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European Annals of Otorhinolaryngology, Head and Neck diseases 132 (2015) 281–285

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Review

Nasal irrigation: From empiricism to evidence-based medicine.


A review
P.-L. Bastier a , A. Lechot a , L. Bordenave b,c , M. Durand c , L. de Gabory a,∗,c
a
Service d’ORL et de chirurgie cervico-faciale, centre Michelet, hôpital Pellegrin, CHU de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux cedex, France
b
U1026, bio-ingénierie tissulaire, université de Bordeaux, 33000 Bordeaux, France
c
CIC-IT, CHU de Bordeaux, 33000 Bordeaux, France

a r t i c l e i n f o a b s t r a c t

Keywords: Nasal irrigation plays a non-negligible role in the treatment of numerous sinonasal pathologies and
Nasal irrigation postoperative care. There is, however, a wide variety of protocols. The present review of the evidence-
Seawater based literature sought objective arguments for optimization and efficacy. It emerged that large-volume
Saline solution
low-pressure nasal douche optimizes the distribution and cleansing power of the irrigation solution in
the nasal cavity. Ionic composition and pH also influence mucociliary clearance and epithelium trophicity.
Seawater is less rich in sodium ions and richer in bicarbonates, potassium, calcium and magnesium than
is isotonic normal saline, while alkaline pH and elevated calcium concentration optimized ciliary motility
in vitro. Bicarbonates reduce secretion viscosity. Potassium and magnesium promote healing and limit
local inflammation. These results show that the efficacy of nasal irrigation is multifactorial. Large-volume
low-pressure nasal irrigation using undiluted seawater seems, in the present state of knowledge, to be
the most effective protocol.
© 2015 Elsevier Masson SAS. All rights reserved.

1. Introduction The heterogeneity of the literature makes it difficult to get any


clear idea concerning the various solutions and means of admin-
Several national and international consensus conferences now istration. Irrigation solution composition would seem to be an
recommend nasal irrigation as adjuvant treatment in numerous important issue: chronic patients sometimes report improvement
sinonasal pathologies [1–6]. It provides mechanical cleansing of with sea bathing, and some studies suggest that irrigation solutions
mucus, crust, cell debris and various air contaminants (pathogens, taken from certain seas provide better functional improvement
allergens, airborne particles, etc.). It enhances mucociliary clear- [12,13].
ance [7,8] and reduces the mucus contact time of airborne elements. The present article comprises a literature review and update on
It reduces local concentrations of pro-inflammatory mediators the various solutions and means of administration available.
[9–11] and humidifies the nasal mucosa, notably postoperatively
and in many chronic sinonasal pathologies. 1.1. Means of irrigation
A recent meta-analysis of 10 controlled trials taken from a
review of 11,500 studies included more than 400 allergic rhini- To the best of our knowledge, there is no consensus regarding
tis patients [7]. Regular saline irrigation in adults and children means of irrigation. A study of the cavity distribution of 40 mL
improved nasal symptomatology in 35% of cases and quality of life of radio-opaque substance in healthy subjects reported benefit
in 30%. Mucociliary clearance on saccharine test was increased by with positive pressure irrigation versus negative pressure admin-
about 30%. The impact on medical drug consumption was harder to istration (by sniffing) or nebulization: nasal cavity and sinus
quantify; moreover, the included population was small for such a distribution was more exhaustive [14]. Wormald et al., using 5 mL
common treatment, and methods and administration times varied Tc99m-labeled irrigation solution, found better nasal cavity and
greatly, limiting the scientific value of the study [7]. sinus distribution with douche administration than nebulization
or sprays [15].
We found no studies, comparative or not, in the literature
focusing on syringe administration, despite this being the most
∗ Corresponding author. widespread method. Several studies reported greater efficacy with
E-mail address: ludovic.de-gabory@chu-bordeaux.fr (L. de Gabory). large-volume irrigation [16,17]. A recent study compared 26 nasal

http://dx.doi.org/10.1016/j.anorl.2015.08.001
1879-7296/© 2015 Elsevier Masson SAS. All rights reserved.
282 P.-L. Bastier et al. / European Annals of Otorhinolaryngology, Head and Neck diseases 132 (2015) 281–285

