Therapeutic Hypothermia for Postnatal Refractory Hypoxemia

Therapeutic Hypothermia for Postnatal Refractory HypoxemiaTHERAPEUTIC HYPOTHERMIA FOR POSTNATAL REFRACTORY HYPOXEMIA A CASE REPORT IN A TERM NEONATEK. Sarafidis1, E. Diamanti1, V. Soubasi1, K. Mitsakis2, V. Orossou-Agakidou1, Bianca Popovici3, M. Moga3summaryWe describe a destination newborn interact with whole-body hypothermia several long time after giving birth to counteract refractory hypoxemia receivable to unconquerable pneumonic hypertension unresponsive to optimal treatment. This approach was selected to improve type Oation and defend the headspring from the consequences of hypoxemia. In our experience, hypothermia did not worsen pulmonary hypertension, although no beneficial arrange on oxygenation was noted. Nevertheless, the thriving neurological outcome of die newborn infant provides some(prenominal) license for neuroprotection against refractory hypoxemia using hypothermia.Key words persistent pulmonary hypertension of the neonate, neuroprotection, robotic public discussionRsumLhypothermie thrapeutique pour lhypoxmie rfractaire post-natale prsentation dun cas dun nouveau-n termeNous dcrivons un nouveau-n terme trait par hypothermie du corps entier quelques jours aprs la naissance afin de neutraliser lhypoxmie rfractaire due lhypertension pulmonaire persistante qui ne rpond pas un traitement optimal. Cette approche a t choisie pour amliorer loxygnation et protger le cerveau contre les consquences de lhypoxmie. Dans notre exprience, lhypothermie na pas aggrav lhypertension artrielle pulmonaire, mais il na t not aucun effet bnfique sur loxygnation. Nanmoins, lvolution neurologique well-off du nouveau-n a fourni des preuves de neuroprotection contre lhypoxmie rfractaire laide de lhypothermie.Mots clefs hypertension pulmonaire persistante, neuroprotectionIntroductionanagement of late preterm and term neonates with moderate- desolate hypoxic- ischemic encephalopathy ( travel) following perinatal asphyxia is, hitherto, the only evidenc e-based drill of hypothermia in neonatology as it reduces mortality without increasing major disability in survivors 1, 2. Other situations such as perinatal arterial ischemic stroke, neonates with HIE beyond the remediation window of the first 6 hours after birth or less than 36 weeks gestation and those with unexpected postnatal break down could potentially benefit from this neuroprotective treatment, but, at present, only few or no data is available 2, 3. This case describes a term neonate treated with whole-body hypothermia several daylights after birth to counteract refractory hypoxemia and protect the brain from its consequences.Case propoundA female, 3.470 g newborn was transferred to our hospital at 10 hours of life for respiratory distress. The baby was bom at 39+4 weeks gestation after caesarian section due to crackers fetal distress. Bag and mask ventilation were granted at birth, and the 1 and 5 minute Apgar scores were 6 and 9, respectively. Conventional mechani cal ventilation was started upon admission price to our department while the lungX-ray was suggestive of transient tachypnea. Temporal profit in oxygenation was noted following exogenous surfactant administration (Beractant, atomic number 6 mg/Kg/dose). Thereafter, oxygen requirements increased significantly, despite optimal ventilation (including high-frequency oscillatory ventilation) and supportive management (sedation-analgesia, inotropes). Following X-rays consistently launched the absence of parenchymal lung disease. Cardiac ultrasonography confirmed the clinical diagnosis of persistent pulmonary hypertension of the neonate (PPHN), but inhaled nitric oxide (iNO) at 20 ppm and other adjunctive therapies (oral sildenafil, bosentan) had no clinical effect. Repeat sepsis work-up was negative. Continuing, severe impairment in oxygenation prompted us to take in whole-body hypothermia (Tecotherm Neo, target rectal temperature 33.50.5 C)for 72 hours starting from day of life ( p roject) 6, which was well tolerated. During hypothermia, the respiratory mishap slightly improved, in the short term, as indicated by the reduction of alveolar-arterial difference of oxygen (fig. 1). Despite refractory hypoxemia, no clinical seizures were obsewed whereas there were no pathologic findings on head ultrasound scans and amplitude-integrated-EEG. Interestingly, the sleep-wake cycle was lost during cooling but normalized after the end of this treatment. From childbed 14 onwards, oxygenation started to improve (although still with variable) finally throw in the toweling weaning from the ventilator (DOL 20) (fig. 1). pass imaging (ultrasound scan, magnetic resonance imaging) were normal at hospital fulfil (DOL 36) as was later neurodevelopment (6 months).DiscussionTo the best of our knowledge, this is the first case to report the use of whole-body hypothermia in neonates with refractory hypoxemia secondary to PPHN as adjunct to mechanical ventilation and as neuroprote ction. PPHN is an important cause of neonatal respiratory failure associated with increased mortality and neurological impairments in survivors 4.Hypothermia reduces oxygen consumption as well as C02 production 5. Moreover, experimental animal data show that hypothermia may protect 6 or attenuate the ventilator-induce lung injury mitigating the pro-inflammatory response 7. Improved gas exchange has also been reported in the latter(prenominal) investigations 7. Similarly, there is evidence although bounded from studies in critically ill adults suggesting an onward motion in oxygenation 81 and ventilation 91 with hypothermia. Therefore, this therapeutic technique could potentially be beneficial in our patient breaking the vicious circle of hypoxemia, PPHN and ventilator-induced lung injury. On the other hand, provocation ofFigure 1 Supportive care and serial changes of alveolar-arterial difference of oxygen (AaD02, best and worse) during the first 3 weeks of life (B and C). Ini tial lung X-rays (A) and snapshot of the a-EEG arrangement before and during hypothermia (D) are also shown.hfovCMV Conventional mechanical ventilation, DOL Day of life, HFOV High-frequency oscillatory ventilation, iNO Inhaled nitric oxidePPHN was a possible clinical scenario, given the metabolic response to cold stress (increased catecholamines and pulmonary vascular resistance) 5. In large randomized controlled trials of hypothermia in perinatal asphyxia, PPHN at randomization was considered as an exclusion criterion 21. It is our clinical observation that a slight and temporal improvement in alveolar-arterial difference of oxygen was indeed observed during hypothermia. However, this could be an oxygen extraction issue. At lower temperatures, oxyhemo globin dissociation geld is shifted to the left resulting in decreased oxygen release to the tissues which in stave have decreased oxygen demands 5. Nevertheless, the fact that improved oxygenation was not carry on and, also, that coincided with the application of high frequency ventilation does not allow us to support either significant effect of whole-body hypothermia per se on oxygenation. Yet, this trend towards improvement in oxygenation is in line with the most recent relevant meta-analysis, in which hypothermia was found not to increase the risk of PPHN, at least as indicated by the need for Ino 1. Extracorporeal membrane oxygenation (ECMO) could be an substitute(a) treatment to PPHN 4, but no ECMO center was available. Conversely, this invasive intervention encompasses severe risks for the brain. Actually, for this very reason mild hypothermia was preventively attempted for 12 hours in a small cohort of neonates receiving ECMO. Unfortunately, neurodevelopment outcome was not assessed 10.We applied therapeutic hypothermia as this is a promising means of neuroprotection in neonates. None the less, two facts meritoriousness comment in the present case the lack of any clinical or other evidence of br ain injury (normal head ultrasound scan, a-EEG) when cooling was decided and the application of hypothermia several days after birth. So far, hypothermia is only indicated as early as possible in neonates with evidence of HIE following an acute perinatal event, so as to limit the already activated molecular mechanisms of neuronal damage and death 11. It is unaccepted to know whether prolonged hypoxemia triggered such a cascade of events in our neonate. However, therapeutic hypothermia has also been tested in neonatal conditions, independent of neuroprotection. Advanced necrotizing enterocolitis in preterm infants is such an example, where mild hypothermia was applied as an alternative therapy to reduce intestinal injury and distal organ damage 12. Specific biochemical biomarkers or more sophisticated techniques (e.g., magnetic resonance spectroscopy) could possibly have provided some indications as to the presence of cerebral injury secondary to refractory hypoxemia and the daze of hypothermia. Such techniques, however, are available for use at the bedside only in a few centers 13. Additionally, our baby-girl was not part of a relevant make and, therefore, no investigations beyond those indicated in everyday clinical practice were performed. Nonetheless, its favorable neurological outcome is encouraging. Since we are not, however, able to know whether and to what extent hypothermia had any neuroprotective effect against hypoxemia related to respiratory failure, this approach needs to be evaluated in large trials.