What Drugs Can Trigger Malignant Hyperthermia?

Patient Presentation
A 4-year-old male was transferred to a regional children’s hospital for continued treatment of malignant hyperthermia.
He had a tonsillectomy the previous day and he tolerated the procedure well.
In the recovery room his heart rate was slightly elevated but he was discharged home.
Over the evening he developed a low grade fever and began to complain of pain in his extremities.
In the morning, the patient had muscular rigidity where his feet were dorsiflexed and relaxed.
His parents took him to see his regular physician who went with him to the emergency room of the local hospital.
His temperature was now elevated to 39 degrees Celsius.
In the emergency room, the patient was given intravenous fluids and dantrolene.
His mother reports that the muscular rigidity was lessened after the dantrolene was given but the muscle pain continued.
Laboratories in the emergency room showed normal electrolytes but a creatinine phosphokinase of 7684 U/L.
The past medical history showed that he had a previous pressure equalizing tube placement but he was not intubated for that surgery.
He also had multiple episodes of otitis medias in the past and significant snoring. He had 3 episodes of strep throat during the previous winter.
The family history revealed his parents had also had surgeries but did not know if they had been intubated. No other family members had problems with anesthesia.
The review of systems was otherwise normal.
The pertinent physical exam showed an anxious male with normal vital signs except for a temperature of 38 degrees Celsius. He could speak clearly, had no masseter muscle rigidity or trismus.
His cranial nerves were intact. Deep tendon reflexes were present without clonus. He had difficulty raising his arms or legs against gravity but could with some effort. He had to be carried.
He had tender muscles to palpation but no bone or joint pain. He did have back pain with flexion of legs to chest. He had full range of motion in all joints.
The diagnosis of malignant hyperthermia was again confirmed.
The laboratory evaluation was repeated as several hours had gone by since the last testing.
The electrolytes, urinalysis, coagulation profile and electrocardiogram were all normal.
The creatine phosphokinase was now 3408 U/L.
He received another dose of dantrolene. Laboratories were repeated every 6 hours.
The Malignant Hyperthermia Association of the United States (MHAUS) protocol was accessed by Internet before the patient arrived.
The MHAUS hotline was contacted and there also was verbal consultation with local anesthesia consultants after the patient was evaluated.
They both agreed with the treating team’s management plan.
The MHAUS also said that they would assist the family with obtaining a medical alert bracelet for the child and with genetic testing of the family.
The patient’s clinical course over the next 2 days found him gradually regaining his strength.
At discharge he had no pain and his neurological examination was normal. His CPK was 172 U/L.
He was to see his primary care physician the next day and genetic testing and counseling would be done at the children’s hospital within the next month.

Discussion
Malignant hyperthermia is a medical emergency. It is caused by an abnormality where the metabolism of intracellular calcium is altered causing a hypermetabolic state.
It is triggered by various drugs used for anesthesia. It may occur during anesthesia and in the post-anesthesia period. Symptoms may not be recognized though until hours later.
Signs and symptoms of malignant hyperthermia include:

  • Tachycardia/tachypnea
  • Increasing temperature (may be a late sign)
  • Body rigidity including trunk or total body
  • Masseter muscle rigidity or trismus
  • Myoglobinuria
  • Increasing end tidal CO2
  • Mixed respiratory and metabolic acidosis

Malignant hyperthermia can cause extreme fever, rhabdomyolysis, coagulopathy and even cardiac arrest.
It should be considered with these signs and symptoms and treatment instituted promptly.
Treatment includes halting the procedure if possible, discontinuing volatile anesthetic agents and succinylcholine and/or changing to non-triggering anesthetic agents,
hyperventilating the patient with 100% oxygen, treating with dantrolene sodium, cooling the patient with ice and/or lavage of body cavities, giving intravenous fluids with bicarbonate and monitoring and treating electrolyte abnormalities particularly hyperkalemia.
Intensive care management and monitoring may be necessary in the acute phase.

Dantrolene sodium is given for acute crisis at a dose of 2.5 mg/kg intravenously. It is also available in oral form.
Intravenous treatment may be repeated as often as necessary until the hypermetabolic state is normalized and all symptoms have disappeared
Usually this is 1-4 doses. Other diagnoses should be considered if more than 20 mg/kg is used without benefit.

The MHAUS has a 24 hour hotline available for consultation in the United States and Canada at 800-644-9737,
and internationally at
0011-315-464-7079.

