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Wpływ propofolu na prędkość przepływu krwi w tętnicy środkowej mózgu (VMCA) u chorych z niepękniętym tętniakiem wewnątrzczaszkowym podczas indukcji znieczulenia ogólnego
Abstract
Background:
The estimated prevalence of unruptured intracranial aneurysms is 3%. Standard monitoring does not enable one to assess the influence of anaesthetics on the factors determining intracranial homeostasis. Thanks to transcranial Doppler ultrasonography, middle cerebral artery flow velocity (VMCA), reflecting cerebral blood flow, can be measured. The aim of the study was to assess the effects of propofol on intracranial homeostasis in patients with unruptured intracranial aneurysms during the induction of anaesthesia based on VMCA changes.
Methods:
The study encompassed 21 patients (group II) anaesthetised for elective craniotomy due to unruptured intracranial aneurysms. The control group (group I) included 21 patients who underwent discoidectomy. VMCA, as well as HR, MAP, etCO2, and SpO2 were monitored at the following time points: T0 — onset of study; T1 — after 1 minute; T2 — onset of preoxygenation; T3 — after 1 minute of preoxygenation; T4 — administration of fentanyl; T5 — 1 minute after fentanyl; T6 — administration of propofol; T7 — 1 minute after propofol; T8 — intubation; T9 — 1 minute after intubation; T10 — 2 minutes after intubation.
Results:
In both groups, no changes in mean HR, etCO2 and SpO2 were observed at the successive time points of observation. In groups I and II, an MAP decrease between T6 and T7 and an MAP increase between T7 and T9 were noted. There were no intergroup differences in mean values of MAP at the times of observation. In both groups and bilaterally, a VMCA decrease was recorded between T6 and T7 and an increase between T7 and T8. There were no intergroup differences in mean values of VMCA at the times of observation. In both groups, a weak correlation between VMCA and MAP changes was found bilaterally.
Conclusions:
Propofol depresses the cerebral circulation during the induction of anaesthesia. The presence of an unruptured aneurysm does not affect the reactivity of the cerebral vessels during the induction of anaesthesia with propofol.
... A more recent study of 15 patients undergoing elective surgery for UIA found that cerebral circulation times were longer during propofol anesthesia compared to sevoflurane-based anesthesia, as were the circulation times in the internal carotid and middle cerebral arteries [30]. The presence of an unruptured intracranial aneurysm also did not affect the propofol-induced reactivity of cerebral vessels [29]. Multiple studies have compared propofol to other anesthetics for neurovascular procedures [29][30][31], but most have focused on the hemodynamic or neuroprotective effects of propofol, with only limited data regarding its effects on neurological outcomes. ...
... The presence of an unruptured intracranial aneurysm also did not affect the propofol-induced reactivity of cerebral vessels [29]. Multiple studies have compared propofol to other anesthetics for neurovascular procedures [29][30][31], but most have focused on the hemodynamic or neuroprotective effects of propofol, with only limited data regarding its effects on neurological outcomes. ...
Intracranial aneurysms (IA) occur in 3–5% of the general population and may require surgical or endovascular obliteration if the patient is symptomatic or has an increased risk of rupture. These procedures carry an inherent risk of neurological complications, and the outcome can be influenced by the physiological and pharmacological effects of the administered anesthetics. Despite the critical role of anesthetic agents, however, there are no current studies to systematically assess the intraoperative anesthetic risks, benefits, and outcome effects in this population. In this systematic review of the literature, we carefully examine the existing evidence on the risks and benefits of common anesthetic agents during IA obliteration, their physiological and clinical characteristics, and effects on neurological outcome. The initial search strategy captured a total of 287 published studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 28 studies were included in the final report. Our data showed that both volatile and intravenous anesthetics are commonly employed, without evidence that either is superior. Although no specific anesthetic regimens are promoted, their unique neurological, cardiovascular, and physiological properties may be critical to the outcome in vulnerable patients. In particular, patients at risk for perioperative ischemia may benefit from timely administration of anesthetic agents with neuroprotective properties and optimization of their physiological parameters. Further studies are warranted to examine if these anesthetic regimens can reduce the risk of neurological injury and improve the overall outcome in these patients.
Background
Cerebrovascular reactivity (CVR) is often impaired in the early phase after aneurysmal subarachnoid hemorrhage. There is, however, little knowledge about the time course of CVR in patients treated for unruptured intracranial aneurysms (UIA).
Methods
CVR, assessed by transcranial Doppler and acetazolamide test, was examined within the first postoperative week after treatment for UIA and reexamined one year later.
Results
Of 37 patients initially assessed, 34 were reexamined after one year. Bilaterally, baseline and acetazolamide-induced blood flow velocities were higher in the postoperative week compared with one year later (p < 0.001). CVR on the ipsilateral side of treatment was lower in the initial examination compared with follow-up (58.9% versus 66.1%, p = 0.04). There was no difference in CVR over time on the contralateral side (63.4% versus 65.0%, p = 0.65). When mean values of right and left sides were considered there was no difference in CVR between exams. Larger aneurysm size was associated with increased change in CVR (p = 0.04), and treatment with clipping was associated with 13.8%-point increased change in CVR compared with coiling (p = 0.03).
Conclusion
Patients with UIA may have a temporary reduction in CVR on the ipsilateral side after aneurysm treatment. The change in CVR appears more pronounced for larger-sized aneurysms and in patients treated with clipping. We recommend that ipsilateral and contralateral CVR should be assessed separately, as mean values can conceal side-differences.
Background:
Only a minority of intracranial aneurysms rupture to cause subarachnoid hemorrhage.
Objective:
To test the hypothesis that unruptured aneurysms have different characteristics and risk factor profiles compared to ruptured aneurysms.
Methods:
We recruited patients with unruptured aneurysms or aneurysmal subarachnoid hemorrhages at 22 UK hospitals between 2011 and 2014. Demographic, clinical, and imaging data were collected using standardized case report forms. We compared risk factors using multivariable logistic regression.
Results:
A total of 2334 patients (1729 with aneurysmal subarachnoid hemorrhage, 605 with unruptured aneurysms) were included (mean age 54.22 yr). In multivariable analyses, the following variables were independently associated with rupture status: black ethnicity (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.29-4.56, compared to white) and aneurysm location (anterior cerebral artery/anterior communicating artery [OR 3.21; 95% CI 2.34-4.40], posterior communicating artery [OR 3.92; 95% CI 2.67-5.74], or posterior circulation [OR 3.12; 95% CI 2.08-4.70], compared to middle cerebral artery). The following variables were inversely associated with rupture status: antihypertensive medication (OR 0.65; 95% CI 0.49-0.84), hypercholesterolemia (0.64 OR; 95% CI 0.48-0.85), aspirin use (OR 0.28; 95% CI 0.20-0.40), internal carotid artery location (OR 0.53; 95% CI 0.38-0.75), and aneurysm size (per mm increase; OR 0.76; 95% CI 0.69-0.84).
Conclusion:
We show substantial differences in patient and aneurysm characteristics between ruptured and unruptured aneurysms. These findings support the hypothesis that different pathological mechanisms are involved in the formation of ruptured aneurysms and incidentally detected unruptured aneurysms. The potential protective effect of aspirin might justify randomized prevention trials in patients with unruptured aneurysms.
Background:
Intracranial aneurysm with and without subarachnoid haemorrhage (SAH) is a relevant health problem: The overall incidence is about 9 per 100,000 with a wide range, in some countries up to 20 per 100,000. Mortality rate with conservative treatment within the first months is 50-60%. About one third of patients left with an untreated aneurysm will die from recurrent bleeding within 6 months after recovering from the first bleeding. The prognosis is further influenced by vasospasm, hydrocephalus, delayed ischaemic deficit and other complications. The aim of these guidelines is to provide comprehensive recommendations on the management of SAH with and without aneurysm as well as on unruptured intracranial aneurysm.
Methods:
We performed an extensive literature search from 1960 to 2011 using Medline and Embase. Members of the writing group met in person and by teleconferences to discuss recommendations. Search results were graded according to the criteria of the European Federation of Neurological Societies. Members of the Guidelines Committee of the European Stroke Organization reviewed the guidelines.
