Kimble Dunster

Optimal Management of the Critically Ill: Anaesthesia, Monitoring, Data Capture, and Point-of-Care Technological Practices in Ovine Models of Critical Care

Animal models of critical illness are vital in biomedical research. They provide possibilities for the investigation of pathophysiological processes that may not otherwise be possible in humans. In order to be clinically applicable, the model should simulate the critical care situation realistically, including anaesthesia, monitoring, sampling, utilising appropriate personnel skill mix, and therapeutic interventions. There are limited data documenting the constitution of ideal technologically advanced large animal critical care practices and all the processes of the animal model. In this paper, we describe the procedure of animal preparation, anaesthesia induction and maintenance, physiologic monitoring, data capture, point-of-care technology, and animal aftercare that has been successfully used to study several novel ovine models of critical illness. The relevant investigations are on respiratory failure due to smoke inhalation, transfusion related acute lung injury, endotoxin-induced proteogenomic alterations, haemorrhagic shock, septic shock, brain death, cerebral microcirculation, and artificial heart studies. We have demonstrated the functionality of monitoring practices during anaesthesia required to provide a platform for undertaking systematic investigations in complex ovine models of critical illness.

Lead macrocyclic complexes : the synthesis, complex formation and X-ray crystal structures of [Pb(L1)(NO3)2] and [Pb(L2)(NO3)2] (L1 = 1,4,7,10-tetraoxa-13-azacyclopentadecane, L2 = 1,4,7,10,13-pentaoxa-16-azacyclooctadecane)

Lead(II) complexes of the 15- and 18-membered ring macrocycles 1,4,7,10- tetraoxa-13-azacyclopentadecane (L1) and 1,4,7,10,13-pentaoxa-16-azacyclooctadecane (L2) have been prepared. The stability constants for the 1 : 1 lead complexes [L1, log β 6.0(1); L2, log β 8.4(1)] have been determined potentiometrically (0. 1 M NEt4ClO4, 95% methanol). The complexes [Pb(L1)(NO3)2] and [Pb(L2)(NO3)2] have been examined by 13C NMR spectroscopy and single-crystal X-ray structural analysis. In the molecule [Pb(L1)(NO3)2] the lead(II) cation is situated 1.52 A above the plane of the macrocyclic ring. The Pb-N(1) distance of 2.465(5) A is the shortest bond to lead(II) in the structure which also exhibits two short [2.627(4) and 2.643(4) A] and two long [2.909(4) and 2.992(5) A] PbOmacrocycle distances. The presence of a stereoactive lone pair of electrons on the cation is inferred from this stereochemistry. In [Pb(L2)(NO3)2] the lead(II) cation lies in the macrocyclic cavity. As for [Pb(L1)(NO3)2], the PbN(1) distance of 2.539(9) A is the shortest bond to lead in this structure, which has in addition two short [2.694(7) and 2.697(8) A] and three long [2.877(10), 2.951(6) and 2.999(9) A] PbOmacrocycle interactions. There is no evidence for a stereoactive lone pair of electrons in this structure.

Electrical impedance tomography in extremely prematurely born infants and during high frequency oscillatory ventilation analyzed in the frequency domain

Functional electrical impedance tomography (EIT) measures relative impedance change that occurs in the chest during a distinct observation period and an EIT image describing regional relative impedance change is generated. Analysis of such an EIT image may be erroneous because it is based on an impedance signal that has several components. Most of the change in relative impedance in the chest is caused by air movement but other physiological events such as cardiac activity change in end expiratory level or pressure swings originating from a ventilator circuit can influence the impedance signal. We obtained EIT images and signals in spontaneously breathing healthy adults, in extremely prematurely born infants on continuous positive airway pressure and in ventilated sheep on conventional mechanical or high frequency oscillatory ventilation (HFOV). Data were analyzed in the frequency domain and results presented after band pass filtering within the frequency range of the physiological event of interest. Band pass filtering of EIT data is necessary in premature infants and on HFOV to differentiate and eliminate relative impedance changes caused by physiological events other than the one of interest.

