Case Report 221
Therapeutic Hypothermia after Cardiopulmonary Resuscitation in a 4-month Infant Therapeutische Hypothermie nach kardiopulmonaler Reanimation bei einem 4 Monate alten Säugling
Affiliations
Key words ▶ therapeutic hypothermia ● ▶ pediatric cardiac arrest ● ▶ resuscitation ● ▶ infant ● Schlüsselwörter ▶ therapeutische Hypothermie ● ▶ Herz-Kreislaufstillstand im ● Kindesalter ▶ Wiederbelebung ● ▶ Säugling ●
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1375699 Klin Padiatr 2014; 226: 221–224 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Dr. Gert Warncke Children’s University Hospital Rostock Pediatric Intensive Care Unit Ernst-Heydemann-Str. 8 18057 Rostock Germany Tel.: + 49/381/494 7126 Fax: + 49/381/494 7002 [email protected]
G. Warncke1, U. N. Osmers2, C. Hauenstein3, M. Scotland1, H. von Osten1, R. Höhn1, D. C. Fischer4 1
Children’s University Hospital, Pediatric Intensive Care Unit, Rostock, Germany Department of Anaesthesiology and Intensive Care Medicine, Medical Center Südstadt, Rostock, Rostock, Germany 3 Deparment of Diagnostic and Interventional Radiography, University Hospital, Rostock, Germany 4 Children’s University Hospital, Rostock, Germany 2
Abstract
Zusammenfassung
Therapeutic hypothermia is currently recommend ed for adult comatose survivors of cardiac arrest and perinatal hypoxic-ischemic encephalopathy. By contrast, current international guidelines on cardiopulmonary resuscitation in children neither refute nor support therapeutic hypothermia. Here we report on a 4-month old infant who survived resuscitation for severe cardiopulmonary insufficiency without neurological impairments. The infant most probably experienced unwitnessed aspiration with subsequent severe cardiopulmonary insufficiency. This was paralleled by incidental hypothermia, i. e. a core body temperature of 32 °C at time of resuscitation. The infant was transported to the pediatric intensive care unit and additional to state-of the art resuscitation therapy (e. g. vasopressors, pressure controlled intermittent mandatory ventilation) therapeutic hypothermia (core body temperature 32.0–34.0 °C) was admininistered for additional 48 h to confer optimal neuroprotection. Subsequently, he was rewarmed (0.25 °C per hour) and sedation was stopped at a core body temperature of 36 °C. Chest X-ray at time of admission to the hospital revealed typical signs of severe aspiration, whereas transthoraic echocardiography, electrocardiography and ultrasound examination of the brain were without pathological findings. Likewise, magnetic resonance imaging of the head performed on days 3 and 32 after resuscitation revealed no signs of hypoxic brain damage and the child was discharged to foster care without neurological deficits 52 days after admission.
Die therapeutische Hypothermie (THT) wird bei Erwachsenen nach erfolgreicher Reanimation z. B. nach Herz-Kreislauf-Stillstand oder in der Altersgruppe der Neugeborenen bei hypoxischischämischer Enzephalopathie seit vielen Jahren erfolgreich angewendet. Im Gegensatz dazu wird die THT in den aktuellen Empfehlungen des European Resuscitation Council (ERC) zur kardiopulmonalen Reanimation für Kinder weder abgelehnt noch eindeutig empfohlen. Wir berichten über einen 4 Monate alten Säugling, der eine schwere kardiopulmonale Insuffizienz nach Reanimation ohne neurologische Beeinträchtigungen überlebte. Vermutlich durch eine Aspiration bedingt kam es in der Folge zu einer schweren Beeinträchtigung des Herz-Kreislauf-Systems sowie der Atmung. Bereits zu Beginn der Reanimation war eine akzidentelle Hypothermie mit einer Körperkerntemperatur von 32 °C nachweisbar. Der Säugling wurde auf unsere interdisziplinäre pädiatrische Intensivstation eingewiesen. Dort führten wir neben einer kreislauf- und atemstabilisierenden Therapie eine therapeutische Hypothermie (Körperkerntemperatur 32,0–34,0 °C) mit dem Ziel einer maximalen Neuroprotektion für 48 Stunden durch. Im Anschluss wurde der Patient mit 0,25 °C pro Stunde wieder erwärmt und die Sedierung bei einer Körperkerntemperatur von 36 °C beendet. Die Röntgenaufnahme des Thorax wies das typische Bild einer schweren Aspiration auf, wohingegen Echokardiografie, EKG, Sonografie des ZNS keine pathologischen Befunde auswiesen. In der an Tag 3 und 32 nach Reanimation durchgeführten kernspintomografischen Untersuchung waren keine hypoxischen Hirnschäden nachweisbar. Der Säugling wurde 52 Tage nach dem Ereignis ohne neurologische Defizite in eine Pflege entlassen.
