Pediatrics

Intranasal Medications

CASE

A 7 year-old girl presents after falling off a jungle gym.  She has a visible deformity of the left humerus and wrist.  She won’t let the nurse get close enough for a blow-dart, let alone an IV, and your attending slaps the IO kit out of your hands as you desperately try to boost your procedure numbers.  She needs pain relief.  Now what?

BACKGROUND

Intranasal (IN) administration of medications enables rapid systemic delivery, avoids first-pass metabolism, and negates the pain associated with IV access.  Delivery is quick and can be accomplished with minimal training.[1]

The rate limiting factor for IN administration is the area of available nasal mucosa, i.e. your absorptive surface.  Typically, IN administration is limited to volumes less than 1 mL per nostril, perhaps less with the presence of intranasal blood or mucous, necessitating a higher concentration to achieve the desired effect.

The most effective method of IN administration is an atomizer (Figure 1).  Crushing medications or using a syringe as a dropper results in incomplete distribution across the nasal mucosa, imprecise delivery, and unpredictable bloods levels.  Atomizers achieve better delivery, less drug loss to the oropharynx, and greater clinical efficacy.[1]

Figure 1: LMA MAD NASAL atomizer attached to 3 mL syringe

Figure 1: LMA MAD NASAL atomizer attached to 3 mL syringe

IN administration carries a low risk of adverse effects and beyond the time saved via ease of IN administration, the cost is comparable to IV delivery, usually under $10.00 per dose.

INDICATIONS

There has been a push in recent years to develop IN formulations of marketed products, including drugs for migraine management, smoking cessation, and even hormone replacement therapy.[2]  The full breadth of indications for the current IN drug pipeline is beyond the scope of this post, in which we will focus on the indications for which IN medications are used in emergency or pre-hospital settings.

Pain.  Acute pain is a common problem in pediatric medicine, and multiple studies have proven IN administration of opioids to be as effective as the IV route without the need to establish access, and faster onset than IM delivery.  The ease of administration has also made it popular with first responders and practitioners in austere environments.  At Hasbro Children’s Hospital, we commonly use fentanyl.  Dose at 1.5 - 2.0 mcg/kg, allow 10-15 minutes for full effect, and consider co-administration of an oral medication or bridge to IV for longer-term analgesia.[1]

Anxiolysis.  There are numerous reasons children need to stay still during treatments, such as procedures, imaging, or dressing changes.  Midazolam is the most commonly used and well-studied IN anxiolytic, although other options include ketamine and dexmedotomidine.  Although IN midazolam is associated with a transient burning sensation (due to a preservative) in the nares during administration, studies have shown monotherapy provides satisfactory anxiolysis, with minimal risk of adverse events.  Dose at 0.3 - 0.5 mg/kg and allow 5-7 minutes for the medication to take effect.

Seizure.  Because the well-vascularized nasal mucosa is brain-adjacent, IN administration can quickly achieve therapeutic levels in CSF.  In cases without IV access, IN midazolam was found to have a more rapid onset of action than rectal diazepam for better seizure control, and decreased need for intubation and hospital admission.[1]

Overdose.  The opioid epidemic is a national emergency, and with the rise in deaths has come a push for first responders to use naloxone in cases of suspected overdose.  Kits come in 2 and 4 mg doses, and include an ampule of naloxone and an atomizer.

Figure 2: Naloxone IN kit

Figure 2: Naloxone IN kit

ADMINISTRATION TECHNIQUE

Approach from the side.  Even without needles, children will react to seeing a syringe with a lot of anxiety.  Approaching from the side will minimize this, allow you to get in a better position, and achieve better drug delivery.

Use both nostrils.  If you only use one nostril, you’re missing out on an entire half of the nasal mucosa!  Instead of spraying the entire volume into your favorite nares, spread the dose equally between right and left.

Direct the spray.  When you introduce the atomizer, point the tip laterally towards the tip of the ear.  This will afford you better coverage of the turbinates and mucosa.