Cerebral impedance and neurological outcome following a mild or severe hypoxic/ischemic episode in neonatal piglets

Multi-frequency bio-impedance has the potential to identify infants at risk of poor neurodevelopmental outcome following hypoxia by detecting cerebral edema. This study investigated the relationship between the severity of an hypoxic/ischemic episode, neurological outcome following the hypoxia and non-invasively measured cerebral bioelectrical impedance in piglets. One-day-old piglets were anaesthetised and ventilated. Hypoxia was induced by reducing the inspired oxygen concentration to 3-5%. Severe hypoxia was defined as hypoxia resulting in at least 30 min of low amplitude EEG (<5 microV) as well as hypotension and acidosis. Cerebral bio-impedance was measured before, during and for up to 6 h post-hypoxia. Neurological outcome was determined by a neurology score at 24 and 48 h after hypoxia, and by histological examination of the brain at 72 h. There was no increase in cerebral impedance in control animals. Following mild hypoxia cerebral impedance increased transiently. Following severe hypoxia, cerebral impedance increased and remained elevated. Cerebral impedance following severe hypoxia was significantly higher than after mild hypoxia at 10 min and from 2 to 6 h after resuscitation. Cerebral impedance measurements made up to 1 h and between 3 and 6 h after resuscitation were significantly correlated with neurological outcome. Results indicate that non-invasive cerebral impedance measurements are able to discriminate early between those individuals who have suffered a mild, acute hypoxic episode, and those who have suffered a severe hypoxic episode. The technique has the potential to predict which individuals will have a poor neurological outcome.

Noninvasive measurement of cerebral bioimpedance for detection of cerebral edema in the neonatal piglet

The association of sustained cerebral edema with poor neurological outcome following hypoxia-ischaemia in the neonate suggests that measurement of cerebral edema may allow early prediction of outcome in these infants. Direct measurements of cerebral impedance have been widely used in animal studies to monitor cerebral edema, but such invasive measurements are not possible in the human neonate. This study investigated the ability of noninvasive cerebral impedance measurements to detect cerebral edema following hypoxia-ischaemia. One-day-old piglets were anaesthetized, intubated and ventilated. Hypoxia was induced by reducing the inspired oxygen concentration to 4-6% O(2). Noninvasive cerebral bioimpedance was measured using gel electrodes attached to the scalp. Cerebral bioimpedance was also measured directly by insertion of two silver-silver chloride electrodes subdurally. Noninvasive and invasive measurements were made before, during and after hypoxia. Whole body impedance was measured to assess overall fluid movements. Intracranial pressure was measured continuously via a catheter inserted subdurally, as an index of cerebral edema. There was good agreement between noninvasive and invasive measurements of cerebral impedance although externally obtained responses were attenuated. Noninvasive measurements were also well correlated with intracranial pressure. Whole body impedance changes did not account for increases in noninvasively measured cerebral impedance. Results suggest that noninvasive cerebral impedance measurements do reflect intracranial events, and are able to detect cerebral edema following hypoxia-ischaemia in the neonate.

Nasal high flow oxygen therapy in patients with COPD reduces respiratory rate and tissue carbon dioxide while increasing tidal and end-expiratory lung volumes: a randomised crossover trial

