Rationale. Ketamine can provide dissociative sedation and analgesia for mechanically ventilated ICU patients, yet it has been utilized less than other drugs for this purpose. Methods. We reviewed the electronic medical record of critically ill adults who received a continuous infusion of ketamine for ≥24 hours during invasive mechanical ventilation in three hospitals over a two-year period. We captured data including ketamine indication, dose, unintended effects, and adjustments to coadministered sedatives or opioids. We analyzed these data to determine the incidence of reported unintended effects of ketamine infusion (primary outcome) and changes in exposure to coadministered sedatives or opioids during ketamine use (secondary outcome). Results. 95 mechanically ventilated adults received a ketamine infusion for a median duration of 75 hours (interquartile range [IQR] 44–115) at a mean ± standard deviation (SD) infusion rate of 1.3 ± 0.5 mg/kg/hour for the first 24 hours. At least one unintended effect attributed to ketamine was documented in 24% of cases, most frequently tachycardia (6%) and sialorrhea (6%). Other sedative or opioid infusions were administered with ketamine in 76% and 92% of cases, respectively. Comparing the total amount of sedative or opioid administered in the 24 hours prior to ketamine infusion with the total amount administered during the first 24 hours on ketamine, there were no significant differences in propofol, midazolam, or dexmedetomidine exposure, but the average fentanyl exposure was higher after ketamine (2740 ± 1812 mcg) than before (1975 ± 1860 mcg) (absolute difference 766 mcg, 95% confidence interval [CI] 442 to 1089 mcg). Conclusions. In this multicenter cohort of critically ill, mechanically ventilated adults, ketamine infusion was primarily used as an adjunct to conventional sedative and opioid infusions, with noticeable but unintended effects potentially related to ketamine in nearly one-quarter of cases.

Introduction: Invasive pulmonary aspergillosis (IPA) is a rare, severe fungal infection with a poor prognosis and high mortality rate. IPA is mainly noted in patients with immunosuppressed status, hematological malignancies and stem cell transplants. Diagnosis is challenging and requires a high index of suspicion. Current literature supports treating patients with severe covid-19 pneumonia with high dose dexamethasone therapy for a prolonged period of time which may cause significant immune suppression. Here, we present a case of a patient with covid-19 pneumonia who developed IPA after dexamethasone and tocilizumab therapy. Case report: Patient is a 75-year-old male who was admitted to the medical ICU with severe hypoxemic respiratory failure secondary to covid-19 pneumonia requiring mechanical ventilation immediately on presentation to the emergency room. The patient had a past history of cavitary lung disease secondary to tuberculosis in 2018 and had completed treatment with 4-drug therapy. During this hospitalization, three sputum samples were negative for acid fast bacillus. He was started on dexamethasone therapy of 6mg daily for 10 days and received a single dose of tocilizumab. The patient initially improved but started to worsen again on the ninth day requiring increased ventilatory support and pronation therapy. His sputum culture grew Aspergillus FLavus. CT chest showed increased parenchymal infiltrates around prior cavitary lung disease. Serum aspergillus galactomannan antigen returned positive. Patient was started on intravenous Voriconazole. After initial improvement, the patient developed hemoptysis and worsening oxygenation. As per the family's wishes, patient was transitioned to comfort care and he passed away after compassionate extubation. Discussion:Treatment of COVID-19 pneumonia with high dose dexamethasone therapy may inadvertently cause an immunosuppressed state. These immunosuppressive effects may be further compounded by concurrent use of tocilizumab. Relative immunosuppression combined with possible epithelial damage due to viral infection may be a mechanism for development of IPA. A case series from France reported possible IPA in 9 of 27 (33.3%) ICU patients with COVID-19 with an expectedly high observed mortality rate. Conclusion: Clinicians should carry a high index of suspicion and pursue early investigations for other infections in COVID-19 patients who are not recovering or have worsened after initial improvement. Careful use of steroids in patients with prior structural lung disease is also warranted as they may be at high risk of developing IPA due to pre-existing aspergillus colonization.