A novel urodynamic model for lower urinary tract assessment in awake rats.

OBJECTIVES: To develop a urodynamic model incorporating external urethral sphincter (EUS) electromyography (EMG) in awake rats. MATERIALS AND METHODS: Bladder catheters and EUS EMG electrodes were implanted in female Sprague Dawley rats. Assessments were performed in awake, lightly restrained rats on postoperative day 12-14. Measurements were repeated in the same rat on day 16 under urethane anaesthesia. Urodynamics and EUS EMG were performed simultaneously. In addition, serum creatinine and bladder histology was assessed. RESULTS: No significant differences in urodynamic parameters were found between bladder catheter only vs bladder catheter and EUS EMG electrode groups. Urethane anaesthesia evoked prominent changes in both urodynamic parameters and EUS EMG. Serum creatinine was within the normal limits in all rats. Bladder weight and bladder wall thickness were significantly increased in both the bladder catheter only and the bladder catheter and EUS EMG group compared with controls. CONCLUSIONS: Our novel urodynamic model allows repetitive measurements of both bladder and EUS function at different time points in the same rat under fully awake conditions and opens promising avenues to investigate lower urinary tract dysfunction in a translational approach.

Assessment of the effect of etomidate on voltage-gated sodium channels and action potentials in rat primary sensory cortex pyramidal neurons.

Although it is known that general anesthetics can suppress cortical neurons׳ activity, the underlying mechanisms are still poorly understood, especially the kinetic changes of voltage-gated Na(+) channels, which are mostly related to neuronal excitability. Some general anesthetics have been reported to affect the voltage-gated Na(+) channels in cell culture derived from humans and animals. However no one has ever investigated the effects of etomidate on voltage-gated Na(+) channels in pyramidal neurons using a brain slice. The present study uses a whole cell patch-clamp technique to investigate the changes of voltage-gated Na(+) channels on primary somatosensory cortex pyramidal neurons under the influence of etomidate. We found that etomidate dose-dependently inhibited Na(+) currents of primary somatosensory cortex pyramidal neurons, while shifted the steady-state inactivation curve towards the left and prolonged the recovery time from inactivation. Conversely, etomidate has no effects on the steady-state activation curve. We demonstrated the detailed suppression process of neural voltage-gated Na(+) channels by etomidate on slice condition. This may offer new insights into the mechanical explanation for the etomidate anesthesia. Finding the effects of anesthetics on primary somatosensory cortex also provides evidence to help elucidate the potential mechanism by which tactile information integrates during general anesthesia.

Pain monitoring in anesthetized children: first assessment of skin conductance and analgesia-nociception index at different infusion rates of remifentanil.

BACKGROUND: Analgesia and nociception can not be specifically monitored during general anesthesia. Movement of the patient or hemodynamic variations are usually considered as symptoms of insufficient analgesia. The measure of skin conductance (SC) allows an assessment of peripheral sympathetic activity. The analgesia-nociception index (ANI) provides an evaluation of the parasympathetic activity based on heart rate variability. These two non-invasive monitors might allow a better assessment of perioperative nociception. OBJECTIVES: Describe the profiles of SC and ANI after a standardized nociceptive stimulation, in anesthetized children, at different infusion rates of remifentanil. MATERIALS/METHODS: For this pilot study, 12 children (8.4 ± 5 years) scheduled for middle-ear surgery were anesthetized with desflurane to maintain a bispectral index at 50. Remifentanil was used for analgesia, at an initial infusion rate of 0.2 µg·kg(-1) ·min(-1) . Remifentanil infusion rate was then decreased: Five steady-state periods of 10 min were obtained at 0.2, 0.16, 0.12, 0.08, and 0.04 µg·kg(-1) ·min(-1) . At the end of each period, a standardized tetanic stimulation was applied to the patient. Variations in heart rate, blood pressure, SC, and ANI were recorded before and after each stimulation. RESULTS: After the stimulation, ANI was significantly decreased compared with prestimulation values for all remifentanil infusion rates. This decrease was greater at 0.04 µg·kg(-1) ·min(-1) than at the other infusion rates. SC, heart rate, and blood pressure were not modified by the stimulations, whatever the dose of remifentanil. CONCLUSION: ANI might provide a more sensitive assessment of nociception in anesthetized children than hemodynamic parameters or skin conductance.

Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil.

Alfentanil (ALF) is a validated probe for hepatic, first-pass, and intestinal cytochrome P450 (CYP) 3A activity, using plasma clearances, single-point concentrations, and noninvasive pupil diameter change (miosis). Assessing intravenous (i.v.) and oral drug disposition typically requires separate dosing. This investigation evaluated concurrent administration of oral deuterated and i.v. unlabeled ALF to assess both intestinal and hepatic CYP3A, and compare sequential and simultaneous dosing. ALF disposition was evaluated after strong hepatic and/or intestinal CYP3A induction and inhibition by rifampin, ketoconazole, and grapefruit juice. Using plasma ALF concentrations and area under the curve (AUC), clearance, or single-point concentrations, both simultaneous and sequential dosing provided equivalent results and detected hepatic and intestinal CYP3A induction and inhibition. Miosis better detected CYP3A modulation with sequential vs. simultaneous dosing. These results show that concurrent administration of oral deuterated and i.v. ALF, either sequentially or simultaneously, is an efficient and effective approach to assessing hepatic and intestinal CYP3A activity.

[The influence of remifentanil on intra- and postoperative drug cost].

BACKGROUND: Intraoperative use of remifentanil requires much more analgesics postoperatively. Moreover, remifentanil causes intraoperative hypotension and bradycardia. METHODS: The objectives are to compare intra- and post-operative drug cost between patients who received remifentanil (Group R, n = 72) and those who received fentanyl (Group F, n = 66) during laparoscopic cholecystectomy retrospectively. RESULTS: The baseline demographics were similar between the two groups. Intraoperative drug costs were 7,782 +/- 1,579 yen in Group R and 6,235 +/- 1,037 yen in Group E Postoperative drug costs were 364 +/- 521 yen in Group R and 146 +/- 153 yen in Group E Total drug costs were 8,167 +/- 1,607 yen in Group R and 6,381 +/- 1,042 yen in Group E These reached statistical significance (P < 0.01). Length of hospital stay (days) between the two groups were comparable. CONCLUSIONS: Remifentanil anesthesia requires much more intra- and post-operative drug cost than fentanyl anesthesia for laparoscopic cholecystectomy.

Should sevoflurane be used in the electrophysiology assessment of accessory pathways?

Sevoflurane has been shown to significantly prolong the action potential duration and the QTc interval. Despite this, clinical studies have shown only minor clinical effects on accessory pathway properties under general anaesthesia with sevoflurane compared with conscious sedation with midazolam. This case demonstrates significant prolongation of accessory pathway effective refractory period (APERP) under general anaesthetic with sevoflurane compared with propofol.

Language assessment in Wada test: comparison of methohexital and amobarbital.

INTRODUCTION: Methohexital has replaced amobarbital during Wada testing at many centers. The objective of our study was to compare the use of methohexital and amobarbital during Wada testing regarding language and memory lateralization quotients as well as speech arrest times. METHODS: A chart review of 582 consecutive patients undergoing 1041 Wada-procedures was performed (left=60, right=63, bilateral=459). Language lateralization was calculated based on duration of speech arrest using a laterality index, defined as (L-R)/(L+R). Memory lateralization was expressed as percentage of retained objects and laterality quotient. RESULTS: Language and memory lateralization revealed a similar distribution with amobarbital and methohexital. Speech arrest after left and right-sided injection was significantly longer in the amobarbital group as compared to the methohexital group. Language lateralization did not differ in the two groups. Percentage of retained memory items was higher in the methohexital group and there were fewer presented test items in the methohexital group. DISCUSSION: Language and memory testing during the Wada test can successfully be performed with methohexital instead of amobarbital. The shorter half-life of methohexital allows repeated injections and shorter interhemispheric testing intervals, but also shortens the testing window.

