老年膿毒癥患者譫妄的診治研究進展_Chinese Journal of Respiratory and Critical Care Medicine

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路佩源 ¹ , 木其爾 ² , 李承方 ¹ , 郭超 ¹ , 何繼星 ¹ , 裴斯彤 ¹ ,  袁媛 ¹

1. ;
2. ;

Corresponding?author：

袁媛, Email: lanzhouyy@163.com

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DOI：

10.7507/1671-6205.202507021

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Citation： 路佩源, 木其爾, 李承方, 郭超, 何繼星, 裴斯彤, 袁媛. 老年膿毒癥患者譫妄的診治研究進展. Chinese Journal of Respiratory and Critical Care Medicine, 2026, 25(5): 376-380. doi: 10.7507/1671-6205.202507021 Copy

1.	Atterton B, Paulino MC, Povoa P, et al. Sepsis associated delirium. Medicina (Kaunas), 2020, 56(5): 240.
2.	趙艷, 謝志娟, 洪莎, 等. 重癥監護病房老年病人膿毒癥相關譫妄的危險因素分析. 實用老年醫學, 2023, 37(7): 705-708.
3.	Yao S, Zhang G, Ni L. Association between red cell distribution width-to-albumin ratio and short-term mortality in patients with sepsis-associated delirium: a retrospective study from the MIMIC-IV database. BMC Anesthesiol, 2025, 25(1): 192.
4.	Chung H, Wickel J, Brunkhorst FM, et al. Sepsis-associated encephalopathy: from delirium to dementia?J Clin Med, 2020, 9(3): 703.
5.	Zheng G, Yan J, Li W, et al. Frailty as an independent risk factor for sepsis-associated delirium: a cohort study of 11, 740 older adult ICU patients. Aging Clin Exp Res, 2025, 37(1): 52.
6.	de Rooij SE, van Munster BC, Korevaar JC, et al. Cytokines and acute phase response in delirium. J Psychosom Res, 2007, 62(5): 521-525.
7.	Beloosesky Y, Hendel D, Weiss A, et al. Cytokines and C-reactive protein production in hip-fracture-operated elderly patients. J Gerontol A Biol Sci Med Sci, 2007, 62(4): 420-426.
8.	Sharshar T, Polito A, Checinski A, et al. Septic-associated encephalopathy-everything starts at a microlevel. Crit Care, 2010, 14(5): 199.
9.	Comim CM, Vilela MC, Constantino LS, et al. Traffic of leukocytes and cytokine up-regulation in the central nervous system in sepsis. Intensive Care Med, 2011, 37(4): 711-718.
10.	Ari I, Kafa IM, Kurt MA. Perimicrovascular edema in the frontal cortex in a rat model of intraperitoneal sepsis. Exp Neurol, 2006, 198(1): 242-249.
11.	Vachharajani V, Cunningham C, Yoza B, et al. Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain. Obesity (Silver Spring), 2012, 20(3): 498-504.
12.	Komici K, Fantini C, Santulli G, et al. The role of diabetes mellitus on delirium onset: a systematic review and meta-analysis. Cardiovasc Diabetol, 2025, 24(1): 216.
13.	van Keulen K, Knol W, Belitser SV, et al. Diabetes and glucose dysregulation and transition to delirium in ICU patients. Crit Care Med, 2018, 46(9): 1444-1449.
14.	Sonneville R, de Montmollin E, Poujade J, et al. Potentially modifiable factors contributing to sepsis-associated encephalopathy. Intensive Care Med, 2017, 43(8): 1075-1084.
15.	Chen J, Shi X, Diao M, et al. A retrospective study of sepsis-associated encephalopathy: epidemiology, clinical features and adverse outcomes. BMC Emerg Med, 2020, 20(1): 77.
16.	Stilling RM, Dinan TG, Cryan J F. Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis. Genes Brain Behav, 2014, 13(1): 69-86.
17.	Ridaura V, Belkaid Y. Gut microbiota: the link to your second brain. Cell, 2015, 161(2): 193-194.
18.	Xu X, Hu Y, Yan E, et al. Perioperative neurocognitive dysfunction: thinking from the gut? Aging (Albany NY), 2020, 12(15): 15797-15817.
19.	Shen L, Liu L, Ji H. Alzheimer's disease histological and behavioral manifestations in transgenic mice correlate with specific gut microbiome state. J Alzheimers Dis, 2017, 56(1): 385-390.
