Comparison of serum and urine lead levels in opium addicts with healthy control group

Abstract

Context:

Lead-contaminated opium is one of the new sources of lead exposure in our region. As far as the literature review is concerned, there are limited comparative studies about comparison of blood lead level (BLL) in addict patients with healthy controls.

Objective:

We aimed to compare BLL and urine lead level (ULL) between opium addicts with the healthy control group.

Materials and Methods:

Forty opium addict subjects (mean age: 43 ± 10 years) as the patient group and 40 healthy subjects (mean age: 41 ± 9 years) as the control group participated. Three milliliter of whole blood and urine was obtained from both groups and lead level was assessed using atomic absorption spectrophotometry.

Results:

The mean value of BLL in patient group was 7.14 ± 1.41 mcg/dL and that in the healthy control group was 5.42 ± 1.46 mcg/dL. The mean value of ULL was 2.62 ± 0.83 mcg/dL in the patient group and 2.50 ± 0.76 mcg/dL in the healthy control group.

BLL was different in the two groups (p < 0.001), but ULL was not (p = 0.5). There was a significant correlation between BLL with duration of opium addiction in the patient group (r = −0.403, p = 0.01). BLL and ULL were significantly correlated in controls (r = 0.436, p = 0.005) and not in patients.

Discussion and conclusion:

It was observed that the BLL in opium addicts was significantly higher than that in the healthy control group. This can be due to use of adulterated opium with lead. Therefore, screening of blood lead concentration is helpful for opium-addict patients especially with nonspecific symptoms.

Introduction

Lead as a heavy metal is a cause for acute and chronic toxicity. ¹ Exposure to different sources of lead including burning fossil fuels, mining, industrial emissions, and contaminated foods through ingestion, inhalation, or dermal contact can cause significant toxicity. ² Some studies have evaluated blood lead levels (BLLs) in bus drivers, copy center workers, and paint factory employees, all of which had significantly higher BLL than control groups. ^3,4

Lead toxicity may have nonspecific manifestations such as nonspecific abdominal pain, constipation, decreased libido, irritability, myalgia, headache, and so on. Besides, lead may cause irreversible neurological damages as well as renal disease, coronary artery disease, and reproductive toxicity. The nonspecific abdominal pain in these patients can be misdiagnosed with acute abdomen, cholecystitis, and pancreatitis. Eventually several unnecessary gastrointestinal evaluation or even surgery may be done. ¹

In recent years, the incidence of adult lead poisoning has declined due to work safety rules, but lead poisoning in opium addicts due to raw opium impurities is one of the major health problems in Middle East countries such as Iran. It has been hypothesized that salesmen and smugglers may add lead to opium to increase its weight for more profit. ⁵ Lead poisoning during heroin addiction and lead toxicity from self-injection of lead and opium have been previously reported. ^6,7

Drug abuse and, especially, opium addiction is one of the most prevalent forms of addiction in countries such as Iran. ⁸ Some studies have reported nonspecific symptoms similar to lead poisoning in opium addicts, which suggests the presence of lead in opium. However, very few studies have been done about this issue in Iran. This study compares the presence and concentration of lead level in serum and urine samples of opium addicts and a control group.

Methods

In this analytical cross-sectional study, 40 opium-addict subjects between 18 and 65 years of age participated as the patient group, and 40 healthy subjects in the same range of age were included as the control group. Patients were selected with a convenient method from subjects who referred to Imam Reza (p) Rehabilitation Center for outpatient opium detoxification. These patients had a history of opium usage (oral or inhalation) for at least 3 years. The control group comprised of patients’ nonaddict family members to reduce the selection bias. These two groups were individually matched according to age, gender, and socioeconomic condition. History of lead poisoning and known occupational contact with lead (e.g. plumber, pottery, solder, battery making, and painting) were considered as exclusion criteria.

During a 6-month period of study, 80 subjects filled the informed consent and demographic information and opium abuse pattern were gathered. For lead-level assay, 3 mL of whole blood and 10 mL of urine were obtained from both groups and lead level was assessed using atomic absorption spectrophotometry (Perkin-Elmer model 3030, Waltham, Massachusetts, USA) in the central toxicology laboratory of Imam Reza Hospital, Iran. For this evaluation, nitric acid was added to blood sample to make a clot. The clot was condensed through a 2500r/min centrifugation and the final sample was obtained from the upper liquid phase. The heating schedule was 120°C for drying, 400°C for extraction of organic solvents, 800°C for extraction of inorganic solvents, and 2000°C for atomization temperature. The evaluation was performed in 283.3 nm wavelength in argon gas (99.99%).

At the end of study, the results were available for the patients and diagnostic and therapeutic interventions (e.g. Peripheral Blood Smear (PBS), complete blood count, and X-ray of wrist and distal of femur) were suggested for individuals who had blood or ULLs above the threshold.

Informed consent was obtained from all patients prior to beginning of study. Ethical committee of Mashhad University of Medical Sciences had approved this study (MUMS-88713).