Laboratory tests to order/monitor include (often done every 6 hours until normalized):

  • Electrolytes – particularly for hyperkalemia
  • Creatinine phosphokinase
  • Myoglobin
  • Arterial blood gas – particularly for acidosis
  • Coagulation profile
  • Electrocardiogram
  • Urine including for myoglobin
  • End tidal CO2

Some patients with malignant hyperthermia have identifiable genetic markers.
These markers may make it possible to identify at risk family members and therefore potentially they can be screened for mutations.
Some patients and family members need to have a muscle biopsy and contracture testing to evaluate malignant hyperthermia susceptibility.

Learning Point

According to the MHAUS, anesthetic agents that are unsafe for patients with malignant hyperthermia are listed below.
“All other anesthetic agents outside of these two categories of Volatile anesthetic agents and depolarizing muscle relaxants are considered safe.”

  • Depolarizing muscle relaxants
    • Succinylcholine (Suxamethonium)
  • Inhaled General Anesthetics
    • Chloroform (Trichloromethane, Methyltrichloride)
    • Desflurane
    • Enflurane
    • Halothane
    • Isoflurane
    • Methoxyflurane
    • Sevoflurane
    • Trichloroethylene
    • Xenon

Questions for Further Discussion
1. What consultants are available locally to manage suspected malignant hyperthermia?
2. How does dantrolene work?
3. Are patients with malignant hyperthermia more susceptible to heat illnesses?

Related Cases

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

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

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

To view images related to this topic check Google Images.

Brandom BW.
The genetics of malignant hyperthermia.
Anesthesiol Clin North America. 2005;23(4):615-9, viii.

Dantrolene: Pediatric Drug Information. UpToDate.
Available from the Internet at http://www.uptodateol.com/online/content/topic.do?topicKey=ped_drug/52419&selectedTitle=23~46&source=search_result (rev. 2008, cited 7/20/08).

Malignant Hyperthermia Association of the United States. Medical Professionals
Available from the Internet at http://medical.mhaus.org/ (rev. 2008, cited 7/20/08).

Malignant Hyperthermia Association of the United States. Anesthetic Agent Choice for the MH-Susceptible Patient.
Available from the Internet at http://medical.mhaus.org/index.cfm/fuseaction/Content.Display/PagePK/AnestheticList.cfm (cited 7/20/08).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    6. Information technology to support patient care decisions and patient education is used.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    15. Information technology to manage information, access on-line medical information and support the healthcare professional’s own education is used.
    16. Learning of students and other health care professionals is facilitated.

  • Interpersonal and Communication Skills

    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

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

    Date
    August 11, 2008

  • How Can I Make My Sexual Interview More Gender Neutral?

    Patient Presentation
    An 18-year-old female came to clinic for a health supervision examination prior to starting college in a distant city.
    During the interview, the physician asked if she had “???been sexually active now or in the past with boys, girls, men or women?”The women paused, took a deep breath and quietly said yes.
    The physician then inquired what she was saying yes to.
    The woman confided that she was in a lesbian relationship for the past 6 months.
    During the discussion, she said that she “always knew that I was a lesbian” and that she could not remember ever being sexually attracted to men or boys.
    Her current relationship was mutually monogamous as far as she knew and she trusted her partner.
    They both had been seen at a local reproductive health clinic for routine gynecological care and testing for sexually transmitted infections and human immunodeficiency virus before beginning their sexual relationship.
    They did not use condoms or dental dams during sexual encounters.
    When asked who knew about her sexual orientation, she stated that a few trusted, same-aged friends, but no family members.
    She denied any harassment or violence, depression, or suicidal ideation.
    The past medical history,
    family history,
    and review of systems were non-contributory.
    The pertinent physical exam showed a quiet female with normal vital signs and growth parameters.
    Her physical examination was normal.
    The diagnosis of a healthy female who had disclosed lesbian homosexual orientation was made.
    At this time, she had no plans to disclose her sexual orientation to her family and a general discussion of possibly how to do so was discussed.
    The physician utilized the room’s computer to access local LGBTQ resources (i.e. lesbian, gay, bisexual, transgender and questioning people) at her college’s health center and community.
    This information was printed after the woman stated she had a safe place to keep the information at home and felt comfortable taking it with her.
    In addition to the other anticipatory guidance and health care provided, the physician reiterated that she could confidentially telephone to the office if she had questions.
    The physician did encourage electronic mail correspondence if the issue was not sensitive, but not for any sensitive information particularly about her sexual orientation.

