Cystic fibrosis (CF) is the most life-threatening, inherited recessive genetic disorder affecting Caucasians. The disease occurs equally in both males and females, with each parent of a CF child being a carrier of the CF gene. In Australia one child in 2500 is born with CF (Cystic Fibrosis Victoria (CFV), 2008), which is caused by a mutated gene resulting in abnormal regulation of chloride and sodium transport. The exocrine glands produce thick and viscous secretions with manifestations most apparent within the lungs and digestive system. The mucous in the lungs cause blockages in the airways which are difficult to shift. Gas trapping from mucous plugs lead to frequent infection and irreversible lung damage. Bronchiectasis occurs which involves dilatation of the airways with pooling of infected secretions. Blood vessels may rupture into the airway causing haemoptysis and death.
In the space of 70 years CF has moved from a little known genetic condition, usually fatal in infancy and early childhood, to a multi-system disorder now affecting as many adults as children (Hodson and Bush, 2007). The Australasian Cystic Fibrosis Data Registry in their 10th annual report recently reported at 31 December 2007 held records for 2639 people with CF, with an average age of 18.2 years. The median age of survival for persons with CF in 2007 was 30.7 years with no deaths reported for persons aged less than 15 years (Cystic Fibrosis in Australia (CFA), 2009). These are promising figures as medical and health services work to improve therapies and treatment plans in order to assist individuals with this chronic disease to have longer survival and greater quality of life. Life expectancy has doubled in the last 25 years, however between 1999 and 2006 life expectancy increased by eight years; from age 29 to 37 (Cystic Fibrosis Foundation (CFF), 2007). Dodge et al report that successive cohorts have realistically indicated that those born in the year 2000 will have a survival over 50 years of age (Dodge et al, 2007), thus emphasising the need for clearer guidelines for clinicians working in the pre-hospital setting. There is no cure for CF, however with better diagnostic tools and increased therapeutic treatment survival is now available. Increased survival brings with it an associated increase in pulmonary complications and disease processes in other organs.
Haemoptysis
Haemoptysis is a commonly reported manifestation within the CF population its incidence increasing with greater life expectancy (Flume et al, 2005). The most common causes of haemoptysis include bronchiectasis, active tuberculosis, fungal infections, lung cancer and mycetoma.
Cystic-fibrosis-related haemoptysis is believed to be a result of erosion of enlarged and tortuous bronchial arteries (Mack, et al, 1965; Schidlow et al, 1993), which arise after years of inflammation, chronic infection and associated bronchiectasis. It has been reported that in 90 % of cases the source of the haemoptysis is from the bronchial circulation (Yoon et al, 2002). Di Sant'Agnese et al reported haemoptysis occurring in 60 % of the adult CF population (di Sant'agnese and Davis, 1979), with massive haemoptysis occurring in approximately 4 % of patients (Flume et al, 2005). Moreover Penketh et al reported 62 % of their CF population suffered mild to moderate airway bleeding, with 10 % experiencing more severe haemoptysis (Penketh et al, 1987).
Minor haemoptysis is defined as blood streaking and is treated conservatively, whereas a major haemoptysis is defined as at least 240 ml in 24 hrs (Schidlow et al, 1993) and requires more aggressive management. Flume et al (2005) reported that massive haemoptysis was more common in those with severe pulmonary impairment (60 % of patients with massive haemoptysis had a forced expiratory volume in 1 second (FEV1), below 40 % predicted) and that such a haemoptysis increased morbidity and mortality, with 35 % of patients dying within a year. Median survival after the first major haemoptysis is 5 years. Other studies however have shown massive haemoptysis is not an independent risk factor for mortality (Schidlow et al, 1993; Barben et al, 2003; Efrati, et al, 2008) with all patients experiencing one such episode surviving 5–10 years following the initial event (Efrati et al, 2008).