▼
▼
Warncke G et al. Therapeutic Hypothermia after Cardiopulmonary … Klin Padiatr 2014; 226: 221–224
Downloaded by: NYU. Copyrighted material.
Authors
222 Case Report
Case report
▼
A 4-months old boy laying pulseless and apneic in his bed was found early in the morning by his 8-year old sister. The emergency medical service arrived 10 min later and diagnosed cardiopulmonary insufficiency (breathing frequency: 30/min, bradycardia of 40/min, undetectable blood pressure), a GlasgowComa Scale score of 8, cyanosis and hypothermia (32 °C, ear probe). Remnants of milk periorally, on his clothes, and in his bed point to severe aspiration, although no such event was noticed by the parents at the time of last control approximately 9 h before. Cardiopulmonary resuscitation was initiated, i. e. chest compression, a laryngeal tube was placed and 0.02 mg adrenaline as well as a complete electrolyte solution (E153) were administered via a peripheral line. The baby recovered (heart rate: 115/min, oxygen saturation of 90–94 % at 100 % oxy-
7.5 7.0 6.5 0
24
48
72
96
120
144
168
192
216
Time [h]
Fig. 1 Core temperature (left axis) and pH (right axis); findings at admission to the PICU, onset of therapeutic hypothermia and rewarming are indicated.
gen via laryngeal tube) within 2 min. He was wrapped in aluminum foil to prevent aggravation of hypothermia and transported to the pediatric intensive care unit (PICU). During transport, the boy experienced one convulsive seizure which persisted after intravenous clonazepame (0.2 mg/kg) administration. The patient arrived at the PICU 30 min after initiation of cardiopulmonary resuscitation. At that time his temperature was 30.8 °C (rectal probe). The laryngeal tube was changed to an endotracheal one and ventilation (pressure controlled intermittent mandatory ventilation) was continued. A central arterial line and central venous catheter were placed. Blood gas analysis ▶ Fig. 1). Due to revealed respiratory and metabolic acidosis (● rather low mean arterial pressure (32 mmHg) vasopressors (noradrenalin: at maximum 0.07 μg/kg/min; dopamine: at maximum 8 μg/kg/min) were administered. The chest X-ray revealed typical signs of severe aspiration and thus confirmed the tentative diagnosis of the emergency medical service. Transthoracic echocardiography, electrocardiography and ultrasound examination of the brain were without pathological findings. Given an interval between aspiration and successful resuscitation of approximately 9 h and an accidental hypothermia at time of resuscitation mild hypothermia was continued as a measure to confer optimal neuroprotection. Cool packs underneath and on top of the patient were used to ensure a target temperature between 32.0–34.0 °C (rectal probe). Hypothermia was continued for 48 h under anesthesia with midazolam (0.1 mg/kg/h), fentanyl (1 μg/kg/h) and cisatracurium (0.1 mg/ kg/h). Antibiotic therapy was initiated and adapted according to ▶ Fig. 1). Rewarming at a rate of laboratory and clinical findings (● 0.25 °C per hour was started on day 3 and sedation was stopped at a core body temperature of 36.0 °C. At that time, thrombocytopenia together with a lengthening of bleeding time and anemia was noted. This resolved rapidly after administration of fresh frozen plasma (5 units) together with transfusion of platelet- and erythrocyte-concentrates (2 each). Whether or not this was related to therapeutic hypothermia or reflected systemic inflammatory response, probably as a combination of postresuscitation disease and aspiration-related infection remains unsolved. The patient remained on the ventilator for 9 days and completely recovered afterwards. Electroencephalogram and ultrasound examinations of the head yielded normal results. Likewise, magnetic resonance imaging of the head performed on days 3 and 32 after resuscitation revealed no signs of hypoxic ▶ Fig. 2). In particular, neither ischemic lesions brain damage (● nor edema were detectable with the corresponding modes of imaging, i. e. diffusion-weighted (DWI) and fluid attenuated inversion recovery (FLAIR). At the same time, lactate mapping ▶ Fig. 2). The patient was was without pathological findings (● discharged without neurological deficits to foster care 52 days after admission.
Warncke G et al. Therapeutic Hypothermia after Cardiopulmonary … Klin Padiatr 2014; 226: 221–224
Downloaded by: NYU. Copyrighted material.
