Preventive strategies and potential therapeutic interventions for delirium in sepsis

Abstract

Delirium is the most frequent and severe clinical presentation of brain dysfunction in critically ill septic patients with an incidence ranging from 9% to 71%. Delirium represents a significant burden for patients and relatives, as well as to the health care system, resulting in higher costs, long-term cognitive impairment and significant risk of death after 6 months. Current interventions for the prevention of delirium typically involve early recognition and amelioration of modifiable risk factors and treatment of underlying conditions that predisposes the individual to delirium. Several pharmacological interventions to prevent and treat delirium have been tested, although their effectiveness remains uncertain, especially in larger and more homogeneous subgroups of ICU patients, like in patients with sepsis. To date, there is inconsistent and conflicting data regarding the efficacy of any particular pharmacological agent, thus substantial attention has been paid to non-pharmacological interventions and preventive strategies should be applied to every patient admitted in the ICU. Future trials should be designed to evaluate the impact of these pharmacologic interventions on the prevention and treatment of delirium on clinically relevant outcomes such as length of stay, hospital mortality and long-term cognitive function. The role of specific medications like statins in delirium prevention is also yet to be evaluated.

Relationship Between Cerebral Hemodynamics, Tissue Oxygen Saturation, and Delirium in Patients With Septic Shock: A Pilot Observational Cohort Study

“…The sepsis-associated delirium (SAD) is regarded as a diffuse cerebral dysfunction, caused by inflammatory responses of the body to infections taking place with no discernible cause of central nervous system, i.e., infection. SAD may have a rapid onset and levels may fluctuate over time (1,2). Research has demonstrated that pathogenesis of SAD can involve neuronal degeneration, neurotransmitter imbalance, abnormal cerebral perfusion, and neuroinflammation (3)(4)(5)(6).…”

Relationship between cerebral hemodynamics, tissue oxygen saturation, and delirium in patients with septic shock: a pilot observational trial

“…The overall median mechanical ventilation time was 5 [1,5] days and median ICU stay was 6 [3,12] days. Compared with the non-SAD group, the SAD group needed a longer mechanical ventilation time (5 [2,6] days vs 1 [1,4] days, p = 0.015), and ICU stay (9 [5,20] days vs 5 [3,9] days, p = 0.042). The 28-day mortality rate was 43% for the entire cohort and was signi cantly higher in the SAD group (65% vs 29%, p = 0.011) ( Table 1).…”

“…Sepsis-associated delirium (SAD) is considered a diffuse cerebral dysfunction caused by a systemic in ammatory response to an infection without evidence of a central nervous system involvement (i.e., infection). SAD can develop in a short time and uctuate transiently with time [1][2]. Studies have found that neuroin ammation, abnormal cerebral perfusion, neurotransmitter imbalances and neuronal degeneration may be involved in the pathogenesis of SAD [3][4][5][6].…”

Sepsis therapies: learning from 30 years of failure of translational research to propose new leads

“…Minimization or avoidance of iatrogenic factors related to treatment (e.g., prolonged use of benzodiazepine sedation, and adequate pain treatment) and non‐pharmacological modalities (e.g., physiological light cycle, cognitive stimulation, and early mobilization) may prove useful (Souza‐Dantas et al , ). Existing drugs such as metformin (Tang et al , ) and minocycline (Adembri et al , ) show brain protective effects in experimental sepsis.…”