Skip to main content
Erschienen in: European Journal of Pediatrics 4/2021

10.11.2020 | Original Article

Efficacy of Citicoline as a Neuroprotector in children with post cardiac arrest: a randomized controlled clinical trial

verfasst von: Abeer Salamah, Mostafa Mehrez, Amany Faheem, Doaa El Amrousy

Erschienen in: European Journal of Pediatrics | Ausgabe 4/2021

Einloggen, um Zugang zu erhalten

Abstract

Brain hypoxia after cardiac arrest leads to damage of the neuronal cell membrane. Citicoline is necessary for the synthesis of cell membrane. We planned to assess the neuroprotective effect of citicoline in children after cardiac arrest. This randomized controlled trial was carried out at pediatric intensive care units (PICU) and surgical ICU at Tanta university hospital on 80 consecutive children surviving in-hospital cardiac arrest who were subdivided into two groups. Group I (citicoline group) included 40 children with post-cardiac arrest who received citicoline 10 mg /kg /12 h IV for 6 weeks plus other supportive measures and group II (control group) included 40 children with post-cardiac arrest who were managed with only supportive measures. All patients were evaluated for Glasgow coma score (GCS), modified Rankin scale (mRS) for children, seizures frequency, type and duration, and serum neuron-specific enolase (NSE) before and 3 months after the treatment. GCS and mRS significantly improved in citicholine group compared to the control group. Seizure frequency and duration, mortality, PICU and hospital stay significantly decreased in citicholine group compared to the control group. Serum NSE levels significantly decreased in citicholine group only. No side effects were recorded.
Conclusion: Citicoline is a promising neuroprotective drug in children with post-cardiac arrest.
Trial Registration: The study was registered at Pan African Clinical Trials Registry (PACTR) www.​pactr.​samrc.​ac.​za with trial number PACTR201907742119058.
What is known?
• Post-resuscitation brain injury is one of the major complications that can lead to death or disability.
• CDP-choline has been studied for acute ischemic stroke in several adult studies because of its reparative effect.
What is new?
• Our study was the first in pediatrics that assessed the neuroprotective effect of CDP-choline on the brain in children after cardiac arrest.
• We found that Citicoline is a promising neuroprotective drug in children with post-cardiac arrest.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Nichol G, Thomas E, Callaway CW, Hedges J, Powell JL, Aufderheide TA, Rea T, Lowe R, Brown T, Dreyer J et al (2008) Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 300:1423–1431CrossRef Nichol G, Thomas E, Callaway CW, Hedges J, Powell JL, Aufderheide TA, Rea T, Lowe R, Brown T, Dreyer J et al (2008) Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 300:1423–1431CrossRef
2.
Zurück zum Zitat Busl K, Greer DM (2010) Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms. Neurohabilitation 26(1):5–13CrossRef Busl K, Greer DM (2010) Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms. Neurohabilitation 26(1):5–13CrossRef
3.
Zurück zum Zitat Agrawal S, Branco RG (2015) Neuroprotective measures in children with traumatic brain injury. World J Crit Care Med 5(1):36–46CrossRef Agrawal S, Branco RG (2015) Neuroprotective measures in children with traumatic brain injury. World J Crit Care Med 5(1):36–46CrossRef
4.
Zurück zum Zitat Sekhon MS, Ainslie PN, Griesdale DE (2017) Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a “two-hit” model. Crit Care 21:90CrossRef Sekhon MS, Ainslie PN, Griesdale DE (2017) Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a “two-hit” model. Crit Care 21:90CrossRef
5.