Abstract Patients with COPD using long-term oxygen therapy (LTOT) over 15 h per day have improved outcomes. As inhalation of dry cold gas is detrimental to mucociliary clearance, humidified nasal high flow (NHF) oxygen may reduce frequency of exacerbations, while improving lung function and quality of life in this cohort. In this randomised crossover study, we assessed short-term physiological responses to NHF therapy in 30 males chronically treated with LTOT. LTOT (2–4 L/min) through nasal cannula was compared with NHF at 30 L/min from an AIRVO through an Optiflow nasal interface with entrained supplemental oxygen. Comparing NHF with LTOT: transcutaneous carbon dioxide (TcCO2) (43.3 vs 46.7 mm Hg, p<0.001), transcutaneous oxygen (TcO2) (97.1 vs 101.2 mm Hg, p=0.01), I:E ratio (0.75 vs 0.86, p=0.02) and respiratory rate (RR) (15.4 vs 19.2 bpm, p<0.001) were lower; and tidal volume (Vt) (0.50 vs 0.40, p=0.003) and end-expiratory lung volume (EELV) (174% vs 113%, p<0.001) were higher. EELV is expressed as relative change from baseline (%Δ). Subjective dyspnoea and interface comfort favoured LTOT. NHF decreased TcCO2, I:E ratio and RR, with a concurrent increase in EELV and Vt compared with LTOT. This demonstrates a potential mechanistic rationale behind the improved outcomes observed in long-term treatment with NHF in oxygen-dependent patients. Trial registration number ACTRN12613000028707.

ECMO – the clinician’s view

Background  Extra corporeal membrane oxygenation (ECMO) is a complex rescue therapy used to provide cardiac and/or respiratory support for critically ill patients who have failed maximal conventional medical management. ECMO is based on a modified cardiopulmonary bypass (CPB) circuit, and can provide cardiopulmonary support for up‐to several months. It can be used in a veno venous configuration for isolated respiratory failure, (VV‐ECMO), or in a veno arterial configuration (VA‐ECMO) where support is necessary for cardiac +/‐ respiratory failure. The ECMO circuit consists of five main components: large bore cannulae (access cannulae) for drainage of the venous system, and return cannulae to either the venous ( in VV‐ECMO) or arterial (in VA ECMO) system. An oxygenator, with a vast surface area of hollow filaments, allows addition of oxygen and removal of carbon dioxide; a centrifugal blood pump allows propulsion of blood through the circuit at upto 10 L/minute; a control module and a thermoregulatory unit, which allows for exact temperature control of the extra corporeal blood.

The assessment of regional lung mechanics with electrical impedance tomography: a pilot study during recruitment manoeuvres

ObjectiveThe purpose of lung recruitment manoeuvres is to open collapsed lung regions, improve gas exchange and optimise regional lung mechanics. This study investigates the efficacy of recruitment manoeuvres for improving regional ventilation distribution as characterised using electrical impedance tomography (EIT).Design, subjects, interventionsA ventilated ovine smoke inhalation lung injury model was used. Respiratory mechanics and regional filling capacity of the lung were measured using EIT pre- and post- recruitment and compared to a control group.MeasurementsEIT, expressed as the time course relation of the regional versus the global impedance change, measured the regional filling capacities of the lung.Main resultsAfter smoke inhalation injury, the dependent lung showed a significantly larger area of collapse and a reduced filling capacity compared to the non-dependent lung. After recruitment the ventilated volume increased and the dependent lung showed improved respiratory mechanics, whereas the non-dependent lung was more likely to be hyper-inflated during tidal breathing.ConclusionsLung recruitment manoeuvres have a significant impact on regional lung mechanics and individual measurement of ventilation distribution using EIT may assist to improve ventilatory management.

Fate Of Abstracts Published In The Proceedings Of The First Annual Perinatal Society Of Australia And New Zealand Congress In 1997

Objectives:  To examine the fate of research presented at the first annual Perinatal Society of Australia and New Zealand (PSANZ) Congress in 1997, by determining: the rate of publication in peer‐reviewed biomedical journals; publication rate by discipline; journals in which work was published; concordance for aims, conclusions, authors and number of study subjects; and time from presentation to publication.

Anetoderma of prematurity in association with electrocardiographic electrodes

Anetoderma in premature infants is an uncommon lesion that may be associated with the use of various types of monitoring leads. In 2 infants multiple papules of anetoderma occurred on the forehead in association with the use of gel electrocardiographic electrodes. It is postulated that the cause of these papules was a local hypoxemia caused by pressure from the electrodes. Growth-restricted infants may be particularly predisposed to iatrogenic anetoderma.