Results:
These guidelines provide evidence-based information on epidemiology, risk factors and prognosis of SAH and recommendations on diagnostic and therapeutic methods of both ruptured and unruptured intracranial aneurysms. Several risk factors of aneurysm growth and rupture have been identified. We provide recommendations on diagnostic work up, monitoring and general management (blood pressure, blood glucose, temperature, thromboprophylaxis, antiepileptic treatment, use of steroids). Specific therapeutic interventions consider timing of procedures, clipping and coiling. Complications such as hydrocephalus, vasospasm and delayed ischaemic deficit were covered. We also thought to add recommendations on SAH without aneurysm and on unruptured aneurysms.
Conclusion:
Ruptured intracranial aneurysm with a high rate of subsequent complications is a serious disease needing prompt treatment in centres having high quality of experience of treatment for these patients. These guidelines provide practical, evidence-based advice for the management of patients with intracranial aneurysm with or without rupture. Applying these measures can improve the prognosis of SAH.
This study was designed to investigate if propofol produced cardiovascular effects by indirect actions or by indirect actions
secondary to depression of the central nervous system. Experiments were performed on chloralose anaesthetized dogs in which
all neurogenic cardiovascular reflexes were abolished by bilateral vagotomy and common carotid ligatures, in combination with
i. v. bretylium and propranolol. Bolus doses of propofol followed by infusions at rates up to 160 mg kg−1 h−1 produced blood concentrations of propofol from 1.99 to 112 μg ml−1. Infusions of hydroxyethyl starch given to maintain central
venous pressures and pulmonary artery occlusion pressures at control values were used as an index of changes in capacitance.
Blood concentrations of propofol less than 10 μg ml−1 caused an increase in mean capacitance of 8.0 (SEM 1) ml kg−1 with no significant changes in systemic vascular resistance, pulmonary vascular resistance or intropic state of the heart.
We conclude that anaesthesia with propofol may be accompained by decreased cardiac output secondary to reduction in preload
by a direct venodilator effect. Our experiments indicate that cardiac output and arterial pressure are preserved well at normal
anaesthetic blood concentrations of propofol if the preload is maintained.
We studied cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced electrical silence of the
electroencephalogram (EEG) in 10 patients. Anaesthesia was induced with propofol 2.5 mg kg−1, fentanyl 3 μg kg−1 and vecuronium 0.1 mg kg−1, and a propofol infusion of 250–300 μg kg−1 min−1 was used to induce EEG silence. Cerebral pressure autoregulation was tested by increasing mean arterial pressure (MAP) by
24 (SEM 5) mm Hg from baseline with an infusion of phenylephrine and simultaneously recording middle cerebral artery blood
flow velocity (vmca) using transcranial Doppler. Carbon dioxide reactivity was tested by varying Paco2 between 4.0 and 7.0 kPa and recording vmca simultaneously. Although absolute carbon dioxide reactivity was reduced, relative carbon dioxide reactivity was within
normal limits for all patients studied (mean 8.5 (SEM 0.8) cm s−1 kPa−1 and 22 (2)% kPa−1, respectively). No significant change in vmca (34 (2) and 35 (2) cm s−1) was observed with the increase in MAP (77 (4) to 101 (4) mm Hg) during autoregulation testing. We conclude that cerebral
carbon dioxide reactivity and pressure autoregulation remain intact during propofol-induced isoelectric EEG.
We have studied the haemodynamic changes, QT intervals and catecholamine responses to induction of anaesthesia and tracheal
intubation in 24 ASA I patients allocated randomly to receive either pro-pofol 2.5 mg kg-1 or thiopentone 5 mg kg-1 over 60 s. After disappearance of the eyelash reflex, the lungs were ventilated with 100% oxygen for 3 min. The trachea was
intubated after administration of vecuronium. With thiopentone, heart rate (HR) was greater than with propofol before intubation
(P < 0.05). During induction, systolic (SAP) and diastolic arterial pressure (DAP) decreased more with propofol than with
thiopentone. The QT interval was prolonged only during induction with thiopentone. In both groups, HR, SAP, DAP and the QT
were increased in response to intubation (P < 0.001). The SAP and QT interval responses to intubation were significantly greater
with thiopentone than with propofol (P < 0.05). One patient in the thiopentone group with a significantly prolonged QT interval
had episodes of bigeminy and ventricular tachycardia. In both groups, concentrations of noradrenaline in mixed venous plasma
increased after intubation (P < 0.001). Concentrations of adrenaline increased after intubation only in the thiopentone group
(P < 0.001). (Br. J. Anaesth. 1993; 70: 306–310)
Rapid i.v. induction of general anaesthesia is indicated in infants at risk of vomiting or regurgitation to reduce the risk of aspiration of gastric contents. Propofol is an alternative to thiopental in infants, and we have compared cardiovascular changes when propofol or thiopental was used for induction of anaesthesia in infants. Twenty infants, ASA I or II, aged 1-11 months, undergoing elective surgery were allocated randomly to receive either thiopental or propofol for i.v. induction. Cardiovascular and echocardiographic data were recorded in both groups before, during and for 5 min after induction of anaesthesia. Doses required to induce anaesthesia in each group were mean 10.3 (SD 0.9) mg kg-1 of thiopental and 6.1 (0.6) mg kg-1 of propofol. Thiopental did not alter significantly systolic or mean arterial pressure, afterload indices, rate-corrected velocity of circumferential fibre shortening or cardiac index, but decreased shortening fraction at 1 and 5 min after induction compared with awake values. Propofol did not alter heart rate, shortening fraction, rate-corrected velocity of circumferential fibre shortening or cardiac index at 1 and 5 min after i.v. induction compared with awake values. After induction, systolic and mean arterial pressures and afterload indices decreased more after induction with both agents, but did not become abnormal. Thus propofol decreased arterial pressure more than thiopental because of an effect on afterload. Cardiac output remained unchanged with both agents.
The study evaluated the effects of premedication with intravenous clonidine on thiopental or propofol requirements for induction and haemodynamic changes associated with both induction and endotracheal intubation. Clonidine administered intravenously before induction of anaesthesia reduced propofol or thiopental requirements. The association of clonidine and propofol caused, after injection of the induction drug, a decrease in mean arterial pressure which was significantly greater than with thiopental. Moreover, a major haemodynamic stability was registered before and after laryngoscopy in the clonidine-thiopental group. These findings might contraindicate the clonidine-propofol combination in patients with cardiovascular disease.
We compared the effects of remifentanil and alfentanil on arterial pressure and heart rate at induction of anaesthesia and tracheal intubation in 40 ASA I-III patients aged greater than 65 yr, in a randomized double-blind study.
Patients received either remifentanil 0.5 microg kg(-1) over 30 s, followed by an infusion of 0.1 microg kg min(-1) (group R) or alfentanil 10 microg kg(-1) over 30 s, followed by an infusion of saline (group A). Anaesthesia was then induced with propofol, rocuronium, and 1% isoflurane with 66% nitrous oxide in oxygen.
Systolic arterial pressure (SAP) and mean arterial pressure (MAP) decreased after the induction of anaesthesia (P<0.05) and increased for 3 min after intubation in both groups (P<0.05), but remained below baseline values throughout. Heart rate remained stable after induction of anaesthesia but increased significantly from baseline after intubation for 1 and 4 min in groups R and A, respectively (P<0.05). There were no significant between-group differences in SAP, MAP, and heart rate. Diastolic pressure was significantly higher in group A than group R at 4 and 5 min after intubation (P<0.05). Hypotension (SAP < 100 mm Hg) occurred in four patients in group R and three patients in group A.
Remifentanil and alfentanil similarly attenuate the pressor response to laryngoscopy and intubation, but the incidence of hypotension confirms that both drugs should be used with caution in elderly patients.
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.
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.
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.
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.
Controlling the cerebral and systemic hemodynamic responses to laryngoscopy and tracheal intubation may play a role in determining clinical outcome in pediatric neurosurgical patients. This study compared the effects of remifentanil and fentanyl on cerebral blood flow velocity (CBFV) and hemodynamic profile during laryngoscopy and tracheal intubation in children under sevoflurane anesthesia.
Sixty healthy children aged two to six years undergoing dental surgery under general anesthesia were enrolled. Each child was randomly assigned to receive a remifentanil or fentanyl infusion, at a rate of 0.75, 1.0, or 1.5 microg x kg(-1) x min(-1) after induction of anesthesia with 2% sevoflurane. Middle cerebral artery blood flow velocity was measured by transcranial Doppler (TCD) sonography. Once a baseline set of hemodynamic variables and TCD measurements were recorded, the opioid infusion was started. Measurements were taken at two-minute intervals, starting four minutes prior to laryngoscopy until four minutes following naso-tracheal intubation.
