SYSTEMATIC REVIEW PROTOCOL

A comparison of the impact of cuffed versus uncuffed endotracheal tubes on the incidence of tracheal tube exchange and on post-extubation airway morbidity in pediatric patients undergoing general anesthesia: a systematic review protocol Amanda T. Spitzer Kathryn M. Sims Texas Christian University, Center for Evidence Based Practice and Research: a Collaborating Centre of the Joanna Briggs Institute, Fort Worth, Texas, USA Review question/objective: The objective of this systematic review is to synthesize the best available evidence regarding the impact of cuffed versus uncuffed endotracheal tubes on the incidence of tracheal tube exchange during the perioperative period and on post-extubation airway morbidity prior to hospital discharge in pediatric patients undergoing general anesthesia. Keywords Cuffed endotracheal tube; pediatric general anesthesia; pediatric intubation; uncuffed endotracheal tube Background I ndications for endotracheal intubation, which refers to the insertion of a breathing tube into the trachea through the nose or mouth, include assisted or controlled ventilation, airway protection against foreign substances and the maintenance of airway patency and adequate oxygenation. 1,2 Prior to the 1940s, endotracheal intubation was infrequently attempted in children due to endotracheal tube (ETT) construction from hard rubber material designed for adult airway dimensions. 1 In the early 1960s, a softer, more flexible ETT crafted from polyvinyl chloride was introduced, revolutionizing pediatric respiratory management. 1 Early recommendations regarding advanced airway placement in children younger than 8 years of age, whether for short- or long-term intubation, included the use of appropriately sized uncuffed ETTs. 1,2 One primary argument for the use of uncuffed ETTs in the pediatric population centered around benefits of an ETT of larger internal diameter (ID), which lowered airway resistance and decreased breathing effort in young patients breathing spontaneously Correspondence: Amanda T. Spitzer, mandy.spitzer@tcu.edu There is no conflict of interest in this project. DOI: 10.11124/JBISRIR-2016-002614 under diethyl ether anesthesia. 2 For example a size of 4-mm ETT has 16 times more resistance to gas flow than a size of 8-mm ETT. The standard practice of placing uncuffed ETTs was also based on the belief that cuffed ETTs were associated with complications such as trauma to the developing airway mucosa caused by the oversized outer tube diameter, poorly designed cuffs, incorrectly positioned tubes and overinflating of the cuff. 2,3 A thorough understanding of anatomical structures and developmental changes unique to the pediatric airway is an essential component of safe and effective clinical care of children undergoing anesthesia. Historically, this understanding was largely based on key differences between adult and pediatric airways such as the position of the larynx, shape of the epiglottis, vocal cords, mucous membranes and cricoid ring. 4 More specifically, the pediatric larynx was noted to be more cephalad with gradual caudad movement during development. 4 The infant epiglottis was described as longer, stiffer, narrower and U or V shaped. 4 Infant vocal cords were noted to be shorter, comprising approximately 50% of the anterior glottis, as opposed to it being two-thirds in older children. 5 Additionally, the narrowest portion of the adult airway was identified as the rima glottidis, whereas cadaver studies led early JBI Database of Systematic Reviews and Implementation Reports ß 2016 THE JOANNA BRIGGS INSTITUTE 10

researchers to believe that the cricoid ring might represent the narrowest portion of the pediatric airway. 4 Perhaps most importantly, these studies identified the pediatric larynx as conical- or funnel-shaped, which develops into a more cylindrical shape in older children. 4 6 More recent studies utilizing bronchoscopic examination or radiological imaging have provided evidence that questions traditional beliefs regarding the pediatric airway. 6 8 According to contemporary studies, the anterior-posterior (AP) dimension of the larynx is cylindrical, and the transverse dimension is conical with the narrowest point at the level of the vocal cords. 6,7 The rigid cricoid ring remains functionally the narrowest portion of the larynx and is prone to mucosal damage and edema. 6 The relationship between the AP and transverse dimensions does not change during development; rather, all dimensions increase linearly with age. 6,7 The AP dimension is larger than the transverse dimension at all levels of the larynx above the cricoid and at the cricoid level in most children, suggesting an elliptical rather than round shape. 6,7 Wani et al. 8 concluded that the subglottic area was elliptical, and the cricoid ring remained generally round; nevertheless, inserting a round uncuffed ETT into an elongated airway lumen results in considerable pressure on the lateroposterior walls needed to achieve a reasonable seal. 9 Despite ensuring an audible air leak at an inspiratory pressure of 20 cmh 2 O, varying degrees of mucosal pressure may still occur at other areas of the cricoid mucosa due to the elliptical shape of the pediatric airway. 9 Initially, mucosal compression leads to decreased blood flow and airway edema; however, prolonged insult may result in increased airway morbidity, including mucosal ulceration, scar formation and laryngotracheal stenosis. 1 Whether or not to use pediatric cuffed ETTs remains an ongoing debate in the pediatric anesthesia community. Despite many clear advantages of cuffed ETTs, there are various design flaws that hinder safe routine use. Weiss et al. evaluated 11 cuffed and four uncuffed tracheal tubes from four different manufacturers with IDs from 2.5 to 7.0 mm. 10 A few problems with cuffed ETTs, which vary from manufacturer to manufacturer, include outer diameter, cuff position, cuff diameter and depth markings. 10 Tubes with identical IDs have different outer diameters, which can cause substantial mucosal damage as tubes are selected on the basis of ID sizes. 10 Prevention of high cuff pressures while maintaining an adequate tracheal seal is achieved through the use of high-volume/lowpressure (HVLP) cuffs in adult patients. 10 The HVLP cuff design features a cross-sectional area that is 150% of the internal cross-sectional area of the trachea at 20 cmh 2 O cuff pressure, resulting in a sufficient seal while maintaining low pressure. 10 Weiss et al. found that tubes with an ID up to 4.5 mm did not meet the HVLP criteria, although some of the larger tube sizes did. 10 An additional issue with pediatric ETTs is the cuff position that should be below the rigid cricoid ring at the level of the expandable tracheal rings. 10 Cuffs placed above the trachea can cause substantial damage to the cricoid cartilage, subglottic area and vocal cords; however, the tip of some tubes terminates too far down the trachea, even when the cuff is in proper position. 10 Consequently, the short pediatric trachea decreases the margin of safe-cuffed ETT placement. 11 Depth markings on ETTs are necessary to ensure proper placement of the tracheal tube cuff and tip. 10 However, only five out of the 11 cuffed tubes examined by Weiss et al. had depth markings, and many of them did not correspond to correct tube placement. 10 In the light of these shortcomings, recent advancements have led to the development of the Microcuff 1 ETT (Halyard Health, Alpharetta, Georgia, USA). 4 In contrast to bulkier high-pressure and low-volume ETTs, the Microcuff 1 has an ultrathin (10 mm) polyurethane cuff, achieving higher volumes at lower pressure, resulting in an adequate tracheal seal with decreased risk of mucosal damage. 4 Additionally, the Murphy eye, a side vent allowing for continued ventilation in the event of occlusion at the tip of the ETT, is omitted to allow distal placement of the cuff on the ETT shaft to accommodate shorter pediatric tracheas. 4 Although the introduction of the laryngeal mask airway has reduced the number of required intubations for general anesthesia in both pediatric and adult patients, the majority of surgical procedures in small children still require tracheal intubation. 11 The Microcuff 1 ETT addresses many of the design flaws of previous cuffed ETTs, but monitoring of intracuff pressure is still necessary to prevent injury. 4 The advantages of cuffed ETTs include reduced risk of aspiration, decreased gas leak around the tube, improved efficacy of ventilation when higher inspiratory pressures are required, more reliable end-tidal carbon dioxide monitoring, less anesthetic gas JBI Database of Systematic Reviews and Implementation Reports ß 2016 THE JOANNA BRIGGS INSTITUTE 11

pollution in the operating room and possibly lower fresh gas flows. 10,13 Proposed additional benefits could be the decreased rate of tracheal tube exchange and decreased use of over-sized uncuffed tubes, which could be a major cause of subglottic mucosal ischemia. 10,12,13 For example, a prospective randomized controlled multi-center trial in Switzerland, studying pediatric patients undergoing general anesthesia, reported a tracheal tube exchange rate of only 2.1% for cuffed ETTs compared with 30.8% for uncuffed ETTs. 14 Tracheal tubes must be exchanged for a different size or type when the leak around the tube is too large to allow effective positive pressure ventilation. 15 As with any medical intervention, endotracheal intubation is associated with risks, including dental injury, laryngotracheal trauma, vocal cord paralysis, neck or cervical problems, uvular damage, corneal abrasion, esophageal or bronchial intubation and subglottic injury. 16 An additional laryngoscopy and intubation for a tracheal tube exchange expose the pediatric patient to these various risks. This systematic review will compare the use of cuffed versus uncuffed ETTs and the impact on tracheal tube exchange rate and on post-extubation airway morbidity in pediatric patients. Inclusion criteria Types of participants The review will consider studies that include all patients within the age range of full-term newborns (>3 kg) up to children 15 years of age undergoing general anesthesia and requiring endotracheal intubation. Pediatric patients requiring long-term intubation and mechanical ventilation in the intensive care unit will not be included in this review. Types of intervention(s)/phenomena of interest The review will consider studies that evaluate cuffed ETTs in comparison with uncuffed ETTs for pediatric patients undergoing general anesthesia. Outcomes The review will consider studies that measure the rate of ETT exchange based on the need for an alternative type or size during the perioperative period, as well as studies measuring post-extubation airway morbidity, defined as stridor and/or croup occurring prior to hospital discharge. Types of studies The review will examine any experimental study design, including randomized controlled trials, non-randomized controlled trials and quasi-experimental studies. Observational study designs, including prospective and retrospective studies, as well as descriptive epidemiological studies, including case series and individual case reports will be also be considered in an effort to evaluate the most current evidence-based research regarding the effectiveness of cuffed versus uncuffed ETTs in pediatric patients undergoing anesthesia. Search strategy The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in each phase of this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Third, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English or English translation will be considered for inclusion in this review. Studies published between the inception of routine endotracheal intubation of pediatric patients in 1960 and December 2015 will be considered for inclusion in this review. 1 Electronic databases to be searched include: EMBASE CINAHL Complete PubMed ProQuest Cochrane Central Register of Controlled Trials Cochrane Database of Systematic Reviews Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports. The search for unpublished studies will include: Google Scholar MedNar ProQuest Dissertations and Theses New York Academy of Medicine Grey Literature Report. JBI Database of Systematic Reviews and Implementation Reports ß 2016 THE JOANNA BRIGGS INSTITUTE 12

Initial keywords to be used will include: cuffed endotracheal tube, uncuffed endotracheal tube, pediatric intubation, pediatric general anesthesia. Assessment of methodological quality Studies selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer. Data extraction Data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. Data synthesis Quantitative data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry to minimize the risk of error. Effect sizes, expressed as odds ratio (for categorical data), and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard x 2. In cases in which statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate. References 1. Aker J. An emerging clinical paradigm: the cuffed pediatric endotracheal tube. AANA J 2008;76(4):293 300. 2. Fine GF, Borland LM. The future of the cuffed endotracheal tube. Paediatr Anaesth 2004;14(1):38 42. 3. Crankshaw D, McViety J, Entwistle M. A review of cuffed vs uncuffed endotracheal tubes in children. Pediatr Anesth Crit Care J 2014;2(2):70 3. 4. Tobias JD. Pediatric airway anatomy may not be what we thought: implications for clinical practice and the use of cuffed endotracheal tubes. Paediatr Anaesth 2015;25(1): 9 19. 5. Schmidt AR, Weiss M, Engelhardt T. The paediatric airway: basic principles and current developments. Eur J Anaesthesiol 2014;31(6):293 9. 6. Litman RS, Weissend EE, Shibata D, Westesson P. Developmental changes of laryngeal dimensions in unparalyzed, sedated children. Anesthesiology 2003;98(1):41 5. 7. Dalal PG, Murray D, Messner AH, Feng A, McAllister J, Molter D. Pediatric laryngeal dimensions: an age-based analysis. Anesth Analg 2009;108(5):1475 9. 8. Wani TM, Bissonnette B, Malik MR, Hayes D Jr, Ramesh AS, Al Sohaibani M, et al. Age-based analysis of pediatric upper airway dimensions using computed tomography imaging. Pediatr Pulmonol 2015. doi:10.1002/ppul. 23232, [published online June 17 2015]. 9. Weiss M, Gerber AC. Cuffed tracheal tubes in children things have changed. Paediatr Anaesth 2006;16(10): 1005 7. 10. Weiss M, Dullenkopf A, Gysin C, Dillier CM, Gerber AC. Shortcomings of cuffed paediatric tracheal tubes. Br J Anaesth 2004;92(1):78 88. 11. Lönnqvist PA. Cuffed or uncuffed tracheal tubes during anesthesia in infants and small children: time to put the eternal discussion to rest? Br J Anaesth 2009;103(6):783 5. 12. Holzki J. Laryngeal damage from tracheal intubation. Paediatr Anaesth 1997;7(6):435 7. 13. Ho AMH, Aun CST, Karmakar MK. The margin of safety associated with the use of cuffed paediatric tracheal tubes. Anaesthesia 2002;57(2):169 82. 14. Weiss M, Dullenkopf A, Fischer JE, Keller C, Gerber AC. European Paediatric Endotracheal Intubation Study Group. Prospective randomized controlled multi-centre trial of cuffed or uncuffed endotracheal tubes in small children. Br J Anaesth 2009;103(6):867 73. 15. Taylor C, Subaiya L, Corsino D. Pediatric cuffed endotracheal tubes: an evolution of care. Ochsner J 2011;11(1): 52 56. 16. Fine GF, Maxwell LG, Gerber AC. New advances in pediatric ventilation: revolutionizing the management of pediatric intubation with cuffed tubes. Roswell, GA: Kimberly-Clark Healthcare; 2008; Supplement. JBI Database of Systematic Reviews and Implementation Reports ß 2016 THE JOANNA BRIGGS INSTITUTE 13

Appendix I: Appraisal instruments aster ¼ }fx1} JBI Database of Systematic Reviews and Implementation Reports ß 2016 THE JOANNA BRIGGS INSTITUTE 14

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Appendix II: Data extraction instruments JBI Database of Systematic Reviews and Implementation Reports ß 2016 THE JOANNA BRIGGS INSTITUTE 16

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