Since the emergence of neuropsychological tests to objectively assess cognitive changes after cardiac surgery in the 1980s, postoperative neurocognitive disorder associated with anesthesia and surgery has become the concern of anesthesiologists [
The underlying pathogenesis of POCD is the neuroinflammation and oxidative stress from anesthesia and surgery [
Thoracic surgery is accompanied with one-lung ventilation (OLV) with double-lumen endotracheal tube or two-lung ventilation with CO2 artificial pneumothorax. No matter which ventilation method is adopted, ventilator-induced lung injury is clinically significant, as it induces direct lung injury and systemic inflammation [
On the basis of the neuroinflammatory hypothesis involved in POCD, anti-inflammatory and antioxidative stress strategies are potential treatments for patients undergoing thoracic surgery [
The prospective, randomized, double-blind, and controlled study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University [2019 (2019042508)] and registered in the Chinese Clinical Trials Registry (ChiCRT-IOR-16008837). We obtained written informed consent from all participants.
We recruited 126 patients aged 45 years or older who underwent elective thoracic surgery with American Society of Anesthesiologists class I–III from July 2019 to December 2019. Twelve nonoperative patients were included to evaluate the learning effects by repeated test of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients would be excluded if they met any of the exclusion criteria: Telephone Interview for Cognitive Status-Modified (TICS-m) score less than 28, a history of neurological disease, psychiatric and antidepression drugs, education level under primary school, inability to communicate because of dysaudia and vision disorder, serious hepatic dysfunction (Child–Pugh class C) and renal dysfunction (undergoing dialysis), sick sinus syndrome, severe sinus bradycardia (<50 beats per min), or second- or third-degree atrioventricular block without pacemaker. The exit criteria were anesthesia duration less than 2 h, inability to accomplish the cognitive assessment, and reoperation after surgery.
Patients were randomized into two groups: (1) Dex group, with a bolus of 0.5
Patients received radial artery cannulation in the preanesthesia care unit, and arterial blood gas analysis was conducted before anesthesia (
All patients were evaluated by the neuropsychological test battery (NTB; i.e., RBANS) [
TICS-m was carried out before surgery and 7 days and 1 month postoperatively. TICS-m consists of 12 items that assess the cognitive function of immediate and delayed memory, orientation, language, calculation, and conceptual knowledge [
POCD was diagnosed according to the International Study of POCD1 definition [
POCD was defined as the
The primary outcome was the incidence of POCD, assessed with RBANS before surgery and 7 days after surgery/before discharge. The secondary outcomes included the scores of TICS-m before the surgery, 7 days and 30 days after the surgery. The ADL scores at 7 and 30 days after surgery and VAS scores during rest and activity from 1 to 3 days after surgery were also evaluated in this study. Other indicators including arterial blood gas at
Sample size was based on a 46% incidence of POCD in thoracic surgery [
Numerical variables were expressed as the
A total of 243 patients were screened. Among them, 126 patients were enrolled and randomly allocated to receive either Dex (
Enrolment flowchart.
Characteristics and intraoperative variables.
Dex group ( | NS group ( | ||
---|---|---|---|
Age (year) | 0.08 | ||
Sex (male, %) | 29 (55.77%) | 31 (62.00%) | 0.52 |
BMI | 0.93 | ||
Educational level | |||
Primary | 7 (13.46%) | 5 (10.00%) | 0.71 |
Junior high school | 12 (23.08%) | 15 (30.00%) | |
Senior high school | 14 (26.92%) | 12 (24.00%) | |
College degree | 19 (36.54%) | 18 (36.00%) | |
TICS-m score (baseline) | 0.14 | ||
Smoking history | 11 (21.15%) | 16 (32.00%) | 0.22 |
Drinking history | 5 (9.62%) | 9 (18.00%) | 0.22 |
Coronary heart disease | 0 (0.00%) | 3 (6.00%) | 0.11 |
Hypertension | 7 (13.46%) | 15 (30.00%) | 0.04 |
Diabetes | 2 (3.85%) | 7 (14.00%) | 0.09 |
Prolonged rSO2 desaturation | 0 [0.00-0.79] | 0.02 [0.00-5.12] | 0.27 |
Oxygenation index | |||
T0 | 0.36 | ||
T1 | 396.00 [323.75-494.25] | 401.00 [361.00-442.00] | 0.86 |
T2 | 0.22 | ||
T3 | 0.80 | ||
Anesthesia duration (min) | 0.27 | ||
Surgery duration (min) | 0.69 | ||
OLV/artificial pneumothorax duration (min) | 80.0 [65.0-99.5] | 87.0 [69.0-112.2] | 0.44 |
Length of stay (day) | 0.02 | ||
The total hospital cost | 0.04 |
BMI: body mass index; TICS-m: Telephone Interview for Cognitive Status-Modified; OLV: one lung ventilation;
A total of 35 patients developed POCD at 7 days postoperatively or before discharge, including 19 in the Dex group (36.54%) and 16 in the NS group (32.00%) (
The incidence of POCD.
