Techniques to ascertain correct endotracheal tube placement in neonates (Review) Schmölzer GM, Roehr CC
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2014, Issue 9 http://www.thecochranelibrary.com
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . ABSTRACT . . . . . . . . . PLAIN LANGUAGE SUMMARY . BACKGROUND . . . . . . . OBJECTIVES . . . . . . . . METHODS . . . . . . . . . RESULTS . . . . . . . . . . DISCUSSION . . . . . . . . AUTHORS’ CONCLUSIONS . . ACKNOWLEDGEMENTS . . . REFERENCES . . . . . . . . CHARACTERISTICS OF STUDIES DATA AND ANALYSES . . . . . CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST . SOURCES OF SUPPORT . . . .
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Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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[Intervention Review]
Techniques to ascertain correct endotracheal tube placement in neonates Georg M Schmölzer1 , Charles C Roehr2 1 Department
of Pediatrics, Division of Neonatology, University of Alberta, Edmonton, Canada. 2 Klinik fur Neonatologie, Berlin,
Germany Contact address: Georg M Schmölzer, Department of Pediatrics, Division of Neonatology, University of Alberta, Royal Alexandra Hospital, Rm. 418 CSC, 10240 Kingsway Ave, Edmonton, AB, T5H 3V9, Canada. [email protected]. Editorial group: Cochrane Neonatal Group. Publication status and date: New, published in Issue 9, 2014. Review content assessed as up-to-date: 17 June 2014. Citation: Schmölzer GM, Roehr CC. Techniques to ascertain correct endotracheal tube placement in neonates. Cochrane Database of Systematic Reviews 2014, Issue 9. Art. No.: CD010221. DOI: 10.1002/14651858.CD010221.pub2. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT Background The success rate of correct endotracheal tube (ETT) placement for junior medical staff is less than 50% and accidental oesophageal intubation is common. Rapid confirmation of correct tube placement is important because tube malposition is associated with serious adverse outcomes including hypoxaemia, death, pneumothorax and right upper lobe collapse. ETT position can be confirmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed. Current neonatal resuscitation guidelines advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of exhaled carbon dioxide (CO2 ). Even though these devices are frequently used in the delivery room to assess tube placement, they can display false-negative results. Recently, newer techniques to assess correct tube placement have emerged (e.g. respiratory function monitor), which have been claimed to be superior in the assessment of tube placement. Objectives To assess various techniques for the identification of correct ETT placement after oral or nasal intubation in newborn infants in either the delivery room or neonatal intensive care unit compared with chest radiography. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL,The Cochrane Library 2012, Issue 4), MEDLINE (January 1996 to June 2014), EMBASE (January 1980 to Juen 2014) and CINAHL (January 1982 to June 2014). We searched clinical trials registers and the abstracts of the Society for Pediatric Research and the European Society for Pediatric Research from 2004 to 2014. We did not apply any language restrictions. Selection criteria We planned to include randomised and quasi-randomised controlled trials and cluster trials that compared chest radiography with clinical signs, respiratory function monitors, exhaled CO2 detectors or ultrasound for the assessment of correct ETT placement either in the delivery room or the neonatal intensive care unit. Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Data collection and analysis Two review authors independently evaluated the search results against the selection criteria. We did not perform data extraction and ’Risk of bias’ assessments because we identified no studies that met our inclusion criteria. Main results We did not identify any studies meeting the criteria for inclusion in this review. Authors’ conclusions There is insufficient evidence to determine the most effective technique for the assessment of correct ETT placement either in the delivery room or the neonatal intensive care unit. Randomised clinical trials comparing either of these techniques with chest radiography are warranted.
PLAIN LANGUAGE SUMMARY Assessment of techniques to ascertain correct placement of a breathing tube in neonates When a newborn baby requires a tube to be inserted into the windpipe to help him/her breathe, the clinical team can take a radiograph (X-ray) to confirm that the tube is correctly positioned. Because this is often delayed, however, newer techniques aimed at rapidly confirming the correct placement of the breathing tube within the windpipe have been developed. The rapid confirmation of correct tube placement is important because a wrongly placed tube can result in serious adverse outcomes, including death, low levels of oxygen in the blood, an abnormal collection of air or gas between the lung and the chest wall, which can interfere with breathing, or the collapse of the lung. New techniques for the rapid determination of tube placement include the use of clinical signs, the measurement of air going in and out of the lung (using a respiratory function monitor), measuring the amount of exhaled carbon dioxide (CO2 ) and using ultrasound to image the tube within the windpipe. The aim of this study was to compare chest X-ray with any of these new techniques for determining the correct placement of the breathing tube in newborn infants, in either the delivery room or the intensive care unit, and to determine subsequent mortality and morbidity in newborn infants who have been intubated. However, we were unable to identify any studies that met our inclusion criteria.
BACKGROUND
Description of the condition Endotracheal intubation remains a common procedure in the delivery room and the neonatal intensive care unit (Roberts 1995; Falck 2003; Leone 2005; O’Donnell 2006). Endotracheal intubation is either performed as an emergency (e.g. for failure of mask ventilation, difficult airway abnormalities, diaphragmatic hernia, prolonged resuscitation or instillation of surfactant) or as an elective/semi-elective procedure (e.g. for prematurity, prolonged ventilation, endotracheal tube (ETT) change, unstable airway) (Wyllie 2008). However, the success rate of correct ETT placement for junior medical staff is less than 50% and accidental oesophageal intubation is common (Roberts 1995; Falck 2003; Leone 2005; O’Donnell 2006; Schmölzer 2011). ETT position can be con-
firmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed. Current neonatal resuscitation guidelines advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of exhaled carbon dioxide (CO2 ) (Kattwinkel 2010). Clinical signs of correct tube placement include a prompt increase in heart rate, adequate chest wall movements, confirmation of position by direct laryngoscopy, observation of ETT passage through the vocal cords, presence of breath sounds in the axilla and absence of such in the epigastrium, and condensation in the ETT during ventilation (Kattwinkel 2010). However, these indicators are subjective and can be misleading even in experienced hands (Birmingham 1986). Recognising that the ETT is in the oesophagus by the use of clinical assessment alone can take several minutes (Roberts 1995; Aziz 1999; Repetto
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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2001; O’Donnell 2006). Critical issues that must be addressed when correctly placing a tracheal tube include: i) correct placement of the tube in the trachea and not the oesophagus; ii) the proper depth of the tube; and iii) the time to complete the procedure. This Cochrane review article focuses on ETT correctly placed in the trachea after intubation in the neonatal intensive care unit or the delivery room.
Description of the intervention ETT position can be confirmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed (e.g. clinical signs, exhaled CO2 , respiratory function monitors (RFMs), ultrasound).
Chest radiography A chest radiograph can be used to confirm correct tube position within the trachea, which should be just below the level of the vocal cords and well above the carina. Various techniques have been described to achieve tube positioning above the carina prior to X-ray confirmation.
Mathematical rules, confirmed by chest radiography
1. Tochen’s rule suggests that orotracheal tubes should be inserted to a length of 6 cm plus the infant’s weight in kg (Tochen 1979); a linear relationship between proper depth of ETT placement and birth weight in 40 preterm infants was reported 2. Peterson et al studied the accuracy of the 7-8-9 rule (6cm + infants weight in kg) for ETT placement (Peterson 2006). Of 75 consecutively intubated infants with a median postmenstrual age of 32 weeks and a mean body weight of 2001 g, the 7-8-9 rule was sufficient to ensure correct tube placement in infants of more than 750 g body weight. The authors concluded that for infants of less than 750 g body weight, the 7-8-9 rule may lead to an overestimation of the intubation depth and hence cause serious consequences 3. Amarilyo 2009 studied the reliability of Tochen’s rule for the orotracheal intubation of extremely low birth weight (ELBW) infants. Thirty-one infants with an ELBW of less than 1000 g were consecutively intubated at birth according to Tochen’s rule (Tochen 1979). ETT placement was tested and confirmed through chest radiography. Application of Tochen’s rule led to inadequate tube placement in almost half the infants (47%) 4. Kempley et al examined the relationship between satisfactory ETT length, gestation and weight in 208 neonates. They were able to determine that ETT length was related to gestation in a linear manner, but the relationship with weight was non-linear (Kempley 2008). This contradicts Tochen’s rule,
which states that there is a linear relationship between proper depth of ETT placement and birth weight (Tochen 1979)
Clinical signs Clinical signs of correct ETT placement include a prompt increase in heart rate, adequate chest wall movements, confirmation of position by direct laryngoscopy, observation of ETT passage through the vocal cords, presence of breath sounds in the axilla and absence of breath sounds in the epigastrium, and condensation in the ETT during ventilation (Kattwinkel 2010). We planned to include studies evaluating any of the clinical signs used to confirm correct tube placement.
