Likely to Be Effective

Non-Invasive Ventilation

for Dyspnea

Noninvasive ventilation supports breathing in patients without the use of a surgical intervention to bypass the upper airway such as an endotracheal tube. Noninvasive ventilation is delivered with a mask or a similar device and has fewer adverse effects than invasive ventilation. Bilevel positive airway pressure (BiPAP) is a type of non-invasive ventilation that is used to treat patients with sleep apnea.

Research Evidence Summaries

Hui, D., Morgado, M., Chisholm, G., Withers, L., Nguyen, Q., Finch, C., . . . Bruera, E. (2013). High-flow oxygen and bilevel positive airway pressure for persistent dyspnea in patients with advanced cancer: A phase II randomized trial. Journal of Pain and Symptom Management, 46, 463–473. 

Study Purpose

To examine changes in dyspnea through a randomized trial of high-flow oxygen (HFO) and bilevel positive airway pressure (BiPAP) in patients with cancer

Intervention Characteristics/Basic Study Process

Patients were randomized using a computer-generated randomization scheme in a 1:1 ratio to receive either two hours of HFO followed by a washout period and then two hours of BiPAP or two hours of BiPAP followed by a washout period followed by two hours of HFO. Data on dyspnea were collected every 10 minutes after the first intervention for as much as one hour. Patients participated in the second intervention if their dyspnea level was ≥ baseline dyspnea level minus one or  ≥ 3/10 after one hour.

Sample Characteristics

  • N = 30
  • AVERAGE AGE = 61 years (range = 29–79 years)
  • MALES: 47% (n = 14), FEMALES: 53% (n = 16)
  • KEY DISEASE CHARACTERISTICS: Lung 43% (n = 13), head and neck 3% (n = 1), genitourinary 3% (n = 1), gastrointestinal 10% (n = 3), breast 17% (n = 5), other 23% (n = 7); cancer stage metastatic 87% (n = 26) and local 13% (n = 4); causes of dyspnea were pulmonary parenchymal lesions 70% (n = 21), pleural effusions 50% (n = 15), lymphangitic carcinomatosis 7% (n = 2), and other noncancer causes; not already on home supplemental oxygen 70% (n = 21); majority of participants (93%) on supplemental oxygen at the time of enrollment with a median of 3 L per minute and an average oxygen saturation of 95% (SD = 4%). 
  • OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria: average intensity of dyspnea at rest over the past week ≥ 3/10 on a numeric rating scale despite the use of supplemental oxygen, life expectancy of more than one week, and English-speaking; exclusion criteria: hemodynamic instability, acute respiratory distress with impending intubation, delirium (Memorial Delirium Assessment Scale > 13/30), Glasgow Coma Scale < 8/15, contraindications to BiPAP, or noncancer-related dyspnea with supplemental home oxygen before hospitalization

Setting

  • SITE: Single site  
  • SETTING TYPE: Inpatient  
  • LOCATION: MD Anderson Cancer Center

Phase of Care and Clinical Applications

  • PHASE OF CARE: End-of-life care
  • APPLICATIONS: Palliative care

Study Design

Randomized, open-label study with a parallel design and an optional second intervention

Measurement Instruments/Methods

  • Numeric Rating Scale (NRS), a measurement of dyspnea on a 0–10 scale
  • Modified Borg Scale (MBS), an assessment scale for dyspnea
  • Global symptom evaluation
  • Memorial Delirium Assessment Scale (MDAS)
  • Glasgow Coma Scale (GCS)

Results

This study found that dyspnea improved with both HFO and BiPAP in a comparison of pre- and post-treatment dyspnea. BiPAP use was associated with an average of a 3.2 dyspnea improvement on the NRS (p = 0.0004) and 1.5 on the MBS (p = 0.13). HFO was associated with an average improvement of 1.9 on the NRS (p = 0.02) and 2.1 on the MBS (p = 0.007). There were no significant differences in dyspnea relief between HFO and BiPAP on the NRS (P = 0.14) or the MBS (P = 0.47). BiPAP use also was associated with average improvements in NRS scores of 3.2 (P = 0.007) and 1.5 on the MBS (P = 0.13).
 
A statistically insignificant decrease in respiratory rate was identified with both devices. BiPAP use was associated with a decrease in heart rate (p = 0.02). HFO was associated with a significant decrease in systolic blood pressure (p = 0.02) and improvements in oxygen saturation (p = 0.003). No adverse effects were noted for either device. The majority of patients reported that HFO (10/13; 17%) and BiPAP (9/10) improved their dyspnea. 

Conclusions

HFO and BiPAP were found to alleviate dyspnea and improve physiologic parameters. The results of this study justify larger randomized, controlled studies to validate these findings. The authors of this study proposed that HFO and BiPAP be examined separately.

Limitations

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Other limitations/explanation: Multiple statistical comparisons were conducted. Baseline arterial blood gas and a measurement of oxygen saturation while on room air were not conducted.

Nursing Implications

Dyspnea is one of the most common symptoms for patients with cancer. This study shows that HFO and BiPAP may alleviate dyspnea. These devices are safe for patients to use. Larger randomized, controlled clinical trials are needed to confirm the findings of this study.

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Nava, S., Ferrer, M., Esquinas, A., Scala, R., Groff, P., Cosentini, R., . . . Grassi, M. (2013). Palliative use of non-invasive ventilation in end-of-life patients with solid tumours: A randomised feasibility trial. The Lancet Oncology, 14, 219–227. 

