Change in Blood Lead Concentration up to 1 Year after a Gunshot Wound with a Retained Bullet

Joseph L. McQuirter1, Stephen J. Rothenberg2,3,4 , Gracie A. Dinkins5, Vladislav Kondrashov2,4, Mario Manalo2,4 and Andrew C. Todd6

1 Department of Oral and Maxillofacial Surgery, Charles R. Drew University of Medicine and Science, Los Angeles, CA.
2 Drew Environmental Research Center, Charles R. Drew University of Medicine and Science, Los Angeles, CA.
3 Center for Research in Population Health, National Institute of Public Health, Cuernavaca, Mexico.
4 Department of Anesthesia, Charles R. Drew University of Medicine and Science, Los Angeles, CA.
5 Department of Surgery, Charles R. Drew University of Medicine and Science, Los Angeles, CA.
6 Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY.

Received for publication December 17, 2002; accepted for publication October 14, 2003.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The authors studied the time course and prevalence of elevated blood lead concentrations and associated injury- and patient-specific factors during the first year following gunshot injury. They determined blood lead levels at mean time points of 0.3, 3.1, 18.7, 94.5, 188.3, and 349.4 days after injury in a volunteer sample of 451 subjects from a Los Angeles, California, trauma center who sustained a first-time gunshot injury with a retained projectile in 2000–2002. In mixed-model analyses, blood lead levels increased with time postinjury (p < 0.0005) up to 3 months, with number of retained fragments (p < 0.0005), and with increasing age (p < 0.0005). Increased blood lead concentration as a function of fragmentation was approximately 30% higher among subjects who had suffered bone fracture in the torso (p < 0.0005). Subjects with bullets or fragments lodged near bone (p < 0.0005) or near joints (p = 0.032) had higher blood lead levels. Logistic models correctly predicted a blood lead elevation of >=20 µg/dl in 81% and 85% of subjects at 3 and 6 months postinjury, respectively. The prevalence of elevated blood lead was 11.8% at 3 months and 2.6% at 12 months. The authors recommend continued surveillance of blood lead levels after gunshot injury for patients with key indicators.

firearms; lead; lead poisoning; wounds and injuries; wounds, gunshot


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The remarkable nationwide reduction in US blood lead concentrations is one of the public health success stories of the past several decades. Successive National Health and Nutrition Examination Surveys have shown a nationwide decrease in the population mean blood lead level from 12.8 µg/dl in the 1970s (1) to 2.3 µg/dl in the 1990s (2). Minimization of exposure to various sources of lead, such as deteriorated leaded paint in old homes, soil and air lead from automobile exhaust, certain home remedies (e.g., azarcon and greta), and cookware containing lead, has played a major role in this downward trend. Only certain segments of the population, notably children from large inner-city areas, remain within the range of concern of the Centers for Disease Control and Prevention.

There has been little study of the lead-related aspects of firearm injuries resulting in retained bullets. The incidence of firearm injuries, though declining since its peak in the early 1990s, still remains at epidemic levels. A study using a stratified sample of reporting hospital emergency rooms estimated that there were more than 475,000 nonfatal firearm-related injuries in the United States in the 6 years between 1993 and 1998 (3).

However, fewer than 100 cases of lead toxicity in patients with retained bullets have been reported in the medical literature, because the onset of symptoms is insidious and a high level of suspicion is needed to prompt testing. These cases demonstrate lead-induced toxicity ranging from joint deterioration to death, sometimes as long as decades after the injury. Such cases come to medical attention only because presenting symptoms disable the patient, but even then lead toxicity is not always immediately suspected by treating physicians. Therefore, we are largely ignorant of the percentage of gunshot victims with retained projectiles whose subclinical and clinical lead intoxication is not diagnosed. Also little studied are the conditions associated with undetected elevated blood lead levels in such patients. Some of our pilot work examining 28 gunshot patients with retained bullets followed for 9 months after injury suggested that bullet fragmentation and bone fracture contributed to elevated blood lead concentrations (4). Reviews of published case studies on gunshot wounds emphasize the critical features of cases that eventually come to the attention of clinicians: fragmentation, a bullet embedded in a bone or joint, and associated inflammatory disease (510). A recent series of three cases involving head, face, and neck wounds also implicated swallowed bullets and fragments in the rapid increase of blood lead levels, followed by a months-long decline after elimination of the material from the gastrointestinal tract (11).

