Anaesthesia and Intensive Care publications

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3-Amino-2-hydroxy-N-(4-nitrophenyl)-propanesulphonamide, a new class of GABAB receptor antagonist in central and peripheral preparations
(North Holland, 1995) Kerr, D.; Ong, J.; Hughes, R.; Prager, R.
Racemic 3-amino-2-hydroxy-N-(4-nitrophenyl)-propanesulphonamide (AHPNS), a sulphonamide analog of GABA, reversibly and competitively antagonised the concentration-dependent depression of cholinergic twitch contractions by baclofen, in the electrically stimulated guinea-pig isolated ileum, with a pA2 of 4.0 +/- 0.2. In the rat neocortex, maintained in Mg(2+)-free medium, AHPNS (100-500 microM) also reversibly antagonised the baclofen (10 microM)-induced suppression of spontaneous discharges. AHPNS is a new class of GABAB receptor antagonist that has central and peripheral blocking actions.
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A classification for incidents and accidents in the health-care system
(Wiley Blackwell, 1998) Runciman, W.; Helps, S.; Sexton, E.; Malpass, A.
Focuses on the classification of incidents and accidents in the health-care systems using software written in Microsoft Visual Basic. Development of a 'Generic Occurrence Classification' system; Reliability of the system in comparing incidents and accidents from different sources.
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A comparison of iatrogenic injury studies in Australia and the USA I: context, methods, casemix, population, patient and hospital characteristics
(Oxford Univ Press, 2000) Thomas, E.; Studdert, D.; Runciman, W.; Webb, R.; Sexton, E.; Wilson, R.; Gibberd, R.; Harrison, B.; Brennan, T.
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A comparison of iatrogenic injury studies in Australia and the USA, II: reviewer behaviour and quality of care
(Oxford Univ Press, 2000) Runciman, W.; Webb, R.; Helps, S.; Thomas, E.; Sexton, E.; Studdert, D.; Brennan, T.
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A method for frequent measurement of sedation and analgesia in sheep using the response to a ramped electrical stimulus
(Elsevier, 1995) Ludbrook, G.; Grant, C.; Upton, R.; Penhall, C.
A method for the frequent, precise measurement of the analgesic and sedative (or anesthetic) effects of drugs after bolus administration to sheep was developed. A ramped pulsed DC electrical stimulus was delivered to the hind limb of sheep via subcutaneous needles by use of a peripheral nerve stimulator modified to allow control of current ramp rate and pulse frequency, and limb withdrawal was used as an endpoint. The optimal stimulus pattern was found to be a pulse frequency of 20 Hz, with a 5-sec ramp time and measurement intervals of 30 sec. The effects of a range of analgesic and sedative drugs on the threshold current to produce limp withdrawal were examined. Administration of the sedative/anesthetic drugs propofol and thiopentone intravenously and of the analgesic xylazine both intravenously and intramuscularly resulted in a reproducible dose-dependent rise in the threshold current required to produce limb withdrawal. Administration of the opioids alfentanil and pethidine produced agitation, making measurements unreliable. It is concluded that this device allows repeated reproducible measurements of analgesia and sedation to be made in sheep at a frequency sufficient to characterize the initial effects of analgesic and sedative drugs, particularly after intravenous administration.
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A mixture of alfentanil and morphine for rapid postoperative loading with opioid: theoretical basis and initial clinical investigation
(Blackwell Science Ltd, 2001) Ludbrook, G.; Macintyre, P.; Douglas, H.; Ong, J.; Upton, R.
Pharmacokinetic modelling of estimated central nervous system concentrations was used to devise the optimal mixture of morphine and alfentanil for the treatment of postoperative pain. Modelling revealed that an intravenous opioid pain protocol using an alfentanil−morphine mixture in the proportions 0.75 : 10 mg would provide a profile of analgesia of rapid onset, yet slow offset. The regimen was evaluated in 58 patients in the recovery ward who were randomly allocated to receive analgesia using pain protocols with either morphine or the mixture. Groups were well matched for age, weight and initial pain scores. The mean (SD) time to patient comfort was 27.6 (20.2) min for the mixture and 41.2 (18.6) min for morphine (p = 0.01). Multiple regression analysis revealed that that initial pain score (p = 0.009) and drug group (p = 0.02), but not age, weight or gender were independent predictors of the time to comfort. Drug group was not a significant predictor of adverse effects.
