Bolus Administration Of Propofol Research Articles

The influence of anesthetic drug strategy on the incidence of post-induction hypotension in elective, non-cardiac surgery – A prospective observational cohort study

Study objectivesTo identify the influence of modifiable factors in anesthesia induction strategy on post-induction hypotension (PIH), specifically the type, dosage and speed of administration of induction agents. A secondary aim was to identify patient related non-modifiable factors associated with PIH. DesignSingle-center, prospective observational cohort study. SettingOperating room. PatientsAdult, ASA I-IV patients undergoing elective, non-cardiac surgery under general anesthesia (GA). InterventionsNone. MeasurementsContinuous non-invasive blood pressure using finger-cuff technology. PIH was defined as mean arterial pressure (MAP) <65 mmHg ≥1 min, and, separately, as a > 30 % decrease from baseline MAP ≥1 min. Main resultsStudy measurements were performed in 760 patients, of which 720 were suitable for analysis. A total of 238 patients (33.1 %) experienced PIH according to the 65 mmHg threshold, and 287 (39.9 %) using the 30 % decrease in MAP threshold. Remifentanil administration was associated with increased risk of PIH according to either definition (MAP <65 mmHg: OR 1.88, 95 %CI 1.31–2.69, p < 0.001, 30 % MAP decrease: OR 1.66, 95 %CI 1.15–2.40, p = 0.007). Pre-emptive vasopressor use (before or during first minute of GA) was associated with reduced risk of PIH (MAP <65 mmHg: OR 0.65, 95 %CI 0.45–0.95, p = 0.027, MAP 30 % decrease: OR 0.58, 95 %CI 0.40–0.84, p = 0.004). Speed of propofol bolus administration, propofol bolus dose, and esketamine use were not associated with PIH in multivariable analysis. Propofol bolus dose decreased with increasing age and American Society of Anesthesiologists physical status classification. ConclusionsPIH was common in this patient cohort, regardless of the definition used. Two of the five examined modifiable factors were associated with PIH: remifentanil infusion was associated with an increased risk, and pre-emptive vasopressor use was associated with a decreased risk of PIH. No association between propofol dose and PIH was found, most likely due dose adjustment based on clinical assessment rather than a true absence of effect. Clinical registration numberThis study was registered in the Dutch Medical Research in Humans (OMON) register on 18 June 2019 (ID: NL7810). The study was approved by the Medical Ethics Committee of the Amsterdam UMC, location AMC, the Netherlands in December 2018 (NL 6748.018.18; 2018).

Safety and efficacy of target-controlled infusion versus intermittent bolus administration of propofol for sedation in colonoscopy: a randomized controlled trial

BackgroundOur objective was to compare the safety and efficacy of Target-Controlled Infusion (TCI) versus intermittent bolus of propofol for colonoscopy sedation. MethodsWe conducted a randomized (1:1), single-blind, parallel-group superiority trial with fifty ASA I or II patients, both sexes, aged 18 to 65 years, Body Mass Index ≤ 30 kg.m−2, undergoing colonoscopy, allocated to receive propofol by TCI (effect-site, 2 μg.mL−1 plus 0.5 μg.mL−1 until unconsciousness and as necessary for agitation) or intermittent bolus (1 mg.kg−1 plus 0.5 mg.kg−1 every 5 minutes or as above). The primary safety outcome was the need for airway maneuvers and the primary efficacy outcome was the need for interventions to adjust the level of sedation. Secondary outcomes included incidence of agitation, propofol dose, and time to recovery. ResultsThe median (IQR) number of airway maneuvers and interventions needed to adjust sedation was 0 (0‒0) vs. 0 (0‒0) (p = 0.239) and 1 (0‒1) vs. 3 (1‒4) (p < 0.001) in the TCI and control groups, respectively. Agitation was more common in the intermittent bolus group ‒ 2 (0‒2) vs. 1 (0‒1), p < 0.001. The mean ± SD time to recovery was 4.9 ± 1.4 minutes in the TCI group vs. 2.3 ± 1.6 minutes in the control group (p < 0.001). The total propofol dose was higher in the TCI group (234 ± 46 µg.kg−1.min−1 vs. 195 ± 44 µg.kg−1.min−1 (p = 0.040)). ConclusionsDuring colonoscopy, TCI is as safe as intermittent bolus of propofol while reducing the incidence of agitation and the need for dose adjustments. However, intermittent bolus administration was associated with lower total propofol dose and earlier recovery.

