What Causes Apnea in a Premature Infant?

Patient Presentation
A 1 week-old, 34-week gestation female began having apnea and feeding intolerance.
The past medical history showed a normal pregnancy until there was spontaneous rupture of membrances and contractions. She was delivered after 20 hours of labor.
She had no respiratory distress and had Apgar scores of 8 and 8.
Postnatally, she had hyperbilirubinemia that was treated with phototherapy. After her initial complete blood count revealed a normal white blood cell count of 4.6 x 1000/mm2 but neutrophils of 75%, she was begun on antibiotics which were discontinued after 3 days when the cultures were negative.
She was begun on oral/nasogastric feeds on day 2 of life which she tolerated. She was slowly advancing on her feedings when the nursing staff noticed that she was having some apneic spells that lasted 25-30 seconds. These responded initially to blow-by oxygen and stimulation. She then had a large gastric aspirate and her abdomen appeared distended on day of life 7.
The pertinent physical exam showed heart rate of 182, respiratory rate of 63 and blood pressure of 82/54 with appropriate for gestatation growth. There was a distended abdomen with no overlying erythema or organomegaly.
During the examination, she passed a stool that appeared to have blood in it and later was found to be hemoccult positive. As she was being evaluated and treated she had more apnea that responded to nasal continuous positive airway pressure.
The laboratory evaluation included an arterial blood gas that showed mild metabolic acidosis. The complete blood count showed a white blood cell count of 14.8 x 1000/mm2 with 80% neutrophils. The platelets were normal. The C-reactive protein was slightly elevated at 2.2 mg/dl.
The radiologic evaluation included an abdominal flat plate and cross-table lateral which showedthickened and dilated bowel loops in teh abdomen with a question of pneumatosis intestinalis. There was no free air in the abdomen or the portal system.
The diagnosis of necrotizing enterocolitis was made. Her feedings were stopped and she was begun on Gentamicin, Clindamycin and Ampicillin. She slowly improved with medical treatment and did not require surgery. On day 14 after the initial presentation, she was begun on enteral feedings that were slowly advanced.
The rest of her nursery stay was uncomplicated and she was discharged at 5 weeks of age.


Figure 34 – Supine AP radiograph of the abdomen shows dilated loops of bowel centered in the right lower quadrant. This alone can suggest early and developing necrotizing enterocolitis. There was a question of pneumatosis intestinalis within these dilated loops of bowel.

Discussion
Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in neonates. Mortality rates are from 0-45% depending on infant weight and gestation. Infants < 1000 g have mortality rates of 40-100%.
NEC usually occurs in premature infants but it also occurs in term infants. The etiology is unknown but is probably multifactorial with ischemia and/or reperfusion playing some role.
There are ‘outbreaks’ of NEC but no causitive organism has been identified. Regardless of the originating cause, inflammation of the intestine and release of inflammatory mediators causes various degrees of damage to the intestine.
Treatment includes stopping gastric feeding, antibiotics, possible surgery and other supportive measures such as treatment for hypotension and respiratory failure.

Presenting signs of NEC can be subtle but can include:

  • Feeding intolerance
  • Delayed gastric emptying – i.e. residual feeding left in the stomach
  • Apnea
  • Abdominal distention and/or tenderness
  • Bleeding diathesis
  • Blood in the stool – obvious or occult
  • Decreased bowel sounds – i.e. ileus
  • Erythema of the abdominal wall
  • Lethargy
  • Poor perfusion
  • Shock

Abnormalities on laboratory testing are nonspecific but can include:

  • Hyponatremia
  • Metabolic acidosis
  • Leukopenia
  • Leukocytosis with left shift
  • Neutropenia
  • Thrombocytopenia
  • Bleeding test abnormalities including prolonged prothrombin time, prolonged activated partial thromboplastin time, decreased fibrinogen and increased fibrin split products

Learning Point
Apnea is defined as a cessation of breathing for more than 20 seconds. It is often associated with bradycardia, cyanosis or both.

