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Clinical Investigations in Critical Care |

Clinical Predictors of Respiratory Failure and Long-term Outcome in Black Tar Heroin-Associated Wound Botulism* FREE TO VIEW

Christian E. Sandrock, MD; Susan Murin, MD, FCCP
Author and Funding Information

*From the Department of Pulmonary and Critical Care Medicine, University of California at Davis Medical Center, Sacramento, CA.

Correspondence to: Susan Murin, MD, FCCP, Associate Professor of Clinical Internal Medicine, Division of Pulmonary and Critical Care Medicine, PSSB, Suite 3400, 4150 V St, University of California, Davis Medical Center, Sacramento, CA 95817; e-mail: sxmurin@ucdavis.edu



Chest. 2001;120(2):562-566. doi:10.1378/chest.120.2.562
Text Size: A A A
Published online

Study objectives: To our knowledge, the predictors of respiratory failure (RF) and long-term mechanical ventilation have not previously been examined in patients with wound botulism associated with black tar heroin use.

Design: Retrospective case series.

Setting: A large university hospital.

Patients: Twenty consecutive patients from 1991 to 1998 with a diagnosis of wound botulism associated with drug use as identified through chart records from a single institution.

Results: The predominant mode of drug use was subcutaneous (75%). Fifteen of 20 patients (75%) developed RF. The clinical presentation was similar in groups with RF and without RF. Of those patients who received antitoxin within 12 h of presentation, 57% required mechanical ventilation compared to 85% of patients receiving the antitoxin after 12 h. The median durations of mechanical ventilation were 11 days for those who received antitoxin within 12 h, and 54 days for those who did not receive antitoxin within 12 h. The duration of mechanical ventilation for patients receiving antibiotics within 12 h was 35 days vs 54 days for patients receiving antibiotics after 12 h. Early tracheostomy (< 10 days after initial intubation) was associated with a shorter duration of mechanical ventilation (median, 45 days vs 60 days, respectively).

Conclusion: Early antitoxin administration may decrease the need for and duration of mechanical ventilation among patients with wound botulism. Early tracheostomy may be beneficial for patients with RF.

Botulism is a potentially lethal paralytic disease caused by the neurotoxin from the spore-forming anaerobic bacterium Clostridium botulinum.1A majority of cases are observed when the toxin is ingested from contaminated food or produced in the intestinal tract of infants colonized with C botulinum, while the reminder are associated with wound botulism.2 Wound botulism occurs when the spores of the organism inoculate the wound and anaerobic conditions allow germination and subsequent production of the toxin.3 Historically, wound botulism has occurred in the setting of penetrating trauma or crush injuries, but within the past decade, drug abuse-related cases have surpassed those secondary to trauma.1,45 Since the first case of wound botulism associated with IV drug use was reported in New York City in 1982,6 there has been a steady increase from approximately 6 cases in 1990 to 29 cases in 1998.2 Most cases are linked to the use of black tar heroin that is imported from Mexico and mostly found in California.1,7

Wound botulism carries a case fatality rate of 15%, largely due to ventilatory failure.3,5,8However, only two reports910 have focused on the pulmonary complications and outcomes in botulism, and both studies focused on outbreaks of food-borne illness. Case reports and series6,1113 have described the clinical presentation and course of a small number of patients with black tar heroin-associated wound botulism, but to our knowledge no study has evaluated the clinical predictors and long-term outcome in a large group of consecutive patients.

Chart Review

Hospital records from 1990 to 1999 with the discharge diagnosis of botulism were reviewed by a single physician. Any patients with food-borne, infant, and unspecified botulism were excluded. All patients required a history of drug use, either IV or subcutaneous (“skin popping”), within the months preceding hospitalization, or if the history was not available, a positive result on toxicology screen. Botulism was defined as ocular or bulbar palsy and/or extremity or respiratory weakness with detection of the botulism toxin from blood or wound, isolation of C botulinum from the wound, or electromyography findings consistent with botulism (failure of neuromuscular transmission coupled with generalized reduction of compound muscle action potential amplitudes). Ventilatory failure was defined as the use of mechanical ventilation, either invasive or noninvasive. Suspicion of clinical pneumonia was based on the criteria established by the American College of Chest Physicians, which include temperature of > 38.3°C, new or persistent infiltrate on chest radiographs, new or increasing purulent sputum production, and increasing oxygen needs.14 Due to the retrospective nature of this study, quantitative cultures or histologic examination of lung tissue were not performed and could not be used in the diagnosis of definite or probable pneumonia. Data extracted included initial symptoms, physical findings, initial chest radiographs, hospital admission arterial blood gas levels, vital capacity, and negative inspiratory force or pressure (if recorded). The time from original presentation to administration of antitoxin and antibiotics, the total number of days of mechanical ventilation (from intubation to extubation), the time to surgical placement of tracheostomy (if done), the time to incision and drainage of abscess, and the total number of hospital days were also recorded. For patients who were discharged from the hospital receiving mechanical ventilatory support after 60 days and for whom a total number of days could not be determined, 60 days was used as the total time of ventilatory support.

