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AM. J. DRUG ALCOHOL ABUSE, 5(1), pp. 39-49 (1978)
Street Heroin Potency and Deaths from Overdose in San Antonio DAVID P. DESMOND,” M.S.W. JAMES F. MADDUX, M.D. AURELIANO TREVINO, M.S.W Department of Psychiatry University of Texas Health Science Center at San Antonio San Antonio, Texas 78284
ABSTRACT Disagreement over the mechanism of death in so-called heroin overdose has been noted in the medical literature for more than a decade. We studied the relationship between the potency of street heroin and the frequency of heroin overdose deaths in San Antonio in order to test the “pharmacologic overdose” hypothesis. We found a small, nonsignificant correlation (r = +.13) between monthly mean heroin dose and monthly number of heroin overdose deaths over a 5-year period. This low correlation contradicts fiidings of previous studies in Washington, D.C. and Atlanta, conducted over shorter periods of time, in which high positive correlations were found. The low correlation does not support the pharmacologic overdose hypothesis. Since there were confounding variables, the data d o not refute the hypothesis. These variables include the use of alcohol and other depressants, hidden suicide, and reduced opioid drug tolerance due to institutional treatment.
What role does fluctuation in the potency of street heroin play in the frequency of death from heroin overdose? Equivocal answers to this question have appeared in the medical literature, partly because the
*To whom requests for reprints should be addressed at the Department of Psychiatry,
7703 Floyd Curl Drive, San Antonio, Texas 78284. 39
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DESMOND, MADDUX, AND TREVINO
minimum lethal dose of this drug in man has not been established [ 1 , 21, and partly because the mechanisms which cause death from heroin overdose are poorly understood. In 1966 Helpern and Rho [3] stated that “More deaths are encountered where heroin is in abundant supply and the samples are more generous in content.” In 1967 Louria and associates [4], after noting the wide range of heroin strength in street samples in New York City, stated that lack of awareness of the potency of the heroin packet is the most frequent cause of overdose. They considered packages containing concentrations of more than 20% heroin to be potentially lethal. Epidemiologists studying the prevalence of narcotic addiction in urban areas have often used frequency of overdose deaths as an indirect measure of the size of an addict population. This practice has been criticized in recent years in part because of the presumed relationship between heroin potency and occurrence of overdose deaths. For example, Hunt [5] stated, “There is no reason to assume that a relationship holds . . . since overdose deaths depend on conditions of the heroin market such as fluctuating purity.” Green [ 6 ] warned against interpreting a decrease in heroin deaths as indicative of a decrease in the number of heroin users, noting that “A decrease in the death rate could be related to a decline in the potency of heroin available on the streets. . . .” The validity of such criticism depends largely on whether or not heroin overdose deaths are in fact the result of a pharmacologic overdose. In their 1966 paper, Helpern and Rho described the characteristic pulmonary edema found in acute heroin deaths and commented, “Whether this acute lung reaction requires absolute or relative overdosage of the narcotic, or is an expression of a specific hypersensitivity to the drug has not yet been resolved.” Five years later, in 1971, Duberstein and Kaufman [7] reported a clinical study of 149 heroin overdose cases and concluded that the mechanism of heroin-induced pulmonary edema was analogous to high altitude pulmonary edema, that is, a cycle of respiratory depression leading to hypoxia, followed by increased capillary permeability, fluid extravasation, edema, and concomitant pulmonary hypertension. They added “We believe that this is the pathogenesis in most cases of heroin-induced pulmonary edema, even though in rare subjects hypersensitivity may be the sole or major cause.” In 1972 Cherubin and associates [8] reported contradictory conclusions. After studying 591 deaths among New York City addicts they concluded that “. . . the main cause of death . . . was an idiosyncratic reaction to an injection of unspecified materials, and probably not a true pharmacologic
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STREET HEROIN POTENCY AND DEATHS FROM OVERDOSE
41
overdose of narcotics.” Among the alternative mechanisms which have been suggested are anaphylaxis or Arthus phenomenon [9] , ventricular arrythmias [ l o ] , reaction to adulterants, and synergistic actions with alcohol or other CNS depressants [2]. Findings of more recent studies tend to support the pharmacological overdose mechanism rather than hypersensitivity or other mechanisms. Garriott and Sturner [I 11 studied 22 acute heroin deaths in Dallas using improved methods to detect drugs in body fluids. They found that blood morphine levels were inversely correlated with survival time following injection. Ethyl alcohol was also present in the blood in 50% of the cases. They concluded that their observations supported the concept of a toxic mechanism of death, and said, “. . . the term overdose is probably an appropriate one.” Greene, Luke, and DuPont [12] compared the monthly average dosage of pure heroin in street level packages in Washington, D.C. with the monthly number of heroin overdose deaths during an 18-month period, 197 1- 1972. They found a strong positive correlation (r = t . 8 3 , p < .01). This correlation, along with autopsy and toxicological data from 58 heroin fatality case records, led the authors to suggest that the lethal effect of heroin was related to the dosage. Lack of opioid drug tolerance and the presence of alcohol in the blood were considered other significant factors. Alexander [13] studied the relationship between heroin content of street level packages and overdose deaths in Atlanta. Bags with gross weights of 25 to 200 rng purchased by undercover police officers were analyzed for a 36month period, 1971-1973. The correlation between monthly average number of milligrams of heroin per bag and monthly frequency of “acute narcotism” deaths was found to be statistically significant (r = t.67, p < .001). After reviewing these reports, Huber [14], in an editorial in the Journal of the American Medical Association, concluded that there was growing evidence that heroin itself was playing a major role in acute heroin deaths, at least in some areas. We felt that this new evidence was important, and that further study of the role of fluctuating heroin potency in the occurrence of overdose deaths might add to our understanding of the mechanisms which cause these deaths. We attempted to replicate the Atlanta study and a portion of the Washington, D.C. study in San Antonio, Texas. San Antonio, with a population of 654,153 in the 1970 census, has had an endemic problem of heroin addiction for several decades. Ample supplies of relatively high potency heroin have usually been available due to the proximity of the city to the Mexican border, the increasing preponderance of Mexican heroin in the
42
DESMOND, MADDUX, AND TREWNO
American market [15], and the relatively high proportion of San Antonio addicts who are middle- and low-level heroin distributors.
