Search

A thorough understanding of the dose–response relationship is required for optimizing the efficacy of anesthetics while minimizing adverse drug effects.1 Nowadays, except for the inhaled anesthetics (for which end-tidal concentrations can be measured online), most of the drugs used in clinical anesthesia are administered using standard dosing guidelines, without giving due consideration to their pharmacokinetics and dynamics in guiding their administration. Various studies have found that introducing pharmacokinetics and pharmacodynamics as part of the inputs in clinical anesthesiology could lead to better patient care.2 With this in mind, it is extremely important that clinicians understand and apply the principles of clinical pharmacology that determine the time course of a drug's disposition and effect.Clinical pharmacology is one of the most challenging topics to teach in anesthesiology. The development of simulators to illustrate the time course of a drug's disposition and effect provides online visualization of pharmacokinetic–pharmacodynamic information during the clinical use of anesthetics. The aim of this review is to discuss the importance of simulation as a clinical pharmacology teaching tool for trainees in anesthesiology.Clinical Pharmacology & Therapeutics (2008); 84, 1, 170–174 doi:10.1038/clpt.2008.76 [ABSTRACT FROM AUTHOR]

Background: Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers.Methods: Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg-1 min-1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring.Results: No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift.Conclusions: Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern.Clinical Trial Registration: NTR4735. [ABSTRACT FROM AUTHOR]

Background: Pharmacokinetic (PK) and pharmacodynamic (PD) models are used in target-controlled-infusion (TCI) systems to determine the optimal drug administration to achieve a desired target concentration in a central or effect-site compartment. Our aim was to develop a PK-PD model for propofol that can predict the bispectral index (BIS) for a broad population, suitable for TCI applications.Methods: Propofol PK data were obtained from 30 previously published studies, five of which also contained BIS observations. A PK-PD model was developed using NONMEM. Weight, age, post-menstrual age (PMA), height, sex, BMI, and presence/absence of concomitant anaesthetic drugs were explored as covariates. The predictive performance was measured across young children, children, adults, elderly, and high-BMI individuals, and in simulated TCI applications.Results: Overall, 15 433 propofol concentration and 28 639 BIS observations from 1033 individuals (672 males and 361 females) were analysed. The age range was from 27 weeks PMA to 88 yr, and the weight range was 0.68-160 kg. The final model uses age, PMA, weight, height, sex, and presence/absence of concomitant anaesthetic drugs as covariates. A 35-yr-old, 170 cm, 70 kg male (without concomitant anaesthetic drugs) has a V1, V2, V3, CL, Q2, Q3, and ke0 of 6.28, 25.5, 273 litres, 1.79, 1.75, 1.11 litres min-1, and 0.146 min-1, respectively. The propofol TCI administration using the model matches well with recommendations for all age groups considered for both anaesthesia and sedation.Conclusions: We developed a PK-PD model to predict the propofol concentrations and BIS for broad, diverse population. This should be useful for TCI in anaesthesia and sedation. [ABSTRACT FROM AUTHOR]

