Abstract
Botulism in children can have severe complications necessitating intensive care. The current literature lacks data of children with botulism requiring critical care. We aim to describe the outcomes of pediatric botulism in the pediatric intensive care unit (PICU). Retrospective cohort data from Virtual Pediatric Systems (VPS, LLC, Los Angeles, California), from 2009 to 2016 including all PICU admissions among children with botulism, were analyzed. Characteristics and outcomes were compared with similar studies. A total of 380 children were identified over 8 years. Our cohort had the shortest length of stay (median 4.6 days), the smallest percent requiring mechanical ventilation (40%), and the highest median age (120 days) amongst comparable studies. Length of mechanical ventilation and PICU stay has decreased among children with botulism. Advances in PICU care may have contributed to these improved outcomes.
Keywords: botulism, pediatrics, pediatric intensive care unit, mechanical ventilation
Introduction
Botulism is a neuroparalytic syndrome resulting from the exposure of a neurotoxin produced by Clostridium botulinum . 1 Clostridium botulinum spores are ubiquitous in soil, water, and in some foods, and the toxin produced by these bacteria can be dangerous, especially in children. When ingested, spores will germinate and bacteria will colonize in the large intestine. Botulinum toxins produced will bind irreversibly to peripheral motor nerve terminals and enters motor neurons, where the toxin inhibits the release of acetylcholine. This results in the characteristic descending and symmetric flaccid paralysis.
The most common form of human botulism in the United States is infant botulism, which unlike foodborne botulism is due to continued production of toxins in the large intestine due to the presence of C. botulinum bacteria. Other clostridia species including Clostridium butyricum and Clostridium barati have also been known to produce botulinum toxin. Although botulism is relatively uncommon in the United States, the Center for Disease Control and Prevention (CDC) confirmed 1,292 cases from 2009 to 2016. A total of 947 (73%) of these were infantile type. 2 The highest incidence of infantile botulism cases are reported in Pennsylvania, Utah, and California where the soil botulinum spore count is high.
With early diagnosis and improved critical care, children with botulism have zero mortality. The most severe complication of botulism is respiratory failure requiring ventilatory support. The management of infants with botulism revolves around meticulous supportive care, use of human botulism immune globulin (Baby BIG, California Department of Public Health, Richmond, California) and avoidance of antibiotics. Since 1992, Baby BIG has been available for infant botulism through the Infant Botulism Treatment and Prevention program. After a randomized controlled trial and later an open label trial, it was licensed by Food and Drug Administration (FDA) for use in infant botulism. 3
For conditions with low frequency, like botulism, national databases provide an excellent opportunity to understand the disease burden and outcomes. In the last 10 to 15 years, there has been a lack of literature on the outcomes of children with botulism requiring critical care services. We are well positioned to query a national database to help understand the epidemiology and outcomes of children with botulism and help families with data-driven information to alleviate their apprehension about this acute debilitating disorder.
Patients and Methods
Data Source
Study data were obtained from Virtual Pediatric Systems (VPS LLC, Los Angeles, California), an online intensive care database, and now part of Children's Hospital Association, Children's Hospital Los Angeles, and Children's Hospital of Wisconsin. This database is an observational cohort of consecutive pediatric intensive care unit (PICU) admissions from various hospitals in the United States. Data are collected in a retrospective manner using standardized definitions and tools ensuring data quality control, and rigorous analysis. Data entry is performed by trained individuals and the VPS staff performs initial and quarterly inter-rater reliability (IRR) testing. The IRR for the VPS database has consistently been above 0.9.
Patient Population
Children less than 18 years of age admitted to the PICU with the diagnosis of botulism were included. Data from January 1, 2009 to December 31, 2016 were included. Approval was obtained from the Institutional Review Board. Patient characteristics, mechanical ventilation necessity, and procedure data were collected.
Statistical Analysis
Descriptive analysis was performed using Microsoft Excel 2013. The outcomes were compared with previous studies and p < 0.005 was considered significant.
Results
We identified 380 children with botulism over an 8-year period (2009–2016). There were 185 (49%) males and 195 (51%) females in our cohort. The median age of presentation was 120 days. A total of 377 (99%) were less than 24 months of age. There were no deaths in the cohort. Three hundred and sixteen (83%) of the patients were discharged to the general floor. One hundred and fifty-two (40%) of the cohort required endotracheal intubation and the median length of mechanical intubation was 6.19 days (range 0.19–81.3 days; Table 1 ). A count of 28 (8%) from this cohort underwent radiologic diagnostic testing including MRI (17; 5%) and CT (11; 3%; Table 2 ).
