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REVIEW ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 1  |  Page : 94-103

Incidence of postoperative delirium in patients with preoperative and postoperative Obstructive Sleep Apnea Syndrome. A Systematic Review of the literature


1 Department of Surgery, Dutch Obesity Clinic West, The Hague, The Netherland
2 Department of Anaesthesiology, Leiden University Medical Center, Leiden, The Netherland
3 Department of Surgery, Groene Hart Hospital, Gouda, The Netherland
4 King Saudi University Hospital, Riyadh, Saudi Arabia

Correspondence Address:
Bart Torensma
Clinical Epidemiologist/CRNA, Dutch Obesity Clinic West and LUMC, The Hague
The Netherland
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sja.sja_559_21

Rights and Permissions
Date of Submission24-Jul-2021
Date of Decision02-Aug-2021
Date of Acceptance08-Aug-2021
Date of Web Publication04-Jan-2022
 

  Abstract 


Introduction: Clinical research has suggested that there might be a correlation between postoperative delirium (POD) and obstructive sleep apnea (OSA) syndrome. We aimed to assess the association between POD and OSA syndrome.
Methods: The electronic database PubMed was searched using combinations of terms for “Delirium,'' “Obstructive Sleep Apnea,'' and “postoperative delirium.'' Excluded were studies without comparison as well as cross-sectional studies, case series, and case reports. The search was conducted with restriction toward English or not to the date of publication.
Results: We included four studies in this review. In two of those studies, an association was found between POD and OSA syndrome. Pooled analysis showed a significant correlation between the two.
Conclusion: High-quality studies regarding the subject are rare and heterogeneous. However, despite the lack of high-quality studies regarding the subject, the ones that are performed well conclude that there is a correlation between POD and OSA syndrome. Future studies addressing the matter should be well set up controlled clinical trials to draw conclusions and be able to investigate modifiable factors that can be used in a standardized protocol.

Keywords: Delirium, OSAS, postoperative


How to cite this article:
Dooijeweerd S, Torensma B, Faraj D, Eldawlatly A A. Incidence of postoperative delirium in patients with preoperative and postoperative Obstructive Sleep Apnea Syndrome. A Systematic Review of the literature. Saudi J Anaesth 2022;16:94-103

How to cite this URL:
Dooijeweerd S, Torensma B, Faraj D, Eldawlatly A A. Incidence of postoperative delirium in patients with preoperative and postoperative Obstructive Sleep Apnea Syndrome. A Systematic Review of the literature. Saudi J Anaesth [serial online] 2022 [cited 2022 Jan 19];16:94-103. Available from: https://www.saudija.org/text.asp?2022/16/1/94/334764




  Introduction Top


Delirium is defined by the Diagnostic and Statistical Manual of Mental disorders (DSM) as an acute and fluctuating disturbance of the consciousness (i.e. reduced clarity of awareness of the environment) which occurs with reduced ability to focus, sustain, or shift attention,[1] a change in cognition (such as memory impairment, disorientation, language disturbance), or the development of perceptual disturbance that is not better accounted for by pre-existing, established, or evolving dementia. Moreover, the disturbance should develop over a short time (hours to days) and tends to fluctuate during the day.[1]

The pathophysiology of delirium remains unclear, but nowadays, it is widely presumed that the mechanism is multifactorial. Recent studies suggest that drug toxicity, inflammation, and acute stress responses can contribute to the development of delirium.[2] Other known risk factors for delirium are medication use, sensory impairment (loss of hearing or vision), immobilization, disturbances in the sleep-wake cycle, male sex, history of delirium, alcohol withdrawal, multiple comorbidities, and surgery.[2] The treatment of delirium depends on the underlying cause. Although there is no scientific tool to measure delirium several criteria and scales have been made to review the severity and categorize the disease.[3]

postoperative delirium (POD) is when the delirium occurs after surgery and anesthesia most of the times within 5 days following general anesthesia. POD differs from emergence delirium, which occurs immediately after waking up from anesthesia. POD is a common complication during the postoperative period and is associated with prolonged postoperative recovery, increased physical and mental morbidity and mortality.[4] The prevalence of POD in adult populations that have been exposed to surgery varies widely in different studies from as low as 1% to as much as 87% and is highly dependent on the type of surgery performed, the type of anesthetics being used, and patient population characteristics.[4]

