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PubMed2000

Oral clonidine premedication reduces propofol requirement for laryngeal mask airway insertion.

PURPOSE: To determine the effect of oral clonidine premedication on propofol requirement (ED(50)) for the insertion of the laryngeal mask airway (LMA) in healthy patients undergoing abdominal hysterectomy. METHODS: After ethics committee approval and informed consent, 41 patients were randomly assigned to receive 5 microg x kg(-1) clonidine po premedication 90 min before entering the operating room (n = 22), or no clonidine (n = 19). To alleviate pain associated with iv propofol, 3 ml lidocaine 2%iv were administered. General anesthesia was induced, 30 sec later, with propofol at a rate of 100 mg x min(-1) (600 ml x hr(-1)) iv. The dose of propofol at which insertion of the LMA was attempted was predetermined by modification of Dixon's up-and-down method with an initial dose of 2.5 mg x kg(-1) and 0.25 mg x kg(-1) as the step size. An LMA was inserted, without muscle relaxants or other adjuvants 90 sec after completion of the propofol injection, by an anesthesiologist blinded to the treatment of the patient. RESULTS: The ED(50) of propofol for LMA insertion in clonidine-treated patients (2.0 +/- 0.2 mg x kg(-1), 1.8-2.3 mg x kg(-1) [95% confidence interval]), was less than that in patients without clonidine (2.5 +/- 0.1 mg x kg(-1), 2.4-2.6 mg x kg(-1), P < 0.01). CONCLUSION: Oral clonidine premedication reduces propofol requirement for LMA insertion.

Administration, Oral↗
PubMed2000

Midazolam premedication reduces propofol requirements for sedation during regional anesthesia.

PURPOSE: Propofol is often used for sedation during spinal anesthesia. We investigated the effects of midazolam premedication on the propofol requirements and incidence of complications during sedation. METHODS: In a prospective randomized, controlled, and single-blinded study, 50 patients undergoing elective gynecological surgery were randomly divided into control and midazolam groups. Patients in the midazolam group received 2 mg midazolam im 30 min before arrival at the operation room. After spinal anesthesia was instituted with intrathecal injection of hyperbaric tetracaine, we provided sedation using continuous infusion of propofol. The level of sedation was controlled at a level between "eyes closed but rousable to command" and "eyes closed but rousable to mild physical stimulation" by adjusting the infusion rate. During sedation, the propofol requirements and complications were recorded and patients were asked, two hours after the end of operation, whether they remembered intraoperative events. RESULTS: In the midazolam group, the loading dose, steady state infusion rate, and overall infusion rate of propofol were 0.74 mg x kg(-1), 2.86 mg x kg(-1) x hr(-1), and 3.32 mg x kg(-1) x hr(-1), respectively, which were about 17% lower than those in the control group (P<0.05). Moreover, midazolam premedication reduced the incidence of intraoperative memory (P < 0.05), but had no effects on other complications. CONCLUSION: Midazolam premedication reduced propofol requirements and the incidence of intraoperative memory during sedation. These effects on sedation using propofol during spinal anesthesia are considered beneficial for patients.

Adult↗
PubMed1995

Actions of propofol on pontine neurons controlling arterial pressure in rats.

Tonic firing of pontine neurons provides excitatory input to the vasomotor centre in the ventrolateral medulla. To increase our understanding of the actions of propofol on CNS neurons controlling the cardiovascular system, we evaluated the effects of propofol on this tonic firing of pontine neurons. The actions of propofol (doses 1-4, respectively: 24 +/- 2, 40 +/- 4, 65 +/- 3 and 104 +/- 3 mg.kg-1.hr-1) on the pontine neurons were studied using eight atropinized Wistar rats. Electrical activity of renal sympathetic nerves, systemic arterial blood pressure and heart rate were recorded. Propofol decreased renal nerve activity by 3 +/- 2%, 23 +/- 3%, 33 +/- 3% and 52 +/- 4% at the four doses. Arterial pressure and heart rate decreased similarly in a dose-dependent manner. Sympathetic and cardiovascular responses to blocking neurons in the pontine reticular formation by microinjection of glycine were depressed by propofol. Renal nerve activity was decreased by 44 +/- 5% 41 +/- 4%, 28 +/- 3% and 13 +/- 2% after pontine blockade during infusion of doses 1 to 4, respectively. Similarly, arterial pressure was decreased by 25 +/- 3, 15 +/- 2, 12 +/- 1 and 5 +/- 2 mmHg. Finally, heart rate decreased by 27 +/- 6, 20 +/- 4, 18 +/- 4 and 13 +/- 5 heats per min as the propofol dose increased. The tonic firing of pontine neurons was minimally depressed by the lower two doses of propofol but higher doses did appear to depress their firing, demonstrating dose-dependence of actions of this anaesthetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Trace element homeostasis during continuous sedation with propofol containing EDTA versus other sedatives in critically ill patients.

