Opioid Toxicity

Abstract

In recent years, there has been a substantial increase in opioid use and abuse, and in opioid-related fatal overdoses. The increase in opioid use has resulted at least in part from individuals transitioning from prescribed opioids to heroin and fentanyl, which can cause significant respiratory depression that can progress to apnea and death. Heroin and fentanyl may be used individually, together, or in combination with other substances such as ethanol, benzodiazepines, or other drugs that can have additional deleterious effects on respiration. Suspicion that a death is drug-related begins with the decedent's medical and social history, and scene investigation, where drugs and drug paraphernalia may be encountered, and examination of the decedent, which may reveal needle punctures and needle track marks. At autopsy, the most significant internal finding that is reflective of opioid toxicity is pulmonary edema and congestion, and frothy watery fluid is often present in the airways. Various medical ailments such as heart and lung disease and obesity may limit an individual's physiologic reserve, rendering them more susceptible to the toxic effects of opioids and other drugs. Although many opioids will be detected on routine toxicology testing, more specialized testing may be warranted for opioid analogs, or other uncommon, synthetic, or semisynthetic drugs.

The Physiology and Maintenance of Respiration: A Narrative Review

“…The further the shift to the right, the more likely respiratory depression is to occur. Opioids and other CNS depressants can also relax airway muscles, decrease upper airway patency, disengage protective arousal mechanisms, and cause obstructed breathing, which further reduces effective ventilation in the setting of decreased respiratory drive [ 47 – 51 ].

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“…These different classes suppress respiration by affecting various components of the respiratory system (Table 1 ; Fig. 5 ) [ 18 , 47 – 51 , 54 – 62 ].…”

“…These agents bind directly to various GABA A receptor subtypes and increase the inhibitory effects of endogenous GABA (Table 1 ) [ 18 , 56 ]. Benzodiazepines can depress central respiratory drive, chemoreceptor responsiveness to hypercapnia, peripheral chemoreceptors, and inspiratory and expiratory respiratory muscle strength in a dose-dependent manner, thus reducing respiration [ 47 , 57 , 58 ]. Benzodiazepines can also cause upper airway obstruction via relaxation of the tongue and neck [ 47 ].…”

“…Benzodiazepines can depress central respiratory drive, chemoreceptor responsiveness to hypercapnia, peripheral chemoreceptors, and inspiratory and expiratory respiratory muscle strength in a dose-dependent manner, thus reducing respiration [ 47 , 57 , 58 ]. Benzodiazepines can also cause upper airway obstruction via relaxation of the tongue and neck [ 47 ]. Dose-dependent effects on reducing resting ventilation and the ventilatory response to hypoxia and hypercapnia can occur [ 18 ].…”

“…Opioids are often prescribed for acute and chronic pain relief, as they provide analgesia by acting on mu-opioid receptors located throughout the CNS (Table 1 ; Fig. 6 ) [ 47 , 50 , 51 ]. Opioid-induced respiratory depression can occur through the suppression of respiratory drive by interacting with neurons in the pons and medulla, including the pre-Bötzinger complex, or suppressing peripheral or central chemoreceptors, which impacts respiratory rhythm and blunts the normal response to hypoxemia and hypercapnia (Fig.…”