Karsten Skovgaard Olsen

Transcranial Doppler is valid for determination of the lower limit of cerebral blood flow autoregulation.

This study validates transcranial Doppler sonography (TCD) for determination of the lower limit of cerebral blood flow (CBF) autoregulation and establishes a relation between global CBF and mean flow velocity (Vmean) in the middle cerebral artery. Methods Relative changes in CBF and in Vmean were compared in 12 normal volunteers (2 women and 10 men; median age, 30 years [range, 21 to 61 years]). Catheters was placed in the left radial artery and in the bulb of the right internal jugular vein, respectively. Baseline CBF was measured by single-photon emission computed tomography scanning; concomitantly, blood samples were drawn for calculation of the cerebral arteriovenous oxygen difference. Then changes in mean arterial pressure (MAP) were induced, and relative changes in global CBF were calculated according to Ficks principle assuming a constant cerebral oxygen metabolism. MAP was increased 30 mm Hg by norepinephrine infusion and was decreased by lower body negative pressure. Vmean was measured in the right middle cerebral artery by a 2-MHz probe, and blood samples were drawn at intervals of 5 mm Hg. Results MAP values between 122 (range, 110 to 140) and 48 (range, 34 to 75) mm Hg were measured. The lower limit of autoregulation (the blood pressure under which autoregulation is off) as determined by Vmean did not differ significantly from that determined by relative changes in global CBF: 91 (range, 41 to 108) and 79 (range, 53 to 113) mm Hg, respectively. A significant correlation between Vmean and relative changes in global CBF was demonstrated below the lower limit of autoregulation (R2=.73, P<.001; CBF=−6.3+1.0· Vmean). Above the lower lim1it both values were stable. Conclusions TCD is valid for determination of the lower limit of CBF autoregulation, and changes in CBF may be reliably evaluated by TCD during changes in cerebral perfusion pressure in normal subjects.

Persistent Resetting of the Cerebral Oxygen/Glucose Uptake Ratio by Brain Activation: Evidence Obtained with the Kety—Schmidt Technique:

Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety–Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation showed that the activation-induced resetting of the relation between CMRglc and CMRO2 persisted virtually unaltered for ≥40 min after the mental activation task was terminated. The activation-induced increase in cerebral lactate efflux measured over the same time period accounted for only a small fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic stress indicators returned to baseline values. Activation-induced resetting of the cerebral oxygen/glucose uptake ratio is not necessarily accounted for by increased lactate production from nonoxidative glucose metabolism.

Intracranial pressure and cerebral hemodynamic in patients with cerebral tumors: a randomized prospective study of patients subjected to craniotomy in propofol-fentanyl, isoflurane-fentanyl, or sevoflurane-fentanyl anesthesia.

Background A critical point during craniotomy is opening of dura, where a high intracranial pressure (ICP) results in swelling of cerebral tissue. Controlled studies concerning ICP, degree of dural tension, and degree of cerebral swelling are therefore warranted. Methods In an open-label study, 117 patients with supratentorial cerebral tumors were randomized to propofol-fentanyl (group 1), isoflurane-fentanyl (group 2), or sevoflurane-fentanyl anesthesia (group 3). Normo- to moderate hypocapnia was applied, with a target level of arterial carbon dioxid tension of 30–40 mmHg. Mean arterial blood pressure was stabilized with intravenous ephedrine (2.5–5 mg) if necessary. Subdural ICP, mean arterial blood pressure, cerebral perfusion pressure (CPP), arteriovenous oxygen difference (AVDo2), internal jugular vein oxygen saturation were monitored before and after a 10-min period of hyperventilation, and the carbon dioxide reactivity was calculated. Furthermore, the tension of dura before and during hyperventilation and the degree of cerebral swelling during hyperventilation and after opening of the dura were estimated by the neurosurgeon. Results No differences were found between groups with regard to demographics, neuroradiologic examination, positioning of the head, and time to ICP measurement. Before and during hyperventilation, ICP was significantly lower and mean arterial blood pressure and CPP significantly higher in group 1 compared with groups 2 and 3 (P < 0.05). The tension of dura before and during hyperventilation was significantly lower in group 1 compared with group2 (P < 0.05), but not significantly different from group 3. In group 1, cerebral swelling after opening of dura was significantly lower compared with groups 2 and 3 (P < 0.05). Furthermore, AVDo2 was significantly higher and jugular vein oxygen saturation and carbon dioxide reactivity were significantly lower in group 1 compared with groups 2 and 3 (P < 0.05). No significant differences with regard to ICP, CPP, AVDo2, carbon dioxide reactivity, and jugular vein oxygen saturation were found between patients anesthetized with isoflurane and sevoflurane. Conclusions The study indicates that before as well as during hyperventilation, subdural ICP and AVDo2 are lower and CPP higher in propofol-anesthetized patients compared with patients anesthetized with isoflurane or sevoflurane. These findings were associated with less tendency for cerebral swelling after opening of dura in the propofol group. The carbon dioxide reactivity in patients anesthetized with isoflurane and sevoflurane was significantly higher than in the propofol group. The differences in subdural ICP between the groups are presumed to be caused by differences in the degree of vasoconstriction elicited by the anesthetic agents, but autoregulatory mechanisms caused by differences in CPP cannot be excluded.

Validation of transcranial near-infrared spectroscopy for evaluation of cerebral blood flow autoregulation.

The aim of the study was to evaluate a new noninvasive transcranial near-infrared spectroscopy (TNIRS) technique for determination of the lower limit of cerebral blood flow (CBF) autoregulation by comparing this technique with the standard cerebral arteriovenous oxygen saturation difference (AVDo2) method. In eight healthy volunteers, mean arterial blood pressure was increased by infusion of angiotensin and decreased by the combination of lower-body negative pressure and labetalol. For each 5-mm Hg change in mean arterial pressure, blood was sampled from the bulb of the internal jugular vein and a radial artery, and simultaneously, the oxygen saturation of hemoglobin in the brain was measured with an INVOS 3100 Cerebral Oximeter (Somanetics). The lower limit of autoregulation was then calculated by a computer using (a) AVDo2 and (b) the difference between arterial oxygen saturation and the saturation determined with the cerebral oximeter (ACDo2). The median lower limit of autoregulation determined by the two methods was 73 and 78.5 mm Hg, respectively (p > 0.05). A statistically significant correlation between relative CBF (percentage of baseline) determined with the two methods was found below the lower limit of autoregulation (1/AVDo2 = 12 + 0.8 x 1/ACDo2; r = 0.55; p < 0.001). For all the 98 pairs of saturations registered, the correlation was 0.37 (p < 0.001), the mean difference was 16%, and the limits of agreement were -2.2 and 33.8%. We conclude that the cerebral oximeter might be useful in evaluation of the lower limit of cerebral autoregulation. This method, however, is of no value for estimation of levels of global cerebral oxygen saturation.

Migraine induced by hypoxia: an MRI spectroscopy and angiography study

Migraine with aura is prevalent in high-altitude populations suggesting an association between migraine aura and hypoxia. We investigated whether experimental hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura. We also investigated the metabolic and vascular response to hypoxia. In a randomized double-blind crossover study design, 15 migraine with aura patients were exposed to 180 min of normobaric hypoxia (capillary oxygen saturation 70-75%) or sham on two separate days and 14 healthy controls were exposed to hypoxia. Glutamate and lactate concentrations in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P < 0.05). We found no difference in the metabolic or vascular responses to hypoxia between migraine patients and controls. In conclusion, hypoxia induced migraine-like attacks with and without aura and dilated the cranial arteries in patients with migraine with aura. Hypoxia-induced attacks were not associated with altered concentration of glutamate or other metabolites. The present study suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated.

Vasoactive modulators during and after craniotomy: relation to postoperative hypertension.

Hypertension after craniotomy is frequent. To establish an association between vasoactive modulators and postoperative hypertension, we followed the arterial blood pressure and plasma concentrations of selected substances in patients undergoing craniotomy. Twelve consecutive patients scheduled for operation of a supratentorial brain tumor were anesthetized with thiopental, fentanyl, isoflurane, and pancuronium. None of the patients had a history of arterial hypertension or were hypertensive before the operation. Arterial blood pressure and heart rate measurements were obtained preoperatively, after incision, during closure, and four times in the 50-minute interval after stopping isoflurane. At the same time, plasma concentrations of norepinephrine, epinephrine, renin, aldosterone, atrial natriuretic peptide, endothelin, and cortisol were measured. Data are given as mean ± SD (range). The postoperative concentrations of these substances were significantly higher than the baseline concentrations measured preoperatively. Six of the patients developed postoperative hypertension defined as a mean arterial pressure (MAP) > 20% more than the baseline MAP (group H), and six had normal blood pressure postoperatively (group N). The mean value of the maximal postoperative MAPs measured in groups H and N, respectively, was 118 ± 16 mm Hg (range: 96–132) and 103 ± 9 mm Hg (range: 92–115) (P = .01). Only renin levels were higher intraoperatively in group H when compared to group N. However, postoperative levels of catecholamines, aldosterone, renin, and endothelin levels were higher in group H patients. The results suggest that in addition to an increased discharge of the sympathetic system, activation of the renin-angiotensin aldosterone system may also play an important role in the development of postoperative hypertension after craniotomy.

Self-positioning followed by induction of anaesthesia and insertion of a laryngeal mask airway versus endotracheal intubation and subsequent positioning for spinal surgery in the prone position: a randomised clinical trial.

BACKGROUND Anaesthesia followed by positioning in the prone position takes time and may have complications. OBJECTIVE The hypothesis was that self-positioning in the prone position followed by anaesthesia and introduction of a laryngeal mask airway (LM method) would be faster with fewer complications than positioning after tracheal intubation (ET method). DESIGN Randomised, controlled trial. SETTING University Hospital, March 2009 to March 2011. PATIENTS One hundred forty patients scheduled for spinal surgery were allocated to the LM or the ET method. Exclusion criteria were surgery expected to last more than 2u200ah, American Society of Anesthesiologists status more than II, age more than 70 years, abnormal neck, throat, and mouth anatomy and function, Mallampati score III–IV, BMI more than 35u200akgu200am−2, anticipated difficult airway/mask ventilation and decreased neck mobility. INTERVENTIONS Patients in the LM group placed themselves in the prone position, anaesthesia was induced and a laryngeal mask was introduced. Patients in the ET group were anaesthetised, intubated and then placed in the prone position. MAIN OUTCOME MEASURES Time taken from identification of the patient at the outset to readiness for radiographic examination following anaesthesia and positioning. Airway problems, sore throat, hoarseness and pain from muscles and joints were also noted. RESULTS One hundred and forty patients were randomised to LM (nu200a=u200a70) and ET (nu200a=u200a70). Data from 64 and 67 patients were analysed. Values are expressed as median (interquartiles) [range]. The primary outcome time was 25u200amin (23 to 29) [16 to 44] in the LM group and 30u200amin (26 to 33) [17 to 47] in the ET group (Pu200a<0.001). In two patients in group LM, a complete seal could not be obtained; one was intubated, and the other had surgery cancelled due to arterial hypotension. There were fewer cases with sore throat, hoarseness and pain from muscles and joints in the LM group at 3u200ah, but not at 24u200ah postoperatively. CONCLUSION Self-positioning and induction of anaesthesia in the prone position saves time. More patients should be studied to confirm safety and examine whether the method reduces the number of severe complications associated with the prone position. TRIAL REGISTRATION www.clinicaltrials.gov identifier: NCT01041352

Evaluation of a 7.5 French pulmonary catheter for continuous monitoring of cerebral venous oxygen saturation.

We studied a 7.5 French Opticat fiberoptic catheter/Oximetrix computer system as a tool for continuous monitoring of oxygen saturation of jugular venous blood. Eight healthy volunteers had a catheter placed with the tip in the bulb of the right internal jugular vein. During baseline condition, hyperventilation, and rebreathing, jugular venous oxygen saturations ranging from 35 to 85% were obtained. Simultaneous with drawing a blood sample, the value obtained with the fiberoptic catheter was recorded. The oxygen saturation of the blood sample was analyzed in vitro using a bench oximeter. A total of 150 paired values was obtained. In 15 of these cases, the computer indicated that the intensity of the reflected light was insufficient. A difference of > 12% oxygen saturation between the paired values was obtained for all of these pairs. The regression coefficient for the remaining 135 data pairs was 0.95, the mean difference was -0.54%, and the limits of agreement were -9.5 to 8.4%. We conclude that the 7.5 French Opticat catheter is useful if values obtained during improper light intensity are excluded.

Effect of ketanserin on cerebral blood flow autoregulation in healthy volunteers.

SummaryThe effect of a clinically relevant dose of ketanserin (10 mg as a bolus followed by an infusion of 6mg/h) on cerebral blood flow (CBF) and CBF autoregulation was examined in 12 healthy volunteers. Changes in CBF were estimated by the cerebral arteriovenous-oxygen saturation difference method, while mean arterial blood pressure (MABP) was increased by norepinephrine and decreased by ganglionic blockade (trimethaphan camphosulphonate) combined with lower body negative pressure one hour after the infusion of ketanserin. During ketanserin infusion, MABP fell insignificantly by 2.5 mmHg (6 to −2), while CBF rose insignificantly by 5 ml/100 g/min. Autoregulation was preserved in all volunteers. CO2-correction factors from 0 to 4.6% CBF/0.1 kPa were used. The lower limit of CBF autoregulation was 82 mmHg (80–86) with an SE of 3 mmHg (1–5) similar to a previous control group of healthy volunteers. Aside from a major decrease in MABP in one subject, no adverse side effects were observed.The present study shows that CBF autoregulation is maintained during ketanserin infusion.

Sumatriptan does not change calcitonin gene-related peptide in the cephalic and extracephalic circulation in healthy volunteers

Triptans are effective and well tolerated in acute migraine management but their exact mechanism of action is still debated. Triptans might exert their antimigraine effect by reducing the levels of circulating calcitonin gene-related peptide (CGRP). To examine this question, we examined whether sumatriptan modulate the baseline CGRP levels in vivo, under conditions without trigeminovascular system activation. We sampled blood from the internal and external jugular, the cubital veins, and the radial artery before and after administration of subcutaneous sumatriptan in 16 healthy volunteers. Repeated-measure ANOVA showed no interaction between catheter and time of sampling and thus no significant difference in CGRP between the four catheters (Pxa0=xa00.75). CGRP did not change over time in the four compartments (Pxa0>xa00.05). The relative changes in CGRP between baseline and maximal sumatriptan concentration did not differ between the four vascular compartments (Pxa0=xa00.49). It was found that Sumatriptan did not change the levels of circulating CGRP in the intra or extracerebral circulation in healthy volunteers. This speaks against a direct CGRP-reducing effect of sumatriptan in vivo in humans when the trigemino vascular system is not activated.