open access
Is there a role for phenobarbital in palliative care: A systematic review
Affiliations- Baycrest Health Sciences, 3560 Bathurst Street, M6A 2E1 Toronto, Canada
- Trinity College Dublin, Ireland
open access
Abstract
Introduction: Seizures are seen in 13% of cases in palliative care. Phenobarbital is a drug from the barbiturates’ family most used for its anticonvulsant and sedative properties, and therefore the drug of choice in palliative care suitable for the management of seizures and agitation. The study aimed to evaluate the role of phenobarbital in palliative care settings.
Methods: A systematic literature review was conducted using predetermined keywords. Data was compiled and inclusion and exclusion criteria were established concerning the role of phenobarbital in palliative care. Five case studies met these criteria and were evaluated. Retrospective analysis of the data in the studies, along with randomized clinical trial about the use of at the end of life were reviewed by two independent reviewers.
Results: Results of this review showed that phenobarbital is efficacious in the management of seizures and agitation, can be easily administered via different routes and utilized in various palliative care settings. No serious adverse skin reactions were noted with the use of phenobarbital and it did not abruptly end a patient’s life when used at appropriate doses.
Conclusions: Although phenobarbital is an old drug and is an approved anticonvulsant, its sedating properties make it to be useful not only for seizure management, but also in patients experiencing agitation, physical and psychological distress, and restlessness. More studies are warranted in the sole practice of using phenobarbital and further explore its role in palliative care.
Abstract
Introduction: Seizures are seen in 13% of cases in palliative care. Phenobarbital is a drug from the barbiturates’ family most used for its anticonvulsant and sedative properties, and therefore the drug of choice in palliative care suitable for the management of seizures and agitation. The study aimed to evaluate the role of phenobarbital in palliative care settings.
Methods: A systematic literature review was conducted using predetermined keywords. Data was compiled and inclusion and exclusion criteria were established concerning the role of phenobarbital in palliative care. Five case studies met these criteria and were evaluated. Retrospective analysis of the data in the studies, along with randomized clinical trial about the use of at the end of life were reviewed by two independent reviewers.
Results: Results of this review showed that phenobarbital is efficacious in the management of seizures and agitation, can be easily administered via different routes and utilized in various palliative care settings. No serious adverse skin reactions were noted with the use of phenobarbital and it did not abruptly end a patient’s life when used at appropriate doses.
Conclusions: Although phenobarbital is an old drug and is an approved anticonvulsant, its sedating properties make it to be useful not only for seizure management, but also in patients experiencing agitation, physical and psychological distress, and restlessness. More studies are warranted in the sole practice of using phenobarbital and further explore its role in palliative care.
Keywords
phenobarbital, barbiturate, palliative care, seizure, end of life
About this articleTitle
Is there a role for phenobarbital in palliative care: A systematic review
Journal
Palliative Medicine in Practice
Issue
Article type
Review paper
Pages
163-171
Published online
2021-04-16
Page views
3172
Article views/downloads
999
DOI
Bibliographic record
Palliat Med Pract 2021;15(2):163-171.
Keywords
phenobarbital
barbiturate
palliative care
seizure
end of life
Authors
Helen Senderovich
Sarah Waicus
References (22)- Stirling LC, Kurowska A, Tookman A, et al. The use of phenobarbitone in the management of agitation and seizures at the end of life. J Pain Symptom Manage. 1999; 17(5): 363–368.
- Tradounsky G. Seizures in palliative care. Can Fam Physician. 2013; 59(9): 951–5, e401.
- Lam YW, Lam A, Macy B, et al. Pharmacokinetics of Phenobarbital in Microenema Via Macy Catheter Versus Suppository. J Pain Symptom Manage. 2016; 51(6): 994–1001.
- Sykes N, Thorns A. Sedative use in the last week of life and the implications for end-of-life decision making. Arch Intern Med. 2003; 163(3): 341–344.
- Yasiry Z, Shorvon SD. How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years. Epilepsia. 2012; 53 Suppl 8: 26–39.
- Pompili A, Telera S, Villani V, et al. Home palliative care and end of life issues in glioblastoma multiforme: results and comments from a homogeneous cohort of patients. Neurosurg Focus. 2014; 37(6): E5.
- Hosgood JR, Kimbrel JM, McCrate Protus B, et al. Evaluation of Subcutaneous Phenobarbital Administration in Hospice Patients. Am J Hosp Palliat Care. 2016; 33(3): 209–213.
- Griebling TL, Kachru N, Carnahan RM, et al. By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel, By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2015; 63(11): 2227–2246.
- Waller DG, Sampson AP. Pharmacol Ther. 2018: 311–323.
- Kale R, Perucca E. Revisiting phenobarbital for epilepsy. BMJ. 2004; 329(7476): 1199–1200.
- Czekaj P. Phenobarbital–induced expression of cytochrome P450 genes. Acta Biochim Pol. 2000; 47 (4): 1093–1105. PMID. ; 11996099.
- Brodie MJ, Mintzer S, Pack AM, et al. Enzyme induction with antiepileptic drugs: cause for concern? Epilepsia. 2013; 54(1): 11–27.
- Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2006; 61(3): 246–255.
- Tradounsky G. Seizures in palliative care. Can Fam Physician. 2013; 59(9): 951–5, e401.
- Grönheit W, Popkirov S, Wehner T, et al. Practical Management of Epileptic Seizures and Status Epilepticus in Adult Palliative Care Patients. Front Neurol. 2018; 9: 595.
- Anderson CM, Norquist BA, Vesce S, et al. Barbiturates induce mitochondrial depolarization and potentiate excitotoxic neuronal death. J Neurosci. 2002; 22(21): 9203–9209.
- Olszewska A, Szewczyk A. Mitochondria as a pharmacological target: magnum overview. IUBMB Life. 2013; 65(3): 273–281.
- Wen X, Wang JS, Kivistö KT, et al. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). Br J Clin Pharmacol. 2001; 52(5): 547–553.
- Favié LMA, Groenendaal F, van den Broek MPH, et al. on behalf of the PharmaCool study group. Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia. Neonatology. 2019; 116(2): 154–162.
- Bush SH, Tierney S, Lawlor PG. Clinical Assessment and Management of Delirium in the Palliative Care Setting. Drugs. 2017; 77(15): 1623–1643.
- Bartz L, Klein C, Seifert A, et al. Subcutaneous administration of drugs in palliative care: results of a systematic observational study. J Pain Symptom Manage. 2014; 48(4): 540–547.
- Cheng C, Roemer-Becuwe C, Pereira J. When midazolam fails. J Pain Symptom Manage. 2002; 23(3): 256–265.
