Use of Cryotherapy for Acute Epistaxis in the First Aid Setting: First Aid Scoping Review

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Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy.

There were no declared conflicts of interest.

Task Force Scoping Review Citation

Berry DC, Carlson, J, Singletary EM, Zideman D, on behalf of the International Liaison Committee on Resuscitation First Aid Task Force. Use of Cryotherapy for Acute Epistaxis in the First Aid Setting Scoping Review and Task Force Insights [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) First Aid Task Force, 2021 February 16. Available from: http://ilcor.org

Collaborators: Charlton NP, Douma M, Ring J

Methodological Preamble and Link to Published Scoping Review

The continuous evidence evaluation process began with a scoping review of cryotherapy as an intervention for acute epistaxis in the first aid setting by non-medical providers (first aid providers, lay responders) conducted by the ILCOR First Aid Task Force. Evidence from adult and pediatric literature was sought and considered by the reviewers.

This scoping review is designed to identify any evidence on the effect of cryotherapy on acute epistaxis that might lead to future systematic reviews on the topic. The question used in this review was developed as a new PICOST.

Scoping Review

Webmaster to insert the Scoping Review citation and link to Pubmed using this format when/if it is available.

PICOST

Among adults and children receiving first aid for acute epistaxis (P), does cryotherapy alone or cryotherapy with nose pinching (I), compared with nose pinching alone (C), change time to hemostasis (min), hemostasis (yes/no), reduction of nasal blood volume (volume), reduction of pain, follow-up care (yes/no), adverse events (yes/no), recovery time (days/min), and reduction of swelling (volume)?

The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)

Population: Adults and children receiving first aid for acute epistaxis

Intervention: Cryotherapy alone or cryotherapy with nose pinching

Comparators: Nose pinching alone

Outcomes: Time to hemostasis control (minutes), hemostasis (yes/no), reduction of nasal blood volume (volume), reduction of pain, need for follow-up care (yes/no), adverse events (yes/no), recovery time (days/min), reduction of swelling (volume)

Study Designs: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) are eligible for inclusion. Case series and gray literature are eligible for inclusion.

Timeframe: The initial search strategy (Embase + Medline and Cochrane) included all years and all languages as long as there was an English abstract; unpublished studies (e.g., conference abstracts, trial protocols) were excluded. Initial literature search was July 13, 2020, updated on January 14, 2021.

A focused literature search (Pubmed.gov) was conducted (DCB, JC) on December 19, 2020. The search was inclusive for all years and all languages as long as an English abstract was available.

A gray literature search (Google.com) was conducted (DCB, JC) on December 21, 2020, and was inclusive for all years.

A gray literature search (Google scholar) was conducted (DCB, JC) on December 28, 2020, and was inclusive for all years.

A final gray literature search was conducted (DCB, JC) on December 28, 2020 and examined the eight-member councils' websites (and sub-councils) of the International Liaison Committee on Resuscitation. We hand examined the organizations for position or guideline statements addressing first aid management of epistaxis.

A hand search for secondary resources (DCB) identified from reviewed manuscripts on acute anterior epistaxis was conducted as needed.

Search Strategies

Search-Strategies-Epistaxis

Inclusion and Exclusion criteria

Inclusion-and-Exclusion-criteria

Data Tables

Data-Tables

Task Force Insights

1. Why this topic was reviewed.

Epistaxis, nasal or nose bleeding is bleeding from the nostril(s), nasal cavity, or nasopharynx {Viehweg 2006 511, McGarry 1993 298}. Approximately 60% of the population worldwide will experience epistaxis, and 6–10% of those affected will need medical care {Beck 2018 12; Tunkel 2020 8}. However, the true prevalence of epistaxis is challenging to measure because most people with a nosebleed experience a minor bleeding episode and opt for conservative self-treatment (first aid) at home {Kucik 2005 305; Tunkel 2020 10} and are therefore not reported {Gifford 2008 525}.

In the first aid environment, direct pressure (compression) for patients with active nasal bleeding is recommended as first-line care by applying pressure to the lower third of the nose (Kiesselbach's area) {NHS Scotland 2020; NICE UK 2019; Tunkel 2020 11}. The use of a compressive force is consistent with the 2000 American Heart Association first aid guideline, which recommends pinching the "nasal alae with the thumb and index finger (Class IIb)" to control bleeding {Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care 2000}.

