Background: Dyspnea is a common, very distressing symptom in advanced cancer patients that challenges them, their relatives, and healthcare professionals. This narrative review summarizes important literature dealing with the evidence for opioids, benzodiazepines, oxygen, and steroids for treating dyspnea in advanced cancer patients.
Methods: A selective literature search was undertaken in PubMed, Embase, and the Cochrane Library and extended with literature from the reference lists of included studies up to April 2016. Inclusion criteria were that patients were suffering from advanced cancer and were receiving either opioids, benzodiazepines, corticosteroids, or oxygen. The outcome of interest was the reduction of dyspnea measured via a visual analogue scale (VAS), a numerical rating scale (NRS), or a Borg scale. This narrative review describes in detail the findings of 13 studies.
Results: Nine studies deal with the effectiveness of opioids for reducing dyspnea in advanced cancer patients. Five of these found a significant benefit to the use of opioids compared to a placebo. Three found no significant improvements, and two favored combinations of opioids and benzodiazepines. Few high-quality studies were available that used benzodiazepines (n = 3, no difference, significant improvement with midazolam + morphine, significant difference for midazolam) or oxygen (n = 2, both without significant difference). Only one study examined treating dyspnea with steroids in patients with advanced cancer, and that study indicated a benefit of steroids compared to a placebo.
Conclusions: Opioids are the drug of choice for treating refractory dyspnea in advanced cancer patients. Neither benzodiazepines nor oxygen showed significant benefit. In addition, there is insufficient literature available to draw a conclusion about the effectiveness of steroids for treating persistent dyspnea in advanced cancer patients.
CONTEXT: Morphine is recommended as the first-line pharmacological therapy for cancer dyspnea. However, the detailed practice of morphine has not been evaluated, and consensus about other opioids for cancer dyspnea has not been established.
OBJECTIVES: To explore the physician-reported practice of opioid for cancer dyspnea.
METHODS: Nationwide mail-questionnaire survey was conducted among 536 Japanese certified palliative care physicians. We randomly selected 268 and asked the following: 1) how the physicians themselves initiate and use morphine for cancer dyspnea, 2) opioid choice for dyspnea in patients who have already used opioid other than morphine regularly, and 3) opioid choice for dyspnea in patients with various degrees of renal impairment in their daily practice.
RESULTS: Overall, 192 physicians responded (response rate, 71.6%). The major (58.3%) practice of initiating morphine was "immediate-release morphine as needed" in opioid-naïve patients and the mean % increase when they titrate morphine for cancer dyspnea was 29.4±11.3% of the baseline dose. Although "titrate baseline oxycodone" was the most frequent (42.3%) for low-to-moderate-dose regular oxycodone cases, "stepwise switch to morphine" (30.0%) and "add morphine on baseline oxycodone" (27.1%) were the more frequent practices for high-dose regular oxycodone. Regardless of the baseline dose, "add morphine on baseline fentanyl" was the most frequent practice for regular transdermal fentanyl cases. Oxycodone was the most frequent choice in renal insufficiency cases, regardless of its degree.
CONCLUSIONS: Among Japanese palliative care physicians, using oxycodone for cancer dyspnea was relatively popular practice, while fentanyl was not. Oxycodone was the most preferred opioid for cancer dyspnea in the setting of renal insufficiency among Japanese palliative care physicians. We should conduct studies to confirm the safety and effectiveness of these opioid practices for cancer dyspnea.
The treatment of the symptom, dyspnea, involves pharmacological and non-pharmacological measures. Palliative care specialists use fewer common strategies for symptomatic control of dyspnea. Medical practice should always respect the autonomy of the patient and the proposed therapeutic plan should be compatible with his/her preferences. The present case report illustrates the above-mentioned aspects in a patient with asthma-COPD overlap syndrome admitted to a Palliative Care Unit.
Introduction: Early integration of palliative interventions in patients with central airway obstruction (CAO) has shown to reduce patients' distress due to breathlessness and achieve better outcomes at lower cost. This retrospective review was performed to determine whether rigid bronchoscopic interventions alleviated the symptom burden and the requirement for continued mechanical ventilation in patients with CAO in a tertiary care hospital.
