Patients with cystic fibrosis should be intubated and ventilated

Introduction

Although chronic respiratory failure remains the primary cause of mortality in cystic fibrosis (CF), the natural history of the disease remains unpredictable. Patients are surviving longer, with an increased incidence of CF-related complications such that the CF team is not infrequently faced acutely with a critically-ill patient.

CF critical care

It was barely conceivable 30 years ago that a CF patient would come under the care of the intensivist, but times have changed and perhaps CF critical care is no longer an oxymoron, as eloquently phrased in a relatively recent editorial on the outcomes of intensive care unit (ICU) care in adults with CF.^1,2 However, ICU outcome data on CF patients remain somewhat sparse, especially with regard to intubation and ventilation. Reports are often from a single centre and retrospective in nature.^2–4 There are also some caveats which need to be taken into consideration. There are clear differences in ICU practice between the USA and the UK in relation to CF patients requiring antibiotic desensitization, intercostal drains, bronchial artery embolization (BAE) and indeed non-invasive ventilation (NIV); such patients are more likely to be managed on the CF unit or a respiratory ward rather than the intensive care unit in the UK.² Furthermore, some reports of ICU survival include patients transplanted from ventilator, which is not usual practice in the UK.^2,3

Are there any circumstances in which a patient with CF should be intubated and ventilated? Almost certainly the answer is ‘Yes’, and there is little debate when it comes to non-respiratory CF complications, such as the need for intubation and anaesthesia for general surgical intervention. There is perhaps more debate when it comes to intubation for respiratory failure precipitated by potentially reversible respiratory complications, such as massive haemoptysis and complex pneumothorax. However, the heart of the debate probably revolves around consideration of intubation for an acute respiratory exacerbation on the background of inexorable chronic respiratory decline. It is this scenario that leaves the CF team, the family and indeed the patient with the most difficult decisions. These scenarios will be discussed in turn.

Intubation for non-respiratory CF complications

Beyond the need for surgical intervention in neonates with complicated meconium ileus, increasing age brings an increased risk of distal intestinal obstruction. Resulting small bowel obstruction unresponsive to conventional treatment will inevitably lead to urgent surgical intervention. In all but those at the end of life, this would be a viable option irrespective of the anaesthetic risk of advancing lung disease. Simple massage of the small bowel contents through the ileocaecal valve, enterotomy and plug removal ± ileostomy formation may all be life-saving.

With early recognition of CF-related liver disease and portal hypertension and the introduction of endoscopic surveillance of varices, it is hoped that variceal bleeding will be less common. However, in a patient presenting with massive haematemesis from oesophageal varices the CF team has no option but to revert to the basics of ABC, airway, breathing and circulation. The need to protect the airway may necessitate intubation, with or without oesophageal balloon tamponade using a Sengstaken-Blakemore tube. Survival following resuscitation and intubation for massive variceal bleeds has been reported.^3,5,6

There are, of course, many situations where a CF patient may present acutely, irrespective of lung function and need intubation for either a surgical procedure or airway protection as illustrated by the above two scenarios, neither of which are likely to cause any great debate. Debate is more likely when it comes to potentially reversible respiratory complications.

Intubation for reversible respiratory CF complications

Minor haemoptysis is common in CF, with up to 60% of adults reporting symptoms at some point in their life. It is relatively easily controlled with treatment of any underlying infection, ± tranexamic acid. Massive haemoptysis (>240 ml in a 24-hr period or recurrent bleeding >100 ml/day over several days) is fortunately less common, occurring in less than 1% of all patients.⁷ Although more common with increasing age and severity of lung disease, massive haemoptysis is not confined to those with severe disease and can rapidly threaten life due to airway obstruction, asphyxiation and hypovolaemia.⁸ Beyond routine treatment with oxygen, fluid resuscitation, correction of coagulopathy and intravenous vasopressin, endobronchial tamponade and selective or double-lumen intubation may need to be considered to control bleeding while awaiting BAE.⁹ Other more stable patients unable to tolerate BAE, especially the young or those unable to lie flat or with intractable coughing, may require intubation and a general anaesthetic to allow BAE to safely proceed. However, massive haemoptysis has been reported during anaesthesia for BAE, probably relating to factors associated with intermittent positive pressure ventilation (IPPV) and, therefore, intubation in a stable patient should not be taken lightly.^8,10