Open Access
A novel technique for post-pyloric feeding tube placement in critically ill patients: A pilot study
(Australian Soc Anaesthetists, 2005) Young, R.; Chapman, M.; Fraser, R.; Yandell, R.; Chorley, D.; O'Connor, S.
Delivery of enteral nutrition in critically ill patients is often hampered by gastric stasis necessitating direct feeding into the small intestine. Current techniques for placement of post-pyloric feeding catheters are complex, time consuming or both, and improvements in feeding tube placement techniques are required. The Cathlocator™ is a novel device that permits real time localisation of the end of feeding tubes via detection of a magnetic field generated by a small electric current in a coil incorporated in the tip of the tube. We performed a pilot study evaluating the feasibility of the Cathlocator™ system to guide and evaluate the placement of (1) nasoduodenal feeding tubes, and (2) nasogastric drainage tubes in critically ill patients with feed intolerance due to slow gastric emptying. A prospective study of eight critically ill patients was undertaken in the intensive care unit of a tertiary hospital. The Cathlocator™ was used to (1) guide the positioning of the tubes post-pylorically and (2) determine whether nasogastric and nasoduodenal tubes were placed correctly. Tube tip position was compared with data obtained by radiology. Data are expressed as median (range). Duodenal tube placement was successful in 7 of 8 patients (insertion time 12.6 min (5.3-34.4)). All nasogastric tube placements were successful (insertion time 3.4 min (0.6-10.0)). The Cathlocator™ accurately determined the position of both tubes without complication in all cases. The Cathlocator™ allows placement and location of an enteral feeding tube in real time in critically ill patients with slow gastric emptying. These findings warrant further studies into the application of this technique for placement of post-pyloric feeding tubes.
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A pharmacokinetic and pharmacodynamic study of oral oxycodone in a human experimental pain model of hyperalgesia
(Adis International Ltd, 2010) Olesen, A.; Upton, R.; Foster, D.; Staahl, C.; Christrup, L.; Arendt-Nielsen, L.; Drewes, A.
Background and Objective: Oxycodone is not as well characterized, with respect to its pharmacokinetic/pharmacodynamic properties, as other opioids. Moreover, the pharmacodynamic profile of oxycodone can be affected by changes in the pain system, e.g. hyperalgesia. Therefore, the aim of this study was to investigate the pharmacokinetic/pharmacodynamic profiles of oxycodone in a human experimental pain model of hyperalgesia. Methods: Twenty-four healthy subjects received oral oxycodone (15 mg) or placebo. Pharmacodynamics were assessed utilizing a multimodal, multi-tissue paradigm where pain was assessed from skin (heat), muscle (pressure) and viscera (heat and electricity) before and 30, 60 and 90 minutes after induction of generalized hyperalgesia evoked by perfusion of acid and capsaicin in the oesophagus. Venous blood samples were obtained for quantification of oxycodone plasma concentrations before and 5, 10, 15, 30, 45, 60, 90 and 120 minutes after drug administration. Results: Oxycodone blood concentrations could be described by a one-compartment model but, given the necessarily short timescale of the study, the concentrations were represented by linear interpolation for subsequent pharmacodynamic models. Time-dependent changes in the pain measures in the placebo arm of the study were represented by linear or quadratic functions. The time course of the pain measures in the oxycodone arm was taken to be the time course for the placebo arm plus a concentration-effect relationship that was either zero (no drug effect), linear or a maximum effect (Emax) model. For three of the four pain measures, there was a time-dependent change after administration of placebo (e.g. due to the development of generalized hyperalgesia). Conclusion: There was a measurable effect of oxycodone, compared with placebo, on all pain measures, and a linear concentration-effect relationship without an effect delay was demonstrated. This could indicate an initial peripheral analgesic effect of oxycodone.
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A physiologically based, recirculatory model of the kinetics and dynamics of propofol in man
(Lippincott Williams & Wilkins, 2005) Upton, R.; Ludbrook, G.
