Prognostic value of patient-reported quality of life for survival in oesophagogastric cancer: analysis from the population-based POCOP study.

BACKGROUND: Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. METHODS: Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. RESULTS: In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. CONCLUSION: In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models.

Postoperative Complications and Long-Term Quality of Life After Multimodality Treatment for Esophageal Cancer: An Analysis of the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP).

BACKGROUND: Esophagectomy has major effects on health-related quality of life (HR-QoL). Postoperative complications might contribute to a decreased HR-QOL. This population-based study aimed to investigate the difference in HR-QoL between patients with and without complications after esophagectomy for cancer. METHODS: A prospective comparative cohort study was performed with data from the Netherlands Cancer Registry (NCR) and Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP). All patients with esophageal and gastroesophageal junction (GEJ) cancer after esophagectomy in the period 2015-2018 were enrolled. The study investigated HR-QoL at baseline, then 3, 6, 9, 12, 18, and 24 months postoperatively, comparing patients with and without complications as well as with and without anastomotic leakage. RESULTS: The 486 enrolled patients comprised 270 patients with complications and 216 patients without complications. Significantly more patients with complications had comorbidities (69.6% vs 57.3%; p = 0.001). No significant difference in HR-QoL was found over time between the patients with and without complications. In both groups, a significant decline in short-term HR-QoL was found in various HR-QoL domains, which were restored to the baseline level during the 12-month follow-up period. No significant difference was found in HR-QoL between the patients with and without anastomotic leakage. The patients with grades 2 and 3 anastomotic leakage reported significantly more "choking when swallowing" at 6 months (ß = 14.5; 95% confidence interval [CI], - 24.833 to - 4.202; p = 0.049), 9 months (ß = 22.4, 95% CI, - 34.259 to - 10.591; p = 0.007), and 24 months (ß = 24.6; 95% CI, - 39.494 to - 9.727; p = 0.007) than the patients with grade 1 or no anastomotic leakage. CONCLUSION: In general, postoperative complications were not associated with decreased short- or long-term HR-QoL for patients after esophagectomy for esophageal or GEJ cancer. The temporary decrease in HR-QoL likely is related to the nature of esophagectomy and reconstruction itself.

Communicating treatment risks and benefits to cancer patients: a systematic review of communication methods.

PURPOSE: Cancer patients are increasingly involved in decision-making processes. Hence, clinicians need to inform patients about the risks and benefits of different treatment options in order for patients to make well informed decisions. The aim of this review is to determine the effects of methods of communicating prognostic information about (1) disease progression (survival, progression, recurrence and remission), (2) side effects and complications and (3) health-related quality of life (HRQL) on cognitive, affective and behavioral outcomes in cancer patients. METHODS: A literature search was performed to select articles that were published up to  November 2019 and that examined verbal and/or visual risk communication interventions in an oncological clinical setting. RESULTS: The search yielded 14,875 studies; 28 studies were ultimately included. For disease progression information, we found that framing affects treatment choice. Furthermore, limiting the amount of progression information in a graphical display could benefit patients' understanding of risks and benefits. For prognostic information about side effects and complications, precise and defined risk information was better understood than information presented in words. When displaying HRQL data, no consensus was found on which graph type to use. CONCLUSION: Great heterogeneity in the results and methodology and in the compared communication formats precluded us from drawing any further conclusions. Practical implications for clinicians are to consider the effects that different types of framing might have on the patient and to not rely exclusively on words to describe risks, but rather include at least some form of numbers or visualization.

External Validation of the Dutch SOURCE Survival Prediction Model in Belgian Metastatic Oesophageal and Gastric Cancer Patients.

