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Evidence-based interventions for dyspnea

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Editor’s note: One of a series of articles on managing cancer-related symptoms from the Oncology Nursing Society.

Dyspnea is “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity” (American Thoracic Society, 1999, p. 322). The causes of dyspnea are multiple, encompassing physiologic, psychological, social, and environmental etiologies that may lead to secondary physiologic and behavioral responses (Oncology Nursing Society [ONS], 2008). Incidence rates at cancer diagnosis range from 15%–55%. Those figures increase to 18%–79% during the last week of life (DiSalvo & Joyce, 2009).

Because dyspnea is “a subjective experience,” patient self-report is the most reliable method of assessment. Detailed assessments should include questions about onset, frequency, and intensity as well as the nature of the respiratory change (DiSalvo & Joyce, 2009). While no one clinical measurement tool covers all of the dimensions of dyspnea, three are recommended based on the purpose of the assessment: the Visual Analog Scale, the Numeric Rating Scale, and the Cancer Dyspnea Scale (Dorman et al., 2007; Gift & Narsavage, 1998; Joyce, 2005).

Oncology nurses are in a key position to review patients’ self-reports of dyspnea and enact evidence-based interventions from ONS’ Putting Evidence Into Practice (PEP) initiative that may ease symptoms and enhance patients’ quality of life.

Putting evidence into practice

To promote nursing practice that is based on evidence, ONS launched the PEP program in 2005. ONS PEP teams consisting of advanced practice nurses, staff nurses, and a nurse scientist were charged with reviewing the literature to determine what treatments and interventions are proven to alleviate many cancer-related problems that are sensitive to nursing interventions. Each team classified interventions under the following categories: recommended for practice, likely to be effective, benefits balanced with harms, effectiveness not established, effectiveness unlikely, and not recommended for practice.

Recommended for practice

Use of immediate-release oral or parenteral opioids is an intervention in which effectiveness has been demonstrated by strong evidence from rigorously designed studies, meta-analysis, or systematic reviews (DiSalvo & Joyce, 2009). These opioids “reduce ventilator demand by decreasing central respiratory drive” (DiSalvo & Joyce, 2009, p. 141). Three systematic reviews, and numerous smaller studies, have reported positive results of dyspnea relief through opioid use (Allard, Lamontagne, Bernard, & Tremblay, 1999; Ben-Ahron, Gafter-Gvili, Paul, Leibovici, & Stemmer, 2008; Bruera, Macmillan, Pither, & MacDonald, 1990; Clemens & Klaschik, 2007; Jennings, Davies, Higgins, Gibbs, & Broadly, 2002; Mazzocato, Buclin, & Rapin, 1999; Viola et al., 2008). In these studies, (a) morphine was the opioid most often studied, (b) patients who were opioid-naïve were given smaller doses than those who were opioid-tolerant, and (c) the opioids were well-tolerated overall. In addition, for patients who had been receiving opioids on a regular basis, Allard et al. (1999) found that supplemental doses at 25% of a regular four-hour dose can reduce dyspnea for as long as four hours.

Likely to be effective

Regarding interventions in which effectiveness has been demonstrated by supportive evidence from a single trial or from a small sample size, the National Comprehensive Cancer Network ([NCCN], 2008) recommends palliative interventions, categorized by life expectancy, to address dyspnea. These interventions include ventilator support, ambient air flow to the face or nose, relaxation and stress reduction, and education for the patient and family, among others (see Likely to be effective interventions.)

Weighted Checklist

Effectiveness not established

Insufficient or conflicting data or data of inadequate quality exists for the following pharmacologic and nonpharmacologic interventions.

Pharmacologic

  • Extended-release morphine: One study (Boyd & Kelly, 1997) examined the use of extended-release morphine on patients suffering from dyspnea and found that no significant reduction occurred. In addition, some patients experienced sedation or dizziness 48 hours after initiation.
  • Midazolam and morphine: Navigante, Cerchietti, Castro, Lutteral, and Cabalar (2006) conducted a trial of patients with severe dyspnea in the last week of life and found positive results. However, more research is needed before this regimen can be recommended.
  • Nebulized or oral transmucosal fentanyl: One small study conducted by Coyne, Viswanathan, and Smith (2002) noted a perceived benefit by a majority of patients in the study. In addition, case reports in Benitez-Rosario, Martin, and Feria (2005) gave anecdotal reports of dyspnea relief.
  • Nebulized furosemide: Conflicting results have been reported with this treatment. Wilcock et al. (2008) found no beneficial effect. However, an uncontrolled study by Shimoyama and Shimoyama (2002) and case reports by Kohara et al. (2003) found that this regimen decreased the sensation of dyspnea.
  • Nebulized lignocaine: One small study evaluated this treatment (Wilcock, Corcoran, & Tattersfield, 1994) and no benefit was noted. In fact, increased distress was noted in patients’ breathing.
  • Nebulized opioids: Various individual studies have indicated potential (Bruera et al., 2005, Joyce, McSweeney, Carrieri-Kohlman, & Hawkins, 2004; Quigley, Joel, Patel, Baksh, & Slevin, 2002; Tanaka et al., 1999); however, higher-level reviews have failed to show the same positive effects (Charles, Raymond, & Israel, 2008; Jennings et al., 2002; Zeppetella, 1997).
  • Palliative oxygen: This treatment focuses on using oxygen to relieve the sensation of dyspnea in patients with advanced cancer. No data currently exist that support this treatment. In fact, one meta-analysis (Uronis, Currow, McCrorry, Samsa, & Abernethy, 2008) and three randomized, controlled trials (Booth, Kelly, Cox, Adams, & Guz, 1996; Bruera et al., 2003; Philip et al., 2006) demonstrated no significant difference between air and oxygen use in this patient population.