Background: Neural inertia is defined as the tendency of the central nervous system to resist transitions between arousal states. This phenomenon has been observed in mice and Drosophila anaesthetized with volatile anaesthetics: the effect-site concentration required to induce anaesthesia in 50% of the population (C50) was significantly higher than the effect-site concentration for 50% of the population to recover from anaesthesia. We evaluated this phenomenon in humans using propofol or sevoflurane (both with or without remifentanil) as anaesthetic agents.Methods: Thirty-six healthy volunteers received four sessions of anaesthesia with different drug combinations in a step-up/step-down design. Propofol or sevoflurane was administered with or without remifentanil. Serum concentrations of propofol and remifentanil were measured from arterial blood samples. Loss and return of responsiveness (LOR-ROR), response to pain (PAIN), Patient State Index (PSI) and spectral edge frequency (SEF) were modeled with NONMEM®.Results: For propofol, the C50 for induction and recovery of anaesthesia was not significantly different across the different endpoints. For sevoflurane, for all endpoints except SEF, significant differences were found. For some endpoints (LOR and PAIN) the difference was significant only when sevoflurane was combined with remifentanil.Conclusions: Our results nuance earlier findings with volatile anaesthetics in mice and Drosophila. Methodological aspects of the study, such as the measured endpoint, influence the detection of neural inertia. A more thorough definition of neural inertia, with a robust methodological framework for clinical studies is required to advance our knowledge of this phenomenon.Clinical Trial Registration: NCT 02043938. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic-pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties.Methods: In a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model. Volunteers were randomized to a session without background noise and a session with pre-recorded looped operating room background noise. Exploratory pharmacokinetic-pharmacodynamic modelling and covariate analysis were conducted in NONMEM using bispectral index (BIS) monitoring of processed EEG.Results: We found that both stimulation at the time of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale scoring and the presence or absence of ambient noise had an effect on the sedative properties of dexmedetomidine. The stimuli associated with MOAA/S scoring increased the BIS of sedated volunteers because of a transient 170% increase in the effect-site concentration necessary to reach half of the maximal effect. In contrast, volunteers deprived of ambient noise were more resistant to dexmedetomidine and required, on average, 32% higher effect-site concentrations for the same effect as subjects who were exposed to background operating room noise.Conclusions: The new pharmacokinetic-pharmacodynamic models might be used for effect-site rather than plasma concentration target-controlled infusion for dexmedetomidine in clinical practice, thereby allowing tighter control over the desired level of sedation.Clinical Trial Registration: NCT01879865. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic-pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate.Methods: Dexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model. Exploratory PKPD modelling and covariate analysis were conducted in NONMEM.Results: Our model adequately describes dexmedetomidine-induced hypotension, hypertension, and bradycardia, with a greater effective concentration for the hypertensive effect. Changes in MAP were best described by a double-sigmoidal E max model with hysteresis. Covariate analysis revealed no significant covariates apart from age on the baseline MAP in the population pharmacokinetic model used to develop this PKPD model. Simulations revealed good general agreement with published descriptive studies of haemodynamics after dexmedetomedine infusion.Conclusions: The present integrated PKPD model should allow tighter control over the desired level of sedation, while limiting potential haemodynamic side-effects.Clinical Trial Registration: NCT01879865. [ABSTRACT FROM AUTHOR]

Background: Models of propofol pharmacokinetics and pharmacodynamics developed in patients without brain pathology are widely used for target-controlled infusion (TCI) during brain tumour excision operations. The goal of this study was to determine if the presence of a frontal brain tumour influences propofol pharmacokinetics and pharmacodynamics and existing PK-PD model performance.Methods: Twenty patients with a frontal brain tumour and 20 control patients received a propofol infusion to achieve an induction-emergence-induction anaesthetic sequence. Propofol plasma concentration was measured every 4 min and at each transition of the conscious state. Bispectral index (BIS) values were continuously recorded. We used non-linear mixed-effects modelling to analyse the effects of the presence of a brain tumour on the pharmacokinetics and pharmacodynamics of propofol. Subsequently we calculated the predictive performance of Marsh, Schnider, and Eleveld models in terms of median prediction error (MdPE) and median absolute prediction error (MdAPE).Results: Patients with brain tumours showed 40% higher propofol clearance than control patients. Performance of the Schnider model (MdPEpk -20.0%, MdAPEpk 23.4%) and Eleveld volunteer model (MdPEpk -8.58%, MdAPEpk 21.6%) were good. The Marsh model performed less well (MdPEpk -14.3%, MdAPEpk 41.4%), as did the Eleveld patient model (MdPEpk -30.8%, MdAPEpk 32.1%).Conclusions: Brain tumours might alter the pharmacokinetics of propofol. Caution should be exerted when using propofol TCI in patients with frontal brain tumours due to higher clearance.Trial Registry Number: NCT01060631. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia-reperfusion injury. Anaesthetic conditioning is a widely described strategy to attenuate ischaemia-reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol- vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation.Methods: Sixty couples were randomly assigned to the following three groups: PROP (donor and recipient propofol), SEVO (donor and recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The primary outcome was renal injury reflected by urinary biomarkers. The follow-up period was 2 yr.Results: Three couples were excluded, leaving 57 couples for analysis. Concentrations of kidney injury molecule-1 (KIM-1), N -acetyl-β- d -glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the first urine upon reperfusion showed no differences. On day 2, KIM-1 concentrations were higher in SEVO [952.8 (interquartile range 311.8-1893.0) pg mmol -1 ] compared with PROP [301.2 (202.0-504.7) pg mmol -1 ]. This was the same for NAG: SEVO, 1.835 (1.162-2.457) IU mmol -1 vs PROP, 1.078 (0.819-1.713) IU mmol -1 . Concentrations of H-FABP showed no differences. Measured glomerular filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there was a difference in the acute rejection rate ( P =0.039). Post hoc testing revealed a difference between PROP (35%) and PROSE (5%; P =0.020). The difference between PROP and SEVO (11%) was not significant ( P =0.110).Conclusions: The SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor kidney transplantation on the second day after transplantation. This was not reflected in inferior graft outcome.Clinical trial registration: NCT01248871. [ABSTRACT FROM AUTHOR]

Background: The steep (40 degrees ) Trendelenburg position optimizes surgical exposure during robotic prostatectomy. The goal of the current study was to investigate the combined effect of this position and CO(2) pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during these procedures.Methods: Physiological data were recorded during the whole surgical procedure in 31 consecutive patients who underwent robotic endoscopic radical prostatectomy under general anaesthesia. Heart rate, mean arterial pressure, central venous pressure, Sp(o(2)), Pe'(co(2)), P(Plat), tidal volume, compliance, and minute ventilation were monitored and recorded. Arterial samples were obtained to determine the arterial-to-end-tidal CO(2) tension gradient. Continuous regional cerebral tissue oxygen saturation (Sct(o(2))) was determined by near-infrared spectroscopy.Results: Although patients were in the Trendelenburg position, all variables investigated remained within a clinically acceptable range. Cerebral perfusion pressure (CPP) decreased from 77 mm Hg at baseline to 71 mm Hg (P=0.07), and Sct(o(2)) increased from 70% to 73% (P<0.001). Pe'(co(2)) increased from 4.12 to 4.79 kPa (P<0.001) and the arterial-to-Pe'(co(2)) tension difference increased from 1.06 kPa in the normal position to a maximum of 1.41 kPa (P<0.001) after 2 h in the Trendelenburg position.Conclusions: The combination of the prolonged steep Trendelenburg position and CO(2) pneumoperitoneum was well tolerated. Haemodynamic and pulmonary variables remained within safe limits. Regional cerebral oxygenation was well preserved and CPP remained within the limits between which cerebral blood flow is usually considered to be maintained by cerebral autoregulation. [ABSTRACT FROM AUTHOR]

Background: In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce(PROP)), for any Ce(PROP), the corresponding hypnotic effect should be constant. We compared three PK-PD models (Marsh PK with Shüttler PD, Schnider PK with fixed ke0, and Schnider PK with Minto PD) in their ability to maintain a constant bispectral index (BIS), while using the respective effect-site-controlled target-controlled infusion (TCI) algorithms.Methods: We randomized 60 patients to Group M (Marsh's model with k(e0)=0.26 min(-1)), Group S1 or Group S2 (Schnider's model with a fixed k(e0)=0.456 min(-1) or a k(e0) adapted to a fixed time-to-peak effect=1.6 min, respectively). All patients received propofol at a constant rate until loss of consciousness. The corresponding Ce(PROP), as calculated by the respective models, was set as a target for effect-site-controlled TCI. We observed BIS for 20 min. We hypothesized that BIS remains constant, if Ce(PROP) remains constant over time.Results: All patients in Group M woke up, one in Group S1 and none in Group S2. In Groups S1 and S2, BIS remained constant after 11 min of constant Ce(PROP), at a more pronounced level of hypnotic drug effect than intended.Conclusions: Targeting Ce(PROP) at which patients lose consciousness with effect-site-controlled TCI does not translate into an immediate constant effect. [ABSTRACT FROM AUTHOR]

The article discusses the implications of administering propofol through target-controlled infusion (TCI) devices. Several issues are cited regarding the confusion among anesthetists on the delivery of propofol by TCI. The rationale for using software solutions in open TCI systems is explained. It is proposed that an induction bolus be manually administered and a manually controlled infusion thereafter.

Post-induction hypotension (MAP < 65 mmHg) occurs frequently and is usually caused by the cardiovascular adverse effects of the anaesthetic induction drugs used. We hypothesize that a clinically significant difference in the incidence and severity of hypotension will be found when different doses of propofol and remifentanil are used for induction of anaesthesia., Methods: This is a secondary analysis of a randomised controlled trial wherein four groups (A-D) of patients received one out of four different combinations of propofol and remifentanil, titrated to a predicted equipotency in probability of tolerance to laryngoscopy (PTOL) according to the Bouillon interaction model. In group A, a high dose of propofol and a low dose of remifentanil was administered, and across the groups this ratio was gradually changed until it was reversed in group D. Mean and systolic arterial blood pressure (MAP, SAP) were compared at four time points (T baseline , T post-bolus , T 3min , T nadir ) within and between groups Heart rate, bispectral index (BIS) and the incidence of hypotension were compared., Results: Data from 76 patients was used. At T post-bolus a statistically significant lower MAP and SAP was found in group A versus D (p = 0.011 and p = 0.002). A significant higher heart rate was found at T 3min and T nadir between groups A and B when compared to groups C and D (p = < 0.001 and p = 0.002). A significant difference in BIS value was found over all groups at T 3min and T nadir (both p < 0.001). All other outcomes did not differ significantly between groups., Conclusion: Induction of anaesthesia with different predicted equipotent combinations of propofol and remifentanil did result in statistically different but clinically irrelevant differences in haemodynamic endpoints during induction of anaesthesia. Our study could not identify preferable drug combinations that decrease the risk for hypotension after induction, although they all yield a similar predicted PTOL., (© 2024. The Author(s).)

Background: Early restoration of normal physiology when return of spontaneous circulation (ROSC) is obtained after an out-of-hospital cardiac arrest (OHCA) reduces the risk of developing post-cardiac arrest syndrome (PCAS). This study aims to investigate if (and to which extent) this can be achieved within the scope of practice of standard emergency medical services (EMS) crews., Methods: A prospective mixed-methods quantitative and qualitative cohort study was performed including adult patients with a non-traumatic OHCA presented to a university hospital emergency department (ED) in the Netherlands after pre-hospital ROSC was obtained. Primary endpoint was the percentage of patients with deranged physiology post-ROSC in whom EMS crews were able to reach recommended treatment targets., Results: During a 32-month period, 160 patients presenting with ROSC after OHCA were included. Median (IQR) pre-hospital treatment duration was 40 (34-51) minutes. When deranged physiology was present (n = 133), it could be restored by EMS crews in 29% of the patients. Although average etCO 2 and SpO 2 improved gradually over time during pre-hospital treatment, recommended treatment targets could not be achieved in respectively 55% (30/55) and 43% (20/46) of the patients. Similarly, airway problems (24/46, 52%), hypotension (20/23, 87%) and post-anoxic agitation (16/43, 37%) could often not be resolved by EMS crews. The ability to restore normal physiology by EMS could not be predicted based on patient characteristics or in-arrest variables., Conclusion: Deranged physiology after an OHCA is commonly encountered, and often difficult to treat within the scope of practice of regular EMS crews. Involvement of advanced critical care teams with a wider scope of practice at an early stage may contribute to a better outcome for these patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Aim: In this predictive modelling study we aimed to investigate how many patients with an out-of-hospital cardiac arrest (OHCA) would benefit from pre-hospital as opposed to in-hospital initiation of extracorporeal cardiopulmonary resuscitation (ECPR)., Methods: A temporal spatial analysis of Utstein data was performed for all adult patients with a non-traumatic OHCA attended by three emergency medical services (EMS) covering the north of the Netherlands during a one-year period. Patients were considered potentially eligible for ECPR if they had a witnessed arrest with immediate bystander CPR, an initial shockable rhythm (or signs of life during resuscitation) and could be presented in an ECPR-centre within 45 minutes of the arrest. Endpoint of interest was defined as the hypothetical number of ECPR eligible patients after 10, 15 and 20 minutes of conventional CPR and upon (hypothetical) arrival in an ECPR-centre as a fraction of the total number of OHCA patients attended by EMS., Results: During the study period 622 OHCA patients were attended, of which 200 (32%) met ECPR eligibility criteria upon EMS arrival. The optimal transition point between conventional CPR and ECPR was found to be after 15 minutes. Hypothetical intra-arrest transport of all patients in whom no return of spontaneous circulation (ROSC) was obtained after that point (n = 84) would have yielded 16/622 (2.5%) patients being potentially ECPR eligible upon hospital arrival (average low-flow time 52 minutes), whereas on-scene initiation of ECPR would have resulted in 84/622 (13.5%) potential candidates (average estimated low-flow time 24 minutes before cannulation)., Conclusion: Even in healthcare systems with relatively short transport distances to hospital, consideration should be given to pre-hospital initiation of ECPR for OHCA as it shortens low-flow time and increases the number of potentially eligible patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Predictive performance of eleven published propofol pharmacokinetic models was evaluated for long-duration propofol infusion in children., Methods: Twenty-one aged three-11 yr ASA I-II patients were included. Anaesthesia was induced with propofol or sevoflurane, and maintained with propofol, remifentanil, and fentanyl. Propofol was continuously infused at rates of 4-14 mg kg  - 1 h - 1 after an initial bolus of 1.5-2.0 mg kg  - 1 . Venous blood samples were obtained every 30-60 min for five h and then every 60-120 min after five h from the start of propofol administration, and immediately after the end of propofol administration. Model performance was assessed with prediction error (PE) derivatives including divergence PE, median PE (MDPE), and median absolute PE (MDAPE) as time-related PE shift, measures for bias, and inaccuracy, respectively., Results: We collected 85 samples over 270 (130) (88-545), mean (SD) (range), min. The Short model for children, and the Schüttler general-purpose model had acceptable performance (-20%≤MDPE ≤ 20%, MDAPE ≤ 30%, -4% h - 1  ≤   divergence PE ≤ 4% h - 1 ). The Short model showed the best performance with the maximum predictive performance metric. Two models developed only using bolus dosing (Shangguan and Saint-Maurice models) and the Paedfusor of the remaining nine models had significant negative divergence PE (≤-6.1% h - 1 )., Conclusions: The Short model performed well during continuous infusion up to 545 min. This model might be preferable for target-controlled infusion for long-duration anaesthesia in children., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

