Organisation and planning of anaesthesia for emergency surgery.

Patients presenting for emergency surgery represent a category at high risk of complications, with substantial morbidity and mortality, whose management may be extremely challenging. In this first of two articles we consider the identification and evaluation of high risk emergency patients, the provision of critical care support, the management of sepsis, common postoperative complications and in-theatre death.

The principles and conduct of anaesthesia for emergency surgery.

In this second article we examine the principles underlying delivery of the components of anaesthesia. Topics considered include anaesthetic technique, management of the airway and lung ventilation, induction and maintenance of anaesthesia, patient monitoring including the place of cardiac output devices. We summarise recent research on the management of shock and sepsis syndromes including goal directed therapy and examine some controversies around intravenous fluid therapy. Finally, we discuss intra-operative awareness and challenges during emergence including peri-operative cognitive dysfunction.

Prediction of mortality in adult emergency department patients with sepsis.

OBJECTIVES: To determine the efficacy of the abbreviated Mortality in Emergency Department Sepsis (MEDS) score, the Modified Early Warning (MEW) score and near-patient-test (NPT) lactate levels in predicting 28-day mortality in adult emergency department (ED) patients with sepsis. METHODS: A retrospective cohort study of adult ED patients with sepsis admitted to hospital was conducted in a large urban teaching and a district general hospital. Data were collected during four time periods between 1 January 2006 and 31 January 2007. Inclusion criteria were age > or =16 years and an ED diagnosis of sepsis. Primary outcome for all patients was 28-day mortality. Patients were preassigned to risk groups according to their abbreviated MEDS score, MEW score and NPT lactate. RESULTS: 307 ED patients with sepsis were included in the study. Among these there were 72 deaths (23%). Mortality rates for the low-, moderate- and high-risk groups of the abbreviated MEDS score were 1/63 (1.6%), 48/205 (23.4%) and 23/39 (59.0%) patients. The MEDS score for low-risk patients was 98.6% (95% CI 92.5% to 99.9%) sensitive and 26.5% (95% CI 21.0% to 32.6%) specific and for high-risk patients it was 31.9% (95% CI 21.4% to 44.0%) sensitive and 93.2% (95% CI 89.2% to 96.1%) specific for death within 28 days. Mortality rates for the low- and high-risk MEW score were 20/159 (12.6%) and 52/148 (35.1%) patients. The MEW score for high-risk patients was 72.2% (95% CI 60.4% to 82.1%) sensitive and 59.2% (95% CI 52.6% to 65.5%) specific for mortality. An NPT lactate level of > or =4 mmol/l was 49.1% (95% CI 35.1% to 63.2%) sensitive and 74.3% (95% CI 64.8% to 82.3%) specific for 28-day mortality. CONCLUSION: These results demonstrate the efficacy of the abbreviated MEDS score, the MEW score and NPT venous lactate levels in predicting 28-day mortality in ED patients with sepsis. The abbreviated MEDS score was found to be the best performing risk assessment model which, with prospective validation, may aid early clinical decision-making in ED patients with sepsis and might affect the outcome from sepsis.

Use and barriers to use of laboratory data by clinical dietitians.

The results of this study reveal two general areas of concern for clinical dietitians in the use of laboratory data--their lack of confidence in their own interpretive skills and the perceived resistance of physicians. Although clinical dietitians receive theoretical and applied training on the use of laboratory values in their undergraduate education and dietetic internship, clinical managers should be aware that they need support and continuing education to use their laboratory assessment skills to the fullest. Also, dietitians should demonstrate more clearly to physicians their knowledge, skill, and needs in this area. They should initiate and continue dialogue about the importance of laboratory analysis to nutrition care and improved patient outcome. Evidence-based data and clear documentation of improved medical outcomes should help overcome barriers to use of laboratory data by clinical dietitians.

The incidence of Mycoplasma pneumoniae pneumonia.

