Poor Agreement Between Preoperative Transthoracic Echocardiography and Intraoperative Transesophageal Echocardiography for Grading Diastolic Dysfunction.

BACKGROUND: Guidelines for the evaluation and grading of diastolic dysfunction are available for transthoracic echocardiography (TTE). Transesophageal echocardiography (TEE) is used for this purpose intraoperatively but the level of agreement between these 2 imaging modalities for grading diastolic dysfunction is unknown. We assessed agreement between awake preoperative TTE and intraoperative TEE for grading diastolic dysfunction. METHODS: In 98 patients undergoing cardiac surgery, key Doppler measurements were obtained using TTE and TEE at the following time points: TTE before anesthesia induction (TTEawake), TTE following anesthesia induction (TTEanesth), and TEE following anesthesia induction (TEEanesth). The primary endpoint was grade of diastolic dysfunction categorized by a simplified algorithm, and measured by TTEawake and TEEanesth, for which the weighted κ statistic assessed observed agreement beyond chance. Secondary endpoints were peak early diastolic lateral mitral annular tissue velocity (e'lat) and the ratio of peak early diastolic mitral inflow velocity (E) to e'lat (E/e'lat), measured by TTEawake and TEEanesth, were compared using Bland-Altman limits of agreement. RESULTS: Disagreement in grading diastolic dysfunction by ≥1 grade occurred in 43 (54%) of 79 patients and by ≥2 grades in 8 (10%) patients with paired measurements for analysis, yielding a weighted κ of 0.35 (95% confidence interval [CI], 0.19-0.51) for the observed level of agreement beyond chance. Bland-Altman analysis of paired data for e'lat and E/e'lat demonstrated a mean difference (95% CI) of 0.51 (-0.06 to 1.09) and 0.70 (0.07-1.34), respectively, for measurements made by TTEawake compared to TEEanesth. The percentage (95% CI) of paired measurements for e'lat and E/e'lat that lay outside the [-2, +2] study-specified boundary of acceptable agreement was 36% (27%-48%) and 39% (29%-51%), respectively. Results were generally robust to sensitivity analyses, including comparing measurements between TTEawake and TTEanesth, between TTEanesth and TEEanesth, and after regrading diastolic dysfunction by the American Society of Echocardiography (ASE)/European Association of CardioVascular Imaging (EACVI) algorithm. CONCLUSIONS: There was poor agreement between TTEawake and TEEanesth for grading diastolic dysfunction by a simplified algorithm, with disagreement by ≥1 grade in 54% and by ≥2 grades in 10% of the evaluable cohort. Future studies, including comparing the prognostic utility of TTEawake and TEEanesth for clinically important adverse outcomes that may be a consequence of diastolic dysfunction, are needed to understand whether this disagreement reflects random variability in Doppler variables, misclassification by the changed technique and physiological conditions of intraoperative TEE, or the accurate detection of a clinically relevant change in diastolic dysfunction.

Intraoperative Transesophageal Echocardiography for the Evaluation and Management of Diastolic Dysfunction in Patients Undergoing Cardiac Surgery: A Survey of Current Practice.

OBJECTIVES: To characterize existing practice patterns for intraoperative evaluation and grading of diastolic dysfunction in patients undergoing cardiac surgery. DESIGN: A 14-question, multiple-choice survey of current practice for patients with diastolic dysfunction and the use of intraoperative transesophageal echocardiography (TEE) to evaluate, grade, and monitor changes in diastolic function. SETTING: Online survey. PARTICIPANTS: Members of the Society of Cardiovascular Anesthesiologists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 515 respondents, there was a near-even spread between those based in an academic setting (53%) and those based in private practice (43%). Most respondents (81%) had completed training with certification in TEE. Most respondents (86%) currently modified their intraoperative management, at least some of the time, if they believed a patient was experiencing diastolic dysfunction, with 72% varying the nature of any modification according to the identified grade of diastolic dysfunction. Although 62% of respondents usually evaluated diastolic dysfunction in the pre-bypass period, only 59% of those evaluating diastolic dysfunction typically graded the dysfunction, with a variety of algorithms used for this purpose. The majority of respondents (62%) typically did not re-evaluate diastolic function using TEE in the post-bypass period. In 2 sample patients with Doppler data provided, there was marked variation in grading of diastolic dysfunction by respondents; this variation remained marked even within subgroups of respondents who typically used the same grading algorithm. CONCLUSIONS: Marked variation currently exists in how intraoperative TEE is used to evaluate, grade, and monitor diastolic function during cardiac surgery. This suggests clinically important knowledge gaps that should be addressed.

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Plasmin, Immunity, and Surgical Site Infection.

