(Cystic fibrosis of the pancreas)
Incidence is approximately 1 in 2500 live births in the Caucasian population; it is less in subjects in the black or asian race. Autosomal recessive transmission of a mutation of the CF gene located on the long arm of chromosome 7. It codes for a membran protein of 1480 amino acids called CFTR (Cystic Fibrosis Transmembrane Regulator), a low conductance Cl channel the opening of which becomes anormal in case of mutation. More than 800 mutations have been described but the most frequent (70% of patients in France) is a deletion of phenylalanine in position 508 (Δ508). Patients who are homozygous for the mutation Δ508 seem to be affected by a more severe form of the disease.
This mutation results in a insufficiency of the serous and mucous secretion of the exocrine glands, in particular of the sweat glands. The sweat test allows the diagnosis by showing high concentration in electrolytes, especially chloride.
The diseases affects mainly the respiratory system, the digestive tract and its exocrine glands (pancreas, liver and biliary tract), the sweat glands, and the reproductive tract. Clinical manifestations are variable and one can distinguish forms that are predominantly digestive and others affecting preferably the respiratory system.
Lung involvement :
A bronchopulmonary disease is constant and the speed of its aggravation determines the prognosis. It appears before the age of 1 year in 90 % of cases. It begins with a chronic cough, firstly dry and then productive and often accompanied by wheezing. The frequent bronchopulmonary infections cause a thoracic dystrophy (barrell chest and thoracic kyphosis) , bronchiectasis and digital clubbing signing the installation of a chronic respiratory failure. Repeated sinusitis and nasal polyposis (rare before the age of 5 years and after 20 years) are present.
The evolution is inexorably towards secondary infections: Staphylococcus aureus, Hemophilus influenza and, above all, Pseudomonas aeroginusa or other multiresistant organisms (Burkholderia cepacia, Aspegillus fumigatus, Mycobacerium avium…).
Respiratory insufficiency evolves by steps favored by secondary infections and eventually causes chronic hypoxia, first during the night then permanent, and lately hypercapnia. Pneumothorax developing from apical bubbles, and sometimes massive hemoptysis can suddenly complicate the condition and lead to death. Finally, pulmonary hypertension occurs because of chronic hypoxia and the hypercarbia. Supplementation of O2 and nocturnal non-invasive ventilation slow evolution. Cystic fibrosis is the main indication of lung transplantation of the young.
Digestive involvement: can occur in various forms
- meconium ileus is indicative of the disease in 10 to 15% of the cases: it can present as a delay in the evacuation of meconium or an occlusive syndrome secondary to obstruction of the terminal ileum by accumulation of thick meconium. Hyperosmolar enemas can soften and liquify this meconium enough to allow its his evacuation but in about half of the cases a laparotomy is necessary to evacuate this meconium by enterotomy. Small bowell obstruction may already be present in utero and produce volvulus, atresia, meconium peritonitis.
- rectal prolapse
- stercoral ileus, or distal intestinal obstruction syndrome, the functional equivalent of meconium ileus in infants and children. It is a source of recurring abdominal pain the differential diagnosis of which is is sometimes difficult with medical (pancreatitis) or surgical (appendicitis) pathologies.
Pancreatic involvement: the involvement of the exocrine pancreas is present in 80 % of cases and results in chronic diarrhea, made of greasy stool due to poor digestion of lipids and protein with multiple malabsorption, in particular of vitamins. It is responsible for failure to thrive that worsens with worsening of lung involvement and secondary infections. Risk of acute or recurrent pancreatitis.
Occlusion of the pancreatic ducts can cause a late destruction of the islets of Langerhans. Prevalence of diabetes mellitus is 30 % at the age of 30 years.
Hepatic impairment :
- 30-40 % of children with cystic fibrosis present liver damage prior to the age of 12 years. This impairment is usually asymptomatic. Histologically, it is sometimes associated with moderate hepatic steatosis with focal biliary cirrhosis.