Obstructive sleep apnea (OSA) is a disease characterized by sleep disturbance due to repeated airway collapses.[5] Thereby, the main risk factor is obesity.[6] The pathological mechanism of OSA is a narrowing of the airway due to the build-up of pressure on the airway or weakening of the surrounding tissue causing airway collapse. The accumulation of fat around the neck inflicts pressure on the airway when lying down during sleep and ultimately causes narrowing of the airway and hypoxia as a result. Other risk factors for the development of OSA are upper-airway abnormalities, male subjects, menopause, age, smoking, and alcohol abuse.[6] OSA has a prevalence of 3–7% in adults in the general population. In the subjects who undergo bariatric surgery, the prevalence of OSA can be as high as 77%.[6] Since the prevalence of OSA is so high in bariatric surgery, which is frequently performed nowadays, this systematic review aims to evaluate the incidence of pre- and POD in bariatric patients with OSA.


  Methods Top


Search strategy

Subjects and methods

This literature review has been conducted in accordance with the The Journal of the American Medical Association guidelines[7] for articles about therapies and Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist for Systematic Reviews [Appendix 1].



Literature search

The literature search was performed using PubMed and consisted of several components. The strategy was to include the components “Delirium'' and “Obstructive Sleep Apnea'' to find references regarding the relationship between delirium and OSA. Because of the interest in delirium after major surgery, the term “postoperative delirium'' was added to the search strategy. We also searched for gray literature, and in addition, the reference lists in relevant publications were searched to detect eligible articles that were not identified through prior searches Appendix 2.

Study eligibility criteria

Included

This review included randomized controlled clinical trials, prospective and respective cohort studies, systematic reviews, and meta-analyses.

Excluded

This review excluded descriptive studies, case series, and case reports because of the lower level of evidence.

Types of participants

The studies on participants who were older than 18 years of age and who underwent surgery and screening for POD were included. Also, studies were included of those who compared the outcome of POD in the groups of patients with pre-existing OSA and patients without obstructive sleep apnea.

Obstructive sleep apnea indicators

Types of assessments for postoperative delirium and obstructive sleep apnea

POD can be assessed through the Delirium Rating Scale, Revised (DRS-R-98)[8] and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).[9]

Study selection and data extraction

Two reviewers (SD and BT) independently screened titles and abstracts based on the inclusion and exclusion criteria. Subsequently, the same reviewers independently checked the remaining full-text reports for eligibility. After completing the definitive inclusion of articles, data from full-text articles were extracted independently. In all the stages, disagreements were solved by discussion or by consulting an independent third reviewer (DF). Data on the outcomes were collected and analyzed.

Assessment of risk of bias

Two reviewers (SD, BT) independently assessed the risk of bias for methodological quality of each included study using the Cochrane Collaboration's Risk of Bias (RoB). Each study was judged on selection bias, performance bias, detection bias, attrition bias, reporting bias, and confounding.


  Results Top


Study selection

The final search strategy yielded 36 references. The studies were included if there was an assessment done for POD. The studies were included if there was an assessment done for OSA or if the medical records reported OSA or if the patients themselves reported to suffer from OSA before and after surgery. The exclusions were done because of not diagnosed or self-reported OSA, age below 18, dementia, and other preoperative existing mental disorders. Furthermore, studies not available in English were excluded. The search strategy is outlined.

Study characteristics of included studies

Four studies, including 8,534 subjects, and one meta-analysis including 12 studies, were included in this review. All the studies were performed in the United States and the studies were published in English. Three out of four studies compared a group of subjects with OSA to a group without OSA. One study compared peri-operative continuous positive airway pressure (CPAP) to routine care to see if CPAP can help in preventing POD with OSA. The primary hypothesis of one study was to examine the molecular markers in POD. The primary hypothesis of the other three studies was related to OSA and POD. The study by Flink et al.[10] investigated whether any of the pre-existing medical conditions contributed to POD. The study by Nadler et al.[11] tested if the use of CPAP could prevent POD in patients who are at risk of OSA. And the study by King et al.[12] tested if there was an association between preoperative sleep apnea and POD. The study done by Wang et al.[13] investigated if thoracic surgery patients were at a high risk for OSA and POD. The meta-analyses conducted by Fadayomi et al.[14] aimed to assess the association between preoperative sleep disturbance and POD.