The most common cause of apnea in premature infants is apnea of prematurity where the mechanisms that usually ensure cerebral blood flow fail and hypoxemia, ischemia and possibly other complications may arise.
During apneic spells, blood is diverted away from the mesenteric arteries to try to preserve cerebral blood flow. This can cause intestinal ischemia and possibly NEC.

Other causes of apnea in premature infants includes:

  • Cardiac
    • Congestive heart failure
    • Cyanotic congenital heart disease
    • Pulmonary edema
  • Gastrointestinal
    • Gastroesophageal reflux
    • NEC
  • Hematologic
    • Anemia
  • Infectious
    • Perinatal infection/sepsis – especially on day of life 1
    • Nosocomial infection
    • Pneumonia
  • Medication
    • Prenatal – transplacental transfer, e.g. narcotics, beta-blockers
    • Postnatal – e.g. hypnotics, narcotics, sedatives
  • Metabolic
    • Acidosis
    • Hypocalcemia
    • Hypoglycemia
    • Hyponatremia
  • Neurologic
    • Increased intracranial pressure
    • Intracranial hemorrhage
    • Intraventricular hemorrhage
    • Perinatal asphyxia
    • Seizures
  • Pulmonary
    • Meconium aspiration
    • Surfactant deficiency
  • Other
    • Unstable temperature

Questions for Further Discussion
1. What evaluation should be completed for a newborn infant with apnea?
2. What causes bradycardia in infants?
3. What are some of the possibilities for surgical treatment for NEC?

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: Premature Babies

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

Klein J. Management of Neonatal Apnea. Iowa Neonatology Handbook.
Available from the Internet at http://www.uihealthcare.com/depts/med/pediatrics/iowaneonatologyhandbook/pulmonary/managementapnea.html (rev. 1/2006, cited 1/30/2006).

Springer, SC. Annibale DJ. Necrotizing Enterocolitis. eMedicine.
Available from the Internet at http://www.emedicine.com/ped/topic2601.htm (rev. 11/25/2002, cited 1/30/2006).

ACGME Competencies Highlighted by Case

  • Patient Care
    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 competency performed.
    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.

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

    Date
    February 27, 2006

  • What Are the Possible Complications of Juvenile Rheumatoid Arthritis?

    Patient Presentation
    A 6-year-old female came to clinic with > 3 week history of her legs bothering her in the night and swelling of both knees.
    The knees had been warm and swollen with intermittent pain unrelieved by ibuprofen.
    There was also occasional pain in both ankles.
    The past medical history revealed ear infections.
    The family history revealed osteoarthritis in grandparents and adult onset diabetes. The family denied other autoimmune or connective tissue disorders.
    The review of systems showed decreased appetite but no fever, weight loss, rashes, recent illnesses, travel history or pets.
    The pertinent physical exam showed normal vital signs, and weight and height were in the 50-75%. HEENT, cardiac and skin examinations were normal.
    Musculoskeletal examination revealed both knees to be swollen with considerable warmth medially but with full range of motion.
    The ankles were also bilaterally swollen with mild erythema and tenderness on range of motion.
    There was normal range of motion and no synovitis in all other joints.
    The laboratory evaluation initially showed a hemoglobin of 10.5 g/dl, hematocrit of 32%, with white blood cell count of 12.2 x 1000/mm2 with 7100 neutrophils.
    Liver function and hepatitis screening tests were normal. Erythrocyte sedimentation rate was elevated at 35 mm/hr, anti-nuclear antibody was elevated at 1:80 dilution, and the rheumatoid factor was negative.
    Because of the patient’s presentation and laboratory testing, the physician suspected juvenile rheumatoid arthritis. The patient was placed on Naproxyn and referred to a rheumatologist.
    Further evaluation and continued symptoms confirmed
    a diagnosis of pauciarticular juvenile rheumatoid arthritis.
    Over the patient’s clinical course a diagnosis of right-sided anterior uveitis was made and was being treated with prednisolone and Cyclogyl® eye drops.
    The patient began treatment with methotrexate and hydroxychloroquin and had improved symptoms 6 weeks later.

