Persistent nausea burden at peak antiemetic therapy in palliative care: an exploratory study

BACKGROUND: Nausea is a common and distressing symptom in palliative care, substantially impairing quality of life. Despite guideline-based antiemetic therapy, a considerable proportion of patients continue to experience substantial nausea burden. Evidence guiding personalised management strategies in this setting remains limited. This study aimed to identify routinely available laboratory markers and clinical factors associated with persistent nausea burden at peak antiemetic therapy. METHODS: In this retrospective exploratory study, 788 admissions to a specialised palliative care unit (2019-2022) were screened, and 223 cases with documented nausea were included. Nausea burden and associated symptom burdens were assessed at the time of "peak antiemetic therapy", defined as the highest level of antiemetic treatment reached during admission beyond which therapy was not further escalated. Symptom burden was measured using the staff-completed Integrated Palliative Outcome Scale (IPOS). Baseline demographic, clinical, and laboratory variables were assessed at admission. Patients were stratified according to persistent nausea burden (IPOS ≥ 2 vs. < 2). Univariable analyses were performed to identify a core set of associated factors. Baseline variables meeting significance criteria were entered into complete-case binary logistic regression with bootstrap validation (1,000 samples; N = 143). Multiple testing was addressed using the Benjamini-Hochberg (BH) procedure. RESULTS: Persistent nausea burden at peak antiemetic therapy was observed in 33% of patients with nausea. After BH adjustment, vomiting and poor appetite (both IPOS ≥ 2), cystatin C levels, broad-spectrum antiemetic therapy, in-house mortality, ileus, and peritoneal carcinomatosis were significantly associated with persistent nausea burden at peak antiemetic therapy in univariable analyses (BH-adjusted p < 0.05). Of these, the baseline variables ileus, peritoneal carcinomatosis, and cystatin C levels constituted the core set for multivariable analysis. In logistic regression, higher cystatin C levels were associated with lower odds of persistent nausea burden (OR = 0.235; 95% CI [0.08-0.47]; BH-adjusted p = 0.003), whereas peritoneal carcinomatosis was associated with higher odds (OR = 3.967; 95% CI [1.54-12.29]; BH-adjusted p = 0.005). CONCLUSIONS: Persistent nausea burden co-occurred with diverse clinical factors, underscoring its multifactorial nature in advanced disease. Nausea management in palliation remains a major challenge far beyond the application of antiemetics. Prospective studies are warranted.