OBJECTIVE: To evaluate changes in serum and urinary zinc, cobalt, copper, iron, and calcium concentrations in critically ill patients receiving propofol containing disodium edetate (disodium ethylenediaminetetraacetic acid [EDTA]) versus sedative agents without EDTA. DESIGN: This was a randomised, open-label, parallel-group study with randomisation stratified by baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. SETTING: Intensive care units (ICU) in 23 medical centres. PATIENTS: Medical, surgical, or trauma ICU patients 17 years of age or older who required mechanical ventilator support and sedation. INTERVENTIONS: A total of 106 patients received propofol containing 0.005 % EDTA (propofol EDTA), and 104 received other sedative agents without EDTA (non-EDTA). Only the first 108 patients were assessed for urinary trace metal excretion. Twenty-four-hour urine samples were collected on days 2, 3, and 7 and every 7 days thereafter for determination of zinc, cobalt, copper, iron, and calcium excretion; EDTA levels; urine osmolality; albumin levels; and glucose levels. The first 143 patients were assessed for serum concentration of zinc, cobalt, copper, iron, and calcium; creatinine; blood urea nitrogen; and albumin at baseline and once during each 24-hour urine collection. MEASUREMENTS AND RESULTS: For the assessment of trace metals, patients receiving propofol EDTA demonstrated increased mean urinary excretion of zinc, copper, and iron compared with the normal range. All patients receiving sedatives demonstrated increased urinary excretion of zinc and copper above normal reference values. Compared with the non-EDTA sedative group, the propofol EDTA group demonstrated increased urinary excretion of zinc and iron. Mean serum concentrations of zinc and total calcium were decreased in both patient groups. Serum zinc concentrations increased from baseline to day 3 in the non-EDTA sedative group but not in the propofol EDTA group. Renal function, measured by blood urea nitrogen, serum creatinine, and creatinine clearance, did not deteriorate during ICU sedation with either regimen. CONCLUSION: This study showed that critical illness is associated with increased urinary losses of zinc, copper, and iron. Propofol EDTA-treated patients had greater urinary losses of zinc and iron and lower serum zinc concentrations compared with the non-EDTA sedative group. No adverse events indicative of trace metal deficiency were observed in either group. The clinical significance of trace metal losses during critical illness is unclear and requires further study.

APACHE↗
PubMed1994

[Local oxygen supply to the cerebral cortex during thiopental and propofol anesthesia. First results].

Because the brain is highly vulnerable to damage from even a brief imbalance of oxygen delivery and demand, intraoperative disturbances of local oxygen supply must be avoided. Until now, there has been no method allowing fast and reliable intraoperative measurement of the local oxygen supply in the human brain. Intraoperative investigations were therefore performed using the Erlangen micro-lightguide spectrophotometer. METHODS. Intraoperative investigations of local intracapillary haemoglobin saturation (SO2) were performed during neurosurgical interventions using the Erlangen microlightguide spectrophotometer (EM-PHO). Measurements were performed in eight patients (age 31-67 years) during neurosurgical interventions. Three received thiopentone anaesthesia, and three received propofol. In two patients thiopentone anaesthesia was later changed to propofol. The EMPHO enables rapid, non-invasive measurement of local intracapillary SO2. White light from a Xenon-arc lamp is transmitted by a 250-microns micro-lightguide to the tissue. The remitted (reflected) light is led by 6 micro-lightguides surrounding the illuminating one to a rotating band-pass interference filter disk. Light in the range of 502 to 630 nm is detected with a photomultiplier. In this range haemoglobin shows an SO2-dependent spectrum, which is then analysed. Because the measurements are performed with micro-lightguides, high spatial resolution is attained. Representative measurements can be performed in a very short period of time (approx. 60 s); thus, the EM-PHO enables rapid monitoring of local SO2 in the brain. RESULTS. The effect of propofol and thiopentone anaesthesia on the distribution of local intracapillary haemoglobin saturation was investigated during neurosurgical interventions. The arterial PCO2 was similar in both groups (31 +/- 0.7 and 31 +/- 0.5 mmHg, respectively). There were also no differences in arterial blood pressure. The FiO2 was 0.28 +/- 0.04 in the thiopentone group and 0.30 +/- 0.1 in the propofol group. In all patients receiving propofol anaesthesia higher local SO2 values were found, even if the patients first received thiopentone (values in parenthesis). The mean local SO2 amounted to 65.4% (57.3%) in the propofol group and 38.8% (45.2%) in the thiopentone group. The number of values below 25% SO2 was 5.6% (5.8%) in the propofol group and 18.7% (19.1%) in the thiopentone group.