Exhaled CO2 CO2 is exhaled from the lungs at concentrations that are much higher than those in air and can be detected using semiquantitative colorimetric devices, or measured with devices that give a numeric or graphic value (Roberts 1995; Aziz 1999; Repetto 2001; O’Donnell 2006; Garey 2008). Thus, CO2 detection in expired gas is a very useful method by which to confirm ETT placement (Kattwinkel 2010). Although they are frequently used to confirm correct ETT placement (Leone 2006; Schmölzer 2010a; Roehr 2010), CO2 detectors can display false-negative results, particularly when cardiac output is low (Bhende 1992; Bhende 1995), after drug administration (e.g. atropine or adrenaline), or when the individual is in severe respiratory failure and the inflation pressure is not high enough to ventilate the lungs (Kamlin 2005; Schmölzer 2011). We planned to include studies evaluating all commercially available CO2 detectors (e.g. Pedi-Cap® , Nellcor Puritan Bennett, Pleasanton, CA; EMMA™ Emergency Capnometer Phasein AB, Danderyd, Sweden, Respironics NICO and NICO2 Philips, Amsterdam, Netherlands; CO2 SMO+® , Novametrix Inc., Wallingford, CT, USA). We also planned to include any studies evaluating similar devices in the review. All of these devices are applicable for use in individuals of different sizes (e.g. neonates, children, adults). • Semiquantitative colorimetric CO2 detectors are disposable non-invasive CO2 detectors. With each inflation and expiration, a pH-sensitive chemical indicator undergoes a colour change, reflecting the change in CO2 concentration in the gas passing through it, even in the presence of low concentrations of CO2 (no colour change indicates that the ETT is not in the trachea, cardiac output is low or the lungs are under ventilated); • Systems using either main stream (in-line), side stream or micro stream (diverting) measurement of end-tidal CO2 : expired CO2 passes between a beam of infrared light and a photodetector and the absorbance is proportional to the concentration of CO2 in the gas sample. Gas samples can be analysed by the main stream or side stream or micro stream techniques:
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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◦ main stream: with each inflation and expiration an infrared sensor emits infrared light and a photodetector measures and displays (either graphically or numerically) the concentration of CO2 (disadvantages can include the heavy weight of the sensor, bulky size or an increased drag on the ETT); ◦ side stream: side stream capnometers are connected to an ETT via a side port and suck some of the expired gas into a detection sensor (this can result in erroneous CO2 measurements in neonates in particular, who have small tidal volumes or high respiratory rates); ◦ micro stream: micro stream capnometers are connected to an ETT via a side port. However, they use lower aspiration flow rates (50 mL.min−1 ), which can improve the possibly erroneous CO2 measurements associated with side stream techniques. The major differences between the available CO2 detectors are given above. These differences might have an impact on the effectiveness of the feedback to the resuscitator after intubation. Inexperience and lack of knowledge about the displayed waveforms may lead to misinterpretation of the signals. Therefore, anyone using a CO2 detector must be trained to interpret the displayed CO2 wave signals. RFM An RFM measures and displays airway pressure, gas flow and tidal volume. A flow sensor is placed between the ETT and the ventilation device. The inspiratory and expiratory tidal volumes passing through the sensor are automatically calculated by integrating the flow signal (Schmölzer 2010c). We planned to include studies evaluating all commercially available RFMs. Any studies evaluating similar devices were to be included in the review. All of these devices are applicable for use in individuals of different sizes (e.g. neonates, children, adults). We planned to include studies evaluating all commercially available RFMs (e.g. Florian Neonatal Respiratory Function Monitor, Acutronic Medical Systems AG, Zug, Switzerland; Respironics NICO and NICO2 Philips, Amsterdam, Netherlands; CO2 SMO +® , Novametrix Inc., Wallingford, CT, USA). Any studies evaluating similar devices were also to be included in the review. All of these devices are applicable to patients of different size (e.g. neonates, children, adults). • A Florian Neonatal Respiratory Monitor (Acutronic Medical Systems AG, Zug, Switzerland) continuously displays pressure, flow and tidal volume waves. It also measures and displays numerical values for PIP, PEEP, VT i , VT e , respiratory rate (RR), expiratory minute ventilation (MVe ) and displays the percentage of the leak between mask and face or around an ETT. • A Respironics NICO2 Monitor (Philips, Amsterdam, Netherlands) continuously measures and displays numerical values for VT e , RR, alveolar minute volume (MValv ), PIP and PEEP.
• The pneumotachograph CO2 SMO+® , (Novametrix Inc., Wellingford, CT, USA) continuously measures and displays numerical values for VT , RR, PIP and PEEP. The information displayed and the design of the screen are the major differences between all available RFMs. These differences might have an impact on the effectiveness of the feedback to the resuscitator after intubation. Lack of experience and knowledge about the displayed waveforms may lead to misinterpretation of the signals. Therefore, anyone using an RFM must be trained to interpret pressure, flow and tidal volume signals (Schmölzer 2010c). Ultrasound In 1986, Slovis et al (Slovis 1986) demonstrated that real-time ultrasound could be used to verify correct tube position in a newborn infant. Slovis et al (Slovis 1986) used the aortic arch as a reference point and showed that tube position could be accurately determined in 18/21 (85%) intubations. Lingle et al (Lingle 1988) reported similar results using the same technique. Galicinao et al (Galicinao 2007) used two views with a linear transducer in infants and children to verify correct tube placement; compared with physical examination plus colorimetric devices plus chest radiography, bedside ultrasound was much faster (Galicinao 2007). Dennington et al reported good correlation between ultrasound and radiography measurements, with most values being within 0.5 cm of each other (Dennington 2012). A recent observational study also reported that ultrasound appears to be as effective as capnography, although slower, for identifying endotracheal intubation (Quintela 2014). Advantages of ultrasonography over radiography include: i) reduced exposure to radiation; ii) less handling, particularly of critically ill infants; iii) the potential to determine ETT position in the delivery room, particularly for the early delivery of surfactant; and iv) earlier detection of complications due to the malposition of the ETT. Disadvantages of ultrasonography are: i) that specialised are skills required; ii) the difficulty in correctly identifying anatomical landmarks; and iii) a lack of widespread availability. The above described observational studies demonstrate that ultrasound can be used to visualise tracheal tube position in infants.
How the intervention might work Rapid confirmation of correct ETT placement at the point of care is important because tube malposition is associated with serious adverse outcomes. These include hypoxaemia, death, pneumothorax, and right upper lobe collapse. ETT position can be confirmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed. Current neonatal resuscitation guidelines advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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exhaled CO2 (Kattwinkel 2010). Clinical signs of correct ETT placement include a prompt increase in heart rate, adequate chest wall movements, confirmation of position by direct laryngoscopy, observation of ETT passage through the vocal cords, presence of breath sounds in the axilla and absence of breath sounds in the epigastrium, and condensation in the ETT during ventilation (Kattwinkel 2010). Even though CO2 detectors are frequently used in the delivery room to assess tube placement (Leone 2006; Roehr 2010; Schmölzer 2011), they can display false-negative results, particularly if cardiac output is low (Aziz 1999) or if the inflation pressure is too low to ventilate the lungs (Roberts 1995; Repetto 2001; Kamlin 2005; Schmölzer 2011). Recently, newer techniques to assess correct tube placement have emerged (e.g. respiratory function monitor, ultrasound), which have been claimed to be superior in the assessment of tube placement (Slovis 1986; Lingle 1988; Galicinao 2007; Schmölzer 2010b; Schmölzer 2010c; Schmölzer 2011).
Why it is important to do this review This systematic review will analyse the literature available on various techniques for the identification of correct ETT placement after oral or nasal intubation in newborn infants managed either in the delivery room or the neonatal intensive care unit. Endotracheal intubation remains a common procedure in both of these settings, is technically difficult (the success rate for correct ETT placement in particular for junior medical staff is less than 50%) and accidental oesophageal intubation is common (Roberts 1995; Falck 2003; Leone 2005; O’Donnell 2006; Schmölzer 2011). An international consensus statement and guidelines on neonatal resuscitation advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of exhaled CO2 (Kattwinkel 2010). However, neither of these techniques are without limitations.
OBJECTIVES To assess various techniques for the identification of correct ETT placement after oral or nasal intubation in newborn infants in either the delivery room or neonatal intensive care unit compared with two-view chest radiography.
METHODS
Criteria for considering studies for this review
Types of studies
We aimed to include all randomised and quasi-randomised controlled trials available as abstracts or peer-reviewed manuscripts. We intended to examine cluster trials individually and, if possible, include them in the meta-analysis.
Types of participants All infants intubated after birth. Infants could be either intubated in the delivery room, a resuscitation room or a neonatal intensive care unit.
Types of interventions • Chest radiograph (control) versus clinical assessment (intervention) • Chest radiograph (control) versus exhaled CO2 (intervention) • Chest radiograph (control) versus RFM (intervention) • Chest radiograph (control) versus ultrasound (intervention)
Types of outcome measures
Primary outcomes
• Success rate of various techniques for the identification of correct ETT placement
Secondary outcomes
• Death before discharge • Neonatal death < 28 days • Success rate of identification of correct ETT placement by two-view chest radiograph versus clinical assessment • Success rate of identification of correct ETT placement by two-view chest radiograph versus exhaled CO2 • Success rate of identification of correct ETT placement by two-view chest radiograph versus RFM • Success rate of identification of correct ETT placement by two-view chest radiograph versus ultrasound examination • Safety of clinical assessment to identify correct ETT placement • Safety of exhaled CO2 to identify correct ETT placement • Safety of RFM to identify correct ETT placement • Safety of ultrasound examination to identify correct ETT placement • Efficacy of clinical assessment to identify correct ETT placement • Efficacy of exhaled CO2 to identify correct ETT placement • Efficacy of RFM to identify correct ETT placement • Efficacy of ultrasound examination to identify correct ETT placement
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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• Maximum number of intubation attempts with each method of identification of correct ETT placement • Death in the delivery room • Number of endotracheal intubation attempts in delivery room • Number of endotracheal intubation attempts in neonatal intensive care unit during hospitalisation • Airway injury • Malposition of the tube • Air leaks (pneumothorax, pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema) reported either individually or as a composite outcome • Duration of supplemental oxygen requirement (number of days) • Duration of respiratory support (i.e. nasal continuous airway pressure and ventilation via an ETT considered separately and in total (number of days)) • Chronic lung disease: need for supplemental oxygen at 28 days of life; need for supplemental oxygen at 36 weeks postmenstrual age for infants born at or before 32 weeks postmenstrual age (Baraldi 2007) • Cranial ultrasound abnormalities: any intraventricular haemorrhage grade 3 or 4 according to the classification of Papile 1978 or cystic periventricular leukomalacia • Seizures, including clinical and electroencephalographic • Hypoxic ischaemic encephalopathy (grades I to III; Sarnat 1976)
ictrp). The strategies we used for searching these trial registries are detailed in Appendix 2.
