Risk Factors of Intraoperative Dysglycemia in Elderly Surgical Patients

BACKGROUNDː Dysglycemia is associated with adverse outcome including increased morbidity and mortality in surgical patients. Acute insulin resistance due to the surgical stress response is seen as a major cause of so-called stress hyperglycemia. However, understanding of factors determining blood glucose (BG) during surgery is limited. Therefore, we investigated risk factors contributing to intraoperative dysglycemia. METHODSː In this subgroup investigation of the BIOCOG study, we analyzed 87 patients of ≥ 65 years with tight intraoperative BG measurement every 20 min during elective surgery. Dysglycemia was defined as at least one intraoperative BG measurement outside the recommended target range of 80-150 mg/dL. Additionally, all postoperative BG measurements in the ICU were obtained. Multivariable logistic regression analysis adjusted for age, sex, American Society of Anesthesiologists (ASA) status, diabetes, type and duration of surgery, minimum Hemoglobin (Hb) and mean intraoperative norepinephrine use was performed to identify risk factors of intraoperative dysglycemia. RESULTSː 46 (52.9%) out of 87 patients developed intraoperative dysglycemia. 31.8% of all intraoperative BG measurements were detected outside the target range. Diabetes [OR 9.263 (95% CI 2.492, 34.433); p=0.001] and duration of surgery [OR 1.005 (1.000, 1.010); p=0.036] were independently associated with the development of intraoperative dysglycemia. Patients who experienced intraoperative dysglycemia had significantly elevated postoperative mean (p<0.001) and maximum BG levels (p=0.001). Length of ICU (p=0.007) as well as hospital stay (p=0.012) were longer in patients with dysglycemia. CONCLUSIONSː Diabetes and duration of surgery were confirmed as independent risk factors for intraoperative dysglycemia, which was associated with adverse outcome. These patients, therefore, might require intensified glycemic control. Increased awareness and management of intraoperative dysglycemia is warranted

Cerebral microbleeds are not associated with postoperative delirium and postoperative cognitive dysfunction in older individuals

BACKGROUND: Cerebral microbleeds (CMB) occur in the context of cerebral small vessel disease. Other brain MRI markers of cerebral small vessel disease are associated with the occurrence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), but for CMB this is unknown. We aimed to study the association between CMB and the occurrence of POD and POCD in older individuals. METHODS: The current study consists of 65 patients (72±5 years) from the BIOCOG study, which is a prospective, observational study of patients who underwent an elective surgery of at least 60 minutes. Patients in the current study received a preoperative cerebral MRI scan including a 3D susceptibility-weighted imaging sequence to detect CMB. The occurrence of POD was screened for twice a day until postoperative day 7 by using the DSM-5, NuDesc, CAM, and CAM-ICU. The occurrence of POCD was determined by the reliable change index model at 7 days after surgery or discharge, respectively, and 3 months after surgery. Statistical analyses consisted of logistic regression adjusted for age and gender. RESULTS: A total of 39 CMB were detected in 17 patients (26%) prior to surgery. POD occurred in 14 out of 65 patients (22%). POCD at 7 days after surgery occurred in 11 out of 54 patients (20%) and in 3 out of 40 patients at the 3 month follow-up (8%). Preoperative CMB were not associated with the occurrence of POD (OR (95%-CI): 0.28 (0.05, 1.57); p = 0.147) or POCD at 7 days after surgery (0.76 (0.16, 3.54); p = 0.727) or at 3 months follow-up (0.61 (0.03, 11.64); p = 0.740). CONCLUSION: We did not find an association between preoperative CMB and the occurrence of POD or POCD. TRIAL REGISTRATION: clinicaltrials.gov (NCT02265263) on 23 September 2014