Haemoptysis has a greater frequency in males and is associated with increased survival rates (Holsclaw et al 1970; Stern et al, 1978). This is supported with reports from The Alfred Hospital, Melbourne, Australia where records between July 1998 and June 2009 show there were 570 patients with CF diagnosed with haemoptysis, the majority of patients being male (58 %).
Major bleeding is a medical emergency given that it can cause obstruction of airways (i.e. asphyxiation), hypotension, infection, anaemia, exacerbations of infection, shock, exsanguination and respiratory failure (Brinson et al, 1998; Hodson and Bush, 2007). Importantly however, it is an avoidable cause of death, which has particular importance for pre-hospital clinicians. Similarly, minor bleeding is also known to cause infection and decrease pulmonary function so it is vital that appropriate treatment is also provided promptly.
In-hospital management
Hospital management of haemoptysis ranges from conservative treatment of bed rest and antibiotics for minor streaking to more aggressive therapies needed for major bleeds, such as bronchial artery embolisation (BAE), ligation or lung resection. In the setting of major haemoptysis using only conservative treatment of transfusions and supportive care, Holsclaw et al found this approach of medical therapy resulted in a high mortality rate (32 % experienced the terminal event within 48 hours of the initial episode) and a high morbidity rate (Holsclaw et al, 1970). Alternatively Stern et al reported more success using only medical management in all of whom survived the acute episode of haemoptysis (Stern et al, 1978).
In the case of major haemoptysis resuscitation may be required. Patients should be placed in a dependant position, to keep the unaffected lung clear. Sufferers should continue with physiotherapy regimes making slight adjustments in regard to vigorous coughing, rather huffing to eliminate clots or plugs (Wilson et al, 2006). Medications which interfere with coagulation should be discontinued (e.g. aspirin, penicillin, and other non-steroidal anti-inflammatory drugs), while vitamin K, to correct coagulopathy, and blood transfusions should be considered (Schidlow et al, 1993; Hodson and Bush, 2007). Supplemental oxygen is essential and should be given as required (Hodson and Bush, 2007). Positive pressure techniques are not recommended for these patients and should be withheld for moderate and major haemoptysis (Flume et al, 2010; Cystic Fibrosis Trust, 2011). Non-invasive ventilation may aggravate vessels and exacerbate bleeding, and it has been suggested that vasopressin be used for its vasoconstriction properties (Schidlow et al, 1993; Hodson and Bush, 2007). Bilton et al reported immediate termination of profuse bleeding in CF with pressor agents; desmopressin and vasopressin (Bilton et al, 1990). Some researchers also propose the use of tranexamic acid (TXA) therapy for patients with CF, reporting effective use of TXA in controlling bleeding (Chang et al, 1996; Wong et al, 1996; Graff, 2001) where repeated BAE is unsuccessful. Astedt reports TXA is an antifibrinolytic agent of high clinical value for the treatment of bleeding (Astedt, 1987).
‘Sufferers should continue with physiotherapy regimes making slight adjustments in regard to vigorous coughing, rather huffing to eliminate clots or plugs’
Prior to the routine use of BAE, patients suffering haemoptysis were treated conservatively, with the above mentioned therapies namely bed rest and antibiotics; otherwise they were considered for surgical intervention. Such surgery has become an increasingly unpopular choice with lung resection and lobectomy reporting high operative mortality (Holsclaw et al, 1970). Use of BAE was first reported in 1973 (Remy et al, 1973), and is considered by many the first line treatment of massive haemoptysis where conservative treatment has failed. The Alfred Hospital CF service reports of their 570 patients diagnosed with haemoptysis, 57 embolisations were performed over an 11-year period from July 1998 to June 2009. Embolisation of blood vessels was performed on 15 females (26 %) and 42 males (74 %). This treatment, which has continuously improving techniques, is considered a safe, nonsurgical, and effective therapeutic tool in the setting of major haemoptysis (King et al, 1989; Cohen et al, 1990; Cipolli et al, 1995; Brinson et al, 1998; Fartoukh et al, 2007; Lee et al, 2008; Serasli et al, 2008; Shigemura et al, 2009).
