Propofol and Thiopental Do Not Interfere with Regional Cerebral Blood Flow Response at Sedative Concentrations

Background: Anesthetics may affect the regional cerebral blood flow (rCBF) response associated with increased brain activity in humans. rCBF was measured as auditory stimulus rate was increased during propofol and thiopental administration.

Methods: After informed consent, 10 right-handed male volunteer participants (aged 33.5 +/- 10.4 yr, weighing 74.5 +/- 8.4 kg) received thiopental (n = 4) or propofol (n = 6) intravenously at stepwise target concentrations of propofol 1.2 and 2.5-3, or thiopental 4 and 7-9 [mu]g/ml, representing sedative and hypnotic drug concentrations. The latter made volunteers unresponsive to voice or mild stimulation. Quantitative positron emission tomographic brain images were obtained at 0, 20, and 40 auditory words per minute at each drug concentration. Using SPM99 analysis, 10-mm spherical regions of interest were identified by peak covariation of word rate with rCBF across all conditions and drug concentrations. Individual mean rCBF responses in these and primary auditory cortex (Heschl's gyri) were obtained.

Results: Significant increases in rCBF with auditory word rate occurred in temporal lobes bilaterally at baseline (significance, T = 4.95). There was no change in this response during sedation (T = 5.60). During unresponsiveness seven of 10 participants had a diminished response in the left temporal lobe (T = 3.18). Global CBF, corrected for changes in Pco2 (3% [middle dot]mmHg Pco2-1), was reduced 15% by sedation and 27% during unresponsiveness.     

Thiopental and propofol affect different regions of the brain at similar pharmacologic effects

Propofol has a greater amnesic effect than thiopental. In this study we tested whether different brain regions were affected by propofol and thiopental at similar drug effects. Changes in regional cerebral blood flow (rCBF) were identified by using SPM99 analysis of images obtained with positron emission tomography with (15)O water. Ten right-handed male volunteers (age, 35 +/- 10 yr; weight, 74.1 +/- 7.5 kg; mean +/- sd) were randomized to receive thiopental (n = 4) or propofol (n = 6) to target sedative and hypnotic concentrations with bispectral index (BIS) monitoring. Four positron emission tomography images were obtained during various tasks at baseline and with sedative and hypnotic effects. Two participants receiving propofol were unresponsive at sedative concentrations and were not included in the final analyses. Median serum concentrations were 1.2 and 2.7 microg/mL for sedative and hypnotic propofol effects, respectively. Similarly, thiopental concentrations were 4.8 and 10.6 microg/mL. BIS decreased similarly in both groups. The pattern of rCBF change was markedly different for propofol and thiopental. Propofol decreased rCBF in the anterior (right-sided during sedation) brain regions, whereas thiopental decreased rCBF primarily in the cerebellar and posterior brain regions. At similar levels of drug effect, propofol and thiopental affect different regions of the brain. These differences may help to identify the loci of action for the nonsedative effects of propofol, such as amnesia.     

Drug-induced amnesia is a separate phenomenon from sedation: electrophysiologic evidence

BACKGROUND: Sedative-hypnotic drugs not only increase sedation, but also impair memory as serum concentration increases. These drugs also produce profound changes in the auditory event-related potential (ERP). The ability of various ERP components to predict changes in sedation and memory produced by various drugs was tested. METHODS: Sixty-five healthy volunteers randomly received intravenous placebo, midazolam, propofol, thiopental, fentanyl with ondansetron, or ondansetron alone at five different stable target concentrations (three increasing, two decreasing) using a computer-controlled infusion pump to produce varying degrees of sedation without loss of consciousness. ERPs were recorded while volunteer participants detected a deviant auditory stimulus and made a button-press response to a target tone (standard oddball paradigm, 80:20 ratio, to elicit a P3 response). At each target concentration, volunteers learned a list of 16 words. The predictive probabilities (Pk) of various ERP components were determined for word recognition at the end of the day (memory) and log reaction time to the deviant stimulus (sedation). RESULTS: The N2 latency of the ERP consistently predicted log reaction time in all groups (Pk +/- SE from 0.58 +/- 0.04 to 0.71 +/- 0.04). The N2P3 amplitude of the ERP was the best predictor of memory performance for midazolam (Pk, 0.63 +/- 0.04), propofol (Pk, 0.62 +/- 0.05), and thiopental (Pk, 0.66 +/- 0.04). There was a differential ability to predict memory performance from sedation for midazolam and propofol. CONCLUSIONS: Midazolam and propofol affect memory differentially from their sedative effects, and these are indexed by specific components of the auditory ERP. These components of the ERP are associated with specific, but not necessarily unique, neuroanatomic structures. Thus, these drugs act by additional mechanisms beyond general central nervous system depression to produce the effects of sedation and memory impairment.     

