CCP Podcast 085: Papers of the Month March 2018

 November 11

by Jonathan Downham

Gavin Denton and I get together again to review a couple of recent papers that have some bearing on our practice. Welcome to the Papers of the month.

This month we cover Check Up- Position- “A Multicenter, Randomized Trial of Ramped Position vs Sniffing Position During Endotracheal Intubation of Critically Ill Adults” and the APRV trial –BILEVEL-APRV 

A Multicenter, Randomized Trial of Ramped Position versus Sniffing Position during Endotracheal Intubation of Critically Ill Adults

Semler et al, 2017.


Clinical question.

In critically ill adults requiring endotracheal intubation, does the ramped position increase the lowest oxygen saturation during rapid sequence induction compared to the supine sniffing position.



  • Multi-centre study involving four tertiary hospitals.
  • Randomisation in a 1:1 ratio using computer generated blocks, seal envelopes assigned treatment groups and were opened on decision to enrol in the study.
  • Unblinded.
  • All patients were simultaneously enrolled in a second study involving the use of intubation checklists.
  • 80% power to detect a 5% difference in the lowest oxygen saturation level with an alpha level of 0.05, 260 participants required, 260 patients enrolled on an intention to treat basis.



Patients in critical care.

Conducted in the United States of America.



  • Adults.
  • 60% were intubated for hypoxia.
  • Exclusions were intubation during cardiac arrest, patients requiring cervical spine precautions, and patients requiring urgent intubation. Patients were also excluded if clinicians thought a specific position was required for the procedure to be safely performed.
  • All patients received sedation and neuromuscular blockade.
  • BMI and use of video laryngoscopy were similar.



  • Ramped position was defined as 25 degrees head up, the occiput was positioned over the end of the mattress, face parallel to the ceiling, sniffing position/ear to sternal notch was achieved using additional pillows or blankets.
  • The sniffing position was achieved by placing pillows or blankets under the head to flex the neck forward of the torso and then extension of the neck. Patients were kept supine and pillows under shoulders were not allowed.
  • There was no control over the pre-oxygenation position, position was at the operators discretion until the point of induction when the patient had to be positioned according to the assigned treatment arm.



  • Primary outcome was the lowest oxygen saturation between induction and two minutes after successful intubation. There was no difference (p value 0.027) between the lowest oxygen saturation in either group.


  • Secondary outcomes;
  • First pass success 85.4% in the supine group vs 76.2% in the ramped group (not statistically significant, and not powered for this outcome P value .02). The glottic view obtained was worse in the ramped group.
  • A trend towards improved oxygenation in the more severely hypoxic patients, but not powered to look at this subgroup.


Author’s conclusion.

The ramped portion does not appear to improve oxygenation during intubation and may result in a worse glottic view and lower the first pass success.



  • Possibly the first randomised study on intubation position in a critically ill population.
  • Multi-centre study.
  • Sub-group analysis of operator experience did not have any impact on the results.



  • Non-blinded study, however blinding impossible in this context.
  • The study does not inform us on the optimal position to pre-oxygenate.
  • Type of laryngoscope was not controlled, but blade type was similar between groups.
  • Pre-oxygenaion position is not  controlled for and may confound results.
  • It is not clear if the use of a checklists in the parallel study could have confounded the data from this study.
  • 53% of patients were ventilated through their apnea, this may also confound the data in regard to patients that were apneic throughout the intubation process.
  • There were 46 exclusions, around 20 were in extremis and it is unknown whether there may have been benefit of ramped position in these cases. I suspect these cases may have been electively intubated head up.


Bottom line.

This study did not demonstrate a benefit in oxygenation during RSI in the ramped position over the supine position and worsened glottic view and first pass success.





In 2017 Zhou et al published a trial called “Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome.”

In order to understand the trial and the results lets first be clear about what is APRV or Airway Pressure Release Ventilation and its basis on the principle of open lung ventilation. Open-lung ventilation refers to the concept of recruiting the lung and then ventilating gently with small tidal volumes, to avoid either over-distension or atelectotrauma (lung damage from cyclical opening/closing of alveoli).


