Ketamine/propofol admixture vs etomidate for intubation in the critically ill: KEEP PACE Randomized clinical trial.

BACKGROUND: Periintubation hypotension is associated with poor outcomes in the critically ill. We aimed to determine if an admixture of ketamine and propofol for emergent endotracheal intubation in critically ill patients was superior to etomidate. Primary endpoint was the change in mean arterial pressure from baseline to 5 minutes postdrug administration. METHODS: Emergent-use, stratified (shock status and unit type), multiunit, randomized, parallel-group superiority clinical trial was conducted at a tertiary academic medical center. Adult medical/surgical and transplant/oncologic intensive care unit patients undergoing emergent intubation were assigned randomly to receive either ketamine/propofol admixture (0.5 mg/kg of ketamine and propofol each) or reduced dose etomidate (0.15 mg/kg) for emergent intubation. RESULTS: One hundred sixty participants were randomized, and 152 (79 ketamine/propofol admixture, 73 etomidate) were included in the intention-to-treat analysis. There was no statistically significant difference in mean arterial pressure change from baseline to 5 minutes postdrug administration (treatment difference [ketamine/propofol admixture-etomidate]: -2.1 mm Hg; 95% confidence interval, -6.9 mm Hg to +2.7 mm Hg; p = 0.385). In addition, no statistically significant difference was demonstrated in the change of mean arterial pressure from baseline at 10 minutes and 15 minutes postdrug administration, no statistical difference in the use of new-onset vasoactive agents or difficulty of intubation between groups. More patients in the etomidate group required non-red blood cell transfusions (16 [22%] vs. 8 [10%], p = 0.046). For patients who had adrenal testing performed, more patients in the etomidate group developed immediate adrenal insufficiency (13 [81%] of 16 vs. 5 [38%] of 13, p = 0.027). Serious adverse events were rare, 2 (3%) (cardiac arrest, hypotension) in ketamine/propofol admixture and 4 (5%) (hypertension, hypotension) in etomidate (p = 0.430). CONCLUSION: In a heterogeneous critically ill population, ketamine/propofol admixture was not superior to a reduced dose of etomidate at preserving per-intubation hemodynamics and appears to be a safe alternative induction agent in the critically ill. LEVEL OF EVIDENCE: Therapeutic/Care Management, level II. TRIAL REGISTRY: ClinicalTrials.gov, NCT02105415, Ketamine/Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial, IRB 13-000506, Trial Registration: March 31, 2014.

Decision Support Tool to Improve Glucose Control Compliance After Cardiac Surgery.

Hyperglycemia control is associated with improved outcomes in patients undergoing cardiac surgery. The Surgical Care Improvement Project metric (SCIP-inf-4) was introduced as a performance measure in surgical patients and included hyperglycemia control. Compliance with the SCIP-inf-4 metric remains suboptimal. A novel real-time decision support tool (DST) with guaranteed feedback that is based on the existing electronic medical record system was developed at a tertiary academic center. Implementation of the DST increased the compliance rate with the SCIP-inf-4 from 87.3% to 96.5%. Changes in tested clinical outcomes were not observed with improved metric compliance. This new framework can serve as a backbone for development of quality control processes for other metrics. Further and, ideally, multicenter studies are required to test if implementation of electronic DSTs will translate into improved resource utilization and outcomes for patients.

Anti-CD48 Monoclonal Antibody Attenuates Experimental Autoimmune Encephalomyelitis by Limiting the Number of Pathogenic CD4+ T Cells.

