Description of the condition

Mechanical ventilation is a life‐saving intervention for critically ill newborn infants with respiratory failure admitted to a neonatal intensive care unit (NICU). A two‐point cross‐sectional study by the Neovent Study Group in 173 European NICUs included 535 infants (mean gestational age 28 weeks and mean birth weight 1024 grams), and revealed that 85% (457) were conventionally ventilated (defined as all modes of mechanical ventilation except those in which high frequency ventilation is used). Time‐cycled, pressure–limited ventilation was used in 59% of these patients, often (51%) combined with synchronized intermittent mandatory ventilation (SIMV). Newer conventional ventilation modes, such as volume‐targeted and pressure support ventilation, were used in 9% and 7% of the patients, respectively (van Kaam 2010).

Ventilating newborn infants can be challenging due to small tidal volumes, high breathing frequencies, and the use of uncuffed endotracheal tubes. Mechanical ventilation has several short‐term complications (atelectasis, air leak syndrome, pneumonia) as well as long‐term complications (neurodevelopmental impairments and bronchopulmonary dysplasia (BPD)) (Walsh 2005; Miller 2008; van Velzen 2009; Gagliardi 2011; Gizzi 2011; Sant'Anna 2012). BPD, in particular, has been described as a major complication of prolonged mechanical ventilation. BPD has been characterized as an arrest in alveolar and vascular development (Jobe 2001). Most clinicians use the National Institute of Child Health and Human Development, the National Heart, Lung, and Blood Institute, and the Office of Rare Diseases Workshop on BPD categorizations of the severity of BPD assessed at 36 weeks postmenstrual age (Jobe 2001). This definition of BPD is simply an assessment of oxygen requirements and supplementary ventilator support, and does not evaluate lung mechanics, gas exchange, lung anatomy, or other markers of disease, such as inflammation (Jobe 2001; Jobe 2012). In recent decades, BPD has been shown to occur almost exclusively in infants born before 30 weeks' gestation. BPD is a multifactorial disease, in which mechanical ventilation plays an important role (Bancalari 2006; Jobe 2012). Although the evidence is limited, BPD causes long‐term sequelae. Wheezing and asthma in later life are associated with lung injury that developed due to mechanical ventilation during the neonatal period. The EPICure study found decreased lung function and increased respiratory morbidity into mid‐childhood (Reyburn 2012).

A meta‐analysis concluded that the use of continuous positive airway pressure compared with intubation and mechanical ventilation reduces the risk of BPD in preterm infants (Schmölzer 2013). Trittmann 2013 described how one of the strongest predictors of poor neurodevelopmental outcome in extremely preterm neonates is prolonged invasive positive pressure support. There is growing evidence that even a short period of mechanical ventilation will cause an inflammation cascade in the lungs (Reyburn 2012). This evidence suggests that weaning from mechanical ventilation should be done as soon as possible, in order to prevent pulmonary sequelae and adverse neurodevelopmental outcomes.

In the large European survey by the Neovent Study Group, the reported average duration of invasive ventilation in NICUs was four days (van Kaam 2010), varying according to age and method of ventilation. For example, Reyes 2006 compared SIMV with and without adding pressure support in a cohort of extremely low birth weight infants and reported a median duration of invasive mechanical ventilation of 25 days without, and 20 days with pressure support (Reyes 2006). Furthermore, since non‐invasive techniques have become more prevalent, the need for invasive mechanical ventilation has decreased significantly (DiBlasi 2011).

Adjunctive therapies ( e.g. diuretics, permissive hypercapnia, nutrition, caffeine) to reduce the length of mechanical ventilation and facilitate weaning from the ventilator are being used to optimize the weaning process. The use of postnatal corticosteroids have been described in several reviews and are used extensively, but the optimum dose and time of administration are still unknown (Sant'Anna 2012).

Three recent Cochrane reviews have concluded that: a synchronized mode of ventilation reduces the duration of mechanical ventilation; volume‐targeted ventilation reduces the duration of mechanical ventilation compared to pressure‐limited ventilation; and high frequency oscillatory ventilation offers no clear advantage over conventional ventilation as an initial ventilation strategy (Greenough 2008; Cools 2009; Wheeler 2010). The most widely used mode of ventilation and weaning in neonates is SIMV (van Kaam 2010; Ålander 2013).

There is no extensive evidence on the testing of newborn infants for extubation readiness. Up to 40% of newborns under 1000 grams will fail extubation (Kamlin 2006). Two instruments have been described for testing extubation readiness in newborn infants at the end of the weaning process. Use of the minute ventilation test led to a shorter time on a ventilator (Gillespie 2003), and use of the spontaneous breathing test demonstrated fewer extubation failures (Kamlin 2006). Giaccone concluded that there is wide variation in the time window used to define extubation success (Giaccone 2014). We will define extubation failure as reintubation within 24 hours after extubation, although we will collect and report other definitions used by study authors.

A recently published review and conference paper showed that guided weaning from mechanical ventilation is still an important clinical issue in neonatal critical care settings that needs to be addressed (Barker 2014; Ventura 2014). The Ventura 2014 review states that the lack of written protocols causes inertia in weaning from mechanical ventilation.

