Measuring workload during a dynamic supervisory control task using cerebral blood flow velocity and the NASA-TLX

BACKGROUND: Short-term fluid loading is used as part of post-spaceflight medical procedures and clinical treatment in hospitals. Hypervolemia with hemodilution induced by rapid fluid infusion reportedly impaired dynamic cerebral autoregulation. However, the effects on intracranial pressure (ICP) remain unknown. Therefore, we estimated ICP noninvasively (nICP) to examine whether rapid fluid infusion would raise ICP.METHODS: Twelve healthy male volunteers underwent two discrete normal saline (NS) infusions (15 and 30 ml · kg-1 stages, NS-15 and NS-30, respectively) at a rate of 100 ml · min-1. The cerebral blood flow (CBF) velocity (CBFv) waveform from the middle cerebral artery obtained by transcranial Doppler ultrasonography was recorded, as was the arterial blood pressure (ABP) waveform at the radial artery obtained by tonometry. We then used these waveforms to calculate nICP, cerebral artery compliance, and the pulsatility index (PI) in an intracranial hydraulic model.RESULTS: nICP increased significantly in both infusion stages from preinfusion (preinfusion: 7.6 ± 3.4 mmHg; NS-15: 10.9 ± 3.3 mmHg; NS-30: 11.7 ± 4.2 mmHg). No significant changes were observed in cerebral artery compliance or PI. Although ABP did not change in any stage, CBFv increased significantly (preinfusion: 67 ± 10 cm · s-1; NS-15: 72 ± 12 cm · s-1; NS-30: 73 ± 12 cm · s-1).DISCUSSION: Hypervolemia with hemodilution induced by rapid fluid infusion caused increases in nICP and CBFv. No changes were observed in cerebral artery compliance or PI related to cerebrovascular impedance. These findings suggest that rapid fluid infusion may raise ICP with increased CBF.Kurazumi T, Ogawa Y, Takko C, Kato T, Konishi T, Iwasaki K. Short-term volume loading effects on estimated intracranial pressure in human volunteers. Aerosp Med Hum Perform. 2022; 93(4):347-353.

the cerebral blood flow velocity (CBFV): Influence of halothane and cerebral CO 2 reactivity. Objective: This controlled study was designed to investigate 1.) the effects of 0,8% halothane and 2.) the effects of a variation in PaCO 2 on the relationship between global cerebral blood flow (CBF) and middle cerebral artery flow velocity (CBFV MCA ). Method: With ethical committee approval and informed patient consent we investigated 10 patients undergoing coronary artery bypass surgery. Measurements were performed under fentanyl/midazolam anaesthesia prior to the start of surgery. First, during a baseline period, ventilation was changed in a random sequence to achieve two different levels of arterial PCO 2 (30 and 50 mmHg, respectively). Consequently, measurements were repeated during application of 0.8% halothane at identical PaCO 2 levels. Measurements of global CBF were performed by the Kety-Schmidt-technique with argon as an indicator. Simultaneously, CBFV MCA was recorded by use of a 2-MHz transcranial Doppler system. Results: Application of 0.8 % halothane caused a significant decrease in cerebrovascular resistance (CVR) both at hypocapnia and hypercapnia by 36 and 23 %, respectively. Because of a concomitant reduction in cerebral perfusion pressure (CPP), however, CBF remained unchanged during application of halothane. The relationship between CBF and CBFV MCA was not altered when compared to the baseline period. Similarly, CO 2 reactivity of CBF and CBFV MCA remained unchanged. CO 2 reactivity of CBF significantly exceeded CO 2 reactivity of CBFV MCA . Conclusion: The results of this clinical study demonstrate that Doppler-sonographic estimation of relative changes in CBF is not altered by application of 1 MAC halothane indicating that the decrease in CVR is not associated with a vasodilation of the proximal segments of basal cerebral arteries. The difference between CO 2 reactivity of CBF and CBFV MCA , however, suggests that CO 2 -induced changes in CBF are slightly underestimated by TCD monitoring of CBFV MCA .