Several reports on the strikingly normal neurological outcome of children and adults after resuscitation from cold-water drowning or severe accidental hypothermia highlight the neuroprotective potential of this apparently unphysiologic condition [6, 8, 10]. Hypothermia is recommended for adult comatose survivors of cardiac arrest [11] and available data on therapeutic hypothermia in stroke, traumatic brain injury and myocardial infarction are promising [3, 16]. However, a recent study has shown, that hypothermia (33 °C) is not superior compared to normothermia (36 °C) in adults suffering from cardiac arrest [21]. Initially encouraging data on neurological outcome after therapeutic hypothermia in perinatal asphyxia were recently confirmed by 2 randomized clinical trials [2, 9]. It has to be noted that the beneficial effects of hypothermia are intimately linked to the time of onset and duration relative to the onset of asphyxia. In newborns, hypothermia has to be initiated within 6 h after onset of asphyxia and has to be prolonged for at least 24 h [23, 24]. In contrast, current guidelines based on retrospective studies of the neurological outcome in pediatric cardiac arrest neither support nor refute therapeutic hypothermia [4, 14, 19, 22]. Retrospective evaluation of the therapeutic potential of hypothermia after pediatric cardiac arrest is mainly hampered by poor standardization. In particular, i) modalities for induction and maintenance of hypothermia, ii) the interval between resuscitation and onset of therapeutic hypothermia, iii) duration of hypothermia and iv) the mode and duration of rewarming to normothermia varied considerably. As a first step towards standardization the feasibility and efficacy of surface cooling protocols for induction and maintenance of therapeutic hypothermia after pediatric cardiac arrest were evaluated in 2 independent prospective clinical trials [5, 25]. While the feasibility and efficacy of the surface cooling protocol was demonstrated, the neurological outcome of these considerably small studies (each n = 12) did neither refute nor support hypothermia. The results of 2 multicenter trials of therapeutic hypothermia in pediatric patients with in- and outof-hospital cardiac arrest provide a better basis for recommendations [20]. However, the documentation even of single cases on therapeutic hypothermia is important. We report the feasibility, efficacy and safety of therapeutic hypothermia in an infant after successful resuscitation, which was possibly responsible for the good neurological outcome.
38.0 36.0 34.0 32.0 30.0
pH
▼
Core Temp [°C]
Introduction
Case Report 223
Discussion and review of published pediatric cases
▼
Beside a rich history for the use of hypothermia as a neuroprotective measure in pediatric intensive care, this therapy was abandoned in the mid to late 1980s. This was mainly due to poor standardization with respect to clinical indications and mode of therapy including supportive measures like ventilation, fluid restriction, and concomitant medication with steroids [15]. Current guidelines recommend induced hypothermia in newborns at risk for developing hypoxic-ischemic encephalopathy and in adults after cardiac arrest, while it is neither recommended nor refuted for children [4]. Whereas adult cardiac arrest is most frequently due to ventricular fibrillation followed by sudden global ischemia, in children except those with congenital heart disease, asphyxia with subsequent hypoxemia, bradycardia and hypotension precede cardiac arrest in the vast majority of cases (ca. 85 %) [18]. The net result is an elongated period of hypoxia with concomitant brain damage, which is aggravated further by reperfusion injury and consequently a general poor neurological outcome after cardiac arrest in infants [1, 12]. Assuming roughly the same interval between cardiac arrest and resuscitation for adults and children, the duration of preceding hypoxia with all consequences given above is most likely crucial for the prognosis, even after initiation of therapeutic hypothermia. In fact, induction of hypothermia at time of resuscitation will attenuate reperfusion injury but can hardly prevent damage due to prolonged normothermic hypoxia. Our case is exceptional in that hypoxia was paralleled by increasing hypothermia and this combination might have been crucial for the overall favorable outcome. In fact, this case fits better to data on near-drowning victims with mild incidental hypothermia [6, 10]. The latter mostly occur as a side-effect of the acci-
dent and is prolonged as a therapeutic measure, i. e. with a core target temperature between 32 and 34 °C. In contrast, data on neurological outcome and mortality after induced mild hypothermia subsequent to near drowning accidents, i. e. after hypoxia with or without global ischemia are conflicting [13]. Prolonged mild hypothermia has been accused to worsen cardiopulmonary function, coagulation and the immune system in patients with submersion injury and traumatic brain injury [7, 13, 17]. Whether or not such effects are related to mild hypothermia in patients with in- and out-of hospital cardiac arrest is still a matter of discussion [20]. Our patient required an intensified antibiotic regimen secondary to the aspiration-related infection. In addition, fresh frozen plasma and transfusion of platelet- and erythrocyte-concentrates were required after rewarming. Most likely, these events are the consequence of aspiration, hypothermia and postresuscitation disease, although it remains impossible to estimate the relative contribution of either factor. Despite the overall favorable outcome this case has to be discussed critically, since we have no information about what exactly has happened to the infant during the last 9 h between feeding and resuscitation. In summary, the preclinical accidental hypothermia, which most likely paralleled the development of hypoxia together with early resuscitation before pulseless cardiac arrest may have contributed to the favorable neurological outcome. At least hypothermia has to be considered as a safe measure in pediatric intensive care medicine.
Conflict of interest: The authors have no conflict of interest to disclose.
Warncke G et al. Therapeutic Hypothermia after Cardiopulmonary … Klin Padiatr 2014; 226: 221–224
Downloaded by: NYU. Copyrighted material.