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METHODS From data provided by the San Antonio-Bexar County Regional Crime Laboratory, we computed the number of milligrams of heroin in retail units of adulterated heroin mixture purchased or seized by San Antonio police officers. The study covered the 5-year period January 1972 through December 1976. Retail units were defined as packages labeled “half-grams” or less in police descriptions of the evidence, or unlabeled packages containing less than 500 mg. “Half-grams” were the usual retail unit sold in San Antonio during most of the study period. Each case made by police was considered one observation in that month’s sample of the heroin market, no matter how many “half-grams’’ were seized or purchased at one time. The number of cases in a month ranged from 4 t o 5 2 , with a mean of 18. The buys and seizures may or may not have constituted a representative sample of heroin available on the illicit retail market, but they were the best data available. The number of heroin overdose deaths each month was obtained from records of the Bexar County Medical Examiner’s office. Deaths from heroin overdose or acute narcotism-heroin were labeled “heroin reaction” by the Bexar County Medical Examiner’s staff, and only deaths so designated were tabulated. Criteria for diagnosis of heroin reaction as a cause of death during the study period emphasized pathological findings of a complete autopsy such as were suggested by Siegel, Helpern, and Ehrenreich [ 161 . Positive toxicology for opiates was not a requirement for the diagnosis.
FINDINGS We found frequent and marked fluctuations in the potency of heroin available to the consumer in San Antonio during the 5 years studied. As shown in Fig. 1, abrupt changes occurred from month to month. For example, the mean monthly dose of heroin in street packages changed from 16 mg in December 1975, to 51 mg in January 1976, to 42 mg in February, and t o 19 mg in March. The monthly mean dose varied from 9 to 110 mg. The mean dose of all street packages for the entire 5 years was 29 mg, the range 1 to 196 mg.
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STREET HEROIN POTENCY AND DEATHS FROM OVERDOSE
43
DEATHS
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DESMOND, MADDUX, AND TREVINO
The monthly mean number of heroin reaction deaths was 1.7, the range 0 to 6. We found a small correlation, not statistically significant, between monthly dosage and frequency of death (r = t.13). Higher positive correlation between the two variables appeared in certain segments of time, such as the period February through October 1973 (r = t.92, p < .Ol) and the period April through December 1975 (r = t.50, N.S.). These are offset by briefer periods, such as January through March 1976, in w h c h there is a negative correlation between dose and death. As a measure of variability within monthly seizures, we computed the standard deviation of each month’s sample. Then we computed the coefficient of correlation between the monthly standard deviation and the monthly number of deaths. We obtained a coefficient of only slightly higher than that for mean dosage with deaths, not statistically significant (r = +.19, N.S.). We also considered another measure of variability, the maximum dosage in each month’s sample. The standard deviation is usually the preferred measure of variability, but because it can be influenced by values in either direction, it could have failed to identify those months in which unusually potent mixtures of heroin were available. The maximum dosage ranged from 19 mg in September 1974 to 196 mg in May 1972. Each month’s maximum dose was correlated with each month’s deaths. The resulting coefficient was slightly higher than either of the previous coefficients, but was not statistically significant (r = t.21, N.S.). The only evidence we found that variation in dosage may contribute to overdose deaths came from studying changes in heroin packaging practices. Prior t o 197 1, a degree of standardization existed in gross weight of retail units of heroin due to the widespread use of No. 5 gelatine capsules for packaging. The gross weight of the contents of these capsules rarely exceeded 60 mg. Due t o action of retail pharmacists in 1970, capsules became unavailable in San Antonio in 1971, and for a time street dealers resorted to wrapping the powder in paper, tinfoil, or cellophane. The years 1971-1972 were a transition era. During this period the “half-gram” packaged in a small rubber balloon became the usual retail unit. Most “half-grams’’ weighed less than 250 mg, but their weight varied considerably. The period 1971-1972 was one of instability, with some “half-grams” containing from 5 to 1 0 times as many milligrams of heroin as other units with the same nominal weight. By 1975, the balloons contained smaller but generally more uniform amounts of heroin mixture. Figure 2 shows the frequency of deaths attributed to heroin reaction in San Antonio during the years 1966 through 1976. As the figure shows, deaths during the 1971-1972 transition era were notably higher than those in the “capsule era,” and slightly higher than those
45
STREET HEROIN POTENCY AND DEATHS FROM OVERDOSE
Mean Annual Deafhs=23
Mean Annual Deaths = 8
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in the “balloon era.” We do not know what changes occurred in the size of the San Antonio addict population during this 11-year period. Probably some growth in the population at risk occurred during the transition period, but a nearly threefold increase, such as occurred in deaths during the transition period, is not likely.
