- Email: [email protected]
Permissive hypercapnia in preterm infants: the discussion continues
Comment
Arg117His-CFTR status has direct relevance to newborn screening programmes for cystic fibrosis. Inclusion of Arg117His-CFTR in screening panels leads to identification of infants who have a very low likelihood of developing cystic fibrosis lung disease, at least during childhood. Removing the Arg117His-CFTR mutation from newborn screening panels has been advocated.9 This position will need to be reassessed in view of Moss and colleagues’ results,6 since ivacaftor will probably play an important part in treating Arg117His/5T-CFTR and might well be of benefit in those few patients with Arg117His/7T-CFTR who have lung disease. These data6 are therefore an important contribution to the medical literature, since they provide clear support for the treatment of patients with Arg117His-CFTR. The results also show CFTR activity in children as well as in adults, providing a rationale for the treatment of some children. Whether patient-specific response to ivacaftor can be predicted from specimens studied ex vivo—eg, nasal epithelial cells or intestinal organoids—remains to be clarified.10 Long-term studies to assess the safety and efficacy of ivacaftor in general are also needed. In this respect, evidence that the drug can modify the rate of decline in lung function or the development of structural injury will be important. Finally, the results from Moss and colleagues’ study reinforce the notion of mutation-specific treatment of CFTR dysfunction—an important step on the road to personalised care for all individuals with cystic fibrosis.
Frank J Accurso University of Colorado and Children’s Hospital Colorado, Aurora, CO 80045, USA [email protected] I have served on the Cystic Fibrosis Foundation Therapeutics, Inc./Vertex Pharmaceuticals, Inc. Joint Development Committee since 2003. The purpose of this committee is to improve the communication between the two groups. I represent Cystic Fibrosis Foundation Therapeutics, Inc. in these discussions and have no ties, financial or otherwise, with Vertex Pharmaceuticals, Inc. I receive reimbursement from Cystic Fibrosis Foundation Therapeutics, Inc. for the twice a year in-person committee meetings only for plane fare, lunch, and parking. I do not receive any remuneration from Cystic Fibrosis Foundation Therapeutics, Inc. for time or effort. I receive no remuneration at all from Vertex Pharmaceuticals, Inc. 1 2 3
4
5
6
7
8 9
10
Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med 2005; 352: 1992–2001. Stoltz DA, Meyerholz DK, Welsh MJ. Origins of cystic fibrosis lung disease. N Engl J Med 2015; 372: 1574–75. Van Goor F, Hadida S, Grootenhuis, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci USA 2009; 106: 18825–30. Ramsey BW, Davies J, McElvaney NG, et al. VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365: 1663–72. De Boeck K, Munck A, Walker S, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros 2014; 13: 674–80. Moss RB, Flume PA, Elborn JS, et al, on behalf of the VX11-770-110 (KONDUCT) Study Group. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med 2015; 3: 524–33. Kiesewetter S, Macek M Jr, Davis C, et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat Genet 1993; 5: 274–78. Witt DR, Schaefer C, Hallam P, et al. Cystic fibrosis heterozygote screening in 5161 pregnant women. Am J Hum Genet 1996; 58: 823–35. Thauvin-Robinet C, Munck A, Huet F, et al. The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening. J Med Genet 2009; 46: 752–58. Dekkers JF, van der Ent CK, Beekman JM. Novel opportunities for CFTR-targeting drug development using organoids. Rare Dis 2013; 1: e27112.
Permissive hypercapnia in preterm infants: the discussion continues During the past decade the threshold of viability in extremely preterm infants has shifted to the lower gestational age of younger than 26 weeks postmenstrual age with subsequent improved survival. As a consequence, more of the survivors have to be treated for typical co-morbidities of extreme prematurity such as brochopulmonary dysplasia. The latter is associated with extreme prematurity and ventilator-induced lung injury. Data from small studies have suggested that permissive hypercapnia might reduce the incidence of lung injury, and as a result the German multicentre PHELBI study group1 embarked on a large randomised www.thelancet.com/respiratory Vol 3 July 2015
controlled study of 830 extremely low birthweight infants testing two levels of partial pressures of carbon dioxide (PCO2) during the first 2 weeks of life. The study was stopped prematurely after an interim analysis of 359 (23%) of 1534 infants screened in 53 months, in which investigators noted no difference in the primary outcome of death or moderate to severe bronchopulmonary dysplasia between groups. We would like to commend the authors and the journal for publishing the no difference findings as the report contains lessons to be learned. The study included preterm infants from 23 to 28 weeks gestation onwards.