Cessation of haemoptysis is achieved more immediately with BAE in 84 %–98 % of cases (Sweezey and Fellows, 1990; Barben et al, 2003). It is stressed that BAE should be done by an experienced interventional radiologist (Brinson et al, 1998). However, treatment of massive haemoptysis with BAE indicated a decreased survival compared with control CF patients matched for age, sex and FEV1 who had never bled severely (Sweezey and Fellows, 1990).
Methods
The following case series from a single centre (The Alfred Hospital, Melbourne, Australia) of adult CF patients experiencing major haemoptysis. This audit was undertaken to better understand the issues or difficulties with such patients and provide important data in the development of a proposed set of prehospital clinical guidelines.
Design
A retrospective single centre experience of four massive CF haemoptysis patients is reported. Patients were adults of The Alfred Hospital CF service. A total of 350 cases were gathered from The Alfred, which has experience of treating CF patients in Victoria, Melbourne over a 15 year period. Medical records were audited and data was extracted of those patients who suffered massive haemoptysis.
Procedures
An ethics application was submitted to audit deceased CF patients with haemoptysis complications to The Alfred ethics committee. Ethical approval was granted (Project 160/09) and medical records were requested for retrospective analysis. The additional medical records of one patient were also sought from health information systems of another hospital for the purposes of gaining a clear history of events. This case was particularly relevant for this paper offering important information towards the proposed recommendations.
Cases reviewed
Case 1
The patient was a 33-year-old male, diagnosed with CF at six weeks of age. He had severe lung disease (FEV1 of 0.98 l; 23 % predicted), and a BMI) of 19.7. He was pancreatic insufficient (PI) and ha bronchiectasis. He was known to have suffered small haemoptysis and received conservative treatment of TXA. Returning to hospital from a day leave the patient developed massive haemoptysis in the taxi. The gentleman was driven back in the taxi to the emergency department in respiratory arrest. He was immediately intubated and ventilated by the attending physician. Bronchoscopy revealed significant bleeding in the major airway, with progressive gas trapping and decreasing tidal volume, manual ventilation was discontinued and on extubation the patient died.
Case 2
The patient was a 49-year-old woman, diagnosed with CF in her mid-thirties. Her lung function was 46 % predicted with a FEV1 of 1.20 l and a BMI of 17.7. She was pancreatic insufficient, had bronchiectasis, and suffered gastroesophageal reflux disease (GORD) for which she underwent a Nissen's fundoplication, a surgical procedure used to strengthen the valve in order to prevent reflux of gastric acid. She suffered ongoing problems with haemoptysis, with multiple admissions to hospital and continued producing fresh blood on a regular basis. After episodes of haemoptysis she was treated with a BAE and transfusions. She was on the transplant waiting list due to life-threatening haemoptysis, however the patient died at home after massive haemoptysis a short time later.
Prior to her death the patient had an episode of life-threatening haemoptysis. The patient experienced a 600–700 ml haemoptysis one night at home and collapsed. The Metropolitan Ambulance Service was called to attend and paramedics arrived shortly after finding the patient unconscious and cyanosed with a soiled airway (blood). Initial oxygen therapy was commenced and Mobile Intensive Care Ambulance (MICA) paramedics were requested by the initial paramedic crew. Pre-hospital management included 100 % oxygen, intravenous access, endotracheal intubation and significant airway suctioning en-route to hospital. The patient was in sinus tachycardia, hypotensive with an oxygen saturation of 46 %, with poor air entry to her left lung. At hospital the patient received crystalloids, blood transfusion, x-ray and continual suctioning of airways. The patient's CF physician was consulted for further treatment plan, who advised to lay patient on her left side, re-intubate with double lumen tube and urgent transfer to The Alfred for further management. The patient was transferred, embolised, extubated and weeks later discharged home.