The SOURCE prediction model predicts individualised survival conditional on various treatments for patients with metastatic oesophageal or gastric cancer. The aim of this study was to validate SOURCE in an external cohort from the Belgian Cancer Registry. Data of Belgian patients diagnosed with metastatic disease between 2004 and 2014 were extracted (n = 4097). Model calibration and discrimination (c-indices) were determined. A total of 2514 patients with oesophageal cancer and 1583 patients with gastric cancer with a median survival of 7.7 and 5.4 months, respectively, were included. The oesophageal cancer model showed poor calibration (intercept: 0.30, slope: 0.42) with an absolute mean prediction error of 14.6%. The mean difference between predicted and observed survival was -2.6%. The concordance index (c-index) of the oesophageal model was 0.64. The gastric cancer model showed good calibration (intercept: 0.02, slope: 0.91) with an absolute mean prediction error of 2.5%. The mean difference between predicted and observed survival was 2.0%. The c-index of the gastric cancer model was 0.66. The SOURCE gastric cancer model was well calibrated and had a similar performance in the Belgian cohort compared with the Dutch internal validation. However, the oesophageal cancer model had not. Our findings underscore the importance of evaluating the performance of prediction models in other populations.

Prediction models for patients with esophageal or gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Clinical prediction models are increasingly used to predict outcomes such as survival in cancer patients. The aim of this study was threefold. First, to perform a systematic review to identify available clinical prediction models for patients with esophageal and/or gastric cancer. Second, to evaluate sources of bias in the included studies. Third, to investigate the predictive performance of the prediction models using meta-analysis. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, and The Cochrane Library were searched for publications from the year 2000 onwards. Studies describing models predicting survival, adverse events and/or health-related quality of life (HRQoL) for esophageal or gastric cancer patients were included. Potential sources of bias were assessed and a meta-analysis, pooled per prediction model, was performed on the discriminative abilities (c-indices). RESULTS: A total of 61 studies were included (45 development and 16 validation studies), describing 47 prediction models. Most models predicted survival after a curative resection. Nearly 75% of the studies exhibited bias in at least 3 areas and model calibration was rarely reported. The meta-analysis showed that the averaged c-index of the models is fair (0.75) and ranges from 0.65 to 0.85. CONCLUSION: Most available prediction models only focus on survival after a curative resection, which is only relevant to a limited patient population. Few models predicted adverse events after resection, and none focused on patient's HRQoL, despite its relevance. Generally, the quality of reporting is poor and external model validation is limited. We conclude that there is a need for prediction models that better meet patients' information needs, and provide information on both the benefits and harms of the various treatment options in terms of survival, adverse events and HRQoL.

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative.

BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

A wearable wireless platform for visually stimulating small flying insects.

Linking neurons and muscles to their roles in behavior requires not only the ability to measure their response during unrestrained movement but also the ability to stimulate them and observe the behavioral results. Current wireless stimulation technologies can be carried by rodent-sized animals and very large insects. However, the mass and volume of these devices make them impractical for studying smaller animals like insects. Here we present a battery-powered electronics platform suitable to be carried on a flying locust (2.7 g). The device has an IR-based (infrared) receiver, can deliver optical or electrical stimulation, occupies a volume of 0.1 cm(3), and weighs ~280 mg. We show the device is capable of powering two white SMD light emitting diodes (LEDs) for ~4 min and can be recharged in ~20 min. We demonstrate that our system shows no crosstalk with an IR-based Vicon tracking system. The entire package is made from commercial off-the-shelf components and requires no microfabrication.

Phase sensitivity of complex cells in primary visual cortex.

Neurons in the primary visual cortex are often classified as either simple or complex based on the linearity (or otherwise) of their response to spatial luminance contrast. In practice, classification is typically based on Fourier analysis of a cell's response to an optimal drifting sine-wave grating. Simple cells are generally considered to be linear and produce responses modulated at the fundamental frequency of the stimulus grating. In contrast, complex cells exhibit significant nonlinearities that reduce the response at the fundamental frequency. Cells can therefore be easily and objectively classified based on the relative modulation of their responses - the ratio of the phase-sensitive response at the fundamental frequency of the stimulus (F1) to the phase-invariant sustained response (F0). Cells are classified as simple if F1/F0>1 and complex if F1/F0<1. This classification is broadly consistent with criteria based on the spatial organisation of cells' receptive fields and is accordingly presumed to reflect disparate functional roles of simple and complex cells in coding visual information. However, Fourier analysis of spiking responses is sensitive to the number of spikes available - F1/F0 increases as the number of spikes is reduced, even for phase-invariant complex cells. Moreover, many complex cells encountered in the laboratory exhibit some phase sensitivity, evident as modulation of their responses at the fundamental frequency. There currently exists no objective quantitative means of assessing the significance or otherwise of these modulations. Here we derive a statistical basis for objectively assessing whether the modulation of neuronal responses is reliable, thereby adding a level of statistical certainty to measures of phase sensitivity. We apply our statistical analysis to neuronal responses to moving sine-wave gratings recorded from 367 cells in cat primary visual cortex. We find that approximately 60% of complex cells exhibit statistically significant (α<0.01) modulation of their responses to optimal moving gratings. These complex cells are phase sensitive and reliably encode spatial phase.

Spectral inputs and ocellar contributions to a pitch-sensitive descending neuron in the honeybee.

By measuring insect compensatory optomotor reflexes to visual motion, researchers have examined the computational mechanisms of the motion processing system. However, establishing the spectral sensitivity of the neural pathways that underlie this motion behavior has been difficult, and the contribution of the simple eyes (ocelli) has been rarely examined. In this study we investigate the spectral response properties and ocellar inputs of an anatomically identified descending neuron (DNII(2)) in the honeybee optomotor pathway. Using a panoramic stimulus, we show that it responds selectively to optic flow associated with pitch rotations. The neuron is also stimulated with a custom-built light-emitting diode array that presented moving bars that were either all-green (spectrum 500-600 nm, peak 530 nm) or all-short wavelength (spectrum 350-430 nm, peak 380 nm). Although the optomotor response is thought to be dominated by green-sensitive inputs, we show that DNII(2) is equally responsive to, and direction selective to, both green- and short-wavelength stimuli. The color of the background image also influences the spontaneous spiking behavior of the cell: a green background produces significantly higher spontaneous spiking rates. Stimulating the ocelli produces strong modulatory effects on DNII(2), significantly increasing the amplitude of its responses in the preferred motion direction and decreasing the response latency by adding a directional, short-latency response component. Our results suggest that the spectral sensitivity of the optomotor response in honeybees may be more complicated than previously thought and that ocelli play a significant role in shaping the timing of motion signals.

Visual response properties of neck motor neurons in the honeybee.

Recent behavioural studies have demonstrated that honeybees use visual feedback to stabilize their gaze. However, little is known about the neural circuits that perform the visual motor computations that underlie this ability. We investigated the motor neurons that innervate two neck muscles (m44 and m51), which produce stabilizing yaw movements of the head. Intracellular recordings were made from five (out of eight) identified neuron types in the first cervical nerve (IK1) of honeybees. Two motor neurons that innervate muscle 51 were found to be direction-selective, with a preference for horizontal image motion from the contralateral to the ipsilateral side of the head. Three neurons that innervate muscle 44 were tuned to detect motion in the opposite direction (from ipsilateral to contralateral). These cells were binocularly sensitive and responded optimally to frontal stimulation. By combining the directional tuning of the motor neurons in an opponent manner, the neck motor system would be able to mediate reflexive optomotor head turns in the direction of image motion, thus stabilising the retinal image. When the dorsal ocelli were covered, the spontaneous activity of neck motor neurons increased and visual responses were modified, suggesting an ocellar input in addition to that from the compound eyes.

Endovascular treatment of acute subclavian pseudo-aneurysm after fracture of the clavicle.

