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Influence of depth of anesthesia on postoperative cognitive dysfunction (POCD) and inflammatory markers
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients may suffer from various forms of postoperative cognitive dysfunction (POCD). In most cases, the impact on cognitive function is relatively transient but POCD can sometimes be long-lasting (> 1 year). Studies showing that up to one in four patients with known risk factors are affected by some form of cognitive loss. The cause of cognitive impairment after surgery and anaesthesia is still unclear. One hypothesis is that anaesthetic drugs may have an impact on the inflammatory process which occurs in conjunction to the tissue trauma caused by surgery. Titrating anaesthetic administration by the use of a depth of anaesthesia (DOA) monitors (AEP or BIS), usually reduce anaesthetic consumption and facilitate early recovery. In the initial two studies, the EEG-based DOA monitoring (AEP) was compared with a control group with standard monitoring for administration of anaesthesia. The AEP group required less anaesthetics and opioids and had faster early recovery but was also associated with a lower number of patients with < 25 MMSE score at 24-hours. We found in study III a relationship between the DOA and postoperative inflammatory response (IL-6). Patients with < 25 MMSE score had higher postoperative 24 hrs IL-6 levels. In the final study, we investigated the attitudes and knowledge among Swedish anaesthesiologists and nurse anaesthetists including the use of DOA, and to what extent written procedures regarding the pre-and postoperative cognitivedysfunction were used.

In conclusion, our studies show, the EEG-based guided DOA monitoring reduces consumption of anaesthetics and opioids during surgery, allows a faster postoperative recovery, and reduces the occurrence of cognitive impairment the first day after surgery and decrease inflammatory response after eye surgery. We found also an association between perioperative DOA, cognitive impairment and an increased inflammatory response after surgery. The interest and knowledge about assessment and management of neurocognitive side-effects before and after anaesthesia was found to be low among anaesthesiologists and nurse anaesthetists. They were critical about the benefits of the DOA monitoring. Swedish anaesthesiologists and nurse anaesthetists need to improve their knowledge of assessment and management of cognitive dysfunction.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2014. , p. 94
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 101
Keywords [en]
Postoperative cognitive dysfunction, minor and major surgery, anaesthesia, depth of anaesthesia monitoring, auditory evoked potential, AAI, inflammatory marker
National Category
Medical and Health Sciences Surgery
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-32842ISBN: 978-91-7668-987-5 (print)OAI: oai:DiVA.org:oru-32842DiVA, id: diva2:681124
Public defence
2014-02-07, Hörsal C2, Campus USÖ, Universitetssjukhuset, S Grev Rosengatan, 701 85 Örebro, 08:45 (Swedish)
Opponent
Supervisors
Available from: 2014-01-23 Created: 2013-12-19 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Effect of auditory evoked potential-guided anaesthesia on consumption of anaesthetics and early postoperative cognitive dysfunction: a randomised controlled trial
Open this publication in new window or tab >>Effect of auditory evoked potential-guided anaesthesia on consumption of anaesthetics and early postoperative cognitive dysfunction: a randomised controlled trial
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2011 (English)In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 28, no 3, p. 213-219Article in journal (Refereed) Published
Abstract [en]

Background: Post-operative cognitive dysfunction (POCD) after non-cardiac surgery is a well known problem in some categories of patients. This study aims to evaluate the influence of auditory evoked potential (AEP)-guided anaesthesia on the requirement for anaesthetic drugs and their influence on POCD.

Methods: Four hundred and fifty patients aged between 18 and 92 years scheduled for ophthalmic surgery under general anaesthesia were assigned randomly to one of two groups. In group A (AEP group), the depth of anaesthesia (DoA) was aimed at an AEP index (AAI) between 15 and 25. In group C (control group), DoA was guided by clinical signs. Hypotension was treated with fluids and vasopressors using a standardised algorithm. A mini-mental test and the Cognitive Failure Questionnaire were used to evaluate cognitive function.