Case 3
The patient was a 39 year-old-male with a FEV1 of 0.85l, 27 % predicted and a body mass index (BMI) of 22.2. He was PI, had CF related diabetes, CF arthropathy, bronchiectasis and GORD. He had continuous therapy for recurrent haemoptysis and had been treated with TXA in the past. En-route home from discharge from hospital the patient experienced an episode of coughing and haemoptysis, major haemoptysis followed. An ambulance was called but the patient unfortunately could not be revived with ambulance patient care record not available for review. Autopsy results revealed bilateral haemorrhage within bronchiectatic cavities, with blood throughout the bronchial tree.
Case 4
The patient was a 22-year-old female; she had moderate lung disease with a FEV1 of 1.72 l, 50 % predicted and a BMI of 18.3. She had bronchiectasis and PI. She had suffered major haemoptysis in the past and was treated conservatively with antibiotics. The patient was admitted to a nearby tertiary hospital (non CF specialist centre) as she suffered a severe and catastrophic haemoptysis. She underwent immediate angiography and BAE. No further bleeding was detected, though she developed severe respiratory failure associated with sepsis and myocardial dysfunction, dying after a few weeks in the intensive care unit.
‘Two patients died in hospital and two out-of-hospital suggesting the need for prompt reactions by pre-hospital clinicians to definitive care’
Case discussion
These four case studies highlighted several similarities. The most important being the fact that all four shared a previous history of haemoptysis, thus indicating their potential for more serious bleeds. Their individual treatments all varied for this condition from the used of TXA, BAE and antibiotic therapy. Thus it would appear that it is important to determine early whether patients are predisposed to such bleeding by obtaining a thorough patient history and undertaking a clinical assessment. The patients also all had PI, bronchiectasis and a BMI < 22.2, though these traits are common among the CF population.
Lung function did not show any association with haemoptysis and severity of pulmonary impairment, with two patients having FEV1 below 27 % with the other two above 46 % predicted. Two patients died in hospital and two out-of-hospital suggesting the need for prompt reactions by pre-hospital clinicians to definitive care. This is paramount, and where possible these individuals should be be taken to a hospital that is aware of the lung condition so that they can receive the correct treatment. If geographical distance to CF specialist centre and patient condition are not optimal, it is recommended the patient be taken to the nearest emergency department for stabilisation and early contact be made with CF specialists for early transfer and optimal treatment regimes.
Based on these findings, this paper proposes a clinical guideline (Table 1) for the pre-hospital clinician to employ in the setting of haemoptysis as a means of providing best available treatment for the CF patient population. This is important as no Australian ambulance service has specific haemoptysis guideline/treatment recommendations, and the literature is replete on any pre-hospital best practice.
| Initial management |
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| If mild or moderate haemoptysis |
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| If Severe haemoptysis |
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Pre-hospital management
The proposed guideline below provides the pre-hospital sector, and more broadly, the paramedic discipline with a body of knowledge yet to undertaken in Australia. The authors of this paper see this recommendation as important for pre-hospital clinicians to correctly identify, and manage the CF patient suffering with haemoptysis. The recommendation is compiled from a combination of hospital practice, available emergency medical resources, and patient need.
While this proposed guideline has the potential to benefit pre-hospital clinicians, it also has the potential to be useful in other non-CF sufferers of haemoptysis. It is hoped that this proposed clinical practice recommendation will be considered by the respective medical standards committee as potential for integration into clinical practice guidelines around Australia. It might also be considered to be included in undergraduate curricula and continuing education programs for qualified paramedic staff.
Discussion
The association between CF and haemoptysis has been widely reported. Bleeds ranging from mild blood streaks or spots in sputum to chronic persisting haemoptysis are commonly experienced by the CF patient. Although in the paediatric population as Roebuck et al report, the incidence of airway bleeding is an unusual event (Roebuck et al, 2008). The US patient data registry reports most sufferers of major haemoptysis being 16 years or over (Cystic Fibrosis Foundation (CFF), 2007). These data are consistent with other literature, that state a greater prevalence occurs in older patients; mean age 24.2 +/− 8.7 years (Flume et al, 2005). These statistics also support the Australian data.
