Through the nose: intranasal diamorphine (IND) analgesia

Through the nose: intranasal diamorphine (IND) analgesia

Through the nose: intranasal diamorphine analgesia

Patricia Richardson, Lucy Evans and Sarah Smailes outline a protocol for using intranasal diamorphine analgesia in patients undergoing rehabilitative physiotherapy after burn injuries

Following burn injury, physiotherapy entailing active and passive exercises is integral to maximising functional recovery. The challenge is to provide adequate analgesia with minimal side-effects or need for starvation to allow physiotherapy to be completed.

Intranasal diamorphine (IND) is established as a rapid-onset, effective and well-tolerated analgesic in accident & emergency units. We evaluated the use of IND in burn patients undergoing physiotherapy.

Thirty patients aged between 5 and 80 years, admitted to our burns ICU, with burns sized between 3 and 85%, were studied during their first experience of IND for their prescribed physiotherapy session.

Using the 0–3 pain score, patients were scored before and after physiotherapy with regard to pain during physiotherapy. Physiotherapy was completed in 28 out of 30 patients, although three patients required top-up analgesia; 25 out of 30 patients and their therapist agreed that the IND alone provided an adequate analgesic effect. No correlation was found between the ability to complete the session and burn size or age. All patients denied experiencing nausea.

We believe that IND has a role to play in the provision of analgesia to patients of all ages undergoing burns rehabilitation physiotherapy.

Physiotherapy is fundamental to maximising physical function recovery of patients following burn injury. Burn areas over joints, such as hands and feet, need particular attention to prevent contracture formation – and the physiotherapist will prescribe active exercise, and perform passive stretches and mobilisation on a daily basis over a prolonged period of time. With their rich afferent nerve supply, hand and feet wounds can be especially painful. One of the challenges for the burn clinician is achieving adequate control of the procedural pain induced to allow satisfactory completion of the therapy, but without the requirement for a period of starvation at a time when calorie requirements – to enable wound healing – remain high.

Early active exercise, in addition to a passive range of motion exercises, is beneficial for ICU patients [1,2], and this should start as soon as patients are physiologically stable. The background and procedural pain from unhealed burn and donor site areas must be specifically addressed to avoid the patient fearing or avoiding movement and activities, necessary to maximise their functional recovery. Otherwise, they may lose faith in the therapist or healthcare professional seen as inflicting it [3], and this is difficult for both the patient and physiotherapist alike. Ideally, the analgesic should provide an effective but timely, predictable onset, yet have a low side-effect profile to avoidance interference with the procedure.

Diamorphine is an effective analgesic agent. Intranasal diamorphine (IND) is absorbed into the rich vascular bed of the nasal mucosa and rapidly hydrolysed to its active metabolites 6-acetylmorphine and the more potent morphine. Peak levels of morphine are dose-dependent in timing, but described as occurring within 10 minutes in small pharmacokinetic studies of adults [4] and children [5], with a half-life of 90–180 minutes. IND has established a place for itself as a safe, well-tolerated, effective, rapid-onset analgesic. This is particularly so in the paediatric population, where its use has been well described in the emergency setting for analgesia following fractures and burns [6,7]; however, there is little published regarding the use of IND in the adult population. Reports do exist of IND use for control of acute pain in the emergency department [8], and in the management of acute post-operative pain [9,10]. A consensus document for pre-hospital burn care advocates intravenous opiates for adult pain relief, but consideration of IND as an analgesic option for children [11]. We have been unable to find a reason precluding its use in the adult population.

Physical rehabilitation after a burn injury continues over a prolonged period of time and can be very painful. To our knowledge, there are no previous reports of IND administration as a way of controlling and minimising the pain experienced during physiotherapy for patients who are undergoing burns rehabilitation. The pharmacokinetic and pharmacodynamic profile [4,5,12], and the benefits of needle-free and intravenous drip-free administration (establishment of intravenous access being notoriously difficult in the long-term burn patient), with no requirement for a period of starvation beforehand, make IND particularly useful in burns patients required to be ambulant for potentially painful physiotherapy treatment.

Believing that IND has much to offer patients requiring procedural analgesia post burn injury, we devised a protocol for use in our burns centre for all age groups. We have found it has been most effective in patients undergoing rehabilitative physiotherapy and we describe our experience of its use in our burn population.

 

Methods

Our hospital guideline committee ratified the protocol we devised for IND administration to all age groups. Contraindications to its use includes patient weight of <10kg or age of less than one year, recent head injury or a known hypersensitivity to opiates. Relative contraindications are nasal pathology, which may hinder adequate absorption, and a history of drug addiction – as patients may be unsuitable for the euphoric high potentially produced by diamorphine. Concomitant, long-acting, regular analgesics are needed by the majority of patients with major burns and are not considered a contraindication, rather the norm. Due to the unpredictable onset of opiates between individuals, we have not found it helpful to define a minimum time limit between last opiate dosing and IND usage, but the timing and effect on the patient should be noted by the nurse prior to IND administration.

The accepted dose of IND in children is 0.1mg/kg diluted into 0.2ml 0.9% saline. We have extrapolated this to give a similar dose in adults, using 7.5mg in those weighing under 65kg and 10mg in those weighing more. A standard chart, shown in Table 1, guides the nurse preparing the drug on the volume of 0.9% saline required to be added to a 5mg vial of diamorphine, such that the patient receives the prescribed dose in 0.2ml of the resultant solution. All doses are administered with a mucosal atomiser device to ensure even coverage of (and hence optimal absorption from) the nasal mucosa. It is our usual routine to administer the IND 3–5 minutes before starting the physiotherapy session, but pause if pain indicates that the maximal effect has not been achieved. Top-up doses, at half the original dose, can be given, if the therapist and patient feel further analgesia is necessary, 15 minutes after the initial dose. Entonox may be used in addition to IND to supplement analgesia further.

 

We examined the outcomes of the first experience of IND use in burn patients receiving physiotherapy in the intensive care and high dependency unit (HDU) of our burns centre. We examined only the first experience of IND use in this smaller group, both for ease of data collection and to capture a more consistent experience in a range of patients rather than a diverse group, where some may have repeated exposure to the drug; however, IND is used in all areas of our burns centre, and often multiple times. Consecutive patients were included when they were self-ventilating, orientated and able to communicate regarding the levels of pain experienced. Physiotherapy procedures undertaken varied between patients but included active and passive limb exercises, and a range of motion exercises and stretches, ambulatory therapy and tilt table mobilisation.

JAP_9.1_IND_72dpi_table1_screenshot

We collected data on age and sex, percentage of burn and site, procedure undertaken, IND dose and the time it was administered prior to starting physiotherapy. Pain was assessed prior to IND administration and commencement of therapy, and during therapy using a 0–3 pain score. This equates to 0 = no pain; 1 = mild pain; 2 = moderate pain; and 3 = severe pain. At the end of the procedure, it was noted if the therapy session was completed and whether supplemental analgesia was required, and the patient was asked specifically about nausea symptoms. Both the therapist and patient judged whether the analgesia provided by IND was adequate for the therapy session.

JAP_9.1_IND_72dpi_table2_screenshot

 

Results

We evaluated the use of IND in 30 burns ICU/HDU patients. Table 2 shows the basic demographic data for the patients studied, and details of IND dose and timing in relation to starting physiotherapy. Five patients included were children, aged 5, 7, 9, 11 and 14 years. Three patients were aged over 80 years.

Figure 1 represents the 0–3 pain scores reported by the patient, to the therapist at rest, prior to and during therapy. Although pain scores reported changed, using the Chi-square test, there is no significant increase in those reporting moderate or severe pain during therapy from at rest (p = 0.58).

The physiotherapists and patients agreed in all cases as to whether the IND provided adequate analgesia or not for the prescribed therapy session to be completed. Table 3 outlines the therapeutic procedures undertaken.

Twenty-five out of 30 patients and their therapist felt that the IND they received was adequate for the therapy session. One of these 25 patients had received oral opiates for breakthrough pain shortly before their session; therefore, 24 out of the 25 sessions were completed with IND at a dose set by the protocol alone. Of the remaining five patients, where IND analgesia was felt inadequate, three completed the physiotherapy session with supplemental analgesia – namely entonox in two cases and an extra IND (at half the original dose) in one case. The remaining two patients who felt analgesia was inadequate abandoned their sessions. Of these, one patient, undergoing a change of dressing and hand stretches, had tried to complete the session following an IND top-up. The second patient refused further analgesia and requested termination of the session.

