Jonathan Fuld

Ethical issues surrounding do not attempt resuscitation orders: decisions, discussions and deleterious effects

Since their introduction as ‘no code’ in the 1980s and their later formalisation to ‘do not resuscitate’ orders, such directions to withhold potentially life-extending treatments have been accompanied by multiple ethical issues. The arguments for when and why to instigate such orders are explored, including a consideration of the concept of futility, allocation of healthcare resources, and reaching a balance between quality of life and quality of death. The merits and perils of discussing such decisions with patients and/or their relatives are reviewed and the unintended implications of ‘do not attempt resuscitation’ orders are examined. Finally, the paper explores some alternative methods to approaching the resuscitation decision, and calls for empirical evaluation of such methods that may reduce the ethical dilemmas physicians currently face.

The Universal Form of Treatment Options (UFTO) as an Alternative to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) Orders: A Mixed Methods Evaluation of the Effects on Clinical Practice and Patient Care

Aims To determine whether the introduction of the Universal Form of Treatment Options (the UFTO), as an alternative approach to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders, reduces harms in patients in whom a decision not to attempt cardiopulmonary resuscitation (CPR) was made, and to understand the mechanism for any observed change. Methods A mixed-methods before-and-after study with contemporaneous case controls was conducted in an acute hospital. We examined DNACPR (103 patients with DNACPR orders in 530 admissions) and UFTO (118 decisions not to attempt resuscitation in 560 admissions) practice. The Global Trigger Tool was used to quantify harms. Qualitative interviews and observations were used to understand mechanisms and effects. Results Rate of harms in patients for whom there was a documented decision not to attempt CPR was reduced: Rate difference per 1000 patient-days was 12.9 (95% CI: 2.6–23.2, p-value = 0.01). There was a difference in the proportion of harms contributing to patient death in the two periods (23/71 in the DNACPR period to 4/44 in the UFTO period (95% CI 7.8–36.1, p-value = 0.006). Significant differences were maintained after adjustment for known confounders. No significant change was seen on contemporaneous case control wards. Interviews with clinicians and observation of ward practice revealed the UFTO helped provide clarity of goals of care and reduced negative associations with resuscitation decisions. Conclusions Introducing the UFTO was associated with a significant reduction in harmful events in patients in whom a decision not to attempt CPR had been made. Coupled with supportive qualitative evidence, this indicates the UFTO improved care for this vulnerable group. Trial Registration Controlled-Trials.com ISRCTN85474986 UK Comprehensive Research Network Portfolio 7932

Documentation of resuscitation decision-making: A survey of practice in the United Kingdom

UNLABELLED Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders have been in use since the 1990s. The Resuscitation Council UK (RCUK) provides guidance on the content and use of such forms in the UK but there is no national policy. AIM To determine the content of DNACPR forms in the UK, and the geographical distribution of the use of different forms. METHODS All acute trusts within the United Kingdom were contacted via a combination of email and telephone, with a request for the current DNACPR form along with information about its development and use. Characteristics of the model RCUK DNACPR form were compared with the non-RCUK DNACPR forms which we received. Free text responses were searched for commonly occurring phrases. RESULTS 118/161 English NHS Acute Trusts (accounting for 377 hospitals), 3/6 Northern Irish NHS Acute Trusts (accounting for 25 hospitals) and 3/7 Welsh Health Boards (accounting for 73 hospitals) responded. All Scottish hospitals have the same form. All responding trusts had active policies and have a DNACPR form in use. 38.9% of respondent hospitals have adopted the RCUK form with minor amendments. The remainder of the responding hospitals reported independent forms. 66.8% of non-RCUK forms include a transfer plan to ambulance staff and 48.4% of non-RCUK forms are valid in the community. Several independent trusts submitted DNACPR forms with escalation plans. CONCLUSIONS There is wide variation in the forms used for indicating DNACPR decisions. Documentation is rapidly evolving to meet the needs of patients and to respond to new evidence.

