Therapeutichypothermia headcooling and its Adverse Effects in Newborns with PerinatalAsphyxia

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1 International Research Journal of Applied and Basic Sciences 2013 Available online at ISSN X / Vol, 5 (12): Science Explorer Publications Therapeutichypothermia headcooling and its Adverse Effects in Newborns with PerinatalAsphyxia Jannatdoost A 1, Assadollahi M 2, Arshadi M 3, Asghari M 4, Mohammadi F 5 1. PhD in infants, Assistant Professor, Faculty member of Tabriz University of Medical Sciences 2. MS in Pediatric Nursing, Faculty Member of Nursing and Midwifery School, Tabriz University of Medical Sciences 3. Student of Nursing Education, Faculty Member of Nursing and Midwifery School, Tabriz University of Medical Sciences 4. PhD, Assistant Professor of Biostatistics, Department of Statistics and Epidemiology,Faculty of Health, Tabriz University of Medical Sciences 5. MS Student Neonatal intensive care nursing, Nursing and Midwifery School, Tabriz University of Medical Sciences Corresponding Author mohammadifateme47@yahoo.com ABSTRACT:Hypothermia is the most promising therapy care in infants with birth asphyxia. However during cooling period brain temperature fluctuation leads to cerebral edema and subsequently adverse effects on hemodynamic status and brain development. Therefore, this study conducted aim to determine side effects of hypothermia during cooling period in newborns with perinatal asphyxia.this is a descriptive- analytical study in which 25 infants with birth asphyxia were selected using census method from a teaching hospital affiliated with Tabriz University of Medical Sciences. These babies underwent topical head cooling up to target rectal of c temperature. They remained in this temperature for 72 hours and then it was gradually increased during 8-12 h to 36.5 c. During the cooling period possible short term side effects were observed and mortality was assessed. Data was analyzed using SPSS/17 and descriptive (mean, standard deviation, number, percent) and repeated ANOVA statistics.according to the findings the mean time to cool newborns was 5.1± 1.6 hours after delivery while temperature fluctuation was about 0.37 c. Meanwhile seizure (n=19, 76%) and pulmonary hemorragia (n=2,8/%) were respectively the most and the least common short time side effects.findings showed reduction in both frequency of incidence of side effects and newborns mortality during the intervention. Thus hypothermia can be one of the most effective therapeutic approaches to increase survival rate and quality of life of infants with birth asphyxia. Keywords: Hypothermia complications, Whole body cooling, Asphyxia INTRODUCTION Birth asphyxia is a major cause of neonatal morbidity and mortality. The incidence of asphyxia in developed and developing country settings are respectively1-6 per thousand and 5-10 per thousand(pfenninger et al., 2001). Although accurate statistics are not available in our country,iran, experts estimate that the asphyxia incidence rate among newborns in Tabriz is 60 per year while 30 of them are eligible for undergoing hypothermia therapy percent of these infants with moderate to severe asphyxia will survive and 60% of the survived babies die within the first 2-4 years due to sustained and severe damage to brain, heart and kidneys and the rest of 40% live with severe neurological impairments and cerebral palsy or mental retardation(kliegman, 2007, Leifer and Hartson, 2003, Thomas et al., 2011). There are some alternative therapies for babies with birth asphyxia including, anticonvulsants, calcium blockers, antioxidants, corticosteroids (Iwata et al., 2003, Jacobs et al., 2007, Kirpalani et al., 2007, Kliegman, 2007). The most common method of treatment is whole body hypothermia used to treat a wide range of patients including cardiac arrest and cardiac surgery in adults, brain trauma injuries, perinatal asphyxia, etc(nicholas Hoque et al., 2010). The outcomes of hypothermia in birth asphyxia are promising so it is considered a standard care procedure for this group of newborns(nicholas Hoque et al., 2010, Simbruner et al., 2010).

