3. Discussion
Oral mucositis (OM) is a common adverse event in patients receiving chemotherapy. Its clinical manifestation ranges from mild erythema and soreness to extreme pain and ulceration, significantly affecting patient’s quality of life3. Specific drug therapy has been associated with an increased risk of developing mucositis; etoposide is excreted in the saliva which increases its oral toxicity1. In rare cases, severe OM can result in significant edema of the upper airway leading to airway obstruction4.
Pediatric patients are more prone to develop OM with increased severity5. Its prevalence is reported to exceed 90% among children under 12 years old receiving chemotherapy for hematological malignancies compared with 40% in the adult counterparts1. This has been attributed to the greater number of mitoses in the basal epithelium in younger patients, making the epithelial cells more vulnerable to cytotoxic effects6. The duration of OM in the pediatric population tends to be shorter reflecting their greater healing capacity6.
Pediatric patients with severe OM are at greater risk of airway compromise due to their narrower airway6. The exact prevalence of upper airway complications in the pediatric patients following chemotherapy is unknown. One study reported that 10.5% of the pediatric patients following bone marrow transplantation required mechanical ventilation, of which upper airway obstruction due to mucositis accounted for 13%7.
Typically, OM develops 10-14 days after initiation of chemotherapy and heals within 2-4 weeks, consistent with the clinical course of neutropenia8. Neutropenia has been reported to play a key role in the development of OM. Severity of OM is associated with the degree of neutropenia, and resolution coincides with granulocyte recovery8. This is assumed to be a result of neutropenia leading to impaired mucosal defence and repair8.
Management of OM is crucial as it provides a portal for potentially life-threatening infection8. Previous studies have shown that the risk of infection increases with increasing grade of OM8. As most patients with OM develop neutropenic fever, broad spectrum beta-lactam with combination of antifungal and antiviral agents is commonly used as a standard treatment to cover gram-negative bacteria, Coagulase-negative Streptococci ,Streptococcus viridans , Candida albicans and Herpes simplex 6, 9, 10. However, fever remains unexplained in 30-50% of neutropenic patients with no evidence of infection11. Furthermore, fever persists for 4-5 days or even longer in approximately 30% of cases despite adequate microbial treatment directed at bacteria and fungi11. In these cases, fever may not be necessarily related to infection and may be a manifestation of the inflammatory process contributed by the mucositis itself9, 11. In a report examining patients receiving chemotherapy for treatment of acute leukemia, inflammation was shown to be correlated with the occurrence of mucositis. The inflammatory response is elicited by formation of reactive oxygen species due to DNA damage of the epithelial cells, followed by amplification of proinflammatory and inflammatory cytokine release triggered by various microbial motifs (Pathogen-associated molecular patterns) released from invading microorganisms and damaged tissues (Damage-associated molecular patterns) through the distorted mucosal barrier, manifesting systemic fever and further tissue damage11.
In the current case, the patient remained febrile despite treatment with broad spectrum antibiotics, antifungal and antiviral agents lacking evidence of infection. Regarding her prompt defervescence coinciding with recovery of mucositis, her fever may have been a manifestation of the inflammation of mucositis, irrelevant of infection. Currently no guideline is provided regarding the use of G-CSF on mucositis due to insufficient evidence12. Yet, the possibility of infection could not be discarded in this circumstance and treatment with broad-spectrum antimicrobials combined with G-CSF was continued.
In the current case, the patient was successfully extubated following recovery of mucositis but required prolonged mechanical ventilation. Determination whether to perform tracheostomy in this case was difficult considering its completely reversible pathology.
Airway management with intubation possesses a significant risk of complete airway obstruction and death in case of accidental extubation, mandating deep sedation (paralysis may be considered) and prolonged mechanical ventilation which significantly delays patient recovery.
Placement of a tracheostomy provides a secure airway and enables safe management of the patient with further advantages of improved patient comfort, reduced sedative requirements and early patient recovery. Although surgical tracheostomy in the presence of severe immunosuppression and thrombocytopenia is not a contraindication, it may be associated with increased risk of surgical complications. Studies regarding this topic are scarce, especially in the pediatric population and do not support a recommendation13-15.
Thus, airway management in these patients must be determined prudently regarding the expected duration of neutropenia, weighting the risks and benefits on an individual case basis.