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Cystic Fibrosis, Emergency Medicine

Basics

Description

- Defect of the cystic fibrosis transmembrane conductance regulator (CFTR) - CFTR functions as an ATP-regulated chloride channel that regulates the activity of chloride and sodium channels on the cell surface: - Abnormal electrolyte transport in exocrine glands and secretory epithelia - Decreased exocrine pancreatic function with malabsorption - Thickened mucus, recurrent pulmonary infections, and progressive obstructive damage to the lungs - Recurrent sinus disease

- General: - Failure to thrive - Recurrent respiratory tract infections - Anasarca in infancy - Salty taste of skin

- Extremities: - Bone pain - Edema/joint effusions - Decreased thickness of cortical bone

- DNA analysis: - Indicated if symptoms are highly suggestive, but sweat test result is negative - 90% of CF chromosomes identified - Positive if 2 abnormal genes present - Genotyping cannot establish the diagnosis. - 1,300 CTFR mutations listed - Ameliorating or neutralizing 2nd mutation may be present.

- Abdominal radiographs and/or CT: - Indicated if abdominal pain, vomiting, or abdominal distention - Distal intestinal obstruction syndrome - Intussusception

- GI: - Chronic diarrhea - Gastroenteritis - Milk allergy

- DIOS: - Hematemesis: - Packed RBCs - Blood products for coagulation abnormalities - Early consultation with endoscopist

- H. influenzae: - Cefotaxime or ceftriaxone

- CFTR modulation: Ivacaftor - Repair of protein function

- Future directions: - Gene therapy: Compacted DNA - Anti-inflammatory: High-dose ibuprofen - Anti-infective agents: - Inhaled tobramycin, aztreonam, colistin - Continuous vancomycin infusion

- Transplantation: Inhaled cyclosporine - Nutrition and exercise

  • Defect of the cystic fibrosis transmembrane conductance regulator (CFTR)
  • CFTR functions as an ATP-regulated chloride channel that regulates the activity of chloride and sodium channels on the cell surface:Abnormal electrolyte transport in exocrine glands and secretory epitheliaDecreased exocrine pancreatic function with malabsorptionThickened mucus, recurrent pulmonary infections, and progressive obstructive damage to the lungsRecurrent sinus disease
  • Occurs in 1:3,600 live births in White population, 1:29,000 in African American population; 1:6,500 in Hispanic population
  • 30% of cases diagnosed by newborn screening
  • 75% cases diagnosed in the 1st 2 yr of life
  • ~30,000 children and young adults in US have CF.
  • Median life expectancy in US about 40 yr.
  • 40% of CF patients are older than 18 yr.
  • 10 million Americans are unknown, asymptomatic carriers of the defective gene.
  • 16% of lung transplants in US due to CF

Risk Factors

Genetics

Recessively inherited genetic disease, involving the CFTR gene on the long arm of chromosome 7: пїЅ

  • Different mutations; variable phenotypes.
  • Classic disease: Homozygous DF508 mutation.
  • Most common lethal genetic disease in US

Etiology

Common organisms in patients with pneumonia; often multiple drug resistance: пїЅ

  • Staphylococcus aureus:
  • Pseudomonas aeruginosa:Prevalence increases with age; >70% of adults are chronically infected.
  • Haemophilus influenzae
  • Stenotrophomonas maltophilia
  • Burkholderia cepacia:Prevalence 3%Associated with rapid clinical deterioration
  • Achromobacter xylosoxidans
  • Mycobacteria (nontuberculous):Mycobacterium avium complex, Mycobacterium abscessus
  • Aspergillus

Diagnosis

Signs and Symptoms

  • General:Failure to thriveRecurrent respiratory tract infectionsAnasarca in infancySalty taste of skin
  • Head, ears, eyes, nose, and throat (HEENT):Nasal polyps; severe headaches due to sinusitis; otitis media
  • Pulmonary:Persistent cough. Initially dry, then productiveRecurrent pneumonitis or bronchiolitis in 1st yr of lifeWheezingHemoptysisPneumoniaChronic bronchitisBronchiectasisRespiratory distressPneumothoraxPneumomediastinumMost common cause of CF hospitalization
  • Cardiac:CHFCor pulmonale; pulmonary hypertension
  • GI:Abdominal painMeconium ileusDistal intestinal obstructive syndrome (DIOS) or "meconium ileus equivalent"пїЅGastroesophageal refluxCholelithiasisPancreatitis/pancreatic insufficiencyIleocecal intussusceptionFoul smelling, fatty stoolsJaundice/cirrhosisRectal prolapseHematemesisSmall intestine bacterial overgrowth
  • Extremities:Bone painEdema/joint effusionsDecreased thickness of cortical bone
  • Recurrent venous thrombosis
  • Cardiorespiratory failure is most common cause of death.

