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Best Practices for Postoperative Brain Health:... : Anesthesia & Analgesia
“There is little evidence that any particular volatile anesthetic agent is associated with an altered risk of PND. Nonetheless, there are clearly age-dependent changes in volatile anesthetic sensitivity. The minimum alveolar concentration (MAC) of a volatile anesthetic necessary to prevent movement in response to surgical incision in 50% of patients declines by ≈6% per decade after 30 years of age.34 , 35 Because volatile anesthetics have one of the narrowest therapeutic indices of any drug used in modern medicine,36 , 37 avoiding volatile anesthetic overdose by closely monitoring the age-adjusted MAC fraction is critical to avoid side effects of these drugs38 and may even help to lower delirium rates.31 , 39 For example, in the cognitive dysfunction after anesthesia (CODA) trial, a 39% decrease in the age-adjusted end-tidal MAC fraction (ie, the inhaled anesthetic dose received by patients) was associated with a 31% reduction in cognitive dysfunction at 3 months after surgery and 35% reduction in postoperative delirium.31 Thus, there was widespread agreement among the participants that anesthesiologists should use age-adjusted MAC fraction in older adults to adjust end-tidal volatile anesthetic concentration during surgery, which at least provides a population-derived starting point for dosing inhaled anesthetics.
Similarly, it may seem intuitive that using a regional anesthetic technique or nerve block to either complement or replace a general anesthetic could help decrease systemic anesthetic administration and thereby might lower the incidence of PND. Yet, this intuition is largely unsupported by data because the majority of studies that have examined this issue have not found an increased risk of delirium or POCD after general as compared to regional anesthesia.40–42 However, many of these studies were confounded by the administration of high doses of intravenous sedatives in the regional anesthesia groups. In fact, many patients in the regional anesthesia groups in these studies may have actually been in a state of general anesthesia from a neuroscience perspective (ie, the patient was sufficiently unconscious during a regional technique as if he/she were receiving general anesthesia). Nonetheless, even in 1 randomized controlled trial that rigorously ensured that patients in the regional group did not receive any intravenous sedation, there was still no difference in delirium rates among the regional versus the general anesthesia groups.42 Thus, the current literature does not support the recommendation that a regional anesthetic technique should be used in place of (or in addition to) general anesthesia to reduce delirium or PND rates. Similarly, a number of studies have examined whether using specific drugs to maintain general anesthesia affect the rates of various types of PND, but no clear consensus recommendations have emerged from these studies.43–49”
Intraoperative EEG Monitoring and Anesthetic Titration
Several studies have also examined whether anesthetic titration in response to processed electroencephalography (EEG) monitoring might lower the risk of delirium or POCD. Two studies have found a statistically significant decrease in delirium rates when anesthetic “depth” was titrated based on monitoring with the Bispectral Index (BIS; Medtronic, Minneapolis, MN) monitor (a processed EEG monitor).31 , 39 Four studies have examined the use of processed EEG monitoring with BIS for POCD prevention, and the results have been mixed. One study found lower POCD rates 3 months after surgery in patients who underwent BIS monitoring,31 a second study found no effect,39 and 2 other studies conversely found that patients with lower processed EEG values actually had improved cognition50or lower rates of delirium and POCD.51
However, the BIS monitor uses a proprietary algorithm and has never been specifically validated for use in older adults. Recent theoretical52 and empirical work53suggests that the BIS algorithm may report erroneously high values in most older adults (which could then lead providers to administer unnecessarily high anesthetic dosage in older patients) and may also report lower than normal values in patients with preexisting cognitive impairment or dementia.54 , 55 Further, there is a roughly flat relationship between end-tidal age-adjusted volatile anesthetic concentrations and BIS values over the clinically used range of volatile anesthetics (ie, 0.5–1.5 MAC).53,56 This roughly flat relationship between MAC fraction and BIS values, and the other issues with the BIS discussed above, suggests that titrating anesthetic concentration to the BIS number may be challenging in older adults. This point may explain the lack of large anesthetic dosage differences between patients in the BIS-guided versus BIS-blinded arms of some of the studies discussed above.39
57 , 58 which raises the possibility that either titrating anesthetic delivery to avoid burst suppression or in response to other raw EEG parameters59 (such as those discussed at icetap.org and eegforanesthesia.iars.org) could help reduce the risk of delirium or POCD. Several current studies are examining this possibility60–62; the results of these studies may provide further guidance on how raw EEG-based anesthetic titration might help lower the rates of PND and improve postoperative cognitive function. While there are clearly challenges in the use of current processed EEG monitors, EEG-based anesthetic titration has nonetheless been shown to lower delirium and POCD rates in multiple independent randomized controlled trials (ie, level 1 evidence). Thus, there is strong support for the general principle of EEG-based anesthetic titration to reduce PND rates in older adults (Back to Top | 63–65 after surgery, although other studies have found conflicting evidence.66 , 67 However, different studies have used different thresholds to define hypotension; a systematic review found over 140 different definitions for hypotension in the literature.68This ambiguity highlights the potential importance of defining hypotension based on individualized patient monitoring rather than population cutoffs. Furthermore, there is a right shift in the cerebral autoregulation curve in patients with chronic hypertension, and because many older patients have chronic hypertension, it is important to titrate blood pressure parameters relative to each patient’s baseline blood pressure while considering head height relative to the blood pressure monitoring site.