Table 1 100% 2
6
Composition (mg/L) of physiological saline, electrodialyzed seawater and Ringer’s 12
8
26
lactate [40,48]. 80%
23 Main elements (calcium,
61 potassium, magnesium)
Physiological Seawater Ringer’s lactate
60% 56
saline (Physiomer® ) (source: Vidal® 40 Buffers (bicarbonate, nitrate,
[40,48] dictionary 2014) 46
sulfate)
40%

Sodium 3500 2400–2600 3000 Chloride


Chloride 5500 5400–6300 3900 20% 39
32 32
Magnesium 1100–1500 19
Sodium
Calcium 280–390 120 0%
Physiological Ringer's Lactate Seawater(pH=8) Electrolyzed
Potassium 44–62 150 saline (pH=5) (pH=6,5) seawater (pH=8)
Sulfates 2755
Lactates 2500 Fig. 1. Physical and chemical characteristics of various isotonic saline solutions
Iron 6 versus seawater (biochemical analyses provided by Laboratoire de la Mer® ).
Zinc 27–90
Selenium 38
Copper 13–40 Although these are marketed as “seawater”, the one-third
pH 4.5–7 8 6–7.5 dilution conserves only part of the naturally present miner-
als, which are themselves proportionally diluted (http://www.
sterimar.com/en/nasal-family-solutions.php). Another product
irrigation devices available on the German market [18], testing consists of electrodialyzed seawater (Physiomer® ), providing
them on a resin nasal cavity model based on normal non-congested an isotonic solution with reliable osmolarity, while conserving
cadaver nostrils. Irrigation volumes ranged from 30 to 500 mL, for high concentrations of the main seawater ions (https://register.
a mean 200–250 mL. The greater the irrigation volume, the larger epo.org/application?lng=en&number=EP98460042). Its composi-
the cavity area covered by the irrigation: large-volume irrigation tion is known and can be compared to physiological saline and
reaches a larger proportion of the nasal cavities. Depending on Ringer’s lactate (Table 1). Products obtained by this procedure are,
volume and device, application time ranged between 6 and 54 s, like Ringer’s lactate, rich in calcium, potassium and magnesium
and output between 3.9 and 27.2 mL/s. Only compression systems ions and buffering (bicarbonates), with low sodium ion content
delivering ≥120 mbar pressure reached the entire nasal cavity. The (Table 1). Like seawater, they have slightly alkaline pH (controlled
authors added that tight fit between nozzle and nostril and the pos- pH close to 8), while normal saline is acidic, with pH varying from
sibility of inserting the nozzle into the vestibule and orienting it 45◦ 4.5 to 7.
upward optimized cavity coverage and minimized loss of irrigation
solution [18]. It also appeared that good ergonomics, irrigation
1.2.2. Role of the various components
quality and microbial safety were associated with devices that were
It is now agreed that, in vitro, these ions show non-negligible
transparent, equipped with an anti-reflux nozzle, in high-quality
action on epithelial cells. Sodium ions can inhibit hair-cell cal-
supple and compressible plastic, with ≥5 mL/s output or ≥120 mbar
cium flow, thus reducing ciliary beat frequency [20]. Magnesium
administration pressure, that could be taken apart and washed by
ions reduce local inflammation by reducing mediator secretion
hand or in a dishwasher, and were adapted for microwave ovens.
[21] and degranulation [22] in cells implicated in allergy. Para-
Clinically, a prospective single-blind randomized study com-
doxically, they increase IL-8 secretion by nasal epithelial cells [23].
pared postoperative efficacy between two commercially available
Finally, magnesium and zinc can reduce respiratory mucosa cell
nasal irrigation devices; in 31 endonasal surgery patients,
apoptosis during inflammatory processes [24]. Calcium is involved
large-volume low-pressure irrigation was associated with better
in regulating ciliary beat frequency and synchronization, via vari-
postoperative nasal cavity cleansing on the Lund-Mackay postop-
ous ciliated cell surface receptors [25], in all of which acetylcholine
erative endoscopy score than low-volume high-pressure irrigation
and serotonin act as messengers by increasing cell calcium intake
[19].
[25]. Airflow also stimulates cell calcium intake and ciliary beat via
shear-stress-induced mechanotransduction [25]. Potassium pro-
1.2. In vitro data motes respiratory epithelium repair via the EGF/EGFR pathway
[26,27]. Bicarbonate ions, as well as acting as buffer, efficiently
1.2.1. Composition of commercially available solutions reduce mucus viscosity, thus facilitating elimination by ciliated cell
It is important to be aware of the fact that the exact compo- movement [28].
sition of the various products and recipes could not be found in
the literature, except for Physiomer®1 and Ringer’s lactate. Table 1
1.2.3. Role of pH and tonicity
and Fig. 1 show the chemical compositions of the various nasal
In vitro, solutions with pH <7 or >10 reduced tracheal mucosa
irrigation solutions. There are several “recipes” for “home-made”
ciliary beat frequency in rats and chicken embryos [29]. In humans,
saline, with or without buffer, that patients can make up themselves
solutions with acidic pH likewise reduced ciliary beat frequency,
at home, using water, salt and, in some cases, sodium bicarbonate.
while slightly alkaline solutions enhanced it [30,31]. In vivo, on the
Unlike normal saline (NaCl 0.9%), composition and sterility are nei-
other hand, in humans, pH impact on mucociliary clearance is more
ther controllable, reproducible or reliable. Home-made solutions
difficult to ascertain. England et al. found no statistical correlation
using “sea” salt contain only chloride ions and sodium.
between pH and mucociliary clearance in 56 healthy non-smokers
There are also commercially available products consist-
[32]. More recently, Chusakul et al. reported clear improvement
ing of seawater diluted to one-third in distilled water (e.g.,
in symptoms with alkaline isotonic solutions in allergic rhinitis;
Stérimar®2 , Marimer®3 , Vicks®4 ) to obtain an isotonic solution.
mucociliary clearance, on the other hand, was unaffected whatever
the pH, in a range from 6.2 to 8.4 [33]. However, change in mucocil-
iary clearance seems not to depend exclusively on pH: in vitro, in
1
Laboratoire de la Mer® , ZAC La Madeleine, avenue du Général-Patton, Saint- chicken embryo tracheal explants, hypertonic (1.5%) and hypotonic
Malo, France.
2
Laboratoires Fumouze, SOFIBEL, Church & Dwight Group, New York, USA.
(0.45%) irrigation both reduced ciliary beat frequency as compared
3
Laboratoire Gilbert, Batteur Group, Hérouville Saint-Clair, France. to physiological (0.9%) saline [29]. Beat arrest was irreversible with
4
Procter and Gamble Pharmaceuticals France, Asnière-sur-Seine, France. a 14% solution, and hypertonicity triggered mucus hypersecretion
Table 2
Main prospective comparative randomized clinical studies comparing efficacy and tolerance for nasal irrigation solutions in various sinonasal indications.