DISCUSSION In marked contrast t o the studies in Washington, D.C. and Atlanta, we found no statistically significant correlation between the monthly mean dose of heroin in street samples and heroin overdose deaths. We also found no significant correlation between the variability of dose and deaths, and no significant correlation between monthly maximum dose and deaths. A pronounced increase in deaths during 1971-1972 may have been associated with instability of dose of street heroin, but the evidence is circumstantial. Consequently we attribute few of the overdose deaths in San Antonio to unexpected variations in the potency of street heroin.
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DESMOND, MADDUX, AND TREVINO
Studies in the United Kingdom also suggest that unexpected variations in dose may have minor importance. Overdose is a common cause of death among British addicts [17], and their mortality rate has been described as higher than that of United States addicts [18, 191. British addicts use larger amounts of heroin than most United States addicts, but heroin is prescribed, and many addicts know the amount they are taking. There is an unstated assumption in this study, and perhaps in other studies cited, that United States heroin users are totally ignorant of the quality of the heroin they buy. We feel this assumption needs to be reevaluated for the following reasons. First, most addicts do not frequently buy drugs from complete strangers. They often know their dealer and know his merchandise. In San Antonio the dealer is frequently a heroin user himself. Second, any misrepresentation of the quality of heroin offered by dealers would usually occur in a way that would reduce probability of overdose rather than enhance it. A dealer would be more likely to exaggerate the potency of h s heroin rather than minimize it. And finally, heroin is frequently shared, and has thus been tested by one or more individuals in a group. We speculate that these procedures, and probably others, are commonly employed by heroin addicts to protect themselves from overdose, and act to modify the impact of wide variations in potency of heroin available at the street level. As we have noted, the minimal lethal dosage of heroin in man has not been established. Huber, Stivers, and Howard [20] considered 20 mg of heroin to be potentially lethal for nontolerant individuals, and Gardner [ 171 reported one death attributed to a dose of 20 mg. Earlier estimates of minimum lethal dose as high as 200 to 500 mg have been reported [2]. We doubt that 20 mg is frequently lethal. If this were so, death from overdose would probably be pandemic among the heroin users of San Antonio because the mean heroin content of retail packages was 29 mg during the 5 years we studied. The low correlation between dose and deaths in San Antonio highlights the need to investigate the role of other factors in these fatalities, especially that of alcohol and similar CNS depressants. Two additional factors, suicide and lack of tolerance, may also contribute notably to heroin overdose deaths. Heroin overdose deaths among heroin users are rarely ruled suicide unless unequivocal evidence is found to indicate that this was the decedent’s intention. The Bexar County Medical Examiner ruled suicide in none of the deaths we studied in San Antonio. However, some investigators have suggested that the frequency of suicide among addicts may be underreported in medical examiner’s data. Mason, in a study of mortality in young New York City addicts [21], found that only two of 74 deaths were labeled suicide, but he
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STREET HEROIN POTENCY AND DEATHS FROM OVERDOSE
47
commented, “It is quite possible that more suicides have occurred without being recognized as such.” In an evaluation of a national sample of 853 narcotic-involved deaths, Gottschalk and McGuire [22] reported that only 2% were listed as “definitely suicide,” but 25% were thought “possible suicide,” and another 19% were considered “suspicious.” Unpublished data from our study of careers of San Antonio opioid drug users also support the notion that suicide may often go officially unrecognized in cases of drug overdose. Six of 23 deaths which occurred among 246 addicts within a 10-year beriod were caused by overdose according to death certificates: Only one was ruled suicide (a note was left). In three other cases a person close to the decedent told our research interviewer that the subject had been despondent and may have committed suicide. Thus four out of six overdose deaths in this sample may have been due to suicide. If suicide is an important element in heroin overdose death, it would help to explain the low correlation between potency of available heroin and deaths. We feel that this question needs further study. Several studies of mortality among opioid addicts have indicated that lack of tolerance to the respiratory depressant effects of opioid drugs contributed to the frequency of death from overdose. Gardner [I71 found that 55% of “accidental overdose” deaths among a group of 47 British addicts occurred shortly after a period of opioid abstinence. Abstinence usually began in an institution. Greene, Luke, and DuPont [I21 stated that lack of tolerance was “documented” in 5 1% of the fatalities they studied in Washington, D.C. We do not know how many of the subjects of this study lacked tolerance before death, but we do know that San Antonio addicts were entering and leaving treatment much more often during most of the study period than before. In a previous study [23] we obtained a census of the number of heroin users in institutional treatment in San Antonio during 10 years, 1965-1974. During the 5-year period 1965-1969, a mean of 20 were in treatment; during the 5-year period 1970-1974, a mean of 80 were in treatment. Patients maintained on methadone are not included in these totals. This increase in availability and utilization of institutional treatment quite likely resulted in additional periods of low or no tolerance for opioid drugs, and greater suspectibility to overdose. As shown in Fig. 2, the annual number of deaths increased markedly after 1970. The data suggest that the use of heroin overdose deaths as an indicator of the prevalence of heroin use should not be abandoned, at least not because of a belief that these deaths are more closely related to drug potency than to the number of users. Considering the multiple, diverse factors which probably
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DESMOND, MADDUX, AND TREVINO
contribute to overdose deaths, we are tempted to describe them as nearly random phenomena. It is not surprising that, as Greene [ 6 ] has noted, prevalence estimates using overdose-multiplier formulas have yielded results remarkably similar to those of other, more sophisticated methods. In summary, our findings neither confirm nor refute the pharmacologic overdose hypothesis of death. We believe that heroin overdose deaths may best be understood by studying not only the pharmacologic properties of the drug itself, but the social context of heroin addiction and the psychosocial characteristics of heroin users as well. We recommend further investigation of the roles of alcohol and other depressants, suicide, and lack of tolerance in heroin overdose deaths.
