What Are Pulmonary Embolism Risk Factors?

Patient Presentation
A 17-year-old female came to clinic for followup of pneumonia that had been diagnosed when she was on vacation 1 week previously. She had been coughing for a couple of days, and the cough was worsening. She developed some shortness of breath and right-sided chest pain, so her parents took her to the local emergency room. “In the emergency room, they thought I might have a blood clot, so I had to have a CAT scan that they said was normal. They gave me medicine in my arm which helped with the chest pain and then gave me some pills for the pain. I took them for a couple of nights to sleep but stopped after that. I’m also almost done with the antibiotic they gave me,” she explained. Her mother said that the doctors were worried about the blood clot because the patient was using birth control pills for dysmenorrhea and the patient’s maternal aunt had had a blood clot that went to her lung. “She found out a few months ago that its a blood problem. I don’t know exactly what it is but my sister is supposed to let me know. I guess we haven’t told you that yet so you don’t know. It’s new in our family,” described the mother. The teenager said, “I’m doing a lot better now with a lot less coughing but some is still there. The pain has gone away.”

The pertinent physical exam showed normal growth parameters and vital signs with a respiratory rate of 18 per minute and an oxygen saturation of 99%. HEENT revealed some minor rhinorrhea with a small amount of serous fluid in her ears bilaterally. Her lung examination still had slightly decreased breath sounds on the right but no obvious crackles. Chest pain could not be provoked.

The diagnosis of right lower lobe pneumonia that was resolving was made. The physician recommended that the mother find out what the cause of the aunt’s blood clot was so that the family members could be evaluated if necessary. He also noted the information in the medical record.

Discussion
Pulmonary embolism (PE) is potentially life-threatening but fortunately rare event especially in the pediatric population. It was first described in children in 1861. PE is likely underreported because of minimal or non-specific clinical symptoms. The incidence is estimated at 0.05-4.2% with the 4.2% based on autopsy reports. It is probably also increasing as more central venous catheters (CVC) are used, and more children are surviving previously poor prognostic diseases. There is a bimodal distribution with cases < 1 year (especially neonates which account for ~50% of this group) and in teenagers. Neonates appear to have a high rate because of increases in CVC use and teenagers risks are felt to be increased with oral contraceptive use. Oral contraceptives alone are rarely felt to be solely responsible for PE though. Recurrence rate is 7-18% and death with PE is ~10% with the main cause being the patient's underlying medical condition.

Venous thrombosis can occur when there is injury to a vessel wall, venous stasis and hypercoagubility. Pulmonary embolism occurs when the thrombus is dislodged, moving through the blood vessels, through the right side of the heart and lodges in the pulmonary arterial system. Patients may have no symptoms if the thrombus involves less than 40-50% of the pulmonary circulation. Through various mechanisms, PE can cause hypoxia, hemodynamic instability and cardiopulmonary collapse. Massive PE where the pulmonary blood flow is occluded to the point of hemodynamic instability is rare in children. Massive PE can present with dyspnea, hypoxemia, hypotension, syncope, right-sided heart failure and sudden death.

Classically, PE presents with shortness of breath, chest pain and hemoptysis. These symptoms only occur in some patients. Deep venous thrombosis (DVT) symptoms of a painful extremity can also occur. In children, upper extremity DVTs are more common than in adults as more upper extremity CVCs are used in children. Unexplained tachypnea may be another non-specific finding that points towards PE. Pleuritic chest pain, shortness of breath and cough were more likely to be found in children evaluated for PE.

PE is rare so the differential diagnosis includes more common disease processes such as pneumonia, atelectasis, pneumothorax, and empyema. Congenital abnormalities and malignancies also need to be considered in the proper circumstances.

The diagnosis of PE can be difficult as noted. D-dimer testing is a sensitive screening test for adults, but can be normal in many children (15-40%) with known PE. Electrocardiogram with right-sided cardiac changes may be seen but again are less common in children. Arterial blood gas can show hypoxemia, hypercapnea and respiratory alkalosis. Echocardiogram can be helpful in some children particularly those with known congenital heart disease. Chest radiographs are frequently normal but can show hypovascularity in affected areas, wedge-shaped densities or a prominent central pulmonary artery. Computer tomography-pulmonary angiography is the primary imaging modality for PE diagnosis but other types of imaging may be used such as magnetic resonance imaging.

Treatment is usually with anticoagulants, potential thrombectomy or thrombolysis, and treatment of any underlying cause identified. Prevention includes ambulation and movement, adequate hydration, anticoagulants (usually for a period of time only), and inferior vena cava filters.

Learning Point
PE usually occurs in children with known risk factors with up to 80-96% having an identifiable problem, whereas in adults up to 30% are idiopathic.

