Drug administration within the pre-hospital setting is currently seen via various routes. Oral, per rectal, intramuscular (IM) and intravenous (IV) are widely accepted for various drug delivery systems. Intranasal (IN) administration is something relatively new and currently relies on evidence–based practice to strengthen its use in the pre-hospital setting. The paramedic profession is progressing and using evidence–besed practice as a reliable and proven scientific route, studied by experts who evaluate evidence critically (College of Paramedics (CoP) 2008).
This article will explore the background of intranasal drug administration within the prehospital setting.There will be discussion around the pathophysiology of intranasal therapy, the different patient groups that would benefit and an awareness of the different types of drugs that could be used from intranasal drug delivery system. Strengths and limitations of intranasal will be reviewed through evaluating research and evidence based practice, while also incorporating arguments for comparison modes of administration, such as IM therapy. An insight regarding ethical issues and the paramedic's accountability will then be discussed before a formative conclusion is reached.
Background of intranasal
Intranasal drug therapy is a well-established route of treatment, accepted on a global level within hospitals and doctors surgeries (Jain, 2008) and is currently being used throughout the US with various ambulance service providers (Kevin et al. 2011). However, its value within the pre-hospital setting in the UK is only now being recognised.
The Joint Royal Colleges Ambulance Liaison Committee (JRCALC) (2006) currently does not express an indication for intranasal therapy in its guidelines, even though the ambulance trusts within the UK have Patient Group Directive medicines and healthcare products regulatory agency set up to allow this method (PGD MHRA) (2012) to allow this method. This is due to the fact the latest guidelines, written in 2006, are somewhat out of date and therefore advances made in the pre-hospital setting since are not addressed. This situation will be discussed in more detail during the ethical evaluation process below.
The term ‘intranasal drug therapy’ refers simply to a drug administered to the patient through their nasal cavity, allowing the drug to enter the body's system with the aim of it interacting with the desired receptors. This method can be used for both local delivery, in such cases of topical disorders, as well as on a more systemic scale insert such as reversing a drug overdose in patients by raising their respiratory rate and GCS.
It is the latter which has seen the greatest pioneering development over the past decades. There are studies that suggest its usage for vaccinations on a national or international scale as in Africa, where blood bourne diseases are of high risk to health care professionals through reading needle stick injuries (Kiderman et al. 2001).
Pathophysiology
The main functions of the nasal cavity are olfaction and to aid breathing (Dekker, 2002), however, its other functions are essential in a protecting capacity by warming, humidifying, and filtering the air before it passes through to the lower airways. This process is achieved by the small mucous membranes and hairs of cilia that line the cavity (Tortora and Derrickson, 2011), therefore the challenge in creating a drug that can successfully pass these functions through the blood brain barrier can prove both difficult and complex. Vyas et al (2005) indicate that a second– line defence mechanism is activated when a drug diffuses across the blood brain barrier, hindering optimal effect of intranasal delivery. This counter mechanism is duly owed to the P-glycoprotein (P-gp) efflux pumps. Mittal et al (2006) denote that the porous endothelial membrane in the nasal cavity does allow small particles of drug medication to transfer across the blood brain barrier, other studies however suggest that by using the intranasal route, the barrier can be bypassed completely via alternative routes such as the olfactory and trigeminal nerve pathway (Thorne et al, 2005).
Ali et al (2010) also explain this evidence by suggesting that the drugs can be a colloid, allowing the medication to be transported directly to the olfactory synaptic junction with protection, ensuring a viable transportation to the olfactory bulb. The work of Ali et al (2010) could be seen as potentially bias as the study was conducted by pharmaceutical industry; however, it does conform to previous studies and results produced by Thorne et al (2005) and Westin et al (2005) also support this theory. This could in the future help with Cerebrovascular accident (CVA) patients as it suggests that the glucose imbalance during a stroke can be reversed and assist the patients recovery by using the intranasal route to treat this symptom.