Impact of Propofol Bolus Administration on the Nociceptive Flexion Reflex Threshold and Bispectral Index in Children—A Case Series

We analyzed the impact of propofol administration during continuous sedation and analgesia on the nociceptive flexion reflex threshold (NFRT) and Bispectral Index (BIS) in ventilated children. We examined patients who received propofol before planned endotracheal suctioning. Patients were clinically assessed using the modified Face, Legs, Activity, Cry, Consolability (mFLACC) scale and COMFORT-B (Comfort Behavior) scale. We continuously recorded the NFRT and BIS. We recorded 23 propofol administrations in eight patients with an average age of 8.6 ± 3.5 years. The median (minimum-maximum) scores for the mFLACC scale and COMFORT-B scale were 0 (0–5) and 6 (6–17), respectively, before the bolus. The administration of a weight-adjusted propofol bolus of 1.03 ± 0.31 mg/kg resulted in an increase in NFRT and burst-suppression ratio; BIS and electromyogram values decreased. Changes from baseline (95% CI) after propofol bolus administration were BIS −23.9 (−30.8 to −17.1), EMG -10.5 dB (−13.3 to −7.7), SR 14.8 % (5.6 to 24.0) and NFRT 13.6 mA (5.5 to 21.7). Further studies are needed to determine whether sedated children may benefit from objective pain and sedation monitoring with BIS and NFRT.

Propofol Target-Controlled Infusion in Emergency Department Sedation (ProTEDS): a multicentre, single-arm feasibility study

BackgroundProcedural sedation is a core skill of the emergency physician. Bolus administration of propofol is widely used in UK EDs. Titrated to an end point of sedation, it has a...

A study protocol for a feasibility study: Propofol Target-Controlled Infusion in Emergency Department Sedation (ProTEDS)\u2014a multi-centre feasibility study protocol

BackgroundProcedural sedation is a core skill of the emergency physician. Bolus administration of propofol is widely utilised in UK emergency departments to provide procedural sedation. Bolus administration of propofol, titrated to an endpoint of sedation, has a rapid effect but can easily result in apnoea and loss of airway patency. The use of a target-controlled infusion of propofol allows for controlled titration to an effect site concentration and may reduce the rate of adverse incidents. Target-controlled infusion of propofol is not currently used in emergency departments.The primary aim of this feasibility study is to ensure that propofol target-controlled infusion (TCI) is acceptable to the patient and that recruitment rates are adequate to power a randomised controlled trial comparing propofol target-controlled infusion versus bolus administration.MethodsThis study will recruit in four emergency departments in Scotland, UK. Patients aged 18–65 years with anterior shoulder dislocation, weighing ≥ 50 kg and fasted ≥ 90 min, will be screened. Recruited patients will undergo emergency reduction of a dislocated shoulder facilitated by procedural sedation utilising TCI of propofol.The widespread adoption of TCI propofol by emergency departments will require evidence that it is safe, potentially effective, patient centred and a timely method of providing procedural sedation. The primary endpoint will be acceptability measured by patient satisfaction. The secondary endpoints will include incidence and severity of adverse events, number of shoulder reduction attempts, nursing opinion of patient experience, patient’s reported pain score and time from commencement of TCI propofol sedation to desired sedation level.The study will be open for recruitment from April 2017 to December 2018.DiscussionIf the study demonstrates patient acceptability with adequate recruitment, we will be in a position to determine the feasibility of progression to a randomised controlled clinical trial of TCI compared to bolus administration of propofol.Trial registrationClinicalTrials.gov Identifier: NCT03442803. Registered retrospectively on 22 February 2018.

