Child Death Due to Dermal Opium Application: A Case Report

Background: Incorrect belief about opioid efficacy is a major cause of acute pediatric poisonings in Iran. We report a rare case of topical opium application that caused death in a 4-year-old child. Case: A 4-year old girl was examined with burns over her abdominal area and lower extremities. Her parents had applied opium on burned area to relieve her pain. She was in delirium state and apnea without any evidence of infection. Immediately, she was administered a single dose of Naloxone (2mg). Results: While blood oxygen saturation was improving, she aspirated her vomitus into the lungs and became hypotensive and pulseless. Her condition deteriorated and the treatment team’s efforts to resuscitate her failed. On her autopsy, there were no other abnormal findings, but codeine and morphine were detected in the autopsied tissue sample. Conclusion: The plausible contributing factors may include: change in morphine pharmacokinetics in the burned skin; the low toxic dose of opium in children due to thin abdominal skin, and high blood perfusion in the burned areas.

Opioids for breathlessness: Psychological and neural factors influencing response variability

ABSTRACTEffective management of distressing bodily symptoms (such as pain and breathlessness) is an important clinical goal. However, extensive variability exists in both symptom perception and treatment response. One theory for understanding variability in bodily perception is the ‘Bayesian Brian Hypothesis’, whereby symptoms may result from the combination of sensory inputs and prior expectations. In light of this theory, we explored the relationships between opioid responsiveness, behavioural/physiological symptom modulators and brain activity during anticipation of breathlessness.MethodsWe utilised two existing opioid datasets to investigate the relationship between opioid efficacy and physiological/behavioural qualities, employing hierarchical cluster analyses in: 1) a clinical study in chronic obstructive pulmonary disease, and 2) a functional magnetic resonance brain imaging study of breathlessness in healthy volunteers. We also investigated how opioid efficacy relates to anticipatory brain activity using linear regression in the healthy volunteers.ResultsConsistent across both datasets, diminished opioid efficacy was more closely associated with negative affect than with other physiological and behavioural properties. Furthermore, in healthy individuals, brain activity in the anterior cingulate and ventromedial prefrontal cortices during anticipation of breathlessness were inversely correlated with opioid effectiveness.ConclusionDiminished opioid efficacy for relief of breathlessness may be associated with high negative affective qualities, and was correlated with the magnitude of brain activity during anticipation of breathlessness.Clinical implicationsNegative affect and symptom expectations may influence perceptual systems to become less responsive to opioid therapy.

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

BACKGROUND The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly. The current problem is determining which of the many potential candidates to focus on for clinical implementation. CONTENT We systematically searched publications on PGx for opioids in 5 databases, aiming to identify PGx markers with sufficient robust data and high enough occurrence for potential clinical application. The initial search yielded 4257 unique citations, eventually resulting in 852 relevant articles covering 24 genes. From these genes, we evaluated the evidence and selected the most promising 10 markers: cytochrome P450 family 2 subfamily D member 6 (CYP2D6), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), cytochrome P450 family 3 subfamily A member 5 (CYP3A5), UDP glucuronosyltransferase family 2 member B7 (UGT2B7), ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C member 3 (ABCC3), solute carrier family 22 member 1 (SLC22A1), opioid receptor kappa 1 (OPRM1), catechol-O-methyltransferase (COMT), and potassium voltage-gated channel subfamily J member 6 (KCNJ6). Treatment guidelines based on genotype are already available only for CYP2D6. SUMMARY The application of PGx in the management of pain with opioids has the potential to improve therapy. We provide a shortlist of 10 genes that are the most promising markers for clinical use in this context.