Published Online June 16, 2015 http://dx.doi.org/10.1016/ S2213-2600(15)00240-4 See Articles page 534
499
Roger Job/Reporters/Science Photo Library
Comment
The incidence of bronchopulmonary dysplasia is highest in infants younger than 28 weeks and therefore this was an appropriate target population. Of note is the long duration of recruitment of more than 4 years. Clinical practice might have changed during this time especially with the increasing use of non-invasive means of respiratory support to wean or avoid intratracheal ventilation altogether.2 During non-invasive ventilator support PCO2 concentrations are established by the breathing efforts of newborn babies and clinicians are less able to affect the concentrations directly. Future studies will need to consider this growing group of patients and would benefit from new non-invasive techniques such as plethysmogram analysis of pulse oximetry traces to measure spontaneous breathing rates together with PCO2 concentrations.3 In the PHELBI study, PCO2 target concentrations were aimed at three increasing levels in the first 14 days of life.1 The study design might have inadvertently affected the clinician’s decision to ventilate newborn babies to achieve the PCO2 targets during the study period. It was not possible to mask the clinicians to group allocations. After 14 days, 25% of infants were still ventilated. In the present trend of neonatal clinical care to wean to non-invasive ventilation as soon as possible, many tertiary care centres would consider this intubation rate to be high.2 The PHELBI study group targeted the lung injury aspect of bronchopulmonary dysplasia by using low tidal volume ventilation strategies without controlling 500
for it with volume-targeted ventilation methods that help to reduce lung injury. Results of recent animal studies have also shown that lung injury starts early at resuscitation at birth and could be improved by allowing redistribution of placental blood through delaying cord cutting and initiating lung expansion first.4 Findings of the study by Polglase and colleagues4 in preterm lambs showed a smoother transition to extrauterine life after birth if the lambs were given inflation breath with their cord intact. This method enabled a smooth increase in pulmonary blood flow with expansion of lung alveoli.4 Benefits of redistribution of placental blood in preterm infants such as better adaptation after birth, less need for blood transfusion, less incidence of intraventricular haemorrhage and necrotising enterocolitis have been widely described and therefore have been incorporated into international guidelines on newborn resuscitation.5–8 The PHELBI study group did not collect information about whether the recruited infants received standardised delivery room management and subsequent stabilisation to minimise lung injury, including any means of redistribution of placental blood before enrolment into the study. Future studies of the reduction of lung injury and the development of bronchopulmonary dysplasia should include this aspect of resuscitation of the preterm infant. This approach would need antenatal consent to enrol the preterm infant into the trial. Findings of a recently published qualitative study of parents showed a positive attitude towards enrolling their unborn preterm baby into a randomised trial to study two different ways of enhancing redistribution of placental blood at birth.9,10 Increasing data seem to suggest that the lower the gestational age the more varying practices between hospitals will affect the outcome of preterm infants.11 With the participation of many centres in increasingly larger randomised controlled trials over a long time (like the PHELBI study), accounting for comparative effectiveness between centres (ie, alternative standards of care, assessing outcomes important to individuals, and incorporating varied settings and participants) becomes an important part of outcome assessment.12 Much still needs to be learnt about lung injury and the development of bronchopulmonary dysplasia in extremely low birthweight infants. The pattern of respiratory distress syndrome in these infants has www.thelancet.com/respiratory Vol 3 July 2015
Comment
changed over the past 10 years. The introduction of antenatal steroids has changed the incidence of severe respiratory distress syndrome. Researchers can now look at other preventive measures at the time of resuscitation at birth,5 which might have more effect than PCO2 concentrations in the first day of life or different ventilation strategies such as low volume ventilation or patient synchronised ventilation. The PHELBI study provides the basis for further discussions on how to design future study protocols. Optional antenatal consent will probably increase recruitment in trials of extremely low birthweight infants of 23 to 28 weeks gestation.