20.	Zhang J, Bi J, Guo G, et al. Abnormal composition of gut microbiota contributes to delirium-like behaviors after abdominal surgery in mice. CNS Neurosci Ther, 2019, 25(6): 685-696.
21.	Huo J, Han S, Hao X, et al. Alterations in the gut microbiome and metabolome in elderly patients with postoperative delirium: A prospective nested case-control study. J Clin Anesth, 2025, 103: 111833.
22.	Haseeb MA, Salwen MJ. Collateral damage: sepsis-induced gut injury. Crit Care Med, 2005, 33(10): 2439-2440.
23.	Salazar N, Arboleya S, Fernández-Navarro T, et al. Age-associated changes in gut microbiota and dietary components related with the immune system in adulthood and old age: a cross-sectional study. Nutrients, 2019, 11(8): 1765.
24.	Mo?si L, Mino J, Guidet B, et al. Frailty assessment in critically ill older adults: a narrative review. Ann Intensive Care, 2024, 14(1): 93.
25.	Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci, 2001, 56(3): M146-M156.
26.	Kukreja D, Günther U, Popp J. Delirium in the elderly: current problems with increasing geriatric age. Indian J Med Res, 2015, 142(6): 655-662.
27.	Guo R, Zhang S, Yu S, et al. Inclusion of frailty improved performance of delirium prediction for elderly patients in the cardiac intensive care unit (D-FRAIL): a prospective derivation and external validation study. Int J Nurs Stud, 2023, 147: 104582.
28.	Dent E, Martin FC, Bergman H, et al. Management of frailty: opportunities, challenges, and future directions. Lancet, 2019, 394(10206): 1376-1386.
29.	Zhang X, Jiao J, Xie X, et al. The association between frailty and delirium among hospitalized patients: an updated meta-analysis. J Am Med Dir Assoc, 2021, 22(3): 527-534.
30.	Ruan H, Hu J, Zhao J, et al. Menopause and frailty: a scoping review. Menopause, 2020, 27(10): 1185-1195.
31.	Ren H, Wang Z, Jiang Y, et al. Antidepressant intervention to possibly delay disease progression and frailty in elderly idiopathic pulmonary fibrosis patients: a clinical trial. Aging Clin Exp Res, 2025, 37(1): 101.
32.	Klawitter F, Jager M, Klinkmann G, et al. Sepsis-associated encephalopathy: a nationwide survey on diagnostic procedures and neuromonitoring in German intensive care units. Anaesthesist, 2021, 70(2): 112-120.
33.	Gusmao-Flores D, Salluh JIF, Chalhub Rá, et al. The confusion assessment method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies. Crit Care, 2012, 16(4): R115.
34.	Luetz A, Balzer F, Radtke FM, et al. Delirium, sedation and analgesia in the intensive care unit: a multinational, two-part survey among intensivists. PLoS One, 2014, 9(11): e110935.
35.	Hu Z, Deng N, Liu K, et al. CNTF-STAT3-IL-6 Axis mediates neuroinflammatory cascade across schwann cell-neuron-microglia. Cell Rep, 2020, 31(7): 107657.
36.	Khan BA, Perkins AJ, Prasad NK, et al. Biomarkers of delirium duration and delirium severity in the ICU. Crit Care Med, 2020, 48(3): 353-361.
37.	Michetti F, D'Ambrosi N, Toesca A, et al. The S100B story: from biomarker to active factor in neural injury. J Neurochem, 2019, 148(2): 168-187.
38.	Erikson K, Ala-Kokko TI, Koskenkari J, et al. Elevated serum S-100β in patients with septic shock is associated with delirium. Acta Anaesthesiol Scand, 2019, 63(1): 69-73.
39.	Honore PM, Redant S, Kaefer K, et al. Higher Levels of S-100β-a biomarker of astrocyte and glial activation were associated with a greater delirium duration in sepsis and traumatic brain injury patients: beware of some confounders!Crit Care Med, 2021, 49(7): e736-e737.
40.	趙孝開, 李曉亮, 肖宏濤, 等. 血清NSE、S100β、IL-6與燒傷患者膿毒癥相關性腦病的相關性分析. 中國燒傷創瘍雜志, 2020, 32(6): 406-408.