The influence of premedication with midazolam on the intraoperative EEG

Objective: The benzodiazepine midazolam, a gamma amino butyric acid receptor A (GABAA-) agonist, is frequently administered as premedication before surgery to reduce anxiety and agitation. However, its effects on electroencephalogram (EEG) dynamics at induction of anesthesia with propofol, a GABAA-agonist as well, and during early phases of general anesthesia are still unknown. This study aims to investigate the influence of premedication with midazolam on the pre-operative, frontal EEG and the impact of this GABAA – receptor pre-activation on the intraoperative EEG spectrum after induction of anesthesia with propofol. Methods: Within the framework of this prospective observational trail patients aged ≥ 65 years, undergoing elective surgery were examined. Patients who received premedication with midazolam (Mid, n=15) were compared to patients who did not (noMid, n=30). A continuous pre- and intraoperative frontal EEG was recorded with the Sedline monitor (Masimo). A pooled electrode that equally weighted the signals recorded at the electrode positions Fp1/2 and F7/8 was calculated to obtain estimates of frontal power spectra. Subsequently, absolute power within the delta (0.5-4Hz), theta (4-8Hz), alpha (8-12Hz), and beta (12-25Hz) frequency-bands was analyzed in 10-second EEG-sections before (pre-induction), and after induction of anesthesia with propofol (post-induction), as well as during a stable intraoperative phase of anesthesia that was maintained with either propofol or volatile-anesthetics (intra-operative). Additionally, a “baseline” EEG recorded on the day before surgery, when patients were under no influence of midazolam or propofol, was analyzed in a post hoc approach to validate the results. Results: There was no significant difference in α-power between Mid and noMid patients during the “baseline” EEG recordings. Pre-induction, α-power of Mid patients was lower compared with noMid-patients (α-power: Mid: -10.75 dB vs. noMid: -9.20 dB; p=0.036). After induction of anesthesia Mid-patients displayed a stronger increase of frontal α-power resulting in higher absolute α-power at post-induction state, (α-power: Mid -3.56 dB vs. noMid: -6.69 dB; p=0.004), which remained higher intraoperatively (α-power: Mid: -2.12 dB vs. noMid: -6.10 dB; p=0.024). Conclusion: Midazolam premedication altered the intraoperative EEG-spectrum in elderly patients. Low-dose GABAA activation in form of premedication with midazolam facilitated the activation of frontal α-power in response to induction of anesthesia with propofol. This finding provides further evidence for the role of GABAergic transmission in the appearance of frontal α-power at loss of consciousness and during general anesthesia.Ziel: Das Benzodiazepin Midazolam wird häufig als Prämedikation vor einer Narkose verordnet. Sowohl Midazolam als auch das häufig zur Narkoseeinleitung verwendete Hypnotikum Propofol wirken als GABAA-Agonisten, allerdings an unterschiedlichen Bindungsstellen des Rezeptors. Es wird vermutet, dass GABAA-vermittelte Feedbackmechanismen für einen Anstieg der frontalen -Power im EEG Spektrum unter Vollnarkose verantwortlich sind. Ziel dieser Studie war es zu untersuchen, wie eine Voraktivierung des GABAA-Rezeptors durch Midazolam das EEG Spektrum bei älteren Patienten vor, während, und nach Narkoseeinleitung mit Propofol beeinflusst. Methoden: Im Rahmen dieser prospektiven Beobachtungsstudie wurden Patienten im Alter von ≥ 65 Jahren, die sich einer elektiven Operation mit einer Dauer von mindestens 60 Minuten unterzogen, untersucht. Ein kontinuierliches prä- und intraoperatives frontales EEG wurde mittels des Sedline EEG Monitors (Masimo) bei Patienten, die eine Prämedikation mit Midazolam erhielten (Mid, n = 15), und bei Patienten ohne Prämedikation (noMid, n = 30) aufgezeichnet. Zur Validierung der Ergebnisse wurde zusätzlich ein am Tag vor der Operation aufgezeichnetes „Baseline“ EEG ohne den Einfluss von Midazolam oder Propofol ausgewertet. Für die Auswertung wurden die EEG-Signale der Elektrodenpositionen Fp1/2 und F7/8 gemittelt. Die absolute spektrale Power in den Frequenzbereichen Delta (0,5-4 Hz), Theta (4-8 Hz), Alpha (8-12 Hz) und Beta (12-25 Hz) wurde in 10 Sekunden langen EEG-Abschnitten vor Narkoseeinleitung, nach Narkoseeinleitung mit Propofol sowie während einer stabilen intraoperativen Narkosephase, die entweder mit Propofol oder volatilen Anästhetika aufrechterhalten wurde, untersucht. Ergebnisse: Die α-Power während der Baseline EEGs unterschied sich nicht zwischen beiden Gruppen. Vor Narkoseeinleitung war die α-Power bei prämedizierten Patienten (Mid-Patienten) im Vergleich zu noMid-Patienten deutlich geringer (α-Power: Mid: -10,75 dB vs. noMid: -9,20 dB; p = 0,036). Während der Narkoseeinleitung zeigten Mid-Patienten einen signifikant stärkeren Anstieg der frontalen α-Power, was zu einer höheren absoluten α-Power führte (α-Power: Mid: - 3,56 dB vs. noMid: - 6,69 dB; p = 0,004). Die α-Power blieb auch intraoperativ signifikant höher im Vergleich zu nicht prämedizierten Patienten (α-Power: Mid: -2,12 dB vs. noMid: -6,10 dB; p = 0,024). Zusammenfassung: Eine Prämedikation mit Midazolam verändert das intraoperative EEG-Spektrum bei älteren Patienten. Die Vor-Aktivierung des GABAA-Rezeptors durch Midazolam führt zu einer höheren intraoperativen α-Power nach Propofol-Gabe. Diese Ergebnisse liefern weitere Hinweise darauf, dass der Anstieg der frontalen α-Power während einer Vollnarkose auf GABA-vermittelten Feedback-Mechanismen beruht

