Effects of propofol on ipecacuanha-induced nausea and vomiting

Background : The purpose of this study was to evaluate if propofol has 5-HT₃ antagonistic effects. Ipecacuanha is known to release serotonin (5-HT) in the gastrointestinal tract and therefore ipecacuanha syrup was used to induce nausea and vomiting. The 5-HT₃ antagonist ondansetron was used as a control substance.
Results : During the first 150 min after ingestion of ipecacuanha there were no retchings during the ondansetron infusion ( P = 0.01 vs placebo, P =0.02 vs propofol) and significantly fewer retchings during propofol infusion compared to placebo ( P <0.02). There was no nausea during the ondansetron infusion ( P <0.01 vs placebo and propofol) but the volunteers experienced nausea both during the placebo and propofol infusion (NS).
Conclusion : This study in volunteers has shown that propofol reduces the intensity of retching after oral intake of ipecacuanha syrup. As ipecacuanha releases 5-hydroxytryptamine, it can be concluded that propofol may have a weak 5-HT₃ antagonistic effect.
Method : Ten healthy male volunteers (20–37 years) were studied on three occasions and were randomly allocated to receive a concomitant infusion of propofol (initial bolus 0.1 mg kg^-1 then 1 mg kg^-1h^-1), ondansetron (initial bolus 0.11 mg kg^-1 then 14 μg kg^-1 h^-1) and placebo on either occasion. The infusions started 30 min before oral ingestion of 30 ml of ipecacuanha and continued until 150 min after the intake. The number of retchings was recorded and the intensity of nausea was estimated by the subjects on a visual analog scale.     

Propofol influences the electroretinogram to a lesser degree than thiopentone

Background: The Electroretinogram (ERG) is used clinically to assess the function of retina. Anaesthetic agents are known to affect ERG, and as anaesthesia is often needed in children and uncooperative patients, knowledge about its effects is of clinical importance. Barbiturates selectively depress ERG components, and we compared thiopentone with propofol to assess if the latter preserved retinal function better.
Methods: Ten pigs, average weight 17 kg (SD ± 2 kg) were anaesthetized randomly with propofol 10 mg kg^-1 or thiopentone 30 mg kg^-1. Anaesthesia was maintained by 65% nitrous oxide in oxygen and continuous infusion of the induction agent, i.e. 10 mg kg^-1 h^-1 of propofol, or 10 mg kg^-1 h^-1 for the first hour, then 5 mg kg^-1 h^-1 of thiopentone, with doses being based on pilot studies. After an interval of one week the programme was repeated using the other agent. After 40 minutes dark-adaptation, responses to single flashes of graded intensities from a xenon flashlamp were recorded at five-minute intervals. The a- and b-wave amplitudes and implicit times (time to peak), and a-wave slopes were determined.
Results: The b-wave implicit time was significantly shorter during propofol anaesthesia than when using thiopentone. The effect was most pronounced at the lowest intensities (P < 0.01). No statistically significant differences were found in the amplitudes of the b-waves. The a-wave appeared at lower stimulus intensity (P < 0.05) and the a-wave slopes were significantly steeper (P < 0.01) during propofol anaesthesia.
Conclusion: Propofol accordingly appeared to preserve the photoreceptor response better than thiopentone, and may therefore be considered to be more suitable for ERG recordings than thiopentone.     

Potency and maintenance requirement of atracurium and vecuronium given alone or together

A synergism exists between some competitive muscle relaxants. However, maintenance requirement of a combination of muscle relaxants has been evaluated only in paediatric patients. We studied 45 elective adult surgical patients (ASA I-II) during propofol-alfentanyl-N₂O-O₂-anaesthesia. The first 30 patients were randomized to receive either atracurium or vecuronium to create individual dose-response curves for these muscle relaxants. ED₉₅-values for atracurium and vecuronium were 260±9 and 59±3 μg · kg^-1, respectively (mean±s.e.mean). Requirements of atracurium and vecuronium to maintain an 85–95% neuromuscular blockade were 301 and 83 μg kg^-1 h^-1, respectively. An additional 15 patients received a combination of atracurium and vecuronium (cAV) in an equipotent dose ratio. An ED₉₅ of a cAV was 94± 7 μg · kg^-1 of atracurium together with 21±2 μg · kg^-1 of vecuronium, or 72±6% of one ED₉₅ dose of a parent agent. Potentiation was significant ( P =0.0001). A maintenance requirement of a cAV was 120 μg kg^-1 h^-1 of atracurium together with 27 μg kg^-1 h^-1 of vecuronium. Thus, a significant potentiation was maintained also during the course of anaesthesia. A cAV had an effect like one intermediate-acting agent. If a cAV is used instead of using atracurium or vecuronium alone, the maximal reduction of drug consumption would be approximately 30%.     