41.	袁繼印, 劉景剛, 張貴真, 等. 慢性阻塞性肺疾病機械通氣患者發生譫妄的危險因素分析. 中國呼吸與危重監護雜志, 2019, 18(6): 522-526.
42.	Sonneville R, Benghanem S, Jeantin L, et al. The spectrum of sepsis-associated encephalopathy: a clinical perspective. Crit Care, 2023, 27(1): 386.
43.	Gofton TE, Young GB. Sepsis-associated encephalopathy. Nat Rev Neurol, 2012, 8(10): 557-566.
44.	Ehler J, Petzold A, Wittstock M, et al. The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - a prospective, pilot observational study. PLoS One, 2019, 14(1): e211184.
45.	Page VJ, Watne O, Heslegrave A, et al. Plasma neurofilament light chain protein as a predictor of days in delirium and deep sedation, mortality and length of stay in critically ill patients. EBioMedicine, 2022, 80: 104043.
46.	Wu L, Ai M, Feng Q, et al. Serum glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 for diagnosis of sepsis-associated encephalopathy and outcome prognostication. J Crit Care, 2019, 52: 172-179.
47.	Ehler J, Saller T, Wittstock M, et al. Diagnostic value of NT-proCNP compared to NSE and S100B in cerebrospinal fluid and plasma of patients with sepsis-associated encephalopathy. Neurosci Lett, 2019, 692: 167-173.
48.	Osca-Verdegal R, Beltrán-García J, Pallardó FV, et al. Role of microRNAs as biomarkers in sepsis-associated encephalopathy. Mol Neurobiol, 2021, 58(9): 4682-4693.
49.	Tomasi CD, Vuolo F, Generoso J, et al. Biomarkers of delirium in a low-risk community-acquired pneumonia-induced sepsis. Mol Neurobiol, 2017, 54(1): 722-726.
50.	Mazeraud A, Righy C, Bouchereau E, et al. Septic-associated encephalopathy: a comprehensive review. Neurotherapeutics, 2020, 17(2): 392-403.
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53.	艾美林, 黃立, 馮清, 等. 經顱多普勒超聲在早期診斷膿毒癥相關性腦病中的臨床意義. 中華內科雜志, 2019, 58(11): 814-818.
54.	Nielsen RM, Olsen KS, Lauritsen AO, et al. Electroconvulsive therapy as a treatment for protracted refractory delirium in the intensive care unit-five cases and a review. J Crit Care, 2014, 29(5): 881.
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1. Atterton B, Paulino MC, Povoa P, et al. Sepsis associated delirium. Medicina (Kaunas), 2020, 56(5): 240.
2. 趙艷, 謝志娟, 洪莎, 等. 重癥監護病房老年病人膿毒癥相關譫妄的危險因素分析. 實用老年醫學, 2023, 37(7): 705-708.
3. Yao S, Zhang G, Ni L. Association between red cell distribution width-to-albumin ratio and short-term mortality in patients with sepsis-associated delirium: a retrospective study from the MIMIC-IV database. BMC Anesthesiol, 2025, 25(1): 192.
4. Chung H, Wickel J, Brunkhorst FM, et al. Sepsis-associated encephalopathy: from delirium to dementia?J Clin Med, 2020, 9(3): 703.
5. Zheng G, Yan J, Li W, et al. Frailty as an independent risk factor for sepsis-associated delirium: a cohort study of 11, 740 older adult ICU patients. Aging Clin Exp Res, 2025, 37(1): 52.
6. de Rooij SE, van Munster BC, Korevaar JC, et al. Cytokines and acute phase response in delirium. J Psychosom Res, 2007, 62(5): 521-525.
7. Beloosesky Y, Hendel D, Weiss A, et al. Cytokines and C-reactive protein production in hip-fracture-operated elderly patients. J Gerontol A Biol Sci Med Sci, 2007, 62(4): 420-426.
8. Sharshar T, Polito A, Checinski A, et al. Septic-associated encephalopathy-everything starts at a microlevel. Crit Care, 2010, 14(5): 199.
9. Comim CM, Vilela MC, Constantino LS, et al. Traffic of leukocytes and cytokine up-regulation in the central nervous system in sepsis. Intensive Care Med, 2011, 37(4): 711-718.
10. Ari I, Kafa IM, Kurt MA. Perimicrovascular edema in the frontal cortex in a rat model of intraperitoneal sepsis. Exp Neurol, 2006, 198(1): 242-249.