ACKNOWLEDGMENTS This study was supported in part by Grant No. DA 00083 from the National Institute on Drug Abuse. The authors wish to thank Ruben C. Santos, M.D., Bexar County Medical Examiner, and Donald R. Krueger of the San Antonio-Bexar County Regional Crime Laboratory for providing the data on overdose deaths and heroin samples.
REFERENCES Reynolds, A. K., and Randall, L. O., Morphine and Allied Drugs, University of Toronto Press, Toronto, 1957, pp. 176-177. Brecher, E. M. (ed.), Licit and Zllicit Drugs, Consumers Union, Mount Vernon, New York, 1972, pp. 101-114. Helpern, M., and Rho, Y., Deaths from narcotism in New York City. N. Y. State J. Med. 66:2391-2408 (1966). Louria, D. B., Hensle, T., and Rose, J., The major medical complications of heroin addiction, Ann. Intern. Med. 67: 1-22 (1967). Hunt, L. G., Prevalence of active heroin use in the United States, in The Epidemiology of Heroin and Other Narcotics (J. D. Rittenhouse, ed.), Stanford Research Institute, Menlo Park, California, 1976, p. 36. Greene, M. H., Estimating the Prevalence of Heroin Use in a Community, Special Action Office for Drug Abuse Prevention, Washington, D.C., 1974, p. 6. Duberstein, J. L., and Kaufman, D. M., A clinical study of an epidemic of heroin intoxication and heroin-induced pulmonary edema, Am. J. Med. 51:704-714
(1971). Cherubin, C., et al., The epidemiology of death in narcotic addicts, Am. J. Epidemiol. 96:ll-22 (1972). Force, E. E., Fisher, R. S., and Millar, J. W., Epidemiological and ecological study of risk factors for narcotics overdose, Arch. Environ. Health 26:111-119 (1973). Stimmel, B., et al., Electrocardiographic changes in heroin, methadone, and multiple drug abuse, in Proceedings of the 5th National Conference on Methadone Treatment, National Association for the Prevention of Addiction to Narcotics, New York, 1972, pp. 706-710.
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by McMaster University on 11/14/14 For personal use only.
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49
Garriott, J. C., and Sturner, W. Q., Morphine concentrations and survival periods in acute heroin fatalities, N. Engl. J. Med. 289:1276-1278 (1973). Greene, M. H., Luke, J. L., and DuPont, R. L., Opiate “overdose” deaths in the District of Columbia. I: Heroin-related fatalities, Med. Ann. D.C.43: 175-181 (1974). 131 Alexander, M., Surveillance of heroin-related deaths in Atlanta, 1971 to 1973, J. A m . Med. Assoc., 229~677-678,1974. 141 Huber, D. H., Heroin deaths-Mystery or overdose?, J. Am. Med. Assoc. 229:689690 (1974). 151 Greene, M. H., Kozel, N. J., and Appletree, R. L., A n Epidemiologic Study of Heroin Use Patterns and Trends in Four Cities on the Mexican-American Border, Special Action Office for Drug Abuse Prevention, Washington, D.C., 1975. Siegel, H., Helpern, M.,and Ehrenreich, T., The diagnosis of death from intravenous narcotism, J. Forensic Sci. 2:l-16 (1966). Gardner, R., Deaths in United Kingdom opioid users 1965-69, Lancet 1:650-653 (19 70). James, I. P., Suicide and mortality amongst heroin addicts in Britain, Er. J. Addict. 62:391, 398 (1976). Bewley, T. H., Ben-Arie, O., and James, I. P., Morbidity and mortality from heroin dependence, Br. Med. J. 1:725-732 (1968). Huber, D. H., Stivers, R. R., and Howard, L. B., Heroin-overdose in deaths in Atlanta: An epidemic, J. A m . Med. Assoc. 228:319-322 (1974). Mason, P., Mortality among young narcotic addicts, J. Mt. Sinai Hosp. 34:4-9 (1967). Gottschalk, L. A., and McGuire, F. L., Psychosocial and biomedical aspects of deaths associated with heroin and other narcotics, in The Epidemiology of Heroin and Other Narcotics (J. Rittenhouse, ed.), Stanford Research Institute, Menlo Park, California, 1976, pp. 77-81. Maddux, J. F., and Desmond, D. P., Crime and treatment of heroin users, To be published in International Journal of the Addictions,
AM. J. DRUG ALCOHOL ABUSE, 5(1), pp. 39-49 (1978)
Street Heroin Potency and Deaths from Overdose in San Antonio DAVID P. DESMOND,” M.S.W. JAMES F. MADDUX, M.D. AURELIANO TREVINO, M.S.W Department of Psychiatry University of Texas Health Science Center at San Antonio San Antonio, Texas 78284
ABSTRACT Disagreement over the mechanism of death in so-called heroin overdose has been noted in the medical literature for more than a decade. We studied the relationship between the potency of street heroin and the frequency of heroin overdose deaths in San Antonio in order to test the “pharmacologic overdose” hypothesis. We found a small, nonsignificant correlation (r = +.13) between monthly mean heroin dose and monthly number of heroin overdose deaths over a 5-year period. This low correlation contradicts fiidings of previous studies in Washington, D.C. and Atlanta, conducted over shorter periods of time, in which high positive correlations were found. The low correlation does not support the pharmacologic overdose hypothesis. Since there were confounding variables, the data d o not refute the hypothesis. These variables include the use of alcohol and other depressants, hidden suicide, and reduced opioid drug tolerance due to institutional treatment.
