Simulation-based optimisation to quantify heterogeneity of specific ventilation and perfusion in the lung by the Inspired Sinewave Test.

The degree of specific ventilatory heterogeneity (spatial unevenness of ventilation) of the lung is a useful marker of early structural lung changes which has the potential to detect early-onset disease. The Inspired Sinewave Test (IST) is an established noninvasive 'gas-distribution' type of respiratory test capable of measuring the cardiopulmonary parameters. We developed a simulation-based optimisation for the IST, with a simulation of a realistic heterogeneous lung, namely a lognormal distribution of spatial ventilation and perfusion. We tested this method in datasets from 13 anaesthetised pigs (pre and post-lung injury) and 104 human subjects (32 healthy and 72 COPD subjects). The 72 COPD subjects were classified into four COPD phenotypes based on 'GOLD' classification. This method allowed IST to identify and quantify heterogeneity of both ventilation and perfusion, permitting diagnostic distinction between health and disease states. In healthy volunteers, we show a linear relationship between the ventilatory heterogeneity versus age ([Formula: see text]). In a mechanically ventilated pig, IST ventilatory heterogeneity in noninjured and injured lungs was significantly different (p < 0.0001). Additionally, measured indices could accurately identify patients with COPD (area under the receiver operating characteristic curve is 0.76, p < 0.0001). The IST also could distinguish different phenotypes of COPD with 73% agreement with spirometry.

Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model.

BACKGROUND: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. METHODS: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O2 (FiO2) of 0.7 and a tidal volume of 10 ml kg-1. Protocolised changes in pressure- and volume-controlled modes, inspiratory:expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. RESULTS: During tidal ventilation, the expiratory lung collapse increased when I:E <1 [mean (standard deviation) lung collapse=15.7 (8.7)%; P<0.05], but the amplitude of respiratory PaO2 oscillations [2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P<0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P<0.0001). CONCLUSIONS: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury.

First-in-human study of the safety and viability of intraocular robotic surgery.

Microsurgery of the retina would be dramatically improved by instruments that offer supra-human precision. Here, we report the results of a first-in-human study of remotely controlled robot-assisted retinal surgery performed through a telemanipulation device. Specifically, 12 patients requiring dissection of the epiretinal or inner limiting membrane over the macula were randomly assigned to either undergo robot-assisted-surgery or manual surgery, under general anaesthesia. We evaluated surgical success, duration of surgery and amount of retinal microtrauma as a proxy for safety. Surgical outcomes were equally successful in the robotic-surgery and manual-surgery groups. Differences in the amount of retinal microtrauma between the two groups were statistically insignificant, yet dissection took longer with robotic surgery (median time, 4 min 5 s) than with manual surgery (1 min 20 s). We also show the feasibility of using the robot to inject recombinant tissue plasminogen activator under the retina to displace sight-threatening haemorrhage in three patients under local anaesthesia. A safe and viable robotic system for intraocular surgery would enable precise and minimally traumatic delivery of gene therapy or cell therapy to the retina.

A modification of the Bohr method to determine airways deadspace for non-uniform inspired gas tensions.

BACKGROUND: The Bohr method is a technique to determine airways deadspace using a tracer gas such as carbon dioxide or nitrogen. It is based on the assumption that the inspired concentration of the tracer gas is constant throughout inspiration. However, in some lung function measurement techniques where inspired concentration of the tracer gas may be required to vary, or where rapid injection of the tracer gas is made in real time, uniform inspired concentration is difficult or impossible to achieve, which leads to inaccurate estimation of deadspace using the Bohr equation. One such lung function measurement technique is the inspired sinewave technique. OBJECTIVE: In this paper, we proposed a modification of the Bohr method, relaxing the requirement of absolute uniformity of tracer concentration in the inspired breath. METHOD: The new method used integration of flow and concentration. A computer algorithm sought an appropriate value of deadspace to satisfy the mass balance equation for each breath. A modern gas mixing apparatus with rapid mass flow controllers was used to verify the procedure. RESULT: Experiments on a tidally ventilated bench lung showed that the new method estimated dead space within 10% of the actual values whereas the traditional Bohr deadspace gave more than 50% error. CONCLUSION: The new method improved the accuracy of deadspace estimation when the inspired concentration is not uniform. This improvement would lead to more accurate diagnosis and more accurate estimations of other lung parameters such as functional residual capacity and pulmonary blood flow.