Compression over the nasal ala can be accomplished with manual or mechanical (ie., clip) pressure {Hajimaghsoudi 2018 150; Tunkel 2020 18}. Expert opinion suggests direct pressure should be applied continuously for 5-10 minutes {Bishow 2003 57; Honeysett 1982 578; McLarnon 2015 587; Svider 2018}, 15-20 minutes {Stoner 2013 795; Vaghela 2005 261}, and up to 30 minutes {Bernius 2006 195; Shellenbarger 2999 50} to provide tamponade of the anterior septal vessels whilst the patient tilts the head forward. Titling the head prevents blood from pooling in the posterior pharynx, thereby avoiding nausea and airway obstruction {Pope 2005 310; Wong 2018 E16}.

Cryotherapy (ice cubes, ice packs, ice collars) is routinely recommended in the gray literature in conjunction with other therapies (i.e., compression) as a means of conservative care {Bishow 2003 52; Honeysett 1982 578; Khan 2017 1035; Ludman 1981 968: McLarnon 2015 587; NHS Scotland 2020; Pope 2005 309; Upile 2008 1349}. However, the usefulness of cryotherapy (ice bags, ice cubes, commercial ice, frozen vegetable packs), applied alone or in conjunction with compression to control active bleeding for anterior epistaxis, is unclear.

Investigators from the 1930s proposed that cooling localized areas of skin, including the hands, feet, or back resulted in shrinkage of nasal mucosa {Drettner 1961 1}, likely due to vasoconstriction. This may, in turn, decrease mucosal blood flow and aid in hemostasis during a nosebleed. However, systematic reviews and clinical guidelines typically focus on first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery in clinical and emergency department settings {Bequignon 2017 185; Khan 2017 1035; NHS Scotland 2020; NICE UK 2020; Tunkel 2020 8}, not in the first aid environment.

The 2000 Emergency Cardiac Care (ECC) guidelines for first aid direct first aid providers to manage acute epistaxis with compression to the nasal alae; however, cryotherapy is not mentioned as a first aid care strategy {Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care 2000}.

The 2005 and 2010 National First Aid Science Advisory Board Consensus on Science {American Heart Association 2005 III-115; Markenson 2010 S582} and the 2015 and 2020 International Liaison Committee on Resuscitation (ILCOR) Consensus on First Aid Science with Treatment Recommendations (CoSTR) {Singletary 2015 S269; Singletary 2020 S284; Zideman 2015 e229} did not review the topic of epistaxis management in First Aid.

Therefore, this topic was prioritized for a scoping review by the First Aid Task Force to review the scientific evidence behind the recommendation for the use of cryotherapy for epistaxis.

2. Narrative summary of evidence identified

Our comprehensive search strategy yielded many scientific publications and informational records in the gray literature; however, after subsequent review, none of these records directly addressed our PICOST. Therefore, there were insufficient studies identified to support a more specific systematic review. As a scoping review, we sought to include indirect evidence and gray literature to identify knowledge gaps and scope the body of literature relative to acute epistaxis management in the first aid setting.

Indirect Application of Cryotherapy to the Nasal Area

Six indirect experimental studies (Turkey, United Kingdom, Germany, Denmark) were identified from the published literature search, which examined the effects of cryotherapy on nasal mucosal blood flow {Porter 1991a 1122, Teymoortash 2003 545}, nasal submucosal temperature {Porter 1991b 11}, nasal blood volume {Scheibe 2006 395}, nose and nasal congestion and nasal cavity volume {Ozturk 2014 1067}, nasal airflow and patency {Teymoortash 2003 545}, and nasal airway volume {Yamagiwa 1990 1050}. Table 2 provides an overview of study characteristics and data findings, all in healthy subjects.

Two randomized (ie., intervention counterbalanced) cross-over studies enrolling 29 adults evaluated the effect of ice applied to forehead, mouth, or a combination of both on nasal mucosal blood flow using a laser Doppler flowmeter (measured in flux) (Porter 1991a 1122) and measured nasal submucosal temperature (°C) using a thermocouple inserted into the submucosa of the inferior turbinate (Porter 1191b 11).