CD48 (SLAMF2) is an adhesion and costimulatory molecule constitutively expressed on hematopoietic cells. Polymorphisms in CD48 have been linked to susceptibility to multiple sclerosis (MS), and altered expression of the structurally related protein CD58 (LFA-3) is associated with disease remission in MS. We examined CD48 expression and function in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We found that a subpopulation of CD4+ T cells highly upregulated CD48 expression during EAE and were enriched for pathogenic CD4+ T cells. These CD48++CD4+ T cells were predominantly CD44+ and Ki67+, included producers of IL-17A, GM-CSF, and IFN-γ, and were most of the CD4+ T cells in the CNS. Administration of anti-CD48 mAb during EAE attenuated clinical disease, limited accumulation of lymphocytes in the CNS, and reduced the number of pathogenic cytokine-secreting CD4+ T cells in the spleen at early time points. These therapeutic effects required CD48 expression on CD4+ T cells but not on APCs. Additionally, the effects of anti-CD48 were partially dependent on FcγRs, as anti-CD48 did not ameliorate EAE or reduce the number of cytokine-producing effector CD4+ T cells in Fcεr1γ-/- mice or in wild-type mice receiving anti-CD16/CD32 mAb. Our data suggest that anti-CD48 mAb exerts its therapeutic effects by both limiting CD4+ T cell proliferation and preferentially eliminating pathogenic CD48++CD4+ T cells during EAE. Our findings indicate that high CD48 expression is a feature of pathogenic CD4+ T cells during EAE and point to CD48 as a potential target for immunotherapy.

Cellular Microbiology of Mycoplasma canis.

Mycoplasma canis can infect many mammalian hosts but is best known as a commensal or opportunistic pathogen of dogs. The unexpected presence of M. canis in brains of dogs with idiopathic meningoencephalitis prompted new in vitro studies to help fill the void of basic knowledge about the organism's candidate virulence factors, the host responses that it elicits, and its potential roles in pathogenesis. Secretion of reactive oxygen species and sialidase varied quantitatively (P < 0.01) among strains of M. canis isolated from canine brain tissue or mucosal surfaces. All strains colonized the surface of canine MDCK epithelial and DH82 histiocyte cells and murine C8-D1A astrocytes. Transit through MDCK and DH82 cells was demonstrated by gentamicin protection assays and three-dimensional immunofluorescence imaging. Strains further varied (P < 0.01) in the extents to which they influenced the secretion of tumor necrosis factor alpha (TNF-α) and the neuroendocrine regulatory peptide endothelin-1 by DH82 cells. Inoculation with M. canis also decreased major histocompatibility complex class II (MHC-II) antigen expression by DH82 cells (P < 0.01), while secretion of gamma interferon (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10), and complement factor H was unaffected. The basis for differences in the responses elicited by these strains was not obvious in their genome sequences. No acute cytopathic effects on any homogeneous cell line, or consistent patterns of M. canis polyvalent antigen distribution in canine meningoencephalitis case brain tissues, were apparent. Thus, while it is not likely a primary neuropathogen, M. canis has the capacity to influence meningoencephalitis through complex interactions within the multicellular and neurochemical in vivo milieu.

Hepatic Responses of Juvenile Fundulus heteroclitus from Pollution-adapted and Nonadapted Populations Exposed to Elizabeth River Sediment Extract.

Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Industries region of the Elizabeth River, Virginia, have passed polycyclic aromatic hydrocarbon (PAH) resistance to their offspring as evidenced by early life stage testing of developmental toxicity after exposure to specific PAHs. Our study focused on environmentally relevant PAH mixtures in the form of Elizabeth River sediment extract (ERSE). Juvenile (5 month) F1 progeny of pollution-adapted Atlantic Wood (AW) parents and of reference site (King's Creek [KC]) parents were exposed as embryos to ERSE. Liver alterations, including nonneoplastic lesions and microvesicular vacuolation, were observed in both populations. ERSE-exposed KC fish developed significantly more alterations than unexposed KC fish. Interestingly, unexposed AW killifish developed significantly more alterations than unexposed KC individuals, suggesting that AW juveniles are not fully protected from liver disease; rapid growth of juvenile fish may also be an accelerating factor for tumorigenesis. Because recent reports show hepatic tumor formation in adult AW fish, the differing responses from the 2 populations provided a way to determine whether embryo toxicity protection extends to juveniles. Future investigations will analyze older life stages of killifish to determine differences in responses related to chronic disease.