Intravascular oxygen sensors with novel applications for bedside respiratory monitoring.

Measurement allows us to quantify various parameters and variables in natural systems. In addition, by measuring the effect by which a perturbation of one part of the system influences the system as a whole, insights into the functional mechanisms of the system can be inferred. Clinical monitoring has a different role to that of scientific measurement. Monitoring describes measurements whose prime purpose is not to give insights into underlying mechanisms, but to provide information to 'warn' of imminent events. What is often more important is the description of trends in measured variables. In this article, we give some examples - focussed around oxygen sensors - of how new sensors can make important measurements and might in the future contribute to improved clinical management.

Intra-breath arterial oxygen oscillations detected by a fast oxygen sensor in an animal model of acute respiratory distress syndrome.

BACKGROUND: There is considerable interest in oxygen partial pressure (Po2) monitoring in physiology, and in tracking Po2 changes dynamically when it varies rapidly. For example, arterial Po2 ([Formula: see text]) can vary within the respiratory cycle in cyclical atelectasis (CA), where [Formula: see text] is thought to increase and decrease during inspiration and expiration, respectively. A sensor that detects these [Formula: see text] oscillations could become a useful diagnostic tool of CA during acute respiratory distress syndrome (ARDS). METHODS: We developed a fibreoptic Po2 sensor (<200 µm diameter), suitable for human use, that has a fast response time, and can measure Po2 continuously in blood. By altering the inspired fraction of oxygen ([Formula: see text]) from 21 to 100% in four healthy animal models, we determined the linearity of the sensor's signal over a wide range of [Formula: see text] values in vivo. We also hypothesized that the sensor could measure rapid intra-breath [Formula: see text] oscillations in a large animal model of ARDS. RESULTS: In the healthy animal models, [Formula: see text] responses to changes in [Formula: see text] were in agreement with conventional intermittent blood-gas analysis (n=39) for a wide range of [Formula: see text] values, from 10 to 73 kPa. In the animal lavage model of CA, the sensor detected [Formula: see text] oscillations, also at clinically relevant [Formula: see text] levels close to 9 kPa. CONCLUSIONS: We conclude that these fibreoptic [Formula: see text] sensors have the potential to become a diagnostic tool for CA in ARDS.

A flowing liquid test system for assessing the linearity and time-response of rapid fibre optic oxygen partial pressure sensors.

The development of a methodology for testing the time response, linearity and performance characteristics of ultra fast fibre optic oxygen sensors in the liquid phase is presented. Two standard medical paediatric oxygenators are arranged to provide two independent extracorporeal circuits. Flow from either circuit can be diverted over the sensor under test by means of a system of rapid cross-over solenoid valves exposing the sensor to an abrupt change in oxygen partial pressure, P O2. The system is also capable of testing the oxygen sensor responses to changes in temperature, carbon dioxide partial pressure P CO2 and pH in situ. Results are presented for a miniature fibre optic oxygen sensor constructed in-house with a response time ≈ 50 ms and a commercial fibre optic sensor (Ocean Optics Foxy), when tested in flowing saline and stored blood.

Simulating hypoxia and modelling the airway.

Apnoea due to airway obstruction is an ever present concern in anaesthesia and critical care practice and results in rapid development of hypoxaemia that is not always remediable by manual bag-mask ventilation. As it is often difficult or impossible to study experimentally (although some historical animal data exist), it is useful to model the kinetics of hypoxaemia following airway obstruction. Despite being a complex event, the consequences of airway obstruction can be predicted with reasonable fidelity using mathematical and computer modelling. Over the last 15 years, a number of high fidelity mathematical and computer models have been developed, that have thrown light on this important event.

Design of a test system for fast time response fibre optic oxygen sensors.

A test system has been developed that can be used to calibrate and determine the time response, linearity and temperature sensitivity of a fibre optic oxygen sensor. The simple system obviates the need for precision gas standards and the requirement to generate a true square wave step response, which is seldom achievable. The sensor is mounted in a small chamber containing air or a known fraction of oxygen. By means of a computer-controlled switch, the absolute pressure within the chamber can be changed rapidly to a new steady state value. The partial pressure of oxygen changes in direct proportion to the absolute pressure, and so the accuracy and linearity and response time of the PO(2) calibration are limited only by those of the absolute pressure sensor. The temperature sensitivity of a commercial sensor and a means of correction are also described.