What role does fluctuation in the potency of street heroin play in the frequency of death from heroin overdose? Equivocal answers to this question have appeared in the medical literature, partly because the
*To whom requests for reprints should be addressed at the Department of Psychiatry,
7703 Floyd Curl Drive, San Antonio, Texas 78284. 39
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40
DESMOND, MADDUX, AND TREVINO
minimum lethal dose of this drug in man has not been established [ 1 , 21, and partly because the mechanisms which cause death from heroin overdose are poorly understood. In 1966 Helpern and Rho [3] stated that “More deaths are encountered where heroin is in abundant supply and the samples are more generous in content.” In 1967 Louria and associates [4], after noting the wide range of heroin strength in street samples in New York City, stated that lack of awareness of the potency of the heroin packet is the most frequent cause of overdose. They considered packages containing concentrations of more than 20% heroin to be potentially lethal. Epidemiologists studying the prevalence of narcotic addiction in urban areas have often used frequency of overdose deaths as an indirect measure of the size of an addict population. This practice has been criticized in recent years in part because of the presumed relationship between heroin potency and occurrence of overdose deaths. For example, Hunt [5] stated, “There is no reason to assume that a relationship holds . . . since overdose deaths depend on conditions of the heroin market such as fluctuating purity.” Green [ 6 ] warned against interpreting a decrease in heroin deaths as indicative of a decrease in the number of heroin users, noting that “A decrease in the death rate could be related to a decline in the potency of heroin available on the streets. . . .” The validity of such criticism depends largely on whether or not heroin overdose deaths are in fact the result of a pharmacologic overdose. In their 1966 paper, Helpern and Rho described the characteristic pulmonary edema found in acute heroin deaths and commented, “Whether this acute lung reaction requires absolute or relative overdosage of the narcotic, or is an expression of a specific hypersensitivity to the drug has not yet been resolved.” Five years later, in 1971, Duberstein and Kaufman [7] reported a clinical study of 149 heroin overdose cases and concluded that the mechanism of heroin-induced pulmonary edema was analogous to high altitude pulmonary edema, that is, a cycle of respiratory depression leading to hypoxia, followed by increased capillary permeability, fluid extravasation, edema, and concomitant pulmonary hypertension. They added “We believe that this is the pathogenesis in most cases of heroin-induced pulmonary edema, even though in rare subjects hypersensitivity may be the sole or major cause.” In 1972 Cherubin and associates [8] reported contradictory conclusions. After studying 591 deaths among New York City addicts they concluded that “. . . the main cause of death . . . was an idiosyncratic reaction to an injection of unspecified materials, and probably not a true pharmacologic
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by McMaster University on 11/14/14 For personal use only.
STREET HEROIN POTENCY AND DEATHS FROM OVERDOSE
41
overdose of narcotics.” Among the alternative mechanisms which have been suggested are anaphylaxis or Arthus phenomenon [9] , ventricular arrythmias [ l o ] , reaction to adulterants, and synergistic actions with alcohol or other CNS depressants [2]. Findings of more recent studies tend to support the pharmacological overdose mechanism rather than hypersensitivity or other mechanisms. Garriott and Sturner [I 11 studied 22 acute heroin deaths in Dallas using improved methods to detect drugs in body fluids. They found that blood morphine levels were inversely correlated with survival time following injection. Ethyl alcohol was also present in the blood in 50% of the cases. They concluded that their observations supported the concept of a toxic mechanism of death, and said, “. . . the term overdose is probably an appropriate one.” Greene, Luke, and DuPont [12] compared the monthly average dosage of pure heroin in street level packages in Washington, D.C. with the monthly number of heroin overdose deaths during an 18-month period, 197 1- 1972. They found a strong positive correlation (r = t . 8 3 , p < .01). This correlation, along with autopsy and toxicological data from 58 heroin fatality case records, led the authors to suggest that the lethal effect of heroin was related to the dosage. Lack of opioid drug tolerance and the presence of alcohol in the blood were considered other significant factors. Alexander [13] studied the relationship between heroin content of street level packages and overdose deaths in Atlanta. Bags with gross weights of 25 to 200 rng purchased by undercover police officers were analyzed for a 36month period, 1971-1973. The correlation between monthly average number of milligrams of heroin per bag and monthly frequency of “acute narcotism” deaths was found to be statistically significant (r = t.67, p < .001). After reviewing these reports, Huber [14], in an editorial in the Journal of the American Medical Association, concluded that there was growing evidence that heroin itself was playing a major role in acute heroin deaths, at least in some areas. We felt that this new evidence was important, and that further study of the role of fluctuating heroin potency in the occurrence of overdose deaths might add to our understanding of the mechanisms which cause these deaths. We attempted to replicate the Atlanta study and a portion of the Washington, D.C. study in San Antonio, Texas. San Antonio, with a population of 654,153 in the 1970 census, has had an endemic problem of heroin addiction for several decades. Ample supplies of relatively high potency heroin have usually been available due to the proximity of the city to the Mexican border, the increasing preponderance of Mexican heroin in the
42
DESMOND, MADDUX, AND TREWNO
American market [15], and the relatively high proportion of San Antonio addicts who are middle- and low-level heroin distributors.
