The New Opioid Epidemic: Prescriptions, Synthetics, and Street Drugs
At the local level, dealers may seek to attract heroin users by adulterating, or even replacing, heroin with fentanyl or novel synthetic opioids, marketing it as a “high-quality” heroin offering more rapid, intense effects. These fentanyl analogs are often hundreds of times more potent than fentanyl, and therefore thousands of times more potent than heroin. Only a miniscule amount increases the perceived potency of the “heroin,” allowing dealers to increase their profit margins.
Selling and using novel synthetic opioids leave little room for error, and small dosing miscalculations have resulted in profound overdoses and deaths. Obviously, the quality control, contents, and dose uniformity of illicitly traded products are poor, adding to the risks of use. In some cases, the novel synthetic opioids are pressed into tablets and marketed as diverted prescription opioids or benzodiazepines. In many, if not most, circumstances, intermediary dealers, as well as users, may be unaware of the product’s contents.5,6 Carfentanil, used as a large-animal tranquilizer, is reportedly 10,000 times more potent than morphine and has recently been implicated in a cluster of deaths of opioid users in the Midwest.7,8 Other synthetic opioids coming to market were initially developed for laboratory research, including W18, which was identified in Canada; and U47700, an opioid identified on autopsy of the musician Prince3,9 (Table 2).
Novel synthetic opioids can be identified only by specific, specialized assays not available in clinical settings. Because their molecular structures differ substantially from morphine, these compounds skirt identification by standard urine “opiate” drug screens. With the exception of fentanyl, pharmacokinetic data for the use of the majority of these agents in humans is unknown.
How are patients who present to EDs with an opioid toxidrome managed in practice today?
Classic teaching for the management of opioid-induced respiratory depression in adults is to provide ventilatory support (ie, BVM or intubation) or administer a low dose of naloxone (0.04 mg IV every 2-5 minutes, up to 2 mg) until adequate respirations are restored. This approach is reasonable for patients exposed to heroin or fentanyl, and provides safer reversal in the ED than administration of a large bolus dose of 0.4 or 2 mg naloxone in opioid-dependent patients.
However, patients exposed to novel synthetic opioids may ultimately require higher than usual doses of naloxone to achieve reversal—reportedly IV doses as high as 6 to 10 mg or more.10 It is not yet fully understood if the need for high-dose naloxone is due to the binding affinity of the opioid or the relatively high dose of opioid administered.
Because the clinical effects of the novel synthetic opioids are generally indistinguishable from those of other opioids, providing respiratory support in the ED remains a critical intervention while awaiting the effect of titrated doses of naloxone. Of concern, though, is that these opioids are so potent that they may cause immediate respiratory arrest, resulting in a more rapid progression to cardiac arrest, limiting the ability to administer rescue breathing or antidote.
In the “bystander” setting, administration of a larger initial dose of naloxone may be reasonable, given the lack of advanced medical supportive care. However, the ability to provide larger doses in these settings is hampered by the accessibility of the antidote. In addition, prehospital-care providers need to consider the possibility of precipitating opioid withdrawal in patients with opioid dependence, which itself can carry significant consequences (eg, aspiration, agitated delirium), as well as the subsequent uncooperativeness of the victim, who may attempt to leave the scene and self-administer an additional dose of opioid or develop recurrent respiratory depression when the naloxone wanes. Since many patients with life-threatening opioid intoxication will suffer long-term consequences if reversal is delayed, the risk of administering high-dose naloxone in the bystander setting generally is worthwhile. However, the risks and benefits of naloxone must still be thoughtfully considered by prehospital-care providers who can provide alternative supportive therapies.
In the ED, the EP must decide whether to intubate the patient directly or first give a brief trial of low-dose naloxone. If a trial of naloxone is unsuccessful at reversing the respiratory depression, dose escalation can be tried while supporting oxygenation and ventilation noninvasively. Administration of naloxone postintubation is not usually necessary or even desired, since respiratory depression, the primary mechanism of death, has been addressed.
Are any special precautions required for health care workers?
Some of the ultra-potent synthetic opioids are available as powders or sprays that can be inadvertently absorbed through the skin (after dissolution in skin moisture) or inhaled.8 The safety of health care providers and law enforcement personnel who may be exposed to synthetic opioids in this manner is currently unknown, though some law enforcement and public health agencies have published warnings in an effort to be proactively cautious.8
While it is highly unlikely that the handling of body fluids of opioid-intoxicated patients poses any health threats, universal safety precautions of wearing disposable gloves should be utilized. As noted, contact with the actual substances may be more concerning, particularly when airborne; in such situations, a particulate mask should also be utilized. Although fentanyl in liquid formulation can slowly enter the skin transdermally (eg, fentanyl patch), there are very limited data to either support or refute the ability of the newer potent opioids to do so. Until more data on these opioid analogs become available, those entering grossly contaminated areas, in which dermal or inhalational exposure is high, should employ a higher level of personal safety precautions.11 In addition, naloxone should be readily available.