A neuroanatomical construct for the amnesic effects of propofol

BACKGROUND: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task. METHODS: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline. RESULTS: Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases. CONCLUSIONS: As amnesia becomes maximal, rCBF reductions induced by propofol occur in brain regions identified with working memory processes. In contrast, medial temporal lobe structures were resistant to the global CBF decrease associated with propofol sedation. The authors postulate that the episodic memory effect of propofol is produced by interference with distributed cortical processes necessary for normal memory function rather than specific effects on medial temporal lobe structures.     

Drug-induced Amnesia Is a Separate Phenomenon from Sedation: Electrophysiologic Evidence

Background: Sedative-hypnotic drugs not only increase sedation, but also impair memory as serum concentration increases. These drugs also produce profound changes in the auditory event-related potential (ERP). The ability of various ERP components to predict changes in sedation and memory produced by various drugs was tested.

Methods: Sixty-five healthy volunteers randomly received intravenous placebo, midazolam, propofol, thiopental, fentanyl with ondansetron, or ondansetron alone at five different stable target concentrations (three increasing, two decreasing) using a computer-controlled infusion pump to produce varying degrees of sedation without loss of consciousness. ERPs were recorded while volunteer participants detected a deviant auditory stimulus and made a button-press response to a target tone (standard oddball paradigm, 80:20 ratio, to elicit a P3 response). At each target concentration, volunteers learned a list of 16 words. The predictive probabilities (Pk) of various ERP components were determined for word recognition at the end of the day (memory) and log reaction time to the deviant stimulus (sedation).

Results: The N2 latency of the ERP consistently predicted log reaction time in all groups (Pk +/- SE from 0.58 +/- 0.04 to 0.71 +/- 0.04). The N2P3 amplitude of the ERP was the best predictor of memory performance for midazolam (Pk, 0.63 +/- 0.04), propofol (Pk, 0.62 +/- 0.05), and thiopental (Pk, 0.66 +/- 0.04). There was a differential ability to predict memory performance from sedation for midazolam and propofol.     

A Neuroanatomical Construct for the Amnesic Effects of Propofol

Background: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task.

Methods: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline.

Results: Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases.     

Information loss over time defines the memory defect of propofol: a comparative response with thiopental and dexmedetomidine

BACKGROUND: Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured. METHODS: Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed. RESULTS: High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups. CONCLUSIONS: Lack of retention of material acquired into long-term memory during propofol administration, associated with minimal sedation, seems to define drug-induced amnesia. Sedation seems to impair the acquisition or encoding of material into long-term memory. Therefore, the putative targets of drug-induced amnesia by propofol are processes associated with retention of material in long-term memory.     

Information Loss over Time Defines the Memory Defect of Propofol: A Comparative Response with Thiopental and Dexmedetomidine

Background: Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured.

Methods: Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed.

Results: High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups.     

The Comparative Amnestic Effects of Midazolam, Propofol, Thiopental, and Fentanyl at Equisedative Concentrations

Background: The authors evaluated the effects of midazolam, propofol, thiopental, and fentanyl on volunteer participants' memory for words and pictures at equisedative concentrations.

Methods: Sixty-seven healthy volunteers were randomized to receive intravenous infusions of midazolam (n = 11), propofol (n = 11), thiopental (n = 10), fentanyl with ondansetron pretreatment (n = 11), ondansetron alone (n = 8), or placebo (n = 16) in a double-blind design. Three increasing and then two decreasing sedative concentrations were achieved by computer-controlled infusion in each volunteer. Measures of sedation, memory, and drug concentration were obtained at each target concentration. Drug concentrations were normalized to equisedative effects using both Emax and logistic regression methods of pharmacodynamic modeling. The serum concentrations at 50% memory effect (Cp50s) were determined using four different memory end points. The relative potencies compared with midazolam for memory impairment were determined.

Results: Equisedative concentrations were midazolam, 64.5 +/- 9.4 ng/ml; propofol, 0.7 +/- 0.2 micro gram/ml; thiopental, 2.9 +/- 1.0 micro gram/ml; and fentanyl, 0.9 +/- 0.2 ng/ml. The Cp50s for 50% loss of memory for words were midazolam, 56 +/- 4 ng/ml; propofol, 0.62 +/- 0.04 micro gram/ml; thiopental, 4.5 +/- 0.3 micro gram/ml; and fentanyl, 3.2 +/- 0.4 ng/ml. Compared with midazolam, relative potencies (with 95% confidence intervals) were propofol, 0.96 (0.44-1.78); thiopental, 0.76 (0.52-0.94); and fentanyl, 0.34 (0.05-0.76). Large effects on memory were only produced by propofol and midazolam.     

Electroencephalograph variables, drug concentrations and sedation scores in children emerging from propofol infusion anaesthesia

BACKGROUND: Inadequate sedation or oversedation are common problems in Paediatric Intensive Care because of wide variations in drug response and the lack of objective tests for sedative depth. We undertook a pilot study to try to identify correlates of propofol drug concentration, electroencephalographic (EEG) variables and observed behaviour during a stepwise reduction in propofol infusion after paediatric cardiac surgery. METHODS: This was a prospective pilot study with 10 children (5 months to 8 years) emerging from propofol anaesthesia following cardiac surgery with cardiopulmonary bypass (CPB). Patients underwent a stepped wake-up from propofol anaesthesia during which the propofol infusion rate was decreased from 4 mg.kg(-1).h(-1) in 1 mg.kg(-1).h(-1) steps at 30 min intervals. EEG variables, propofol blood concentrations and clinical sedation scores (COMFORT scale) were recorded during the stepped wakeup. Analgesia was maintained with a standardized continuous infusion of fentanyl. RESULTS: : Mean (SD) whole blood propofol concentrations at arousal varied considerably [973 ng.ml(-1) (SD 523 ng.ml(-1))]. The summed ratio (SR) of high frequency to low frequency bands correlated with both propofol infusion rate (R2 value=0.47) and propofol blood concentrations (R2 value=0.64). The mean SR in deeply sedated patients was significantly different from that in the 5 min prior to wakening (6.84 vs 1.55, P=0.00002). There was no relationship between COMFORT scores and SR. CONCLUSIONS: In this group of patients receiving opioid analgesia and relatively high doses of propofol, sedation scores were unhelpful in predicting arousal. The SR correlated with propofol blood concentrations and clinical arousal and may have potential as a predictive tool for arousal in children.     

Measuring depth of sedation with auditory evoked potentials during controlled infusion of propofol and remifentanil in healthy volunteers

Avoiding excessively deep levels of sedation is a major problem in intensive care patients. We studied whether clinically relevant levels of sedation can be objectively assessed using long latency auditory evoked potentials. We measured the auditory evoked potentials at 100 ms after the stimulus (N100) in 10 healthy volunteers during stepwise increasing, clinically relevant levels of sedation (Ramsay score [RS] 2-4). The volunteers were studied on three separate occasions and received an infusion of either propofol or a combination of propofol and remifentanil. Effects of remifentanil infusion alone were tested during target controlled infusion (target plasma concentrations: 1, 2, and 3 ng/mL). Remifentanil did not affect evoked potential amplitudes and latencies. During both propofol-induced and propofol/remifentanil-induced sedation, the N100 amplitude decreased similarly without an effect on the latencies as the level of sedation increased from Ramsay score 2 to Ramsay score 4 (P < 0.01). At the same clinical level of sedation, propofol plasma concentrations were larger when sedation was achieved by propofol alone (propofol versus propofol/remifentanil, RS 3: 2.12 mug/mL +/- 0.51 versus 1.32 +/- 0.43, P < 0.01; RS 4: 3.37 +/- 0.47 versus 1.86 +/- 0.34, P < 0.01). Our results suggest that long latency auditory evoked potentials provide an objective electrophysiological analog to the clinical assessment of sedation independent of the sedation regime used.     

Auditory steady-state response and bispectral index for assessing level of consciousness during propofol sedation and hypnosis

We assessed the effect of propofol on the auditory steady-state response (ASSR), bispectral (BIS) index, and level of consciousness in two experiments. In Experiment 1, propofol was infused in 11 subjects to obtain effect-site concentrations of 1, 2, 3, and 4 microg/mL. The ASSR and BIS index were recorded during baseline and at each concentration. The ASSR was evoked by monaural stimuli. Propofol caused a concentration-dependent decrease of the ASSR and BIS index values (r(2) = 0.76 and 0.93, respectively; P<0.0001). The prediction probability for loss of consciousness was 0.89, 0.96, and 0.94 for ASSR, BIS, and arterial blood concentration of propofol, respectively. In Experiment 2, we compared the effects of binaural versus monaural stimulus delivery on the ASSR in six subjects during awake baseline and propofol-induced unconsciousness. During baseline, the ASSR amplitude with binaural stimulation (0.47+/-0.13 microV, mean +/- SD) was significantly (P<0.002) larger than with monaural stimulation (0.35+/-0.11 microV). During unconsciousness, the amplitude was 0.09+/-0.09 microV with monaural and 0.06+/-0.04 microV with binaural stimulation (NS). The prediction probability for loss of consciousness was 0.97 (0.04 SE) for monaural and 1.00 (0.00 SE) for binaural delivery. We conclude that the ASSR and BIS index are attenuated in a concentration-dependent manner by propofol and provide a useful measure of its sedative and hypnotic effect. BIS was easier to use and slightly more sensitive. The ASSR should be recorded with binaural stimulation. The ASSR and BIS index are both useful for assessing the level of consciousness during sedation and hypnosis with propofol. However, the BIS index was simpler to use and provided a more sensitive measure of sedation. Implications: We have compared two methods for predicting whether the amount of propofol given to a human subject is sufficient to cause unconsciousness, defined as failure to respond to a simple verbal command. The two methods studied are the auditory steady-state response, which measures the electrical response of the brain to sound, and the bispectral index, which is a number derived from the electroencephalogram. The results showed that both methods are very good predictors of the level of consciousness; however, bispectral was easier to use.     

Low-dose Propofol-induced Amnesia Is Not due to a Failure of Encoding: Left Inferior Prefrontal Cortex Is Still Active

Background: Propofol may produce amnesia by affecting encoding. The hypothesis that propofol weakens encoding was tested by measuring regional cerebral blood flow during verbal encoding.

Methods: Seventeen volunteer participants (12 men; aged 30.4 +/- 6.5 yr) had regional cerebral blood flow measured using H2O15 positron emission tomography during complex and simple encoding tasks (deep vs. shallow level of processing) to identify a region of interest in the left inferior prefrontal cortex (LIPFC). The effect of either propofol (n = 6, 0.9 [mu]g/ml target concentration), placebo with a divided attention task (n = 5), or thiopental at sedative doses (n = 6, 3 [mu]g/ml) on regional cerebral blood flow activation in the LIPFC was tested. The divided attention task was expected to decrease activation in the LIPFC.

Results: Propofol did not impair encoding performance or reaction times, but impaired recognition memory of deeply encoded words 4 h later (median recognition of 35% [interquartile range, 17-54%] of words presented during propofol vs. 65% [38-91%] before drug; P < 0.05). Statistical parametric mapping analysis identified a region of interest of 6.6 cm2 in the LIPFC (T = 7.44, P = 0.014). Regional cerebral blood flow response to deep encoding was present in this region of interest in each group before drug (T > 4.41, P < 0.04). During drug infusion, only the propofol group continued to have borderline significant activation in this region (T = 4.00, P = 0.063).     

Propofol and memory: a study using a process dissociation procedure and functional magnetic resonance imaging

Thirty volunteers randomly received either mild or deep propofol sedation, to assess its effect on explicit and implicit memory. Blood oxygen level‐dependent functional magnetic resonance during sedation examined brain activation by auditory word stimulus and a process dissociation procedure was performed 4 h after scanning. Explicit memory formation did not occur in either group. Implicit memories were formed during mild but not deep sedation (p = 0.04). Mild propofol sedation inhibited superior temporal gyrus activation (Z value 4.37, voxel 167). Deep propofol sedation inhibited superior temporal gyrus (Z value 4.25, voxel 351), middle temporal gyrus (Z value 4.39, voxel 351) and inferior parietal lobule (Z value 5.06, voxel 239) activation. Propofol only abolishes implicit memory during deep sedation. The superior temporal gyrus is associated with explicit memory processing, while the formation of both implicit and explicit memories is associated with superior and middle temporal gyri and inferior parietal lobule activation.     

A comparison of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging

We compared the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging procedures. Sixty children were randomly distributed into two groups: The dexmedetomidine (D) group received 1 microg/kg initial dose followed by continuous infusion of 0.5 microg.kg(-1).h(-1) and a propofol group (P) received 3 mg/kg initial dose followed by a continuous infusion of 100 microg.kg(-1).min(-1). Inadequate sedation was defined as difficulty in completing the procedure because of the child's movement during magnetic resonance imaging. Mean arterial pressure (MAP), heart rate, peripheral oxygen saturation, and respiratory rate (RR) were recorded during the study. The onset of sedation, recovery, and discharge time were significantly shorter in group P than in group D. MAP, heart rate, and RR decreased during sedation from the baseline values in both groups. MAP and RR were significantly lower in group P than in group D during sedation. Desaturation was observed in four children of group P. Dexmedetomidine and propofol provided adequate sedation in most of the children. We conclude that although propofol provided faster anesthetic induction and recovery times, it caused hypotension and desaturation. Thus, dexmedetomidine could be an alternative reliable sedative drug to propofol in selected patients.     

The cost-effectiveness of methohexital versus propofol for sedation during monitored anesthesia care

We designed this study to test the hypothesis that methohexital is a cost-effective alternative to propofol for sedation during local anesthesia. Sixty consenting women undergoing breast biopsy procedures under local anesthesia were randomly assigned to receive an infusion of either propofol (50 microg x kg(-1) x min(-1)) or methohexital (40 microg x kg(-1) x min(-1)). The sedative infusion rate was titrated to maintain an observer's assessment of alertness/sedation (OAA/S) score of 3 (with 1 = awake/alert to 5 = asleep). Fentanyl 25 microg i.v. was administered as a "rescue" analgesic during the operation. We assessed the level of sedation (OAA/S score), vital signs, time to achieve an OAA/S score of 3 at the onset and a score of 1 after discontinuing the infusion, discharge times, perioperative side effects, and patient satisfaction. The direct cost of methohexital was lower than that of propofol, based on the milligram dosage infused during the operation. The sedative onset (to achieve an OAA/S score of 3) and the recovery (to return to an OAA/S score of 1) times, as well as discharge times, did not differ between the two groups. Patients receiving methohexital had a significantly lower incidence of pain on initial injection compared with those receiving propofol (10% vs 23%). Because the use of methohexital (29.4 +/- 2.7 microg x kg(-1) x min(-1)) for sedation during breast biopsy procedures has a similar efficacy and recovery profile to that of propofol (36.8 +/- 15.9 microg x kg(-1) x min(-1)) and is less costly based on the amount infused, it seems to be a cost-effective alternative to propofol for sedation during local anesthesia. However, when the cost of the drug infused and drug wasted was calculated, there was no difference in the overall drug cost. Implications: When administered to maintain a stable level of sedation during local anesthesia, methohexital is an acceptable alternative to propofol. However, the overall drug costs were similar with the two drugs.     