JAP_9.1_IND_72dpi_figure1_screenshot

Using the Mann Whitney Rank Sum test, no correlation was found between the ability to complete the procedure (with or without top-up analgesia) and age (p = 0.7) or burn size (0.61). Although not achieving statistical significance (p = 0.068), the two patients unable to complete their therapy sessions were noted to have longer sessions (mean 25 mins) than those 28 who completed therapy (mean 15.3 mins).

No patient described nausea at any time.

 

Discussion

Prior to the introduction of IND use in our unit, procedural pain has been addressed using either deeply sedating techniques, such as general anaesthesia, ketamine and midazolam combinations, or intravenous remifentanil. A period of starvation is recommended; the hypnotic effect induced hinders the active participation of the patient; and the presence of an anaesthetist is required. Alternative analgesic agents have includes oral opiates, which are notoriously unpredictable in onset and offset. Entonox is a useful agent but some patients are limited by nausea.

Our findings suggest that IND is a well-tolerated form of analgesia for physiotherapy interventions in burns patients in the intensive care unit. Our cohort included five children aged 5–14 years as well as three patients aged >80 years, suggesting that IND use can play a role in all age groups. During the procedure, 19 out of 30 patients reported no or only mild pain. Three patients reported an improvement in pain scores during physiotherapy, demonstrating the analgesic benefit from IND.

JAP_9.1_IND_72dpi_table3_screenshot

Twenty-five out of 30 (83%) patients were afforded adequate analgesia by a single dose of IND suggested by our protocol. Twenty-eight out of 30 (93%) completed therapy with either a single dose or following standard top-up analgesia. We use a standardised protocol for the administration of IND based on weight as described in Table 1. Any patient over 65kg will be administered 10mg. For the majority of patients this seems sufficient; however, this is not a strict 0.1mg/kg dosing as would be used in children (particularly smaller children), so it may be that patients who weigh in excess of 100kg may not be receiving sufficient analgesia to prevent pain during physiotherapy with an initial dose of 10mg. We did not collect data on patients’ weight and so cannot explore this theorem further.

Burn injuries are known to induce patho-physiological changes that can interfere with the pharmacokinetics and pharmacodynamics of a drug, with wide inter-individual variation [14]. Therefore individual responses to IND doses may also not be predictable. It is important to note that at this time there is no pharmacokinetic information specifically related to the intranasal administration of diamorphine in the patient with a burn injury. Studies have examined the pharmacokinetics of morphine administered orally, as an intravenous bolus and as an intravenous infusion in burns [15–17]. However, these studies are based on small numbers of adult patients and the possibility of altered pharmacokinetics may mean pharmacokinetic data related to morphine cannot be extrapolated to diamorphine. This emphasises the importance of monitoring pain scores during physiotherapy sessions so that the optimal IND dose for physiotherapy can be titrated for subsequent sessions.

There was a wide variation in the size of the burn area (3–85%) among the 30 patients in this cohort. We found no evidence that burn size or patient age predicted the efficacy of IND. This is in keeping with our experience that the magnitude of pain felt by burn victims does not relate to the burn size, as many physical and psychological factors come into play [3]. We did note that patients who were unable to complete sessions were undertaking longer sessions. This information will be useful in the future in guiding us how and when to select the option of IND.

In this cohort, patients underwent different physiotherapy techniques. These included walking and active exercises for all limbs, and hand exercises and stretches. Due to the small size of this cohort, it is not possible to identify a relationship between the type of physiotherapy performed and whether IND is sufficient, however, our results are very promising. Investigating larger numbers of patients undergoing more and different types of physiotherapy techniques would be useful in the future.

Side-effects appear to be minimal from IND in this setting. Nausea and vomiting were not a problem in this cohort of patients; of the 30 patients studied, none reported nausea or vomiting as a side-effect after IND administration.

In conclusion, despite the small group studied, our findings suggest that most burn intensive care and high-dependency patients completed physiotherapy sessions and found IND analgesia alone adequate. IND in this setting is suitable for all age groups, with minimal side-effects, making it attractive as an analgesic choice for burns physiotherapy.

 

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Authors

Patricia Richardson and Lucy Evans are consultant anaesthetists.

Sarah Smailes is a consultant physiotherapist.

 

Acknowledgements

The authors have all actively contributed the work and none of them has any conflict of interest or source of funding to declare in relation to the study or the contents of the manuscript.

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