A Frailty Index to Predict Mortality, Resource Utilization and Costs in Patients Undergoing Coronary Artery Bypass Graft Surgery in Ontario.

Background: People living with frailty are vulnerable to poor outcomes and incur higher health care costs after coronary artery bypass graft (CABG) surgery. Frailty-defining instruments for population-level research in the CABG setting have not been established. The objectives of the study were to develop a preoperative frailty index for CABG (pFI-C) surgery using Ontario administrative data; assess pFI-C suitability in predicting clinical and economic outcomes; and compare pFI-C predictive capabilities with other indices. Methods: A retrospective cohort study was conducted using health administrative data of 50,682 CABG patients. The pFI-C comprised 27 frailty-related health deficits. Associations between index scores and mortality, resource use and health care costs (2022 Canadian dollars [CAD]) were assessed using multivariable regression models. Capabilities of the pFI-C in predicting mortality were evaluated using concordance statistics; goodness of fit of the models was assessed using Akakie Information Criterion. Results: As assessed by the pFI-C, 22% of the cohort lived with frailty. The pFI-C score was strongly associated with mortality per 10% increase (odds ratio [OR], 3.04; 95% confidence interval [CI], [2.83,3.27]), and was significantly associated with resource utilization and costs. The predictive performances of the pFI-C, Charlson, and Elixhauser indices and Johns Hopkins Aggregated Diagnostic Groups were similar, and mortality models containing the pFI-C had a concordance (C)-statistic of 0.784. Cost models containing the pFI-C showed the best fit. Conclusions: The pFI-C is predictive of mortality and associated with resource utilization and costs during the year following CABG. This index could aid in identifying a subgroup of high-risk CABG patients who could benefit from targeted perioperative health care interventions.

Contexte: Les personnes dont l'état de santé est fragilisé sont susceptibles de connaître des issues défavorables et de générer des coûts plus élevés pour le système de santé après un pontage aortocoronarien. Aucun instrument n'a été établi pour définir la fragilité dans la recherche populationnelle en contexte de pontage aortocoronarien. Les objectifs de l'étude étaient les suivants : 1) concevoir un indice de fragilité préopératoire en vue d'un pontage aortocoronarien (preoperative frailty index for CABG surgery, pFI-C) en utilisant des données administratives de l'Ontario; 2) évaluer la capacité de cet indice à prédire les issues cliniques et économiques; et 3) comparer la valeur prédictive de cet indice avec celle d'autres indices. Méthodologie: Une étude de cohorte rétrospective a été menée à partir de données médico-administratives portant sur 50 682 patients ayant subi un pontage aortocoronarien. Le pFI-C comprenait 27 déficits de santé liés à la fragilité. Des liens entre les scores de l'indice et la mortalité, l'utilisation des ressources et les coûts de soins de santé (en $ CA de 2022) ont été évalués à l'aide de modèles de régression multivariable. La capacité du pFI-C à prédire la mortalité a été évaluée à l'aide de la statistique de concordance; la qualité de l'ajustement des modèles a été évaluée en fonction du critère d'information d'Akaike. Résultats: Selon l'évaluation par le pFI-C, 22 % de la cohorte vivait avec une fragilité. Le score de l'indice était fortement corrélé à la mortalité par tranche d'augmentation de 10 % (rapport de cotes de 3,04; intervalle de confiance à 95 % de 2,83 à 3,27) et était corrélé de manière significative à l'utilisation des ressources et aux coûts. La valeur prédictive du pFI-C, des indices de Charlson et Elixhauser, et de Johns Hopkins Aggregated Diagnostic Groups était similaire, et les modèles de mortalité contenant le pFI-C affichaient une valeur statistique C de 0,784. Les modèles de coûts contenant le pFI-C affichaient le meilleur ajustement. Conclusions: Le pFI-C est un facteur prédictif de mortalité et est corrélé à l'utilisation des ressources et aux coûts engagés durant l'année qui suit un pontage aortocoronarien. Cet indice pourrait faciliter la détection d'un sous-groupe de patients subissant un pontage aortocoronarien et présentant un risque élevé qui pourraient bénéficier de soins périopératoires ciblés.