Risk factors for PE in children include:

  • Congenital heart disease
  • Central venous catheters
  • Deep venous thrombosis – current or previous
  • Hypercoagulable states including malignancies, nephrotic syndrome and sickle cell disease
  • Immobilization
  • Obesity
  • Medications including oral contraceptives or other estrogen use
  • Prothrombic states including anti-phospholipid antibodies, Factor V Leiden, Protein C, and Protein S
  • Pulmonary embolism – previous
  • Recent surgeries
  • Trauma

Questions for Further Discussion
1. What are causes of sudden death in children? A review can be found here
2. What are causes of wheezing? A review can be found here
3. What are causes of chest pain? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Pulmonary Embolism

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Navanandan N, Stein J, Mistry RD. Pulmonary Embolism in Children. Pediatr Emerg Care. 2019;35(2):143-151. doi:10.1097/PEC.0000000000001730

Ramiz S, Rajpurkar M. Pulmonary Embolism in Children. Pediatr Clin North Am. 2018;65(3):495-507. doi:10.1016/j.pcl.2018.02.002

Ignjatovic V. Paediatric pulmonary embolism: a pathway to improved outcomes. Lancet Haematol. 2019;6(3):e115-e116. doi:10.1016/S2352-3026(19)30012-2

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Is This a Fasciculation?

Patient Presentation
A 17-year-old male came to clinic with a two week history of eye twitching. It occurred fairly often throughout the day and would last only for a very brief time. He said it only occurred in his right upper eyelid and did not progress to other areas. He denied actual eye blinking or any other muscle twitching. He also denied any other neurological symptoms such as visual or auditory changes, headache, muscle aches, or changes in mental status or mood. He also denied any drugs or chemical exposures. “It’s the end of the school year and I have a lot of tests. So I’ve been noticing it more I think because I am studying so much,” he stated.
The past medical and family history were non-contributory.

The pertinent physical exam showed a healthy male with normal vital signs and what appeared to be normal mood. His vision screening was 20/25 for both eyes. He did have a brief right eye twitch during the examination that lasted 2-3 seconds at the most. His complete eye and neurological examinations were normal.

The diagnosis of benign muscle fasciculations was made. “Are you drinking a lot of caffeine?” asked the pediatrician. “Yes, with all the studying I’m drinking a lot of Mountain Dew® and Red Bull®,” he answered. “I think that your eye twitching will get better if you cut back on the caffeine and also get some good sleep. These usually are worse when people are stressed and not sleeping well,” he said. I’ll go over the things you should come back for, but I think this will get better once your exams are done and you are sleeping better,” he continued. At the teenager’s well child examination later that summer, the eye twitching had ceased.

Discussion
Benign fasciculations are very common and occur in up to 70% of the general population. They occur at different points in people’s lives. They can be brought out by stress, poor sleep hygiene and caffeine.

Caffeine has numerous uses especially for regulating sleep and attention. However too much can cause restlessness, jitteriness and sleep deprivation too. The recommended amount of caffeine for a teenager is < 2.5 mg/kg or 100-175 mg/day. A Red Bull® beverage has 80 mg of caffeine /12 ounces, while Mountain Dew® has 55 mg caffeine/12 ounces. A review of caffeine can be found here.

Adolescents, if left alone without external influences, will sleep slightly more than 9 hours. However, often they will not achieve 9 hours for many external causes. There are many health problems associated with inadequate sleep and they can be reviewed here.

A new onset of simple partial seizures could also be a consideration for the patient above. Simple partial seizures can occur with or without consciousness being impaired. Those without consciousness impairment are classified according to other symptoms such as motor, sensory, autonomic or psychic symptoms or signs.

Simple tics are also common and can get worse in times of stress too. A review can be found here.

Learning Point
Benign fasciculations occur in a single muscle group and are not multifocal or continuous. They are felt to not progress to other neurological problems, but in very rare cases have been reported to precede motor neuron disease. Amyotrophic lateral sclerosis, a progressive motor neuron degenerative disease, is associated with fasciculations and muscle weakness. Because of this association, there can be anxiety associated with benign fasciculations especially in men working in health care.

Questions for Further Discussion
1. How are seizures classified? A review can be found here
2. What causes muscle cramps? A review can be found here
3. What causes nystagmus?
4. What is a tremor?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Neuromuscular Disorders and Muscle Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Filippakis A, Jara J, Ventura N, et al. A prospective study of benign fasciculation syndrome and anxiety. Muscle Nerve. 2018;58(6):852-854. doi:10.1002/mus.26193

de Carvalho M, Turkman A, Swash M. Sensory modulation of fasciculation discharge frequency. Muscle Nerve. 2019;59(6):688-693. doi:10.1002/mus.26456

How Much Caffeine in Drinks — Coffee, Tea, Soft Drinks — Caffeine Content. https://www.math.utah.edu/~yplee/fun/caffeine.html. Accessed June 25, 2019.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

How Good are Masks for Preventing Infection?

