Therapeutic
Intranasal Drug DeliveryFeatured new articles related to intranasal drug delivery:
January - March 2011
Wolfe, T. R. and D. A. Braude (2010). "Intranasal medication delivery for children: a brief review and update." Pediatrics 126(3): 532-537.
Abstract: With the exception of oral medications, most traditional forms of drug delivery outside the operating suite require an injection with a needle-a process that is painful and anxiety-provoking, risks needle stick injury, and consumes valuable staff time. In addition, intravenous access in pediatrics may be difficult for inexperienced providers. Intranasal medication delivery offers an alternative method of drug delivery that is often as fast in onset as intravenous medication, usually painless, inexpensive, easy to deliver, and effective in a variety of acute pediatric medical conditions. This article briefly reviews the most common uses for intranasal medication delivery in pediatrics: pain control, anxiolysis, and seizure control.
Web site Editorial comments:
This is a concise review of the topic of IN drug delivery. The entire article is less than 3 pages so can be read quickly. It contains a nice table with recommended drug doses and key concepts related to successful intranasal medication delivery. The bibliography is up to date as of mid 2010. For anyone interested in a white paper regarding nasal drug delivery in pediatrics, this should be part of your files.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/20696726?dopt=Citation
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Chiaretti, A., G. Barone, et al. (2011) Intranasal lidocaine and midazolam for procedural sedation in children. Arch Dis Child (96):160-163
Abstract: Objective - To evaluate the safety and efficacy of a sedation protocol based on intranasal lidocaine spray and midazolam (INM) in children who are anxious and uncooperative when undergoing minor painful or diagnostic procedures, such as peripheral line insertion, venipuncture, intramuscular injection, echocardiogram, CT scan, audiometry testing and dental examination and extractions. Patients and design 46 children, aged 5-50 months, received INM (0.5 mg/kg) via a mucosal atomiser device. To avoid any nasal discomfort a puff of lidocaine spray (10 mg/puff) was administered before INM. The child's degree of sedation was scored using a modified Ramsay sedation scale. A questionnaire was designed to evaluate the parents' and doctors' opinions on the efficacy of the sedation. Statistical analysis was used to compare sedation times with children's age and weight. Results The degree of sedation achieved by INM enabled all procedures to be completed without additional drugs. Premedication with lidocaine spray prevented any nasal discomfort related to the INM. The mean duration of sedation was 23.1 min. The depth of sedation was 1 on the modified Ramsay scale. The questionnaire revealed high levels of satisfaction by both doctors and parents. Sedation start and end times were significantly correlated with age only. No side effects were recorded in the cohort of children studied. Conclusions This study has shown that the combined use of lidocaine spray and atomised INM appears to be a safe and effective method to achieve short-term sedation in children to facilitate medical care and procedures.
Web site Editorial comments:
This is an important paper - one of the downsides to IN midazolam is that it burns for about 30 seconds and you must warn the parents in advance that their child will probably cry briefly prior to sedation onset (but not as much crying as starting an IV line or getting a shot). The key is PRIOR application of the lidocaine (it requires a few minutes to really take effect). These authors used a separate device to delivery lidocaine, but it could just as easily have been given via the atomizer they were using to deliver the midazolam. They used 0.1 ml of 10% lidocaine. In the US we get lidocaine as 4% - I now use 0.2 ml per nostril of the 4% lidocaine, wait 3-5 minutes and then give the midazolam using the same device. Interestingly their most common use was to start IV lines in infants. I have found this concept also very useful to start IV lines in mentally disabled or agitated adults.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/21030365?dopt=Citation
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Arya, R., S. Gulati, et al. (2011). "Intranasal versus intravenous lorazepam for control of acute seizures in children: A randomized open-label study." Epilepsia.
Abstract: Purpose - Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6-14 years who presented with acute seizures. Methods: This was a randomized open-label study conducted at an Indian hospital from August 2008 to April 2009. One hundred forty-one consecutive children aged 6-14 years who presented convulsing to the emergency room were included. After stabilization, the children were randomized to receive either intravenous or intranasal lorazepam (0.1 mg/kg, maximum 4 mg). The primary outcome measure was clinical seizure remission within 10 min of drug administration. The study was registered with clinicaltrials.gov (NCT00735527). Key Findings: Seventy patients were randomized to receive intravenous and 71 to receive intranasal lorazepam. The patients in the two groups were comparable at baseline. Clinical seizure remission within 10 min of drug administration was found in 80% of the intravenous group as compared to 83.1% of intranasal group. The lower limit of 95% confidence interval for effect size was approximately -9.7%, with an a priori cutoff for noninferiority of -10%. Significance: Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.
Web site Editorial comments:
This is another practice changing article. The authors conducted a randomized trial comparing what many of us consider the gold standard for status epilepticus initial therapy - IV lorazepam - to the same dose of lorazepam given intranasally. The results showed identical efficacy and identical suppression of recurrent seizures over the next hour. Not mentioned in the abstract is the fact that the results are based on seizure control from the time of drug administration. They admit the nasal drug was given "virtually instantaneously" whereas the IV drug took between 1 and 25 minutes (median 4 minutes) to administer (due to difficulty of experience pediatric clinicians successfully starting an IV in a seizing child). This concept needs to be studied in adults - lorazepam is more potent than midazolam and may be a better drug for both seizure control and excited delirium control in a full grown adult due to this potency difference.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/21275979?dopt=Citation
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Bendall, J. C., P. M. Simpson, et al. (2011). "Effectiveness of Prehospital Morphine, Fentanyl, and Methoxyflurane in Pediatric Patients." Prehosp Emerg Care.