Assessment of cardiac troponin I and C-reactive protein concentrations associated with anesthetic protocols using sevoflurane or a combination of fentanyl, midazolam, and sevoflurane in dogs.

OBJECTIVE: To report serum cardiac troponin I (cTnI) and C-reactive protein (CRP) concentrations in dogs anesthetized for elective surgery using two anesthetic protocols. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Twenty client-owned dogs presenting for elective ovariohysterectomy or castration. METHODS: The dogs were randomized into two groups. All dogs were premedicated with glycopyrrolate (0.011 mg kg(-1)) and hydromorphone (0.1 mg kg(-1)) i.m. approximately 30 minutes prior to induction of anesthesia. Anesthesia in dogs in group 1 was induced with propofol (6 mg kg(-1)) i.v. to effect and in dogs in group 2 with diazepam (0.2 mg kg(-1)) i.v. followed by etomidate (2 mg kg(-1)) i.v. to effect. For maintenance of anesthesia, group 1 received sevoflurane (adjustable vaporizer setting 0.5-4%) and group 2 received a combination of fentanyl (0.8 microg kg(-1) minute(-1)) and midazolam (8.0 microg kg(-1) minute(-1)) i.v. plus sevoflurane (adjustable vaporizer setting 0.5-4%) to maintain anesthesia. Serum cTnI and CRP concentrations were measured at baseline and 6, 18, and 24 hours post-anesthetic induction. Biochemical analysis was performed at baseline. Lactate was obtained at baseline and 6 hours post-anesthetic induction. Heart rate and mean arterial blood pressure were measured intra-operatively. RESULTS: Baseline serum cTnI and CRP concentrations were comparable between groups. A significant difference in serum cTnI or CRP concentrations was not detected post-operatively between groups at any time point. Serum CRP concentrations were significantly increased post-anesthetic induction in both groups, which was attributed to surgical trauma. CONCLUSIONS AND CLINICAL RELEVANCE: There was no significant difference in serum cTnI and CRP concentrations between anesthetic protocols. Further investigation in a larger number of dogs is necessary to confirm the current findings.

Clinical assessment of propofol-induced yawning with heart rate variability: a pilot study.

STUDY OBJECTIVES: To investigate the proportion of propofol-induced yawning and sympathovagal balance during propofol-induced yawning. DESIGN: Prospective, observational, clinical study. SETTING: University hospital and 2400-bed tertiary medical center. PATIENTS: 546 ASA physical status I and II patients undergoing elective surgery with general anesthesia. INTERVENTIONS: Standard induction of anesthesia was performed with intravenous (IV) propofol two to four mg/kg (group P), or pretreatment with atropine 0.1 mg/kg (group AP) or with fentanyl 1 to 3 microg/kg (group FP) before propofol. Continuous standard electrocardiogram for heart rate variability (HRV) was performed in another 20 patients to investigate sympathovagal balance during propofol-induced yawning. MEASUREMENTS AND MAIN RESULTS: The proportions of yawning were 53.5% (207/386), 61.1% (55/90), and 0% (0/50) in the P, AP, and FP groups, respectively. Propofol-induced yawning could be dramatically decreased by pretreatment with IV fentanyl (P < 0.001, chi2 test). Significant increased ratio of low-frequency/high-frequency power was detected during HRV monitoring in 9 patients with yawning in comparison with 11 patients without yawning (P < 0.05, Wilcoxon signed-rank test). CONCLUSIONS: Pretreatment with fentanyl may inhibit propofol-induced yawning. Fluctuations in autonomic function have been noted during propofol-induced yawning.

Assessment of small-dose fentanyl and sufentanil blunting the cardiovascular responses to laryngoscopy and intubation in children.