BACKGROUND: Mycoplasma pneumoniae has been considered a pathogen for humans since the 1940s. Of the 12 species of Mycoplasma found in humans, M pneumoniae is the most widely recognized pathogen. Morbidity from M pneumoniae results from the combined direct effect of cytotoxins produced by the organisms and the indirect effect of inflammatory responses to the presence of the organisms. Several studies have reviewed the incidence of M pneumoniae pneumonia in selected populations with variable results. By using tests that were not definitive detectors of the organism, earlier studies cited have overestimated the true incidence of this infection. We reevaluate several of these early studies in the light of newer findings. METHODS: Using the key words "Mycoplasma pneumoniae," "pneumonia," "prevalence," "incidence," and "community acquired," the MEDLINE files from 1992 to the present were searched. Articles dating before 1992 were accessed from cross-reference of the more recent articles. Only clinical trials with a sample size greater than 125 were considered. RESULTS AND CONCLUSIONS: M pneumoniae pneumonia occurs in 4- to 5-year cycles and in densely populated areas. Clinical symptoms of M pneumoniae pneumonia include dry cough, sore throat, middle ear involvement, and low-grade fever, as well as additional extrapulmonary manifestations. Bullous myringitis is not a common finding in M pneumoniae infection. Diagnostic tests include cold agglutinins, complement fixation, culture, and enzyme immunoassay. A fourfold rise in M pneumoniae-specific antibody in serum from acutely ill and convalescent patients remains the reference standard for diagnosing the infection. The incidence of M pneumoniae is probably lower than reported in many studies. Using tests that are not diagnostic of the infection can give a falsely elevated incidence of M pneumoniae infection in specific populations.

Performance of Meridian ImmunoCard Mycoplasma test in a multicenter clinical trial.

Serology is the principal laboratory method used to diagnose Mycoplasma pneumoniae infection. Meridian Diagnostics has developed the ImmunoCard Mycoplasma kit, a 10-min card-based enzyme-linked immunosorbent assay (ELISA) designed to detect immunoglobulin M (IgM) antibodies to M. pneumoniae. We compared the ImmunoCard with two M. pneumoniae IgM-specific assays (immunofluorescence assay [IFA] and ELISA) and a standard complement fixation (CF) procedure using 896 specimens submitted to clinical laboratories for M. pneumoniae serology. Equivocal results obtained by CF, IFA, or ELISA were resolved by testing with an additional method or by reviewing patient chart information. The ImmunoCard had sensitivities ranging from 74% compared with the ELISA to 96% compared with CF results with IFA. ImmunoCard specificities ranged from 85% compared with the IgM-specific ELISA to 98% compared with IgM-specific IFA results resolved with clinical chart review. We also compared the ImmunoCard results with consensus results of 694 specimens tested on at least two non-ImmunoCard methods because of the lack of a "gold standard" for M. pneumoniae serology. Overall, the ImmunoCard Mycoplasma IgM assay had 90% sensitivity, 93% specificity, and 92% agreement with the consensus results. The ImmunoCard is technically less complex and requires less equipment that the three other assays. Our results indicate that the ImmunoCard Mycoplasma IgM assay is a valid and simple procedure which can reduce technologist time (and, thus, labor cost) and turnaround time for laboratories analyzing small numbers of specimens (< 10 per batch) submitted for IgM anti-M. pneumoniae testing.

Interleukin-1-mediated release of interleukin-8 by asbestos-stimulated human pleural mesothelial cells.