The aim of this study was to differentiate the mechanical effects of the Valsalva maneuver (VM) from the effects of changes in autonomic neural activity on cerebral hemodynamics in humans. Nine healthy subjects performed the VM before and after autonomic ganglionic blockade with trimethaphan. Blood pressure (BP) was measured in the radial artery with an indwelling catheter or at the finger by Finapres. Cerebral blood flow (CBF) velocity was measured in the middle cerebral artery with transcranial Doppler; end-tidal CO2 was measured by mass spectrometry. Before blockade, during phase II of the VM, BP was reduced by 27% and CBF velocity was reduced by 33% (magnitude of changes during phase II divided by baseline measurements before the VM, P<0.05). Cerebrovascular conductance index (CVCI) increased by 21%. During phase IV, overshoot of CBF velocity was proportionately greater than that of BP (46% versus 30%). After blockade, during phase II, BP fell to a much greater degree by 50%, while CBF velocity decreased even more by 60% associated with an increase in CVCI by 33%. During phase IV, despite the absence of BP overshoot, CBF velocity still increased by 55% and CVCI by 33%. Both were significantly greater than before blockade. After ganglionic blockade, cerebral autoregulation is unable to prevent the substantial fall in CBF induced by the marked reduction in BP during the VM. Enhanced phase IV increases in both CBF velocity and CVCI reflect the intrinsic characteristics of cerebral hyperemic responses, which are likely modified in part by the removal of vasoconstrictor effects of autonomic neural activity elicited during the VM.

The aim of this study was to determine whether inhibition of nitric oxide synthase (NOS) alters dynamic cerebral autoregulation in humans. Beat-to-beat blood pressure (BP) and cerebral blood flow (CBF) velocity (transcranial Doppler) were measured in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). NOS was inhibited by intravenous NG-monomethyl-L-arginine (L-NMMA) infusion. Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. Pressor effects of L-NMMA on cerebral hemodynamics were compared with those of phenylephrine infusion. In the supine position, L-NMMA increased mean BP from 83+/-3 to 94+/-3 mmHg (P < 0.01). However, CBF velocity remained unchanged. Consequently, cerebrovascular resistance index (CVRI) increased by 15% (P < 0.05). BP and CBF velocity variability and transfer function gain at the low frequencies of 0.07-0.20 Hz did not change with L-NMMA infusion. Similar changes in mean BP, CBF velocity, and CVRI were observed after phenylephrine infusion, suggesting that increase in CVRI after L-NMMA was mediated myogenically by increase in arterial pressure rather than a direct effect of cerebrovascular NOS inhibition. During baseline tilt without L-NMMA, steady-state BP increased and CBF velocity decreased. BP and CBF velocity variability at low frequencies increased in parallel by 277% and 217%, respectively (P < 0.05). However, transfer function gain remained unchanged. During tilt with L-NMMA, changes in steady-state hemodynamics and BP and CBF velocity variability as well as transfer gain and phase were similar to those without L-NMMA. These data suggest that inhibition of tonic production of NO does not appear to alter dynamic cerebral autoregulation in humans.

To assess the effects of the tilt test on cerebral blood flow velocity (CBFV), blood pressure, and heart rate in patients with Parkinson's disease (PD) without symptomatic orthostatic dysautonomia. Thirty patients with idiopathic PD and 15 healthy controls were included. Mean middle cerebral artery blood flow velocity (CBFV) was recorded with transcranial Doppler sonography, while systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure and heart rate were measured in the supine position and after passive tilting. There was no difference in resting SBP, DBP, or MBP between patients and controls. CBFV was lower at rest in patients than in controls and dropped significantly and similarly after tilting in both groups. SBP decreased in patients during the first 5 minutes of tilting (p < 0.05), whereas it increased progressively after the first minute in controls. In patients, DBP decreased slightly and MBP dropped during the first 2 minutes, then increased. Baseline heart rate was higher in patients than in controls (p < 0.05) and increased in both groups during tilting. Our results suggest that cardiovascular responses to tilting are delayed in PD patients and that subclinical autonomic dysfunction may be present even in the absence of symptomatic orthostatic dysautonomia.

