Machine learning to predict myocardial injury and death after non-cardiac surgery.

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively.

A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery.

Chronic postoperative pain is common after breast cancer surgery. Peri-operative lidocaine infusion may prevent the development of chronic postoperative pain, but a large-scale trial is required to test this hypothesis. It is unclear whether a pragmatic, multicentre trial design that is consistent with expert guidance, addresses the limitations of previous studies, and overcomes existing translational barriers is safe, effective and feasible. We conducted a double-blind, randomised controlled pilot study in 150 patients undergoing breast cancer surgery across three hospitals in Western Australia. Patients received lidocaine, or equivalent volumes of saline, as an intravenous bolus (1.5 mg.kg-1 ) and infusion (2 mg.kg-1 .h-1 ) intra-operatively, and a subcutaneous infusion (1.33 mg.kg-1 .h-1 ) postoperatively for up to 12 h on a standard surgical ward, with novel safety monitoring tools in place. The co-primary outcomes were: in-hospital safety events; serum levels of lidocaine during intravenous and subcutaneous infusion; and annualised enrolment rates per site with long-term data capture. In-hospital safety events were rare, and similar in the placebo and lidocaine arms (3% vs. 1%). Median (IQR [range]) serum lidocaine levels during intravenous (2.16 (1.74-2.83 [1.12-6.06]) µg.ml-1 , n = 41) and subcutaneous (1.52 (1.28-1.83 [0.64-2.85]) µg.ml-1 , n = 48) infusion were comparable with previous trials reporting improved pain outcomes. Annualised enrolment approximated 50 patients per site per year, with high levels of protocol adherence and ≥ 99% capture of outcomes at 3 and 6 months. The adjusted odds ratio (95%CI) for postoperative pain at 6 months in the lidocaine arm was 0.790 (0.370-1.684). We conclude that this trial, as designed, is safe, effective and feasible in patients undergoing breast cancer surgery, and a larger-scale trial is planned.

Data on the modulatory effects of a single bolus dexamethasone on the surface marker expression of various leucocyte subsets.

Dexamethasone is frequently administered to surgical patients for anti-emetic prophylaxis. We have examined the immunomodulatory effects of a single bolus of dexamethasone on circulating peripheral blood mononuclear cells (PBMCs) in the same 10 healthy male volunteers, previously used in our investigation on early in vivo effects of a single anti-emetic dose of dexamethasone on innate immune cell gene expression and activation [1]. Blood samples were drawn at baseline, 2 h, 4 h and 24 h. Immune cell phenotypes were examined with flow cytometry. In this data article the expression strength of markers involved in immune activation and immunosuppression as well as maturation, migration, cell death and responsiveness to signalling on monocyte and cDC subsets, as well as NK cells, CD4+ and CD8+ T cells and regulatory T cells (Treg) are presented. These data improve our understanding of the immunomodulatory effects of the glucocorticoid dexamethasone in-vivo, which may be important for the optimisation of treatment regimens as well as the evaluation of new indications for glucocorticoid treatment.

The early in-vivo effects of a single anti-emetic dose of dexamethasone on innate immune cell gene expression and activation in healthy volunteers.

Dexamethasone is often administered to surgical patients for anti-emetic prophylaxis. This study examined the early (up to 24 h) in-vivo effects of dexamethasone (8 mg) to demonstrate the magnitude and temporal nature of changes on circulating peripheral blood mononuclear cell gene expression and activation in 10 healthy male volunteers. Blood samples were drawn at baseline, 2 h, 4 h and 24 h. Gene expression was measured using quantitative real-time polymerase chain reaction. Cytokine expression was measured using multiplex immuno-assays. Innate immune cell phenotypes were examined with flow cytometry. Dexamethasone resulted in rapid transient changes in immunophilin (p = 0.0247), plasminogen activator inhibitor-1 (p = 0.0004), forkhead box P3 (p = 0.0068) and dual specific phosphatase-1 (p = 0.0157) gene expression at 4 h compared with pre-dexamethasone. Plasma interleukin-10 levels increased within 2 h (p = 0.0071) and returned to baseline at 24 h. Reductions in classical (p = 0.0009) and intermediate monocytes (p = 0.0178) and dendritic cells (p = 0.0012) were followed by increases in the level of these populations at 24 h compared with pre-dexamethasone (classical monocytes p = 0.0073, intermediate monocytes p = 0.0271, dendritic cells p = 0.0142). There was a profound reduction in the mean fluorescence intensity of the maturation marker, human histocompatibility leucocyte antigen, at 24 h in all monocyte subsets (p = 0.0002 for classical and non-classical monocytes, p = 0.0001 for intermediate monocytes) and dendritic cells (p = 0.0001). This study confirms rapid transient effects of 8 mg dexamethasone on innate immune cells with the potential to alter the inflammatory response to surgery and provides support for the hypothesis that intra-operative administration may be both immunosuppressive and immune-activating in the immediate peri-operative period.