2
Heike Rabe, Jose Ramon Fernandez-Alvarez
9
Brighton and Sussex Medical School and University Hospitals, Academic Department of Paediatrics, Royal Alexandra Children’s Hospital, Brighton BN2 5BE, UK [email protected]
10
We declare no competing interests.
11
1
Thome UH, Genzel-Boroviczeny O, Bohnhorst B, et al, for the PHELBI Study Group. Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. Lancet Resp Med 2015; published online June 16. http://dx.doi.org/10.1016/S22132600(15)00204-0.
3
4
5
6
7
8
12
Fernandez-Alvarez R, Gandhi RS, Amess PN, et al. Heated humidified high flow nasal cannula versus low flow nasal cannula as weaning mode from nasal CPAP in infants ≤28 weeks gestation. Eur J Pediatr 2014; 173: 93–98. Wertheim D, Olden C, Symes L, et al. Monitoring respiration in wheezy preschool children by pulse oximetry plethysmogram analysis. Med Biol Eng Comput 2013; 51: 965–70. Polglase GR, Dawson JA, Kluckow M, et al. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping) improves systemic and cerebral oxygenation in preterm lambs. PLoS One 2015; 10: e0117504. Sweet D, Carnielli V, Greisen G, et al. European Consensus Guidelines on the management of neonatal respiratory distress syndrome in preterm infants: 2010 Update. Neonatology 2010; 97: 402–17. The American College of Obstetricians and Gynecologists. Committee on Obstetric Practice. Timing of umbilical cord clamping after birth. Obstet Gynecol 2012; 120: 1522–26. The National Institute for Health and Care Excellence. Intrapartum care: care of healthy women and their babies during childbirth. December, 2014. http://www.nice.org.uk/guidance/cg190 (accessed Feb 25, 2015). WHO. Every Newborn: an action plan to end preventable deaths. http://www.everynewborn.org/Documents/Full-action-plan-EN.pdf (accessed March 10, 2015). Ayers S, Sawyers A, During C, et al. Parents report positive experiences about enrolling babies in a cord-related trial before birth. Acta Pediatr 2015; 104: e164–e170. Rabe H, Jewison A, Fernandez Alvarez R, et al. Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates. A randomized controlled trial. Obstet & Gynecol 2011; 117: 205–11. Rysavy MA, Li L, Bell EF, et al. Between-hospital variation in treatment and outcomes in extremely preterm Infants. New Engl J Med 2015; 372: 1801–11. Lagatta J, Uhing M, Panepinto J. Comparative effectiveness and practice variation in neonatal care. Clin Perinatol 2014; 41: 833–45.
About 5–10% of patients on mechanical ventilation will have persistent respiratory failure necessitating prolonged mechanical ventilation.1 This condition is part of the larger syndrome of chronic critical illness, in which critically ill patients have continuing organ failures leading to protracted periods of organ support.2 Both prolonged mechanical ventilation and chronic critical illness are important public health problems. In the USA, for example, more than 380 000 individuals are estimated to have chronic critical illness every year, with costs exceeding US$50 billion annually.3 A meta-analysis of studies reporting clinical outcomes in prolonged mechanical ventilation published in The Lancet Respiratory Medicine further highlights the challenges posed by these patients.4 Emily Damuth and colleagues4 systematically reviewed 124 studies from 16 different countries worldwide, with sobering results. Pooled mortality at hospital discharge was 26%, 57% of www.thelancet.com/respiratory Vol 3 July 2015
patients were liberated from mechanical ventilation by the end of their hospital stay, and 22% of patients were discharged home. Perhaps most concerning was that 59% of patients were dead at 1 year. These findings should serve as a wake-up call to clinicians, hospital administrators, and health policy makers involved in the care of patients with prolonged mechanical ventilation. Efforts are urgently needed to increase liberation rates and improve survival. Unfortunately, the way to proceed in this area is not at all clear. Despite the increasing recognition of the immense clinical and financial burden chronic critical illness puts on health systems, evidence-based strategies to guide clinical care in this population are lacking. This situation is the real wake-up call— not that outcomes must be improved, but that how to improve them is simply not known. Immediate, targeted research is needed to fill this knowledge gap
Jade/Blend Images/Corbis
Improving outcomes in prolonged mechanical ventilation: a road map
Published Online May 21, 2015 http://dx.doi.org/10.1016/ S2213-2600(15)00205-2 See Articles page 544
501
