Effect of the UK Psychoactive Substances Act 2016 on episodes of toxicity related to new psychoactive substances as reported to the National Poisons Information Service. A time series analysis.

BACKGROUND: There have been recent increases in use of new psychoactive substances (NPS) associated with acute health harms including hospital presentations due to toxicity and increasing numbers of deaths. In response, the UK Government enacted generic legislation on 26th May 2016 (the Psychoactive Substances Act) making it an offence to produce, possess with intent to supply, supply, import or export, or possess within a custodial setting a psychoactive substance. We studied the impact of this Act on monthly frequency of enquiries made by health professionals to the UK National Poisons Information Service (NPIS) about NPS. We also studied five commonly used 'conventional' drugs of misuse that had been controlled prior to January 2009. METHOD: Anonymised clinical enquiries to the NPIS and accesses to the poisons information database TOXBASE were reviewed retrospectively from January 2009 to December 2018 to ascertain the trends in reported toxicity for NPS, cocaine, heroin, cannabis, amphetamines and MDMA. Data were analysed using interrupted time series analysis with the date of the PSA used as an independent predictor. RESULTS: Over the period of study there were 3,866 NPIS telephone enquiries and 79,271 TOXBASE user accesses made by UK health professionals concerning NPS. There were increases in monthly TOXBASE accesses (t = 7.408, P < 0.0001) and telephone enquiries (t = 4.74, P < 0.001) over the pre-specified period January 2009 to May 2016. Comparing the period after the PSA with that before, there were significant reductions in TOXBASE accesses (t = -3.327, P < 0.001) and telephone enquiries (t = -6.97, P < 0.001), although reductions started before May 2016. There were no significant changes for the five conventional drugs. There were significant reductions in telephone enquiries (t = -3.418, P < 0.001) and non-significant reductions in TOXBASE accesses (t = -1.713, P = 0.089) for NPS between June 2016 and December 2018. Increases in telephone enquiries for cocaine and reductions TOXBASE accesses for MDMA were also observed over that period. CONCLUSIONS: There have been significant recent reductions in NPIS enquiry activity relating to NPS; although these began before enactment of the PSA in May 2016.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Late Survival in Nonoperated Patients with Infrarenal Abdominal Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Historical studies report high rupture rates in patients with nonoperated abdominal aortic aneurysms (AAAs) of > 5.5 cm diameter, although a recent audit has questioned this. METHODS: This was a retrospective review of 138/764 (18%) patients with AAAs evaluated in a preassessment anaesthetic clinic (PAC) between 2006 and 2012, who either did not undergo elective AAA repair or who underwent deferred repair. The remaining 626 underwent repair. Patients with severe comorbidities (dementia, advanced malignancy, life-expectancy < 1 year) and not referred to PAC were excluded. RESULTS: At a median of 27 months, 71 (52%) died, 36 (51%) following rupture. Cumulative survival, free from rupture or surgery for acute symptoms, was 96% at 1 year, 84% at 3 years, and 64% at 5 years, where baseline AAA diameters were 5.5-6.9 cm. For diameters ≥ 7 cm, survival, free from rupture, was 65% at 1 year, 29% at 3 years, and 0% at 5 years. Median interval to rupture was 47 months (AAA diameter 5.5-6.9 cm) and 21 months where baseline diameters were ≥ 7 cm. Rupture accounted for 32% of late deaths in patients with AAAs of 5.5-5.9 cm diameter, 46% in those with AAAs measuring 6.0-6.9 cm in diameter, and 71% in patients with AAA measuring ≥ 7 cm in diameter. CONCLUSION: Approximately half of all late deaths in this nonoperated cohort were not AAA related, suggesting that even had repair been undertaken, it would not have prolonged patient survival. The incidence of rupture in "high-risk" patients with an AAA < 7 cm diameter was < 5% at 1 year, thereby giving ample time to optimise risk factors and improve pre-existing medical conditions prior to undertaking a deferred intervention. Even if these patients did not undergo surgical repair, the risk of late rupture was relatively low. By contrast, nonoperated patients with AAAs ≥ 7 cm in diameter face a very high risk of rupture and will probably benefit from elective surgery, with the caveat that a higher procedural risk might have to be incurred.