Implantable cardioverter-defibrillator placement in patients with mild-to- moderate left ventricular dysfunction: hemodynamics and recovery profile with two different anesthetics used during deep sedation

OBJECTIVE: To compare the effects of thiopental and propofol during defibrillation threshold testing (DFT) on hemodynamics and recovery profile in patients requiring automatic internal cardioverter-defibrilator placement. DESIGN: Prospective clinical investigation. SETTING: University hospital. PARTICIPANTS: Thirty-four adult patients. INTERVENTIONS: After administration of midazolam, 0.025 mg/kg, and fentanyl, 0.5 to 1 mug/kg, surgery was performed under topical infiltration with 1% lidocaine. In group I (GI) (n = 17), patients received thiopental by slow injection and patients in group II (GII) (n = 17) received propofol before induction of ventricular fibrillation (VF). MEASUREMENTS AND MAIN RESULTS: Patients received 4.1 +/- 1.4 mg of midazolam, 114 +/- 34 mug of fentanyl, and 280 +/- 78 mg of thiopental in GI; and 4.6 +/- 1.7 mg of midazolam, 119 +/- 62 mug of fentanyl, and 147 +/- 40 mg of propofol in GII (p > 0.05). Hemodynamics did not show significant differences between the groups at any recording time. Average time needed to regain the pretest sedation level was 16.4 +/- 8.8 minutes in GI and 10.9 +/- 5.5 minutes in GII (p = 0.03). Time required to achieve a score of 10 using a modified Aldrete score was 26.4 +/- 9.3 minutes in GI and 17.4 +/- 4.9 in GII (p = 0.001). Seven patients in GII (41%) and 1 patient in GI (6%) became hypotensive after DFT (p = 0.04). CONCLUSIONS: Deepening the sedation level by slow injection of thiopental or propofol before DFT provided satisfactory conditions during brief episodes of VF. Delay in recovery of arterial pressure after DFT with propofol and delay in arousal and discharge of patients with thiopental are major disadvantages of the regimens.     

Comparison of the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol,thiopental or etomidate

BACKGROUND AND OBJECTIVE: This prospective, randomized, double-blinded study was designed to compare the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol, thiopental or etomidate. METHODS: Seventy-two patients were enrolled in six groups of 12 individuals each. In three groups, fentanyl was given as a bolus dose of 1.5 microg kg(-1), whereas the others received a remifentanil infusion at 0.5 microg kg(-1) min(-1). Five minutes later, propofol, thiopental or etomidate were titrated to a state of unresponsiveness. Assessment included the amounts of drug necessary for induction, haemodynamics and the times to apnoea, loss of eyelash reflex, and the release of a water-filled syringe held in the patient's hand. RESULTS: Induction times to loss of the eyelash reflex were significantly shorter in the remifentanil than in the fentanyl groups: with propofol 50.7 +/- 13.6s (mean +/- SD) versus 74.9 +/- 27.0s (P < 0.01), with thiopental 42.9 +/- 16.8s versus 77.2 +/- 27.8s (P < 0.01) and with etomidate 54.7 +/- 17.6s versus 72.3 +/- 24.0s (P < 0.05). The times to respiratory arrest or for the syringe to fall were significantly shorter with remifentanil than with fentanyl for propofol and for thiopental, but not for etomidate. In terms of dosages per kg body weight necessary to achieve unresponsiveness, less propofol (-29%, P < 0.05), thiopental (-25%, P < 0.05) or etomidate (-32%, P < 0.01) was necessary with remifentanil than with fentanyl. Haemodynamic responses to tracheal intubation were controlled more effectively with remifentanil. However, within the remifentanil groups, mean arterial pressure significantly decreased during induction: -26% with propofol, -181% with thiopental and -14% with etomidate (all P < 0.01). CONCLUSIONS: During anaesthetic induction, a remifentanil infusion of 0.5 microg kg(-1) min(-1) over 5 min is a suitable alternative to a 1.5 microg kg(-1) bolus dose of fentanyl: induction times are shorter with reduced amounts of propofol, thiopental or etomidate.     

