The ageing practitioner: ANZCA's recommendations.

OBJECTIVES: The aim is to present recommendations of the Australian and New Zealand College of Anaesthetists (ANZCA) with respect to practice implications for ageing specialists, together with brief discussion of effects of ageing on professional medical capabilities and recommendations on preparing to retire from medical practice. CONCLUSIONS: Practitioners should recognise that planning for retirement is part of good management of a medical career, and that the ageing process will inevitably compromise their ability to treat patients safely unless they retire at the appropriate time. Planning should include adequate financial preparation, and cultivation of interests and friends outside medicine. Practitioners should also realise that insight is likely to be compromised, so that they should seek colleagues who are trusted to advise them if/when they begin to lose competency. Lastly all practitioners should ensure that they consult a General Practitioner frequently, and that they have arranged all the proper legal instructions such as a Will, a Power of Attorney and an Advanced Health Directive.The ANZCA recommendations concerning ageing specialists have wide application to all medical specialties, not just for anaesthetists, and therefore all Medical Colleges should generate their own specific recommendations for ageing practitioners and the general effects of fatigue particularly for aged practitioners.

High stretch induces endothelial dysfunction accompanied by oxidative stress and actin remodeling in human saphenous vein endothelial cells.

The rate of the remodeling of the arterialized saphenous vein conduit limits the outcomes of coronary artery bypass graft surgery (CABG), which may be influenced by endothelial dysfunction. We tested the hypothesis that high stretch (HS) induces human saphenous vein endothelial cell (hSVEC) dysfunction and examined candidate underlying mechanisms. Our results showed that in vitro HS reduces NO bioavailability, increases inflammatory adhesion molecule expression (E-selectin and VCAM1) and THP-1 cell adhesion. HS decreases F-actin in hSVECs, but not in human arterial endothelial cells, and is accompanied by G-actin and cofilin's nuclear shuttling and increased reactive oxidative species (ROS). Pre-treatment with the broad-acting antioxidant N-acetylcysteine (NAC) supported this observation and diminished stretch-induced actin remodeling and inflammatory adhesive molecule expression. Altogether, we provide evidence that increased oxidative stress and actin cytoskeleton remodeling play a role in HS-induced saphenous vein endothelial cell dysfunction, which may contribute to predisposing saphenous vein graft to failure.

Anaesthesia for endoscopic sinus surgery.

Endoscopic sinus surgery is commonly performed and has a low risk of major complications. Intraoperative bleeding impairs surgical conditions and increases the risk of complications. Remifentanil appears to produce better surgical conditions than other opioid analgesics, and total intravenous anaesthesia with propofol may provide superior conditions to a volatile-based technique. Moderate hypotension with intraoperative beta blockade is associated with better operating conditions than when vasodilating agents are used. Tight control of CO(2) does not affect the surgical view. The use of a laryngeal mask may be associated with improved surgical conditions and a smoother emergence. It provides airway protection equivalent to that provided by an endotracheal tube in well-selected patients, but offers less protection from gastric regurgitation. Post-operatively, multimodal oral analgesia provides good pain relief, while long-acting local anaesthetics have been shown not to improve analgesia.

Professor Ross Holland: The Special Committee Investigating Deaths Under Anaesthesia (SCIDUA) and his other contributions to anaesthesia.

As a young anaesthetic trainee in 1959 Ross Holland persuaded the Minister of Health in NSW, Australia, to establish SCIDUA, which by law required compulsory reporting for all deaths occurring during anaesthesia or up to 24 hours after cessation of the anaesthetic. The committee was multidisciplinary and, most importantly, had statutory privilege so that no discussions or findings were able to be subpoenaed for other legal investigations or case law. Holland was the foundation secretary of SCIDUA and later Chair. Apart from three years in the 1980s when there were political issues with legal privilege, the committee has met monthly and still meets. Holland was a major figure in antipodean anaesthesia, setting up in 1978 the clinical department at Westmead Hospital Sydney, then in 1987 becoming the foundation Professor to the Department of Anaesthesiology at the University of Hong Kong, and in 1990 foundation Professor and Chair, Department of Anaesthesia and Intensive Care at the University of Newcastle, NSW. Holland had strong historical interests and was responsible for founding the Society for the Preservation of Artefacts of Surgery and Medicine (SPASM) and its associated museum. He also served an important term as Dean of the Faculty of Anaesthetists, Royal Australasian College of Surgeons prior to that Faculty becoming independent as the Australian and New Zealand College of Anaesthetists (ANZCA). Professor Holland received many accolades for these activities during his life, which are noted. It is fitting to recognise his seminal contributions to patient safety over more than 50 years.

Genesis of the College of Intensive Care Medicine of Australia and New Zealand.