A survey of antiemetic dexamethasone administration-frequency of use and perceptions of benefits and risks.

Postoperative nausea and vomiting (PONV) is a significant concern for anaesthetists. There are many agents from different classes that are effective in both preventing and treating PONV. Dexamethasone is a very effective antiemetic, but there are concerns regarding its safety. We performed an anonymous survey of a random selection of the fellows of the Australian and New Zealand College of Anaesthetists to ascertain patterns of practice in relation to PONV prophylaxis and treatment and also to determine awareness of the risks and benefits of perioperative dexamethasone administration. The response rate was 33%. From the responses, 71.2% of all patients undergoing general anaesthesia in the respondents' institutions receive PONV prophylaxis in total and 46.6% receive dexamethasone. No respondent gives more than a single dose of dexamethasone and there was an almost equal split between those who administer 4 and 8 mg, with a smaller number dosing on a weight basis. 5HT-3 receptor antagonists and dexamethasone are the preferred first-line PONV prophylactic agents and 5HT-3 receptor antagonists and droperidol are the preferred first-line PONV therapeutic agents. Concerns relating to the safety of dexamethasone were expressed by 80% of respondents. From this survey, we concluded that the PONV practice of the respondents is largely compliant with recent consensus guidelines, although PONV prophylaxis appears to be given more routinely. It also appears that more education is required on issues regarding dexamethasone safety.

The relationship between patient data and pooled clinical management decisions.

A strong relationship between patient data and preoperative clinical decisions could potentially be used to support clinical decisions in preoperative management. The aim of this exploratory study was to determine the relationship between key patient data and pooled clinical opinions on management. In a previous study, panels of anaesthetists compared the quality of computer-assisted patient health assessments with outpatient consultations and made decisions on the need for preoperative tests, no preoperative outpatient assessment, possible postoperative intensive care unit/high dependency unit requirements and aspiration prophylaxis. In the current study, the relationship between patient data and these decisions was examined using binomial logistic regression analysis. Backward stepwise regression was used to identify independent predictors of each decision (at P >0.15), which were then incorporated into a predictive model. The number of factors related to each decision varied: blood picture (four factors), biochemistry (six factors), coagulation studies (three factors), electrocardiography (eight factors), chest X-ray (seven factors), preoperative outpatient assessment (17 factors), intensive care unit requirement (eight factors) and aspiration prophylaxis (one factor). The factor types also varied, but included surgical complexity, age, gender, number of medications or comorbidities, body mass index, hypertension, central nervous system condition, heart disease, sleep apnoea, smoking, persistent pain and stroke. Models based on these relationships usually demonstrated good sensitivity and specificity, with receiver operating characteristics in the following areas under curve: blood picture (0.75), biochemistry (0.86), coagulation studies (0.71), electrocardiography (0.90), chest X-ray (0.85), outpatient assessment (0.85), postoperative intensive care unit requirement (0.88) and aspiration prophylaxis (0.85). These initial results suggest modelling of patient data may have utility supporting clinicians' preoperative decisions.

An analysis of computer-assisted pre-screening prior to elective surgery.

In order to assess the potential utility of guided patient self-assessment as an early preoperative triage tool, a computer-assisted questionnaire delivered by a non-clinician via telephone was 1) compared to face-to-face interview and examination by anaesthetists in outpatient clinics and 2) evaluated as a mechanism to stream patients to day of surgery assessment. In total, 514 patients scheduled for elective surgery in two tertiary public hospitals were assessed initially by telephone and then in an outpatient clinic. Both forms of assessment were marked by panels of specialist anaesthetists, who also provided an opinion on which patients would have been suitable to bypass preoperative anaesthetic outpatient assessment based upon information provided by the telephone interview. Overall, the quality of assessment provided by non-clinician telephone interview was comparable to face-to-face interview by anaesthetists, although more complex issues required face-to-face assessment. Panel review considered that 398 patients (60%) would not have required evaluation by an anaesthetist until the day of surgery, thus avoiding the need to separately attend a preoperative outpatient clinic. The sensitivity of telephone interview provided information to correctly classify patients as suitable for day of surgery evaluation was 98% (95% confidence interval 96 to 99%) with a specificity of 97% (95% confidence interval 92 to 98%). This study demonstrates that remote computer-assisted assessment can produce quality patient health information and enable early patient work-up and triage with the potential to reduce costs through more efficient use of resources.