Pseudo-aneurysms of the subclavian artery remain a rare complication after fracture of the clavicle. Nerve compression has been described with delayed paralysis as a consequence. We report a case of delayed diagnosis of a subclavian pseudo-aneurysm after a closed fracture of the clavicle in a 93-year-old patient. Diagnosis was confirmed by ultrasound and multi-slice-Ct. Two attempts to treat the pseudo-aneurysm with percutaneous thrombin injection failed. Considering the age of the patient, it was decided to exclude the pseudo-aneurysm by endovascular approach. A Hemobahn endoprosthesis was inserted by the introduction of an 11F sheath after cutting down the brachial artery under local anaesthesia. Angiography revealed complete exclusion of the pseudo-aneurysm. Follow-up at 9 months by ultrasound confirmed exclusion of the pseudo-aneurysm. Plain X-ray of the endograft showed no stent fractures. Paresis of the arm had improved. This case illustrates that endovascular exclusion is a safe approach, with reduced morbidity, compared with open surgery. Concern about stent deformation and stent fractures has been expressed. With the introduction of highly flexible stents, one can hope that this complication is less likely to occur. Although follow-up is relatively short, we believe that endovascular exclusion of subclavian pseudo-aneurysms is preferable to a surgical approach.

Complex cells increase their phase sensitivity at low contrasts and following adaptation.

One of the best-known dichotomies in neuroscience is the division of neurons in the mammalian primary visual cortex into simple and complex cells. Simple cells have receptive fields with separate on and off subregions and give phase-sensitive responses to moving gratings, whereas complex cells have uniform receptive fields and are phase invariant. The phase sensitivity of a cell is calculated as the ratio of the first Fourier coefficient (F1) to the mean time-average (Fo) of the response to moving sinusoidal gratings at 100% contrast. Cells are then classified as simple (F1/Fo >1) or complex (F1/Fo <1). We manipulated cell responses by changing the stimulus contrast or through adaptation. The F(1)/F(0) ratios of cells defined as complex at 100% contrast increased at low contrasts and following adaptation. Conversely, the F1/Fo ratios remained constant for cells defined as simple at 100% contrast. The latter cell type was primarily located in thalamorecipient layers 4 and 6. Many cells initially classified as complex exhibit F1/Fo >1 at low contrasts and after adaptation (particularly in layer 4). The results are consistent with the spike-threshold hypothesis, which suggests that the division of cells into two types arises from the nonlinear interaction of spike threshold with membrane potential responses.

Lumbar epidural catheter insertion: the midline vs. the paramedian approach.

BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the characteristics of epidural catheter insertion via the midline or the paramedian approach with regard to ease of catheter insertion, incidence of paraesthesias and efficacy of epidural block. In addition to the type of approach, the prognostic value of Patients characteristics variables with regard to the incidence of paraesthesias was assessed. METHODS: Thirty patients scheduled for surgery under epidural anaesthesia were randomly assigned to one of two groups of 15 patients each. Epidural anaesthesia was performed via a midline or paramedian approach using loss of resistance to saline. Variables measured were: time needed to identify the epidural space, time needed for and ease of epidural catheter insertion and the incidence of paraesthesias. After completion of these observations, epidural anaesthesia was established with 150 mg ropivacaine 1%. Efficacy of the epidural block was assessed by the need for intraoperative analgesics and by the patient on a three-point scale (good/fair/poor). RESULTS: Quality of sensory blockade was adequate in both groups. Catheter insertion was significantly faster using the paramedian approach. The difference between the two approaches with regard to the incidence of paraesthesias was not significant, however, there was a trend towards more paraesthesias in the midline group. In the multivariate analysis, type of approach was an independent significant predictor of paraesthesias and we found a trend towards a higher incidence of paraesthesias in female patients. CONCLUSIONS: Catheter insertion was faster in the paramedian group and we found a trend towards a higher incidence of paraesthesias with the midline approach.

Transient neurological symptoms with subarachnoid lidocaine: effect of early mobilization.