Data collection and analysis We used the standard methods of the Cochrane Neonatal Review Group. Selection of studies No study meeting our search criteria was identified. We planned for each review author to independently select studies for inclusion, based on the criteria set out above, by screening the titles and abstracts obtained through the searches. We planned to obtain the full-text articles in cases where studies appeared to be eligible for inclusion, and to resolve all disagreements by discussion. Data extraction and management We planned for each review author to independently assess methodology and extract data for each included study, and then compare the results; we aimed to resolve any disagreements at any stage by discussion. We also intended to carry out an assessment of methodology regarding the blinding of randomisation, the intervention and outcome measurements, as well as completeness of follow up. Assessment of risk of bias in included studies
Search methods for identification of studies We used the standard methods of the Cochrane Neonatal Review Group. Electronic searches We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 3), MEDLINE via PubMed (January 1968 to December 2012), EMBASE (January 1980 to December 2012) and CINAHL (January 1982 to December 2012) using the search terms Infant, Newborn, Endotracheal Intubation, Respiratory Function Tests, Monitoring, physiologic, Signs and Symptoms, Respiratory, Respiratory Sounds, Radiography and X-ray tube placement. We included all languages. The full search strategies used are detailed in Appendix 1. Searching other resources Published abstracts: we searched the abstracts of the Society for Pediatric Research from 2004 to 2012 electronically through the PAS website (http://www.pas-meeting.org/abstracts/default.asp) (abstracts online). We also searched clinical trial registries for ongoing or recently completed trials (clinicaltrials.gov and who.int/
We intended to independently review the methodological quality of each trial according to guidance given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), including an assessment of: i) masking of allocation; ii) masking of intervention; iii) completeness of follow up; and iv) masking of outcome assessment. We planned to include this information in a ’Characteristics of included studies’ table. In addition, we planned to complete a ’Risk of bias’ table addressing the following methodological issues. 1. Sequence generation: was the allocation sequence adequately generated? For each included study, we planned to describe the method used to generate the allocation sequence as: adequate (any truly random process, e.g. random number table; computer random number generator); inadequate (any non-random process, e.g. odd or even date of birth; hospital or clinic record number) or unclear. 2. Allocation concealment: was allocation adequately concealed? For each included study, we planned to describe the method used to conceal the allocation sequence as: adequate (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes); inadequate (open random allocation; unsealed or nonopaque envelopes, alternation; date of birth) or unclear.
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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3. Blinding of participants, personnel and outcome assessors: was knowledge of the allocated intervention adequately prevented during the study? At the time of study entry? At the time of outcome assessment? For each included study, we planned to describe the methods used to blind study personnel from knowledge of which intervention a participant received. We planned to assess the methods as: adequate, inadequate or unclear for participants; adequate, inadequate or unclear for study personnel; and adequate, inadequate or unclear for outcome assessors and specific outcomes assessed. 4. Incomplete outcome data: were incomplete outcome data adequately addressed? For each included study and for each outcome, we planned to describe the completeness of data, including attrition and exclusions from the analysis. We planned to address whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. We planned to assess methods as: adequate (≤ 20% missing data), inadequate (> 20% missing data) or unclear. 5. Selective outcome reporting: were reports of the study free of suggestion of selective outcome reporting? For each included study, we planned to assess the possibility of selective outcome reporting bias as: adequate (where it was clear that all of the study’s prespecified outcomes and all expected outcomes of interest to the review had been reported); inadequate (where not all the study’s prespecified outcomes had been reported; one or more reported primary outcomes were not prespecified; outcomes of interest were reported incompletely and so could not be used; study failed to include results of a key outcome that would have been expected to have been reported); or unclear. 6. Other sources of bias: was the study apparently free of other problems that could put it at a high risk of bias? For each included study, we planned to note any important concerns regarding other possible sources of bias (e.g. whether there was a potential source of bias related to the specific study design or whether the trial was stopped early due to some data-dependent process). We planned to assess whether each study was free of other problems that could put it at risk of bias as: yes, no or unclear.
Measures of treatment effect We planned to analyse data using The Cochrane Collaboration’s statistical software, Review Manager (Review Manager 2011). We planned to evaluate the treatment effect using a fixed-effect model as follows: • categorical data using risk ratios (RRs), relative risk reductions, risk differences (RDs) and numbers needed to treat for an additional beneficial outcome or an additional harmful outcome;
• continuous data using means and standard deviations, and mean differences; • the 95% confidence intervals for each measure of effect; • for cluster trials, analysis at the level of the individual while accounting for the clustering. Unit of analysis issues We planned that the unit of analysis would be the participating infant in individually randomised trials and the neonatal unit (or subunit) in cluster randomised trials. We planned to include cluster-randomised trials in the analyses along with individually randomised trials. We planned to analyse them using the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) using an estimate of the intracluster correlation coefficient (ICC) derived from the trial (if possible) or from another source. If ICCs from other sources were used, we planned to report this and conduct sensitivity analyses to investigate the effect of variation in the ICC. If we identified both cluster-randomised trials and individually randomised trials, we planned to synthesise the relevant information. We planned to consider it reasonable to combine the results from both if there was little heterogeneity between the study designs and the interaction between the effect of intervention and the choice of randomisation unit was considered to be unlikely. We planned to acknowledge heterogeneity in the randomisation unit and perform a separate meta-analysis. Dealing with missing data We planned to contact the authors of included studies to supply missing data. In the case of missing data, we planned to describe the number of participants with missing data in the ’Results’ section and in a ’Characteristics of included studies’ table. We intended to present results only for the participants available. We planned to discuss the implications of the missing data in the ’Discussion’ of the review. Assessment of heterogeneity We planned to use Review Manager 2011 to assess the heterogeneity of treatment effects between trials. We planned to use the two formal statistics described below. 1. The Chi2 test for homogeneity. We planned to calculate whether statistical heterogeneity was present using the Chi2 test for homogeneity (P value < 0.1). Since this test has low power when the number of studies included in the meta-analysis is small, we intended to set the probability at the 10% level of significance (Higgins 2011) 2. The I2 statistic, to ensure that any pooling of data was valid. The impact of statistical heterogeneity was to be quantified using the I2 statistic available in Review Manager 2011, which describes the percentage of total variation across studies due to
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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heterogeneity rather than sampling error. We planned to grade the degree of heterogeneity as: 0% to 30%: might be important; 31% to 50%: moderate heterogeneity; 51% to 75%: substantial heterogeneity; 76% to 100%: considerable heterogeneity. Where there was evidence of apparent or statistical heterogeneity, we planned to assess the source of the heterogeneity using sensitivity and subgroup analyses looking for evidence of bias or methodological differences between trials.
• type of exhaled CO2 monitoring (semiquantitative colorimetric versus main stream versus side stream versus micro stream CO2 detectors); • type of RFM; • skill level of operator (< 1 year; 2 to 5 years; > 5 to 10 years; > 10 years); • discipline of operator (medical, nursing, respiratory therapist).
Assessment of reporting biases
Sensitivity analysis
We planned to obtain copies of the study protocols of all included studies and compare outcomes reported in the protocol to those reported in the findings for each of the included studies. We planned to investigate reporting and publication bias by examining the degree of asymmetry of a funnel plot. Where we suspected reporting bias (see ’Selective reporting bias’ above), we planned to attempt to contact study authors, asking them to provide missing outcome data. Where this was not possible, and the missing data could have been thought to introduce serious bias, we planned to explore the impact of including such studies in the overall assessment of results by a sensitivity analysis.
We planned to perform sensitivity analyses if issues that were suitable for sensitivity analysis were identified during the review process.
RESULTS
Description of studies Data synthesis We planned to perform statistical analyses according to the recommendations of the Cochrane Neonatal Review Group (http:/ /neonatal.cochrane.org/en/index.html). We planned to analyse all infants randomised on an intention-to-treat (ITT) basis. We planned to analyse treatment effects in the individual trials and planned to use a fixed-effect model for meta-analysis in the first instance to combine the data. Where substantial heterogeneity existed, we planned to examine the potential cause of heterogeneity in subgroup and sensitivity analyses. When we judged metaanalysis to be inappropriate, we planned to analyse and interpret individual trials separately. For estimates of typical RRs and RDs, we planned to use the Mantel-Haenszel method. For measured quantities, we planned to use the inverse variance method.
Results of the search We did not identify any studies meeting the criteria for inclusion in this review.
Included studies We did not identify any studies meeting the criteria for inclusion in this review.
Excluded studies We did not identify any studies which should be recorded as excluded from this review.
Subgroup analysis and investigation of heterogeneity We planned to perform subgroup analyses to determine whether safety and efficacy varied according to: • postmenstrual age: term (37 weeks’ postmenstrual age and above) versus preterm (between 29 and 36 weeks) versus preterm (< 29 weeks) infants; • type of clinical assessment (heart rate versus adequate chest wall movements versus confirmation of position by direct laryngoscopy versus observation of ETT passage through the vocal cords versus presence of breath sounds in the axilla and absence of breath sounds in the epigastrium versus condensation in the ETT during ventilation);
Risk of bias in included studies We did not identify any studies meeting the criteria for inclusion in this review.
Effects of interventions We did not identify any studies meeting the criteria for inclusion in this review.
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DISCUSSION Critical issues that must be addressed when correctly placing a tracheal tube include: i) correct placement of the tube in the trachea and not the oesophagus; ii) proper depth of the tube; and iii) time to complete the procedure. Rapid confirmation of correct tube placement is important because tube malposition is associated with serious adverse outcomes. The current gold standard test to confirm tube position is chest radiography; however, this is often delayed until after ventilation has commenced. Hence, pointof-care methods to confirm correct tube placement have been developed (Schmölzer 2012). The aim of the current Cochrane Review was to summarise the use of chest radiograph, clinical signs, RFMs, exhaled CO2 detectors or ultrasound to assess correct ETT placement after intubation in newborn infants either in the delivery room or the neonatal intensive care unit. We did not find any randomised or quasirandomised controlled trials addressing the use of any of these techniques to assess correct ETT placement either in the delivery room or the neonatal intensive care unit; hence, this systematic review can not establish whether their use reduces safety, or efficacy. We conclude that the additional use of clinical signs, respiratory function monitors or exhaled CO2 detectors to assess correct ETT placement in this context is based only on evidence derived from observational studies and case reports. Future studies should enrol both term and preterm infants who require endotracheal intubation to assess correct ETT placement either in the delivery room or the neonatal intensive care unit. Studies should aim to assess the selection of infants for intubation, the performance of the endotracheal intubation, the assessment of tube position, and the stabilisation of the tube and its maintenance and monitoring during intubation. Important outcomes would include those specified in our criteria for considering studies for this review.
intubation in newborn infants either in the delivery room or the neonatal intensive care unit.