Arg117His-CFTR status has direct relevance to newborn screening programmes for cystic fibrosis. Inclusion of Arg117His-CFTR in screening panels leads to identification of infants who have a very low likelihood of developing cystic fibrosis lung disease, at least during childhood. Removing the Arg117His-CFTR mutation from newborn screening panels has been advocated.9 This position will need to be reassessed in view of Moss and colleagues’ results,6 since ivacaftor will probably play an important part in treating Arg117His/5T-CFTR and might well be of benefit in those few patients with Arg117His/7T-CFTR who have lung disease. These data6 are therefore an important contribution to the medical literature, since they provide clear support for the treatment of patients with Arg117His-CFTR. The results also show CFTR activity in children as well as in adults, providing a rationale for the treatment of some children. Whether patient-specific response to ivacaftor can be predicted from specimens studied ex vivo—eg, nasal epithelial cells or intestinal organoids—remains to be clarified.10 Long-term studies to assess the safety and efficacy of ivacaftor in general are also needed. In this respect, evidence that the drug can modify the rate of decline in lung function or the development of structural injury will be important. Finally, the results from Moss and colleagues’ study reinforce the notion of mutation-specific treatment of CFTR dysfunction—an important step on the road to personalised care for all individuals with cystic fibrosis.
Frank J Accurso University of Colorado and Children’s Hospital Colorado, Aurora, CO 80045, USA [email protected] I have served on the Cystic Fibrosis Foundation Therapeutics, Inc./Vertex Pharmaceuticals, Inc. Joint Development Committee since 2003. The purpose of this committee is to improve the communication between the two groups. I represent Cystic Fibrosis Foundation Therapeutics, Inc. in these discussions and have no ties, financial or otherwise, with Vertex Pharmaceuticals, Inc. I receive reimbursement from Cystic Fibrosis Foundation Therapeutics, Inc. for the twice a year in-person committee meetings only for plane fare, lunch, and parking. I do not receive any remuneration from Cystic Fibrosis Foundation Therapeutics, Inc. for time or effort. I receive no remuneration at all from Vertex Pharmaceuticals, Inc. 1 2 3
4
5
6
7
8 9
10
Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med 2005; 352: 1992–2001. Stoltz DA, Meyerholz DK, Welsh MJ. Origins of cystic fibrosis lung disease. N Engl J Med 2015; 372: 1574–75. Van Goor F, Hadida S, Grootenhuis, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci USA 2009; 106: 18825–30. Ramsey BW, Davies J, McElvaney NG, et al. VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365: 1663–72. De Boeck K, Munck A, Walker S, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros 2014; 13: 674–80. Moss RB, Flume PA, Elborn JS, et al, on behalf of the VX11-770-110 (KONDUCT) Study Group. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med 2015; 3: 524–33. Kiesewetter S, Macek M Jr, Davis C, et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat Genet 1993; 5: 274–78. Witt DR, Schaefer C, Hallam P, et al. Cystic fibrosis heterozygote screening in 5161 pregnant women. Am J Hum Genet 1996; 58: 823–35. Thauvin-Robinet C, Munck A, Huet F, et al. The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening. J Med Genet 2009; 46: 752–58. Dekkers JF, van der Ent CK, Beekman JM. Novel opportunities for CFTR-targeting drug development using organoids. Rare Dis 2013; 1: e27112.
Permissive hypercapnia in preterm infants: the discussion continues During the past decade the threshold of viability in extremely preterm infants has shifted to the lower gestational age of younger than 26 weeks postmenstrual age with subsequent improved survival. As a consequence, more of the survivors have to be treated for typical co-morbidities of extreme prematurity such as brochopulmonary dysplasia. The latter is associated with extreme prematurity and ventilator-induced lung injury. Data from small studies have suggested that permissive hypercapnia might reduce the incidence of lung injury, and as a result the German multicentre PHELBI study group1 embarked on a large randomised www.thelancet.com/respiratory Vol 3 July 2015
controlled study of 830 extremely low birthweight infants testing two levels of partial pressures of carbon dioxide (PCO2) during the first 2 weeks of life. The study was stopped prematurely after an interim analysis of 359 (23%) of 1534 infants screened in 53 months, in which investigators noted no difference in the primary outcome of death or moderate to severe bronchopulmonary dysplasia between groups. We would like to commend the authors and the journal for publishing the no difference findings as the report contains lessons to be learned. The study included preterm infants from 23 to 28 weeks gestation onwards.
