Semimechanistic models to relate noxious stimulation, movement, and pupillary dilation responses in the presence of opioids.

Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2 ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%.

Influence of an "Electroencephalogram-Based" Monitor Choice on the Delay Between the Predicted Propofol Effect-Site Concentration and the Measured Drug Effect.

BACKGROUND: Clinicians can optimize propofol titration by using 2 sources of pharmacodynamic (PD) information: the predicted effect-site concentration for propofol (Ceprop) and the electroencephalographically (EEG) measured drug effect. Relation between these sources should be time independent, that is, perfectly synchronized. In reality, various issues corrupt time independency, leading to asynchrony or, in other words, hysteresis. This asynchrony can lead to conflicting information, making effective drug dosing challenging. In this study, we tried to quantify and minimize the hysteresis between the Ceprop (calculated using the Schnider model for propofol) and EEG measured drug effect, using nonlinear mixed-effects modeling (NONMEM). Further, we measured the influence of EEG-based monitor choice, namely Bispectral index (BIS) versus qCON index (qCON) monitor, on propofol PD hysteresis. METHODS: We analyzed the PD data from 165 patients undergoing propofol-remifentanil anesthesia for outpatient surgery. Drugs were administered using target-controlled infusion (TCI) pumps. Pumps were programmed with Schnider model for propofol and Minto model for remifentanil. We constructed 2 PD models (direct models) relating the Schnider Ceprop to the measured BIS and qCON monitor values. We quantified the models' misspecification due to hysteresis, on an individual level, using the root mean squared errors (RMSEs). Subsequently, we optimized the PD models' predictions by adding a lag term to both models (lag-time PD models) and quantified the optimization using the RMSE. RESULTS: There is a counterclockwise hysteresis between Ceprop and BIS/qCON values. Not accounting for this hysteresis results in a direct PD model with an effect-site concentration which produces 50% of the maximal drug effect (Ce50) of 6.24 and 8.62 µg/mL and RMSE (median and interquartile range [IQR]) of 9.38 (7.92-11.23) and 8.41(7.04-10.2) for BIS and qCON, respectively. Adding a modeled lag factor of 49 seconds to the BIS model and 53 seconds to the qCON model improved both models' prediction, resulting in similar Ce50 (3.66 and 3.62 µg/mL for BIS and qCON) and lower RMSE (median (IQR) of 7.87 (6.49-9.90) and 6.56 (5.28-8.57) for BIS and qCON. CONCLUSIONS: There is a significant "Ceprop versus EEG measured drug effect" hysteresis. Not accounting for it leads to conflicting PD information and false high Ce50 for propofol in both monitors. Adding a lag term improved the PD model performance, improved the "pump-monitor" synchrony, and made the estimates of Ce50 for propofol more realistic and less monitor dependent.

Grado de satisfacción de los usuarios del circuito de diagnóstico rápido del cáncer / Patients' satisfaction with the rapid diagnosis and treatment programme for cancer (RDTPC). Observational study

Objetivo. Conocer el grado de satis-facción de los usuarios del Circuito de Diagnóstico Rápido del Cáncer (CDRC) así como la percepción de ansiedad. Método. Estudio transversal de una muestra de personas (n=294) atendidas de forma consecutiva en un CDRC de pulmón, mama y colon. La recogida de datos se realizó median-te cuestionario en la primera visita al CDRC y llamada telefónica al mes de la última visita al CDRC. El cuestionario contenía 23 preguntas que exploraban distintas dimensiones de satisfacción (accesibilidad, trato personal, información y coordinación), una sobre ansiedad percibida y una de satisfacción global. También se recogieron variables sociodemográficas, procedencia de la derivación y diagnóstico de cáncer. Resultados. La media de edad fue de 60,1 años (DE =1 2,9) con un 57,8% de mujeres. Fueron diagnosticados de cáncer el 34,4%. El grado de satis-facción global con la asistencia recibida en el CDRC fue de 9,3 (DE = 1,2) sobre 10. El 92,2% de los pacientes afirmó que el hecho de haber entrado en el CDRC le había ayudado a disminuir la ansiedad de todo el proceso. Según el diagnóstico final de cáncer o no, observamos diferencias significativas en las áreas de accesibilidad y trato. Los pacientes diagnosticados de cáncer estuvieron más satisfechos con el tiempo trascurrido entre la primera visita y el diagnóstico y entre el diagnóstico e inicio del tratamiento y valoraron mejor el trato de la enfermera gestora. Conclusiones. La satisfacción de los pacientes que entran en el CDRC es muy alta. Su evaluación complementa otros indicadores de eficacia del programa