    Discussion
    Juvenile rheumatoid arthritis (JRA) is a group of diseases which have chronic joint inflammation and an unknown cause.
    Chronic synovial inflammation is associated with B cell lymphocyte, T cell lymphocyte and macrophage invasion and release of cytokines, which promote inflammation and sometimes destruction.
    Overall, ~10-20 cases/100,000 children occur in the U.S.

    The major classifications of JRA by the American College of Rheumatology are based on the clinical course over the first 6 months of illness.

    • Pauciarticular JRA
      • 60% of patients
      • Less than 4 joints, can occur in any joint but often knees and ankles, generally does not occur in hips and generally does not cause destructive arthritis
      • Two types:
        • Type 1, females > males, often patients are preschool age, rare in children > 10 years
        • Type 2, males > females, often patients are 9-11 years old
      • Extraarticular manifestations – uncommon except for uveitis occurs in ~20% of patients
      • Lab tests
        • Antinuclear antibody (ANA) – low titer
        • Rheumatoid factor – generally absent
        • HLA-B27 often present in Type 2
    • Polyarticular JRA
      • 30% of patients
      • More than 5 joints, can occur in any joint but often larger joints with symmetric involvement, generally does not occur in hips, destructive arthritis occurs in > 50% of patients
      • Females > males
      • Ages 2-5 years and 10-18 years
      • Extraarticular manifestations – fever, hepatosplenomegaly and lymphadenopathy, uveitis occurs in ~ 5% of patients
      • Lab tests
        • ANA – low titer in younger age group
        • Rheumatoid factor – common in older age group
    • Systemic-onset (also known as Still’s disease)
      • 10% of patients
      • Number of joints is variable with any joint possibly involved including hips, destructive arthritis occurs in > 50% of patients
      • Extraarticular manifestations – fever, hepatosplenomegaly, lymphadenopathy, polyserositis, rash, uveitis is rare
      • Lab tests
        • ANA – generally absent
        • Rheumatoid factor – rare

    Evaluation for possible JRA includes:

    • Laboratory testing
      • ANA
      • Complete blood count with differential – reduction of any and all cell lines may occur
      • Rheumatoid factor
      • Erythrocyte sedimentation rate – generally elevated
      • Alanine aminotransferase – to exclude hepatitis
      • Urinalysis – to exclude infection and nephritis
      • Other tests for systemic JRA
        • Total protein and albumin – increase or decrease with disease progression
        • Fibrinogen and D-dimer – increased with active disease
      • Radiographic evaluation
        • Plain film – for single joints to exclude other causes such as osteomyelitis or septic arthritis
        • Magnetic resonance imaging – with gadolinium injection can show increased inflammation of synovium
        • Computed tomography – to exclude osteoid osteoma as cause of bone pain
    • Other testing
      • Arthrocentesis – to exclude septic arthritis
      • Synovial biopsy – to esclude other diagnoses (e.g. granulomatous arthritis)
      • Echocardiogram – for possible systemic onset JRA with fever, to exclude pericarditis (pericardiocentesis may be needed to treat this), to help make the diagnosis of Kawasaki Disease or Systemic Lupus Erythematosis
      • Dual-Energy X-ray Absorptiometry (DEXA scanning) – to document osteopenia in polyarticular JRA

    Pharmacologic treatment mainly includes anti-inflammatory, immunosuppressive, and immunomodulator (e.g. tumor necrosis factor inhibitors, cyclooxygenase-2 inhibitors, etc.) medications. Consultations and co-management may be needed from social work, psychology, school, physical therapy, occupational therapy, surgery, ophthalmology, hematology, and gastroenterology.

