Publications by authors named "Douglas C Crockett"

11 Publications

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Bedside monitoring of lung volume available for gas exchange.

Intensive Care Med Exp 2021 Jan 11;9(1). Epub 2021 Jan 11.

Nuffield Division of Anaesthetics, University of Oxford, Oxford, UK.

Background: Bedside measurement of lung volume may provide guidance in the personalised setting of respiratory support, especially in patients with the acute respiratory distress syndrome at risk of ventilator-induced lung injury. We propose here a novel operator-independent technique, enabled by a fibre optic oxygen sensor, to quantify the lung volume available for gas exchange. We hypothesised that the continuous measurement of arterial partial pressure of oxygen (PaO) decline during a breath-holding manoeuvre could be used to estimate lung volume in a single-compartment physiological model of the respiratory system.

Methods: Thirteen pigs with a saline lavage lung injury model and six control pigs were studied under general anaesthesia during mechanical ventilation. Lung volumes were measured by simultaneous PaO rate of decline (V) and whole-lung computed tomography scan (V) during apnoea at different positive end-expiratory and end-inspiratory pressures.

Results: A total of 146 volume measurements was completed (range 134 to 1869 mL). A linear correlation between V and V was found both in control (slope = 0.9, R = 0.88) and in saline-lavaged pigs (slope = 0.64, R = 0.70). The bias from Bland-Altman analysis for the agreement between the V and V was - 84 mL (limits of agreement ± 301 mL) in control and + 2 mL (LoA ± 406 mL) in saline-lavaged pigs. The concordance for changes in lung volume, quantified with polar plot analysis, was - 4º (LoA ± 19°) in control and - 9° (LoA ± 33°) in saline-lavaged pigs.

Conclusion: Bedside measurement of PaO rate of decline during apnoea is a potential approach for estimation of lung volume changes associated with different levels of airway pressure.
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http://dx.doi.org/10.1186/s40635-020-00364-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835652PMC
January 2021

Lung heterogeneity and deadspace volume in acute respiratory distress syndrome animals using the inspired sinewave test.

Physiol Meas 2020 Oct 13. Epub 2020 Oct 13.

University of Oxford Medical Sciences Division, Oxford, Oxfordshire, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.

The acute respiratory distress syndrome is associated with a high rate of morbidity and mortality, as patients undergoing mechanical ventilation are at risk of ventilator-induced lung injuries.

Objective: To measure the lung heterogeneity and deadspace volume to find safer ventilator strategies. Then, the ventilator settings could offer homogeneous ventilation and theoretically equalise and reduce tidal strain/stress in the lung parenchyma.

Approach: The Inspired Sinewave Test (IST) is a non-invasive lung measurement tool, which does not require patients' cooperation. The IST can measure the effective lung volume, pulmonary blood flow and deadspace volume. We developed a computational simulation of the cardiopulmonary system to allow lung heterogeneity to be quantified using data solely derived from the IST. Then, the method to quantify lung heterogeneity using two IST tracer gas frequencies (180s and 60s) was introduced and experimented in the simulation lungs and in animal models. Thirteen anaesthetised pigs were studied with the IST, both before and after experimental lung injury (saline-lavage ARDS model). The deadspace volume is compared between IST and the SF_{6} Washout method.

Results: The IST could measure the lung heterogeneity using two frequencies tracer gases. Furthermore, the value of IST ventilation heterogeneity in ARDS lungs were higher than in control lungs at PEEP 10cmH_{2}O (AuC=0.85, p<0.001). Deadspace volume values measured by the IST has a strong relationship with the measured values of the SF_{6} (9mL bias and limits of agreement from -79mL to 57mL in control animals).

Significance: the potential impact of the IST technique in the identification of ventilation and perfusion heterogeneity during ventilator support.
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http://dx.doi.org/10.1088/1361-6579/abc0b5DOI Listing
October 2020

A tidal lung simulation to quantify lung heterogeneity with the Inspired Sinewave Test.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:2438-2441

We have created a lung simulation to quantify lung heterogeneity from the results of the inspired sinewave test (IST). The IST is a lung function test that is non-invasive, non-ionising and does not require patients' cooperation. A tidal lung simulation is developed to assess this test and also a method is proposed to calculate lung heterogeneity from IST results. A sensitivity analysis based on the Morris method and linear regression were applied to verify and to validate the simulation. Additionally, simulated emphysema and pulmonary embolism conditions were created using the simulation to assess the ability of the IST to identify these conditions. Experimental data from five pigs (pre-injured vs injured) were used for validation. This paper contributes to the development of the IST. Firstly, our sensitivity analysis reveals that the IST is highly accurate with an underestimation of about 5% of the simulated values. Sensitivity analysis suggested that both instability in tidal volume and extreme expiratory flow coefficients during the test cause random errors in the IST results. Secondly, the ratios of IST results obtained at two tracer gas oscillation frequencies can identify lung heterogeneity (ELV/ELV and Qp/Qp). There was dissimilarity between simulated emphysema and pulmonary embolism (p < 0.0001). In the animal model, the control group had ELV/ELV = 0.58 compared with 0.39 in injured animals (p < 0.0001).
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http://dx.doi.org/10.1109/EMBC44109.2020.9176375DOI Listing
July 2020

Real-time effects of PEEP and tidal volume on regional ventilation and perfusion in experimental lung injury.

Intensive Care Med Exp 2020 Feb 21;8(1):10. Epub 2020 Feb 21.

Centre for Human and Applied Physiological Sciences, King's College London, London, UK.

Background: Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (V) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs.

Methods: One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three V (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmHO) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and V) was used, with a three-way mixed analysis of variance (ANOVA).

Results: Two-way interactions between PEEP and group, and V and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and V in the injured group than in the control group. A two-way interaction between PEEP and V was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups.

Conclusions: Large PEEP and V levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.
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http://dx.doi.org/10.1186/s40635-020-0298-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035410PMC
February 2020

Validating the inspired sinewave technique to measure the volume of the 'baby lung' in a porcine lung-injury model.

Br J Anaesth 2020 03 14;124(3):345-353. Epub 2020 Jan 14.

Nuffield Division of Anaesthetics, University of Oxford, Oxford, UK.

Background: Bedside lung volume measurement could personalise ventilation and reduce driving pressure in patients with acute respiratory distress syndrome (ARDS). We investigated a modified gas-dilution method, the inspired sinewave technique (IST), to measure the effective lung volume (ELV) in pigs with uninjured lungs and in an ARDS model.

Methods: Anaesthetised mechanically ventilated pigs were studied before and after surfactant depletion by saline lavage. Changes in PEEP were used to change ELV. Paired measurements of absolute ELV were taken with IST (ELV) and compared with gold-standard measures (sulphur hexafluoride wash in/washout [ELV] and computed tomography (CT) [ELV]). Measured volumes were used to calculate changes in ELV (ΔELV) between PEEP levels for each method (ΔELV, ΔELV, and ΔELV).

Results: The coefficient of variation was <5% for repeated ELV measurements (n=13 pigs). There was a strong linear relationship between ELV and ELV in uninjured lungs (r=0.97), and with both ELV and ELV in the ARDS model (r=0.87 and 0.92, respectively). ELV had a mean bias of -12 to 13% (95% limits=±17 - 25%) compared with ELV and ELV. ΔELV was concordant with ΔELV and ΔELV in 98-100% of measurements, and had a mean bias of -73 to -77 ml (95% limits=±128 - 186 ml) compared with ΔELV and -1 ml (95% limits ±333 ml) compared with ΔELV.

Conclusions: IST provides a repeatable measure of absolute ELV and shows minimal bias when tracking PEEP-induced changes in lung volume compared with CT in a saline-lavage model of ARDS.
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http://dx.doi.org/10.1016/j.bja.2019.11.030DOI Listing
March 2020

Mechanical Ventilation Redistributes Blood to Poorly Ventilated Areas in Experimental Lung Injury.

Crit Care Med 2020 03;48(3):e200-e208

Centre for Human and Applied Physiological Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Objectives: Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia.

Design: Preclinical study.

Setting: Research laboratory.

Subjects: Seven anesthetized pigs 28.7 kg (SD, 2.1 kg).

Interventions: All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis.

Measurements And Main Results: Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20-40%, and ≥ 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 µL/g [95% CI, 729-908 µL/g]) than the dependent region (149 µL/g [120-178 µL/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 µL/g [12-46 µL/g]) and increased in the dependent region (39 µL/g [30-48 µL/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20-40% groups (r = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with PaO2/FIO2 ratio (ρ = -0.77 and -0.93, respectively).

Conclusions: In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening PaO2/FIO2.
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http://dx.doi.org/10.1097/CCM.0000000000004141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017942PMC
March 2020

Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury.

Intensive Care Med Exp 2019 Nov 1;7(1):59. Epub 2019 Nov 1.

Centre for Human and Applied Physiological Sciences, King's College London, London, UK.

Background: Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified.

Methods: Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmHO. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images.

Results: Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r 0.75-0.94) with agreement between CT density distributions (r 0.89-0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology.

Conclusions: Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.
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http://dx.doi.org/10.1186/s40635-019-0273-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825104PMC
November 2019

Effect of nitrite on the electroencephalographic activity in the healthy brain.

Nitric Oxide 2019 09 27;90:47-54. Epub 2019 Jun 27.

Nuffield Department of Clinical Neurosciences, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.

Background: Nitrite is a major intravascular store for nitric oxide. The conversion of nitrite to the active nitric oxide occurs mainly under hypoxic conditions to increase blood flow where it is needed the most. The use of nitrite is, therefore, being evaluated widely to reduce the brain injury in conditions resulting in cerebral hypoxia, such as cardiac arrest, ischaemic stroke or subarachnoid haemorrhage. However, as it is still unknown how exogenous nitrite affects the brain activity of healthy individuals, it is difficult to clearly understand how it affects the ischaemic brain.

Objective: Here we performed a double-blind placebo-controlled crossover study to investigate the effects of nitrite on neural activity in the healthy brain.

Methods: Twenty-one healthy volunteers were recruited into the study. All participants received a continuous infusion of sodium nitrite (0.6 mg/kg/h) on one occasion and placebo (sodium chloride) on another occasion. Electroencephalogram was recorded before the start and during the infusion. We computed the power spectrum density within the conventional frequency bands (delta, theta, alpha, beta), and the ratio of the power within the alpha and delta bands. We also measured peripheral cardiorespiratory physiology and cerebral blood flow velocities.

Results: We found no significant effect of nitrite on the power spectrum density in any frequency band. Similarly, the alpha-delta power ratio did not differ between the two conditions. The peripheral cardiorespiratory physiology and middle cerebral artery velocity and associated indices were also unaffected by the nitrite infusion. However, nitrite infusion decreased the mean blood pressure and increased the methaemoglobin concentration in the blood.

Conclusion: Our study shows that exogenous sodium nitrite does not alter the electrical activity in the healthy brain. This might be because the sodium nitrite is converted to vasoactive nitric oxide in areas of hypoxia, and in the healthy brain there is no significant amount of conversion due to lack of hypoxia. However, this lack of change in the power spectrum density in healthy people emphasises the specificity of the brain's response to nitrite in disease.
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http://dx.doi.org/10.1016/j.niox.2019.06.002DOI Listing
September 2019

Noninvasive cardiac output monitoring in a porcine model using the inspired sinewave technique: a proof-of-concept study.

Br J Anaesth 2019 Aug 4;123(2):126-134. Epub 2019 Apr 4.

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Background: Cardiac output (Q˙) monitoring can support the management of high-risk surgical patients, but the pulmonary artery catheterisation required by the current 'gold standard'-bolus thermodilution (Q˙)-has the potential to cause life-threatening complications. We present a novel noninvasive and fully automated method that uses the inspired sinewave technique to continuously monitor cardiac output (Q˙).

Methods: Over successive breaths the inspired nitrous oxide (NO) concentration was forced to oscillate sinusoidally with a fixed mean (4%), amplitude (3%), and period (60 s). Q˙ was determined in a single-compartment tidal ventilation lung model that used the resulting amplitude/phase of the expired NO sinewave. The agreement and trending ability of Q˙ were compared with Q˙ during pharmacologically induced haemodynamic changes, before and after repeated lung lavages, in eight anaesthetised pigs.

Results: Before lung lavage, changes in Q˙ and Q˙ from baseline had a mean bias of -0.52 L min (95% confidence interval [CI], -0.41 to -0.63). The concordance between Q˙ and Q˙ was 92.5% as assessed by four-quadrant analysis, and polar plot analysis revealed a mean angular bias of 5.98° (95% CI, -24.4°-36.3°). After lung lavage, concordance was slightly reduced (89.4%), and the mean angular bias widened to 21.8° (-4.2°, 47.6°). Impaired trending ability correlated with shunt fraction (r=0.79, P<0.05).

Conclusions: The inspired sinewave technique provides continuous and noninvasive monitoring of cardiac output, with a 'marginal-good' trending ability compared with cardiac output based on thermodilution. However, the trending ability can be reduced with increasing shunt fraction, such as in acute lung injury.
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http://dx.doi.org/10.1016/j.bja.2019.02.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676057PMC
August 2019
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