    Discussion
    Sexuality and social and family functioning and relationships are important components of comprehensive medical care and should be discussed at every health supervision for children and adolescents.
    Homosexuality in children and/or their parents is common and pediatric health care providers should be aware of the specific needs of each child, adolescent and family.
    Some sexual definitions include:

    • Sexual orientation is the sexual desire for a particular gender, or an intensive internal physiological desire for a particular gender. Homosexual, heterosexual and bisexual are examples of sexual orientation.
      Sexual orientation is stable over time, and is resistant to conscious control. It is not a choice.

    • Sexual behavior are physical behaviors that are conscious choices. These behaviors are usually motor, (e.g. “he plays with dolls”, “she’s so macho”) and may or may not change over time.
    • Gender identity is a person’s self concept of their own gender and includes an integration of the person’s biological sex, gender role expression and sexual orientation.
    • Gay refers to a male whose primary, loving, sexual and/or intimate relationships are with men.
    • Lesbian refers to a woman whose primary, loving, sexual and/or intimate relationships are with women.
    • Bisexual refers to a person who is sexually, emotionally and/or intimately attracted to either sex but not necessarily at the same time.
    • Transgender is a general term for crossing gender lines. It may refer to persons who are transsexuals or transvestites/cross-dressers.
    • Questioning refers to individual who is not sure about their sexual orientation.
    • LGBTQ (lesbian, gay, bisexual, transgender and questioning people) terminology describes sexual orientation, not sexual behavior.

    It is very common for adolescents and adults to engage in sexual behaviors that others may define as homosexual in nature.
    Since these are sexual behaviors, they are subject to conscious choice and can change over time.
    Many of these “experimenting” individuals would identify themselves as having a heterosexual orientation.
    Individuals may also consider themselves heterosexual but may engage in homosexual sexual behaviors to gain money and /or favors. One example is prostitution.

    This confusion between sexual orientation and sexual behavior can lead to imprecise/inaccurate communication and even research.
    In a recent study in The Lancet of global sexual behavior, it appears that there was significant underreporting of homosexual sexual behavior in persons who report themselves as heterosexuals.
    This is particularly true of men who are married to women.

    Persons who are homosexual may experience a variety of medical or social problems that can affect their health.
    These include:

    • Mental health – including isolation, depression, suicide, poor self-esteem, fear
    • Sexually transmitted infections and pregnancy – especially Gonorrhea, Hepatitis B and C, Human Immunodeficiency Virus, Syphilis.
    • Social and legal – difficulties identifying where and how to socialize, discrimination in employment, housing, public accommodations, public events
    • Substance abuse
    • Violence – including bullying, harassment, sexual violence/abuse, physical violence/abuse or death

    It is not uncommon for adolescents to “experiment” with different sexual behaviors and therefore even those persons who have a homosexual orientation should be counseled about safe-sex practices and contraception options.

    Learning Point
    In addition to assuring and maintaining information confidentiality with all patients, using gender-neutral questions on health questionnaires and during the health interview may allow youth and their families to give more accurate information.
    For example, health questionnaires that ask for information about a mother and a father, may not gather all the pertinent information in a 2-adult gay/lesbian household or a foster care family.
    Using a generic term such as “Guardian” as the header with a follow-up question about the “Relationship to Patient” offers more flexibility.
    Some people recommend to have at least 4 spaces on the health form for “Guardian” because of the high rate of divorce, kinship care, and foster and adoptive care.

    The following are some suggestions for gender-neutral sexual questions. The terms men and women can be substituted or added as is appropriate to the terms boys and girls used below:

    • Many of my patients are dating other boys, girls or both. Are you interested in dating?
    • Have you ever dated or gone out with someone? Are you dating or going out with someone now?
    • Have you ever been attracted to girls, boys or both? Are you especially attracted to any boys or girls?
    • Many boys and girls are sexual with other boys or girls. They may kiss, hug, pet or have oral, anal or vaginal intercourse. Have you every had any sexual experiences like these or other experiences with girls or boys or both?
    • What kind of sexual experiences have you had? Did you have them with boys? Did you have them with girls? Did you have them with both?
    • What kind of protection did you and your partner(s) use for pregnancy and sexually transmitted diseases?
    • Do you have any concerns about your sexual feelings or the sexual things you have been doing or want to do in the future?
    • Have you ever talked with someone about your sexual feelings?
    • Do you consider yourself to be gay/lesbian, bisexual or straight (heterosexual)? Are you asking/questioning what you want to call yourself?

