In this study, we investigated risk factors for pediatric SSIs after CSF diversion surgery at a single quaternary care pediatric center. We found that comorbid cardiac disease and the presence of a brain tumor were independent risk factors for SSI. In patients who underwent shunt procedures, comorbid cardiac disease was the only independent risk factor for SSI.
In our study, the incidence of SSI in combined CSF diversion surgery was 3.6%, while SSI rates for shunt surgery and ETV were 4.9% and 0.5%, respectively. ETV is an important procedure for hydrocephalus that serves as an alternative to shunt device implantation. The success rate of ETV and its use in various ages and background diseases vary across reports [11]. ETV can be done with or without CPC. In our institution, CPC is generally done together with ETV. In general, the SSI rate of ETV is lower than that of a shunt device implantation procedure, but the post-ETV SSI rate depends on background and age [12]. In our institution, ETV was often performed for hydrocephalus due to congenital diseases in infancy, but it was also performed in cases of repeated shunting and brain tumor complications.
There is no previous study showing that a history of brain tumor is an independent risk factor in pediatric SSI after CSF diversion surgery, but a number of studies have examined the rate of infection and prognosis after brain tumor surgery [13–15]. The cohort in our study had a higher rate (26.2%) of infection in patients with a diagnosis of brain tumor than found in previous studies investigating risk factors for shunt malfunction and infection (8% [16] and 17% [17]). Although results may vary depending on the distribution of causative diseases of hydrocephalus in each center as well as the chemotherapy regimens, our result was somewhat novel. The association of cardiac disease with shunt infection was previously described in a study of children who underwent shunt surgery within the first year of life [18]. Our study consisting of older children also demonstrated that comorbid cardiac disease was associated with an increased risk of shunt SSI. Although not directly related to infection, cardiac anomalies were associated with shunt failure in the prospective study of children from six Hydrocephalus Clinical Research Network Centers [16]. The authors suggested that this finding may be related to repeated hospitalizations and surgeries or immunodeficiencies, but they did not formally analyze these exposures. Immunological profiles for patients with a history of brain tumor and cardiac disease who present for CSF diversion procedures are not known, and could be a topic of future investigation.
The association between age and SSIs varies across studies. While some studies have identified younger age, particularly infancy, as a risk factor for SSI [19–22], other studies have demonstrated that age is not a risk factor for shunt failure or infection [23, 24]. In our cohort, older patients tended to have a higher SSI rate in univariate analysis. Most of the patients in our cohort were beyond infancy. Post- intraventricular hemorrhage (IVH) hydrocephalus secondary to prematurity occurs in infants, but most of the tumor-related hydrocephalus occurs in older children. However, age was not an independent risk factor in the multivariate analysis after the adjustment for comorbidities and the number of shunt revisions. The effects of residual tumor, chemotherapy and radiation should also be considered in future studies.
The risk of shunt failure or infection generally increases with each subsequent shunt replacement, resulting in a rising cumulative risk of SSIs [17, 22, 25]. However, in the present study, the number of shunt revisions was not an independent risk factor for SSIs in multivariate analysis, although there was a significant difference in univariate analysis. Previously, other investigators found that the presence of a gastrostomy tube was associated with infection risk in the larger study [17], but this did not substantially contribute to infections in this study. Some studies showed that lower gestational age (GA) at the time of procedures and prematurity were significant risk factors for infection after shunt surgery [21, 26]. In our study cohort, there was no incidence of SSIs in patients with a history of preterm birth, although a number of patients did not have detailed perinatal information available. Although it is difficult to determine the association between GA at birth and SSIs, GA was not a risk factor for SSI in our study. Further investigation is needed to clarify why our result differs from the previous reports.
Research on modifiable perioperative risk factors and interventions to reduce the risk of shunt infection has been done for many years. Traditional risk factors include the duration of surgery [27], the experience of the surgeon [28], hair shaving [29], prophylactic systemic antibiotics [8], antibiotic-impregnated sutures [30] and skin preparation [5, 6]. In our cohort, surgeon, prophylactic antibiotics, duration of surgery, and skin preparation agent were not associated with SSIs. In addition, our institution routinely utilizes antibiotic-impregnated shunt tubing (Bactiseal tubing) [10, 31]. In our cohort, patient factors were suggested to be more relevant as risk factors for SSIs than perioperative factors. Among the perioperative factors other than those mentioned above, there have been no reports that have examined the type and dose of anesthetics and the amount of oxygen administered in shunt surgery. Intraoperative factors such as oxygen dosage, and temperature control are known to play a role in SSI following adult general surgery [32–34]. The effect of volatile anesthetics on immune function have been reported previously [35–41]. In our previous work using a preclinical model, a long exposure (6-hour) of volatile anesthetics was associated with increased infection, while a short exposure (2-hour) was not [42]. In a study at our institution, we previously showed that higher volatile anesthetic dose was an independent risk factor for SSI in pediatric gastrointestinal surgery [43]. Anesthetic drugs and oxygen dosage also had no impact on the incidence of SSIs. The operative duration was less than 80 minutes for the groups with and without SSIs. Our result was in line with the finding in our preclinical study. In the present study, the median number of days to the date of SSI onset after surgery was 13.5 days, but more than 75% of the patients with SSI had a postoperative period of more than 30 days. In previous reports, the risk of infection was shown to be highest in the first eight weeks after a shunt procedure, and the risk decreased substantially after six months [44]. Because of relatively late onset of SSI postoperatively and the short surgical duration, it is perhaps not surprising that the impact of intraoperative drugs and oxygen dose on immune function was less after CSF diversion surgery.
The most common bacteria detected in our cohort were Staphylococcus epidermidis and Cutibacterium acnes, generally consistent with previous reports [19, 20, 45, 46]. Staphylococcus aureus was detected in a smaller proportion of cases. While the effectiveness of antimicrobial-impregnated and -coated shunts (AIS) has been described [46, 47], there are concerns including the emergence of methicillin-resistant Staphylococcus aureus (MRSA) and resistant gram negative rods (GNR) with repeated use [45, 46]. Although we routinely use antimicrobial impregnated shunting, MRSA was not detected in our cohort.
Our study has several limitations. First, it was limited as a single-center study and was retrospective. Second, the low SSI rate and small sample size may impair statistical power to find associations. Third, we did not examine the type of device implanted, when the brain tumor or cardiac diseases were diagnosed, or the history of treatment.
In conclusion, we have shown that comorbidities of cardiac disease and brain tumor are independent risk factors for SSIs in children undergoing CSF diversion procedures. In the presence of routine evidence-based bundles of SSI prevention measures, patient-level factors remain important predictors; future research should evaluate the mechanism underlying these associations, including the investigation of underlying immunological profiling, to further optimize prevention of infection.