Certain limitations and influential factors surrounding its efficiency are still under investigation. Nasal mucosa damage could impact the absorption rate of medication as suggested by Huizing and De Groot (2003). The drug's molecular weight, its lipophilicity and other physicochemical properties hold a significant relevance in the rate of absorption (Arora et al. 2002). Dae-Duk Ki (2007) states that drugs will pass through the nasal mucosa via two different paths. One of these routes is through passive diffusion (involving predominantly lipophilic drugs) and the other is transcellularly transported by a means of endocytosis. The tight junctions open and close accordingly after activation, however, the space between junctions is limited and therefore larger molecular drugs are unable to pass through. For this reason, the type of drugs which can be administered via the intranasal route is currently quite limited, however, research studies are still developing and this scope is expected to increase.
Blood flow is a vital key in delivering the drug to the receptor site and the nasal cavity, enriched with good blood supply and many blood vessels, aids this therapeutic process on a systematic level, though the absorption efficiency is dependent upon the blood flow itself. A study, lead by Kao et al (2000) showed that vasoconstriction will hinder the rate of drug absorption across the membrane, meaning that hormones such as dopamine would take longer to diffuse across into the bloodstream due to its vasoconstricting properties. There are other influential factors relating to the absorption rate of intranasal drugs. The area in which the drug is administered is crucial as it changes the regional site, differing dosages and altering efficiency that depends on the individual who is administering it. The anterior aspect of the nasal cavity will show a faster absorption rate and conversely, the posterior aspect promotes a slower process due to the mucocilary clearance system. In short, this system is made up of cilia and mucus production cells. These cilia and cells are designed to filter and protect the airway. More mucosa is produced towards the posterior region of the nasal cavity so absorption is slowed. When administered correctly this body function can aid in successful treatment, for instance, if a small rapid dose was needed to be absorbed then the best place would be to administer it in the anterior part of the cavity, whereas a strong dose, using nasal drops to be absorbed at a much slower rate over a period of time would be preferable, therefore the area of preference would be to the posterior region (Illum, 2003).
Patient groups
The medications that can be distributed intranasally are associated with treatment for paediatric Alzheimer's disease, brain tumours, pain management, opiate overdoses and sleep disorders. There is also evidence for its use in other medical conditions; however, research in these areas are rather limited as it is a relatively new approach for neurological diseases (Pires et al, 2009).
Opiate overdose patients
Naloxone can be delivered through this route and evidence–based practice suggest that apart from the fact that it has a rapid absorption rate (Turker et al. 2004), intranasal administration of naloxone during the treatment of an opiate overdose also offers benefits to both the patient and the paramedic, eliminates needlestick injuries, is quick to adminster and is single patient use. It eliminates needlestick injuries, is quick to administer and is designed for single patient use.
| Intramuscular approximate cost (per unit): | Intranasal approximate cost (per unit): | ||
|---|---|---|---|
| The pharmaceutical cost of one dose | £3.00 | The pharmaceutical cost of one dose | £3.00 |
| Per needle | £0.04 | The mucosal atomisers attachment (each) | £3.78 |
| Per syringe | £0.06 | One clinical bag £0.13 10 % is a part cost of the bag | £0.01 |
| Per surgical wipe | £0.07 | Per dose UNIT | £6.79 |
| Sharps bin £2.34 10 % of a bin | £0.20 | ||
| Per dose | £4.00 | Per dose | £6.79 |
Paediatric usage
Intranasal delivery is also proving to be a useful means of drug administration when treating children. Children can often become anxious and agitated at the site of a practitioner and their anxiety can increase dramatically when the clinician is presenting a intravenous cannula (Figure 2). Gregory and Mursell (2010) suggest a structured approach towards effective communication with a critically ill patient, and especially an ill child is vital to gain an accurate history and provide prompt abd relevant treatment. The intranasal route encourages them to be less anxious and allow care to commence quickly. Yamaski et al (2001) suggest it could be used as a non-parental approach if the child needs to treat themselves. The nasal catheter offers less daunting approach and one which doesn’t involve pain (Taddio et al, 2009), as well as having the same absorption as intramusculor drug administration. Holsti et al (2007) demonstrate that the effects of drugs such as benzodiazepines have a far greater effect in convulsing children when administered intranasally (versus per rectum), they further illustrate their findings by noting that during their study, convulsing patients made a full recovery and average of eight minutes faster when given drugs intranasally as opposed to per rectum diazepam. Midazolam intranasal route saw less reoccurring seizures in this randomised control trial. Anaesthetist find the intranasal route easier to medicate children (Ghali et al. 2011). This route was proven in a randomised control trial to be a more resourceful mode of gaining access to the central nervous system, especially in children, (Stenninger and Aman, 1993).