An audit of propofol administration in the intensive care unit: Infusion pump–recorded versus electronically documented amounts

BackgroundAlthough propofol is widely used for sedation in intensive care units around Australia, evaluation of bedside nursing practices of the administration of propofol have been limited. We investigated whether there was a discrepancy between the amount of propofol delivered by the infusion pump and that recorded electronically and consequently patient exposure to avoidable harms. AimsThe aim of this research was to compare the total amount of propofol administered to intensive care patients via a programmable infusion pump with that documented in the electronic medical record (EMR). Secondary objectives were to ascertain the percentage of 1) patients exposed to a propofol dose greater than recommended and 2) daily energy requirements administered as propofol infusion. MethodsThis was a prospective, observational study of total propofol delivered to 50 patients in a 14-bed metropolitan, Australian intensive care unit. Infusion pump data and entries from the EMR were collated. ResultsPropofol sedation was administered for a median 18 (interquartile range: 14–47) hours with median total propofol 3025 mg (interquartile range: 1840–7755 mg) by pump and 3250 mg (interquartile range: 1915–6960 mg) by EMR, i.e. 1.9 (interquartile range: 1.3–2.3) mg/kg/hour by pump (correlation coefficient = 0.99). The total bolus propofol documented in the EMR was a median 330 mg (interquartile range: −838 to −124) less than the pump amount. Nineteen (38%) patients had no EMR-documented propofol boluses yet had received at least one bolus via the pump. In two of 50 (4%) patients, the pump propofol infusion dose was above the recommended maximum safe dose of 4 mg/kg/h. ConclusionIn this cohort of patients, the bolus administration of propofol was frequently not documented, potentially placing some patients at risk of drug-related toxicity. Further research to develop and implement strategies to improve the documentation of propofol administration is indicated.

Dopamine D1 Receptor Within Basolateral Amygdala Is Involved in Propofol Relapse Behavior Induced by Cues.

Propofol has been proven to be potentially abused by humans and laboratory animals; however, studies that have examined propofol relapse behavior are limited, and its underlying mechanism remains unclear. In this study, we examined whether basolateral amygdala-specific or systematic administration of the dopamine receptor antagonist alters cue-induced propofol-seeking behaviors in a rat model. Male Sprague-Dawley rats first received 14 days of propofol self-administration training, where active nose poke resulted in the delivery of propofol infusion paired with a tone and light cues. After 1-30 days of forced abstinence, the cue-induced propofol-seeking behaviors were tested in the operant chamber. We demonstrated, for the first time, after a few days of withdrawal from intravenous bolus administration of propofol, propofol-related cues could induce robust reinstatement of drug-seeking behavior. Systematic administration of dopamine D1 receptor antagonist (SCH-23390) or dopamine D2 receptor antagonist (spiperone) inhibited propofol relapse behavior induced by drug-related cues. Furthermore, we show that microinfusion of SCH-23390 into basolateral amygdala dose-dependently attenuated cue-induced propofol drug-seeking behavior, whereas infusion of spiperone had no effect on the propofol relapse behavior. Our results reveal the involvement of dopamine receptors within the basolateral amygdala in the cue-induced propofol relapse behavior in rats.

Diagnostic Yield and Safety of Bronchoscopist-directed Moderate Sedation With a Bolus Dose Administration of Propofol During Endobronchial Ultrasound Bronchoscopy.

The propofol use for moderate sedation (MS) during endobronchial ultrasound (EBUS) bronchoscopy is primarily restricted for use by an anesthesiologist because of safety concerns. The goals of this study were to demonstrate the safety and the diagnostic yield of the use of propofol by bronchoscopists and trained endoscopy nurses during EBUS bronchoscopy without intubation. We tested a bolus propofol administration protocol targeting MS for EBUS bronchoscopy. A fixed initial dose of 40 mg of propofol along with a fixed 50 mcg fentanyl dose were administered. Sedation assessment was performed every 2 minutes, and repeated bolus doses of propofol were given to maintain MS under the direction of the bronchoscopist. A total of 122 subjects underwent EBUS bronchoscopy with a goal of MS from August 2015 to April 2017. In total, 110 subjects who underwent convex EBUS bronchoscopy under MS with propofol were included in the analysis. Median procedure duration was 57 minutes (range, 15 to 97 min). Deep sedation and agitation-related delay were occurred in 14 and 21 subjects, respectively. Hemodynamic instability and hypoxemia occurred in 23 subjects. However, there was no need for vasopressors or artificial airway placement. Median of total propofol dose per case was 560 mg. Diagnostic yield for malignancy and granuloma was 68%, and a median of 4 lymph node stations were sampled per subject. All specimens with adenocarcinoma were sufficient for genetic marker analysis. There were no major sedation-related complications. A bolus administration of propofol during EBUS bronchoscopy provided excellent adequacy of sedation and well tolerance safety profile.

A new method for determining levels of sedation in dogs: A pilot study with propofol and a novel neuroactive steroid anesthetic

BackgroundDifferent levels of consciousness are required in order to perform different medical procedures. Sedation scales established to objectively define various levels of sedation in humans have not been thoroughly characterized in non-human species. Postural changes in rats or dogs are useful as gross measures of sedation but are inadequate for quantitative assessment since graded levels of sedation are difficult to delineate and obscured by movement abnormalities. New methodA new canine sedation scoring (CSS) method was developed based on the modified observer’s assessment of alertness and sedation score (MOAA/S) used in humans. The method employed a combination of physical, auditory and somatosensory stimuli of increasing intensity. Cardiovascular, respiratory, and a neurophysiological measure of sedation (bispectral index: BIS) data were recorded. Validation studies were performed following intravenous loading and constant rate infusion of propofol or a novel synthetic neuroactive steroid (SGE-746). ResultsFour levels of consciousness were identified: 1) Awake, 2) Moderate Sedation (MS), 3) Deep Sedation (DS) and 4) General Anesthesia (GA). Cardiorespiratory measurements obtained after bolus administration of propofol and SGE-746 and at the end of each CRI remained within normal limits. Canine sedation scores correlated with BIS for SGE-746. SGE-746 exhibited a more gradual exposure-response relationship than propofol. Larger increases in the plasma concentration from awake values were required to achieve different levels of sedation with SGE-746 compared to propofol. Comparison with existing methodsNo other canine sedation scoring methods are widely accepted. ConclusionA CSS method, based on the human MOAA/S scale defined four levels of consciousness in dogs and provided better resolution of sedation depth than BIS alone.

Pediatric emergence agitation

The origin of emergence agitation in children remains unclear; however, an association between surgical procedure, patient age and anesthetic regimen and the incidence of postoperative agitation has been described in the literature. The aim of this survey performed between February and April 2014 was to collect data from the daily clinical practice by experienced pediatric anesthesiologists regarding documentation, premedication, anesthesia regimen and postoperative treatment with respect to children with emergence agitation. An online questionnaire with 33 items was developed and sent to all 525 members of the scientific committee of pediatric anesthesia (WAKKA) of the German Society of Anesthesiology and Intensive Care (DGAI). Members were asked to respond within a time period of 1 month but no reminders were sent out via email or telephone. A total of 156 members participated in the survey and of these 143 questionnaires were fully completed and included in the final evaluation (27 %). Of the participants 77 % had more than 6 years professional experience in the field of pediatric anesthesia and for 87 % emergence agitation remains a relevant clinical problem. The estimated incidence of emergence agitation was given as 1-10 % and as high as 11-20 % by 56% and 20 % of the participants, respectively. The incidence of postoperative agitation is documented by only 11 % of the participants with a validated score, such as the pediatric anesthesia emergence delirium (PEAD) scale and 89 % of the participants use midazolam for premedication. As a preemptive intervention total intravenous anesthesia is performed by 56 % whereas clonidine is used as first line prevention by 30 %. Postoperative pharmacological treatment is performed by a bolus administration of propofol (56 %) and clonidine (26 %). Postoperative parental presence was considered beneficial by 82 %. Emergence agitation is still seen as a relevant clinical problem by experienced pediatric anesthesiologists. Propofol is first choice when it comes to pharmacological prevention and treatment of emergence agitation. Postoperative parental presence was considered beneficial by the majority of anesthesiologists.

