A 45 year old female presented to A&E with a 5 day history of worsening SOB, cough productive of green sputum, lethargy, anorexia, fever and rigors. She had no co- morbidities and was active and independent with a good exercise tolerance. On examination she looked unwell, clammy and drowsy. Her respiratory rate was 35 breaths per minute and SpO2 of 84% on 15 Litres of oxygen via a non-rebreathing mask. Her blood pressure was 88/40 mmHg with a heart rate of 140 per minute despite having received 3 litres of fluid. Arterial blood gas showed PaO2 6.0kPa, pH 7.28, PaCO2 7.1 kPa, Bicarbonate 14 mmol/l, BE -11 and Lactate 8.6 mmol/l. Chest radiograph demonstrated significant bilateral consolidation with infiltrates consistent with ARDS. PaO2:FiO2 was calculated as 15 indicating severe ARDS presumed secondary to CAP.
She was managed as per sepsis guidelines. Oxygen therapy was continued and CPAP was initiated due to the hypoxia whilst an ICU bed was being prepared for admission. Noradrenaline was commenced at 0.2mcg/kg/min which continued to increase. Repeat arterial blood gases confirmed worsening type 2 respiratory failure and the patient was clinically exhausted. A modified rapid sequence induction was performed and IPPV commenced. Her oxygenation remained a problem and despite a FiO2 of 1.0 and PEEP of 20 his SpO2 remained 85% and PaO2 6kPa. The patients’ sedation was deepened and muscle relaxant administered. Lung protective ventilation was continued however arterial blood gases continued to worsen. The decision was made to convert the patient from conventional ventilation (CV) to High-Frequency Oscillator Ventilation (HFOV). The initial ABGs after an hour of HFOV showed an improvement as did subsequent numbers. This mode of ventilation was continued for a further 48 hours and then converted to CV. Gas exchange continued to improve. Over the course of the following 4 weeks the patient had a tracheostomy performed to aid weaning. She subsequently developed a Ventilator Associated Pneumonia and worsening ARDS required a further period of HFOV. Improvement continued and the patient was successfully decannulated and discharged from ICU.
What is the evidence base for high frequency oscillatory ventilation in ARDS?
Evidence of mechanical ventilation can be traced well before biblical times. Hippocrates (460-375 BC) wrote about endotracheal intubation in his book ‘Treatise on Air’. The Old Testament describes Prophet Elisha inducing pressure breathing from his mouth into the mouth of a child who was dying (Kings 4:44-35). Since then various scientists have performed some form of mechanical ventilation including Galen (175 AD) Paracelsus (1550), Versalius (1543), Fathergill (1744), Hunter (1775) and the well known negative pressure ventilators during the polio epidemic in the 1800-1900s. In the 1960s post polio epidemic the advances in modes and understanding of mechanical ventilation has improved exponentially.
Various complications of mechanical ventilation have been recognised including pneumothorax, airway injury, alveolar damage (barotrauma, volutrauma, atelectatrauma) and ventilator-associated pneumonia.(2) Apart from mechanical ventilation and the associated complications a better understanding of respiratory physiology has allowed various methods of ventilation to be developed and tried.
The key principle of ‘safe’ ventilation can be illustrated on a lung pressure-volume loop.(3)
The ‘safety zone’ illustrated by the dotted line in the centre of the loop represents normal tidal respiration where lungs are not over-distended (upper zone) or undergoes derecruitement/atelectasis (lower zone).(3,4) In diseased lungs such as ARDS/ALI there was a tendancy to aim to normalise arterial blood gases which inevitably resulted in the use of larger tidal volumes which resulted in alveolar damage. The ARDSNet guidelines therefore suggested lower tidal volumes and higher PEEP with the aim to ventilate as much in the ‘safety zone’ as possible as well as accepting higher than normal PaCO2.
High frequency ventilation (oscillation) works on this principle of ventilation within the ‘safety zone’ thus allowing continuous recruitment of collapsed alveoli and preventing/reducing atelectasis due to maintenance of a high PEEP above the inflection point. The frequency of oscillation about the fixed point is used to clear CO2. This would appear to be ideal in disordered lungs where the safe window is too small for conventional ventilation.(5)
Types of high frequency ventilation (HFV)
All modes of HFV are characterised by a frequency of 1 Hz (60 breaths per minute) and tidal volumes (VT) lower than dead-space volume.6 They can be classified into four types:
- High-frequency positive pressure ventilation (HFPPV)
- High-frequency jet ventilation (HFJV)
- High-frequency flow interrupter (HFFI)
- High-frequency oscillatory ventilation (HFOV)
Sanders introduced HFJV in 1967 to facilitate gas exchange during bronchoscopy while Oberg and Sjostrand used HFPPV in the 1970s to eliminate the effect of respiratory variations on the carotid sinus reflexes.(6) Oberg and Sjostrand overcame the increased dead space by insufflating gas directly into the trachea therefore providing VT’s of 3-4 mL/kg, high flow rates and frequencies of 60-100 breaths/min.(6)
In 1977 Klain and Smith combined the two above methods to introduce high frequency transtracheal jet ventilation.(6) ‘Jets’ of gas under pressure were introduced through a small catheter placed in the tube and VT’s of 2-5 ml/kg delivered at frequencies of 100-200 breaths/min. the continuous high flow system allowed entrainment of additional gas via the Venturi principle. The disadvantages of HFJV were the inability to accurately control VT and humidify gases.
