Ventilation – Journal Summaries
11/11/10
NIV
Lightowler, J.V., et al (2003) “Non-invasive positive pressure ventilation to treat respiratory failure
resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and
meta-analysis” BMJ 236:185
- 8 studies
- patients with hypercapnic respiratory failure from an exacerbation of COPD
- NIV vs standard care
-> reduced mortality
-> reduced need for intubation
Masip, J et al (2005) “Noninvasive ventilation in acute cardiogenic pulmonary oedema” JAMA 294:31243130
- systematic review (15 trials)
- CPAP vs BIPAP in APO
-> decreased mortality in CPAP group
Mehta, S. et al (1997) “Randomized, prospective trial of bilevel versus continuous positive airway
pressure in acute pulmonary oedema” Crit Care Med 25:620-628
- BIPAP vs CPAP
- APO
-> prematurely terminated after only 27 patients as increased risk of MI in BIPAP group
- criticisms: unmatched groups with a higher incidence of patients with chest pain in BIPAP group
Other indications for NIV with less compelling evidence =
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pneumonia in the immunosuppressed
isolated chest trauma with rib #’s + regional analgesia
acute-on-chronic hypercapnic respiratory failure due to chest wall deformity or neuromuscular disease
acute asthma
Nava, S., et al (2005) “Noninvasvie ventilation to prevent respiratory failure after extubation in high risk
patients” Crit Care Med 33:2465-2470
- MRCT
- n = 97
- inclusion criteria: ventilated for more than 48 hours + risk of developing post extubation respiratory
failure (hypercapnia, CHF, weak cough, secretion retention, co-morbidities, upper airway obstruction)
- extubation to NIV for atleast 8 hours VS extubation to O2
Jeremy Fernando (2011)
-> significant reduction in re-intubation rate
-> extubate high risk patients to NIV (data no so convincing for extubating everyone to NIV)
Esteban, A. et al (2004) “Noninvasive Positive-Pressure Ventilation for Respiratory Failure after
Extubation” NEJM 350:2452-60
- MRCT
- 37 centers (8 countries)
- n = 221
- extubated after at least 48 hours of MV who developed respiratory failure within 48 hours -> NIV vs
standard medical therapy
-> trial stopped early because of increased mortality in NIV group (risk of death: NIV group 25% and
invasive group 14% -> absolute risk increase = 11% -> NNH 10)
-> in unselected patients NIV didn’t prevent re-intubation, it delayed it and was associated with a higher
rate of death!
Weaknesses
- waited until respiratory failure developed prior to instituting NIV
- unselected patients
- contamination from cross over to the NIV group
Ferrer, M. et al (2009) “Non-invasive ventilation after extubation in hypercapnic patients with chronic
respiratory disorders: randomized controlled trial” Lancet, 374:1082-88
- RCT
- single center (Spain)
- n = 106
- inclusion criteria: ventilated with chronic respiratory disorders and hypercapnia (>45mmHg) after a
successful spontaneous breathing trial -> NIV for 24 hours vs O2
- primary end point: avoidance of respiratory failure after extubation
-> respiratory failure less likely in patients assigned to NIV (ARR 33% -> NNT 3)
-> NIV group had a lower 90 day mortality (ARR 20% -> 5)
Weaknesses
- ICU length of stay not changed -> it could be argued that you should just keep them ventilated for
longer and wait until their hypercapnic respiratory failure resolves!