The goal of this analysis was to determine subject- and injury-specific factors that would allow prediction of change in blood lead concentration over time after a gunshot injury, thus helping to identify patients requiring careful postinjury monitoring. Here we report the results of a prospective cohort study in which blood lead levels were measured repeatedly in 451 surviving gunshot patients with retained projectiles over the first 12 months postinjury.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
We recruited 502 subjects with gunshot injuries and retained bullets or fragments who received care at the King-Drew Medical Center in south-central Los Angeles, California, between mid-December 2000 and December 2002. Patients with a prior history of gunshot injury with a retained bullet, patients with no retained bullets or fragments, pregnant women in the first two trimesters of pregnancy, children under 7 years of age, and persons who were unable to give informed consent were excluded from the study.

The institutional review board of the King-Drew Medical Center approved the study protocol, and written informed consent was given by each study participant.

Data collection
Blood lead measurements
Blood lead concentration was measured via graphite furnace atomic absorption spectrometry, using Zeeman background correction (12). Blood lead measurements were taken at admission from remnants of clinical blood draws (number of days postinjury: range, 0–2 days; mean = 0.3 days); at the time of informed consent (range, 3–17 days; mean = 3.1 days); and at approximately 3 weeks postinjury (range, 18–45 days; mean = 18.9 days), 3 months postinjury (range, 46–144 days; mean = 94.4 days), 6 months postinjury (range, 147–288 days; mean = 188.3 days), and 12 months postinjury (range, 309–440 days; mean = 349.4 days). A smaller set of subjects was followed to 18 months (range, 480–640 days; mean = 544.9 days) and 24 months (range, 642–758 days; mean = 713.8 days) postinjury.

The blood lead laboratory used in the study has successfully participated in the College of American Pathologists and Centers for Disease Control and Prevention (now administered by the state of Wisconsin) quality assurance programs for more than 6 years, with no out-of-limits blood lead measurements. The laboratory has also been registered as an approved blood lead testing facility by the Occupational Safety and Health Administration and has Clinical Laboratories Improvement Act laboratory certification of compliance. Quality control data have been published elsewhere (13).

Bone lead measurements
In vivo bone lead concentration was measured in study subjects at the time of the 3-week blood lead determination via K-shell X-ray fluorescence (14). Bone lead measurements were made at the mediolateral and proximodistal midpoint of the anterior right tibia diaphysis and at the lateral surface of the right calcaneus. Estimated levels of bone lead were calculated from X-ray fluorescence spectra using the recently corrected formulation (15). Because of measurement error, estimates of bone lead concentration are sometimes negative, especially when the true bone lead level approaches zero. Bone lead slowly accumulates during a person’s lifetime (16), with residence times for calcaneus and tibia bone lead being estimated at 11–29 years (95 percent confidence interval) and 16–98 years (95 percent confidence interval), respectively (17). Thus, measurement of bone lead within the first 2 months of injury effectively provides an estimate of the subject’s cumulative past exposure prior to the gunshot injury.

Medical radiographs
We reviewed radiographs of all injury sites to identify the presence of retained bullet fragments, associated bony fracture, fragmentation and deformation of the bullet, penetration path of the bullet, and the proximity of bullets and/or fragments to bone, spine, or joint spaces. We also reviewed all clinical radiographs taken on follow-up visits to determine any dispersion or migration of the retained bullet fragments, to detect signs of associated pathology (cysts, proliferative or degenerative diseases, infections, etc.), and to evaluate the status of bony healing in cases where fracture was sustained.

Health and risk questionnaires
We administered structured questionnaires to obtain demographic and medical information and to determine risk factors for lead exposure (13).

Hospital medical records
We reviewed medical records to confirm the number of gunshot injuries sustained, whether the projectile(s) had been retained, findings of bone fractures, wound complications, and any procedures undertaken for the removal of the projectile(s).

Statistical analysis
We used a linear mixed model (SPSS; SPSS, Inc., Chicago, Illinois) to analyze injury and subject characteristics associated with changes in blood lead with time after injury. Mixed-model analyses allow modeling of the variance-covariance structure among repeated measures of blood lead; use of variables (e.g., number of days postinjury for each stage) whose values change for each subject according to the different stages of the protocol; and inclusion of subjects with incomplete blood lead data over the six stages. We used a model with an unstructured covariance structure of blood lead, since it provided the best model of the covariance structure of repeated blood lead results measured by the Akaike (18) and Bozdogan (19) information criteria and by examination of the covariance matrix. Number of days postinjury, number of bullet fragments, and calcaneus and tibia bone lead levels were modeled as random-effects variables. The remaining variables were modeled as fixed-effects variables. We allowed nonlinear terms for "days postinjury" to model the nonlinear relation between postinjury time and blood lead level.

