Sevoflurane based anaesthesia does not affect already impaired cerebral autoregulation in patients with type 2 diabetes mellitus.

BACKGROUND: The baroreflex regulates arterial blood pressure (BP). During periods when blood pressure changes, cerebral blood flow (CBF) is kept constant by cerebral autoregulation (CA). In patients with diabetes mellitus (DM), low baroreflex sensitivity (BRS) is associated with impaired CA. As sevoflurane-based anaesthesia obliterates BRS, we hypothesised that this could aggravate the already impaired CA in patients with DM resulting in a 'double-hit' on cerebral perfusion leading to increased fluctuations in blood pressure and cerebral perfusion. METHODS: On the day before surgery, we measured CBF velocity (CBFV), heart rate, and BP to determine BRS and CA efficacy (CBFVmean-to-BPmean-phase lead) in 25 patients with DM and in 14 controls. During the operation, BRS and CA efficacy were determined during sevoflurane-based anaesthesia. Patients with DM were divided into a group with high BRS (DMBRS↑) and a group with low BRS (DMBRS↓). Values presented are median (inter-quartile range). RESULTS: Preoperative vs intraoperative BRS was 6.2 (4.5-8.5) vs 1.9 (1.1-2.5, P<0.001) ms mm Hg-1 for controls, 5.8 (4.9-7.6) vs 2.7 (1.5-3.9, P<0.001) ms mm Hg-1 for patients with DMBRS↑, and 1.9 (1.5-2.8) vs 1.1 (0.6-2.5, P=0.31) ms mm Hg-1 for patients with DMBRS↓. Preoperative vs intraoperative CA efficacy was 43° (38-46) vs 43° (38-51, P=0.30), 44° (36-49) vs 41° (32-49, P=0.52), and 34° (28-40) vs 30° (27-38, P=0.64) for controls, DMBRS↑, and DMBRS↓ patients, respectively. CONCLUSIONS: In diabetic patients with low preoperative BRS, preoperative CA efficacy was also impaired. In controls and diabetic patients, CA was unaffected by sevoflurane-based anaesthesia. We therefore conclude that sevoflurane-based anaesthesia does not contribute to a 'double-hit' phenomenon on cerebral perfusion. CLINICAL TRIAL REGISTRATION: NCT 03071432.

Novel method for intraoperative assessment of cerebral autoregulation by paced breathing.

Background: Cerebral autoregulation (CA) is the mechanism that maintains constancy of cerebral blood flow (CBF) despite variations in blood pressure (BP). Patients with attenuated CA have been shown to have an increased incidence of peri-operative stroke. Studies of CA in anaesthetized subjects are rare, because a simple and non-invasive method to quantify the integrity of CA is not available. In this study, we set out to improve non-invasive quantification of CA during surgery. For this purpose, we introduce a novel method to amplify spontaneous BP fluctuations during surgery by imposing mechanical positive pressure ventilation at three different frequencies and quantify CA from the resulting BP oscillations. Methods: Fourteen patients undergoing sevoflurane anaesthesia were included in the study. Continuous non-invasive BP and transcranial Doppler-derived CBF velocity (CBF V ) were obtained before surgery during 3 min of paced breathing at 6, 10, and 15 bpm and during surgery from mechanical positive pressure ventilation at identical frequencies. Data were analysed using frequency domain analysis to obtain CBF V -to-BP phase lead as a continuous measure of CA efficacy. Group averages were calculated. Values are means ( sd ), and P <0.05 was used to indicate statistical significance. Results: Preoperative vs intraoperative CBF V -to-BP phase lead was 43 (9) vs 45 (8)°, 25 (8) vs 24 (10)°, and 4 (6) vs -2 (12)° during 6, 10, and 15 bpm, respectively (all P =NS). Conclusions: During surgery, cerebral autoregulation indices were similar to values determined before surgery. This indicates that CA can be quantified reliably and non-invasively using this novel method and confirms earlier evidence that CA is unaffected by sevoflurane anaesthesia. Clinical trial registration: NCT03071432.

Cerebral oxygenation during changes in vascular resistance and flow in patients on cardiopulmonary bypass - a physiological proof of concept study.

Despite a rise in blood pressure, cerebral oxygenation decreases following phenylephrine administration, and we hypothesised that phenylephrine reduces cerebral oxygenation by activating cerebral α1 receptors. We studied patients on cardiopulmonary bypass during constant flow. Phenylephrine raised mean arterial pressure (α1 -mediated) from mean (SD) 69 (8) mmHg to 79 (8) mmHg; p = 0.001, and vasopressin raised mean arterial pressure (V1 mediated) from 69 (8) mmHg to 83 (6) mmHg; p = 0.001. Both drugs elicited a comparable decrease in cerebral oxygenation from 61 (7)% to 60 (7)%; p = 0.023 and 61 (8)% to 59 (8)%; p = 0.022, respectively. This implies that after phenylephrine or vasopressin administration, cerebral oxygenation declines as a result of cerebral vasoconstriction, due to either both cerebral α1 and V1 receptors being equipotentially activated or to an intrinsic myogenic mechanism of cerebral vasculature in reaction to blood pressure elevation.