Published Online June 16, 2015 http://dx.doi.org/10.1016/ S2213-2600(15)00240-4 See Articles page 534
499
Roger Job/Reporters/Science Photo Library
Comment
The incidence of bronchopulmonary dysplasia is highest in infants younger than 28 weeks and therefore this was an appropriate target population. Of note is the long duration of recruitment of more than 4 years. Clinical practice might have changed during this time especially with the increasing use of non-invasive means of respiratory support to wean or avoid intratracheal ventilation altogether.2 During non-invasive ventilator support PCO2 concentrations are established by the breathing efforts of newborn babies and clinicians are less able to affect the concentrations directly. Future studies will need to consider this growing group of patients and would benefit from new non-invasive techniques such as plethysmogram analysis of pulse oximetry traces to measure spontaneous breathing rates together with PCO2 concentrations.3 In the PHELBI study, PCO2 target concentrations were aimed at three increasing levels in the first 14 days of life.1 The study design might have inadvertently affected the clinician’s decision to ventilate newborn babies to achieve the PCO2 targets during the study period. It was not possible to mask the clinicians to group allocations. After 14 days, 25% of infants were still ventilated. In the present trend of neonatal clinical care to wean to non-invasive ventilation as soon as possible, many tertiary care centres would consider this intubation rate to be high.2 The PHELBI study group targeted the lung injury aspect of bronchopulmonary dysplasia by using low tidal volume ventilation strategies without controlling 500
for it with volume-targeted ventilation methods that help to reduce lung injury. Results of recent animal studies have also shown that lung injury starts early at resuscitation at birth and could be improved by allowing redistribution of placental blood through delaying cord cutting and initiating lung expansion first.4 Findings of the study by Polglase and colleagues4 in preterm lambs showed a smoother transition to extrauterine life after birth if the lambs were given inflation breath with their cord intact. This method enabled a smooth increase in pulmonary blood flow with expansion of lung alveoli.4 Benefits of redistribution of placental blood in preterm infants such as better adaptation after birth, less need for blood transfusion, less incidence of intraventricular haemorrhage and necrotising enterocolitis have been widely described and therefore have been incorporated into international guidelines on newborn resuscitation.5–8 The PHELBI study group did not collect information about whether the recruited infants received standardised delivery room management and subsequent stabilisation to minimise lung injury, including any means of redistribution of placental blood before enrolment into the study. Future studies of the reduction of lung injury and the development of bronchopulmonary dysplasia should include this aspect of resuscitation of the preterm infant. This approach would need antenatal consent to enrol the preterm infant into the trial. Findings of a recently published qualitative study of parents showed a positive attitude towards enrolling their unborn preterm baby into a randomised trial to study two different ways of enhancing redistribution of placental blood at birth.9,10 Increasing data seem to suggest that the lower the gestational age the more varying practices between hospitals will affect the outcome of preterm infants.11 With the participation of many centres in increasingly larger randomised controlled trials over a long time (like the PHELBI study), accounting for comparative effectiveness between centres (ie, alternative standards of care, assessing outcomes important to individuals, and incorporating varied settings and participants) becomes an important part of outcome assessment.12 Much still needs to be learnt about lung injury and the development of bronchopulmonary dysplasia in extremely low birthweight infants. The pattern of respiratory distress syndrome in these infants has www.thelancet.com/respiratory Vol 3 July 2015
Comment
changed over the past 10 years. The introduction of antenatal steroids has changed the incidence of severe respiratory distress syndrome. Researchers can now look at other preventive measures at the time of resuscitation at birth,5 which might have more effect than PCO2 concentrations in the first day of life or different ventilation strategies such as low volume ventilation or patient synchronised ventilation. The PHELBI study provides the basis for further discussions on how to design future study protocols. Optional antenatal consent will probably increase recruitment in trials of extremely low birthweight infants of 23 to 28 weeks gestation.
2
Heike Rabe, Jose Ramon Fernandez-Alvarez
9
Brighton and Sussex Medical School and University Hospitals, Academic Department of Paediatrics, Royal Alexandra Children’s Hospital, Brighton BN2 5BE, UK [email protected]
10
We declare no competing interests.
