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““Woe to the child who tastes salty from a kiss on the brow, for Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die”.he is cursed and soon must die”.
Cystic FibrosisCystic Fibrosis
Overview Definition.
Epidemiology.
Pathophysiology.
Diagnosis and clinical manifestations.
Treatment and outcome.
Anaesthetic implications.
Lung transplant.
Cystic fibrosis
Inherited disease that primarily affects the lungs and digestive tract of about 1200 children and adults in Ireland
Cystic Fibrosis in Ireland
Most common life threatening genetically inherited disease.
Highest proportion of CF population in world.
Carriers of CF gene 1 in 19.
About 50 new cases diagnosed each year.
About 55% of CF patient population aged 18 or older.
Median age of survival 20’S.In 2011 28 patients died aged between 13 and 54 yrs with average age at death of 23.5 yrs.
Demographic data from CFRI 2011.
Year 2011 %
Age range* <1-61
Mean age (yrs)* 19.6
Median age (yrs)* 18.8
Number diagnosed during year 22
Number of males* 612 57.0%
Number of females* 461 43.0%
Number <18 yrs* 514 47.9%
Number ≥18 yrs* 559 52.1%
Number males ≥18 yrs¥ 324 52.9%
Number females ≥18yrs¥ 235 51.0%
Irish ethnicity* 1049 97.8%
Deaths during year ∞ 28
CFRI enrolees alive at the end of 2011 1073
Pathophysiology -Cystic fibrosis
Genetics: Mutations in gene on long arm of chromosome 7 encoding for cystic fibrosis trans-membrane conductance regulator (CFTR) gene which encodes an epithelial chloride channel .
Cystic fibrosis gene mutations
•Commonest mutation – Delta F508
UK and Ireland Caucasians - 75%
UK and Ireland Asians - 29%
•Common mutation found in 1 in 10 UK Asians - Y569D (substitution G - T)
•Delta F508 and 28 others account for 85% mutations in the Northern European Caucasian population
Cystic fibrosis•Gland secretions thicker or more viscous than normal
•Small bowel: obstruction (meconium ileus in the newborn)
•Lungs : thick bronchial mucous, recurrent chest infections, progressive lung damage, heart/lung transplantation
Respiratory Viscid mucous secretion.
Decreased mucous clearance.
Bacterial trapping, proliferation and inflamation.
Chronic colonization of airway with microbes.
Bronchiectasis, cor pulmonale, death.
Cystic fibrosis
Microbiology Nearly half of all patients with CF are infected
with harmful bacteria such as S.aureus and/or P.aerginosa in their lungs.
Prevalance of A.fumigatus,S.maltophilia and MRSA have increased in last few years.
Microbiology S. aureus and H. influenza is more pravelent
in children with CF whereas P. aeruginosa, B. cepacia complex and A. fumigatus is more prevalent in adults with CF.
Antibiotics in trouble!
Gastrointestinal manifestations.
Obstructed pancreatic duct, decreased enzyme secretion, malabsorbtion of vitamin A, D, E, K, elevated fecal fat excretion and steatorrhoea.
CF related DM.
Focal biliary cirrhosis progressing to portal hypertension and multinodular biliary cirrhosis.
Bowel obstruction.
Other clinical manifestations
Nasal pathology
Skin.
Osteoporosis.
Infertility.
DiagnosisHistory and physical examination Clinical manifestations. History of cystic fibrosis in immediate family. Positive newborn screening test.Plus Sweat chloride levels Concentration >60 mEq/l. Genetic testing Documentation of dual CFTR mutation.
Median age at diagnosis in months by
symptom category, 2011.
Treatment Aims Minimize pulmonary infections.
Optimize nutritional status.
Slow disease progress.
Ease symptoms.
Respiratory
Physiotherapy. Inhaled bronchodilators,
hypertonic saline and mucolytics ( DNA ase).
Anti-inflamatory drugs. Oxygen therapy. Antibiotics.
Nutrition Requirements may be difficult to meet as
Increased requirement.
Pancreatic Insufficiency.
Lung disease.
CF Related DM.
Gastrointestinal treatment
Modified Diet
Vitamin supplements
High calorie diet
High Protein diet
Gene Therapy Gene therapy is the use of
normal DNA to "correct" for the damaged genes that cause disease.
In the case of CF, gene therapy involves inhaling a spray that delivers normal DNA to the lungs.
The goal is to replace the defective CF gene in the lungs to cure CF or slow the progression of the disease.
Treatment
•Gene replacement.
•Lung transplant for advanced disease..
•Treating the symptoms does not cure the disease, it can greatly improve the quality of life for most patients and has, over the years, increased the average life span of CF patients to 40 years.
Total number of deaths and median age at
death of PWCF, 1995-2011.
Principal cause of death 2002-2011.
Anesthetic implications
Major or minor surgery.
Site of surgery.
Duration of surgery.
Emergency or elective procedure.
Not suitable for day case surgery usually.
Preoperative assessment
Goal-Optimize patient as much as possible.
History, examination.
Continue regular medications, physiotherapy, nebulized drugs as late as possible pre-op.
Chest radiograph, baseline ABG, bedside spirometry (FEV1),Echocardiography.
Multidisciplionary approach.
Conduct of anaesthesia
Monitoring. Routine plus aterial line, CVC and cardiac output monitoring depending on patient and type of surgery.
Regional or General anaesthesia.
Airway management LMA or oral ETT. Humidified gases and low airway pressures.
TIVA or Volatile anaesthesia.
Limited use of NMB.
Intraoperative physiotherapy.
Post operative managment
Goal –minimize development of postoperative respiratory tract infection.