Statistical Analysis

For comparison of dichotomous variables, Fisher’s Exact Test was used. Continuous variables were compared with either the Student’s t test or Wilcoxon test.

A total of 20 patients received a diagnosis of wound botulism associated with drug use. Fifteen patients (75%) developed respiratory failure (RF). Fifteen patients (75%) were male (Table 1 ). The median age for those patients with RF (the RF group) was 47 years vs 40 years for those without RF (the non-RF group). All patients actively used only heroin (there was no cocaine or methamphetamine use in the patients). Five patients used only the IV route of administration (all in the RF group), while the other 15 patients actively administered the heroin subcutaneously. The median time of heroin use prior to presentation was 36 h in the non-RF group and 48 h in the RF group (p = 0.4266; Table 1). All patients with detectable toxin in the bloodstream developed RF, compared with 55% of those patients without detectable toxin (p = 0.0195). All isolated toxin was type A. Seven patients had isolation of the organism from their wound, with two patients having both toxin and organism isolated. An electromyogram was performed on all patients, and in all cases was consistent with botulism. Electromyography confirmed the diagnosis in the six remaining patients from whom neither the toxin nor organism was isolated. All patients were symptomatic at presentation (Table 2 ). The major symptoms were bulbar. A majority of patients had ptosis, dysarthria, abnormal gag reflex, and extraoccular muscle paresis with no significant difference noted between the two groups. Of interest, five patients (30%) in the RF group and three patients (60%) in the non-RF group had unilateral ocular muscle paresis involving the lateral rectus only. Three patients had GI symptoms. Extremity weakness was noted in 75% of patients (10 patients in RF group [66%] and 4 patients in the non-RF group [80%]). No patients in either group were febrile or hypotensive on presentation. Abnormal lung auscultory findings or initial chest radiograph findings were uncommon (Table 3 ). Seven patients in the RF group and three patients in the non-RF group had a visibly infected abscess on examination.

Eight patients in the RF group developed pneumonia within 48 h of hospital admission, while those in the non-RF group had no episodes of pneumonia (p = 0.0186). The median number of hospital days for those patients with RF was 50 days vs 4 days in the non-RF group (p = 0.0002). Subsequently, 12 patients (80%) with RF required a skilled nursing facility or rehabilitation center at hospital discharge, with 5 of these patients being discharged while still requiring ventilatory support. None of the patients in the non-RF group were discharged to skilled nursing facility (p = 0.0016; Table 1). All 20 patients survived to hospital discharge.

A total of seven patients received equine type A antitoxin within 12 h; of these, 57% (four patients) developed RF. The remaining 13 patients either received the antitoxin after 12 h or not at all. Eighty-five percent (11 patients) developed RF. Of those patients who had antibiotics administered within 12 h of presentation, 71% required mechanical ventilation compared to 77% of those receiving antibiotics after 12 h. Finally, a total of 10 patients had visible abscesses on presentation. Eight of these patients had either a spontaneously draining abscess on hospital admission or had surgical debridement done within 24 h of hospital admission. Six of these patients required mechanical ventilation. Two patients had abscesses drained after 24 h, and one patient required mechanical ventilation.

The median total time of mechanical ventilation for the group who received the antitoxin within 12 h was 11 days compared to 54 days for those patients receiving the antitoxin after 12 h (p = 0.1897; Tables 4 , 5 ). For those patients who received antibiotics within 12 h, the median duration of mechanical ventilation was 35 days as opposed to 54 days in those patients receiving antibiotics after 12 h. A tracheotomy was performed in 12 patients (86%) in the RF group. Four patients received a tracheotomy within 10 days, while eight patients received the tracheotomy after 10 days. Three patients in the RF group did not have a tracheotomy performed. The total duration receiving mechanical ventilation was shorter for those who received a tracheostomy within 10 days of onset of mechanical ventilation when compared to those who received a tracheostomy after 10 days (median, 45 days vs 60 days, respectively; p = 0.3712; Table 5).