11. Vachharajani V, Cunningham C, Yoza B, et al. Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain. Obesity (Silver Spring), 2012, 20(3): 498-504.
12. Komici K, Fantini C, Santulli G, et al. The role of diabetes mellitus on delirium onset: a systematic review and meta-analysis. Cardiovasc Diabetol, 2025, 24(1): 216.
13. van Keulen K, Knol W, Belitser SV, et al. Diabetes and glucose dysregulation and transition to delirium in ICU patients. Crit Care Med, 2018, 46(9): 1444-1449.
14. Sonneville R, de Montmollin E, Poujade J, et al. Potentially modifiable factors contributing to sepsis-associated encephalopathy. Intensive Care Med, 2017, 43(8): 1075-1084.
15. Chen J, Shi X, Diao M, et al. A retrospective study of sepsis-associated encephalopathy: epidemiology, clinical features and adverse outcomes. BMC Emerg Med, 2020, 20(1): 77.
16. Stilling RM, Dinan TG, Cryan J F. Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis. Genes Brain Behav, 2014, 13(1): 69-86.
17. Ridaura V, Belkaid Y. Gut microbiota: the link to your second brain. Cell, 2015, 161(2): 193-194.
18. Xu X, Hu Y, Yan E, et al. Perioperative neurocognitive dysfunction: thinking from the gut? Aging (Albany NY), 2020, 12(15): 15797-15817.
19. Shen L, Liu L, Ji H. Alzheimer's disease histological and behavioral manifestations in transgenic mice correlate with specific gut microbiome state. J Alzheimers Dis, 2017, 56(1): 385-390.
20. Zhang J, Bi J, Guo G, et al. Abnormal composition of gut microbiota contributes to delirium-like behaviors after abdominal surgery in mice. CNS Neurosci Ther, 2019, 25(6): 685-696.
21. Huo J, Han S, Hao X, et al. Alterations in the gut microbiome and metabolome in elderly patients with postoperative delirium: A prospective nested case-control study. J Clin Anesth, 2025, 103: 111833.
22. Haseeb MA, Salwen MJ. Collateral damage: sepsis-induced gut injury. Crit Care Med, 2005, 33(10): 2439-2440.
23. Salazar N, Arboleya S, Fernández-Navarro T, et al. Age-associated changes in gut microbiota and dietary components related with the immune system in adulthood and old age: a cross-sectional study. Nutrients, 2019, 11(8): 1765.
24. Mo?si L, Mino J, Guidet B, et al. Frailty assessment in critically ill older adults: a narrative review. Ann Intensive Care, 2024, 14(1): 93.
25. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci, 2001, 56(3): M146-M156.
26. Kukreja D, Günther U, Popp J. Delirium in the elderly: current problems with increasing geriatric age. Indian J Med Res, 2015, 142(6): 655-662.
27. Guo R, Zhang S, Yu S, et al. Inclusion of frailty improved performance of delirium prediction for elderly patients in the cardiac intensive care unit (D-FRAIL): a prospective derivation and external validation study. Int J Nurs Stud, 2023, 147: 104582.
28. Dent E, Martin FC, Bergman H, et al. Management of frailty: opportunities, challenges, and future directions. Lancet, 2019, 394(10206): 1376-1386.
29. Zhang X, Jiao J, Xie X, et al. The association between frailty and delirium among hospitalized patients: an updated meta-analysis. J Am Med Dir Assoc, 2021, 22(3): 527-534.
30. Ruan H, Hu J, Zhao J, et al. Menopause and frailty: a scoping review. Menopause, 2020, 27(10): 1185-1195.
31. Ren H, Wang Z, Jiang Y, et al. Antidepressant intervention to possibly delay disease progression and frailty in elderly idiopathic pulmonary fibrosis patients: a clinical trial. Aging Clin Exp Res, 2025, 37(1): 101.
32. Klawitter F, Jager M, Klinkmann G, et al. Sepsis-associated encephalopathy: a nationwide survey on diagnostic procedures and neuromonitoring in German intensive care units. Anaesthesist, 2021, 70(2): 112-120.