Essential Workup

  • Sweat chloride test
  • DNA analysis if sweat test equivocal
  • Nasal potential difference if DNA inconclusive

Diagnosis Tests & Interpretation

Lab

  • Sweat chloride test:Chloride concentration >60 mEq/LWith classic signs and symptoms, a positive test result confirms the diagnosis.
  • Stool sample:Decreased elastase, trypsin, or chymotrypsinIncreased fat in 72-hr fecal fat excretion
  • Immunoreactive trypsin (IRT):Defines increased risk and/or diagnosisMay be falsely positive or negative
  • DNA analysis:Indicated if symptoms are highly suggestive, but sweat test result is negative90% of CF chromosomes identifiedPositive if 2 abnormal genes presentGenotyping cannot establish the diagnosis.1,300 CTFR mutations listedAmeliorating or neutralizing 2nd mutation may be present.
  • CBC:
  • Serum electrolytes:Hyponatremic, hypochloremic alkalosis
  • Serum glucose:Hyperglycemia and new-onset diabetes in adolescents and adults; ketoacidosis is rare.
  • Liver function tests and PT:Obtain if hematemesis or hemoptysis or signs of liver failure
  • ABG:Hypoxemia. Metabolic alkalosis
  • Sputum culture:May have pseudomonal colonization.
  • Studies indicated in high-risk patients with unclear diagnosis:Nasal potential-difference measurements:Complex and time-consuming studySemen analysis:

Imaging

  • Chest radiograph:HyperaerationPeribronchial thickeningAtelectasisHilar lymphadenopathyPneumothorax/pneumomediastinumBronchiectasisBlebsChest CT identifies blebs/bronchiectasis
  • Abdominal radiographs and/or CT:Indicated if abdominal pain, vomiting, or abdominal distentionDistal intestinal obstruction syndromeIntussusception
  • Barium enema:Indicated if suspicion of intussusception
  • Sinus films:Limited use because routine sinus films are always cloudyCT scan is needed to assess sinuses for pre-operative planning.

Diagnostic Procedures/Surgery

Bronchoalveolar lavage: пїЅ

  • High percentage of neutrophils and absolute neutrophil count
  • Unnecessary if obvious pulmonary symptoms

Differential Diagnosis

  • Respiratory:AsthmaRecurrent pneumoniaBronchiectasisPertussisImmunodeficiencyForeign body aspirationО±1-Antitrypsin deficiencyCiliary agenesis
  • GI:Chronic diarrheaGastroenteritisMilk allergy
  • Elevated electrolyte levels in sweat:FucosidosisGlycogen storage disease type IMucopolysaccharidosisHypothyroidismVasopressin-resistant diabetes insipidusAdrenal insufficiencyFamilial cholestasisFamilial hypoparathyroidismMalnutritionEctodermal dysplasiaAtopic dermatitisInfusion of prostaglandin E1

Treatment

Pre-Hospital

  • Transcutaneous pacing for unstable type II 2nd- or 3rd-degree block
  • Atropine:Avoid with type II 2nd-degree block because it may precipitate 3rd-degree block.

Ed Treatment/Procedures

  • Stabilize airway, breathing, and circulation:Correct fluid, respiratory, electrolyte, and glucose abnormalities.Bronchodilators/steroids if wheezing.
  • Pneumothorax:Observe if <5-10%.Thoracostomy
  • Consultation with the primary CF physician or pulmonary specialist
  • Right heart failure:
  • Hemoptysis:Blood products as indicated (check INR)Ventilatory support
  • DIOS:
  • Hematemesis:Packed RBCsBlood products for coagulation abnormalitiesEarly consultation with endoscopist
  • Intussusception:Correct with barium/air enemaMay require surgery
  • Rectal prolapse:Manual reductionConsider surgical consult
  • Respiratory care:Pulmonary toilet/physical therapyMucous thinning inhaled agents
  • Antibiotics for pneumonia:Based on culture and sensitivityS. aureus (MSSA):S. aureus (MRSA):P. aeruginosa:(Tobramycin or amikacin or colistin) + (piperacillin/tazobactam or ticarcillin/clavulanate or ceftazidime or imipenem/cilastatin or meropenem)S. aureus (MSSA) and P. aeruginosa:(Piperacillin/tazobactam or ticarcillin/clavulanate or cefepime or imipenem/cilastatin or meropenem) + (tobramycin or amikacin or colistin)S. aureus (MRSA) and P. aeruginosa:(Vancomycin or linezolid) + coverage for Pseudomonas aloneB. cepacia:Trimethoprim-sulfamethoxazole and/or meropenem and/or cipro and/or minocycline and/or chloramphenicolH. influenzae:Cefotaxime or ceftriaxoneSinusitisBased on cultures and sensitivities

Note: Ciprofloxacin may replace the aminoglycoside if sensitive pseudomonas пїЅ

  • CFTR modulation: IvacaftorRepair of protein function
  • Restore airway surface liquid:Nebulized hypertonic saline
  • Mucous alteration:Dornase alpha to thin mucus in lungs
  • Future directions:Gene therapy: Compacted DNAAnti-inflammatory: High-dose ibuprofenAnti-infective agents:Inhaled tobramycin, aztreonam, colistinContinuous vancomycin infusionTransplantation: Inhaled cyclosporineNutrition and exercise

Medication

  • Amikacin: 7.5-10 mg/kg IV q8h
  • Cefazolin: 100 mg/kg/d IV (max.: 6 g/d)
  • Cefepime: 50 mg/kg IV q8h (max.: 2 g/8hr)
  • Ceftazidime: 50 mg/kg IV q8h (max.: 6 g/d)
  • Colistin: 2.5-5 mg/kg/d IV, div. BID-QID
  • Imipenem/cilastatin: 15-25 mg/kg IV q6h
  • Meropenem: 40 mg/kg IV q8h (max.: 2 g/8hr)
  • Nafcillin: 25-50 mg/kg IV q6h (max. 2-3 g q6h)
  • Piperacillin/tazobactam: 350-450 mg/kg/d IV (max.: 4.5 g q6h)
  • Ticarcillin/clavulanate:300-400 mg/kg/d IV q6h
  • Tobramycin: 2.5-3.3 mg/kg/dose IV q8h
  • TMP-SMX: 5-10 mg/kg IV q12h (max.: 160 mg TMP q12h)
  • Vancomycin: 15 mg/kg q6h (max.: 1 g q6h)
  • Note: Because many patients are undernourished, pharmacokinetics of antibiotics (especially aminoglycosides, penicillins, and cephalosporins) may be altered, requiring careful monitoring.

Follow-Up

Disposition

Admission Criteria

  • Pulmonary exacerbation with significant deterioration from baseline, hypoxemia, resistant bacteria, failure of outpatient therapy
  • Pneumothorax
  • Hemoptysis
  • Hematemesis
  • Intussusception or unexplained abdominal pain or bowel obstruction
  • Hyperglycemia

Discharge Criteria

  • Close follow-up to verify the sensitivities of culture results and change therapy as needed
  • Avoid hot weather.
  • Oral salt supplement when profuse sweating

Issues for Referral

All patients followed by a pediatric pulmonary center. Consultation during acute exacerbations. пїЅ

Follow-Up Recommendations

  • Team approach of specialists
  • Breathing treatments, chest PT, exercise programs, antibiotics, replacement of pancreatic enzymes

Pearls and Pitfalls

  • With CF patients in respiratory distress, always consider pneumothorax: Obtain CXR.
  • For CF patients with abdominal pain/vomiting, always consider DIOS and intussusception

Additional Reading

  • Hoffman пїЅLR, Ramsey пїЅBW. Cystic fibrosis therapeutics: The road ahead. Chest. 2013;143:207-213.
  • Ryan пїЅG, Jahnke пїЅN, Remmington пїЅT. Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. Cochrane Database Syst Rev. 2012.
  • Willey-Courand пїЅDB, Marshall пїЅBC. Cystic Fibrosis. AAP: Pediatric Care Online 2013, www.pediatriccareonline.org.

Codes

ICD9

  • 277.00 Cystic fibrosis without mention of meconium ileus
  • 277.02 Cystic fibrosis with pulmonary manifestations
  • 277.03 Cystic fibrosis with gastrointestinal manifestations
  • 277.01 Cystic fibrosis with meconium ileus
  • 277.09 Cystic fibrosis with other manifestations
  • 277.0 Cystic fibrosis

ICD10

  • E84.0 Cystic fibrosis with pulmonary manifestations
  • E84.9 Cystic fibrosis, unspecified
  • E84.19 Cystic fibrosis with other intestinal manifestations
  • E84.11 Meconium ileus in cystic fibrosis
  • E84.1 Cystic fibrosis with intestinal manifestations
  • E84.8 Cystic fibrosis with other manifestations
  • E84 Cystic fibrosis

SNOMED

  • 190905008 Cystic fibrosis (disorder)
  • 86555001 Cystic fibrosis of the lung (disorder)
  • 190909002 Cystic fibrosis with intestinal manifestations (disorder)
  • 86092005 Cystic fibrosis with meconium ileus (disorder)
  • 81423003 Cystic fibrosis without meconium ileus (disorder)