ARDS
Amanto, M.B., et al (1998) “Effect of a protective-ventilation strategy on mortality in the acute respiratory
distress syndrome” N Engl J Med 338:347-354
- single centre
- n = 53
Jeremy Fernando (2011)
- RCT
- conventional ventilation (lowest PEEP to maintain oxygenation and TV 12mL/kg, normal PaCO2)
VS
- protective ventilation (PEEP above the lowest inflection point on static pressure-volume curve, TV
6mL/kg, inspiratory pressures of < 20cmH2O above PEEP, permissive hypercapnia)
-> significant reduction in 28 day mortality
-> no change in hospital mortality
-> decreased barotraumas
-> decreased duration of MV
The Acute Respiratory Distress Syndrome Network (2000) “Ventilation with low volumes as compared
with traditional tidal volumes for acute lung injury and acute respiratory distress syndrome ” N Engl J Med
342:1301-1308
- MRCT
- n = 861
- 75 ICU’s
- 10 cities
- ALI/ARDS: bilateral infiltrates, P/F ratio < 300 in the first 36 hrs
- traditional: TV 12mL/kg (plateau pressures of < 50cmH2O)
VS
- protective: TV 6mL/kg (plateau pressure of < 30cmH2O)
- inclusion criteria: intubated and ventilated, ALI or ARDS
- exclusion criteria: > 36 hours of ventilation, < 18 years, pregnancy, increased ICP, severe
neuromuscular disease, sickle cell, severe chronic lung disease, obesity, large burns, severe chronic liver
disease, vasculitis with diffuse alveolar haemorrhage, history of bone marrow or lung transplantation.
-> in hospital mortality: high TV group 40%, low TV group 30%
-> significant reduction in duration of MV
-> reduction in in-hospital mortality
-> use 6mL/kg, inspiratory plateau pressure < 30cmH2O, use predicted body weight from height and
gender not actual body weight
Strengths
- base line characteristics similar (except high minute ventilation in low TV group)
- good separation
Weaknesses
- low TV group received high PEEP to maintain oxygenation (this was a co-intervention) -> subsequently
looked at in the ALVEOLI study which showed no mortality benefit of high PEEP levels.
Gattinoni, L. et al (2001) “Effect of prone positioning on the survival of patients with acute respiratory
failure” N Engl J Med 345:568-573
- MRCT
- n = 304
Jeremy Fernando (2011)
- supine positioning VS prone positioning (for 10 days, 6 hours per day)
-> improved oxygenation
-> no increase in survival
-> no increase in accidental extubation
Meduri, G.U., et al (1998) “Effect of prolonged methylprednisolone therapy in unresolving acute
respiratory distress syndrome: a randomized controlled trial” JAMA 280:159-165
- RCT
- double blind (placebo controlled)
- n = 24
- inclusion criteria: severe ARDS who failed to improve by day 7 of respiratory failure
- methylpredisolone VS placebo
-> reduction in ICU mortality
-> reduced oxygenation requirement
-> reduction in MODS score
- criticisms: small numbers, differences in baseline characteristics between groups.
National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials
Network – N Engl J Med 354:1671-1684
- RCT
- n = 180
- randomised after 7-28 days
- placebo VS methylprednisolone
-> no difference in 60 day mortality
-> increased death rate in those commenced on steroids after 2 weeks
-> no increase in nosocomial infections
-> trend towards increased neuromyopathy
-> increase in number of ventilator-free, ICU and free days in the first 28 days after treatment
National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials
Network. (2006) “Comparison of two fluid-management strategies in acute lung injury ” N Engl J Med
354:2564-2575
- RCT
= n = 1000
- conservative VS liberal fluid strategy
-> no difference in 60 day mortality
-> in conservative group: improved respiratory function, reduced duration of MV, no increase in nonpulmonary failures
- criticisms: high exclusion rate (no CHF, young patients), patients enrolled @ 24 hours -> what to do
early in admission is unanswered
Papazian, L. et al (2010) “Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome” NEJM
363:12 pages 1107-1116
- MRCT (French study) – 20 ICU’s
- n = 340
Jeremy Fernando (2011)
- cis-atracurim vs placebo in early severe ARDS for 48 hrs
- inclusion criteria: intubated for hypoxic respiratory failure for less than 48 hours, ARDS (PF ratio < 150)
- exclusion criteria: age < 18, no consent, already paralysed by infusion, pregnancy, increased ICP,
severe COPD, fat, severe liver disease, bone marrow transplantation or chemo induced neutropenia,
pneumothorax, expected duration of MV < 48 hrs, withdrawal of care imminent, ‘other reasons = 10%”
- primary outcome: 90 day mortality
- secondary outcomes: 28 day mortality, outside ICU days, organ failure free days, barotraumas, ICUacquired paresis, ventilator free days, ICU discharge
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no significant difference in 90 day mortality (as underpowered)
significant difference in mortality when looking at hazard ratio.