Spontaneous pneumothorax is not unusual in CF, with an annual incidence of 0.64%, and is more common in older patients with more severe lung disease.¹¹ Approximately 16–20% of patients with CF >18 years of age will experience a pneumothorax at some time in their lives, and 75% of those will have an FEV₁ <40% of predicted.¹¹ Intercostal drain insertion (ICD) ± suction may provide a simple and rapid solution. However, pneumothoraces are often complicated in CF, may not respond to such measures, and may precipitate respiratory failure. It is suggested that such patients be referred after ∼3 days to the local cardiothoracic surgeons for possible video-assisted thoroscopic surgery (VATS) to staple blebs and/or to abrade the pleura under general anaesthetic using double-lumen intubation. Thomas et al. reported an excellent outcome, with 14 of 16 patients admitted to ICU surviving to hospital discharge and 11 alive 6 months following surgical procedures on 18 occasions (16 for surgical pleurodesis).⁴ Furthermore, pleural procedures are generally not considered a contraindication in the assessment of suitability for lung transplantation.¹²

Predicting survival in these scenarios is hampered by the scarcity of published data. Sood et al. reported on 33 admissions to ICU among 15 patients with massive haemoptysis: 12 patients had BAE and 86% were alive at 1 year.² It is unclear how many, if any, were intubated. A further three patients admitted with respiratory failure precipitated by pneumothoraces were also alive at 1 year.² All three required an ICD, but only one required intubation, another required non-invasive ventilation (NIV), and the third neither. Two received transplants although it is not clear how long after the pneumothorax this occurred.

Massive haemoptysis and pneumothorax are both bad prognostic indicators and survival following intubation may be an indication for early transplant assessment, even with an FEV₁ >30% of predicted, as these patients have a greater 2-year mortality rate compared to uncomplicated patients with comparable lung function.^7,11

Intubation for respiratory exacerbations in CF

Predicting survival in CF is notoriously difficult, with the cut-off value of an FEV₁ of less than 30% being an unreliable predictor of high risk of death and more complex predictive models being of little additional benefit.^13,14 Nevertheless, a palliative approach would be more appropriate for a patient in the terminal phase of chronic respiratory decline and the pros and cons of intubation and resuscitation should be discussed well in advance with both the patient and the family. When intubation would clearly not be in the patient's best interests then there is likely to be little debate about the palliative approach being more appropriate. The current debate centres more on those patients with sudden respiratory decline, perhaps secondary to a bacterial or viral pneumonia.

Invasive mechanical ventilation (IMV) with the need for sedation has clear detrimental effects in CF, not least the ensuing hindrance to physiotherapy, communication with family, friends and the CF team, and should of course be avoided where possible. Non-invasive ventilation may help with sputum clearance and gas exchange and although the impact on exacerbations and disease progression remains unclear, in the longer term it may provide a bridge to transplantation in those with more severe lung disease.^15–18 It is clear, therefore, that NIV should be tried first in acute respiratory failure, but what happens when this fails? Is there a place for intubation? Before commenting further we should review the evidence available.

Survival following intubation for respiratory exacerbations in CF

When it comes to intubation and invasive mechanical ventilation (IMV) for acute respiratory failure in CF, on first glance at the early evidence available it is perhaps not surprising that global pessimism prevails. In the late 1970s, Davis and di Sant' Agnese reported on the outcome of 51 episodes of assisted ventilation in 46 patients aged 1 month to 32 years.¹⁹ In 35 (69%) of the episodes, the patient died on IMV and only 10 (20%) left hospital, with just three (6%) of patients surviving longer than 1 year. Only one of nine infants survived 1 year post-discharge. Similarly, Lloyd-Still et al. reported that five of six infants mechanically ventilated for respiratory failure died within 6 months.²⁰ However, more recent studies suggest that outcomes in early childhood are far more promising, with Garland et al. reporting 100% survival in five infants under 1 year of age, Slieker et al. reporting 100% survival infive children aged between 2 months and 18 monthsrequiring IMV for pneumonia, and Berlinski et al. reporting 7/9 (78%) survival in patients under 5 years of age.^21–23 Despite the small, single-centre retrospective nature of these studies, it has been speculated that early diagnosis, intervention, improvements in paediatric critical care, use of parenteral nutrition and availability of newer more organism-specific antibiotics may be contributing factors to increased survival in this age group.²¹