    Some adolescents may be reticent to disclose their sexual behaviors or use different terminology to describe them. Therefore the healthcare provider may need to be very explicit when describing sexual behaviors to elicit precise information from patients.

    Questions for Further Discussion
    1. When compared to children raised in other households, do children raised in gay/lesbian homes differ in psychosocial development?
    2. Parents who find out they have a daughter or son who is gay/lesbian have what characteristic psychological reaction?
    3. In your state, what is the legal status of same-sex households?

    Related Cases

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

    Information prescriptions for patients can be found at MedlinePlus for these topics: Gay, Lesbian and Transgender Health and Teen Sexual Health.

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

    To view images related to this topic check Google Images.

    Perrin EC, Cohen KM, Gold M, Ryan C, Savin-Williams RC, Schorzman CM.
    Gay and lesbian issues in pediatric health care.
    Curr Probl Pediatr Adolesc Health Care. 2004 Nov-Dec;34(10):355-98.

    Tasker F.
    Lesbian mothers, gay fathers, and their children: a review.
    J Dev Behav Pediatr. 2005 Jun;26(3):224-4.

    Wellings K, Collumbien M, Slaymaker E, Singh S, Hodges Z, Patel D, Bajos N.
    Sexual behaviour in context: a global perspective.
    Lancet. 2006 Nov 11;368(9548):1706-28.

    Selekman J.
    Homosexuality in children and/or their parents.
    Pediatr Nurs. 2007 Sep-Oct;33(5)453-7.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    6. Information technology to support patient care decisions and patient education is used.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Interpersonal and Communication Skills
    17. A therapeutic and ethically sound relationship with patients is created and sustained.
    18. Using effective nonverbal, explanatory, questioning, and writing skills, the healthcare professional uses effective listening skills and elicits and provides information.

  • Professionalism
    20. Respect, compassion, and integrity; a responsiveness to the needs of patients and society that supercedes self-interest; accountability to patients, society, and the profession; and a commitment to excellence and on-going professional development are demonstrated.
    21. A commitment to ethical principles pertaining to provision or withholding of clinical care, confidentiality of patient information, informed consent, and business practices are demonstrated.
    22. Sensitivity and responsiveness to patients’ culture, age, gender, and disabilities are demonstrated.

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

    Date
    August 4, 2008

  • What Causes Sweaty Babies?

    Patient Presentation
    A 9 month-old male came to clinic for his health supervision visit.
    His parents had no complaints but when discussing sleeping they asked why his head always seemed sweaty at night.
    Originally they thought that he was overdressed, but even with different temperatures or clothing his head always sweats at night.
    They report that he occasionally does this during naps also, but not when awake. He is afebrile and the rest of his body does not seem to sweat during these episodes. He others apepars to sweat normally when exposed to excessive heat or if febrile.
    His past medical history, family history and review of systems are all negative.
    The pertinent physical exam shows a developmentally appropriate male with growth parameters in the 75-90% and normal growth curves.
    His physical examination was unremarkable.
    The diagnosis of idiopathic hyperhidrosis of the scalp was made. The pediatrician told the parents that this is fairly common but the cause is unknown.
    As the patient had an otherwise normal history and physical examination the pediatrician recommended monitoring and to call if the sweating occurs at other times, changes or new symptoms occur.
    The patient’s clinical course over the next 5 years showed almost nightly hyperhidrosis of the scalp but the child continued to grow and develop normally.

    Discussion
    Sweating is made by the eccrine glands and is a normal physiologic response that helps to maintain body temperature.

    Hyperhidrosis is sweating beyond what is needed to maintain normal temperature regulation.
    It can be primary or secondary, and generalized, regional or focal, regional.
    Some studies report a prevalence of 1-2.8%, but this may be underreported.
    Hyperhidrosis can be not only socially a problem, but may not allow people to have careers in areas that contact paper, metal or electrical components.
    Hyperhidrosis can also damage clothing, shoes and furniture too.

    Sweating around the head particularly during sleep is a common finding especially in children. The cause is not understood.
    Sweating of the palms and soles is also common particularly if in a stressful situation or if in an enclosed environment (i.e. shoes, coat pockets, etc.).
    Axillary sweating is often caused by anxiety and thermal stimuli.

    Treatment for hyperhidrosis includes many options depending on the location, potential cause, and severity.
    Topical treatments include antiperspirants, tannic acid, formalin, glutaraldyde and anticholinergics.
    System treatment includes anticholinergics, botulinum toxin, calcium-channel blockers, clonidine, and non-steroidal antiinflammatory drugs.
    Surgical treatment includes excision of axillary sweat glands, liposuction, and sympathectomy.
    Electrical treatment includes iontophoresis.

