The effects of propofol with and without ketamine on human cerebral blood flow velocity and CO(2) response

The combination of propofol and ketamine has been used for total IV anesthesia. This study was designed to clarify the effects of propofol-ketamine anesthesia on cerebral circulation by using transcranial Doppler ultrasonography. In Study 1, we examined the time course of time-mean middle cerebral artery blood flow velocity (Vmca) after ketamine (n = 10) or saline (n = 6) administration during propofol anesthesia. In Study 2, CO(2) responses were measured under the following conditions: awake (Group C, n = 7), propofol anesthesia (Group D, n = 7), and propofol-ketamine anesthesia (Group E, n = 8). Ketamine administration during propofol anesthesia administration did not affect Vmca, mean arterial pressure, or heart rate. Vmca under normocapnia in Groups D and E were 36 +/- 3 and 37 +/- 3 cm/s (mean +/- SE), respectively. The values were significantly lower than that of Group C (70 +/- 3 cm/s). The CO(2) response slopes of Groups D and E were significantly lower than that of Group C, although there was no significant difference between Groups D and E. These results suggest that ketamine does not influence Vmca or the cerebrovascular CO(2) response during propofol anesthesia administration, although the sample size in each group was small. IMPLICATIONS: Our study suggests that ketamine does not influence middle cerebral artery blood flow velocity or the cerebrovascular CO(2) response assessed by transcranial Doppler ultrasonography during propofol anesthesia administration in patients without neurological complications.     

The effects of propofol or sevoflurane on the estimated cerebral perfusion pressure and zero flow pressure

The zero flow pressure (ZFP) is the pressure at which blood flow ceases through a vascular bed. Using transcranial Doppler ultrasonography, we investigated the effects of propofol or sevoflurane on the estimated cerebral perfusion pressure (eCPP) and ZFP in the cerebral circulation. Twenty-three healthy patients undergoing nonneurosurgical procedures under general anesthesia were studied. After induction of anesthesia using propofol, the anesthesia was maintained with either propofol infusion (n = 13) or sevoflurane (n = 10). Middle cerebral artery flow velocity, noninvasive arterial blood pressure, and end-tidal carbon dioxide partial pressure were recorded awake as a baseline, and during steady-state anesthesia at normocapnia (baseline end-tidal carbon dioxide partial pressure) and hypocapnia (1 kPa below baseline). The eCPP and ZFP were calculated using an established formula. The mean arterial blood pressure decreased in both groups. The eCPP decreased significantly in the propofol group (median, from 58 to 41 mm Hg) but not in the sevoflurane group (from 60 to 62 mm Hg). Correspondingly, ZFP increased significantly in the propofol group (from 25 to 33 mm Hg) and it decreased significantly in the sevoflurane group (from 27 to 7 mm Hg). Hypocapnia did not change eCPP or ZFP in the propofol group, but it significantly decreased eCPP and increased ZFP in the sevoflurane group.     

Effect of propofol on cerebral circulation and autoregulation in the baboon

The purpose of this study was to investigate the effect of propofol on cerebral blood flow, cerebral metabolism, and cerebrovascular autoregulatory capability. Seven anesthetized baboons were given propofol at three different infusion rates. An infusion of 3 mg.kg-1.h-1 caused minimal changes, but infusion rates of 6 and 12 mg.kg-1.h-1 decreased cerebral blood flow by 28% and 39%, respectively. The changes in cerebral metabolic rate of oxygen were not statistically significant. However, with the two higher infusion rates, there was a trend toward decrease, by 5% and 22%, respectively, for the cerebral metabolic rate of oxygen, and by 18% and 36% for the cerebral metabolic rate of glucose. A 25-30 mm Hg increase in arterial blood pressure had no influence on cerebral blood flow. Replacement of nitrous oxide by nitrogen had no significant influence on cerebral blood flow or metabolism. It is concluded that propofol causes a dose-dependent decrease in cerebral blood flow. However, the study does not prove that this decrease in cerebral blood flow is accompanied by the same degree of decrease in cerebral metabolism. Further studies are clearly needed to clarify propofol's influence on the coupling between cerebral metabolism and blood flow. The physiologic responsiveness of the cerebral circulation to alterations in arterial pressure is well preserved. Propofol appears to prevent the metabolic stimulation and increased cerebral blood flow that has been associated with the administration of nitrous oxide.     

