5 min), repeated on two consecutive days.OutcomesThe primary outcomes were (1) feasibility defined as RIC being performed as planned in the protocol, and (2) safety defined as perfusion returning to baseline within 4 min after cuff deflation.ResultsFour cycles/day of limb ischaemia (4 min) followed by reperfusion (4 min) and a 5 min gap, repeated on two consecutive days was feasible and safe in all neonates with suspected or confirmed NEC.ConclusionsThis study is pivotal for designing a future randomised controlled trial to assess the efficacy of RIC in preterm infants with NEC.Trial registration numberNCT03860701.

Remote Ischemic Conditioning for Neonatal Hypoxic-Ischemic Encephalopathy: A Safety and Feasibility Trial

“…This is consistent with preclinical rodent studies of stroke where RIC significantly reduced the extent of ischemia and neurological deficits (7). Furthermore, RIC was found to be safe and feasible in neonates of younger gestational age and lower birth weight (8). However, the effects of RIC on neonates with HIE undergoing TH has not been explored.…”

Recent advances in our understanding of NEC diagnosis, prognosis and surgical approach

“…Animal studies have shown that this method is particularly effective and significantly reduces the extent and severity of bowel injury compared to controls ( 24 ). At this stage human studies have not progressed beyond safety studies but further clinical research is in progress included a feasibility randomised controlled trial ( 25 , 26 ). Human breast milk, either maternal or donor, has been shown to almost half the risk of NEC vs. formula feed in meta-analysis ( 27 ).…”