Severe anxiety, depression, and sleep disorders worsen prognosis in patients with septic shock

Abstract

Recent studies have revealed that patients with septic shock and acute skin failure (ASF) exhibit significantly higher levels of inflammatory cytokines, lactate, and C-reactive protein, along with elevated skin mottling score; modified early warning score (MEWS); and anxiety, depression, and Pittsburgh sleep quality index scores compared to those without ASF. Notably, these indicators are significantly correlated. Patients with septic shock accompanied by ASF tend to have a mean MEWS greater than 9, indicating severe disease progression. Therefore, it is essential to not only manage septic shock but also mitigate anxiety, depression, sleep disorders, and disturbances of consciousness. This article explores the impact of severe anxiety, depression, and sleep disorders on the prognosis of septic shock and discusses intervention strategies.

Key Words: Septic shock; Poor prognosis; Anxiety; Depression; Sleep disorders; Inflammatory cytokines; Acute skin failure; Psychological interventions; Mortality; Critical care

Core Tip: Patients with septic shock and acute skin failure (ASF) exhibited significantly higher levels of inflammatory cytokines, lactate, and clinical severity scores compared to those without ASF, accompanied by severe anxiety and depression, as well as sleep disorders. These pathological changes are significantly correlated. Severe anxiety, depression, and sleep disorders may serve as important indicators of disease progression and poor prognosis in patients with septic shock and ASF. Psychological interventions, psychotropic medications, and meticulous nursing care for anxiety, depression, and sleep disorders may improve the prognosis of patients with septic shock.

TO THE EDITOR

Sepsis often leads to complications such as septic shock. Despite advancements in medical technology, the sepsis-related mortality rate has decreased in recent years; however, this reduction remains modest[1,2]. In particular, when sepsis shock is accompanied by acute skin failure (ASF) and hyperlactatemia, patients tend to experience more complex pathological changes, increased treatment challenges, and persistently high mortality rates[3]. When pathological reductions in blood flow perfusion affect the skin and subcutaneous tissues, the skin, similar to other organs, may suffer from pathological damage and failure, referred to as ASF. The main pathophysiological changes include hypoperfusion, hypoxia, inflammation, increased vascular permeability, and edema, among others[4]. Recently, a study titled “Relationship between inflammatory factors, lactic acid levels, ASF, bad mood, and sleep quality” was published in the World Journal of Psychiatry by Liu et al[5] from the Second Affiliated Hospital of Dalian Medical University. This study provides a new perspective on deepening our understanding of the pathological mechanisms of septic shock, optimizing treatment protocols, and improving prognosis.

In this study, 150 patients with septic shock were enrolled in the research cohort. Patients were divided into ASF (n = 35) and non-ASF (n = 115) groups based on the presence of ASF. Statistical analysis results of the t-test revealed that compared to patients with septic shock without ASF, those with ASF had significantly elevated levels of inflammatory cytokines (ICs) such as interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and the specific inflammation marker C-reactive protein (CRP). Additionally, lactate levels, skin mottling score (SMS), and modified early warning score (MEWS) were significantly higher in the ASF group. Furthermore, patients with septic shock and ASF scored significantly higher on the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Pittsburgh sleep quality index (PSQI) than those without ASF. Pearson correlation analysis revealed a positive correlation between IL-6, CRP, TNF-α, and lactate levels in peripheral blood with SMS, MEWS, SAS, SDS, and PSQI scores[5]. This discovery suggests that high levels of ICs, lactate, and ASF complications play a crucial role in septic shock. However, severe anxiety, depression (negative emotions) and sleep disorders also contribute significantly to disease progression. The emergence and interaction of these factors may collectively influence the prognosis of patients with septic shock. This study is the first to systematically investigate the interaction between negative emotions and inflammatory markers in patients with ASF, providing new insights into the pathological mechanisms underlying septic shock and offering potential therapeutic targets for improving patient prognosis and reducing mortality rates.

INTERPLAY OF PSYCHOLOGICAL AND BIOMEDICAL FACTORS IN SEPTIC SHOCK

Patients with sepsis often experience negative emotions and sleep disorders. As sepsis progresses to severe stages, complications such as septic shock, a life-threatening condition with a high risk of poor prognosis, can develop. This progression often triggers intense fear, anxiety, and pessimism in patients, which may even lead to post-traumatic stress disorder[6]. Studies have shown that patients with depression exhibit elevated levels of ICs in their bodies, with high levels of IL-1β and TNF-α being associated with moderate-to-severe depressive symptoms and suicidal ideation and behavior, respectively[7]. Depression may stem from neuroinflammation and an imbalance of IC[8], with increased levels of IC such as IL-1, IL-6, IL-12, TNF-α, prostaglandin E2, and certain negative immune-regulatory cytokines in patients[8-10]. Moreover, elevated levels of IL-6, TNF-α, and CRP have been identified as predictors of depression onset[11,12]. Consistently increased inflammatory markers in patients with depression include IL-3, IL-6, IL-12, IL-18, soluble IL-2 receptor, TNF-α, and CRP[13]. The activation of inflammatory processes and elevated levels of ICs can lead to structural and functional changes in neurons, thereby contributing to the development of depression[14]. Increased IL-1β, TNF-α and IL-6 activity may induce depression by activating the hypothalamic-pituitary-adrenal axis or by affecting neurotransmitter metabolism[15]. Meanwhile, a depressive mood may affect the hypothalamic-pituitary axis, autonomic nervous system, and metabolic factors through high levels of ICs, thereby worsening the prognosis of patients with various diseases[16,17]. The causal relationship remains unclear: Whether septic shock with ASF triggers anxiety and depression through high ICs or whether the stress of severe illness induces anxiety and depression, leading to elevated ICs. However, based on the observed severity of depression and the pathological phenomenon of hyperinflammatory cytokines in septic shock with ASF, the two may interact. Severe negative emotions, sleep disorders, or disturbances of consciousness, along with high levels of ICs, lactate, and CRP, combined with ASF, may indicate the progression and poor prognosis of septic shock. Therefore, both biomedical and psychological factors, as well as their mutual interactions, should be considered for the treatment of septic shock, and comprehensive measures should be taken to improve patient prognosis.

