Potential Complications and Risk Factors Associated with Therapeutic Hypothermia

Therapeutic hypothermia (TH) has become widely accepted as the standard of care for the treatment of term or near-term newborn babies with moderate to severe hypoxic injury (HI) who meet the inclusion criteria. Several randomized controlled trials and systematic analyses have been published which show benefit in this patient population, with a reduction in mortality and improvement in neurodevelopmental outcomes at 18 to 24 months1. The research demonstrated references to both high and low-tech methods to induce therapeutic hypothermia, which include both selectively head cooling or whole-body hypothermia using servo controlled and manual cooling technologies.

As more neonatal care facilities start to offer whole body cooling, there is a growing importance to understand the physiological effects of hypothermia on the cooled infant, the effect on medications administered under lower core body temperature, and the serious side effects that might occur during the process of induction of cooling, maintenance of low core body temperatures and later re-warming of patients.

Potential Complications and Risk Factors Associated with Therapeutic Hypothermia

Cardiovascular complications

Lowering core temperature results in:

  • Decreased heart rate: in neonates undergoing whole body cooling for neuroprotection, heart rate drops to about 45 b.p.m. and returns to normal on rewarming. 3, 5, 9. 
  • Decreased cardiac contractility and cardiac output (CO):  mainly driven by decrease in oxygen consumption.
  • Increase in blood pressure due to hypothermic stress: caused by the initial increase in vascular resistance as the body attempts to conserve heat through vasoconstriction combined with release cortisol20.

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Respiratory system complications

Lowering core temperature results in:

  • Decrease in basal metabolic rate and reduced CO2 production: The recommended range for targeting PCO2 is between 40 and 50 mmHg in mechanically ventilated infants undergoing TH when blood gases are measured at 37 °C (9).
  • Decreased oxygen demand: minimum FiO2 to maintain normoxia is recommended in babies with HIE. Increased FiO2 has been shown to be associated with worse outcome in newborns undergoing whole body cooling.
  • Higher risk of pulmonary hypertension of newborn: pulmonary vascular resistance may be increased at lower core temperatures,38,39 Persistent pulmonary hypertension can be managed according to standard protocol in the hospital with inhaled nitric oxide.

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Rewarming challenges

During rewarming the following reactions may be observed:

  • Higher risk of seizures as cerebral metabolic rate increases: These seizures are often subclinical, and therefore consideration should be given to performing continuous EEG monitoring during rewarming.
  • Higher risk of hypotension: During rewarming the skin vasoconstriction undergoes dilation and the infant may require a fluid bolus if this occurs. 
  • Apnea has also been seen to occur in spontaneously breathing infants in the rewarming phase, with respiratory support required.

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About the author

Dr Yaseen Joolay

M.B.Ch.B.(Stell), FC Paed (SA), Cert Neonatology (CMSA), M.Phil. Neonatology (UCT)

Consultant Neonatologist, Groote Schuur Hospital, Cape Town South Africa Senior Lecturer, Department of Paediatrics, University of Cape Town.


1. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD003311.

2. S Zanelli, M Buck, and K Fairchild, Physiologic and pharmacologic considerations for hypothermia therapy in neonates, J Perinatol. 2011 Jun; 31(6): 377–386.

3. Gambassi G, Cerbai E, Pahor M, Capogrossi MC, Carbonin P, Mugelli A. Temperature modulates calcium homeostasis and ventricular arrhythmias in myocardial preparations. Cardiovasc Res. 1994;28(3):391–399. (PubMed)

4. Groenendaal F, Brouwer AJ. Clinical aspects of induced hypothermia in full term neonates with perinatal asphyxia. Early Hum Dev. 2009;85(2):73–76. (PubMed)

5. Zhou WH, Cheng GQ, Shao XM, Liu XZ, Shan RB, Zhuang DY, et al. Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr. 2010;157(3):367–372. (PubMed)

6. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574–1584. (PubMed)

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Neonatal therapeutic hypothermia


Hypoxic-Ischemic Encephalopathy


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