Comparison of vestipitant with ondansetron for the treatment of breakthrough postoperative nausea and vomiting after failed prophylaxis with ondansetron.

BACKGROUND: Postoperative nausea and vomiting (PONV) is common; ondansetron is often used as prophylaxis or for breakthrough episodes. Vestipitant is a neurokinin 1 (NK-1) receptor antagonist that is effective for prophylaxis, but its efficacy for treating established PONV is unknown. This study was performed to evaluate the efficacy and safety of vestipitant, compared with ondansetron for the treatment of breakthrough PONV in patients who had already received prophylactic ondansetron before surgery. METHODS: A multicentre, randomized, single-blind (sponsor-open), parallel group study. Of 527 surgical patients, 130 (25%) had breakthrough PONV and were equally randomized to one of six i.v. doses of vestipitant (4-36 mg) or ondansetron 4 mg. The primary endpoint was the rate of patients exhibiting complete response, defined as no emesis and no further rescue medication from 10 min after infusion up to 24 h after surgery or hospital discharge. RESULTS: All doses of vestipitant were non-inferior to ondansetron in treating PONV after failed prophylaxis with ondansetron. However, vestipitant was superior to ondansetron in decreasing episodes of postoperative emesis and retching. The complete response rate analysis using Bayesian model averaging indicated that no vestipitant dose was superior to ondansetron. Nausea numerical rating scale scores and the times-to-PONV or discharge were similar between the vestipitant and ondansetron treatment groups. CONCLUSIONS: Although overall efficacy was non-inferior between vestipitant and ondansetron, the rate of emesis was lower with vestipitant. These data suggest that vestipitant may be a useful agent for the management of PONV, similar to other NK-1 antagonists. CLINICAL TRIAL REGISTRATION: NCT01507194.

Carotid and coronary disease management prior to open and endovascular aortic surgery. What are the current guidelines?

Several bodies produce broadly concurring and updated guidelines for the evaluation and treatment of cardiovascular disease in both surgical and non-surgical patients. Recent developments include revised recommendations on preoperative stress testing, referral for possible coronary revascularization and medical management. It is recognized that non-invasive cardiac tests are relatively poor at predicting perioperative risk, and "prophylactic" coronary revascularization has a limited role. The planned aortic intervention (open or endovascular repair) also influences preoperative management. Patients presenting for elective abdominal aortic aneurysm (AAA) repair should only be referred for cardiological testing if they have active symptoms of coronary artery disease (CAD), known CAD and poor functional exercise capacity, or multiple risk factors for CAD. Coronary revascularization before AAA surgery should be limited to patients with established indications, so cardiac stress testing should only be performed if it would change management i.e. the patient is a candidate for and would benefit from coronary revascularization. When endovascular aortic repair is planned, it is reasonable to proceed to surgery without further cardiac stress testing or evaluation unless otherwise indicated. All non-emergency patients require medical optimization, but perioperative beta blockade benefits only certain patients. Some of the data informing recent guidelines have been questioned and some guidelines are being revised. Current guidelines do not specifically address the management of patients with known or suspected carotid artery disease who may require aortic surgery. For these patients, an individualized approach is required. This review considers recent guidelines. Algorithms for investigation and management based on their recommendations are included.

Factors influencing short- and long-term mortality after lower limb amputation.

