Nebulized opioids are a formulation of the drug that is diluted and provided in a form that can be inhaled. Nebulized opioids have been evaluated in patients for the management of dyspnea.
Effectiveness Not Established
Ben-Aharon, I., Gafter-Gvili, A., Paul, M., Leibovici, L., & Stemmer, S.M. (2008). Interventions for alleviating cancer-related dyspnea: A systematic review. Journal of Clinical Oncology, 26(14), 2396-2404.doi: 10.1200/JCO.2007.15.5796
The objective of this study was to systematically review the evidence for the efficacy of pharmacologic and nonpharmacologic treatments in alleviating dyspnea in patients with terminal cancer.
Databases searched were Cochrane Library up to 2007, MEDLINE (PubMed) (1966–2007), American Society of Clinical Oncology conference proceedings, and references of all included documents. In addition to databases, the search included the reference lists of key studies, the reference lists of 16 review articles on the topic, reference lists from 16 textbooks, and seven websites. Authors (15) of main investigations were contacted, and all members of the Association of Palliative Care and users of the www.palliativedrugs.com bulletin board were contacted for additional information and unpublished data.
Search keywords were opiate, opioid, morphine, benzodiazepine, furosemide, steroids, corticosteroids, oxygen, nonpharmacological, acupuncture, nursing, cancer, carcinoma, malignancy, dyspnea and breathlessness.
Studies were included in the review if they were a randomized controlled trial assessing dyspnea in patients with terminal cancer in which any intervention for dyspnea relief was compared with no intervention, placebo, or another intervention.
Studies were excluded if they were nonrandomized studies or trials in which only a minority of the patients had a cancer diagnosis.
Literature evaluated included 37 studies, plus one abstract initially reviewed. A final set of 18 studies was included; 7 assessed opioids, 6 assessed oxygen- or helium-enriched air, 1 assessed furosemide, and 4 assessed nonpharmacologic interventions. Meta-analysis was not completed due to the paucity of studies and heterogeneous outcome measures.
Sample Size Across Studies:
- Opioid intervention = 256 patients
- Oxygen or helium = 148 patients
- Furosemide intervention = 7 patients
- Nonpharmacologic intervention = 403 patients
Sample Range Across Studies:
- Opioids = 9–101 patients
- Oxygen or helium = 12–51 patients
- Nonpharmacologic = 34–203 patients
With respect to gender, age, and diagnosis within the sample, the opioids subgroup included both genders. The median age range was 56–73 years. The majority had primary lung cancer, and both opioid-tolerant and opioid-naïve participants were included.
The oxygen or helium subgroup included both genders. The median age range was 64–72 years. The majority had primary lung cancer.
No comment was available on gender or age for the nonpharmacologic subgroup, but the primary diagnosis was lung cancer.
The primary outcome was subjective dyspnea relief according to the visual analog scale (VAS) or dyspnea intensity according to the modified Borg scale. The secondary outcome was oxygen saturation and adverse effects.
- The administration of subcutaneous morphine resulted in significant reduction in dyspnea according to the VAS compared with placebo.
- Nebulized morphine versus placebo failed to demonstrate a significant effect of nebulized morphine. No difference in dyspnea VAS score was observed in one trial when nebulized morphine was compared with subcutaneous morphine, although patients preferred the nebulized route.
- In one trial, the addition of benzodiazepines (midazolam) to morphine was significantly more effective than morphine alone, without additional adverse effects.
- Oxygen was not superior to medical air for alleviating dyspnea, except for patients with hypoxemia.
- One small trial assessed the use of nebulized furosemide with a trend toward worsening dyspnea.
- Nurse-led interventions improved breathlessness.
- Acupuncture was not beneficial.
- Nurse-led interventions encompassed routine follow-up by nurses performing methods of counseling and relaxation and teaching coping strategies.
- The nurse-led breathlessness rehabilitation techniques and education and advice regarding coping with the psychological aspects of the symptoms assessed the primary outcome of dyspnea relief after weeks.
- All nurse-led interventions proved to be beneficial, improving breathlessness and quality of life in terms of physical, psychological, and emotional aspects.
- No evidence supports subcutaneous morphine as effective in treating dyspnea in patients with advanced cancer.
- Use of oxygen to alleviate dyspnea in nonhypoxic patients with cancer cannot be recommended. Supplemental oxygen is expensive and can restrict mobility with possible decrease in quality of life. Use of medical air (78.9% nitrogen, 21.1% oxygen) was shown to be effective in reducing the sensation of dyspnea. However, this intervention is not used routinely in care settings.