The pleuropulmonary response to inhaled asbestos frequently involves inflammation and release of various cytokines from lung cells. Among these, interleukin-8 (IL-8) released from the mesothelium could augment inflammation of the pleura by attracting neutrophils to the pleural space. We used cultures of human pleural mesothelial cells (HPMC) to examine the mechanism of IL-8 production by asbestos and cytokines. Suspensions of amosite, chrysotile, or crocidolite asbestos in concentrations as low as 5 micrograms/ml enhanced release of IL-8 from HPMC during 6 h of incubation at 37 degrees C. Electron microscopy of asbestos-treated HPMC showed that the cells avidly engulfed each of the different types of asbestos fibers. Two proinflammatory cytokines, interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha, enhanced IL-8 release within 2 h and had an even greater effect after 6 h. Release of IL-8 was measured by an enzyme-linked immunosorbent assay, and functional activity of the cytokine was assessed by chemotaxis of human neutrophils. Identity of IL-8 in HPMC supernatants was established by absorption with an antibody to IL-8. Preincubation of HPMC with IL-1 receptor antagonist (IL-1ra) significantly decreased release of IL-8 after stimulation with amosite or crocidolite asbestos. We conclude that HPMC release IL-8 in response to asbestos stimulation and that the response is, in part, mediated by IL-1, mainly in the form of IL-1 alpha.

A bacterial protease perturbs the paracellular barrier function of transporting epithelial monolayers in culture.

Tight junctions between cells and adhesion to the substratum maintain the barrier function of epithelia throughout the body. Damage to the epithelial barrier by microbial products allows penetration of bacteria and promotion of infection. We studied the effects of Pseudomonas elastase (PE) on the barrier function of epithelia by using Madin-Darby canine kidney (MDCK) epithelial cells; these cells form tight junctions (zonula occludens [ZO]) in vitro. PE decreased electrical resistance across the monolayers in a concentration- and time-dependent manner. Immunostaining of selected proteins of the ZO and zonula adherens was used to explore the effects of PE on junctional proteins. PE-treated monolayers of MDCK cells had markedly decreased immunostaining of ZO-1, a protein of the ZO, but light microscopy of PE-treated cells revealed no obvious morphologic changes. A chromium release assay indicated that, even with marked changes in transmonolayer electrical resistance, the permeability defect was not due to membrane disruption. Fluorescence staining of F-actin indicated diminution of cellular microfilaments in PE-treated cells, but E cadherin (uvomorulin), a protein of the zonula adherens, was unaffected by the enzyme. Elastases from porcine pancreas and human leukocytes with similar enzymatic activity (6 U/ml) did not decrease transmonolayer electrical resistance or degrade ZO-1. These results suggest that PE disturbs the barrier function of epithelial monolayers, in part, by changing the cell architecture and altering at least one protein of the ZO.

Aerosolized Pseudomonas elastase and lung fluid balance in anesthetized sheep.

The role of the lung epithelium in lung fluid balance was studied by ventilating anesthetized sheep with an aerosol of 20 mg of elastase from Pseudomonas aeruginosa (Ps. elastase) to increase lung epithelial permeability without affecting lung endothelial permeability or lung vascular pressures. Ps. elastase had no effect on the lung vascular pressures, the alveolar-arterial PO2 gradient (A-aPO2), the flow or protein concentration of the lung lymph, or the postmortem water volume of the lungs. The morphological alveolar flooding score in these sheep was 2.5 times the control level, but this was only marginally significant. Elevation of the left atrial pressure by 20 cmH2O alone increased the postmortem lung water volume but had no effect on A-aPO2, the alveolar flooding score, or the lung epithelial permeability assessed by the clearance of 99mTc-labeled human serum albumin. Addition of aerosolized Ps. elastase to these sheep had no effect on the total lung water volume, but it caused a redistribution of water into the air spaces, as evidenced by significant increases in the alveolar flooding score and A-aPO2 (P less than 0.01). Elevation of the left atrial pressure by 40 cmH2O without elastase caused the same response as elevation of the left atrial pressure by 20 cmH2O with elastase, except the higher pressure caused a greater increase in the total lung water volume. We conclude that alteration of the integrity of the lung epithelium with aerosolized Ps. elastase causes a redistribution of lung water into the alveoli without affecting the total lung water volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Laboratory diagnosis of bacterial meningitis.

Bacterial meningitis is relatively common, can progress rapidly, and can result in death or permanent debilitation. This infection justifiably elicits strong emotional reactions and, hopefully, immediate medical intervention. This review is a brief presentation of the pathogenesis of bacterial meningitis and a review of current knowledge, literature, and recommendations on the subject of laboratory diagnosis of bacterial meningitis. Those who work in clinical microbiology laboratories should be familiar with the tests used in detecting bacteria and bacterial antigens in cerebrospinal fluid (CSF) and should always have the utmost appreciation for the fact that results of such tests must always be reported immediately. Academic and practical aspects of the laboratory diagnosis of bacterial meningitis presented in this review include the following: anatomy of the meninges; pathogenesis; changes in the composition of CSF; etiological agents; processing CSF; microscopic examination of CSF; culturing CSF; methods of detecting bacterial antigens and bacterial components in CSF (counter-immunoelectrophoresis, coagglutination, latex agglutination, enzyme-linked immunosorbent assay, Limulus amebocyte lysate assay, and gas-liquid chromatography); use of the polymerase chain reaction; and practical considerations for testing CSF for bacterial antigens.

Neutral endopeptidase from nuchal ligament of fetal calves.

The nuchal ligament of unborn calves contains a neutral endopeptidase that is biochemically and immunologically similar to the neutral endopeptidase (NEP), or enkephalinase, from human kidney. Enzymatic activity was inhibited more than 90% by phosphoramidon (1 microM). The specific activity in membrane fractions, as determined by hydrolysis of the dansylated substrate, DAPGN, was similar in tissue from fetuses of gestational ages ranging from 100 to 280 days. NEP activity in adult ligament tissue, however, was less than 10% of that in fetal tissue. Fibroblasts dissociated from ligament tissue by collagenase displayed less NEP activity than did preparations of intact ligament, and activity was even lower in cultured cells. By contrast, fibroblasts cultured from fetal calf lungs had NEP activity comparable to that in the ligament tissue. When ligament fibroblasts were cultured on subcellular matrices derived from fetal lung fibroblasts the NEP activity increased relative to those cultured on plastic alone. These studies confirm the presence of neutral endopeptidase (NEP) in the nuchal ligament of the fetal calf. The consistent activity through a range of gestational ages and the influence of the subcellular matrix suggest that this enzyme might be involved in growth of the ligament during fetal life.

Liberation of a neutrophil enzyme-releasing peptide from the surface of human alveolar macrophages.

The human alveolar macrophage product, enzyme-releasing peptide (ERP), has a molecular mass of 8,000 Da, and releases azurophilic and specific granule constituents from neutrophils. A murine monoclonal anti-ERP antibody (12E10H), previously used to show a lack of antigenic identity between ERP and C5a, interleukin 1, tumor necrosis factor, and gamma-interferon, showed no cross-reactivity with interleukin 8. 12E10H and a fluorescein-labeled second antibody were used to visualize ERP on the macrophage surface. ERP was removed from alveolar macrophages by a 3-min incubation with 5 X 10(-7) M bovine pancreatic trypsin at 37 degrees C. The washed trypsinized cells could readhere to plastic and exclude trypan blue. Dilution of the trypsin-derived ERP released myeloperoxidase from cytochalasin-B-treated neutrophils dose dependently. The enzyme-releasing ability of the trypsin-derived material was removed by immunoprecipitation using antibody 12E10H bound to Staphylococcal protein A Sepharose 4B. The estimated molecular mass of the trypsin-derived ERP (by molecular sieve chromatography on HPLC) was approximately 8,500 Da. Other proteases (plasmin, thrombin, and cathepsin G) also released ERP from the cell surface, but the ERP was not an active secretagogue for neutrophils. However, macrophages cultured with protease inhibitors did not show decreased ERP accumulation in the medium. Our data indicate that ERP exists on the surface of human alveolar macrophages and can be released by proteases found within the lung environment in some disease states.

A modified bronchoalveolar lavage procedure that allows measurement of lung epithelial lining fluid volume.