    Learning Point
    Common complications for JRA include:

    • Pauciarticular JRA
      • Knee flexion contractures
      • Leg length discrepencies
      • Uveitis – Screening for uveitis is recommended every 4 months for ANA+ patients and every 6 months for ANA- patients.
    • Polyarticular JRA
      • Cervical spine abnormalities – subluxation, flexion difficulties
      • Skeletal abnormalities – accelerated bone age, narrow joint spaces, joint subluxation, increase in size of epiphyses
    • Systemic-onset JRA
      • Disseminated intravascular coagulation
      • Endarteritis with threatened digital autoamputation
      • Hemolytic anemia
      • Macrophage activation syndrome – all three hematological cell lines become rapidly decreased with massive release of cytokines
      • Pericarditis

    Questions for Further Discussion
    1. What specific medications are commonly used to treat JRA? What are their side effects?
    2. How is uveitis treated?

    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: Juvenile Rheumatoid Arthritis
    and at Pediatric Common Questions, Quick Answers for this topic: Juvenile Rheumatoid Arthritis (JRA).

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

    Miller M. Juvenile Rheumatoid Arthritis. eMedicine.
    Available from the Internet at http://www.emedicine.com/ped/topic1749.htm (rev. 1/4/2005, cited 12/12/2005).

    Robertson J, Shilkofski N. The Harriet Lane Handbook. 17th. Edit. Mosby Publications: St. Louis. 2005:648-652.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effecively 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.
    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.

  • Systems Based Practice
    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
    Associate Professor of Pediatrics, Children’s Hospital of Iowa

    Date
    February 20, 2006

  • What Evaluation Should be Done for Carbon Monoxide Poisoning?

    Patient Presentation
    A 14-year-old male was brought to the emergency room by ambulance after he was found sitting in his room groaning in pain in the early morning after his mother returned from her overnight work shift.
    The adolescent was lethargic but could answer questions. His mother quickly checked on other people in the home who were also either unarousable or in pain.
    The mother suspected carbon monoxide poisoning, tried to move all the family out of the home, and called for emergency services.
    With later questioning, the history revealed that a fireplace fire was lit in the late evening the previous night and was lit throughout the night.
    No carbon monoxide detector was in the home.
    Upon the ambulance’s arrival, he was placed on 100% oxygen. In the emergency room he complained of headache, nausea and vomitted once.
    The pertinent physical exam showed a lethargic but appropriate adolescent with a Glascow Coma Scale of 13. His heart rate was 145, respiratory rate was 22 and he had normal blood pressure.
    He was described as having reddish skin with bluish fingernail beds. He complained of muscle pain but had normal strength and tone. The rest of his examination was normal.
    The work-up included an electrocardiogram which showed sinus tachycardia.
    The radiologic evaluation showed a normal chest x-ray.
    The laboratory evaluation revealed an arterial blood gas of 7.4/40/300/-1 (pH/Carbon Dioxide/Oxygen/Base excess).
    The hemoglobin was 16.2 mg/dl, hematocrit of 47% with a white blood cell count of 25.6 WBC x 1000/mm2 with predominant polymorphonuclear cells.
    A creatinine phosphokinase level was 580 U/L (normal 40-200 U/L).
    The carboxyhemoglobin level was 26% (normal 1-3%) confirming the diagnosis of carbon monoxide poisoning.
    During the patient’s clinical course he was transferred to a regional children’s hospital which had hyperbaric oxygen treatment available and he received two treatments because of continued confusion and lethargy. His carboxyhemoglobin decreased to 0.5% with treatment.
    A consultation for neuropsychiatric testing was completed and showed some discrepancy between verbal and non-verbal testing but no memory problems.
    There was no previous testing available for comparison.
    He was discharged to home after the fireplace was fixed and the furnace also inspected. Other family members were discharged to home after appropriate treatment also. He was to follow-up with neurology and have repeated neuropsychiatric testing in 1-2 months.

