OBJECTIVES: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation. METHODS: This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation. RESULTS: Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05). CONCLUSIONS Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.
Aged ; Aged, 80 and over ; Bradycardia ; Cognitive Dysfunction/prevention & control* ; Delirium/prevention & control* ; Dexmedetomidine/therapeutic use* ; Humans ; Hypotension/drug therapy* ; Interleukin-10 ; Middle Aged ; Postoperative Cognitive Complications/prevention & control* ; Postoperative Complications/epidemiology* ; Prospective Studies ; Tumor Necrosis Factor-alpha

To observe the impacts of continuous lumbar plexus block (CLPB) on postoperative cognitive dysfunction (POCD) in elderly patients undergoing hip arthroplasty.
 Methods: Sixty elderly patients scheduled for hip arthroplasty with general anesthesia, were randomly allocated into a CLPB group and a PCIA group (n=30 each). In the CLPB group, lumbar plexus block was performed before trachea intubation, and CLPB was used for postoperative analgesia. In the PCIA group, intravenous analgesia was controlled in patients after operation. Visual Analogue Scale (VAS) at 12, 24, and 48 h after operation was recorded. Mini-Mental State Examination (MMSE) scale was used to evaluate the cognitive dysfunction at the 1st day before operation (D0) and at the 1st (D1), 3rd (D3), and 7th (D7) days after operation and the occurrence of POCD was recorded. S-100β concentrations were detected by ELISA at D1, D3, and D7. Postoperative adverse events were recorded.
 Results: VAS scores at 12, 24, and 48 h after operation in the CLPB group were significantly lower than those in the PCIA group (P<0.05). Compared with the PCIA group, the MMSE scores were significantly higher (P<0.05), and the incidence of POCD at D1 and D3 was obviously reduced in the CLPB group (P<0.05). S-100β concentration at D1 and D3 in the CLPB group was significantly lower than that in the PCIA group (P<0.05).
 Conclusion: Application of CLPB in elderly patients undergoing hip arthroplasty could obviously relieve their postoperative pain, inhibit the production of S-100β, and reduce the incidence of early postoperative cognitive dysfunction.
Aged ; Analgesics ; administration & dosage ; Arthroplasty, Replacement, Hip ; adverse effects ; Cognitive Dysfunction ; prevention & control ; Humans ; Incidence ; Lumbosacral Plexus ; Nerve Block ; methods ; Pain Measurement ; Pain, Postoperative ; prevention & control ; Postoperative Complications ; prevention & control

OBJECTIVEAnesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress.

METHODSFive-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA.

RESULTSHere we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus.

CONCLUSIONThese results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Anesthetics, Inhalation ; adverse effects ; Animals ; Cognition ; Cognitive Dysfunction ; etiology ; prevention & control ; Female ; Ginsenosides ; pharmacology ; Hippocampus ; drug effects ; Inflammation ; etiology ; prevention & control ; Isoflurane ; adverse effects ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Postoperative Complications ; etiology ; prevention & control ; Random Allocation ; Surgical Procedures, Operative ; adverse effects ; Synapses ; metabolism