Objective. Evaluation of patients' satisfaction with the Rapid Diagnosis and Treatment Programme for Cancer (RDTPC) and perception of anxiety Method. A cross-sectional study was performed on a sample (n = 294) of patients who subsequently were followed at the RDTPC for lung, breast and colon cancer. Data collection was carried out using a questionnaire administered to users during their first visit at the RDTPC and a tele-phone call one month after their last visit. The questionnaire included 23 items that explore different aspects of satisfaction (accessibility, personal treatment, information and coordination), one item on perceived anxiety and one on overall satisfaction. Socio-demographic variables, origin of referral and diagnosis of cancer were also collected. Results. The mean age was 60.1 years (SD=12.9); 57.8% were women. A total of 34.4%. were diagnosed of cancer. The level of overall satisfaction with the care received at the RDTPC was 9.3 (SD =1.2) out of 10 and 92.2% of patients reported that entering the RDTPC had helped them decrease their anxiety throughout the whole process. Depending on whether cancer was finally diagnosed or not, significant differences were observed in areas of accessibility and attention received. Patients diagnosed with cancer were more satisfied with the time period between the initial visit and diagnosis and between time of diagnosis and start of treatment. They also reported a higher satisfaction with the attention they received from the nurse in charge. Conclusions. The satisfaction of patients on the RDTPC is very high. Their assessment completes other indicators of the efficacy of the programme

A randomized comparison of the Ambu AuraGain versus the LMA supreme in patients undergoing gynaecologic laparoscopic surgery.

Second generation supraglottic airway devices providing high seal airway pressures are suitable for patients undergoing gynecologic laparoscopy. We compared the seal pressure achieved by the new Ambu AuraGain™ versus LMA Supreme™ following pneumoperitoneum in the Trendelenburg position. Sixty female patients were randomly allocated to ventilation with either the AuraGain or the Supreme. A target-controlled system was used to administer total intravenous anesthesia. Intracuff pressure was maintained below 60 cm H2O. The following parameters were registered: Time, number of attempts and manoeuvres required for insertion; seal pressure and peak inspiratory pressure at four time points; ease of gastric tube insertion, flexible scope view, complications and postoperative morbidity. Both devices were quick and easily inserted, although the Supreme required less rotation manoeuvres (16 in AuraGain vs. 6 in LMA Supreme; p = 0.01). The AuraGain achieved higher seal pressures (34 ± 5 in AuraGain vs. 29 ± 5 in LMA Supreme; p = 0.0002). Following pneumoperitoneum in head-down position, peak airway pressure increased 9 ± 3 cm H2O in both groups, exceeding seal pressure in 3 patients in the Supreme group (p = 0.06). The vocal cords were seen through all AuraGain and 90% of the Supreme devices; epiglottis was often visible inside the tube (68%). No differences were found in the incidence of traces of blood on the mask or postoperative symptoms. Both devices allowed effective ventilation in patients undergoing gynaecologic laparoscopic surgery with a low rate of complications. The Ambu AuraGain provided higher seal pressures and a clear view of glottic inlet in all patients offering the possibility to guide direct tracheal intubation if required.

Comparison of the qCON and qNOX indices for the assessment of unconsciousness level and noxious stimulation response during surgery.