BACKGROUND AND OBJECTIVE: Although lidocaine has been used extensively for spinal anaesthesia since 1949, it has been associated with transient neurological symptoms only in the past 10 yr. It has been suggested that early ambulation after spinal anaesthesia, as opposed to traditional 24 h recumbency, might be the causative factor for the development of transient neurological symptoms. The purpose of this study was to examine the effect of early ambulation on the incidence of transient neurological symptoms after single injection spinal anaesthesia with lidocaine 2%. METHODS: Sixty patients undergoing minor surgery under spinal anaesthesia were included. All patients received lidocaine 60 mg. After the establishment of successful subarachnoid block, patients were randomly allocated to two groups of 30 patients. Patients in Group 1 were ambulated as soon as possible, whereas patients in Group 2 were kept recumbent until 6 h after subarachnoid injection. Two days after surgery patients were contacted by a blinded observer and interviewed of transient neurological symptoms using a standardized questionnaire. Patients were asked to express the intensity of pain/discomfort on a verbal rating scale from 0 (no pain) to 10 (worst pain imaginable). RESULTS: There was no significant difference in the incidence of transient neurological symptoms (23% vs. 27%). In all patients, symptoms resolved completely within 6-24 h. The median pain score was 5 (range 2-8) in Group 1 and 7 (range 1-8) in Group 2. CONCLUSIONS: Under the conditions of this study, there is no correlation between the time of ambulation after spinal anaesthesia with lidocaine and the incidence of transient neurological symptoms.

[The practice guideline 'Neuraxis blockade and anticoagulation']. / Richtlijn 'Neuraxisblokkade en antistolling'.

In a patient with a coagulation disorder, the administration of a local anaesthetic by means of a needle or via the insertion of a catheter into the epidural space or spinal cavity may lead to bleeding and haematoma formation, with a danger of pressure on the spinal cord or nerve roots. Employing the method of the Dutch Institute for Healthcare (CBO) for the development of practice guidelines, a working group of anaesthesiologists, a haematologist and a hospital chemist have drawn up recommendations for neuraxis blockade in combination with anticoagulant therapy. In patients with a clinically acquired tendency toward increased bleeding, the management is highly dependent on the cause of the bleeding tendency. If the patient uses acetylsalicylic acid or clopidogrel, the medication must be withdrawn at least 10 days before neuraxis blockade is started. Therapy with glycoprotein-IIb/IIIa-receptor antagonists is an absolute contra-indication for neuraxis blockade. In patients who are using coumarin derivatives, neuraxis blockade results in an increased risk of a neuraxial haematoma. The coumarin derivative should then be withdrawn and replaced by a different form of anticoagulation. The use of low-molecular-weight heparin at the usual prophylactic dosage is not a contra-indication for neuraxis blockade and the risk of a neuraxial haematoma following neuraxis blockade is also not increased significantly by the subcutaneous administration of unfractionated heparin.

Effect of age on the clinical profile and systemic absorption and disposition of levobupivacaine after epidural administration.

BACKGROUND: Pharmacokinetic and/or pharmacodynamic changes, which may occur with increasing age, could alter the clinical profile of the new local anaesthetic levobupivacaine. We investigated the effect of age on the absorption and disposition kinetics and the neural block characteristics after epidural administration of levobupivacaine 0.75%. METHODS: Thirty-one patients were enrolled in one of three age groups (Group 1, 18-44 yr; Group 2, 45-70 yr; Group 3, >70 yr). Twenty-five minutes after epidural administration of levobupivacaine (127.5 mg), they received approximately 25 mg deuterium-labelled levobupivacaine (D(3)-levobupivacaine) intravenously. Arterial blood samples were collected until 24 h after the epidural administration. Plasma concentrations were determined using liquid chromatography mass spectrometry. Plasma concentration-time data were analyzed by compartmental and non-compartmental analysis. Assessments of analgesia and motor block were made at set intervals until complete regression of the block. RESULTS: The upper levels of analgesia in the two oldest groups of patients were 3 dermatomes (95% confidence interval (95% CI): 0.5-5.0 dermatomes) higher than in the youngest group. The fraction absorbed (F(1)) was 0.07 (95% CI: 0.02-013) smaller and the absorption half-life (t(1/2,a1)), characterizing the initial fast absorption phase, 3.6 min (95% CI: 0.8-6.4) shorter in the oldest group compared with the youngest group. CONCLUSIONS: Age influences the pharmacokinetics, in particular the early absorption kinetics, and the neural block characteristics after epidural administration of levobupivacaine. Changes in the upper level of analgesia are best explained by anatomical considerations and possibly pharmacodynamic changes in the elderly.