In 2009 the College of Intensive Care Medicine (CICM) of Australia and New Zealand was inaugurated in Melbourne, Australia. This College now regulates the education, training and accreditation for specialist intensivists for Australia and New Zealand. CICM origins started in 1975 with the formation of the Section of Intensive Care of the Faculty of Anaesthetists, Royal Australasian College of Surgeons (RACS), which moved through intermediary stages as the Faculty of Intensive Care, Australian and New Zealand College of Anaesthetists (ANZCA) when that College was formed from the former Faculty of Anaesthetists RACS, and then the Joint Faculty of Intensive Care Medicine (ANZCA and the Royal Australasian College of Physicians [RACP]), until becoming completely independent as CICM in 2010. There was a period of about 40-50 years evolution from the first formations of intensive care units in Australia and New Zealand, and discussions by the personnel staffing those units amongst themselves and with Members of the Board of the Faculty of Anaesthetists RACS, to the formation of the Section of Intensive Care, then through two intermediary Faculties of Intensive Care Medicine, to the final independent formation of the College of Intensive Care Medicine of Australia and New Zealand in 2010.

A high-throughput mechanofluidic screening platform for investigating tumor cell adhesion during metastasis.

The metastatic spread of cancer is a major barrier to effective and curative therapies for cancer. During metastasis, tumor cells intravasate into the vascular system, survive in the shear forces and immunological environment of the circulation, and then extravasate into secondary tumor sites. Biophysical forces are potent regulators of cancer biology and are key in many of the steps of metastasis. In particular, the adhesion of circulating cells is highly dependent upon competing forces between cell adhesion receptors and the shear stresses due to fluid flow. Conventional in vitro assays for drug development and the mechanistic study of metastasis are often carried out in the absence of fluidic forces and, consequently, are poorly representative of the true biology of metastasis. Here, we present a novel high-throughput approach to studying cell adhesion under flow that uses a multi-well, mechanofluidic flow system to interrogate adhesion of cancer cell to endothelial cells, extracellular matrix and platelets under physiological shear stresses. We use this system to identify pathways and compounds that can potentially be used to inhibit cancer adhesion under flow by screening anti-inflammatory compounds, integrin inhibitors and a kinase inhibitor library. In particular, we identify several small molecule inhibitors of FLT-3 and AKT that are potent inhibitors of cancer cell adhesion to endothelial cells and platelets under flow. In addition, we found that many kinase inhibitors lead to increased adhesion of cancer cells in flow-based but not static assays. This finding suggests that even compounds that reduce cell proliferation might also enhance cancer cell adhesion during metastasis. Overall, our results validate a novel platform for investigating the mechanisms of cell adhesion under biophysical flow conditions and identify several potential inhibitors of cancer cell adhesion during metastasis.

Gas uptake from an unventilated area of lung: computer model of absorption atelectasis.

A computer model of gas uptake from an area of nonventilated lung, such as a pulmonary lobe with an occluded bronchus or an alveolus with an occluded airway, is presented. Previous analyses have assumed that when an inert gas is present, equilibration of O2 and CO2 with mixed venous blood is sufficiently rapid to be treated as instantaneous. This is valid for insoluble gases such as N2 or He when the fractional concentration of inspired O2 (FIO2) is < or = 0.6 but is invalid for a relatively soluble gas such as N2O. When a mixture of O2 and an inert gas is breathed, the time for an area of unventilated lung to collapse depends on the solubility of the inert gas and FIO2. When the solubility is low (N2 or He), collapse takes longer than when 100% O2 is breathed, and the lower the FIO2 the longer the time to collapse. When the gas is more soluble (N2O) and FIO2 is > 0.3, collapse is more rapid than when 100% O2 is breathed.

Droperidol elimination after cardiopulmonary bypass surgery.

A high-dose (0.75 to 2.8 mg/kg) pharmacokinetic study of droperidol was undertaken in patients during the recovery phase after cardiac surgery involving hypothermic cardiopulmonary bypass (CPB). The elimination half-life of droperidol in these patients, determined from concentration-time data obtained after CPB, was significantly prolonged relative to previously reported mean values in younger surgical patients not undergoing CPB and receiving lower doses of the drug (0.05-0.20 mg/kg). On stratification of the patients by droperidol dose, there was an inverse correlation between the size of the dose and the elimination half-life of droperidol: mean half-life decreased as mean dose increased. This difference in elimination half-life was not related to the duration of the CPB procedure, or the total anesthetic time, both of which were not significantly different between the patient groups receiving the three different doses of droperidol. The magnitude or duration of hypothermia after CPB did not differ between the three patient groups. The differences in half-lives are more likely due to the clinical condition of the patients, such that the patients who received the higher doses of droperidol were also judged clinically to be less ill and thus eliminated droperidol more efficiently. This hypothesis, however, could not be supported due to the small number of patients studied. The results obtained in this study indicate that droperidol elimination is significantly prolonged after high-dose administration to elderly patients undergoing hypothermic CPB procedures during cardiac surgery.