Remifentanil caused a more significant decrease in mean arterial pressure and CBFV prior to tracheal intubation than did fentanyl (P < 0.001). During laryngoscopy and for two minutes following tracheal intubation, CBFV increased in all remifentanil groups (P < 0.05), whereas it remained stable in all fentanyl groups.
This study suggests that fentanyl was more effective than remifentanil at preventing increases in CBFV during and immediately following laryngoscopy and tracheal intubation in children undergoing sevoflurane anesthesia. Fentanyl also seemed to provide a more stable hemodynamic profile prior to laryngoscopy and tracheal intubation when compared to remifentanil.
Administration of remifentanil followed by propofol provides adequate conditions for tracheal intubation without muscle relaxants. Other hypnotic drugs have not been thoroughly investigated in this regard. Intubating conditions with remifentanil followed by propofol, thiopentone or etomidate are compared in this study.
In a randomized, double-blind study 45 healthy males were assigned to one of three groups (n = 15). After iv atropine, remifentanil 3 microg x kg(-1) were injected over 90 sec followed by propofol 2 mg x kg(-1) (Group I), thiopentone 6 mg x kg(-1) (Group II) or etomidate 0.3 mg x kg(-1) (Group III). Ninety seconds after the administration of the hypnotic agent, laryngoscopy and intubation were attempted. Intubating conditions were assessed as excellent, good or poor on the basis of ease of ventilation, jaw relaxation, position of the vocal cords, and patient response to intubation and slow inflation of the endotracheal tube cuff.
One patient in Group I, three patients in Group II and five patients in Group III could not be intubated on the first attempt. Clinically acceptable intubating conditions were observed in 93.3%, 66.7%, 40.0% of patients in Groups I, II and III, respectively. Overall conditions at intubation were significantly (P < 0.05) better, and the frequency of excellent conditions was significantly (P < 0.05) higher in the propofol group compared with the thiopentone and etomidate groups. No patient was treated for hypotension or bradycardia.
Propofol 2 mg x kg(-1) was superior to thiopentone 6 mg x kg(-1) and etomidate 0.3 mg x kg(-1) for tracheal intubation when combined with remifentanil 3 microg x kg(-1) and no muscle relaxant.
Cerebral blood flow is affected by painful stimuli, and analgesic agents may alter the response of cerebral blood flow to pain. We set out to quantify the effects of remifentanil and nitrous oxide on blood flow changes caused by experimental pain.
We simulated surgical pain in 10 conscious volunteers using increasing mechanical pressure to the tibia. We measured changes in cerebral blood flow velocity in the middle cerebral artery (CBFV(MCA)) caused by the pain, using transcranial Doppler sonography. We gave increasing doses of remifentanil (0.025, 0.05 and 0.1 micro g kg(-1) min(-1)) or nitrous oxide [20%, 35% and 50% end-tidal concentration (FE'(N(2)O))] and compared these effects on blood flow changes.
Nitrous oxide increased CBFV(MCA) only when given at 50% FE'(N(2)O). Remifentanil did not affect CBFV(MCA). Pain increased CBFV(MCA). Both agents attenuated this pain-induced change in CBFV(MCA) with the exception of nitrous oxide at 20% FE'(N(2)O).
Inhalation of nitrous oxide or adminstration of remifentanil attenuated pain-induced changes in CBFV(MCA).
Background: Although the effects of propofol on cerebral metabolism have been studied in animals, these effects have yet to be directly examined in humans. Consequently, we used positron emission tomography (PET) to demonstrate in vivo the regional cerebral metabolic changes that occur in humans during propofol anesthesia, Methods: Six volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism, and the other assessed metabolism during anesthesia with a propofol infusion titrated to the point of unresponsiveness (mean rate +/- SD = 7.8 +/- 1.5 mg.kg(-1).h(-1)). Scans were obtained using the (18)fluorodeoxyglucose technique. Results: Awake whole-brain glucose metabolic rates (GMR) averaged 29 +/- 8 mu moles.100g(-1)min(-1) (mean +/- SD). Anesthetized whole-brain GMR averaged 13 +/- 4 mu moles.100g(-1).min(-1) (paired t test, P less than or equal to 0.007), GMR decreased in all measured areas during anesthesia. However, the decrease in GMR was not uniform. Cortical metabolism was depressed 58%, whereas subcortical metabolism was depressed 48% (P less than or equal to 0.001). Marked differences within cortical regions also occurred. In the medial and subcortical regions, the largest percent decreases occurred in the left anterior cingulate and the inferior colliculus. Conclusion: Propofol produced a global metabolic depression on the human central nervous system, The metabolic pattern evident during anesthesia was reproducible and differed from that seen in the awake condition. These findings are consistent with those from previous animal studies and suggest PET may be useful for investigating the mechanisms of anesthesia in humans.
Formation and rupture of cerebral aneurysms have been associated with chronic hypertension. The effect of transient increase in blood pressure and its effect on intra-aneurysmal hemodynamics have not been studied. We examined the effects of controlled increases in blood pressure on different pressure parameters inside the sac of human cerebral aneurysms and corresponding parent arteries using invasive technology. Twelve patients (10 female, 2 male, age 54±15 years) with unruptured cerebral aneurysms undergoing endovascular coiling were recruited. Dual-sensor microwires with the capacity to simultaneously measure flow velocity and pressure were used to measure systolic, diastolic, and mean pressure inside the aneurysm sac and to measure both pressures and flow velocities in the feeder vessel just outside the aneurysm. These pressures were recorded simultaneously with pressures from a radial arterial catheter. Measurements were taken at baseline and then during a gradual increase in systemic systolic blood pressure to a target value of ≈25 mm Hg above baseline, using a phenylephrine infusion. The dose needed to achieve the required increase in radial arterial systolic blood pressure was 0.8±0.2 μg/kg/min. There was a clear linear relationship between changes in radial and aneurysmal pressures with substantial patient-by-patient variation in the slopes of those relationships. The overall increases in systolic and mean pressures in both radial artery and in the aneurysms were similar. Pressures in the aneurysm and in the parent vessels were similar. Peak and mean flow velocities in the parent arteries did not change significantly with phenylephrine infusion, nor did vessel diameters as measured angiographically.
© 2015 American Heart Association, Inc.
Purpose
To observe the changes in EEG bispectral index (BIS), 95% spectral edge frequency (95% SEF) and median frequency (MF) with haemodynamic changes to intubation during induction with propofol or propofol and 2 μg· kg−1 fentanyliv.
Methods
Twenty four ASA 1–11 patients were randomized to receive either propofol infusion preceded by normal saline (group P, n= 12) or propofol preceded by 2 μg· kg−1 fentanyl (group PF, n= 12). Intubation was performed five minutes after maintenance of BIS within 45 ± 5. EEG and haemodynamic variables were recorded at before induction, and before and after intubation.
Results
Haemodynamic responses to intubation were greater in group P than in group PF (P < 0.05). Postintubation SBP, DBP and HR increased, compared with preinduction values, more in group P than in group PF Postintubation BIS values increased from 45.5 ± 3.5 and 44.2 ± 4.1 to 51.1 ± 4.1 and 50.9 ± 5.3 in groups P and PF, respectively, compared with preintubation values. The BIS values were not different between treatment groups before and after intubation, and 95% SEF and MF values did not increase after intubation.
Conclusion
Fentanyl, 2 μg· kg−1iv, blunted the haemodynamic responses to intubation, but failed to attenuate the arousal of cerebral cortical activity. The different haemodynamic responses postintubation but similar BIS and 95% SEF changes in the two groups suggest that BIS or 95% SEF cannot predict the haemodynamic responses to intubation during anaesthesia induction with propofol and fentanyl.
Changes in cardiac index (Cl) and estimated systemic vascular resistance (ESVR) were assessed non-invasively using pulsed
Doppler ultrasound during induction of anaesthesia. Ninety-six ASA I patients were allocated randomly to one of four groups
to receive alfentanil 8 μg kg1 followed by a dose of thiopentone, methohexitone, propofol or etomidate sufficient to obtund the eyelash reflex. Cl increased
significantly by 8% 1 min after administration of both methohexitone (? < 0.05) and propofol (P < 0.05), returning to pre-induction
values thereafter. Cl increased after thiopentone but the increase was not statatistically significant. There was a significant
decrease in Cl of 16% after induction with etomidate (P < 0.001). ESVR decreased significantly from pre-induction values by
18% after methohexitone (P < 0.001) and 23% after propofol (P < 0.001). ESVR in the thiopentone group decreased, but this
was not statistically significant. ESVR increased significantly by 12% 1 min after induction of anaesthesia with etomidate
(P < 0.05) and then decreased towards pre-induction values. The results suggest that the cardiostability of etomidate may
not be as complete in all groups of patients as previous studies have suggested.
