Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
Using adrenaline during neonatal resuscitation may have an impact on serum cardiac troponin-T levels Caroline Helmer1, Janne H. Skranes2,3, Knut Liestøl4, Drude Fugelseth ([email protected])2,3 1.Faculty of Medicine, Medical School, University of Oslo, Oslo, Norway 2.Department of Neonatal Intensive Care, Oslo University Hospital Ullev al, Oslo, Norway 3.Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway 4.Institute of Informatic, University of Oslo, Oslo, Norway
Keywords Apgar scores, Cardiac troponin-T, Cardiopulmonary resuscitation, Hypoxic–ischaemic encephalopathy, Newborn infants Correspondence Drude Fugelseth, Department of Neonatal Intensive Care, Oslo University Hospital Ullev al, Kirkeveien 166, 0450 Oslo, Norway. Tel: +47 22118765 | Fax: +47 22118663 | Email: [email protected] Received 17 December 2014; revised 5 February 2015; accepted 11 March 2015. DOI:10.1111/apa.13055
ABSTRACT Aim: It has been suggested that serum cardiac troponin-T (cTnT) can predict the severity of neonatal hypoxic–ischaemic encephalopathy. We evaluated whether cTnT was better correlated with adrenaline during cardiopulmonary resuscitation (CPR) than with the severity of the insult itself, based on the Apgar scores. Methods: Serum cTnT was analysed in 47 asphyxiated newborn infants treated with hypothermia. Blood samples and resuscitation data were collected from medical records, and multiple linear regressions were used to evaluate the effect of the treatment and the Apgar scores on cTnT levels. Results: The infants were divided into three groups: the no CPR group (n = 29) just received stimulation and ventilation, the CPR minus adrenaline group (n = 9) received cardiac compression and ventilation and the CPR plus adrenaline group (n = 9) received complete CPR, including adrenaline. In the univariate analysis, the five and ten-minute Apgar scores were significantly lower in the CPR plus adrenaline group and the cTnT was significantly higher. Multiple regression analysis showed significantly higher cTnT values in the CPR plus adrenaline group, but no significant relationship between cTnT and the Apgar scores. Conclusion: Although cTnT correlated with the severity of the insult in neonatal hypoxic– ischaemic encephalopathy, the levels may have been affected by adrenaline administered during CPR.
INTRODUCTION Neonatal hypoxic–ischaemic encephalopathy (HIE) is characterised by low Apgar scores after birth, the need for resuscitation, acidosis and clinical and laboratory evidence of brain injury (1,2). HIE is a major cause of death and disability in the newborn period (1). Pathophysiological processes after birth asphyxia may result in vascular changes in vital organs such as the brain, heart, lungs and kidneys (3,4), and hypoxaemia and acidosis can cause myocardial dysfunction, leading to hypotension and ischaemia. Heart involvement is usually transient and presents as impaired myocardial contractility and decreased cardiac output (4). Several randomised control trials have shown that hypothermia treatment (HT) can have neuroprotective Abbreviations aEEG, Amplitude-integrated electroencephalography; bpm, Beats per minutes; CPR, Cardiopulmonary resuscitation; cTnI, Cardiac troponin-I; cTnT, Cardiac troponin-T; HIE, Hypoxic– ischaemic encephalopathy; HT, Hypothermia treatment.
e378
(5–10) and cardioprotective (2,4,11) effects in moderate to severe encephalopathy, following a perinatal hypoxic– ischaemic insult, if it is initiated in the first six hours of life. Serum cardiac troponin-T (cTnT) and cardiac troponin-I (cTnI) are used as clinical markers for myocardial injury and have been proved to have high specificity and
Key Notes
It has been suggested that serum cardiac troponin-T (cTnT) can predict the severity of neonatal hypoxic– ischaemic encephalopathy. We analysed serum cTnT levels in 47 asphyxiated newborn infants treated with hypothermia who received no cardiopulmonary resuscitation (CPR), CPR without adrenaline and CPR plus adrenaline. Although cTnT correlated with the severity of the insult in neonatal hypoxic–ischaemic encephalopathy, the levels may have been affected by adrenaline administered during CPR.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e378–e383
Helmer et al.