Quality of the evidence There is insufficient evidence to determine the efficacy and safety of chest radiograph compared to clinical signs, RFMs, ultrasound or exhaled CO2 detectors in assessing correct ETT placement after intubation in newborn infants either in the delivery room or the neonatal intensive care unit.
Potential biases in the review process We did not identify any studies meeting the criteria for inclusion in this review.
Agreements and disagreements with other studies or reviews We did not identify any studies meeting the criteria for inclusion in this review.
AUTHORS’ CONCLUSIONS Implications for practice There is insufficient evidence to determine the efficacy and safety of clinical signs, RFMs, ultrasound or exhaled CO2 detectors in assessing correct ETT placement after intubation in newborn infants either in the delivery room or the neonatal intensive care unit.
Implications for research Summary of main results We did not identify any studies that met the criteria for inclusion in this review.
Randomised clinical trials comparing chest radiographs to clinical signs, RFMs, ultrasound or exhaled CO2 detectors with radiography for the assessment of correct ETT placement after intubation in newborn infants, either in the delivery room or the neonatal intensive care unit, are warranted.
Overall completeness and applicability of evidence There is insufficient evidence to determine the efficacy and safety of chest radiograph compared to clinical signs, RFMs, ultrasound or exhaled CO2 detectors in assessing correct ETT placement after
ACKNOWLEDGEMENTS
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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REFERENCES
References to studies awaiting assessment Schmölzer 2014 {published data only}
Additional references Amarilyo 2009 Amarilyo G, Mimouni FB, Oren A, Tsyrkin S, Mandel D. Orotracheal tube insertion in extremely low birth weight infants. Journal of Pediatrics 2009;154(5):764–5.
[updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Kamlin 2005 Kamlin CO, O’Donnell CP, Davis PG, Morley CJ. Colorimetric end-tidal carbon dioxide detectors in the delivery room: strengths and limitations. A case report. Journal of Pediatrics 2005;147(4):547–8.
Aziz 1999 Aziz HF, Martin JB, Moore JJ. The pediatric disposable endtidal carbon dioxide detector in endotracheal intubations in newborns. Journal of Perinatology 1999;19(2):110–3.
Kattwinkel 2010 Kattwinkel J, Perlman JM, Aziz K, Colby C, Fairchild K, Gallagher J, et al.Neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics 2010;126(5):e1400–13.
Baraldi 2007 Baraldi E, Filippone M. Chronic lung disease after premature birth. The New England Journal of Medicine 2007;357(19):1946–55.
Kempley 2008 Kempley ST, Moreiras JW, Petrone FL. Endotracheal tube length for neonatal intubation. Resuscitation 2008;77(3): 369–73.
Bhende 1992 Bhende MS, Thompson AE, Cook DR, Saville AL. Validity of a disposable end-tidal CO2 detector in verifying endotracheal tube placement in infants and children. Annals of Emergency Medicine 1992;21(2):142–5.
Leone 2005 Leone TA, Rich W, Finer NN. Neonatal intubation: success of pediatric trainees. Journal of Pediatrics 2005;146(5): 638–41.
Bhende 1995 Bhende MS, Thompson AE. Evaluation of an endtidal CO2 detector during pediatric cardiopulmonary resuscitation. Pediatrics 1995;95(3):395–9. Birmingham 1986 Birmingham PK, Cheney FW, Ward RJ. Esophageal intubation: a review of detection techniques. Anesthesia and Analgesia 1986;65(8):886–91.
Leone 2006 Leone TA, Rich W, Finer NN. A survey of delivery room resuscitation practices in the United States. Pediatrics 2006; 117(2):e164–75. Lingle 1988 Lingle PA. Sonographic verification of endotracheal tube position in neonates: a modified technique. Journal of Clinical Ultrasound 1988;16(8):605-9.
Dennington 2012 Dennington D, Vali P, Finer NN, Kim JH. Ultrasound confirmation of endotracheal tube position in neonates. Neonatology 2012;102(3):185-9.
O’Donnell 2006 O’Donnell CP, Kamlin CO, Davis PG, Morley CJ. Endotracheal intubation attempts during neonatal resuscitation: success rates, duration, and adverse effects. Pediatrics 2006;117(1):e16–21.
Falck 2003 Falck AJ, Escobedo MB, Baillargeon JG, Villard LG, Gunkel JH. Proficiency of pediatric residents in performing neonatal endotracheal intubation. Pediatrics 2003;112(6 Pt 1):1242–7.
Papile 1978 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. Journal of Pediatrics 1978;92(4):529–34.
Galicinao 2007 Galicinao J, Bush AJ, Godambe SA. Use of bedside ultrasonography for endotracheal tube placement in pediatric patients: a feasibility study. Pediatrics 2007;120 (6):1297-303.
Peterson 2006 Peterson J, Johnson N, Deakins K, Wilson-Costello D, Jelovsek JE, Chatburn R. Accuracy of the 7-8-9 rule for endotracheal tube placement in the neonate. Journal of Perinatology 2006;26(6):333–6.
Garey 2008 Garey DM, Ward R, Rich W, Heldt G, Leone T, Finer NN. Tidal volume threshold for colorimetric carbon dioxide detectors available for use in neonates. Pediatrics 2008;121 (6):e1524–7.
Quintela 2014 Quintela AP, Erroz OI, Matilla MM, Blanco RS, Zubillaga MD, Santos RL. Usefulness of bedside ultrasound compared to capnography and X-ray for tracheal intubation. Anales de pediatria (Barcelona, Spain) 2014;S1695-4033:25–3.
Higgins 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0
Repetto 2001 Repetto JE, Donohue PA-C PK, Baker SF, Kelly L, Nogee LM. Use of capnography in the delivery room for assessment
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of endotracheal tube placement. Journal of Perinatology 2001;21(5):284–7. Review Manager 2011 The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011. Roberts 1995 Roberts WA, Maniscalco WM, Cohen AR, Litman RS, Chhibber A. The use of capnography for recognition of esophageal intubation in the neonatal intensive care unit. Pediatric Pulmonology 1995;19(5):262–8. Roehr 2010 Roehr CC, Grobe S, Rudiger M, Hummler H, Nelle M, Proquitte H, et al.Delivery room management of very low birth weight infants in Germany, Austria and Switzerland - a comparison of protocols. European Journal of Medical Research 2010;15(11):493–503. Sarnat 1976 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Archives of Neurology 1976;33(10):696–705. Schmölzer 2010a Schmölzer GM, Olischar M, Raith W, Mueller W, Urlesberger B. Erstversorgung von Neugeborenen Kreissaalausttattung und - management in Oesterreich. Monatsschrift Kinderheilkunde 2010;158(5):471–6. Schmölzer 2010b Schmölzer GM, Hooper SB, Crossley KJ, Allison BJ, Morley CJ, Davis PG. Assessment of gas flow waves for
endotracheal tube placement in an ovine model of neonatal resuscitation. Resuscitation 2010;81(6):737–41. Schmölzer 2010c Schmölzer GM, Kamlin OC, Dawson JA, te Pas AB, Morley CJ, Davis PG. Respiratory monitoring of neonatal resuscitation. Archives of Disease in Childhood. Fetal and Neonatal Edition 2010;95(4):F295–303. Schmölzer 2011 Schmölzer GM, Poulton DA, Dawson JA, Kamlin CO, Morley CJ, Davis PG. Assessment of flow waves and colorimetric CO2 detector for endotracheal tube placement during neonatal resuscitation. Resuscitation 2011;82(3): 307–12. Schmölzer 2012 Schmölzer GM, O’Reilly M, Davis PG, Cheung PY, Roehr CC. Confirmation of correct tracheal tube placement in newborn infants. Resuscitation 2013;84(6):731–7. Slovis 1986 Slovis TL, Poland RL. Endotracheal tubes in neonates: sonographic positioning. Radiology 1986;160:262-3. Tochen 1979 Tochen ML. Orotracheal intubation in the newborn infant: a method for determining depth of tube insertion. Journal of Pediatrics 1979;95(6):1050–1. Wyllie 2008 Wyllie JP. Neonatal endotracheal intubation. Archives of Disease in Childhood. Education and Practice Edition 2008; 93(2):44–9. ∗ Indicates the major publication for the study
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CHARACTERISTICS OF STUDIES
Characteristics of studies awaiting assessment [ordered by study ID] Schmölzer 2014 Methods
Randomized control trial
Participants
Newborns
Interventions
Respiratory function Monitor compared to CO2 detector
Outcomes
Using flow waves will increase the percentage of correct tube placement in newborn infants
Notes
https://clinicaltrials.gov/ct2/show/NCT01870622
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DATA AND ANALYSES This review has no analyses.
CONTRIBUTIONS OF AUTHORS Dr Georg Schmölzer and Dr Charles-Christoph Roehr were both involved in identifying the topic for review, taking the project forward and were actively involved in writing the review, from the draft stage to the final version.
DECLARATIONS OF INTEREST Dr Georg Schmölzer is an investigator with an ongoing studies cited in this reviewSchmölzer 2014).
SOURCES OF SUPPORT Internal sources • Royal Alexandra Hospital, Canada. • University of Alberta, Canada. • Charité Berlin University Medical Center, Berlin, Germany, Germany.