The cerebrovascular response to CO2 has been reported to be preserved during propofol anesthesia, but no comparison with awake control values has been made, and the additional influence of N2O has not been investigated. Using the noninvasive technique of transcranial Doppler ultrasonography, this study investigated the cerebrovascular response to varying levels of PaCO2 while awake and during anesthesia with propofol and propofol/N2O. Seven adults without systemic diseases undergoing nonneurologic surgery were studied. A pulsed-wave Doppler monitor was used to measure the mean middle cerebral artery flow velocity (Vmca) during varying levels of PaCO2 (25-55 mmHg) under the following conditions: 1) awake; 2) propofol 2.5 mg.kg-1 bolus followed by continuous infusion of 150 micrograms.kg-1.min-1; and 3) propofol as in the condition above plus 70% N2O. During the awake study condition, hypocapnia was induced by voluntary hyperventilation, and hypercapnia was induced with rebreathing of 7% CO2 in a closed circuit. During the anesthetized study conditions, hypocapnia and hypercapnia were induced by adjustment of minute ventilation. A minimum of five to six simultaneous Vmca and PaCO2 measurements were obtained under each of the study conditions. Systemic blood pressure was monitored via a radial arterial catheter, and phenylephrine was administered if mean arterial blood pressure decreased below 60 mmHg (phenylephrine was used in three of five patients in the propofol-N2O group). Linear regression and analysis of covariance were used for statistical analysis of Vmca-PaCO2 relationships.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of sufentanil on human cerebral blood flow (CBF) was studied in seven unpremedicated, healthy volunteers 31 +/- 3.5 yr of age (mean +/- SD) and either sex. CBF (ml.100 g-1.min-1) was measured noninvasively with the 133Xe clearance technique and a scintillation camera before and after sufentanil 0.5 micrograms/kg administered intravenously. This technique provides values for global blood flow and for gray and white matter blood flow, and from 13 preselected regions in one hemisphere. After the administration of sufentanil, the volunteers were stimulated verbally in order to prevent their loss of consciousness and hypercarbia. Heart rate (HR), arterial pressure, oxyhemoglobin saturation, and end-tidal CO2 (ETCO2 were recorded during the measurements. Neither global CBF (46.1 +/- 1.6 control and 43 +/- 1.9 after sufentanil, mean +/- SEM) nor gray (76.5 +/- 3.2 and 70.9 +/- 6.1) or white (22.7 +/- 1.5 and 24.2 +/- 1.6) matter blood flow changed significantly after sufentanil administration. As well, no significant differences in HR (72 +/- 4 control and 79 +/- 4 beats per min after sufentanil) and ETCO2 (39.8 +/- 1.4 and 41.1 +/- 1.1 mmHg) were observed. It is concluded that sufentanil has no significant effect on CBF in healthy human volunteers.
Cerebral blood flow, cerebral oxygen consumption, lactate and glucose metabolism were measured in 13 patients during anaesthesia with nitrous oxide, oxygen and enflurane 0.5% and after 30 minutes infusion of propofol. The mean blood concentration of propofol was 4.06 micrograms/ml. Cerebral blood flow decreased by 27.6% and cerebral vascular resistance by 51%. There were no changes in lactate and glucose metabolism. Cerebral oxygen consumption decreased by 18.25%. Changes in the electro-encephalograph were related to the blood levels of propofol.
The haemodynamic response to tracheal intubation was compared in 303 patients in whom anaesthesia was induced with either thiopentone 4 mg/kg, etomidate 0.3 mg/kg or propofol 2.5 mg/kg, with and without fentanyl 2 micrograms/kg. There was after propofol alone a significant decrease in arterial blood pressure, which did not increase above control values after intubation. Significant increases in arterial pressure followed intubation in patients induced with thiopentone or etomidate alone. Increases in heart rate occurred with all agents after laryngoscopy. The use of fentanyl resulted in arterial pressures lower than those after the induction agent alone, and in an attenuation, but not abolition of the responses to laryngoscopy and intubation.
Measurement of intracranial arterial blood flow velocity is a new technique with potentially a number of very useful applications. This study validates the technique by comparing it to cerebral blood flow (CBF) measured using intravenous Xenon133 and extracranial clearance recording. We have measured the middle cerebral artery (MCA) blood flow velocity in 17 symptomatic patients with the EME TC 264 transcranial Doppler velocimeter and compared these measurements to the ipsilateral hemispheric cerebral blood flow measured with an intravenous Xenon133 technique (Novo Cerebrograph 10A). Measurements were made at rest and during hypercapnia. The absolute measurement of MCA velocity and hemispheric CBF showed a poor correlation (r = 0.424, p less than 0.01) due to wide between-patient variations at rest but the blood flow response to hypercapnia, expressed as a reactivity index, showed a good correlation (r = 0.849, p less than 0.001). Thus changes in MCA velocity reliably correlate with changes in cerebral blood flow but the absolute velocity cannot be used as an indicator of CBF.
The cardiovascular response to laryngoscopy and intubation was investigated in lightly anaesthetised patients admitted to hospital for elective intracranial surgery. One group of patients was given fentanyl 5 μg/kg body weight before induction with thiopentone and suxamethonium. The other group served as controls. Fentanyl treatment caused a significant attenuation of the blood pressure and pulse response to laryngoscopy and intubation.
Different techniques for induction of anaesthesia are discussed in relation to the demands of neuroanaesthesia.
The purpose of this study was to correlate changes in cerebral blood flow velocity (Vmean) with cerebral blood flow (CBF) during isoflurane anesthesia in dogs. The relation between cerebral oxygen consumption (CMRO2) and electroencephalogram (EEG) analysis also was investigated. Blood flow velocity was measured in the middle cerebral artery using a pulsed transcranial Doppler (TCD). CBF was measured with radioactive microspheres. EEG was measured over both hemispheres and median EEG frequency (median frequency) was calculated after fast Fourier transformation. Baseline anesthesia was maintained with 50% nitrous oxide in oxygen and 50 micrograms.kg-1 x h-1 fentanyl. Animals of Group I (control, n = 6) were not given isoflurane. Data were recorded at baseline, and at 30, 60, and 90 min. There was no significant change in any variable over time. In Group II (n = 7), data were recorded at baseline and at 1%, 2%, and 3% end-tidal isoflurane. Mean arterial pressure was maintained at baseline levels by phenylephrine infusion. CBF increased from 70.8 +/- 10.6 mL.100g-1 x min-1 at baseline to 146.1 +/- 36.9 mL.100 g-1 x min-1 with 3% isoflurane (P < 0.01). Vmean increased from 38.3 +/- 6.7 cm/s to 65.6 +/- 9.7 cm/s (P < 0.01). The correlation between relative changes in CBF and Vmean was r = 0.94 (P < 0.01). With 1% isoflurane the EEG shifted to slow-wave, high-voltage activity, and median frequency decreased from 5.9 +/- 0.7 Hz to 1.4 +/- 0.4 Hz (P < 0.05). Median frequency was not decreased further during 2% and 3% isoflurane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
The hemodynamic response to the stress of laryngoscopy and endotracheal intubation does not present a problem for most patients. However, patients with cardiovascular or cerebral disease may be at increased risk of morbidity and mortality from the tachycardia and hypertension resulting from this stress. These hemodynamic effects gained notice after the introduction and use of muscle relaxants, such as curare and succinylcholine, for endotracheal intubation at the time of anesthesia induction. A variety of anesthetic techniques and drugs are available to control the hemodynamic response to laryngoscopy and intubation. The method or drug of choice depends on many factors, including the urgency and length of surgery, choice of anesthetic technique, route of administration, medical condition of the patient, and individual preference. The possible solutions number as many as the medications and techniques available and depend on the individual patient and anesthesia care provider. This paper reviews these medications and techniques to guide the clinician in choosing the best methods.
The purpose of this project was to develop a computer model of cerebrovascular hemodynamics interacting with a pharmacokinetic drug model to examine the effects of various stimuli on cerebral blood flow and intracranial pressure during anesthesia.
