Cerebral perfusion in sepsis-associated delirium

INTRODUCTION: The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium. METHODS: We investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100beta, and cortisol were measured during each data acquisition. RESULTS: Data from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100beta (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010). CONCLUSION: In this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100beta and cortisol in the diagnosis of sepsis-associated delirium are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410111

Near-infrared spectroscopy can monitor dynamic cerebral autoregulation in adults

OBJECTIVE: To study the correlation between a dynamic index of cerebral autoregulation assessed with blood flow velocity (FV) using transcranial Doppler, and a tissue oxygenation index (TOI) recorded with near-infrared spectroscopy (NIRS). METHODS: Twenty-three patients with sepsis, severe sepsis, or septic shock were monitored daily on up to four consecutive days. FV, TOI, and mean arterial blood pressure (ABP) were recorded for 60 min every day. An index of autoregulation (Mx) was calculated as the moving correlation coefficient between 10-s averaged values of FV and ABP over moving 5 min time-windows. The index Tox was evaluated as the correlation coefficient between TOI and ABP in the same way. The indices Mx and Tox, ABP and arterial partial pressure of CO(2) were averaged for each patient. RESULTS: Synchronized slow waves, presenting with periods from 20 s to 2 min, were seen in the TOI and FV of most patients, with a reasonable coherence between the signals in this bandwidth (coherence 0.0001) in the whole group of patients. Both indices showed a significant (P > 0.05) tendency to indicate weaker autoregulation in the state of vasodilatation associated with greater values of arterial partial pressure of CO(2) or lower values of ABP. CONCLUSION: NIRS shows promise for the continuous assessment of cerebral autoregulation in adults

Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients

Cerebral cholinergic transmission plays a key role in cognitive function, and anticholinergic drugs administered during the perioperative phase are a hypothetical cause of postoperative cognitive dysfunction (POCD). We hypothesized that a perioperative increase in serum anticholinergic activity (SAA) is associated with POCD in elderly patients.; Seventy-nine patients aged >65 years undergoing elective major surgery under standardized general anesthesia (thiopental, sevoflurane, fentanyl, and atracurium) were investigated. Cognitive functions were assessed preoperatively and 7 days postoperatively using the extended version of the CERAD-Neuropsychological Assessment Battery. POCD was defined as a postoperative decline >1 z-score in at least 2 test variables. SAA was measured preoperatively and 7 days postoperatively at the time of cognitive testing. Hodges-Lehmann median differences and their 95% confidence intervals were calculated for between-group comparisons.; Of the patients who completed the study, 46% developed POCD. Patients with POCD were slightly older and less educated than patients without POCD. There were no relevant differences between patients with and without POCD regarding gender, demographically corrected baseline cognitive functions, and duration of anesthesia. There were no large differences between patients with and without POCD regarding SAA preoperatively (pmol/mL, median [interquartile range]/median difference [95% CI], P; 1.14 [0.72, 2.37] vs 1.13 [0.68, 1.68]/0.12 [-0.31, 0.57], P = 0.56), SAA 7 days postoperatively (1.32 [0.68, 2.59] vs 0.97 [0.65, 1.83]/0.25 [-0.26, 0.81], P = 0.37), or changes in SAA (0.08 [-0.50, 0.70] vs -0.02 [-0.53, 0.41]/0.1 [-0.31, 0.52], P = 0.62). There was no significant relationship between changes in SAA and changes in cognitive function (Spearman rank correlation coefficient preoperatively of 0.03 [95% CI, -0.21, 0.26] and postoperatively of -0.002 [95% CI, -0.24, 0.23]).; In this panel of patients with low baseline SAA and clinically insignificant perioperative anticholinergic burden, although a relationship cannot be excluded in some patients, our analysis suggests that POCD is probably not a substantial consequence of anticholinergic medications administered perioperatively but rather due to other mechanisms

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial

OBJECTIVE: Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. DESIGN:: Double-blind, randomized, placebo-controlled trial. SETTING: One Swiss University Hospital. PATIENTS: One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. MEASUREMENTS AND MAIN RESULTS: The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. CONCLUSION: This negative or, because of methodologic issues, possibly failed trial does no support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass

Monitoring of cerebral blood flow autoregulation in adults undergoing sevoflurane anesthesia: a prospective cohort study of two age groups.

Autoregulation of blood flow is a key feature of the human cerebral vascular system to assure adequate oxygenation and metabolism of the brain under changing physiological conditions. The impact of advanced age and anesthesia on cerebral autoregulation remains unclear. The primary objective of this study was to determine the effect of sevoflurane anesthesia on cerebral autoregulation in two different age groups. This is a follow-up analysis of data acquired in a prospective observational cohort study. One hundred thirty-three patients aged 18-40 and ≥65 years scheduled for major noncardiac surgery under general anesthesia were included. Cerebral autoregulation indices, limits, and ranges were compared in young and elderly patient groups. Forty-nine patients (37 %) aged 18-40 years and 84 patients (63 %) aged ≥65 years were included in the study. Age-adjusted minimum alveolar concentrations of sevoflurane were 0.89 ± 0.07 in young and 0.99 ± 0.14 in older subjects (P < 0.001). Effective autoregulation was found in a blood pressure range of 13.8 ± 9.8 mmHg in young and 10.2 ± 8.6 mmHg in older patients (P = 0.079). The lower limit of autoregulation was 66 ± 12 mmHg and 73 ± 14 mmHg in young and older patients, respectively (P = 0.075). The association between sevoflurane concentrations and autoregulatory capacity was similar in both age groups. Our data suggests that the autoregulatory plateau is shortened in both young and older patients under sevoflurane anesthesia with approximately 1 MAC. Lower and upper limits of cerebral blood flow autoregulation, as well as the autoregulatory range, are not influenced by the age of anesthetized patients. Trial registration ClinicalTrials.gov (NCT00512200)