Table 1. Characteristics of patients admitted to the PICU with botulism.
| Patient Demographics | N = 380 (%) |
|---|---|
| Age | |
| < 1 mo | 12 (3.2) |
| 1–23 mo | 365 (96) |
| 24 mo–5 y | 0 (0) |
| 6–12 y | 2 (0.5) |
| 13–18 y | 1 (0.3) |
| Sex | |
| Female | 185 (49) |
| Male | 195 (51) |
| Weight | |
| <10 kg | 370 (97) |
| 10–19.99 kg | 7 (2) |
| >20 kg | 3 (1) |
| Race | |
| White | 200 (53) |
| African-American | 64 (17) |
| Hispanic | 64 (17) |
| Asian/Indian/Pacific Islander | 13 (3) |
| Native American/Pacific Islander | 3 (1) |
| Mixed/other | 23 (6) |
| Unspecified/not reported | 61 (16) |
| Clinical Characteristics | |
| Median PICU LOS (d) | 4.63 |
| Outcome | |
| Survived | 380 (100) |
| Disposition | |
| General floor | 316 (83) |
| Step-down unit | 28 (2.1) |
| NICU | 14 (4) |
| Another hospital ICU | 2 (0.5) |
| Another hospital general floor | 2 (0.5) |
| Another ICU in current hospital | 1 (0.3) |
| Physical rehabilitation center | 4 (1) |
| Home | 13 (3) |
Abbreviations: ICU, intensive care unit; LOS, length of stay; PICU, pediatric intensive care unit.
Table 2. Interventions and diagnostics of patients admitted to the PICU with botulism.
| Interventions and Diagnostics | N = 380 (%) |
|---|---|
| Endotracheal intubation | 152 (40) |
| Median LOMV (d) | 6.19 |
| HFNC/supplemental O 2 | 51 (13.4) |
| CPAP | 13 (3.4) |
| PICC/peripheral CVL | 47 (12 ) |
| Percutaneous CVL | 36 (10) |
| Arterial line | 16 (4) |
| Enteric tube | 74 (20) |
| Magnetic resonance imaging | 17 (5) |
| Computed tomography | 11 (3) |
| Lumbar puncture | 21 (6) |
| Bronchoscopy | 5 (1) |
| Electroencephalography | 13 (3.4) |
| Echocardiogram | 3 (<1) |
Abbreviations: CPAP, continuous positive airway pressure; CVL, central venous line; HFNC, high flown nasal cannula; LOMV, length of mechanical ventilation; LOS, length of stay; PICC, peripherally inserted central catheter; PICU, pediatric intensive care unit.
We compared our study to three previous studies ( Table 3 ). 3 4 5 Study duration, participant numbers, hospital length of stay, PICU length of stay, percentage of children requiring mechanical ventilation, and length of mechanical ventilation were compared. Our study had the largest number of patients across multiple institutes. The median age for our cohort was 120 days, which was the highest amongst these studies ( Table 1 ). Our cohort also had the shortest length of PICU stay (mean 4.6 days). Forty percent of our cohort required mechanical ventilation which was the smallest percentage of children with botulism compared with the other studies. Our database does not have information on the use of Baby BIG and length of hospital stay.
Table 3. Comparison of pediatric botulism data over the last 3 decades.
| Characteristics | Underwood et al 3 | Tseng-Ong et al 6 | Arnon et al 5 | Present study | |||
|---|---|---|---|---|---|---|---|
| Institution | Single-center | Single-center | Multi-center | Multi-center | |||
| Total number of patients | 67 | 44 | 122 | 380 | |||
| Duration (y) | 30 (1976–2005) | 20 (1985–2004) | 5 (1992–1997) | 8 (2009–2016) | |||
| Median age (d) | 84 | 91 | – | 120 | |||
| Male | 33 | – | 48 | 185 | |||
| Female | 34 | – | 74 | 195 | |||
| No BIG | BIG | No BIG | BIG | No BIG | BIG | – | |
| Hospital LOS (d) | 31.5 | 15 | 23.5 | 13.5 | 39.9 | 18.2 | – |
| ICU LOS (d) | 22.5 | 9 | – | – | 35 | 12.6 | 4.6 |
| % MV | 76 | 80 | 62 | 67 | 58 | 57 | 40 |
| LOMV (d) | 16.5 | 6 | 6 | 6 | 30.8 | 12.6 | 6.1 |
Abbreviations: BIG, botulism immune globulin; LOMV, length of mechanical ventilation; LOS, length of stay; MV, mechanical ventilation.