Fig. 2 MRI a, b and single voxel-spectroscopy c, d of the head at day 3 a, c and day 32 b, d after resuscitation. Images were taken at the level of basal ganglia and revealed no signs of edema or gliosis. The small insets in c and d denote positions of the single voxel-spectroscopy. Cr1, creatine; Cr2, creatine phosphate; Cho, cholin; NAA, N-acetylaspartate specific peaks.
References 1 Atkins DL, Everson-Stewart S, Sears GK et al. Epidemiology and Outcomes from Out-of-Hospital cardiac arrest in children: The Resuscitation outcomes consortium epistry-cardiac arrest. Circulation 2009; 119: 1484–1491 2 Azzopardi DV, Strohm B, Edwards AD et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. The New England journal of medicine 2009; 361: 1349–1358 3 Bernard SA, Buist M. Induced hypothermia in critical care medicine: a review. Crit Care Med 2003; 31: 2041–2051 4 Biarent D, Bingham R, Eich C et al. European resuscitation council guidelines for resuscitation 2010 section 6. Paediatric life support. In: 2010; 1364–1388 5 Bustos R. Therapeutic hypothermia after pediatric cardiac arrest. Anales de pediatria 2012; 76: 98–102 6 Conn AW. Near-drowning and hypothermia. Can Med Assoc J 1979; 120: 397–400 7 Doherty DR, Parshuram CS, Gaboury I et al. Hypothermia therapy after pediatric cardiac arrest. Circulation 2009; 119: 1492–1500 8 Gilbert M, Busund R, Skagseth A et al. Resuscitation from accidental hypothermia of 13.7 ℃ with circulatory arrest. Lancet 2000; 355: 375–376 9 Gluckman PD, Wyatt JS, Azzopardi D et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. The Lancet 2005; 365: 663–670 10 Hein OV, Triltsch A, von Buch C et al. Mild hypothermia after near drowning in twin toddlers. Crit Care 2004; 8: R353–R357 11 Holzer M. Targeted temperature management for comatose survivors of cardiac arrest. The New England journal of medicine 2010; 363: 1256–1264 12 Hutchison JS, Doherty DR, Orlowski JP et al. Hypothermia therapy for cardiac arrest in pediatric patients. Pediatr Clin North Am 2008; 55: 529–544 13 Ibsen LM, Koch T. Submersion and asphyxial injury. Crit Care Med 2002; 30: S402–S408
14 Kessler SK, Topjian AA, Gutierrez-Colina AM et al. Short-term outcome prediction by electroencephalographic features in children treated with therapeutic hypothermia after cardiac arrest. Neurocrit Care 2011; 14: 37–43 15 Kochanek PM, Fink EL, Bell MJ et al. Therapeutic hypothermia: applications in pediatric cardiac arrest. J Neurotrauma 2009; 26: 421–427 16 Lampe JW, Becker LB. State of the art in therapeutic hypothermia. Annu Rev Med 2011; 62: 79–93 17 Lavelle JM, Shaw KN. Near drowning: is emergency department cardiopulmonary resuscitation or intensive care unit cerebral resuscitation indicated? Crit Care Med 1993; 21: 368–373 18 Manole MD, Kochanek PM, Fink EL et al. Postcardiac arrest syndrome: focus on the brain. Curr Opin Pediatr 2009; 21: 745–750 19 Moler FW, Donaldson AE, Meert K et al. Multicenter cohort study of out-of-hospital pediatric cardiac arrest. Crit Care Med 2011; 39: 141–149 20 Moler FW, Silverstein FS, Meert KL et al. Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials. Pediatr Crit Care Med 2013; 14: e304–e315 21 Nielsen N, Wetterslev J, Cronberg T et al. Targeted temperature management at 33 °C vs. 36 °C after cardiac arrest. The New England Journal of Medicine 2013; 369: 2197–2206 22 Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. The Lancet 2008; 371: 1955–1969 23 Sirimanne ES, Blumberg RM, Bossano D et al. The effect of prolonged modification of cerebral temperature on outcome after hypoxicischemic brain injury in the infant rat. Pediatr Res 1996; 39: 591–597 24 Timischl M, Simbruner G. Therapeutische Hypothermie nach Asphyxie aus neonatologischer Sicht. Intensivmedup2date 2006; 2: 245–254 25 Topjian A, Hutchins L, DiLiberto MA et al. Induction and maintenance of therapeutic hypothermia after pediatric cardiac arrest: efficacy of a surface cooling protocol. Pediatric critical care medicine: a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2011; 12: e127–e135
Warncke G et al. Therapeutic Hypothermia after Cardiopulmonary … Klin Padiatr 2014; 226: 221–224
Downloaded by: NYU. Copyrighted material.