Materials and Methods: Detailed records of 105 patients with CAO were retrospectively studied. The Numerical Rating Scale (NRS) score for cough and dyspnea before and after the intervention was noted. A need for an escalation or reduction in level of care was also noted.
Results: The mean NRS score for dyspnea (n = 84) reduced from 7.5 (4-9) (before procedure) to 2.5 (2-6) after intervention (P < 0.01). The mean NRS score for cough (n = 68) also reduced from 6.5 (4-8) (before procedure) to 4 (3-7) after intervention (P < 0.01). Of these patients, bronchoscopic intervention allowed transfer out of the ICU in 14 patients (42%) and immediate withdrawal of mechanical ventilation in 8 patients (42%).
Conclusion: There is an instantaneous valuable palliation of symptoms and improved health-care utilization with airway tumor debulking and stenting. Multidisciplinary interventions with emphasis delivery of palliative care provide better care of patients with CAO.
Advanced chronic obstructive pulmonary disease (COPD), is characterized by high morbidity and mortality. Patients with COPD and their families experience a range of stresses and suffering from a variety of sources throughout the disease's progression. COPD is the fourth leading cause of death in the world. It exists as a significant contributor to global morbidity and mortality, and it results in substantial economic and social burden. This review provides some key facts regarding disease burden and encourages clinician to familiarize themselves and use both conventional and palliative approach early in the disease progression for a better quality of life.
BACKGROUND: More than 15,000 children die annually in the United States due to an underlying life-limiting disease and the majority of those children experience distressing symptoms, which are not adequately relieved, such as pain and dyspnea. Multimodal analgesia, that is multiple agents, interventions, rehabilitation, psychological modalities, and integrative (nonpharmacologic) therapies, act synergistically for more effective pediatric pain and symptom control with fewer side effects than a single analgesic or modality. However, opioids, such as morphine, fentanyl, hydromorphone, oxycodone, and methadone (in the United Kingdom: diamorphine) remain the mainstay medication to effectively treat pain and dyspnea in children with serious illness.
METHODS: This article reviews commonly used opioids in Pediatric Palliative Care, which a special emphasis on 2 potentially particularly effective multimechanistic opioids: tramadol and methadone.
RESULTS: Methadone, due to its multimechanistic action profile, is possibly among the most effective and most underutilized opioid analgesics in children with severe unrelieved pain at end of life. However, methadone should not be prescribed by those unfamiliar with its use: Its effects should be closely monitored for several days, particularly when it is first started and after any dose changes.
CONCLUSIONS: Tramadol appears to play a key role in treating episodes of inconsolability in children with progressive neurologic, metabolic, or chromosomally based condition with impairment of the central nervous system. However, the recent 2017 United States Food and Drug Administration (FDA) warning against pediatric use of tramadol does not seem to be based on clinical evidence, and therefore puts children at risk for unrelieved pain or increased respiratory depression.
BACKGROUND: Dyspnea is commonly found in most conditions among patients with progressive noncancer disease.
OBJECTIVE: To clarify the effectiveness and safety of opioid administration for the treatment of dyspnea immediately before death in patients with noncancer disease.
METHODS: A retrospective case-series study involving 13 consecutive terminally ill patients who were near death and diagnosed with noncancer disease, and had refractory dyspnea and received opioid therapy, was performed. The authors investigated the route of administration, period, dosage of opioids, intensity of dyspnea-scored according to the Japanese version of the Support Team Assessment Schedule-and clinical course from a review of medical records.
RESULTS: The mean age of the patients was 86.5 ± 7.6years (range: 72-98years). The primary causes of dyspnea that led to opioid administration were heart failure (n = 10) and respiratory failure (n = 3). Oxycodone was used in one patient who experienced a complication of chronic renal failure; morphine was used in the other 12 patients. The route of opioid administration was continuous infusions in 11 patients, suppository in one, and oral administration in one. The final dose of oral morphine equivalents was 20.1 ± 8.1 mg/d (range: 5-36 mg [median: 18 mg]). All patients improved in symptom score after opioid administration. The score was significantly decreased from 3.2 ± 0.7 at the beginning of opioid administration to 1.2 ± 0.6 at final estimation ( P < .001). No severe adverse events occurred.