Discussion
This is the largest multi-institutional data review for children with botulism admitted to the PICU in United States. Several observations were made using this PICU focused database. Review of this national database shows that fewer children with botulism admitted to the PICU are being intubated. This decreasing trend of intubation has been seen in other respiratory causes like bronchiolitis and respiratory distress. 6 7 This can be partially explained by the increase in the use of noninvasive methods of ventilation such as high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and biphasic positive airway pressure (BiPAP). 8 In our cohort 13.4% received HFNC and 3.4% received CPAP ( Table 2 ). Comparatively, there was no data on HFNC or CPAP in the Underwood et al or Arnon et al studies. 3 4
The length of mechanical ventilation in our cohort was comparable to children receiving Baby BIG in two single-center studies and was shorter than the group receiving Baby BIG in the multicenter randomized control trial (RCT). 3 4 5 The lengths of PICU stay were also shortest in our study group. The median length of intubation for acute respiratory illness in the PICU is 7 days and for botulism, the reported length of stay has been longer. 9 10 Our cohort had a median length of intubation of 6.19 days ( Fig. 1 ) compared with a range of 6 to 30.8 days previously reported in various studies. 3 4 5 Underwood et al and Arnon et al showed that use of Baby BIG decreased the duration of mechanical ventilation, duration of ICU stay, and overall hospital stay in children. 3 4 Even though our data lack information on the use of Baby BIG, over the last 3 decades the length of mechanical ventilation and length of ICU stay has been decreasing ( Table 3 ). This may suggest that advances in PICU care have had a positive impact on the outcomes of children with botulism. There has been considerable improvement in the judicious use of sedation and paralytics for mechanical ventilation, nutrition, physical therapy, early mobilization, and general hospital care which has led to considerable improvement in the outcomes of children with respiratory failure. 11
Fig. 1.
Duration of mechanical ventilation among children admitted to the PICU with botulism. PICU, pediatric intensive care unit.
The median age for our cohort was 120 days which is approximately 1 month older than the compared studies as well as the CDC data from 2015. 2 4 The 2016 data from the CDC has a median age of 120 days which is similar to our study. 2 It will be essential to investigate another PICU database to understand this trend.
Our data also indicate that very few children with botulism received lumbar punctures or neurologic imaging studies such as magnetic resonance imaging (MRI) or computed tomography (CT). Since botulism is a clinical diagnosis, very few neurologic investigations should be warranted. Although general pediatricians may not have significant experience with the diagnosis of pediatric botulism; pediatric neurologists and intensivists are accustomed to the diagnosis and management of children with this disease. Given their familiarity with the disease presentation and diagnosis, physicians caring for this patient population are expected to recommend fewer invasive tests than they would for other unknown neurologic diseases in the PICU.
VPS provides an excellent resource to understand the disease burden for rare diseases in the PICU. It allows for a comprehensive review of patients and diseases across numerous hospital systems and geographic areas. 12 Querying such databases allow researchers to access significantly more data than each individual center would otherwise have.
The most significant limitation of this study is the unavailability of the data on the use of Baby BIG. This prevents us from making conclusions regarding the effectiveness of Baby BIG on reducing length of mechanical ventilation and hospital length of stay. Lack of other interventional data limits ability to draw conclusions about impacts on outcomes. The other limitation of this study was largely related to the retrospective design. There may be children with botulism who were not coded with the appropriate diagnosis leading to data entry errors. There may be children with botulism being admitted to the regular pediatric wards when there is lower suspicion for respiratory failure.
Only 40% of children with botulism admitted to the PICU require mechanical ventilation. The length of mechanical ventilation and duration of PICU stay have decreased in recent years. This decrease may be partially attributed to advances in general PICU care. Lack of interventional data prevents us from making conclusions about the impact of Baby BIG on outcomes in this study.
Footnotes
Conflict of Interest None declared.
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