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by McMaster University on 11/14/14 For personal use only.
METHODS From data provided by the San Antonio-Bexar County Regional Crime Laboratory, we computed the number of milligrams of heroin in retail units of adulterated heroin mixture purchased or seized by San Antonio police officers. The study covered the 5-year period January 1972 through December 1976. Retail units were defined as packages labeled “half-grams” or less in police descriptions of the evidence, or unlabeled packages containing less than 500 mg. “Half-grams” were the usual retail unit sold in San Antonio during most of the study period. Each case made by police was considered one observation in that month’s sample of the heroin market, no matter how many “half-grams’’ were seized or purchased at one time. The number of cases in a month ranged from 4 t o 5 2 , with a mean of 18. The buys and seizures may or may not have constituted a representative sample of heroin available on the illicit retail market, but they were the best data available. The number of heroin overdose deaths each month was obtained from records of the Bexar County Medical Examiner’s office. Deaths from heroin overdose or acute narcotism-heroin were labeled “heroin reaction” by the Bexar County Medical Examiner’s staff, and only deaths so designated were tabulated. Criteria for diagnosis of heroin reaction as a cause of death during the study period emphasized pathological findings of a complete autopsy such as were suggested by Siegel, Helpern, and Ehrenreich [ 161 . Positive toxicology for opiates was not a requirement for the diagnosis.
FINDINGS We found frequent and marked fluctuations in the potency of heroin available to the consumer in San Antonio during the 5 years studied. As shown in Fig. 1, abrupt changes occurred from month to month. For example, the mean monthly dose of heroin in street packages changed from 16 mg in December 1975, to 51 mg in January 1976, to 42 mg in February, and t o 19 mg in March. The monthly mean dose varied from 9 to 110 mg. The mean dose of all street packages for the entire 5 years was 29 mg, the range 1 to 196 mg.
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DEATHS
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DESMOND, MADDUX, AND TREVINO
The monthly mean number of heroin reaction deaths was 1.7, the range 0 to 6. We found a small correlation, not statistically significant, between monthly dosage and frequency of death (r = t.13). Higher positive correlation between the two variables appeared in certain segments of time, such as the period February through October 1973 (r = t.92, p < .Ol) and the period April through December 1975 (r = t.50, N.S.). These are offset by briefer periods, such as January through March 1976, in w h c h there is a negative correlation between dose and death. As a measure of variability within monthly seizures, we computed the standard deviation of each month’s sample. Then we computed the coefficient of correlation between the monthly standard deviation and the monthly number of deaths. We obtained a coefficient of only slightly higher than that for mean dosage with deaths, not statistically significant (r = +.19, N.S.). We also considered another measure of variability, the maximum dosage in each month’s sample. The standard deviation is usually the preferred measure of variability, but because it can be influenced by values in either direction, it could have failed to identify those months in which unusually potent mixtures of heroin were available. The maximum dosage ranged from 19 mg in September 1974 to 196 mg in May 1972. Each month’s maximum dose was correlated with each month’s deaths. The resulting coefficient was slightly higher than either of the previous coefficients, but was not statistically significant (r = t.21, N.S.). The only evidence we found that variation in dosage may contribute to overdose deaths came from studying changes in heroin packaging practices. Prior t o 197 1, a degree of standardization existed in gross weight of retail units of heroin due to the widespread use of No. 5 gelatine capsules for packaging. The gross weight of the contents of these capsules rarely exceeded 60 mg. Due t o action of retail pharmacists in 1970, capsules became unavailable in San Antonio in 1971, and for a time street dealers resorted to wrapping the powder in paper, tinfoil, or cellophane. The years 1971-1972 were a transition era. During this period the “half-gram” packaged in a small rubber balloon became the usual retail unit. Most “half-grams’’ weighed less than 250 mg, but their weight varied considerably. The period 1971-1972 was one of instability, with some “half-grams” containing from 5 to 1 0 times as many milligrams of heroin as other units with the same nominal weight. By 1975, the balloons contained smaller but generally more uniform amounts of heroin mixture. Figure 2 shows the frequency of deaths attributed to heroin reaction in San Antonio during the years 1966 through 1976. As the figure shows, deaths during the 1971-1972 transition era were notably higher than those in the “capsule era,” and slightly higher than those
45
STREET HEROIN POTENCY AND DEATHS FROM OVERDOSE
Mean Annual Deafhs=23
Mean Annual Deaths = 8
30
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in the “balloon era.” We do not know what changes occurred in the size of the San Antonio addict population during this 11-year period. Probably some growth in the population at risk occurred during the transition period, but a nearly threefold increase, such as occurred in deaths during the transition period, is not likely.