CONCLUSIONS:: Low-dose opioid administration in patients with terminally ill noncancer improved dyspnea and occurred no severe adverse events.
An 86-year-old white female was admitted to hospice care with lung cancer. Even with optimal medical management, she suffered from dyspnea and required opioid therapy. However, the patient had a true morphine and hydromorphone allergy. She was administered nebulized fentanyl for symptomatic relief of dyspnea with good effect and she did not experience any allergic response.
This study aimed to determine the range of mean cumulative corticosteroid doses that could effectively palliate dyspnea in opioid-treated patients with terminal cancer and to investigate the demographic or biochemical factors predictive of corticosteroid responsiveness. To this end, responders and nonresponders were compared with regard to corticosteroid dose and whether they had initiated opioid use before or concomitantly with corticosteroid use. A logistic regression analysis was conducted to assess the impacts of demographic and biochemical factors on corticosteroid effectiveness. The final sample comprised 20 patients who satisfied the selection criteria. The responders accounted for 70% of the total sample (n = 14) and experienced the strongest effect with regard to dyspnea palliation at a mean cumulative dose equivalent to 64.4 mg prednisolone. However, no factors predictive of response were identified. In summary, this retrospective study identified effective corticosteroid doses for dyspnea alleviation in terminal cancer patients. Although our study sample was limited in size, the results support further prospective research.
Dyspnea in cancer patients can lead to significant deleterious effects. There are multiple conditions that can cause dyspnea. It is important to determine which of these causes are potentially reversible and treatable, so that they can be promptly addressed. Both pharmacologic and nonpharmacologic approaches should be used to treat this difficult condition. As patients advance in their illness, palliative treatments can be considered, such as low-dose opioids, oxygen therapy, and treatments directed at anxiety relief. Physicians should also discuss goals of care with their patients.
Several children receiving palliative care experience dyspnea and pain. An order protocol for distress (OPD) is available at Sainte-Justine Hospital, aimed at alleviating respiratory distress, pain and anxiety in pediatric palliative care patients. This study evaluates the clinical use of the OPD at Sainte-Justine Hospital, through a retrospective chart review of all patients for whom the OPD was prescribed between September 2009 and September 2012. Effectiveness of the OPD was assessed using chart documentation of the patient's symptoms, or the modified Borg scale. Safety of the OPD was evaluated by measuring the time between administration of the first medication and the patient's death, and clinical evolution of the patient as recorded in the chart. One hundred and four (104) patients were included in the study. The OPD was administered at least once to 78 (75%) patients. A total of 350 episodes of administration occurred, mainly for respiratory distress (89%). Relief was provided in 90% of cases. The interval between administration of the first protocol and death was 17 h; the interval was longer in children with cancer compared to other illnesses (p = 0.02). Data from this study support the effectiveness and safety of using an OPD for children receiving palliative care.
Chronic obstructive pulmonary disease (COPD) poses challenges not only in symptom management but also in prognostication. Managing COPD requires clinicians to be proficient in the primary palliative care skills of symptom management and communication focused on eliciting goals and preferences. Dyspnea should initially be managed with the combination of long-acting muscarinic antagonists and long-acting ß-agonist inhalers, adding inhaled corticosteroids if symptoms persist. Opioids for the relief of dyspnea are safe when used at appropriate doses. Oxygen is only effective for relieving dyspnea in patients with severe hypoxemia. The relapsing-remitting nature of COPD makes prognostication challenging; however, there are tools to guide clinicians and patients in making plans both with respect to prognosis and symptom burden. Preparedness planning techniques promote detailed culturally appropriate conversations which allow patients and clinicians to consider disease-specific complications and develop goal-concordant treatment plans.
Rationale: Dyspnea is a common and distressing physical symptom among patients in the intensive care unit, which may be underdetected and undertreated.
Objective: To determine the frequency of dyspnea relative to pain, the accuracy of nurses and personal caregiver dyspnea ratings relative to patient-reported dyspnea, and the relationship between nurse-detected dyspnea and treatment.
