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Blog articles are provided as informational purposes only and are not intended to constitute medical advice. Medication protocols are subject to patient’s medical provider’s authorization.

 

Benzodiazepines are used for a variety of indications in the hospice setting, including insomnia, breathlessness, agitation, seizures, nausea/vomiting, myoclonus, and palliative sedation (see details outlined below).

Although they share many class effects, unique properties of individual benzodiazepines have clinical implications. For example, benzodiazepines can be classified based on their half-life (short, intermediate, and long). The benzodiazepine with the shortest half-life is triazolam. The longest is diazepam. The terminal half-life may be affected by liver or kidney dysfunction, age, drug-drug interactions, gender, race, or even route of administration. For example, the half-life of diazepam may be up to 174 hours when administered intramuscularly.

The side effect profile of benzodiazepines is similar, varying slightly among different agents. Some of the most common include: CNS depressant effects (altered mental status, anterograde amnesia, paradoxical reactions), gastrointestinal (constipation, appetite changes), genitourinary (urinary retention), cardiovascular (hypotension), and ophthalmic (visual disturbance).

Older adults have increased sensitivity to benzodiazepines and decreased metabolism of long-acting agents, and thus adverse effects may be more pronounced. The American Geriatrics Society (AGS) Beers Criteria recommends the use of short-acting benzodiazepines in appropriate circumstances.  Short-acting agents (classified by AGS) are alprazolam, estazolam, lorazepam, oxazepam, temazepam, and triazolam. The “L.O.T.” benzodiazepines are lorazepam, oxazepam, and temazepam. They are metabolized by direct, rapid conjugation in the liver, a process that is not altered in the setting of liver disease, so they do not produce active metabolites. Thus, “L.O.T” benzodiazepines may be considered lower risk than others for accumulation and related side effects.

Insomnia

  • It is recommended to use a short-acting benzodiazepine for patients with difficulty falling asleep, such as triazolam.
  • For patients with trouble maintaining sleep, consider a benzodiazepine with a longer half-life, such as temazepam.

 Breathlessness

  • Benzodiazepines actually have no effect on respiration at normal doses.
    • Slight depression of ventilation at higher doses
  • Relief comes from anxiolytic effects (reserve for breathlessness caused by anxiety/fear).
  • Consider as 2nd or 3rd line agent after opioids and non-pharmacological treatment options.

 Agitation

  • They only have sedative effects when used alone in a patient with psychosis (do not have anti-psychotic properties by themselves).

 Seizures

  • First-line agents include, midazolam IM, lorazepam IV, or diazepam IV.
  • In the home setting, or where parenteral therapy is not feasible, consider lorazepam PO/SL/PR, diazepam PO/SL/PR, or midazolam intranasally.
  • For seizure maintenance therapy, lorazepam, diazepam, or clonazepam may be given routinely.

 Myoclonus

  • Benzodiazepines can be considered for treatment of opioid-induced myoclonus.
  • Diazepam, clonazepam, or lorazepam are typically used.

 Nausea/Vomiting

  • Proven effective as an adjunct for chemotherapy induced nausea/ vomiting (CINV) and anticipatory nausea/ vomiting (ANV).
  • Relief mainly comes from anxiolytic effects (reserve for nausea /vomiting caused by anxiety/fear).
  • Lorazepam is most commonly used.

 Palliative Sedation

  • Midazolam rapidly penetrates the CNS and can be given as an IV or sub-cut infusion.
  • Use of midazolam in this setting should be done in close consult with or by an experienced palliative care provider.

 Other Uses for Benzodiazepines at End-of-Life

  • Hiccups
  • Restless leg syndrome
  • Essential tremor

Benzodiazepines are useful in the management of various symptoms encountered in hospice and palliative care. Knowledge of the pharmacology of these medications will aid in choosing the most effective and safest agent.

 

Written by: Shaun Gutstein, Pharm.D.

 

 Reference

  1. 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): 2227-46.
  2. Benzodiazepine Comparison Table. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. New York, NY. Available at: http://online.lexi.com. Accessed June 22, 2019.
  3. Berger MJ, Ettinger DS, Aston J, et. al. NCCN Guidelines Insights: Antiemesis, Version 2.2017. J Natl Compr Canc Netw. 2017; 15(7): 883-893.
  4. Buysse DJ. Insomnia. JAMA. 2013; 309(7): 706-16.
  5. Carlos K, Prado GF, Teixeira CD, et. al. Benzodiazepines for restless legs syndrome. Cochrane Database Syst Rev. 2017; 3: CD00693
  6. Caviness JN. Treatment of Myoclonus. Neurotherapeutics. 2014; 11(1): 188–200.
  7. Cherny NI, ESMO Guidelines Working Group. ESMO Clinical Practice Guidelines for the management of refractory symptoms at the end of life and the use of palliative sedation. Ann Oncol. 2014; 25 Suppl 3: iii143-52.
  8. Glauser T, Shinnar S, Gloss D, et. al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016; 16(1): 48-61.
  9. Hui D, Frisbee-Hume S, Wilson A. et. al. Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial. JAMA. 2017; 318(11): 1047-1056.
  10. Jeon YS, Kearney AM, Baker PG. Management of hiccups in palliative care patients. BMJ Support Palliat Care. 2018; 8(1)
  11. Maltoni M, Scarpi E, Rosati M, et. al. Palliative sedation in end-of-life care and survival: a systematic review. J Clin Oncol. 2012; 30(12): 1378-83.
  12. Simon ST, Higginson IJ, Booth S, et. al. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016; 10:CD007354.
  13. Wick J. The History of Benzodiazepines. Consult Pharm. 2013; 28(9): 538-48.
  14. Wilson MP, Pepper D, Currier GW, et. al. The psychopharmacology of agitation: consensus statement of the American association for emergency psychiatry project Beta psychopharmacology workgroup. West J Emerg Med. 2012; 13(1): 26-34.
  15. Zesiewicz TA, Elble R, Louis ED, et. al. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005; 64(12): 2008-20.

 

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