Opioid Use Increases the Risk of Delirium in Critically Ill Adults Independently of Pain

Impact of the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Guidelines on Nonopioid Analgesic Use and Related Outcomes in Critically Ill Adults After Major Surgery

“…It also remains unclear why more 2019 patients experienced delirium given baseline age and severity of illness and ICU coma, opioid exposure, and mechanical ventilation days were similar between the 2 years ( 6 , 10 , 12 ). However, important factors known to affect ICU delirium occurrence (e.g., blood transfusions, worsening ICU severity of illness) were not collected as part of the study ( 6 ).…”

“…The primary study outcome was daily ICU use of nonopioid analgesics either recommended (i.e., acetaminophen [either IV or oral], ketamine, neuropathic medications [i.e., gabapentin, pregabalin], or not recommended [i.e., lidocaine patches, nonsteroidal anti-inflammatory drugs (NSAIDs)]) by the PADIS guidelines ( 6 ). Secondary outcomes included: 1) baseline patient variables; 2) ICU use of epidural blocks, peripheral nerve blocks, and liposomal bupivacaine; 3) daily ICU opioid (both scheduled and as needed IV and oral/enteral) exposure; 4) daily ICU pain scores (both Visual Analog Scale-10 [VAS-10] and Clinical Pain Observation Tool [CPOT] scores) ( 6 , 8 ); and 5) clinically important sequelae associated with opioid use: coma (Richmond Agitation-Sedation Scale score = –4 or –5) ( 9 , 10 ), delirium (positive Confusion Assessment Method for the ICU) ( 11 , 12 ), constipation (≥ 3 d without a spontaneous bowel movement) ( 13 ), and ICU mechanical ventilation requirements (presented as ICU days without mechanical ventilation and time from ICU admission to extubation ≥ 48 hr [ 6 , 10 ]).…”

“…For the purposes of the study, moderate pain was deemed to be present during an ICU day when greater than or equal to 1 VAS-10 score was 5–6 or CPOT score was 3–4. Severe pain was deemed to be present during an ICU day when greater than or equal to 1 VAS-10 score was greater than or equal to 7 or CPOT score was greater than or equal to 5 ( 8 , 12 , 15 , 16 ). All data were extracted from the MGB Epic (Verona, WI) electronic health record by trained research personnel.…”

Risk Factors for Delirium in the Palliative Care Population: A Systematic Review and Meta-Analysis

“…However, the impact of opioid dose on delirium is still controversial. Some studies considered that the risk of delirium was increased with higher doses of opioids (43,44), but others found that receiving no opioids or very low doses of opioids could increase risk of delirium in patients with severe pain (45)(46)(47). So, pain may act as a confounding factor in the relationship between opioids and delirium.…”

“…Therefore, further research is required to clarify the relationships among opioid dose, pain, and delirium. To reduce delirium occurrence, we should take some strategies, such as routine measurements for delirium, regular opioid dose titration, and adequate pain control ( 44 ). Furthermore, the opioid rotation could also be beneficial for reducing delirium since the risk of delirium may differ in various opioids due to their specific pharmacokinetic and pharmacodynamic properties ( 48 , 49 ).…”