Methods: An observational study of patients (n=138) hospitalized in a medical intensive care unit (MICU). Nurses and patients’ personal caregivers at the bedside reported on their perception of patients’ symptoms.
Measurements and Main Results: Dyspnea was assessed by patients, caregivers, and nurses with a numerical rating scale. Across all three raters, the frequency of moderate-to-severe dyspnea was similar or greater than that of pain (p < .05 for caregiver and nurse ratings). Personal caregivers’ ratings of dyspnea had substantial agreement with patient ratings ( = 0.65, p <0.001), but nurses’ ratings were not significantly related to patient ratings ( = 0.19, p = 0.39). Nurse detection of moderate-to-severe pain was significantly associated with opioid treatment (OR = 2.70, 95% CI = 1.10 to 6.60, p = 0.03); however, nurse detection of moderate-to-severe dyspnea was not significantly associated with any assessed treatment.
Conclusions: Dyspnea was reported at least as frequently as pain among the sampled MICU patients. Personal caregivers had good agreement with patient reports of moderate-to-severe dyspnea. However, even when detected by nurses, dyspnea appeared to be undertreated. These findings suggest the need for improved detection and treatment of dyspnea in the MICU.
BACKGROUND: The prevalence and severity of dyspnea increases at the end of life. Many of these patients have difficulty in reporting their symptoms. Accurate surrogate measures are needed for appropriate assessment and treatment. The Respiratory Distress Observation Scale (RDOS) is proposed as a possible scale although more external validation is needed. We set out to validate the RDOS in the context of palliative care patients near the end of life.
METHODS: We prospectively studied 122 palliative care patients in a tertiary hospital in Singapore. Prior RDOS scale training was done using a standardised instructional video. Dyspnea was assessed by RDOS, Dypsnea Numerical Rating Scale (Dyspnea-NRS) and Dyspnea Categorical Scale (Dyspnea-Cat). Pain was assessed by Pain Numerical Rating Scale (Pain-NRS). We measured RDOS interrater reliability, convergent validity and divergent validity. We utilised Area under Receiver Operating Characteristics Curve Analysis (AUC) to examine the discriminant properties of RDOS using dyspnea self-report as benchmark.
RESULTS: RDOS had good inter-rater reliability with an Intraclass Correlation (ICC) of 0.947 (95% CI 0.919-0.976). It showed moderate to strong correlation with Dyspnea-NRS (r=0.702) and Dyspnea-Cat (r=0.677) and negligible correlation to Pain-NRS (r=0.080). It showed good discriminant properties of identifying patients with moderate and severe dyspnea with AUC of 0.874 (95% CI 0.812-0.936). RDOS = 4 predicted patients with moderate and severe dyspnea with a sensitivity of 76.6%, specificity of 86.2%, positive predictive value of 86.0% and negative predictive value of 76.9%.
CONCLUSIONS: The RDOS shows promise and clinical utility as a observational dyspnea assessment tool. Further studies in uncommunicative patients are needed to determine clinical usefulness and generalizability of results.
Objectif de l’étude: Le médecin généraliste est un pivot de la prise en charge de la fin de vie à domicile. La dyspnée, symptôme fréquent à cette période est un facteur de souffrance et de stress pour le malade, les proches et les soignants. L’objectif de cette étude était de décrire sa prise en charge diagnostique et thérapeutique symptomatique en phase terminale à domicile par les médecins généralistes.
Méthode: Il s’agit d’une étude descriptive. Un questionnaire a été adressé par courrier postal aux 59 généralistes du nord des Landes.
Résultats: Vingt-neuf questionnaires ont été analysés (49 % de réponse). Les médecins ont déclaré principalement suivre leur malade avec le soutien de l’infirmier à domicile seul (10 cas sur 27) ou d’une structure d’hospitalisation à domicile (7cas sur 27). Le principal symptôme recherché à l’entretien médical était la sensation de manque d’air (18 réponses 27). L’augmentation de la fréquence respiratoire (25 réponses sur 27) et la présence de signes de luttes (24 réponses sur 27) étaient les signes physiques les plus recherchés. L’échelle verbale simple était la plus utilisée (23 réponses sur 27). Parmi les thérapeutiques non médicamenteuses, le positionnement demi-assis du patient faisait l’unanimité (27 réponses sur 27). L’association morphinique et anxiolytique était le traitement médicamenteux le plus utilisé (20 réponses sur 27). En cas d’urgence, les 20 médecins confrontés à cette situation, ont informé les proches (17 réponses sur 20), utilisé l’oxygène (16 réponses sur 20) et administré un traitement médicamenteux (17 réponses sur 20). La sédation était peu employée dans cette situation (4 réponses sur 20).