Author, year Study design Indication Population Series Treatment Groups Group size Assessment criterion P Level of
size time (weeks) evidence

Multicenter Type of
comparison

Slapak et al., 2008 Yes Open Acute rhinitis Children 401 12 A Standard treatment 101 Nasal secretion P < 0.05* (B > A) I
[48] or non- B Standard treatment 289 abundance and
complicated + electrodialyzed type
flu seawater

P.-L. Bastier et al. / European Annals of Otorhinolaryngology, Head and Neck diseases 132 (2015) 281–285
Strnad et al., 2007 Yes Open Allergic and Adults and 238 6 A Rhinocorticoids 78 Nasal index P < 0.05* (B > A I
[46] non-allergic children + antihistamines score and C > A)
rhinosinusitis B Electrodialyzed 80
seawater
+ rhinocorticoids
+ antihistamines
C Electrodialyzed 80
seawater
+ antihistamines
Friedman et al., No Double-blind Chronic Adults 114 4 A Hypertonic Dead Sea 59 SNOT P = 0.082 I
2012 [47] rhinosinusitis water 20
B Hypertonic saline 55
+ rhinocorticoids
Wang et al., 2009 No Open Acute sinusitis Children 69 3 A Isotonic saline 30 PRQLQ (Pediatric P < 0.05* II
[49] B No irrigation 39 Rhinoconjunctivitis (A > B)
Quality of Life
Questionnaire)
Friedman et al., No Double-blind Chronic Adults 42 4 A Hypertonic Dead Sea 22 Rhinosinusitis P = 0.003* (A > B) II
2006 [13] rhinosinusitis water symptoms
B Hypertonic saline 20