Quantifying the interaction of vecuronium with enflurane using closed-loop feedback control of vecuronium infusion

The influence of different levels of enflurane anaesthesia on infusion requirements of vecuronium was studied in 40 adult surgical patients. Ninety percent neuromuscular block was maintained by computer controlled infusion of vecuronium. During the first 90 min study period all patients received fentanyl-nitrous oxide-oxygen (2:1) anaesthesia. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: group I, control, fentanyl-nitrous oxide anaesthesia; group II, enflurane 0.3%-nitrous oxide; group III, enflurane 0.6%-nitrous oxide; group IV, enflurane 0.9%-nitrous oxide. Every patient served as his/her own control and the changes of vecuronium infusion requirements were determined individually. When the administration of enflurane was started, vecuronium infusion requirements decreased progressively until 90 min. In group II the infusion rate lowered from 80±28 to 56±20 μg . kg^-1 . h ^-1, in group III from 61 ±29 to 34±17 μg . kg^-1 . h^-1 and in group IV from 65±20 to 30± 14 μg . kg^-1 . h^-1. In the control group the infusion rate decreased during the three hour study period from 69± 17 (first 90 min period) to 59± 16 μg . kg^-1 . h^-1 (second 90 min period). Enflurane reduces the dose requirements of vecuronium administered by continuous infusion in a dose- and time-dependent manner.     

A comparison of the effects of fentanyl and propofol on left ventricular contractility during myocardial stunning

Background : The intravenous anaesthetic propofol has been shown to possess free radical scavenging activity and calcium channel blocking effects in a number of in vitro models. We decided to compare the effects of propofol with those of fentanyl on myocardial contractility during and after ischaemia to determine whether propofol could protect the heart and improve recovery of ventricular contractile function in open-chested dogs.
Methods : Twenty adult beagles were acutely instrumented, under halothane anaesthesia, to measure ECG; aortic, left ventricular pressures; cardiac output; coronary flow; and segmental lengths in the regions perfused by the left anterior and left circumflex coronary arteries. After surgery and a stabilisation period halothane anaesthesia was terminated and fentanyl (100 μg. kg^-1 bolus followed by 2 μ.kg^-1·min^-1 infusion; n=10) or propofol (5 mg. kg^-1 bolus followed by 0.3 mg· kg^-1 min^-1 infusion; n=10) anaesthesia commenced. After a stabilisation period the LAD coronary artery was occluded for 10 min and then reperfused for 3 h. Measurements were taken throughout the protocol.
Results : We found no significant difference in recovery of contractile function between propofol and fentanyl as assessed by normalised preload recruitable work area (50±10 vs 47±16%), normalised systolic shortening (36±12 vs 48±14%) and peak left ventricular dP/dt (1665±276 vs 1846±151 mmHg.s^-1) at the end of reperfusion.
Conclusion : We conclude that at the concentration used in this study propofol shows no improvement in contractility during "stunning" when compared to fentanyl.     