We used several versions of logistic regression analysis (Stata; Stata Corporation, College Station, Texas) to determine the injury and subject characteristics associated with blood lead levels greater than or equal to 20 µg/dl at 3 and 6 months postinjury and with blood lead levels greater than or equal to 10 µg/dl at 12 months postinjury (there were too few cases with blood lead levels greater than or equal to 20 µg/dl to model at 12 months). Ordinary logistic regression (logit) produces biased estimates and standard errors when the prevalence of the outcome of interest is low; therefore, we present results from robust logistic regression, which provides corrected values and more accurate estimates and standard errors when prevalence is below 50 percent (20, 21). Number of days around the target measurement day was added to each model as a centered continuous variable. We calculated logit model sensitivities and specificities by setting the cutoff probabilities to the posterior probabilities of exceeding the criterion blood lead level at each time point. All models satisfied required statistical assumptions. Results of Hosmer-Lemeshow chi-squared tests were insignificant for all logit models, indicating a good fit of data to the models.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Table 1 shows summary statistics for the study subjects. Most subjects were African-American males under age 30 years, with a substantial minority (26.8 percent) being Latino; 20.6 percent of all subjects were aged 18 years or less, and 2.4 percent were over age 50. The geometric mean blood lead concentration at admission (an average of 0.3 days postinjury) was 1.9 µg/dl, approximately the expected national population mean. There were no significant differences in sex, age, or blood lead level at admission between omitted subjects and subjects used in the analyses. The wounding weapons involved in the gunshot injuries were handguns (95.6 percent), shotguns (3.2 percent), and rifles (1.2 percent).


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TABLE 1. Characteristics of subjects with gunshot wounds involving retained bullets, King-Drew Medical Center, Los Angeles, California, 2000–2002
 
The prevalence of blood lead levels elevated to >=10 µg/dl and >=20 µg/dl increased with time after injury, from 2.1 percent and 0.2 percent, respectively, at admission, to maxima of 38.1 percent and 11.8 percent at 3 months (table 2). Prevalence slowly declined to 20.1 percent and 2.6 percent at 12 months. The limited amount of data available at 18 and 24 months postinjury suggests that the 12-month prevalences may represent longer-term prevalences (table 2).


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TABLE 2. Prevalence of a blood lead concentration exceeding criterion limits as a function of time after injury among gunshot victims, King-Drew Medical Center, Los Angeles, California, 2000–2002
 
The mixed-model analysis (table 3) showed that blood lead concentration for the group increased significantly (p < 0.0005) with time after injury (days postinjury); the significant (p < 0.0005) negative quadratic term, days postinjury squared, indicated lower blood lead levels after 3 months (figure 1). Subjects who had bullets or fragments lodged near a bone had 32 percent higher blood lead levels than subjects who did not (p < 0.0005). Subjects who had bullets or fragments in or near a joint had 17.0 percent higher blood lead levels than subjects who did not (p = 0.032). Both increasing age and increasing number of retained fragments were associated with increased blood lead levels (p < 0.0005) over the ranges of 9–70 years (2.0 natural log years) and 1–228 fragments (5.4 natural log fragments). Blood lead level marginally increased 4.5 percent for every additional 10 µg/g of calcaneus lead over the >80-µg/g calcaneus lead range of –21.3 µg/g to 63.0 µg/g (p = 0.060) measured at 18 days postinjury. Blood lead increase as a function of fragmentation was 11.3 percent higher in males than in females (p = 0.016) and 29.5 percent higher in subjects with a torso bone fracture (chest, abdomen, and pelvic regions) than in subjects without such a fracture (p < 0.0005) (figure 2), for each natural-log increase in the number of fragments. There was no effect of tibia lead or ethnicity on blood lead levels in the mixed-model analysis.


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TABLE 3. Natural log of blood lead concentration (µg/dl)* through 12 months postinjury among gunshot victims (n = 451), King-Drew Medical Center, Los Angeles, California, 2000–2002
 


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FIGURE 1. Measured blood lead concentration as a function of time after injury in 451 gunshot victims, King-Drew Medical Center, Los Angeles, California, 2000–2002. The curved line is a LOWESS smoothed regression showing that for the group as a whole, the peak blood lead level is reached approximately 90 days after injury and then decreases for the remainder of the year. Note the rapid increase in blood lead concentration over the first 25 days postinjury and the higher outlying points throughout the duration displayed. Conversion factor: 10 µg/dl = 0.483 µmol/liter.