Chusakul et al., No Double-blind Allergic rhinitis Adults 36 1.5 A Isotonic saline 12 Rhinologic P > 0.05 II
2013 [33] B Buffered moderately 12 symptoms
alkaline isotonic saline
C Buffered strongly 12
alkaline isotonic saline
Ünal et al., 2001 No nk Post- Adults 32 3 A Ringer’s lactate nk Saccharine P < 0.05* (A > B) II
[50] septoplasty B Isotonic saline nk mucociliary
clearance test
Li et al., 2009 [43] No Open Moderate to Children 26 12 A Rhinocorticoids 6 Rhinologic P < 0.05* (C > A II
severe + antihistamines symptoms and C > B)
permanent B Isotonic saline 9
allergic rhinitis + antihistamines
C Isotonic saline 12
+ rhinocorticoids
+ antihistamines
Garavello et al., No Open Seasonal Children 20 6 A Hypertonic saline 10 Daily rhinitis P < 0.05* II
2003 [42] allergic rhinitis B No irrigation 10 score (A > B)

Pigret and No Single-blind Post- Adults 20 3 A Electrodialyzed 10 Weight of P > 0.05 II


Jankowski, 1996 endoscopic seawater crusts and
[51] ethmoidec- B Isotonic physiological 10 secretions
tomy for saline
sinonasal + benzododecinium
polyposis + oleosorbate

* Statistical significative difference; nk: not known.

283
284 P.-L. Bastier et al. / European Annals of Otorhinolaryngology, Head and Neck diseases 132 (2015) 281–285