Use the right concentration.  Using a higher concentration of medication allows you to use less volume, and since absorption is limited by volume when it comes to IN delivery, less drug will be lost.[3] 

SUMMARY 

IN administration of medications is a safe and effective way to manage a number of conditions in situations where other means of drug delivery are inefficient, ineffective, or not available.  As for the patient from our introductory case, she received 25 mcg of IN fentanyl with great improvement in her pain, got x-rays that confirmed a displaced fracture, and tolerated reduction of her wrist with procedural sedation.

Faculty Reviewer: Dr. Chris Merritt

references 

  1. Wolfe TR, Braude DA. Intranasal Medication Delivery for Children: A Brief Review and Update. Pediatrics. 2010; 126: 532-537.

  2. Fortuna A, Alves G, Serralheiro A, Sousa J, Falcao A. Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules. Eur J Pharm Biopharm. 2014; 88(1): 8-27.

  3. Using the MAD Nasal Intranasal Mucosal Atomization Device. Teleflex Medical Europe Ltd. Ireland. www.lmaco.com/products. Accessed August 24, 2017.

 

A Bowel Inside a Bowel: Intussusception

The Case

A 14 month-old female with no significant PMH who presented to the Emergency Department with vomiting. Per mom, patient was well yesterday, but today has been refusing food, crying and vomiting. Patient has had no known sick contacts and her vaccinations are up to date. A review of systems was performed and was otherwise negative.

Physical Exam

Vital signs were within normal limits. Patient was listless with decreased responsiveness, but not in distress. No evidence of respiratory compromise. Abdominal exam was unremarkable, with no focal tenderness and no guarding, rigidity or rebound. During the time the examiner was present in the room, the patient had one episode of crying inconsolably and then vomiting.

An abdominal ultrasound was performed and the diagnosis was revealed to be Intussusception

Ultrasound

Ultrasound has been shown to be 97.9% sensitive and 97.8% specific for diagnosing ileocolic intussusception. To evaluate for intussusception, start with the high frequency low penetration linear transducer. In most young children this transducer will provide adequate depth. In an older child, you may have to use the higher penetration curvilinear transducer. If available, use warm gel to minimize patient discomfort and thereby increasing your changes of obtaining clear images. Begin in the transverse plane and slide your probe up to the right upper quadrant, across, and then down the left side, interrogating for the intussusception (Figure 1).

Figure 1: Suggested path of the ultrasound transducer to evaluate for intussusception.  (https://www.acep.org/how-we-serve/sections/emergency-ultrasound/news/september-2018/pediatric-emergency-ultrasound-deep-dive-on-pocus-for-intussusception/)

Figure 1: Suggested path of the ultrasound transducer to evaluate for intussusception.

(https://www.acep.org/how-we-serve/sections/emergency-ultrasound/news/september-2018/pediatric-emergency-ultrasound-deep-dive-on-pocus-for-intussusception/)

Most of the intussusceptions will be found on the right hand side, and are described as a “target sign” when you are viewing the intestinal intussusception in transverse or the “sandwich sign” in long axis.  The “lawn-mower” approach can be used, similar to the approach for SBO, and graded compression along your path can help move bowel gas out of the way to better evaluate the intestine. The hyperechoic rings are the mucosa and muscularis and the hypoechoic portion is the submucosa.  

Case Discussion

Intussusception is the most common abdominal emergency in early childhood, with the majority of cases occurring in patients <2 years of age. It occurs when the bowel telescopes in on itself and gets stuck. The peristaltic waves of the bowel causes waves of pain in the patient. The classic triad is described as pain, vomiting and bloody stools. Ultrasonography is the preferred diagnostic modality to evaluate for intussusception, given the high sensitivity and specificity (97.9% and 97.8% respectively) when performed by a skilled clinician. Ultrasound also has a high negative predictive value (approaching 99.7%) and can rule out intussusception in a majority of patients. Intussusception presents on ultrasound as a peripheral hypoechoic ring surrounding a central echogenic focus described as either a "target sign” or a “doughnut sign.” (Figure 2a) The visualized doughnut represents the layers of the intestinal wall that have invaginated into themselves. Color doppler can be applied to evaluate for tissue ischemia. (Figure 2b) The most common type of intussusception, ileocolic (as in this case) is usually found in the right lower quadrant. There is usually associated focal tenderness in the right lower quadrant (though this patient was non-tender). Treatment of a non-perforated intussusception typically consists of reduction via air enema, but sometimes operative management is indicated.