Acute fasting has been adopted in fitness communities, and has been practiced for religious purposes. Short‐term fasting does not affect cognitive function, and therefore may not affect cerebrovascular responsiveness. Cerebral blood flow velocity increases with mental stress, however the combined influences of an acute fast and mental stress on cerebrovascular responses are unknown. The purpose of this study was to describe the effects of a 24‐hour, water‐only fast on cerebral blood flow velocity responses to mental stress in a small cohort of research volunteers. Eight young healthy participants (7 males, average age of 25 yrs) completed the protocol in a fed state (4 hours post‐prandial) and in a fasted state (24–25 hours post‐prandial). Whole blood was collected and analyzed before experimentation for β‐Ketones, total cholesterol, HDL, LDL, triglycerides (TRG), and glucose. With participants in a supine position, we recorded the electrocardiogram, beat‐to‐beat arterial pressure (finger plethysmography), and cerebral artery blood flow velocity (transcranial Doppler). After a 5‐min baseline, participants performed 5‐min of mental stress via mental arithmetic (rapid continuous subtraction). Mental stress reactivity was calculated as the mean stress response for each minute of mental stress minus the corresponding 5‐min baseline. The minute‐by‐minute reactivity was analyzed with repeated measures ANOVA. Blood variables were analyzed with paired t‐tests. Data were expressed as mean ± SE. Baseline blood variables were different in the fasted compared with the fed state: TRG (112±14 fed vs. 68±13 mg/dL fasted; p&lt;.01) Glucose (101±5 fed vs. 79±6 mg/dL fasted; p&lt;.01) and β‐Ketone (.1±.01 fed vs. .5±.2 mmol/L fasted; p&lt;.05). Mean arterial pressures and heart rate reactivities to mental stress were not affected by fasting. Mean cerebral blood flow velocity reactivity to mental stress was reduced in the fasted compared with the fed condition (condition × time, p&lt;.01), with a particular divergent responsiveness during the third minute of mental stress. The results we present are new, but preliminary. We did not attempt to ascribe mechanisms to fasting and cerebral blood flow velocity reactivity during mental stress. The changes we observed with our preliminary data set suggest that fasting, and associated changes of plasma glucose, β‐Ketone and TRG may be associated with reductions of cerebral blood flow velocity during mental stress.Support or Funding InformationSupport was provided by the Michigan Space Grant Consortium and The Portage Health Foundation of Michigan.

Cerebral vasomotor reactivity (CVMR) reflects the ability of cerebral blood vessels to regulate cerebral blood flow (CBF) in response to changes in carbon dioxide (CO2). Transcranial Doppler (TCD) measurement of CBF velocity (CBFV) in the large cerebral arteries has been widely used to evaluate CVMR. However, assessment of CVMR in the cerebral microcirculation using near infrared spectroscopy (NIRS) has not been fully explored. The aims of this study are to characterize CVMR during hypo‐ and hypercapnia using NIRS, and to investigate the relationship between CVMRs assessed by NIRS and TCD. Thirty‐six healthy adults aged 21 to 45 (women: n=23) underwent CBFV and brain tissue oxygenation measurements using both NIRS and TCD during hyperventilation (hypocapnia) and modified CO2 rebreathing (hypercapnia). NIRS was placed on the forehead to measure brain tissue oxygenation index (TOI), TCD was used to measure CBFV in the middle cerebral artery, and capnography was used to measure end‐tidal CO2 (EtCO2). The percentage changes in TOI and CBFV relative to the baseline level in response to changes in EtCO2 were calculated to assess CVMR. Both TOI (−6±2 %) and CBFV (−41±10 %) were reduced during hypocapnia, and elevated during hypercapnia (TOI: 6±2 %, CBFV: 62±20 %) (Fig. 1). CVMR assessed by NIRS was significantly lower than that measured with TCD in both hypocapnia (0.33±0.16 vs. 2.21±0.43 %/mmHg, p&lt; 0.001) and hypercapnia (0.52±0.19 vs. 3.88±1.22 %/mmHg, p&lt; 0.001, Fig. 2). CVMRs assessed by NIRS and TCD were correlated in hypocapnia (r=0.40, p=0.02), but not in hypercapnia (r=0.10, p=0.55). These findings suggest that NIRS measurement of TOI in responses to changes in CO2 likely reflects CVMR of the cerebral microcirculation, which is in difference from that measured in the large cerebral arteries using TCDSupport or Funding InformationThe study was supported by National Institutes of Health (R01AG033106 and R01HL102457). JingShang was supported by the China Scholarship Council.The typical recordings of hyperventilation (hypocapnia) and the modified CO2 rebreathing (hypercapnia).Figure 1Average values of the relative change in CBFV and TOI in 4‐mmHg bins of ΔEtCO2 during hypercapnia induced by CO2 rebreathing. Error bars indicate standard deviation. ΔEtCO2 refers to change in EtCO2 from baseline.Figure 2