The objective of this work is to compare the performances of two electroencephalogram based indices for detecting loss of consciousness and loss of response to nociceptive stimulation. Specifically, their behaviour after drug induction and during recovery of consciousness was pointed out. Data was recorded from 140 patients scheduled for general anaesthesia with a combination of propofol and remifentanil. The qCON 2000 monitor (Quantium Medical, Barcelona, Spain) was used to calculate the qCON and qNOX. Loss of response to verbal command and loss of eye-lash reflex were assessed during the transition from awake to anesthetized, defining the state of loss of consciousness. Movement as a response to laryngeal mask (LMA) insertion was interpreted as the response to the nociceptive stimuli. The patients were classified as movers or non-movers. The values of qCON and qNOX were statistically compared. Their fall times and rise times defined at the start and at the end of the surgery were calculated and compared. The results showed that the qCON was able to predict loss of consciousness such as loss of verbal command and eyelash reflex better than qNOX, while the qNOX has a better predictive value for response to noxious stimulation such as LMA insertion. From the analysis of the fall and rise times, it was found that the qNOX fall time (median: 217 s) was significantly longer (p value <0.05) than the qCON fall time (median: 150 s). At the end of the surgery, the qNOX started to increase in median at 45 s before the first annotation related to response to stimuli or recovery of consciousness, while the qCON at 88 s after the first annotation related to response to stimuli or recovery of consciousness (p value <0.05). The indices qCON and qNOX showed different performances in the detection of loss of consciousness and loss of response to stimuli during induction and recovery of consciousness. Furthermore, the qCON showed faster decrease during induction. This behaviour is associated with the hypothesis that the loss of response to stimuli (analgesic effect) might be reached after the loss of consciousness (hypnotic effect). On the contrary, the qNOX showed a faster increase at the end of the surgery, associated with the hypothesis that a higher probability of response to stimuli might be reached before the recovery of consciousness.

Passive smoking at home is a risk factor for community-acquired pneumonia in older adults: a population-based case-control study.

OBJECTIVE: To assess whether passive smoking exposure at home is a risk factor for community-acquired pneumonia (CAP) in adults. SETTING: A population-based case-control study was designed in a Mediterranean area with 860 000 inhabitants >14 years of age. PARTICIPANTS: 1003 participants who had never smoked were recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: Risk factors for CAP, including home exposure to passive smoking, were registered. All new cases of CAP in a well-defined population were consecutively recruited during a 12-month period. METHODS: A population-based case-control study was designed to assess risk factors for CAP, including home exposure to passive smoking. All new cases of CAP in a well-defined population were consecutively recruited during a 12-month period. The subgroup of never smokers was selected for the present analysis. RESULTS: The study sample included 471 patients with CAP and 532 controls who had never smoked. The annual incidence of CAP was estimated to be 1.14 cases×10(-3) inhabitants in passive smokers and 0.90×10(-3) in non-passive smokers (risk ratio (RR) 1.26; 95% CI 1.02 to 1.55) in the whole sample. In participants ≥65 years of age, this incidence was 2.50×10(-3) in passive smokers and 1.69×10(-3) in non-passive smokers (RR 1.48, 95% CI 1.08 to 2.03). In this last age group, the percentage of passive smokers in cases and controls was 26% and 18.1%, respectively (p=0.039), with a crude OR of 1.59 (95% CI 1.02 to 2.38) and an adjusted (by age and sex) OR of 1.56 (95% CI 1.00 to 2.45). CONCLUSIONS: Passive smoking at home is a risk factor for CAP in older adults (65 years or more).

Relationship between the use of inhaled steroids for chronic respiratory diseases and early outcomes in community-acquired pneumonia.