Mortality after lower limb amputation is high, with UK 30-day mortality rates of 9-17%. We performed a retrospective analysis of factors affecting early and late outcome after lower limb amputation for peripheral vascular disease or diabetic complications at a UK tertiary referral vascular centre between 2003 and 2010. Three hundred and thirty-nine patients (233 male), of median (IQR [range]) age 73 (62-79 [26-92]) years underwent amputation. Thirty-day mortality was 12.4%. On regression modelling, the risk of 30-day mortality was increased in patients of ASA grade ≥ 4 (OR 4.23, 95% CI 2.07-8.63), p < 0.001 and age between 74 and 79 years (OR 3.8, 95% CI 1.10-13.13), p = 0.04 and older than 79 years (OR 4.08, 95% CI 1.25-13.25), p = 0.02. Peri-operative (30-day) mortality for these groups was 23.2%, 13.7% and 18.8%, respectively. Survival and Cox regression analysis demonstrated that long-term mortality was associated with: age 74-79 years (HR 2.15, 95% CI 1.38-3.35), p = 0.001; age > 79 years (HR 2.78, 95% CI 1.82-4.25), p < 0.001; ASA grade ≥ 4 (HR 2.04, 95% CI 1.51-2.75), p < 0.001; out-of-hours operating (HR 1.51, 95% CI 1.08-2.10), p = 0.02; and chronic kidney disease stage 4-5 (1.57, 95% CI 1.07-2.30), p = 0.02. Anaesthetic technique was associated with long-term mortality on survival analysis (p = 0.04), but not when analysed using regression modelling. Mortality after lower limb amputation relates to patient age, ASA, out-of-hours surgery and renal dysfunction. These data support lower limb amputations' being performed during daytime hours and after modification replace with 'of ' correctable risk factors.

Acute ill-health in sheep farmers following use of pesticides.

BACKGROUND: Sheep farmers often complain of acute ill-health, known colloquially as 'dipper's flu', immediately after treating sheep with pesticides. There have been few prospective epidemiological studies to determine it's nature and incidence. Aims To determine the nature and frequency of symptoms occurring in farmers treating sheep for ectoparasites. METHODS: In a longitudinal study, farmers who planned to treat their sheep for ectoparasites were recruited. Farmers kept a symptom diary for 7 days after starting pesticide treatment. Symptoms reported on days 1-6 were compared to those reported on day 7 via the McNemar's test and with previously published literature definitions of dipper's flu. A principal component analysis (PCA) was carried out on new symptoms occurring on days 1 and 2. RESULTS: Of 781 farmers recruited, 352 farmers (45%) completed the symptom diary. In the 7 days after starting pesticide treatment, symptom complex reporting typically peaked on day 2, but few farmers (7 or less; <2%) were identified as having dipper's flu using literature definitions. However, PCA identified two new patterns of symptom complexes that accounted for 35% of the variance. A pyrexial factor consisted of four symptom complexes (feeling generally ill; feeling sweaty, shivery, feverish, hot or cold; feeling unusually tired; and having a headache) and a respiratory factor consisted of three symptom complexes (runny, stuffy, blocked or irritated nose; cough, shortness of breath or wheeze; and eye irritation). CONCLUSIONS: Existing definitions of dipper's flu do not adequately describe symptoms that occur following the treatment of sheep for ectoparasites.

Assessment of nociceptin/orphanin FQ and micro-opioid receptor mRNA in the human right atrium.