Wound botulism is a rare disease, but its incidence has increased substantially over the past decade, from approximately 6 cases in 1990 to 29 cases in 1998.2 Wound botulism now accounts for 25% of the total annual cases of botulism in the United States. Botulism associated with black tar heroin use has largely been responsible for this increase in cases, and this increase in the number of cases has been likely due to the rapid and unclean production of the heroin, thereby leading to spore contamination of the drug.7 RF is a major complication of botulism; in food-borne outbreaks, RF has been a major cause of morbidity and mortality of the disease.3,910 Case reports and small case series6,11,13 have touched on the clinical findings in black tar-heroin associated wound botulism, but none have evaluated the clinical predictors of RF, long-term outcome, and the potential benefits of antitoxin administration in these patients.

In this study, we focused on clinical presentation and potential predictors of the occurrence and natural history of RF in wound botulism. As described in food-borne outbreaks, bulbar signs and symptoms were the predominant findings at presentation.9 Interestingly, a number of patients had asymmetric bulbar findings, particularly involving the lateral rectus muscle. Weakness was common but not always present in the patients who developed RF. Only half of the patients had an abscess at hospital admission, and not all patients were administering the heroin subcutaneously, a finding previously described by Passaro and Werner7 in 1998. The only significant finding between the two groups was the isolation of type A toxin in > 50% of those patients who developed RF, suggesting they may have a higher toxin load than those without RF. But overall, there was no significant difference in clinical characteristics, signs, and symptoms at presentation between the two groups.

In a review of the 132 cases of food-borne botulism from the Centers for Disease Control and Prevention from 1973 to 1980, equine antitoxin administered within 24 h of the onset of symptoms was shown to decrease the development of RF.15 In our evaluation of these 20 cases, we chose a 12-h window for our analysis of the potential benefits of antitoxin administration. Patients who did not receive antitoxin within 12 h after presentation were three times more likely to develop RF (odds ratio, 3.0; confidence interval, 0.37 to 24.17), although this did not reach statistical significance because of a small sample size and insufficient statistical power. Additionally, this variable presentation of symptoms and the sporadic nature of wound botulism (in comparison to food-borne outbreaks) added to the difficulty in the diagnosis of wound botulism and hence affected the time to antitoxin administration and subsequent results. For example, one patient had presented to an outside hospital a day prior to her hospital admission, but still received antitoxin within 12 h of her second hospital admission. Other patients had the diagnosis delayed for the first 3 to 4 days before receiving antitoxin or, in the case of four patients, received no antitoxin at all. A better measure of duration would be from the initial onset of symptoms rather than presentation to the hospital, but these data could not be reliably extracted from the medical records. Despite these difficulties, antitoxin administration within 12 h of presentation appeared to be beneficial.

Both early antibiotic administration and abscess drainage appeared to have no effect on the incidence of RF. The role of antibiotic administration has been debated because botulism is a toxin-mediated disease; overall, it appeared that antibiotic administration had no effect on the development of RF.16 However, it is clearly necessary if the patient has an infected abscess. Furthermore, surgical debridement of an infected abscess is also indicated, but a benefit in the development of RF was also difficult to assess again due to the small sample size and variable presentation. Some patients had no evidence of subcutaneous heroin use or an infected abscess, and others had draining abscesses yet still progressed to RF.

In the patients who developed RF, the duration of mechanical ventilation was prolonged, with 80% (12 patients) requiring > 30 days of ventilatory support. The botulism toxin binds irreversibly to the presynaptic nerve terminal and inhibits the release of acetylcholine.1 Recovery usually requires regeneration of the presynaptic nerve terminal and is typically prolonged. Patients with RF, not surprisingly, had prolonged hospital stays and a majority were discharged to a long-term care facility. The placement of an early tracheostomy (within 10 days of the onset of mechanical ventilation) appeared to decrease the total time of mechanical ventilation. This decrease in duration was likely due to improved weaning from mechanical ventilation, shorter ICU stays, and less ventilator-associated pneumonia as has been previously described in the literature.17 Additionally, pneumonia is the largest cause of morbidity and is often seen in the more severe cases of botulism.3,9 More than 50% of the patients who developed RF had pneumonia develop within the first 2 days of hospitalization, most likely from the aspiration of oral secretions. Despite the high frequency of RF and its prolonged course, there was no attributable mortality to botulism among the 20 patients studied.

