Introduction: Patients with chronic kidney disease (CKD), especially in advanced stages, face elevated risks for sedation- and analgesia-related adverse events when managed outside intensive care units (ICUs). These events often present atypically and can progress severely, yet risk factors for ICU transfer in this population remain poorly characterized, complicating timely escalation decisions.
Methods: We performed a systematic review of 28 studies (39 adult cases) from 2007 to 2024 across seven countries. Included patients had CKD and experienced sedation-/analgesia-related complications in non-ICU settings. Analyses were conducted using Google Colab; our protocol is registered to OSF. Using age- & sex-adjusted meta-regression, we examined associations between clinical and pharmacologic factors and ICU transfer.
Results: Demographics (age 68±14 years; 59% male), CKD stage distribution (41% ESRD, 21% CKD 5, 18% CKD 4, 18% CKD 3, 15% unclassified), drug exposures, polypharmacy, comorbidities, complication types, and ICU transfers. Sedation-related complications occurred in 69% of cases. Neurologic complications dominated (46%), followed by metabolic (27%), cardiac (19%), and respiratory (12%). Opioids were implicated in 59% of events, with local anesthetics and NMDA antagonists also involved. ICU transfer was necessary in 29%, usually due to respiratory failure, hemodynamic instability, or severe neurotoxicity.
Three independent predictors of ICU transfer emerged: ESRD/CKD5 vs. CKD 3–4 (adjusted odds ratio 3.1, [95% CI] 1.2–8.0, p=0.02), opioid exposure (2.8, [1.1–7.3], p=0.04), and poly-sedation (2.7, [1.0–7.0], p=0.05). Age and sex were not independently linked to ICU transfer. Although 82% of patients recovered, 18% suffered significant morbidity or death. Recovery was least common in ESRD patients exposed to opioids and polypharmacy (60% vs. 88%, p=0.03). In 18% of cases, sedatives were employed to manage refractory symptoms, highlighting treatment complexity.
Conclusions: Nearly 1 in 3 sedation-related complications required ICU care, driven by kidney disease severity, opioid use, and sedative polypharmacy. These findings emphasize the importance of proactive monitoring, cautious drug selection, and prompt critical care involvement to minimize avoidable critical illness in this vulnerable group.