BACKGROUND: The expression of micro (mu: MOP) and nociceptin/orphanin FQ (NOP) receptors in the human myocardium is controversial. In this polymerase chain reaction (PCR)-based study using human right atrial biopsies, we have (i) probed for mRNA encoding NOP receptor and its endogenous peptide precursor, ppN/OFQ, and mRNA encoding MOP and (ii) attempted to correlate expression with cardiac function. METHODS: mRNA encoding MOP, NOP, and the precursor for NOP (ppN/OFQ) was assessed by quantitative real-time PCR (Q-PCR) using validated TaqMan primers and compared with a housekeeper (glyceraldehyde-3-phosphate dehydrogenase, GAPDH). Q-PCR data are expressed as the difference in cycle threshold (DeltaC(t)=C(tGene of interest)-C(tGAPDH): high value, low expression) and patients were grouped according to left ventricular ejection fraction (LVEF). RESULTS: Forty patients were recruited; NOP, MOP, and ppN/OFQ mRNA were measured in 38, 29, and 10 patients, respectively. DeltaC(t) (median and range) values for NOP and MOP were 10.9 (7.8-13.7) and 16.0 (12.3-18.9), respectively, representing low expression of MOP and approximately 34-fold more NOP. MOP mRNA was not detected in seven samples and with DeltaC(t) values of approximately 20, ppN/OFQ was considered absent. When patients were grouped into normal (>50%) and impaired (<50%) LVEF, there was no difference between the groups for either NOP or MOP. In some patients, intraoperative LVEF was estimated using transoesophageal echocardiography, and there was no correlation with either NOP or MOP. CONCLUSIONS: The human right atrium of patients with coronary artery disease and heart failure expresses mRNA encoding NOP and possibly low levels of MOP. This does not correlate with degree of cardiac dysfunction. In addition, the atrium does not express ppN/OFQ mRNA.

Urotensin II receptor expression in human right atrium and aorta: effects of ischaemic heart disease.

BACKGROUND: Urotensin II (UII) and its receptor UT are involved in control of the cardiovascular system and are implicated in heart failure. We measured UT expression by quantitative PCR (Q-PCR) in atrial and aortic tissue, and plasma UII while simultaneously assessing cardiac function in 40 patients undergoing coronary artery bypass surgery. METHODS: RNA extracted from atrial and aortic samples was probed with specific Q-PCR UT and housekeeper (glyceraldehyde-3-phosphate dehydrogenase, GAPDH) TaqMan primers. Plasma UII was measured using radioimmunoassay. Left ventricular ejection fraction (LVEF) was measured using preoperative trans-thoracic echocardiography and ventriculography, and intraoperatively using transoesophageal echocardiography. Q-PCR data are expressed as difference in cycle threshold (DeltaC(t)=C(tUT)-C(tGAPDH): high number indicates low expression). RESULTS: There was no difference in DeltaC(t) in either atrium or aorta between patients with normal (LVEF >50%) or those with impaired (LVEF <50%) preoperative systolic function. There was a weak negative correlation (r(2)=0.245, P=0.031) between intraoperative LVEF and DeltaC(t) in 19 patients possibly indicating down-regulation of UT with worsening LVEF. Atria expressed significantly more UT than aorta (P=0.011). In the absence of non-diseased controls, plasma UII was higher than a historical control group. CONCLUSIONS: This is the first study to simultaneously measure UT (mRNA), UII, and cardiovascular function. Collectively, these pilot data may suggest a down-regulation of UT within the right atrium of patients with heart failure.

Arterial pressure management and carotid endarterectomy.

Acute perioperative changes in arterial pressure occur frequently, particularly in patients with cardiovascular disease or those receiving vasoactive medications, or in relation to certain cardiovascular surgical procedures. Both hypo- and hypertension are common in patients undergoing carotid surgery because of unique patho-physiological and surgical factors. Poor arterial pressure control is associated with increased morbidity and mortality after carotid endarterectomy, but good control of arterial pressure is often difficult to achieve in practice. New guidelines have emphasized the benefits of performing carotid surgery urgently in patients with acute neurological symptoms. This strategy may make perioperative arterial pressure control more challenging. However, few specific data are available to guide individual drug therapy. The incidence, implications, and aetiology of haemodynamic instability associated with carotid surgery are reviewed, and some recommendations made for its management. Close monitoring and titration of therapy are probably the most important considerations rather than specific choice of agents.

Quantitative risk-benefit analysis of natalizumab.