- This review recommended integration of pharmacologic and nonpharmacologic interventions, such as those used in nurse-led programs to relieve dyspnea.
Acknowledging the paucity of evidence from randomized controlled trials to support the interventions is important.
Limitations of this review were
- Few randomized controlled trials
- Small studies
- Short follow-up in opioid studies
- Lack of consistency regarding opioid doses.
A major research opportunity exists to further document outcomes from nurse-led dyspnea interventions.
Jennings, A.L., Davies, A.N., Higgins, J.P., Gibbs, J.S., & Broadley, K.E. (2002). A systematic review of the use of opioids in the management of dyspnoea. Thorax, 57(11), 939–944.
This systematic review included trials of opioids for the treatment of dyspnea secondary to any cause.
Eighteen randomized, double-blind, placebo-controlled crossover trials were evaluated. Meta-analyses were performed on all included studies and on various subgroups (e.g., nebulized opioids).
Patient populations were mixed, with 2 of the 18 trials including patients with a cancer diagnosis only and one of the 18 trials including patients with cancer with other advanced diseases.
A strong effect of non-nebulized opioids relative to placebo in reducing breathlessness was found. The subgroup analysis failed to show a positive effect of nebulized opioids on the sensation of breathlessness. Evidence supports the use of oral and parenteral opioids to treat dyspnea and argues against the use of nebulized opioids.
All but one study had a small sample size (n = 6–18 subjects); cancer-related dyspnea was included but was not a main focus of the research.
Viola, R., Kiteley, C., Lloyd, N.S., Mackay, J.A., Wilson, J., Wong, R.K., & Supportive Care Guidelines Group of the Cancer Care Ontario Program in Evidence-Based Care. (2008). The management of dyspnea in cancer patients: A systematic review. Supportive Care in Cancer, 16(4), 329-337.doi: 10.1007/s00520-007-0389-6
The objective of this study was to evaluate the effectiveness of four drug classes: opioids, phenothiazines, benzodiazepines, and systemic.
Databases searched were HealthSTAR, MEDLINE, CINAHL, EMBASE, Cochrane Library and Database of Abstracts and Reviews of Effects Issue 2, American Society of Clinical Oncology conference proceedings (1995-2006), Canadian Medical Association Infobase, and National Guidelines Clearing House. Reference lists from relevant articles were searched for additional trials
Search keywords were dyspnea, breathlessness, shortness of breath, respiratory distress, breath and shortness, and breath and difficult combined with terms for pharmacologic agnets, study designs, and publication types.
Inclusion criteria included
• Systematic reviews
• Evidence-based practice guidelines
• Fully published or abstract reports of randomized or nonrandomized controlled studies of opioids, phenothiazines, or benzodiazepines administered by any route involving adult patients with dyspnea
• Subjects with any advanced disease
• Studies involving corticosteroids, only if the primary advanced disease was cancer
• Studies in which one of the outcomes reported was dyspnea, measured by a patient-reported scale.
Exclusion criteria included
• Studies in languages other than English
• Stuides eported in letters or editorials.
- The search identified two practice guidelines, three systematic reviews, 23 published randomized controlled trials (RCTs), two abstracts of RCTs, and three published nonrandomized trials, for a total of 33 references.
- The review did not identify the number of excluded items from the initial search.
- Study quality was evaluated formally using the Jadad scale.
The total sample across 29 trials was 600 patients, with individual sample sizes ranging from 4-101. Trials included involved
- 6 trials of opiods in only patients with cancer
- 10 trials of systemic opioids including patients who did not have cancer
- 7 trials of nebulized opioids including patients with and without cancer
- 4 trials of benzodiazepines
2 trials of phenothiazines.
- Search sources and criteria were not reported in either of the two practice guidelines. One indicated that both corticosteroids and opioids were options for managing dyspnea but that the evidence was poor. The other, a Finnish guideline, recommended opioids, steroids, and benzodiazepines, but evidence was only cited for opiods.
- Opioids studied included morphine orally, subcutaneously, or via nebulizer; dihydrocodeine; diamorphine; and promethazine with morphine. All but three studies examined the effects of a single dose on dyspnea via use of a visual analogue scale or exercise tolerance.