Two levels of PEEP: high (P-high) and low (P-low)

patient breaths spontaneously during P-high and P-low

time in P-high (T-high) is longer than P-low (T-low) to maintain recruitment (85-95%)

results in a degree of autoPEEP due to the short release time (T-low)



alveolar recruitment and improved oxygenation

preservation of spontaneous breathing

reduction of left ventricular transmural pressure and therefore reduction of left ventricular afterload

potential lung-protective effect

better ventilation of dependent areas

lower sedation requirements to allow spontaneous breathing



risks of volutrauma from increased transpulmonary pressure

increased work of breathing due to spontaneous breathing

increased energy expenditure due to spontaneous breathing

worsening of air leaks (bronchopleural fistula)

Increased right ventricular afterload, worsening of pulmonary hypertension

Reduction of right ventricular venous return: may worsen intracranial hypertension, may worsen cardiac output in hypovolemia

Risk of dynamic hyperinflation


There have been animal studies demonstrating that APRV can increase alveolar recruitment gas exchange and therefore reducing lung injury.

The ARDSnet trial established that mechanical ventilation at a six mls per kilo set tidal volume was superior to 12 mls per kilo in patients meeting criteria for ARDS. Several studies since have demonstrated that this target is often not adhered to.


The comment in Rob McSweeney’s review is that the use of APRV in patients with ARDS has been led by enthusiasm rather than rigorous evidence of benefit.

As Jonny points out here, ARDS is an inflammatory process leading to increased lung vascular permeability which further leads on to hypoxaemia and reduced lung compliance. As a consequence we tend to ventilate this type of patient with low tidal volume ventilation.


The aim of this study therefore was to establish whether the use of APRV will reduce the duration of mechanical ventilation versus low tidal volume ventilation.

So this was a single centre, randomised controlled trial comparing APRV against low tidal volume lung protective ventilation in patients with ARDS conducted in China. Eligible patients were having mechanical ventilation for greater than 48 hours and met the Berlin diagnostic criteria for ARDS.

Amongst the exclusions were those with relative contraindications to APRV including those with barotrauma, severe chronic obstructive pulmonary disease and intracranial hypertension.

You can see from Johnny’s info graphic the settings here in the intervention arm and the primary outcome to be measured was the number of ventilator free days up to date 28.

Secondary endpoints included clinical outcomes (including mortality) and respiratory mechanics.

Overall over 16 months 138 patients were enrolled. Raised intracranial pressure and unexpected early extubation were the commonest exclusion reasons.

So patients in the APRV group had significantly more ventilator free days by day 28 than those in the low tidal volume group-  p value 0.001 more patients receiving APRV were successfully extirpated and fewer required tracking ostomy.

Neuromuscular blockade, prone positioning, nitric oxide or high frequency oscillators ventilation was required in 34% of patients in the low tidal ventilation arm and 8% of patients receiving APRV.

Length of stay was significantly reduced in ICU but not in hospital stay. Intensive care unit mortality and hospital mortality were not significantly reduced with APRV.

At day three patients receiving APRV had significantly lowerFiO2 and higher mean airway pressures and pAO2.

Patients receiving APRV also had a lower mean heart rate and higher mean arterial pressure.

Finally at day three and a seven APRV patients were less sedated by RASS scoring and receiving less sedatives by infusion.


Whilst these results also and very encouraging there are a number of problems with this study which should lead us to view the results with care.

Firstly this was a single centre study with relatively small numbers which could mean that rare, but serious adverse events of either therapy may have been missed.


The trial was conducted in China which may lead to differences in both the patient population and the type of health care system to that found in the West. Due to the nature of the trial those treating the patients were unblinded to the treatment allocation which could raise a possible bias.


Tidal volumes of up to 8 mills per kilo were allowed in the low tidal volume ventilation group. This is higher than that recommended in the ARDSnet trial.

The P low was also set to 5 cm whereas a P low of zero is more commonly advocated.

So due to some of these issues and the fact that the results from this study are not in agreement with previous randomised studies, which have found in the past that APRV leads to increased time to extubation, and also having shown improved outcomes with low tidal volume ventilation in ARDS it is felt that repetition of this study in a large multicentre setting would be advisable.




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