224 Case Report
Therapeutic Hypothermia after Cardiopulmonary Resuscitation in a 4-month Infant Therapeutische Hypothermie nach kardiopulmonaler Reanimation bei einem 4 Monate alten Säugling
Affiliations
Key words ▶ therapeutic hypothermia ● ▶ pediatric cardiac arrest ● ▶ resuscitation ● ▶ infant ● Schlüsselwörter ▶ therapeutische Hypothermie ● ▶ Herz-Kreislaufstillstand im ● Kindesalter ▶ Wiederbelebung ● ▶ Säugling ●
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1375699 Klin Padiatr 2014; 226: 221–224 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Dr. Gert Warncke Children’s University Hospital Rostock Pediatric Intensive Care Unit Ernst-Heydemann-Str. 8 18057 Rostock Germany Tel.: + 49/381/494 7126 Fax: + 49/381/494 7002 [email protected]
G. Warncke1, U. N. Osmers2, C. Hauenstein3, M. Scotland1, H. von Osten1, R. Höhn1, D. C. Fischer4 1
Children’s University Hospital, Pediatric Intensive Care Unit, Rostock, Germany Department of Anaesthesiology and Intensive Care Medicine, Medical Center Südstadt, Rostock, Rostock, Germany 3 Deparment of Diagnostic and Interventional Radiography, University Hospital, Rostock, Germany 4 Children’s University Hospital, Rostock, Germany 2
Abstract
Zusammenfassung
Therapeutic hypothermia is currently recommend ed for adult comatose survivors of cardiac arrest and perinatal hypoxic-ischemic encephalopathy. By contrast, current international guidelines on cardiopulmonary resuscitation in children neither refute nor support therapeutic hypothermia. Here we report on a 4-month old infant who survived resuscitation for severe cardiopulmonary insufficiency without neurological impairments. The infant most probably experienced unwitnessed aspiration with subsequent severe cardiopulmonary insufficiency. This was paralleled by incidental hypothermia, i. e. a core body temperature of 32 °C at time of resuscitation. The infant was transported to the pediatric intensive care unit and additional to state-of the art resuscitation therapy (e. g. vasopressors, pressure controlled intermittent mandatory ventilation) therapeutic hypothermia (core body temperature 32.0–34.0 °C) was admininistered for additional 48 h to confer optimal neuroprotection. Subsequently, he was rewarmed (0.25 °C per hour) and sedation was stopped at a core body temperature of 36 °C. Chest X-ray at time of admission to the hospital revealed typical signs of severe aspiration, whereas transthoraic echocardiography, electrocardiography and ultrasound examination of the brain were without pathological findings. Likewise, magnetic resonance imaging of the head performed on days 3 and 32 after resuscitation revealed no signs of hypoxic brain damage and the child was discharged to foster care without neurological deficits 52 days after admission.
Die therapeutische Hypothermie (THT) wird bei Erwachsenen nach erfolgreicher Reanimation z. B. nach Herz-Kreislauf-Stillstand oder in der Altersgruppe der Neugeborenen bei hypoxischischämischer Enzephalopathie seit vielen Jahren erfolgreich angewendet. Im Gegensatz dazu wird die THT in den aktuellen Empfehlungen des European Resuscitation Council (ERC) zur kardiopulmonalen Reanimation für Kinder weder abgelehnt noch eindeutig empfohlen. Wir berichten über einen 4 Monate alten Säugling, der eine schwere kardiopulmonale Insuffizienz nach Reanimation ohne neurologische Beeinträchtigungen überlebte. Vermutlich durch eine Aspiration bedingt kam es in der Folge zu einer schweren Beeinträchtigung des Herz-Kreislauf-Systems sowie der Atmung. Bereits zu Beginn der Reanimation war eine akzidentelle Hypothermie mit einer Körperkerntemperatur von 32 °C nachweisbar. Der Säugling wurde auf unsere interdisziplinäre pädiatrische Intensivstation eingewiesen. Dort führten wir neben einer kreislauf- und atemstabilisierenden Therapie eine therapeutische Hypothermie (Körperkerntemperatur 32,0–34,0 °C) mit dem Ziel einer maximalen Neuroprotektion für 48 Stunden durch. Im Anschluss wurde der Patient mit 0,25 °C pro Stunde wieder erwärmt und die Sedierung bei einer Körperkerntemperatur von 36 °C beendet. Die Röntgenaufnahme des Thorax wies das typische Bild einer schweren Aspiration auf, wohingegen Echokardiografie, EKG, Sonografie des ZNS keine pathologischen Befunde auswiesen. In der an Tag 3 und 32 nach Reanimation durchgeführten kernspintomografischen Untersuchung waren keine hypoxischen Hirnschäden nachweisbar. Der Säugling wurde 52 Tage nach dem Ereignis ohne neurologische Defizite in eine Pflege entlassen.