This review describes the basics of pharmacokinetic and pharmacodynamic drug interactions and methodological points of particular interest when designing drug interaction studies. It also provides an overview of the available literature concerning interactions, with emphasis on graphic representation of interactions using isoboles and response surface models. It gives examples on how to transform this knowledge into clinically and educationally applicable (bedside) tools., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The probability to tolerate laryngoscopy (PTOL) and its derivative, the noxious stimulation response index (NSRI), have been proposed as measures of potency of a propofol-remifentanil drug combination. This study aims at developing a triple drug interaction model to estimate the combined potency of sevoflurane, propofol, and remifentanil in terms of PTOL. We compare the predictive performance of PTOL and the NSRI with various anaesthetic depth monitors., Methods: Data from three previous studies (n=120) were pooled and reanalysed. Movement response after laryngoscopy was observed with different combinations of propofol-remifentanil, sevoflurane-propofol, and sevoflurane-remifentanil. A triple interaction model to estimate PTOL was developed. The NSRI was derived from PTOL. The ability of PTOL and the NSRI to predict observed tolerance of laryngoscopy (TOL) was compared with the following other measures: (i) effect-site concentrations of sevoflurane, propofol, and remifentanil (CeSEVO, CePROP, and CeREMI); (ii) bispectral index; (iii) two measures of spectral entropy; (iv) composite variability index; and (v) surgical pleth index., Results: Sevoflurane and propofol interact additively, whereas remifentanil interacts in a strongly synergistic manner. The effect-site concentrations of sevoflurane and propofol at a PTOL of 50% (Ce50; se) were 2.59 (0.13) vol % and 7.58 (0.49) µg ml(-1). A CeREMI of 1.36 (0.15) ng ml(-1) reduced the Ce50 of sevoflurane and propofol by 50%. The common slope factor was 5.22 (0.52). The PTOL and NSRI predict the movement response to laryngoscopy best., Conclusions: The triple interaction model estimates the potency of any combination of sevoflurane, propofol, and remifentanil expressed as either PTOL or NSRI., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Cognitive-behavioural treatment can nowadays be delivered through the Internet. This form of treatment can have various advantages with regard to availability and accessibility. Previous studies showed that Internet-based treatment for chronic pain is effective compared to waiting-list control groups., Methods: We conducted a randomized controlled trial comparing an Internet-based cognitive-behavioural intervention with e-mail therapist contact to a face-to-face cognitive-behavioural group intervention. Of the 72 participants who were randomly assigned to an Internet or a group course, 50 participants completed the intervention. Participants were assessed at baseline (T0), immediately after the 7-week course (T1) and at the booster session 2 months later (T2). Pain-related catastrophizing was the primary outcome measure. Pain intensity, fatigue, pain-related interference, locus of control, pain coping, global health-related quality of life and medical expenses were secondary outcome variables., Results: Significant improvement was found on catastrophizing, pain coping, locus of control and aspects of global health-related quality of life in both the Internet and the group courses directly after the course and at the booster session. Pain intensity was improved in both courses at the booster session. At T2, improvement in catastrophizing, pain intensity, pain coping and some quality of life dimensions was significantly greater in completers of the Internet course than in the group course. Furthermore, the Internet course was cost-effective compared to the group course., Conclusions: We conclude that the Internet-based cognitive-behavioural intervention was at least as effective as the face-to-face group intervention and, on some outcome measures appeared to be even more effective., (© 2014 European Pain Federation - EFIC®)