TREATMENT STRATEGIES FOR SEPTIC SHOCK ACCOMPANIED BY NEGATIVE EMOTIONS

Septic shock is often accompanied by multi-organ damage. Therefore, in clinical practice, it is essential not only to closely monitor patients’ somatic symptoms and organic pathological changes but also to emphasize the importance of psychiatric consultations for prompt detection, accurate assessment, and effective intervention for patients’ negative emotions and sleep disorders. The integration of psychiatrists and nurses skilled in psychological care and meticulous nursing into multidisciplinary teams is crucial, as their specialized skills can be utilized to mitigate the reciprocal interactions between patients' negative emotions, sleep disturbances, and pathophysiological processes. Interventions targeting these psychological disorders may positively affect the prognosis of patients with septic shock. While treating septic shock and its various complications, supportive psychotherapy and attentive nursing care are of great significance for patient rehabilitation[18]. To mitigate the impact of negative emotions during the septic crisis period, proactive symptomatic management of pain, physical discomfort, anxiety, and sleep disturbances helps reduce stress-related consequences. In the recovery period, early physical activity combined with appropriate attention training, resilience exercises, and cognitive behavioral therapy contributes to the improvement of negative emotional states[19]. Psychopharmacological interventions may be beneficial in septic shock[20]; however, caution is warranted when using benzodiazepines because of their potential to increase the mortality risk[21], especially in patients with severe consciousness and respiratory disorders, for whom the use of such drugs should be carefully considered. The Japanese Clinical Practice Guidelines for Sepsis and Septic Shock recommend non-pharmacological sleep management techniques, such as earplugs, eye masks, and music therapy, to improve sleep quality. Additionally, for patients with delirium, vigilance should be maintained for factors such as alcohol or benzodiazepine withdrawal[22], and pressure-controlled ventilation may improve sleep quality in mechanically ventilated patients[23].

Studies have shown that most non-survivor patients with coronavirus disease 2019 (COVID-19) (70%) had septic shock. Despite differing causative pathogens, both septic shock and COVID-19 are systemic inflammatory diseases that share numerous pathological similarities[24]. Antidepressants can reduce the levels of ICs and increase those of anti-IC[25]. This finding has also been validated in patients with COVID-19, some of whom exhibit a pattern of multi-organ failure similar to that observed in patients with bacterial sepsis[26]. Antidepressants exert a favorable impact on COVID-19 prognosis by reducing IL-6-induced acute inflammation[27]. A meta-analysis further revealed that the use of antidepressants such as fluvoxamine, escitalopram, fluoxetine, paroxetine, and venlafaxine was associated with a reduced risk of intubation or death in COVID-19 patients, with fluvoxamine significantly mitigating the severity of COVID-19[28]. Antidepressants (e.g., fluvoxamine, fluoxetine, venlafaxine, mirtazapine, and escitalopram) not only reduce the risk of intubation or death related to COVID-19 and decrease the need for intensive care but also significantly inhibit viral titers[29]. This suggests that in patients with severe respiratory diseases, even in the presence of comorbidities, antidepressants may be appropriately utilized to improve negative emotions and sleep disorders. In addition, some antidepressants can improve sleep while alleviating depressive symptoms, such as low doses of mirtazapine, trazodone, and agomelatine[30,31]. Therefore, in patients with sepsis and septic shock accompanied by negative emotions and sleep disorders, antidepressants may help improve their quality of life and prognosis. New-generation antidepressants demonstrate good safety profiles, favorable tolerability, and lower treatment failure rates[32]. However, special consideration should be given to patients with cardiovascular diseases or advanced age, as these medications may potentially exacerbate cardiovascular conditions. Tricyclic antidepressants should be avoided in such populations. Although some studies report no association between selective serotonin reuptake inhibitors and cerebrocardiovascular events—with some even suggesting a potential risk reduction, it remains prudent to initiate therapy at low doses and titrate gradually based on individual patient factors[33]. As the clinical condition of septic shock improves and negative emotions alleviate the antidepressant dosage may be appropriately reduced to half of the therapeutic dose, with maintenance therapy continued for at least six months. The optimal duration of application should be determined based on a comprehensive assessment of the patient's individual condition.

LIMITATION AND FUTURE DIRECTIONS

Accurately assessing the severity of negative emotions in patients with septic shock is challenging. Although SDS, SAS, and PSQI are commonly used psychological self-assessment scales, their sensitivity to detect psychological symptoms in septic shock may be attenuated by disease-specific factors such as cognitive impairment and fatigue severity. Future studies should incorporate objective biomarkers, such as cortisol, brain derived neurotrophic factor levels, to complement these assessments[34]. Additionally, many factors influence the prognosis of septic shock, such as the patient's comorbidities, medication history, age, and physical constitution. Among these various influencing factors, the impact of severe negative emotions and sleep disorders on the prognosis of septic shock warrants further in-depth research.

CONCLUSION

In the management of septic shock, it is crucial not only to focus on correcting the patient’s physical pathological changes but also to prioritize the recognition and treatment of severe emotional disorders, sleep disorders, and consciousness impairments. Psychological interventions, meticulous nursing care, and antidepressant therapy may significantly improve patient prognosis. To further enhance treatment effectiveness, more in-depth research in this area is required to develop more effective treatment methods, thereby making significant contributions to reducing mortality rates among patients with septic shock.