External sources • Medical University Graz, Austria. • Charité Berlin University Medical Center, Berlin, Germany. • Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA. Editorial support of the Cochrane Neonatal Review Group has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN275201100016C
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2014, Issue 9 http://www.thecochranelibrary.com
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . ABSTRACT . . . . . . . . . PLAIN LANGUAGE SUMMARY . BACKGROUND . . . . . . . OBJECTIVES . . . . . . . . METHODS . . . . . . . . . RESULTS . . . . . . . . . . DISCUSSION . . . . . . . . AUTHORS’ CONCLUSIONS . . ACKNOWLEDGEMENTS . . . REFERENCES . . . . . . . . CHARACTERISTICS OF STUDIES DATA AND ANALYSES . . . . . CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST . SOURCES OF SUPPORT . . . .
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[Intervention Review]
Techniques to ascertain correct endotracheal tube placement in neonates Georg M Schmölzer1 , Charles C Roehr2 1 Department
of Pediatrics, Division of Neonatology, University of Alberta, Edmonton, Canada. 2 Klinik fur Neonatologie, Berlin,
Germany Contact address: Georg M Schmölzer, Department of Pediatrics, Division of Neonatology, University of Alberta, Royal Alexandra Hospital, Rm. 418 CSC, 10240 Kingsway Ave, Edmonton, AB, T5H 3V9, Canada. [email protected]. Editorial group: Cochrane Neonatal Group. Publication status and date: New, published in Issue 9, 2014. Review content assessed as up-to-date: 17 June 2014. Citation: Schmölzer GM, Roehr CC. Techniques to ascertain correct endotracheal tube placement in neonates. Cochrane Database of Systematic Reviews 2014, Issue 9. Art. No.: CD010221. DOI: 10.1002/14651858.CD010221.pub2. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT Background The success rate of correct endotracheal tube (ETT) placement for junior medical staff is less than 50% and accidental oesophageal intubation is common. Rapid confirmation of correct tube placement is important because tube malposition is associated with serious adverse outcomes including hypoxaemia, death, pneumothorax and right upper lobe collapse. ETT position can be confirmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed. Current neonatal resuscitation guidelines advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of exhaled carbon dioxide (CO2 ). Even though these devices are frequently used in the delivery room to assess tube placement, they can display false-negative results. Recently, newer techniques to assess correct tube placement have emerged (e.g. respiratory function monitor), which have been claimed to be superior in the assessment of tube placement. Objectives To assess various techniques for the identification of correct ETT placement after oral or nasal intubation in newborn infants in either the delivery room or neonatal intensive care unit compared with chest radiography. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL,The Cochrane Library 2012, Issue 4), MEDLINE (January 1996 to June 2014), EMBASE (January 1980 to Juen 2014) and CINAHL (January 1982 to June 2014). We searched clinical trials registers and the abstracts of the Society for Pediatric Research and the European Society for Pediatric Research from 2004 to 2014. We did not apply any language restrictions. Selection criteria We planned to include randomised and quasi-randomised controlled trials and cluster trials that compared chest radiography with clinical signs, respiratory function monitors, exhaled CO2 detectors or ultrasound for the assessment of correct ETT placement either in the delivery room or the neonatal intensive care unit. Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Data collection and analysis Two review authors independently evaluated the search results against the selection criteria. We did not perform data extraction and ’Risk of bias’ assessments because we identified no studies that met our inclusion criteria. Main results We did not identify any studies meeting the criteria for inclusion in this review. Authors’ conclusions There is insufficient evidence to determine the most effective technique for the assessment of correct ETT placement either in the delivery room or the neonatal intensive care unit. Randomised clinical trials comparing either of these techniques with chest radiography are warranted.
PLAIN LANGUAGE SUMMARY Assessment of techniques to ascertain correct placement of a breathing tube in neonates When a newborn baby requires a tube to be inserted into the windpipe to help him/her breathe, the clinical team can take a radiograph (X-ray) to confirm that the tube is correctly positioned. Because this is often delayed, however, newer techniques aimed at rapidly confirming the correct placement of the breathing tube within the windpipe have been developed. The rapid confirmation of correct tube placement is important because a wrongly placed tube can result in serious adverse outcomes, including death, low levels of oxygen in the blood, an abnormal collection of air or gas between the lung and the chest wall, which can interfere with breathing, or the collapse of the lung. New techniques for the rapid determination of tube placement include the use of clinical signs, the measurement of air going in and out of the lung (using a respiratory function monitor), measuring the amount of exhaled carbon dioxide (CO2 ) and using ultrasound to image the tube within the windpipe. The aim of this study was to compare chest X-ray with any of these new techniques for determining the correct placement of the breathing tube in newborn infants, in either the delivery room or the intensive care unit, and to determine subsequent mortality and morbidity in newborn infants who have been intubated. However, we were unable to identify any studies that met our inclusion criteria.
BACKGROUND
Description of the condition Endotracheal intubation remains a common procedure in the delivery room and the neonatal intensive care unit (Roberts 1995; Falck 2003; Leone 2005; O’Donnell 2006). Endotracheal intubation is either performed as an emergency (e.g. for failure of mask ventilation, difficult airway abnormalities, diaphragmatic hernia, prolonged resuscitation or instillation of surfactant) or as an elective/semi-elective procedure (e.g. for prematurity, prolonged ventilation, endotracheal tube (ETT) change, unstable airway) (Wyllie 2008). However, the success rate of correct ETT placement for junior medical staff is less than 50% and accidental oesophageal intubation is common (Roberts 1995; Falck 2003; Leone 2005; O’Donnell 2006; Schmölzer 2011). ETT position can be con-
firmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed. Current neonatal resuscitation guidelines advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of exhaled carbon dioxide (CO2 ) (Kattwinkel 2010). Clinical signs of correct tube placement include a prompt increase in heart rate, adequate chest wall movements, confirmation of position by direct laryngoscopy, observation of ETT passage through the vocal cords, presence of breath sounds in the axilla and absence of such in the epigastrium, and condensation in the ETT during ventilation (Kattwinkel 2010). However, these indicators are subjective and can be misleading even in experienced hands (Birmingham 1986). Recognising that the ETT is in the oesophagus by the use of clinical assessment alone can take several minutes (Roberts 1995; Aziz 1999; Repetto
Techniques to ascertain correct endotracheal tube placement in neonates (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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2001; O’Donnell 2006). Critical issues that must be addressed when correctly placing a tracheal tube include: i) correct placement of the tube in the trachea and not the oesophagus; ii) the proper depth of the tube; and iii) the time to complete the procedure. This Cochrane review article focuses on ETT correctly placed in the trachea after intubation in the neonatal intensive care unit or the delivery room.
Description of the intervention ETT position can be confirmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed (e.g. clinical signs, exhaled CO2 , respiratory function monitors (RFMs), ultrasound).
Chest radiography A chest radiograph can be used to confirm correct tube position within the trachea, which should be just below the level of the vocal cords and well above the carina. Various techniques have been described to achieve tube positioning above the carina prior to X-ray confirmation.
Mathematical rules, confirmed by chest radiography
1. Tochen’s rule suggests that orotracheal tubes should be inserted to a length of 6 cm plus the infant’s weight in kg (Tochen 1979); a linear relationship between proper depth of ETT placement and birth weight in 40 preterm infants was reported 2. Peterson et al studied the accuracy of the 7-8-9 rule (6cm + infants weight in kg) for ETT placement (Peterson 2006). Of 75 consecutively intubated infants with a median postmenstrual age of 32 weeks and a mean body weight of 2001 g, the 7-8-9 rule was sufficient to ensure correct tube placement in infants of more than 750 g body weight. The authors concluded that for infants of less than 750 g body weight, the 7-8-9 rule may lead to an overestimation of the intubation depth and hence cause serious consequences 3. Amarilyo 2009 studied the reliability of Tochen’s rule for the orotracheal intubation of extremely low birth weight (ELBW) infants. Thirty-one infants with an ELBW of less than 1000 g were consecutively intubated at birth according to Tochen’s rule (Tochen 1979). ETT placement was tested and confirmed through chest radiography. Application of Tochen’s rule led to inadequate tube placement in almost half the infants (47%) 4. Kempley et al examined the relationship between satisfactory ETT length, gestation and weight in 208 neonates. They were able to determine that ETT length was related to gestation in a linear manner, but the relationship with weight was non-linear (Kempley 2008). This contradicts Tochen’s rule,
which states that there is a linear relationship between proper depth of ETT placement and birth weight (Tochen 1979)
Clinical signs Clinical signs of correct ETT placement include a prompt increase in heart rate, adequate chest wall movements, confirmation of position by direct laryngoscopy, observation of ETT passage through the vocal cords, presence of breath sounds in the axilla and absence of breath sounds in the epigastrium, and condensation in the ETT during ventilation (Kattwinkel 2010). We planned to include studies evaluating any of the clinical signs used to confirm correct tube placement.