The first study {Porter 1991a 1122} (n=16 adults) assessed nasal mucosal blood flow following the application of ice within a surgical glove applied to the forehead for 3 minutes compared with application of ice contained within a surgical glove placed into the mouth for 3 minutes. The application of ice packs within the mouth was reported to produce a significant decrease in nasal mucosal blood flow (p<0.05, average fall was 23% [standard error 5.9]) compared with the control (average decrease=5%; standard error not calculated). Oral ice packs produced a decrease in flux (velocity and concentration of the moving blood cells) in 9 out of 16 (56%) subjects, one (6%) experienced an increase in flux, and in 6 (37%), there was no change.

The second study {Porter 1991b 11} (n=13 adults) assessed nasal submucosal temperature at the inferior turbinate following 15-minute periods of cryotherapy using ice packs (ice packs alone) wrapped in a paper towel applied to the forehead, ice cubes (ice cubes alone) “sucked” in mouth, and a combination of both therapies (ice pack + ice cubes). A significant difference in nasal submucosal temperature was reported between the ‘ice pack alone’ and the ‘ice cubes alone’ groups (p=0.026), favoring a lower nasal submucosal temperature in the ‘ice cubes alone’ group (mean and standard deviation not provided). There was a significant submucosal temperature difference between the ‘ice pack alone’ group and the combination group (p=0.006), favoring a lower nasal submucosal temperature in the combination group (mean and standard deviation not provided). 100% of subjects in the ‘ice cube alone’ group produced a fall in submucosal temperature compared to 54% (7/13) in the ‘ice pack alone’ group. A decrease in submucosal temperature was demonstrated in 100% (13/13) of participants in the ice cubes alone group compared with 7/13 (54%) participants in the ice pack alone group.

Teymoortash et al. {Teymoortash 2003 546} performed an observational before and after study with 56 healthy adults comparing no use of ice packs (before) with ice packs (no specific descriptive provided) applied for 5 minutes all around the neck (after). Outcomes included nasal mucosal microcirculatory blood flow in Kiesselbach’s area measured via laser Doppler flowmeter and nasal mucosal blood content estimates using a computer-aided anterior rhinomanometry made by alterations in nasal airflow and airway patency. The fall in nasal mucosal microcirculatory blood flow before (1368.8±927.9 arbitrary unit) and after (1130.5±792.2) ice application was not statistically significant (p=0.11; MD -238.3 95% CI -559.6, 83.0). The fall in total nasal inspiratory airflow before (474.2±211.7 cm3/s) and after (443.1±162.4 cm3/s) ice application was also not statistically significant (p=0.30, MD -31.1 95% CI -101.7, 39.5).

Scheibe et al.’s {Scheibe 2006 395} cross-over before and after study with 15 healthy adult participants compared no use of ice collar (4°C) (pre) with ice collar applied to the neck (post) for 10 minutes on nasal blood volume for the whole nose and septum (Kiesselbach’s area) using optical rhinometry. The authors report no significant effect in whole nose blood volume using ice collars to the neck. There was a significant (p<0.01) decrease in blood volume reported for regional measurements at the septum. However, data were only reported graphically; therefore we are unable to extract exact values. The reduction in nasal blood volume at the nasal septum was, on average, observed after approximately 120 seconds (111±73) and reached its maximum after about 360 seconds (337±119) {Scheibe 2006 395}.

Ozturk et al.’s {Ozturk 2014 1067} observational study enrolling 15 healthy adults compared no application of a cold compress (before) with the application of a cold compress to the left (L) and right (R) nasal dorsal skin for five minutes and 10 minutes on the outcomes of the nose and nasal congestion (cross-sectional area, cm2) and nasal cavity volume (cm3) using acoustic rhinometry. No statistical difference was reported in mean values for the sum of left and right (L+R) first minimal cross-sectional area (cm2) and second minimal cross-sectional area measurements (cm2) at any time point (0 versus five minutes, five minutes versus 10 minutes, 0 versus 10 minutes). The mean values for the sum of nasal cavity volume (cm3) revealed no statistical differences, for any parameter, between 0 minutes versus five minutes (7.53 vs. 7.26, MD: 0.27); 0 minutes versus 10 minutes (7.53 vs. 6.88, MD: 0.65); or five minutes versus 10 minutes measurements (7.26 vs. 6.88, MD: 0.38).