Chronic opioid use after joint replacement surgery in seniors is associated with increased healthcare utilization and costs: a historical cohort study.

PURPOSE: Postoperative opioid use may be associated with increased healthcare utilization and costs. We sought to examine the relationship between duration of postoperative opioid prescriptions and healthcare costs and resource utilization in senior patients following hip and knee replacement. METHODS: We conducted a historical cohort study evaluating postoperative opioid use and healthcare costs in patients over the age of 65 yr undergoing primary total hip or knee arthroplasty over a ten-year period from 1 April 2006 to 31 March 2016. The last follow-up date was 31 March 2017. We identified preoperative and postoperative opioid prescriptions, patient characteristics, and healthcare costs using deidentified Ontario administrative databases (Institute of Clinical Evaluative Sciences). Duration of postoperative opioid use was divided into four categories: short-term (1-90 days), prolonged (91-180 days), chronic (181-365 days), and undocumented. RESULTS: The study included 49,638 hip and 85,558 knee replacement patients. Although the initial hospitalization accounted for the greatest cost in all patients, over the following year patients in the short-term opioid use group incurred the lowest average costs, and those in the chronic group incurred the highest (hip, CAD 17,528 vs CAD 26,736; knee, CAD 16,043 vs CAD 23,007), driven by increased healthcare resource utilization. CONCLUSION: Chronic opioid use after arthroplasty was associated with higher resource utilization and healthcare costs during the year following surgery. These results can be used to develop predictors of longer opioid use and higher costs. Further research is planned to determine whether recently implemented opioid reduction strategies can reduce healthcare resource utilization.

RéSUMé: OBJECTIF: L'utilisation postopératoire d'opioïdes peut être associée à une augmentation de l'utilisation et des coûts des soins de santé. Nous avons cherché à examiner la relation entre la durée des ordonnances d'opioïdes postopératoires, les coûts des soins de santé et l'utilisation des ressources chez les patients âgés après une arthroplastie de la hanche et du genou. MéTHODE: Nous avons réalisé une étude de cohorte historique évaluant la consommation postopératoire d'opioïdes et les coûts des soins de santé chez les patients de plus de 65 ans subissant une arthroplastie totale primaire de la hanche ou du genou sur une période de dix ans allant du 1er avril 2006 au 31 mars 2016. La dernière date de suivi était le 31 mars 2017. Nous avons identifié les ordonnances pré- et postopératoires d'opioïdes, les caractéristiques des patients et les coûts des soins de santé à l'aide de bases de données administratives de l'Ontario désidentifiées (ICES). La durée de la consommation d'opioïdes postopératoires était divisée en quatre catégories : à court terme (1 à 90 jours), prolongée (91 à 180 jours), chronique (181 à 365 jours) et non documentée. RéSULTATS: L'étude a porté sur 49 638 patients ayant subi une arthroplastie de la hanche et 85 558 patients une arthroplastie du genou. Bien que l'hospitalisation initiale ait représenté le coût le plus élevé chez tous les patients, au cours de l'année suivante, les patients du groupe de consommation d'opioïdes à court terme ont encouru les coûts moyens les plus bas et ceux du groupe chronique les coûts les plus élevés (hanche, 17 528 CAD vs 26 736 CAD; genou, 16 043 CAD vs 23 007 CAD) en raison de l'utilisation accrue des ressources de soins de santé. CONCLUSION: La consommation chronique d'opioïdes après une arthroplastie a été associée à une augmentation de l'utilisation des ressources et des coûts des soins de santé au cours de l'année suivant la chirurgie. Ces résultats peuvent être utilisés pour développer des modèles de prédiction d'une consommation prolongée d'opioïdes et de coûts plus élevés. D'autres recherches sont prévues pour déterminer si les stratégies de réduction de la consommation d'opioïdes récemment mises en œuvre pourront réduire l'utilisation des ressources en soins de santé.

Long-term opioid use in seniors following hip and knee arthroplasty in Ontario: a historical cohort study.

