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PubMed1992

[Propofol for sedation during postoperative mechanical ventilation. A comparative study with Lytic Mixture].

Propofol infusion was found to provide excellent sedation and rapid recovery in intensive care. The present study compared Propofol with lytic solution (lytic solution = mixture of 100 mg Pethidine, 50 mg Promethazine and 0.6 mg Dihydroergotamine) during 6 hours of postoperative artificial ventilation. 60 patients after major abdominal surgical procedures were studied with ethical committee approval and informed consent. Patients were randomly allocated to receive either Propofol or lytic solution. We aimed at a sedation level of stage 5 according to the Ramsey score. The mean drug dosages were 3.9 mg/kg/h of Propofol and 4.2 ml/h of lytic solution. Hemodynamic values, blood gases as well as various biochemical measures did not show any difference between the groups. At the end of the sedation period triglyceride concentrations were significantly higher in patients receiving Propofol (166 + 79 mg/dl) compared to the control group (97 + 60 mg/dl). Significant and relevant differences were found for the times of recovery after discontinuation of the sedative. These times were very short in the Propofol group. Furthermore, in view of a longer recovery time after lytic solution in this group the respiratory rate was significantly slower up to the end of the observation period. We conclude that a major advantage of Propofol in the present study was the rapid recovery after 6 hour sedation. Patients gain vigilance rapidly and sufficient spontaneous respiration within minutes. Not at least thanks to these facts patient's safety can be improved in the recovery period.

Abdomen↗

PubMed1992

Cardiovascular and respiratory effects of propofol administration in hypovolemic dogs.

Cardiopulmonary effects of propofol were studied in hypovolemic dogs from completion of, until 1 hour after administration. Hypovolemia was induced by withdrawal of blood from dogs until mean arterial pressure of 60 mm of Hg was achieved. After stabilization at this pressure for 1 hour, 6 mg of propofol/kg of body weight was administered IV to 7 dogs, and cardiopulmonary effects were measured. After blood withdrawal and prior to propofol administration, oxygen utilization ratio increased, whereas mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, oxygen delivery, mixed venous oxygen tension, and mixed venous oxygen content decreased from baseline. Three minutes after propofol administration, mean pulmonary arterial pressure, pulmonary vascular resistance, oxygen utilization ratio, venous admixture, and arterial and mixed venous carbon dioxide tensions increased, whereas mean arterial pressure, arterial oxygen tension, mixed venous oxygen content, arterial and mixed venous pH decreased from values measured prior to propofol administration. Fifteen minutes after propofol administration, mixed venous carbon dioxide tension was still increased; however by 30 minutes after propofol administration, all measurements had returned to values similar to those measured prior to propofol administration.

Animals↗

PubMed1992

Propofol potentiates the binding of [3H]flunitrazepam to the GABAA receptor complex.

Propofol (2,6-diisopropylphenol) robustly stimulated the binding of 1 nM [3H]flunitrazepam (FNZ) to rat brain membranes with an EC50 of 146 microM in chloride-free buffer and 23 microM in buffer containing 200 mM NaCl. NaCl showed an EC50 of 40 mM for its ability to increase the potency of propofol. The ability of a range of anions to potentiate propofol's interactions with the GABAA-benzodiazepine receptor was closely correlated with their permeabilities at this ion channel. Propofol, at a concentration of 300 microM, decreased the EC50 for the potentiation of FNZ binding by NaCl from 39 mM to 13 mM, with no change in the maximal potentiation. At a concentration of 30 microM, propofol significantly decreased the EC50 for potentiation of FNZ binding by the neurosteroid alphaxalone whilst increasing that for potentiation by pentobarbitone. We conclude that propofol is a potent barbiturate-like modulator of [3H]flunitrazepam binding.

Animals↗

PubMed1992

An electroencephalographic comparison of effects of propofol and methohexital.

Thirty-eight patients were randomly allocated to receive propofol 1 mg/kg (group A, N = 10), methohexital 0.7 mg/kg (group B, N = 9), propofol 2 mg/kg (group C, N = 10), methohexital 1.5 mg/kg (group D, N = 9). They were all male with a mean age of 65.8 years (range, 46-85) and a mean weight of 76.2 kg (range, 50-109). Patients received no premedication. All drugs were administered as a single i.v. bolus. After baseline EEG recordings were obtained, i.v. bolus doses were given and the recording continued until the patients became fully responsive to verbal commands. The EEGs were visually analyzed and classified into 4 phases: phase 0, the wake physiologic pattern; phase 1, initial changes after i.v. bolus doses; phase 2, state of deep anesthesia; and phase 3, stage of recovery. The main change during phase 1 was increase in the amplitude of the background rhythms. Phase 2 was characterized by theta and delta activity and burst suppression in some patients. During phase 3 beta activity was seen following methohexital. Propofol produced a much deeper level of anesthesia compared to methohexital. The stage of deep anesthesia was prolonged following propofol. The clinical and EEG recoveries were prolonged after induction doses of propofol. The quality of recovery, however, was far superior with propofol. Methohexital produces a "hang over" effect which delays full recovery.

Aged↗

PubMed1992

Propofol potentiates both pre- and postsynaptic effects of vecuronium in the rat hemidiaphragm.

We have measured twitch tension in response to train-of-four stimulation in rat isolated phrenic nerve-hemidiaphragm preparations. Propofol inhibited nerve evoked twitch tension, with 50% inhibition occurring at 420 (SD 29) mumol litre-1. Although propofol 100 mumol litre-1 by itself had no effect on nerve evoked twitch tension, it potentiated the neuromuscular blocking effects of vecuronium. The decrease in train-of-four ratio with vecuronium was directly proportional to the degree of twitch inhibition, regardless of whether twitch was depressed by vecuronium alone or in combination with propofol. The finding that the train-of-four ratio was a function of the degree of block, rather than simply a function of vecuronium concentration, indicates that propofol also contributed to train-of-four fade and potentiated both pre- and postsynaptic effects of the neuromuscular blocker. The concentrations of propofol used in this study are much greater than human therapeutic blood concentrations, which are typically 25-35 mumol litre-1 (4-6 micrograms ml-1) immediately after a bolus dose of 2 mg kg-1, suggesting that neither muscle weakness nor potentiation of vecuronium-induced neuromuscular block should be of concern at propofol concentrations occurring clinically.

Animals↗

PubMed1992

Propofol anticonvulsant activity in experimental epileptic status.

We have examined the anticonvulsant properties of propofol in high doses in two experimental models of status epilepticus: generalized pentylenetetrazol (PTZ)-induced seizures and partial, cortically applied penicillin G-induced seizures. Propofol was administered either as a single bolus injection or as a bolus injection followed by an infusion for 1 h. When administered as a single bolus injection, propofol 12 mg kg-1 suppressed electrical and clinical seizures in PTZ generalized epileptic status, and an infusion of 50 mg kg-1 h-1 prevented the reappearance of electrical and clinical signs. In focal epileptic status, the single dose stopped paroxysmal activity and the associated clonic jerks for a few seconds. When the bolus dose was followed by an infusion, the firing bursts were replaced by isolated spikes, and contralateral jerks became sporadic and feeble. The greater efficacy of propofol against PTZ convulsions may be a reflection of the opposite action of the two drugs on neural membrane conductance: PTZ induces paroxysmal neural discharge by enhancing membrane conductance while propofol appears to decrease membrane conductance, thus suppressing paroxysmal discharge. There was no close relationship between blood concentration of the anaesthetic and its clinical effects, at least after a short-term infusion, as used in the present experiments. We suggest that propofol may be a potentially useful drug in status epilepticus in patients in whom benzodiazepines, barbiturates and phenytoin have failed.

Action Potentials↗

PubMed1992

EEG and memory effects of low-dose infusions of propofol.

The purpose of this study was to identify EEG changes associated with low-dose propofol infusion producing only sedative effects, and to describe the memory effects of low-dose propofol infusion. Ten healthy volunteers underwent EEG monitoring (at Fz, Cz, Pz and Oz electrode sites) before, during and after propofol 0.5 mg kg-1 i.v. bolus and 75 micrograms kg-1 min-1 as an infusion. Mean serum concentration of propofol during infusion was 0.86 (SD 0.14) micrograms ml-1. The EEG changed significantly during infusion, with increased power in the beta 1 (15-20 Hz), beta 2 (20.5-30 Hz) and delta (1-3.5 Hz) frequencies. Beta 1 and beta 2 power changes were most marked at the Fz and Cz electrodes. Subjects were sedated, but able to complete cognitive tasks. Visual analogue scales of attention and sleepiness were obtained throughout the study and demonstrated a sedative effect during propofol infusion, but were not a significant factor in memory performance or EEG changes. A verbal learning task (Rey Auditory-Verbal Learning Task) administered before, during and after infusion showed a marked reduction in short-term memory capacity and dramatically impaired free recall and recognition during infusion. Nine of 10 subjects had partial amnesia for complex visual scenes presented during infusion, recalling less than 50% of the material. Stronger cueing was required to retrieve information presented during propofol infusion, with an increase in mean retrieval time from 95.4 (41.2) s to 426.8 (83.1) s. EEG and memory effects resolved quickly after the end of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Lack of interaction between propofol and vecuronium.