Partial preservation of cerebral vascular responsiveness to hypocapnia during isoflurane-induced hypotension in dogs

This study was undertaken to determine whether the cerebral vascular response to hypocapnia is preserved during isoflurane-induced hypotension. In six dogs (group 1) cerebral vascular resistance and cerebral blood flow were determined at normocapnia (PaCO2 40 mm Hg) and at hypocapnia (PaCO2 20 mm Hg) while mean arterial pressure was normal, and then again during isoflurane-induced hypotension to a mean arterial pressure of 50 mm Hg. Hypocapnia increased cerebral vascular resistance and decreased cerebral blood flow during both normotension and isoflurane-induced hypotension. However, the magnitude of these responses was greater when mean arterial pressure was normal. In another six dogs (group 2), CO2 responsiveness was examined during isoflurane-induced hypotension without prior determination of CO2 responsiveness at normal mean arterial pressure and during sodium nitroprusside-induced hypotension to a mean arterial pressure of 50 mm Hg. As in group 1, partial preservation of CO2 responsiveness was observed during isoflurane-induced hypotension; the magnitude of the response in group 2 during isoflurane-induced hypotension was similar to that in group 1. In contrast, in group 2 during sodium nitroprusside-induced hypotension, hypocapnia caused no significant change of cerebral vascular resistance or cerebral blood flow. It is concluded that cerebral vessels respond to changes in PaCO2 differently during isoflurane-induced hypotension than during hypotension with other commonly used hypotensive treatments. Hypocapnia decreases cerebral blood flow during isoflurane-induced hypotension and, therefore, may also decrease cerebral blood volume, brain bulk, and intracranial pressure.     

A randomized crossover comparison of the effects of propofol and sevoflurane on cerebral hemodynamics during carotid endarterectomy

BACKGROUND: Intravenous and inhalational anesthetic agents have differing effects on cerebral hemodynamics: Sevoflurane causes some vasodilation, whereas propofol does not. The authors hypothesized that these differences affect internal carotid artery pressure (ICAP) and the apparent zero flow pressure (critical closing pressure) during carotid endarterectomy. Vasodilation is expected to increase blood flow, reduce ICAP, and reduce apparent zero flow pressure. METHODS: In a randomized crossover study, the gradient between systemic arterial pressure and ICAP during carotid clamping was measured while changing between sevoflurane and propofol in 32 patients. Middle cerebral artery blood velocity, recorded by transcranial Doppler, and ICAP waveforms were analyzed to determine the apparent zero flow pressure. RESULTS: ICAP increased when changing from sevoflurane to propofol, causing the mean gradient between arterial pressure and ICAP to decrease by 10 mmHg (95% confidence interval, 6-14 mmHg; P<0.0001). Changing from propofol to sevoflurane had the opposite effect: The pressure gradient increased by 5 mmHg (95% confidence interval, 2-7 mmHg; P=0.002). Ipsilateral middle cerebral artery blood velocity decreased when changing from sevoflurane to propofol. Cerebral steal was detected in one patient after changing from propofol to sevoflurane. The apparent zero flow pressure (mean+/-SD) was 22+/-10 mmHg with sevoflurane and 30+/-14 mmHg with propofol (P<0.01). There was incomplete drug crossover due to the limited duration of carotid clamping. CONCLUSIONS: Compared with sevoflurane, ipsilateral ICAP and apparent zero flow pressure are both higher with propofol. Vasodilatation associated with sevoflurane can cause cerebral steal.     