Nonpharmacologic

  • Acupuncture: A randomized, controlled study by Vickers, Feinstein, Deng, and Cassileth (2005) failed to show a significant effect.

Nurses are in a unique position to support patients suffering from dyspnea by using evidence-based interventions, such as immediate-release oral or parenteral opioids. In addition to initiating treatments, nurses should assess breathlessness; provide support and information to patients and their families about dyspnea; instruct patients in breathing control, relaxation, and distraction methods; and help patients set realistic goals for participation in social activities.

Sean Pieszak is a copy editor in the publishing division at the Oncology Nursing Society in Pittsburgh, PA. More information about the ONS PEP classification for dyspnea can be found at http://www.ons.org/Research/PEP/Dyspnea.

References

Allard, P., Lamontagne, C., Bernard, P., & Tremblay, C. (1999). How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial. Journal of Pain and Symptom Management, 17, 256–265. doi: 10.1016/S0885-3924(98)00157-2

American Thoracic Society. (1999). Dyspnea. Mechanisms, assessment, and management: A consensus statement. American Journal of Respiratory and Critical Care Medicine, 159, 321–340.

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, 2396–2404. doi: 10.1200/JCO.2007.15.5796

Benitez-Rosario, M.A., Martin, A.S., & Feria, M. (2005). Oral transmucosal fentanyl citrate in the management of dyspnea crises in cancer patients. Journal of Pain and Symptom Management, 30, 395–397. doi: 10.1016/j.jpainsymman.2005.10.002M

Booth, S., Kelly, M.J., Cox, N.P., Adams, L., & Guz, A. (1996). Does oxygen help dyspnea in patients with cancer? American Journal of Respiratory and Critical Care Medicine, 153, 1515–1518.

Boyd, K.J., & Kelly, M. (1997). Oral morphine as symptomatic treatment of dyspnoea in patients with advanced cancer. Palliative Medicine, 11, 277–281. doi: 10.1177/026921639701100403

Bruera, E., Macmillan, K., Pither, J., & MacDonald, R.N. (1990). Effects of morphine on the
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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

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DiSalvo, W.M., & Joyce, M.M. (2009). Dyspnea. In L.H. Eaton and J.M. Tipton (Eds.), Putting Evidence Into Practice: Improving oncology patient outcomes (pp. 135–148). Pittsburgh, PA: Oncology Nursing Society.

Dorman, S., Byrne, A., & Edwards, A. (2007). Which measurement scale should we use to measure breathlessness in palliative care? A systematic review. Palliative Medicine, 21(3), 177–191. doi: 10.1177/0269216307076398

Gift, A., & Narsavage, G. (1998). Validity of the numeric rating scale as a measurement of dyspnea. American Journal of Critical Care, 7(3), 200–204.

Jennings, A.L., Davies, A.N., Higgins, J.P., Gibbs, J.S., & Broadly, K.E. (2002). A systematic review of the use of opioids in the management of dyspnoea. Thorax, 57, 939–944. doi: 10.1136/thorax.57.11.939

Joyce, M. (2005). Measuring oncology-nursing sensitive patient outcomes: Evidence-based summary. Retrieved from http://www.ons.org/outcomes/measures/dyspnea.shtml

Kohara, H., Ueoka, H., Maeda, T., Takeyama, H., Saito, R., Shima, Y., & Uchitomi, Y. (2003). Effect of nebulized furosemide in terminally ill cancer patients with dyspnea. Journal of Pain and Symptom Management, 26, 962–967. doi: 10.1016/S0885-3924(03)00322-1

Joyce, M., McSweeney, M., Carrieri-Kohlman, V.L., & Hawkins, J. (2004). The use of nebulized opioids in the management of dyspnea: Evidence synthesis. Oncology Nursing Forum, 31, 551–561. doi: 10.1188/04.ONF.551-561

Mazzocato, C., Buclin, T., & Rapin, C.H. (1999). The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: A randomized double-blind controlled trial. Annals of Oncology, 10, 1511–1514. doi: 10.1023/A:1008337624200

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Navigante, A.H., Cerchietti, L.C., Castro, M.A., Lutteral, M.A., & Cabalar, M.E. (2006). Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer. Journal of Pain and Symptom Management, 31, 38–47. doi: 10.1016/j.jpainsymman.2005.06.009

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Philip, J., Gold, M., Milner, A., Di Iulio, J., Miller, B., & Spruyt, O. (2006). A randomized, double-blind, crossover trial of the effect of oxygen on dyspnea in patients with advanced cancer. Journal of Pain and Symptom Management, 32, 541–550. doi: 10.1016/j.jpainsymman.2006.06.009

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. doi: 10.1016/S0885-3924(01)00381-5

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Tanaka, K., Shima, Y., Kakinuma, R., Kubota, K., Ohe, Y., Hojo, F., Nishiwaki, 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

Uronis, H.E., Currow, D.C., McCrory, D.C., Samsa, G.P., & Abernethy, A.P. (2008). Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: A systematic review and meta-analysis. British Journal of Cancer, 98, 294–299. doi: 10.1038/sj.bjc.6604161

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