11
1
Thome UH, Genzel-Boroviczeny O, Bohnhorst B, et al, for the PHELBI Study Group. Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. Lancet Resp Med 2015; published online June 16. http://dx.doi.org/10.1016/S22132600(15)00204-0.
3
4
5
6
7
8
12
Fernandez-Alvarez R, Gandhi RS, Amess PN, et al. Heated humidified high flow nasal cannula versus low flow nasal cannula as weaning mode from nasal CPAP in infants ≤28 weeks gestation. Eur J Pediatr 2014; 173: 93–98. Wertheim D, Olden C, Symes L, et al. Monitoring respiration in wheezy preschool children by pulse oximetry plethysmogram analysis. Med Biol Eng Comput 2013; 51: 965–70. Polglase GR, Dawson JA, Kluckow M, et al. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping) improves systemic and cerebral oxygenation in preterm lambs. PLoS One 2015; 10: e0117504. Sweet D, Carnielli V, Greisen G, et al. European Consensus Guidelines on the management of neonatal respiratory distress syndrome in preterm infants: 2010 Update. Neonatology 2010; 97: 402–17. The American College of Obstetricians and Gynecologists. Committee on Obstetric Practice. Timing of umbilical cord clamping after birth. Obstet Gynecol 2012; 120: 1522–26. The National Institute for Health and Care Excellence. Intrapartum care: care of healthy women and their babies during childbirth. December, 2014. http://www.nice.org.uk/guidance/cg190 (accessed Feb 25, 2015). WHO. Every Newborn: an action plan to end preventable deaths. http://www.everynewborn.org/Documents/Full-action-plan-EN.pdf (accessed March 10, 2015). Ayers S, Sawyers A, During C, et al. Parents report positive experiences about enrolling babies in a cord-related trial before birth. Acta Pediatr 2015; 104: e164–e170. Rabe H, Jewison A, Fernandez Alvarez R, et al. Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates. A randomized controlled trial. Obstet & Gynecol 2011; 117: 205–11. Rysavy MA, Li L, Bell EF, et al. Between-hospital variation in treatment and outcomes in extremely preterm Infants. New Engl J Med 2015; 372: 1801–11. Lagatta J, Uhing M, Panepinto J. Comparative effectiveness and practice variation in neonatal care. Clin Perinatol 2014; 41: 833–45.
About 5–10% of patients on mechanical ventilation will have persistent respiratory failure necessitating prolonged mechanical ventilation.1 This condition is part of the larger syndrome of chronic critical illness, in which critically ill patients have continuing organ failures leading to protracted periods of organ support.2 Both prolonged mechanical ventilation and chronic critical illness are important public health problems. In the USA, for example, more than 380 000 individuals are estimated to have chronic critical illness every year, with costs exceeding US$50 billion annually.3 A meta-analysis of studies reporting clinical outcomes in prolonged mechanical ventilation published in The Lancet Respiratory Medicine further highlights the challenges posed by these patients.4 Emily Damuth and colleagues4 systematically reviewed 124 studies from 16 different countries worldwide, with sobering results. Pooled mortality at hospital discharge was 26%, 57% of www.thelancet.com/respiratory Vol 3 July 2015
patients were liberated from mechanical ventilation by the end of their hospital stay, and 22% of patients were discharged home. Perhaps most concerning was that 59% of patients were dead at 1 year. These findings should serve as a wake-up call to clinicians, hospital administrators, and health policy makers involved in the care of patients with prolonged mechanical ventilation. Efforts are urgently needed to increase liberation rates and improve survival. Unfortunately, the way to proceed in this area is not at all clear. Despite the increasing recognition of the immense clinical and financial burden chronic critical illness puts on health systems, evidence-based strategies to guide clinical care in this population are lacking. This situation is the real wake-up call— not that outcomes must be improved, but that how to improve them is simply not known. Immediate, targeted research is needed to fill this knowledge gap
Jade/Blend Images/Corbis
Improving outcomes in prolonged mechanical ventilation: a road map
Published Online May 21, 2015 http://dx.doi.org/10.1016/ S2213-2600(15)00205-2 See Articles page 544
501