NNT = 7
suggestion of increased survival in the patients with lower P:F ratios
no difference in 28 day mortality
Cis-atracurium group:
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had significantly more ventilator free days
less organ failure days
spend more days outside ICU
less pneumothoraces
no difference in ICU-acquired paresis!
Weaknesses
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heaps assessed for eligibility
‘others’ excluded = 10%
seems like a quick wean
control group received open-label atracurium (received more but allegedly not significant)
underpowered given assumed a 50% mortality rate at it was actually 40% in control group.
Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT;
National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher vs. lower positive endexpiration pressures in patients with the acute respiratory distress syndrome . N Engl J Med. 2004 Jul
22;351(4):327-36).
- ALVEOLI Study
- MRCT
- n = 549
- patients with ALI or ARDS
- high PEEP + lower FiO2 vs low PEEP + high FiO2
-> no improvement in survival
-> can use high or low levels of PEEP depending on clinician’s preference (balancing oxygenation,
reduction in deadspace, improved compliance VS barotrauma and hypotension)
TRACHEOSTOMY
Griffiths, J. et al (2005) “Systematic review and meta-analysis of the timing of tracheostomy in adults
patients undergoing artificial ventilation” BMJ 330:1243-1247
Jeremy Fernando (2011)
- systematic review of randomized and controlled studies looking at early tracheostomy VS later
tracheostomy VS prolonged endotracheal intubation
- 15,950 articles -> 5 papers analysed
- n = 406
-> no difference in mortality or risk of pneumonia
-> significant difference in duration of MV and ICU stay
WEANING
Brochard, L. et al (1994) “Comparison of three methods of gradual withdrawal from ventilatory support
during weaning from mechanical ventilation” Am J Respir Crit Care Med 150:896-903
- RCT
- n = 109
- inclusion criteria: deemed ready for weaning, failed to sustain 2 hours on a T piece
- SIMV VS PSV VS further T piece sessions
-> significant increase in number of patients successfully weaned on PSV
Esteban, A., et al (1995) “A comparison of four methods of weaning patients from mechanical ventilation”
N Engl J Med 332:345-350
-> one daily spontaneous breathing trials are equally as effective as multiple daily trials
-> spontaneous breathing trials led to extubation 3 times more rapidly than SIMV and 2 times as quickly
as PSV
Girard, T. D., et al (2008)– “The Awake and Breathing Controlled Trial” Lancet; 371:126-134
- 4 Centers is North American
- RCT – 2003-2006
- inclusion criteria: > 18 years, on MV for > 12 hours
- exclusion criteria: post cardiac arrest, moribund, > 2 weeks ventilatory support, severe dementia, coenrolled in another trial
- intervention = SBT vs SAT -> SBT
- primary end points = ventilator free days
- secondary end points = delirium, 28 day -> 1 year mortality, length of stay in ICU and hospital
- n = 334 (powered of 80%)
- intention to treat analysis
RESULTS
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reduction in ventilator free days
reduced mortality at 1 year
similar delirium rates but less coma
increased risk of extubation -> however, risk of re-intubation same in control arm
higher rate of successful extubation
lower trachestomy rate
Jeremy Fernando (2011)
Strengths
- protocolised
- multi-centre
Weaknesses
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not blinded
not generalisable to Australasia (North America has Ventilator Technician)
surgical patients not enrolled
sedation time and practice not recorded
Jeremy Fernando (2011)