PURPOSE: Canadian seniors who undergo hip and knee arthroplasty often experience significant postoperative pain, which could result in persistent opioid use. We aimed to document the impact of preoperative opioid use and other characteristics on postoperative opioid prescriptions in elderly patients following hip and knee replacement before widespread dissemination of opioid reduction strategies. METHODS: We conducted a historical cohort study to evaluate postoperative opioid use in patients over 65 yr undergoing primary total hip and knee replacement over a ten-year period from 1 April 2006 to 31 March 2016, using linked de-identified Ontario administrative data. We determined the use of preoperative opioids and the duration of postoperative opioid prescriptions (short-term [1-90 days], prolonged [91-180 days], chronic [181-365 days], or undocumented). RESULTS: The study included 49,638 hip and 85,558 knee replacement patients. Eighteen percent of hip and 21% of knee replacement patients received an opioid prescription within 90 days before surgery. Postoperatively, 51% of patients filled opioid prescriptions for 1-90 days, while 24% of hip and 29% of knee replacement patients filled prescriptions between 6 and 12 months, with no impact of preoperative opioid use. Residence in long-term care was a significant predictor of chronic opioid use (hip: odds ratio [OR], 2.64; 95% confidence interval [CI], 1.93 to 3.59; knee: OR, 2.46; 95% CI, 1.75 to 3.45); other risk factors included female sex and increased comorbidities. CONCLUSION: Despite a main goal of joint arthroplasty being relief of pain, seniors commonly remained on postoperative opioids, even if not receiving opioids before surgery. Opioid reduction strategies need to be implemented at the surgical, primary physician, long-term care, and patient levels. These findings form a basis for future investigations following implementation of opioid reduction approaches.

RéSUMé: OBJECTIF: Les aînés canadiens subissant une arthroplastie de la hanche ou du genou éprouvent souvent une douleur postopératoire importante, ce qui pourrait entraîner la consommation persistante d'opioïdes. Nous avons cherché à documenter l'impact d'une utilisation préopératoire d'opioïdes et d'autres caractéristiques sur les prescriptions postopératoires d'opioïdes chez les patients âgés suivant un remplacement de hanche ou de genou avant l'utilisation répandue de stratégies de réduction d'opioïdes. MéTHODE: Nous avons réalisé une étude de cohorte historique pour évaluer la consommation postopératoire d'opioïdes chez les patients de plus de 65 ans subissant une arthroplastie totale primaire de la hanche ou du genou sur une période de dix ans du 1er avril 2006 au 31 mars 2016, à l'aide de données administratives dépersonnalisées et codées de l'Ontario. Nous avons déterminé la durée des ordonnances préopératoires et postopératoires d'opioïdes (à court terme [1-90 jours], prolongées [91-180 jours], chroniques [181-365 jours] ou non documentées). RéSULTATS: L'étude a porté sur 49 638 patients ayant subi une arthroplastie de la hanche et 85 558 patients une arthroplastie du genou. Dix-huit pour cent des patients ayant subi une arthroplastie de la hanche et 21 % des patients ayant subi une arthroplastie du genou ont reçu une ordonnance d'opioïdes dans les 90 jours précédant leur chirurgie. En période postopératoire, 51 % des patients ont utilisé leurs ordonnances d'opioïdes pendant 1 à 90 jours, tandis que 24 % des patients d'arthroplastie de la hanche et 29 % des patients d'arthroplastie du genou ont utilisé leurs ordonnances entre six et 12 mois. Le fait d'habiter dans un établissement de soins de longue durée était un prédicteur important de consommation chronique d'opioïdes (hanche : rapport de cotes [RC], 2,64; intervalle de confiance [IC] à 95 %, 1,93 à 3,59; genou : RC, 2,46; IC 95 %, 1,75 à 3,45); le sexe féminin et l'augmentation des comorbidités constituaient d'autres facteurs de risque. CONCLUSION: Bien que l'un des principaux objectifs de l'arthroplastie articulaire soit le soulagement de la douleur, les personnes âgées continuent généralement à consommer des opioïdes en période postopératoire, même si elles ne prenaient pas d'opioïdes avant leur chirurgie. Il est nécessaire de mettre en œuvre des stratégies de réduction des opioïdes qui s'adressent aux chirurgiens, aux médecins traitants, aux soins de longue durée et aux patients. Ces constatations constituent la base d'études futures réalisées à la suite de la mise en œuvre d'approches de réduction des opioïdes.