The mathematical model of intracranial hemodynamics is a seven-compartment, constant-volume system. A series of resistance relate blood and cerebrospinal fluid fluxes to pressure gradients between compartments. Arterial, venous, and tissue compliance are also included. Autoregulation is modeled by transmural pressure-dependent, arterial-arteriolar resistance. The effect of a drug (thiopental) on cerebrovascular circulation was simulated by a variable arteriolar-capillary resistance. Thiopental concentration was predicted by a three-compartment, pharmacokinetic model. The effect site compartment was included to account for a disequilibrium between drug plasma and biophase concentrations. The model was validated by comparing simulation results with available experimental observations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible PC.
The model developed was used to calculate the cerebral blood flow and intracranial pressure changes that occur during the induction phase of general anesthesia. Responses to laryngoscopy and intubation were predicted for simulated patients with elevated intracranial pressure and non-autoregulated cerebral circulation. Simulation shows that the induction dose of thiopental reduces intracranial pressure up to 15%. The duration of this effect is limited to less than 3 minutes by rapid redistribution of thiopental and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial intracranial pressure. Further simulation predicts that this untoward effect can be minimized by an additional dose of thiopental administered immediately prior to intubation.
The presented simulation allows comparison of various drug administration schedules to control intracranial pressure and preserve cerebral blood flow during induction of anesthesia. The model developed can be extended to analyze more complex intraoperative events by adding new submodels.
Although the anesthetic effects of the intravenous anesthetic agent propofol have been studied in the living human brain using brain imaging technology, the nature of the anesthetic state evident in the human brain during inhalational anesthesia remains unknown. To examine this issue, the authors studied the effects of isoflurane anesthesia on human cerebral glucose metabolism using positron emission tomography (PET).
Five volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism and the other scan assessed metabolism during isoflurane anesthesia titrated to the point of unresponsiveness (means +/- SD; expired = 0.5 +/- 0.1%). Scans were obtained with a GE2048 scanner (4.5-mm resolution-FWHM) using the 18fluorodeoxyglucose technique.
Awake whole-brain glucose metabolism averaged 6.9 +/- 1.5 mg.100 g-1.min-1 (means +/- SD). Isoflurane reduced whole-brain metabolism 46 +/- 11% to 3.6 +/- 0.3 mg.100 g-1.min-1 (P < or = 0.005). Regional metabolism decreased fairly uniformly throughout the brain, and no evidence of any regional metabolic increases were found in any brain region for any participant. A region-of-interest analysis showed that the pattern of regional metabolism evident during isoflurane anesthesia was not significantly different from that seen when participants were awake.
These data clarify that the anesthetic state evident in the living human brain during unresponsiveness induced with isoflurane is associated with a global, fairly uniform, whole-brain glucose metabolic reduction of 46 +/- 11%.
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We investigated the cerebral hemodynamic effects of 0.5 and 1.5 minimum alveolar anesthetic concentration (MAC) sevoflurane during propofol anesthesia in 10 patients undergoing supratentorial tumor resection. All patients received a standardized anesthetic, and their lungs were ventilated with a mixture of air and oxygen to produce mild hypocapnia. Anesthesia was then maintained with a propofol infusion. Muscle relaxation was obtained by infusion of atracurium. A transcranial Doppler probe was used to measure red cell flow velocity in the right middle cerebral artery (Vmca). A right-sided jugular bulb catheter was inserted for sampling of jugular bulb blood. After a 30-min period of stabilization and before the start of surgery, baseline arterial and jugular bulb blood samples were drawn to define the arterial-venous oxygen content difference (AVDO2). Mean arterial pressure and Vmca were recorded. Sevoflurane (0.5 and 1.5 MAC) in oxygen/air was then administered, and all measurements were repeated. Administration of sevoflurane at 0.5 MAC did not change Vmca or AVDO2. Sevoflurane (1.5 MAC) did not change Vmca. There was an approximately 25% reduction in AVDO2 (P < 0.05). This suggests that during propofol anesthesia, although 1.5 MAC sevoflurane does not increase red blood cell velocity, there is a relative increase in flow with respect to metabolism. Administration of large-dose sevoflurane may be associated with a degree of luxury perfusion.
Implications:
We investigated the cerebral hemodynamic effects of sevoflurane in patients undergoing neurosurgery. Small-dose sevoflurane (1%) did not change brain blood flow or oxygen consumption. Large-dose sevoflurane (3%) did not change flow velocity but reduced brain oxygen consumption by 25%. Sevoflurane may provide a degree of luxury perfusion.
An important limitation of transcranial Doppler (TCD) ultrasonography is its inability to directly measure blood flow or vessel diameter. To extend the ability of TCD ultrasonography, indices were derived from an intensity-weighted mean of the entire Doppler spectrum. The objective of this article is to test the behavior of these indices under conditions of diameter constancy (hyper- and hypoventilation) and when vessel diameter decreases (vasospasm).
A flow index (FI) was calculated by averaging several heartbeats of spectral data and calculating the first spectral moment. An area index (AI) was defined as the FI divided by the mean velocity, motivated by the knowledge that vessel flow is the product of vessel diameter and mean velocity. To test the FI and the AI under conditions of diameter constancy, middle cerebral artery Doppler signals were obtained from 20 patients during conditions of hypercarbia, hypocarbia, and normocarbia. To test the ability of these indices to evaluate a decrease in vessel diameter, signals from 41 sites on 23 arteries were obtained from patients who underwent both TCD and angiographic studies on two separate occasions after the occurrence of subarachnoid hemorrhage. The changes in the AI were compared with the arterial diameters measured from angiograms.
The FI was proportional to the mean velocity in the cohort of healthy patients (r=0.97). The AI changed by less than 3% in the same cohort. The AI predicted the direction of the diameter change in all vessels showing angiographic changes in area. Changes in the AI and the measured angiographic changes in cross-sectional areas were correlated (overall, r=0.90; with two outlines removed, r=0.86).
This variant of the intensity-weighted mean predicts changes in vessel cross-sectional area under conditions of changes in CO2 and cerebral vasospasm. This preliminary study suggests that careful use of this tool may provide accurate evaluation of cerebral blood flow through the large vessels and quantitative changes in diameter, which occur frequently after subarachnoid hemorrhage.
Venodilation is thought to be one of the mechanisms underlying propofol-induced hypotension. The purpose of this study is to test two hypotheses: (1) propofol increases systemic vascular capacitance, and (2) the capacitance change produced by propofol is a result of an inhibition of sympathetic vasoconstrictor activity.
In 33 Wistar rats previously anesthetized with urethane and ketamine, vascular capacitance was examined before and after propofol infusion by measuring mean circulatory filling pressure (Pmcf). The Pmcf was measured during a brief period of circulatory arrest produced by inflating an indwelling balloon in the right atrium. Rats were assigned into four groups: an intact group, a sympathetic nervous system (SNS)-block group produced by hexamethonium infusion, a SNS-block + noradrenaline (NA) group, and a hypovolemic group. The Pmcf was measured at a control state and 2 min after a bolus administration of 2, 10, and 20 mg/kg of propofol.
The mean arterial pressure (MAP) was decreased by propofol dose-dependently in intact, hypovolemic, and SNS-block groups, but the decrease in MAP was less in the SNS-block group (-25%) than in the intact (-50%) and hypovolemic (-61%) groups. In the SNS-block + NA group, MAP decreased only at 20 mg/kg of propofol (-18%). The Pmcf decreased in intact and hypovolemic groups in a dose-dependent fashion but was unchanged in the SNS-block and SNS-block + NA groups.
The results have provided two principal findings: (1) propofol decreases Pmcf dose-dependently, and (2) the decrease in Pmcf by propofol is elicited only when the sympathetic nervous system is intact, suggesting that propofol increases systemic vascular capacitance as a result of an inhibition of sympathetic nervous system.
Although serial transcranial Doppler measurements of blood flow velocity are of considerable clinical utility, their use assumes that the velocity signals are stable and unchanging during short time periods. Contrary to this assumption, the authors found significant variations in mean velocity signals in both normal subjects and patients, which may confound the interpretation of serial studies. Signals were continuously obtained for 5 to 10 minutes from the middle cerebral artery of 11 normal subjects and 18 patients (22 studies) with a variety of neurosurgical disorders. The average difference between the peak and the trough in the waves observed in the normal population was 11 +/- 4% (standard error of mean), and 5 of the 11 had at least one wave with a difference of more than 20%. The average difference between the peak and trough signals in the neurosurgical population was 14 +/- 13% (SEM) and 13 of the 22 studies showed at least one wave with a difference of more than 20%. These variations were consistently seen and may be related to similar variations in blood pressure or intracranial pressure waves. Whatever the origin, these variations should be recognized during the interpretation of transcranial Doppler signal in clinical practice.