Cerebrovascular tone rather than intracranial pressure determines the effective downstream pressure of the cerebral circulation in the absence of intracranial hypertension

Cerebral perfusion pressure is commonly calculated from the difference between mean arterial pressure and intracranial pressure because intracranial pressure is known to represent the effective downstream pressure of the cerebral circulation. Studies of other organs, however, have shown that effective downstream pressure is determined by a critical closing pressure located at the arteriolar level. This study was designed to investigate the effects of PCO2-induced variations in cerebrovascular tone on the effective downstream pressure of the cerebral circulation. Sixteen patients recovering from head injury were studied. Intracranial pressure was assessed by epidural pressure transducers. Blood flow velocity in the middle cerebral artery was monitored by transcranial Doppler sonography. Effective downstream pressure was derived from the zero flow pressure as extrapolated by regression analysis of instantaneous arterial pressure/middle cerebral artery flow velocity relationships. PaCO2 was varied between 30 and 47 mm Hg in randomized sequence. Intracranial pressure decreased from 18.5+/-5.2 mm Hg during hypercapnia to 9.9+/-3.1 mm Hg during hypocapnia. In contrast, effective downstream pressure increased from 13.7+/-9.6 mm Hg to 23.4+/-8.6 mm Hg and exceeded intracranial pressure at hypocapnic PaCO2 levels. Our results demonstrate that, in the absence of intracranial hypertension, intracranial pressure does not necessarily represent the effective downstream pressure of the cerebral circulation. Instead, the tone of cerebral resistance vessels seems to determine effective downstream pressure. This suggests a modified model of the cerebral circulation based on the existence of two Starling resistors in a series connection.     

A clinical study of cerebral circulation during extracorporeal circulation

The objective of this study is to clarify the relationship of cerebral blood flow to extracorporeal circulation flow and mean arterial pressure during nonpulsatile extracorporeal circulation under moderate hypothermia. Cerebral blood flow was determined by an argon saturation and desaturation method after that of Pevsner and colleagues with a mass spectrometer in 21 adult patients undergoing cardiac operations. Cerebral blood flow was 25, 33, 35, and 42 ml/100 gm/min, ranging from 19 to 50 ml/100 gm/min, at extracorporeal circulation flow rates of 40, 50, 60, and 70 ml/kg/min, respectively. Cerebral blood flow increased proportionally to extracorporeal circulation flow. Cerebral blood flow scattered almost transversely to mean arterial pressure and was 31 ml/100 gm/min in a hypotensive group (mean arterial pressure 34 to 50 mm Hg) and 34 ml/100 gm/min in another group (mean arterial pressure 51 to 94 mm Hg). Mean arterial pressure did not significantly influence cerebral blood flow. Cerebral oxygen consumption did not remarkably decrease and remained in the reasonable range when cerebral blood flow was 23 to 40 ml/100 gm/min. Subsequently, we assumed that the average cerebral blood flow value of 25 ml/100 gm/min at an extracorporeal circulation flow rate of 40 ml/kg/min also would be in the safe range. All of the patients are living without cerebral complications. We conclude that (1) cerebral blood flow was extracorporeal circulation flow dependent and (2) cerebral blood flow in the safe range was maintained even in the hypotensive range, provided the extracorporeal circulation flow rate was 40 ml/kg/min or higher.     

A Randomized Crossover Comparison of the Effects of Propofol and Sevoflurane on Cerebral Hemodynamics during Carotid Endarterectomy

Background: Intravenous and inhalational anesthetic agents have differing effects on cerebral hemodynamics: Sevoflurane causes some vasodilation, whereas propofol does not. The authors hypothesized that these differences affect internal carotid artery pressure (ICAP) and the apparent zero flow pressure (critical closing pressure) during carotid endarterectomy. Vasodilation is expected to increase blood flow, reduce ICAP, and reduce apparent zero flow pressure.

Methods: In a randomized crossover study, the gradient between systemic arterial pressure and ICAP during carotid clamping was measured while changing between sevoflurane and propofol in 32 patients. Middle cerebral artery blood velocity, recorded by transcranial Doppler, and ICAP waveforms were analyzed to determine the apparent zero flow pressure.

Results: ICAP increased when changing from sevoflurane to propofol, causing the mean gradient between arterial pressure and ICAP to decrease by 10 mmHg (95% confidence interval, 6-14 mmHg; P < 0.0001). Changing from propofol to sevoflurane had the opposite effect: The pressure gradient increased by 5 mmHg (95% confidence interval, 2-7 mmHg; P = 0.002). Ipsilateral middle cerebral artery blood velocity decreased when changing from sevoflurane to propofol. Cerebral steal was detected in one patient after changing from propofol to sevoflurane. The apparent zero flow pressure (mean +/- SD) was 22 +/- 10 mmHg with sevoflurane and 30 +/- 14 mmHg with propofol (P < 0.01). There was incomplete drug crossover due to the limited duration of carotid clamping.     