Comparison of subhypnotic doses of thiopentone vs propofol on the incidence of postoperative nausea and vomiting following middle ear surgery

Background : Middle ear surgery is associated with a high incidence of emetic sequelae and propofol has been reported to have antiemetic activity in subhypnotic doses.
Methods : In a double-blind, randomized study, the patients received either thiopentone 1.0 mg.kg^-1 (n=26) or 0.5 mg.kg^-1 propofol (n=26) at the end of middle ear surgery under isoflurane-N₂O-fentanyl-vecuronium anaesthesia. Trained nurses, unaware of the group assignment, assessed postoperative nausea, retching and vomiting up to 24 h after the end of anaesthesia. Droperidol 10μg.kg^-1 was used as a "rescue" antiemetic.
Results : The main result was that the patients in the propofol group did not suffer from retching and vomiting (R&V) during the first 6 h, whereas these symptoms occurred in 46% ( P <0.001) of the patients in the thiopentone group. The patients in the propofol group needed significantly less droperidol during the first 24 h (mean number of doses 0.39 ± 0.57 (SD)) than the patients in the thiopentone group (1.35 ± 1.47, P <0.005). Treatment with propofol was a predictor for lowered incidence of R&V, as well as male gender and negative history of motion sickness.
Conclusion : Propofol at a subhypnotic dose of 0.5 mg.kg^-1 provides prophylaxis against retching and vomiting for the first 6 h postoperatively after middle ear surgery. The incidence of nausea was not reduced by propofol.     

Lack of effect of flumazenil on the reversal of propofol anaesthesia

Propofol, like the benzodiazepines, activates the GABA_A receptor-chloride ionophore complex; they potentiate one another. Since neither pharmacodynamic nor pharmacokinetic data concerning drug interaction between flumazenil and propofol is available, and especially considering the relationship of binding sites, flumazenil, the antagonist of benzodiazepines, was investigated to determine its effect upon recovery from propofol anaesthesia. Forty women receiving dilatation and curettage procedures were included in this double-blind test. After 50 μg fentanyl, propofol 2 mg · kg^-1 was injected for induction and followed by infusion at the rate of 15 mg · kg^-1 · hr^-1. After the operation, patients were given normal saline (Group A) or flumazenil 10 μg · kg^-1 (Group B) randomly.
Recovery time in Group A was 15.2±5.1 min and Group B 15.8±4.8 min. Propofol concentrations at the end of infusion were 4.17±1.33 μg ·ml^-1 (Group A) and 4.03±1.45 μg · ml^-1 (Group B); these then declined to 1.22±0.17 μg · ml^-1 (Group A) and 1.18±0.15 μg · ml^-1 (Group B) when patients were able to open their eyes on command. No significant differences were found between the groups based on propofol concentrations and recovery time, nor did haemodynamic changes differ between them after administration of reversal agents. It was concluded that flumazenil 10 μg · ml^-1 does not influence recovery from propofol anaesthesia.     

Mivazerol prevents the tachycardia caused by emergence from halothane anesthesia partly through activation of spinalα2-adrenoceptors

Background : Mivazerol (MIV) is anα₂-adrenoceptor agonist designed to prevent adverse cardiac outcome in perioperative patients. The present study was undertaken to determine whether the hyperdynamic state observed at emergence from halothane (HAL) anesthesia in rats could be modulated by MIV and to explore the mode of action of MIV under such conditions.
Methods : Male Sprague Dawley rats were anesthetized with 1% HAL and assisted for respiration (N₂O-O₂: 70-30%). MIV 2.2–15.3μg.kg^-1.h^-1 i.v. was infused 30 min before withdrawal of anesthesia and compared for heart rate (HR) and systolic arterial blood pressure (SAP) to control animals treated with saline. In some experiments, animals were pretreated with intrathecal pertussis toxin (T2 level, 0.5μg, 7 d), or i.v. rauwolscine (0.34 mg/kg, 5 min) or were bilaterally stellectomized (30 min) prior to withdrawal of HAL.
Results : Increases in HR (65 bpm, +20%) and in SAP (25 mmHg, +26%) were observed immediately upon discontinuation of HAL and remained constant for at least 30 min. The increase in HR was abolished by removal of the stellate ganglia. MIV dose-dependently inhibited the increase in HR from 4.8μg.kg^-1.h^-1 (68% reduction, P <0.05) without affecting HR or SAP during anesthesia. Inhibition of HR increase was of 98% at 15.3μg.kg^-1.h^-1. This effect was abolished by rauwolscine, and partially (50%) inhibited by pertussis toxin pre-treatment.
Conclusion : These results demonstrate that withdrawal of HAL anesthesia in the rat produces a sustained increase in HR due to activation of the sympathetic system and that MIV inhibits this tachycardia via activation ofα₂-adrenoceptors located at least in part in the spinal cord.     