- In opioid trials involving only patients with cancer, four examined systemic opioids, one used nebulized opiods, and one included both systemic and nebulized administration. One trial used a combination of morphine and midazolam. Systemic opioid studies tended to show significant decrement in mean dyspnea and respiratory rate with morphine. In the trial that included midazolam, more patients on the combined regimen reported relief from dyspnea at 24 and 48 hours and had fewer episodes of breakthrough dyspnea. However, no differences were seen in mean dyspnea scores and exercise tolerance between groups overall.
- Nebulized opioids did not show significant differences compared to systemic morphine in one trial.
- One benzodiazepine trial involved patients with cancer. In trials with other patients, none of the studies demonstrated a significant reduction in dyspnea when compared to placebo.
- No trials were on phenothiazines in patients with cancer. One study showed a benefit with promethazine compared to placebo on dyspnea and exercise tolerance.
- Adverse effects reported across trials included drowsiness, nausea and vomiting, and constipation in opioid trials. Results of opioids on oxygen level were mixed.
- Results of benzodiazepines and phenothiazines on oxygen and carbon dioxide levels were mixed. Drowsiness was the most frequent adverse effect reported with benzodiazepine.
- Overall evidence favors a beneficial effect of systemic opioids on dyspnea and exercise tolerance.
- None of the studies comparing nebulized morphine with placebo or systemic opioids found it to be beneficial.
- Whether studies with opioids indicate a drug class effect is not clear because only a few drugs have been studied.
- Studies of benzodiazepines did not suggest any benefit.
- Studies of phenothiazines gave conflicting results.
- Overall evidence in this area demonstrate conflicting results, and this systematic review also gives conflicting results and conclusions within the article.
- Most studies had very small sample sizes, and doses, dose schedules, routes, and outcome measures varied greatly, making overall conclusions difficult.
- While the stated purpose of the review was to determine effects within a cancer population, most of the research reviewed was not in this population.
- While use of opioids may be of benefit for patients with cancer in reducing the sensation of dyspnea, this effect needs to be balanced with the adverse effects that can be expected with such treatment, including symptoms of constipation, drowsiness, and nausea and vomiting. Interventions to prevent or manage these effects would also be essential.
Research Evidence Summaries
Bruera, E., Sala, R., Spruyt, O., Palmer, J. L., Zhang, T., & Willey, J. (2005). Nebulized versus subcutaneous morphine for patients with cancer dyspnea: a preliminary study. Journal of Pain and Symptom Management, 29, 613–618.doi: 10.1016/j.jpainsymman.2004.08.016
To compare subcutaneous (SC) injection versus nebulized morphine (median dose of 45 mg, equal to half of the scheduled equivalent opioid dose) on two separate days; because nebulized morphine is thought to have rapid onset of action and low systemic absorption, adverse effects may be avoided.
- The sample was comprised of 11 patients.
- Median age was 58 years.
Patients were included if they
- Had dyspnea (at least 3 on a scale of 0–10 in which 10 = worst dyspnea not related to acute complication) and advanced cancer with no clinical evidence of bronchospasm (predominant restrictive ventilation)
- Were receiving regular oral or parenteral opioids
- Had normal cognition.
The study used a double-blind, randomized crossover trial design.
- Dyspnea self-reports on a 0–10 scale were measured at baseline (end of one hour of rest) and every 15 minutes for 1.5 hours and then every 30 minutes for the next three hours.
- The main outcome was dyspnea score at 60 minutes.
- Blind preference of treatment was assessed by patients and investigators.
Significant improvement occurred in dyspnea scores from baseline to 60 minutes measured at 15-minute intervals for both SC (dyspnea score decreased from 5 to 3; p = 0.025) and nebulized morphine (dyspnea score decreased from 4 to 2; p = 0.007). No significant difference was found between SC and nebulized morphine for each time period. Bronchospasm was not observed in the nebulized treatment group.
Both routes were effective in this sample. The number of patients was insufficient to determine a difference between the routes.
- The study had a very small sample size and insufficient power to rule out a significant difference between the two routes.
- Recruiting patients with continuous dyspnea (at rest) was very difficult.
Charles, M. A., Reymond, L., & Israel, F. (2008). Relief of incident dyspnea in palliative cancer patients: a pilot, randomized, controlled trial comparing nebulized hydromorphone, systemic hydromorphone, and nebulized saline. Journal of Pain and Symptom Management, 36, 29–38.doi: 10.1016/j.jpainsymman.2007.08.016
To compare the efficacy of nebulized hydromorphone, systemic hydromorphone, and nebulized saline for incident dyspnea in patients with advanced cancer.