Remote Ischemic Preconditioning in High-risk Cardiovascular Surgery Patients: A Randomized-controlled Trial.

Remote ischemic preconditioning (RIPC) may reduce biomarkers of ischemic injury after cardiovascular surgery. However, it is unclear whether RIPC has a positive impact on clinical outcomes. We performed a blinded, randomized controlled trial to determine if RIPC resulted in fewer adverse clinical outcomes after cardiac or vascular surgery. The intervention consisted of 3 cycles of RIPC on the upper limb for 5 minutes alternated with 5 minutes of rest. A sham intervention was performed on the control group. Patients were recruited who were undergoing (1) high-risk cardiac or vascular surgery or (2) cardiac or vascular surgery and were at high risk of ischemic complications. The primary end point was a composite outcome of mortality, myocardial infarction, stroke, renal failure, respiratory failure, and low cardiac output syndrome, and the secondary end points included the individual outcome parameters that made up this score, as well as troponin-I values. A total of 436 patients were randomized and analysis was performed on 215 patients in the control group and on 213 patients in the RIPC group. There were no differences in the composite outcome between the 2 groups (RIPC: 67 [32%] and control: 72 [34%], relative risk [0.94 {0.72-1.24}]) or in any of the individual components that made up the composite outcome. Additionally, we did not observe any differences between the groups in troponin-I values, the length of intensive care unit stay, or the total hospital stay. RIPC did not have a beneficial effect on clinical outcomes in patients who had cardiovascular surgery.

Economies of scale: body mass index and costs of cardiac surgery in Ontario, Canada.

An obesity paradox has been described, whereby obese patients have better health outcomes than normal weight patients in certain clinical situations, including cardiac surgery. However, the relationship between body mass index (BMI) and resource utilization and costs in patients undergoing coronary artery bypass graft (CABG) surgery is largely unknown. We examined resource utilization and cost data for 53,224 patients undergoing CABG in Ontario, Canada over a 10-year period between 2002 and 2011. Data for costs during hospital admission and for a 1-year follow-up period were derived from the Institute for Clinical Evaluative Sciences, and analyzed according to pre-defined BMI categories using analysis of variance and multivariate models. BMI independently influenced healthcare costs. Underweight patients had the highest per patient costs ($50,124 ± $36,495), with the next highest costs incurred by morbidly obese ($43,770 ± $31,747) and normal weight patients ($42,564 ± $30,630). Obese and overweight patients had the lowest per patient costs ($40,760 ± $30,664 and $39,960 ± $25,422, respectively). Conversely, at the population level, overweight and obese patients were responsible for the highest total yearly population costs to the healthcare system ($92 million and $50 million, respectively, compared to $4.2 million for underweight patients). This is most likely due to the high proportion of CABG patients falling into the overweight and obese BMI groups. In the future, preoperative risk stratification and preparation based on BMI may assist in reducing surgical costs, and may inform health policy measures aimed at the management of weight extremes in the population.

Body Mass Index, Outcomes, and Mortality Following Cardiac Surgery in Ontario, Canada.

BACKGROUND: The "obesity paradox" reflects an observed relationship between obesity and decreased morbidity and mortality, suggesting improved health outcomes for obese individuals. Studies examining the relationship between high body mass index (BMI) and adverse outcomes after cardiac surgery have reported conflicting results. METHODS AND RESULTS: The study population (N=78 762) was comprised of adult patients who had undergone first-time coronary artery bypass (CABG) or combined CABG/aortic valve replacement (AVR) surgery from April 1, 1998 to October 31, 2011 in Ontario (data from the Institute for Clinical Evaluative Sciences). Perioperative outcomes and 5-year mortality among pre-defined BMI (kg/m(2)) categories (underweight <20, normal weight 20 to 24.9, overweight 25 to 29.9, obese 30 to 34.9, morbidly obese >34.9) were compared using Bivariate analyses and Cox multivariate regression analysis to investigate multiple confounders on the relationship between BMI and adverse outcomes. A reverse J-shaped curve was found between BMI and mortality with their respective hazard ratios. Independent of confounding variables, 30-day, 1-year, and 5-year survival rates were highest for the obese group of patients (99.1% [95% Confidence Interval {CI}, 98.9 to 99.2], 97.6% [95% CI, 97.3 to 97.8], and 90.0% [95% CI, 89.5 to 90.5], respectively), and perioperative complications lowest. Underweight and morbidly obese patients had higher mortality and incidence of adverse outcomes. CONCLUSIONS: Overweight and obese patients had lower mortality and adverse perioperative outcomes after cardiac surgery compared with normal weight, underweight, and morbidly obese patients. The "obesity paradox" was confirmed for overweight and moderately obese patients. This may impact health resource planning, shifting the focus to morbidly obese and underweight patients prior to, during, and after cardiac surgery.

A novel software program for detection of potential air emboli during cardiac surgery.

BACKGROUND: Risks associated with air emboli introduced during cardiac surgery have been highlighted by reports of postoperative neuropsychological dysfunction, myocardial dysfunction, and mortality. Presently, there are no standard effective methods for quantifying potential emboli in the bloodstream during cardiac surgery. Our objective was to develop software that can automatically detect and quantify air bubbles within the ascending aorta and/or cardiac chambers during cardiac surgery in real time. FINDINGS: We created a software algorithm ("Detection of Emboli using Transesophageal Echocardiography for Counting, Total volume, and Size estimation", or DETECTS™) to identify and measure potential emboli present during cardiac surgery using two-dimensional ultrasound. An in vitro experiment was used to validate the accuracy of DETECTS™ at identifying and measuring air emboli. An experimental rig was built to correlate the ultrasound images to high definition camera images of air bubbles created in water by an automatic bubbler system. There was a correlation between true bubble size and the size reported by DETECTS™ in our in vitro experiment (r = 0.76). We also tested DETECTS™ using TEE images obtained during cardiac surgery, and provide visualization of the software interface. CONCLUSIONS: While monitoring the heart during cardiac surgery using existing ultrasound technology and DETECTS™, the operative team can obtain real-time data on the number and volume of potential air emboli. This system will potentially allow de-airing techniques to be evaluated and improved upon. This could lead to reduced air in the cardiac chambers after cardiopulmonary bypass, possibly reducing the risk of neurological dysfunction following cardiac surgery.

Modified electroconvulsive therapy in a patient with gastric adenocarcinoma and metastases to bone and liver.

Background. In addition to general anesthesia, muscle relaxants are given prior to electroconvulsive therapy (ECT) in order to prevent musculoskeletal injury. Higher doses of muscle relaxants have been suggested for patients at high risk for bone fractures; however, there are adverse side effects associated with these higher doses. Aims. We present a successful case of ECT to treat chronic major depressive disorder in a 62-year-old woman at high risk of bone fracture due to gastric adenocarcinoma with metastases to bone and liver. Case. Increasing doses of the muscle relaxant succinylcholine (0.45-0.74 mg/kg) were sufficient to prevent musculoskeletal complications throughout the course of 9 bifrontal ECT treatments. Following treatment, the patient reported and demonstrated markedly improved mood and functionality, enabling her transfer to a palliative care facility. Conclusion. Standard doses of succinylcholine were sufficient to mitigate the risk of pathological fractures in this patient with metastatic bone lesions. As there are established risks to using high doses of succinylcholine, with no evidence that higher doses reduce the incidence of fractures in high-risk populations, we suggest taking a conservative approach, using clinical observation and periodic plain radiography to dictate succinylcholine dose titration in such high-risk patients.

Analgesia, enhancement of spinal morphine antinociception, and inhibition of tolerance by ultra-low dose of the α2A-adrenoceptor selective antagonist BRL44408.