    Discussion
    Carbon monoxide (CO) is a by-product of incomplete burning of carbon fuels.
    It is colorless and odorless and therefore difficult to detect.
    Common causes of CO poisoning are faulty or inadequately ventilated home heating sources (e.g. furnaces, fireplaces, kerosene heaters, etc.), automobiles with obstructed exhaust systems, gas-powered generators, home fires or tobacco smoke.
    Other sources may be recreational or employment related including propane-fueled forklifts, gas-powered concrete saws, swimming behind motorboats, being in enclosed spaces with ice-cleaning machines (i.e. Zamboni&reg) or automobiles (e.g. indoor tractor pulls, demolition derbys). Inhalation of methylene chloride vapors also can cause CO poisoning.

    CO binds to hemoglobin significantly more readily than oxygen (230-270 times more) and therefore, it causes toxicity by cellular hypoxia. CO can cause problems whether it is a chronic or acute exposure.
    CO binds to myocardial tissue even more readily than hemoglobin and therefore the heart is at high risk. Obviously the brain is also at high risk because of its need for a consistent oxygen supply.
    CO is eliminated through the lungs with a half-life at room air of 3-4 hours.
    Supplemental oxygen reduces the half-life to 30-90 minutes and hyperbaric oxygen (2.5 atmospheres at 100% oxygen) reduces it to 15-23 minutes.

    Chronic CO poisoning may present with the same symptoms but often presents with new changes in cognitive ability or gradual onset of neuropsychiatric symptoms.

    Common acute signs and symptoms:

    • Dermatologic
      • Cherry-red skin - is the classic description, often remembered by the saying, “cherry-red, you’re dead!”
      • Pallor

      • Cyanosis
    • Cardiac
      • Chest pain
      • Hypotension
      • Palpitations
      • Tachycardia
    • Gastrointestinal
      • Abdominal pain
      • Diarrhea
      • Emesis
      • Nausea
    • Musculoskeletal
      • Muscle pain secondary to rhabdomyolysis
    • Neurologic
      • Ataxia
      • Aggitation
      • Amnesia
      • Coma
      • Confabulation
      • Confusion
      • Depression
      • Distractability
      • Dizziness
      • Emotional lability
      • Gait disturbances
      • Hallucination
      • Headache – one of the earliest signs
      • Hearing and vestibular problems
      • Impaired cognition
      • Impaired judgement
      • Impulsivenss
      • Increased reflexes
      • Memory impairment – the most common neuropsychiatric finding
      • Papilledema
      • Psychosis
      • Seizures
      • Retinal hemorrhages
      • Visual acuity changes including hemianopsia
    • Respiratory
      • Dyspnea on exertion
      • Tachypnea (mild generally)
      • Pulmonary edema
    • Other
      • Fatigue

    Treatment includes:

    • Oxygen – 100% at room air begun immediately and possibly hyperbaric oxygen. The Undersea and Hyperbaric Medical Society offers a directory of locations where hyperbaric oxygen is available at: http://www.uhms.org/Chambers/Chambersearch.asp or Divers Alert Network (DAN) at Duke University can be contacted at (919) 684-2948.
    • Intensive care unit admission for management of neurological, cardiac, respiratory, renal or muscular disease
    • Outpatients who are asymptomatic with a carboxyhemoglobin levels less than 10% generally can be discharged home but with early follow-up and reduced activity for 2-4 weeks.
    • Prevention should be discussed at health maintenance visits including the importance of CO detectors with audible alarms in the home and proper maintenance of home heating equipment. In areas with snow fall, reminding parents to keep the exhaust system clear if stranded and running the motor for heat is important.

    Patients usually (~67%) have a full recovery. Variability of clinical severity, lab values, and outcome all limit prognostic accuracy.
    Poor outcomes are associated with cardiac arrest, coma, metabolic acidosis, extremely high carboxyhemoglobin levels, and head imaging abnormalities.
    Neuropsychiatric testing may have some prognostic ability in determining delayed cognitive problems.