BACKGROUND: The disposition of propofol in man is commonly described using a three-compartment mamillary model. However, these models do not incorporate blood flows as parameters. This complicates the representation of the changes in blood flows that may occur in surgical patients. In contrast, complex physiologically based models are derived from data sets (e.g., tissue:blood partition coefficients) that may not be readily collected in man. METHODS: Alternatively, the authors report a recirculatory model of propofol disposition in a "standard" man that incorporates detailed descriptions of the lungs and brain, but with a lumped description of the remainder of the body. The model was parameterized from data in the literature using a "meta-modeling" approach. The first-pass passage of propofol through the venous vasculature and the lungs was a function of the injected drug mixing with cardiac output and passing through a three-"tank in series" model for the lungs. The brain was represented as a two-compartment model defined by cerebral blood flow and a permeability term. The Bispectral Index was a linear function of the mean brain concentration. The remainder of the body was represented by compartment systems for the liver, fast distribution and slow distribution. RESULTS: The model was a good fit of the data and was able to predict other data not used in the development of the model. CONCLUSIONS: The model may ultimately find a role in improving the fidelity of patient simulators currently used to train anesthetists and for clinical practice simulation to optimize dosing and management strategies.
Open Access
A prospective clinical comparison of two intravenous polyurethane cannulae
(Australian Society of Anaesthetists, 1997) Russell, W.; Micik, S.; Gourd, S.; Mackay, H.; Wright, S.
Tissue irritation, as evidenced by phlebitis, associated with Optiva™ (Johnson & Johnson Medical) and Insyte™ (Becton Dickinson) polyurethane cannulae was studied. The integrity of the cannulae on removal, the incidence of infection at the cannula site and the factors which influence phlebitis were also examined. One thousand and eight patients had a polyurethane cannula placed for induction of anaesthesia for cardiac surgery. After surgery, the cannula was examined every 24 hours. If evidence of phlebitis occurred, the cannula was removed and sent for culture. All remaining cannulae were removed at 72 hours and the site examined daily for a further three days. There were 503 Optiva™ and 505 Insyte™ cannulae studied. The distributions between the two cannulae with respect to patient characteristics, gauge of cannula, number of attempts and difficulty of insertion, cannula site and anaesthetist inserting were similar. The early removal rate for both groups was 47%. Overall phlebitis rate with Optiva™ was 31% and Insyte™ 33%. This difference is not statistically significant. The cumulative phlebitis rate increased with time but did not differ between the two types of cannulae. Minor tip distortion or shaft kinking of the cannulae occurred in 16.2% of Optiva™ and 23.5% of Insyte™. This difference is statistically significant and may relate to the slightly more acute taper at the Optiva™ cannula tip. Both cannulae were similar in clinical performance.
Open Access
A prospective, multi-method, multi-disciplinary, multi-level, collaborative, social-organisational design for researching health sector accreditation [LP0560737]
(BioMed Central Ltd., 2006) Braithwaite, J.; Westbrook, J.; Pawsey, M.; Greenfield, D.; Naylor, J.; Iedema, R.; Runciman, W.; Redman, S.; Jorm, C.; Robinson, M.; Nathan, S.; Gibberd, R.
BACKGROUND: Accreditation has become ubiquitous across the international health care landscape. Award of full accreditation status in health care is viewed, as it is in other sectors, as a valid indicator of high quality organisational performance. However, few studies have empirically demonstrated this assertion. The value of accreditation, therefore, remains uncertain, and this persists as a central legitimacy problem for accreditation providers, policymakers and researchers. The question arises as to how best to research the validity, impact and value of accreditation processes in health care. Most health care organisations participate in some sort of accreditation process and thus it is not possible to study its merits using a randomised controlled strategy. Further, tools and processes for accreditation and organisational performance are multifaceted. METHODS/DESIGN: To understand the relationship between them a multi-method research approach is required which incorporates both quantitative and qualitative data. The generic nature of accreditation standard development and inspection within different sectors enhances the extent to which the findings of in-depth study of accreditation process in one industry can be generalised to other industries. This paper presents a research design which comprises a prospective, multi-method, multi-level, multi-disciplinary approach to assess the validity, impact and value of accreditation. DISCUSSION: The accreditation program which assesses over 1,000 health services in Australia is used as an exemplar for testing this design. The paper proposes this design as a framework suitable for application to future international research into accreditation. Our aim is to stimulate debate on the role of accreditation and how to research it.
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A quantitative alternative to the hysteresis plot for measurement of drug transit time
(Elsevier Science Inc, 2002) Upton, R.; Doolette, D.
Introduction
Hysteresis plots can be used to examine pharmacokinetic data in which there is a transport delay between drug concentrations at two sites in the body (e.g., in blood entering and leaving an organ). However, the area enclosed by the hysteresis "loop" does not provide quantitative information about the magnitude of the delay.