Patient Presentation
A teenaged female asked her pediatrician father how well masks were at preventing the spread of colds to other people. One of her friends had a respiratory illness and could not attend an important extra-curricular event and the girl was looking for possible ways to still have the friend attend. The pediatrician discussed how the friend should take care of her own health needs first and foremost. He also offered that masks can be quite helpful but they are only one part of the protective equipment used in hospitals and do have limitations including mask contamination and how the mask is actually used. It also depended on the actual illness and the type of mask used. He emphathized with his daughter and discussed other potential options for the friend to still be involved such as appropriate videochatting before and after the event.

Discussion
With continued exposure to respiratory pathogens and the emergence of novel respiratory pathogens, personal protective equipment (PPE) and procedures are important for decreasing occupational exposure to respiratory pathogens. PPE and procedures are particularly important when anti-infective treatments or vaccination are unavailable or have limited effectiveness. Medical masks are “[a]lso known as a surgical or procedure mask. As personal protective equipment, a facial mask is intended to protect caregivers and health-care workers against droplet-transmitted pathogens, or to serve as part of facial protection for patient-care activities that are likely to generate splashes or sprays of blood, body fluids, secretions or excretions. ” “N95 respirators are specifically designed to protect users from small airborne particles including aerosols…. Strict regulations dictate the filtration efficiency and breathing resistance for N95 respirators, which also require fit-testing to ensure a tight seal around the user’s face….” Mask and respirator studies are difficult to conduct because of user compliance and limited statistical power to evaluate mask and respiratory effectiveness. Therefore guidelines are based on limited evidence of their effectiveness.

Various other types of masks can be used for other protective measures such as reducing particulate matter in areas of air pollution. Other masks used for recreational and occupational activities will obviously have different effectiveness.

Learning Point
A 2017 meta-analysis designed to quantify the effectiveness of respiratory PPE among heathcare workers found:

  • In randomized controlled trials, masks and respirators had a protective effect against clinical respiratory illnesses (CRI) and influenza-like illness (ILL) when worn throughout the healthcare workers’ (HCWs) work shift.
  • Respirators offered superior protection over masks for CRI and bacterial diseases, but not viral infections or ILL.
  • In observational studies, masks and respirators provided some protection against severe acute respiratory syndrome (SARS).

There were several problems including definitions, self-report, actual mask use through the entire shift or intermittently.
The authors state that they found evidence to support using masks and respirators for CRI and ILI with respirators offering great protection to HCWs but consistent use throughout an entire work shift is less likely due to greater discomfort in using them.
In lower-resource setting they note that “….single-use medical masks are preferable to cloth masks, for which there is no evidence of protection and which might facilitate transmission of pathogens when use repeatedly without adequate sterilization.”

In a mathematical model of using PPE to reduce an influenza outbreak in a general population found that 50% compliance with using a mask or respirator resulted in a significant risk reduction, and with “an 80% compliance rate essentially eliminated the influenza outbreak.”

A study of contamination of medical masks worn by hospital HCWs found that overall contamination rate with respiratory viruses was ~10%. This increased with the duration of use, increased numbers of patients examined. They found a slightly decreased rate in pediatric and respiratory departments. Maximum contamination was found on the upper sections of the masks testing.

The authors recommend some basic practices, stating “[a]s a general rule, HCWs should not reuse masks, should restrict use to less than 6 h and avoid touching the outer surface of mask during doffing, and practice hand hygiene after removal.”

Per the World Health Organization “[w]ear medical masks fitted tightly to the face, and discard immediately after use…. If the mask gets wet or dirty with secretions, it must be changed immediately.”

The World Health Organization also states “[t]here is no evidence to suggest a difference in the effectiveness of particulate respirators over medical masks as a component in the use of PPE for routine care. However, it is not known whether there is any difference in the setting of care involving aerosol-generating procedures. When performing such procedures associated with an increased risk of transmission of [acute respiratory infections] pathogens, it may be preferable to use particulate respirators.”

Questions for Further Discussion
1. What types of PPE are available at your location and do you know how to effectively use them?
2. How contagious is tuberculosis to close contacts? A review can be found here
3. On board airplanes, where is the greatest infectious disease risk? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for this topic: Infection Control

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Offeddu V, Yung CF, Low MSF, Tam CC. Effectiveness of Masks and Respirators Against Respiratory Infections in Healthcare Workers: A Systematic Review and Meta-Analysis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2017;65(11):1934-1942. doi:10.1093/cid/cix681

Chughtai AA, Stelzer-Braid S, Rawlinson W, et al. Contamination by respiratory viruses on outer surface of medical masks used by hospital healthcare workers. BMC Infect Dis. 2019;19(1):491. doi:10.1186/s12879-019-4109-x