Adult↗
PubMed1994

[Comparative study of the recovery phase. Laparoscopic cholecystectomy following isoflurane, methohexital and propofol anesthesia].

Total intravenous anaesthesia (TIVA) is increasingly used in short-stay surgery such as laparoscopic cholecystectomy. TIVA may provide fast recovery of psychomotor function, thus being of benefit to both the patient's behaviour and postoperative management. The purpose of this prospective study was to compare postoperative recovery from TIVA using propofol or methohexitone as the hypnotic component and balanced anaesthesia with isoflurane. PATIENTS AND METHODS. After giving informed consent and approval by the ethical committee of our hospital, 51 patients (ASA I, II) were investigated in a prospective study. Patients were randomised to receive either isoflurane, methohexitone, or propofol. Perioperative management with regard to premedication, intraoperative analgesia, relaxation, ventilation, and postoperative analgesia was carried out identically for all groups. Postoperative vigilance, pain, and nausea scores were assessed 15, 30, 60, 120, and 360 min after extubation with a visual analogue scale (VAS). At the same points, psychomotor recovery was investigated with the following assays: sedation as shown in Table 1; orientation with ten questions as to person, time, and location; memory as expressed by the patient's ability to repeat five words; a calculation test with five subtractions of the number 7 beginning from 100; and word generation by the number of words with an initial "m" given within 1 min and with animal names. Data were analysed with Kruskal Wallis' test for multiple comparisons between the groups and with Friedman's test for repeated measurements. All values are given as medians (interquartile range) or ranges. RESULTS. There was no difference between the groups' physical condition (Table 2). All intraoperative parameters compared well between groups; the management of anaesthesia was smoother with isoflurane than with the other anaesthetics. Psychomotor recovery was somewhat faster in the propofol group than the methohexitone group, as indicated by sedation score, orientation, memory and calculation tests (Table 4), word generation tests (Fig. 4), and subjective vigilance score (Fig. 3). The difference in recovery time between the propofol and isoflurane groups was minimal and without any significance or relevance. The incidence of postoperative nausea was significantly lower after balanced anaesthesia with isoflurane (24%, P < 0.05) as compared to TIVA with either propofol (53%) or methohexitone (41%). However, there were only minor differences between the groups; the ability to cooperate and be mobilised was not limited. DISCUSSION. Each of the three techniques used in this study is suitable for anaesthesia in patients undergoing laparoscopic cholecystectomy. Since fast recovery of vigilance and psychomotor function is very important in outpatient surgery, opioid-supplemented propofol anaesthesia is well established. Inhalation anaesthesia with isoflurane in air/oxygen without adding nitrous oxide compares well to propofol TIVA for laparoscopic surgery.

Adult↗
PubMed1994

[Endocrine stress reaction, hemodynamics and recovery in total intravenous and inhalation anesthesia. Propofol versus isoflurane].

