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 Table of Contents  
Year : 2020  |  Volume : 2  |  Issue : 4  |  Page : 83-89

The Relationship Between Perioperative Regional Cerebral Oxygen Saturation and Postoperative Cognitive Dysfunction: A Systematic Review and Meta-Analysis

1 Department of Intensive Care Unit, Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province; Department of Intensive Care Unit, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
2 Department of Intensive Care Unit, Xiangya Hospital, Central South University, Changsha, Hunan Province, China

Date of Submission09-Jan-2021
Date of Acceptance31-Mar-2021
Date of Web Publication25-Jun-2021

Correspondence Address:
Prof. Lina Zhang
Department of Intensive Care Unit, Xiangya Hospital, Central South University, Changsha 41008, Hunan Province
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jtccm.jtccm_2_21

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Objective: Postoperative cognitive dysfunction (POCD) and neurologic deficit continues to be an important neuropsychological adverse affecting patients' outcome. We conducted this systematic review to investigate the relationship between regional cerebral oxygen saturation (rSO2) and early POCD in postoperative patients. Materials and Methods: Our search included MEDLINE (PubMed) and Cochrane library, from inception to October 31, 2018. We included studies reporting values of rSO2 at the beginning of and/or during surgery, and the primary outcome was POCD, and excluded articles who do not put postoperative cognitive function as the main observation. Two reviewers assessed the quality of the included articles using the Newcastle-Ottawa Scale and extracted the data. Results: Seven prospective cohort studies that included 532 patients incorporate into this systematic review. About 37.78% (201/532) patients achieved POCD. POCD was associated with significantly lower overall values of rSO2 during surgery compared to the population that did not achieve POCD (mean difference [MD] −1.98; 95% confidence interval [CI] −3.30 to −0.66; P = 0.003). In the subgroup, the lowest rSO2 values intraoperative period were a better predictor of POCD (MD −2.91; 95% CI −4.37 to − 1.46; P < 0.0001) than the mean rSO2 values (MD − 2.94; 95% CI −5.71 to − 0.17; P = 0.04). However, all of two were proved superior to baseline rSO2 values (MD −0.13; 95% CI -1.33 to 1.07; P = 0.83); patients with intraoperative cerebral oxygen <50% are nearly four times more likely to have early POCD (odds ratio = 3.65; 95% CI 1.62–8.23, P = 0.002). Conclusions: Patients with POCD have significantly lower cerebral oxygenation during operation than their counterparts. The lowest rSO2 values intraoperative period and patients with intraoperative cerebral oxygen <50% were a better predictor of POCD.

Keywords: Intraoperative, meta-analysis, near-infrared spectrometry, postoperative cognitive dysfunction, regional cerebral oxygen saturation, surgery

How to cite this article:
Feng Q, Jiang S, Deng S, Ai Y, Peng Q, Mo Y, Zhang L. The Relationship Between Perioperative Regional Cerebral Oxygen Saturation and Postoperative Cognitive Dysfunction: A Systematic Review and Meta-Analysis. J Transl Crit Care Med 2020;2:83-9

How to cite this URL:
Feng Q, Jiang S, Deng S, Ai Y, Peng Q, Mo Y, Zhang L. The Relationship Between Perioperative Regional Cerebral Oxygen Saturation and Postoperative Cognitive Dysfunction: A Systematic Review and Meta-Analysis. J Transl Crit Care Med [serial online] 2020 [cited 2023 Mar 31];2:83-9. Available from: http://www.tccmjournal.com/text.asp?2020/2/4/83/319412

  Introduction Top

Postoperative cognitive dysfunction (POCD) in the early postoperative period is a commonly occurring phenomenon with an incidence varying from 30% to 60%.[1] They always appear to a depressed level of consciousness, impairments in attention, memory, and reaction time. Despite advances in surgical and anesthetic techniques over the years, POCD and neurologic deficit related to surgery continues to be a problem affecting patients' outcome.[2] POCD has repercussions such as the length of hospital stay, quality of life, psychosocial functioning, and the patient's ability to be involved in his/her rehabilitation. More importantly, persistent POCD may actually herald an increase in both morbidity and mortality in elderly patients.[3]