2 Intl. Res. J. Appl. Basic. Sci. Vol., 5 (12), , 2013 Different methods used for cooling include head cooling using Cool Cap system, cooling mattress (automatic or manual), cold water mittens(battin et al., 2001, Debillon et al., 2003, Fairchild et al., 2009, Nicholas Hoque et al., 2010)The basis for cooling is always the same for various methods but different surveys have reported different outcomes(lin et al., 2006, Nicholas Hoque et al., 2010). In this regard, the most practical method of hypothermia is head cooling by cool cup that lower body temperature to c. (Guidelines, 2012) However, no study was found on temperature fluctuations of perinatal asphyxia in newborns and hemodynamic management in cooling methods (head cooling and whole body cooling)(nicholas Hoque et al., 2010, Shankaran, 2009). Body temperature fluctuation that causes brain temperature fluctuation can affect permeability of the blood brain barrier and more often occur during hypothermia. Re-warming procedures also negatively affect cerebral hemodynamics and brain development leading to increased mortality as well as short term and long term complications (Lin et al., 2006, Nicholas Hoque et al., 2010, Pfister and Soll, 2010, Shankaran, 2009)his indicates the importance of nursing care plan for hypothermia (Shankaran et al., 2002). In recent years therapeutic cooling after perinatal asphyxia has been executed in one of the research and training hospitals of Tabrizby using head cooling system, turning off the warmer and using cold water bag. To date, despite extensive and repeated internet searchesno study was found done in this regard. Therefore this survey aimed to determine hypothermia side effects on the babies with moderate to severe birth asphyxia. METHODS This analytical descriptive study was conducted through October 2010 and April 2013 in one of the research and training hospitals of Tabriz 25 neonates with perinatal asphyxia were selected by using census method. The inclusion criteria included the subject babies born at 35 weeks gestational age, postnatal age less than 6 hours,weighing more than 1800 gr, Apgar Score at less than 6 minutes at birth, umbilical artery PH=7 and base deficit 12 within the first 60 minutes of birth, moderate to severe hypoxic ischemic encephalopathy, absence of congenital anomalies and lack of IUGR. Obtaining informed consent from their parents, cooling procedure was carried out in three different times using head cooling(cool cap): 1)Passive and rapid cooling phase (within 1 hour) was initiated to reach the rectal goal temperature of c. 2)They were remained in goal temperature for 72 hours. 3) The subjects were re-warmed within 8-12 hours until the normal body temperature of c was reached. Short term effects of hypothermia were compared and the incidence of any adverse events were recorded. The subjects were excluded in the case of any adverse effects including bradycardia less than 70, hypertension unresponsive to vasoconstriction drugs, pulmonary hemorrhage, coagulopathies, resistant to hypoxia and supplemental oxygen (100%). Data was assessed using SPSS/ 17 and descriptive statistics (mean, SD, number, percentage) also variance analysis. RESULTS Of the 25 samples subjected to the study, there were 22 full- term infants (88%). 16 cases were female (64%), 13 were delivered vaginally(52%) and 11 infants had severe asphyxia (44%). During the cooling procedure (respectively) 15and 10 neonates were receiving respectively mechanical ventilation using a ventilator (60%) and oxygen therapy using oxygen hood (40%).Among mothers of babies with asphyxia, respectively, 20% (5 ones), 4% (1 ones) and 0% (0 ones) had (respectively) gestational hypertension, gestational diabetes mellitus and gestational coagulopathies. The mean temperature before cooling initiation was 35.97± 0.60 while the mean time to start the cooling process was 4.7± 1.8h after delivery.the subjects received whole body cooling therapy by turning off the warmer and preparing cold water bag. In 16 cases the body temperature was decreased during the first hour of cooling while the mean time required to reach a rectal temperature of degrees C was 90 minutes. The subjects were kept at this target temperature for a period of 72 hours. Temperature fluctuations was about ±0.37 0c and mean re-warming rate was ±0.50 degrees C/h (mean re-warming duration = 14.5±8.2 hours). Table 2 shows short time side effects of hypothermia. According to it the most and the least common complications were, respectively, seizure (n=19, 76%) and pulmonary hemorrhage (n=2, 8%). Figures 1 to 6 show fluctuations on blood pressures, heartbeat, platelets and seizure in subjects during five cooling process (baseline,during first 24 hours, the first 72 hours and at the end of the intervention). 1547

3 Intl. Res. J. Appl. Basic. Sci. Vol., 5 (12), , 2013 DISCUSSION The intervention resulted in a reduction in incidence of short time complications as well as mortality rate for hypothermia in babies with severe asphyxia. Hypothermia can be used as an additional therapeutic intervention in order to increase survival and improve quality of life. Optimal therapeutic hypothermia allows rapid cooling to target temperature without any adverse effects (Gluckman et al., 2005) while avoiding temperature fluctuations during cooling and re-warming operations(lin et al., 2006, Nicholas Hoque et al., 2010). In our study the adverse effects of hypothermia included: bradycardia (n=6, 24%), hypotension (n=3, 12%), seizure (n=19, 27%), pulmonary hemorrhage (n=2, 8%), skin injuries (n=7, 28%), thrombocytopenia (n=5, 20%). Our findings were consistent with those reported by George Sim Bruner: hypertension (n=33, 53.2%), seizure (n=26, 41.9%), pulmonary hemorrhage (n= 3, 4.8%), thrombocytopenia (n=16, 25.8%), cardiac arrhythmias (n-3, 4.8%)(Simbruner et al., 2010). They were also consistent with the results of the studies performed on 2010 by Wen hao zhou that showed incidence of cardiac arrhythmias (n=0, 0%), persistent acidosis (n=7, 7%), severe hemorrhage (n=0, 0%), skin injuries (n=0, 0%) and hypertension (n= 0, 0%),thrombus(3,3%).(Zhou et al., 2010) According to the findings of a research conducted by Gluckman, hypertension (n=62, 55%), seizure (n=93, 80%),thrombocytopenia (n=36, 32%), cardiac arrhythmias (n=10, 9%),persistent acidosis (n=22, 20%),(Gluckman et al., 2005)which was consistent with ours, too. A study by Gunn indicated: persistent acidosis (n=6, 100%), thrombocytopenia (n=1, 16.66%)(Gunn et al., 1998),which was consistent with the findings of Mete Akisu and lin. (Akisu et al., 2003, Lin et al., 2006) The overall morbidity and mortality rate in our study (9 babies, 27.5%) was consistent with the results of the studies by George Sim Bruner et al 2012 (n=5, 8.1%), Shakaran et al (n=13, 13%), Nicholas Hoque (n=8, 10.96%), Hannah Glass (n=2, 6%), Thoresen et al (n=18). In another study Shakaran (2012) reported mortality rate of these newborns 41 ones (42%) which was consistent with ours, too. There was no significant statistical relationship between maternal age, blood pressure, diabetes or coagulopathies status during pregnancy as well as birth weight, gestational age, pre-cooling temperature and the severity of hypoxic ischemic encephalopathy, the incidence of hypothermia short-term adverse effects, morbidity and mortality. It was consistent with the findings of a survey by W-H Zhou that showed no relationship among mortality rates, sever injuries, febrile seizures, hypoxic ischemic encephalopathy(zhou et al., 2010). But there was no significant relation between severity of hypoxic ischemic encephalopathy and incidence of hypothermia short term side effects, morbidity and mortality rates in these babies (P=0.001). The main limitation of the present study was the relatively small sample size due to time and place constraint that reduced the power of the study on short term adverse effects of hypothermia head cooling method, mortality and morbidity rates. Therefore, it is suggested that further studies be conducted in our country with a larger sample sizes and a larger spatial and temporal coverage. These validated findings will be utilized by medical services to identify training deficiencies and weaknesses during hypothermia treatment of babies with perinatal asphyxia. This can minimize or prevent subsequent short term side effectsresulting in sustained neurological disturbances, mental retardation, longer hospital stay and higher treatment cost as well as mortality rate. ACKNOWLEDGEMENT Authors would like to acknowledge all the staff at Nursing and Midwifery School of Tabriz University of Medical Sciences, all Tabriz Taleghani Hospital staff and also the parents of children participated in the research. 1548