DISCUSSION In marked contrast t o the studies in Washington, D.C. and Atlanta, we found no statistically significant correlation between the monthly mean dose of heroin in street samples and heroin overdose deaths. We also found no significant correlation between the variability of dose and deaths, and no significant correlation between monthly maximum dose and deaths. A pronounced increase in deaths during 1971-1972 may have been associated with instability of dose of street heroin, but the evidence is circumstantial. Consequently we attribute few of the overdose deaths in San Antonio to unexpected variations in the potency of street heroin.
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DESMOND, MADDUX, AND TREVINO
Studies in the United Kingdom also suggest that unexpected variations in dose may have minor importance. Overdose is a common cause of death among British addicts [17], and their mortality rate has been described as higher than that of United States addicts [18, 191. British addicts use larger amounts of heroin than most United States addicts, but heroin is prescribed, and many addicts know the amount they are taking. There is an unstated assumption in this study, and perhaps in other studies cited, that United States heroin users are totally ignorant of the quality of the heroin they buy. We feel this assumption needs to be reevaluated for the following reasons. First, most addicts do not frequently buy drugs from complete strangers. They often know their dealer and know his merchandise. In San Antonio the dealer is frequently a heroin user himself. Second, any misrepresentation of the quality of heroin offered by dealers would usually occur in a way that would reduce probability of overdose rather than enhance it. A dealer would be more likely to exaggerate the potency of h s heroin rather than minimize it. And finally, heroin is frequently shared, and has thus been tested by one or more individuals in a group. We speculate that these procedures, and probably others, are commonly employed by heroin addicts to protect themselves from overdose, and act to modify the impact of wide variations in potency of heroin available at the street level. As we have noted, the minimal lethal dosage of heroin in man has not been established. Huber, Stivers, and Howard [20] considered 20 mg of heroin to be potentially lethal for nontolerant individuals, and Gardner [ 171 reported one death attributed to a dose of 20 mg. Earlier estimates of minimum lethal dose as high as 200 to 500 mg have been reported [2]. We doubt that 20 mg is frequently lethal. If this were so, death from overdose would probably be pandemic among the heroin users of San Antonio because the mean heroin content of retail packages was 29 mg during the 5 years we studied. The low correlation between dose and deaths in San Antonio highlights the need to investigate the role of other factors in these fatalities, especially that of alcohol and similar CNS depressants. Two additional factors, suicide and lack of tolerance, may also contribute notably to heroin overdose deaths. Heroin overdose deaths among heroin users are rarely ruled suicide unless unequivocal evidence is found to indicate that this was the decedent’s intention. The Bexar County Medical Examiner ruled suicide in none of the deaths we studied in San Antonio. However, some investigators have suggested that the frequency of suicide among addicts may be underreported in medical examiner’s data. Mason, in a study of mortality in young New York City addicts [21], found that only two of 74 deaths were labeled suicide, but he
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STREET HEROIN POTENCY AND DEATHS FROM OVERDOSE
47
commented, “It is quite possible that more suicides have occurred without being recognized as such.” In an evaluation of a national sample of 853 narcotic-involved deaths, Gottschalk and McGuire [22] reported that only 2% were listed as “definitely suicide,” but 25% were thought “possible suicide,” and another 19% were considered “suspicious.” Unpublished data from our study of careers of San Antonio opioid drug users also support the notion that suicide may often go officially unrecognized in cases of drug overdose. Six of 23 deaths which occurred among 246 addicts within a 10-year beriod were caused by overdose according to death certificates: Only one was ruled suicide (a note was left). In three other cases a person close to the decedent told our research interviewer that the subject had been despondent and may have committed suicide. Thus four out of six overdose deaths in this sample may have been due to suicide. If suicide is an important element in heroin overdose death, it would help to explain the low correlation between potency of available heroin and deaths. We feel that this question needs further study. Several studies of mortality among opioid addicts have indicated that lack of tolerance to the respiratory depressant effects of opioid drugs contributed to the frequency of death from overdose. Gardner [I71 found that 55% of “accidental overdose” deaths among a group of 47 British addicts occurred shortly after a period of opioid abstinence. Abstinence usually began in an institution. Greene, Luke, and DuPont [I21 stated that lack of tolerance was “documented” in 5 1% of the fatalities they studied in Washington, D.C. We do not know how many of the subjects of this study lacked tolerance before death, but we do know that San Antonio addicts were entering and leaving treatment much more often during most of the study period than before. In a previous study [23] we obtained a census of the number of heroin users in institutional treatment in San Antonio during 10 years, 1965-1974. During the 5-year period 1965-1969, a mean of 20 were in treatment; during the 5-year period 1970-1974, a mean of 80 were in treatment. Patients maintained on methadone are not included in these totals. This increase in availability and utilization of institutional treatment quite likely resulted in additional periods of low or no tolerance for opioid drugs, and greater suspectibility to overdose. As shown in Fig. 2, the annual number of deaths increased markedly after 1970. The data suggest that the use of heroin overdose deaths as an indicator of the prevalence of heroin use should not be abandoned, at least not because of a belief that these deaths are more closely related to drug potency than to the number of users. Considering the multiple, diverse factors which probably
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DESMOND, MADDUX, AND TREVINO
contribute to overdose deaths, we are tempted to describe them as nearly random phenomena. It is not surprising that, as Greene [ 6 ] has noted, prevalence estimates using overdose-multiplier formulas have yielded results remarkably similar to those of other, more sophisticated methods. In summary, our findings neither confirm nor refute the pharmacologic overdose hypothesis of death. We believe that heroin overdose deaths may best be understood by studying not only the pharmacologic properties of the drug itself, but the social context of heroin addiction and the psychosocial characteristics of heroin users as well. We recommend further investigation of the roles of alcohol and other depressants, suicide, and lack of tolerance in heroin overdose deaths.