Plasma concentrations after rectal administration of acetaminophen in preterm neonates

Acetaminophen is frequently administered to infants and children for its antipyretic and analgesic properties. Oral administration is the route of choice in daily practice. In some circumstances this is impractical. Rectal administration of acetaminophen is an alternative route. This study measures plasma concentrations following rectal administration of acetaminophen 20 mg·kg⁻¹ (10% Infants' Tylenol Drops, McNeil Consumer Product Co., diluted with an equal volume of sterile water) in five preterm neonates. Serial arterial blood samples were obtained at 0, 15, 30, 60, 120, and 240 min. Pharmacokinetic parameters were (mean± sd ): C_max (maximum plasma concentration) of 8.38±3.92 μg·ml⁻¹ and T_max (time to reach maximum plasma concentration) of 78.0±40.2 min. Our results show that 20 mg·kg⁻¹ of acetaminophen rectally results in low plasma levels in preterm neonates.     

Propofol infusion anaesthesia and immune response in minor surgery

This study was set up to evaluate the effects of propofol infusion anaesthesia on immunological function in minor surgery. Twenty-seven patients (median age 51 years, ASA 1-2) scheduled for minor breast surgery were randomly assigned to two groups. Anaesthesia was induced in group 1 with propofol 2.5 mg.kg^-1 and maintained with propofol 12 mg.kg^-1.h^-1 and 30% O₂ in air, whereas in group 2 anaesthesia was induced with thiopentone 4 mg.kg^-1 and maintained with 70% N₂O in O₂. Fentanyl and vecuronium were used in both groups. The percentages of T cells (p < 0.001), B cells (p < 0.01) and memory T cells increased (p < 0.01) in both groups. T helper cell percentages increased in the propofol but not in the thiopentone group (p < 0.05). The percentages of natural killer cells decreased from pre-induction values in both groups (p < 0.001). No changes were seen in lymphocyte proliferative responses. Minor breast surgery under propofol or conventional combined anaesthesia had only minor effects on the immune response. The higher percentage of T helper cells after propofol anaesthesia compared to conventional combined anaesthesia is beneficial, but its clinical importance remains to be determined.     

Intrathoracic and pulmonary blood volume during CO2-pneumoperitoneum in humans

Background : Induction of CO₂-pneumoperitoneum may have significant effects on systemic and pulmonary haemodynamics. We hypothesized, that intrathoracic (ITBV) and pulmonary blood volume (PBV) are affected during intra-abdominal CO₂-insufflation, which may be pronounced by positional changes of the patient.
Methods : Sixteen anaesthetized patients were studied before, during and after CO₂-pneumoperitoneum for laparoscopic cholecystectomy. A dye indicator technique was used to assess ITBV and PBV. In addition, gas exchange and haemodynamics were recorded.
Results : In the supine position, induction of CO₂-pneumoperitoneum had no effects on ITBV, PBV and cardiac output. Mean systemic arterial pressure increased from 10.9±1.5 kPa (82±11 mmHg) to 12.7±1.5 kPa (95±11 mmHg, P<0.01). In the reverse Trendelenburg position ITBV decreased from 19.8±5.1 ml . kg^-1 to 16.7±3.7 ml . kg¹ ( P <0.05) during CO₂-insufflation, but increased to control values after 20 min. PBV decreased from 4.2±1.2 ml . kg^-1 to 3.4±1.1 ml . kg^-1 (P<0.05) and remained decreased during CO₂-pneumoperitoneum. Calculated venous admixture was unchanged throughout the study. Deflation of CO₂-pneumoperitoneum increased ITBV (22.4±5.2 ml . kg^-1, P<0.05) and cardiac output above control values.
Conclusions : In anaesthetized-paralyzed patients in the reverse Trendelenburg position intra-abdominal CO₂-insufflation is associated with significant alterations of ITBV and PBV. The release of CO₂-pneumoperitoneum is associated with a re-distribution of blood into the thorax.     

Comparison of propofol/alfentanil anaesthesia with isoflurane/N2O/fentanyl anaesthesia for renal transplantation

Total intavenous anaesthesia (TIVA) with propofol and alfentanil was compared with balanced anaesthesia (BA) in 30 uraemic patients undergoing renal transplantation. TIVA (n=15) was induced with propofol and alfentanil and maintained with propofol and alfentanil infusions, which were started immediately after induction. Thereafter the infusion rates were adjusted as needed. Ventilation was with oxygen in air. BA (n= 15) was induced with thiopentone and fentanyl and maintained with isoflurane/N20/fentanyl. Vecuronium was used for muscle relaxation in both groups. Mean infusion rates for propofol and alfentanil were 10 1.8 mg kg^-1 h^-1 and 70 9 μg kg^-1 h^-1, respectively. To control hypertension during TIVA, larger amounts of propofol and alfentanil were needed and slower recovery was observed than in previous studies in ASA 1–2 patients. Also, significantly more vecuronium was needed during TIVA than during BA ( P < 0.05). The recovery parameters were similar in both groups, except for the occurrence of nausea, which was less after TIVA. In conclusion, TIVA had no clinical advantages over BA.     

Desflurane versus propofol maintenance for outpatient laparoscopic cholecystectomy

Background : The aims of the study were to evaluate costs and clinical characteristics of desflurane-based anaesthetic maintenance versus propofol for outpatient cholecystectomy.
Methods : All 60 patients received ketamine 0.2 mg kg^-1, fentanyl 2 μg kg^-1 and propofol 2 mg kg^-1 for induction. Ketorolac 0.4 mg kg^-1 and ondansetron 0.05 mg kg^-1 +droperidol 20 μg Kg^-1 was given as prophylaxis for postoperative pain and emesis, respectively. The patients were randomly assigned into Group P with propofol maintenance and opioid supplements, or Group D with desflurane in a low-flow circuit system.
Results : All the patients were successfully discharged within 8 h without any serious complications. Emergence from anaesthesia was more rapid after desflurane; they opened their eyes and stated date of birth at mean 6.4 and 8.4 min respectively, compared with 9.6 and 12 min in the propofol group (P<0.05). Nausea and pain were more frequent in Group D, 40% and 80% respectively; versus 17% and 50% in Group P (P<0.05). By telephone interview at 24 h and 7 d after the procedure, there was no major difference between the groups. With desflurane, drug costs per case were 10 $ lower than with propofol.
Conclusion : We conclude that desflurane is cheaper and has a more rapid emergence than propofol for outpatient cholecystectomy. However, propofol results in less pain and nausea in the recovery unit. Despite ondansetron and droperidol prophylaxis, there was still a substantial amount of nausea and vomiting after desflurane.     

The duration of action of mivacurium is prolonged if preceded by atracurium or vecuronium

We studied 45 patients (ASA I-II) during propofol-alfentanil-N₂O-O₂ anaesthesia to determine if recovery from neuromuscular block induced by mivacurium is influenced differently by prior injection of atracurium or vecuronium. Neuromuscular function was monitored by adductor pollicis EMG. Patients were randomized to receive two dosesof either mivacurium (150 and 70 μg kg^-1), atracurium (350 and 75 μg kg^-1) or vecuronium (70 and 15 μg kg^-1) followed by a final dose of mivacurium 70 μg kg^-1. The second and third doses of the muscle relaxants were administered at 25–30% recovery of the E₁ (first EMG response in the train-of-four series). Following the final dose of mivacurium, the EMG response recovered to 25 and 95% in 10.4±3.9 and 19.7±5.7 min (mean±SD), respectively, if mivacurium was the only muscle relaxant. Respective times were 100% longer if mivacurium had been preceded by atracurium (23.8 ± 3.3 and 39.8±6.9 mm) or vecuronium (22.6±3.5 and 44.1 ±7.9 min) ( P =0.000l). The 25–75% recovery times in the three groups were 4.9±1.0, 8.7±2.4 and 10.5±2.5 min, respectively ( P =0.0001). Our results indicate that there is no benefit in giving mivacurium at the end of surgery after peroperative use of atracurium or vecuronium.     

