General Background
1.1 What is hypertonic saline?
- A saline solution with a concentration below 0.9% is called HYPOtonic saline
- A saline solution with a concentration equal to 0.9% is called ISOtonic or NORMAL saline
- A saline solution with a concentration above 0.9% is called HYPERtonic saline
1.2 How does hypertonic saline work?
- Hypertonic saline, when delivered to the airway surfaces, promotes through its osmotic properties, the movement of fluids from the mucosa region, making it less viscous (viscoelasticity), and helping patients expectorate the excess mucus.
1.2a How does isotonic saline (0.9%) compare with hypertonic saline (>0.9%)?
- Isotonic saline is a wetting agent that can to a certain extent generate mucociliary thinning by moistening the airway surface. Isotonic saline does not have osmotic properties.
1.3 How was the use of hypertonic saline for inhalation discovered?
- General History: It has been long believed that breathing “salty air” helped patients with respiratory problems. Seaside clinics were popular in the late 1800s to mid 1900s. The average ocean or sea saline concentration is about 3.5%. Patients in these areas felt the salty air helped their breathing.
- Linked to CF: In the early 2000s an Australian physician who treated Cystic Fibrosis patients noticed that some of his patients were doing better than some of their peers. When the physician investigated why was there a difference among the patients, he found that the patients with fewer symptoms were surfers. It was hypothesized that the surfing patients were receiving a benefit from breathing the aerosolized sea air generated as the waves would break [read more].
- Ideas into action: The Australian Cystic Fibrosis Foundation along with the U.S. Cystic Fibrosis Foundation sponsored a study: “A Controlled Trial of Long-Term Inhaled Hypertonic Saline in Patients with Cystic Fibrosis.” This study was conducted between September 2000 and November 2003. The study was published in The New England Journal of Medicine in June 2006. The findings were that 7% hypertonic saline use for these patients was “an inexpensive, safe and effective additional therapy for patients with Cystic Fibrosis.”
1.4 Why is hypertonic saline believed to be helpful for patients needing assistance with sputum induction / clearance?
- Hypertonic saline concentrations greater than 0.9% have osmotic actions. These actions draw additional water into the sputum, thinning it, making it less viscous (viscoelasticity), and helping patients expectorate the excess mucus.
1.5 At what age can patients begin using hypertonic saline?
- Hypertonic saline is believed to be most effective in patients six years or older. However, initiating and evaluating hypertonic saline use is the responsibility of the treating physician, who can best advise on the individual situation.
Sodium Chloride and pH (Acid / Base)
2.1 Is there a correct or preferred pH in human lungs?
- General: Healthy human blood and the human respiratory system have a pH ranging from 7.35 to 7.45, with an average pH of 7.4. Deviation from these pH values, particularly toward acidity / lower pH, has been found to be a predictor of respiratory issues.
- Innate Immune Defense: The pH of Airway Surface Liquid (ASL) can be depressed by disease or inflammation. Low pH is predicted to suppress microbe clearance from the airways and alveoli, increase pathogen survival in both regions. (Ref.: No AW, et.al.,Innate host defense of the lung: effects of lung-lining fluid pH, Lung 2004;182(5): 297-317, http://www.ncbi.nlm.nih.gov/pubmed/15742242)
2.2 Is there a specific or preferred inhaled sodium chloride concentration for mucus clearance?
- In general, increasing the concentration of sodium chloride in the inhaled solution increases the osmotic effect and, thus, the amount of mucus cleared. To illustrate the change in mucus clearance when changing sodium concentrations please refer to this study: Ref: E. Daviskas et.al., Osmotic stimuli increase clearance of mucus in patients with mucociliary dysfunction, J o Aer Med. Sep, 15(3): 331-341. Doi:10.1089/089426802760292681.
- Most commonly used concentrations of hypertonic saline are 3%, 6%, and 7%. Results may vary depending on the underlying patient diagnosis requiring induction of sputum, and a physician should determine the correct concentration for each patient.
2.3 Is hypertonic saline only helpful at 7% sodium chloride or can I use 3% if I am uncomfortable with the higher concentration?
- Despite evidence of increased clearance at higher concentrations of sodium chloride, the 3% hypertonic saline solution is considered effective for a significant clearance of mucus.