An observational study by Yamagiwa et al. {Yamagiwa 1990 1050} enrolling ten healthy adults compared five minutes of cooling of both feet using ice-water immersion at 0-4°C with the cooling of one hand and forearm (23 cm from middle fingertip) for the same duration, on the outcome of nasal cavity mean volume (mL), as measured by acoustic rhinometry. Nasal cavity volume was measured before cooling, during cooling, and up to 40-60 minutes after five cooling minutes. During the cooling phase, the foot-cooling group's nasal airway volume was significantly higher than before cooling in four of 10 (40%) subjects. In the hand-cooling arm (nine subjects), the nasal cavity volume increased significantly during cooling in only one of nine (11%) subjects. It was noted that comparing the average nasal cavity volume during each of the three periods did not provide an estimate of a rapid change in nasal volume during cooling. When volume changes were analyzed over time, most subjects were noted to have an increase in nasal volume just after the start of cooling, but the volume decreased before the end of the cooling period.

Additional Embase Full-Text Record Review

Seven additional full-text papers; five narratives {Bird 1999 10; Honeysett 1982 578; Ludman 1981 967; McLarnon 2015 587, Shellenbarger 2000 50}, one editorial {Nicolas 2013 702}, and one technique {Vaghela, 2005 261} were reviewed as they specifically addressed cryotherapy for acute epistaxis in the first aid setting (Table 3). All papers recommend direction pressure to the nostril between the thumb and index finger between 5-30 minutes. Six papers recommend applying cryotherapy to the face or nose (ice packs) or mouth (sucking) narratives {Honeysett 1982 578; Ludman 1981 967; McLarnon 2015 587, Nicolas 2013 702; Shellenbarger 2000 50; Vaghela, 2005 261}; however, no evidence for these recommendations was provided. Bird (1999) suggests that ice application to the nose does little to reduce blood flow; however, the authors referenced this to a textbook.

Data Tables

Table 3. Additional Embase full text paper characteristics and findings.

Author, year, country

Study design, setting/audience

Intervention Concepts

Cryotherapy

Statements

Direct Pressure Application Time

Bird, 1999, United Kingdom

{Bird 1999 10}

Narrative:

A&E department

Direct pressure

Cryotherapy

“Local vasoconstriction induced by the application of ice to the nose, neck or mouth appears to do little in reducing blood flow…” p.11

NA

Honeysett,1982, United States

{Honeysett 1982 578}

Narrative:

Nursing

Direct pressure

Patient position

& reassurance

Cryotherapy

“…application of ice packs or cubes is useful as they can be soothing as well as causing local vasoconstriction with encourages the bleeding to stop.” p.578

5 min

Ludman, 1981, United Kingdom

{Ludman 1981 967}

Narrative:

Clinical practice

Direct pressure

Cryotherapy

“…pinching the nostril between a finger and thumb and applying ice packs to the bridge of the nose.” p.968

N/A

McLarnon, 2015, United Kingdom

{McLarnon 2015 587}

Narrative:

Clinical practice

Direct pressure

Patient position

Cryotherapy

“…alongside cooling with an ice pack on the nose or sucking an ice lolly if available.” p.589

5-10 min

Persistent, 20 min

Nicolas, 2013, United Kingdom

{Nicolas 2013 702}

Editorial:

Clinical practice

Direct pressure

Patient position

Cryotherapy

“…cold compress to the nose, is often used in addition to, sucking ice cubes, which is thought to help vasoconstrict the blood vessels within the nasal mucosa; however, there is little clinical evidence to support this as a treatment option.” p.704

10 min

Shellenbarger, 2000, United States

{Shellenbarger 2000 50}

Narrative:

Nursing

Direct pressure

Patient position

Cryotherapy

“…ice compresses over the middle face to promote vasoconstriction.” p.50

5-30 min

Vaghela, 2005, United Kingdom

{Vaghela, 2005 261}

Technique:

A&E department

Direct pressure

Patient position

Cryotherapy

“…ice pack applied to the nasal bridge.” p.261

20 min

Focused (Pubmed) and Gray Literature Search

Several focused and gray literature records were reviewed including two professional clinical guidelines {Tunkel 2020 8; Bequignon 2017 185}, three endorsement statements {American College of Emergency Physicians 2019; American Academy of Pediatrics 2020; Society of Interventional Radiology ND}, one systematic review {Khan 2017 1035}, two narrative reviews {Pope 2005 309, Wong 2018 E13}, one practice guideline {Record 2015 484}, one review {Beck 2018 12}, one protocol {Upile 2008 1349}, and one website {O’Sullivan 2020}.