Near-infrared spectroscopy (NIRS) is commonly used during cardiac surgery as a real-time continuous monitor of cerebral perfusion. In several studies, an intraoperative decline in NIRS values has been associated with postoperative delirium and/or cognitive change.69 , 70 However, general limitations of these studies include small size, short follow-up, and inconsistent results.71 One randomized study examined the benefit of an intervention protocol based on NIRS values and demonstrated an improvement in major morbidity and mortality in cardiac surgery patients in the intervention arm.72 Importantly, cognitive outcomes were not measured, and these results72 have not been reproduced. However, 2 pilot trials have established feasibility for future, large randomized controlled trials using NIRS to reduce PND,73 , 74 and another study found that the combination of BIS-based and cerebral oximetry–based anesthetic titration reduced POCD in older adults.75 Overall, though, the meeting participants thought that the evidence in support of NIRS to reduce PND was less strong than the evidence in support of EEG-based anesthetic titration to reduce PND.
An alternative method of measuring cerebral perfusion is real-time monitoring of cerebral autoregulation, which can be used to maintain mean arterial pressure above the lower limit of cerebral autoregulation. In patients with traumatic brain injury, deviations of blood pressure above or below the limits of autoregulation have been associated with poor neurological outcomes.76 An investigation in a cardiac surgery population demonstrated that the mean arterial pressure at the lower limit of autoregulation varied widely and could not be predicted using patient variables.77 Further, deviations of blood pressure below the lower limit of autoregulation during cardiac surgery have been associated with both acute kidney injury78 and major morbidity and mortality,79 while deviations above the upper limit of autoregulation have been associated with delirium.80 Together, these results underscore the need for individualized monitoring of cerebral perfusion, and the need for further studies to elucidate the effect of reduced cerebral perfusion on neurocognitive outcomes.
Back to Top | Article Outline
Consensus Statement
“Anesthesiologists should monitor age-adjusted end-tidal MAC fraction, strive to optimize cerebral perfusion, and perform EEG-based anesthetic management in older adults. Further research is needed to evaluate and compare specific brain function monitors, methods, and approaches.”
“There is little evidence that any particular volatile anesthetic agent is associated with an altered risk of PND. Nonetheless, there are clearly age-dependent changes in volatile anesthetic sensitivity. The minimum alveolar concentration (MAC) of a volatile anesthetic necessary to prevent movement in response to surgical incision in 50% of patients declines by ≈6% per decade after 30 years of age.34 , 35 Because volatile anesthetics have one of the narrowest therapeutic indices of any drug used in modern medicine,36 , 37 avoiding volatile anesthetic overdose by closely monitoring the age-adjusted MAC fraction is critical to avoid side effects of these drugs38 and may even help to lower delirium rates.31 , 39 For example, in the cognitive dysfunction after anesthesia (CODA) trial, a 39% decrease in the age-adjusted end-tidal MAC fraction (ie, the inhaled anesthetic dose received by patients) was associated with a 31% reduction in cognitive dysfunction at 3 months after surgery and 35% reduction in postoperative delirium.31 Thus, there was widespread agreement among the participants that anesthesiologists should use age-adjusted MAC fraction in older adults to adjust end-tidal volatile anesthetic concentration during surgery, which at least provides a population-derived starting point for dosing inhaled anesthetics.