- Patients often start with 3% hypertonic saline to accustom themselves to the treatments, and then they increase the titration up to 7%. Other patients start with 7% and back down to 3% if they want to increase airway comfort level.
- Tolerability is important for a successful inhalation treatment. At the onset of ANY IRRITITION or ADVERSE EVENT, the patient or caregiver should discontinue use of the saline and contact their physician, or in extreme events call 911.
- Consult your physician. Sometimes a downward titration from 7% to 3% can help with a patient’s own treatment comfort levels.
Delivery to the Airways
3.1 How is hypertonic saline delivered to the airways?
- Hypertonic saline is delivered to the airways via a nebulizer.
3.2 How much solution should be nebulized and how often?
- The current standard practice prescribed by physicians is 4 ml of the solution, twice a day. This may vary in accordance to the physician’s orders.
3.3 Is there a preferred nebulizer for hypertonic saline?
- Any of the three main types of nebulizers can be used for hypertonic saline: ultra-sonic, pneumatic, and vibrating-mesh. The most commonly used device is the pneumatic nebulizer. The vibrating-mesh devices are gaining in popularity, but tend to be more expensive.
3.4 Is there a preferred PSI my compressor should be set to?
- The power of a compressor is measured in PSI (Pressure per Square Inch) and measures the backpressure between compressor and nebulizer nozzle.
- Usually patients are dispensed a compressor nebulizer combination where the operating pressure is not variable. When patients are issued a compressor with a variable operating the question then is what is the preferred pressure setting (PSI rate) for inhalation of Hypertonic saline?
- PharmaCaribe’s hypertonic saline solutions have been cleared by FDA for use in conjunction with a nebulizer. Please contact your nebulizer manufacturer for the safe and effective (preferred) PSI setting for nebulizing a hypertonic saline solution, or contact your Doctor and/or a Respiratory therapist for the right setting on your compressor
Taking Hypertonic Saline with Other Drugs
4.1 When should hypertonic saline be nebulized relative to other inhaled medications?
- Pulmonologists generally suggests that patients use a bronchodilator (albuterol, or similar agent) prior to doing a hypertonic saline or other mucolytic treatment.
4.2 Will hypertonic saline interact with other medications in the nebulizer cup?
- It is not recommended to mix hypertonic saline with any other solutions.
4.3 Is there a correct order for hypertonic saline in patients taking multiple inhalation treatments.
- There is no established order on when to do a hypertonic saline inhalation treatment. However your physician may suggest that you take an albuterol treatment prior to you inhaling hypertonic saline.
- If you are taking several inhaled medications, the recommended order may be as follows:
- Bronchodilators
- Mucolytics (e.g. hypertonic saline)
- Airway clearance (e.g. chest physiotherapy)
- Antibiotics
- Ask your physician or health care team what order of treatments is best for you or your child.
- Hypertonic saline is indicated for “induction of sputum” in patients with over production of mucus and where sputum production is indicated, whatever the underlying condition. It’s use is not CF specific.
Hypertonic saline vs Pulmozyme
5.1 How is hypertonic saline different from Pulmozyme?
- The two solutions are different and SHOULD NOT BE INTERCHANGED or SUBSTITUTED.
- Pulmozyme is a drug classed as Recombinant Human Deoxyribonuclease, which hydrolyzes the DNA in sputum and reduces the viscous properties (viscoelasticity). In contrast, hypertonic saline has no pharmacologic activities and its actions are based on the natural osmotic properties of sodium chloride. However, both are considered mucolytics and help clear mucus from the airways.
5.2 Should a person take hypertonic saline and Pulmozyme?
- A person should take these medications as directed by their prescribing physician.
5.3 Does it do the same thing as Pulmozyme?
- Pulmozyme hydrolyzes the DNA in sputum and reduces the viscous properties (viscoelasticity). Hypertonic saline has no pharmacologic activities and it actions are of natural osmotic properties of sodium chloride. However, both help with mucus clearance from the airways
Getting Hypertonic Saline
6.1 Can I buy hypertonic saline over the counter?
- In the United States, hypertonic saline is a prescription product.
- Internationally, the mechanisms by which hypertonic saline is dispensed vary from country to country.
6.2 Why does the U.S. require a prescription for hypertonic saline?
- The U.S. Food and Drug Administration considers hypertonic saline an “Rx Only” product.