Results: Anaesthetic drug requirements were significantly lower in group A than in group C: propofol 92.526.5 vs. 103.839.5mg (P¼<0.001) and desflurane end-tidal concentration 2.50.58 vs. 3.30.79% (P<0.001). In group A, 36 patients (16%) received additional fluids and vasopressors compared to 65 patients (29%) in group C (P<0.01). AAI values differed significantly between the groups: 18 (11–21) in group A vs. 12 (10–19) in group C (P<0.001). The number of patients with POCD was 16 in group C compared to two in group A (P<0.001) at day 1 post-operation.

Conclusion: AEP monitoring allows dose reduction of anaesthetic agents, leading to better cardiovascular stability and decreased requirements for intra-operative fluids and vasopressors. Cognitive decline seen following minor ophthalmic surgery, even when anaesthesia is assessed clinically, is short-lived with no long-term sequelae.

Place, publisher, year, edition, pages
Philadelphia, USA: Lippincott Williams & Wilkins, 2011
Keywords
Auditory evoked potential monitoring, cognitive decline, general anaesthesia, minor surgery
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology
Identifiers
urn:nbn:se:oru:diva-34015 (URN)10.1097/EJA.0b013e328340dbb9 (DOI)000287439400014 ()21088592 (PubMedID)2-s2.0-79953879703 (Scopus ID)
Available from: 2014-03-03 Created: 2014-03-03 Last updated: 2018-05-05Bibliographically approved
2. Does depth of anesthesia influence postoperative cognitive dysfunction or inflammatory response following major ENT surgery?
Open this publication in new window or tab >>Does depth of anesthesia influence postoperative cognitive dysfunction or inflammatory response following major ENT surgery?
2012 (English)In: Journal of Anesthesia & Clinical Research, ISSN 2155-6148, Vol. 3, no 6, p. 220-Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to evaluate the role of depth of anesthesia on POCD after major ENT surgery and to assess changes in postoperative inflammatory markers in patients undergoing major ENT surgery. Thirty two patients aged 40 to 94 yrs, scheduled for surgery under general anesthesia were randomly assigned to one of two groups. In group A (AEP group) depth of anesthesia (DOA) was measured with auditory evoked potential (AEP). In the control group (group C) DOA was monitored according to clinical signs. Cognitive function was evaluated using Mini-Mental State Examination (MMSE), Confusion Assessment Method (CAM) and Cognitive Failure Questionnaire (CFQ). Inflammatory markers were measured before and after anesthesia. Perioperative requirements for desflurane and fentanyl were significantly lower in group A. On the first postoperative day MMSE changes indicating POCD were noted in 1 patient in group A and 7 patients in group C (P<0.03). One month follow up did not show any difference between the groups regarding POCD. Our study indicates that AEP-guided anesthesia allows dose reduction of anesthetic agents including opioids leading to better cardiovascular stability and less early POCD. Anesthesia depth did not influence the inflammatory response to surgery.

Keywords
Cognitive decline, general anesthesia, auditory evoked potential (AEP)
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology
Identifiers
urn:nbn:se:oru:diva-34016 (URN)10.4172/2155-6148.1000220 (DOI)2-s2.0-84880002452 (Scopus ID)
Available from: 2014-03-03 Created: 2014-03-03 Last updated: 2018-09-11Bibliographically approved
3. AAI-guided anaesthesia is associated with lower incidence of 24-hour MMSE<25 and may impact the IL-6 response
Open this publication in new window or tab >>AAI-guided anaesthesia is associated with lower incidence of 24-hour MMSE<25 and may impact the IL-6 response
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: Trauma stress and neuro-inflammation caused by surgery/anaesthesia releases cytokines. This study analysed impact of Auditory Evoked Potential Index (AAI) depth-of-anaesthesia titration on the early plasma IL-6 release after eye surgery under general anaesthesia.

