Andrew D. Farmery

Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic

Background: Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known. Method: Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4–7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout. Results: Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25–168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring. Conclusion: This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop.

A Cylindrical-Core Fiber-Optic Oxygen Sensor Based on Fluorescence Quenching of a Platinum Complex Immobilized in a Polymer Matrix

A miniature (200 μm in diameter) cylindrical-core fiber-optic oxygen sensor has been developed for measuring rapid change in oxygen partial pressure (pO2). The fiber-optic sensing element is based on a cylindrical-core waveguide structure formed by coating a thin medical grade polymer sensing film that contains immobilized Pt(II) complexes on silica optical fiber. The performance such as sensitivity and time response of the fiber-optic oxygen sensors were evaluated using luminescence intensity measurement. To determine accurately the response time of the fiber optic oxygen sensors, a test chamber was used to provide rapid changes in the partial pressure of oxygen. The result showed that the time response (time-constant, τ) of this cylindrical-core fiber optic oxygen sensor is less than 50 ms. To our knowledge, this is the fastest such sensor of this size covering the full dynamic range of pO2 from 0 to 100 kPa.

A fibre optic oxygen sensor that detects rapid PO2 changes under simulated conditions of cyclical atelectasis in vitro

Highlights • Real time detection of cyclical atelectasis is fundamental for individualised mechanical-ventilation therapy in ARDS.• Intra-arterial oxygen sensors could be used to detect the breath-by-breath oscillations in PO2 during cyclical atelectasis.• The fidelity with which oxygen sensors can detect these arterial PO2 oscillations depends on the sensors’ speed of response.• We present a system for testing fast-response fibre optic oxygen sensors under simulated conditions of cyclical atelectasis.• We show that a prototype fibre optic oxygen sensor, compatible with clinical use, can detect rapid PO2 changes in vitro.

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.

Experimental investigation of the effect of polymer matrices on polymer fibre optic oxygen sensors and their time response characteristics using a vacuum testing chamber and a liquid flow apparatus

Very fast sensors that are able to track rapid changes in oxygen partial pressure (PO2) in the gas and liquid phases are increasingly required in scientific research – particularly in the life sciences. Recent interest in monitoring very fast changes in the PO2 of arterial blood in some respiratory failure conditions is one such example. Previous attempts to design fast intravascular electrochemical oxygen sensors for use in physiology and medicine have failed to meet the criteria that are now required in modern investigations. However, miniature photonic devices are capable of meeting this need. In this article, we present an inexpensive polymer type fibre-optic, oxygen sensor that is two orders of magnitude faster than conventional electrochemical oxygen sensors. It is constructed with biologically inert polymer materials and is both sufficiently small and robust for direct insertion in to a human artery. The sensors were tested and evaluated in both a gas testing chamber and in a flowing liquid test system. The results showed a very fast T90 response time, typically circa 20 ms when tested in the gas phase, and circa 100 ms in flowing liquid.

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.

Optimizing design for polymer fiber optic oxygen sensors

The development of a clinically useful fiber-optic oxygen sensor based on oxygen fluorescence quenching is described in this paper. The fiber optic oxygen sensor was formed by coating a thin polymer matrix, which contains an oxygen sensitive fluorophore, on the tapered end of a polymer optical fiber. Three acrylate polymers have been used for the matrix, and the sensitivity and time-response of the oxygen sensors were tested. The results showed that the sensitivity and time response of the sensors can be modified using different polymer matrices. Using these modifications, a very fast time response of the polymer fiber-based oxygen sensor could be readily achieved and the fastest T10-90 response time were <;100 ms.

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.

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 (PaO2) can vary within the respiratory cycle in cyclical atelectasis (CA), where PaO2 is thought to increase and decrease during inspiration and expiration, respectively. A sensor that detects these PaO2 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 (FIO2) from 21 to 100% in four healthy animal models, we determined the linearity of the sensors signal over a wide range of PaO2 values in vivo. We also hypothesized that the sensor could measure rapid intra-breath PaO2 oscillations in a large animal model of ARDS. Results In the healthy animal models, PaO2 responses to changes in FIO2 were in agreement with conventional intermittent blood-gas analysis (n=39) for a wide range of PaO2 values, from 10 to 73 kPa. In the animal lavage model of CA, the sensor detected PaO2 oscillations, also at clinically relevant PaO2 levels close to 9 kPa. Conclusions We conclude that these fibreoptic PaO2 sensors have the potential to become a diagnostic tool for CA in ARDS.