OBJECTIVE: To model the long-term risks and benefits of natalizumab in individuals with relapsing multiple sclerosis (MS). METHODS: We created a Markov model to evaluate treatment effects on reducing relapses and slowing disease progression using published natural history data and clinical trial results. Health changes, measured in quality-adjusted life-years (QALYs), were based on patient health preferences. Patient cohorts treated with no disease-modifying treatment, natalizumab, subcutaneous interferon beta-1a, and a theoretical "perfect" MS treatment were modeled. Sensitivity analysis was used to explore model uncertainty, including varying risks of developing progressive multifocal leukoencephalopathy (PML). RESULTS: Treatment with natalizumab resulted in 9.50 QALYs over a 20-year time horizon, a gain of 0.80 QALYs over the untreated cohort and 0.38 QALYs over interferon beta-1a. The health loss due to PML was small (-0.06 QALYs). To offset natalizumab's incremental health gain over interferon beta-1a, the risk had to increase from 1 to 7.6 PML per 1,000 patients treated over 17.9 months. The "perfect" MS treatment accumulated 10.59 QALYs over the 20-year time horizon, 1.89 QALYs above the untreated cohort. Interferon beta-1a resulted in greater QALY gains compared with natalizumab if natalizumab's relative relapse reduction was reduced from 68% to 35% or if interferon beta-1a's relative reduction was increased from 32% to 65%. CONCLUSIONS: A more than sevenfold increase in actual risk of progressive multifocal leukoencephalopathy was required to decrease natalizumab's health gain below that of interferon beta-1a, and there remains considerable room for additional gains in health (>50%) beyond those already achieved with current therapies.

Comparison of central venous and external jugular venous pressures during repair of proximal femoral fracture.

BACKGROUND: External jugular venous pressure (EJVP) is a close estimate of central venous pressure (CVP) in patients undergoing mechanical ventilation in the supine position, but the effects of spontaneous respiration and posture on this relationship are not known. In this study, we compared CVP with EJVP measurements in 36 patients undergoing repair of proximal femoral fracture breathing spontaneously in the supine or lateral positions. METHODS: A standard general anaesthetic was administered with patients breathing spontaneously via a laryngeal mask airway and i.v. fluids administered according to an algorithm guided by CVP measurements. CVP and EJVP catheters were placed on the right side of the neck where possible. RESULTS: In the supine position, 185 paired measurements of CVP and EJVP and 79 in the lateral position were recorded by a blinded observer during surgery. In the supine position, the mean difference between CVP and EJVP was -0.3 mm Hg (limits of agreement -2.6 to +1.9 mm Hg, 95% confidence intervals for both upper and lower limits of agreement, respectively, were -2.9 to -2.2 and +1.6 to +2.2 mm Hg). In the lateral position, the mean difference was -1.2 mm Hg (limits of agreement -5.8 to +3.8 mm Hg, 95% confidence intervals -6.8 to -4.5 and +2.7 to +4.9 mm Hg). CONCLUSIONS: These data suggest that EJVP is an acceptable estimate of CVP in the supine position. Agreement was poor in the lateral position but was stronger for estimates of trend rather than absolute values. This could be explained by the direct effects of posture.

Nociceptin and urotensin-II concentrations in critically ill patients with sepsis.

BACKGROUND: The systemic inflammatory response to infection (sepsis) involves widespread organ dysfunction, including changes in immune modulation, cardiovascular derangements, and neural activation. Two neuropeptide/receptor systems, nociceptin/orphanin FQ (N/OFQ) which acts at the non-classical opioid receptor NOP and urotensin-II (U-II) which acts at the urotensin receptor (UT), have been implicated in neural, immune, and cardiovascular system function. In this study, we make measurements of these peptides in critically ill patients. METHODS: Plasma samples from 21 critically ill patients with sepsis were collected over four consecutive days. Plasma N/OFQ and U-II concentrations were determined by radioimmunoassay and compared with biochemical and clinical markers of illness severity, including serum creatinine, bilirubin, platelet and white cell counts, admission APACHE II and serial SOFA scores. RESULTS: Median (inter-quartile range) admission plasma N/OFQ concentrations in sepsis were higher in patients who died within 30 days (n=4) compared with survivors (n=17); 3.0 (2.5-5.0) vs 1.0 (1.0-2.5) pg ml(-1) (P=0.028). Plasma N/OFQ concentrations were increased in a subgroup of five patients who had undergone major gastrointestinal surgery. There were no significant changes in plasma U-II concentrations. There were no correlations between plasma U-II and N/OFQ concentrations and markers of illness severity and organ system dysfunction. CONCLUSIONS: Plasma N/OFQ concentrations were increased in critically ill patients with sepsis who had undergone major gastrointestinal surgery and in patients who subsequently died. Further work is required to clarify the significance of plasma N/OFQ concentrations in sepsis.