Extending epidural analgesia for emergency Caesarean section: a meta-analysis.

There is no high-level evidence supporting an optimal top-up solution to convert labour epidural analgesia to surgical anaesthesia for Caesarean section. The aim of this meta-analysis was to identify the best epidural solutions for emergency Caesarean section anaesthesia, with respect to rapid onset and low supplementation of intraoperative block. Eleven randomized controlled trials, involving 779 parturients, were identified for inclusion after a systematic literature search and risk of bias assessment. 'Top-up' boluses were classified into three groups: 0.5% bupivacaine or levobupivacaine (Bup/Levo); lidocaine and epinephrine, with or without fentanyl (LE ± F); and 0.75% ropivacaine (Ropi). Pooled analysis using the fixed-effects method was used to calculate the mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Lidocaine and epinephrine, with or without fentanyl, resulted in a significantly faster onset of sensory block [MD -4.51 min, 95% confidence interval (CI) -5.89 to -3.13 min, P < 0.00001]. Bup/Levo was associated with a significantly increased risk of intraoperative supplementation compared with the other groups (RR 2.03; 95% CI 1.22-3.39; P = 0.007), especially compared with Ropi (RR 3.24, 95% CI 1.26-8.33, P=0.01). Adding fentanyl to a local anaesthetic resulted in a significantly faster onset but did not affect the need for intraoperative supplementation. Bupivacaine or levobupivacaine 0.5% was the least effective solution. If the speed of onset is important, then a lidocaine and epinephrine solution, with or without fentanyl, appears optimal. If the quality of epidural block is paramount, then 0.75% ropivacaine is suggested.

Anti-emetic dexamethasone and postoperative infection risk: a retrospective cohort study.

Nausea and vomiting are common complications of anaesthesia. Dexamethasone is an effective prophylaxis but is immunosuppressive and may increase postoperative infection risk. This retrospective cohort study examined the association between the administration of a single intraoperative anti-emetic dose of dexamethasone (4 to 8 mg) and postoperative infection in 439 patients undergoing single procedure, non-emergency surgery in a university trauma centre. Exclusion criteria included comorbidities, immunosuppressive medications or procedures that confer an increased infection risk. In the 10-week study period and three-month follow-up period, there were 98 documented infections (22.3% of the cohort), of which 43 were detected only on post-discharge follow-up. Anti-emetic dexamethasone was given to 108 patients (24.6%). Stepwise, multivariate logistic regression modelling identified significant associations between female gender, symptomatic reflux, respiratory disease and the risk of infection. The adjusted odds ratio for dexamethasone was 0.88 (0.5 to 1.5, P = 0.656). We did not demonstrate an association between anti-emetic doses of dexamethasone and postoperative infection.

Single dose dexamethasone for postoperative nausea and vomiting--a matched case-control study of postoperative infection risk.

Dexamethasone is an effective prophylaxis against postoperative nausea and vomiting but is immunosuppressive and may predispose patients to an increased postoperative infection risk. This matched case-control study examined the association between the administration of a single intraoperative anti-emetic dose of dexamethasone (4 to 8 mg) and postoperative infection in patients undergoing non-emergency surgery in a university trauma centre. Cases were defined as patients who developed infection between one day and one month following an operative procedure under general anaesthesia. Controls who did not develop infection were matched for procedure, age and gender Exclusion criteria included immunosuppressive medications, chronic glucocorticoid therapy, cardiac surgical and solid-organ transplantation procedures. Sixty-three cases and 172 controls were identified. Cases were more likely to have received dexamethasone intraoperatively (25.4 vs. 11%, P = 0.006), and less likely to have received perioperative antibiotic prophylaxis (60.3 vs. 84.3%, P = 0.001). Stepwise, multivariate conditional logistic regression confirmed these associations, with adjusted odds ratios of 3.03 (1.06 to 19.3, P = 0.035) and 0.12 (0.02 to 0.7, P = 0.004) respectively for the associations between dexamethasone and perioperative antibiotic prophylaxis, with postoperative infection. We conclude that intraoperative administration of dexamethasone for anti-emetic purposes may confer an increased risk of postoperative infection.