Abstract: Objectives. To compare the effectiveness of intravenous morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane for managing moderate to severe pain in pediatric patients in the out-of-hospital setting. Methods. We conducted a retrospective comparative study of 3,312 pediatric patients aged between 5 and 15 years who had moderate to severe pain (pain score over 5) and who received intravenous morphine, IN fentanyl, or inhaled methoxyflurane, either alone or in combination, between January 1, 2004, and November 30, 2006. Multivariate logistic regression was used to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of over 30% of initial pain score using an 11-point verbal numeric rating scale. Results. Effective analgesia was achieved in 82.5% of cases overall. All analgesic agents were effective in the majority of patients (87.5%, 89.5%, and 78.3% for morphine, fentanyl, and methoxyflurane, respectively). There was evidence that methoxyflurane was less effective than both morphine (odds ratio [OR] 0.52; 95% confidence interval [CI] 0.36-0.74) and fentanyl (OR 0.43; 95% CI 0.29-0.62; p < 0.0001). There was no clinical or statistical evidence of difference in the effectiveness of fentanyl and morphine in this population (OR 1.22; 95% CI 0.74-2.01). There was no evidence that combination analgesia was better than either fentanyl or morphine alone. Conclusion. Intranasal fentanyl and intravenous morphine are equally effective analgesic agents in pediatric patients with moderate to severe acute pain in the out-of-hospital setting. Methoxyflurane is less effective in comparison with both morphine and fentanyl, but is an effective analgesic in the majority of children.
Web site Editorial comments:
This is yet another article of many noting that IN fentanyl is just as good as IV morphine for controlling acute pain. The authors were allowed to titrate IV and IN drugs to effect allowing customization to the patients needs. The unique feature of this article is the clinical setting of EMS where IV lines in children are even more difficult and time consuming due to a variety of factors. The authors appropriately conclude that in light of the non-invasive route of administration and equivalence to IV morphine, IN fentanyl is the most suitable analgesic agent for managing pediatric patients with moderate to severe pain in the EMS setting.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/21294628?dopt=Citation
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Johnston, S., G. J. Wilkes, et al. (2011). "Inhaled methoxyflurane and intranasal fentanyl for prehospital management of visceral pain in an Australian ambulance service." Emerg Med J 28(1): 57-63.
Abstract: OBJECTIVE - This study analysed the analgesic effect and changes in vital signs associated with administration of inhaled Methoxyflurane (MTX) and/or intranasal Fentanyl (INF) for prehospital management of visceral pain. METHOD: A retrospective, observational study reviewing 1024 randomly selected records of patients with presumed visceral pain administered MTX (465), INF (397) or both (162) by the Western Australian Ambulance Service between January 2004 and February 2006. Clinical variables assessed included systolic blood pressure, pulse rate, respiration rate and Glasgow Coma Scale score. Pain was assessed utilising Visual/Verbal Analogue Scale pain scores. RESULTS: Overall effects on vital signs appeared favourable 5 min after use and at hospital arrival with either agent alone or in combination. As sole agents, MTX produced the greatest initial pain scores reduction (2.0 (1.7 to 2.2) vs 1.6 (1.4 to 1.8)) (mean (95% CI), and INF provided greater pain reduction by hospital arrival (3.2 (2.9 to 3.5) vs 2.5 (2.1 to 2.9)). While both agents were effective, INF provided a greater pain score reduction for cardiac (3.0 (2.6 to 3.4) vs 2.3 (1.8 to 2.8)), female (3.4 (2.9 to 4.0) v 2.5 (2.0 to 3.0)) and age 75+ patients (3.2 (2.5 to 3.8) vs 1.8 (1.0 to 2.5)). Combined use of agents was not advantageous. CONCLUSIONS: MTX and INF are effective agents for providing visceral pain analgesia in the prehospital setting. While MTX provided a more rapid onset of pain relief, INF provided superior analgesia after subsequent doses and in female, cardiac and older patients.
Web site Editorial comments:
As in the above discussion related to EMS use of IN fentanyl for children, here is another EMS article noting IN fentanyl is very effective in adults with Non-traumatic painful conditions. Yet more evidence to use IN fentanyl as primary therapy for most painful conditions that do not clearly need an IV line.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/20466829?dopt=Citation
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Case report: prehospital use of intranasal ketamine for paediatric burn injury
Abstract: In this study, the administration of an intravenous ketamine formulation to the nasal mucosa of a paediatric burn victim is described in the prehospital environment. Effective analgesia was achieved without the need for vascular or osseous access. Intranasal ketamine has been previously described for chronic pain and anaesthetic premedication. This case highlights its potential as an option for prehospital analgesia.
Web site Editorial comments:
Although this article is only a case report, we chose it as a featured article due to the potential impact this concept - intranasal ketamine - may have on EMS both at an advanced and basic level. Ketamine in sub-anesthetic doses (about 10-15 times less than doses used for deep sedation) is an excellent pain killer, yet does not cause any respiratory depression so it is very safe. This lack of respiratory depression has led to intranasal ketamine introduction to use by lay people suffering pain in the military and hospice setting. Why not EMS? With a little more research defining the proper dose and confirming the safety we suspect this may be a great method for wilderness medics, rural EMS and BLS services to treat patients suffering from acutely painful conditions.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/21292791?dopt=Citation
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