We replaced the standard serial bronchoalveolar lavage technique with a new "rewash" lavage procedure to allow estimation of the volume and protein concentration of the epithelial lining fluid (ELF) in anesthetized sheep. A bronchoscope 6.0 mm in diameter wedged in an airway was used to lavage a segment of lung with four cycles of instillation and aspiration of the lavage solution containing a radioactive tracer (technetium pertechnetate, 99mTcO4-). Errors caused by the fall in concentration of the tracer during the lavage were minimized by extrapolating the tracer concentration back to time zero when the lavage solution had mixed with the ELF, but had not had time to be affected by loss of the tracer or influx of fluid from the interstitium. In control sheep, the ELF of these lavaged segments had a mean volume of 1.6 +/- 1.0 ml and a mean protein concentration that was 26 +/- 19% of the protein concentration measured in the plasma. Increasing the left atrial pressure 19 +/- 5 cm H2O to cause "cardiac lung edema" had no significant effect on the ELF volume, but it increased the mean protein concentration to 57 +/- 30% of the plasma value (p less than 0.01). Lung injury caused by intravenous oleic acid caused lung edema, increased the mean ELF volume to 6.8 +/- 2.2 ml, and increased the mean ELF protein concentration to 86 +/- 26% of the plasma value (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Pseudomonas aeruginosa elastase on alveolar epithelial permeability in guinea pigs.

Elastase-deficient mutants of Pseudomonas aeruginosa are less virulent than the wild type and are easily cleared from the lungs of guinea pigs. The effect of P. aeruginosa elastase on lung epithelium, however, is not yet understood. We addressed the hypothesis that breach of the epithelial barrier by elastase from P. aeruginosa allows invading organisms and toxic substances to penetrate the interstitium. We measured the clearance of aerosolized technetium-labeled albumin (molecular weight, 69,000) from the lungs of anesthetized guinea pigs with the aid of a gamma camera and a dedicated computer. Aerosols of the elastase (0.1 to 5 micrograms) increased the rate of clearance of labeled albumin from the lungs in proportion to the elastase dose. Electron microscopic studies using horseradish peroxidase as a tracer revealed that elastase interrupts intercellular tight junctions of the epithelial lining, thereby increasing the permeability to macromolecules. The amounts of elastase used in this report did not cause interstitial or alveolar edema, as determined by both postmortem extravascular lung water volume measurement and morphological examination. The data indicate that the elastase is a potentially important virulence factor in acute lung infection.

Wound infection caused by Branhamella catarrhalis.

Branhamella catarrhalis was isolated from sputum, tracheal secretions, and a nonhealing and infected thoracic surgical wound in a 59-year-old woman who had a history of a chronic, interstitial fibrosis and who had undergone an open lung biopsy procedure. The patient's upper respiratory tract was the likely source of the organism. To our knowledge, this is the first report of a wound infection caused by B. catarrhalis.

Correlation of urine pH with the detection of cytomegalovirus by the shell vial technique.

The influence of the pH of urine on the detection of cytomegalovirus (CMV) by the shell vial assay was evaluated. The pH values of 295 urine specimens ranged from 4.7 to 8.5 (mean 6.3) and were not significantly different in culture-positive versus culture-negative samples. None of the urine specimens appeared to be toxic for the cells used in the shell vial assay. We recommend inoculation of urine specimens into shell vials without adjustment of pH.

Detection of Vibrio vulnificus cytolysin in V. vulnificus-infected mice.

Enzyme-linked immunosorbent assays using polyclonal and monoclonal antibodies specific for V. vulnificus cytolysin detected the toxin in an extract of skin lesions and in serum from mice showing local and systemic V. vulnificus disease after subcutaneous injection of the bacterium. The cytolysin also was detected in skin lesions by an indirect immunofluorescence procedure using polyclonal and monoclonal antibodies. Our findings provide direct evidence that the cytolysin is produced in vivo during the development of the disease process, and this observation is consistent with the hypothesis that the toxin is involved in the pathogenesis of V. vulnificus disease.

Laboratory diagnosis of systemic fungal diseases.