Methods
A quick, graphical, and model independent alternative to the hysteresis plot (an "area fraction plot") was developed for a spreadsheet program on a personal computer. It has the advantage that the area enclosed by the "loop" is the mean transit time (MTT) of the transport delay. The method was based on plotting the cumulative area under the concentration-time curve as a fraction of the total area under curve for each site, and is a type of moment analysis. The method is described and was validated by application to simulated data sets. It was also applied to previously published data to calculate the MTT of lidocaine in the lungs and hindquarters of conscious, instrumented sheep.
Results
The validation process showed the area fraction plot was relatively insensitive to integration errors even with moderately noisy data sets. However, failing to analyse the data up to the time point where pseudo-equilibrium was re-established could result in potentially large underestimates of the transit time. The MTT of lidocaine (mean+/-S.E.M.) in the lungs of five sheep was rapid (0.61+/-0.15 min), and 14.2+/-3.1% of the lidocaine was retained in the lungs. The values were in good agreement with values obtained via structural modelling of the same data. The MTT of lidocaine in the hindquarters was 10.6+/-0.9 min, and the retention was 25.2+/-3.1%.
Discussion
The method can be used in the same situations as a hysteresis plot, but provides additional quantitative information about the transport delay causing the hysteresis.
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A randomized controlled trial comparing the AccuVein AV300 device to standard insertion technique for intravenous cannulation of anesthetized children
(Blackwell Publishing Ltd, 2012) Kaddoum, R.; Anghelescu, D.; Parish, M.; Wright, B.; Trujillo, L.; Wu, J.; Wu, Y.; Burgoyne, L.
Objectives and Aims: To evaluate the efficacy of the AccuVein AV300 device in improving the first-time success rate of intravenous cannulation of anesthetized pediatric patients. Background: The AccuVein AV300 device was developed to assist venepuncture and intravenous cannulation by enhancing the visibility of superficial veins. It uses infrared light to highlight hemoglobin so that blood vessels are darkly delineated against a red background. Methods/Materials: Patients were randomized to cannulation with the AccuVein AV300 device or standard insertion by experienced pediatric anesthesiologists. An observer recorded the number of skin punctures and cannulation attempts required, and the time between tourniquet application and successful cannulation or four skin punctures, whichever came first. Results and Conclusions: There were 146 patients with a median age of 4.6 years (range, 0.18–17.1 years), 46.6% were male, 80.8% were light skin colored, and 15.7% were younger than 2 years. The first-attempt success rates were 75% (95% CI, 63.8–84.2%) using AV300 and 73% (95% CI, 61.9–81.9%) using the standard method (P = 0.85). Patients with dark or medium skin color were 0.38 times less likely to have a successful first attempt than patients with light skin color. The difference between the two treatment groups in number of skin punctures and the time to insertion was not significant. Although the AV300 was easy to use and improved visualization of the veins, we found no evidence that it was superior to the standard method of intravenous cannulation in unselected pediatric patients under anesthesia.
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A randomized controlled trial to determine the effects of humidified carbon dioxide insufflation during thoracoscopy
(Springer-Verlag New York, Inc., 1999) Mouton, W.; Bessell, J.; Pfitzner, J.; Dymock, R.; Brealey, J.; Maddern, G.
Background: The humidification of gas insufflated during laparoscopy can reduce the degree of postoperative hypothermia and may result in less peritoneal reaction and less postoperative pain. The present study was designed to determine whether the beneficial effects of humidified gas insufflation also applied to thoracoscopy. Methods: Six pigs were each studied on three separate occasions with insufflation into the right thoracic cavity of either humidified gas, standard dry gas, or with no insufflation (control procedure). Core body temperature was recorded every 15 min, and biopsies of the parietal pleura were taken at the end of each study for electron microscopy. Results: Humidification of insufflated gas significantly minimized the fall in core temperature during the procedure. Electron microscopy showed that dry gas insufflation resulted in greater structural injury to the pleura than humidified gas insufflation. Conclusions: The potential benefits of humidifying insufflation gas during thoracoscopy warrant its evaluation in the clinical setting.
Open Access
A tragic death: a time to blame or a time to learn?
(British Med Journal Publ Group, 2003) Runciman, W.; Merry, A.
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A xylazine infusion regimen to provide analgesia in sheep
(Royal Soc Medicine Press Ltd, 2001) Grant, C.; Summersides, G.; Kuchel, T.