Pulmonary oedema in chronic bronchitis - a haemodynamic study.

Right heart catheterization was performed in ten patients with pulmonary oedema. Mean wedge pressures in excess of 12 mmHg above the mid-axillary line were regarded as abnormal and indicating left heart failure. If the wedge pressure was less than 12 mmHg, and pulmonary congestion was present, frusemide was given. Brief descriptions of the ten cases are given.

The effects of ventilation pattern on carbon dioxide transfer in three computer models of the airways.

We investigate the effects on arterial P(CO(2)) and on arterial-end tidal P(CO(2)) difference of six different ventilation patterns of equal tidal volume, and also of various combinations of tidal volume and respiratory rate that maintain a constant alveolar ventilation. We use predictions from three different mathematical models. Models 1 (distributed) and 2 (compartmental) include combined convection and diffusion effects. Model 3 incorporates a single well-mixed alveolar compartment and an anatomical dead-space in which plug flow occurs. We found that: (i) breathing patterns with longer inspiratory times yield lower arterial P(CO(2)); (ii) varying tidal volume and respiratory rate so that alveolar ventilation is kept constant may change both PA(CO(2)) and the PA(CO(2))-PET(CO(2)) difference; (iii) the distributed model predicts higher end-tidal and arterial P(CO(2)) than the compartmental models under similar conditions; and (iv) P(CO(2)) capnograms predicted by the distributed model exhibit longer phase I and steeper phase II than other models.

Fluid mechanics analysis of a spring-loaded jet injector.

A syringe jet injector is a device designed to administer a drug quickly and painlessly through the skin. Though syringe jet injectors have been in use for almost 50 years, current designs still suffer from inconsistent performance. To better understand the fluid mechanics of jet injection and gain insight into how the design might influence performance, two theoretical analyses to determine the fluid pressure profile at the exit orifice were conducted. The first was a continuum analysis assuming static incompressibility. Results demonstrated that the maximum jet pressure was highly sensitive to the spring constant, initial piston velocity, and piston cross-sectional area while the time to achieve the maximum pressure was most sensitive to the injection chamber length, initial piston velocity, bulk modulus of the injectant, and the piston cross-sectional area. The second analysis was a shock wave analysis. Results demonstrated a stepwise pressure-time plot that was similar in magnitude to that for the continuum analysis assuming static incompressibility. Results from these two investigations are useful for design modification of the jet injector to achieve desired pressure-time profiles at the orifice. Control of pressure-time profiles may help to achieve a more consistent and effective injection process.

Determination of droperidol in plasma by liquid chromatography.

A reversed-phase high performance liquid chromatographic method is described for the determination of droperidol concentrations in plasma. Following extraction, separation of droperidol and the internal standard flurazepam was achieved with a Spherisorb Nitrile, 5 microns, S5CN 250 mm x 4.6 mm column at 200 nm. The mobile phase was phosphate buffer (0.05 M, pH 2.4), acetonitrile and ethanol (65:20:15, v/v/v). The assay was rapid, sensitive and linear over the range 2-4000 ng ml-1. Precision of the assay expressed as the intra- and inter-day relative standard deviations (%RSD) did not exceed 10%. Flunitrazepam, midazolam and nitrazepam were also resolved with this technique and did not interfere with droperidol or flurazepam. Resolution of all five compounds was complete in less than 6 min. The assay was used to study the pharmacokinetics of high dose droperidol infusions during and after cardiac surgery.

A sensitive assay for the simultaneous measurement of alfentanil and fentanyl in plasma.

A reversed-phase high-performance liquid chromatography method for the simultaneous determination of plasma concentrations of the narcotic analgesics alfentanil and fentanyl using papaverine hydrochloride as the internal standard is presented. Chromatographic separations were achieved with an Econosphere CN, 5 microns, 25 cm x 4.6 mm i.d. column and the effluent was monitored at 195 nm. The assay was linear over the clinically relevant plasma range of 2-2000 ng ml-1 for alfentanil and 2-100 ng ml-1 for fentanyl and has the sensitivity and specificity necessary to determine plasma concentrations of these compounds. Inter- and intra-day precision (RSD) for both compounds did not exceed 10% in these ranges. The assay procedure was utilized for pharmacokinetic studies of plasma concentrations in subjects receiving alfentanil and fentanyl during and after cardiac surgery. This will allow better elucidation of pharmacokinetic variables in this populace.

Effects of changes in cadence, prosthetic componentry, and time on interface pressures and shear stresses of three trans-tibial amputees.