sensitivity in adults (12–15). cTnT is a structural protein located on the thin myofilament on the contractile apparatus of the myocardium and is a tropomyosin-binding protein. cTnT has been shown to provide three advantages in adults compared to the classical cardiac injury markers. Firstly, cTnT has a unique structure that differs from skeletal muscle TnT, which enables assessment of myocardial injury in the presence of skeletal muscle damage. Secondly, cTnT is proven to be more favourable for detecting minor cardiac injuries. Thirdly, the diagnostic time window for cTnT is considered to be unusually wide, despite its short half-life (16). At birth, cTnT is co-expressed in small amounts in skeletal muscle in infants and is later down-regulated with further development (17). Higher cut-off values for pathological cTnT are suggested in newborn infants than adults (18,19). cTnI measured from the umbilical cord blood at birth, or from the baby during the first 36 hours of its life, has been used as early markers for the severity of HIE (20). In addition, cTnT has been shown to increase during asphyxia and the levels may differentiate severe from mild and moderate HIE (14). The aim of this study was to explore whether serum cTnT values were better correlated with the use of adrenaline during cardiopulmonary resuscitation (CPR) than with the severity of the insult per se, as assessed by Apgar scores, and whether this affected its predictive value for long-term neurodevelopmental outcome.
MATERIALS AND METHODS Study population This single centre, prospective cohort study was carried out at the Department of Neonatal Intensive Care, Oslo University Hospital Ullev al, Norway. It comprised 47 neonates who were treated with HT for perinatal asphyxia between 1 January 2010 and 31 December 2011. The neonates all fulfilled the Norwegian National Guidelines for HT (21). They received whole body cooling as standard care using a servo-controlled cooling jacket circulated with water (CritiCoolTM; MTRE, Yavne, Israel) to a rectal temperature of 33.5°C for 72 hours followed by rewarming to 37.0°C by 0.5°C per hour. The inclusion criteria were adapted and modified from the Toby study protocol (1) for HT. The neonates included in the study all had moderate to severe HIE (21). They had a gestational age of 36 weeks or more and demonstrated at least one of the following: a) an Apgar score of five or less at 10 minutes, b) the need for respiratory support 10 minutes after birth and c) a pH of
REGULAR ARTICLE
Using adrenaline during neonatal resuscitation may have an impact on serum cardiac troponin-T levels Caroline Helmer1, Janne H. Skranes2,3, Knut Liestøl4, Drude Fugelseth ([email protected])2,3 1.Faculty of Medicine, Medical School, University of Oslo, Oslo, Norway 2.Department of Neonatal Intensive Care, Oslo University Hospital Ullev al, Oslo, Norway 3.Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway 4.Institute of Informatic, University of Oslo, Oslo, Norway
Keywords Apgar scores, Cardiac troponin-T, Cardiopulmonary resuscitation, Hypoxic–ischaemic encephalopathy, Newborn infants Correspondence Drude Fugelseth, Department of Neonatal Intensive Care, Oslo University Hospital Ullev al, Kirkeveien 166, 0450 Oslo, Norway. Tel: +47 22118765 | Fax: +47 22118663 | Email: [email protected] Received 17 December 2014; revised 5 February 2015; accepted 11 March 2015. DOI:10.1111/apa.13055
ABSTRACT Aim: It has been suggested that serum cardiac troponin-T (cTnT) can predict the severity of neonatal hypoxic–ischaemic encephalopathy. We evaluated whether cTnT was better correlated with adrenaline during cardiopulmonary resuscitation (CPR) than with the severity of the insult itself, based on the Apgar scores. Methods: Serum cTnT was analysed in 47 asphyxiated newborn infants treated with hypothermia. Blood samples and resuscitation data were collected from medical records, and multiple linear regressions were used to evaluate the effect of the treatment and the Apgar scores on cTnT levels. Results: The infants were divided into three groups: the no CPR group (n = 29) just received stimulation and ventilation, the CPR minus adrenaline group (n = 9) received cardiac compression and ventilation and the CPR plus adrenaline group (n = 9) received complete CPR, including adrenaline. In the univariate analysis, the five and ten-minute Apgar scores were significantly lower in the CPR plus adrenaline group and the cTnT was significantly higher. Multiple regression analysis showed significantly higher cTnT values in the CPR plus adrenaline group, but no significant relationship between cTnT and the Apgar scores. Conclusion: Although cTnT correlated with the severity of the insult in neonatal hypoxic– ischaemic encephalopathy, the levels may have been affected by adrenaline administered during CPR.
INTRODUCTION Neonatal hypoxic–ischaemic encephalopathy (HIE) is characterised by low Apgar scores after birth, the need for resuscitation, acidosis and clinical and laboratory evidence of brain injury (1,2). HIE is a major cause of death and disability in the newborn period (1). Pathophysiological processes after birth asphyxia may result in vascular changes in vital organs such as the brain, heart, lungs and kidneys (3,4), and hypoxaemia and acidosis can cause myocardial dysfunction, leading to hypotension and ischaemia. Heart involvement is usually transient and presents as impaired myocardial contractility and decreased cardiac output (4). Several randomised control trials have shown that hypothermia treatment (HT) can have neuroprotective Abbreviations aEEG, Amplitude-integrated electroencephalography; bpm, Beats per minutes; CPR, Cardiopulmonary resuscitation; cTnI, Cardiac troponin-I; cTnT, Cardiac troponin-T; HIE, Hypoxic– ischaemic encephalopathy; HT, Hypothermia treatment.
e378
(5–10) and cardioprotective (2,4,11) effects in moderate to severe encephalopathy, following a perinatal hypoxic– ischaemic insult, if it is initiated in the first six hours of life. Serum cardiac troponin-T (cTnT) and cardiac troponin-I (cTnI) are used as clinical markers for myocardial injury and have been proved to have high specificity and
Key Notes
It has been suggested that serum cardiac troponin-T (cTnT) can predict the severity of neonatal hypoxic– ischaemic encephalopathy. We analysed serum cTnT levels in 47 asphyxiated newborn infants treated with hypothermia who received no cardiopulmonary resuscitation (CPR), CPR without adrenaline and CPR plus adrenaline. Although cTnT correlated with the severity of the insult in neonatal hypoxic–ischaemic encephalopathy, the levels may have been affected by adrenaline administered during CPR.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e378–e383
Helmer et al.
sensitivity in adults (12–15). cTnT is a structural protein located on the thin myofilament on the contractile apparatus of the myocardium and is a tropomyosin-binding protein. cTnT has been shown to provide three advantages in adults compared to the classical cardiac injury markers. Firstly, cTnT has a unique structure that differs from skeletal muscle TnT, which enables assessment of myocardial injury in the presence of skeletal muscle damage. Secondly, cTnT is proven to be more favourable for detecting minor cardiac injuries. Thirdly, the diagnostic time window for cTnT is considered to be unusually wide, despite its short half-life (16). At birth, cTnT is co-expressed in small amounts in skeletal muscle in infants and is later down-regulated with further development (17). Higher cut-off values for pathological cTnT are suggested in newborn infants than adults (18,19). cTnI measured from the umbilical cord blood at birth, or from the baby during the first 36 hours of its life, has been used as early markers for the severity of HIE (20). In addition, cTnT has been shown to increase during asphyxia and the levels may differentiate severe from mild and moderate HIE (14). The aim of this study was to explore whether serum cTnT values were better correlated with the use of adrenaline during cardiopulmonary resuscitation (CPR) than with the severity of the insult per se, as assessed by Apgar scores, and whether this affected its predictive value for long-term neurodevelopmental outcome.
MATERIALS AND METHODS Study population This single centre, prospective cohort study was carried out at the Department of Neonatal Intensive Care, Oslo University Hospital Ullev al, Norway. It comprised 47 neonates who were treated with HT for perinatal asphyxia between 1 January 2010 and 31 December 2011. The neonates all fulfilled the Norwegian National Guidelines for HT (21). They received whole body cooling as standard care using a servo-controlled cooling jacket circulated with water (CritiCoolTM; MTRE, Yavne, Israel) to a rectal temperature of 33.5°C for 72 hours followed by rewarming to 37.0°C by 0.5°C per hour. The inclusion criteria were adapted and modified from the Toby study protocol (1) for HT. The neonates included in the study all had moderate to severe HIE (21). They had a gestational age of 36 weeks or more and demonstrated at least one of the following: a) an Apgar score of five or less at 10 minutes, b) the need for respiratory support 10 minutes after birth and c) a pH of