The effect of droperidol on fentanyl-influenced gastric emptying in man

The effect of droperidol on gastric emptying was determined from the rate of paracetamol absorption in seven healthy adult volunteers who received fentanyl, each acting as his/her own control. On each occasion the subjects were given droperidol 2.5 mg or normal saline (placebo) i.v. in double-blind fashion. On both occasions, 20 and 50 min later a dose of 0.0015 mg kg^-1 fentanyl was given. Ten minutes after the first fentanyl dose, the subjects ingested 20 mg kg^-1 paracetamol with 200 ml of water. Our findings demonstrate that droperidol was not able to accelerate gastric emptying in subjects receiving subsequent small doses of fentanyl. Furthermore, the delayed absorption pattern of paracetamol on both occasions suggests that gastric emptying is retarded with or without droperidol.     

Propofol–nitrous oxide versus thiopentone–isoflurane–nitrous oxide anaesthesia for uvulopalatopharyngoplasty in patients with sleep apnea

A randomized prospective study was performed to compare the recovery in 41 patients undergoing uvulopalatopharyngoplasty (UPPP) with either propofol-nitrous oxide-fentanyl or thiopentone-isoflurane-nitrous oxide-fentanyl anaesthesia. The patients were referred to UPPP after examination including polysomnography and otorhinolaryngological examination. The propofol group received propofol 2 mg·kg^-1 for induction followed by an infusion of 10 mg·kg^-1·h^-1 after intubation. The thiopentone-isofiurane group received 5 mg·kg^-1 of thiopentone for induction followed by isoflurane (0.5–2%) after intubation. Other medication was similar in both groups. In the propofol group the patients had a significantly better oxygen saturation during the first postoperative hour ( P < 0.05), and a higher rate of breathing ( P < 0.05), indicating a more rapid recovery of the physiologic control of breathing. Pain as measured by visual analogue score was lower ( P < 0.05) during the second postoperative hour compared with the isoflurane group. Apneic episodes occurred with similar frequency in both groups, and they were related to the severity of obstructive sleep apnea (OSA). We conclude that propofol is preferable to thiopentone-isofiurane in UPPP operations, because physiologic respiratory control recovers faster and postoperative pain is less intense.     

The respiratory effects of reversing midazolarn sedation with flumazenil in the presence or absence of narcotics

The purpose of this study was to determine the effects of reversal of sedation with flumazenil (F), in the presence or absence of opiates, on arterial oxygen saturation (Sao₂) and cnd-tidal CO₂ (E_Tco₂). Twenty-four patients undergoing surgery and epidural anaesthesia were studied. Twelve patients (Group A) were orally premedicated with diazepam and 0.1 mg·kg^-1 morphine i.m. Intraoperative sedation consisted of midazolam 0.1 mg·kg^-1 and pethidine 0.7 mg·kg^-1 i.v. Twelve patients (Group B) were premedicated with diazepam and sedated intraoperatively with 0.1 mg·kg^-1 midazolam. In the recovery room, six patients in each group were randomly allocated to receive 1 mg of flumazenil while the others were allowed to awaken spontaneously (control). Sedation (eyes open vs closed), Sao₂, E_Tco₂, respiratory rate, blood pressure and pulse were non-invasively monitored for 90 min. Administration of flumazenil resulted in a statistically significant increase in the number of patients with eyes open in both groups at 5 min, lasting 15 min in Group A and 30 min in Group B patients. An increase in Sao₂ from 15–45 min after injection of flumazenil was observed only in Group B. No significant difference between groups in any other parameter was found. We concluded that reversal of benzodiazepine (BZ) sedation with flumazenil improved Sao₂ in patients sedated with only BZ; in the presence of BZ and opiates, flumazenil did not affect respiratory parameters.     