The incidence of spontaneous movements (myoclonus) in dogs undergoing total intravenous anaesthesia with propofol

ObjectiveTo evaluate the incidence of myoclonus (involuntary movements during anaesthesia, unrelated to inadequate hypnosis or analgesia, and of sufficient severity to require treatment) in dogs anaesthetized with a TIVA of propofol with or without the use of fentanyl. Study designRetrospective clinical study. AnimalsDogs, undergoing general anaesthesia for clinical procedures between January 2012 and January 2013 and subject to TIVA with propofol. MethodsA retrospective analysis reviewed the medical and anaesthetic records. Animals with existing or potential neurological or neuromuscular pathology in the anamnesis or upon clinical examination and cases with incomplete clinical records were excluded. Myoclonus was considered as involuntary muscle contractions which did not cease following a bolus administration of propofol or fentanyl and, due to their intensity and duration, made continuation of the procedure impracticable without other drug administration. Tremors, paddling or muscle spasms, explicable as insufficient hypnosis or analgesia, and transient excitatory phenomena only present during the awakening phase, were not considered as myoclonus. ResultsOut of a total of 492 dogs undergoing anaesthesia, six mixed breed dogs (1.2%), one male and five females, American Society of Anaesthesiologists (ASA) physical status I, median (range) weight 20.5 (7–37) kg and age 1.5 (1–5) years had myoclonus according to the aforementioned definition. In all subjects, myoclonus appeared within 20 minutes after induction of anaesthesia, and mainly involved the limb muscles. All subjects appeared to be in an adequate plane of anaesthesia before and during myoclonus. Conclusions and clinical relevanceThis study shows that 1.2% of dogs, undergoing TIVA with propofol with or without fentanyl administration, developed myoclonus, which required to be, and were treated successfully pharmacologically. The cause of this phenomenon is yet to be determined.

Are Muscle Relaxants Needed for Nasal Intubation in Propofol and Remifentanil Anesthesia?

The authors hypothesized that a muscle relaxant would have no meaningful difference in intubation conditions during nasal intubation under remifentanil and propofol anesthesia. This parallel-group, double-blinded, randomized controlled trial included 44 patients who received saline (S group; n = 22) or rocuronium (R group; n = 22). In addition to remifentanil 0.5 μg/kg per minute and propofol 5 mg/kg per hour, propofol 0.5 mg/kg was administered until loss of consciousness. Nasal intubation was performed 10 minutes after administration of R or S 0.6 mg/kg. Significant differences in intubation conditions and salivary amylase levels before and after intubation were tested (P < .05). Vocal cord status (P = .003) and response to intubation or cuff filling (P = .008) were significantly different, but intubation conditions were not. Salivary amylase level was significantly lower with R administration (P = .022). No patient complained of postoperative throat pain and hoarseness. Muscle relaxants during nasal intubation performed after bolus administration of propofol 0.9 mg/kg in addition to 10 minutes of remifentanil 0.5 μg/kg per minute plus propofol 5 mg/kg per hour are unnecessary.

Effect of Propofol on Anal Sphincter Pressure During Anorectal Manometry

We evaluated the effect of propofol on resting anal sphincter pressure (RP) during anorectal manometry performed under general anesthesia in 20 children with chronic constipation. After propofol bolus administration, there was a significant decrease in the RP in 95% of children from a mean of 51.5 ± 15.3 to a mean nadir of 21.7 ± 10.5 mmHg (P < 0.001). The new postpropofol RP of 47.0 ± 12.4 mmHg was significantly lower compared with prepropofol RP (P < 0.0001). Propofol should be used with caution as an anesthetic agent for anorectal manometry, given the potential for confounding RP measurements.

Is Indirect Hyperbilirubinemia a Useful Biomarker of Reduced Propofol Clearance in Neonates?

Large interindividual variability in neonatal propofol clearance is documented which, in part, can be explained by postmenstrual age (PMA) and postnatal age (PNA). We aimed to document whether indirect bilirubin, instead of or in addition to PNA, could improve predictability of propofol clearance and serve as a useful biomarker of reduced propofol clearance in neonates. Indirect serum bilirubin was introduced as a dichotomous or continuous variable (both age-normalized) in a previously developed three-compartment pharmacokinetic model, based on 235 concentration-time points obtained in 25 neonates after single bolus administration of propofol. For pharmacokinetic analysis, nonlinear mixed effect modeling 6.2 was used. The covariates PMA and PNA explained 67% of the interindividual variability compared with 45% in the model with PMA and bilirubin. Age, reflected by PMA and PNA, is a more relevant clinical predictor of neonatal propofol clearance compared with PMA and raised indirect hyperbilirubinemia.