Botulism should be suspected in black tar heroin users (either IV of subcutaneous) who present with bulbar signs. RF develops in the majority of patients (75%). All patients with detectable toxin in the bloodstream developed RF. Prompt (< 12 h after presentation) antitoxin administration is associated with a decreased likelihood of developing RF, while neither antibiotic administration nor surgical debridement appears to affect the course of the disease. Patients who develop RF usually have a protracted course, with > 80% requiring ventilatory support for > 30 days. Pneumonia is a common complication within the first several days of development of RF. Early tracheostomy appears to be beneficial and may decrease the total time of ventilatory support.

Abbreviation: RF = respiratory failure

Table Graphic Jump Location
Table 1. Baseline Clinical Characteristics for Patients With Black Tar Heroin-Associated Wound Botulism *
* 

Data are presented as No. (%) unless otherwise indicated. NS = not significant.

 

Information was not available for five patients.

 

Two patients had both toxin detection and organism isolation.

Table Graphic Jump Location
Table 2. Symptoms at Presentation in Black Tar Heroin-Associated Wound Botulism *
* 

Data are presented as No. (%).

 

p value not significant for all symptoms.

Table Graphic Jump Location
Table 3. Signs on Physical Examination at Presentation in Black Tar Heroin-Associated Wound Botulism *
* 

Data are presented as No. (%).

 

p value not significant for all physical findings.

Table Graphic Jump Location
Table 4. Comparison of Equine Antitoxin, Antibiotics, and Abscess Drainage on RF *
* 

Data are presented as No. or No. (%).

 

Four patients total did not receive antitoxin; of these, three patients were in the RF group.

 

Five patients total did not receive antibiotics within 72 h of hospital admission; of these, three patients were in the RF group.

§ 

Four patients total had active draining abscesses upon hospital admission; of these, three patients were in the RF group.

Table Graphic Jump Location
Table 5. Effects of Equine Antitoxin, Antibiotics, and Tracheostomy on Mechanical Ventilation *
* 

Data are presented as median (interquartile range).

 

Two patients did not undergo tracheostomy and were included in this group.

 

p value = 0.1897.

§ 

p value = 0.4389.

 

p value = 0.3712.

Smith, L (1988)Botulism: the organism, its toxins, and the disease 2nd ed. Charles C. Thomas. Springfield, IL:
 
Centers for Disease Control and Prevention. Summary of notifiable diseases, United States.MMWR Morb Mortal Wkly Rep1998;47,78-79
 
Merson, MH, Dowell, VR Epidemiologic, clinical, and laboratory aspects of wound botulism.N Engl J Med1973;289,1105-1110
 
California Department of Health Services.. Wound botulism in California, 1951–1985. Calif Morb. 1986;;26 ,.:1
 
Shapiro, R, Hatheway, C, Swerdlow, DL Botulism in the United States: a clinical and epidemiologic review.Ann Intern Med1998;129; 102,221-228
 
MacDonald, KL, Rutherford, GW, Friedman, SM, et al Botulism and botulism like illness in chronic drug users.Ann Intern Med1985;102,616-618. [PubMed]
 
Passaro, DJ, Werner, B Wound botulism associated with black tar heroin among injection drug users.JAMA1998;279,859-863. [PubMed] [CrossRef]
 
Hathway CL. Botulism: the present status of disease. In: Montecocco C, ed. Clostridial neurotoxins: current topics in microbiology and immunology. (vol 195). New York, NY: Springer, 1995; 55.
 
Schmidt-Nowara, WW, Samet, JM, Rosario, RA Early and late pulmonary complications of botulism.Arch Intern Med1983;143,451-456. [PubMed]
 
Paust, J Respiratory care in acute botulism: a report of four cases.Anesth Analg1971;50,1003-1009. [PubMed]
 
Rapoport, S, Watkins, PB Descending paralysis from occult wound botulism.Ann Neurol1984;16,359-361. [PubMed]
 
Anderson, MW, Sharma, K, Feeney, CM Wound botulism associated with black tar heroin.Acad Emerg Med1997;4,805-809. [PubMed]
 
Swedberg, J, Wendel, T Wound botulism.West J Med1987;147,3335-3338
 
Pingleton, SK, Fagon, JY, Leeper, KV Patient selection for clinical investigation of ventilator-associated pneumonia: criteria for evaluation diagnostic techniques.Chest1992;102(suppl),553S-556S
 
Tacket, CO, Shandera, WV Equine antitoxin use and other factors that predict outcome in type A foodborne botulism.Am J Med1989;76,744-748
 
MacDonald, KL The changing epidemiology of adult botulism in the United States.Am J Epidemiol1986;124,4-9
 
Brook, AD, Sherman, G, Malen, J, et al Early versus late tracheostomy in patients who require prolonged mechanical ventilation.Am J Crit Care2000;9,352-359. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Baseline Clinical Characteristics for Patients With Black Tar Heroin-Associated Wound Botulism *
* 

Data are presented as No. (%) unless otherwise indicated. NS = not significant.