Tolerance to propofol's sedative effect in mechanically ventilated Rabbits

Propofol is commonly used for the sedation of critically ill patients undergoing mechanical ventilation. These patients may develop tolerance during long-term administration. Here, we describe the development of tolerance to propofol's sedative effect in rabbits during prolonged mechanical ventilation. Six healthy male New Zealand White rabbits were endotracheally intubated and received propofol by continuous IV infusion to maintain sedation for 48 h. The propofol infusion rate (IR) was adjusted to maintain the desired level of sedation. Assessments of the sedation level were made every 30 min or earlier if there were signs of awakening. Propofol concentrations were measured in arterial plasma after every other IR adjustment, provided there was an adequate level of sedation, using high performance liquid chromatography, and calculations of systemic clearance rates were made. The mortality rate was 100% with a survival period of 30.8 +/- 6.0 h (mean +/- sd). The course of IR adjustments followed a 5-phase pattern: 1) steady IR (mean +/- sd duration; 1.2 +/- 0.6 h), 2) increasing IR (9.4 +/- 5.5 h), 3) steady high-IR (2.3 +/- 1.2 h), 4) decreasing IR (13.7 +/- 1.9 h), and 5) steady low-IR (5.0 +/- 2.7 h). The course of propofol concentrations during the experiment in relation to propofol IR followed a 3-phase pattern: 1) steady concentration with increasing IRs (6.0 +/- 2.7 h), 2) increasing concentrations with increasing IR (5.8 +/- 2.5 h), and 3) increasing concentrations with decreasing IR (18.8 +/- 3.3 h). Propofol systemic clearance rates were progressively increased for 6.0 +/- 2.7 h and then gradually decreased for 24.6 +/- 4.7 h. In conclusion, all rabbits developed tolerance to propofol's sedative effect within the first hours of administration related to changes to the drug's metabolic clearance.     

Clinical assessment of target-controlled infusion of propofol during monitored anesthesia care

PURPOSE: To determine the plasma concentrations of propofol required to achieve different levels of sedation during monitored anesthesia care. METHODS: Sixty ASA I-II, 18-65 yr-old patients, received a target-controlled continuous iv infusion of propofol. The target plasma concentration of propofol (Cpt) was initially set at 0.4 microg x ml(-1). Two minutes after calculated equilibrium between plasma and effect-site concentrations, the Cpt of propofol was increased by 0.2 microg x ml(-1) steps until the patient showed no reaction to squeezing the trapezius. The level of sedation was assessed immediately before each increase in propofol Cpt using the Observer's Assessment of Alertness/Sedation (OAA/S) scale. RESULTS: The Cpt of propofol required to induce lethargic response to name was 1.3 microg x ml(-1) (5 degrees and 95 degrees percentiles: 1.0 - 1.8 microg x ml(-1)), to obtain response after loud and repeated calling name was 1.7 microg x ml(-1) (1.2 - 2.2 microg x ml(-1)), to obtain response after prodding or shaking was 2.0 microg x ml(-1) (1.6 - 2.6 microg x ml(-1)), to obtain response after squeezing the trapezius was 2.4 microg x ml(-1) (1.8 - 3.0 microg x ml(-1)). Patients showed no response after squeezing the trapezius at 2.8 microg x ml(-1) (2.0 - 3.6 microg x ml(-1)). Correlation between Cpt propofol and sedation scores were r = 0.76, P < 0.0001. CONCLUSIONS: Target-controlled infusion of propofol provided easy and safe management of intraoperative sedation, allowing fast and predictable deepening in the level of sedation, while minimizing systemic side effects of intravenous sedation due to the minimal risk of overdosing the drug.