Ultra-low doses of non-selective α2-adrenoceptor antagonists augment acute spinal morphine antinociception and block morphine tolerance; however, the receptor involved in mediating these effects is currently unknown. Here, we used tail flick and paw pressure tests on the rat to investigate the acute analgesic and tolerance-inducing effects of spinal morphine and norepinephrine alone or in combination with an ultra-low dose of the α2A-adrenoceptor antagonist, BRL44408. We also assessed the potential antinociceptive effects of BRL44408 alone following spinal administration. A spinal dose of BRL44408, over 1000-fold lower than that required to inhibit clonidine-induced antinociception (1.65ng/10µL), significantly prolonged morphine and norepinephrine action in both nociception tests. Following repeated morphine or norepinephrine injections, 1.65ng BRL44408 attenuated both the decline of antinociceptive effect and increase in morphine ED50 values, responses indicative of acute morphine tolerance. BRL44408 administered alone produced a delayed antinociceptive effect unrelated to repeated nociceptive testing. This response was partially reduced by the α2-adrenoceptor antagonist atipamezole (10µg). Ultra-low dose BRL44408 was able to inhibit the loss of morphine- and norepinephrine-induced antinociceptive response, and prevent the loss of drug potency due to repeated agonist exposure. This implicates the spinal α2A-adrenoceptor subtype in the action of ultra-low dose α2-adrenoceptor antagonists on morphine and norepinephrine tolerance. The BRL44408-induced analgesia is partially dependent on its interaction with the α2-adrenoceptors. Thus, this agent class may be useful in pain therapy.

Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.

The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4). Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal) were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (-) naloxone, an opioid receptor antagonist, and (+) naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence.

A clinical tool to predict adverse behaviour in children at the induction of anesthesia.

PURPOSE: To develop and validate a parent questionnaire to aid in predicting which children are likely to exhibit significant adverse behaviour at anesthetic induction. METHODS: Parents of 209 children, ages two to 13 yr, completed a brief questionnaire prior (13 items) to their child's anesthetic induction for surgery. The questionnaire included content drawn from both the literature and clinical experience. Results from the questionnaire were compared with the Induction Compliance Checklist (ICC), a validated tool to measure adverse behaviour at induction. Analyses assessing the correlation between each of the items and the total questionnaire score and between each item and the ICC score resulted in three items being removed from the questionnaire because they provided no predictive power. The association between the resulting ten-item parent questionnaire and the ICC was re-assessed using correlation. Hierarchical regression was used to evaluate the added value of our tool compared with the modified Yale Preoperative Anxiety Scale (mYPAS) in the prediction of ICC scores. RESULTS: The Cronbach's alpha reliability coefficient for the ten-item parent questionnaire was 0.73. The Pearson product-moment correlation between the ten-item questionnaire and the ICC was 0.34 (P < 0.001) for all children and 0.38 (P < 0.001) for children not preoperatively sedated. Values represent medium effect sizes for the new questionnaire's predictive power. The parent questionnaire provided added value relative to the mYPAS in terms of correlation with the ICC. CONCLUSION: Adverse behaviour at anesthesia induction is significantly predicted by our new parent questionnaire. Further refinement may improve predictive power beyond the observed medium effect size.

The utility of transthoracic echocardiography to confirm central line placement: an observational study.

BACKGROUND: Ultrasound visualization of neck vessels is the standard method used to assist with internal jugular vein (IJV) central line placement. Nevertheless, this practice has not eliminated the risk of carotid puncture and/or inadvertent arterial cannulation. Transesophageal echocardiography (TEE) effectively verifies wire placement within the heart but is invasive and not always available. We examined the feasibility and potential utility of using transthoracic echocardiography (TTE) to verify the distal wire in the right atrium (RA) before dilation and cannulation of the IJV. METHODS: Following institutional Research Ethics Board approval and signed consent, 100 patients scheduled for elective cardiac surgery were recruited. As per standard practice at our institution, all patients were to have a central line inserted under general anesthesia with TEE visualization of the guidewire. Transesophageal echocardiography (apical or subcostal four-chamber images) was performed by one of four operators while another anesthesiologist performed central line placement. Following IJV puncture, blood was rapidly aspirated and reinjected to produce microbubbles. Subsequently, a 0.035-inch j-tipped flexible guidewire was inserted and visualized with TEE. The wire was then reinserted into the RA under TTE visualization. RESULTS: Overall, the RA was viewed 94% (95% confidence interval [CI] 87 to 98) of the time with TTE, and both the microbubbles and guidewire were detected 91% (95% CI 84 to 96) of the time. The subjects in whom the guidewire could not be well visualized had a higher mean body mass index (33.6 vs 28.8; P = 0.01). CONCLUSIONS: Transthoracic echocardiography [corrected] is a feasible, noninvasive, and potentially useful method to confirm appropriate placement of the guidewire before dilation and cannulation of the IJV.

Stereo-selective inhibition of spinal morphine tolerance and hyperalgesia by an ultra-low dose of the alpha-2-adrenoceptor antagonist efaroxan.

Ultra-low doses of alpha-2 (α2)-adrenoceptor antagonists augment spinal morphine antinociception and inhibit tolerance, but the role of receptor specificity in these actions is unknown. We used the stereo-isomers of the α2 adrenoceptor antagonist, efaroxan to evaluate the effect of receptor specificity on the induction of spinal morphine tolerance and hyperalgesia. Tail flick and paw pressure tests were first used to evaluate high dose efaroxan (12.6 µg) and its stereo-isomers on clonidine analgesia in intrathecally catheterized rats. Ultra-low doses of individual isomers (1.3 ng) were then co-administered with morphine (15 µg) to determine their effects on acute antinociceptive tolerance and hyperalgesia induced by low dose spinal morphine (0.05 ng). Results demonstrate that high dose (+) efaroxan antagonized clonidine-induced antinociception, while (-) efaroxan had minimal effect. In addition, an ultra-low dose of (+) efaroxan (1.3 ng), substantially lower than required for receptor blockade, inhibited the development of acute morphine tolerance, while (-) efaroxan was less effective. Racemic (±) efaroxan effects were similar to those of (+) efaroxan. Furthermore, low dose morphine (0.05 ng) produced sustained hyperalgesia in the tail flick test and this was blocked by co-injection of (+) but not (-) efaroxan (1.3 ng). Given the isomer-specific efaroxan effects and their different receptor potencies, we suggest that inhibition of opioid tolerance by ultra-low dose efaroxan involves a specific interaction with spinal α2-adrenoceptors in this model. Likewise, inhibitory effects of adrenoceptor antagonists on morphine tolerance may be due to blockade of opioid-induced hyperalgesia.

Intraoperative diagnosis of unroofed coronary sinus after aortic valve replacement.

A patient with combined aortic insufficiency and stenosis underwent aortic valve replacement. After weaning off cardiopulmonary bypass, a new shunt into the left atrium was noted that had not been apparent on multiple previous echocardiographs. Using an agitated saline test, we confirmed a shunt between the coronary sinus and left atrium. The assumption was made that there had been an iatrogenic fistula created with placement of the retrograde catheter; however, upon opening the left atrium it was realized that the patient had a previously undiagnosed, congenitally unroofed coronary sinus. It was repaired primarily and the patient had an uneventful recovery.

Intrathecal catheterization influences tolerance to chronic morphine in rats.

We evaluated the antinociceptive effects of acute and chronic morphine administered spinally via lumbar puncture in intrathecally catheterized and sham-surgery rats. The effects of acute morphine did not differ between groups. Catheterized rats developed tolerance to chronic morphine more rapidly, compared with sham and naive rats. Therefore, catheter presence facilitated development of opioid antinociceptive tolerance. Spinal astrogliosis, determined by measurement of 3-dimensional cell volumes, was observed in catheterized rats as indicated by significantly larger cell volumes compared with surgery-naive controls. Gliosis induced by chronic intrathecal morphine administered to surgery-naive animals was comparable to that observed in saline-treated catheterized rats.

Low dose alpha-2 antagonist paradoxically enhances rat norepinephrine and clonidine analgesia.

Ultralow-dose opioid antagonists prolong opioid antinociception and block tolerance. In this study we determined whether low doses of the α-2 adrenergic receptor (A2-R) antagonist, atipamezole, similarly influenced A2-R-induced antinociception and tolerance. In rats, intrathecal norepinephrine (NE) or clonidine in combination with atipamezole was tested using tail-flick and paw pressure tests. Acute tolerance to NE was induced by serial injections. Low-dose atipamezole significantly prolonged NE and clonidine-induced antinociception. Coadministration of atipamezole with A2-R agonists also prevented loss of agonist potency in the acute tolerance model. This study demonstrates paradoxical effects of low-dose A2-R antagonists augmenting A2-R agonist-induced analgesia.