ACKNOWLEDGMENTS This study was supported in part by Grant No. DA 00083 from the National Institute on Drug Abuse. The authors wish to thank Ruben C. Santos, M.D., Bexar County Medical Examiner, and Donald R. Krueger of the San Antonio-Bexar County Regional Crime Laboratory for providing the data on overdose deaths and heroin samples.
REFERENCES Reynolds, A. K., and Randall, L. O., Morphine and Allied Drugs, University of Toronto Press, Toronto, 1957, pp. 176-177. Brecher, E. M. (ed.), Licit and Zllicit Drugs, Consumers Union, Mount Vernon, New York, 1972, pp. 101-114. Helpern, M., and Rho, Y., Deaths from narcotism in New York City. N. Y. State J. Med. 66:2391-2408 (1966). Louria, D. B., Hensle, T., and Rose, J., The major medical complications of heroin addiction, Ann. Intern. Med. 67: 1-22 (1967). Hunt, L. G., Prevalence of active heroin use in the United States, in The Epidemiology of Heroin and Other Narcotics (J. D. Rittenhouse, ed.), Stanford Research Institute, Menlo Park, California, 1976, p. 36. Greene, M. H., Estimating the Prevalence of Heroin Use in a Community, Special Action Office for Drug Abuse Prevention, Washington, D.C., 1974, p. 6. Duberstein, J. L., and Kaufman, D. M., A clinical study of an epidemic of heroin intoxication and heroin-induced pulmonary edema, Am. J. Med. 51:704-714
(1971). Cherubin, C., et al., The epidemiology of death in narcotic addicts, Am. J. Epidemiol. 96:ll-22 (1972). Force, E. E., Fisher, R. S., and Millar, J. W., Epidemiological and ecological study of risk factors for narcotics overdose, Arch. Environ. Health 26:111-119 (1973). Stimmel, B., et al., Electrocardiographic changes in heroin, methadone, and multiple drug abuse, in Proceedings of the 5th National Conference on Methadone Treatment, National Association for the Prevention of Addiction to Narcotics, New York, 1972, pp. 706-710.
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Garriott, J. C., and Sturner, W. Q., Morphine concentrations and survival periods in acute heroin fatalities, N. Engl. J. Med. 289:1276-1278 (1973). Greene, M. H., Luke, J. L., and DuPont, R. L., Opiate “overdose” deaths in the District of Columbia. I: Heroin-related fatalities, Med. Ann. D.C.43: 175-181 (1974). 131 Alexander, M., Surveillance of heroin-related deaths in Atlanta, 1971 to 1973, J. A m . Med. Assoc., 229~677-678,1974. 141 Huber, D. H., Heroin deaths-Mystery or overdose?, J. Am. Med. Assoc. 229:689690 (1974). 151 Greene, M. H., Kozel, N. J., and Appletree, R. L., A n Epidemiologic Study of Heroin Use Patterns and Trends in Four Cities on the Mexican-American Border, Special Action Office for Drug Abuse Prevention, Washington, D.C., 1975. Siegel, H., Helpern, M.,and Ehrenreich, T., The diagnosis of death from intravenous narcotism, J. Forensic Sci. 2:l-16 (1966). Gardner, R., Deaths in United Kingdom opioid users 1965-69, Lancet 1:650-653 (19 70). James, I. P., Suicide and mortality amongst heroin addicts in Britain, Er. J. Addict. 62:391, 398 (1976). Bewley, T. H., Ben-Arie, O., and James, I. P., Morbidity and mortality from heroin dependence, Br. Med. J. 1:725-732 (1968). Huber, D. H., Stivers, R. R., and Howard, L. B., Heroin-overdose in deaths in Atlanta: An epidemic, J. A m . Med. Assoc. 228:319-322 (1974). Mason, P., Mortality among young narcotic addicts, J. Mt. Sinai Hosp. 34:4-9 (1967). Gottschalk, L. A., and McGuire, F. L., Psychosocial and biomedical aspects of deaths associated with heroin and other narcotics, in The Epidemiology of Heroin and Other Narcotics (J. Rittenhouse, ed.), Stanford Research Institute, Menlo Park, California, 1976, pp. 77-81. Maddux, J. F., and Desmond, D. P., Crime and treatment of heroin users, To be published in International Journal of the Addictions,