Dex group ( | NS group ( | ||
---|---|---|---|
Incidence ( | 19 (36.54%) | 16 (32.00%) | 0.63 |
The preoperative and postoperative/before discharge RBANS scores are listed in Table
RBANS scores in both groups.
Preoperation | Postoperation | |||||
---|---|---|---|---|---|---|
Dex group | NS group | Dex group | NS group | |||
List learning | 0.53 | 0.66 | ||||
Story memory | 0.85 | 0.59 | ||||
Figure copy | 0.27 | 0.67 | ||||
Line orientation | 0.24 | 0.87 | ||||
Picture naming | 0.39 | 0.99 | ||||
Semantic fluency | 0.73 | 0.08 | ||||
Digit span | 0.25 | 0.06 | ||||
Coding | 0.08 | 0.29 | ||||
List recall | 0.75 | 0.18 | ||||
List recognition | 0.93 | 0.98 | ||||
Story recall | 0.63 | 0.22 | ||||
Figure recall | 0.33 | 0.38 |
The different interventions, Dex or NS, had no influence on the TICS-m score at different times (intervention effect,
The TICS-m scores between both groups.
Group | Time | |||||
---|---|---|---|---|---|---|
Preoperative | Postoperative 7 days | Postoperative 1 month | Interactive effect | Time effect | Intervention effect | |
Dex group | 0.74 | 0.02 | 0.04 | |||
NS group |
Tics-m score in both groups.
Tics-m score at different times.
The VAS scores in the Dex group were significantly lower than those in the NS group 1 day postoperation at rest and activity (Figure
The VAS score after surgery at rest and activity in both groups. #
Patients receiving Dex vs. NS had no statistical difference in ADL scores at 7 and 30 days after surgery, but the ADL scores at 30 days after surgery were significantly reduced compared with those at 7 days (Figure
The ADL score in both groups 7 days and 1 month after surgery.
In our study, we found that Dex did not reduce the incidence of early POCD in thoracic surgery. POCD developed in 36.54% (19/52) of patients in the Dex group and 32.00% (16/50) of patients in the NS group. No significant statistical and clinical difference was observed between the two groups. The incidence of POCD 7 days after surgery ranges from 17% to 40% in patients with noncardiac surgery [
Our results showed that low-dose Dex in the perioperative period could not improve early cognitive function after thoracic surgery. This finding was in line with a multicenter prospective trial, which was unable to demonstrate a benefit of Dex in POD and POCD and prematurely terminated for futility [
Meanwhile, the incidence of POCD varies with the diagnosis method. The Nomenclature Consensus Working Group recommends that objective cognition decline requires an NTB. So far, there is no unified NTB. As a kind of NTB, RBANS can be used for the repeated measurement of cognitive function, and its validity and test–retest reliability have been determined [
In the telephone follow-up, we found that 102 patients had better cognitive function at 1 month after surgery than 7 days after surgery. However, compared with the NS group, Dex could not improve the cognitive function and ADLs at 7 days and 1 month after surgery.
Finally, we found that Dex could relieve the postoperative pain at the first day after thoracic surgery, shorten the hospital stay, and reduce the hospitalization cost. The possible reasons are as follows: (1) postoperative analgesia can promote patients’ early activities; enable patients to effectively cough and discharge secretions; and reduce complications such as atelectasis, pneumonia, and deep vein thrombosis. It plays an important role in rapid recovery after thoracic surgery [
This study has several limitations. First, the sample size was small, because many patients could not complete the repeated cognition evaluation, especially the elderly and the less-educated patients. Second, patients were not categorized based on age. The applicability of this conclusion needs further research in elderly thoracic surgery patients. Finally, the long-term cognitive function was not evaluated.
Complex mechanisms and factors are involved in cognitive function. It is difficult to improve patient’s cognitive function only by medical treatments. Some studies have shown that multidisciplinary interventions, such as physical exercise; cognitive function training; and improvement of sleep, postoperative anxiety, and depression, may be beneficial for POCD [
Low-dose Dex in the perioperative period did not reduce the incidence of early POCD in thoracic surgery. However, it relieved postoperative pain, decreased hospitalization expenses, and shortened the length of stay.
Data for the study can be found in the study. More information concerning the data can be obtained from the corresponding authors.
The authors declare that they have no conflicts of interest.
Jiao Ran and Xiao Bai collected and analyzed the data, interpreted the data, and wrote and edited the manuscript. Xuehan Li and Rurong Wang designed the study and revised the manuscript. Jiao Ran and Xiao Bai equally contributed to the manuscript.