Quantifying the risks and benefits of natalizumab in relapsing multiple sclerosis.

Using published data, we quantified the risk and benefits of natalizumab in relapsing multiple sclerosis using quality-adjusted life years (QALYs) as a metric. Over the first 2 years of therapy, the negative health effects from progressive multifocal leukoencephalopathy were small (loss of 0.001 QALYs) relative to the positive effects on relapses and disability resulting in 0.033 QALYs (12 quality-adjusted days) gained. For context, we performed an analogous calculation for interferon beta-1a, which also had a net health benefit of 0.033 QALYs (12 quality-adjusted days).

Does cigarette smoking increase plasma urotensin II concentrations?

OBJECTIVE: Human urotensin II (UII) acts on the urotensin (UT) receptor and is the most potent mammalian vasoconstrictor identified to date. The role of UII in human cardiovascular regulation remains unclear, and the results of plasma measurements have been conflicting, perhaps because different measurement techniques have been used. The effects of cigarette smoking on plasma UII concentrations are unknown. The primary aim of our study was to demonstrate whether cigarette smoking had any effect on plasma UII concentrations in otherwise healthy volunteers. Our secondary aim was to compare the results obtained from assaying simultaneously using both radioimmunoassay (RIA) and immunoluminometric assay (ILMA). METHODS: Blood was taken from 20 healthy male non-smokers and 20 healthy male cigarette smokers. Plasma was separated and stored at -70 degrees C. Samples were batch analysed simultaneously for UII using RIA and ILMA. RESULTS: Median (range) plasma UII concentrations were lower in non-smokers [1.67 (1.0-2.27) pg ml(-1)] compared to smokers [2.62 (1.87-3.46) pg ml(-1)] (P = 0.03) measured using RIA. Those who had smoked a cigarette in the 10 min before sampling had greater concentrations of UII [3.10 (1.87-4.60) pg ml(-1)] compared to controls (P = 0.01). Plasma UII concentrations determined by ILMA were consistently low with no differences between groups. CONCLUSION: The data obtained by RIA show that smoking may increase plasma concentrations of UII with a more pronounced increase when a cigarette has been smoked recently. There was a complete lack of correlation between RIA and ILMA for the whole data set, which suggests that some of the variability in plasma UII reported in the literature may result from differences between assays.

Relationship between perioperative troponin elevation and other indicators of myocardial injury in vascular surgery patients.

BACKGROUND: In 2000 the European Society of Cardiology and the American College of Cardiology published a consensus document revising the definition of myocardial infarction. The usefulness of this revised definition has been challenged. It has been suggested that, rather than any release of cardiac troponin being potentially diagnostic of myocardial infarction, a diagnostic threshold consistent with significant myocardial injury should be defined. METHODS: We studied 65 patients undergoing elective major vascular surgery to examine the relationship between the magnitude of cardiac troponin I (cTnI) and creatine kinase MB fraction (CK-MB) release and clinical signs or symptoms of myocardial injury. cTnI and CK-MB concentrations were measured preoperatively and on the first 4 postoperative days using the ACCESS assay (Beckmann). Patients were considered to have suffered a perioperative myocardial infarction if they had either symptoms or ECG changes consistent with this diagnosis, together with cTnI release. RESULTS: Peak postoperative cTnI concentrations above the lower detection limit of the ACCESS assay (0.06 microg litre(-1)) occurred in 26 patients. Eight of these patients displayed symptoms or ECG changes consistent with myocardial injury. A cTnI level greater than 0.68 microg litre(-1) was found to be consistent with the clinical diagnosis of myocardial infarction. The optimal cut-off for the diagnosis of MI using CK-MB was 40.4 microg litre(-1). CONCLUSIONS: These data suggest that further studies are required to define the optimal cardiac troponin diagnostic threshold for the diagnosis of myocardial infarction in the non-cardiac surgery population.