Characteristics of subjects in the individual studies

The study conducted by Flink et al.[10] described the results of 106 patients who had undergone elective knee surgery. Of the 106 subjects, 15 had OSA, and of these, 8 patients (53%) experienced POD versus 19 (21%) out of 91 subjects who experienced POD without having OSA. The DSM-IV criteria for delirium were used to diagnose POD. To determine if a subject has OSA, medical records were used as well as patient interviews. Having a delirium was expressed in a DRS-R-98 severity score. Age was expressed as mean in years (+SD). Several other risk factors for developing delirium were evaluated. Dementia was evaluated with the Minimal Mental State Exam score and by reviewing medical records.

The study conducted by Nadler et al.[11] describes the results of 135 subjects of whom 114 completed the study. The study groups were divided into CPAP and NON-CPAP groups. Delirium was equally common in both groups. OSA was described using the Snoring, Tiredness, Observed apnea, blood Pressure, Body mass index, Age, Neck circumference and Gender score.[15] Age was described using mean years (+SD). The assessment for delirium was done using the DRS-R-98[8] diagnostic tool.

King et al.[12] described a cohort of 7,792 subjects admitted to the intensive care unit after surgery. The evaluation of OSA included medial history, self-reported OSA, self-reported adherence to CPAP, and after April 2014, the STOP-BANG questionnaire was included. POD was assessed with the CAM-ICU.

Wang et al.[13] described a cohort of 126 patients admitted to the ICU after undergoing thoracic surgery. The assessment for OSA was done using the STOP-BANG questionnaire and the CAM-ICU was used to assess delirium.

Fadayomi et al.[14] performed a meta-analysis of the available literature. They described the results of 12 included studies. The included studies used different methods for the assessment of OSA and POD, with STOP-BANG scores and the CAM-ICU as the most prevalent methods used.

Risk of bias and methodological quality

The studies conducted, except for one,[14] had a high risk of performance bias since none of them blinded the subjects to the intervention. However, Nadler et al.[11] did blind the assessors. The subjects cannot be blinded in most cases due to the nature of the intervention.

In the study conducted by Flink et al.[10] also, no randomization was performed. Nadler et al.[11] did perform computerized randomization. Wang et al. also performed randomization.

The main outcomes were clearly described in all the studies. The confounders were unclear in most studies. The selection bias was unclear, but the risk of selection bias was high in two out of four studies since they were retrospective studies. The risk of detection bias was high in two[10],[11] studies since there was no double-blinding. The risk was also high in all studies. Because blinding of the subjects was not possible due to the nature of the intervention. The risk of attrition bias was high in three[10],[11],[13] of four studies due to the subjects enrolled not completing the study.

Fadayomi et al.[14] performed Begg's and Egger's tests for publication bias and confirmed a null result for publication bias, (P = 0.371 and 0.103, respectively)

Heterogeneity between the studies was high due to different research questions and methods of testing for obstructive sleep apnea syndrome (OSAS) and different cut-off points. Only Nadler et al.[11] described a formal power analysis. It is not possible to assess whether the number of included subjects was sufficient for a powerful statistical analysis in the remaining studies.[10],[13] The methodological quality of the included studies is outlined in [Table 1].
Table 1: Methodological quality of included studies

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Results of the individual studies

Flink et al.[10] found that the incidence of POD was higher in the OSA group (53,3%) than in the patients without OSA (20. 9%) (P = 0.0123, odds ratio = 4.3, 95% CI 1.2–15.8). In their study, there was no difference found in other baseline medical conditions between delirious and non-delirious patients. When the patients with OSA and without OSA were compared, the OSA group was younger and suffered more comorbidities.

The study conducted by Nadler et al.[11] found that the incidence of POD was the same in the groups which received CPAP therapy compared with the group which received only routine care (OR = 1.36 [95% CI 0.52–3.54], P = 0.53). The investigators did find that the severity of preoperative apnea is associated with the severity of POD (P = 0.0002). They did not find CPAP therapy shortly before surgery to have any effect on the incidence of POD.

The study by King et al.[12] found that the patients with OSA had a lower incidence of POD than patients without OSA, but after adjustment, this difference was not significant.

Wang et al.[13] found that there was no significant difference in the incidence of delirium between the high-risk group and low-risk group for OSA (P = 0.7). There was also no difference found between the high- and low-risk group for the duration of POD.

