Acute amiodarone-induced pulmonary toxicity in adult ICU patients with new-onset atrial fibrillation — A systematic review

Background: New-onset atrial fibrillation or flutter (NOAF) is a common arrhythmia in adult intensive care unit (ICU) patients. Intravenous amiodarone is one of the most used anti-arrhythmic drugs, despite its risk of inducing acute amiodarone-induced pulmonary toxicity (APT). We aimed to outline the body of evidence on acute APT in ICU patients with NOAF. Methods: We performed a systematic search using the population, intervention, comparison, and outcome (PICO) approach. We included studies of adults admitted to the ICU, who developed NOAF during their ICU stay, were treated with amiodarone, and reported on acute APT, irrespective of research design. The CASE guidelines were applied to evaluate the quality of the included studies, and study results are reported in accordance with the preferred reporting items for systematic reviews and meta-analyses. Results: No randomised controlled trials or observational studies were identified. Nine case reports and one retrospective case series of fatal outcomes in ICU patients treated with amiodarone for NOAF constituted the evidence base. The quality of the included studies was high with a mean of 10 (range 8–12) of the 13 CASE guideline criteria fulfilled. The studies included a total of 16 critically ill adults who was diagnosed with acute APT after a mean of 9 days (range 2–20 days) following initiation of amiodarone with a mean total dose of amiodarone of 4553 mg (range 1100–13,500 mg) predominantly administrated intravenously. Three out of nine patients in the case reports died in the ICU during the amiodarone treatment. No long-term follow-up was conducted for the survivors. Conclusion: Acute APT in adult ICU patients treated with amiodarone for NOAF is poorly described and is based on a total of 16 reported cases. Additional studies assessing the safety of amiodarone in critically ill adults with NOAF in the ICU is warranted.