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In 2013, Guérin and colleagues published a multicenter randomized trial (PROSEVA) examining the effect of prone positioning for 16 hours, followed by 8 hours supine, in patients with ARDS. 26 They reported an overall reduction in mortality of 16.8%. In 2010, Papazian and colleagues published a multicenter, randomized, double-blind study (ACURASYS) that demonstrated a reduction in the hazard ratio for death from ARDS when a cisatracurium infusion was used for 48 hours early in the treatment of moderate-to-severe ARDS. 27 The publication of these two papers led to the inclusion of these therapies in professional guidelines and has prompted interest in these, and other, strategies for the treatment of ARDS .

Despite the enthusiasm that has greeted these findings, it's important to keep in mind that there are limitations with these and other studies, and that their findings should not result in wholesale application of prone positioning and neuromuscular blockade in every patient with ARDS. In this chapter, the pros and cons of each treatment will be discussed. If this seems like hedging, well, that's because it is. Both prone positioning and neuromuscular blockade have a place in the treatment of ARDS, and both have significant risks. Neither is a magic bullet, and neither is a substitute for lung-protective ventilation and good supportive critical care. By the time you're reading this, there may be new developments either supporting or refuting (or both!) these therapies. For now, the focus should be on identifying the patients who may benefit while minimizing the risks.

Previous studies of prone positioning were able to show improvement in pulmonary blood flow and oxygenation, but did not improve mortality. 28 , 29 This may have been due to using prone positioning in patients with less-severe ARDS, poorly-defined protocols, and a shorter duration of the time spent prone. The 2013 Guérin study, on the other hand, was well-defined and included patients with a PaO 2 /FiO 2 ratio ≤ 150. These patients were sufficiently ill enough to where a treatment benefit might become evident. This study also mandated that the time spent prone (16 hours at a time) was long enough for any physiologic benefit to occur. Earlier studies had prone times of 6-8 hours.

The PROSEVA trial did show a mortality benefit, but it's important to note that it was the first trial of prone positioning in ARDS to do so after numerous other clinical trials had failed. This may have been due to improvement in the process and a refinement of the indications and duration of treatment. It could also easily reflect the fact that clinical statistics are not exact and that occasionally a trial can demonstrate a benefit when none actually exists. The PROSEVA trial was very similar to another clinical study of prone positioning published in 2009. 30 That study looked at a similar number of patients (466, vs. 342 in PROSEVA) and included patients with a PaO 2 /FiO 2 ratio ≤ 200. It also used a similar duration of proning (20 hours at a time, vs. 16 hours in PROSEVA). There was the expected improvement in oxygenation, but no statistically significant difference in mortality. The fact that two very similar clinical trials reached very different conclusions suggests that a much larger tiebreaker trial is needed.

The ACURASYS trial used a bolus of cisatracurium, followed by a continuous infusion, for 48 hours early in the treatment of moderate-to-severe ARDS (PaO 2 /FiO 2 ≤ 150). This led to an improvement in the hazard ratio of death at 90 days, along with a reduction in the incidence of pneumothorax (4% vs. 11.7%). The benefit was most pronounced in patients with a PaO 2 /FiO 2 ratio ≤ 120, suggesting that neuromuscular blockade is most effective in the sickest patients. Other, smaller clinical trials have also suggested that a cisatracurium infusion may be beneficial. 31 , 32 Importantly, these trials did not show a higher risk of prolonged myopathy or ICU-acquired weakness when compared with the control groups.

The ACURASYS trial claimed a reduction in the 90-day hazard ratio of death, but the overall reduction in mortality was not statistically significant. In other words, patients who received cisatracurium lived longer than the control arm, but a similar number were dead by the 90-day mark. A reduction in the hazard ratio may be a meaningful outcome in a trial looking at a new treatment for, say, lung cancer—the five-year mortality may not be different, but the new drug may prolong life for another year or two. Most people would consider that successful. Most people would probably not consider an additional week or two of life in the ICU, intubated and attached to machines, to be a successful result.