Sub-Tenon's block reduces both intraoperative and postoperative analgesia requirement in vitreo-retinal surgery under general anaesthesia.

BACKGROUND AND OBJECTIVE: We compared the effects of sub-Tenon's local anaesthetic block and placebo on peri-operative opioid requirement and cardiovascular stability and on postoperative pain, nausea and vomiting in patients undergoing vitreo-retinal surgery under general anaesthesia. METHODS: We studied 43 patients undergoing vitreo-retinal surgery under general anaesthesia in a randomized double blind study. Patients received a standard general anaesthetic followed by a sub-Tenon's injection of 4-5 mL of either bupivacaine 0.75% or saline. We recorded intraoperative invasive arterial pressure, then the incidence and severity of pain and of nausea and vomiting, for 24 h postoperatively. RESULTS: In the sub-Tenon's bupivacaine group, there was a significant reduction in the perioperative opioid use and a reduction in the frequency of bradycardia and hypertensive episodes, defined as a rise > 25% of baseline for a duration of > 3 min. The sub-Tenon's bupivacaine group also had significantly lower pain scores and nausea scores at 12 h, concomitant with a lower consumption of analgesia and antiemetics. CONCLUSIONS: This local anaesthetic technique is effective in vitreo-retinal surgery and can be safely applied to this population of patients regardless of axial length.

Outcome for cardiothoracic surgical patients requiring multidisciplinary intensive care.

BACKGROUND AND OBJECTIVE: Patients who require multidisciplinary intensive care after cardiac surgery have a poor prognosis. The aim was to investigate factors in the mortality of this group of patients at 6 months. METHODS: A retrospective analysis was made of the 6-month mortality rate in 301 adults who required admission to a multidisciplinary intensive care unit following cardiac surgery from 1991 to 1997. Mortality was correlated with clinical and patient characteristic variables. RESULTS: The intensive care mortality rate was 34% and at 6 months after patients' discharge from intensive care it was 51%. There were positive correlations with death at 6 months for ventricular failure (odds ratio of death 3.4, P = 0.002), sepsis (odds ratio 3.0, P = 0.004) and age over 80 yr (odds ratio of death 9.2, P = 0.034). Patients who had undergone isolated coronary artery graft surgery (odds ratio of death 0.28, P = 0.036) or thoracic surgery (odds ratio of death 0.22, P = 0.042) had better 6-month outcomes. Patients with respiratory or renal failure in the absence of ventricular failure or sepsis had a 6-month mortality rate of 36%; but the lower mortality rate did not achieve statistical significance. CONCLUSIONS: The 6-month mortality rate of 51% in a group of patients requiring multidisciplinary intensive care after cardiac surgery is consistent with previous studies; mortality was particularly high in extreme old age and in patients referred with sepsis or ventricular failure. Those patients with uncomplicated respiratory or renal failure had a better outcome than the group as a whole.

A tidal ventilation model for oxygenation in respiratory failure.

We develop tidal-ventilation pulmonary gas-exchange equations that allow pulmonary shunt to have different values during expiration and inspiration, in accordance with lung collapse and recruitment during lung dysfunction (Am. J. Respir. Crit. Care Med. 158 (1998) 1636). Their solutions are tested against published animal data from intravascular oxygen tension and saturation sensors. These equations provide one explanation for (i) observed physiological phenomena, such as within-breath fluctuations in arterial oxygen saturation and blood-gas tension; and (ii) conventional (time averaged) blood-gas sample oxygen tensions. We suggest that tidal-ventilation models are needed to describe within-breath fluctuations in arterial oxygen saturation and blood-gas tension in acute respiratory distress syndrome (ARDS) subjects. Both the amplitude of these oxygen saturation and tension fluctuations, and the mean oxygen blood-gas values, are affected by physiological variables such as inspired oxygen concentration, lung volume, and the inspiratory:expiratory (I:E) ratio, as well as by changes in pulmonary shunt during the respiratory cycle.

How high do the subclavian arteries ascend into the neck? A population study using magnetic resonance imaging.

