By Betty Tran, MD, MSc
Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago
SYNOPSIS: In this single-center, retrospective cohort study, intensive care unit (ICU) delirium was associated with a higher rate of cancer treatment modification, only partly due to worsening performance status, after discharge and higher one-year mortality.
SOURCE: Vizzacchi BA, Dettino ALA, Besen BAMP, et al. Delirium during critical illness and subsequent change of treatment in patients with cancer: A mediation analysis. Crit Care Med 2024;52:102-111.
This was a retrospective cohort study from a single dedicated cancer center in Brazil that included patients with active plans for cancer-related treatment admitted to the intensive care unit (ICU) between January 2015 and December 2018. As such, patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 3 (limited self-care) or 4 (completely disabled) were excluded. The exposure of interest was delirium at any point in the ICU, which was assessed twice a day via the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was treatment change, defined as discontinuation of any of the previously planned cancer treatment, at the first outpatient visit after hospital discharge. Secondary outcomes included self-care dependence after hospital discharge, resumption of cancer treatment at six months after hospital discharge, and one-year mortality.
Overall, 1,134 patients were included, of whom 189 (16.7%) developed delirium at some point during their ICU stay. Most patients had metastatic solid tumors (58%) of breast, colorectal, or lung origin and were predominantly admitted for sepsis (32.1%). Patients with delirium more commonly were admitted from the wards, tended to be older, male, had worse performance status at baseline (PS 1 or 2), had higher Simplified Acute Physiology Score 3 (SAPS 3) scores, were more likely to receive invasive mechanical ventilation and renal replacement therapy, and had longer ICU and hospital length of stay (LOS).
Patients returned for their first office visit post-hospital discharge at a median of nine days (interquartile range [IQR], 5-16 days). In models adjusted for age, sex, ECOG PS, Charlson Comorbidity Index (CCI), and SAPS 3, delirium at any time point in the ICU was associated with a higher likelihood of change in previously planned cancer treatment (odds ratio [OR], 3.80; 95% confidence interval [CI], 2.72-5.35). Delirium also was associated with functional dependence after hospital discharge (OR, 7.29; 95% CI, 4.11-13.14). However, a mediation analysis assessing whether the effect of delirium on change in cancer treatment was mediated by functional dependence showed that this factor accounted for only 33.0% of the total effect. Of the 360 patients who had their cancer treatment interrupted, 206 (57.2%) died by six months, with seven patients (1.9%) lost to follow-up. Of the remaining 147 patients, 108 resumed their cancer treatment at six months; the proportion resuming treatment at six months was similar among those with delirium in the ICU (31/41, 75.7%) compared to those who did not have delirium in the ICU (77/106, 72.6%) (P = 0.71). Finally, change in cancer treatment after hospital discharge was associated with lower one-year survival with an increased likelihood of mortality at one year after adjustment for multiple confounders (OR, 2.68; 95% CI, 2.01-3.60).
COMMENTARY
Delirium is common in the ICU and associated with a multitude of patient-related outcomes, including cognitive and functional impairment, emergency department visits and hospital readmissions, and higher mortality.1-3 Depending on the hospital setting, cancer patients may account for approximately 15% of ICU admissions and have significantly high mortality rates, up to nearly 40% for patients with hematologic malignancies, despite oncologic advances over the years.4,5 Even if they survive their ICU and hospital stay, this subpopulation may be at risk for additional post-discharge morbidity, as explored in this study.
There are several notable points in this study. First, the incidence of delirium of 16.7% is much lower than cited in other studies.6 Although this may be due to a highly selective population at a center with no step-down unit, the low frequency of CAM-ICU assessment also could account for this. Second, the primary outcome is not necessarily surprising, but the strength of the OR is notable. Third, the mediation analysis performed by the investigators is intriguing. A large part of decision-making in formulating cancer-related treatment plans is based on a patient’s performance status. Although there is a clear association between ICU delirium and the development of functional dependence post-hospital discharge, both in this study and supported by the literature, this factor did not fully explain why cancer treatment was stopped in these patients. Delirium, therefore, likely has other untoward consequences that make patients less than ideal candidates for continuing cancer treatment. These may include cognitive decline, new medical comorbidities, and overall frailty. As a result of their ICU hospitalization, patients and/or surrogates also may change their goals of care based on the aforementioned conditions. This also could contribute to the increased one-year mortality finding among patients who stopped cancer-related treatment.
In summary, this study highlights the overwhelming importance of delirium in terms of patient outcomes. Interventions to both treat and prevent its occurrence in the ICU and hospital are vital, but recognition and discussion of the impact of delirium on post-discharge management are warranted among oncologists and intensivists whilst the patient is in the hospital and during oncologic follow-up.
REFERENCES
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- Martos-Benítez FD, de Dios Soler-Morejón C, Lara-Ponce KX, et al. Critically ill patients with cancer: A clinical perspective. World J Clin Oncol 2020;11:809-835.
- Kiehl MG, Beutel G, Böll B, et al. Consensus statement for cancer patients requiring intensive care support. Ann Hematol 2018;97:1271-1282.
- Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Crit Care 2008;12(Suppl 3):S3.