The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) recently recommended the use of nasal compression with "firm sustained compression to the lower third of the nose with or without the assistance of the patient or caregiver, for 5 minutes or longer" {Tunkel 2020 16}. The AA0-HNS does not advocate for or address the utilization of cryotherapy as a first-line treatment. This statement is further endorsed by the American Academy of Pediatrics {American College of Emergency Physicians 2019}, the American Academy of Pediatrics {American Academy of Pediatrics 2020}, and the Society of Interventional Radiology {Society of Interventional Radiology ND}. Furthermore, the Goggle.com gray literature search (i.e., "practice guideline" AND Epistaxis) identified 26/50 (52%) websites referencing back to the AAO-HNS clinical practice guideline for the management of epistaxis without recommending cryotherapy.

In 2017, The French Society of Otorhinolaryngology (SFORL) published guidelines for the first-line treatment of epistaxis in adults {Bequignon 2017 185}. Similar to the AAO-HNS recommendations, the SFORL guidelines for epistaxis first aid include nasal cavity cleaning, head raised slightly forward, and anterior bi-digital compression for 10 minutes, based on expert opinion. The SFORL guidelines also do not advocate for or address the utilization of cryotherapy as a first-line treatment.

Khan et al.'s {Khan 2017 1035} systemic review of initial assessment in the management of adults with epistaxis included two randomized controlled trials on the effects of topical ice pack previously addressed in this scoping review {Porter 1991a 1122; Teymoortash 2003 545}. Khan et al. concluded the application of an intra-oral ice pack is a simple first-aid measure with the potential to decrease bleeding severity and should be considered from the onset of epistaxis to the point of hospital care while evidence supporting the efficacy of other topical ice packs is insufficient.

Six gray literature documents examined the use of cryotherapy as first-line treatment in acute epistaxis; specifically, application of cryotherapy to the face or nose {Pope 2005 309; Upile 2008 1349}, sucking on ice {Pope 2005 209; Wong 2018 E13}, application around {Pope 2005 209} and to the back of the neck {Beck 2018 12}, or forehead {Record 2015 484; O'Sullivan 2020} (Table 4). No evidence for these recommendations was provided in three records {Pope 2005 209; O'Sullivan 2020; Upile 2008 1349}. A narrative review by Wong and Anat (2008) suggested ice packs around the neck and intra-oral significantly reduced nasal mucosa blood flow and could slow down nasal bleeding. However, they referenced Porter et al. (1991a 1122), who measured blood flow in healthy adults. Two reviews by Record (2015 484) and Beck et al. (2018 12) suggested the use of cryotherapy is inconclusive and controversial, citing work by Scheibe et al. (2006 394) and Teymoortash et al. (2003 545).

Table 4. Gray literatrue study characteristics and findings.

Author, year, country

Study design, setting/audience

Intervention Concepts

Cryotherapy

Statements

Direct Pressure Application Time

Pope, 2005, UK

{Pope 2005 309}

Narrative:

Clinical practice

Direct pressure

Patient position

Cryotherapy

“...improved by a cold compress or the patient sucking on ice.” p.310

NA

Wong, 2018, Australia

{Wong 2018 E13}

Narrative:

Family practice

Direct pressure

Patient position

Cryotherapy

“Applying ice packs around the neck and having the patient suck

on ice significantly reduces nasal mucosa blood flow and can slow down the bleeding.7” p.E16

10 min

Record, 2015, United States

{Record 2015 484}

Practice guideline: Nursing

Direct pressure

Patient position

Cryotherapy

“Ice compresses to the forehead or neck may be used, but studies are inconclusive as to the usefulness of this maneuver (Teymoortash 2003; Scheibe, 2006).” p.487

10 min

Upile, 2008, United Kingdom

{Upile 2008 1349}

Protocol:

United Kingdom Healthcare System, first aid

Direct pressure

Cryotherapy

“…pinching the whole of the cartilaginous tip of the nose for 30 min followed by another 30 min of pressure and pack of ice on bridge of nose if bleeding continued.”

