Nigel J. Hall, Simon Eaton, Mark J. Peters, Melanie P. Hiorns, Nicholas Alexander, Denis V. Azzopardi, Agostino Pierro.  Mild Controlled Hypothermia in Preterm Neonates With Advanced Necrotizing Enterocolitis.   PEDIATRICS Vol. 125 No. 2 February 2010, pp. e300-e308  | PubMed  Pediatrics |

 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°C (±0.5°C), 34.5°C, and 33.5°C, respectively, for 48 hours before rewarming to 37°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.

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 Comments:  This was a pilot study to demonstrate that controlled hypothermia for VLBW patients with multiple organ dysfunction syndrome from NEC could safely be achieved with no adverse effects.  They do not predict the efficacy of this therapy, only note that therapeutic hypothermia is emerging as potentially beneficial treatment in many clinical situations and should be investigated as a randomized control study for this disease.   A review of VON cumulative data for all centers from 2001 to 2008, demonstrates that some of the major morbidities such as CLD (31.5% to 26.9%) and Nosocomial Infection (21.2% to 18.5%) have improved, however rates of NEC have increased (5.6% to 6.9%).  This clearly continues to be an area of great concern in caring for our patient population. 

Mindy Morris