BACKGROUND: The authors found no study assessing the efficacy of small-dose narcotics on the cardiovascular response from intubation in children, so they observed the effects of fentanyl 2 microg x kg(-1) and sufentanil 0.2 microg x kg(-1) on the cardiovascular changes during laryngoscopy and intubation in children. METHODS: Ninety-three children aged 3-9 years were randomized to one of three groups to receive the following treatments in a double-blind manner: normal saline (group C), fentanyl 2 microg x kg(-1) (group F) and sufentanil 0.2 microg x kg(-1) (group S) 2 min before induction. Noninvasive blood pressure (BP) and heart rate (HR) were recorded before anesthesia induction (baseline value), immediately before intubation (postinduction values), at intubation and 5 min after intubation at 1-min interval. RESULTS: Tracheal intubation caused significant increases in BP and HR in the three groups compared with baseline values. BP and HR at intubation and after intubation and their maximum values during observation were significantly lower in groups F and S than in group C (P < 0.05). The mean percent increases of systolic blood pressure (SBP) and HR at intubation were significantly lower in group S, 7% and 10%, than in group F, 17% and 25% (P < 0.05). The increases in SBP and HR of more than 30% of baseline values during the observation period were significantly higher in group F, 27% and 43%, than in group S, 0% and 3% (P < 0.05). CONCLUSIONS: When used as part of anesthesia induction with propofol in children, sufentanil 0.2 microg x kg(-1) 2 min before induction is more effective in attenuating the cardiovascular intubation response than fentanyl 2 microg x kg(-1).

Pharmacological assessment of the freezing, antinociception, and exploratory behavior organized in the ventrolateral periaqueductal gray.

Opioid and serotonergic mechanisms of the ventrolateral periaqueductal gray (vlPAG) are recruited by conditioned freezing and antinociception. However, it is unclear whether freezing and antinociception induced by stimulation of the vlPAG are interrelated. To address this issue we looked at the effects of the opioid antagonist naltrexone, the 5-HT2 antagonist ketanserin, and the benzodiazepine agonist midazolam injected into the vlPAG on the freezing and antinociception induced by electrical stimulation of this region. This antinociception was evaluated by the tail-flick and formalin tests. To further characterize the involvement of the vlPAG in unconditioned fear, the effects of intra-vlPAG injections of midazolam on the exploratory behavior were also assessed in independent groups of rats submitted to the elevated plus-maze test (EPM). The data obtained showed that: (i) electrical stimulation of the vlPAG causes freezing blocked by midazolam but not by naltrexone and ketanserin; (ii) antinociception generated at the level of the vlPAG is inhibited by naltrexone, ketanserin, and midazolam; (iii) activation of benzodiazepine-mediated mechanisms in the vlPAG increased the exploratory behavior of rats in the closed arms but not the avoidance behavior of open arms of the EPM. Thus, freezing and antinociception generated in the vlPAG are dissociated pharmacologically. Whereas antinociception is a multimediated process sensitive to naltrexone, ketanserin, and midazolam, the freezing induced by vlPAG stimulation was reversed only by the benzodiazepine compound. As injections of midazolam into the vlPAG do not cause anxiolytic effects in the EPM, the aversive stimuli inherent of this test seem to bypass the vlPAG.

The clinical development of gamma-hydroxybutyrate (GHB).

The discovery of gamma-hydroxybutyrate (GHB) over 40 years ago led to its immediate use as a general anesthetic agent. Subsequent research demonstrated that GHB is an endogenous compound in the mammalian brain and current research suggests that GHB is a probable neurotransmitter. In the United States, reports of anabolic effects lead to its misuse among body builders during the 1980's while the intoxicating properties of the drug lead to its popularization as a substance of abuse during the 1990's. GHB became associated with reports of drug-facilitated sexual assault and cases of physical dependence and withdrawal. Efforts to ban GHB caused increased use of GHB analogues and pro-drugs. Against this backdrop, GHB was being developed for the treatment of narcolepsy, leading to the approval of Xyrem (sodium oxybate) oral solution in 2002 for the treatment of cataplexy in patients with narcolepsy. A risk management program permits the safe handling and distribution of the approved product, minimizes the risk for diversion, provides professional and patient education about the risks and benefits of sodium oxybate, and includes physician and patient registries. Post-marketing surveillance indicates sodium oxybate has an acceptable safety profile and presents minimal risk for the development of physical dependence.

Assessment of the cough reflex after propofol anaesthesia for colonoscopy.

BACKGROUND: Dysfunction of the cough reflex as a result of the lingering effects of anaesthetics may lead to aspiration pneumonia or retained secretions after general anaesthesia. It is unknown whether low concentrations of propofol alter the cough reflex in the early period after anaesthesia. The objective of this study was to investigate the effect of low concentrations of propofol on the cough reflex sensitivity as assessed by the cough reflex threshold to an inhaled irritant. METHODS: Fifteen, ASA I-II, non-smoking patients undergoing elective colonoscopy were studied. Anaesthesia was induced and maintained with a blood target-controlled propofol infusion. Cough reflex threshold was measured with citric acid. Increasing concentrations of nebulized citric acid (2.5, 5, 10, 20, 40, 80, 160, 320, and 640 mg ml(-1)) were delivered during inspiration until a cough was evoked. The citric acid concentration eliciting one cough (C1) was defined as the cough reflex threshold. C1 was log transformed for statistical analysis (Log C1). Log C1 was measured before anaesthesia and during the recovery period with estimated decreasing propofol concentrations of 1.2, 0.9, 0.6, and 0.3 microg ml(-1). RESULTS: Log C1 (median; interquartile range) measured with propofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 microg ml(-1) were 1.9 (0.6), 1.9 (1.0), 1.9 (1.1), 1.9 (0.6), and 1.9 (0.7) mg ml(-1) (NS), respectively. However, light sedation was observed with propofol concentrations of 1.2 and 0.9 microg ml(-1). CONCLUSION: This study indicates that residual sedation after propofol anaesthesia for colonoscopy does not adversely affect the cough reflex.

Assessment of the hemodynamic effects of lidocaine administered IV in isoflurane-anesthetized cats.

OBJECTIVE: To determine the hemodynamic effects of lidocaine (administered IV to achieve 6 plasma concentrations) in isoflurane-anesthetized cats. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized with isoflurane in oxygen (end-tidal isoflurane concentration set at 1.25 times the predetermined individual minimum alveolar concentration). Lidocaine was administered IV to each cat to achieve target pseudo-steady-state plasma concentrations of 0, 3, 5, 7 9, and 11 microg/mL, and isoflurane concentration was reduced to an equipotent concentration. At each plasma lidocaine concentration, cardiovascular and blood gas variables; PCV; and plasma total protein, lactate, lidocaine, and monoethylglycinexylidide concentrations were measured in cats before and during noxious stimulation. Derived variables were calculated. RESULTS: n isoflurane-anesthetized cats, heart rate, cardiac index, stroke index, right ventricular stroke work index, plasma total protein concentration, mixed-venous PO2 and hemoglobin oxygen saturation, arterial and mixed-venous bicarbonate concentrations, and oxygen delivery were significantly lower during lidocaine administration, compared with values determined without lidocaine administration. Mean arterial pressure, central venous pressure, pulmonary artery pressure, systemic and pulmonary vascular resistance indices, PCV, arterial and mixed-venous hemoglobin concentrations, plasma lactate concentration, arterial oxygen concentration, and oxygen extraction ratio were significantly higher during administration of lidocaine, compared with values determined without lidocaine administration. Noxious stimulation did not significantly affect most variables. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane-anesthetized cats, although IV administration of lidocaine significantly decreased inhalant requirements, it appeared to be associated with greater cardiovascular depression than an equipotent dose of isoflurane alone. Administration of lidocaine to reduce isoflurane requirements is not recommended in cats.

Influence of formulation on propofol pharmacokinetics and pharmacodynamics in anesthetized patients.