Yan J, Guha S, Hariharan P, Myers M. Modeling the Effectiveness of Respiratory Protective Devices in Reducing Influenza Outbreak. Risk Anal Off Publ Soc Risk Anal. 2019;39(3):647-661. doi:10.1111/risa.13181

Pacitto A, Amato F, Salmatonidis A, et al. Effectiveness of commercial face masks to reduce personal PM exposure. Sci Total Environ. 2019;650(Pt 1):1582-1590. doi:10.1016/j.scitotenv.2018.09.109

World Health Organization. Infection prevention and control of epidemic-and pandemic prone acute respiratory infections in health care. 2014. pp. xviii, pp 25-26, and Annex A2.2 pp. 40-41. https://www.who.int/csr/bioriskreduction/infection_control/publication/en/. Accessed June 24, 2019.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What is the Dosing of CBD Oil?

Patient Presentation
An attending physician overheard a resident talking with a father on the telephone in clinic. The parent had asked the resident to give a dosing schedule for over-the-counter cannabidiol (CBD) oil for a 7 year old with attentional issues because the bottle said to consult a physician for children under 12 years of age. The resident discussed that that he could not do this as the preparations varied so much from vendor to vendor and this was not an approved use. The parent was fairly insistent that with the dosing for adults that the resident could “just figure it out,” and give him a dose for his child. The resident said that these preparations are not regulated the way other medications are in the United States and therefore couldn’t give a dosing recommendation. He went on to try to engage the father in discussing why he wanted to give the CBD oil and eventually was able to convince the father to come to clinic to discuss the underlying problems with their regular primary care physician.

Discussion
Cannabis sativa makes small fruits which are usually named “seeds” although they are not technically a seed. Hemp oil is derived from the hemp seeds by cold-pressing or other means of macerating or squashing the seeds. Cold pressed oil is high in polyunsaturated fatty acids including various omega-3 and linolenic acids and antioxidants. It is used by some people for its nutritional value and “[a]ccording to an old legend, Buddha (Prince Siddharta Gautama) founder of Buddism, was able to survive eating only one hemp seed each day for six years.” The seeds themselves do not contain any psychoactive compounds (specifically THC or tetrahydrocannabinol) but during processing they can become contaminated with these compounds. The THC impurity concentration is highly variable among different cultivars, processing and storage methods and thermal stress also increases the THC levels. In Europe there are strict limits on THC impurity levels and the oil is recommended to be consumed without heating.

A review of cannabis can be found here.

Learning Point
“…Cultivars used for seed production with a low THC levels generally contain a high concentration of cannabidiol (CBD) which has no THC activity.” An analysis study of cannabinoids in 13 commercial hemp seed oil preparations found that “concentrations of cannabinoids can be extremely variable among different oil varieties.” The authors also state that other methodologies they outline can be used to help determine storage conditions of the oil.

Medical use of cannabis has been proposed and mainly studied in adult populations. Potential indications include cancer-related nausea, appetite enhancement, neurogenic pain, glaucoma and epilepsy. In pediatrics some of the most common use is for seizures, but also chronic pain and muscle spasms. CBD is the more common form of cannabis used for seizures. Epidiolex® is a liquid cannabis-derived medication, that is FDA approved in the United States for the treatment of patients 2 years and older with Lennox-Gastaut syndrome seizures or Dravot Syndrome. The starting dose is 2.5 mg/kg twice a day orally with increases based on response and side effects.

Questions for Further Discussion
1. What is Lorenzo’s oil used for?
2. What is the legal status of medical cannabis in your location?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Marijuana and Pregnancy and Substance Abuse.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Citti C, Pacchetti B, Vandelli MA, Forni F, Cannazza G. Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA). J Pharm Biomed Anal. 2018;149:532-540. doi:10.1016/j.jpba.2017.11.044

Samanta D. Cannabidiol: A Review of Clinical Efficacy and Safety in Epilepsy. Pediatr Neurol. March 2019. doi:10.1016/j.pediatrneurol.2019.03.014

Hoffenberg EJ, McWilliams S, Mikulich-Gilbertson S, Murphy B, Hoffenberg A, Hopfer CJ. Cannabis Oil Use by Adolescents and Young Adults With Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2019;68(3):348-352. doi:10.1097/MPG.0000000000002189

RxList. Epidiolex (Cannabidiol Oral Solution): Side Effects, Interactions, Warning, Dosage & Uses. https://www.rxlist.com/epidiolex-drug.htm. Accessed June 10, 2019.

Commissioner of the Federal Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on new steps to advance agency’s continued evaluation of potential regulatory pathways for cannabis-containing and cannabis-derived products. FDA. http://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-steps-advance-agencys-continued-evaluation. Published May 3, 2019. Accessed June 10, 2019.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa