Brain protection by anesthetics

Many investigators have attempted to protect the brain against ischemia by reducing the cerebral metabolic rate using anesthetic agents. However, the magnitude of suppression of the cerebral metabolic rate does not correlate with neuroprotective effects of anesthetics, suggesting that other factors besides reduction in the cerebral metabolic rate contribute to the protection. Facilitation of protein synthesis, GABAergic activity, and anti-oxidant action are likely factors responsible for beneficial effects of barbiturates and propofol. Although the brain is protected during anesthesia, anesthetics cannot provide effects sufficiently enough to recover damage caused by severe ischemia. Further, no desired outcome has been reported by treatments after ischemic events.     

Propofol in der Neuroanästhesie

The quality, result, and prognosis of neurosurgery relies heavily on the anaesthetic technique. Many different classes of drugs have been used during neurosurgical anaesthesia. This article reviews the use of intravenous (IV) propofol as an alternative to volatile anaesthetic techniques. Anaesthesia requirements for neurosurgical procedures are elaborated upon in the first part of the article. The priority of neuroanaesthesia is to preserve neuronal function by avoiding complications such as hypoxia, hypercarbia, and cardiovascular instability. Thereafter, the chosen anaesthetic technique should minimally interfere with cerebral autoregulation and CO₂ responsiveness, while brain relaxation is encouraged by decreasing the cerebral metabolic rate for oxygen (CMRO₂) and cerebral blood flow (CBF). In addition, the anaesthetic technique should be associated with rapid and predictable recovery in the operating theatre in order to allow early evaluation of the surgery. The second part of the article describes IV techniques for neurosurgery as an alternative to volatile anaesthetics, all of which increase CBF, cerebral blood volume, and intracranial pressure (ICP) in a dose-related manner and diminish cerebral autoregulation and interfere with cerebrovascular CO₂ reactivity. Nitrous oxide has a stimulant effect on cerebral metabolism and is associated with an increase in CBF. On the other hand, all IV agents except ketamine are associated with decreases in CMRO₂ and are cerebral vasoconstrictors. For this reason, it is rational to use them for the induction and maintenance of anaesthesia for neurosurgery as part of a total IV anaesthetic technique. The third part of the article focuses on propofol as the newest representative of IV anaesthetics. It is a sedative-hypnotic agent that has a pharmacokinetic-dynamic profile ideally suited for continuous infusion. Propofol reduces ICP, CBF, and CMRO₂. Animal models have suggested the possibility of cerebral protection. The responsiveness of the cerebral circulation to alterations in arterial blood pressure is maintained. Evaluating propofol for major neurosurgery demonstrated good quality and depth of anaesthesia, excellent brain relaxation, and minimal surgical bleeding. In conclusion, total IV anaesthesia with propofol has proven to be a valid alternative to conventional thiopentone-isoflurane anaesthesia for intracranial surgery.     

Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism

BACKGROUND: Propofol (2,6-diisopropylphenol) has been shown to attenuate neuronal injury in a number of experimental conditions, but studies in models of cerebral ischemia have yielded conflicting results. Moreover, the mechanisms involved in its neuroprotective effects are yet unclear. METHODS: The authors evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-glucose deprivation in CA1 pyramidal cells by transmission electron microscopy. Finally, they evaluated whether propofol could attenuate the infarct size and improve the neurobehavioral outcome in rats subjected to permanent middle cerebral artery occlusion in vivo. RESULTS: When present in the incubation medium during oxygen-glucose deprivation and the subsequent 24 h recovery period, propofol (10-100 microM) attenuated CA1 injury in hippocampal slices in vitro. Ca2+-induced brain mitochondrial swelling was prevented by 30-100 microM propofol, and so were the ultrastructural mitochondrial changes in CA1 pyramidal cells exposed to oxygen-glucose deprivation. Twenty-four hours after permanent middle cerebral artery occlusion, propofol (100 mg/kg, intraperitoneal) reduced the infarct size by approximately 30% when administered immediately after and up to 30 min after the occlusion. Finally, propofol administered within 30 min after middle cerebral artery occlusion was unable to affect the global neurobehavioral score but significantly preserved spontaneous activity in ischemic rats. CONCLUSIONS: These results show that propofol, at clinically relevant concentrations, is neuroprotective in models of cerebral ischemia in vitro and in vivo and that it may act by preventing the increase in neuronal mitochondrial swelling.     