and increased the permeability of tight junctions [34–36]. These symptoms more effectively when associated to nasal irrigation
data correlated in vivo with increased secretion and exudation in with an isotonic solution [49]. Both studies showed the efficacy of
response to hypertonic solutions [37]. Paradoxically, other authors irrigation in these respective pathologies, but did not demonstrate
reported improved in vivo mucociliary clearance on saccharine test the superiority of either solution, as there was no comparative arm.
in healthy subjects with hypertonic solutions between 3% and 5% In postoperative use, nasal irrigation is essential for cleansing
[38,39]. the crusts and secretions inherent to any sinonasal surgery. It sig-
nificantly reduces nasal secretion and shows a tendency to reduce
1.2.4. Advantages of seawater postsurgical edema. Ringer’s lactate, which is rich in calcium and
Since 1995, it has been shown that seawater promotes cell potassium and less rich in sodium and chloride ions than isotonic
growth, with a significantly stronger eutrophic effect than nor- saline, provided a stronger increase in mucociliary transport than
mal saline or seawater at one-third dilution [40]. In a more recent isotonic saline after endonasal surgery [50].
in vitro study, 2 to 4 hours’ exposure to electrodialyzed seawa- Few studies have focused on postoperative seawater irrigation
ter enhanced viability in deprived bronchial epithelial cells as [51–53], and they lacked control groups without postoperative care
compared to isotonic normal saline [11]. In other studies, seawa- to remove clots, crusts and secretion. Pigret and Jankowski found
ter significantly protected pig nasal mucosa against the effects of no significant difference between the effects of pressurized seawa-
twice-daily 0.1% oxymetazoline (inflammation, fibrosis, metapla- ter and saline with antiseptics and mucolytics, in a small series (10
sia) [41]. patients per group) [51]. Keerl et al., in an observational study of 121
In vitro, electrodialyzed seawater reduced production of pro- patients, found nasal irrigation to be well tolerated, and that some
inflammatory molecules such as IL-8 or RANTES [10,11], involved patients continued in the long-term, including irrigation in their
in the recruitment and activation of polynuclear neutrophils and daily life routine [52]. Pinto et al. found no symptomatic benefit
eosinophils. of irrigation, whether iso- or hypertonic [53], and recommended
Thus, in vitro at least, it would seem that limited sodium chlo- not implementing postoperative irrigation; their study, however
ride content is important for nasal irrigation solutions. Conversely, involved certain defects: no inclusion criteria, and no details of sur-
calcium provides an advantage in terms of restoring epithelial gical technique, numerous revision surgeries and application of an
trophicity and mucociliary efficacy. Potassium should provide ben- endonasal hemostasis substance. Moreover, the symptoms scores
efit in postoperative situations and/or certain chronic rhinosinusitis used were not validated, and final nasal cavity status was not noted
via its action on anti-inflammatory response; slightly alkaline pH [53].
with isotonic composition should have a similar effect. Finally, certain preservatives, antiseptics and mucolytics have
sometimes been associated to irrigation solutions. They slowed
1.3. Clinical advantages of undiluted seawater over other or arrested ciliary beat, and showed no clinical benefit [51,54,55].
irrigation solutions A recent meta-analysis confirmed the non-superiority of adding
an antibiotic and an antifungal agent to the irrigation solution in
Certain studies reported clinical superiority for mineral-rich chronic rhinosinusitis [6].
solutions compared to classic saline, but data are sparse (Table 2).
In allergic rhinitis, iso- and hypertonic saline improved all 2. Conclusion
symptoms in children, reducing recourse to antihistamines and
corticosteroids [42,43], with excellent tolerance [44,45]. In 2007, Founded on empirical practice and common sense, nasal
a multicenter randomized study assessed the efficacy of electro- irrigation now plays an essential and self-evident role for the
dialyzed 2.2% hypertonic Saint-Malo seawater in 238 allergic or large majority of practitioners. The heterogeneity of protocols and
non-allergic chronic rhinosinusitis patients, and found strongly sig- studies make for confusion. It would, however, appear that: large-
nificantly superiority for nasal irrigation (with or without local volume irrigation provides good distribution over the sinonasal
corticosteroids) versus controls (antihistamines with local cortico- cavities as a whole; and a stable, reproducible isotonic solution
steroids, without irrigation) in terms of symptoms and of recourse with slightly alkaline pH and a composition close to that of sea-
to corticosteroids [46]. Cordray et al. likewise reported that nasal water optimizes trophic and functional recovery of the respiratory
irrigation with water from the Dead Sea, without antihistamines, epithelium. Clinically, the literature fails to prove any clear superi-
was as effective as local corticosteroids in controlling nasal and ocu- ority of one product over the others; however, the in vitro properties
lar symptoms in mild-to-moderate seasonal allergic rhinitis [12]. of undiluted seawater seem to provide definite advantage in many
Friedman et al., in a prospective randomized double-blind study, clinical situations, as compared with physiological saline. Further
found greater improvement in symptom scores in 42 allergic or studies will be needed to confirm the present findings.
non-allergic chronic rhinosinusitis patients with Dead Sea water
versus hypertonic saline [13]. The same author, using the same Disclosure of interest
methodology, more recently reported a similar improvement in
symptoms in 114 patients with irrigation with hypertonic Dead Sea L. de Gabory: occasional expert reports, consultancy and guest
water without corticotherapy versus hypertonic saline with local speaker for Laboratoire de la Mer® .
corticosteroids [47]. The other authors declare that they have no conflicts of interest
In acute infection, two prospective randomized studies showed concerning this article.
better treatment with nasal irrigation. The first, a controlled mul-
ticenter study of 390 children with rhinitis, found faster improve- Acknowledgments
ment in nasal permeability and the quality and quantity of secretion
with electrodialyzed seawater irrigation than in a control group The authors thank Laboratoire de la Mer® for the data for the
without irrigation [48]. It also demonstrated that irrigation reduced composition of the irrigation solutions shown in Fig. 1.
number of episodes, ENT complications and medication (antipyret-
ics, antibiotics, mucolytics and decongestants) in children suffering
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