Successful postoperative management depends on early detection and correction of circulatory insufficiency. However, the prediction of POCD during surgery is challenging. The most commonly cited etiologies of POCD are embolization and hypo-perfusion of the brain.[4] Cerebral oximetry, a Near-infrared spectroscopy (NIRS) noninvasive technology approved by the US Food and Drug Administration, allowing the monitoring of regional cerebral oxygen saturation (rSO2) in accessible superficial brain cortex regions.[5] It provides real-time information assessing the adequacy of cerebral perfusion, although not cerebral perfusion per se.[6],[7] Values of rSO2 have shown a correlation with those of jugular venous bulb oxygenation.[8] Emerging evidence shows that NIRS can prediction circulatory inadequacy in specific organ systems, such as the brain, kidney, and gut. Its provides continuous, noninvasive measures that are suitable targets for goal-directed therapy to treat deficiencies in global and regional perfusion and should be standard of care.[9]

The feasibility of rSO2 monitoring in surgery patients has already been demonstrated in several studies.[10],[11],[12] Some studies investigated the cut-off values of rSO2 can be used to predict POCD after surgery.[13] However, a literature review question that the current literature on the use of NIRS alone does not demonstrate improvement in neurologic outcome. Data correlating NIRS findings with indirect measures of neurologic outcome or mortality are limited.[14] There are still many controversies about the monitoring of rSO2.

The relationship of rSO2 with neurologic complications on postoperative patient's such as POCD remain unknown. Recent studies using NIRS have shown a significant relationship between low rSO2 values and neurologic complications,[15],[16] POCD[17],[18],[19] and prolonged hospital stay[15],[16],[19] in CABG patients. In light of this controversial evidence, we conducted a meta-analysis with the hypothesis that lower values of rSO2 would have been positively correlated with achievement of POCD.

  Materials and Methods Top

Search strategy

The computerized search included MEDLINE (PubMed) and Cochran Library, from inception to October 31, 2018. The core search was structured by the combination of terms obtained from the following three groups. The first one included in alphabetical order: cerebral oximetry, cerebral oxygen saturation, cerebral oxygenation, near-infrared, near-infrared spectroscopies, oxygen consumption, spectrophotometry, spectroscopy, and NIR spectrometry. The second group consisted of the following: perioperative, intraoperative, preoperative, surgery, and operations. The third group consisted of the following: POCD, neurologic outcomes, cognitive decline, neurocognitive disorder, cognitive impairments, and cognitive dysfunctions.

Inclusion and exclusion criteria and outcomes

Inclusion criteria were prespecified according to the PICOS approach [Table 1]. Since we only observe the relationship between intraoperative rSO2 and POCD and did not involve interventions, so a priori decision to include nonrandomized prospective and retrospective clinical studies was made. The search strategy was limited to clinical (human) studies. The article type was limited to original articles. Language restrictions were applied only articles published in English were considered. The included patient must be undergoing surgery. We excluded articles referring to the pediatric population, and excluded articles who do not put POCD as the main observation.
Table 1: “PICOS” approach for selecting clinical studies in the systematic search

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Study selection

Two authors (QF and YLM) independently searched these databases. Duplicates were initially filtered through automated software function and afterwards screened manually by two authors (SYD and YLM). Study selection for determining the eligibility for inclusion in the systematic review and data extraction from the selected full-text studies were performed independently by two reviewers (QF and SJ). Discordances were resolved by involving another reviewer (QYP) and/or by consensus. We have contacted via E-mail to the corresponding authors for retrieving the largest amount of available data. Meta-analysis was performed independently by two experienced authors (LNZ and SJ).

Quality assessment

Two authors (SYD and QYP) independently assessed the methodological quality of the included studies using the Newcastle Ottawa Assessment Scale (NOS) which is a tool recommended by the Cochrane collaboration for assessing the quality of nonrandomized studies.[20] The NOS scale has three main domains and assigns one point for each subset of assessment criteria within the selection and exposure domains. Studies can obtain up to two points within the comparability domain. We then classified studies as high risk (1–3 points), intermediate risk (4–6 points), and low risk of bias (7–9 points).