Comparison of the Effects of Propofol and Pentobarbital on Neurologic Outcome and Cerebral Infarct Size after Temporary Focal Ischemia in the Rat

Background: Although propofol is known to have effects on cerebral physiology similar to the barbiturates, a direct comparison of the relative effects of these drugs on outcome from cerebral ischemia has not been performed. The authors postulated that pentobarbital or propofol would yield similar effects on neurologic and histologic outcome from temporary focal ischemia in the rat.

Methods: Wistar rats were anesthetized with sufficient doses of pentobarbital (n = 20) or propofol (n = 20) to cause electroencephalographic burst suppression. The middle cerebral artery was then occluded for 75 min. Animals were awakened 4-6 h after onset of reperfusion and allowed to recover for 1 week. Neurologic function and infarct size were then assessed.

Results: Relevant physiologic values were similar between groups during ischemia and early reperfusion. No difference between groups was observed for severity of hemiparesis (P = 0.10). Total cerebral infarct volumes (median +/- quartile deviation) were similar for the two groups (pentobarbital = 190 +/- 36 mm3; propofol = 200 +/- 24 mm3, P = 0.35).     

Current applications of laser Doppler in the neurosurgical intensive care unit

The invasive monitoring of the microcirculatory cerebral blood flow by laser Doppler flowmetry has been proposed as means for the detection and prevention of cerebral ischemia in comatose patients. However, the use of this technique is not widespread, nor has it proven to influence the patient's outcome. Recent reports selected from the literature are reviewed in order to define the indications, usefulness, limitations, and potential complications of the available methodology for the clinical monitoring of cerebral blood flow in neurosurgical patients by laser Doppler flowmetry.     

Neuroprotective Effects of Propofol in Models of Cerebral Ischemia: Inhibition of Mitochondrial Swelling as a Possible Mechanism

Background: Propofol (2,6-diisopropylphenol) has been shown to attenuate neuronal injury in a number of experimental conditions, but studies in models of cerebral ischemia have yielded conflicting results. Moreover, the mechanisms involved in its neuroprotective effects are yet unclear.

Methods: The authors evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-glucose deprivation in CA1 pyramidal cells by transmission electron microscopy. Finally, they evaluated whether propofol could attenuate the infarct size and improve the neurobehavioral outcome in rats subjected to permanent middle cerebral artery occlusion in vivo.

Results: When present in the incubation medium during oxygen-glucose deprivation and the subsequent 24 h recovery period, propofol (10-100 [mu]m) attenuated CA1 injury in hippocampal slices in vitro. Ca2+-induced brain mitochondrial swelling was prevented by 30-100 [mu]m propofol, and so were the ultrastructural mitochondrial changes in CA1 pyramidal cells exposed to oxygen-glucose deprivation. Twenty-four hours after permanent middle cerebral artery occlusion, propofol (100 mg/kg, intraperitoneal) reduced the infarct size by approximately 30% when administered immediately after and up to 30 min after the occlusion. Finally, propofol administered within 30 min after middle cerebral artery occlusion was unable to affect the global neurobehavioral score but significantly preserved spontaneous activity in ischemic rats.     

Effect of propofol on pathologic time-course and apoptosis after cerebral ischemia-reperfusion injury