For cases involving children, the child can be included in the decision regarding their health aslong as the gillick competency is used along with the parents wishes (Daniel et al. 2010; Scottish Government, 2010)
Paramedic responsibility
When any form of treatment is brought into place during a situation ethical issues have to be addressed. First and foremost, the paramedic must gain consent from the patient before they can proceed with assessment and treatment. Consent can be gained verbally and the patient must possess full capacity (Health Care Professions Council (HCPC), 2012). If the patient is unconscious or not in possession of full capacity, then, in accordance with the HCPC code of ethics (2008), the paramedic may act in the best interest of the patient and deliver lifesaving treatment without consent. In the case of intranasal drug therapy, the paramedic should, if possible, explain all the relevant information to the patient.
Both the benefits and potential side effects should be conveyed to the patient so that they can formulate a conclusive decision. As previously stated, the JRCALC does not have written indication for intranasal drug administration, and as paramedics within the UK work in accordance with these guidelines it could be argued that the paramedic would be held accountable for working outside of these guidelines. The important factor in this debate would be that the ambulance trust in which the paramedic works will have their own protocols that collaborate with current evidence– based practice and the trust will have formulated an opinion that the research is credible and conform to the new treatment procedure. In some cases, the trust may be bias if they are involved in trials in order to determine wheather of not the treatment method is deemed beneficial within the pre-hospital setting. In any case, the paramedic is always accountable for their actions, and they may be required to explain reasons for giving or withholding certain treatment procedure. For the paramedic to form any basis of approval they must show a high level of knowledge surrounding the subject area (Health Care Professions Council, 2007) and must also be able to equip this knowledge with sufficient reasoning and evidence based research.
Research that possesses validity and reliability will enhance the paramedics case further and will ultimately see them through any questioning process.
Paramedic safety
Notably, intrnasal administration is a safe and secure means of drug administration for all concerned. The patient is not required to have an invasive procedure, which could ultimately lead to infection ( Jain, 2008) or complications, such as the patient running off with cannulae still insitu, the paramedic's risk of needle stick injuries is withdrawn totally (Boal et al, 2008; Kerr et al. 2009; Barton et al, 2012) support this theory. Intranasal treatment for opiate overdoses is proving to be so efficient and safe that now in some parts of the US, a patient's own family member is given the medication and equipment in cases of emergency (Phillips et al, 2011) therefore stabilising the patient and proving how simple and effective the procedure can be in reducing mortality rates.
Conclusions
It can be seen that intranasal drug administration has developed due to the performance of evidence–based research studies on both animals and humans. Physiologically, it holds a complicated but efficient process and one that can be manipulated in order to deliver the correct dose over the correct period of time. Intranasal is seen to hold advantages over other competing administration methods, especially in paediatric treatment, as well as for patients who are in pain or suffering from an opiate overdose.
The intranasal method can encounter certain limitations, such as particular drugs not being able to pass through the tight junction sites, however, research is on-going and more evidence is yet to be finalised. It would be difficult to surmise if the intranasal mode of administration will be seen on a wider scale within the UK's pre-hospital setting in the near future but the method is definitely starting to take recognition. It may be that financial limitations have inhibited the use of pre-hospital intranasal therapy, however, this may soon change with the progresseion of new foundation trust services, GP funding and, most importantly, updated JRCALC guidelines that are likely to include indications for intranasal drug delivery.