▼
▼
Warncke G et al. Therapeutic Hypothermia after Cardiopulmonary … Klin Padiatr 2014; 226: 221–224
Downloaded by: NYU. Copyrighted material.
Authors
222 Case Report
Case report
▼
A 4-months old boy laying pulseless and apneic in his bed was found early in the morning by his 8-year old sister. The emergency medical service arrived 10 min later and diagnosed cardiopulmonary insufficiency (breathing frequency: 30/min, bradycardia of 40/min, undetectable blood pressure), a GlasgowComa Scale score of 8, cyanosis and hypothermia (32 °C, ear probe). Remnants of milk periorally, on his clothes, and in his bed point to severe aspiration, although no such event was noticed by the parents at the time of last control approximately 9 h before. Cardiopulmonary resuscitation was initiated, i. e. chest compression, a laryngeal tube was placed and 0.02 mg adrenaline as well as a complete electrolyte solution (E153) were administered via a peripheral line. The baby recovered (heart rate: 115/min, oxygen saturation of 90–94 % at 100 % oxy-
7.5 7.0 6.5 0
24
48
72
96
120
144
168
192
216
Time [h]
Fig. 1 Core temperature (left axis) and pH (right axis); findings at admission to the PICU, onset of therapeutic hypothermia and rewarming are indicated.
gen via laryngeal tube) within 2 min. He was wrapped in aluminum foil to prevent aggravation of hypothermia and transported to the pediatric intensive care unit (PICU). During transport, the boy experienced one convulsive seizure which persisted after intravenous clonazepame (0.2 mg/kg) administration. The patient arrived at the PICU 30 min after initiation of cardiopulmonary resuscitation. At that time his temperature was 30.8 °C (rectal probe). The laryngeal tube was changed to an endotracheal one and ventilation (pressure controlled intermittent mandatory ventilation) was continued. A central arterial line and central venous catheter were placed. Blood gas analysis ▶ Fig. 1). Due to revealed respiratory and metabolic acidosis (● rather low mean arterial pressure (32 mmHg) vasopressors (noradrenalin: at maximum 0.07 μg/kg/min; dopamine: at maximum 8 μg/kg/min) were administered. The chest X-ray revealed typical signs of severe aspiration and thus confirmed the tentative diagnosis of the emergency medical service. Transthoracic echocardiography, electrocardiography and ultrasound examination of the brain were without pathological findings. Given an interval between aspiration and successful resuscitation of approximately 9 h and an accidental hypothermia at time of resuscitation mild hypothermia was continued as a measure to confer optimal neuroprotection. Cool packs underneath and on top of the patient were used to ensure a target temperature between 32.0–34.0 °C (rectal probe). Hypothermia was continued for 48 h under anesthesia with midazolam (0.1 mg/kg/h), fentanyl (1 μg/kg/h) and cisatracurium (0.1 mg/ kg/h). Antibiotic therapy was initiated and adapted according to ▶ Fig. 1). Rewarming at a rate of laboratory and clinical findings (● 0.25 °C per hour was started on day 3 and sedation was stopped at a core body temperature of 36.0 °C. At that time, thrombocytopenia together with a lengthening of bleeding time and anemia was noted. This resolved rapidly after administration of fresh frozen plasma (5 units) together with transfusion of platelet- and erythrocyte-concentrates (2 each). Whether or not this was related to therapeutic hypothermia or reflected systemic inflammatory response, probably as a combination of postresuscitation disease and aspiration-related infection remains unsolved. The patient remained on the ventilator for 9 days and completely recovered afterwards. Electroencephalogram and ultrasound examinations of the head yielded normal results. Likewise, magnetic resonance imaging of the head performed on days 3 and 32 after resuscitation revealed no signs of hypoxic ▶ Fig. 2). In particular, neither ischemic lesions brain damage (● nor edema were detectable with the corresponding modes of imaging, i. e. diffusion-weighted (DWI) and fluid attenuated inversion recovery (FLAIR). At the same time, lactate mapping ▶ Fig. 2). The patient was was without pathological findings (● discharged without neurological deficits to foster care 52 days after admission.
Warncke G et al. Therapeutic Hypothermia after Cardiopulmonary … Klin Padiatr 2014; 226: 221–224
Downloaded by: NYU. Copyrighted material.