The systematic review by Fadayomi et al.[14] found that the pooled odds ratio for the association between sleep disturbance POD was 5.24 (95% CI 3.61–7.60; P < 0.001 and I2 = 0.0%; P = 0.76). The pooled risk ratio for the association between sleep disturbance and POD in prospective studies (n = 6) was 2.90 (95% CI 2.28–3.69; P < 0.001 and I2 = 0.0%; P = 0.89). The odds ratio associated with OSA, and unspecified types of sleep disorders were 4.75 (95% CI 2.65–8.54; P < 0.001 and I2 = 0.0%; P = 0.85) and 5.60 (95% CI 3.46–9.07; P < 0.001 and I2 = 0.0%; P = 0.41), respectively.


  Discussion Top


The association between OSA and POD has been a subject of discussion in recent years. However, the amount of evidence provided for such an association is limited and of low quality. The first point of discussion is the fact that a meta-analysis was not possible due to the high heterogeneity between the studies. The assumption for meta-analysis could therefore not apply.

In 2020, King et al.[12] found no association between preoperative OSA and POD so the existence of an association is questioned and uncertain. They also concluded that it is unlikely that there is an intervention that may help to reduce the incidence of POD after surgery with preoperative existing OSA. Their cohort is the largest that was encountered in this research, but it was another retrospective observational study, so there was no natural experiment to give a strong causal implication. Moreover, they included a wide array of diverse surgical procedures in a single-center cohort setting. This type of setting is likely to be different elsewhere, so caution is advised when generalizing these findings. They also report that incomplete data and the observational nature of their study could explain their null findings.

In 2017, a systematic review by Fadayomi et al.[14] of the available literature in PubMed, Embase, and other medical databases concluded that there was likely an association between sleep disturbances and POD. The authors included 12 studies, but only 4 of those studies specified OSA as the type of sleep disorder evaluated. The types of assessment for determining OSA and POD also differed in the included studies. Overall, they reported heterogeneity between the studies evaluated and concluded that there was an association between preoperative sleep disturbances and POD. They also reported that if there was some intervention that helps to reduce the incidence of POD, it is yet to be determined.

Nadler et al.[11] mentioned that their results might be interfered with because of the low adherence to the CPAP therapy because of discomfort or other reasons. This could mean that the people who did adhere to the CPAP therapy were more likely to have a decreased risk for POD.

Flink et al.[10] did find an association between OSA and POD. This first prospective study employing validated measures of delirium to identify an association between pre-existing OSA and POD found a more-than-fourfold increased risk for POD. Since this is the only prospective study researching this matter, it is quite remarkable that they found an association whereas other retrospective studies did not. The authors mentioned that their sample size was small, but since this is the only prospective study with published results to date, the findings by the authors were of significant clinical importance and deserve replication in larger numbers. Another limitation to their findings was that the patients with OSA had significantly more comorbidities that could increase the risk for delirium in those patients. Although the authors took several predisposing factors for delirium into account, like dementia, they did not account for a history of stroke and electrolyte disturbance which are also known predisposing factors for delirium.

Wang et al.[13] only found that patients with a high risk of OSA had a longer duration of POD. There was no difference in the incidence between the high- and low-risk groups.

Although some studies used the same methods for the assessment of POD and OSA, they did differ in a lot of other factors, like the time of assessment and the scale used for assessing POD. Overall, the results yielded by the studies were not of high quality and convincing enough that there was an association between OSA and POD. Due to the heterogeneity between the studies, it was hard to draw conclusions about the association between OSA and POD. This is due to the difference in the study sample sizes, the different methods for assessment used, and the different key questions used in the studies. And because some studies included that the primary aim of the studies was never to find an association between OSA and POD. Another interesting factor in this review is that none of the studies hold into account what kind of anesthetics was given to the subjects. They all report that the patients received general anesthesia but did not specify the types of medication used. This might be a factor that contributes to the different findings of the studies because some medications may have a longer half-life than others, meaning they could contribute to a longer duration of sedative state, and therefore, to the severity and/or duration of POD.

Considering the described heterogeneity and overall quality of the included studies, it is hard to draw conclusions.

To determine whether there is in fact an association between OSA and POD, larger prospective randomized clinical trials are needed with less heterogeneity between studies. The same is applicable to whether there is a modifiable intervention to prevent POD in the case of pre-existing OSA.