4 Mean BP MIN (mmhg) Mean tempreture (C ) Intl. Res. J. Appl. Basic. Sci. Vol., 5 (12), , 2013 Table1. Neonatal characteristics variable Birth weight gestational age arterial or cord PH arterial or cord Sio2 Apgar score at 1 min Apgar score at 5 min Apgar score at 10 min Mean temperature in the beginning Mean temperature in the end Mean temperature in the during Means ±std ± ± ± ± ± ± ± ± ± ±0.46 Table2. hypothermia side effects variable Sub numbe group r Brady cardia yes 6 no 19 hypotension yes 3 no 22 thrombocytopenia yes 5 no 20 skin damage yes 7 no 18 Pulmonary hemorrhage yes 2 no 23 seizure yes 19 no 6 Result discha 6 rge Stay in 9 ward Death 10 percen t before. tempreture 24H 48H 72H 84H Figure1:temperature Influence head cooling before.bp min 24H 48H 72H 84H Figure2:BP MIN Influence 1549

5 Mean Convulsion ( N/MIN ) Mean HR (N/min) Mean BP MAX (MMhg ) Intl. Res. J. Appl. Basic. Sci. Vol., 5 (12), , before.bpmax 24H 48H 72H 84H Figure3: BP MAX Influence before.hr 24h 48 h 72h 84h Figure4:HR Influence before. Convulsion 24H 48H 72H 84H Figure 5:Convulsion Influence REFERENCES AKISU M, HUSEYINOV A, YALAZ M, CETIN H, KULTURSAY N Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia. Prostaglandins, leukotrienes, and essential fatty acids, 69, 45. BATTIN MR, DEZOETE JA, GUNN TR, GLUCKMAN PD, GUNN AJ Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics, 107, DEBILLON T, DAOUD P, DURAND P, CANTAGREL S, JOUVET P, SAIZOU C, ZUPAN V Whole-body cooling after perinatal asphyxia: a pilot study in term neonates. Developmental Medicine & Child Neurology, 45, FAIRCHILD K, SOKORA D, SCOTT J, ZANELLI S Therapeutic hypothermia on neonatal transport: 4-year experience in a single NICU. Journal of Perinatology, 30, GLUCKMAN PD, WYATT JS, AZZOPARDI D, BALLARD R, EDWARDS AD, FERRIERO DM, POLIN RA, ROBERTSON CM, THORESEN M, WHITELAW A Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. The Lancet, 365, GUIDELINES NC Head Cooling Guideline Head Cooling at ACH NICU Pediatric Hospital Services and Centers. Perth Western Australia: King Edward Memorial. GUNN AJ, GLUCKMAN PD, GUNN TR Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics, 102, IWATA O, IWATA S, TAMURA M, NAKAMURA T, SUGIURA M, OGISO Y, TAKASHIMA S Early head cooling in newborn piglets is neuroprotective even in the absence of profound systemic hypothermia. Pediatrics international, 45, JACOBS S, HUNT R, TARNOW-MORDI W, INDER T, DAVIS P Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev, 4. KIRPALANI H, BARKS J, THORLUND K, GUYATT G Cooling for neonatal hypoxic ischemic encephalopathy: do we have the answer? Pediatrics, 120, KLIEGMAN R Nelson textbook of pediatrics, Saunders Elsevier Philadelphia. 1550

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