Definitive airway management of patients presenting with a pre-hospital inserted King LT(S)-D laryngeal tube airway: a historical cohort study.

PURPOSE: The King LT(S)-D laryngeal tube (King LT) has gained popularity as a bridge airway for pre-hospital airway management. In this study, we retrospectively reviewed the use of the King LT and its associated airway outcomes at a single Level 1 trauma centre. METHODS: The data on all adult patients presenting to the Mayo Clinic in Rochester, Minnesota with a King LT in situ from July 1, 2007 to October 10, 2012 were retrospectively evaluated. Data collected and descriptively analyzed included patient demographics, comorbidities, etiology of respiratory failure, airway complications, subsequent definitive airway management technique, duration of mechanical ventilation, and status at discharge. RESULTS: Forty-eight adult patients met inclusion criteria. The most common etiology for respiratory failure requiring an artificial airway was cardiac arrest [28 (58%) patients] or trauma [9 (19%) patients]. Four of the nine trauma patients had facial trauma. Surgical tracheostomy was the definitive airway management technique in 14 (29%) patients. An airway exchange catheter, direct laryngoscopy, and video laryngoscopy were used in 11 (23%), ten (21%), and ten (21%) cases, respectively. Seven (78%) of the trauma patients underwent surgical tracheostomy compared with seven (18%) of the medical patients. Adverse events associated with King LT use occurred in 13 (27%) patients, with upper airway edema (i.e., tongue engorgement and glottic edema) being most common (19%). CONCLUSION: In this study of patients presenting to a hospital with a King LT, the majority of airway exchanges required an advanced airway management technique beyond direct laryngoscopy. Upper airway edema was the most common adverse observation associated with King LT use.

Nitrogen stress response and stringent response are coupled in Escherichia coli.

Assimilation of nitrogen is an essential process in bacteria. The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of relA, a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria.

Anesthesiology critical care medicine: a fellowship and faculty recruitment program.

STUDY OBJECTIVE: To review national data on anesthesiology critical care medicine (ACCM) fellowship program enrollment and to describe a program that successfully recruited ACCM fellows and faculty at a single academic medical center. DESIGN: An incentive program known as the Mayo Clinic Scholar program, designed to recruit ACCM fellows and faculty, was reviewed. Interviews were conducted to assess the impact of the Mayo Clinic Scholar program. SETTING: Academic health center. MEASUREMENTS: ACCM fellowship program enrollment data were compared with similar data for critical care medicine fellowship programs in internal medicine, pulmonary medicine, pediatrics, and surgery.The results of a program to recruit ACCM fellows and faculty were reviewed. MAIN RESULTS: Only 89 of 147 (60.5%) ACCM fellowship positions available nationally were filled during the 2010-2011 academic year, and only 89 of the 896 (9.9%) critical care medicine fellows anticipated to graduate in 2011 were in ACCM programs. The Mayo Clinic ACCM fellowship enrolled 28 fellows from January 1, 2000 through July 1, 2010 (range 0-6 per yr). Ten of the 28 (35.7%) were United States medical graduates (USMGs) and 6 of the 10 (60.0%) USMGs who were graduates of the Mayo Clinic residency were appointed as Mayo Clinic Scholars. All 6 Mayo Clinic Scholars were retained as ACCM faculty. Only two of the 6 (33.3%) Mayo Clinic Scholars would have completed ACCM training without a Mayo Clinic Scholar appointment. All recommend ACCM training to others and plan to continue to practice ACCM. CONCLUSIONS: The Mayo Clinic Scholar program effectively recruited ACCM fellows and faculty in a single institution. Incentive-based programs should be considered to support the involvement of anesthesiologists in perioperative medicine.

A prospective trial of elective extubation in brain injured patients meeting extubation criteria for ventilatory support: a feasibility study.

INTRODUCTION: To assess the safety and feasibility of recruiting mechanically ventilated patients with brain injury who are solely intubated for airway protection and randomising them into early or delayed extubation, and to obtain estimates to refine sample-size calculations for a larger study. The design is a single-blinded block randomised controlled trial. A single large academic medical centre is the setting. METHODS: Sixteen neurologically stable but severely brain injured patients with a Glasgow Coma Score (GCS) of 8 or less were randomised to early or delayed extubation until their neurological examination improved. Eligible patients met standard respiratory criteria for extubation and passed a modified Airway Care Score (ACS) to ensure adequate control of respiratory secretions. The primary outcome measured between groups was the functional status of the patient at hospital discharge as measured by a Modified Rankin Score (MRS) and Functional Independence Measure (FIM). Secondary measurements included the number of nosocomial pneumonias and re-intubations, and intensive care unit (ICU) and hospital length of stay. Standard statistical assessments were employed for analysis. RESULTS: Five female and eleven male patients ranging in age from 30 to 93 years were enrolled. Aetiologies responsible for the neurological injury included six head traumas, three brain tumours, two intracerebral haemorrhages, two subarachnoid haemorrhages and three ischaemic strokes. There were no demographic differences between the groups. There were no unexpected deaths and no significant differences in secondary measures. The difference in means between the MRS and FIM were small (0.25 and 5.62, respectively). These results suggest that between 64 and 110 patients are needed in each treatment arm to detect a treatment effect with 80% power. CONCLUSIONS: Recruitment and randomisation of severely brain injured patients appears to be safe and feasible. A large multicentre trial will be needed to determine if stable, severely brain injured patients who meet respiratory and airway control criteria for extubation need to remain intubated.

Acute Physiology and Chronic Health Evaluation (APACHE) III outcome prediction after major vascular surgery.

OBJECTIVE: To investigate the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) III scoring system in patients admitted to the intensive care unit (ICU) after major vascular surgery. DESIGN: Retrospective cohort study. SETTING: A tertiary referral center. PARTICIPANTS: Three thousand one hundred forty-eight patients who underwent major vascular surgery between October 1994 and March 2006. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were abstracted from an institutional APACHE III database. Standardized mortality ratios (SMRs) (with 95% confidence intervals) were calculated. The area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow C statistic were used to assess discrimination and calibration, respectively. The mean age of 3,148 patients studied was 70.5 years (+/- standard deviation 9.6). The mean Acute Physiology Score and the APACHE III score on the day of ICU admission were 31.0 (+/- 17.5) and 45.1 (+/- 18.8), respectively. The mean predicted ICU and hospital mortality rates were 3.2% (+/- 7.8%) and 5.0% (+/- 9.5%), respectively. The median (and interquartile range) ICU and hospital lengths of stay were 4.3 (3.6-5.1) and 14 days (11.9-16.8 days), respectively. The observed ICU mortality rate was 2.4% (75/3, 148 patients) and hospital mortality rate was 3.7% (116/3,148). The ICU and hospital SMRs were 0.74 (0.58-0.91) and 0.74 (0.61-0.88), respectively. The AUC of APACHE III-derived prediction of hospital mortality was 0.840 (95% confidence interval, 0.799-0.880), indicating excellent discrimination. The Hosmer-Lemeshow C statistic was 28.492, with a p value <0.01, indicating poor calibration. CONCLUSIONS: The APACHE III scoring system discriminates well between survivors and nonsurvivors after major vascular surgery, but calibration of the model is poor.

Appropriate ventilatory settings for thoracic surgery: intraoperative and postoperative.

Mechanical ventilation of patients undergoing thoracic surgery is often challenging. These patients frequently have significant underlying comorbidities, including cardiopulmonary disease, and often must undergo 1-lung ventilation. Perioperative respiratory complications are common and are multifactorial in etiology. Increasing evidence suggests that mechanical ventilation is associated with, and may even cause, lung damage in both sick and healthy patients. Gas exchange to provide acceptable end-organ oxygenation remains a primary goal but so too is minimization of risks for acute lung injury. Every ventilator strategy is associated with potential beneficial and adverse side effects. Understanding the impact of various ventilation strategies allows clinicians to provide optimal care for patients.