 


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FIGURE 2. Estimated blood lead concentration as a function of the number of retained bullet fragments and the presence or absence of torso bone fracture (chest, abdomen, or pelvis) in 451 gunshot victims (mixed-model analysis), King-Drew Medical Center, Los Angeles, California, 2000–2002. The plotted functions are displayed at the maximum number of fragments encountered. Open circles, torso fracture (maximum no. of fragments = 188); filled circles, no torso fracture (maximum no. of fragments = 228). Bars, 95% confidence interval. Confidence intervals are asymmetric about the mean values, since the dependent variable in the mixed model was natural log blood lead concentration. Conversion factor: 10 µg/dl = 0.483 µmol/liter.

 
There were three factors that, in conjunction, predicted elevated blood lead levels in the logit models at 3, 6, and 12 months (table 4): number of fragments (a highly significant predictor either alone or in combination with other factors; increasing fragmentation was always associated with significant odds of a blood lead level greater than or equal to the criterion level throughout the study), torso bone fracture, and bullets or fragments in the humerus.


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TABLE 4. Odds of reaching or exceeding criterion blood lead concentrations at 3, 6, and 12 months after gunshot injury with a retained bullet in logistic regression analyses, King-Drew Medical Center, Los Angeles, California, 2000–2002
 
Head, face, and neck bone fractures, along with increasing age and weapon type, were associated with significant odds of a blood lead level >=20 µg/dl at 3 months. At 6 months, bullets near joints and the interaction between torso fracture and calcaneus bone lead were associated with significant odds of blood lead >=20 µg/dl. Bullets or fragments near bone were significantly associated with odds of blood lead >=10 µg/dl at 12 months. At 12 months, both tibia and calcaneus bone lead were also significantly related to exceeding the criterion level of blood lead—although, because the bone lead measurements were contemporaneous with the blood lead measurements, they might not be considered predictors of blood lead. Females had lower odds of blood lead >=20 µg/dl than males at 3 and 6 months, but there was no significant effect of sex on reaching or exceeding a level of 10 µg/dl at 12 months. There were no significant effects of ethnicity in any of the logit models.

Changes in the position or number of bullets or fragments were not noted in follow-up radiographs.

Figure 3 shows change in blood lead level over time for two cases whose blood lead levels remained high up to and beyond 12 months postinjury.



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FIGURE 3. Measured blood lead concentration as a function of days after injury in two gunshot victims, King-Drew Medical Center, Los Angeles, California, 2000–2002. The filled circles show data for a married male African-American high school graduate aged 20 years. He was employed as a hospital worker and had no reported occupational or avocational lead exposure. He had two recorded wounds from a handgun, both in the femur, with a total of 33 fragments, all near fractured bone. At admission, his hemoglobin level was 13.4 g/dl and his hematocrit concentration was 39.4%. The open circles show data for a married male Latino high school graduate aged 21 years. He was employed at a liquid oxygen company with occasional soldering jobs. He had one recorded wound in the proximal humerus from a handgun, with a deformed bullet, a cloud of particles distal and proximal to the joint, and no fracture. At admission, his hemoglobin level was 14.7 g/dl and his hematocrit concentration was 42.1%. Conversion factor: 10 µg/dl = 0.483 µmol/liter.

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
These results replicate the limited, preexisting evidence in the case study literature reporting frank lead toxicity in patients with bullet fragmentation and bullets lodged in or near joints or bones, but at shorter times postinjury and much lower blood lead levels. Our results also point to other factors that predict increases in blood lead concentration at various times after injury up to 1 year, such as age, sex, and bone fracture.

Retained lead bullets are often fragmented (69.2 percent in this study), especially if the bullet ricocheted or struck hard tissues such as teeth or bone. Blood lead concentration increased with number of retained bullet fragments by 25.6 percent (95 percent confidence interval: 12.2, 39.0) for every natural-log increase in the number of fragments (from 1 to 2.7, 2.7 to 7.4, 7.4 to 20.1, etc.).

The bullets and shotgun pellets encountered most frequently by US civilian populations in urban areas are 50–100 percent lead (2225). As was seen in our study group, these bullets are typically made from a lead alloy or are clad bullets with a lead core. The outer material is made of a metal or alloy harder than lead (copper, nickel, steel, or aluminum). Copper-clad bullets with a tip or base of exposed lead are more commonly seen in gunshot injuries in urban areas (22). Fully clad rifle bullets used for big game hunting and in military weapons are less frequently seen in such a population, especially as a retained bullet in a surviving victim. The vast majority of shotgun injuries in our sample involved lead pellets; steel shot used for hunting waterfowl was rarely seen in the population studied. Fragmentation of lead bullets, originally clad or not, increases the surface area of lead in contact with tissues, which in turn increases the likelihood that lead will be absorbed and thus the chance that blood lead concentrations will increase to levels of clinical concern.