The objective of this study was to determine the age‐related differences in cerebral vasomotor reactivity (CVMR) to carbon dioxide. Methods: 92 healthy adults aged 23‐77 underwent measurements of cerebral blood flow velocity (CBFV) using transcranial Doppler, mean arterial pressure, and end‐tidal CO2 (EtCO2) during baseline, hyperventilation (HVT), and modified rebreathing (RB). CVMR was determined by the maximal gain between changes in normalized CBFV (CBFV%) and EtCO2 using a 3rd order polynomial model and its derivative. Results: Lower CBFV and EtCO2 were related to increasing age at baseline. HVT decreased EtCO2 by 21±4 mmHg while RB increased by 19±3 mmHg. Increasing age was related to smaller hypocapnic but larger hypercapnic changes in CBFV% at the end of HVT and RB, respectively. The maximal gain between CBFV% and EtCO2 did not differ by age. Advanced age was associated with greater differences in EtCO2 between the baseline and the level at which the maximum gain in CBFV% occurred. Conclusions: These findings suggest that age‐related reductions in baseline CBFV and EtCO2 may lead to a decrease in hypocapnic but an increase in hypercapnic CBFV response. The larger differences in EtCO2 between baseline and the maximal gain of CBFV% with aging may lead to blunted response of CBF to given changes in arterial CO2 at levels close to baseline.Grant Funding Source: Supported by National Institute on Aging

Biomarkers of Disease Severity Predict Neurocognitive Functioning in Pediatric SCD

In community-acquired bacterial meningitis (CABM) intracranial vascular alterations are devastating complications which are triggered by neuroinflammation and result in worse clinical outcome. The Neutrophil-to-Lymphocyte ratio (NLR) represents a reliable parameter of the inflammatory response. In this study we analyzed the association between NLR and elevated cerebral blood flow velocity (CBFv) in CABM-patients. This study included all (CABM)-patients admitted to a German tertiary center between 2006 and 2016. Patients’ demographics, in-hospital measures, neuroradiological data and clinical outcome were retrieved from institutional databases. CBFv was assessed by transcranial doppler (TCD). Patients’, radiological and laboratory characteristics were compared between patients with/without elevated CBFv. Multivariate-analysis investigated parameters independently associated with elevated CBFv. Receiver operating characteristic(ROC-)curve analysis was undertaken to identify the best cut-off for NLR to discriminate between increased CBFv. 108 patients with CABM were identified. 27.8% (30/108) showed elevated CBFv. Patients with elevated CBFv and normal CBFv, respectively had a worse clinical status on admission (Glasgow Coma Scale: 12 [9–14] vs. 14 [11–15]; p = 0.005) and required more often intensive care (30/30 [100.0%] vs. 63/78 [80.8%]; p = 0.01).The causative pathogen was S. pneumoniae in 70%. Patients with elevated CBFv developed more often cerebrovascular complications with delayed cerebral ischemia (DCI) within hospital stay (p = 0.031). A significantly higher admission-NLR was observed in patients with elevated CBFv (median [IQR]: elevated CBFv:24.0 [20.4–30.2] vs. normal CBFv:13.5 [8.4–19.5]; p < 0.001). Multivariate analysis, revealed NLR to be significantly associated with increased CBFv (Odds ratio [95%CI] 1.042 [1.003–1.084]; p = 0.036). ROC-analysis identified a NLR of 20.9 as best cut-off value to discriminate between elevated CBFv (AUC = 0.713, p < 0.0001, Youden's Index = 0.441;elevated CBFv: NLR ≥ 20.9 19/30[63.5%] vs. normal CBFv: NLR > 20.9 15/78[19.2%]; p < 0.001). Intracranial vascular complications are common among CABM-patients and are a risk factor for unfavorable outcome at discharge. Elevated NLR is independently associated with high CBFv and may be useful in predicting patients’ prognosis.