We estimated the potency of vecuronium and measured the onset and duration of its action during total intravenous anesthesia with propofol to examine the possibility of any interaction between these two drugs. Propofol infusion was administered according to a three-step dosage scheme, and neuromuscular block was monitored by measuring the force of contraction of the adductor pollicis muscle after single-twitch stimulation of the ulnar nerve at 0.1 Hz. A control group of patients were similarly studied during anesthesia with thiopental, nitrous oxide, oxygen, and fentanyl. The ED50 and ED95 (dose required to produce a 50% and 95% depression of twitch tension, respectively) of vecuronium in patients given total intravenous anesthesia (n = 24) were 24 (22-27, 95% confidence limits) and 41 (37-48, 95% confidence limits) micrograms/kg, respectively, and in the control group (n = 24), 20 (17-24) and 39 (34-37) micrograms/kg, respectively. The onset of action of an 80-micrograms/kg dose (2 x ED95) of vecuronium was 3.6 +/- 1.2 and 4.1 +/- 1.7 min (mean +/- SD), in the propofol (n = 10) and control (n = 10) groups, respectively. The respective times to recovery of the twitch height to 25% of control and the recovery indices (25%-75% recovery of twitch height) in the propofol versus control groups were 28.3 +/- 6.6 and 28.0 +/- 1.7 min and 13.3 +/- 6.8 and 15.4 +/- 11.9 min, respectively. There were no significant differences in any of the measured variables between the propofol and control groups, indicating the lack of any interaction between propofol and vecuronium.

Adult↗

PubMed1992

Propofol requirements for induction of anesthesia in children of different age groups.

To demonstrate any age-related differences in propofol requirements for induction of anesthesia, 150 healthy children aged 3-5 yr (n = 50), 6-9 yr (n = 50), and 10-15 yr (n = 50) scheduled for outpatient surgery were randomly assigned to receive an induction dose of propofol of 1.5, 2.0, 2.5, 3.0, or 3.5 mg/kg. To limit pain during injection, alfentanil (5 micrograms/kg) was administered before the propofol. Patients were classified as asleep or not asleep 30 s after the propofol. Incidence of excitation, injection pain, and apnea during induction of anesthesia were noted; arterial blood pressure and heart rate were recorded for 5 min after induction. More than 95% of the children were asleep in the dose groups receiving > or = 2.5 mg/kg. The number of patients falling asleep after receiving 1.5 mg/kg of propofol increased significantly with increasing age (P < 0.05); the difference between the oldest and the youngest age groups was the most significant (P < 0.05). Significant decreases in mean arterial blood pressure and heart rate occurred after induction in all dose and age groups without any systematic intergroup differences. Apnea occurred more frequently in older children (P < 0.01) and with larger doses (P < 0.01). The most frequent side effect was erythema near the site of injection, and its occurrence was dose dependent. The authors conclude that 2.5 mg/kg of propofol, if preceded by 5 micrograms/kg of alfentanil, is an appropriate induction dose for children aged 3-15 yr and that the sleep response to 1.5 mg/kg is more in older children.

Adolescent↗

PubMed1992

Midazolam-flumazenil vs. propofol in ambulatory ENT endoscopic procedures.

Two total intravenous anaesthesia techniques were compared in an open study of 80 ambulatory patients undergoing ENT endoscopic procedures randomly assigned to two groups: Group I midazolam-flumazenil n = 40, Group II propofol n = 40. The mean doses including induction were 0.75 +/- 0.31 mg kg-1 h-1 for midazolam and 171 +/- 64 micrograms kg-1 min-1 for propofol for 46.3 +/- 17.7 min and 50.3 +/- 24.8 min respectively. At the end of the procedure flumazenil 8.1 +/- 1.9 micrograms kg-1 was administered to Group I patients followed by a flumazenil continuous infusion at a minimal arousal rate (MAR) of 0.24 +/- 0.1 micrograms kg-1 min-1, and propofol discontinued in Group II patients. Baseline mean arterial pressure (MAP) and heart rate (HR) were similar in both groups and remained so during the procedure and recovery. In patients with cardiovascular disease, large variations (greater than or equal to 40% of baseline values) occurred more frequently in the propofol group whereas large variations in patients with no cardiovascular disease occurred more frequently in the midazolam group (P less than 0.05). Early recovery was more rapid after midazolam (P less than 0.05) whereas late criteria for recovery (maze and ambulation tests) were met more rapidly after propofol (P less than 0.05). It is concluded that with the midazolam-flumazenil sequence, early recovery is faster and haemodynamic stability better maintained in poor cardiovascular risk patients, whereas with propofol, street-fitness is more rapidly obtained, and haemodynamic stability better maintained in good risk patients.