While bullet fragmentation per se leads to higher blood lead levels over time, when fragmentation is combined with torso bone fracture there is a further increase in blood lead of 29.5 percent for each natural-log unit increase in the number of fragments (see table 3 and figure 2). Another view of this effect is provided by the 3-month logit model (table 4). This model shows that the probability of having a blood lead level >=20 µg/dl as the number of retained fragments increases from 1 to 188 rises from 0.012 to 0.262 in cases without torso fracture (keeping all other variables at their mean values). In cases with torso fracture, the probability of a blood lead level >=20 µg/dl with an increasing number of fragments from 1 to 188 rises from 0.002 to 0.999.

The significant interaction between torso fracture and fragmentation has at least two possible origins. The torso contains several body cavities with mobile organs and a large extravascular fluid volume. Following a penetrating injury, lead fragments will be exposed to this large volume of extracellular fluids, including blood clots undergoing lysis, inflammatory exudates, occasional pus from these compound fracture wounds, and fluids from joints and pleural and bursal spaces located in the penetration path of the bullet. In such an environment, bullet fragments will have a greater chance of being absorbed, rather than encapsulated by scar tissue as is frequently seen with fragments embedded in muscle and bone. The development of cysts near joint spaces that contain finely dispersed lead fragments has been described in the literature (9, 10). Bone fragments associated with a fracture are reabsorbed during healing. During bone resorption, lead in bone fragments will be returned to blood circulation, as it is during physiologic bone resorption (26). Osteoclasts active in bone resorption (27) will be working in an environment containing bullet fragments with a high lead content. In vitro studies show that osteoclasts actively absorb lead (28) in lead-containing environments. In combination with the original lead content of the bone, such activity could lead to higher blood lead levels, principally in the first months after injury with fracture, when osteoclast activity is at its highest.

We note the marginally significant main effect of calcaneus bone lead in the mixed model (subjects with higher calcaneus lead at the start of the study tended to have higher blood lead levels throughout the study than subjects with lower calcaneus lead) as partial support for the thesis that resorbed bone fragments containing lead contribute to higher blood lead concentrations. Whether or not the calcaneus effect is due to continued release of lead from intact (29) or fragmented bone into blood circulation, it indicates that gunshot patients with retained bullets with higher past lead exposure will have higher blood lead levels after injury than such patients with lower past lead exposure.

The skeleton is the largest natural reservoir of lead in the adult body. An adult male skeleton containing 2.5–3.5 kg of bone mineral (30) with a bone lead concentration of 10 µg/g will contain 25–35 mg of lead. This compares with the 5,500 mg of lead in a typical 95-grain 0.38-caliber (9.56-mm) bullet with 90 percent lead content, a 160–220:1 ratio with the skeleton. Some of the bullet lead will be available for eventual absorption and redistribution to blood and bone.

Public health implications and clinical recommendations
The blood lead criteria of >=10 µg/dl and >=20 µg/dl may seem low by reference to the Occupational Safety and Health Administration standards (31), but they are well within the current Centers for Disease Control and Prevention guidelines for levels of concern in childhood lead exposure (32). More than 20 percent of our subjects were aged 18 years or younger. Furthermore, the current Occupational Safety and Health Administration lead regulations and guidelines were based only on research published through the mid-1970s and have not been revised in over 25 years. During that interval, a substantial body of literature has appeared indicating that there are health effects associated with blood lead levels less than 20 µg/dl in adults (3335). Given the sensitivity of the human fetus to very low levels of maternal blood lead, the current regulations and guidelines for adults are especially obsolete, since they do not protect women of childbearing age. The blood lead criteria used in our logit models have important public health implications—if not for all individual cases, then for populations—considering that an estimated 1–2 million residents of the United States are survivors of gunshot injuries with retained bullets, and tens of thousands are being added yearly. Since most case subjects in our sample were under 30 years of age at injury, the majority of surviving gunshot victims will be carrying an additional body burden of lead for 40 or more years, regardless of further reductions in environmental and occupational sources of lead that may occur.