6.3 Can I make my own hypertonic saline?
- Physicians recommend purchase of hypertonic saline in 4 mL ampoules because it is sterile, non-pyrogenic and preservative free. Also, commercial hypertonic saline has a precise concentration of sodium chloride.
6.4 Is hypertonic saline covered by insurance?
- Most patients find that their hypertonic saline is covered by insurance. However, coverage varies by type of insurance (private or government), and the stipulations of the individual insurance carrier and the individual insurance plan.
PharmaCaribe’s Second Generation Hypertonic Saline
7.1 What are the pH characteristics of existing hypertonic saline choices on the market today?
- United States Pharmacopeia (USP) guidelines for Sodium Chloride Solutions for Inhalation permit a pH between 4.5 (acidic like tomato juice) and 7.0 (neutral like pure water). The average pH of hypertonic saline produced to USP guidelines is 6.2, but patients, pharmacists and physicians do not know what pH the patient is receiving with USP hypertonic saline, and it may be as low as 4.5.
- Innate Immune defense: Healthy lungs have Airway Surface Liquid (ASL) with a pH of 7.4. In contrast, compromised lungs may have a lower pH, which is correlated with suppressed microbe clearance. (Ref.: No AW, et.al., Innate host defense of the lung: effects of lung-lining fluid pH, Lung 2004;182(5): 297-317, http://www.ncbi.nlm.nih.gov/pubmed/15742242)
7.2 What is unique about the new PulmoSal™ 7%?
- PulmoSal™ 7% (pH+) is the only FDA cleared hypertonic saline. It is bio-balanced to a pH of 7.4, the same physiologic pH as the homeostatic pH in the airways of healthy lungs.
- This is in contrast to all other hypertonic saline products, which have pH levels ranging from 4.5 to 7.
7.3 What is the science behind the new PulmoSal™ 7% with pH of 7.4?
- PulmoSal™ 7% maintains the same indication and rate of induction of sputum without adding acidity to pH-depressed airways. With low pH predicted to suppress microbe clearance from the lungs, striving to maintain a pH at or close to 7.4 is likely to be beneficial to patients.(Ref.: No AW, et.al., Innate host defense of the lung: effects of lung-lining fluid pH, Lung 2004;182(5): 297-317, http://www.ncbi.nlm.nih.gov/pubmed/15742242 )
- For further questions regarding the importance of airway pH, please call 804-212-2480.
7.4 How is PulmoSal™ 7% better than current choices on the market?
- The rate of sputum induction is the same as other products because the concentration of sodium chloride is the same. However, PulmoSal is “Bio-Balanced” to the natural pH of the lung lining and airway surface liquid, which may help the body’s own immune defense fight various pathogens.
- PulmoSal 7% (pH+) is a 2nd Generation Bio-Balanced TM Hypertonic Saline. We combined the clinically proven 7% hypertonic saline concentration with a pH of 7.4 which is the physiologic pH of healthy respiratory systems (Ref.: press release 2013). At NACFC 2014 a poster presentation comparing Hypertonic Saline made to USP and PulmoSal 7% (pH+) concludes that “These data show approximately 5 log decrease in bacterial density in the pH 7.4 solution compared with approximately 2 log decrease in the two commercially available HS’s having pH 5.86 and pH 6.60 solutions at 24 hours” (ref: pH+ pH differential PA killing.pdf)
7.5 Is PulmoSal™ 7% compliant with current regulatory standards? (i.e. FDA approved)
- Yes, PulmoSal™ 7% is cleared for commerce by the FDA / CDRH under 510(k) 130091.
7.6 How do I get PulmoSal™ 7% in the U.S. and internationally?
- PulmoSal™ 7% is available by prescription at any U.S. pharmacy. Pharmacists can order it from their drug wholesalers using the National Drug Code (NDC) # 50190-740-60. For information on international orders please call 1-804-212-2480
7.7 What is the retail cost of PulmoSal™ 7%?
- The price can vary greatly from pharmacy to pharmacy but PulmoSal™ 7% is usually comparably priced to other hypertonic saline solutions.
7.8 Is PulmoSal™ 7% covered by insurance?
- Insurance coverage for PulmoSal™ 7% is similar to coverage for other hypertonic saline, and thus varies by type of insurance (private or government), the stipulations that the individual insurance carrier has for inhaled hypertonic saline and the individual insurance plan.