Zurück zum Zitat Hurtado O, Cárdenas A, Pradillo JM, Morales JR, Ortego F, Sobrino T, Castillo J, Moro MA, Lizasoain I (2007) A chronic treatment with CDP-choline improves functional recovery and increases neuronal plasticity after experimental stroke. Neurobiol Dis 26:105–111CrossRef Hurtado O, Cárdenas A, Pradillo JM, Morales JR, Ortego F, Sobrino T, Castillo J, Moro MA, Lizasoain I (2007) A chronic treatment with CDP-choline improves functional recovery and increases neuronal plasticity after experimental stroke. Neurobiol Dis 26:105–111CrossRef
6.
Zurück zum Zitat Adibhatla RM, Hatcher JF, Dempsey RJ (2001) Effects of citicholine on phospholipid and glutathione levels in transient cerebral ischemia. Stroke 32(10):2376–2381CrossRef Adibhatla RM, Hatcher JF, Dempsey RJ (2001) Effects of citicholine on phospholipid and glutathione levels in transient cerebral ischemia. Stroke 32(10):2376–2381CrossRef
7.
Zurück zum Zitat Secades JJ, Lorenzo JL (2006) Citicoline: pharmacological and clinical review. Clin Pharmacol 28:1–56 Secades JJ, Lorenzo JL (2006) Citicoline: pharmacological and clinical review. Clin Pharmacol 28:1–56
8.
Zurück zum Zitat García-Cobos R, Frank-Garcia A, Gutiérrez-Fernández M, Díez-Tejedor E (2010) Citicoline, use in cognitive decline: vascular and degenerative. J Neurol Sci 299:188–192CrossRef García-Cobos R, Frank-Garcia A, Gutiérrez-Fernández M, Díez-Tejedor E (2010) Citicoline, use in cognitive decline: vascular and degenerative. J Neurol Sci 299:188–192CrossRef
9.
Zurück zum Zitat Álvarez-Sabín J, Román GC (2013) The role of citicholine in neuroprotection and neurorepair in ischemic stroke. Brain Sci 3(3):1395–1414CrossRef Álvarez-Sabín J, Román GC (2013) The role of citicholine in neuroprotection and neurorepair in ischemic stroke. Brain Sci 3(3):1395–1414CrossRef
10.
Zurück zum Zitat Duff JP, Topjian A, Berg MD, Chan M, Haskell SE, JoynerJr BL, Lasa JJ, Ley SJ, Raymond TT, Sutton RM et al (2018) 2018 American heart association focused update on pediatric advanced life support: an update to the American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 138:e731–e739CrossRef Duff JP, Topjian A, Berg MD, Chan M, Haskell SE, JoynerJr BL, Lasa JJ, Ley SJ, Raymond TT, Sutton RM et al (2018) 2018 American heart association focused update on pediatric advanced life support: an update to the American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 138:e731–e739CrossRef
11.
Zurück zum Zitat SavioK PGLD, Oddone E, Reggiani M, Leone MA (2013) Reliability of the modified Rankin scale applied by telephone. Neurol Int 5(1):e2CrossRef SavioK PGLD, Oddone E, Reggiani M, Leone MA (2013) Reliability of the modified Rankin scale applied by telephone. Neurol Int 5(1):e2CrossRef
12.
Zurück zum Zitat Wang JN, Wu JN, Chen YJ (2001) Validity of the updated pediatric risk of mortality score (PRISM III) in predicting the probability of mortality in a pediatric intensive care unit. Acta Paediatr Taiwan 42(6):333–337PubMed Wang JN, Wu JN, Chen YJ (2001) Validity of the updated pediatric risk of mortality score (PRISM III) in predicting the probability of mortality in a pediatric intensive care unit. Acta Paediatr Taiwan 42(6):333–337PubMed
13.
Zurück zum Zitat Grieb P (2014) Neuroprotective properties of citicholine: facts, doubts and unresolved issues. CNS Drugs 28:185–193CrossRef Grieb P (2014) Neuroprotective properties of citicholine: facts, doubts and unresolved issues. CNS Drugs 28:185–193CrossRef
14.
Zurück zum Zitat Rech TH, Vieira SR, Nagel F, Brauner JS, Scalco R (2006) Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest: a cohort study. Crit Care 10(5):R133CrossRef Rech TH, Vieira SR, Nagel F, Brauner JS, Scalco R (2006) Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest: a cohort study. Crit Care 10(5):R133CrossRef
15.
Zurück zum Zitat Pfeifer R, Borner A, Krack A, Sigusch HH, Surber R, Figulla HR (2005) Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow coma scale. Resuscitation 65:49–55CrossRef Pfeifer R, Borner A, Krack A, Sigusch HH, Surber R, Figulla HR (2005) Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow coma scale. Resuscitation 65:49–55CrossRef