Effect of diclofenac on cerebral blood flow velocity in patients with supratentorial tumours

Patients with aneurysmal subarachnoid haemorrhage (SAH) might have impaired cerebral autoregulation, that is, CBF - and thereby oxygen delivery - passively increase with an increase in CPP. This physiological study aimed to investigate the cerebral haemodynamic effects of controlled blood pressure increase in the early phase after SAH before any signs of delayed cerebral ischaemia (DCI) occurred. The study was carried out within 5 days after ictus. Data were recorded at baseline and after 20 min of noradrenaline infusion to increase mean arterial blood pressure (MAP) by a maximum of 30 mmHg and to an absolute level of no more than 130 mmHg. The primary outcome was the difference in middle cerebral artery blood flow velocity (MCAv) measured by transcranial Doppler (TCD), while differences in intracranial pressure (ICP), brain tissue oxygen tension (PbtO2 ), and microdialysis markers of cerebral oxidative metabolism and cell injury were assessed as exploratory outcomes. Data were analysed using Wilcoxon signed-rank test with correction for multiplicity for the exploratory outcomes using the Benjamini-Hochberg correction. Thirty-six participants underwent the intervention 4 (median, IQR: 3-4.75) days after ictus. MAP was increased from 82 (IQR: 76-85) to 95 (IQR: 88-98) mmHg (p-value: <.001). MCAv remained stable (baseline, median 57, IQR: 46-70 cm/s; controlled blood pressure increase, median: 55, IQR: 48-71 cm/s; p-value: .054), whereas PbtO2 increased significantly (baseline, median: 24, 95%CI: 19-31 mmHg; controlled blood pressure increase, median: 27, 95%CI: 24-33 mmHg; p-value <.001). The remaining exploratory outcomes were unchanged. In this study of patients with SAH, MCAv was not significantly affected by a brief course of controlled blood pressure increase; despite this, PbtO2 increased. This suggests that autoregulation might not be impaired in these patients or other mechanisms could mediate the increase in brain oxygenation. Alternatively, a CBF increase did occur that, in turn, increased cerebral oxygenation, but was not detected by TCD. clinicaltrials.gov (NCT03987139; 14 June 2019).