BACKGROUND: The role of inhaled steroids in patients with chronic respiratory diseases is a matter of debate due to the potential effect on the development and prognosis of community-acquired pneumonia (CAP). We assessed whether treatment with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP may affect early outcome of the acute pneumonic episode. METHODS: Over 1-year period, all population-based cases of CAP in patients with chronic bronchitis, COPD or asthma were registered. Use of inhaled steroids were registered and patients were followed up to 30 days after diagnosis to assess severity of CAP and clinical course (hospital admission, ICU admission and mortality). RESULTS: Of 473 patients who fulfilled the selection criteria, inhaled steroids were regularly used by 109 (23%). In the overall sample, inhaled steroids were associated with a higher risk of hospitalization (OR=1.96, p = 0.002) in the bivariate analysis, but this effect disappeared after adjusting by other severity-related factors (adjusted OR=1.08, p=0.787). This effect on hospitalization also disappeared when considering only patients with asthma (OR=1.38, p=0.542), with COPD alone (OR=4.68, p=0.194), but a protective effect was observed in CB patients (OR=0.15, p=0.027). Inhaled steroids showed no association with ICU admission, days to clinical recovery and mortality in the overall sample and in any disease subgroup. CONCLUSIONS: Treatment with inhaled steroids is not a prognostic factor in COPD and asthmatic patients with CAP, but could prevent hospitalization for CAP in patients with clinical criteria of chronic bronchitis.

Monitoring in resuscitation: comparison of cardiac output measurement between pulmonary artery catheter and NICO.

AIM: The cardiac output and coronary perfusion pressure generated from chest compressions during resuscitation manoeuvres can predict effectiveness and successful outcome. Until now, there is no good method for haemodynamic monitoring during resuscitation. Noninvasive partial carbon dioxide rebreathing system (NICO, Novametrix Medical Systems, Inc., Wallingford, CT, USA) is a relatively new non-invasive alternative to thermodilution for measuring cardiac output. The accuracy of the NICO system has not been evaluated during resuscitation. The aim of this study is to compare thermodilution cardiac output method with NICO system and to assess the utility of NICO during resuscitation. METHODS AND DESIGN: Experimental study in 24 Yorkshire pigs. Paired measurements of cardiac output were determined during resuscitation (before ventricular fibrillation and after 5, 15, 30 and 45 min of resuscitation) in the supine position. The average of 3 consecutive thermodilution cardiac output measurements (10 ml 20 degrees C saline) was compared with the corresponding NICO measurement. RESULTS: Bland and Altman plot and Lin's concordance coefficient showed a high correlation between NICO and thermodilution cardiac output measurements although NICO has a tendency to underestimate cardiac output when compared to thermodilution at normal values of cardiac output. CONCLUSIONS: There is a high degree of agreement between cardiac output measurements obtained with NICO and thermodilution cardiac output during resuscitation. The present study suggests that the NICO system may be useful to measure cardiac output generated during cardiopulmonary resuscitation.

Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors.

BACKGROUND: This study ascertained the effect of S-adenosyl-L-methionine (SAMe) administration on the ischemia-reperfusion injury associated with pig liver transplantation from non-heart-beating donors (NHBDs) after prolonged warm ischemia. METHOD: Twenty-five animals underwent transplantation with an allograft from an NHBD. After donor cardiac arrest, cardiopulmonary bypass and normothermic recirculation (NR) were performed for 30 min. Ten animals were given SAMe during NR. Donors were cooled to 15 degrees C, and liver procurement was performed. RESULTS: SAMe reduced histologic liver damage 5 days after transplantation. The necrotic area affected 15.9%+/-14.5% of the liver biopsies in controls and 7.4%+/-9% in SAMe livers. Six of eight controls and only one of eight survivors in the SAMe group developed ischemic cholangitis. SAMe reduced apoptosis of hepatocytes 5 days after transplantation and apoptosis of sinusoidal endothelial cells at reperfusion and at 5 days. SAMe increased energy charge at the end of NR and favored the balance between adenosine and xanthine. It was also associated with higher portal blood flow (740+/-59.2 vs. 475.2+/-65.0 mL/min-1/m-2), hepatic hyaluronic acid extraction (132+/-72.2 vs. -205.8+/-64.6 microg/L), and lower levels of alpha-glutathione-S-transferase after reperfusion (2,601%+/-581% with respect to baseline vs. 6,488%+/-5,612%). CONCLUSION: SAMe administration during liver procurement from NHBDs prevents liver endothelial, parenchymal, and biliary tract damage. The protective role of SAMe may be partially mediated by the effect of adenosine during liver procurement.