Forensic Toxicological and Medico-Legal Evaluation in a Case of Incongruous Drug Administration in Terminal Cancer Patients

Background: In most cases, palliative care is prescribed to adults diagnosed with cancer. The definition of the most suitable therapy for an effective sedation in terminal cancer patients still represents one of the most challenging goals in medical practice. Due to their poor health, the correct dosing of drugs used for deep palliative sedation in terminal cancer patients, often already on polypharmacological therapy, can be extremely complicated, also considering possible drug-to-drug interactions that could lead to an increased risk of overdose and/or incongruous administration with fatal outcomes. The case of a terminal cancer patient is presented, focusing on the "adequacy" of administered therapy. Materials and Methods: A young male, affected by Ewing sarcoma, attending a palliative care at his own home, died soon after midazolam administration. Toxicological and histological analyses were performed on body fluids and organ fragments. Results and Discussion: Morphological reliefs evidenced a neoplastic mass, composed of lobulated tissue with a lardy, pinkish-gray consistency, extending from the pleural surface to the lung parenchyma, also present at the sacrum region (S1-S5), at the anterior mediastinum level, occupying the entire left pleural cavity, and infiltrating the ipsilateral lung. Metastatic lesions diffused to rachis and lumbar structures. The brain presented edema and congestion. Toxicological analyses evidenced blood midazolam concentrations in the range of 0.931-1.690 mu g/mL, while morphine was between 0.266 and 0.909 mu g/mL. Death was attributed to cardiorespiratory depression because of a synergic action between morphine and midazolam. The pharmacological interaction between midazolam and morphine is discussed considering the clinical situation of the patient. The opportunity to proceed with midazolam administration is discussed starting from guidelines recommendation. Finally, professional liability outlines are highlighted.