Cerebral vasospasm (CV) is a delayed, sustained contraction of the cerebral arteries that tends to occur 3-14 days after aneurysmal subarachnoid hemorrhage (aSAH) from a ruptured aneurysm. Vasospasm potentially leads to delayed cerebral ischemia, and despite medical treatment, 1 of 3 patients suffer a persistent neurological deficit. Bedside transcranial Doppler (TCD) ultrasonography is used to indirectly detect CV through recognition of an increase in cerebral blood flow velocity (CBFV). The present study aimed to use TCD ultrasonography to monitor how CBFV changes on both the ipsi- and contralateral sides of the brain in the first 24 hours after patients have received a stellate ganglion block (SGB) to treat CV that persists despite maximum standard therapy. The data were culled from records of patients treated between 2013 and 2017. Patients were included if an SGB was administered following aSAH, whose CBFV was ≥ 120 cm/sec and who had either a focal neurological deficit or reduced consciousness despite having received medical treatment and blood pressure management. The SGB was performed on the side where the highest CBFV had been recorded with 8-10 ml ropivacaine 0.2%. The patient's CBFV was reassessed after 2 and 24 hours. Thirty-seven patients (male/female ratio 18:19), age 17-70 years (mean age 49.9 ± 11.1), who harbored 13 clipped and 22 coiled aneurysms (1 patient received both a coil and a clip, and 3 patients had 3 untreated aneurysms) had at least one SGB. Patients received up to 4 SGBs, and thus the study comprised a total of 76 SGBs.After the first SGB, CBFV decreased in 80.5% of patients after 2 hours, from a mean of 160.3 ± 28.2 cm/sec to 127.5 ± 34.3 cm/sec (p < 0.001), and it further decreased in 63.4% after 24 hours to 137.2 ± 38.2 cm/sec (p = 0.007). A similar significant effect was found for the subsequent SGB. Adding clonidine showed no significant effect on either the onset or the duration of the SGB. Contralateral middle cerebral artery (MCA) blood flow was not reduced by the SGB. To the authors' knowledge, this is the largest study on the effects of administering an SGB to aSAH patients after aneurysm rupture. The data showed a significant reduction in ipsilateral CBFV (MCA 20.5%) after SGB, lasting in about two-thirds of cases for over 24 hours with no major complications resulting from the SGB.

Comparison of transcranial Doppler flow velocity and cerebral blood flow during focal ischemia in rabbits

Prone positioning (PP) is necessary for surgical access during posterior spine procedure. However, physiological changes occur in the PP. Typical findings are a decrease in arterial blood pressure and in cardiac output that could potentially lead to an alteration in cerebral perfusion. Therefore, we decided to study cerebral blood flow velocity (CBFV) with transcranial Doppler ultrasonography to evaluate the effect of the PP on cerebral hemodynamics. Twenty-two patients undergoing spine surgery in the PP were studied. General anesthesia was induced using 250 μg of fentanyl, 2 mg/kg of propofol, and 0.1 mg/kg of vecuronium, and was maintained with 0.25%-0.5% isoflurane, 50% nitrous oxide in oxygen, continuous infusion of 100 μg/kg/min of propofol, 1.5 μg/kg/h of fentanyl, and 0.15 mg/kg/h of ketamine. Continuous invasive arterial blood pressure, heart rate, electrocardiogram, and end-tidal carbon dioxide were monitored. CBFV with transcranial Doppler in the middle cerebral artery was first measured with the patients under general anesthesia in the supine position. Patients were then placed in the PP and remained in this position throughout surgery. CBFV, end-tidal carbon dioxide, heart rate, and blood pressure were measured continuously for 75 minutes after initiation of PP. This coincided with surgical exposure and minimal blood loss. Data were analyzed every 15 minutes for statistical significant change over time. Mean arterial blood pressure decreased 15 minutes after the installation of the PP and onward, but this decrease was not statistically significant. CBFVsyst (the maximal CBFV during the systolic phase of a cardiac cycle) and CBFVmean (the time averaged value of the maximal velocity envelope over 1 cardiac cycle) did not vary at any time points. CBFVdiast (the CBFV just before the acceleration phase [systole] of the next waveform) was lower at T3 (30 minutes after PP) compared to T1 (value derived averaging the first measure in the PP with the ones at 5 and 10 minutes) (P = .01), and the pulsatility index was higher at T5 (60 minutes after PP) compared to T0 (baseline, patient supine under general anesthesia) (P = .04). Data were analyzed at specific time points (T0 and T1). This value was derived by computing an average of the CBFV values collected at the first measure in the PP and at 5 and 10 minutes thereafter: T2, 15 minutes after PP; T3, 30 minutes after PP; T4, 45 minutes after PP; T5, 60 minutes after PP; and T6, 75 minutes after PP. Our data on CBFV during PP for spine surgery demonstrate preservation of cerebral perfusion during stable systemic hemodynamic conditions. The present results do not allow us to determine whether the PP would be similarly tolerated with increasing length of surgery, variations in systemic hemodynamics, and in different patient populations.