    Learning Point

    The causes of hyperhidrosis include:

    • Endocrine
      • Acromegaly
      • Diabetes mellitus
      • Gout
      • Hyperpituitarism
      • Hypoglycemia
      • Menopause – secondary
      • Thyrotoxicosis
    • Environment (most common)- heat illnesses, elevated humidity, exercise
    • Dermatologic
      • Eccrine nevus
    • Drugs
      • Alcohol
      • Amitriptyline
      • Amphetamine
      • Antihistamine
      • Ephedrine
      • Haloperidol
      • Methylphenidate
      • Propanolol
      • Phenothiazine
      • Physostigmine
      • Pilocarpine
    • Drug withdrawal
    • Fever
      • Infections, acute and chronic
    • Genetic
      • Episodic spontaneous hypothermia with hyperhidrosis
      • Familial dysautononia (i.e. Riley-Day syndrome)
    • Idiopathic
      • Primary or essential hyperhidrosis
    • Oncologic (may have fever also)
      • Carcinoid tumor
      • Neoplasia, general
      • Neuroblastoma
      • Pheochromocytoma
    • Neurologic
      • Generalized
        • Anxiety
        • Fainting
        • Gustatory or Olfactory
          • Citric acid
          • Coffee
          • Chocolate
          • Peanut butter
          • Spicy foods
        • Pain
        • Shock
      • Focal or regional
        • Peripheral nerve damage
          • Auriculotemporal syndrome (i.e. Frey’s Syndrome, nerve damage near parotid gland with focal sweating in area)
        • Ross syndrome ( e.g. sweating associated with areflexia and tonic pupil)
        • Spinal cord lesion
        • Stroke

    Questions for Further Discussion
    1. How does iontophoresis work to decrease hyperhidrosis?
    2. When should hyperhidrosis prompt an evaluation for a possible neoplasm?

    Related Cases

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

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

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

    To view images related to this topic check Google Images.

    Illingworth RS. Common Symptoms of Disease in Children. Blackwell Scientific Publications: Oxford. 1988:45-56.

    Greenberg RA, Rittichier KK.
    Pediatric nonenvironmental hypothermia presenting to the emergency department:
    Episodic spontaneous hypothermia with hyperhidrosis. Pediatr Emerg Care. 2003 Feb;19(1):32-4.

    Stolman LP.
    Treatment of hyperhidrosis.
    Dermatol Clin. 1998 Oct;16(4):863-9.

    Hornberger J, Grimes K, Naumann M, Glaser DA, Lowe NJ, Naver H, Ahn S, Stolman LP; Multi-Specialty Working Group on the Recognition, Diagnosis, and Treatment of Primary Focal Hyperhidrosis.
    Recognition, diagnosis, and treatment of primary focal hyperhidrosis.
    J Am Acad Dermatol. 2004 Aug;51(2):274-86.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge

    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement

    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    17. A therapeutic and ethically sound relationship with patients is created and sustained.

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

    Date
    July 28, 2008

  • What Causes Congenital Cholesteatomas?

    Patient Presentation
    A 3-year-old female came to clinic with a report from the local preschool that she had failed her screening hearing test in her right ear.
    Mother had not noted any problems hearing and said that she had 2 ear infections previously with the last one being more than 1 year ago.
    The patient was otherwise well except for an upper respiratory infection about 1 month ago.
    The family history was negative for any hearing problems and kidney problems.
    The review of systems was negative.
    The pertinent physical exam showed a happy, interactive female with no obvious gross hearing deficits during examination.
    Growth parameters were 75-90%. HEENT showed a small amount of fluid behind the tympanic membrane with no erythema and normal mobility bilaterally.
    The posterior 1/2 of the right tympanic membrane was obscured by cerumen.
    The physician diagnosed bilateral middle ear effusion. He ordered an audiogram to be done in 2 weeks to allow time for the effusion to clear.
    He also recommended over-the-counter cerumen drops to aid visualization at her follow-up appointment in 2 weeks.
    Two weeks later, the effusions had cleared but he thought that there was a possible mass behind the right tympanic membrane posteriorly.
    The audiogram also showed a persistent conductive hearing loss on the right.
    The patient was referred to an otolaryngologist who also agreed that there was possibly a mass behind the tympanic membrane.
    The radiologic evaluation by computed tomography of the head revealed a 2×3 cm mass inferior to the ossicles without erosion into the skull bones, clinically consistent with a diagnosis of a congenital cholesteatoma.
    The patient’s clinical course had her taken to the operating room for removal of the cholesteatoma. Unfortunately, it had eroded into the incus and head of the malleus but the other ossicles were salvaged.
    Ossicular reconstruction was planned in the future. A 2-week post-operative audiogram showed mild-moderate conductive hearing loss at some frequencies but improvement to normal at higher frequencies.
    A hearing aid was also prescribed to increase amplification.