Changes in intensive care unit performance measures associated with opening a dedicated thoracic surgical progressive care unit.

OBJECTIVES: To determine the effect of the introduction of a specialty-specific progressive care unit (PCU) on the intensive care unit (ICU) to which relatively low-acuity patients had previously been admitted. DESIGN: Retrospective cohort study. SETTING: The thoracic (noncardiac) surgical ICU of a tertiary referral institution. PATIENTS: Four thousand fifty-three patients admitted to the ICU after thoracic surgery between October 1994 and December 2003. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The institutional Acute Physiology and Chronic Health Evaluation (APACHE) III database was searched to compare the number of admissions, severity of illness, mortality, and other aspects of care for periods before and after the introduction of the PCU. Patients in the post-PCU group were more severely ill by APACHE criteria. The ICU mortality rates for the periods before and after the introduction of the PCU were 1.14% (32/2,801 patients) and 7.27% (91/1,252 patients), respectively. The performance of the ICU appeared to be worse in the period after the opening of the PCU. The ICU- and hospital-customized standardized mortality ratio increased from 0.68 (95% confidence interval [CI], 0.47-0.96) in the pre-PCU group to 1.20 (95% CI, 0.96-1.47) in the post-PCU group and from 0.83 (95% CI, 0.66-1.03) to 1.24 (95% CI, 1.05-1.46). CONCLUSIONS: The introduction of a nonintensivist-directed PCU to care for thoracic surgical patients had a significant impact on the parent ICU. Of concern is that outcome and quality measures appeared to worsen and ICU readmission rate increased.

Perioperative statin therapy and renal outcomes after major vascular surgery: a propensity-based analysis.

OBJECTIVE: To evaluate how the presence and timing of statin therapy affect perioperative renal outcomes after major vascular surgery. DESIGN: Retrospective cohort study. SETTING: Surgical intensive care unit at a single academic medical center. PARTICIPANTS: Patients undergoing major vascular surgery between July 2004 and October 2005. MEASUREMENTS AND MAIN RESULTS: The presence and timing of perioperative statin administration and the propensity for receiving such therapy were noted. Renal outcomes, lengths of stay, and mortality were reviewed. One hundred fifty-one procedures were performed. Eighty-nine patients (59%) received statin therapy. There was no evidence for renal protection with perioperative statin therapy (Delta creatinine 0.2 mg/dL v 0.2 mg/dL, p = 0.41; acute renal injury/acute renal failure 8% v 6%, p = 1.00; renal replacement therapy 3% v 3%, p = 1.00; all statin v no statin, respectively). With the possible exception of early reinstitution of statin therapy in chronic statin users, subgroup analyses failed to confirm an association between statin timing and prevention of postoperative renal dysfunction. CONCLUSIONS: In the present investigation, neither the presence nor timing of perioperative statin therapy was associated with improved renal outcomes in patients undergoing a range of major vascular procedures. A possible exception is early postoperative reinitiation of statin therapy in chronic statin users. The discrepant results of available literature preclude a definitive statement on the use of statin therapy as a means of preventing postoperative renal dysfunction. An adequately powered prospective trial is needed before advocating the routine use of statin therapy for perioperative renal protection.

The acute physiology and chronic health evaluation III outcome prediction in patients admitted to the intensive care unit after pneumonectomy.