Several reports on the strikingly normal neurological outcome of children and adults after resuscitation from cold-water drowning or severe accidental hypothermia highlight the neuroprotective potential of this apparently unphysiologic condition [6, 8, 10]. Hypothermia is recommended for adult comatose survivors of cardiac arrest [11] and available data on therapeutic hypothermia in stroke, traumatic brain injury and myocardial infarction are promising [3, 16]. However, a recent study has shown, that hypothermia (33 °C) is not superior compared to normothermia (36 °C) in adults suffering from cardiac arrest [21]. Initially encouraging data on neurological outcome after therapeutic hypothermia in perinatal asphyxia were recently confirmed by 2 randomized clinical trials [2, 9]. It has to be noted that the beneficial effects of hypothermia are intimately linked to the time of onset and duration relative to the onset of asphyxia. In newborns, hypothermia has to be initiated within 6 h after onset of asphyxia and has to be prolonged for at least 24 h [23, 24]. In contrast, current guidelines based on retrospective studies of the neurological outcome in pediatric cardiac arrest neither support nor refute therapeutic hypothermia [4, 14, 19, 22]. Retrospective evaluation of the therapeutic potential of hypothermia after pediatric cardiac arrest is mainly hampered by poor standardization. In particular, i) modalities for induction and maintenance of hypothermia, ii) the interval between resuscitation and onset of therapeutic hypothermia, iii) duration of hypothermia and iv) the mode and duration of rewarming to normothermia varied considerably. As a first step towards standardization the feasibility and efficacy of surface cooling protocols for induction and maintenance of therapeutic hypothermia after pediatric cardiac arrest were evaluated in 2 independent prospective clinical trials [5, 25]. While the feasibility and efficacy of the surface cooling protocol was demonstrated, the neurological outcome of these considerably small studies (each n = 12) did neither refute nor support hypothermia. The results of 2 multicenter trials of therapeutic hypothermia in pediatric patients with in- and outof-hospital cardiac arrest provide a better basis for recommendations [20]. However, the documentation even of single cases on therapeutic hypothermia is important. We report the feasibility, efficacy and safety of therapeutic hypothermia in an infant after successful resuscitation, which was possibly responsible for the good neurological outcome.
38.0 36.0 34.0 32.0 30.0
pH
▼
Core Temp [°C]
Introduction
Case Report 223
Discussion and review of published pediatric cases
▼
Beside a rich history for the use of hypothermia as a neuroprotective measure in pediatric intensive care, this therapy was abandoned in the mid to late 1980s. This was mainly due to poor standardization with respect to clinical indications and mode of therapy including supportive measures like ventilation, fluid restriction, and concomitant medication with steroids [15]. Current guidelines recommend induced hypothermia in newborns at risk for developing hypoxic-ischemic encephalopathy and in adults after cardiac arrest, while it is neither recommended nor refuted for children [4]. Whereas adult cardiac arrest is most frequently due to ventricular fibrillation followed by sudden global ischemia, in children except those with congenital heart disease, asphyxia with subsequent hypoxemia, bradycardia and hypotension precede cardiac arrest in the vast majority of cases (ca. 85 %) [18]. The net result is an elongated period of hypoxia with concomitant brain damage, which is aggravated further by reperfusion injury and consequently a general poor neurological outcome after cardiac arrest in infants [1, 12]. Assuming roughly the same interval between cardiac arrest and resuscitation for adults and children, the duration of preceding hypoxia with all consequences given above is most likely crucial for the prognosis, even after initiation of therapeutic hypothermia. In fact, induction of hypothermia at time of resuscitation will attenuate reperfusion injury but can hardly prevent damage due to prolonged normothermic hypoxia. Our case is exceptional in that hypoxia was paralleled by increasing hypothermia and this combination might have been crucial for the overall favorable outcome. In fact, this case fits better to data on near-drowning victims with mild incidental hypothermia [6, 10]. The latter mostly occur as a side-effect of the acci-
dent and is prolonged as a therapeutic measure, i. e. with a core target temperature between 32 and 34 °C. In contrast, data on neurological outcome and mortality after induced mild hypothermia subsequent to near drowning accidents, i. e. after hypoxia with or without global ischemia are conflicting [13]. Prolonged mild hypothermia has been accused to worsen cardiopulmonary function, coagulation and the immune system in patients with submersion injury and traumatic brain injury [7, 13, 17]. Whether or not such effects are related to mild hypothermia in patients with in- and out-of hospital cardiac arrest is still a matter of discussion [20]. Our patient required an intensified antibiotic regimen secondary to the aspiration-related infection. In addition, fresh frozen plasma and transfusion of platelet- and erythrocyte-concentrates were required after rewarming. Most likely, these events are the consequence of aspiration, hypothermia and postresuscitation disease, although it remains impossible to estimate the relative contribution of either factor. Despite the overall favorable outcome this case has to be discussed critically, since we have no information about what exactly has happened to the infant during the last 9 h between feeding and resuscitation. In summary, the preclinical accidental hypothermia, which most likely paralleled the development of hypoxia together with early resuscitation before pulseless cardiac arrest may have contributed to the favorable neurological outcome. At least hypothermia has to be considered as a safe measure in pediatric intensive care medicine.
Conflict of interest: The authors have no conflict of interest to disclose.
Warncke G et al. Therapeutic Hypothermia after Cardiopulmonary … Klin Padiatr 2014; 226: 221–224
Downloaded by: NYU. Copyrighted material.