Survival in intubated older patients in acute respiratory failure appears less promising, with little reported improvement in the last 30 years. In Davis and di Sant'Agnese's original report 24/34 >5 years died while ventilated, with 4/34 surviving >2 months and only 2/34 surviving more than one year.¹⁹ In adults, fewer than 10% survived more than one year. More recently Sood et al. reported the outcome of 65 adult admissions to ICU in 42 patients with CF exacerbations and respiratory failure.² Thirty patients required intubation and 18 (60%) survived, which initially looks encouraging but eight of these were transplanted from ventilator and a further two within 6 months of ICU discharge. Assuming these would not have survived 6 months without a transplant, we can assume a 6-month survival rate of 27%. Vedam et al. reported on nine adult patients admitted to ICU with respiratory exacerbations requiring IMV, six after failed NIV. Four (44%) survived &gt;1 year but again one was transplanted from ventilator and another at 1 year.³ Without transplantation we can assume a survival rate between 33% and 22%, if one or none was transplanted. Within this series, a further three patients had respiratory exacerbations complicated by massive haemoptysis: all three were intubated and two had BAE, but all three died. Texereau et al. reported the outcome of 19 adult patients requiring IMV for respiratory exacerbations, including 11 for failed NIV.²⁴ Although 42% survived ICU, only three of the 11 who failed NIV survived (27%). Similarly, Berlinski et al. reported 20% ICU survival in patients older than 15 years of age intubated for acute respiratory failure and suggested that use of steroids, a history of previous haemoptysis or pneumothorax and CF-related diabetes were predictors of mortality.²³ In contrast to the reported 100% infant survival, Slieker et al. report 18% one-year survival in patients over 15 years of age.²² In the only UK study, Thomas et al. reported 38% ICU survival but only 16% at 6 months.⁴

How does this compare to survival following intubation for other causes of respiratory failure?

Survival following intubation in acute on chronic respiratory failure

Perhaps not surprisingly prognostic pessimism also prevails in predicting survival in patients with chronic obstructive airways disease (COPD) or asthma admitted to intensive care in the UK.²⁵ Despite this, 80% of consultants responsible for COPD admissions in one critical care network would intubate a patient if they thought there was a >30% chance of hospital survival.²⁶ Wildman et al. reported 62% actual survival in 832 patients aged 45 years and older with an exacerbation of COPD, asthma or a combination of the two at 180 days.²⁵ Sixty-five percent ICU survival following intubation for respiratory failure in non-CF bronchiectasis has also been reported, but again studies are small, single-centre and retrospective in nature.^27,28

With the evidence in hand it is for the CF team to discuss each case individually, addressing the wider issues of the wishes of the patient and family when providing a management plan.

Wishes of the patient and family

Although it is preferable not to discuss end-of-life issues in a crisis, in the event of acute respiratory failure it is important to establish the patient's and family's wishes early, acknowledging cultural diversity in decision-making and separating one's own values and beliefs, especially when it comes to the issue of quality of life.²⁹ There is often a sudden shift from active to palliative care when caring for CF patients with end-stage lung disease, especially when patients are on a waiting list for lung transplantation. As such it is hoped that conflict does not occur in decision-making, if it does, support may be available from the local palliative care and ethics teams. The CF team should also be aware of any advance directive such as a living will. However, despite best intentions, one study suggests that palliative care is not discussed until the final month of life in 40% of patients, and not at all in a further 25%. In another study, only 15% of patients had a ‘do not resuscitate order’ in the final week prior to death.^30,31

Conclusions

Intubation provides acute relief of distress, may provide additional time for life-prolonging interventions to take effect, and in some transplant centres, time to find a donor. Transplantation from ventilator is not an option in the UK and any plan for intubation in the case of acute respiratory failure must come with an honest discussion of the benefits and burdens of intubation as well as the prognosis and expected clinical course. It would be reasonable to suggest that infants have a favourable prognosis whereas current data suggest that adult survival following intubation for acute respiratory failure is in the region of 25%. When there is uncertainty it is appropriate to treat and reassess; with this in mind it is appropriate to maximize therapy but also to address the issue of ceiling/duration of therapy. Sending strong messages of futility is unhelpful but the team should establish goals, with regular communication and reviews of intention to treat. Provision of psychological, social and spiritual care is very important and the team should, when appropriate, be able to provide a plan of withdrawal, advocating quality of life and dignity.

Footnotes

DECLARATIONS —

Competing interests None declared

Funding None

Ethical approval Not applicable

Guarantor IK

Contributorship IK is the sole contributor