Intervention Characteristics/Basic Study Process:
On three occasions when patients requested treatment for incident breathlessness, they randomly received one of the following:
- 5 mg of nebulized hydromorphone
- A systemic breakthrough dose of hydromorphone
- 3 mL of nebulized saline and an agent to maintain double blinding.
If patients felt the intervention was not effective, they could ask for additional pharmaceutical interventions. Patients scored breathlessness at 10, 20, 30, and 60 minutes from completion of treatment. Treatment order was randomized.
- The sample was comprised of 20 patients (11 men, 9 women) receiving palliative care.
- Mean age was 69 years (range 48–83).
- Diagnoses included primary lung cancer or secondary lung pathology, including lung metastases, pleural effusion, or pulmonary emboli.
- To be eligible, patients had to have Mini Mental State Exam (MMSE) results of at least 24 out of 30.
- Thirteen patients were on continuous oxygen.
- Mean baseline total opioid dose in morphine equivalent mg was 82 (range 10–540).
- Inpatient- and community-based hospice service in Brisbane, Australia
- Single site
Phase of Care and Clinical Applications:
Patients were undergoing the palliative and end of life phases of care.
The study was a pilot, double-blind, randomized, crossover, controlled trial.
- Perceived intensity of breathlessness was measured on a vertical 100-mm visual analog scale (VAS).
- Pulse rate and peripheral oxygen saturation were measured with a pulse oximeter.
- Respiratory rate was counted by the research nurse over two 30-second intervals.
There were no differences between treatments in improvement scores. Improvement in breathlessness at 10 minutes post intervention completion was seen in each of the treatment conditions. Improvement considered to be clinically significant (≥1 cm on the VAS) was only seen with the nebulized hydromorphone. Respiratory rate improved over time from 10 to 60 minutes (p < 0.05), with no difference between treatments. There were no clear, consistent preferences among patients for any particular intervention.
The results suggest that nebulized saline provides relief of incident breathlessness; its effect is ongoing and does not differ significantly from the effects of nebulized opioid treatments.
- The study was appropriately powered to answer the study questions, but the study had a small sample size.
- A change of 1 cm on the VAS was used as a clinically significant symptom change, in concert with the work of others.
- Further research to define clinically significant differences in patient perception would be beneficial.
- It is not clear if higher doses of hydromorphone might yield differences across groups.
- The authors suggested that improvements in respiratory rates and peripheral oxygen over time likely represent Type I error in this study because the patients had a background of irreversible baseline dyspnea.
- The presence of the research nurse, to specifically administer this protocol, may have had an effect in terms of reassuring patients and confounded the overall results. Similar research having patients self-administer treatments might address this aspect.
- It is unclear if findings represent placebo effects.
Coyne, P. J., Viswanathan, R., & Smith, T. J. (2002). Nebulized fentanyl citrate improves patients’ perception of breathing, respiratory rate, and oxygen saturation in dyspnea. Journal of Pain and Symptom Management, 23, 157–160.
To test the theory: "Inhaled opioids usually are ineffective with report of respiratory depression; however, fentanyl may be more readily absorbed with less bronchospasm and thus relieve dyspnea."
Intervention Characteristics/Basic Study Process:
Patients were given 25 mcg of fentanyl with 2 mL of saline via a nebulizer.
- The sample was comprised of 35 patients (20 women, 15 men) with terminal cancer who reported shortness of breath.
- Average age was 56 years.
- Thirty-four patients were on oxygen.
- Oncology unit
The study used a convenience sample, uncontrolled design.
- Patients’ perceptions of breathing (same, worse, or improved) were measured one hour after treatment.
- Respiratory rate and oxygen saturation were measured at baseline and at 5 and 60 minutes following the intervention.
- Twenty-six of 32 patients (81%) reported improvement in breathing.
- Three of 32 (9%) patients were unsure of their results.
- Three of 32 (9%) patients reported no improvement.
- Mean oxygen saturation significantly improved from 94.6% to 96.8% (p < 0.001) at five minutes and to 96.7% (p < 0.006) at 60 minutes.
- Mean respiratory rate significantly decreased from 28.4 at baseline to 25.8 at five minutes (p < 0.03) and to 24.1 at 60 minutes (p < 0.02).
Fentanyl improved all three measures and may offer substantial relief of dyspnea. No significant side effects were reported.
- The study was not randomized and needs confirmation in a randomized, controlled trial.