Statistical analysis

Meta-analysis was performed using RevMan 5.3 software developed by the Cochrane Collaboration. Subgroup analyzes of continuous outcome differences were analyzed using an inverse variance model with a 95% confidence interval (CI), values are reported as mean difference (MD); the Mantel-Haenszel method was used to calculate odds ratio (OR) and its 95% CI, P values were two-tailed and considered significant if <0.05. Heterogeneity test (Q test) was conducted on the data, and the P and I2 values were used to measure the heterogeneity of the same study statistics. With P > 0.1, I2 < 50% homogeneity test level. If there is no heterogeneity, a fixed effect model was used to calculate the point estimate and the interval estimate of the effect consolidation value, otherwise, analyze the cause, perform subgroup analysis or sensitivity analysis, and use random effects model analysis. Qualitative funnel plots were used to explore possible publication bias.

  Results Top

Study inclusion

The literature search with the above-mentioned criteria produced 2058 total findings, 1036 on MEDLINE and 684 on Cochran Library; 330 duplicates were removed via automatic software and 9 removed manually leaving a total of 1719 publication. We excluded 1648 findings as judged to be not relevant to our search target, leaving potentially 35 studies. Of the remaining 27 were excluded; 5 studies cannot find the full text, 11 studies had interventions, 3 case reports, 1 foreign language, 4 have no data on neurological outcome, 3 absences of NIRS values.

A total of 8 articles remained for possible inclusion in the qualitative synthesis but only 7 were included in the meta-analysis since one group of authors[21] did not have the NIRS data requested. The article selection process is depicted in the [Figure 1].
Figure 1: Flow diagram of the systematic search. NIRS: Near-infrared spectrometry, POCD: Postoperative cognitive dysfunction

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All 7 studies included in this meta-analysis were nonrandomized observational studies published in peer-reviewed journals. Our study included three cardiac surgeries, three noncardiac surgery for the elderly, and one abdominal surgery. Patients enrolled ranged in age from 40 to 80 years, with an average age of 68.7 ± 6.4. POCD was assessed 1 day preoperatively and 7 days after surgery. Some studies assessed 1 month after surgery, and partially assessed 3 months after surgery. Since our study was to observe the relationship between early POCD and intraoperative rSO2, we selected neurocognitive assessment data on the 7th postoperative day. Different devices have been used in these studies. The included studies characteristics are presented in Supplemental [Table 1].

Risk of bias of included studies

Among the included studies, no studies were evaluated as being at high risk of bias. There of the remaining studies were at intermediate risk of bias[13],[22],[23] and four were at low risk of bias.[24],[25],[26],[27] The description of the risk of bias for each included study is presented in Supplemental [Table 1][Additional file 1] and [Table 2][Additional file 2].{Table 2}

The incidence of postoperative cognitive dysfunction in perioperative patients

A total of 532 patients (number of patients per study ranging from 50 to100 patients) were included in the selected studies for meta-analysis. Of these, 201 patients achieved POCD (37.78%), while 331 (62.22%) did not. Cardiac surgery was the majority of surgery in patients suffered of POCD (cardiac surgery n = 257, 48.31% vs. noncardiac surgery n = 275, 51.69%).

The relationship between rSO2 with postoperative cognitive dysfunction

Only two studies reported rSO2 data both at the baseline recording before surgery and the mean and minimum value during the surgery period.[13],[24] Four studies provided data on baseline values of NIRS before surgery.[13],[23],[24],[25] Four studies recorded the average rSO2 value from the initial recording until the surgery was ended.[13],[22],[24],[27] Moreover, three studies recorded the minimum rSO2 value during the surgery.[13],[23],[25]