Propofol in single bolus for treatment of elevated intracranial hypertension]

Eleven patients with intracranial pressure (ICP) above 20 mmHg despite hyperventilation and neurosedation were treated with a bolus of propofol (1.5 mg/kg) i.v. At baseline and 1-2-5-10-15-30-45 minutes after propofol administration we recorded the values of PIC, systolic arterial pressure (SAP) and mean arterial pressure (MAP), heart rate (HR) and cerebral perfusion pressure (CPP), calculated as MAP less PIC. In the first ten minutes after propofol we observed a statistically significant (p less than 0.05) decrease of ICP and SAP. MAP decreased in the first five minutes only. Consequently HR increased at the same time. CPP decreased in the first two minutes after administration of the drug, but without statistical evidence. We conclude that propofol, in our opinion, can be used to treat intracranial hypertension but the hemodynamic effects in hypovolemic patients must be taken into consideration.     

The Impact of Systemic Vasoconstrictors on the Cerebral Circulation of Anesthetized Patients

Background: The effect of vasoconstrictors on intracerebral hemodynamics in anesthetized patients is controversial. The influence of phenylephrine and norepinephrine on the cerebral circulation was investigated in isoflurane- or propofol-anesthetized patients using transcranial Doppler ultrasonography.

Methods: Forty patients were randomly assigned to have vasoconstrictor tests with norepinephrine or phenylephrine during either isoflurane or propofol anesthesia. Blood flow velocities were simultaneously measured in the middle cerebral artery and ipsilateral extracranial internal carotid artery. Baseline recordings were done during stable anesthesia in a supine position (test 0). A second series of measurements were performed after norepinephrine or phenylephrine had increased mean arterial blood pressure by about 20% (test 1). With maintained norepinephrine or phenylephrine infusion, a final series of results were obtained after the increased mean arterial blood pressure was counteracted by a slightly head-up patient position (test 2).

Results: Both vasoconstrictors significantly increased mean flow velocities in the middle cerebral artery (norepinephrine: 43 +/- 11 cm/s to 49 +/- 11 cm/s; phenylephrine: 43 +/- 8 cm/s to 48 +/- 9 cm/s; +/- SD) and internal carotid artery (norepinephrine: 27 +/- 7 cm/s to 31 +/- 8 cm/s; phenylephrine: 27 +/- 9 cm/s to 31 +/- 10 cm/s) in the isoflurane-but not in the propofol-anesthetized patients. In the head-up position, only small and insignificant flow velocity changes were observed in both cerebral arteries independent of the vasoconstrictor or background anesthetic.     

HAEMODYNAMIC AND CEREBRAL EFFECTS OF ATP-INDUCED HYPOTENSION

Controlled decreases in mean arterial pressure to 20%, 40% and60% of baseline were produced by the administration of increasingconcentrations of adenosine triphosphate (ATP) i.v. in fiveanaesthetized baboons. Indices of the systemic circulation (arterialpressure, right atrial pressure, pulmonary artery pressures,cardiac output) and of the cerebral circulation (cerebral bloodflow, cerebral metabolic rate for oxygen, ccrebrovascular reactivity)were obtained as arterial pressure was decreased, and followingdiscontinuation of the infusion of ATP. A neuropathologicalinvestigation was undertaken at the end of the experimentalprocedure. The infusion of ATP produced dose-dependent decreasesin systemic vascular resistance and mean arterial pressure (MAP).Cardiac output and stroke volume were mninmini-H close to baselinevalues, or increased slightly. Cerebral blood flow (CBF) increasedinitially (48 ± 4 ml min^–1/100 g to 68 ±9 ml min^–1/100 g) and then decreased progressively asMAP was decreased to 40% and 60% of baseline. Cerebrovascularreactivity was shown to be impaired during, and for up to 90min following, the administration of ATP. However, there wasno morphological evidence of ischaemic cell damage in any animal.Tachyphylaxis was not observed during, and there were no instancesof rebound hypertension following, the infusion of ATP. Theconcentration of uric acid had increased significantly by the40% decrement in MAP, and remained so 60 min after the restorationof the arterial pressure.     

Esmolol and anesthetic requirement for loss of responsiveness during propofol anesthesia.

The administration of esmolol decreases the propofol blood concentration, preventing movement after skin incision during propofol/morphine/nitrous oxide anesthesia. However, interaction with esmolol has not been tested when propofol is infused alone. Accordingly, we tested the hypothesis that esmolol decreases the propofol blood concentration, preventing response to command (CP50-awake) when propofol is infused alone in healthy patients presenting for minor surgery. With approval and consent, we studied 30 healthy patients, who were randomized to esmolol bolus (1 mg/kg) and then infusion (250 microg x kg(-1) x min(-1)) or placebo. Five minutes later, a target-controlled infusion of propofol was commenced. Ten minutes later, responsiveness was assessed by a blinded observer. Oxygen saturation, heart rate, and noninvasive arterial blood pressure were recorded every 2 min. Arterial blood samples were taken at 5 and 10 min of propofol infusion for propofol assay. Results were analyzed with a generalized linear regression model: P <0.05 was considered statistically significant. The probability of response to command decreased with increasing propofol blood concentration (CP50-awake = 3.42 microg/mL). Esmolol did not alter the relative risk of response to command. We conclude that the previously observed effect of esmolol on propofol CP50 was not caused by an interaction between these two drugs. IMPLICATIONS: There is no evidence to suggest that esmolol, an ultra-short-acting cardioselective beta-blocker, affects anesthetic requirement for loss of responsiveness during propofol anesthesia.     

The effects of propofol on intracranial pressure and cerebral perfusion pressure in patients with brain tumors

In 7 patients with a brain tumor and intracranial hypertension treated by ventriculosubcutaneous drainage, intracranial pressure and cerebral perfusion pressure were continuously monitored during induction of anesthesia with fentanyl 1.5 micrograms/kg, propofol 2.5 mg/kg and vecuronium 0.1 mg/kg. End-tidal pCO2 was kept constant by manual ventilation and arterial pCO2 was verified before induction and before and after intubation. Five minutes after induction the patients were intubated and measurements continued for five more minutes. Mean arterial pressure decreased from 102 (+/- 9.8) mmHg to 57 (+/- 11.6) mmHg (p less than 0.01). Intracranial pressure did not change significantly before intubation. However in two patients intracranial pressure increased before intubation due to a significant rise in arterial pCO2. In 4 of the 7 patients an important increase to 25 (+/- 4.6) mmHg in intracranial pressure was observed during intubation. Cerebral perfusion pressure decreased from 88 (+/- 4.6) to 45 (+/- 9.8) mmHg (p less than 0.01) before intubation, but did not differ from the baseline during and after intubation. It is concluded that propofol 2.5 mg/kg in a bolus injection does not increase ICP but can produce a significant decrease of the cerebral perfusion pressure due to a marked decrease in mean arterial pressure in patients with a brain tumor.     

The effects of indomethacin on intracranial pressure and cerebral hemodynamics during isoflurane or propofol anesthesia in sheep with intracranial hypertension

The effect of indomethacin in reducing intracranial pressure (ICP) may be dependent on the choice of anesthetic regimen. We studied the effects of indomethacin on ICP and cerebral blood flow (CBF) during isoflurane or propofol anesthesia in a sheep model of intracranial hypertension. A crossover design was applied in which six sheep were anesthetized with isoflurane and propofol in a random order. Anesthetic depth was measured with response and state entropy. Changes in CBF, ICP, mean arterial blood pressure, arterio-venous oxygen difference, and Paco2 were measured at specific times before and after an IV indomethacin bolus (0.2 mg/kg). Response and state entropy values during anesthesia were similar in both groups. Isoflurane and propofol reduced CBF by 11% and 34%, respectively. Indomethacin caused a reduction in ICP within 15 s during both anesthetic regimens, with the decrease in ICP being significantly more pronounced during isoflurane (P = 0.009). In both anesthetic groups, indomethacin caused a simultaneous increase in mean arterial blood pressure and a further 17% versus 14% decrease in CBF from predrug values for isoflurane and propofol, respectively. The reduction in CBF was significantly more pronounced for propofol (P = 0.02). The effect on ICP, however, was most pronounced during isoflurane anesthesia. We suggest that the effect of indomethacin is partly mediated by an autoregulatory response.     