BACKGROUND: In anesthesia with propofol, variability persists besides sophisticated effect targeting. Drug formulation may be another factor. We have analyzed, retrospectively, the pharmacokinetics (PK) and pharmacodynamics (PD) in monitored surgery patients anesthetized with one each of five formulations of propofol. METHODS: Propofol 1% ('form' 1: Diprivan(Zeneca Limited, Macclesfield, UK), 2: Recofol(Schering Espana, Madrid, Spain), 3: Ivofol(Juste, Madrid, Spain), 4: Propofol Abbott (Abbott Laboratories, Madrid, Spain), 5: Fresenius (Fresenius Kabi Espana, Barcelona, Spain)) was administered to 77 ASA I-II patients of age [mean (range) 44 (18-65) years]. Induction of anesthesia was with varying propofol doses up to endpoints of either 60 on the Bispectral Index system (BIS) in group I (n = 48, model development) or standard clinical signs in group II (n = 29, validation). Maintenance was with three 10-min infusions of 10, 8 and 6 mg kg(-1) h(-1). Three blood samples were obtained from each subject, immediately after induction, and at 15 and 30 min on maintenance, with BIS and hemodynamic variables recorded at these times also. Total and free blood concentrations (Cb) of propofol were determined with HPLC. Pharmacokinetic and PD models with link equilibration rate ke0, were studied with a mixed-effects procedure (NONMEM). RESULTS: The induction dose (group I) showed large interindividual variability [mean (range) 163 (90-290 mg)] that correlated significantly with age, basal systolic blood pressure and formulation. The PK of propofol (basic model) was described by a one-compartment model with (typical value [interindividual coefficient of variation percent (CV%)]) CL=2.30 l min(-1) (27%) and V=8.40 l (80%). Weight (WT) and formulation, within NONMEM, were found to be significant covariates for CL and V, reducing their CV% to 25% and 74%, respectively. The final PK/PD model, which includes formulation, showed a 50% reduction in the CV% for both the ke0 and the residual error. This PK/PD model was validated in group II with 33% precision and no bias. CONCLUSION: The PK and PD are not equal for all formulations, which contributes to an increase in variability of the observed effect.

Does the A-line ARX-lndex provide a reasonable assessment of anaesthetic depth in dogs undergoing routine surgery?

The monitoring of anaesthetic depth is usually based on the subjective assessment of the patient. An objective assessment of anaesthesia has only recently become possible. The auditory-evoked response has predictable changes in response to increasing doses of anaesthetic agents. Recent advances have brought about a regression model with exogenous input of the auditory-evoked response, the A-line ARX-Index (AAI Index). The AAI Index is a dimensionless number between 0 and 100. This technology has been incorporated into the AEP (auditory-evoked potential) monitor that is utilised to assess anaesthetic depth in humans. This study was undertaken to determine if the AEP monitor was useful in dogs. Ten dogs were enrolled in the study. After a full clinical and otoscopic examination, dogs were premedicated with acetylpromazine and morphine. Anaesthesia was induced with thiopentone and maintained with halothane. End-tidal carbon dioxide, temperature, pulse oximetry, blood pressure and the electrocardiogram were monitored and recorded every 5 minutes. Anaesthetic depth was assessed as either being adequate or inadequate by the anaesthetist during surgery. An AEP monitor was attached to the patient and automatically collected AAI Index data. The anaesthetist was blinded to the AEP monitor. Following the completion of the surgical procedure, the patient was allowed to wake up with the AEP monitor attached. The AAI Index was analysed to compare adequate with inadequate anaesthesia during the period of surgery and awake with sleep data during recovery. All AAI Index values associated with inadequate anaesthesia were greater than 31 while adequate values were less than 35. The difference between the groups was statistically significant and the power was 0.97. Statistically, the awake and sleep values were significantly different with a power of 0.99. From this study it can be concluded that the AAI Index shows good prospect for the evaluation of anaesthetic depth in dogs undergoing surgery. A larger study is needed to confirm these results.

[Usefulness of bispectral index in pharmaceutical cost reduction for anesthesia]. / Utilidad del índice biespectral (BIS) en la reducción del costo de fármacos para la anestesia.