Out-of-hours surgery--a snapshot in time.

Anaesthesia in Australia is amongst the safest in the world. This record of safety is under threat from increasing pressures to operate at times of poor human performance, particularly late at night. Our institution has a policy mandating the prioritisation of surgery based on clinical need while minimising the risks associated with after-hours surgery. The policy states that "only Category 1 (urgent, needing immediate surgery) and Category 2 cases which cannot wait until the morning should be done between 2230 and 0800". From 5 March 2007 we performed an eight-week prospective audit of all cases where surgery occurred in this time period. The anaesthetic senior registrar on duty recorded the clinical priority of the case. There were 95 cases commenced between 2230 and 0800 hours during the audit period, of which 28 (30%) were in clear breach of this policy, in some cases delaying urgent surgery. The potential implications of such breaches are significant in the context of worse outcomes for patients undergoing surgery in the after-hours period. When non-urgent cases occupy resources, the capacity of the system to deal with the truly urgent case is significantly impaired. Adequate 'in-hours' resourcing, capacity and appropriate scheduling may be key to maintaining the excellent safety record of anaesthesia. A large study prospectively examining morbidity, error and outcomes of after-hours operating would serve to further elucidate the risk benefit ratio of after-hours operating.

Inflammation, vitamin deficiencies and organ failure in critically ill patients.

It is unknown whether biochemical vitamin deficiencies in critical illness are associated with severity of illness, organ dysfunction, inflammation or mortality. This nested cohort study recruited 98 patients admitted as emergencies to the intensive care unit, who had a stay of greater than 48 hours. Patient data were prospectively collected. Within the first 48 hours of admission, concentrations of C-reactive protein, vitamins A, E, B1, B12 and folate were measured on arterial blood. These measures were then repeated at least once during the later (> 48 hours) period of their stay. Seventy patients (71%) had completed vitamin studies eligible for inclusion in the analysis. Ten patients died (14.3%) during their hospital stay and mortality was associated with age, admission source and severity of illness scores. Vitamin B12 concentration was weakly associated with C-reactive protein concentrations on admission to the intensive care unit (r on days one and two = 0.4 [P = 0.002], 0.36 [P = 0.04], respectively) and with the Sequential Organ Failure Assessment score between days two and four (Spearman's r = 0.361 [P = 0.04], 0.42 [P = 0.02] and 0.48 [P = 0.02], respectively). Vitamin A concentration was weakly associated with the C-reactive protein concentrations on days one and five (Spearman's r = -0.5 [P = 0.001], -0.4 [P = 0.03], respectively). Change in deficiency status of any of the vitamins over time in the first week of intensive care admission did not appear to influence mortality. We conclude that while weak correlations were identified between vitamins A and B12 and C-reactive protein and Sequential Organ Failure Assessment scores, the importance of these associations and their relationship to hospital mortality remain to be determined.

Prevalence of vitamin deficiencies on admission: relationship to hospital mortality in critically ill patients.

Vitamin deficiency is believed to be common in critical illness. Water soluble and antioxidant vitamins are those most frequently used for supplementation in these patients. There are no data to confirm the prevalence of vitamin deficiencies in high-risk emergently admitted intensive care patients, nor their association with hospital mortality. One hundred and twenty-nine consecutive, critically ill patients who were emergently admitted to intensive care were enrolled in this prospective observational cohort study. Patient data including diagnosis, source of admission and severity of illness scores were prospectively collected. Within the first 48 hours of admission, concentrations of C-reactive protein, Vitamins A, E, B1, B12 and folate were measured on arterial blood. Multivariate stepwise logistic regression modelling was performed to examine the association of vitamin concentrations with hospital mortality. Fifty-five patients (43%) had a biochemical deficiency of one of the five vitamins on admission to the intensive care unit. A total of 18 patients died (14%) during their hospital stay (15 of those in the intensive care unit). Moderate correlations with C-reactive protein concentrations were demonstrated for Vitamins B12, A and E (Spearman's r = 0.309, -0.541 and -0.299, P = 0.001, 0.001 and 0.007 respectively). Hospital mortality was significantly associated with age, APACHE II score, admission and maximum Sequential Organ Failure Assessment scores and admission source in the univariate analyses. Multivariate analysis did not demonstrate an association between biochemical deficiency and mortality. Biochemical deficiencies of water-soluble and antioxidant vitamins are common on admission in unplanned or emergency admissions to the intensive care unit, but we could not demonstrate an independent association with hospital mortality.