Figure 2: Ultrasound image of intussusception

Figure 2: Ultrasound image of intussusception

Non-Accidental Trauma

Case

A hypothetical 7 month-old infant presents to the emergency department for mild respiratory distress. There is no recent illness or symptoms to explain the infant’s tachypnea and mild hypoxia. There is no visible bruising on exam. The parent states that the infant is starting to pull to stand but does not yet cruise. They have had several falls onto their tile kitchen floor. The CXR (below) is read by the radiologist left posterior rib fractures in ribs 4-8.

Case courtesy of Dr. George Harisis, Radiopaedia.org. From the case Non-Accidental Injury

Case courtesy of Dr. George Harisis, Radiopaedia.org. From the case Non-Accidental Injury

Highly Specific Fracture Patterns for Non-Accidental Trauma

A helpful adage: “Those that don’t cruise rarely bruise.” Approximately 80% of NAT occur in children less than 18 months old. A study evaluating bruising in normal infants demonstrated that only 0.01% (6 of 465) of pre-cruisers had ecchymoses. Soft tissue findings, like bruises, may tip you off to underlying or fractures either underlying or elsewhere. Pierce et al. (2010) highlighted the value of the TEN 4 FACES mnemonic to highlight concerning bruises that should prompt a workup for NAT: bruises to the Torso, Ears, and Neck in children < 4, any bruising on immobile children < 4 months, or bruising to the Frenulum, Angle of the mandible, Cheek, Eyelid, or Sclera. 

Fractures are the second most common finding in pediatric non-accidental trauma after bruising or other soft-tissue injuries. Although there are often similar fracture patterns seen in both accidental and non-accidental trauma, the fractures described below are the most highly specific for non-accidental trauma and should heighten your suspicion for intentional physical abuse:

Metaphyseal Fracture (aka “Corner” or “Bucket Handle” fractures)

A metaphyseal fracture is made up of microfractures perpendicular to the long axis of the bone, most commonly the distal ends of the tibia, femur, humerus. These microfractures are caused by the shearing forces of ligaments when a child who cannot control their limbs is shaken forcefully while held around their torso. It is highly specific fracture and is almost universally considered pathognomonic for non-accidental trauma.

Case courtesy of Dr. Basab Bhattacharya, Radiopaedia.org. From the case Non-Accidental Injuries

Case courtesy of Dr. Basab Bhattacharya, Radiopaedia.org. From the case Non-Accidental Injuries

Case courtesy of Dr. JR Dwek. From the The Radiographic Approach to Child Abuse.

Case courtesy of Dr. JR Dwek. From the The Radiographic Approach to Child Abuse.

Posterior Rib Fractures

Posterior rib fractures occur when enough anteroposterior chest compression is generated to cause movement of the posterior rib that acts as a lever over the transverse spinal process. This, like with metaphyseal fractures, can be caused by holding and shaking an infant with two hands around the ribcage. Other mechanisms include “marked forward decceleration into a solid object” in MVCs or in other non-accidental trauma. Biomechanically, the amount of force needed to cause leverage against the transverse process cannot be replicated when the patient is lying with their back against a flat surface, as is the case in CPR. A small post-mortem study of infants that had received even two-handed CPR supports this: they found anterolateral fractures but no occurrences of posterior rib fractures. In studies by Kleinman et al. (1997) and by Barsness et al. (2003) Posteromedial rib fractures have a very high positive predictive value (95%) for NAT and have the highest specificity for NAT.

Case courtesy of Dr. Paula Brill, Radiopaedia.org. From the case Non-Accidental Trauma.

Case courtesy of Dr. Paula Brill, Radiopaedia.org. From the case Non-Accidental Trauma.

The Three S’s: Spinous Process, Scapular, and Sternal Fractures

Though seen less often, spinous process, scapula, and sternum fractures round out the top most specific fractures for non-accidental trauma. Sternum and scapular fractures occur in the setting of a direct blow of unusual amounts force and are unexplained in the normal handling of most infants. As with other fractures, it is important to determine if the provided history matches the mechanism.