33. Gusmao-Flores D, Salluh JIF, Chalhub Rá, et al. The confusion assessment method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies. Crit Care, 2012, 16(4): R115.
34. Luetz A, Balzer F, Radtke FM, et al. Delirium, sedation and analgesia in the intensive care unit: a multinational, two-part survey among intensivists. PLoS One, 2014, 9(11): e110935.
35. Hu Z, Deng N, Liu K, et al. CNTF-STAT3-IL-6 Axis mediates neuroinflammatory cascade across schwann cell-neuron-microglia. Cell Rep, 2020, 31(7): 107657.
36. Khan BA, Perkins AJ, Prasad NK, et al. Biomarkers of delirium duration and delirium severity in the ICU. Crit Care Med, 2020, 48(3): 353-361.
37. Michetti F, D'Ambrosi N, Toesca A, et al. The S100B story: from biomarker to active factor in neural injury. J Neurochem, 2019, 148(2): 168-187.
38. Erikson K, Ala-Kokko TI, Koskenkari J, et al. Elevated serum S-100β in patients with septic shock is associated with delirium. Acta Anaesthesiol Scand, 2019, 63(1): 69-73.
39. Honore PM, Redant S, Kaefer K, et al. Higher Levels of S-100β-a biomarker of astrocyte and glial activation were associated with a greater delirium duration in sepsis and traumatic brain injury patients: beware of some confounders!Crit Care Med, 2021, 49(7): e736-e737.
40. 趙孝開, 李曉亮, 肖宏濤, 等. 血清NSE、S100β、IL-6與燒傷患者膿毒癥相關性腦病的相關性分析. 中國燒傷創瘍雜志, 2020, 32(6): 406-408.
41. 袁繼印, 劉景剛, 張貴真, 等. 慢性阻塞性肺疾病機械通氣患者發生譫妄的危險因素分析. 中國呼吸與危重監護雜志, 2019, 18(6): 522-526.
42. Sonneville R, Benghanem S, Jeantin L, et al. The spectrum of sepsis-associated encephalopathy: a clinical perspective. Crit Care, 2023, 27(1): 386.
43. Gofton TE, Young GB. Sepsis-associated encephalopathy. Nat Rev Neurol, 2012, 8(10): 557-566.
44. Ehler J, Petzold A, Wittstock M, et al. The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - a prospective, pilot observational study. PLoS One, 2019, 14(1): e211184.
45. Page VJ, Watne O, Heslegrave A, et al. Plasma neurofilament light chain protein as a predictor of days in delirium and deep sedation, mortality and length of stay in critically ill patients. EBioMedicine, 2022, 80: 104043.
46. Wu L, Ai M, Feng Q, et al. Serum glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 for diagnosis of sepsis-associated encephalopathy and outcome prognostication. J Crit Care, 2019, 52: 172-179.
47. Ehler J, Saller T, Wittstock M, et al. Diagnostic value of NT-proCNP compared to NSE and S100B in cerebrospinal fluid and plasma of patients with sepsis-associated encephalopathy. Neurosci Lett, 2019, 692: 167-173.
48. Osca-Verdegal R, Beltrán-García J, Pallardó FV, et al. Role of microRNAs as biomarkers in sepsis-associated encephalopathy. Mol Neurobiol, 2021, 58(9): 4682-4693.
49. Tomasi CD, Vuolo F, Generoso J, et al. Biomarkers of delirium in a low-risk community-acquired pneumonia-induced sepsis. Mol Neurobiol, 2017, 54(1): 722-726.
50. Mazeraud A, Righy C, Bouchereau E, et al. Septic-associated encephalopathy: a comprehensive review. Neurotherapeutics, 2020, 17(2): 392-403.
51. Pierrakos C, Antoine A, Velissaris D, et al. Transcranial doppler assessment of cerebral perfusion in critically ill septic patients: a pilot study. Ann Intensive Care, 2013, 3: 28.
52. Pierrakos C, Attou R, Decorte L, et al. Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill patients. BMC Anesthesiol, 2014, 14: 45.
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Chinese Journal of Respiratory and Critical Care Medicine

老年膿毒癥患者譫妄的診治研究進展

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