Critically evaluate the use of neuromuscular blocking agents in severe respiratory failure due to acute respiratory distress syndrome (ARDS).
Rationale & Theoretical Benefits
- In general will reduce O2 consumption & CO2 production
- Avoids patient ventilator dys-synchrony
- Allows evaluation of respiratory mechanics
- Generally required to perform a recruitment manoeuvre
- In patients with pronounced spontaneous respiratory effort:
- They may draw large spontaneous tidal volumes well in excess of appropriate ARDSnet values (pulmonary stress)
- They may generate large spontaneous negative trans-pulmonary pressures during controlled breaths (pulmonary strain)
- Spontaneous respiratory activity is difficult to otherwise supress (with sedation only), particularly in the setting of permissive hypercapnia
- Observationally improves oxygenation in the short term
- May reduce cytokine release and biotrauma
- Facilitates prone positioning
- Contradicts strategies of maintaining spontaneous efforts and respiratory muscle strength.
- May unmask poor compliance in patients who were generating very negative inspiratory pressures while breathing spontaneously, with consequent difficulties maintaining adequate tidal volume.
- Potential for awareness during paralysis
- Risks of ‘Critical Illness Weakness’ associated with use of NMBA.
- Risks of accumulation of NMBA drug in critical illness.
- Increased risk of positive fluid balance and thromboembolic risks.
- Timing / duration of paralysis not known – Papazian used 48 hr
- Which NMB – non-steroid based may be better for reducing risk of weakness (Papazian used cisatracurium)
- Train of four monitoring needed
- Single French RCT (Papazian, NEnglJM Sept 2010)
- Severe ARDS, P/F < 150
- Showed mortality improvement at 90 days with paralysis for 48 hrs in early severe ARDS hours (hazard ratio for death 0.68). No increase in weakness.
- Evidence for improved oxygenation beyond period of paralysis.
- 25% of eligible patients enrolled, limits external validity
- study used low levels of PEEP (lower than the control of several high vs. low PEEP
Anything reasonable – for example:
I do not use NMBs routinely in severe ARDS but in selected patients e.g. those difficult to ventilate / oxygenate I use cistracurium infusion with train of four monitoring
Rationale for the use of neuromuscular blockade in ARDS
- Improve chest wall compliance: The lung compliance is already poor enough; removing chest wall compliance from the equation helps to prevent absurdly high peak pressures
- Improved patient-ventilator synchrony: Many of these patients end up ventilated with such perverse pressure/volume combinations that without paralysis there would be a constant and counterproductive battle of patient versus ventilator. True, this is something one could achieve with haemodynamically disastrous doses of sedation, but ... why would you?
- Recruitment manoeuvres generally require paralysis for the abovementioned reasons; if the patient tries to exhale or cough during one of these manoeuvres, a pneumothorax may occur.
- Prone ventilation usually requires paralysis
- Decrease skeletal muscle metabolism: this is a hidden benefit, which is frequently overlooked. Neuromuscular blockade prevents the skeletal muscle from performing anything but the very barest baseline of metabolic work; the ATP production in the muscle fibres drops to whatever is required to maintain ionic concentration gradients. This decreases the oxygen extraction ratio for a large percentage of your patients tissues. Oxygenated blood, formerly directed into muscles, is redistributed into splanchnic vascular beds. Indeed, in a study performed on ICU patients with respiratory failure, the oxygen extraction ratio was found to by decrease 5% (from 36% to 31%).
- Improved assessment of respiratory mechanics: without the interference of respiratory muscles, the lung compliance can be assessed more correctly, and the pressure-volume loops are more meaningful
Disadvantages of sustained neuromuscular blockade
- This strategy is contrary to the normal strategy of ventilating patients with the most spontaneous mode possible, to preserve their muscle strength and to increase their comfort.
- Longer duration of ventilation and longer ICU stay (Arroliga et al, 2005)
- Increased risk of critical illness polyneuromyopathy
- Increased risk of pressure areas
- Increased risk of DVTs
- Accumulation of paralytic agents (unless you use something like cisatracurium)
- Risk of paralysed awareness
- Increased nursing care
Evidence for the efficacy of neuromuscular blockade in ARDS
- Papazian et al, 2010 - a 48 hour course of cisatracurium early in the progress of severe ARDS. The authors found a 10% absolute risk reduction of 90-day mortality (31.6% vs 40.7%) associated with the use of neuromuscular blockade, without any increase in the risk of ICU-acquired weakness. , This places cisatracurium in the rare category of things which have been supported by positive trials. Alongside low tidal volume ventilation and low delta-P, this is one of the strategies which can be strongly recommended. Unfortunately, as the college mention, the study has several weak points:
- Papazian et al only enrolled 25% of the eligible patients. 10% of patients excluded due to 'other reason', whatever that means.
- 21% of the patients had PA catheters, which is totally contrary to modern Australian practice
- 30% of the patients received nitric oxide, which has been thoroughly discredited in the literature and has fallen into disuse in Australia
- Papazian et al used a surprisingly low PEEP, around 9 cmH2O on average.
- The groups differed in their use of steroids (39% in treatment arm, 45% in placebo)
- The mortality from ARDS was much lower than predicted, which underpowered the study.
- Blanch et al, 2015 - a prospective study which observed that ventilator asynchrony is associated with a higher in-hospital mortality.
Papazian, Laurent, et al. "Neuromuscular blockers in early acute respiratory distress syndrome." N Engl J Med 363.12 (2010): 1107-1116.
Neto, Ary Serpa, et al. "Neuromuscular blocking agents in patients with acute respiratory distress syndrome: a summary of the current evidence from three randomized controlled trials." Annals of intensive care 2.1 (2012): 1-8.