    Learning Point

    Workup for CO poisoning often includes:

      Laboratory
      • Carboxyhemoglobin – confirmation of disease process and treatment indications
      • Arterial blood gas – screening for acid/base deficit, metabolic and respiratory status
      • Creatine kinase with MB fraction – screening for rhabdomyolysis and myocardial injury
      • Myoglobin – screening for rhabdomyolysis
      • Complete blood count – usually mild leukocytosis
      • Electrolytes and glucose screening for lactic acidosis, hypokalemia, and hyperglycemia seen in severe poisoning
      • BUN and creatinine – screening for acute renal failure secondary to myoglobinuria.
      • Liver function tests – screening for hepatic failure
      • Urine analysis – screening for chronic poisoning which may show albumin and glucose
      • Cyanide levels – screening if industrial fire or other possible exposure
      • Blood alcohol levels – screening for intentional and unintentional injury
      • Toxicology screens – screening for possible suicide attempt or co-toxicity

      Imaging Studies are sometimes done

      • Chest x-ray – usually normal
      • Computed tomography scan or magnetic resonance imaging of the head – looking for cerebral edema and focal lesions, most typically of the basil ganglia.
        Other tests

        • Electrocardiogram – screening for arrhythmias
        • Neuropsychologic testing – screening for cognitive deficits

    Questions for Further Discussion
    1. What are the components of the Glascow Coma Scale?
    2. What are the indications for hyperbaric oxygen treatment?

    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: Carbon Monoxide Poisoning
    and at Pediatric Common Questions, Quick Answers for this topic: Fire Safety.

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

    Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:363-364.

    Lucchesi M, Schochat G. Toxicity, Carbon Monoxide. eMedicine.
    Available from the Internet at http://www.emedicine.com/ped/topic315.htm (rev. 11/1/2004, cited 12/12/05).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effecively 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.
    7. All medical and invasive procedures considered essential for the area of practice are competency 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.

  • 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.

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

    Date
    February 13, 2006

  • What is the Differential Diagnosis of Hypokalemia?

    Patient Presentation
    A 14-year-old male came to the emergency room after he had an episode of loss of consciousness for 1-2 minutes.
    He regained consciousness on the way to the emergency room.
    He said he felt his heart racing and then loss consciousness. He has had 1 previous episode 9-12 months ago where he felt “shaky and weak”. Over the past month he has complained of general “weakness” but cannot describe it further. he says he has had fatigue for 4-5 years.
    He has missed some school because of the weakness. He has also had some muscle cramps that were short-lived.
    The family history was positive for heart attacks at an advanced age and some anxiety and depression. No arrhythmias or neurological problems were in the family.
    The review of systems was negative including fever, recent illnesses, travel, unusual diets or eating behaviors, and sexual activity.
    The pertinent physical exam reveals a well-developed adolescent with normal vital signs and growth parameters. He has normal skin and subcutaneous fat. HEENT had a normal dental examination. His heart had a normal rate and rhythm with no murmurs and good pulses.
    He had a normal neurological evaluation. His mood revealed some minor symptoms of depression. The rest of his examination was normal.
    The laboratory evaluation in the emergency room showed a potassium level of 2.6 mEq/L (normal 3.4-4.7 mEq/L) and magnesium of 1.0 mEq/L (normal 1.3-2.0 mEq/L).
    He received potassium and magnesium supplementation by IV. An electrocardiogram was normal and his beta-HCG was negative. The rest of his laboratory evaluation was normal at that time including electrolytes, BUN, creatinine, phosphorous, glucose, liver and pancreatic enzymes.
    He was hospitalized and repeated electrolytes, BUN, creatinine, glucose, creatinine phosphokinase, urinalysis, urine electrolytes and osmolality were negative.
    An abdominal ultrasound and urine toxicology screen were also normal.
    Consultation with cardiology and neurology were negative.
    A screening evaluation for psychiatric illness confirmed some concerns for depression but a fuller evaluation was needed.
    A nephrology consult was obtained and the diagnosis of Gitelman’s syndrome was considered.
    As the patient’s clinical course had shown no abnormalities since initial presentation, he was discharged to home on oral potassium and magnesium.
    He was to follow up with his local physician, psychiatrist and nephrologist for further evaluation and monitoring.