Fig. 2 MRI a, b and single voxel-spectroscopy c, d of the head at day 3 a, c and day 32 b, d after resuscitation. Images were taken at the level of basal ganglia and revealed no signs of edema or gliosis. The small insets in c and d denote positions of the single voxel-spectroscopy. Cr1, creatine; Cr2, creatine phosphate; Cho, cholin; NAA, N-acetylaspartate specific peaks.
References 1 Atkins DL, Everson-Stewart S, Sears GK et al. Epidemiology and Outcomes from Out-of-Hospital cardiac arrest in children: The Resuscitation outcomes consortium epistry-cardiac arrest. Circulation 2009; 119: 1484–1491 2 Azzopardi DV, Strohm B, Edwards AD et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. The New England journal of medicine 2009; 361: 1349–1358 3 Bernard SA, Buist M. Induced hypothermia in critical care medicine: a review. Crit Care Med 2003; 31: 2041–2051 4 Biarent D, Bingham R, Eich C et al. European resuscitation council guidelines for resuscitation 2010 section 6. Paediatric life support. In: 2010; 1364–1388 5 Bustos R. Therapeutic hypothermia after pediatric cardiac arrest. Anales de pediatria 2012; 76: 98–102 6 Conn AW. Near-drowning and hypothermia. Can Med Assoc J 1979; 120: 397–400 7 Doherty DR, Parshuram CS, Gaboury I et al. Hypothermia therapy after pediatric cardiac arrest. Circulation 2009; 119: 1492–1500 8 Gilbert M, Busund R, Skagseth A et al. Resuscitation from accidental hypothermia of 13.7 ℃ with circulatory arrest. Lancet 2000; 355: 375–376 9 Gluckman PD, Wyatt JS, Azzopardi D et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. The Lancet 2005; 365: 663–670 10 Hein OV, Triltsch A, von Buch C et al. Mild hypothermia after near drowning in twin toddlers. Crit Care 2004; 8: R353–R357 11 Holzer M. Targeted temperature management for comatose survivors of cardiac arrest. The New England journal of medicine 2010; 363: 1256–1264 12 Hutchison JS, Doherty DR, Orlowski JP et al. Hypothermia therapy for cardiac arrest in pediatric patients. Pediatr Clin North Am 2008; 55: 529–544 13 Ibsen LM, Koch T. Submersion and asphyxial injury. Crit Care Med 2002; 30: S402–S408
14 Kessler SK, Topjian AA, Gutierrez-Colina AM et al. Short-term outcome prediction by electroencephalographic features in children treated with therapeutic hypothermia after cardiac arrest. Neurocrit Care 2011; 14: 37–43 15 Kochanek PM, Fink EL, Bell MJ et al. Therapeutic hypothermia: applications in pediatric cardiac arrest. J Neurotrauma 2009; 26: 421–427 16 Lampe JW, Becker LB. State of the art in therapeutic hypothermia. Annu Rev Med 2011; 62: 79–93 17 Lavelle JM, Shaw KN. Near drowning: is emergency department cardiopulmonary resuscitation or intensive care unit cerebral resuscitation indicated? Crit Care Med 1993; 21: 368–373 18 Manole MD, Kochanek PM, Fink EL et al. Postcardiac arrest syndrome: focus on the brain. Curr Opin Pediatr 2009; 21: 745–750 19 Moler FW, Donaldson AE, Meert K et al. Multicenter cohort study of out-of-hospital pediatric cardiac arrest. Crit Care Med 2011; 39: 141–149 20 Moler FW, Silverstein FS, Meert KL et al. Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials. Pediatr Crit Care Med 2013; 14: e304–e315 21 Nielsen N, Wetterslev J, Cronberg T et al. Targeted temperature management at 33 °C vs. 36 °C after cardiac arrest. The New England Journal of Medicine 2013; 369: 2197–2206 22 Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. The Lancet 2008; 371: 1955–1969 23 Sirimanne ES, Blumberg RM, Bossano D et al. The effect of prolonged modification of cerebral temperature on outcome after hypoxicischemic brain injury in the infant rat. Pediatr Res 1996; 39: 591–597 24 Timischl M, Simbruner G. Therapeutische Hypothermie nach Asphyxie aus neonatologischer Sicht. Intensivmedup2date 2006; 2: 245–254 25 Topjian A, Hutchins L, DiLiberto MA et al. Induction and maintenance of therapeutic hypothermia after pediatric cardiac arrest: efficacy of a surface cooling protocol. Pediatric critical care medicine: a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2011; 12: e127–e135
Warncke G et al. Therapeutic Hypothermia after Cardiopulmonary … Klin Padiatr 2014; 226: 221–224
Downloaded by: NYU. Copyrighted material.
224 Case Report
![[Mild therapeutic hypothermia: Improved survival after resuscitation].](/assets/img/hold.png)