We have developed a computer model of cerebrovascular hemodynamics that interacts with a pharmacokinetic drug model. We used this model to examine the effects of various stimuli occurring during anesthesia on cerebral blood flow (CBF) and intracranial pressure (ICP). The model is a seven-compartment constant-volume system. A series of resistances and compliances relate blood and cerebrovascular fluid fluxes to pressure gradients between compartments. Variable arterial-arteriolar resistance (Ra-ar) and arteriolar-capillary resistance (Rar-c) simulate autoregulation and drug effects, respectively. Rar-c is also used to account for the effect of CO2 on the cerebral circulation. A three-compartment pharmacokinetic model predicts concentration-time profiles of intravenous induction agents. The effect-site compartment is included to account for disequilibrium between drug plasma and biophase concentrations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible personal computer. Using the model, we have predicted ICP responses during induction of anesthesia for a simulated patient with normal as well as elevated ICP. Simulation shows that the induction dose of intravenous anesthetic reduces ICP up to 30% (propofol > thiopental > etomidate). The duration of this effect is limited to less than 5 minutes by rapid drug redistribution and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial ICP. ICP elevation is more pronounced in a nonautoregulated cerebral circulation. Simulation results are in good agreement with the available experimental data. The presented model allows comparison of various drug administration schedules to control ICP.
The effect of three bolus doses of remifentanil on the pressor response to laryngoscopy and tracheal intubation during rapid
sequence induction of anaesthesia was assessed in a randomized, double-blind, placebo-controlled study in four groups of 20
patients each. After preoxygenation, anaesthesia was induced with thiopental 5-7 mg kg-1 followed immediately by saline (placebo)
or remifentanil 0.5, 1.0 or 1.25 micrograms kg-1 given as a bolus over 30 s. Cricoid pressure was applied just after loss
of consciousness. Succinylcholine 1 mg kg-1 was given for neuromuscular block. Laryngoscopy and tracheal intubation were performed
1 min later. Arterial pressure and heart rate were recorded at intervals until 5 min after intubation. Remifentanil 0.5 microgram
kg-1 was ineffective in controlling the increase in heart rate and arterial pressure after intubation but the 1.0 and 1.25
micrograms kg-1 doses were effective in controlling the response. The use of the 1.25 micrograms kg-1 dose was however, associated
with a decrease in systolic arterial pressure to less than 90 mm Hg in seven of 20 patients.
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We investigated, in brain tumor patients, the jugular bulb venous oxygen partial pressure (PjO2) and hemoglobin saturation (SjO2), the arterial to jugular bulb venous oxygen content difference (AJDO2), and middle cerebral artery blood flow velocity (Vmca) during anesthesia, and the effect of hyperventilation on these variables. Twenty patients were randomized to receive either isoflurane/ nitrous oxide/fentanyl (Group 1) or propofol/fentanyl (Group 2). At normoventilation (PacO2 35 +/- 2 mm Hg in Group 1 and 33 +/- 3 mm Hg in Group 2), SjO2 and PjO2 were significantly higher in Group 1 than in Group 2 (SjO2 60% +/- 6% and 49% +/- 13%, respectively; P = 0.019) (PjO2 32 +/- 3 and 27 +/- 5 mm Hg, respectively; P = 0.027). In Group 2, 5 of 10 patients had SjO2 < 50%, and 3 of these patients had SjO2 < 40% and AJDO2 > 9 mL/dL. All patients in Group 1 had SjO2 > 50%. During hyperventilation, there were no differences in SjO2, PjO2, or AJDO2 between the two groups. On hyperventilation, there was no correlation between the relative decreases of Vmca and 1/AJDO2 (r = 0.21, P = 0.41). The results indicate during propofol anesthesia, half of the brain tumor patients showed signs of cerebral hypoperfusion, but not during isoflurane/nitrous oxide anesthesia. Furthermore, during PacO2 manipulations, shifts in Vmca are inadequate to evaluate brian oxygen delivery in these patients.
Implications:
During propofol anesthesia at normoventilation, 50% of brain tumor patients showed signs suggesting cerebral hypoperfusion, but this could not be demonstrated during isoflurane/nitrous oxide anesthesia. During PacO2 manipulations, consecutive measurements of the cerebral blood flow velocity may be inadequate to assess cerebral oxygenation.
Metabolic suppression may have a role in cerebral protection. It is often assumed that the cerebral metabolic and protective effects of qualitative burst suppression are similar to those of the isoelectric encephalogram (EEG). We have examined the effect of different degrees of EEG suppression on blood flow and oxygen difference during general anaesthesia. We studied 11 patients undergoing general anaesthesia for resection of acoustic neuromas. The study was performed after surgery with propofol and remifentanil anaesthesia. Transcranial Doppler ultrasonography and jugular bulb venous saturations were measured at values of EEG suppression: 0%, 50% and 100% (isoelectric EEG). Data from nine patients were suitable for analysis. There were no significant differences in mean arterial pressure, heart rate or PaCO2 during EEG activity, 50% burst suppression ratio or isoelectric EEG. There was a significant decrease in middle cerebral artery flow velocity (vmca) with increasing EEG suppression (0% suppression, mean 38 (SEM 4) cm s-1; 50% suppression, 29 (3) cm s-1; and 100% suppression, 24 (2) cm s-1; P < 0.05). Jugular bulb venous saturations did not change consistently with the change in EEG activity, indicating intact flow-metabolism coupling. We conclude that the degree of EEG suppression had a significant effect on blood flow. If flow-metabolism coupling is maintained, the assumption that cerebral metabolism during 50% EEG burst suppression is equivalent to isoelectric EEG may not be justified. If cerebral protection is related to brain metabolism, then an isoelectric EEG may give more cerebral protection than 50% burst suppression.
We assessed the haemodynamic changes after a propofol infusion at two rates in low-risk unpremedicated patients (ASA I-II). To determine contractility changes and loading conditions, we measured the ejection fraction, end-systolic quotient and fractional shortening on transthoracic echocardiograms. We studied 40 patients undergoing peripheral neurosurgical procedures under general anaesthesia induced by propofol alone (total dose 2.5 mg.kg-1). Patients were randomly assigned to receive propofol at an infusion rate of 10 mg.s-1; or 2 mg.s-1. Haemodynamic data were recorded simultaneously immediately before propofol infusion, at the end of infusion, and 5 and 10 min after the infusion ended. The higher infusion rate induced a larger decrease in mean arterial pressure than the lower infusion rate (- 20% vs. - 10% from baseline, p = 0.01). In both groups, global and segmental ventricular function remained unchanged throughout the study. In both groups, there were markedly reduced end-systolic quotients--presumably related to diminished afterload, and in the higher infusion-rate group a significant reduction in fractional shortening--presumably related principally to diminished preload.
To examine the relation between the effect of intravenous anesthetics on ischemic neurotransmission damage and their actions on N-methyl-d-aspartate (NMDA) receptors in an in vitro cerebral ischemic model.
Prospective, randomized study in freshly prepared rat hippocampal slices.
University research laboratory.
Hippocampal slices were prepared from male Wistar rats (4-5 wks old).
In vitro ischemia was induced by exposing slices to glucose-free Krebs solution gassed with 95% N2 /5% CO2 at 37.1-37.3 degrees C. Ischemic neurotransmission damage was indicated by the amplitudes of population spikes (PS) recorded from the CA1 pyramidal layer after stimulation of the Schaffer collaterals. The effect of anesthetics on NMDA receptors was determined by measuring the NMDA-mediated changes in intracellular calcium in the CA1 pyramidal layer with a calcium indicator, fura-2.
Following 4, 6, and 7.5 mins ischemia in vitro, the recoveries of PS (% control) were 100%, 17.5 +/- 21.8%, and 5.4 +/- 2.1%, respectively. 3-(R)-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 5 microM), an NMDA receptor antagonist, increased the recovery of PS to 88.3 +/- 24.5% after 6 mins ischemia, and to 42.1 +/- 18.7% after 7.5 mins ischemia. Thiopental (400 microM), thiamylal (400 microM), and ketamine (100 microM), but not propofol (100 microM) and etomidate (10 microM), improved the recovery of PS after 6 and 7.5 mins ischemia; the degrees of their protection were comparable to that of 5 microM CPP. The NMDA-mediated increases in intracellular calcium were almost completely inhibited by thiamylal, reduced to half by ketamine and thiopental, augmented by propofol, and not affected by etomidate.