    Discussion
    Gitelman syndrome is a renal salt-wasting disorder that causes volume contraction and hypokalemia alkalosis. Hypomagnesemia occurs in ~50% of patients. It is an autosomal recessive disorder. Patients are born full term without polyhydramnios have normal weight gain and usually present in late childhood. They often crave salt. They may present with tetany or weakness secondary to hypomagnesemia. They also have low urinary calcium excretion.
    Treatment is potassium and magnesium supplementation.

    Bartter syndrome is often confused with Gitelman syndrome. Bartter syndrome also is a renal salt-wasting disorder that is autosomal recessive. These patients often have a history of polyhydramnios and prematurity. They commonly have failure to thrive in the first year of life. Older children also crave salt and may complain of muscle cramps or constipation because of chronic volume depletion secondary to renal salt losses.
    Treatment is centered on electrolyte supplementation but hypotonia and failiure to thrive can be difficult to treat.

    Learning Point
    Potassium is important for cellular homeostasis and is the most common intracellular cation. Most potassium is intracellular and total body potassium is ~50 meq/kg of body weight. The kidney is the final homeostatic mechanism for total body potassium.
    Potassium is filtered in the kidney and ~80% is reabsortion in the proximal tubule. Potassium is secreted in the descending limb of Henle
    with reabsorbing in the ascending limb. Potassium is again secreted in the distal tubules and collecting duct. Overall renal handing of potassium is affected by urine flow rate, plasma and luminal potassium concentration, delivery of sodium and chloride, availability of other nonabsorbable ions (e.g. sulfate, phosphate) and diuretics.

    The differential diagnosis of hypokalemia includes:

    • Gastrointestinal losses – normally the bowel secretes potassium into the lumen and reabsorbs sodium chloride
      • Stomach
        • Emesis
        • Nasogastric suctioning
        • Pyloric stenosis
      • Intestine
        • Diarrhea
        • Enema and laxatives
        • Enteric fistula
        • Malabsorption
        • Villous adenoma
      • Biliary system
        • Biliary drainage
    • Renal losses
      • Electrolyte abnormalities
        • Hypomagnesemia
      • Endocrine abnormalities
        • Cushing disease or syndrome
        • Congenital adrenal hyperplasia
        • Hyperaldosteronism
        • High renin states
        • Increased mineralocorticoid – medications such as Florinef&reg, chewing tobacco, licorice
      • Intrinsic renal abnormalities
        • Bartter’s Syndrome
        • Gitelman’s Syndrome
        • Renal tubular acidosis, types I or II
      • Medications
        • Antibiotics – e.g. amphotericin B, carbenicillin
        • Diuretics – especially thiazide, loop diuretics, osmotic diuretics
    • Shift to Intracellular space
      • Alkalosis
      • Barium intoxication
      • Familial hypokalemia Periodic Paralysis
      • Hypothismia
      • Na-K-ATPase stimulation – e.g. beta-2 agonists, catecholamines, insulin
    • Othis
      • Excessive sweating
      • Inadequate intake – e.g. anorexia nervosa or abnormal diets, over long time periods only 10 meq/L/day of K is sufficient to sustain life

    Questions for Further Discussion
    1. What is the laboratory evaluation for hypokalemia?
    2. What is the differential diagnosis for hyperkalemia?

    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: Metabolic Disorders

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

    Bakerman S. Bakerman’s ABC’s of Interpretive Laboratory Data. 3rd Edit. Interpretive Laboratory Data, Inc. Myrtle Beach, SC. 412.

    Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1652-53,1713.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effecively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients is gathised.
    3. Informed decisions about diagnostic and thisapeutic 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.
    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 othis 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.

  • 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
    Associate Professor of Pediatrics, Children’s Hospital of Iowa

    Date
    February 6, 2006