BACKGROUND: The bispectral index (BIS) is a value derived from an electroencephalograph (EEG); it is correlated with depth of sedation and loss of consciousness. Therefore, it has been considered that its control on sedation depth could influence cost saving in drugs as well as decreased anesthesia costs. METHODS: A total of 175 patients were studied. One hundred patients were given intravenous (i.v.) anesthesia, 50 were observed with a BIS monitor, and the remainder went into the control group. Seventy five patients were given balanced general anesthesia: fifty were observed with BIS monitor, while the remainder functioned as the control group. Drug consumption per patient was measured a to maintain BIS value between 60 and 40, and the cost was calculated. RESULTS: Average drug costs for anesthesia were greater in BIS-controlled groups. Anesthesia cost/h was lower in prolonged procedures (>4 h). The bispectral Index as a sedation monitor during anesthesia is an excellent tool, although it did not show a real economic advantage, and we considered that it world only be feasible during long-term procedures.

[Total intravenous anesthesia. On the way to standard practice in pediatrics]. / Total intravenöse Anästhesie. Auf dem Weg zum Standardverfahren bei Kindern.

Since venous cannulation in children has become easier and extensive experience has been gained with total intravenous anaesthesia (TIVA) in adults, the interest in TIVA for children has recently increased. An intensified sensitivity of the operating room atmosphere to contamination with volatile anaesthetic agents is another important reason to choose intravenous techniques for paediatric anaesthesia. One of the most interesting agents for TIVA in paediatric anaesthesia is propofol. The pharmacokinetic and pharmacodynamic data for modern intravenous drugs is poor. Because the interpatient variability is relatively large, pharmacokinetic data can only provide guidelines for the dosage of propofol. Propofol has a rapid and smooth onset of action and is as easy to titrate in children as in adults. Propofol can be excellently controlled. Severe haemodynamic side-effects are missing in healthy children and plasma is cleared rapidly of propofol by redistribution and metabolism. There is no evidence of significant accumulation, not even after prolonged infusion times. Because propofol has no analgetic properties it must be combined with analgetics or a regional block for all painful procedures. The combination with the ultra-short acting remifentanil is a major advantage, but requires effective analgetic concepts for painful procedures. In comparison the combination of propofol with long acting opioids abolishes some of the favourable properties of propofol. Further studies of the kinetics and dynamics of propofol and other intravenous agents are needed in paediatrics which should focus on age, maturity and severity of illness. The whole importance of the propofol-infusion syndrome has to be cleared up urgently. TIVA has an important significance in paediatric anaesthesia for diagnostic and therapeutic procedures, especially where these have to be repeated. In day-case anaesthesia TIVA has advantages for all short procedures and for ENT and ophthalmic surgery: even after prolonged infusion children have an short recovery time. There is no evidence of agitation or other behavioural disorders after TIVA with propofol in paediatric anaesthesia. Propofol has anti-emetic properties. TIVA with propofol can be combined with regional anaesthesia advantageously to provide long-lasting analgesia after surgery. TIVA with propofol has been used successfully for sedation of spontaneously breathing children for MRI and CT and other procedures with open airways like bronchoscopy or endoscopy. Propofol facilitates endotracheal intubation without the use of muscle relaxants. Of course, in malignant hyperthermia TIVA will continue to be the technique of choice. Nothing is known about awareness under TIVA in paediatric patients. TIVA must be considered by comparison with the volatile agents. The use of ultra-short acting agents may cause problems such as awareness, vagal response, involuntary movements and in some cases slow recovery after prolonged infusion of propofol. But it is not known exactly how often this happens during paediatric anaesthesia. With TIVA an effective postoperative analgesia must be provided. Newer administration techniques such as the target-controlled infusions or closed-loop control systems are under development and will help to minimise the potential risk of overdosage with TIVA in paediatrics. At the present TIVA is an interesting and practicable alternative to volatile anaesthesia for pre-school and school children. TIVA with propofol in infants younger than 1 year old requires extensive experience with TIVA in older children and with the handling of this special age group and should be undertaken with maximum precautionary measures.