16.
Zurück zum Zitat Fiedorowicz M1, Makarewicz D, Stańczak-Mrozek KI, Grieb P (2008) CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia. Acta Neurobiol Exp (Wars) 68(3):389–397 Fiedorowicz M1, Makarewicz D, Stańczak-Mrozek KI, Grieb P (2008) CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia. Acta Neurobiol Exp (Wars) 68(3):389–397
17.
Zurück zum Zitat Álvarez-Sabín J, Ortega G, Jacas C, Santamarina E, Maisterra O, Ribo M, Molina C, Quintana M, Román GC (2013) Long-term treatment with citicoline may improve post-stroke vascular cognitive impairment. Cerebrovasc Dis 35:146–154CrossRef Álvarez-Sabín J, Ortega G, Jacas C, Santamarina E, Maisterra O, Ribo M, Molina C, Quintana M, Román GC (2013) Long-term treatment with citicoline may improve post-stroke vascular cognitive impairment. Cerebrovasc Dis 35:146–154CrossRef
18.
Zurück zum Zitat Tazaki Y, Sakai F, Otomo E, Kutsuzawa T, Kameyama M, Omae T, Fujishima M, Sakuma A (1988) Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke 19(2):211–216CrossRef Tazaki Y, Sakai F, Otomo E, Kutsuzawa T, Kameyama M, Omae T, Fujishima M, Sakuma A (1988) Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke 19(2):211–216CrossRef
19.
Zurück zum Zitat Clark WM, Warach SJ, Pettigrew LC, Gammans RE, Sabounjian LA (1997) A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline stroke study group. Neurology. 49(3):671–678CrossRef Clark WM, Warach SJ, Pettigrew LC, Gammans RE, Sabounjian LA (1997) A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline stroke study group. Neurology. 49(3):671–678CrossRef
20.
Zurück zum Zitat Hurtado O, Moro MA, Cárdenas A, Sánchez V, Fernández-Tomé P, Leza JC, Lorenzo P, Secades JJ, Lozano R, Dávalos A, Castillo J, Lizasoain I (2005) Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis 18:336–345CrossRef Hurtado O, Moro MA, Cárdenas A, Sánchez V, Fernández-Tomé P, Leza JC, Lorenzo P, Secades JJ, Lozano R, Dávalos A, Castillo J, Lizasoain I (2005) Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis 18:336–345CrossRef
21.
Zurück zum Zitat Sahota P, Savitz SI (2011) Investigational therapies for ischemic stroke: Neuroprotection and neurorecovery. Neurotherapeutics 8:434–451CrossRef Sahota P, Savitz SI (2011) Investigational therapies for ischemic stroke: Neuroprotection and neurorecovery. Neurotherapeutics 8:434–451CrossRef
22.
Zurück zum Zitat Kim KS, Suh GJ, Kwon WY, Lee HJ, Jeong KY, Jung SK, Kwak YH (2013) The effect of glutamine on cerebral ischaemic injury after cardiac arrest. Resuscitation 84(9):1285–1290CrossRef Kim KS, Suh GJ, Kwon WY, Lee HJ, Jeong KY, Jung SK, Kwak YH (2013) The effect of glutamine on cerebral ischaemic injury after cardiac arrest. Resuscitation 84(9):1285–1290CrossRef
23.
Zurück zum Zitat Kohnke R, Mei J, Park M, York DA, Erlanson-Albertsson C (2007) Fatty acids and glucose in high concentration down-regulates ATP synthase beta-subunit protein expression in INS-1 cells. Nutr Neurosci 10:273–278CrossRef Kohnke R, Mei J, Park M, York DA, Erlanson-Albertsson C (2007) Fatty acids and glucose in high concentration down-regulates ATP synthase beta-subunit protein expression in INS-1 cells. Nutr Neurosci 10:273–278CrossRef
24.
Zurück zum Zitat Secadesm JJ, Lorenzo JL (2006) Citicoline: pharmacological and clinical review. Clin Pharmacol 28:1–56 Secadesm JJ, Lorenzo JL (2006) Citicoline: pharmacological and clinical review. Clin Pharmacol 28:1–56
Metadaten
Titel
Efficacy of Citicoline as a Neuroprotector in children with post cardiac arrest: a randomized controlled clinical trial
verfasst von
Abeer Salamah
Mostafa Mehrez
Amany Faheem
Doaa El Amrousy
Publikationsdatum
10.11.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Pediatrics / Ausgabe 4/2021
Print ISSN: 0340-6199
Elektronische ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-020-03871-6

Weitere Artikel der Ausgabe 4/2021

European Journal of Pediatrics 4/2021 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.