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Preventing heroin overdose: do not forget circadian rhythms
- Roberto Manfredini, Benedetta Boari, Massimo Gallerani (24 February 2003)
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Roberto Manfredini, Assistant professor of Internal Medicine Section of Internal Medicine, University of Ferrara, via Savonarola 9, 44100 Ferrara, Italyi, Benedetta Boari, Massimo Gallerani
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EDITOR – We read with interest the article by dr Sporer (1), dealing with prevention strategies for heroin overdose. However, we would add some considerations. Like several acute cardiovascular events, eg, myocardial infarction, sudden death, and stroke (2), the existence of a circadian variability has been reported for heroin overdose as well (3). Since the higher frequency peak was found in the afternoon and evening hours (acrophase: 7 PM, 95% confidence limits: 18–20 PM), the first and simplest hypothesis was that probably heroin abusers consumed a higher amount of heroin in the evening, due to preferences related to the hours of work and the need for staying employed. However, the results of a 8-year prospective study by our group (4), confirmed our previous hypothesis of a possible existence of circadian differences in the individual sensitivity to heroin. In fact, although a circadian higher frequency peak in the evening hours was confirmed for nonlethal overdoses, analysis of the distribution of the hourly average amount of naloxone to rescue comatose patients showed an opposite pattern, with a significant peak in the early morning. Moreover, when analyzing overdose severity (on the basis of: a) the dose of naloxone needed for rescue; b) the frequency of hospitalizations; and c) the frequency of lethal overdoses), the peak time span was shifted to the late night-early morning hours (3–9 AM). Thus, heroin overdoses are more frequent in late afternoon–early evening, but they need a smaller amount of naloxone and are less severe. On the other hand, nocturnal and early morning overdoses are less frequent, but more severe and complicated by hospitalization or death. At today, the possible interpretation of a circadian difference in the effects of opiates is merely speculative, although indirect confirmation data exist. In fact, daily variations in the analgesic effects of morphine in patients treated for cancer (who self-administer the least in the late night to early morning hours) have been reported (5), suggesting the possibility that patients may be more sensitive to opiates in that hours. Overdoses commonly occur in the users’ home, and this may represent a risk in the case of night overdoses. Since often heroin abuse is done in company of others, educational programs for drug users could include the recommendation to win the natural reluctance and make a prompt call the emergency services, to avoid delay in the intervention and reduce the risk of fatal complications. References 1) Sporer KA. Strategies for preventing heroin overdose. BMJ 2002;326:442- 444. 2) Portaluppi F, Manfredini R, Fersini C. From a static to a dynamic concept of risk: the circadian epidemiology of cardiovascular events. Chronobiol Int 1999;16:33-49. 3) Manfredini R, Gallerani M, Calò G, Pasin M, Govoni M, Fersini C. Emergency admissions of opioid drug abusers for overdose: a chronobiological study of enhanced risk. Ann Emerg Med 1994;24:615-618. 4) Gallerani M, Manfredini R, Dal Monte D, Calò G, Brunaldi V, Simonato M. Circadian differences in the individual sensitivity to opiate overdose. Crit Care Med 2001;29:96-101. 5) Citron ML, Kaira J, Seltzer VL, Chen S, Hoffman M, Walczach MB. Patient -controlled analgesia for cancer pain: a long-term study of inpatient and outpatient use. Cancer Invest 1992;10:335-341. Competing interests: None declared |
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