The efficacy of continuous low-dose xylazine infusion following an initial loading dose in providing analgesia in sheep was examined using an algesimetry method based on a leg lifting response to an electrical stimulus. Sheep received a 5 mg intramuscular injection of xylazine followed by continuous infusion of intravenous xylazine (2 mg/h) for 90 min. This treatment resulted in significant increases in the level of current required to elicit a leg lifting response (287% of baseline) and steady state analgesia was maintained from 10 min after the start of the infusion until the end of the experimental period. This protocol appears to be a simple and effective regimen for providing steady state analgesia in sheep.
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Accidental bronchial intubation - an analysis of AIMS incident reports from 1988 to 1994 inclusive
(Blackwell Science, 1997) McCoy, E.; Russell, W.; Webb, R.
Accidental bronchial intubation was examined in the first 3947 cases reported to the Australian Incident Monitoring Study and was found to have accounted for 154 (3.7%) of the total incidents reported. Most incidents were detected in the operating theatre (93.5%) and during maintenance of anaesthesia (77.9%), by unexplained oxygen desaturation alone (63.6%). Capnography remained normal or unremarkable during 88.5% of the episodes. One-third of cases were associated with head or neck surgery and possible flexion of the patient’s head. A RAE tube was used in 20% of incidents, a greater frequency than occurred in the study overall. A third party was implicated in 36 (23.4%) of cases. Ninety per cent of cases were considered preventable. Major morbidity occurred in three cases and unplanned intensive care admission was required in a further five. Almost two-thirds (61.1%) of the incidents might have been avoided by the proposed markings on the tracheal tube. We conclude that when arterial desaturation occurs at any stage during anaesthesia the possibility of bronchial intubation must be considered. Asymmetrical ventilation may be difficult to detect clinically and in most cases there is no change in capnography.
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Accidental oesophageal intubation
(Macmillan Journals, 1995) Russell, W.
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Actions of thienyl analogs of baclofen at GABAB receptors in rat neocortical slices
(Elsevier BV, 1997) Ong, J.; Kerr, D.; Vaccher, C.; Berthelot, P.
In rat neocortical slices maintained in Mg2+-free Krebs medium, baclofen and its thienyl analogs, 4-amino-3-(5-chlorothien-2-yl)-butanoic acid (5h), 4-amino-3-(5-methylthien-2-yl)-butanoic acid (5d), 4-amino-3-(5-bromothien-2-yl)-butanoic acid (5f) and 4-amino-3-(thien-3-yl)-butanoic acid (5j) dose-dependently suppressed the spontaneous discharges, antagonised by the GABA(B) receptor antagonist 2-hydroxysaclofen (200 microM). Their relative potencies were baclofen > 5h > 5d > 5f > 5j. These heterocyclic analogs may prove useful as GABA(B) receptor agonists in functional studies.
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Acute cardiovascular effects of magnesium and their relationship to systemic and myocardial magnesium concentrations after short infusion in awake sheep
(Amer Soc Pharmacology Experimental Therapeutics, 2001) Zheng, D.; Upton, R.; Ludbrook, G.; Martinez, A.
The temporal relationship between the systemic and myocardial concentrations of magnesium and some of its acute cardiovascular effects were examined after short i.v. infusion administration of magnesium (30 mmol over 2 min) in five awake chronically instrumented sheep. Magnesium decreased mean arterial blood pressure and systemic vascular resistance (SVR) by 23 and 41% from baseline, respectively. These hemodynamic changes were consistent with magnesium producing primary reductions in SVR with partial heart rate (HR)-mediated compensation of blood pressure. Cardiac output and HR increased by 38 and 38% from baseline, respectively. Magnesium had little effect on myocardial contractility, but substantially increased myocardial blood flow (MBF, 77% above baseline) primarily due to direct myocardial vasodilation. The peak arterial and coronary sinus serum magnesium concentrations were 6.94 ± 0.26 (mean ± S.E.M.) and 6.51 ± 0.20 mM, respectively, at 2 min. Both arterial and coronary sinus magnesium concentrations at the end of the study were still more than 3 mM, whereas all the cardiovascular effects were back to baseline. The myocardial kinetics of magnesium was consistent with rapid equilibration of magnesium (half-life 0.4 min) with a small distribution volume (71 ml) consistent with the extracellular space of the heart. In conclusion, magnesium was shown to have a rapid equilibration between the plasma/serum concentrations of magnesium and its extracellular concentration in the myocardium. However, the primary cardiovascular effect of magnesium (reductions in SVR) preceded its extracellular concentrations, and was a direct function of its arterial concentration. A "threshold" model for changes in SVR was preferred when linked to the arterial magnesium concentration.

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