    Figure 65 – Axial computed tomography images obtained
    without contrast of the right and left temporal bones at the same
    level demonstrate a 2 mm x 3 mm soft tissue lesion within the right
    middle ear cavity, inferior to the ossicles. The ossicular chain was
    intact. The lesion was felt to be compatible in appearance with a
    cholesteatoma.

    Discussion
    Cholesteatomas are an epithelial-lined sac that contains squamous debris that progressively expands, potentially causing morbidity and even mortality.
    They most often are acquired but can be congenital.
    Morbidity includes secondary infection of the lesion and/or middle ear structures, destruction of the ossicles with potentially permanent hearing loss, destruction of the skull bones, invasion into the cranial vault with compression of the brain and surrounding structures, and infection of the brain including abscess.

    Surgery usually is curative but recurrences of cholesteatomas do occur.
    One retrospective case review of 51 patients (35 of which were <18 years of age) found in patients with normal hearing prior to surgery, 72% of patients had their hearing preserved within 10 decibels of their preoperative level.
    However, 26% of patients had cholesteatoma recurrence and had worse hearing outcomes.

    Acquired cholesteatomas usually are due to chronic middle-ear disease.
    They can occur when squamous epithelium enters the middle ear in some manne: after placement of pressure-equalizing tubes or other surgery, through a spontaneous perforation of the tympanic membrane, or most commonly through a retraction pocket.
    Retraction pockets are invaginations of the tympanic membrane.
    Chronic eustachian tube dysfunction causes a vacuun to be created in the middle ear.
    This vacuun then causes collapse in a focal area of the tympanic membrane most commonly in the posterior-superior segment of the pars tensa, or in the pars flaccida toward the attic, or in an old perforation or instrumented portion of the tympanic membrane.
    As the collapsed area invaginates and expands, it closes up into itself creating a space that is lined with squamous epithelium. The squamous epithelium produces keratin debris, further increasing the size of the lesion and expanding locally into contiguous structures.
    The expanding lesion can also become infected itself or cause infections in the middle ear secondary to further obstruction of the eustachian tube.

    Cholesteatomas can be difficult to diagnose. Sometimes there is only an impression that something is behind the tympanic membrane or that the structures look different than other middle ear disease.
    Cholesteatomas should be considered if there is a whitish mass behind the tympanic membrane, there is focal granulation tissue of the tympanic membrane, a deep retraction pocket, a draining ear that doesn’t improve after 2 weeks of treatment or new onset hearing loss in a previously operated ear.

    Learning Point
    Congenital cholesteatomas occur anywhere in the temporal bone but most often in the anterosuperior quadrant of the middle ear.
    The exact origin of congenital cholesteatomas is unknown but many people believe these come from squamous inclusion cysts arising from epithelial rests in the middle ear. These are seen during fetal development, but most disappear by the third trimester. The failed involution of these epithelial rests leads to the congenital cholesteatoma.
    Other theories include infection and microperforation of the tympanic membrane leading to introduction of squamous epithelium into the middle ear or seeding of the middle ear with squamous cells from the amniotic fluid.

    Questions for Further Discussion
    1. How are the ossicles reconstructed after cholesteatoma removal?
    2. How should patients with abnormal screening audiograms be evaluated and/or treated?
    3. What chronic diseases have an increased risk of middle ear disease and therefore an increased risk of cholesteatomas?

    Related Cases

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

    Information prescriptions for patients can be found at MedlinePlus for these topics: Ear Disorders and Ear Infections and at Pediatric Common Questions, Quick Answers for this topic: Chronic Middle Ear Infections

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

    To view images related to this topic check Google Images.

    Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1255.

    Smouha EE, Javanshir J. Cholesteatoma in the Normal Hearing Ear. Layngoscope. 2007;117;854-858.

    Isaacson G. Diagnosis of Pediatric Cholesteatoma. Pediatrics. 2007:120;603-608.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

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

    Date
    July 21, 2008