This prospective, randomised study compared total intravenous anaesthesia (TIVA) and inhalation anaesthesia with respect to endocrine stress response, haemodynamic reactions, and recovery. METHODS. The investigation included two groups of 20 ASA I-II patients 18-60 years of age scheduled for orthopaedic surgery. For premedication of both groups, 0.1 mg/kg midazolam was injected IM. Patients in the propofol group received TIVA (CPPV, PEEP 5 mbar, air with oxygen FiO2 33%) with propofol (2 mg/kg for induction followed by an infusion of 12-6 mg/kg.h) and fentanyl (0.1 mg before intubation, total dose 0.005 mg/kg before surgery, repetition doses 0.1 mg). For induction of patients in the isoflurane-group, 5 mg/kg thiopentone and 0.1 mg fentanyl was administered. Inhalation anaesthesia was maintained with 1.2-2.4 vol.% isoflurane in nitrous oxide and oxygen at a ratio of 2:1 (CPPV, PEEP 5 mbar). For intubation of both groups, 2 mg vecuronium and 1.5 mg/kg suxamethonium were injected, followed by a total dose of 0.1 mg/kg vecuronium. Blood samples were taken through a central venous line at eight time points from before induction until 60 min after extubation for analysis of adrenaline, noradrenaline (by HPLC/ECD), antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and cortisol (by RIA). In addition, systolic arterial pressure (SAP) heart rate (HR), arterial oxygen saturation (SpO2), and recovery from anaesthesia were observed. RESULTS. Group mean values are reported; biometric data from both collectives were comparable (Table 1). Plasma levels of adrenaline (52 vs. 79 pg/ml), noradrenaline 146 vs. 217 pg/ml), and cortisol (82 vs. 165 ng/ml) were significantly lower in the propofol group (Table 2, Figs. 1 and 3). Plasma levels of ADH (4.8 vs. 6.1 pg/ml) and ACTH (20 vs. 28 pg/ml) did not differ between the groups (Table 2, Figs 2 and 3). SAP (128 vs. 131 mmHg) was comparable in both groups, HR (68/min vs. 83/min) was significantly lower in the propofol group, and SpO2 (97.1 vs 97.4%) showed no significant difference (Table 3). Recovery from anaesthesia was slightly faster in the propofol group (following of simple orders 1.9 vs. 2.4 min, orientation with respect to person 2.4 vs. 3.4 min, orientation with respect to time and space 2.8 vs. 3.7 min), but differences failed to reach statistical significance. CONCLUSIONS. When compared with isoflurane inhalation anaesthesia, moderation of the endocrine stress response was significantly improved during and after TIVA with propofol and fentanyl. Slightly shorter recovery times did not lead to an increased stress response. With respect to intra- and postoperative stress reduction, significant attenuation of sympatho-adrenergic reaction comparable SAP and reduced HR, sympatholytic and hypodynamic anaesthesia with propofol and fentanyl seems to be advantageous for patients with cardiovascular and metabolic disorders. For this aim, careful induction and application of individual doses is essential.

Adolescent↗
PubMed1995

[Intravenous anesthesia with propofol versus thiopental-/enflurane anesthesia. A consumption and cost analysis].

It may be possible to reduce costs in anaesthesia when there is a choice of drugs and methods. Two of the most widespread techniques are inhalation anaesthesia with enflurane following induction with thiopentone, and intravenous anaesthesia (IVA) with propofol. The aims of our study were to compare the costs, effectiveness and side effects of the anaesthetics involved in these two techniques, and to measure significant clinical parameters. METHODS. After approval by the hospital ethics committee, 40 adult patients of ASA physical status 1 and 2 who had been scheduled for elective septorhinoplasty and had given informed consent were entered in our prospective, single-blind randomized study. In 20 patients anaesthesia was induced with thiopentone (4-5 mg/kg) and suxamethonium (1-1.5 mg/kg) and maintained with enflurane. The other 20 patients received an initial i.v. bolus of propofol (2-2.5 mg/kg) followed by a propofol infusion adjusted to their individual clinical needs. Ventilation was performed in both groups with 70% nitrous oxide in oxygen, using a nonrebreathing system. Muscle relaxation was maintained with atracurium. The amounts of anaesthetics, oxygen, nitrous oxide, and muscle relaxants used were measured and a record of the costs was kept. In addition, circulatory and respiratory parameters and quantitative and qualitative aspects of recovery from anaesthesia were recorded. RESULTS. The biometric and clinical data did not differ significantly between the two groups. For induction, 382 (+/- 55.9) mg thiopentone costing 1.24 Swiss francs (SFr), or 172 (+/- 25.1) mg propofol costing 11.87 (SFr) was used. For maintenance, 28.3 (+/- 6.4) ml enflurane costing 21.96 SFr/h, or 450.7 (+/- 247) mg propofol costing 29.75 SFr/h was required. The need for muscle relaxants, oxygen, and nitrous oxide was also not significantly different in the two groups. Additional expenses were due to relaxation antagonists (1.91 SFr per patient in both groups) and to the perfusion pump system (8.60 SFr per patient in the IVA group only). Circulatory and respiratory parameters remained normal in both groups. In the propofol group, the heart rate tended to increase more at the beginning of anaesthesia, whereas later on it showed a tendency to lower values than in the thiopentone/enflurane group. Patients receiving IVA generally had a shorter awakening period, a higher degree of wellbeing during recovery, and needed less systemic analgesics (P < 0.05). CONCLUSIONS. Costs of anaesthetic drugs in the IV group totalled 54.50 SFr during the first hour, i.e. 1.65 times the costs in the thiopentone/enflurane group for the same time. However, with continuing duration of anaesthesia this ratio declines to 1.43 in anaesthesia lasting 2 h. In addition, IVA patients had a noticeably faster and far more pleasant recovery. Minute ventilation, oxygen consumption, heart rate and CO2 production indicated a less pronounced stress response and sympathetic activity during and after propofol. Quicker recovery of cognitive and psychomotor abilities, less postoperative pain and less impairment of respiratory function after IVA may lead to an earlier release from the postoperative recovery unit. This might be a cost-reducing factor that should be taken into account when these two anaesthetic regimens are concerned.