Other Specific Fracture Findings

  • Clavicular fractures (after the period explained by birth trauma)

  • Epiphyseal separations

  • Vertebral body fractures/separations

  • Digital fractures

  • Complex skull fractures

Next Steps

  • Mandatory reporting to Child Protective Services

  • Per the American Academy of Pediatrics, all patients undergoing workup for non-accidental trauma should be admitted to the hospital.

  • Complete a skeletal survey, which involves approximately 21 x-rays focusing on each individual limb or body part.

  • Order a CT brain to evaluate both the skull and underlying brain. Reconstructions of specific CTs may allow rotation of images and better identification of fractures.  

What Are We Missing?

In the most recent data published by the National Child Abuse and Neglect Data System, there were 1,585 fatalities due to child abuse and neglect in 2015. Approximately 44% percent of those suffered death due to physical abuse and almost 75% were children <3 years old.

A small study comparing known instances of child abuse fatalities with local medical records found that 30% of children who subsequently died from non-accidental trauma had interactions with health care for reasons other than well-child checks. Nearly 20% of those visits occurred within one month of their death. Albeit brief, emergency department visits may be the only interaction these children have with the health care system represent a critical opportunity for intervention.

 

Faculty Reviewer: Dr. Adam Aluisio

References

  1. Baldwin K, Pandya NK, Wolfgruber BA, et al. Femur Fractures in Pediatric Population: Abuse or Accidental Trauma? Clin Orthop Relat Res. 2011 Mar; 469(3):798-804.

  2. Barsness KA, Cha ES, Bensard DD, Calkins CM, Partrick DA, et al. The positive predictive value of rib fractures as an indicator of nonaccidental trauma in children. J Trauma. 2003;54:1107–1110.

  3. Bechtel K. Physical Abuse of Children: Epidemiology of Child Abuse in the United States. Emergency Medicine Reports. 2003 Mar.

  4.  Child Welfare Information Gateway. (2017). Child abuse and neglect fatalities 2015: Statistics and interventions. Washington, DC: U.S. Department of Health and Human Services, Children’s Bureau.

  5. Christian CW. Committee on Child Abuse and Neglect. The Evaluation of Suspected Child Physical Abuse. Pediatrics. 2015; 135(5):1337-1354. 

  6. Dwek JR. The Radiographic Approach to Child Abuse. Clinical Orthopaedics and Related Research. 2011;469(3):776-789.

  7. King WK, Kiesel EL, Simon HK. Child Abuse Fatalities: Are We Missing Opportunities for Intervention? Pediatric Emerg Care. 2006;22(4):211-214.

  8. Kleinman PK, Perez-Rossello JM, Newton AW, et al. Prevalence of the classic metaphyseal lesion in infants at low versus high risk for abuse. AJR Am J Roentgenol. 2011 Oct;197(4):1005-8.

  9. Kleinman PK, Schlesinger AE. Mechanical factors associated with posterior rib fractures: laboratory and case studies. Pediatr Radiol. 1997(27): 87-91.

  10.  Leaman LA, Hennrikus WL, Bresnahan JJ. Identifying non-accidental fractures in children aged <2 years . Journal of Children’s Orthopaedics. 2016;10(4):335-341.

  11. Matshes EW, Lew EO. Two-Handed Cardiopulmonary Resuscitation Can Cause Rib Fractures In Infants. Amer Journal of Forensic Med and Pathology. 2010 Dec; 31(4): 303-307.

  12. Paddock M, Sprigg A, Offiah AC. Imaging and reporting considerations for suspected physical abuse (non-accidental injury) in infants and young children. Part 1: initial considerations and appendicular skeleton. Clinical Radiology. 2017 Mar;72(3):179-188

  13. Pierce MC, Kaczor K, Aldridge S, O'Flynn J, Lorenza DJ. Bruising Characteristics Discriminating Physical Child Abuse From Accidental Trauma. Pediatrics. 2019;125(1):67-74.

  14. Sugar NF, Taylor JA, Feldman KW, and the Puget Sound Pediatric Research Network. Bruises in Infants and Toddlers Those Who Don't Cruise Rarely Bruise. Arch Pediatr Adolesc Med. 1999;153(4):399–403.