Conclusion: La majorité des médecins répondeurs diagnostiquaient la dyspnée par la sensation de manque d’air et la présence de signes de lutte. Son évaluation se faisait par l’échelle verbale simple et les traitements employés étaient le positionnement demi-assis du patient et l’association de morphiniques et d’anxiolytiques. Une étude précisant le sentiment des médecins, les molécules et les dosages des médicaments employés serait à envisager pour compléter les données recueillies.
BACKGROUND: Episodic dyspnea is an increasingly recognized phenomenon that occurs frequently in patients with cancer. Although numerous definitions have been proposed to describe episodic dyspnea, to date, no common widely accepted definition in Spanish has yet emerged. Without a clear well-accepted definition, it is difficult to design rigorous clinical trials to evaluate candidate treatments for this emerging entity and to compare outcomes among studies.
OBJECTIVE: The aim of the study was to reach a consensus definition of episodic dyspnea in the Spanish language based on professional criteria in cancer patients.
DESIGN: A two-round Delphi study.
SETTING/SUBJECTS: Sixty-one Spanish specialists in medical oncology, radiation oncology, pneumology, palliative care, and pain management participated in the study.
MEASUREMENTS: Sixteen different questions on dyspnea-related terminology, including the definition of episodic dyspnea, were assessed.
RESULTS: The panel of experts reached a consensus on 75% of the 16 assessments proposed: 56.25% in agreement and 18.75% in disagreement. The term that most panelists considered most appropriate to define dyspnea exacerbation was dyspnea crisis. The panelists disagreed that dyspnea exacerbation is equivalent to dyspnea at effort and that the presence of dyspnea at rest is required for exacerbation to occur. However, there was wide agreement that exacerbation may or may not be predictable and can be triggered by comorbidities as well as emotional, environmental, or effort factors.
CONCLUSIONS: The broad consensus reached in this study is a necessary first step to design high-quality methodological studies to better understand episodic dyspnea and improve treatment.
AIM: The aim of this study was to assess the Personalized Dyspnea Intensity Goal, and the achievement of Personalized Goal Response and Patient Global impression, after comprehensive symptom management. The secondary outcome was to assess factors related to personalized goal response.
PATIENTS AND METHODS: Advanced cancer patients admitted to palliative care units rated pain and symptoms intensity, and their Personalized Dyspnea Intensity Goal , by using the Edmonton Symptom Assessment Score (ESAS). After a comprehensive symptom management, achievement of target patients' response and Patient Global Impression were evaluated.
RESULTS: 279 patients were analyzed in this study. The mean Personalized Dyspnea Intensity Goal at T0 and T7 were 0.97 (SD 1.3), and 0.71 (SD 2.1), respectively. 263 (94.2%) indicated a Personalized Dyspnea Intensity Goal of =3 as a target at T0. Patients perceived a bit better, a better improvement, and a much better improvement with a mean decrease in dyspnea intensity of – 2.1, –3.5, and -4.3 points on the dyspnea intensity scale, respectively. In 60 patients (21.5 %), dyspnea intensity did not change, and in 4.7%, dyspnea intensity worsened. Patients perceived a Minimal Clinically Important Difference (little worse) with a mean increase in dyspnea intensity of 0.10, and they perceived a worse with a mean increase of 1.7 points. Higher dyspnea intensity at T0 and lower dyspnea intensity at T7 were independently related to Patient Global Impression. At T7, 93 (33.3%) patients achieved their Personalized Goal Response, based on Personalized Dyspnea Intensity. Patient Dyspnea Goal Response was associated with Memorial Delirium Assessment Scale score and Personalized Dyspnea Intensity Goal at T0, and inversely associated with dyspnea intensity at T0 and T7, and lower Karnofsky level. For Patient Dyspnea Goal Response, no significant differences among categories of dyspnea intensity were found (P>0.05).