Adolescent↗
PubMed1996

[Age-related correlation between EEG parameters and depth of anesthesia under propofol. Effect of fentanyl].

UNLABELLED: This study was designed to determine the relationship between the electroencephalogram (EEG) and clinical signs of depth of anaesthesia during induction of anaesthesia by slow infusion of propofol (18 mg/kg.h). METHODS: Four groups of 12 patients each were studied (groups I and II: 18-50 years; groups III and IV: > 70 years). Groups II and IV were given 0.15 mg fentanyl before the infusion of propofol was started. The clinical signs recorded were: (1) loss of eyelash reflex; (2) respiratory insufficiency; (3) tolerance to painful stimuli; and (4) intubation. Cardiovascular reactions were documented. The dosage was calculated from the infusion time (time from start of infusion until specific clinical event). Bipolar electrodes were placed at the C4/P4 positions (10-20 placement system) to record the EEG, which was processed by a personal computer (Narkograph) using fast-fourier transformation. The Narkograph calculates multiparametric EEG stages ranging from A to F (according to Kugler) as well as median frequency and spectral-edge frequency 95% (SEF). Stage A represents alpha rhythm, stage F is equivalent to a burst suppression pattern. For statistical analysis a Student t-test was performed. RESULTS: The infusion of propofol led to slowly developing anaesthesia with loss of eyelash reflex followed by loss of pain response, respiratory insufficiency, and intubation. In the younger patients the clinical signs coincided with well-differentiable EEG patterns. Above 70 years of age there were problems in distinguishing the EEG patterns, as there are alterations of the EEG with advanced age. The multiparametric EEG stage calculated by the Narkograph showed a better correlation with the clinical signs than median or SEF. Fentanyl shortened the induction time remarkably: less propofol was needed to achieve corresponding clinical signs when fentanyl was added. The EEG patterns typical for a specific clinical condition remained unchanged by fentanyl. Similar clinical situations showed equal EEG stages in all groups. Different clinical situations could be distinguished by significant changes in the EEG. The infusion times for tolerance to pain and respiratory insufficiency were not significantly different, and there were no significant differences between the EEG patterns and propofol doses for these two clinical parameters. Intubation was performed after 18.5 +/- 4.6 min in group I with a propofol dose of 5.6 +/- 1.4 mg/kg. This time was shortened by fentanyl in group II to 10.1 +/- 3.7 min and a propofol dose of 3.0 +/- 1.1 mg/kg. CONCLUSION: Different clinical signs corresponding to different levels of depth of anaesthesia could be differentiated by their EEG parameters. The EEG stage allowed better differentiation of the clinical conditions than the single-parameter EEG derivatives median and SEF. The results of this study show that EEG monitoring provides information about depth of anaesthesia.

Adjuvants, Anesthesia↗
PubMed1997

[Remifentanil with propofol or isoflurane. A comparison of the recovery times after arthroscopic surgery].

OBJECTIVES: Due to its unique pharmacokinetics, the new esterase-metabolised opioid remifentanil results in rapid post-anesthesia recovery. The aim of this clinical investigation was to compare recovery times after remifentanil anaesthesia in combination with hypnotic concentrations of either propofol or isoflurane. Dosages used in the study protocol were based on recommendations by the pharmaceutical manufacturer. METHODS: Patients (ASA status I-II) scheduled for elective arthroscopy were included in this trial. Without premedication in the morning, anaesthesia was induced identically in both groups: remifentanil bolus (1 microgram/kg), start of remifentanil-infusion (0.5 micrograms/kg/min), followed immediately by propofol (ca. 2 mg/kg). For maintenance of anaesthesia remifentanil (0.25 micrograms/kg/min) was combined with either a propofol infusion of 0.1 mg/kg/min or 0.5 MAC isoflurane (= 0.6 vol. %) in O2/air. Anaesthetic delivery was discontinued simultaneously with termination of surgery and recovery times were recorded. RESULTS: A total of 40 patients were studied at random in two groups of 20 each with comparable demographic data and anaesthetic technique (Tables 1 and 2). In both groups emergence was very rapid. Recovery times were significantly shorter for remifentanil-isoflurane than for remifentanil-propofol (Table 3): spontaneous ventilation 5.1 vs 8.1 min (P < 0.05), extubation 5.5 vs 8.6 min (P < 0.02), post-anaesthesia recovery score > or = 9 of 10 points 6.2 vs 11.3 min (P < 0.01), and arrival at PACU 16.2 vs 19.2 min (P < 0.01). Mild to moderate shivering was noted in 40% of all patients (9 cases following isoflurane, 7 following propofol). CONCLUSIONS: Using the manufacturer's recommended dosages, emergence after remifentanil anaesthesia is more rapid with 0.5 MAC isoflurane than with 0.1 mg/kg/min propofol. These results are most probably due to the different pharmacological properties of both co-anaesthetics, especially the applied dosages, and to different interactions with remifentanil. Present clinical experience suggests that a further dose reduction, especially for propofol, is possible. For both remifentanil groups emergence was remarkably rapid between return of consciousness and the awake state (on-off phenomenon), which might contribute to post-anaesthesia safety.

Adult↗
PubMed1998

[Predictability and precision of "target-controlled infusion" (TCI) of propofol with the "Disoprifusor TCI" system].

UNLABELLED: In Germany a TCI-system for propofol (Disoprifusor-TCI) has been commercially available since spring 1997. We investigated the prediction error and precision of this TCI system as part of a multicentre study. Bias, precision, blood concentrations and dosage of propofol were compared with patients receiving propofol via a manually controlled infusion device. METHODS: After approval by the local Ethics Committee and written informed consent, 21 patients of ASA-classification I to III scheduled for major abdominal surgery received either a target controlled infusion (group T, Disoprifusor-TCI) or a manually controlled infusion (group M) of propofol. The propofol plasma concentrations were measured by HPLC. The prediction error for each measurement, the median prediction error (MDPE) or bias, the median absolute prediction error (MDAPE) or precision and the divergence (change of the prediction error over infusion time) were calculated for both groups. RESULTS: For all patients in group T (n = 12) the bias of the TCI system was 6.7% and the precision 27.5%. For 70% of all measured plasma concentrations the absolute prediction error was < or = 37%. The divergence was -5.4% per hour. For all patients in group M (n = 9) the bias was 44.2% and the precision 50%. The mean amount of propofol infused per kilogram body weight and hour was significant higher in T (9.0 +/- 1.2 mg/kg/h) than in M (6.6 +/- 1.2 mg/kg/h, p < 0.005). CONCLUSIONS: With a precision of 27.5% the investigated TCI system (Diprifusor-TCI) showed an acceptable inaccuracy, as for TCI-systems a median prediction error of +/- 30% has to be expected due to the inherent variability of pharmacokinetic parameters. Further studies will be necessary to find out whether the investigated TCI system for propofol may offer substantial advantages.

Abdomen↗
PubMed2006

Propofol in the treatment of refractory status epilepticus.

OBJECTIVES: To study prospectively the effects of propofol anesthesia on seizure control, hemodynamics and course of intensive care in patients with refractory status epilepticus. DESIGN AND SETTING: Prospective observational study in the general intensive care unit in a tertiary university hospital. PATIENTS: Ten patients with refractory status epilepticus. INTERVENTIONS: Patients received propofol anesthesia aiming to burst suppression EEG pattern for 12 h. MEASUREMENTS AND RESULTS: Dose of propofol, quality of burst suppression EEG, hemodynamics and the course of intensive care were recorded. Clinical and electrophysiological seizures terminated quickly, but maintaining burst suppression EEG pattern required incremental doses of propofol. Despite high doses of propofol, recovery from anesthesia was fast. CONCLUSIONS: High doses of propofol are needed in the treatment of refractory status epilepticus. The maintenance of continuous-burst suppression is difficult, and vigilant titrating of dosage of propofol is necessary under continuous EEG monitoring.

Adult↗
PubMed2000

Propofol improves recovery from paraquat acute toxicity in vitro and in vivo.

OBJECTIVE: To investigate whether the antioxidative sedatives propofol and thiopental can improve recovery from acute paraquat toxicity in A549 cells and in mice. DESIGN: Prospective, controlled, dose-response, in vitro study and prospective, controlled animal study. SETTING: A university animal research laboratory. SUBJECTS: Established human lung cultured cells and male SPF ICR mice. INTERVENTIONS: Paraquat-treated (0.2 mM) A549 cells were incubated either with the antioxidative sedatives propofol (0-0.56 mM) or thiopental (0-2.0 mM), or the nonantioxidative sedatives diazepam (0-3.0 mM), midazolam (0-3.0 mM) and ketamine (0-9.0 mM), as well as the antioxidative drugs, trolox (0-2.0 mM), alpha-tocopherol (0-4.4 mM), antioxidative-processed food (AOB; 0-1.0 mg/ml), superoxide dismutase (SOD; 0 and 3,000 U/ml) and ulinastatin (0 and 50,000 U/ml), for 48 h. Paraquat-treated mice received i.v. injections of 10 mg/kg propofol, 5 mg/kg thiopental, 4.0 mg/kg trolox, 100 mg/kg alpha-tocopherol, 10 mg/kg AOB or 5,000 U/kg SOD, b.i.d. for 4 days (n = 10 each). MEASUREMENTS AND RESULTS: Post-administered propofol and thiopental, as well as the antioxidative drugs, trolox, alpha-tocopherol and AOB, improved A549 cell survival in vitro. The non-antioxidative sedatives SOD and ulinastatin were not protective. An i.p. injection of 50 mg/kg of paraquat resulted in a survival rate of 40% in mice at day 6. Propofol, trolox, alpha-tocopherol and AOB significantly lowered the mortality rate (80% survival), while thiopental did not. CONCLUSION: Post i.v. injection of propofol is protective against paraquat-induced damage. Propofol can be given during mechanical ventilatory support after paraquat poisoning.

Anesthetics, Intravenous↗
PubMed2004

Relative antioxidant capacities of propofol and its main metabolites.

The antioxidant activity of propofol, a widely used anesthetic, has previously been demonstrated, but no study has focused on propofol metabolites although propofol undergoes extensive metabolism. In the present study, the antioxidant properties of propofol and its metabolites were studied by measuring malondialdehyde (MDA) produced from lipid peroxidation by microsomes triggered with several free radical generating systems. True MDA determination was performed using a specific high performance liquid chromatography technique. Gas chromatography-isotope ratio mass spectrometry methodology was also used to assess the antioxidant action in a homogeneous aqueous environment. Propofol, 2,6-di-isopropyl-1,4-quinol (1,4-quinol) metabolite and 3,5-di- tert-butyl-4-hydroxytoluene markedly inhibit lipid peroxidation at concentrations lower than 5 microM. The binding of the glucuroconjugated moiety to either one of two hydroxyl groups of 1,4-quinol lowers the radical scavenging activity. Propofol glucuronide did not exert any radical scavenging activity except when peroxidation was induced with tert-butylhydroperoxide. Our data demonstrate that propofol and its metabolites inhibit lipid peroxidation at concentrations similar to those measured in human plasma during anesthesia. Their antioxidant efficiency is influenced by several factors, including the type of radical initiator involved and the site of radical production.

Animals↗
PubMed2002

'In vitro' binding of propofol to serum lipoproteins in thyroid dysfunction.

OBJECTIVE: To determine a regression relationship between the unbound fraction (fu percent) of propofol, a highly lipophilic intravenous anaesthetic agent, and demographic and biochemical variables in a thyroid dysfunction population. METHODS: Serum samples from patients with hypo- (n=33) and hyperthyroidism (n=33) and also from healthy volunteers (control group; n=9) were spiked with propofol to a total (bound + unbound propofol) concentration of 10 microg/ml. The unbound concentration was determined using ultrafiltration followed by high-performance liquid chromatography with fluorimetric detection and the unbound fraction percent (fu) and the binding ratio [bound/free concentration (B/F)] were calculated. Albumin, alpha(1)-acid glycoprotein, cholesterol, triglycerides, HDL, LDL, VLDL lipoproteins, and T3 and T4 hormone concentrations were measured. B/F has a linear relationship with lipoprotein concentration--unlike that for fu which is curvilinear - so, we developed a linear regression model of B/F for propofol with the above biochemical variables and with gender. RESULTS: The fu in hypothyroidism was significantly lower than in the healthy control (mean +/- standard deviation 0.74 +/- 0.13% vs 0.87 +/- 0.12%, P < 0.01) but the fu was no different in hyperthyroid subjects than controls (0.94 +/- 0.16% vs 0.87 +/- 0.12%, P > 0.05). HDL, LDL and VLDL lipoproteins were significant predictors of B/F (P < 0.05) and were capable of explaining 54% of the variability in the 'in vitro' binding of propofol in thyroid disease. CONCLUSION: These results could help explain the interindividual variability in the protein binding of propofol in thyroid dysfunction patients and suggest the inclusion of lipoproteins in covariate model development for the pharmacokinetic/pharmacodynamic parameters of propofol.

Adult↗
PubMed2004

Propofol attenuates reperfusion injury after testicular torsion and detorsion.

Propofol, which is widely used as an intravenous anesthetic, has been shown to have an antioxidant activity on several tissues. This study was designed to investigate the prevention of reperfusion injury with propofol after testicular torsion. Five groups of rats (seven in each group) were used. Animals in the control group (group I) did not received any treatment, while animals in the sham group (group II) underwent scrotal incision and testicular fixation only. After 2 h of 720 degrees left testicular torsion in groups III, IV and V, subsequent detorsion was done for 2 h in groups IV and V. Propofol (50 mg/kg) was injected transperitoneally 30 min prior to detorsion in group V. Both testicles in all rats were retrieved and tissue malondialdeyhde (MDA) level, which is a measure of the amount of free oxygen radicals, and enzymatic activity of xanthine oxidase (XO), which converts hypoxanthine to xanthine and uric acid were studied. In addition, tissue catalase (CAT) and glutathione peroxidase (GSH-Px) activities, which are endogenous scavenger enzymes, protecting tissues against free radicals, were studied. Additionally, histological evaluations were performed after hematoxylin and eosin staining. Testicular MDA levels, and XO and CAT activities were higher in the torsion group compared to sham control group (P<0.05). Detorsion caused a further increase in MDA levels, contrasting with a decrease in the levels of XO activity, while CAT activity was not changed. Pretreatment with propofol prevented a further increase in MDA levels and significantly decreased CAT activity following detorsion. GSH-Px activities were not effected either by torsion/detorsion or propofol pretreatment. Histologically, torsion caused some separation between germinal cells in the seminiferous tubules, which became much more prominent in the detorsion group and attenuated with propofol pretreatment. There was no significant change in any of the above-mentioned enzymatic activities nor were there histopathological changes in the contralateral testicle in any groups. It is concluded that biochemically and histologically reperfusion injury occurs in the ipsilateral testis following detorsion up to 2 h. Preference of propofol for anaesthesia during the detorsion procedure may attenuate such reperfusion injury.

Animals↗
PubMed2005

Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model.

PURPOSE: Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant potential. We hypothesized that propofol may attenuate ALI by acting as a free-radical scavenger. METHODS: We investigated the effects of propofol on oxidant-induced ALI induced by purine and xanthine oxidase (XO), in isolated perfused rabbit lung, in two series of experiments. In series 1, we examined the relationship between the severity of ALI and the presence of hydrogen peroxide (H2O2). In series 2, we evaluated the effects of propofol on attenuating ALI and the dose dependence of these effects. The lungs were perfused for 90 min, and we evaluated the effects on the severity of ALI by monitoring the pulmonary capillary filtration coefficient (Kfc), pulmonary arterial pressure (Ppa), and the pulmonary capillary hydrostatic pressure (Ppc). RESULTS: In series 1, treatment with catalase (an H2O2 scavenger) prior to the addition of purine and XO resulted in complete prevention of ALI, suggesting that H2O2 may be involved closely in the pathogenesis of ALI. In series 2, pretreatment with propofol at concentrations in excess of 0.5 mM significantly inhibited the increases in the Kfc values, and that in excess of 0.75 mM significantly inhibited the increase in the Ppa values. CONCLUSION: Propofol attenuates oxidant-induced ALI in an isolated perfused rabbit lung model, probably due to its antioxidant action.

Animals↗
PubMed2005

Target-controlled infusion of propofol for a patient with myotonic dystrophy.

We present a patient with myotonic dystrophy (MD) who was anesthetized with propofol using a target-controlled technique for electrophysiologic examination and cardiac catheter ablation. The patient became apneic unexpectedly at the same time when he fell asleep, with effect-site propofol concentration of 1.6 microg ml(-1). We had to insert a laryngeal mask airway (LMA), and mechanical ventilation was performed. The patient opened his eyes on verbal command at an effect-site concentration of 1.2 microg ml(-1) after the procedure. This concentration (1.2 microg ml(-1)) was slightly lower than our institutional average for adult male patients (1.5 +/- 0.2 microg ml(-1)). However, the time from the end of anesthesia to the patient's awakening was about 10 min. We considered that emergence from anesthesia was not delayed in this case. Careful titration of propofol by target-controlled infusion (TCI) enabled to evaluate the patient's sensitivity to propofol. We conclude that TCI of propofol was a useful anesthetic technique in the MD patient. Respiratory depression might occur in MD patients at low propofol concentrations. Precise control and titration over target propofol concentration is important in anesthetic management for MD patients.

Adult↗