Measured prevalence rates of 38.1 percent and 11.8 percent at 3 months postinjury for criterion blood lead levels of >=10 µg/dl and >=20 µg/dl, respectively, suggest the need for a number of surveillance and treatment procedures for gunshot patients with retained bullets. First, such patients should have a blood lead determination made at hospital admission for a baseline record. Second, they should have their blood lead level retested before discharge or within 2 weeks following injury. If the patient’s history indicates occupational or avocational exposure to lead, the patient should be counseled to avoid further exogenous lead exposure. Third, these patients should have their blood lead level retested at monthly intervals until 3 months postinjury and then tested again at 1 year postinjury. If there are limited resources available for blood lead testing, a special effort should be made to track all patients with one or more of the risk factors indicated by the logit models. Patients should be advised to obtain yearly blood lead determinations thereafter.

In gunshot victims with an elevated blood lead level, chelation will reduce blood lead concentration only temporarily, since the major source of lead exposure will remain in the body.

Because the probability of elevated blood lead increases with increased fragmentation, surgical removal of fragments in patients most likely to benefit from this procedure will be most difficult. Removal of bullets and fragments from joint spaces and bones, combined with chelation to reduce perioperative increases in blood lead, might be the most effective surgical procedure for reducing blood lead levels in such patients (36, 37). The treating physician should consult with qualified specialists to determine the risk-benefit ratio of surgical intervention for fragment removal, since tissue and organ damage due to surgery may well outweigh the known risks from elevated blood lead in individual patients.

All gunshot patients (including those without retained bullets or fragments observed at the injury site) with head, face, and neck injuries and a penetration path that includes the oral, nasal, or pharyngeal passageway should have chest and abdominal radiographs taken for determination of the presence of ingested or inhaled bullets or fragments. All particles remaining in the gastrointestinal tract for more than 48 hours should be removed using cathartics, bowel irrigation, or endoscopic procedures. Radiographs should be taken to confirm the successful removal of all lead particles (11).

In the absence of effective surgical intervention to remove bullet fragments, there are currently no treatment methods available for reducing blood lead levels in victims of gunshot wounds. Limited data on nutritional factors influencing blood lead levels are available only for ingested lead, not implanted lead. There has been almost no research into methods of reducing lead toxicity, as opposed to lead absorption, since the standard treatment for reducing elevated blood lead starts with separation of the patient from the exposure source (9, 38). Nevertheless, the substantial population at risk from retained bullets and the continued inadequate efforts to reduce such injuries suggest that research into toxicity reduction in the presence of elevated and irreducible blood lead levels may pay for itself in public health benefits. Continued surveillance of the present group of gunshot patients will both confirm the prevalence of elevated blood lead levels over the long term and identify characteristics associated with sustained elevations in blood lead.

Limitations of this study
Many of our subjects received blood volume expanders or packed red blood cells in the first hours after their arrival at the hospital. Incomplete hospital data on hemoglobin or hematocrit levels prevented correction of individual blood lead values for such dilution. Thus, blood lead concentrations may have been underestimated at admission (mean = 0.3 days postinjury) and at the time of informed consent (mean = 3.1 days postinjury). The rate of increase in blood lead during the first weeks after injury, as estimated by the mixed model, may have been overestimated; but the logit model results, starting at 3 months postinjury, should have been free of any error from this source.

Despite the 72–84 percent rate of correct classification by the logit models, the models incorrectly classified at least as many subjects as false-positive as correct-positive. Over half of the false-positive cases had blood lead levels approaching the criterion limit, but a substantial minority of false-positive cases had blood lead levels less than half those of the criterion limit. We cannot account for this proportion of false positives (subjects having some or all of the clinical and subject characteristics associated with significant variables in the model), but we were clearly not capturing all relevant variables in our models. Such "missing" variables might include variability in the lead content and metal alloy of bullets; variability in the volume and surface area of fragments; accurate measurement of the proximity of bullets and fragments to bones and joints using clinical radiographs (tomography would be a useful alternative radiographic technique); visualization of vascular density in the vicinity of bullets; and visualization and quantification of very fine bullet particles (sometimes visible as a hazy density around fragments in radiographs). Even with as many or more subjects identified as false positives as correctly classified, the models are useful in carrying out the surveillance recommendations noted above.

The high false-positive rate also draws attention to the weakness of models using a dichotomous outcome criterion instead of the full information available in the original blood lead variable. Although logit models provide information useful to clinicians in the form of risk factors with odds ratios, models such as the mixed model presented in table 3 may capture effects at blood lead levels too low for detection by the logit models. Inability to significantly detect critical defining characteristics is all the more likely for logit models when the prevalence of cases exceeding the criterion limits is substantially lower than 50 percent, especially for studies with small and moderate sample sizes. Finally, dichotomous-outcome models such as the logit model are unstable with small and moderate study sizes. Because the logit model with the largest number of subjects in this study had only 365 subjects, the results obtained should be considered provisional until replicated with an independent and preferably larger sample. Ongoing follow-up of these subjects will reveal factors associated with continuously or newly elevated blood lead levels and the ultimate long-term prevalence rate.


    ACKNOWLEDGMENTS
 
This study was supported in part by the National Institute of Environmental Health Sciences (grant ES10166), the Research Centers for Minority Institutions (grant RR03026), and the National Center for Research Resources (grant RR11145).

The authors thank Drs. Arthur Fleming, Janis Fay Goolsby-Owens, Calvin Johnson, Robert Morris (Orthopaedic Hospital, Los Angeles, California), Keith Norris, and Elerby R. Washington III of the study’s Clinical Advisory Committee. Located primarily at the King-Drew Medical Center in Los Angeles, California, the panel provided discussions that were useful in arriving at the presented recommendations for surveillance and treatment. The authors also thank the staff of the King-Drew Medical Center Pathology Department for their cooperation in preserving remnant blood samples of patients until informed consent could be obtained.


    NOTES
 
Reprint requests to Dr. Stephen Rothenberg, Center for Research in Population Health, National Institute of Public Health, Ave. Universidad 655, Sta. Ma. Ahuacatitlán, CP 06250 Cuernavaca, Mexico (e-mail: drlead{at}prodigy.net.mx). Back


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Pirkle JL, Brody DJ, Gunter EW, et al. The decline in blood lead levels in the United States: the National Health and Nutrition Examination Surveys (NHANES). JAMA 1994;272:284–91.[Abstract]
  2. Pirkle JL, Kaufmann RB, Brody DJ, et al. Exposure of the U.S. population to lead, 1991–1994. Environ Health Perspect 1998;106:745–50.[ISI][Medline]
  3. Gotsch KE, Annest JL, Mercy JA, et al. Surveillance for fatal and nonfatal firearm-related injuries—United States, 1993–1998. MMWR Morb Mortal Wkly Rep CDC Surveill Summ 2001;50:1–32.
  4. McQuirter JL, Rothenberg SJ, Dinkins GA, et al. The effects of retained lead bullets on body lead burden. J Trauma 2001;50:892–9.[ISI][Medline]
  5. Machle W. Lead absorption from bullets lodged in tissues: report of two cases. JAMA 1940;115:1536.
  6. Dillman RO, Crumb CK, Lidsky MJ. Lead poisoning from a gunshot wound: report of a case and review of the literature. Am J Med 1979;66:509–14.[ISI][Medline]
  7. Manton WI. Lead poisoning from gunshots—a five century heritage. J Toxicol Clin Toxicol 1994;32:387–9.[ISI][Medline]
  8. Magos L. Lead poisoning from retained lead projectiles: a critical review of case reports. Hum Exp Toxicol 1999;13:735–42.[CrossRef]
  9. Linden MA, Manton WI, Stewart RM, et al. Lead poisoning from retained bullets: pathogenesis, diagnosis, and management. Ann Surg 1982;195:305–13.[ISI][Medline]
  10. Senturia HR. The roentgen findings in increased lead absorption due to retained projectiles. AJR 1942;47:381–91.
  11. McQuirter JL, Rothenberg SJ, Dinkins GA, et al. Elevated blood lead resulting from maxillofacial gunshot injuries with lead ingestion. J Oral Maxillofac Surg 2003;61:593–603.[CrossRef][ISI][Medline]
  12. Fernandez F, Hilligoss D. An improved graphite furnace method for the determination of lead in blood using matrix modification and the L’vov platform. Atomic Spectrosc 1982;3:130–1.
  13. Rothenberg SJ, Manalo M, Jiang J, et al. Maternal blood lead level during pregnancy in south central Los Angeles. Arch Environ Health 1999;54:382–9.[ISI][Medline]
  14. Rothenberg SJ, Khan FA, Manalo MA, et al. Maternal bone lead contribution to blood lead during and after pregnancy. Environ Res 2000;82:81–90.[CrossRef][ISI][Medline]
  15. Chettle DR, Arnold ML, Aro AC, et al. An agreed statement on calculating lead concentration and uncertainty in XRF in vivo bone lead analysis. Appl Radiat Isot 2003;58:603–5.[CrossRef][ISI][Medline]
  16. Heard MJ, Chamberlain AC. Uptake of Pb by human skeleton and comparative metabolism of Pb and alkaline earth elements. Health Phys 1984;47:857–65.[ISI][Medline]
  17. Gerhardsson I, Attewell R, Chettle DR, et al. In vivo measurements of lead in bone in long-term exposed lead smelter workers. Arch Environ Health 1993;48:147–56.[ISI][Medline]