  Conclusion Top


The recommendation for studies regarding the matter in the future is to study in a large cohort the association between pre-existing OSA and the incidence of POD. Because it is assumed that the pathophysiological mechanism of delirium is multifactorial, other factors such as type of anesthesia, kind of surgery, duration of surgery, and other factors that might have an influence on POD have to be considered.

If an association is found between the two in a large Randomized Clinical Trial, then it should be investigated if there is a modifiable factor to prevent the POD in these OSA patients and how such an intervention can be implemented in a standardized protocol.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6 (6): e1000097. doi: 10.1371/journal.pmed1000097

For more information, visit: www.prisma-statement.org.

Appendix 2: Search Strategy

Clinical question



Literature Search in PubMed

Component 1: Delirium

Search strategy for component 1:

“'Delirium'' '[MeSH Terms] OR “'Delirium'' '[Tiab] OR “'delirium'' '[Tw] OR “'Postoperative delirium'' '[Tw] OR “post-operative delirium''[Tiab]

Component 2: Obstructive sleep apnea

Search strategy for component 2:

“'Sleep Anea, Obstructive'' “'[MeSH] OR “'Obstructive Sleep Apnea'' “'[Tiab] OR “'Obstructive sleep apnea'' “'[Tw] OR “OSA''[Tw] OR “OSAS'' [Tw] OR OSA[Tiab] OR OSAS [Tiab]

Combined strategy

('“Delirium'”[MeSH Terms] OR '“Delirium'”[Tiab] OR '“delirium'”[Tw] OR '“Post-operative delirium'”[Tw] OR “post-operative delirium”[Tiab]) AND ('“Sleep Anea, Obstructive'”[MeSH] OR '“Obstructive Sleep Apnea'”[Tiab] OR '”Obstructive sleep apnea'”[Tw] OR “OSA”[Tw] OR “OSAS” [Tw] OR OSA[Tiab] OR OSAS [Tiab])

Number of references: 37

Date 16-05-2020

The number of articles yielded with this strategy is not very high, but the relevance of the articles found was good.

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6 (6): e1000097. doi: 10.1371/journal.pmed1000097

For more information, visit: www.prisma-statement.org.



 
  References Top

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2.
Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: Diagnosis, prevention and treatment. Nat Rev Neurol 2009;5:210-20.  Back to cited text no. 2
    
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4.
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Miranda F, Arevalo-Rodriguez I, Díaz G, Gonzalez F, Plana MN, Zamora J, et al. Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) for the diagnosis of delirium in adults in critical care settings. Cochrane Database Syst Rev 2018;2018:CD013126.  Back to cited text no. 9
    
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Flink BJ, Rivelli SK, Cox EA, White WD, Falcone G, Vail TP, et al. Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly. Anesthesiology 2012;116:788-96.  Back to cited text no. 10
    
11.
Nadler JW, Evans JL, Fang E, Preud'Homme XA, Daughtry RL, Chapman JB, et al. A randomized trial of peri-operative positive airway pressure for postoperative delirium in patients at risk for obstructive sleep apnoea after regional anaesthesia with sedation or general anaesthesia for joint arthroplasty. Anaesthesia 2017;72:729-36.  Back to cited text no. 11
    
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King CR, Fritz BA, Escallier K, Ju YE, Lin N, McKinnon S, et al. Association between preoperative obstructive sleep apnea and preoperative positive airway pressure with postoperative intensive care unit delirium. JAMA Netw Open 2020;3:e203125.  Back to cited text no. 12
    
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Wang S, Sigua NL, Manchanda S, Gradney S, Khan SH, Perkins A, et al. Preoperative STOP-BANG scores and postoperative delirium and coma in thoracic surgery patients. Ann Thorac Surg 2018;106:966-72.  Back to cited text no. 13
    
14.
Fadayomi AB, Ibala R, Bilotta F, Westover MB, Akeju O. A systematic review and meta-analysis examining the impact of sleep disturbance on postoperative delirium. Crit Care Med 2018;46:e1204-12.  Back to cited text no. 14
    
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Chung F, Abdullah HR, Liao P. STOP-Bang questionnaire: A practical approach to screen for obstructive sleep apnea. Chest 2016;149:631-8.  Back to cited text no. 15
    



 
 
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