The Australian Cystic Fibrosis Data Registry (ACFDR) reports major haemoptysis is most prevalent in the 15–19 year-old aged group, followed by those aged between 20–24 years (Cystic Fibrosis in Australia (CFA), 2009). The amount of blood lost can be difficult to estimate, although as stated by Jones and Davies in episodes of massive haemoptysis it is not the volume of blood loss which is important, but the threat of asphyxiation (Jones and Davis, 1990). The surface of gas exchange must be protected, else poor prognosis and fatal outcome follows. Moreover, even much milder recurrent episodes of haemoptysis can cause increase in exacerbations and infection leading to devastating decreases in pulmonary function and destruction of lung parenchyma, therefore resulting in lower survival rates (Cohen et al, 1990; Vidal et al, 2006). Therefore, it is paramount that all episodes of haemoptysis are treated promptly and effectively to achieve best outcome for patients. Even small decreases in lung function can lead to decline in patients' quality of life. This point is emphasised as an important factor in the pre-hospital recommendation above, whereby early detection and identification is seen as critical in the patient management continua. It also raises other issues surrounding the level of education and training pre-hospital clinicians receive on respiratory emergencies such as CF.
The incidence of airway bleeding increases as life expectancy trends continue to improve and the erosion of bronchial arteries from years of the disease progression rupture. Episodes of haemoptysis occurring in patients with CF can result in fatal outcomes as previously mentioned. In the four cases investigated patients' age ranged from 22 to 49 years with lung function varying from moderate to severe impairment. Comparison between these patients showed all suffered from bronchiectasis and PI, with some patients also having disease processes present in other organs. Efrati et al in a recent study, which compared CF haemoptysis with control groups, reported no significant difference between groups when looking at PI, BMI or severity of lung disease (Efrati et al, 2008). Also evident was the fact that for all patients this was not the first episode of haemoptysis. All had suffered mild, moderate and/or severe bleeds in the past. Brinson et al suggests mild episodes of airway bleeding may be cautionary of impending massive haemoptysis (Brinson et al, 1998). Though it is reported that such episodes of major haemoptysis do not have a poorer prognosis than patients with comparable disease who have never bled profusely (Stern et al, 1978; Schidlow et al, 1993).
As the retrospective review demonstrated, the four cases of massive haemoptysis in patients suffering with CF all ended with fatal outcomes, and unfortunately for the sufferers, severe haemoptysis came without notice or warning. In these cases appropriate treatment regimes were followed or treatment with definitive care was simply out of reach and unavailable. Two of the patients were able receive care from tertiary hospitals with the other two patient's dying before reaching definitive care. Treatment of haemoptysis in the hospital setting is widely reported, with regimes ranging from the ultra conservative option of bed rest to radical lung resections. Though the hospital setting has many treatments and protocols in place to treat such an event the Australian pre-hospital sector appears to have no policy to follow or literature in which to make recommendations. It is important the pre-hospital clinician is well informed of the evidence-based treatment when faced with the CF patient suffering haemoptysis.
The study is not without its limitations however, as the examination of only four patients from one geographic location reduces the generalisability of results. However, clinical findings from this review at worse should serve the pre-hospital clinician with a simple guideline when faced with such an episode of airway bleeding in CF patients. The authors would encourage further examination of this proposed guideline by international colleagues.
Conclusion
By introducing pre-hospital clinicians with a proposed haemoptysis clinical guideline, it is hoped CF haemoptysis sufferers can be recipients of improved outcomes with correct, appropriate and expedient delivery of care. It is paramount that early recognition precipitate prompt delivery of treatment, ensuring patients and professionals alike can be confident all is being done to accomplish positive outcomes for long term health of CF suffers.