Efficacy of manual jet ventilation using Manujet III for bronchoscopic airway foreign body removal in children

Objectives To evaluate the efficacy of a manual jet ventilation device for bronchoscopic removal of foreign bodies in children. Methods 360 children aged from 10 months to 12 years old undergoing rigid bronchoscopy for airway foreign body (FB) removal from February 2005 to June 2009 were included in the study. Patients were randomly divided into three groups of 120 patients per group (S, P and J). In group S, anesthesia was induced with propofol and γ-hydroxybutyrate sodium and maintained by intermittent bolus administration of propofol; the patients were breathing spontaneously throughout the procedure. In group P, anesthesia was induced with propofol (4–5 mg/kg), fentanyl (1–2 μg/kg) and succinylcholine (2 mg/kg). Mechanical ventilation was performed through the side arm of the rigid bronchoscope. In group J, the patient received propofol, fentanyl and succinylcholine as the same doses administered in group P, and manual jet ventilation was performed by using the Manujet III device. Condition for insertion of bronchoscope, occurrence of hypoxemia, successful rate of FB removal, the duration of the operation, the time of emergence and recovery from anesthesia, and perioperative complications (adverse events) were recorded. Results Groups P and J had significantly higher rates of successful bronchoscope insertion ( P < 0.05), significantly higher success rates for FB removal ( P < 0.05), and lower incidences of hypoxemia during intra- and post-operative periods when compared with group S. Perioperative complications were lower ( P < 0.05), duration of operation was shorter, and emergence from anesthesia was faster ( P < 0.05) in groups P and J when compared with group S. Incidences of hypoxemia were lower in Group J when compared with Group P ( P < 0.05). Conclusion This study confirmed the safety and efficacy of performing manual jet ventilation with Manujet III in foreign body removal by rigid bronchoscopy in children.

Cerebral and Systemic Hemodynamic Effects of Intravenous Bolus Administration of Propofol in Neonates

Objectives: To assess variability of systemic hemodynamics and its covariates following bolus propofol administration in (pre)term neonates, and to analyze the effect of propofol on cerebral tissue oxygenation index (TOI) and fractional tissue oxygen extraction measured by near-infrared spectroscopy. Methods: In (pre)term neonates, we recorded mean arterial blood pressure (MABP), saturation (SaO₂), heart rate (HR) and TOI from 5 min before up to 60 min after intravenous bolus propofol (3 mg kg^–1) administration during elective chest tube removal. Covariate analysis included postmenstrual age (PMA ≤ or >37 weeks), postnatal age (PNA ≤ or >10 days), comedication (fentanyl +/– midazolam) and congenital cardiopathy (yes/no). Fractional tissue oxygen extraction was calculated as (SaO₂ – TOI)/SaO₂. Results: Twenty recordings in 19 neonates were assessed. Following propofol administration, an abrupt, minor decrease in HR and SaO₂ was seen with fast recovery, while MABP decreased up to 1 h. TOI decreased during the first 3 min, reflecting an imbalance between cerebral oxygen delivery and demand. Despite sustained decrease in MABP, TOI then returned to baseline, suggesting a better balance between oxygen delivery and demand. PNA ≤10 days, comedication and absence of cardiopathy were associated with more subtle decreases in cerebral oxygenation and faster recovery. Conclusions: Propofol-induced decrease in HR, SaO₂ and cerebral oxygenation is short lasting while a decrease in MABP is observed up to 60 min. The variability in the effects of propofol is influenced by PNA, comedication or cardiopathy. Near-infrared spectroscopy can be used to assess hemodynamic effects of hypnotics on the cerebral oxygenation.

Is Propofol the Perfect Hypnotic Agent for Procedural Sedation in Neonates?