The pulmonary artery catheter sleeve--protective or infective?

The use of sterile plastic sleeves to protect pulmonary artery catheters (PAC) may decrease infection risk. The catheter may require manipulation but contamination of the sleeve risks inoculating organisms into the patients. We sought to determine whether the sleeve remains sterile and for how long. We conducted a prospective observational study to culture the components of the PAC in a critically ill population. Upon removal we cultured 1) the PAC tip, 2) the PAC introducer exit site, 3) the PAC introducer hub and 4) a sterile irrigant solution which ran down the inside of the protective sleeve. Demographic, catheter and disease variables were also collected. There were 102 PAC episodes amounting to 3952 catheter hours with a mean duration of catheterisation of 39.1 (24.2) hours. There were 17 positive culture results, of which six were positive sleeve fluid cultures. In three of these patients the exit site was culture positive, and the same organism was isolated as within the sleeve. No patient had a positive blood culture. There was no difference between those with and without a positive sleeve culture in terms of demographic or disease variables. The protective sleeve of the pulmonary artery catheter does not remain sterile and should not be considered as a sterile barrier. We believe that manipulating the PAC within the sleeve carries the risk of inoculating the patient with pathogenic organisms. The duration of sterility remains to be determined.

The evaluation of anaesthesia-related information on the Internet.

The quality and accessibility of anaesthesia-related information available to patients on the Internet is a growing concern for the specialty. We sought to evaluate the quality of anaesthesia-related websites using a simple scoring system. The scoring system comprised quality and technical scores individually, and these were also combined into a total score. Test-retest reliability was assessed by calculating intraclass correlation coefficients. We employed the four most popular search engines and one meta-search engine, using the search term "general anaesthesia". Only the first 10 sites retrieved were scored. The intraclass correlation coefficients for all terms demonstrated at least moderate agreement and the total scores demonstrated high consistency r = 0.852, 0.774 (P < 0.001, and P < 0.003 respectively). There were 18 duplicate websites and 32 were scored. There was no difference between search engines for any of the three scores awarded. The majority of websites were rated as either 'poor' or fair' across all scores. Our study indicates that quality anaesthesia-related information is unlikely to be retrieved by patients using the Internet.

The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function.

BACKGROUND: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass elicits a potent reperfusion injury and inflammatory response, more intense in patients with impaired myocardial function. Propofol has antioxidant properties which may attenuate such a response. METHODS: In total, 27 patients with impaired left ventricular function undergoing CABG were randomly allocated to receive either target-controlled infusion propofol (P) or saline (S) immediately before aortic cross-clamp release until 4 h after reperfusion. Troponin-I, Urinary 8-epi PGF-2alpha isoprostane, coronary sinus and systemic malondialdehyde concentrations, Interleukin-6 (IL-6), -8 and -10 concentrations and leucocytes function studies (neutrophil respiratory burst, phagocytosis, CD-11b and CD-18 expression) were measured. RESULTS: Propofol decreased MDA coronary sinus concentration at 1, 3 and 5 min after reperfusion (P<0.01); 60 min after reperfusion a significant difference between the two groups in systemic MDA concentrations was also seen. IL-6 concentration increases were significantly greater in Group S than Group P, 4 h after reperfusion [1118 (1333) pg ml(-1) vs 228 (105) pg ml(-1), P<0.01]. Serum IL-8 concentrations did not increase significantly in either group. Compared with baseline values IL-10 concentrations decreased after reperfusion but the values were higher in the propofol group than in the control group [22 (16) vs 11 (4) pg ml(-1), P<0.05]. No difference in leucocyte function or urinary isoprostane concentrations was demonstrated. CONCLUSION: Propofol attenuates free-radical-mediated lipid peroxidation and systemic inflammation in patients with impaired myocardial function undergoing CABG.

The influence of propofol on the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in reoxygenated human umbilical vein endothelial cells.