Right ventricular end–systolic pressure–volume relation during propofol infusion

The effects of propofol on right ventricular function were studied in 11 ICU patients who needed sedation for acute respiratory failure or neurological diseases. Right ventricular function was studied using a thermodilution method at patients' bedside. Right ventricular ejection fraction (RVEF), cardiac output (CO), right ventricular end–diastolic volume (RVEDV), right ventricular end–systolic volume (RVESV), right ventricular end–systolic pressure (RVESP) and pulmonary capillary wedge pressure (PCWP) were obtained from a modified Swan–Ganz catheter. Calculation of right ventricular end–systolic pressure–volume relation (ESPVR) allowed to assess changes in right ventricular inotropic state. A baseline ESPVR was obtained before propofol infusion: RVESP = 0.21 RVESV + 2.4, r = 0.83, P < 0.0001. Then, patients were given an induction dose of 1 to 2.5 mg kg^-1 propofol over 1 min followed by a continuous infusion of 3 mg kg^-1 h^-1. During propofol infusion heart rate, mean arterial pressure, PCWP, CO, systemic vascular resistance and RVEF significantly decreased. No change in RVEDV and RVESV was observed. ESPVR was significantly altered with a dramatic decrease in the slope of the relation: RVESP = 0.12 RVESV + 6.9 ( P < 0.001 from baseline). Dobutamine was used in five patients with clinically significantly cardiac dysfunction and restored the slope of the ESPVR to the baseline value: RVESP = 0.22 RVESV + 6.3 (NS from baseline). In the study patients, propofol altered the inotropic state of the right ventricle.     

Topographical analysis of the EEG effects of a subconvulsive dose of lidocaine in healthy volunteers

Background: The purpose of the present study was to assess the effects of intravenous lidocaine on spatial changes of electroen-cephalographic power and on psychomotoric status in conscious volunteers.
Methods: In 11 healthy volunteers lidocaine (2-min bolus, 100 mg; 15-min infusion, 40 μg kg^-1 min^-1) or placebo were given intravenously in a randomized, single-blinded, two-way crossover study. Haemodynamics and lidocaine plasma concentrations were measured at baseline and within a period of 30 min following bolus injection. Vigilance and emotional status were tested using visual analogue scales (VAS). Toxic CNS effects were evaluated by a questionnaire. The raw EEG (17 leads, reference C_z) and computed power spectra were continuously recorded.
Results: The chosen lidocaine dosage led to nearly constant plasma concentrations (unbound lidocaine 2.5 min and 15 min after bolus 0.36±0.14 μg/ml and 0.30±0.06 μg/ml, respectively [mean±SD]). The placebo caused no symptoms, changes in VAS-scores or EEG-parameters. Lidocaine induced pronounced subjective symptoms and significant increases in delta activity for 15 min, most dominant at the frontotemporal and occipital leads (max. +219% O₁). Frontal and occipital beta1 and beta2 power (max. +131% and +124% at O₁, respectively) was immediately increased after the bolus injection. No EEG changes occurred at central region C_z, and no interhemispheric EEG differences were noted. Theta, alphal, and alpha2 power remained unchanged.
Conclusion: The current data demonstrate simultaneous changes in psychomotoric status as well as delta and beta spectral power during lidocaine infusion. These data could be an indication that the pronounced frontotemporal and occipital EEG changes are the electroencephalographic expression of subjective sensations.     

Multiple Dose Kinetics of Ketobemidone in Surgical Patients

Twelve patients scheduled for major abdominal surgery were selected for a study of the kinetics of ketobemidone during the day of surgery and in a follow-up study 3–5 days after surgery. In six patients ketobemidone was administered as ketobemidone plain and in the other six, it was given as Ketogin®, a combination formula containing a spasmolytic substance in addition to ketobemidone. Plasma samples were collected for approximately 24 h following induction of anesthesia, during which time multiple doses of ketobemidone were administered. A single-dose study was performed 3–5 days after surgery using the same drug. No significant differences were found between the two formulations of ketobemidone. Plasma clearance did not change significantly between the two periods of study, being 18.0±4.4 ml · kg^-1 · min^-1 peroperatively and 21.7±7.6 ml · kg^-1 · min^-1 postoperatively. Peroperative V_{d area} was significantly larger than post-operative V_{d area}, 5.84±2.621 · kg^-1 and 3.63±0.381 ·; kg^-1, respectively. T1/2 terminal decreased from 3.84±1.6 h peroperatively to 2.06±0.44 h postoperatively.