  18. Akaike H. A new look at the statistical model identification. IEEE Trans Automat Control 1973;19:716–23.
  19. Bozdogan H. Akaike’s Information Criterion and recent developments in information complexity. J Math Psychol 2000;44:62–91.[CrossRef][ISI][Medline]
  20. King G, Zeng L. Logistic regression in rare events data. Polit Anal 2001;9:137–63.
  21. Tomz M, King G, Zeng L. ReLogit: rare events logistic regression. Version 1.1. (Software). Available from Dr. Gary King, Harvard University, Boston, Massachusetts (http://gking.harvard.edu/).
  22. Teitelbaum GP, Yee CA, Van Horn DD, et al. Metallic ballistic fragments: MR imaging safety and artifacts. Radiology 1990;175:855–9.[Abstract]
  23. Matunas EA. Reloading handbook. 47th ed. Middlefield, CT: Lyman Products Corporation, 1997.
  24. Remington Arms Company. Remington Arms material safety data sheets. Madison, NC: Remington Arms Company, Inc. 2004. (World Wide Web URLs: http://www.remington.com/pdfs/msds/ssldcomp.pdf (shots and slugs); http://www.remington.com/pdfs/msds/bullets (bullets)).
  25. Winchester Ammunition. Olin Winchester ammunition material safety data sheets. East Alton, IL: Winchester Ammunition, 2004. (World Wide Web URLs: http://www.winchester.com/pdfs/msds_w65.pdf (bullets); http://www.winchester.com/pdfs/msds_w89.pdf (jacketed lead-core bullets); http://www.winchester.com/pdfs/msds_w77.pdf (shots and slugs)).
  26. Tsaih SW, Korrick S, Schwartz J, et al. Influence of bone resorption on mobilization of lead from bone among middle-aged and elderly men: The Normative Aging Study. Environ Health Perspect 2001;109:995–9.[ISI][Medline]
  27. Rousselle AV, Heymann D. Osteoclastic acidification pathways during bone resorption. Bone 2002;30:533–40.[CrossRef][ISI][Medline]
  28. Rosen JF. The metabolism of lead isolated bone cell populations: interactions between lead and calcium. Toxicol Appl Pharmacol 1983;71:101–12.[ISI][Medline]
  29. Tsiah SW, Schwartz J, Lee ML, et al. The independent contribution of bone and erythrocyte lead to urinary lead among middle-aged and elderly men: The Normative Aging Study. Environ Health Perspect 1999;107:391–6.
  30. Armstrong DW, Shakir KM, Drake AJ III. Dual x-ray absorptiometry total bone mineral content and bone mineral density in 18- to 22-year-old Caucasian men. Bone 2000;47:835–9.[CrossRef]
  31. Occupational Safety and Health Administration, US Department of Labor. Code of Federal Regulations. OSHA lead standard for general industry. 29 CFR, part 1910.1025. Washington, DC: Office of the Federal Register, US GPO, 1990.
  32. Centers for Disease Control and Prevention. Screening young children for lead poisoning: guidance for state and local public health officials. Atlanta, GA: Centers for Disease Control and Prevention, 1997.
  33. Muntner P, He J, Vupputuri S, et al. Blood lead and chronic kidney disease in the general United States population: results from NHANES III. Kidney Int 2003;63:1044–50.[CrossRef][ISI][Medline]
  34. Lin JL, Lin-Tan DT, Hsu KH, et al. Environmental lead exposure and progression of chronic renal disease in patients without diabetes. N Engl J Med 2003;348:277–86.[Abstract/Free Full Text]
  35. Vupputuri S, He J, Muntner P, et al. Blood lead level is associated with elevated blood pressure in blacks. Hypertension 2003;41:463–8.[Abstract/Free Full Text]
  36. Meggs WJ, Gerr F, Aly MH, et al. The treatment of lead poisoning from gunshot wounds with succimer (DMSA). J Toxicol Clin Toxicol 1994;32:377–85.[ISI][Medline]
  37. Bolanos AA, Demizio JP Jr, Vigorita VJ, et al. Lead poisoning from an intra-articular shotgun pellet treated with arthroscopic extraction and chelation therapy: a case report. J Bone Joint Surg Am 1996;78:422–6.[Free Full Text]
  38. Kosnett MJ. Lead. In: Ford MD, Delaney KA, et al, eds. Clinical toxicology. New York, NY: W B Saunders Company, 2001:723–6.