Impairment of sustained attention after major gynaecological surgery.

BACKGROUND AND OBJECTIVES: The sustained attention to response task (SART) test is a sensitive indicator of deficits in sustained attention and is simple to perform. Sustained attention is impaired for a short period after minor surgery under general anaesthesia but the magnitude and duration of this effect after major surgery is unknown. We used the SART test to investigate deficits in sustained attention in patients undergoing major surgery under general anaesthesia. METHODS: The SART test was completed before surgery and at 24, 48 and 72 h postoperatively by 20 ASA I-II female patients (mean age 48.6 yr) undergoing total abdominal hysterectomy under general anaesthesia. It was also completed by 20 age-matched female controls at similar time intervals to evaluate the effect of repeated test performance. RESULTS: There was a significant (P < 0.05) interaction between the groups in number of errors made (a measure of sustained attention deficit). The number of errors decreased in control subjects on repeated performance of the SART test but remained unchanged in patients undergoing total abdominal hysterectomy. The differences between groups remained significant after 72 h (P < 0.05). Patients' overall response times slowed significantly at 24-48 h (P < 0.05), but this recovered by 72 h after surgery. In contrast, overall response times in the control group tended to accelerate on repeated performance of the SART. CONCLUSIONS: The results of this study suggest that 72 h following major surgery patients have deficits in sustained attention compared with controls. Control subjects demonstrated a marked learning effect on repeated test performance compared with patients.

Using the Sustained Attention to Response Test to detect cognitive dysfunction after day case surgery.

BACKGROUND AND OBJECTIVE: Cognitive dysfunction has been reported after general anaesthesia, but its assessment is time consuming and difficult to evaluate. This pilot study assessed the feasibility of using the Sustained Attention to Response Test to assess 35 ASA I-II adults (mean age 31.6 yr) undergoing day case surgery under general anaesthesia, and 25 ASA I-II adults (mean age 47.8 yr) undergoing day case surgery under local anaesthesia. METHODS: The Sustained Attention to Response Test was performed before surgery and repeated 2 h after surgery. RESULTS: When patients repeated the test after surgery under local anaesthesia, the number of incorrect responses increased, but reaction times decreased (P < 0.05). Following general anaesthesia, the number of incorrect responses increased (P < 0.05), but reaction times remained unchanged. CONCLUSIONS: The Sustained Attention to Response Test is simple to administer and may be a useful tool when comparing different anaesthetic techniques and their effects on postoperative deficits in sustained attention.

Comparison of external jugular and central venous pressures in mechanically ventilated patient.

We compared central venous pressures, measured via a 150 mm triple lumen catheter in the internal jugular vein with simultaneous external jugular venous pressures, measured with a 5 mm cannula in the external jugular vein, in 24 patients undergoing major surgery. Patients were mechanically ventilated in the supine position. Six sets of paired measurements of mean central venous pressure and mean external jugular venous pressure were taken by a blinded observer, in random order and at end-expiration at 30-min intervals during surgery. Four patients were not studied because of a failure to cannulate the external jugular vein. The remaining 20 patients yielded 111 sets of paired measurements. The mean difference between external jugular venous pressure and central venous pressure was 0.3 mmHg over a range of central venous pressure of 0-22 mmHg. Limits of agreement were 3.6 to +3.0 mmHg (95% CI 4.1 to +3.5 mmHg). We conclude that external jugular venous pressure is an accurate estimate of central venous pressure in surgical patients undergoing mechanical ventilation.