The results indicate that the efficacy of intravenous anesthetics in attenuating ischemic neuronal damage varies among agents, relating to their effects on NMDA receptors.
To evaluate the cerebral vascular effects of cis-atracurium and rocuronium given after thiopental induction of anesthesia.
Randomized, single-blinded study.
University-affiliated hospital.
39 adult ASA physical status I and II patients undergoing nonintracranial procedures.
Patients received intravenously (IV), either saline placebo, cis-atracurium, or rocuronium after induction of general anesthesia with thiopental sodium.
The right middle cerebral artery was insonated using a pulsed-wave range-gated transcranial Doppler, and data were recorded at preinduction, immediately postinduction, at injection of the study drug, and at 15-second intervals for 3 minutes thereafter. The variables recorded for each subject included the systolic, diastolic, and mean flow velocity, as well as pulsality index, systolic, diastolic, and mean arterial blood pressure (MAP), and end-tidal carbon dioxide concentration.
No significant differences between the groups were present in the postanesthetic induction maximal or minimal mean flow velocity.
cis-Atracurium and rocuronium, administered after thiopental, do not produce clinically relevant changes in cerebral blood flow velocity.
The mechanisms of arterial hypotension following intravenous anesthetic induction agents are multifactorial. The purpose of this study was to evaluate and compare the effects of thiopental, propofol and etomidate on hemodynamics, sympathetic outflow and arterial baroreflex sensitivity using not only neuraxis-intact but also totally baro-denervated rabbits. A total of 60 rabbits was anesthetized with urethane, tracheotomized, and mechanically ventilated with oxygen in nitrogen (FiO2 0.5). The left renal sympathetic nerve was isolated and placed on a bipolar electrode to record renal sympathetic nerve activity (RSNA). Thirty animals underwent a surgical preparation of total baroreceptor denervation. Bolus injections of an anesthesia induction dose of thiopental 4 mg/kg and twice the induction dose of propofol 4 mg/kg significantly decreased RSNA to the same extent (19.4+/-6.7 and 19.7+/-5.2% reduction, mean +/- SEM) and mean arterial pressure (MAP) also to the same extent (19.5+/-4.6 and 22.1+/-3.1% reduction) in the neuraxis-intact animals. RSNA was increased (34.5+/-6%) without reduction of MAP by an induction dose of etomidate, 0.3 mg/kg. Sympathetic barosensitivity was attenuated even 10 min after thiopental at 4 mg/kg or propofol at 4 mg/kg (68% and 54% of control, respectively). Propofol at 2 mg/kg (induction dose) and etomidate at 0.6 mg/kg decreased RSNA and MAP only in the baro-denervated animals. It was found from the barosensitivity study that patients can be hemodynamically unstable even though blood pressure has returned to normal after thiopental and propofol administration. Data suggest that etomidate can even stimulate the sympathetic nervous system and increase sympathetic outflow. It was also clearly found from the baro-denervated animal study that thiopental was stronger than propofol in directly suppressing sympathetic outflow at the induction dose.
Adrenergic stress response induced by laryngoscopy and tracheal intubation (LTI) appears to be attenuated by esmolol, but its potential clinical benefits have not been fully weighed against possible adverse effects.
A systematic search up to May 2000 was performed using MEDLINE, EMBASE, LILACS, Cochrane library, manual searching and bibliographies in all languages. All randomised comparisons of esmolol with placebo on the haemodynamic changes elicited by LTI were obtained. Trials were included in the present meta-analysis if they recorded heart rate (HR), systolic pressure (SBP), mean arterial pressure (MAP) or diastolic pressure (DBP) at three different stages: pre-induction, immediately prior to intubation, and in the post-intubation period. Weighted mean differences (WMD) and 95% confidence intervals (CI) of the changes in the haemodynamic variables between treatment and placebo groups were calculated.
Of 72 publications identified, 38 randomised controlled trials containing a total of 2009 patients were finally included. Eleven different regimens and doses of esmolol demonstrated effectiveness in the attenuation of HR and BP after LTI in a dose-dependent manner. The most effective regimen was a loading dose of 500 microg x kg(-1) x min(-1) over 4 min followed by continuous infusion dose of 200-300 microg x kg(-1) x min(-1) [WMD: 20.2 bpm (95% CI: 15.6 to 24.7)]. High bolus dose (200 mg) of esmolol produced a considerable decrease in DBP [WMD 10.1 mmHg (95% CI: 7.3 to 12.8)].
Esmolol is effective, in a dose-dependent manner, in the attenuation of the adrenergic response to LTI. To minimise its adverse effects it should be administered, when considered clinically appropriate, as a continuous infusion regimen.
Transcranial Doppler (TCD) is used for diagnosis of vasospasm in patients with subarachnoid hemorrhage due to a ruptured aneurysm. Our aim was to evaluate both the accuracy of TCD compared with angiography and its usefulness as a screening method in this setting.
A search (MEDLINE, EMBASE, Cochrane Library, bibliographies, hand searching, any language, through January 31, 2001) was performed for studies comparing TCD with angiography. Data were critically appraised using a modified published 10-point score and were combined using a random-effects model.
Twenty-six reports compared TCD with angiography. Median validity score was 4.5 (range 1 to 8). Meta-analyses could be performed with data from 7 trials. For the middle cerebral artery (5 trials, 317 tests), sensitivity was 67% (95% CI 48% to 87%), specificity was 99% (98% to 100%), positive predictive value (PPV) was 97% (95% to 98%), and negative predictive value (NPV) was 78% (65% to 91%). For the anterior cerebral artery (3 trials, 171 tests), sensitivity was 42% (11% to 72%), specificity was 76% (53% to 100%), PPV was 56% (27% to 84%), and NPV was 69% (43% to 95%). Three of these 7 studies reported on the same patients, each on another artery, and for 4, data recycling could not be disproved. Other arteries were tested in only 1 trial each.
For the middle cerebral artery, TCD is not likely to indicate a spasm when angiography does not show one (high specificity), and TCD may be used to identify patients with a spasm (high PPV). For all other situations and arteries, there is either lack of evidence of accuracy or of any usefulness of TCD. Most of these data are of low methodological quality, bias cannot not be ruled out, and data reporting is often uncritical.
The potential benefit of propofol dose regimens that use physiologic pharmacokinetic modeling to target the brain has been demonstrated in animals, but no data are available on the rate of propofol distribution to the brain in humans. This study measured the brain uptake of propofol in humans and the simultaneous effects on electroencephalography, cerebral blood flow velocity (V(mca)), and cerebral oxygen extraction.
Seven subjects had arterial and jugular bulb catheters placed before induction. Electroencephalography and V(mca) were recorded during induction with propofol while blood samples were taken from both catheters for later propofol analysis. Brain uptake of propofol was calculated using mass balance principles, with effect compartment modeling used to quantitate the rate of uptake.
Bispectral index (electroencephalogram) values decreased to a minimum value of approximately 4 at around 7 min from the onset of propofol administration and then slowly recovered. This was accompanied by decreases in V(mca), reaching a minimum value of approximately 40% of baseline. Cerebral oxygen extraction did not change, suggesting parallel changes in cerebral metabolism. There was slow equilibrium of propofol between the blood and the brain (t(1/2keo) of 6.5 min), with a close relation between brain concentrations and bispectral index, although with considerable interpatient variability. The majority of the decreases in V(mca), and presumably cerebral metabolism, corresponded with bispectral index values reaching 40-50 and the onset of burst suppression.
Description of brain distribution of propofol will allow development of physiologic pharmacokinetic models for propofol and evaluation of dose regimens that target the brain.
Nitrous oxide (N2O) and propofol exhibit directionally opposite effects on the cerebral circulation, vasodilation and vasoconstriction, respectively. The authors investigated an interaction between the two anesthetic agents on the dynamic cerebrovascular response to step changes in end-tidal pressure of carbon dioxide (PetCO2) in humans.
Participants with no systemic diseases were allocated into two groups, each of which was anesthetized sequentially with two protocols. Patients in group 1 were anesthetized with 30% O2 + 70% N2O. A continuous intravenous infusion of propofol (7-10 mg x kg(-1) x h(-1)) was then added to the N2O. Patients in group 2 were anesthetized first with continuous infusion of propofol (10 mg x kg(-1) h(-1)), and then 30% O2 + 70% N2O was added to the propofol anesthesia. Using transcranial Doppler ultrasonography, blood flow velocity at the middle cerebral artery (FV(MCA)) was measured during a step increase (on-response) followed by a step decrease (off-response) in PetCO2, with PetCO2 ranging between approximately 28 and 50 mmHg. The dynamic FV(MCA)-PetCO2 relationship was analyzed using a mathematical model that was characterized with a pure time delay, and a time constant and a gain each for the on- or off-response.