Background: Propofol has been demonstrated to ameliorate cerebral ischemic injury and attenuate changes in multiple links of molecular reaction included in the paths to apoptosis. The experiment was aimed to evaluate whether propofol neuroprotection was mediated through the ability to regulate pathologic time-course of apoptosis.
Methods: The effect of propofol given at a series of time points during ischemia–reperfusion period was determined using an intraluminal middle cerebral artery occlusion model in rats. The morphological changes of apoptosis under different duration of ischemia were detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin in situ nick labeling staining, and the effect of propofol on apoptosis was observed. The expression of anti-apoptotic protein bcl-2 in post-ischemia neurons and the influence of propofol was analyzed by immunochemistry staining.
Results: Propofol attenuated neurological deficit, reduced infarct volumes, when given prior the onset of ischemia, during ischemia or 3 h after reperfusion. Apoptosis obviously appeared at 6 h post-reperfusion preceded by 90 min ischemia, rose to the maximum value at 24 h post-reperfusion and gradually diminished after 3 days reperfusion. Propofol inhibited apoptotic morphological changes between 6 h and 3 days post-reperfusion. Propofol enhanced the expression of anti-apoptotic protein bcl-2 in post-reperfusion neurons.
Conclusions: The pathologic outcome of focal cerebral ischemia–reperfusion injury was displayed by co-existence of apoptosis and necrosis. A short duration of ischemia induced apoptosis. The therapeutic window for propofol initiated before the onset of ischemia and lasted until early stage of reperfusion. The neuroprotection of propofol might be attributed to the inhibition of apoptosis.     

Clinical experience with transcranial cerebral oximetry

Transcranial cerebral oximetry based on the principle of near-infrared spectroscopy has been successfully used in a variety of neurosurgical conditions, primarily those associated with disturbed cerebral circulation. The non-invasive technique of cerebral oximetry provides valuable information about brain oxygenation in patients with cerebral ischemia (due to occlusion or stenosis of the internal carotid artery). It is also used in intraoperative monitoring of carotid endarterectomy and surgical procedures performed under deep hypothermia and circulatory arrest, during neuroendovascular procedures, and in critical care settings (in patients with arterial vasospasm and during the terminal period). This article describes our preliminary clinical experience with the use of this new technique and summarizes the current literature on clinical and experimental use of transcranial cerebral oximetry.     

Quantitative evaluation of the neuroprotective effects of thiopental sodium, propofol, and halothane on brain ischemia in the gerbil: effects of the anesthetics on ischemic depolarization and extracellular glutamate concentration

Although propofol and thiopental are commonly used as neuroprotective agents, it has not been determined which is more neuroprotective. This study was designed to quantitatively evaluate the neuroprotective effects of thiopental, propofol, and halothane on brain ischemia by determining P50, ischemic time necessary for causing 50% neuronal damage. Gerbils were anesthetized with thiopental, propofol, or halothane and underwent 2-vessel occlusion (0, 3, 5 or 10 min). Direct current potentials were measured in bilateral CA1 regions, in which histologic evaluation was performed 5 days later. In some animals, extracellular glutamate concentrations (microdialysis) were measured during 7.5 minutes of ischemia. P50 in the thiopental, propofol, and halothane groups were estimated to be 8.4, 6.5 (P<0.05, vs. thiopental), and 5.1 (P<0.05) minutes, respectively. Durations of ischemic depolarization were equally reduced in the thiopental and propofol groups compared with that in the halothane group. Severity of neuronal damage with identical duration of ischemic depolarization was attenuated by thiopental compared with the effect of propofol. Maximum glutamate concentrations in the thiopental and propofol group were significantly reduced compared with that in the halothane groups but were comparable. By using P50, we found that the neuroprotective effect of thiopental was greater than that of propofol. Although duration of ischemic depolarization was equally reduced in thiopental and propofol groups, thiopental has a greater suppressive effect on neuronal injury during identical duration of ischemic depolarization than propofol does. Glutamate concentration during brain ischemia tended to be attenuated more by thiopental than by propofol, but it was not statistically significant.     

Stewart's physicochemical approach in neurosurgical patients with hyperchloremic metabolic acidosis during propofol anesthesia