OBJECTIVE: To evaluate the effects of changes in cadence, prosthetic componentry, and time on interface pressures and resultant shear stresses in trans-tibial amputee case studies. DESIGN: Interface stresses were monitored using custom-designed instrumentation at 13 sites on three subjects with unilateral trans-tibial amputation walking with patellar-tendon-bearing prosthetic limbs. BACKGROUND: Previous studies suggested that week-to-week residual limb changes altered interface stresses more than did alterations in prosthetic alignment. No studies investigating effects of changes in cadence or componentry on interface stress distributions nor comparing their influence with week-to-week changes have been conducted previously. METHODS: Five different prosthetic componentry configurations were tested at each of three cadences in four sessions. Data were analysed for the magnitudes and timings of peak pressures and resultant shear stresses as well as corresponding resultant shear angles. RESULTS: None of the three cadences or five componentry configurations consistently induced significantly (P<0.05) higher or lower interface stress magnitudes for all subjects. However, an Aluminium Pylon/SACH Foot combination compared with an AirStance (pneumatic shank)/Seattle LightFoot unit induced later peak interface stress timings as a percentage of stance phase. Higher and more frequent interface stress changes were seen between the weekly sessions than between different cadences or between different componentry configurations. CONCLUSION: The amputees' capabilities to compensate for week-to-week residual limb changes were less than those for intra-session cadence or componentry alterations. RELEVANCE: Results suggest that effective techniques to accommodate week-to-week residual limb fluctuations could have a greater impact on maintaining consistent interface stress distributions than do adjustments in cadence or componentry.

Childhood cancer survivors: attained adult heights. Compared with sibling controls.

As part of a large collaborative study, the authors administered a pretested questionnaire to 62 childhood and adolescent cancer survivors and 62 same-sex sibling controls. The authors requested information regarding attained adult height on the questionnaire. Mean adult height of survivors (172.2 cm) was less than that of controls (174.1 cm), at a borderline significant difference of p = 0.0757. Multivariate analysis examined four potential, independent variables as possible predictors of this difference. The presence of brain tumor (vs. nonbrain tumor) (p less than .0001) and diagnosis at an early age (less than or equal to 8 years vs. 9-15 years) (p = .05) were factors significantly related to the differential; sex of patient and type of therapy were not. Our findings thus identify malignancy site and age at diagnosis as important predictors of adult height in childhood and adolescent cancer survivors.

The effect of oral pyridostigmine bromide nerve agent prophylaxis on return of twitch height in persons receiving succinylcholine.

Prophylactic pyridostigmine is used for troops under threat of organophosphate exposure and can affect the neuromuscular blocking agent succinylcholine. The purpose of this study was to determine what effect pyridostigmine would have on neuromuscular blockade from succinylcholine. Thirty-nine subjects were enrolled in this double-blind, placebo-controlled investigation and assigned to either the pyridostigmine or the placebo group. All subjects were evaluated for pyridostigmine or placebo side effects and given an anesthesia induction that included the neuromuscular blocking agent succinylcholine. Neuromuscular blockade was measured by twitch height with a nerve stimulator. Interval data were analyzed using the chi 2 test and Student's t test. The pyridostigmine group demonstrated a prolonged recovery time to return of 25% (p = 0.003) and 75% (p = 0.028) of twitch height compared with the placebo group. No differences were noted for any other parameter measured. We conclude that the recovery from neuromuscular blockade after succinylcholine is prolonged while the intubating conditions remain unaffected.

The registered nurse student: a teaching challenge.

Nurse-students present a challenge to a nursing faculty. These students are articulate, experienced, persistent, and motivated. Professors must work with nurse-students in a collegial effort, allowing them input and ventilation of concerns. Professors must learn to listen to adult students, to share resources, and to build a trusting relationship. The result will be a collegial relationship--one in which students and professors will both learn a great deal.

Effectiveness of preoperative analgesics on postoperative dental pain: a study.

Patients undergoing extractions of third molar teeth under general anesthesia were given a placebo, diclofenac (a nonsteroidal anti-inflammatory drug) 100 mg, or methadone (an opiate) 10 mg 60 to 90 min prior to surgery, and their pain scores and postoperative medication requirements were measured for 3 days. All patients received local anesthetic blocks and analgesic drugs during the perioperative period. There were no significant differences between the three groups in the pain scores and medication requirements during the period of study. It was concluded that preoperative use of nonsteroidal anti-inflammatory drugs and opiates may not offer a preemptive analgesic effect in patients who have had adequate analgesia during the surgery. Continued use of analgesic drugs during the postoperative period is perhaps more useful for this purpose. There appears to be a higher incidence of vomiting following opiates (methadone), precluding its clinical use in day-care patients.