SSI are a universal economic burden and increase individual patient morbidity and mortality. While antibiotic prophylaxis is the primary preventative intervention, these agents are not themselves benign and may be less effective in the context of emerging antibiotic resistant organisms. Exploration of novel therapies as an adjunct to antimicrobials is warranted. Plasmin and the plasminogen activating system has a complex role in immune function. The immunothrombotic role of plasmin is densely interwoven with the coagulation system and has a multitude of effects on the immune system constituents, which may not always be beneficial. Tranexamic acid is an antifibrinolytic agent which inhibits the conversion of plasminogen to plasmin. Clinical trials have demonstrated a reduction in surgical site infection in TXA exposed patients, however the mechanism and magnitude of this benefit is incompletely understood. This effect may be through the reduction of local wound haematoma, decreased allogenic blood transfusion or a direct immunomodulatory effect. Large scale randomised clinical trial are currently being undertaken to better explain this association. Importantly, TXA is a safe and widely available pharmacological agent which may have a role in the reduction of SSI.

Steady-state analysis of a continuum model for super-infection.

A large system of N strains of parasite and a single host is analyzed as a function of the degree of virulence in the strains when there is super-infection between hosts (more virulent strains can infect hosts that are already infected) and within-host transition between strains that is neutral. When this small amount of local switching is allowed, steady-state solutions converge to a continuous distribution as the number of strains increases. The resulting nonlinear-nonautonomous integro-differential equation is reduced to a fourth order boundary value problem (BVP) and the existence of positive solutions is proven. The methods here and associated BVP allow for a thorough exploration of parameter space for this class of models.

Rhodanine derivatives as novel inhibitors of PDE4.

The discovery, synthesis and in vitro activity of a novel series of rhodanine based phosphodiesterase-4 (PDE4) inhibitors is described. Structure-activity relationship studies directed toward improving potency led to the development of submicromolar inhibitors 2n and 3i (IC(50)=0.89 & 0.74 microM). The replacement of rhodanine with structurally related heterocycles was also investigated and led to the synthesis of pseudothiohydantoin 7 (IC(50)=0.31 microM).

The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family.

Ibudilast is widely used in Japan to treat ischemic stroke and bronchial asthma. Its mode of action is through the inhibition of cyclic nucleotide phosphodiesterases (PDEs). Growing evidence suggests this compound has utility in a range of neurological conditions linked to its ability to elevate cellular cyclic nucleotide concentrations, however limited data exists on Ibudilast's action on individual PDE families. We therefore used an extensive panel of human PDE enzymes to define the PDE inhibitory profile of this compound. Ibudilast preferentially inhibits PDE3A, PDE4, PDE10 and PDE11 with lesser inhibition of a number of other families. The significance of these findings is discussed in relation to Ibudilast's observed effects on certain disease states.

The effect of selective phosphodiesterase inhibitors, alone and in combination, on a murine model of allergic asthma.

BACKGROUND: The anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control. METHODS: Control and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days. RESULTS: When used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-alpha, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil. CONCLUSIONS: These results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor.

Survey of adult extracorporeal membrane oxygenation (ECMO) practice and attitudes among Australian and New Zealand intensivists.

OBJECTIVE: To gauge use of extracorporeal membrane oxygenation (ECMO) in Australian and New Zealand intensive care units, to investigate attitudes to and experience with ECMO, and to assess interest in contributing to a national database of ECMO use. METHODS: The survey was conducted by email in July 2004. A targeted cohort of ICUs across the two countries was chosen, comprising JFICM (Joint Faculty of Intensive Care Medicine) Approved Training Centres, and large regional and private institutions. Directors of the ICUs were invited to participate in the survey of department demographics, ECMO practice rates and experience, and attitudes to ECMO. The survey was registered (http://clinicaltrials.gov registration number NCT00157144), and local ethics approval was obtained. RESULTS: Response rate was 56% (39/70), with 49% of responses (19/39) from JFICM Approved Training Centres. ECMO practice in responding centres was low, with 69% (27/39) having managed no ECMO patients in the past year, and 62% (24/39) having managed none in the past 3 years. Only one centre had managed more than eight patients in the past year. Individual respondents had limited ECMO experience, with 56% (22/39) having ever managed two or fewer patients. The most common reasons given for not providing ECMO were lack of staff skill/training and lack of access to support services. Cost, high mortality and lack of evidence for ECMO efficacy were not regarded as significant factors preventing its use. Seventy-two per cent (28/39) of respondents supported ECMO use outside a randomised controlled trial, and 49% (19/39) would conduct ECMO at their own institution, while 74% (29/39) felt it a useful tool to facilitate transport to specialist centres. CONCLUSION: ECMO use in Australian and New Zealand ICUs is limited, but there is support for its use among survey respondents. Lack of training and experience with ECMO may be restricting its use.