The addition of propofol to the N2O anesthesia increased the on-response time constant (P < 0.01), whereas the addition of N2O to the propofol anesthesia increased the time constants for on- (P < 0.01) and off-responses (P < 0.05). However, the addition of either anesthetic did not affect the gains.
Propofol and N2O, when one is added to the other, produce similar dynamic FV(MCA) responses to sudden changes in PetCO2. Addition of each anesthetic slows the dynamic response and produces the response whose magnitude is proportional to the baseline FV(MCA).
To compare intubation conditions and hemodynamic effects resulting from thiopental-rapacuronium, propofol-rapacuronium, and etomidate-rapacuronium intravenous (IV) induction.
Randomized, blinded study.
Operating suites of a large university-affiliated medical center.
60 ASA physical status I and II adult patients without airway abnormalities, who were scheduled for elective surgery requiring endotracheal intubation. Patients were randomly allocated to receive IV thiopental sodium 5 mg/kg (Group 1), propofol 2 mg/kg (Group 2), or etomidate 0.3 mg/kg (Group 3) followed by rapacuronium 1.5 mg/kg. Fifty seconds later, an anesthesiologist, who had no knowledge of the induction drug used, entered the operating room and attempted laryngoscopy and intubation.
Intubation conditions were graded as excellent, good, poor, or impossible according to Good Clinical Research Practice criteria. Arterial blood pressure and heart rate changes accompanying both induction techniques were also monitored and recorded.
All patients were intubated within 55 to 70 seconds. Clinically acceptable intubation conditions were not statistically different among the three groups. Moderate tachycardia after induction was seen in all three groups, and blood pressure was significantly lower in Group 2 than in Groups 1 or 3.
Clinically acceptable intubation conditions are similar after either thiopental, propofol, or etomidate when a fast-onset neuromuscular blocking drug (rapacuronium 1.5 mg/kg) is used to facilitate tracheal intubation.
Unlabelled:
In healthy individuals, cerebrovascular pressure autoregulation is preserved or even improved when propofol is infused. We examined the effect of an increase in propofol plasma concentration on pressure autoregulation in 10 head-injured patients. Using target-controlled infusions, the static rate of autoregulation was determined at a moderate (2.3 +/- 0.4 microg/mL) and a large (4.3 +/- 0.04 microg/mL) plasma target concentration of propofol. Using norepinephrine to control cerebral perfusion pressure, transcranial Doppler measurements from the middle cerebral artery were made at a cerebral perfusion pressure of 70 and 85 mm Hg at each propofol concentration. Middle cerebral artery flow velocities at the large propofol concentration were significantly lower than at the moderate concentration, without any concurrent increase in arterio-jugular difference in oxygen content, a finding compatible with maintained flow-metabolism coupling. Despite this, static rate of autoregulation decreased significantly from 54% +/- 36% to 28% +/- 35% (P = 0.029). Our data suggest that after head injury, the cerebrovascular effects of propofol are different from those observed in healthy individuals. We propose that large doses of propofol should be used cautiously in head-injured patients, because there is the potential to increase the injured brain's vulnerability to secondary insults.
Implications:
Propofol is used for sedation and control of intracranial pressure in head-injured patients. In contrast to previous data from healthy individuals, we show a deterioration of cerebrovascular pressure autoregulation with fast propofol infusion rates after head injury. Large propofol doses may increase the injured brain's vulnerability to secondary insults.
Etomidate-associated hypnosis has only been studied using standard clinical criteria and raw EEG variables. We conducted a BIS-based investigation of etomidate induction of general anaesthesia.
Thirty hydroxyzine-premedicated ASA I patients were randomly allocated to receive etomidate 0.2, 0.3, or 0.4 mg kg(-1) intravenously over 30 s. The BIS was continuously recorded. A tourniquet was placed on a lower limb to record purposeful movements and myoclonia. Tracheal intubation was facilitated using rocuronium 0.6 mg kg(-1) when the BIS value was 50. The times to disappearance of the eyelash reflex, to a decrease in the BIS to 50, and to tracheal intubation were compared. The BIS values 30 s following tracheal intubation, and mean arterial pressure (MAP) and heart rate (HR) at all time points were also recorded.
The BIS value decreased to 50 for tracheal intubation with no purposeful movement in all but one patient in the 0.2 mg kg(-1) group. There was no difference between the etomidate groups (0.2, 0.3, and 0.4 mg kg(-1)) in regards to time to loss of the eyelash reflex (103 (67), 65 (34), 116 (86) s, P=0.2), or to a decrease in BIS to 50 (135 (81), 82 (36), 150 (84) s, P=0.1). Also, the BIS value 30 s after intubation (41 (10), 37 (4), 37 (4), P=0.4), and plasma etomidate concentrations (161 [29-998], 308 [111-730], 310 [90-869] ng ml(-1), P=0.2) did not differ between groups. The time to loss of the eyelash reflex was 12-140 s shorter than the time to a decrease in BIS to 50 in three patients in each group who received etomidate 0.2 and 0.4 mg kg(-1), and in four patients who received 0.3 mg kg(-1). No awareness was recorded. MAP and HR increases following tracheal intubation were comparable between groups.
Etomidate induction doses do not predict the time for BIS to decrease to 50 as this variable varies markedly following three etomidate dose regimen.
This study was designed to evaluate the effects of propofol alone and propofol-clonidine combination on human middle cerebral artery blood flow velocity (Vmca) and cerebrovascular carbon dioxide (CO2) response by using transcranial Doppler ultrasonography. Mean Vmca in response to changes in arterial partial pressure of CO2 (Paco2) was determined under the following conditions: awake (group 1), propofol anesthesia (group 2), and combined propofol-clonidine anesthesia (group 3). Normocapnic, hypercapnic, and hypocapnic values of heart rate, mean arterial pressure, partial end-tidal CO2 pressure, Paco2, and Vmca were obtained. The mean Vmca in groups 2 and 3 was significantly lower than that in group 1 at each level of Paco2. The calculated Vmca at each level of Paco2 was not different between groups 2 and 3. There was a correlation between Paco2 and Vmca in all groups, but in the anesthetized groups the effect of Paco2 on Vmca was attenuated. The present data demonstrated that clonidine-propofol does not change CO2 reactivity compared with propofol alone, but both anesthetics attenuate cerebral blood flow compared with awake controls.
The responsiveness of the cerebral circulation to acute increases in mean arterial pressure was studied before and during the administration of propofol 3, 6, or 12 mg/kg/h in the anaesthetised baboon. Although mean arterial pressure increased significantly on each occasion, there were no significant changes in cerebral blood flow. This indicates that the physiological responsiveness of the cerebral circulation to alterations in mean arterial pressure was preserved during the administration of propofol in the concentrations studied.
Hypotension after induction of general anesthesia is a common event. In the current investigation, we sought to identify the predictors of clinically significant hypotension after the induction of general anesthesia. Computerized anesthesia records of 4096 patients undergoing general anesthesia were queried for arterial blood pressure (BP), demographic information, preoperative drug history, and anesthetic induction regimen. The median BP was determined preinduction and for 0-5 and 5-10 min postinduction of anesthesia. Hypotension was defined as either: mean arterial blood pressure (MAP) decrease of >40% and MAP <70 mm Hg or MAP <60 mm Hg. Overall, 9% of patients experienced severe hypotension 0-10 min postinduction of general anesthesia. Hypotension was more prevalent in the second half of the 0-10 min interval after anesthetic induction (P < 0.001). In 2406 patients with retrievable outcome data, prolonged postoperative stay and/or death was more common in patients with versus those without postinduction hypotension (13.3% and 8.6%, respectively, multivariate P < 0.02). Statistically significant multivariate predictors of hypotension 0-10 min after anesthetic induction included: ASA III-V, baseline MAP <70 mm Hg, age > or =50 yr, the use of propofol for induction of anesthesia, and increasing induction dosage of fentanyl. Smaller doses of propofol, etomidate, and thiopental were not associated with less hypotension. To avoid severe hypotension, alternatives to propofol anesthetic induction (e.g., etomidate) should be considered in patients older than 50 yr of age with ASA physical status > or =3. We conclude that it is advisable to avoid propofol induction in patients who present with baseline MAP <70 mm Hg.