CONCLUSION: Patient Dyspnea Goal Response and Patient Global Impression seem to be relevant for evaluating the effects of a comprehensive management of symptoms, including dyspnea, assisting decision making process. Some factors may be implicated in determining the individual target and clinical response.
INTRODUCTION: Dyspnea is prominently observed in palliative care (PC). Dyspnea can be multifactorial, primarily caused by obstructive or restrictive lung diseases or secondarily induced by various comorbidities. Numerous interventions exist, with route of administration and efficacy requiring further discussion. Despite opioids being the first line of treatment, their adverse effects lead to reluctance on the side of patients to take them, creating limitations in patient management planning.
OBJECTIVES: This paper reviews and highlights the role of inhalers for dyspnea management in PC.
METHODS: The CINAHL, CENTRAL, and OVID databases were searched for scholarly articles on the role of inhalers in dyspnea management from 1998 to the present. A grey literature Internet search was also performed via Google, the World Health Organization, and CareSearch. Twenty-five articles relevant to the subject at hand were located and summarized. The Cochrane Systematic Reviews of Health Promotion and Public Health Interventions Handbook was consulted for structuring.
RESULT: Isolated bronchodilators can be effective in dyspnea management. However, combination with opioids leads to a 52% reduction of dyspnea, demonstrating efficacy of their combined use. There is a role for conventional inhalers not only in patients afflicted with chronic obstructive pulmonary disease, but also in those where obstruction is reversible, and in cases of dyspnea not yet diagnosed.
CONCLUSION: Inhalers can be utilized as adjuvant therapy to opioids, to limit opioid use, augment responses to dyspnea, and/or minimize opioid side effects, especially in opioid-naïve patients. Correct administration can increase the efficacy of short-acting beta-agonists, long-acting beta-agonists, short- and long-acting anticholinergic agents, and inhaled corticosteroids, achieving reduction and alleviation of dyspnea.
Dyspnea is one of the most distressing symptoms experienced by dying patients, and it is a common reason for such patients to seek care in the emergency department. Many underlying disease states and acute illnesses cause shortness of breath at the end of life, and management tends to be symptomatic rather than diagnostic, particularly in those for whom comfort is the most important goal. Opioids are the most effective and widely studied agents available for palliation of dyspnea in this population, while adjuvant therapies such as oxygen, noninvasive positive pressure ventilation, and hand-held fans may also be used. Benzodiazepines may also be helpful in select patients. The early involvement of palliative medicine specialists and/or hospice services for dying patients can facilitate optimal symptom management and transitions of care.
CONTEXT: Breathlessness is common and distressing in advanced illness. It is a challenge to assess, with few effective treatment options. To evaluate new treatments, appropriate outcome measures which reflect the concerns of people experiencing breathlessness are needed.
OBJECTIVES: To systematically review and synthesise the main concerns of people with advanced illness experiencing breathlessness to guide comprehensive clinical assessment and inform future outcome measurement in clinical practice and research.
METHODS: Systematic review following PRISMA methodology. MEDLINE (1946-2017), PsycINFO (1806-2017), and EMBASE (1974-2017), as well as key journals, grey literature, reference lists, and citation searches identified qualitative studies exploring the concerns of people living with breathlessness. Included studies were quality assessed using the Critical Appraisal Skills Program checklist, and analysed using thematic synthesis.
RESULTS: We included thirty-eight studies with 672 participants. Concerns were identified across six domains of 'total' breathlessness; physical, emotional, spiritual, social, control, and context (chronic and episodic breathlessness). Four of these have been previously identified in the concept of 'total dyspnoea'. Control and context have been newly identified as important, particularly in their influence on coping and help-seeking behaviour. The importance of social participation, impact on relationships, and loss of perceived role within social and spiritual domains also emerged as being significant to individuals.
CONCLUSION: People with advanced illness living with breathlessness have concerns in multiple domains, supporting a concept of 'total breathlessness'. This adapted model can help to guide comprehensive clinical assessment, and inform future outcome measurement in clinical practice and research.