Exhaled CO2 CO2 is exhaled from the lungs at concentrations that are much higher than those in air and can be detected using semiquantitative colorimetric devices, or measured with devices that give a numeric or graphic value (Roberts 1995; Aziz 1999; Repetto 2001; O’Donnell 2006; Garey 2008). Thus, CO2 detection in expired gas is a very useful method by which to confirm ETT placement (Kattwinkel 2010). Although they are frequently used to confirm correct ETT placement (Leone 2006; Schmölzer 2010a; Roehr 2010), CO2 detectors can display false-negative results, particularly when cardiac output is low (Bhende 1992; Bhende 1995), after drug administration (e.g. atropine or adrenaline), or when the individual is in severe respiratory failure and the inflation pressure is not high enough to ventilate the lungs (Kamlin 2005; Schmölzer 2011). We planned to include studies evaluating all commercially available CO2 detectors (e.g. Pedi-Cap® , Nellcor Puritan Bennett, Pleasanton, CA; EMMA™ Emergency Capnometer Phasein AB, Danderyd, Sweden, Respironics NICO and NICO2 Philips, Amsterdam, Netherlands; CO2 SMO+® , Novametrix Inc., Wallingford, CT, USA). We also planned to include any studies evaluating similar devices in the review. All of these devices are applicable for use in individuals of different sizes (e.g. neonates, children, adults). • Semiquantitative colorimetric CO2 detectors are disposable non-invasive CO2 detectors. With each inflation and expiration, a pH-sensitive chemical indicator undergoes a colour change, reflecting the change in CO2 concentration in the gas passing through it, even in the presence of low concentrations of CO2 (no colour change indicates that the ETT is not in the trachea, cardiac output is low or the lungs are under ventilated); • Systems using either main stream (in-line), side stream or micro stream (diverting) measurement of end-tidal CO2 : expired CO2 passes between a beam of infrared light and a photodetector and the absorbance is proportional to the concentration of CO2 in the gas sample. Gas samples can be analysed by the main stream or side stream or micro stream techniques:
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◦ main stream: with each inflation and expiration an infrared sensor emits infrared light and a photodetector measures and displays (either graphically or numerically) the concentration of CO2 (disadvantages can include the heavy weight of the sensor, bulky size or an increased drag on the ETT); ◦ side stream: side stream capnometers are connected to an ETT via a side port and suck some of the expired gas into a detection sensor (this can result in erroneous CO2 measurements in neonates in particular, who have small tidal volumes or high respiratory rates); ◦ micro stream: micro stream capnometers are connected to an ETT via a side port. However, they use lower aspiration flow rates (50 mL.min−1 ), which can improve the possibly erroneous CO2 measurements associated with side stream techniques. The major differences between the available CO2 detectors are given above. These differences might have an impact on the effectiveness of the feedback to the resuscitator after intubation. Inexperience and lack of knowledge about the displayed waveforms may lead to misinterpretation of the signals. Therefore, anyone using a CO2 detector must be trained to interpret the displayed CO2 wave signals. RFM An RFM measures and displays airway pressure, gas flow and tidal volume. A flow sensor is placed between the ETT and the ventilation device. The inspiratory and expiratory tidal volumes passing through the sensor are automatically calculated by integrating the flow signal (Schmölzer 2010c). We planned to include studies evaluating all commercially available RFMs. Any studies evaluating similar devices were to be included in the review. All of these devices are applicable for use in individuals of different sizes (e.g. neonates, children, adults). We planned to include studies evaluating all commercially available RFMs (e.g. Florian Neonatal Respiratory Function Monitor, Acutronic Medical Systems AG, Zug, Switzerland; Respironics NICO and NICO2 Philips, Amsterdam, Netherlands; CO2 SMO +® , Novametrix Inc., Wallingford, CT, USA). Any studies evaluating similar devices were also to be included in the review. All of these devices are applicable to patients of different size (e.g. neonates, children, adults). • A Florian Neonatal Respiratory Monitor (Acutronic Medical Systems AG, Zug, Switzerland) continuously displays pressure, flow and tidal volume waves. It also measures and displays numerical values for PIP, PEEP, VT i , VT e , respiratory rate (RR), expiratory minute ventilation (MVe ) and displays the percentage of the leak between mask and face or around an ETT. • A Respironics NICO2 Monitor (Philips, Amsterdam, Netherlands) continuously measures and displays numerical values for VT e , RR, alveolar minute volume (MValv ), PIP and PEEP.
• The pneumotachograph CO2 SMO+® , (Novametrix Inc., Wellingford, CT, USA) continuously measures and displays numerical values for VT , RR, PIP and PEEP. The information displayed and the design of the screen are the major differences between all available RFMs. These differences might have an impact on the effectiveness of the feedback to the resuscitator after intubation. Lack of experience and knowledge about the displayed waveforms may lead to misinterpretation of the signals. Therefore, anyone using an RFM must be trained to interpret pressure, flow and tidal volume signals (Schmölzer 2010c). Ultrasound In 1986, Slovis et al (Slovis 1986) demonstrated that real-time ultrasound could be used to verify correct tube position in a newborn infant. Slovis et al (Slovis 1986) used the aortic arch as a reference point and showed that tube position could be accurately determined in 18/21 (85%) intubations. Lingle et al (Lingle 1988) reported similar results using the same technique. Galicinao et al (Galicinao 2007) used two views with a linear transducer in infants and children to verify correct tube placement; compared with physical examination plus colorimetric devices plus chest radiography, bedside ultrasound was much faster (Galicinao 2007). Dennington et al reported good correlation between ultrasound and radiography measurements, with most values being within 0.5 cm of each other (Dennington 2012). A recent observational study also reported that ultrasound appears to be as effective as capnography, although slower, for identifying endotracheal intubation (Quintela 2014). Advantages of ultrasonography over radiography include: i) reduced exposure to radiation; ii) less handling, particularly of critically ill infants; iii) the potential to determine ETT position in the delivery room, particularly for the early delivery of surfactant; and iv) earlier detection of complications due to the malposition of the ETT. Disadvantages of ultrasonography are: i) that specialised are skills required; ii) the difficulty in correctly identifying anatomical landmarks; and iii) a lack of widespread availability. The above described observational studies demonstrate that ultrasound can be used to visualise tracheal tube position in infants.
How the intervention might work Rapid confirmation of correct ETT placement at the point of care is important because tube malposition is associated with serious adverse outcomes. These include hypoxaemia, death, pneumothorax, and right upper lobe collapse. ETT position can be confirmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed. Current neonatal resuscitation guidelines advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of
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exhaled CO2 (Kattwinkel 2010). Clinical signs of correct ETT placement include a prompt increase in heart rate, adequate chest wall movements, confirmation of position by direct laryngoscopy, observation of ETT passage through the vocal cords, presence of breath sounds in the axilla and absence of breath sounds in the epigastrium, and condensation in the ETT during ventilation (Kattwinkel 2010). Even though CO2 detectors are frequently used in the delivery room to assess tube placement (Leone 2006; Roehr 2010; Schmölzer 2011), they can display false-negative results, particularly if cardiac output is low (Aziz 1999) or if the inflation pressure is too low to ventilate the lungs (Roberts 1995; Repetto 2001; Kamlin 2005; Schmölzer 2011). Recently, newer techniques to assess correct tube placement have emerged (e.g. respiratory function monitor, ultrasound), which have been claimed to be superior in the assessment of tube placement (Slovis 1986; Lingle 1988; Galicinao 2007; Schmölzer 2010b; Schmölzer 2010c; Schmölzer 2011).
Why it is important to do this review This systematic review will analyse the literature available on various techniques for the identification of correct ETT placement after oral or nasal intubation in newborn infants managed either in the delivery room or the neonatal intensive care unit. Endotracheal intubation remains a common procedure in both of these settings, is technically difficult (the success rate for correct ETT placement in particular for junior medical staff is less than 50%) and accidental oesophageal intubation is common (Roberts 1995; Falck 2003; Leone 2005; O’Donnell 2006; Schmölzer 2011). An international consensus statement and guidelines on neonatal resuscitation advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of exhaled CO2 (Kattwinkel 2010). However, neither of these techniques are without limitations.
OBJECTIVES To assess various techniques for the identification of correct ETT placement after oral or nasal intubation in newborn infants in either the delivery room or neonatal intensive care unit compared with two-view chest radiography.
METHODS
Criteria for considering studies for this review
Types of studies
We aimed to include all randomised and quasi-randomised controlled trials available as abstracts or peer-reviewed manuscripts. We intended to examine cluster trials individually and, if possible, include them in the meta-analysis.
Types of participants All infants intubated after birth. Infants could be either intubated in the delivery room, a resuscitation room or a neonatal intensive care unit.
Types of interventions • Chest radiograph (control) versus clinical assessment (intervention) • Chest radiograph (control) versus exhaled CO2 (intervention) • Chest radiograph (control) versus RFM (intervention) • Chest radiograph (control) versus ultrasound (intervention)
Types of outcome measures
Primary outcomes
• Success rate of various techniques for the identification of correct ETT placement
Secondary outcomes
• Death before discharge • Neonatal death < 28 days • Success rate of identification of correct ETT placement by two-view chest radiograph versus clinical assessment • Success rate of identification of correct ETT placement by two-view chest radiograph versus exhaled CO2 • Success rate of identification of correct ETT placement by two-view chest radiograph versus RFM • Success rate of identification of correct ETT placement by two-view chest radiograph versus ultrasound examination • Safety of clinical assessment to identify correct ETT placement • Safety of exhaled CO2 to identify correct ETT placement • Safety of RFM to identify correct ETT placement • Safety of ultrasound examination to identify correct ETT placement • Efficacy of clinical assessment to identify correct ETT placement • Efficacy of exhaled CO2 to identify correct ETT placement • Efficacy of RFM to identify correct ETT placement • Efficacy of ultrasound examination to identify correct ETT placement
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• Maximum number of intubation attempts with each method of identification of correct ETT placement • Death in the delivery room • Number of endotracheal intubation attempts in delivery room • Number of endotracheal intubation attempts in neonatal intensive care unit during hospitalisation • Airway injury • Malposition of the tube • Air leaks (pneumothorax, pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema) reported either individually or as a composite outcome • Duration of supplemental oxygen requirement (number of days) • Duration of respiratory support (i.e. nasal continuous airway pressure and ventilation via an ETT considered separately and in total (number of days)) • Chronic lung disease: need for supplemental oxygen at 28 days of life; need for supplemental oxygen at 36 weeks postmenstrual age for infants born at or before 32 weeks postmenstrual age (Baraldi 2007) • Cranial ultrasound abnormalities: any intraventricular haemorrhage grade 3 or 4 according to the classification of Papile 1978 or cystic periventricular leukomalacia • Seizures, including clinical and electroencephalographic • Hypoxic ischaemic encephalopathy (grades I to III; Sarnat 1976)
ictrp). The strategies we used for searching these trial registries are detailed in Appendix 2.
Data collection and analysis We used the standard methods of the Cochrane Neonatal Review Group. Selection of studies No study meeting our search criteria was identified. We planned for each review author to independently select studies for inclusion, based on the criteria set out above, by screening the titles and abstracts obtained through the searches. We planned to obtain the full-text articles in cases where studies appeared to be eligible for inclusion, and to resolve all disagreements by discussion. Data extraction and management We planned for each review author to independently assess methodology and extract data for each included study, and then compare the results; we aimed to resolve any disagreements at any stage by discussion. We also intended to carry out an assessment of methodology regarding the blinding of randomisation, the intervention and outcome measurements, as well as completeness of follow up. Assessment of risk of bias in included studies
Search methods for identification of studies We used the standard methods of the Cochrane Neonatal Review Group. Electronic searches We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 3), MEDLINE via PubMed (January 1968 to December 2012), EMBASE (January 1980 to December 2012) and CINAHL (January 1982 to December 2012) using the search terms Infant, Newborn, Endotracheal Intubation, Respiratory Function Tests, Monitoring, physiologic, Signs and Symptoms, Respiratory, Respiratory Sounds, Radiography and X-ray tube placement. We included all languages. The full search strategies used are detailed in Appendix 1. Searching other resources Published abstracts: we searched the abstracts of the Society for Pediatric Research from 2004 to 2012 electronically through the PAS website (http://www.pas-meeting.org/abstracts/default.asp) (abstracts online). We also searched clinical trial registries for ongoing or recently completed trials (clinicaltrials.gov and who.int/
We intended to independently review the methodological quality of each trial according to guidance given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), including an assessment of: i) masking of allocation; ii) masking of intervention; iii) completeness of follow up; and iv) masking of outcome assessment. We planned to include this information in a ’Characteristics of included studies’ table. In addition, we planned to complete a ’Risk of bias’ table addressing the following methodological issues. 1. Sequence generation: was the allocation sequence adequately generated? For each included study, we planned to describe the method used to generate the allocation sequence as: adequate (any truly random process, e.g. random number table; computer random number generator); inadequate (any non-random process, e.g. odd or even date of birth; hospital or clinic record number) or unclear. 2. Allocation concealment: was allocation adequately concealed? For each included study, we planned to describe the method used to conceal the allocation sequence as: adequate (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes); inadequate (open random allocation; unsealed or nonopaque envelopes, alternation; date of birth) or unclear.
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3. Blinding of participants, personnel and outcome assessors: was knowledge of the allocated intervention adequately prevented during the study? At the time of study entry? At the time of outcome assessment? For each included study, we planned to describe the methods used to blind study personnel from knowledge of which intervention a participant received. We planned to assess the methods as: adequate, inadequate or unclear for participants; adequate, inadequate or unclear for study personnel; and adequate, inadequate or unclear for outcome assessors and specific outcomes assessed. 4. Incomplete outcome data: were incomplete outcome data adequately addressed? For each included study and for each outcome, we planned to describe the completeness of data, including attrition and exclusions from the analysis. We planned to address whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. We planned to assess methods as: adequate (≤ 20% missing data), inadequate (> 20% missing data) or unclear. 5. Selective outcome reporting: were reports of the study free of suggestion of selective outcome reporting? For each included study, we planned to assess the possibility of selective outcome reporting bias as: adequate (where it was clear that all of the study’s prespecified outcomes and all expected outcomes of interest to the review had been reported); inadequate (where not all the study’s prespecified outcomes had been reported; one or more reported primary outcomes were not prespecified; outcomes of interest were reported incompletely and so could not be used; study failed to include results of a key outcome that would have been expected to have been reported); or unclear. 6. Other sources of bias: was the study apparently free of other problems that could put it at a high risk of bias? For each included study, we planned to note any important concerns regarding other possible sources of bias (e.g. whether there was a potential source of bias related to the specific study design or whether the trial was stopped early due to some data-dependent process). We planned to assess whether each study was free of other problems that could put it at risk of bias as: yes, no or unclear.
Measures of treatment effect We planned to analyse data using The Cochrane Collaboration’s statistical software, Review Manager (Review Manager 2011). We planned to evaluate the treatment effect using a fixed-effect model as follows: • categorical data using risk ratios (RRs), relative risk reductions, risk differences (RDs) and numbers needed to treat for an additional beneficial outcome or an additional harmful outcome;
• continuous data using means and standard deviations, and mean differences; • the 95% confidence intervals for each measure of effect; • for cluster trials, analysis at the level of the individual while accounting for the clustering. Unit of analysis issues We planned that the unit of analysis would be the participating infant in individually randomised trials and the neonatal unit (or subunit) in cluster randomised trials. We planned to include cluster-randomised trials in the analyses along with individually randomised trials. We planned to analyse them using the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) using an estimate of the intracluster correlation coefficient (ICC) derived from the trial (if possible) or from another source. If ICCs from other sources were used, we planned to report this and conduct sensitivity analyses to investigate the effect of variation in the ICC. If we identified both cluster-randomised trials and individually randomised trials, we planned to synthesise the relevant information. We planned to consider it reasonable to combine the results from both if there was little heterogeneity between the study designs and the interaction between the effect of intervention and the choice of randomisation unit was considered to be unlikely. We planned to acknowledge heterogeneity in the randomisation unit and perform a separate meta-analysis. Dealing with missing data We planned to contact the authors of included studies to supply missing data. In the case of missing data, we planned to describe the number of participants with missing data in the ’Results’ section and in a ’Characteristics of included studies’ table. We intended to present results only for the participants available. We planned to discuss the implications of the missing data in the ’Discussion’ of the review. Assessment of heterogeneity We planned to use Review Manager 2011 to assess the heterogeneity of treatment effects between trials. We planned to use the two formal statistics described below. 1. The Chi2 test for homogeneity. We planned to calculate whether statistical heterogeneity was present using the Chi2 test for homogeneity (P value < 0.1). Since this test has low power when the number of studies included in the meta-analysis is small, we intended to set the probability at the 10% level of significance (Higgins 2011) 2. The I2 statistic, to ensure that any pooling of data was valid. The impact of statistical heterogeneity was to be quantified using the I2 statistic available in Review Manager 2011, which describes the percentage of total variation across studies due to
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heterogeneity rather than sampling error. We planned to grade the degree of heterogeneity as: 0% to 30%: might be important; 31% to 50%: moderate heterogeneity; 51% to 75%: substantial heterogeneity; 76% to 100%: considerable heterogeneity. Where there was evidence of apparent or statistical heterogeneity, we planned to assess the source of the heterogeneity using sensitivity and subgroup analyses looking for evidence of bias or methodological differences between trials.
• type of exhaled CO2 monitoring (semiquantitative colorimetric versus main stream versus side stream versus micro stream CO2 detectors); • type of RFM; • skill level of operator (< 1 year; 2 to 5 years; > 5 to 10 years; > 10 years); • discipline of operator (medical, nursing, respiratory therapist).
Assessment of reporting biases
Sensitivity analysis
We planned to obtain copies of the study protocols of all included studies and compare outcomes reported in the protocol to those reported in the findings for each of the included studies. We planned to investigate reporting and publication bias by examining the degree of asymmetry of a funnel plot. Where we suspected reporting bias (see ’Selective reporting bias’ above), we planned to attempt to contact study authors, asking them to provide missing outcome data. Where this was not possible, and the missing data could have been thought to introduce serious bias, we planned to explore the impact of including such studies in the overall assessment of results by a sensitivity analysis.
We planned to perform sensitivity analyses if issues that were suitable for sensitivity analysis were identified during the review process.
RESULTS
Description of studies Data synthesis We planned to perform statistical analyses according to the recommendations of the Cochrane Neonatal Review Group (http:/ /neonatal.cochrane.org/en/index.html). We planned to analyse all infants randomised on an intention-to-treat (ITT) basis. We planned to analyse treatment effects in the individual trials and planned to use a fixed-effect model for meta-analysis in the first instance to combine the data. Where substantial heterogeneity existed, we planned to examine the potential cause of heterogeneity in subgroup and sensitivity analyses. When we judged metaanalysis to be inappropriate, we planned to analyse and interpret individual trials separately. For estimates of typical RRs and RDs, we planned to use the Mantel-Haenszel method. For measured quantities, we planned to use the inverse variance method.
Results of the search We did not identify any studies meeting the criteria for inclusion in this review.
Included studies We did not identify any studies meeting the criteria for inclusion in this review.
Excluded studies We did not identify any studies which should be recorded as excluded from this review.
Subgroup analysis and investigation of heterogeneity We planned to perform subgroup analyses to determine whether safety and efficacy varied according to: • postmenstrual age: term (37 weeks’ postmenstrual age and above) versus preterm (between 29 and 36 weeks) versus preterm (< 29 weeks) infants; • type of clinical assessment (heart rate versus adequate chest wall movements versus confirmation of position by direct laryngoscopy versus observation of ETT passage through the vocal cords versus presence of breath sounds in the axilla and absence of breath sounds in the epigastrium versus condensation in the ETT during ventilation);
Risk of bias in included studies We did not identify any studies meeting the criteria for inclusion in this review.
Effects of interventions We did not identify any studies meeting the criteria for inclusion in this review.
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DISCUSSION Critical issues that must be addressed when correctly placing a tracheal tube include: i) correct placement of the tube in the trachea and not the oesophagus; ii) proper depth of the tube; and iii) time to complete the procedure. Rapid confirmation of correct tube placement is important because tube malposition is associated with serious adverse outcomes. The current gold standard test to confirm tube position is chest radiography; however, this is often delayed until after ventilation has commenced. Hence, pointof-care methods to confirm correct tube placement have been developed (Schmölzer 2012). The aim of the current Cochrane Review was to summarise the use of chest radiograph, clinical signs, RFMs, exhaled CO2 detectors or ultrasound to assess correct ETT placement after intubation in newborn infants either in the delivery room or the neonatal intensive care unit. We did not find any randomised or quasirandomised controlled trials addressing the use of any of these techniques to assess correct ETT placement either in the delivery room or the neonatal intensive care unit; hence, this systematic review can not establish whether their use reduces safety, or efficacy. We conclude that the additional use of clinical signs, respiratory function monitors or exhaled CO2 detectors to assess correct ETT placement in this context is based only on evidence derived from observational studies and case reports. Future studies should enrol both term and preterm infants who require endotracheal intubation to assess correct ETT placement either in the delivery room or the neonatal intensive care unit. Studies should aim to assess the selection of infants for intubation, the performance of the endotracheal intubation, the assessment of tube position, and the stabilisation of the tube and its maintenance and monitoring during intubation. Important outcomes would include those specified in our criteria for considering studies for this review.
intubation in newborn infants either in the delivery room or the neonatal intensive care unit.