HFFI works on a principle similar to HFJV however uses a rotating bar or ball with a small opening in the path of a high-pressure gas. As the bar/ball rotates, a pulse of gas enters the airway.(6) Expiration is passive in all the above mentioned methods.
In 1980 Bohn et al. and Butler et al. introduced HFOV where they demonstrated that adequate gas exchange was possible by generating oscillations in the airways at a frequency of 15 Hz. The oscillations could be achieved using a loudspeaker or electronically driven piston pump. The pressure oscillates around a constant distending pressure (CDP) which aims to keep the lung volume stable and controllable. CDP can be considered as CPAP which provides the constant pressure for alveolar recruitment and therefore, together with FiO2, regulates oxygenation.
Ventilation on the other hand is regulated using the frequency of oscillation and hence VT. As the frequency decreases the VT increases and therefore more CO2 can be cleared. Compared to the previous modes of high frequency ventilation, HFOV is an active process both during inspiration and expiration.
Evidence in neonates
HFOV is mainly used in neonates mainly as a rescue therapy in children with Diffuse Alveolar Damage (DAD) secondary to ARDS, lung contusion, pneumonia. Set criteria need to be met however early commencement of HFOV is left at the discretion of the clinical judgment of the physician. The criteria include ventilatory failure with plateau pressures of 30 cmH2O despite the use of permissive hypercapnia for at least two hours, or oxygenatory failure i.e. oxygenation index ≥13 demonstrated by two blood gas measurements over a six hour period.(7)
The validity of elective commencement of HFOV in preterm infants requiring mechanical ventilation for respiratory distress syndrome (RDS) was investigated in a Cochrane review in 2009. Seventeen studies of 3,652 infants were included comparing HFOV and conventional ventilation (CV) in preterm/low birth weight infants with RDS. There was no effect on mortality at 28 – 30 days of age and was a borderline significant reduction in the rate of chronic lung disease with HFOV.(8)
Evidence in adults
The evidence in adults was limited and similar to neonates; HFOV was used as a last resort ‘when all else failed’. In 2010 a systematic review and meta-analysis investigated eight randomised controlled trials (n=419 patients). Nearly all patients had ARDS and those randomised to HFOV had a significantly reduced mortality and treatment failure.
Numerous critical care units therefore purchased and started to use HFOV in patients with severe ARDS.
Two international random controlled trials (RCTs) aimed to further assess the validity of HFOV; Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) and Oscillation in ARDS (OSCAR). The OSCAR trial compared HFOV using a Novalung R100 (Metran) with conventional ventilation. There was no significant difference in 30-day mortality in either groups (398 patients in HFOV group and 397 in conventional-ventilation group).(10)
The OSCILLATE trial was a multicentre RCT conducted at 39 intensive care units in five countries. The trial had to be stopped after 548 of a planned 1200 patients had undergone randomisation. The in-hospital mortality was 47% in the HFOV group compared with 35% in the control group (statistically significant difference).(11) Various other factors may have resulted in these outcomes for example increased requirements for sedation, paralysis, and vasoactive drugs in the HFOV group however the results were significant enough to terminate the trial.
The use of HFOV in neonates is still an option in severe ARDS when conventional ventilation have failed however it is not an option in adults based on the current best evidence.
- CawleyMJ.Mechanicalventilation:atutorialforpharmacists:historyof mechanical ventilation. Pharmacotherapy 2007;27:250–66.
- HessDR(2011).”Approachestoconventionalmechanicalventilationofthe patient with acute respiratory distress syndrome”. Respir Care 56 (10): 1555–72.
- LachmannB.Openupthelungandkeepthelungopen.IntensiveCareMed 1992;18:319–21.
- ARDS-Network.Ventilationwithlowertidalvolumesascomparedwithtraditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The acute respiratory distress syndrome network. N Engl J Med 2000;342:1301– 8.
- .High-frequencyoscillatoryventilationforadultrespiratorydistress syndrome: let’s get it right this time! Crit Care Med 1997;25:906–8.
- StandifordTJ,MorganrothML.High-frequencyventilation.Chest1989;96:1380– 9.
- DuvalE.L.IM.,MarkhorstD.G.,vanVughtA.J.Highfrequencyoscillatory ventilation in children: an overview. Respiratory Medicine CME 2 (2009) 155–161
- CoolsF,Henderson-SmartDJ,OffringaM,AskieLM.Electivehighfrequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants (Review). The Cochrane Library. 2009. Issue 3.
- SudS,SudM,FriedrichJO,etal.Highfrequencyoscillationinpatientswith acute lung injury and acute respiratory distress syndrome (ARDS): systematic review and meta-analysis. BMJ 2010;340: c2327.
- Young D., Lamb S. E., Shah S. et al. High-Frequency Oscillation for Acute Respiratory Distress Syndrome. NEJM 2013; 368:9.
- Ferguson N. D., Cook D. J., Guyatt G. H. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome. NEJM 2013; 368:9.