Nearly 22% of the control group in the ACURASYS trial received open-label cisatracurium. This makes interpretation of the results difficult, as the study wasn't completely blinded. Patients with more pronounced dyssynchrony with the ventilator would be the ones expected to receive open-label neuromuscular blockade, and these would also be the ones in the control group. In an effort to preserve blinding, all patients in the study had to be sedated to the point of complete unresponsiveness prior to receiving either the cisatracurium infusion or placebo. Heavy sedation is also known to be associated with higher risks. These issues should not be discounted.

The point of the preceding arguments was not to convince you that all patients with ARDS should be proned and paralyzed, and it wasn't intended to say that proning and neuromuscular blockade are worthless. The truth is that both may have a role in moderate-to-severe ARDS (PaO 2 /FiO 2 ≤ 150), and they should be considered on a case-by-case basis. The patients most likely to benefit from prone positioning are those with significant dorsal consolidation as seen on CT imaging. Patients with more diffuse infiltrates may not see as much of a response to changes in respiratory mechanics and pulmonary blood flow. Additionally, the nursing care of other issues (long bone fractures, recent chest or abdominal surgery, brain injury, etc.) may be adversely affected with proning. Proper training and drilling of ICU staff, along with the use of a proning checklist, should minimize the risk of turning to both patients and caregivers.

Prone Positioning Checklist

Indications For Prone Positioning

Hypoxemic respiratory failure with the following features:

• PaO 2 /FiO 2 ratio ≤ 150

• Diffuse bilateral lung infiltrates

• Dorsal consolidation on CT (if available)

Minimum Necessary Personnel

• 2 respiratory therapists (or other qualified personnel) to control the airway and ventilator

• 4 turners (may be nurse, physician, patient care tech, respiratory therapist, or student)

• 1 supervisor, who should not be involved in the proning process itself

Turning Process

PREPARE

• Apply lubricant to eyes and tape eyelids closed

• Remove any jewelry from the patient's head or neck

• Remove any bite blocks

• Bolus necessary analgesia/sedation/neuromuscular blocker

• Confirm SpO 2 and ETCO 2 monitors are in place and functional

POSITION

• Two turners on either side of the patient (four total)

• Two respiratory therapists at the head of the patient

o One to manage the head, airway, and face pillow

o One to manage ventilator tubing and provide backup

• Supervisor at the foot of the be d

PAD (if going from SUPINE to PRONE)

• Foam face pillow, making sure the endotracheal tube is not kinked (it may be necessary to cut out some of the foam padding)

• Two pillows each on the chest, lower pelvis, and shins

• Place a sheet over the patient (head to toe) and wrap snugly, bundling the pillows to the patient

DISCONNECT

• Central lines (after necessary boluses)

• Arterial lines

• Hemodialysis lines

• Cardiac monitor leads

• The endotracheal tube from the ventilator

o Attach a self-inflating bag connected to oxygen

o Adjust the PEEP valve on the bag to the appropriate level, based on the patient's oxygenation

o Put the ventilator on standby

TURN

Supervisor should read each step aloud, with verbal confirmation by the team members

o Supervisor confirms that the airway and ventilator tubing are under control by the respiratory therapists

o Supervisor confirms that all lines and leads have been disconnected (SpO 2 and ETCO 2 monitors may be left in place, unless they interfere with the turning process)

o On the supervisor's count, the team will turn the patient onto his left/right (specify which) side, keeping the pillows tight against the body using the sheet

o Supervisor confirms that nothing needs to be repositione d

o On the supervisor's count, the team will turn the patient to the PRONE or SUPINE position, ensuring that the pillows and face pad are kept in the proper position

o Respiratory therapists confirm to the supervisor that the endotracheal tube is at the proper depth and that the tube is not obstructed, with an appropriate ETCO2 waveform

o If PRONE , Turners confirm to the supervisor that the patient is appropriately padded and that arms and legs are positioned comfortably

o If SUPINE , Turners remove padding

o Reattach cardiac monitor leads, arterial line, and restart infusions

Prone position should be maintained for 16 hours, followed by 8 hours in the supine position. Eye and mouth care is essential. Tube feeding in the prone position is permissible if the tube is post-pyloric; otherwise, hold tube feeding while prone and increase the rate of feeding while supine.