30 min + 30 min

O’Sullivan, 2020, Ireland

{O’Sullivan 2020}

Informational:

Website

Direct pressure

Cryotherapy

“…putting an ice pack on to their forehead.”

20 min

Beck, 2018, German

[Beck 2018 12}

Review:

primary and secondary care

Direct pressure

Patient position

Cryotherapy

“Local application of ice, e.g., at the back of the neck, is intended to encourage vasoconstriction of the blood vessels of the nose.” Its therapeutic value is a matter of debate and has been challenged in the literature (38).”

15-20

ILCOR Sub-Council Resuscitation Guideline Review

A review of the eight-member councils (and sub-councils) of the International Liaison Committee on Resuscitation websites for guideline statement documentation (n = 29) found two sub-council guideline statements specifically addressing epistaxis. The 2000 American Heart Association first aid guideline-recommended pinching the "nasal alae with the thumb and index finger" to control bleeding; however, cryotherapy as an intervention is not addressed (Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care 2000). The Australian and New Zealand Resuscitation Council (ANZCOR) Guideline 9.1.1 states, "pressure must be applied equally to both sides of the nose, over the soft part below the bony bridge (usually between the thumb and index finger)" (ANZCOR 2017). And similar to the 2000 American Heart Association guideline, no reference to cryotherapy is addressed. Eleven guideline statement documents did not address epistaxis, three were inaccessible, seven offered no identifiable statement, and four could not be translated and offered no English documentation.

3. Narrative Reporting of the Task Force Discussions

This scoping review demonstrates that most manuscripts in the in the full-text and gray literature focused on the management of acute epistaxis in the first aid setting are based on expert opinion or indirect evidence. Accordingly, expert opinion believes that cryotherapy can vasoconstrict the nasal mucosa's blood vessels and reduce the flowing blood and blood volume when applied to the nose. The recommendation for the use of cryotherapy for acute epistaxis is based on extrapolated data from studies examining nasal blood flow and nasal blood volume. These studies were indirect as they were conducted in healthy subjects (pooled sample n=44, 20-40 years, mean age 31 [mean age reported in on 2 of 3 studies) who lacked current epistaxis {Porter 1991a 1122, Porter 1991b 11, Scheibe 2006 395}. These small studies only addressed a narrow spectrum of the population and did not address cryotherapy's effects on nasal blood flow and volume in children or in the elderly.

We identified the cryotherapy application methods were inconsistent and never applied directly to the nose, but instead to the forehead, in the mouth, around the neck, or in a combination.

We identified that the cryotherapy application times also varied between the three studies (3-minutes, 10-minutes, 15-minutes) {Porter 1991a 1122, Porter 1991b 11, Scheibe 2006 395}.

We acknowledged the literature lacks the evidence to support some recommendations for using cryotherapy as an intervention for acute epistaxis in the first aid setting found in the gray literature.

We acknowledged the literature identified was insufficient to support a systematic review examining cryotherapy applied to the nose as an intervention for acute epistaxis in the first aid setting.

Knowledge Gaps

There were no studies identified evaluating cryotherapy (either alone or in conjunction with nose pinching) in the management of acute epistasis by a first aid provider for both adults and children in the first aid setting.

The apparent lack of studies highlights significant gaps in the research on this topic.

We identified many gaps in the published literature, highlighting a significant research gap in the first aid context. These gaps included:

  1. The lack of clinical trials examining the effectiveness of cryotherapy (alone or in conjunction with nose pinching) in patients with acute epistaxis.
  2. The lack of clinical trials investigating the effectiveness of cryotherapy (alone or in conjunction with nose pinching) in the first aid setting.
  3. The lack of clinical trials examining the effectiveness of cryotherapy (alone or in conjunction with nose pinching) by first aid providers.

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