- The impact of the carrier saline is unknown.
- Also unknown is the cause of attrition of three patients and whether patients were opioid tolerant or naïve.
Clinical questions about repeated dosing and method of administration (mask or mouthpiece) remain.
Quigley, C., Joel, S., Patel, N., Baksh, A., & Slevin, M. (2002). A phase I/II study of nebulized morphine-6-glucuronide in patients with cancer-related breathlessness. Journal of Pain and Symptom Management, 23, 7–9.
Intervention Characteristics/Basic Study Process:
A single dose of nebulized morphine-6-glucuronide (M6G) (the active metabolite of morphine) was given to patients with cancer who had breathlessness. Three dose levels were studied: 5, 10, and 20 mg of M6G. The single dose of morphine was inhaled using an Acorn Porta-Neb jet nebulizer over 15 minutes.
- The sample was comprised of nine patients.
- No patient characteristics were reported other than age (median = 51 years; range 45–77).
- Six patients were already receiving morphine.
- Results were reported from St. Bartholomew Hospital in London, United Kingdom.
This was an open, uncontrolled study that randomized patients to one of three dose levels.
- 100-mm visual analog scale (VAS) and modified Borg scale were used to quantify breathlessness, anxiety, and effort of breathing at pretreatment and at 15, 30, and 60 minutes posttreatment.
- VAS and verbal rating scales were used to assess nausea, drowsiness, and other side effects.
All patients reported a subjective improvement in breathlessness by the VAS and the Borg scale. A significant difference (p = 0.023) in dyspnea VAS was observed with time across all time points. No significant difference existed among the three treatment groups across all time points (p = 0.176), suggesting no difference among the three doses. A significant difference in dyspnea was found between patients. No significant changes existed in anxiety VAS and effort of breathing VAS with time or with dose. Minimal adverse effects were noted.
Nebulized M6G was relatively safe and possibly therapeutic in patients with cancer-related breathlessness.
- A small number of patients were studied.
- The study was reported as a letter to the editor.
A randomized study is planned.
Tanaka, K., Shima, Y., Kakinuma, R., Kubota, K., Ohe, Y., Hojo, F., . . . Nishiwaka, Y. (1999). Effect of nebulized morphine in cancer patients with dyspnea: a pilot study. Japanese Journal of Clinical Oncology, 29, 600–603.doi: 10.1093/jjco/29.12.600
To test the theory that the local benefit of opioids is related to opioid binding sites in peripheral bronchus.
Intervention Characteristics/Basic Study Process:
Patients were given 20 mg of morphine dissolved in 5 mL of normal saline administered through an ultranebulizer. If no subjective relief resulted, the dose was increased to 40 mg and was tried again after four hours.
- The sample was comprised of 15 patients with thoracic cancer without cognitive changes who had dyspnea that was difficult to control with standard treatment (e.g., pleural drainage, antibiotics, and diuretics).
- Median age was 61 years.
- Seven patients were on continuous oxygen by cannula.
- Ten patients were already on systemic opioids.
Inpatient hospital in Japan
This was a pilot, open-label, nonrandomized, uncontrolled study.
- Dyspnea visual analog scale (VAS) was measured at baseline and at 60 minutes after inhalation.
- Outcome criteria was an improvement greater than 10% decrease in VAS.
- Respiratory rate (RR), hemoglobin, and oxygen saturation were also measured.
- A questionnaire about adverse effects and preferences was administered.
Significant decrease occurred in VAS after nebulization (p = 0.005). Eight of 15 patients evaluated treatment effective and requested continuation. No significant change occurred in RR or oxygenation. A not statistically significance tendency was found for patients on systemic opioids to benefit more compared to nonopioid patients.
- The study had a small sample size and was uncontrolled.
- The intervention placebo effect cannot be ruled out.
- The dose increase without a washout period possibly contaminated the findings.
Zeppetella, G. (1997). Nebulized morphine in the palliation of dyspnoea. Palliative Medicine, 11, 267–275.
Intervention Characteristics/Basic Study Process:
Nebulized morphine 20 mg mixed with 2 mL of saline was administered using a face mask every four hours for 48 hours.
- The sample was comprised of 17 patients in hospice care with nonreversible dyspnea, either at rest or on exertion, associated with primary or secondary malignant intrathoracic disease; six patients also had chronic obstructive pulmonary disease (COPD).
- Mean age was 68 years.
- Of the patients, 12 (71%) were male.