PURPOSE: The Acute Physiology and Chronic Health Evaluation (APACHE) III prognostic system has not been previously validated in patients admitted to the intensive care unit (ICU) after pneumonectomy. The purpose of this study was to determine if the APACHE III predicts hospital mortality after pneumonectomy. METHODS: A retrospective review of all adult patients admitted to a single thoracic surgical intensive care unit after pneumonectomy between October 1994 and December 2004. Patient demographics, ICU admission day APACHE III score, actual and predicted hospital mortality, and length of hospital and ICU stay data were collected. Data on preoperative pulmonary function tests and smoking habits were also collected. Univariate statistical methods and logistic regression were used. The performance of the APACHE III prognostic system was assessed by the Hosmer-Lemeshow statistic for calibration and area under receiver operating characteristic curve (AUC) for discrimination. RESULTS: There were 417 pneumonectomies performed during the study period, of which 281 patients were admitted to the ICU. The mean age was 61.1 years, and 67.2% were men; 88.2% were smokers with a median of 40.0 (interquartile range, 18-62) pack-years of tobacco use. The mean APACHE III score on the day of ICU admission was 37.7 (+/- standard deviation 17.8), and the mean predicted hospital mortality rate was 6.4% (+/-10.4). The median (and interquartile range) lengths of ICU and hospital stay were 1.7 (0.9-3.1) and 9.0 (7.0-17.0) days, respectively. The observed ICU and hospital mortality rates were 4.6% (13/281 patients) and 8.2% (23/281), respectively. The standardized ICU and hospital mortality ratios with their 95% confidence intervals (CIs) were 1.55 (0.71-2.39) and 1.27 (0.75-1.78), respectively. There were significant differences in the mean APACHE III score (p < 0.001) and the predicted mortality rate (p < .001) between survivors and nonsurvivors. In predicting mortality, the AUC of APACHE III prediction was 0.801 (95% CI, 0.711-0.891), and the Hosmer-Lemeshow statistic was 9.898 with a p value of 0.272. Diffusion capacity of the lung for carbon monoxide (DLCO) and percentage predicted DLCO were higher in survivors, but the addition of either of these variables to a logistic regression model did not improve APACHE III mortality prediction. CONCLUSIONS: In patients admitted to the ICU after pneumonectomy, the APACHE III discriminates moderately well between survivors and nonsurvivors. The calibration of the model appears to be good, although the low number of deaths limits the power of the calibration analysis. The use of APACHE III data in outcomes research involving patients who have undergone pneumonectomy is acceptable.

Improved enzyme-linked immunosorbent assay to reveal Mycoplasma agassizii exposure: a valuable tool in the management of environmentally sensitive tortoise populations.

The precarious status of desert (Gopherus agassizii) and gopher (Gopherus polyphemus) tortoises has resulted in research and conservation efforts that include health assessments as a substantial component of management decision-making. Therefore, it is critical that available diagnostic tests for diseases impacting these species undergo rigorous standardization and validation. Since 1992, analysis of exposure of tortoises to Mycoplasma agassizii, an etiological agent of upper respiratory tract disease, has relied on the detection of specific M. agassizii antibody by enzyme-linked immunosorbent assay (ELISA). We report here substantive refinements in the diagnostic assay and discuss the implications of its use in wildlife conservation and management. The ELISA has been refined to include more stringent quality control measures and has been converted to a clinically more meaningful titer reporting system, consistent with other diagnostic serologic tests. The ELISA results for 5,954 desert and gopher tortoises were plotted, and a subset of these serum samples (n = 90) was used to determine end-point titers, to establish an optimum serum dilution for analyzing samples, and to construct a standard curve. The relationship between titer and A405 was validated using 77 serum samples from known positive (n = 48) and negative (n = 29) control tortoises from prior transmission studies. The Youden index, J, and the optimal cut point, c, were estimated using ELISA results from the 77 control sera. Based on this evaluation, the refinement has substantially improved the performance of the assay (sensitivity of 0.98, specificity of 0.99, and J of 0.98), thus providing a clinically more reliable diagnostic test for this important infection of tortoises.

Role of sialidase in Mycoplasma alligatoris-induced pulmonary fibroblast apoptosis.

