Opioid Use and the Risk of Respiratory Depression and Death in the Pediatric Population

Whittaker, Marianne R

doi:10.5863/1551-6776-18.4.269

Cited by 16 publications

(11 citation statements)

References 23 publications

(24 reference statements)

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“…During cancer progression, increasing doses of opioids are required for proper pain management not only because of the pain resulted from cancer enlargement and metastasis, but also because of the development of opioid tolerance. The side effects of opioid like sedation and respiratory depression prevent us to treat tolerance by simply and un-limitedly increasing opioid doses [ 28 , 29 ]. Therefore, reducing the overall usage of opioids slows the development of tolerance down, increases the available time for opioids to control cancer pain and subsequent improves quality-of-life.…”

Section: Discussionmentioning

confidence: 99%

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels

Huang

Liang

et al. 2016

Lipids Health Dis

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BackgroundPain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer.MethodsMedical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5–8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared.ResultsPatients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed.ConclusionsTherefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0212-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels

Huang

Liang

et al. 2016

Lipids Health Dis

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“…Until recently, youth opioid abuse was under represented in scientific literature and poorly documented outside of case studies [285]. Outcomes following opioid abuse range from mild cognitive disorders to severe respiratory issues [286], resulting in increased hospitalizations and deaths in recent decades [287,288]. Rising numbers of adolescents exposed to opioids warrant further research on opioid alterations to the developing brain, in addition to public health prevention efforts [287].…”

Section: Opioid Exposure During Childhood and Adolescencementioning

confidence: 99%

The Developmental Neuroepigenetics of Substance Abuse

Mason¹,

Donaldson²,

Hunter³

2018

J Drug Alcohol Res

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Advances in technology have allowed for the expansion of the field of epigenetics, providing a deeper understanding of geneenvironment interactions. Investigations into the neurobiological basis of substance abuse have benefitted from these advances, with findings suggesting that epigenetic mechanisms underlie drug-induced modifications of brain morphology, synaptic plasticity, and behavior. Epigenetic marks likely mediate the long-lasting and potentially transgenerational alterations of neuronal chromatin and subsequent gene expression that may lead to persistent relapse vulnerability and/or offspring vulnerability to addiction. Understanding the epigenetic mechanisms as well as potential sensitive windows for these alterations may provide novel insight into how epigenetics factor into the individual vulnerability and unique time periods for added vulnerability to illicit drug exposure. In the current review, we outline recent literature that provides evidence for early epigenetic changes in several addiction models. We begin the review with an overview of epigenetics as they relate to drug use and abuse, and next focus on findings in the context of prenatal, childhood, and adolescent stages with additional references to adult models of addiction. Further, we also focus on studies that discuss the transgenerational inheritance of epigenetic changes, and how they may affect the individual across development. Lastly, the work presented here and potential future studies focus on demonstrating early disruptions in epigenetic marks following acute or repeated drug exposure that may be of relevance in the broader goal of identifying risk factors and novel targets for addiction treatment.

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“…Children who are ultra-rapid metabolizers convert 5 to 30 times more codeine to morphine than do normal metabolizers, [1][2][3] which can lead to fatal toxicity. [4][5][6] There have been several reports of fatalities associated with standard doses of codeine among ultra-rapid metabolizers, [4][5][6] although these fatal case reports have been limited to children who underwent tonsillectomy and=or adenoidectomy. 5 For children, national and international guidelines recommend against all use of codeine for the common indications of analgesia and cough suppression because of the uncertain benefits of codeine 7 and its potential risk of death.…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Severe Respiratory Depression and Codeine-Containing Antitussives in Children: A Nested Case-Control Study

Ono

Koide

et al. 2020

Journal of Epidemiology

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Background: Guidelines recommend against all codeine use in children for its common indications of analgesia and cough suppression because of uncertain benefits and potential risk of death. However, because of its rarity, the occurrence of severe respiratory depression associated with codeine-containing antitussives has been poorly investigated. The objective of this study was to investigate the association between codeine-containing antitussives and severe respiratory depression in children. Methods: We retrospectively identified Japanese children who were prescribed antitussives for respiratory diseases from a large Japanese administrative claims database (JMDC, Tokyo, Japan). We collected data on baseline characteristics including age, sex, and comorbidity. Each case was matched with four controls with the same sex and age in the same year from the same type of medical institution. We then examined the association between codeine-containing antitussives and subsequent severe respiratory depression using multivariable conditional logistic regression analysis. Results: Of 164,047 children, 18,210 (11.1%) were prescribed codeine-containing antitussives. Of the children who took codeine-containing drugs, seven experienced severe respiratory depression. After adjusting for confounding factors, there was no significant difference in the proportion of severe respiratory depression between children with and without codeinecontaining antitussives (odds ratio 1.15; 95% confidence interval, 0.48-2.78). Conclusion: Occurrence of respiratory depression was very rare, and the association of codeine with respiratory depression was insignificant, even in a large sample of children in Japan.

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Opioid Use and the Risk of Respiratory Depression and Death in the Pediatric Population

Cited by 16 publications

References 23 publications

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels

The Developmental Neuroepigenetics of Substance Abuse

Relationship Between Severe Respiratory Depression and Codeine-Containing Antitussives in Children: A Nested Case-Control Study

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