- Thirteen patients were already taking opioids.
- Fourteen patients completed the trial.
Unknown but assumed to be in a hospital
The study used an open, uncontrolled, nonrandomized design.
The Dyspnea Assessment Questionnaire (DAQ) and a recalled 24-hour visual analog scale (VAS) were used. Three subscales of the DAQ—Total Severity Score, Percentage Total Severity Score (PTSS), and Dyspnea Quality-Quantity Score (DQQS)—were also analyzed. DQQS was the primary outcome measure. Measurements were taken at baseline (one hour before the first dose of nebulized medication) and were repeated at 24 and 48 hours.
Sixteen patients (94%) reported significantly lower (p = 0.0005) DQQS scores at 24 hours. The four opioid-naïve patients showed no significant benefit from the nebulized treatment. (The theory is that the prevalence of binding receptors in airways is influenced by systemic use of opioids.) Improvement appeared greater in the qualitative aspect of dyspnea as shown by PTTS versus VAS. Benefits were noted at 24 hours and did not improve from there. Change in DQQS scores from 24 to 48 hours was not significant (p-value not given).
Qualitative aspects of dyspnea improved more than quantitative aspects.
- The study had a small sample size.
- Due to the uncontrolled nature of the study, the placebo effect cannot be ruled out.
- One patient refused to participate after the first dose, reporting claustrophobia.
- Fourteen patients completed the trial. Three patients dropped out after 24 hours (two because of a dislike for the nebulizer and one because of weakness); otherwise, no significant side effects were reported.
- Six patients who discontinued nebulized treatments after 24 hours did so because of weakness. Weakness appeared to reduce the acceptability of the nebulized intervention.
Parshall, M.B., Schwartzstein, R.M., Adams, L., Banzett, R.B., Manning, H.L., Bourbeau, J., . . . American Thoracic Society Committee on Dyspnea. (2012). An official American Thoracic Society statement: Update on the mechanisms, assessment, and management of dyspnea. American Journal of Respiratory and Critical Care Medicine, 185(4), 435-452.doi: 10.1164/rccm.201111-2042ST
Purpose & Patient Population:
- The objective was to update the 1999 ATS consensus statement on dyspnea based upon new knowledge of neurophysiology and increasing interest in dyspnea as a patient-reported outcome.
- Included were patients who experience dyspnea from any etiology.
Type of Resource/Evidence-Based Process:
A multidisciplinary group of international experts determined the overall scope of these guidelines according to group consensus. This was followed by evidence reviews in key topic areas conducted by committee members with relevant expertise, and all group members agreed on final content.
Databases searched were PubMed and CINAHL (1999- 2009).
Search keywords were dyspnea, breathlessness, and respiratory sensation, with additional keywords according to specific sections. Reference lists of the articles were hand-searched.
- Mechanisms underlying dyspnea
- Instruments used to measure dyspnea
- The clinical approach to patients who complain of dyspnea
- The treatment of dyspnea that persists despite maximal treatment of underlying pathologic processes responsible for breathing discomfort
- Topics that should be in the focus of future research.
The exclusion criteria were not clearly described.
Phase of Care and Clinical Applications:
- Patients were undergoing multiple phases of care.
- The guidelines have clinical applicability for elder care and palliative care.
Results Provided in the Reference:
- Results were not clearly defined.
- Literature was summarized in a general fashion with strong referencing, but levels and strength of evidence were not noted.
Guidelines & Recommendations:
- Evidence describing the pathophysiology and measurement of dyspnea was comprehensive and well referenced.
- Management of refractory dyspnea despite aggressive assessment and attempts to control the etiology was the focus of the treatment section of the document.
- Therapies with strong evidence to support use include opiates, but adverse effects may interfere with acceptance.
- Therapies with limited evidence to support use include oxygen therapy, nebulized morphine, nebulized furosemide, heliox, anxiolytics, pulmonary rehabilitation, inspiratory respiratory muscle training, chest wall vibration, cool air movement on the face, noninvasive ventilation, acupuncture, and acupressure.
- The consensus document does not use systematic review techniques.
- Although dated 2012, key high-level evidence articles used in the ONS PEP review process (Cochrane Reviews) were not included in the references.
- In these guidelines is limited reference to patients with cancer.
These consensus guidelines from a respected professional organization fill an important void in the literature by describing the pathobiology and measurement instruments for dyspnea. The brief review of treatment options provides information for clinicians to consider for patients with refractory dyspnea.