There is both in vitro and clinical evidence that high-dose propofol can inhibit mitochondrial respiration, resulting in metabolic acidosis. The purpose of this study was to evaluate the effects of propofol anesthesia on the acid-base status in neurosurgical patients with large amount of normal saline administration. Thirty patients undergoing clipping of cerebral aneurysm were randomly assigned to receive propofol (n=15) or isoflurane (n=15). Propofol dose (mean+/-standard error) infused for maintenance was 5.7+/-0.2 mg/kg/h in propofol group. Acid-base parameters such as PaCO2, pH, serum bicarbonate concentration, standard base excess, serum electrolyte concentration, total protein, albumin, lactate, and phosphate were measured before and 4 hours after the induction of anesthesia, and after surgery. The apparent strong ion difference (SIDa), the effective SID (SIDe), and the amount of weak plasma acid were calculated using the Stewart equation. There were no significant differences in pH, PaCO2, bicarbonate, and lactate between 2 groups throughout the whole investigation period. After surgery, standard base excess significantly decreased in both groups without intergroup difference. SIDa and SIDe significantly decreased in both groups, and lactate and strong ion gap significantly increased after surgery in propofol group, but there were no significant differences between 2 groups. Both propofol and isoflurane were associated with hyperchloremic metabolic acidosis in neurosurgical patients with large amount of normal saline administration. The acid-base balance between the 2 anesthetics was similar using Stewart's physicochemical approach.     

Propofol for induction and maintenance of anesthesia during heart surgery. Results of pharmacological studies in man

Numerous reports have concluded that propofol is suitable for maintenance of anesthesia by continuous infusion. The aim of this study was to evaluate the use of propofol and fentanyl for coronary bypass surgery in patients with good left ventricular function. The effects of this anesthetic combination on quality of anesthesia, hemodynamic status, and endocrine and metabolic responses were assessed. Postoperative recovery and side effects were also noted. The effects were compared with those of a standard method using etomidate, midazolam, and fentanyl. METHODS. Twenty patients who presented for aortocoronary bypass surgery (NYHA class II-III) were randomly allocated to one of two groups: propofol-fentanyl (group A) or etomidate-midazolam-fentanyl (group B). In each patient the dosage of the drugs was adjusted to obtain the optimum responses during induction and maintenance. RESULTS. Propofol in combination with fentanyl diminished mean arterial pressure (-28.7%) and heart rate (-17.3%) when used for induction in patients with ischemic heart disease, even in low doses and with slow administration. In 5 of the 10 patients it was impossible to prevent a critical fall in coronary perfusion without active intervention. However, during maintenance anesthesia, stable circulatory parameters were obtained with both drug regimens. Clinical signs thought to reflect myocardial ischemia were not observed. In both groups reductions in basal and stimulated catecholamine secretion were demonstrated. Similarly, perioperative cortisol secretion was reduced with both techniques. Despite all the complicated metabolic inhibitory effects seen, preoperative hormonal levels were restored within 1 h of the end of anesthesia. The magnitude and duration of the metabolic changes were found to be related to the duration of surgery. There was no evidence of non-homogeneous tissue perfusion as assessed by increases in lactate concentration, cardiac ischemia, or liver dysfunction in any of the patients. There were no postoperative complications in either group, but the return of consciousness, adequate spontaneous ventilation, and psychomotor activity was more rapid in the propofol patients. CONCLUSION. In summary, it can be concluded that a propofol infusion technique positively enhances the recovery period after cardiac surgery and provides good control during anesthesia. However, the use of propofolfentanyl for induction of anesthesia in patients with limited coronary perfusion is not recommended because of its hypotensive effect.     

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.     

Positron emission tomography study of regional cerebral metabolism during general anesthesia with xenon in humans

BACKGROUND: The precise mechanism by which the gaseous anesthetic xenon exerts its effects in the human brain remains unknown. Xenon has only negligible effects on inhibitory gamma-aminobutyric acid receptors, one of the putative molecular targets for most general anesthetics. Instead, xenon has been suggested to induce anesthesia by inhibiting excitatory glutamatergic signaling. Therefore, the authors hypothesized that xenon, similar to ketamine and nitrous oxide, increases global and regional cerebral metabolism in humans. METHODS: The regional cerebral metabolic rate of glucose (rcMRGlu) was sequentially assessed in two groups of six volunteers each, using F-fluorodeoxyglucose as tracer. In the xenon group, rcMRGlu was determined at baseline and during general anesthesia induced with propofol and maintained with 1 minimum alveolar concentration xenon. In the control group, rcMRGlu was measured using the identical study protocol but without administration of xenon. rcMRGlu was assessed after the plasma concentration of propofol had decreased to subanesthetic levels (< 1.0 microg/ml). rcMRGlu was quantified in 10 cerebral volumes of interest. In addition, voxel-wise changes in rcMRGlu were analyzed using statistical parametric mapping. RESULTS: Xenon reduced whole-brain metabolic rate of glucose by 26 +/- 7% (from 43 +/- 5 micromol x 100 g x min to 31 +/- 3 micromol x 100 g x min; P < 0.005) and significantly decreased rcMRGlu in all volumes of interest compared with the control group receiving propofol only. Voxel-based analysis revealed metabolic depression within the orbitofrontal, frontomesial, temporomesial, occipital, dorsolateral frontal, and lateral temporal cortices and thalami. No increases in rcMRGlu were detected during xenon anesthesia. CONCLUSIONS: Xenon induces metabolic depression in the human brain, suggesting that the inhibition of the glutamatergic system is likely to be of minor significance for the anesthetic action of xenon in vivo.     