POCD was associated with significantly lower overall values of rSO2 during surgery compared to the population that did not achieve POCD (MD −1.98; 95% CI − 3.30 to −0.66; P = 0.003). In the subgroup, the lowest rSO2 values intraoperative period were a better predictor of POCD (MD −2.91; 95% CI −4.37 to −1.46; P < 0.0001) than the mean rSO2 values (MD −2.94; 95% CI −5.71 to − 0.17; P = 0.04). However, all of two were proved superior to baseline rSO2 values (MD −0.13; 95% CI −1.33–1.07; P = 0.83) [Figure 2]. There was low heterogeneity in the subgroup of baseline rSO2 values (I2 = 0%), high heterogeneity in the subgroup of average rSO2 values (I2 = 85%) and low heterogeneity in the subgroup of lowest rSO2 values during resuscitation (I2 = 0%), resulting in an overall high heterogeneity (I2 = 68%) [Figure 2].
Figure 2: Difference in NIRS measures between patients achieving early POCD and those non-POCD. NIRS: Near-infrared spectrometry, POCD: Postoperative cognitive dysfunction

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The relationship between regional cerebral oxygen saturation <50% with postoperative cognitive dysfunction

Five studies[23],[24],[25],[26],[27] stratified the decline of intraoperative oxygen saturation to further investigate the relationship between POCD and cerebral oxygen saturation. The other two studies were not stratified. We have contacted the relevant authors for specific data, but no results were found. As the stratification of each study is inconsistent, we use Regional cerebral oxygen saturation <50% as a more uniform value. Of the five studies to stratified and carry out comprehensive statistics. A total of 404 patients include in these five studies, 107 (26.49%) of whom achieved POCD, among the 107 patients, 66 (61.68%) had achieved intraoperative regional cerebral oxygen <50%. The patients with intraoperative regional cerebral oxygen <50% are more likely to have POCD (OR = 3.65; 95% CI 1.62–8.23, P = 0.002). There was high heterogeneity in the subgroup of the patients' numbers (I2 = 54%) [Figure 3].
Figure 3: Difference in intraoperative cerebral oxygen <50% between patients achieving early POCD and those non-POCD. POCD: Postoperative cognitive dysfunction

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Sensitivity analyses and publication bias

There was high heterogeneity in the subgroup of mean rSO2 values (I2 = 85%) during surgery, resulting in an overall moderate heterogeneity (I2 = 68%). We found no clear asymmetry in the funnel plot used to evaluate publication bias in the 11 studies addressing the POCD outcome [Figure 4]. There was high heterogeneity in the subgroup of the patients' numbers (I2 = 54%). Two sensitivity analyses were conducted: The first one included study with low risk of bias and the second one included study at intermediate risk of bias. In both analyses, the overall and the subgroups yielded same significant association between lower values of rSO2 and POCD.
Figure 4: Funnel plot for the evaluation of publication bias. SMD: Standardized mean difference

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  Discussion Top

POCD has received considerable attention as one of the main postoperative complications, which with significant clinical, social and financial impacts for patients and their communities. It can occur in 25% of patients displaying significant impairments in executive functions and/or memory functions following surgical intervention.[28] Our study showed 37.78% patients achieved POCD. Most of POCD patients originate from cardiac surgery.

Neuroinflammation is likely an essential element underpinning the development of POCD, preexisting conditions or demographics may also act to decrease cognitive reserve, such as the presence of physical illness, frailty, lower education levels, history of alcohol or opiate use, and the presence of anticholinergic medication to risk postoperative cognitive change appear to be essential in patients with POCD.[29],[30],[31] Other predictors of cognitive decline were older age, higher EuroSCORE and SAPS II (Simplified Acute Physiology Score) values, lower educational level and persistence of preoperative atrial fibrillation.[17] In the surgical setting, anesthetic-related modifiable factors such as hypotension, hypoxia, and altered cerebral perfusion may contributing to POCD. Studies have shown that elderly patients undergoing major surgery were found to experience a higher incidence of POCD following inhalational anesthesia with sevoflurane than those who received intravenous Propofol.[32] However, a cohort study prospectively recruited 1218 patients aged over 60 year of age in 13 countries who were undergoing major noncardiac surgery have failed to show an association between either hypotension or hypoxia and POCD.[33] Study showed that during cardiac surgery maintaining mean arterial pressures of 80–90 mm Hg may reduce the incidence of both postoperative delirium and cognitive dysfunction, which suggest that cerebral hypo perfusion or hypoxia could be a contributing factor to changes in cognition.[34] Therefore, it appears that current levels of knowledge regarding the impact of anaesthesia and surgery on POCD are incomplete, and there is considerable need for focus on areas where we can identify and support patients at risk in the perioperative period.