Adolescent↗

PubMed1992

[Long-term sedation with propofol in ICU: hemocoagulation problems].

The Authors have studied the effects of propofol on coagulation in 15 patients admitted to ICU. Propofol was used for long-term sedation (therapeutic range 3 mg/kg/h). Variables monitored included: platelets, PTT, PT, Fibrinogen, FDP, AT III. The effects on coagulation has been investigated in three groups of patients: group I) 5 patients that received propofol for 1-3 days; group II) 5 patients that received propofol for 4-10 days; group III) 5 patients that received propofol for 11-35 days. No difference were found about blood coagulation in this groups of patients before and after administration of propofol.

Adult↗

PubMed1992

The comparative effects of propofol, thiopental, and diazepam, administered intravenously, on pentylenetetrazol seizure threshold in the rabbit.

The anticonvulsant effects of propofol, thiopental, and diazepam, administered intravenously, on pentylenetetrazol (PTZ) seizure threshold were studied and compared in the rabbit. The PTZ seizure threshold determined in various rabbit groups during the control phase of conducted experiments, was found to be in the range of 10.1 +/- 2.0 to 13.5 +/- 3.7 mg/kg. Intravenous administration of comparable doses of propofol, thiopental, and diazepam resulted in marked and significant increases in PTZ seizure threshold. At all administered doses (1.25-10.0 mg/kg), propofol was found to be more effective than thiopental in increasing the PTZ threshold dose. However, the anticonvulsant effects of diazepam were more marked than those of propofol, except at a dose of 10 mg/kg where both agents exhibited equipotent activities. These data demonstrate that propofol enjoys a considerable degree of anticonvulsant activity in the rabbit. This anticonvulsant action is greater than that of thiopental at doses ranging from 2.5 to 10 mg/kg and equipotent with diazepam at the 10 mg/kg dose.

Animals↗

PubMed1992

[Sedation with propofol and fentanyl in patients under intensive care].

This study investigated the efficacy of a constant rate infusion of propofol and fentanyl in thirty patients requiring artificial ventilation for more than 24 h. A loading dose, which differed according to the patient's age, was administered over a 30 min period: 2.5 mg.kg-1 for patients less than 50 (G1) (n = 9), 2 mg.kg-1 for patients between 50 and 60 years old (G2) (n = 9), and 1.5 mg.kg-1 for patients over 60 (G3) (n = 12). This was followed by an infusion of 3 mg.kg-1.h-1 in G1 and G2, and 2 mg.kg-1.h-1 in G3. A 1 microgram.kg-1.h-1 infusion of fentanyl was also given. The degree of sedation was assessed with the Ramsay scale before starting, after induction, and every four hours thereafter. When this proved to be insufficient, the dose of propofol was increased by 0.5 mg.kg-1.h-1 as well as that of fentanyl by 0.5 microgram.kg-1.h-1. Heart rate, mean arterial blood pressure, blood propofol, creatinine, transaminase and lipid levels, and urine output were measured before, during, and after the infusion. The blood propofol level increased during the infusion, being correlated to the doses given (r = 0.64, p less than 0.001). Sedation lasted 91.7 +/- 57.7 h. After stopping the infusion of propofol, mean recovery times were 7.5 +/- 5.9 min (G1), 11.4 +/- 11.4 min, and 14.4 +/- 13.5 min (G3) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Propofol inhibits enzymatic degradation of alfentanil and sufentanil by isolated liver microsomes in vitro.