BACKGROUND: The relationship between the larynx and the subclavian arteries was studied in a series of magnetic resonance images (MRIs) from 50 patients without neck pathology. METHODS: The vertical distances of the excursion of the subclavian arteries into the neck was measured, as was the distance from the cricoid cartilage to the highest point of this excursion. Statistical analysis allows the probability of any given cricoid-subclavian distance occurring in the population to be estimated. RESULTS: The mean (SD) excursion of the right subclavian artery above the clavicle was 10.4 (11.4) mm. The mean (SD) distance from the cricoid cartilage to the right subclavian artery was 30.6 (14.3) mm, and the data showed a high degree of variance. There was a linear relationship between neck length and cricoid-subclavian distance (r=0.58), which explained some of the variance in the latter, but there was also wide individual variance, which was independent of this regression. CONCLUSIONS: When performing a percutaneous tracheostomy, a 'safe' distance between the incision site and subclavian artery cannot be assumed or reliably predicted from the neck length.

A method of reconstruction of clinical gas-analyzer signals corrupted by positive-pressure ventilation.

The use of sidestream infrared and paramagnetic clinical gas analyzers is widespread in anesthesiology and respiratory medicine. For most clinical applications, these instruments are entirely satisfactory. However, their ability to measure breath-by-breath volumetric gas fluxes, as required for measurement of airway dead space, oxygen uptake, and so on, is usually inferior to that of the mass spectrometer, and this is thought to be due, in part, to their slower response times. We describe how volumetric gas analysis with the Datex Ultima analyzer, although reasonably accurate for spontaneous ventilation, gives very inaccurate results in conditions of positive-pressure ventilation. We show that this problem is a property of the gas sampling system rather than the technique of gas analysis itself. We examine the source of this error and describe how cyclic changes in airway pressure result in variations in the flow rate of the gas within the sampling catheter. This results in the phenomenon of "time distortion," and the resultant gas concentration signal becomes a nonlinear time series. This corrupted signal cannot be aligned or integrated with the measured flow signal. We describe a method to correct for this effect. With the use of this method, measurements required for breath-by-breath gas-exchange models can be made easily and reliably in the clinical setting.

A mathematical model of electron transfer within the mitochondrial respiratory cytochromes.

A simple mathematical model of electron flow along the mitochondrial respiratory cytochrome assembly and the transfer of electrons to molecular oxygen is presented. First, an expression for the current-voltage relationship for a biological oxygen electrode is derived, and from this the relationship between oxygen consumption rate and oxygen partial pressure is determined. An independent relationship between mitochondrial oxygen partial pressure and oxygen supply rate is then derived. By eliminating oxygen partial pressure from these two expressions, we may obtain a relationship between oxygen supply rate and oxygen consumption rate. This model is then used to investigate the effects of tissue dysoxia, uncoupling of oxidative phosphorylation, increased cellular diffusional resistance and inhomogeneities in oxygen supply on oxygen consumption. It is concluded that each of the above contribute in varying degrees to the phenomenon of "pathological oxygen supply dependency".

Response-time enhancement of a clinical gas analyzer facilitates measurement of breath-by-breath gas exchange.

Tidal ventilation gas-exchange models in respiratory physiology and medicine not only require solution of mass balance equations breath-by-breath but also may require within-breath measurements, which are instantaneous functions of time. This demands a degree of temporal resolution and fidelity of integration of gas flow and concentration signals that cannot be provided by most clinical gas analyzers because of their slow response times. We have characterized the step responses of the Datex Ultima (Datex Instrumentation, Helsinki, Finland) gas analyzer to oxygen, carbon dioxide, and nitrous oxide in terms of a Gompertz four-parameter sigmoidal function. By inversion of this function, we were able to reduce the rise times for all these gases almost fivefold, and, by its application to real on-line respiratory gas signals, it is possible to achieve a performance comparable to the fastest mass spectrometers. With the use of this technique, measurements required for non-steady-state and tidal gas-exchange models can be made easily and reliably in the clinical setting.

Severe unilateral bronchospasm mimicking inadvertent endobronchial intubation: a complication of the use of a topical lidocaine Laryngojet injector.

A healthy young woman is described in whom the left chest was unable to be inflated after intubation. The differential diagnosis and management are discussed. Severe unilateral bronchospasm was probably caused by topical lidocaine injected at the vocal cords and, inadvertently, into the left main bronchus with a Laryngojet device.