Method: This is a subgroup analysis of a prospective randomized study on the effect of auditory evoked potential guided anaesthesia for eye surgery. Plasma IL-6 levels taken before, 5 and 24 h after end of surgery from 450 patients undergoing elective ophthalmic surgery under desflurane anaesthesia were analysed. Minimal mental state examination (MMSE) was also tested at 24-hours.

Results: IL- 6 increased significantly at both 5 and further at 24 hours after surgery (3.2, 4.5 and 5.1 base-line, 5 and 24- hours respectively), the IL-6 increase showed different patterns between the 2 groups; IL-6 was significantly increased in the control group of patients between preoperative baseline and 24 h after surgery (p= 0.008) also between 5 h and 24 h, (p= 0.006) after surgery while the AAI-group had only minor non-significant changes. The 18 patients that showed a 24-hour MMSE score less than 25 had a significant higher 24-hour IL-6 compared to the 390 patients with a MMSE score > 24 (p = 0.002).

Conclusion: The IL-6 increase after surgery was less pronounced in patients where anaesthesia was titrated by AAI compared to anaesthesia adjusted on clinical signs only. IL-6 were also found to be higher in patients with a MMSE <25 at 24-hours. Further studies are warranted evaluating the role of depth of anaesthesia monitoring on the risk for early cognitive impairment and neuro-inflammation.

Keywords
Cognitive decline, general anaesthesia, auditory evoked potential (AEP) monitoring, minor surgery
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology
Identifiers
urn:nbn:se:oru:diva-34018 (URN)
Available from: 2014-03-03 Created: 2014-03-03 Last updated: 2017-10-17Bibliographically approved
4. Swedish anaesthesiologists and nurse anaesthetists routines for evaluation and management of cognitive function: a nationwide survey
Open this publication in new window or tab >>Swedish anaesthesiologists and nurse anaesthetists routines for evaluation and management of cognitive function: a nationwide survey
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(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Abstract [en]

Introduction: In clinical practice efforts have mainly been focused on cardiovascular and pulmonary risks, there is less attention on postoperative delirium (POD) and postoperative cognitive dysfunction (POCD).

Methods: An online questionnaire regarding cognitive decline after anaesthesia and surgery was sent nationwide to a total of 2 626 anaesthesiologists and nurse anaesthetists. The questionnaire consisted of 3 parts, subjective preferences, routines and practices based on four typical case scenarios i.e. POCD, POD, emergence agitation (EA) and awareness.

Results: The response rate was n=417 (45%) and n=669 (55%) for anaesthesiologists and nurse anaesthetists respectively. Only 10% of the responders consider cognitive function, assessment of preoperatively and risk for cognitive side-effects postoperatively important. The concern regarding awareness was far greater (90%) than for EA, POD and POCD, 30- 45%. EEG based depth of anaesthetic monitoring (DOA) is used regularly by 10% and in 22% in patients with increased risk. Regarding treatment, investigation and follow-up routines, less than 15% had written structured protocols. Sixty percent of the respondents do not consider POCD as an important outcome. Anaesthesiologists have a better knowledge of screening methods, management and follow-up routines and drug treatment for POD, POCD and EA compared to nurse anaesthetists.

Conclusions: Our nationwide survey of anaesthesiologists and nurse anaesthetists shows that there is a general lack of knowledge about assessment and management of postoperative cognitive dysfunction. They are more concerned about awareness than the much more frequent and serious problems such as POD and POCD. In general DOA monitoring is not considered necessary. This survey shows that there is a clear need for improvement regarding knowledge of cognitive function.

Keywords
Anaesthesia, Surgery, adverse effects; cognitive dysfunction, postoperative delirium, emergence agitation, POCD, depth of anaesthesia monitoring, AAI
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology
Identifiers
urn:nbn:se:oru:diva-34020 (URN)
Available from: 2014-03-03 Created: 2014-03-03 Last updated: 2017-10-17Bibliographically approved

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Jildenstål, Pether

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