OBJECTIVES: Necrotizing enterocolitis (NEC) with multiple organ dysfunction 
syndrome (MODS) carries significant morbidity and mortality. There is extensive 
experimental evidence to support investigation of therapeutic hypothermia in 
infants with these conditions. We aimed to establish the feasibility and safety 
of mild hypothermia in preterm neonates with NEC and MODS as a prelude to a 
randomized trial.
METHODS: This was a prospective, nonrandomized pilot study of 15 preterm infants 
who were referred for surgical intervention of advanced NEC and failure of at 
least 3 organs. Whole-body cooling was achieved by ambient temperature 
adjustment with or without cooling mattress. Three groups (n = 5 per group) were 
cooled to core temperatures of 35.5 degrees C (+/-0.5 degrees C), 34.5 degrees 
C, and 33.5 degrees C, respectively, for 48 hours before rewarming to 37 degrees 
C. Infants were carefully assessed to identify adverse effects that potentially 
were related to cooling and rewarming. A noncooled group (n = 10) with advanced 
surgical NEC and MODS was used for comparison. Data are medians (interquartile 
range).
RESULTS: Gestational age at birth was 27 weeks (26-30), admission weight was 1.1 
kg (1.0-1.7), and admission age was 31 days (12-45). Core temperature was 
maintained within target range for 90% (88%-97%) of the intended time. 
Statistically significant relationships were identified between core temperature 
and heart rate (P < .0001), pH (P < .0001), base excess (P = .003), and blood 
clot dynamics (longer time to initial clot formation, slower rate of clot 
formation, and decrease in clot strength; all P < .001) as assessed by 
thromboelastography. No major clinical problems or adverse events were noted 
during cooling or rewarming. Comparison with the noncooled group revealed no 
increase in mortality, bleeding, infection, or need for inotropes in infants who 
were cooled.
CONCLUSIONS: Mild hypothermia for 48 hours in preterm neonates with severe NEC 
seems both feasible and safe. Additional investigation of the efficacy of this 
therapeutic intervention in this population is warranted.