Validation of non-invasive arterial pressure monitoring during carotid endarterectomy.

BACKGROUND: Patients undergoing carotid endarterectomy require strict arterial blood pressure (BP) control to maintain adequate cerebral perfusion. In this study we tested whether non-invasive beat-to-beat Nexfin finger BP (BPfin) can replace invasive beat-to-beat radial artery BP (BPrad) in this setting. METHODS: In 25 consecutive patients (median age 71 yr) scheduled for carotid endarterectomy and receiving general anaesthesia, BPfin and BPrad were monitored simultaneously and ipsilaterally during the 30-min period surrounding carotid artery cross-clamping. Validation was guided by the standard set by the Association for the Advancement of Medical Instrumentation (AAMI), which considers a BP monitor adequate when bias (precision) is <5 (8) mm Hg, respectively. RESULTS: BPfin vs BPrad bias (precision) was -3.3 (10.8), 6.1 (5.7) and 3.5 (5.2) mm Hg for systolic, diastolic, and mean BP, respectively. One subject was excluded due to a poor quality BP curve. In another subject, mean BPfin overestimated mean BPrad by 13.5 mm Hg. CONCLUSION: Mean BPfin could be considered as an alternative for mean BPrad during a carotid endarterectomy, based on the AAMI criteria. In 23 of 24 patients, the use of mean BPfin would not lead to decisions to adjust mean BPrad values outside the predefined BP threshold. CLINICALTRIALSGOV: NCT01451294.

Hyperventilation, cerebral perfusion, and syncope.

This review summarizes evidence in humans for an association between hyperventilation (HV)-induced hypocapnia and a reduction in cerebral perfusion leading to syncope defined as transient loss of consciousness (TLOC). The cerebral vasculature is sensitive to changes in both the arterial carbon dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2 the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established.

Near-infrared spectroscopy to indicate selective shunt use during carotid endarterectomy.

OBJECTIVES: This study assessed the value of cerebral near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) in relation to electroencephalography (EEG) changes for the detection of cerebral hypoperfusion necessitating shunt placement during carotid endarterectomy (CEA). METHODS: This was a prospective cohort study. Patients with a sufficient TCD window undergoing CEA from February 2009 to June 2011 were included. All patients were continuously monitored with NIRS and EEG. An intraluminal shunt was placed, selectively determined by predefined EEG changes in alpha, beta, theta, or delta activity. Relative changes in regional cerebral oxygen saturation (rSO2) in the frontal lobe and mean blood flow velocity (Vmean) 30 seconds before carotid cross-clamping versus 2 minutes after carotid cross-clamping were related to shunt placement. Receiver operating characteristic curve analysis was performed to determine the optimal thresholds. Diagnostic values were reported as positive and negative predictive value (PPV and NPV). RESULTS: Of a cohort of 151 patients, 17(11%) showed EEG changes requiring shunt placement. The rSO2 and Vmean decreased more in the shunt group than in the non-shunt group (mean ± standard error of the mean) 21 ± 4% versus 7 ± 5% and 76 ± 6% versus 12 ± 3%, respectively (p < .005), Receiver operating characteristic curve analysis revealed a threshold of 16% decrease in rSO2 (PPV 76% and NPV 99%) and 48% decrease in Vmean (PPV 53% and NPV 99%) as the optimal cut-off value to detect cerebral ischemia during CEA under general anesthesia. CONCLUSIONS: Compared with EEG, we found moderate PPV but high NPV for NIRS and TCD to detect cerebral ischemia during CEA under general anesthesia, meaning that both techniques independently may be suitable to exclude patients for unnecessary shunt use and to direct the use of selective shunting. However, the optimal thresholds for NIRS remain to be determined.

Near-infrared spectroscopy can predict the onset of cerebral hyperperfusion syndrome after carotid endarterectomy.

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA) is a potential life-threatening complication. Therefore, early identification and treatment of patients at risk is essential. CHS can be predicted by a doubling of postoperative transcranial Doppler (TCD)-derived mean middle cerebral artery blood velocity (V(mean)) compared to preoperative values. However, in approximately 15% of CEA patients, an adequate TCD signal cannot be obtained due to an insufficient temporal bone window. Moreover, the use of TCD requires specifically skilled personnel. An alternative and promising technique of noninvasive cerebral monitoring is relative frontal lobe oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS), which offers on-line information about cerebral oxygenation without the need for specialized personnel. In this study, we assess whether NIRS and perioperative TCD are related to the onset CHS following CEA. METHODS: Patients who underwent CEA under general anesthesia and had a sufficient TCD window were prospectively included. The V(mean) and rSO(2) measured before induction of anesthesia were compared to measurements performed in the first postoperative hour (ΔV(mean), ΔrSO(2), respectively). Logistic regression analysis was performed to determine the relationship between ΔV and ΔrSO(2) and the occurrence of CHS. Subsequently, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values. Diagnostic values were shown as positive and negative predictive values (PPV and NPV). RESULTS: In total, 151 patients were included, of which 7 patients developed CHS. The ΔV(mean) and ΔrSO(2) differed between CHS and non-CHS patients (median, interquartile range), i.e. 74% (67-103) versus 16% (-2 to 41), p = 0.001, and 7% (4-15) versus 1% (-6 to 7), p = 0.009, respectively. The mean arterial blood pressure did not change. Postoperative ΔV(mean) and ΔrSO(2) were significantly related to the occurrence of CHS [odds ratio (OR) 1.40 (95% CI 1.02-1.93) per 30% increase in V(mean) and OR 1.82 (95% CI 1.11-2.99) per 5% increase in rSO(2)]. ROC curve analysis showed an area under the curve of 0.88 (p = 0.001) for ΔV(mean) and an optimal cutoff value of 67% increase (PPV 38% and NPV 99%), and an area under the curve of 0.79 (p = 0.009) for ΔrSO(2) and an optimal cutoff value of 3% rSO(2) increase (PPV 11% and NPV 100%). The combination of both monitoring techniques provided a PPV of 58% and an NPV of 99%. CONCLUSIONS: Both TCD and NIRS measurements can be used to safely identify patients not at risk of developing CHS. It appears that NIRS is a good alternative when a TCD signal cannot be obtained.

Prediction of cerebral hyperperfusion after carotid endarterectomy with transcranial Doppler.

OBJECTIVES: To determine the diagnostic value for predicting cerebral hyperperfusion syndrome (CHS) by adding a transcranial Doppler (TCD) measurement in the early postoperative phase after carotid endarterectomy (CEA). DESIGN: Patients who underwent carotid endarterectomy between January 2004 and August 2010 and in whom both intra- and postoperative TCD monitoring were performed were included. METHODS: In 184 CEA patients the mean velocity (V(mean)) preoperatively (V1), pre-clamping (V2), post-declamping (V3) and postoperatively (V4) was measured using TCD. The intra-operative V(mean) increase ((V3 - V2)/V2) was compared to the postoperative increase ((V4 - V1)/V1) in relation to CHS. CHS was diagnosed if the patient developed neurological complaints in the presence of a preoperative V(mean) increase >100%. RESULTS: Sixteen patients (9%) had an intra-operative V(mean) increase >100% and 22 patients (12%) a postoperative V(mean) increase of >100%. In 10 patients (5%) CHS was diagnosed; two of those had an intra-operative V(mean) increase of >100% and nine postoperative V(mean) increase >100%. This results in a positive predictive value of 13% for the intra-operative and 41% for the postoperative measurement. CONCLUSIONS: Besides the commonly used intra-operative TCD monitoring additional TCD measurement in the early postoperative phase is useful to more accurately predict CHS after CEA.

The postural reduction in middle cerebral artery blood velocity is not explained by PaCO2.

In the normocapnic range, middle cerebral artery mean velocity (MCA Vmean) changes approximately 3.5% per mmHg carbon-dioxide tension in arterial blood (PaCO2) and a decrease in PaCO2 will reduce the cerebral blood flow by vasoconstriction (the CO2 reactivity of the brain). When standing up MCA Vmean and the end-tidal carbon-dioxide tension (PETCO2) decrease, suggesting that PaCO2 contributes to the reduction in MCA Vmean. In a fixed body position, PETCO2 tracks changes in the PaCO2 but when assuming the upright position, cardiac output (Q) decreases and its distribution over the lung changes, while ventilation (VE) increases suggesting that PETCO2 decreases more than PaCO2. This study evaluated whether the postural reduction in PaCO2 accounts for the postural decline in MCA Vmean). From the supine to the upright position, VE, Q, PETCO2, PaCO2, MCA Vmean, and the near-infrared spectrophotometry determined cerebral tissue oxygenation (CO2Hb) were followed in seven subjects. When standing up, MCA Vmean (from 65.3+/-3.8 to 54.6+/-3.3 cm s(-1) ; mean +/- SEM; P<0.05) and cO2Hb (-7.2+/-2.2 micromol l(-1) ; P<0.05) decreased. At the same time, the VE/Q ratio increased 49+/-14% (P<0.05) with the postural reduction in PETCO2 overestimating the decline in PaCO2 (-4.8+/-0.9 mmHg vs. -3.0+/-1.1 mmHg; P<0.05). When assuming the upright position, the postural decrease in MCA Vmean seems to be explained by the reduction in PETCO2 but the small decrease in PaCO2 makes it unlikely that the postural decrease in MCA Vmean can be accounted for by the cerebral CO2 reactivity alone.

Orthostatic blood pressure control before and after spaceflight, determined by time-domain baroreflex method.

Reduction in plasma volume is a major contributor to orthostatic tachycardia and hypotension after spaceflight. We set out to determine time- and frequency-domain baroreflex (BRS) function during preflight baseline and venous occlusion and postflight orthostatic stress, testing the hypothesis that a reduction in central blood volume could mimic the postflight orthostatic response. In five cosmonauts, we measured finger arterial pressure noninvasively in supine and upright positions. Preflight measurements were repeated using venous occlusion thigh cuffs to impede venous return and "trap" an increased blood volume in the lower extremities; postflight sessions were between 1 and 3 days after return from 10- to 11-day spaceflight. BRS was determined by spectral analysis and by PRVXBRS, a time-domain BRS computation method. Although all completed the stand tests, two of five cosmonauts had drastically reduced pulse pressures and an increase in heart rate of approximately 30 beats/min or more during standing after spaceflight. Averaged for all five subjects in standing position, high-frequency interbeat interval spectral power or transfer gain did not decrease postflight. Low-frequency gain decreased from 8.1 (SD 4.0) preflight baseline to 6.8 (SD 3.4) postflight (P = 0.033); preflight with thigh cuffs inflated, low-frequency gain was 9.4 (SD 4.3) ms/mmHg. There was a shift in time-domain-determined pulse interval-to-pressure lag, Tau, toward higher values (P < 0.001). None of the postflight results were mimicked during preflight venous occlusion. In conclusion, two of five cosmonauts showed abnormal orthostatic response 1 and 2 days after spaceflight. Overall, there were indications of increased sympathetic response to standing, even though we can expect (partial) restoration of plasma volume to have taken place. Preflight venous occlusion did not mimic the postflight orthostatic response.

Twenty-four-hour non-invasive monitoring of systemic haemodynamics and cerebral blood flow velocity in healthy humans.

Acute short-term changes in blood pressure (BP) and cardiac output (CO) affect cerebral blood flow (CBF) in healthy subjects. As yet, however, we do not know how spontaneous fluctuations in BP and CO influence cerebral circulation throughout 24 h. We performed simultaneous monitoring of BP, systemic haemodynamic parameters and blood flow velocity in the middle cerebral artery (MCAV) in seven healthy subjects during a 24-h period. Finger BP was recorded continuously during 24 h by Portapres and bilateral MCAV was measured by transcranial Doppler (TCD) during the first 15 min of every hour. The subjects remained supine during TCD recordings and during the night, otherwise they were seated upright in bed. Stroke volume (SV), CO and total peripheral resistance (TPR) were determined by Modelflow analysis. The 15 min mean value of each parameter was assumed to represent the mean of the corresponding hour. There were no significant differences between right vs. left, nor between mean daytime vs. night time MCAV. Intrasubject comparison of the twenty-four 15-min MCAV recordings showed marked variations (P < 0.001). Within each single 15-min recording period, however, MCAV was stable whereas BP showed significant short-term variations (P < 0.01). A day-night difference in BP was only observed when daytime BP was evaluated from recordings in the seated position (P < 0.02), not in supine recordings. Throughout 24 h, MCAV was associated with SV and CO (P < 0.001), to a lesser extent with mean arterial pressure (MAP; P < 0.005), not with heart rate (HR) or TPR. These results indicate that in healthy subjects MCAV remains stable when measured under constant supine conditions but shows significant variations throughout 24 h because of activity. Moreover, changes in SV and CO, and to a lesser extent BP variations, affect MCAV throughout 24 h.

Dynamic cerebral autoregulation under sinusoidal gravitational loading.

Dynamic cerebral autoregulation (CA) has been studied previously using spectral analysis of oscillations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). The dynamics of the CA can be modeled as a high-pass filter. The purpose of this study is to compare CA of blood pressure oscillations induced by gravitational loading to CA during resting conditions. We subjected twelve healthy subjects to repeated sinusoidal head-up (0 degrees - 60 degrees) tilts at several set frequencies (0.07 to 0.25 Hz) on a computer controlled tilt table while we recorded ABP (Finapres) and CBFV (transcranial Doppler ultrasound). We fitted the data sets to a high-pass filter model and computed an average time constant (T). Our results show similar phase leads of CBFV to ABPbrain in the rest recording and in sinusoidal tilting, in the studied frequency range. The transfer function gain of the resting spectra increased with increasing frequency, the gain of the tilting spectra did not. Fitting the phase responses of both data sets to a high pass filter model yielded similar time constants.