Data analysis was performed using statistical package for social sciences version 11.5. Significant level was considered as p < 0.05.

Results

Demographic

In total, 35 males and 5 females were included in each group. Mean (SD, min–max) age of cases was 43 (10, 27–62) years and 41 (9, 26–60) years in controls. The mean age for starting drug abuse was 25.1 (6, 13–45) years. The mean duration of opium abuse was 17 (10, 3–43) years. The patient group had a mean opium consumption of 4.3 (1.4, 2–7) g/day. Among cases, 24 (62%) used ingestion root and the rest smoked. The majority of cases (23 subjects, 58%) used the opium three times a day while the second rank was for four times a day (9 subjects, 23%). Only one subject (2%) had a drug abuse of once daily.

Lead levels

BLLs were 7.14 (1.41) µg/dl in cases and 5.42 (1.46) µg/dl in controls, which was significantly different (p < 0.001; Figure 1).

Figure 1.

Distribution of BLLs and ULLs (µg/dl) in cases and controls. BLL: blood lead level; ULL: urine lead level.

ULL was 2.62 (0.83) µg/dl in cases and 2.50 (0.76) µg/dl in controls. Their difference was not significant (Figure 1).

BLL but not ULL was significantly correlated with duration of opium consumption (r = −0.403, p = 0.01). Age was significantly correlated with BLL (r = −0.380, p = 0.016) but not with ULL.

BLL and ULL were not different according to root, dose, and intermittency of consumption. Also, blood and ULLs were not statistically different in two genders.

BLL to ULL ratio was 3.1(1.3) in cases and 2.3(0.7) in controls, which had a significant difference between two groups (p = 0.001). This ratio was not statistically different in two genders.

BLL and ULL were significantly correlated in controls (r = 0.436, p = 0.005) but not in cases. (Figure 2(a) and (b))

Figure 2.

Correlation of BLLs and ULLs in (a) cases and (b) controls. BLL: blood lead level; ULL: urine lead level.

Discussion

Opium abuse is common in Iran. ⁹ In this study, we showed that BLL was significantly higher in opium addicts compared to control group. This is congruent with previous studies in Iran (1, 5). Moreover it has been previously reported that illicit drugs are contaminated with steroids and thallium. ¹⁰ A previously published case report from Mashhad Rehabilitation Center has discussed the possibility of lead toxicity in an overdosed opium-addict patient. ¹¹ Some studies have showed that nonspecific signs and symptoms including abdominal pain, neuropathy, and anemia have been alleviated by specific treatment for lead toxicity in opium addicts. ^{1,12 –14}

Above all, it is shown that higher lead levels (not always leading to toxicity) ¹¹ are not limited to reported cases. ¹⁵ The mean BLL was higher in a sample of opium addicts referred to Imam Reza Rehabilitation Center. A hypothesis is that somewhere in the chain of farm to customer, other substances may be added to illicit drugs, including raw opium. This addition is for gaining more profit so that drug dealers choose heavy metals like lead.

We did not find a significant difference in ULL between cases and controls, which could be due to lower secretion of lead in urine in chronic addicts with high sedimentation of lead in the bones. ¹⁶ It seems that ULL is not a good measure for evaluating the patients’ lead level. There was a significant correlation between the duration of opium consumption and BLL, which is inconsistent with the findings of previous studies in which the absence of this correlation was explained by short half-life of lead in blood. ^1,17,18

Although some studies have suggested a higher bioavailability of lead when using inhalation method, but similar to previous studies done in Iran, we did not find a correlation between the method of consumption and BLL. ^1,5,19

Although we did not find a relation between dose of opium and lead level, however, one study had previously reported this relation. ¹ This could be due to different methods for data collection or even a not precise estimation of consumption dose reported by addicts.

Normal lead levels are different in each region. For example, in Tehran 12.3, Australia 10, New York 1.7, and in Pakistan 13.9 are considered as normal lead levels. However, we did not find a toxic level in our sample.

So, nonspecific lead toxicity signs and symptoms should be considered in opium addicts in any emergency room or ward. Besides, we suggest that a revision in medical educational curriculum should be considered in order to cover important topics in addiction. This is especially important in regions in which illicit drug abuse is common. ²⁰ As Afghanistan is the east neighbor of our country, this revision may be much needed in Mashhad and Zahedan University of Medical Sciences.

One of the limitations of our study was the finding of matched controls. Because of lower socio-cultural status of opium addicts, even explaining the simplest objectives of the study was quite difficult. Besides we have just evaluated lead toxicity in opium addicts while other contaminations could be present in opium that need further study. However, this type of study was not done before in Mashhad. Now there is a base study to start taking bigger samples, which are more representative of the whole addicts’ population.

Conclusion

Opium impurities are complex and lead is one of them. It is essential to consider all possible diagnosis – including chronic toxicity – and request proper laboratory exams. Also, performing such studies on different samples obtained from different drug dealers may be of interest.