Validity of Reporting Oxygen Uptake Efficiency Slope from Submaximal Exercise Using Respiratory Exchange Ratio as Secondary Criterion

Background. Oxygen uptake efficiency slope (OUES) is a reproducible, objective marker of cardiopulmonary function. OUES is reported as being relatively independent of exercise intensity. Practical guidance and criteria for reporting OUES from submaximal tests has not been established. Objective. Evaluate the use of respiratory exchange ratio (RER) as a secondary criterion for reporting OUES. Design. 100 healthy volunteers (53 women) completed a ramped treadmill protocol to exhaustive exercise. OUES was calculated from data truncated to RER levels from 0.85 to 1.2 and compared to values generated from full test data. Results. Mean (sd) OUES from full test data and data truncated to RER 1.0 and RER 0.9 was 2814 (718), 2895 (730), and 2810 (789) mL/min per 10-fold increase in VE, respectively. Full test OUES was highly correlated with OUES from RER 1.0 (r = 0.9) and moderately correlated with OUES from RER 0.9 (r = 0.79). Conclusion. OUES values peaked in association with an RER level of 1.0. Sub-maximal OUES values are not independent of exercise intensity. There is a significant increase in OUES value as exercise moves from low to moderate intensity. RER can be used as a secondary criterion to define this transition.

Evaluating the Role of Inflammation in Chronic Airways Disease: The ERICA Study

Abstract Extrapulmonary manifestations are recognized to be of increasing clinical importance in Chronic Obstructive Pulmonary disease. To investigate cardiovascular and skeletal muscle manifestations of COPD, we developed a unique UK consortium funded by the Technology Strategy Board and Medical Research Council comprising industry in partnership with 5 academic centres. ERICA (Evaluating the Role of Inflammation in Chronic Airways disease) is a prospective, longitudinal, observational study investigating the prevalence and significance of cardiovascular and skeletal muscle manifestations of COPD in 800 subjects. Six monthly follow up will assess the predictive value of plasma fibrinogen, cardiovascular abnormalities and skeletal muscle weakness for death or hospitalization. As ERICA is a multicentre study, to ensure data quality we sought to minimise systematic observer error due to variations in investigator skill, or adherence to operating procedures, by staff training followed by assessment of inter- and intra-observer reliability of the four key measurements used in the study: pulse wave velocity (PWV), carotid intima media thickness (CIMT), quadriceps maximal voluntary contraction force (QMVC) and 6-minute walk distance (6MWT). This report describes the objectives and methods of the ERICA trial, as well as the inter- and intra-observer reliability of these measurements.

Development of the Universal Form of Treatment Options (UFTO) as an alternative to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders: a cross‐disciplinary approach

Rationale aims and objectives Problems exist with Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders: they are often misinterpreted by clinicians to mean that other treatments should be withheld; resuscitation decision discussions are difficult; patients remain inappropriately for resuscitation. We developed an alternative approach. Methods An adapted Delphi method was used. Senior clinicians were interviewed about the strengths and weakness of current practice. Teams who had initiated alternative approaches internationally were contacted. Focus groups were conducted with doctors, nurses and patients to further understand problems with DNACPR orders and establish essential aspects of a new approach. A behavioral economist and management consultant contributed advice. The resulting form was recirculated and further refined. It was: snowballed out to others with specialist expertise (palliative care physicians, intensivists, etc) for further feedback; assessed in simulated clinical encounters before being piloted; further adjusted once in clinical practice. In parallel, a patient information leaflet was developed along with education materials. Results Consensus was achieved that the new approach should: be universal; have discussions and clinical conditions documented first; clarify goals of overall treatment (active treatment or optimal supportive care); contextualize the resuscitation decision among other treatment decisions; have a free text box for ‘opting out’ of invasive treatments, rather than tick boxes; be green; be limited to one page. Conclusions The Universal Form of Treatment Options was developed iteratively with patients, doctors and nurses as an alternative approach to resuscitation decisions. This paper illustrates a cross-disciplinary approach to developing practical alternatives in health care.

Skeletal muscle dysfunction: a ubiquitous outcome in chronic disease?

Skeletal muscle wasting is a debilitating consequence of respiratory disease, particularly well characterised in individuals with chronic obstructive pulmonary disease (COPD). However, it remains controversial whether peripheral muscle dysfunction is an intrinsic part of the respiratory disease process, or a generalised response to multiple atrophy stimuli. Such debate has not only informed the subtleties of pathophysiology, but has also instigated detailed analyses of the molecular mechanisms involved in the induction of muscle atrophy, identifying the ubiquitin–proteasome system (UPS) as the predominant pathway required for the rapid proteolysis seen in muscle wasting. In this issue of Thorax ( see page 113 ), Mainguy et al contribute to our knowledge of muscle weakness in chronic respiratory disease, characterising peripheral muscle function in patients with idiopathic pulmonary arterial hypertension (IPAH).1 Ten WHO functional class II–III patients with IPAH and 10 matched healthy controls underwent exercise capacity assessment, quadriceps strength testing and peripheral muscle morphology analysis. Patients with IPAH demonstrated a lower proportion of type I fibres in vastus lateralis muscle biopsies than healthy controls (38% vs 50%), and this was associated with reduced quadriceps strength and a relatively higher potential for anaerobic metabolism (enzymatic ratio of phosphofructokinase (PFK)/3-hydroxyacyl CoA dehydrogenase (HDAH)). While there was no correlation between the proportion of type I fibres and muscle strength with pulmonary haemodynamic parameters, a positive correlation was demonstrated for peripheral muscle strength and exercise capacity ( R 2=0.42, p=0.04). The authors conclude that peripheral muscle dysfunction may contribute to exercise intolerance in patients with IPAH. With relatively small numbers in the study groups, …

Patient agenda setting in respiratory outpatients A randomized controlled trial

Soliciting a patient’s agenda (the reason for their visit, concerns and expectations) is fundamental to health care but if not done effectively outcomes can be adversely affected. Forms to help patients consider important issues prior to a consultation have been tested with mixed results. We hypothesized that using an agenda form would impact the extent to which patients felt their doctor discussed the issues that were important to them. Patients were randomized to receive an agenda form to complete whilst waiting or usual care. The primary outcome measure was the proportion of patients agreeing with the statement ‘My doctor discussed the issues that were important to me’ rated on a four-point scale. Secondary outcomes included other experience and satisfaction measures, consultation duration and patient confidence. There was no significant effect of agenda form use on primary or secondary outcomes. Post hoc exploratory analyses suggested possible differential effects for new compared to follow-up patients. There was no overall benefit from the form and a risk of detrimental impact on patient experience for some patients. There is a need for greater understanding of what works for whom in supporting patients to get the most from their consultation.

The p38 mitogen activated protein kinase inhibitor losmapimod in chronic obstructive pulmonary disease patients with systemic inflammation, stratified by fibrinogen: A randomised double-blind placebo-controlled trial

Background Cardiovascular disease is a major cause of morbidity and mortality in COPD patients. Systemic inflammation associated with COPD, is often hypothesised as a causal factor. p38 mitogen-activated protein kinases play a key role in the inflammatory pathogenesis of COPD and atherosclerosis. Objectives This study sought to evaluate the effects of losmapimod, a p38 mitogen-activated protein kinase (MAPK) inhibitor, on vascular inflammation and endothelial function in chronic obstructive pulmonary disease (COPD) patients with systemic inflammation (defined by plasma fibrinogen >2·8g/l). Methods This was a randomised, double-blind, placebo-controlled, Phase II trial that recruited COPD patients with plasma fibrinogen >2.8g/l. Participants were randomly assigned by an online program to losmapimod 7·5mg or placebo tablets twice daily for 16 weeks. Pre- and post-dose 18F-Fluorodeoxyglucose positron emission tomography co-registered with computed tomography (FDG PET/CT) imaging of the aorta and carotid arteries was performed to quantify arterial inflammation, defined by the tissue-to-blood ratio (TBR) from scan images. Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Results We screened 160 patients, of whom, 36 and 37 were randomised to losmapimod or placebo. The treatment effect of losmapimod compared to placebo was not significant, at -0·05 for TBR (95% CI: -0·17, 0·07), p = 0·42, and +0·40% for FMD (95% CI: -1·66, 2·47), p = 0·70. The frequency of adverse events reported was similar in both treatment groups. Conclusions In this plasma fibrinogen-enriched study, losmapimod had no effect on arterial inflammation and endothelial function at 16 weeks of treatment, although it was well tolerated with no significant safety concerns. These findings do not support the concept that losmapimod is an effective treatment for the adverse cardiovascular manifestations of COPD.

Surrogate markers of cardiovascular risk and chronic obstructive pulmonary disease

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid–femoral (aortic) pulse wave velocity, augmentation index, and carotid intima–media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima–media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease.