Cystic Fibrosis an update for the Pediatric Anesthesiologist

Myron Yaster MD and Lynne G. Maxwell MD

When I was a pediatric intern in the 1970s, there were few patients I dreaded more than the patient with cystic fibrosis (CF) presenting in respiratory failure.  Treatment options were so very limited and most patients did not survive the first decade of life.  In fact, because it was so hopeless, patients who presented in respiratory failure were not intubated and ventilated and were provided morphine as palliative therapy.  How times have changed!  The last 50 years have shown remarkable improvements in longevity and quality of life.  Indeed, there are now more adults with CF than pediatric patients and the average age of patients with the disease is in the 50s.  As my wife Dr. Pam Zeitlin, an author of one of these articles, likes to say: “CF is now Cure Found”.  These 2 articles published within a month of each other describe the disease, its genetics, the various organ systems involved, new therapeutics, and perioperative anesthetic management.  Myron Yaster MD

Original articles

Amy J Lee, Julie L Huffmyer, Eryn L Thiele, Pamela L Zeitlin, Debnath Chatterjee.  The Changing Face of Cystic Fibrosis: An Update for Anesthesiologists. Anesth Analg. 2022 Jan 12. doi: 10.1213/ANE.0000000000005856. Online ahead of print. PMID: 35020677

Danielle M Williamson, Anshuman Sharma.   Cystic fibrosis in children: A pediatric anesthesiologist's perspective.  Paediatr Anaesth. 2022 Feb;32(2):167-173.  PMID: 34963200

Cystic fibrosis is caused by mutations in a gene on chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein.  CFTR is expressed in many epithelial cells including the airways, intestines, liver, reproductive organs, and sweat glands.  The abnormal CFTR produces multi-system organ disease primarily affecting the lungs, sinuses, pancreas, hepatobiliary system, and reproductive organs.(1,2)

We think most of you are familiar with the organ system manifestations of CF and we will refer you to these articles for more details.  We are going to concentrate today’s PAAD on new developments in CF, specifically modulator therapy and perioperative anesthetic management. 

Modulator Therapy

Aside from antibiotic, anti-inflammatory and chest physical therapies, modulator therapies are what have made CF “cured found”. The most important “CFTR modulators improve lung function, respiratory quality of life and reduce pulmonary exacerbations.  These are a group of novel drugs that improve the production, intracellular processing, and function of the defective CFTR protein. CFTR modulators are classified into 5 main groups: potentiators, correctors, stabilizers, read-through agents, and amplifiers. Potentiators are compounds that enhance the opening of the membrane channel, thus allowing anion conductance. Correctors enhance the conformational stability of CFTR, resulting in greater efficacy of protein folding and trafficking of mature CFTR protein to the plasma membrane. Stabilizers anchor the CFTR channel at the plasma membrane, thus preventing its removal and degradation. Read-through agents induce a ribosomal “over-reading” of a premature termination codon into the CFTR mRNA, thus enabling the continued translation to the normal end of the transcript. Amplifiers increase the biosynthesis of CFTR protein and are currently being investigated in clinical trials.” (1)

Anesthetic considerations

“Patients with CF are scheduled for various surgical and medical procedures, depending on the age group. Neonates may require a laparotomy or laparoscopy for meconium peritonitis or intestinal atresia. Children and adolescents with CF are frequently scheduled for nasal polypectomy, central venous access, or bronchoscopy and lavage. Adults with CF commonly present for cholecystectomy, endoscopic retrograde cholangiopancreatography, endoscopy for esophageal varices, chest tubes for recurrent pneumothorax, obstetric care, etc. Patients with advanced CF may undergo lung or liver transplantation.(3) 

“The patient’s scheduled nebulizer treatments (inhaled DNase, hypertonic saline, etc) should be continued until the start of the anesthetic and resumed postoperatively. Ideally, these procedures should be scheduled later in the day to allow ambulation and chest physiotherapy in the morning to assist with the expectoration of retained secretions. Short-term administration of inhaled beta-2 receptor agonists can be used as a rescue for CF patients with airway hyperresponsiveness from concomitant asthma or allergic bronchopulmonary aspergillosis.”(1)  Because many CF patients have insulin dependent diabetes routine perioperative insulin therapy to manage hyperglycemia is necessary. “CF patients commonly develop sinus disease and nasal polyps; therefore, nasopharyngeal airways must be avoided. There is a paucity of data comparing endotracheal intubation and supraglottic airways in patients with CF. The widespread use of laryngeal mask airways (LMA) has likely improved outcomes by facilitating spontaneous ventilation and avoiding tracheal instrumentation. The reduced ability to suction the trachea with an LMA does not appear to adversely affect postoperative pulmonary function.” In our experience, humidified vapor anesthetics (sevoflurane) help prevent inspissation of airway secretions and are potent bronchodilators.  We also recommend placing the largest endotracheal tube possible to facilitate suctioning and lavage and limiting tube obstruction.  “Early extubation is critical to avoid prolonged mechanical ventilation, which increases morbidity and mortality. Before extubation, chest physical therapy, lung recruitment maneuvers, and endotracheal suctioning should be considered to mobilize secretions and avoid atelectasis.”(1)  Finally, “patients with mild CF may be discharged home if they meet discharge criteria. On the other hand, patients with advanced CF on home oxygen and non-invasive ventilation (NIV) will require longer postoperative monitoring”.  NSAiDs are invaluable in post operative pain management and opioids may be used but cautiously.

Both articles review liver and lung transplantation management. The article by Lee et al also discusses the perioperative management of pregnancy.    

References

1.           Lee AJ, Huffmyer JL, Thiele EL, Zeitlin PL, Chatterjee D. The Changing Face of Cystic Fibrosis: An Update for Anesthesiologists. Anesth Analg 2022.

2.           Williamson DM, Sharma A. Cystic fibrosis in children: A pediatric anesthesiologist's perspective. Paediatr Anaesth 2022;32:167-73.

3.           Huffmyer JL, Littlewood KE, Nemergut EC. Perioperative management of the adult with cystic fibrosis. Anesth Analg 2009;109:1949-61.