Study Purpose

To determine the acceptability of solely using palliative noninvasive ventilation (NIV) versus oxygen therapy to manage breathlessness in patients with end-stage cancer and its effects in reducing dyspnea and opioid requirement

Intervention Characteristics/Basic Study Process

  • All patients received a 5–10 minute demonstration on NIV prior to randomization.
  • Patients were randomly assigned to either NIV (pressure-support mode and initiation based on patients’ request and mask comfort) or oxygen (Venturi or reservoir mask) group to achieve oxygen saturation > 90%.
  • Based on a computerized randomization sequence, patients were further stratified and randomly assigned to hypercapnic (PaCO2 > 45 mm Hg) or nonhypercapnic (PaCO2 < 45 mm Hg) groups.
  • An independent biostatistitian placed patients’ information in an opaque, sealed envelope.
  • Subcutaneous morphine was given to reduce dyspnea scores by at least one point on the Borg scale (BS), and the total dose requirements over the first 48 hours were calculated.
  • Arterial blood gas, vital signs, quantity of secretion, and dyspnea scores were measured at baseline and at one hour, 24 hours, and 48 hours.
  • Mortality causes were recorded in the hospital and at three and six months after discharge.

Sample Characteristics

  • N = 200
  • MEAN AGE = 71 years (NIV group), 70 years (oxygen group)
  • MALES: 62%, FEMALES: 38%
  • KEY DISEASE CHARACTERISTICS: Solid tumor cancers included lung, gastrointestinal, breast, head and neck, and esophageal. Respiratory failures included obstructive bronchus, carcinomatous, lymphangitis, and pleural effusion. Life expectancy was less than six months.
  • OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria were a P/F ratio of 1:250 and one of the following: dyspnea with a BS ≥ 4, signs of respiratory distress, or a respiratory rate ≥ 30. Exclusion criteria were reversible respiratory failure such as cardiogenic pulmonary edema or the exacerbation of chronic pulmonary disorders, treatment refusal, a weak cough reflex, agitation or uncooperative behavior, anatomical abnormalities with mask fitting, uncontrolled cardiac ischemia or arrhythmias, ≥ 2 organ failure, opioid use within past two weeks, adverse effects to opioids, substance misuse history, contraindication to morphine use, acute renal failure, and recent head injury.

Setting

  • SITE: Multi-site  
  • SETTING TYPE: Inpatient  
  • LOCATION: Seven intensive care units and critical care units in Italy, Spain, and Taiwan

Phase of Care and Clinical Applications

  • PHASE OF CARE: End-of-life care
  • APPLICATIONS: Palliative care

Study Design

Multi-center, randomized, controlled trial

Measurement Instruments/Methods

  • McCabe Cyclomatic Complexity Index (MCCI) to record demographic information
  • Simplified Acute Physiology Score II (SAPS) and Palliative Prognostic Index Score (PPIS) to determine mortality risk
  • Kelly and Matthay Scale (KMS) to assess neurological status in patient with respiratory disease
  • Modified Borg Scale (BS) to assess intensity of dyspnea
  • Symptom Distress Scale (SDS) self-administered questionnaire to assess cancer-related symptoms

Results

  • In the NIV group, 11 patients (11%) dropped out of the study, but there was no attrition in the oxygen group.
  • The NIV group had a statistically significant reduction in dyspnea levels at one hour, 24 hours, and 48 hours (BS = -0.58; 95% CI -0.92, -0.23; p = 0.0012). The greatest reduction was seen in the hypercapnic NIV group after the first hour (BS = -0.91; 95% CI -1.42, -0.46; p < 0.0001). 
  • The total amount of morphine required over 48 hours was lower in the NIV group (SD = 37.3 mg) compared to the oxygen group (SD = 67.1mg) with a mean difference of -32.4 mg (95% CI -47.5, -17.4).
  • In-hospital mortality was the same between the groups.
  • The NIV hypercapnic group had better expected survival rates than the oxygen hypercapnic group.
  • At discharge, symptom distress scores were statistically improved in the NIV group compared to the oxygen group (SD = 10 versus SD = 7.6; p = 0.001).

Conclusions

NIV was feasible and effective in decreasing dyspnea intensity and reducing morphine requirements in patients with end-stage cancer experiencing respiratory failure. However, additional studies validating these findings and determining the effects of NIV on survival and quality of life are needed.

Limitations

  • Risk of bias (no blinding)
  • Key sample group differences that could influence results
  • Findings not generalizable
  • Intervention expensive, impractical, or training needs
  • Subject withdrawals ≥ 10% 
  • Other limitations/explanation: The benefit of performing a blinded study using a sham ventilation could have potentially caused harm to the patients in the oxygen group. Therefore, the researchers chose to maintain patient safety.
  • The NIV group had an attrition bias. Also, the duration and timing of the NIV treatment was based on patients’ preferences and mask comfort, leading to a threat in internal validity. The NIV treatment may not be practical or cost effective in all palliative care centers because specialized training and equipment are needed. 

Nursing Implications

This study offers clinicians a treatment modality that can be used in adjunct with opioids to significantly reduce breathlessness in patients with end-stage cancer. Additional studies are needed to determine the specific patient population that would benefit the most from this treatment, its cost effectiveness, patient satisfaction, the adverse effects of NIV, and the survival rate.

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