Comparison of intracarotid and intravenous propofol for electrocerebral silence in rabbits

BACKGROUND: The high lipid solubility that permits rapid transfer across the blood-brain barrier makes propofol attractive for intracarotid injection. The authors hypothesized that intracarotid injection produces electrocerebral silence at a fraction of the intravenous dose and with less adverse systemic and cerebrovascular side effects. METHODS: The authors compared the systemic and cerebrovascular effects of intracarotid and intravenous propofol during transient (10 s) and sustained (1 h) electrocerebral silence in anesthetized New Zealand White rabbits. Hemispheric electrocerebral activity, mean arterial blood pressure, ipsilateral and contralateral cerebral blood flow, tympanic temperature, and end-tidal carbon dioxide were continuously monitored in these animals. Changes in outcome variables were analyzed at four time points: at baseline, during electrical silence, during burst suppression, and after recovery of electrocerebral activity. Propofol (1%) was injected as intracarotid (0.1 ml) or intravenous (0.5 ml) boluses. RESULTS: Intracarotid propofol produced electrocerebral silence at one fifth (sustained silence) to one tenth (transient silence) of the intravenous dose. Compared with baseline values, the mean arterial pressure and ipsilateral cerebral blood flow remained unchanged or decreased transiently during electrocerebral silence with intracarotid propofol. In contrast, intravenous propofol resulted in systemic hypotension and a decrease in ipsilateral cerebral blood flow. CONCLUSIONS: Intracarotid propofol resulted in electrocerebral silence at a fraction of the intravenous dose that was not associated with systemic hypotension or a sustained decrease in the cerebral blood flow. Intracarotid propofol could be potentially useful for providing electrocerebral silence when cerebral perfusion is at risk.     

Propofol infusion for sedation of patients with head injury in intensive care

Propofol was given by continuous intravenous infusion to 10 patients with severe head injuries in the intensive care unit. Heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, pupil size and arterial carbon dioxide tension were recorded throughout the study period. A mean infusion rate of 2.88 mg/kg/hour provided satisfactory sedation, and recovery from the propofol was often rapid. Cerebral perfusion pressure was significantly increased at 24 hours.     

Comparison of Intracarotid and Intravenous Propofol for Electrocerebral Silence in Rabbits

Background: The high lipid solubility that permits rapid transfer across the blood-brain barrier makes propofol attractive for intracarotid injection. The authors hypothesized that intracarotid injection produces electrocerebral silence at a fraction of the intravenous dose and with less adverse systemic and cerebrovascular side effects.

Methods: The authors compared the systemic and cerebrovascular effects of intracarotid and intravenous propofol during transient (10 s) and sustained (1 h) electrocerebral silence in anesthetized New Zealand White rabbits. Hemispheric electrocerebral activity, mean arterial blood pressure, ipsilateral and contralateral cerebral blood flow, tympanic temperature, and end-tidal carbon dioxide were continuously monitored in these animals. Changes in outcome variables were analyzed at four time points: at baseline, during electrical silence, during burst suppression, and after recovery of electrocerebral activity. Propofol (1%) was injected as intracarotid (0.1 ml) or intravenous (0.5 ml) boluses.

Results: Intracarotid propofol produced electrocerebral silence at one fifth (sustained silence) to one tenth (transient silence) of the intravenous dose. Compared with baseline values, the mean arterial pressure and ipsilateral cerebral blood flow remained unchanged or decreased transiently during electrocerebral silence with intracarotid propofol. In contrast, intravenous propofol resulted in systemic hypotension and a decrease in ipsilateral cerebral blood flow.     