A comparison of frontal and occipital bispectral index values obtained during neurosurgical procedures

We placed bispectral index (BIS) sensors on the frontal and occipital areas of neurosurgical patients and compared BIS values obtained from both areas during propofol/fentanyl anesthesia. BIS showed a strong correlation between frontal and occipital montages (r(2) = 0.96; P = 0.03). It may be valid to measure BIS with the sensor on the occipital area if required during frontal neurosurgical procedures. IMPLICATIONS: Bispectral values were positively correlated when recorded from frontal and occipital sensors in patients undergoing clipping of unruptured cerebral aneurysms while anesthetized with propofol and fentanyl.     

Consequences of Electroencephalographic-suppressive Doses of Propofol in Conjunction with Deep Hypothermic Circulatory Arrest

Background: Some patients who undergo cerebral aneurysm surgery require cardiopulmonary bypass and deep hypothermic circulatory arrest. During bypass, these patients often are given large doses of a supplemental anesthetic agent in the hope that additional cerebral protection will be provided. Pharmacologic brain protection, however, has been associated with undesirable side effects. These side effects were evaluated in patients who received large doses of propofol.

Methods: Thirteen neurosurgical patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest to facilitate clip application to a giant or otherwise high-risk cerebral aneurysm. Electroencephalographic burst suppression was established before bypass with an infusion of propofol, and the infusion was continued until the end of surgery. Hemodynamic and echocardiographic measurements were made before and during the prebypass propofol infusion and again after bypass. Emergence time also was determined.

Results: Prebypass propofol at 243 plus/minus 57 micro gram *symbol* kg sup -1 *symbol* min sup -1 decreased vascular resistance from 34 plus/minus 8 to 27 plus/minus 8 units without changing heart rate, arterial or filling pressures, cardiac index, stroke volume, or ejection fraction. Propofol blood concentration was 8 plus/minus 2 micro gram/ml. Myocardial wall motion appeared hyperdynamic at the end of cardiopulmonary bypass, and all patients were weaned therefrom without inotropic support. After bypass, vascular resistance decreased further, and cardiovascular performance was improved compared to baseline values. Nine of the 13 patients emerged from anesthesia and were able to follow commands at 3.1 plus/minus 1.4 h. Three others had strokes and a fourth had cerebral swelling.     

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.     

Invasive monitoring of cerebral oxygenation

Despite medical and technological advances in neurosurgical intensive care, severe traumatic brain injury still carries a poor prognosis. Invasive monitoring of cerebral oxygenation has recently been proposed as a means for the detection and prevention of cerebral ischemia in comatose patients; however, it has not proven to influence the patient’s outcome after severe brain injury. Eight recent reports selected from the literature are reviewed, and the authors’ own clinical experience is presented in order to define the indications, usefulness, limitations, and potential complications of the available methodology for the invasive monitoring of cerebral interstitial oxygen saturation.     