Influence of midazolam premedication on intraoperative EEG signatures in elderly patients

Objective: To investigate the influence of midazolam premedication on the EEG-spectrum before and during general anesthesia in elderly patients. Methods: Patients aged ≥65 years, undergoing elective surgery were included in this prospective observational study. A continuous pre- and intraoperative frontal EEG was recorded in patients who received premedication with midazolam (Mid, n = 15) and patients who did not (noMid, n = 30). Absolute power within the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–25 Hz) frequency-bands was analyzed in EEG-sections before (pre-induction), and after induction of anesthesia with propofol (post-induction), as well as during general anesthesia with either propofol or volatile-anesthetics (intra-operative). Results: Pre-induction, α-power of Mid patients was lower compared with noMid-patients (α-power: Mid: −10.75 dB vs. noMid: −9.20 dB; p = 0.036). After induction of anesthesia Mid-patients displayed a stronger increase of frontal α-power resulting in higher absolute α-power at post-induction state, (α-power: Mid −3.56 dB vs. noMid: −6.69 dB; p = 0.004), which remained higher intraoperatively (α-power: Mid: −2.12 dB vs. noMid: −6.10 dB; p = 0.024). Conclusion: Midazolam premedication alters the intraoperative EEG-spectrum in elderly patients. Significance: This finding provides further evidence for the role of GABAergic activation in the induction of elevated, frontal α-power during general anesthesia. Keywords: Physiology (medical); Sensory Systems; Neurology; Clinical Neurology; Premedication; Benzodiazepines – midazolam; EEG; Geriatric anesthesia; Propofol anesthesiaSeventh Framework Programme (European Commission) (Grant HEALTH-F2-2014-60246

Perioperative Electroencephalogram Spectral Dynamics Related to Postoperative Delirium in Older Patients

BACKGROUND: Intraoperative electroencephalography (EEG) signatures related to the development of postoperative delirium (POD) in older patients are frequently studied. However, a broad analysis of the EEG dynamics including preoperative, postinduction, intraoperative and postoperative scenarios and its correlation to POD development is still lacking. We explored the relationship between perioperative EEG spectra-derived parameters and POD development, aiming to ascertain the diagnostic utility of these parameters to detect patients developing POD. METHODS: Patients aged ≥65 years undergoing elective surgeries that were expected to last more than 60 minutes were included in this prospective, observational single center study (Biomarker Development for Postoperative Cognitive Impairment [BioCog] study). Frontal EEGs were recorded, starting before induction of anesthesia and lasting until recovery of consciousness. EEG data were analyzed based on raw EEG files and downloaded excel data files. We performed multitaper spectral analyses of relevant EEG epochs and further used multitaper spectral estimate to calculate a corresponding spectral parameter. POD assessments were performed twice daily up to the seventh postoperative day. Our primary aim was to analyze the relation between the perioperative spectral edge frequency (SEF) and the development of POD. RESULTS: Of the 237 included patients, 41 (17%) patients developed POD. The preoperative EEG in POD patients was associated with lower values in both SEF (POD 13.1 ± 4.6 Hz versus no postoperative delirium [NoPOD] 17.4 ± 6.9 Hz; P = .002) and corresponding γ-band power (POD -24.33 ± 2.8 dB versus NoPOD -17.9 ± 4.81 dB), as well as reduced postinduction absolute α-band power (POD -7.37 ± 4.52 dB versus NoPOD -5 ± 5.03 dB). The ratio of SEF from the preoperative to postinduction state (SEF ratio) was ~1 in POD patients, whereas NoPOD patients showed a SEF ratio >1, thus indicating a slowing of EEG with loss of unconscious. Preoperative SEF, preoperative γ-band power, and SEF ratio were independently associated with POD (P = .025; odds ratio [OR] = 0.892, 95% confidence interval [CI], 0.808-0.986; P = .029; OR = 0.568, 95% CI, 0.342-0.944; and P = .009; OR = 0.108, 95% CI, 0.021-0.568, respectively). CONCLUSIONS: Lower preoperative SEF, absence of slowing in EEG while transitioning from preoperative state to unconscious state, and lower EEG power in relevant frequency bands in both these states are related to POD development. These findings may suggest an underlying pathophysiology and might be used as EEG-based marker for early identification of patients at risk to develop POD