Description of the intervention

Weaning is the gradual reduction of ventilator support and the transfer of respiratory control and the work of breathing back to the patient, eventually resulting in the discontinuation of mechanical ventilation. Which mode of ventilation facilitates optimal weaning is still under debate. A protocol is defined by the UK National Health Service Institute as, "descriptions of the steps taken to care for and treat a patient..." enabling "...staff to put evidence into practice by addressing the key questions of what should be done, when, where and by whom at a local level" (NHS 2010). Protocolized weaning refers to a standardized process, in accordance with a defined sequential reduction in invasive ventilation. Three general methods are used in weaning protocols: (1) an incremental reduction of invasive ventilation support (stepwise reduction protocols); (2) an abrupt interruption of the ventilation support (a spontaneous breathing trial); or (3) a combination of the two. These methods aim to support the safe and quick transfer from full mechanical ventilation support to spontaneous breathing activity, resulting in the discontinuation of mechanical ventilation (Intensive Care Society 2007; Byrd 2010). Weaning by stepwise reduction involves titration of ventilation according to a patient's physical response and monitored respiratory parameters, such as oxygen saturation, transcutaneous carbon dioxide (CO₂), blood gas analyses, and chest radiographs. This type of weaning protocol generally specifies criteria indicating (1) that the patient is ready to start the weaning process, (2) when to reduce the amount of ventilator support gradually in a stepwise fashion, (3) when to recognize difficulties (complications) and increase ventilator support, and (4) when to extubate the patient. The protocols for spontaneous breathing trials usually include (1) a set of readiness to wean criteria, followed by (2) a trial of spontaneous breathing on continuous positive airway pressure or minimal pressure support for a prespecified time (between 30 to 120 minutes in adults Blackwood 2014), and (3) extubation criteria.

A weaning protocol can be written guidance delivered by healthcare professionals or can be supported by a computer algorithm that involves a partial or fully automated closed loop system controlled by the ventilator itself (Blackwood 2013b). Automated closed loop systems may improve the titration of mechanical support to the needs of the patients by continuously monitoring the patient's physiological changes and adapting ventilation in response to those changes. There are currently several automated systems commercially available. Examples include Mandatory Minute Ventilation, Adaptive Support Ventilation (Hamilton Medical AG, Bonaduz, Switzerland), SmartCare™/PS (Dräger Medical, Lübeck, Germany), Proportional Assist Ventilation, Neurally Adjusted Ventilatory Assist (Maquet, Solna, Sweden), and Automode® (Maquet, Solna, Sweden). A fully automated loop controlled ventilator will make the adjustment according to the ventilator's programmed software. In contrast, a written protocol delivered by healthcare professionals requires manual adjustment of the ventilator settings, usually when there is time available to do so.

How the intervention might work

Traditionally, the weaning process is driven by medical professionals. This requires the availability of a physician to adjust and stop mechanical ventilation based on the patient's weaning progress. There may be considerable variation between physicians due to different experience, skills and weaning procedures. Protocols have been shown to facilitate the weaning process because they are developed by expert clinical groups and based on the best available evidence, which in most cases is better than the decision of an individual clinician. Protocolized weaning potentially eliminates unwanted clinical variation, prevents errors, improves effectiveness and efficiency (Heymann 1994), and potentially provides better outcomes. Protocols also have the advantage of enabling other healthcare professionals (e.g. nurses and allied health professionals) to participate in the weaning process (Jubran 2012), thus reducing delays caused by the unavailability of medical staff. Furthermore, weaning protocols have been shown to be beneficial in increasing confidence by providing valuable guidance for junior nursing staff in the weaning process (Blackwood 2007).

If used incorrectly by inexperienced healthcare professionals, there are potential safety issues. There is a risk that the protocol rules may be followed blindly without due concern for the patient's weaning progress and weaning may be accelerated too quickly, resulting in increased reintubation rates. Theoretically, compliance in using the weaning protocol should not be an issue as the intention is that all mechanically ventilated patients need to come off ventilation at some point, and protocols provide guidance to measure and adjust support in accordance with patient need. However, in the hands of relatively inexperienced staff, protocol steps may be delayed due to lack of confidence. For these reasons, implementation of weaning protocols should be accompanied by training and education for all staff involved in the process.

Why it is important to do this review

The use of automated and written weaning protocols in children and adults is increasing worldwide (Rose 2011; Blackwood 2013a). This has prompted a number of systematic reviews and meta‐analyses on their effectiveness, to evaluate their benefits and harms. In adults, Blackwood 2014 reported that in comparison with usual care, protocolized weaning reduced the geometric mean duration of mechanical ventilation by 26% and weaning by 70%. With automated weaning systems in adults and children, Rose 2014 reported a 17% reduction in the geometric mean duration of mechanical ventilation and a 32% reduction in weaning duration in comparison with non‐automated systems. Both of these reviews reported that protocolized and automated weaning systems were safe, with no significant difference in adverse events compared to non‐automated or non‐protocolized methods. In children, Blackwood 2013b reported limited evidence that protocolized weaning reduces the duration of mechanical ventilation and weaning, but with only three trials in this review the evidence is inadequate to show whether achieving shorter ventilation times causes benefit or harm.

In relation to neonates, preliminary observations show promising results. A before and after observational study of the impact of a ventilation weaning protocol on outcomes of 301 premature infants with birth weight < or = 1250 grams, showed a significant decrease in the median duration of mechanical ventilation before, and one year after implementation (18 days [IQR 4, 40] versus 5 days [IQR 1, 17], P < 0.05) (Hermeto 2009). Additionally, the first extubation attempt was significantly earlier (5 days [IQR 2, 23] versus 1.5 days [IQR 1, 17], P < 0.05), and there was a significantly lower extubation failure rate (40% versus 26%, P < 0.05).

Given the growing interest in optimising the duration of mechanical ventilation, and preventing short‐ and long‐term complications in ventilated neonates, it is important to synthesize the evidence, if available, on weaning and mechanical ventilation to determine the benefits and harms in newborns, in order to provide reliable evidence to guide clinical practice.

This review planned to identify, critically appraise, and synthesize the best current evidence supporting the use of weaning protocols compared with non‐protocolized practice in reducing the duration of invasive mechanical ventilation in newborn infants.