Background: For a majority of patients undergoing anaesthesia for general surgery, mean arterial pressure (MAP) is only measured intermittently by arm cuff oscillometry (MAPiNIAP). In contrast, the Nexfin(®) device provides continuous non-invasive measurement of MAP (MAPcNIAP) using a finger cuff. We explored the agreement of MAPcNIAP and MAPiNIAP with the gold standard: continuous invasive MAP measurement by placement of a radial artery catheter (MAPinvasive)., Methods: In a total of 120 patients undergoing elective general surgery and clinically requiring MAPinvasive measurement, MAPiNIAP and MAPcNIAP were measured in a 30 min time period at an arbitrary moment during surgery with stable haemodynamics. MAPiNIAP was measured every 5 min., Results: Data from 112 patients were analysed. Compared with MAPinvasive, modified Bland-Altman analysis revealed a bias (sd) of 2 (9) mm Hg for MAPcNIAP and -2 (12) mm Hg for MAPiNIAP. Percentage errors for MAPcNIAP and MAPiNIAP were 22% and 32%, respectively., Conclusions: In a haemodynamically stable phase in patients undergoing general anaesthesia, the agreement with invasive MAP of continuous non-invasive measurement using a finger cuff was not inferior to the agreement of intermittent arm cuff oscillometry. Continuous measurements using a finger cuff can interchangeably be used as an alternative for intermittent arm cuff oscillometry in haemodynamically stable patients, with the advantage of beat-to-beat haemodynamic monitoring., Clinical Trial Registration: NCT 01362335 (clinicaltrials.gov)., (© The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Catastrophizing is a defining factor in the pain experience and strongly contributes to the prediction of various aspects of health. Catastrophizing is not just present in pain patients, but may also be present in people with non-clinical pain. The aim of the present study is to investigate levels of catastrophizing in pain patients and people with pain from the general population. Also, the relationship between catastrophizing and pain intensity, specialist consultation and use of pain medication is studied., Methods: A cross-sectional survey design was used, including 150 pain patients and 376 respondents from the general population., Results: The results show that pain is highly prevalent in the general population. The pain patients reported significantly higher levels of pain intensity and catastrophizing than the community pain sample. In both samples, significant positive correlations between catastrophizing and pain intensity were found. The data show a linear relationship between catastrophizing and pain intensity, which can be interpreted as evidence for a dose-response pattern in pain-related catastrophizing. Furthermore, catastrophizing predicted specialist consultation and medication use in the community pain sample., Conclusions: It can be concluded that pain-related catastrophizing is present in pain patients as well as people with pain from the general population in a dose-response pattern. Catastrophizing seems to be an important factor determining certain aspects of pain-related medical consumption, even in non-clinical pain, and should therefore be a target of the screening procedure and early intervention., (© 2012 European Federation of International Association for the Study of Pain Chapters.)

The recently introduced open-target-controlled infusion (TCI) systems can be programmed with any pharmacokinetic model, and allow either plasma- or effect-site targeting. With effect-site targeting the goal is to achieve a user-defined target effect-site concentration as rapidly as possible, by manipulating the plasma concentration around the target. Currently systems are pre-programmed with the Marsh and Schnider pharmacokinetic models for propofol. The former is an adapted version of the Gepts model, in which the rate constants are fixed, whereas compartment volumes and clearances are weight proportional. The Schnider model was developed during combined pharmacokinetic-pharmacodynamic modelling studies. It has fixed values for V1, V3, k(13), and k(31), adjusts V2, k(12), and k(21) for age, and adjusts k(10) according to total weight, lean body mass (LBM), and height. In plasma targeting mode, the small, fixed V1 results in very small initial doses on starting the system or on increasing the target concentration in comparison with the Marsh model. The Schnider model should thus always be used in effect-site targeting mode, in which larger initial doses are administered, albeit still smaller than for the Marsh model. Users of the Schnider model should be aware that in the morbidly obese the LBM equation can generate paradoxical values resulting in excessive increases in maintenance infusion rates. Finally, the two currently available open TCI systems implement different methods of effect-site targeting for the Schnider model, and in a small subset of patients the induction doses generated by the two methods can differ significantly.