The systemic absorption and disposition of levobupivacaine 0.5% after epidural administration in surgical patients: a stable-isotope study.

BACKGROUND AND OBJECTIVE: Absorption and disposition kinetics can be studied with a stable-isotope method. The aim of this study was to validate a stable-isotope method for levobupivacaine and to derive the relevant pharmacokinetics after epidural administration. METHODS: Eight volunteers (18-32 yr) received approximately 23 mg of both levobupivacaine and deuterium-labelled levobupivacaine simultaneously by intravenous infusion. Venous blood samples were taken for 8 h. Fifteen patients (23-85 yr) received 19 mL levobupivacaine 0.5% (including a 3 mL test dose) epidurally and, 25 min later, approximately 25 mg deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial blood samples were collected for 24 h. Plasma concentrations were determined using liquid chromatography-mass spectrometry. Plasma concentration-time data were analysed by compartmental and non-compartmental analysis. RESULTS: Based on the ratio of the normalized areas under the curve of unlabelled and deuterium-labelled levobupivacaine in volunteers, as determined by both compartmental (mean ratio: 1.02, 90% CI: 1.00-1.04) and non-compartmental analysis (mean ratio: 1.02, 90% CI: 1.00-1.03) the two formulations were considered equivalent. In surgical patients the elimination half-life (mean +/- SD: 196 +/- 65 min), total body clearanc (349 +/- 114 mL min(-1)) and volume of distribution at steady state (56 +/- 14 L), derived by compartmental analysis, were similar to those obtained by non-compartmental analysis. The absorption was bi-phasic. The fractio absorbed and half-life of the fast absorption process were 0.22 +/- 0.06 and 5.2 +/- 2.7 min, respectively. Th values for the slow absorption process were 0.84 +/- 0.14 and 386 +/- 91 min, respectively. CONCLUSIONS: D3-levobupivacaine is pharmacokinetically equivalent to unlabelled levobupivacaine and can be used to study the absorption and disposition kinetics after perineural administration of levobupivacaine in a single experiment.

Mortality associated with anaesthesia: a qualitative analysis to identify risk factors.

From a prospectively defined cohort of patients who underwent either general, regional or combined anaesthesia from 1 January 1995 to 1 January 1997 (n = 869 483), all consecutive patients (n = 811) who died within 24 h or remained unintentionally comatose 24 h after anaesthesia were classified to determine a relationship with anaesthesia. These deaths (n = 119; 15%) were further analysed to identify contributing aspects of the anaesthetic management, other factors and the appropriateness of care. The incidence of 24-h peri-operative death per 10 000 anaesthetics was 8.8 (95% CI 8.2-9.5), of peri-operative coma was 0.5 (0.3-0.6) and of anaesthesia-related death 1.4 (1.1-1.6). Of the 119 anaesthesia-related deaths, 62 (52%) were associated with cardiovascular management, 57 (48%) with other anaesthetic management, 12 (10%) with ventilatory management and 12 (10%) with patient monitoring. Inadequate preparation of the patient contributed to 30 (25%) of the anaesthesia-related deaths. During induction of anaesthesia, choice of anaesthetic technique (n = 18 (15%)) and performance of the anaesthesiologist (n = 8 (7%)) were most commonly associated with death. During maintenance, the most common factors were cardiovascular management (n = 43 (36%)), ventilatory management (n = 12 (10%)) and patient monitoring (n = 12 (10%)). In both the recovery and the postoperative phases, patient monitoring was the most common factor (n = 12 (10%) for both). For cardiovascular, ventilatory and other anaesthetic management, human failure contributed to 89 (75%) deaths and organisational factors to 12 (10%). For inadequate patient monitoring, human factors contributed to 71 (60%) deaths and organisational factors to 48 (40%). Other contributing factors were inadequate communication (30 deaths (25%) for all four aspects of the anaesthetic management) and lack of supervision (particularly for ventilatory management). Inadequate care was delivered in 19 (16%) of the anaesthesia-related deaths with respect to cardiovascular management, in 20 (17%) with respect to ventilatory management, in 18 (15%) with respect to patient monitoring and in 23 (19%) with respect to other anaesthetic management.