Similarly, it may seem intuitive that using a regional anesthetic technique or nerve block to either complement or replace a general anesthetic could help decrease systemic anesthetic administration and thereby might lower the incidence of PND. Yet, this intuition is largely unsupported by data because the majority of studies that have examined this issue have not found an increased risk of delirium or POCD after general as compared to regional anesthesia.40–42 However, many of these studies were confounded by the administration of high doses of intravenous sedatives in the regional anesthesia groups. In fact, many patients in the regional anesthesia groups in these studies may have actually been in a state of general anesthesia from a neuroscience perspective (ie, the patient was sufficiently unconscious during a regional technique as if he/she were receiving general anesthesia). Nonetheless, even in 1 randomized controlled trial that rigorously ensured that patients in the regional group did not receive any intravenous sedation, there was still no difference in delirium rates among the regional versus the general anesthesia groups.42 Thus, the current literature does not support the recommendation that a regional anesthetic technique should be used in place of (or in addition to) general anesthesia to reduce delirium or PND rates. Similarly, a number of studies have examined whether using specific drugs to maintain general anesthesia affect the rates of various types of PND, but no clear consensus recommendations have emerged from these studies.43–49”
Intraoperative EEG Monitoring and Anesthetic Titration
Several studies have also examined whether anesthetic titration in response to processed electroencephalography (EEG) monitoring might lower the risk of delirium or POCD. Two studies have found a statistically significant decrease in delirium rates when anesthetic “depth” was titrated based on monitoring with the Bispectral Index (BIS; Medtronic, Minneapolis, MN) monitor (a processed EEG monitor).31 , 39 Four studies have examined the use of processed EEG monitoring with BIS for POCD prevention, and the results have been mixed. One study found lower POCD rates 3 months after surgery in patients who underwent BIS monitoring,31 a second study found no effect,39 and 2 other studies conversely found that patients with lower processed EEG values actually had improved cognition50or lower rates of delirium and POCD.51
However, the BIS monitor uses a proprietary algorithm and has never been specifically validated for use in older adults. Recent theoretical52 and empirical work53suggests that the BIS algorithm may report erroneously high values in most older adults (which could then lead providers to administer unnecessarily high anesthetic dosage in older patients) and may also report lower than normal values in patients with preexisting cognitive impairment or dementia.54 , 55 Further, there is a roughly flat relationship between end-tidal age-adjusted volatile anesthetic concentrations and BIS values over the clinically used range of volatile anesthetics (ie, 0.5–1.5 MAC).53,56 This roughly flat relationship between MAC fraction and BIS values, and the other issues with the BIS discussed above, suggests that titrating anesthetic concentration to the BIS number may be challenging in older adults. This point may explain the lack of large anesthetic dosage differences between patients in the BIS-guided versus BIS-blinded arms of some of the studies discussed above.39
57 , 58 which raises the possibility that either titrating anesthetic delivery to avoid burst suppression or in response to other raw EEG parameters59 (such as those discussed at icetap.org and eegforanesthesia.iars.org) could help reduce the risk of delirium or POCD. Several current studies are examining this possibility60–62; the results of these studies may provide further guidance on how raw EEG-based anesthetic titration might help lower the rates of PND and improve postoperative cognitive function. While there are clearly challenges in the use of current processed EEG monitors, EEG-based anesthetic titration has nonetheless been shown to lower delirium and POCD rates in multiple independent randomized controlled trials (ie, level 1 evidence). Thus, there is strong support for the general principle of EEG-based anesthetic titration to reduce PND rates in older adults (Back to Top | 63–65 after surgery, although other studies have found conflicting evidence.66 , 67 However, different studies have used different thresholds to define hypotension; a systematic review found over 140 different definitions for hypotension in the literature.68This ambiguity highlights the potential importance of defining hypotension based on individualized patient monitoring rather than population cutoffs. Furthermore, there is a right shift in the cerebral autoregulation curve in patients with chronic hypertension, and because many older patients have chronic hypertension, it is important to titrate blood pressure parameters relative to each patient’s baseline blood pressure while considering head height relative to the blood pressure monitoring site.
Near-infrared spectroscopy (NIRS) is commonly used during cardiac surgery as a real-time continuous monitor of cerebral perfusion. In several studies, an intraoperative decline in NIRS values has been associated with postoperative delirium and/or cognitive change.69 , 70 However, general limitations of these studies include small size, short follow-up, and inconsistent results.71 One randomized study examined the benefit of an intervention protocol based on NIRS values and demonstrated an improvement in major morbidity and mortality in cardiac surgery patients in the intervention arm.72 Importantly, cognitive outcomes were not measured, and these results72 have not been reproduced. However, 2 pilot trials have established feasibility for future, large randomized controlled trials using NIRS to reduce PND,73 , 74 and another study found that the combination of BIS-based and cerebral oximetry–based anesthetic titration reduced POCD in older adults.75 Overall, though, the meeting participants thought that the evidence in support of NIRS to reduce PND was less strong than the evidence in support of EEG-based anesthetic titration to reduce PND.
An alternative method of measuring cerebral perfusion is real-time monitoring of cerebral autoregulation, which can be used to maintain mean arterial pressure above the lower limit of cerebral autoregulation. In patients with traumatic brain injury, deviations of blood pressure above or below the limits of autoregulation have been associated with poor neurological outcomes.76 An investigation in a cardiac surgery population demonstrated that the mean arterial pressure at the lower limit of autoregulation varied widely and could not be predicted using patient variables.77 Further, deviations of blood pressure below the lower limit of autoregulation during cardiac surgery have been associated with both acute kidney injury78 and major morbidity and mortality,79 while deviations above the upper limit of autoregulation have been associated with delirium.80 Together, these results underscore the need for individualized monitoring of cerebral perfusion, and the need for further studies to elucidate the effect of reduced cerebral perfusion on neurocognitive outcomes.
Back to Top | Article Outline
Consensus Statement
“Anesthesiologists should monitor age-adjusted end-tidal MAC fraction, strive to optimize cerebral perfusion, and perform EEG-based anesthetic management in older adults. Further research is needed to evaluate and compare specific brain function monitors, methods, and approaches.”
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