- 5-10 % of patients develop multilobular cirrhosis before the age of 10 years with important portal hypertension at the origin of bleeding complications; the hepatocellular function is generally well preserved into adulthood.
- a gallstone disease is common.
Abnormalities of liver function tests are usually moderate: it is important to eliminate other causes of acute or chronic cytolysis before attributing them to cystic fibrosis. However, 50 % of infants with cystic fibrosis have abnormal liver function tests up to the age of 2-3 years. Treatment with ursodeoxycholic acid (20 mg/kg/d) started at the beginning of liver damage seems to slow the progression of liver fibrosis. One should look for sequelae of a hypersplenism , and the emergence of a hepato-pulmonary syndrome or pulmonary hypertension. Treatment: ligation of esophageal varices, prevention of malnutrition, possibly liver transplantation.
- frequent osteopenia, which can lead to costal or vertebral fractures: it is due to the combined effects of malnutrition, malabsorption of vitamin D, steroid treatment and a deficiency in sex hormones. Important source of chronic pain.
- children are particularly vulnerable to heat stroke following massive loss of NaCl in sweat.
Treatment is complex :
- digestive: pancreatic extracts, anti-acid agents, activators of peristalsis (cisapride, domperidone), bile acids;
- respiratory: bronchodilators, daily chest physiotherapy with 7 % hypertonic serum or specific secretions loosening agents such as dornase alfa (Pulmozyme®) ; anti-inflammatory (NSAIDs or corticosteroids), non-invasive ventilatory support (nasal mask) in the advanced forms;
- anti-infectious agents: IV or inhaled antibiotics (tobramycin, for example)
- nutrition: vitamins, trace elements, salt, nutrition assistance (enteral or parenteral), insulin therapy
- check SpO2 at room air, auscultation, pulmonary functional tests, liver function and blood : hemoglobin, platelets
- the criteria for severe respiratory impairment are a PaCO2 > 50 mmHg, a PaO2 < 55 mmHg at room air and a < 50 % FEV1.
- even in emergencies, take time shoud be taken to perform chest physiotherapy immediately before surgery: the goal is to reduce the risk of perioperative atelectasis and obstruction of the endotracheal tube. The usual treatments of the child will be continued on the morning of the intervention with the exception of aerosols of dornase (they increase secretions)
- anticholinergics are classically contraindicated
- inhalation induction can be used in advanced forms and children in unstable situations, IV induction is preferred. Induction dose of propofol often needs to be increased. In case of superficial surgery which does not lead to significant post-operative pain (PICC-line placement, for example), a well conducted general anesthesia does not lead to degradation of the clinical status or post-operative respiratory functional tests.
- if possible, regional anesthesia should be to improve postoperative comfort (and thus respiratory function) without using large doses of opiates
- intubation should be performed under deep anesthesia to prevent cough and bronchospasm. Ventilation should as gentle as possible to reduce the risk of barotrauma: the goal is to maintain the usual (room air) patient’s PaCO2 of the patient. Any sharp increase in ventilation pressures can be the first sign of a bronchospasm, tracheal tube obstruction or a tension pneumothorax.
- management of a gastro-esophageal reflux
- management of portal hypertension
- management of insulin-dependent diabetes
- management of hemoptysis: intubation with a double lumen tracheal tube or a bronchial blocker, embolization
- you can take the opportunity of a general anaesthesia with intubation for a bronchial toilet before the awakening of the child: this causes increased inspiratory pressure and breathing resistance and a decrease in respiratory compliance immediately after the respiratory physiotherapy. Even if this degradation is transient, the expected benefits (decrease of the risk of atelectasis and cough?) must be weighted against the risks and it helps to deepen the anesthesia during their realization.
- morbidity and postoperative mortality are correlated with the duration of intra- and especially postoperative ventilation the patient should be extubated as soon as possible. In case of abdominal surgery, the resumption of intestinal transit is slower and a subocclusive episode can occurs that is difficult to distinguish from a surgical or medical complication (e.g., hypokalemic ileus).
Updated: December 2018