Quality of the evidence There is insufficient evidence to determine the efficacy and safety of chest radiograph compared to clinical signs, RFMs, ultrasound or exhaled CO2 detectors in assessing correct ETT placement after intubation in newborn infants either in the delivery room or the neonatal intensive care unit.
Potential biases in the review process We did not identify any studies meeting the criteria for inclusion in this review.
Agreements and disagreements with other studies or reviews We did not identify any studies meeting the criteria for inclusion in this review.
AUTHORS’ CONCLUSIONS Implications for practice There is insufficient evidence to determine the efficacy and safety of clinical signs, RFMs, ultrasound or exhaled CO2 detectors in assessing correct ETT placement after intubation in newborn infants either in the delivery room or the neonatal intensive care unit.
Implications for research Summary of main results We did not identify any studies that met the criteria for inclusion in this review.
Randomised clinical trials comparing chest radiographs to clinical signs, RFMs, ultrasound or exhaled CO2 detectors with radiography for the assessment of correct ETT placement after intubation in newborn infants, either in the delivery room or the neonatal intensive care unit, are warranted.
Overall completeness and applicability of evidence There is insufficient evidence to determine the efficacy and safety of chest radiograph compared to clinical signs, RFMs, ultrasound or exhaled CO2 detectors in assessing correct ETT placement after
ACKNOWLEDGEMENTS
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REFERENCES
References to studies awaiting assessment Schmölzer 2014 {published data only}
Additional references Amarilyo 2009 Amarilyo G, Mimouni FB, Oren A, Tsyrkin S, Mandel D. Orotracheal tube insertion in extremely low birth weight infants. Journal of Pediatrics 2009;154(5):764–5.
[updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Kamlin 2005 Kamlin CO, O’Donnell CP, Davis PG, Morley CJ. Colorimetric end-tidal carbon dioxide detectors in the delivery room: strengths and limitations. A case report. Journal of Pediatrics 2005;147(4):547–8.
Aziz 1999 Aziz HF, Martin JB, Moore JJ. The pediatric disposable endtidal carbon dioxide detector in endotracheal intubations in newborns. Journal of Perinatology 1999;19(2):110–3.
Kattwinkel 2010 Kattwinkel J, Perlman JM, Aziz K, Colby C, Fairchild K, Gallagher J, et al.Neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics 2010;126(5):e1400–13.
Baraldi 2007 Baraldi E, Filippone M. Chronic lung disease after premature birth. The New England Journal of Medicine 2007;357(19):1946–55.
Kempley 2008 Kempley ST, Moreiras JW, Petrone FL. Endotracheal tube length for neonatal intubation. Resuscitation 2008;77(3): 369–73.
Bhende 1992 Bhende MS, Thompson AE, Cook DR, Saville AL. Validity of a disposable end-tidal CO2 detector in verifying endotracheal tube placement in infants and children. Annals of Emergency Medicine 1992;21(2):142–5.
Leone 2005 Leone TA, Rich W, Finer NN. Neonatal intubation: success of pediatric trainees. Journal of Pediatrics 2005;146(5): 638–41.
Bhende 1995 Bhende MS, Thompson AE. Evaluation of an endtidal CO2 detector during pediatric cardiopulmonary resuscitation. Pediatrics 1995;95(3):395–9. Birmingham 1986 Birmingham PK, Cheney FW, Ward RJ. Esophageal intubation: a review of detection techniques. Anesthesia and Analgesia 1986;65(8):886–91.
Leone 2006 Leone TA, Rich W, Finer NN. A survey of delivery room resuscitation practices in the United States. Pediatrics 2006; 117(2):e164–75. Lingle 1988 Lingle PA. Sonographic verification of endotracheal tube position in neonates: a modified technique. Journal of Clinical Ultrasound 1988;16(8):605-9.
Dennington 2012 Dennington D, Vali P, Finer NN, Kim JH. Ultrasound confirmation of endotracheal tube position in neonates. Neonatology 2012;102(3):185-9.
O’Donnell 2006 O’Donnell CP, Kamlin CO, Davis PG, Morley CJ. Endotracheal intubation attempts during neonatal resuscitation: success rates, duration, and adverse effects. Pediatrics 2006;117(1):e16–21.
Falck 2003 Falck AJ, Escobedo MB, Baillargeon JG, Villard LG, Gunkel JH. Proficiency of pediatric residents in performing neonatal endotracheal intubation. Pediatrics 2003;112(6 Pt 1):1242–7.
Papile 1978 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. Journal of Pediatrics 1978;92(4):529–34.
Galicinao 2007 Galicinao J, Bush AJ, Godambe SA. Use of bedside ultrasonography for endotracheal tube placement in pediatric patients: a feasibility study. Pediatrics 2007;120 (6):1297-303.
Peterson 2006 Peterson J, Johnson N, Deakins K, Wilson-Costello D, Jelovsek JE, Chatburn R. Accuracy of the 7-8-9 rule for endotracheal tube placement in the neonate. Journal of Perinatology 2006;26(6):333–6.
Garey 2008 Garey DM, Ward R, Rich W, Heldt G, Leone T, Finer NN. Tidal volume threshold for colorimetric carbon dioxide detectors available for use in neonates. Pediatrics 2008;121 (6):e1524–7.
Quintela 2014 Quintela AP, Erroz OI, Matilla MM, Blanco RS, Zubillaga MD, Santos RL. Usefulness of bedside ultrasound compared to capnography and X-ray for tracheal intubation. Anales de pediatria (Barcelona, Spain) 2014;S1695-4033:25–3.
Higgins 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0
Repetto 2001 Repetto JE, Donohue PA-C PK, Baker SF, Kelly L, Nogee LM. Use of capnography in the delivery room for assessment
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of endotracheal tube placement. Journal of Perinatology 2001;21(5):284–7. Review Manager 2011 The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011. Roberts 1995 Roberts WA, Maniscalco WM, Cohen AR, Litman RS, Chhibber A. The use of capnography for recognition of esophageal intubation in the neonatal intensive care unit. Pediatric Pulmonology 1995;19(5):262–8. Roehr 2010 Roehr CC, Grobe S, Rudiger M, Hummler H, Nelle M, Proquitte H, et al.Delivery room management of very low birth weight infants in Germany, Austria and Switzerland - a comparison of protocols. European Journal of Medical Research 2010;15(11):493–503. Sarnat 1976 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Archives of Neurology 1976;33(10):696–705. Schmölzer 2010a Schmölzer GM, Olischar M, Raith W, Mueller W, Urlesberger B. Erstversorgung von Neugeborenen Kreissaalausttattung und - management in Oesterreich. Monatsschrift Kinderheilkunde 2010;158(5):471–6. Schmölzer 2010b Schmölzer GM, Hooper SB, Crossley KJ, Allison BJ, Morley CJ, Davis PG. Assessment of gas flow waves for
endotracheal tube placement in an ovine model of neonatal resuscitation. Resuscitation 2010;81(6):737–41. Schmölzer 2010c Schmölzer GM, Kamlin OC, Dawson JA, te Pas AB, Morley CJ, Davis PG. Respiratory monitoring of neonatal resuscitation. Archives of Disease in Childhood. Fetal and Neonatal Edition 2010;95(4):F295–303. Schmölzer 2011 Schmölzer GM, Poulton DA, Dawson JA, Kamlin CO, Morley CJ, Davis PG. Assessment of flow waves and colorimetric CO2 detector for endotracheal tube placement during neonatal resuscitation. Resuscitation 2011;82(3): 307–12. Schmölzer 2012 Schmölzer GM, O’Reilly M, Davis PG, Cheung PY, Roehr CC. Confirmation of correct tracheal tube placement in newborn infants. Resuscitation 2013;84(6):731–7. Slovis 1986 Slovis TL, Poland RL. Endotracheal tubes in neonates: sonographic positioning. Radiology 1986;160:262-3. Tochen 1979 Tochen ML. Orotracheal intubation in the newborn infant: a method for determining depth of tube insertion. Journal of Pediatrics 1979;95(6):1050–1. Wyllie 2008 Wyllie JP. Neonatal endotracheal intubation. Archives of Disease in Childhood. Education and Practice Edition 2008; 93(2):44–9. ∗ Indicates the major publication for the study
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CHARACTERISTICS OF STUDIES
Characteristics of studies awaiting assessment [ordered by study ID] Schmölzer 2014 Methods
Randomized control trial
Participants
Newborns
Interventions
Respiratory function Monitor compared to CO2 detector
Outcomes
Using flow waves will increase the percentage of correct tube placement in newborn infants
Notes
https://clinicaltrials.gov/ct2/show/NCT01870622
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DATA AND ANALYSES This review has no analyses.
CONTRIBUTIONS OF AUTHORS Dr Georg Schmölzer and Dr Charles-Christoph Roehr were both involved in identifying the topic for review, taking the project forward and were actively involved in writing the review, from the draft stage to the final version.
DECLARATIONS OF INTEREST Dr Georg Schmölzer is an investigator with an ongoing studies cited in this reviewSchmölzer 2014).
SOURCES OF SUPPORT Internal sources • Royal Alexandra Hospital, Canada. • University of Alberta, Canada. • Charité Berlin University Medical Center, Berlin, Germany, Germany.
External sources • Medical University Graz, Austria. • Charité Berlin University Medical Center, Berlin, Germany. • Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA. Editorial support of the Cochrane Neonatal Review Group has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN275201100016C
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