Following the landmark observations on the relevance of adequate analgesia and sedation in neonates, neonatologists are in search for short acting agents for procedural sedation. Propofol (2,6 di-isopropylphenol) is considered to be a short acting anaesthetic that is both rapid in onset and short in duration after cessation, but data on pharmacokinetics and metabolism in neonates were absent. In 3 consecutive studies, data on propofol pharmacokinetics and metabolism were collected in neonates after single intravenous (3 mg/kg) bolus administration. Median propofol clearance (19.6 mL kg(-1) min(-1)) is significantly lower and interindividual variability (range 3.7-78 mL kg(-1) min(-1)) in propofol clearance in neonates is extensive. Simultaneous introduction of postmenstrual and postnatal age as covariates resulted in a reduction of this interindividual clearance from 322 to 84 %. Finally, differences in clearance are due to limited capacity for glucuronidation in neonates, only in part compensated by hydroxylation. Clinicians should remain careful with propofol in neonates because of the reduced clearance and extensive interindividual variability. We strongly dissuade the use of continuous or repeated intermittent administration of propofol in the first weeks of life and suggest to study the pharmacodynamics of single bolus administration of propofol in neonates.

Inter-individual variability in propofol pharmacokinetics in preterm and term neonates

To document covariates which contribute to inter-individual variability in propofol pharmacokinetics in preterm and term neonates. Population pharmacokinetics were estimated (non-linear mixed effect modelling) based on the arterial blood samples collected in (pre)term neonates after i.v. bolus administration of propofol (3 mg kg(-1), 10 s). Covariate analysis included postmenstrual age (PMA), postnatal age (PNA), gestational age, weight, and serum creatinine. Two hundred and thirty-five arterial concentration-time points were collected in 25 neonates. Median weight was 2930 (range 680-4030) g, PMA 38 (27-43) weeks, and PNA 8 (1-25) days. In a three-compartment model, PMA was the most predictive covariate for clearance (P<0.001) when parameterized as [CL(std).(PMA/38)(11.5)]. Standardized propofol clearance (CL(std)) at 38 weeks PMA was 0.029 litre min(-1). The addition of a fixed value in neonates with a PNA of >/=10 days further improved the model (P<0.001) and resulted in the equation [CL(std).(PMA/38)(11.5) +0.03] for neonates >/=10 days. Values for central volume (1.32 litre), peripheral volume 1 (15.4 litre), and peripheral volume 2 (1.29 litre) were not significantly influenced by any of the covariates (P>0.001). PMA and PNA contribute to the inter-individual variability of propofol clearance with very fast maturation of clearance in neonatal life. This implicates that preterm neonates and neonates in the first week of postnatal life are at an increased risk for accumulation during either intermittent bolus or continuous administration of propofol.

Maturational pharmacokinetics of single intravenous bolus of propofol

Our aim was to document propofol pharmacokinetics in preterm and term neonates following a single intravenous bolus and compare these estimates with pharmacokinetics findings in toddlers and young children. Newly collected observations following intravenous bolus administration of propofol in preterm and term neonates (n = 9) were compared with earlier reported pharmacokinetic estimates in toddlers and young children. Data are reported by median and range. Mann-Whitney U-test or correlation was used to analyze differences in pharmacokinetic findings between neonates, toddlers and young children. Concentration-time profiles obtained were interpreted by two-stage analysis as a three compartment open model in nine neonates with a median weight of 2.51 (range 0.91-3.8) kg and a median postmenstrual age (PMA) of 36 (range 27-43) weeks. Median clearance (CL) was 13.6 (range 3.7-78.2) ml.min(-1).kg(-1) and median apparent volume of distribution at steady state (V(ss)) was 3.7 (1.33-7.96) l.kg(-1). Following allometric scaling and standardization to 70 kg, median CL was 442 (range 97-2184) ml.min(-1).70 kg(-1). Compared with earlier reported observations in toddlers and children, median clearance (kg.min(-1)) was significantly lower in neonates (P < 0.01) and these differences remained significant after allometric scaling (70 kg.min(-1)) while V(ss) (l.kg(-1)) was significantly lower in neonates (P < 0.01). Propofol disposition is significantly different in neonates compared with toddlers and young children, reflecting both ontogeny and differences in body composition. Based on the reduced clearance of propofol, a longer recovery time is more likely to occur in neonates.

Maturational pharmacokinetics of single intravenous bolus administration of propofol during childhood

Maturational pharmacokinetics of single intravenous bolus administration of propofol during childhood