The increase in the number of fungal infections seen in debilitated and immunocompromised patients in the last several years makes it necessary to consider all fungi as potential pathogens. Clinical microbiology laboratories are playing increasingly important roles in the recovery, isolation, and identification of these fungi. This article contains specific recommendations and references concerning a practical approach to the laboratory identification of systemic fungi. The proper and timely selection, collection, and transport of specimens is imperative, and clinicians are responsible for appropriate specimen selection to ensure optimal chances of recovery of pathogens. Respiratory tract secretions and blood are excellent sources for detection of disseminated fungal infection. Specimens should be placed into transport media if the sample size is small or if only a small number of organisms are thought to be present. Direct microscopic examination of specimens can provide valuable information, often allowing a clinician to initiate immediate therapy. Specimens that are more likely than others to contain systemic fungi and that should be examined routinely include the following: pulmonary biopsy material, bronchial washes and lavages, specimens from immunocompromised patients, purulent specimens, and specimens suspected of containing a specific fungus. Valuable methods of examining specimens directly include treatment with KOH and calcofluor white. Use of media to recover fungi is the basis of making a laboratory diagnosis of a fungal disease, and the use of proper recovery and subculture media is imperative. Noninhibitory media allow contaminants to grow readily and should be used only to recover fungi from normally sterile body sites or for subculture. Blood-enriched media allow almost all pathogenic and saprophytic fungi to flourish. Therefore, such media, unless they contain antibiotics, should not be used as primary recovery media. Media that contain antibiotics should be used as primary recovery media to prevent overgrowth of pathogenic fungi by contaminants. Yeasts recovered from clinical specimens can be identified by a combination of tests, which include direct microscopic examination, germ tube formation, microscopic morphology of growth on corn meal agar, and ability to utilize certain carbohydrates. Molds recovered from clinical specimens are identified by a combination of growth rate, colonial characteristics, size and shape of hyphae, and microscopic examination of reproductive structures and other fungal elements.(ABSTRACT TRUNCATED AT 400 WORDS)

Local abnormalities of coagulation and fibrinolysis and alveolar fibrin deposition in sheep with oleic acid-induced lung injury.

Extravascular, primarily intra-alveolar, fibrin deposition is a histologic hallmark of acute lung injury in humans and experimental animals, but the mechanisms leading to this finding are poorly understood. To determine whether local abnormalities in the fibrinolytic-procoagulant balance contribute to alveolar fibrin deposition in acute lung injury, we studied bronchoalveolar lavage (BAL) fluids of anesthetized sheep that received intravenous oleic acid. Prominent alveolar fibrin deposition was observed within 2 h after oleic acid-induced lung injury. Procoagulant and fibrinolytic activities were determined in BAL samples of anesthetized, mechanically ventilated sheep before and 2 h after intravenous oleic acid or saline. BAL procoagulant activity was found to be due mainly to tissue factor associated with Factor VII. In baseline BAL samples, we found relatively low levels of procoagulant activity and relatively high levels of fibrinolytic activity. After induction of oleic acid-induced lung injury, the procoagulant activity of BAL was markedly increased, whereas fibrinolytic activity was either depressed or undetectable. Antiplasmin activity was detectable in BAL of sheep after oleic acid-induced lung injury, which contributed at least in part to the depressed fibrinolytic activity observed. These perturbations occurred with the appearance of extensive alveolar fibrin deposition. In control sheep, BAL fibrinolytic activity was decreased, and antiplasmin activity increased modestly after 2 h of mechanical ventilation, but procoagulant activity was unchanged and alveolar fibrin was not observed. Procoagulant activity in lung lymph and plasma after lung injury did not differ from baseline values, and fibrinolytic activity was undetectable in lymph or plasma samples. These data indicate that increased procoagulant activity and concurrent disruption of the balance of coagulation and fibrinolysis establish local conditions that promote acute fibrin deposition in the alveoli of mechanically ventilated, oleic acid-injured sheep.