We have studied the effect of propofol on the enzymatic degradation of alfentanil and sufentanil utilizing isolated liver microsomes obtained from pig and human liver. Propofol inhibited dose-dependently the oxidative metabolic degradation of alfentanil and sufentanil by both microsomal preparations. The calculated concentration of propofol causing 50% inhibition of metabolic degradation (IC50) was 32.6 mumol litre-1 for alfentanil and 22.1 mumol litre-1 for sufentanil in pig liver microsomes. Similar values of inhibitory activity of propofol (IC50 values 62.8 and 52.9 mumol litre-1, respectively) were observed using human microsomes prepared from liver taken from an organ transplant donor. We suggest that propofol in clinically relevant concentrations interferes with oxidative metabolic degradation of alfentanil and sufentanil in the microsomal fraction of pig and human liver.

Alfentanil↗

PubMed1992

The influence of propofol with and without nitrous oxide on cerebral blood flow velocity and CO2 reactivity in humans.

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)

Adult↗

PubMed1992

Propofol induction for laryngeal mask airway insertion: dose requirement and cardiorespiratory effects.

The dosage, haemodynamic and respiratory effects of propofol for laryngeal mask airway (LMA) insertion were investigated. Fifty patients (ASA I-II) were randomly assigned one of four induction doses of propofol (1.5-2.5 mg/kg) delivered over 30 seconds and the first attempt at LMA insertion was made at 90 seconds. The LMA was inserted at 90 seconds in 35 patients and by 300 seconds in 13 others (mean plasma concentration at 90 seconds was 7.7 mcg/ml (no delay) versus 5.2 mcg/ml (insertion delayed), P < 0.01). Insertion was less successful after 1.5 mcg/kg (failed at 90 seconds in 6 of 12 patients), but did not vary with the other doses. Additional propofol (0.5 mg/kg/30s) was required in 22 patients for LMA insertion or to prevent movement, resulting in propofol concentrations at 120-180 seconds above 7 mcg/ml. Respiratory effects were minor, but MAP decreased by 18 +/- 1.4 mmHg at 90 seconds. Cardiovascular effects did not differ significantly between dosage groups or with the use of additional propofol.

Adult↗

PubMed1992

[A myoclonic seizure during propofol-alfentanil anesthesia?].

Total intravenous anaesthesia with propofol and alfentanil is an established alternative to inhalation anaesthesia for intracranial neurosurgical procedures. Its usefulness has been somewhat overshadowed by reports of seizure-like movements, both during anaesthesia and in the recovery period. These can be related to the use of either anaesthetic agent, but true epileptogenic properties still remain to be demonstrated in man. Opioid-induced rigidity is a well known phenomenon and must not be mistaken for an epileptic seizure. Myoclonic motor activity can be observed even under physiological conditions, e.g. sleep. Almost all anaesthetic agents have been found to produce "epileptic" EEG changes (spikes, polyspikes, spike-wave complexes), but in man these have never been correlated to motor reactions. Propofol's pro- or anticonvulsive action is unclear. While some groups found shortened convulsing times in patients undergoing electroconvulsive therapy with propofol instead of methohexitone, others have reported activation of epileptogenic foci in the EEGs of known epileptic patients. A synergistic effect of propofol and alfentanil in the generation of seizure-like movements cannot be excluded. Whether seizure-like movements indicate a true "epileptogenic potency" of the anaesthetic drugs or are related to other phenomena remains to be studied. Electro-encephalographic monitoring during anaesthesia as well as careful observation and documentation of motor reactions may contribute to elucidation of the problem. We report a case of seizure-like movements during propofol-alfentanil anaesthesia for an elective craniotomy. A 52-year-old patient presented with a history of headaches of increasing frequency. A CT brain scan demonstrated a tumor in the left occipital region.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗

PubMed1992

Hypotensive anesthesia for middle ear surgery: a comparison of propofol infusion and isoflurane.

An infusion of propofol (2,6-diisopropylphenol) was compared with isoflurane to induce hypotension for middle ear surgery. Forty patients (ASA physical status I-II, 16-55 years) scheduled for elective surgery were included in an open randomized study. The pharmacokinetics of propofol infusion were also studied in 6 patients. Both agents produced controlled hypotension (MAP reduction of 30% from the baseline values) with an acceptable visibility of the surgical field. No major complications occurred. The mean total dose of propofol infusion was 6.4 +/- 2.7 mg/kg and the mean concentration of isoflurane was 0.9 +/- 0.4%. Considerable interindividual pharmacokinetic variability was found and propofol was extensively distributed and rapidly cleared from the body after the infusion. Propofol infusion may be a new alternative as a hypotensive agent in middle ear surgery.

Adolescent↗