Electroencephalogram, cerebral metabolic, and vascular responses to propofol anesthesia in dogs

Previous studies on the cerebral effects of propofol report conflicting results regarding the cerebral metabolic rate for oxygen (CMRO2), cerebral blood flow (CBF), autoregulation of CBF, intracranial pressure, and cerebral perfusion pressure (CPP). The present studies were designed to examine these issues as well as propofol effects on the CBF responses to hypocapnia and on the electroencephalogram (EEG) in a well-known canine model that permits continuous determination of EEG activity, CMRO2, CBF, and cerebrospinal fluid (CSF) pressure. Dogs were studied at normocapnia (n = 6) and at hypocapnia (n = 6) during three doses of propofol (12, 24, and 48 mg kg(-1) h(-1)) and during a combination of propofol and elevated (20-25 mm Hg) CSF pressure. In both groups propofol caused dose-related decreases of EEG power and number of waveforms, CMRO2 (by 25-30%), and CBF (by 73-76%). The cerebral vasoconstrictor response to hypocapnia was preserved at all three doses of propofol. Autoregulation of CBF was preserved at the low and moderate doses of propofol but was impaired at the high dose of propofol (where CPP decreased significantly to approximately 41 +/- 13 mm Hg) and at the high dose of propofol combined with elevated CSF pressure (where CPP decreased significantly to approximately 32 +/- 12 mm Hg). Cerebrospinal fluid pressure decreased (by 33-42%) when the continuous infusion of propofol was begun, but returned to prepropofol values as infusion of propofol continued. The authors conclude that low and moderate doses of propofol decrease EEG activity and CMRO2, causing an associated decrease of CBF and CSF pressure. Autoregulation of CBF and cerebral vascular CO2 reactivity are preserved at these propofol doses. In contrast, high dose propofol significantly decreases CPP, resulting in impaired autoregulation of CBF.     

Propofol-Infusionssyndrom

Propofol infusion syndrome has not only been observed in patients undergoing long-term sedation with propofol, but also during propofol anesthesia lasting 5 h. It has been assumed that the pathophysiologic cause is propofol’s impairment of oxidation of fatty acid chains and inhibition of oxidative phosphorylation in the mitochondria, leading to lactate acidosis and muscular necrosis. It has been postulated that propofol might act as a trigger substrate in the presence of priming factors. Severe diseases in which the patient has been exposed to high catecholamine and cortisol levels have been identified as trigger substrates. Once the development of propofol infusion syndrome is suspected, propofol infusion has to be stopped immediately and specific therapeutic measures initiated, including cardiocirculatory stabilization and correction of metabolic acidosis. To increase elimination of propofol and its potential toxic metabolites, hemodialysis or hemofiltration are recommended. Due to its possible fatal side effects, the use of propofol for long-term sedation in critically ill patients should be reconsidered. In cases of unexplained lactate acidosis occurring during continuous propofol infusion, propofol infusion syndrome must be taken into consideration.     

The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats.

This study compares the effects of propofol and fentanyl/N2O on spontaneous brain electrical activity, neurologic outcome, and neuronal damage due to incomplete cerebral ischemia in rats. Thirty Sprague-Dawley rats were assigned to one of three groups: group 1 (n = 10) received 70% N2O in O2 plus fentanyl (bolus 10 micrograms.kg-1, infusion 25 micrograms.kg-1.h-1); group 2 (n = 10) received 70% N2 in O2 and propofol (infusion 0.8-1.2 mg.kg-1.min-1) adjusted to maintain EEG burst suppression during ischemia; group 3 (n = 10) was anesthetized with propofol and received 6 ml.kg-1 10% glucose intraperitoneally 15 min before the start of ischemia. Incomplete cerebral ischemia was produced by right common carotid artery occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Arterial blood gases, pH, and rectal temperature were kept constant in all groups. Plasma glucose was lower during ischemia in propofol-anesthetized rats compared to that in fentanyl/N2O- (P = 0.009) and glucose-loaded propofol-treated rats (P = 0.008). Neurologic outcome and brain tissue injury were significantly better in propofol-anesthetized compared to fentanyl/N2O-anesthetized rats (P less than 0.05). Elevated plasma glucose in propofol-treated rats resulted in similar neurologic outcome and histopathologic injury as seen in propofol-anesthetized rats given no glucose. Recovery of EEG theta-alpha activity after ischemia was inversely correlated to neurologic deficit (fentanyl/N2O: r = -0.71; propofol: r = -0.83; P less than 0.01). These results show that propofol improves neurologic outcome and decreases neuronal damage from incomplete cerebral ischemia when compared to fentanyl/N2O. This effect is not dependent on plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)