BACKGROUND: Leucocytes are a pivotal component of the inflammatory cascade that results in tissue injury in a large group of disorders. Free radical production and endothelial activation promote leucocyte-endothelium interactions via endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) which augment these processes, particularly in the setting of reperfusion injury. Propofol has antioxidant properties which may attenuate the increased expression of these molecules that is observed. METHODS: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia, then returned to normoxic conditions. Cells were treated with saline, Diprivan 5 microg mL(-1) or propofol 5 microg mL(-1), for 4 h after reoxygenation and were examined for ICAM-1 and VCAM-1 expression. RESULTS: Hypoxia did not increase the expression of ICAM-1/VCAM-1. ICAM-1 expression peaked 12 h after reoxygenation (21.75(0.6) vs. 9.6(1.3), P = 0.02). Propofol, but not Diprivan, prevented this increase (8.2(2.9) vs. 21.75(0.6), P = 0.009). VCAM-1 expression peaked 24 h after reoxygenation (9.8(0.9) vs. 6.6(0.6), P = 0.03). Propofol and Diprivan prevented this increase, with no difference between the two treatments observed (4.3(0.3) and 6.4(0.5) vs. 9.8(0.9), P = 0.001, 0.02, respectively). CONCLUSION: These effects are likely to be attributable to the antioxidant properties of propofol, and suggest that propofol may have a protective role in disorders where free radical mediated injury promotes leucocyte-endothelium adhesive interactions.

The influence of propofol on P-selectin expression and nitric oxide production in re-oxygenated human umbilical vein endothelial cells.

BACKGROUND: Reperfusion injury is characterized by free radical production and endothelial inflammation. Neutrophils mediate much of the end-organ injury that occurs, requiring P-selectin-mediated neutrophil-endothelial adhesion, and this is associated with decreased endothelial nitric oxide production. Propofol has antioxidant properties in vitro which might abrogate this inflammation. METHODS: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia and then returned to normoxic conditions. Cells were treated with saline, Diprivan 5 microg/l or propofol 5 microg/l for 4 h after re-oxygenation and were then examined for P-selectin expression and supernatant nitric oxide concentrations for 24 h. P-selectin was determined by flow cytometry, and culture supernatant nitric oxide was measured as nitrite. RESULTS: In saline-treated cells, a biphasic increase in P-selectin expression was demonstrated at 30 min (P = 0.01) and 4 h (P = 0.023) after re-oxygenation. Propofol and Diprivan prevented these increases in P-selectin expression (P < 0.05). Four hours after re-oxygenation, propofol decreased endothelial nitric oxide production (P = 0.035). CONCLUSION: This is the first study to demonstrate an effect of propofol upon endothelial P-selectin expression. Such an effect may be important in situations of reperfusion injury such as cardiac transplantation and coronary artery bypass surgery. We conclude that propofol attenuates re-oxygenation-induced endothelial inflammation in vitro.

Isoprostanes--markers of ischaemia reperfusion injury.

Ischaemia reperfusion injury is a common and important phenomenon that occurs predictably in patients undergoing such procedures as cardiopulmonary bypass, thrombolysis, surgery under tourniquet, organ transplantation or embolectomy. Oxidative stress and the resulting lipid peroxidation play a major role in reperfusion injury. Membrane and cellular dysfunction result and, subsequently, organ injury or failure may ensue. Traditional methods of quantifying ischaemia reperfusion injury, including measurement of malondialdehyde, lack specificity and sensitivity. It was reported in 1990 that isoprostanes, a series of prostaglandin-like compounds, are produced by the free radical-catalyzed peroxidation of arachidonic acid. Measurement of the isoprostane concentration in urine or plasma provides the most reliable, non-invasive method currently available to assess oxidative stress in vivo. Serial measurement of isoprostanes in biological fluids has enhanced our understanding of the mechanisms underlying ischaemia reperfusion injury itself and its role in certain diseases. Furthermore, measurement of the isoprostane concentration provides a means to assess the effects of prophylactic and therapeutic interventions. In the future, the development of rapid, simple assays for isoprostanes offers the potential to assess prognosis during and after ischaemia reperfusion events.

Shoshin beri-beri precipitated by intravenous glucose.

A thiamine deficient patient presented to the emergency department with an acute confusional state, becoming unconscious and hypotensive following the administration of 32 g of intravenous glucose over 4 hr. A dramatic clinical improvement in his cardiovascular and neurological status followed a single intra-venous dose of 250 mg of thiamine. Profound thiamine deficiency was confirmed on biochemical testing. A substantial proportion of hospital patients are thiamine deficient and intravenous dextrose may precipitate cardiovascular collapse and lactic acidosis due to the development of 'shoshin' beriberi. A rapid response to intravenous thiamine may confirm the diagnosis. All patients presenting with acute neurological dysfunction should receive thiamine before glucose-containing solutions are administered.