Discussion
cognitive decline, paralysis, psychiatric, PTSD, sepsis
NEUROMUSCULAR BLOCKADE, INFLAMMATION, SECONDARY, CRITICAL ILLNESS, OXIDATIVE STRESS, SEPSIS, SEQUELAE, ENDOTHELIAL DYSFUNCTION
In this prespecified secondary analysis of sepsis survivors in the VICTAS trial, we found no evidence of the benefit of early treatment with vitamin C, thiamine, and hydrocortisone on 6-month cognitive, psychological, and functional outcomes. On the contrary, participants in the intervention group had lower immediate memory scores and higher odds of PTSD compared with participants in the control group. These findings refute the hypothesis that antioxidant and anti-inflammatory therapy during critical illness might mitigate the development of long-term, PICS-related disabilities in survivors of sepsis. The absence of benefit is consistent with results of prior randomized clinical trials that found no improvement in mortality and other hospital-based outcomes with vitamin C therapy.The cognitive scores of both the intervention and control groups were similar in magnitude to those reported in other cohorts of ICU survivors.Could antioxidant-based therapy truly play a role in increased risk of adverse cognitive, psychological, and functional sequelae among sepsis survivors? The increased odds of PTSD that was observed in the intervention group may have been mediated less by the role of vitamin C as an antioxidant and more by its modulation of neurotransmitter metabolism in the brain. Vitamin C facilitates the conversion of dopamine to norepinephrine (also known as noradrenaline).Putative mechanisms of postsepsis cognitive decline include intracerebral oxidative stress, inflammation, and endothelial dysfunction.Sedation and paralysis practices—in particular, number of ICU days with opiates or neuromuscular blockade—may contribute to psychiatric symptoms after critical illness.