Philip Hughes

Measurement of twitch transdiaphragmatic, esophageal, and endotracheal tube pressure with bilateral anterolateral magnetic phrenic nerve stimulation in patients in the intensive care unit.

ObjectiveIn the critically ill, respiratory muscle strength usually has been assessed by measuring maximum inspiratory pressure. The maneuver is volitional, and results can be unreliable. The nonvolitional technique of bilateral anterolateral magnetic stimulation of the phrenic nerves, producing twitch transdiaphragmatic pressure, has been successful in normal subjects and ambulatory patients. In this study we used the technique in the intensive care unit and explored the measurement of twitch endotracheal tube pressure as a less invasive technique to assess diaphragmatic contractility. DesignClinical study to quantify diaphragm strength in the intensive care unit. SettingPatients from three London teaching hospital intensive care units and high-dependency units. PatientsForty-one intensive care patients were recruited. Of these, 33 (20 men, 13 women) were studied. InterventionsEsophageal and gastric balloon catheters were passed through the anaesthetized nose, and an endotracheal tube occlusion device was placed in the ventilation circuit, next to the endotracheal tube. Two 43-mm magnetic coils were placed anteriorly on the patient’s neck, and the phrenic nerves were stimulated magnetically. Measurements and Main Results On phrenic nerve stimulation, twitch gastric pressure, twitch esophageal pressure, twitch transdiaphragmatic pressure, and twitch endotracheal tube pressure were measured. Forty-one consecutive patients consented to take part in the study, and twitch pressure data were obtained in 33 of these. Mean transdiaphragmatic pressure was 10.7 cm H2O, mean twitch esophageal pressure was 6.7 cm H2O, and mean twitch endotracheal tube pressure was 6.7 cm H2O. The mean difference between twitch esophageal pressure and twitch endotracheal tube pressure was 0.02 cm H2O. Correlation of the means of twitch endotracheal tube pressure to twitch esophageal pressure was 0.93, and that for twitch endotracheal tube pressure to transdiaphragmatic pressure was 0.78. ConclusionsTransdiaphragmatic pressure can be measured in the critically ill to give a nonvolitional assessment of diaphragm contractility, but not all patients can be studied. At present, the relationship of twitch endotracheal tube pressure to transdiaphragmatic pressure is too variable to reliably represent a less invasive measure of diaphragm strength.

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial

Importance Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants A randomized clinical trial of patients with persistent hypercapnia (PaCO2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] PaCO2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. Conclusions and Relevance Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. Trial Registration clinicaltrials.gov Identifier: NCT00990132

DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis - a randomised controlled trial.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4(®) diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure. OBJECTIVE The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure. DESIGN The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy. PARTICIPANTS Eligible participants had a diagnosis of ALS (ALS laboratory-supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria), had been stabilised on riluzole for 30 days, were aged ≥ 18 years and were in respiratory failure. We planned to recruit 108 patients from seven UK-based specialist ALS or respiratory centres. Allocation was performed using 1 : 1 non-deterministic minimisation. INTERVENTIONS Participants were randomised to either standard care (NIV alone) or standard care (NIV) plus DP using the NeuRX/4 DPS. MAIN OUTCOME MEASURES The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Secondary outcomes were patient quality of life [assessed by European Quality of Life-5 Dimensions, three levels (EQ-5D-3L), Short Form questionnaire-36 items and Sleep Apnoea Quality of Life Index questionnaire]; carer quality of life (EQ-5D-3L and Caregiver Burden Inventory); cost-utility analysis and health-care resource use; tolerability and adverse events. Acceptability and attitudes to DP were assessed in a qualitative substudy. RESULTS In total, 74 participants were randomised into the trial and analysed, 37 participants to NIV plus pacing and 37 to standard care, before the Data Monitoring and Ethics Committee advised initial suspension of recruitment (December 2013) and subsequent discontinuation of pacing (on safety grounds) in all patients (June 2014). Follow-up assessments continued until the planned end of the study in December 2014. The median survival (interquartile range) was 22.5 months (lower quartile 11.8 months; upper quartile not reached) in the NIV arm and 11.0 months (6.7 to 17.0 months) in the NIV plus pacing arm, with an adjusted hazard ratio of 2.27 (95% confidence interval 1.22 to 4.25; p = 0.01). CONCLUSIONS Diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure. FUTURE WORK It may be that certain population subgroups benefit from DP. We are unable to explain the mechanism behind the excess mortality in the pacing arm, something the small trial size cannot help address. Future research should investigate the mechanism by which harm or benefit occurs further. TRIAL REGISTRATION Current Controlled Trials ISRCTN53817913. FUNDING This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 45. See the HTA programme website for further project information. Additional funding was provided by the Motor Neurone Disease Association of England, Wales and Northern Ireland.

A non-invasive system to evaluate diaphragmatic strength in ventilated patients

In this paper we describe a system that allows an indicator of diaphragmatic strength to be determined non-invasively in mechanically ventilated patients. The system is comprised of an occlusion device that can be incorporated into the ventilator tubing and an occlusion control unit to operate the occlusion. The system electronically coordinates the timing of airway occlusion at the mouthpiece, application of a magnetic phrenic nerve stimulus and rapid removal of the occlusion once the measurement has been made. The system therefore permits measurement of the change in airway pressure produced by a stimulated diaphragm contraction, without disconnection from the ventilator. Other important respiratory measurements such as twitch mouth pressure, simulated cough and P0.1 can also be performed on non-ventilated patients in a repeatable and systematic manner.