 

Information was not available for five patients.

 

Two patients had both toxin detection and organism isolation.

Table Graphic Jump Location
Table 2. Symptoms at Presentation in Black Tar Heroin-Associated Wound Botulism *
* 

Data are presented as No. (%).

 

p value not significant for all symptoms.

Table Graphic Jump Location
Table 3. Signs on Physical Examination at Presentation in Black Tar Heroin-Associated Wound Botulism *
* 

Data are presented as No. (%).

 

p value not significant for all physical findings.

Table Graphic Jump Location
Table 4. Comparison of Equine Antitoxin, Antibiotics, and Abscess Drainage on RF *
* 

Data are presented as No. or No. (%).

 

Four patients total did not receive antitoxin; of these, three patients were in the RF group.

 

Five patients total did not receive antibiotics within 72 h of hospital admission; of these, three patients were in the RF group.

§ 

Four patients total had active draining abscesses upon hospital admission; of these, three patients were in the RF group.

Table Graphic Jump Location
Table 5. Effects of Equine Antitoxin, Antibiotics, and Tracheostomy on Mechanical Ventilation *
* 

Data are presented as median (interquartile range).

 

Two patients did not undergo tracheostomy and were included in this group.

 

p value = 0.1897.

§ 

p value = 0.4389.

 

p value = 0.3712.

References

Smith, L (1988)Botulism: the organism, its toxins, and the disease 2nd ed. Charles C. Thomas. Springfield, IL:
 
Centers for Disease Control and Prevention. Summary of notifiable diseases, United States.MMWR Morb Mortal Wkly Rep1998;47,78-79
 
Merson, MH, Dowell, VR Epidemiologic, clinical, and laboratory aspects of wound botulism.N Engl J Med1973;289,1105-1110
 
California Department of Health Services.. Wound botulism in California, 1951–1985. Calif Morb. 1986;;26 ,.:1
 
Shapiro, R, Hatheway, C, Swerdlow, DL Botulism in the United States: a clinical and epidemiologic review.Ann Intern Med1998;129; 102,221-228
 
MacDonald, KL, Rutherford, GW, Friedman, SM, et al Botulism and botulism like illness in chronic drug users.Ann Intern Med1985;102,616-618. [PubMed]
 
Passaro, DJ, Werner, B Wound botulism associated with black tar heroin among injection drug users.JAMA1998;279,859-863. [PubMed] [CrossRef]
 
Hathway CL. Botulism: the present status of disease. In: Montecocco C, ed. Clostridial neurotoxins: current topics in microbiology and immunology. (vol 195). New York, NY: Springer, 1995; 55.
 
Schmidt-Nowara, WW, Samet, JM, Rosario, RA Early and late pulmonary complications of botulism.Arch Intern Med1983;143,451-456. [PubMed]
 
Paust, J Respiratory care in acute botulism: a report of four cases.Anesth Analg1971;50,1003-1009. [PubMed]
 
Rapoport, S, Watkins, PB Descending paralysis from occult wound botulism.Ann Neurol1984;16,359-361. [PubMed]
 
Anderson, MW, Sharma, K, Feeney, CM Wound botulism associated with black tar heroin.Acad Emerg Med1997;4,805-809. [PubMed]
 
Swedberg, J, Wendel, T Wound botulism.West J Med1987;147,3335-3338
 
Pingleton, SK, Fagon, JY, Leeper, KV Patient selection for clinical investigation of ventilator-associated pneumonia: criteria for evaluation diagnostic techniques.Chest1992;102(suppl),553S-556S
 
Tacket, CO, Shandera, WV Equine antitoxin use and other factors that predict outcome in type A foodborne botulism.Am J Med1989;76,744-748
 
MacDonald, KL The changing epidemiology of adult botulism in the United States.Am J Epidemiol1986;124,4-9
 
Brook, AD, Sherman, G, Malen, J, et al Early versus late tracheostomy in patients who require prolonged mechanical ventilation.Am J Crit Care2000;9,352-359. [PubMed]
 
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