Respiratory sites of action of propofol: absence of depression of peripheral chemoreflex loop by low-dose propofol.

BACKGROUND: Propofol has a depressant effect on metabolic ventilatory control, causing depression of the ventilatory response to acute isocapnic hypoxia, a response mediated via the peripheral chemoreflex loop. In this study, the authors examined the effect of sedative concentrations of propofol on the dynamic ventilatory response to carbon dioxide to obtain information about the respiratory sites of action of propofol. METHODS: In 10 healthy volunteers, the end-tidal carbon dioxide concentration was varied according to a multifrequency binary sequence that involved 13 steps into and 13 steps out of hypercapnia (total duration, 1,408 s). In each subject, two control studies, two studies at a plasma target propofol concentration of 0.75 microg/ml (P(low)), and two studies at a target propofol concentration of 1.5 microg/ml (P(high)) were performed. The ventilatory responses were separated into a fast peripheral component and a slow central component, characterized by a time constant, carbon dioxide sensitivity, and apneic threshold. Values are mean +/- SD. RESULTS: Plasma propofol concentrations were approximately 0.5 microg/ml for P(low) and approximately 1.3 mg/ml for P(high), Propofol reduced the central carbon dioxide sensitivity from 1.5 +/- 0.4 to 1.2 +/- 0.3 (P(low); P < 0.01 vs. control) and 0.9 +/- 0.1 l x min(-1) x mmHg(-1) (P(high); P < 0.001 vs. control). The peripheral carbon dioxide sensitivity remained unaffected by propofol (control, 0.5 +/- 0.3; P(low), 0.5 +/- 0.2; P(high), 0.5 +/- 0.2 l x min(-1) x mmHg(-1)). The apneic threshold was reduced from 36.3 +/- 2.7 (control) to 35.0 +/- 2.1 (P(low); P < 0.01 vs. control) and to 34.6 +/- 1.9 mmHg (P(high); P < 0.01 vs. control). CONCLUSIONS: Sedative concentrations of propofol have an important effect on the control of breathing, showing depression of the ventilatory response to hypercapnia. The depression is attributed to an exclusive effect within the central chemoreflex loop at the central chemoreceptors. In contrast to low-dose inhalational anesthetics, the peripheral chemoreflex loop, when stimulated with carbon dioxide, remains unaffected by propofol.

Spinal anaesthesia with 0.5% hyperbaric bupivacaine in elderly patients: effects of duration spent in the sitting position.

Sixty patients, aged 65-84 yr, undergoing minor urological surgery under spinal anaesthesia remained sitting for 2 (group 1, n = 15), 5 (group 2, n = 15), 10 (group 3, n = 15), or 20 (group 4, n = 15) min after completion of the subarachnoid administration of 3 ml of a 0.5% hyperbaric bupivacaine solution. They were then placed in the supine position. Analgesia levels were assessed bilaterally using pinprick. Motor block was scored using a 12-point scale. Systolic and diastolic arterial pressures and heart rate were also recorded. Twenty minutes after the injection the upper analgesia levels were lower (P<0.05) in group 4 (median T9.0) than in the groups 1-3 (medians T6.6-T8.5). The highest obtained levels (medians T5.7-T8.0) did not differ between the groups, but occurred later (P<0.05) in group 4 (median 35 min) than in groups 1-3 (medians 19-24 min). There were no significant differences in the maximum degree of motor block or haemodynamic changes between the four study groups.