Near-infrared spectroscopy (NIRS), as a noninvasive cerebral oxygen supply and demand monitoring technology, provides a measure of rSO2 in response to cerebrovascular oxygen metabolism. It has been widely used in clinical practice.[35] Sun et al. study[36] illustrated that patients with an rSO2 below 60% experienced higher operative mortality (P < 0.001) and after adjustment this determination emerged as an independent predictor of increased mortality. As hypothesized, lower cerebral oximetry saturations during surgery were associated with early POCD. Our meta found that patients with intraoperative cerebral oxygen <50% are nearly four times more likely to have early POCD (OR = 3.65; 95% CI 1.62–8.23, P = 0.002).

The application of NIRS sensors on the forehead of unconscious patients is feasible. Studies reported that NIRS can detect abnormalities of cerebral oxygen metabolism in cardiopulmonary bypass, guide clinical operation and avoid serious postoperative complications of nervous system.[37] In addition, some studies have shown that monitoring and management of intraoperative cerebral rSO2 is not only associated with a lower incidence of cognitive decline but also with significantly lower incidences of complications and shorter postoperative lengths of stay.[15],[38] The present meta-analysis sought to evaluate the association between different types of regional cerebral oxygen metabolism (rSO2) monitoring measurements (baseline, mean, the lowest values) and POCD. The association of NIRS saturation with early POCD varied depending on the timing and different value of measurement used. The lowest rSO2 values were a better predictor of POCD than baseline and mean rSO2 value. This finding is not unexpected, since lower values of cerebral oxygenation are likely to indicate a worse brain perfusion pressure during surgery.

Of course, our meta-analysis has several limitations. First, the meta included three studies of cardiac surgery, and some cardiac surgery involved cardiopulmonary bypass. We cannot rule out the effects of these confounding factors. Second, all the studies included are small range of 50–100 patients and were single center based. In addition, due to the small number of articles included, the sample size and number of studies used in meta-analysis were not sufficient and would have some impact on the reliability of the results of this study. Third, conflicting results can be caused by differences in the definition of POCD. Hence, agreed definitions for cognitive dysfunction and identification of appropriate assessment tools are needed in order to ensure consistency of research approaches. Forth, different devices have been used to measure cerebral oximetry in the studies, leading to a possible bias due to the different calibration and algorithms of each device. Fifth, fewer studies meet our data extraction requirements, suggested that the current research on intraoperative oxygen saturation and POCD is irregular, with low consolidation, the meta-analysis of high-quality and adequately powered RCTs are warranted. Finally, Li et al.[13] have shown that the maximum percentage drop in rSO2 (ΔrSO2%max) during surgery was significantly higher in the POCD group than in the non-POCD group. When ΔrSO2%max >10.2% was taken as the cut-off value, the specificity and sensitivity of ΔrSO2%max in predicting POCD were 88.0% and 85.7%, respectively. Since our meta-design only calculated baseline, mean and minimum values during surgery, a receiver curve operator cannot be calculated with the available data, therefore, this article was excluded.

  Conclusions Top

POCD is a commonly occurring phenomenon in the early postoperative period. The meta-analysis found that intraoperative low cerebral oxygen saturation was associated with POCD. However, this finding largely relies on data from observational studies and is potentially subject to selection bias; before approaching conclusions, it seems reasonable to wait for larger and homogeneous studies that may provide a sensitivity/specificity values for prediction of POCD during surgery. Hence, the meta-analysis of high-quality and adequately powered RCTs are warranted.

Ethical approval and consent to participate

As this was not a manuscript study of human subjects but rather a synthesis of the previously published literature, it was exempt from institutional review board approval.

Availability of supporting data

All data generated or analyzed during this study are included in this manuscripts and supplementary materials.

Financial support and sponsorship

No financial support and sponsorship were provided.

Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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