Mycoplasma alligatoris causes acute lethal cardiopulmonary disease of susceptible hosts. A survey of its genome implicated sialidase and hyaluronidase, synergistic regulators of hyaluronan receptor CD44-mediated signal transduction leading to apoptotic cell death, as virulence factors of M. alligatoris. In this study, after the existence of a CD44 homolog in alligators was established by immunolabeling primary pulmonary fibroblasts with monoclonal antibody IM7 against murine CD44, the sialidase inhibitor 2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA) was used to examine the effects of sialidase on fibroblast apoptosis following in vitro infection with M. alligatoris. While their CD44 expression remained constant, infected cells exhibited morphologic changes characteristic of apoptosis including decreased size, rounding, disordered alpha-tubulin, and nuclear disintegration compared to untreated controls. DANA was a potent, non-toxic inhibitor of the sialidase activity, equivalent to about 1mU of Clostridium perfringens Type VI sialidase, expressed by M. alligatoris in the inoculum. Although DANA did not measurably reduce the proportion of infected fibroblasts labeled by a specific ligand of activated caspases, co-incubation with DANA protected (P<0.01) fibroblasts in a concentration-dependent fashion from the M. alligatoris-induced trends toward increased apoptosis receptor CD95 expression, and increased 5-bromo-2'-deoxyuridine incorporation measured in a terminal dUTP nick end-labeling apoptosis assay. In contrast, incubation with 200-fold excess purified C. perfringens sialidase alone did not affect CD95 expression or chromatin integrity, or induce fibroblast apoptosis. From those observations we conclude that interaction of its sialidase with hyaluronidase or another virulence factor(s) is necessary to elicit the pro-apoptotic effects of M. alligatoris infection.

Acute coronary syndrome and myocardial infarction after orthopedic surgery in a patient with a recently placed drug-eluting stent.

Providing anesthesia care for patients who have recently undergone intracoronary drug-eluting stent placement presents unique clinical challenges. It is currently recommended that these patients remain on antiplatelet therapy until reendothelialization of the vessel has occurred (ie, 3-6 months, depending on the eluting medication) to prevent stent restenosis. In the setting of urgent or emergent surgery, it may not be possible to wait until a full course of antiplatelet therapy has been completed. We report an unusual case of postoperative acute coronary syndrome in a gentleman who underwent intracoronary stenting 7 weeks before nonelective revision hip arthroplasty. To our knowledge, this is the first case in the anesthesia literature to report postoperative cardiac morbidity after recent drug-eluting stent deployment.

Intraoperative tidal volume as a risk factor for respiratory failure after pneumonectomy.

BACKGROUND: Respiratory failure is a leading cause of postoperative morbidity and mortality in patients undergoing pneumonectomy. The authors hypothesized that intraoperative mechanical ventilation with large tidal volumes (VTs) would be associated with increased risk of postpneumonectomy respiratory failure. METHODS: Patients undergoing elective pneumonectomy at the authors' institution from January 1999 to January 2003 were studied. The authors collected data on demographics, relevant comorbidities, neoadjuvant therapy, pulmonary function tests, site and type of operation, duration of surgery, intraoperative ventilator settings, and intraoperative fluid administration. The primary outcome measure was postoperative respiratory failure, defined as the need for continuation of mechanical ventilation for greater than 48 h postoperatively or the need for reinstitution of mechanical ventilation after extubation. RESULTS: Of 170 pneumonectomy patients who met inclusion criteria, 30 (18%) developed postoperative respiratory failure. Causes of postoperative respiratory failure were acute lung injury in 50% (n = 15), cardiogenic pulmonary edema in 17% (n = 5), pneumonia in 23% (n = 7), bronchopleural fistula in 7% (n = 2), and pulmonary thromboembolism in 3% (n = 1). Patients who developed respiratory failure were ventilated with larger intraoperative VT than those who did not (median, 8.3 vs. 6.7 ml/kg predicted body weight; P < 0.001). In a multivariate regression analysis, larger intraoperative VT (odds ratio, 1.56 for each ml/kg increase; 95% confidence interval, 1.12-2.23) was associated with development of postoperative respiratory failure. The interaction between larger VT and fluid administration was also statistically significant (odds ratio, 1.36; 95% confidence interval, 1.05-1.97). CONCLUSION: Mechanical ventilation with large intraoperative VT is associated with increased risk of postpneumonectomy respiratory failure.