Data_Sheet_1_Desflurane is risk factor for postoperative delirium in older patients’ independent from intraoperative burst suppression duration.pdf

BackgroundPostoperative Delirium (POD) is the most frequent neurocognitive complication after general anesthesia in older patients. The development of POD is associated with prolonged periods of burst suppression activity in the intraoperative electroencephalogram (EEG). The risk to present burst suppression activity depends not only on the age of the patient but is also more frequent during propofol anesthesia as compared to inhalative anesthesia. The aim of our study is to determine, if the risk to develop POD differs depending on the anesthetic agent given and if this correlates with a longer duration of intraoperative burst suppression.MethodsIn this secondary analysis of the SuDoCo trail [ISRCTN 36437985] 1277 patients, older than 60 years undergoing general anesthesia were included. We preprocessed and analyzed the raw EEG files from each patient and evaluated the intraoperative burst suppression duration. In a logistic regression analysis, we assessed the impact of burst suppression duration and anesthetic agent used for maintenance on the risk to develop POD.Results18.7% of patients developed POD. Burst suppression duration was prolonged in POD patients (POD 27.5 min ± 21.3 min vs. NoPOD 21.4 ± 16.2 min, p ConclusionWe found a significantly increased risk to develop POD after desflurane anesthesia in older patients, even though burst suppression duration was shorter under desflurane anesthesia as compared to propofol anesthesia. Our finding might help to explain some discrepancies in studies analyzing the impact of burst suppression duration and EEG-guided anesthesia on the risk to develop POD.</p

Cognitive Impairment Is Associated with Absolute Intraoperative Frontal α-Band Power but Not with Baseline α-Band Power: A Pilot Study

Background: Cognitive abilities decline with aging, leading to a higher risk for the development of postoperative delirium or postoperative neurocognitive disorders after general anesthesia. Since frontal alpha-band power is known to be highly correlated with cognitive function in general, we hypothesized that preoperative cognitive impairment is associated with lower baseline and intraoperative frontal alpha-band power in older adults. Methods: Patients aged >= 65 years undergoing elective surgery were included in this prospective observational study. Cognitive function was assessed on the day before surgery using six age-sensitive cognitive tests. Scores on those tests were entered into a principal component analysis to calculate a composite "g score" of global cognitive ability. Patient groups were dichotomized into a lower cognitive group (LC) reaching the lower 1/3 of "g scores" and a normal cognitive group (NC) consisting of the upper 2/3 of "g scores." Continuous pre- and intraoperative frontal electroencephalograms (EEGs) were recorded. EEG spectra were analyzed at baseline, before start of anesthesia medication, and during a stable intraoperative period. Significant differences in band power between the NC and LC groups were computed by using a frequency domain (delta 0.5-3 Hz, theta 4-7 Hz, alpha 8-12 Hz, beta 13-30 Hz)-based bootstrapping algorithm. Results: Of 38 included patients (mean age 72 years), 24 patients were in the NC group, and 14 patients had lower cognitive abilities (LC). Intraoperative alpha-band power was significantly reduced in the LC group compared to the NC group (NC -1.6 [-4.48/1.17] dB vs. LC -6.0 [-9.02/-2.64] dB), and intraoperative alpha-band power was positively correlated with "g score" (Spearman correlation: r = 0.381; p = 0.018). Baseline EEG power did not show any associations with "g." Conclusions: Preoperative cognitive impairment in older adults is associated with intraoperative absolute frontal alpha-band power, but not baseline alpha-band power