Propofol decreases cerebral blood flow velocity in anesthetized children

PURPOSE: Propofol, by virtue of its favourable pharmacokinetic profile, is suitable for maintenance of anesthesia by continuous infusion during neurosurgical procedures in adults. It is gaining popularity for use in pediatric patients. To determine the effects of propofol on cerebral blood flow in children, middle cerebral artery blood flow velocity (Vmca) was measured at different levels of propofol administration by transcranial Doppler (TCD) sonography. METHODS: Twelve ASA I or II children, aged one to six years undergoing elective urological surgery were randomized to receive one of two propofol dosing regimens. Half of the patients received propofol in an escalating fashion, initially targeting an estimated steady-state serum concentration of 3 microg x mL-1, which was then doubled. The other half received propofol designed initially to target the high concentration followed by the lower one. In each child anesthesia was induced and maintained with propofol according to the protocol, rocuronium was given to facilitate tracheal intubation, and a caudal epidural block was performed. A TCD probe was placed appropriately to measure Vmca. Cerebral blood flow velocity (CBFV), mean arterial pressure (MAP) and heart rate (HR) were recorded simultaneously at both levels of propofol administration. RESULTS: Twelve patients were studied. At the higher estimated target serum propofol concentration there were significant decreases in Vmca (17%, P < 0.001), MAP (6%, P < 0.002) and HR (8%, P < 0.05) when compared to the lower targeted concentration. CONCLUSION: This study shows that a higher rate of propofol infusion is associated with lower CBFV and MAP values in children. Propofol's cerebral vasoconstrictive properties may be responsible for this finding.     

The effects of nicardipine on dynamic cerebral autoregulation in patients anesthetized with propofol and fentanyl

We investigated the effects of nicardipine on dynamic cerebral pressure autoregulation in 13 normal adult patients undergoing gynecologic or orthopedic surgery. Anesthesia was induced and maintained with propofol and fentanyl. Hypotension to a mean arterial pressure of 60-65 mm Hg was induced and maintained with a continuous infusion of nicardipine. Time-averaged mean blood flow velocity in the right middle cerebral artery was measured continuously by using transcranial Doppler ultrasonography. The cerebral autoregulatory responses were activated by releasing thigh cuffs. The actual blood flow velocity in the right middle cerebral artery response to acute change in mean arterial pressure was fitted to 1 of 10 computer-generated curves to determine the dynamic rate of cerebral autoregulation (dRoR), and the best fitting curve was used. The autoregulation test was repeated until two values of dRoR were obtained at baseline and during induced hypotension. Nicardipine significantly reduced dRoR values of 13.1% +/- 3.6%/s at baseline to 8.3% +/- 2.6%/s during hypotension (P: < 0.01). During deliberate hypotension induced by nicardipine, the cerebral dynamic autoregulatory response is impaired in normal adult patients. IMPLICATIONS: During deliberate hypotension induced by nicardipine, the cerebral dynamic autoregulatory response is impaired in normal adult patients.     

The effect of sevoflurane and propofol on cerebral neurotransmitter concentrations during cerebral ischemia in rats

Sevoflurane and propofol are neuroprotective possibly by attenuating central or peripheral catecholamines. We evaluated the effect of these anesthetics on circulating catecholamines and brain neurotransmitters during ischemia in rats. Forty male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: fentanyl and N(2)O/O(2) (control), 2.0% sevoflurane, 0.8-1.2 mg x kg(-1) x min(-1) of propofol, and sham-operated rats with fentanyl and N(2)O/O(2). Ischemia (30 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 32 +/- 2 mm Hg. Pericranial temperature, arterial blood gases, and pH value were maintained constant. Cerebral catecholamine and glutamate concentrations, sampled by microdialysis, and plasma catecholamine concentrations were analyzed using high-pressure liquid chromatography. During ischemia, circulating catecholamines were almost completely suppressed by propofol but only modestly decreased with sevoflurane. Sevoflurane and propofol suppressed brain norepinephrine concentration increases by 75% and 58%, respectively, compared with controls. Intra-ischemia cerebral glutamate concentration was decreased by 60% with both sevoflurane and propofol. These results question a role of circulating catecholamines as a common mechanism for cerebral protection during sevoflurane and propofol. A role of brain tissue catecholamines in mediating ischemic injury is consistent with our results. IMPLICATIONS: During incomplete cerebral ischemia, the neuroprotective anesthetics sevoflurane and propofol suppressed cerebral increases in norepinephrine and glutamate concentrations. In contrast, propofol, but not sevoflurane, suppressed the ischemia-induced increase in circulating catecholamines to baseline levels. The results question a role for plasma catecholamines in cerebral ischemic injury.