Good reversal of NMB,s.
Early extubation.
Early NIV.
Chest physiotherapy.
HDU monitoring or ICU ventillation.
Lung transplant in cystic fibrosis
The course of CF is very unpredictable, and that makes the timing for transplant more difficult
About 1600 CF recipients since 1991
120-150 recipients each year
Third largest group to get transplanted
CF recipients do better in general than non-CF recipients
Lung transplant and CF in Ireland
1991-2011-total number of lung transplants on Irish patients 134.(102 in UK and 32 in Ireland)
Total lung transplants-Cystic fibrosis 52%, Emphysema 15% and Idiopathic pulmonary fibrosis 15%.
Matter Lung transplants- 44% IPF, Emphysema 31% and 16% cystic fibrosis.
Transplantation Window of Opportunity—in an
Ideal World
Time
Clin
ical cou
rse
TOO SOON TOO LATE
Marshall SE, et al. Chest.
“Transplant window”
Transplantation Window
of Opportunity—in Reality
Time
Clin
ical cou
rse
TOO SOON? TOO LATE?
“Transplant window??”
Difficult Questions to Ask Before Organ Transplantation
When should a patient be referred for evaluation?
When should a patient be placed on the waiting list?
When should a patient have a transplant?
Referral for Lung Transplant
Patient readiness
Transplant team readiness and comfort level
Local transplant center culture
Wait times (less important now because of LAS)
Lung Allocation Score New scoring system since May 2005
“How bad you need it + How well you’ll do with it”
Applies to transplant candidates > 12 yrs
Scores range from 0-100
Scores can be updated
Lung Allocation Score: Clinical Information
Diagnosis
Age
Height and Weight (BMI)
Diabetes
Use of supplemental oxygen
Six minute walk distance
PASP
PCWP
FVC
Serum Creatinine
Functional Status
Assisted Ventilation
Consensus Guidelines for Referral of Lung Transplant Candidates
with CF FEV1 ≤30% of predicted with rapid, progressive respiratory deterioration Increasing number of hospitalizations Massive hemoptysis Recurrent pneumothorax Increasing cachexia Rapid fall in FEV1
Hypoxemia: PaO2 <7.3 kPa
Hypercapnia: PaCO2 >6.7 kPa
Early referral is recommended for young female patients, who have particularly poor prognosis
American Thoracic Society. Am J Respir Crit Care Med. 1998.Boehler A. Swiss Med Wkly. 2003.
Lung Transplantation in Adult CF Patients with History of Acute
Respiratory Failure
n = 17 (40%) Received lung transplants
n = 14 (82%) Alive at 1 year postoperation
N = 42 Admitted to ICU with hypercapnic respiratory failure
n = 19 (45%) Died in ICU
n = 3 (7%) Died within 6 months of ICU discharge
n = 3 (7%) Alive at 1 year without lung transplant
Sood N, et al. Am J Respir Crit Care Med.
Absolute Contraindications to Lung Transplantation
Cystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic Fibrosis. 1997.American Thoracic Society. Am J Respir Crit Care Med. 1998.
LungTransplant
Other major organ dysfunction
Infections affectinglong-term survival
Cardiovascular diseaseHIV
Liver disease: hepatitis CHepatitis B or C
Tuberculosis
Active malignancy <5 years
Renal failure: ClCr <50 mL/min
Other organ damage
Relative Contraindications to Lung Transplantation
Symptomatic osteoporosis
Substance addiction
Psychosocial problems
Nutritional status (<70% or >130% IBW)
High-dose corticosteroid use
Kyphoscoliosis
Invasive ventilation
Fungi or atypical mycobacteria
Pan-resistant organisms
American Thoracic Society. Am J Respir Crit Care Med. 1998.
LungTransplant
CF-relatedarthropathy
Survival of Transplant Recipients by Procedure Type
Trulock EP, et al. J Heart Lung Transplant. 2004.
0
20
40
60
80
100
Su
rviv
al (%
)
0 2 4 6 8 10 12 14 16 18 20
Years
Bilateral lung (N = 6686)
Single lung (N = 8581)
All lungs (N = 15,267)
Potential Surgical Complications of Lung
TransplantationComplication Prevalence (%)
Most serious
•Primary graft failure due to ischemia-reperfusion injury/diffuse alveolar damage
15-35
•Anastomotic complications: vascular or airway
7
Most common
•Phrenic/vocal cord paresis 3-30
•Gastroparesis 25-30
Zuckerman JB, et al. Clin Chest Med.Trulock EP. Am J Respir Crit Care Med.
Akindipe OA, et al. Chest.
Potential Medical Complications Following Lung Transplantation
Obliterative bronchiolitis (BOS/chronic rejection)
Acute rejection
Infection: viral, bacterial, fungal, protozoal
Toxicity of immunosuppressives Nephrotoxicity Hypertension Hirsutism, gingival hyperplasia
Diabetes
Hyperlipidemia
Post-transplant lymphoproliferative disease (EBV)
Zuckerman JB, et al. Clin Chest Med.Kurland G, et al. Curr Opin Pediatr.
Causes of Death in Lung Transplant Recipients
Trulock EP, et al. J Heart Lung Transplant. 2004.
0
10
20
30
40
50
60
70
80
90
0-30 days 31 days-1 year >1-3 years >3-5 years >5 years
Time after transplantation
Perc
en
t of
death
s
Technical complication Graft failure Cardiovascular diseaseInfection – Non-CMV Chronic rejection Malignancy – Non-lymphoma
Early complications Late complications
PROGNOSIS HAS IMPROVED,
BUT LIFE IS STILL SHORTER.