Upper Respiratory Infections and Airway Adverse Events in Pediatric Procedural Sedation

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Upper Respiratory Infections Michael D. Mallory, MD, MPH,a Curtis Travers, MPH,b Courtney E. McCracken, PhD,b Jamesand Hertzog, Airway MD,c Joseph P. Cravero, Adverse MDd Events in Pediatric Procedural Sedation BACKGROUND: abstract

Upper respiratory infections (URIs) are associated with airway adverse events (AAEs) during general anesthesia. There have been no large studies examining the relationship between URIs and AAEs during pediatric procedural sedation. We hypothesized that there would be a relationship between URI status and AAEs in pediatric METHODS: procedural sedation. We examined prospectively collected data from the Pediatric Sedation Research Consortium database. Specific questions regarding URI status were added to the database to facilitate our analysis. Characteristics of patients, procedure types, adjunctive medications, adverse events, and airway interventions (AIs) were reported. We performed bivariate analysis of adverse events and URI status, then used a multivariable logistic regression model to assess the relationship between URI status and adverse events. We RESULTS: examined the secondary outcome of AI similarly.

Of the 105728 sedations entered into the Pediatric Sedation Research Consortium database during the study period, we were able to use 83491 for analysis. Controlling for multiple patient, drug, and procedure characteristics, recent and current URI were associated with increased frequency of AAEs. In general, the frequency of AAEs and AIs increased from recent URI, to current URI-clear secretions to current URI-thick secretions. CONCLUSIONS: We did not find a relationship between URI status and non-AAEs. URI status is associated with a statistically significant increase in frequency of AAEs and AI during pediatric procedural sedation for the population sedated by our consortium. Although URI status merits consideration in determining potential risk for sedation, rates of some AAEs and AIs remained low regardless of URI status.

Wha w t’s Kno n on This Subject: Several studies aPediatric Emergency Medicine Associates, Children’s Healthcare of Atlanta at Scottish Rite, Atlanta, Georgia; bDepartment of Pediatrics, Emory University, Children’s Healthcare of Atlanta, Atlanta, Georgia; cDepartment suggest that when anesthesia is administered to of Pediatrics, Division of Critical Care Medicine, Nemours Alfred I. DuPont Hospital for Children, Wilmington, patients with a URI there are increased AAEs. Until Delaware; and dDepartment of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, now, there have been no studies that assess the Harvard University, Boston, Massachusetts relationship between URI and AAEs in pediatric Dr Mallory conceptualized and designed the study, assisted in statistical analysis, reviewed the procedural sedation. analysis, drafted the initial manuscript, and approved the final manuscript as submitted; Drs What This Study Adds: We examine data from Cravero and Hertzog conceptualized and designed the study, drafted the initial manuscript, and 83491 sedations and demonstrate that URIs approved the final manuscript as submitted; and Mr Travers and Dr McCracken conducted the are associated with an increased rate of AAEs. initial analyses and provided critical review of the manuscript. Regardless, the rates of AAEs remain low even in DOI: https://doi.org/10.1542/peds.2017-0009 children with recent or current URIs. Accepted for publication Apr 19, 2017 To cite: Mallory MD, Travers C, McCracken CE, et al. Upper Respiratory Infections and Airway Adverse Events in Pediatric Procedural Sedation. Pediatrics. 2017;140(1): e20170009

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The identification of potential patient find an increased incidence of AAEs 25 separate areas of inquiry or procedural factors associated with in patients with current URIs. We and collected information on the occurrence of adverse outcomes also examined airway interventions patient demographics, diagnostic during pediatric procedural sedation (AIs) as a secondary outcome, and categories associated with the can be used to enhance patient hypothesized that we would find an procedure, coexisting diagnoses, safety. Upper respiratory infections increased incidence of AIs in patients procedures performed, medications (URIs) are the most common with current URI as well. administered, adverse events and illnesses in children. Estimates of Methods interventions. To ensure consistency the prevalence of these infections in data entry, for any field that The Pediatric Sedation Research indicate as many as 30% of children involves interpretation, pop-up text Consortium have a URI during the winter1, months2 was available to explain the field. in the Northern Hemisphere. ‍ The Only deidentified data were collected. impact of this disease burden on pediatric procedural sedation is The PSRC was established in 2003 In 2012, questions designed to unclear. Numerous studies suggest as a collaborative, multidisciplinary specifically identify patients with that when anesthesia is administered group of sedation practitioners a URI were added to the PSRC to patients with a current or dedicated to promoting the delivery data collection tool (Supplemental of optimal sedation for children recent URI– there is an increased Figure 2). Parents were asked undergoing tests and procedures. incidence3 6 of perioperative adverse about symptoms related to the events. ‍‍ These studies suggest The PSRC database was initiated in upper respiratory tract. If the child that the incidence of airway adverse 2004 for the purpose of collecting had runny nose, nasal congestion, events (AAEs) such as coughing, information on a large number of sneezing, or mild cough (without bronchospasm, and laryngospasm pediatric procedural sedations to sputum production), and the parent is higher not only during an active better understand and improve the and sedation provider agreed that URI, but may also be increased in the practice of sedation in children. these symptoms were because of 2 to 4 weeks after the infection. On Participation in the PSRC database a current URI, they were eligible the other hand, there are no studies is voluntary, but participating for inclusion in the URI cohort. that specifically address the issue institutions are required to obtain This definition is similar to that approval from their respective as to whether the presence of a URI previously6, used13 in the anesthesiology at the time of pediatric procedural institutional review boards, identify literature. ‍ The instructions to sedation is associated with an a primary investigator, and agree to PSRC members was to make this increase in similar adverse events. standardized methodology for data decision in conjunction with the Because it is impossible to study this collection and quality oversight. families. The nature of secretions was subject in a randomized, controlled, Audits are required every 6 months based on the parental description. or blinded manner, we used an to include an accounting of numbers The symptoms and signs of URI observational methodology in a large, of sedation encounters and quality of were collected before sedation as ongoing, multicenter collaborative data entry to ensure data integrity. part of the standard data collection data sharing effort (the Pediatric To avoid selection bias, primary for presedation assessment. Sedation Research Consortium investigators agree to only enter Patients were excluded from being [PSRC] database) to investigate the data from sedation areas in which categorized as having a URI if they relationship between URI symptoms >90% of sedation encounters can exhibited systemic symptoms such and the frequency of AAEs as be reliably captured. Data collection as fever, or if they had physical methodology has been described reported by our member institutions. examination findings suggesting This database is designed to collect in a detailed report of the first specific lower respiratory tract data on sedation demographics, 300007 sedations– published in pathophysiology such as wheezing practice characteristics, and 2006 and in7 numerous12 subsequent or rales. The URI variable was adverse events that occur during publications. ‍ ‍ coded as either no URI, recent URI, procedural sedation or immediately Data were entered into the PSRC meaning that the patient had URI afterward. To facilitate this study, database via a standardized, web- symptoms within the past 2 weeks, we customized the data collection based data collection tool. A secure but none currently, or current URI interface for a defined period, adding site, web-based data system, at the time of sedation. Because questions about URI symptoms maintained by the Dartmouth there may be a spectrum of severity specifically so that we could Bioinformatics Group was employed of URI, the data entry tool had the investigate this potential association. for data collection and storage. user specify whether a current We hypothesized that we would The data entry tool consisted of URI at time of sedation was most Downloaded from www.aappublications.org/news by guest on October 1, 2021 2 Mallory et al Statistical Analysis accurately characterized by thin and/ the model for suction. Obesity was or clear secretions or thick and/ defined as a weight greater than the Descriptive statistics were used to or green secretions by the parent 95th percentile for sex and age based examine patient characteristics, or the provider. Data for this study on the Centers for Disease Control procedures performed, and were collected between November and Prevention growth curves. medications used. For ease of 10, 2012 and July 7, 2015. Forty- presentation, nil per os (NPO) data Results five centers contributed data to the were collapsed into a single variable PSRC database during this period to indicate the presence of one or (Supplemental Table 6). more NPO violations. A patient was During the study period, information on 105728 sedations were entered The PSRC database collects data deemed to have had an NPO violation on multiple potential adverse if before sedation they had clear into the PSRC database. We excluded events. Definitions for the adverse liquids within 2 hours, breast milk 19282 (18.2%) for missing URI status information and 2948 events have been agreed on and within 4 hours, nonfat solids within 6 are available to all participants as hours,χ or a full meal within 8 hours. (2.8%) for missing other important “ 2 demographic data, leaving 83491 a part of the data entry tool. The tests were used to assess for ” sedations in our analysis data set. data collection tool includes hover differences in variables based on text that defines each element we URI status. A multivariable logistic Patient demographics are presented are collecting. For example, if the “ ” regression model was developed in Table 1. Patients with no URI PSRC member places the cursor over to assess the adjusted association were older than those with recent or oxygen desaturation , the definition “ of URI status with AAEs and AIs. current URI. The boy to girl ratio was pops up in text. This definition reads, ” Variables shown to be associated similar in each group, but trended oxygen saturation decreased to “ with adverse events in our data and toward a higher proportion of boys in <90% for more than 30 seconds. ” “ previous studies were included in the the current URI categories compared There is also an option for <80% for ” initial model. Interactions between with recent and no URI categories. more than 30 seconds and <70% medication variables were assessed The majority of each group had for more than 30 seconds. Our and significant interaction terms ASA classification I or II, but the definition of laryngospasm requires were retained in the model. Models current URI with thick and/or green evidence of stridorous breathing with were assessed for collinearity and secretion group did have a higher or without evidence of frank airway adjusted by removing variables, proportion of classification III or IV obstruction. We do not require that if necessary. Because of the large patients, and fewer classification I an intervention was taken to reverse number of sedations in our dataset, patients. The proportion of patients the event. we could control for a large number who had at least 1 NPO violation was In collaboration with the of variables in the model. We lowest in the current URI groups. controlled for demographic factors, participating centers, the authors ‍Table 2 lists the 6 most commonly comorbidities, procedure types, and (a priori) defined those events that performed procedure categories locations as well as sedative agents seemed directly related to the airway broken down by URI status. and adjunctive medications. The final as AAEs. This category included Regardless of URI status, the model included American Society of airway obstruction, apnea oxygen majority of patients were sedated Anesthesiology (ASA) classification, desaturation, cough, secretions for radiology procedures, followed age, obesity, sex, NPO status, asthma, requiring suction, laryngospasm, by hematology and/or oncology developmental delay, metabolic stridor, wheezing, emergent AI, and procedures. Eighty percent of and/or genetic, neurologic, seasonal snoring. radiology procedures were MRIs. allergy, procedure type (bone, dental, AIs collected by the PSRC include gastrointestinal, hematology and/ A synopsis of sedative, analgesic, bag-mask ventilation, continuous or oncology, neurologic, radiology, and adjunctive medication use is positive airway pressure, surgery, painful, other), propofol, provided in Table 3. Propofol was endotracheal tube placement, jaw ketamine, dexmedetomidine, the most commonly used sedative in thrust or chin lift, nasotracheal tube atropine, glycopyrrolate, fentanyl, all groups. Ketamine was the second placement, nasopharyngeal airway and the interaction between propofol most commonly given sedative. placement, oxygen delivery (blowby, and fentayl. Because suction and Opioid analgesics were administered nasal cannula, or mask blowby), dental procedures were highly in 23.3%P of cases, and were more oral airway placement, airway correlated (suction was performed commonly used in patients with repositioning, suction, laryngeal in >80% of dental procedures), we no URI ( < .001). Atropine and mask airway placement, and other. removed dental procedures from glycopyrrolate were given to 2.7% Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 140, number 1, July 2017 3 TABLE 1 Demographic Characteristics by URI Status No URI (n = 70 830) Recent URI (n = 3354) Current URI With Clear Current URI With Thick Secretion (n = 9307) Secretion (n = 658) Mean age in months (median; IQR) 79.1 (60; 33–120) 55.8 (36; 20–72) 54.1 (36; 20–72) 57.6 (36; 19–84) Girl, n (%) 31 995 (45.2) 1483 (44.2) 3736 (43.2) 271 (41.2) ASA status, n (%) I 15 129 (21.4) 728 (21.7) 1573 (18.2) 62 (9.4) II 45 023 (63.6) 2189 (65.3) 5662 (65.5) 415 (63.1) III 10 512 (14.8) 430 (12.8) 1393 (16.1) 169 (25.7) IV 166 (0.2) 7 (0.2) 21 (0.2) 12 (1.8) ≥1 NPO violation (%) 8861 (12.5) 688 (20.5) 798 (9.2) 78 (11.9) Clear liquids within 2 h 763 (1.1) 37 (1.1) 110 (1.3) 10 (1.5) Breast milk within 4 h (n = 5981) 18 (0.4) 0 (0.0) 4 (1.3) 1 (3.1) Nonfat solids within 6 h 1096 (1.6) 48 (1.4) 123 (1.4) 13 (2.0) Full meal within 8 h (n = 78 950) 7946 (11.9) 648 (20.4) 664 (8.2) 67 (10.9) IQR, interquartile range.

TABLE 2 Most Common Procedures by URI Status Procedure Overall (n = 83 491) No URI (n = 70 830) Recent URI (n = 3354) Current URI With Clear Current URI With Thick Secretion (n = 8649) Secretion (n = 658) Any radiology 46 183 (55.3) 37 935 (53.6) 2056 (61.3) 5751 (66.5) 441 (67.0) MRI 36 715 (44.0) 30 167 (42.6) 1544 (46.0) 4687 (54.2) 317 (48.2) Other radiology 9946 (11.9) 8164 (11.5) 533 (15.9) 1121 (13.0) 128 (19.5) Hematology and/or 16 068 (19.3) 13 976 (19.7) 536 (16.0) 1459 (16.9) 97 (14.7) Oncology Gastrointestinal 6796 (8.1) 6176 (8.7) 130 (3.9) 466 (5.4) 24 (3.7) Neurological 4791 (5.7) 4084 (5.8) 206 (6.1) 461 (5.3) 40 (6.1) Other 3887 (4.7) 3433 (4.9) 144 (4.3) 276 (3.2) 34 (5.2) Painful procedurea 33 856 (40.6) 29 924 (42.3) 1155 (34.4) 2553 (29.5) 224 (34.0) Data are presented as n (%). a Includes bone marrow biopsy, cardiac (other), dental, fracture reduction, gastrointestinal (other), joint injection, LP (lumbar puncture—diagnostic and/or therapeutic), other painful procedure, orthopedic (other), PICC (peripherally inserted central catheter), renal biopsy, minor surgical, and upper endoscopy procedures.

TABLE 3 Sedatives, Analgesics, and Adjunctive Medications by URI Category Medication Overall (n = 83 491) No URI (n = 70 830) Recent URI (n = 3354) Current URI With Clear Current URI With Thick Secretion (n = 8649) Secretion (n = 658) Sedatives Propofol 72 627 (87.0) 61 413 (86.7) 2777 (82.8) 7874 (91.0) 563 (85.6) Ketamine 5576 (6.7) 4966 (7.0) 193 (5.8) 391 (4.5) 26 (4.0) Pentobarbital 628 (0.8) 522 (0.7) 22 (0.7) 80 (0.9) 4 (0.6) Dexmedetomidine 3344 (4.0) 2830 (4.0) 206 (6.1) 278 (3.2) 30 (4.6) Analgesics Fentanyl 19 005 (22.8) 16 604 (23.4) 721 (21.5) 1551 (17.9) 129 (19.6) Morphine 394 (0.5) 375 (0.5) 3 (0.1) 16 (0.2) 0 (0.0) Adjunctive medications Atropine 2278 (2.7) 1860 (2.6) 291 (8.7) 123 (1.4) 4 (0.6) Glycopyrrolate 5442 (6.5) 3921 (5.5) 180 (5.4) 1210 (14.0) 131 (19.9) Medication combinations Propofol + ketamine 2122 (2.5) 1937 (2.7) 43 (1.3) 135 (1.6) 7 (1.1) Propofol + fentanyl 17 582 (21.1) 15 362 (21.7) 639 (19.1) 1467 (17.0) 114 (17.3) Data are presented as n (%).

and 6.5% of all patientsP respectively. to current URI with thin and/or clear current URI with thick and/or green Administration of these agents did secretions, and then to current URI secretions). All of the AAEs except vary by URI status ( < .001). with thick and/or green secretions. apnea demonstrated a statistically χ Rates of adverse events by URI status Exceptions included stridor (only significant2 association with URI are provided in Table 4. Most of 2 recorded for current URI with status in analysis. Occurrence of the AAEs occurred with increasing thick and/or green secretions), and any AAE increased progressively frequency from no URI to recent URI, emergent AI (only 1 recorded for from 6.3% for those with no URI to Downloaded from www.aappublications.org/news by guest on October 1, 2021 4 Mallory et al TABLE 4 Adverse Events by URI Status No URI (n = 70 830) Recent URI (n = 3354) Current URI With Clear Current URI With Thick URI (n P Secretion (n = 9307) = 658) Any complication 5560 (7.9) 348 (10.4) 1381 (16.0) 158 (24.0) <.001 AAEs Wheezing 29 (0.04) 8 (0.2) 26 (0.3) 12 (1.8) <.001 Secretions requiring 482 (0.7) 48 (1.4) 352 (4.1) 59 (9.0) <.001 treatment Cough 1026 (1.5) 113 (3.4) 508 (5.9) 57 (8.7) <.001 Stridor 100 (0.1) 10 (0.3) 37 (0.4) 2 (0.3) <.001 Desaturation 1213 (1.7) 72 (2.2) 325 (3.8) 53 (8.1) <.001 Emergent AI 111 (0.2) 10 (0.3) 23 (0.3) 1 (0.2) .038 Airway obstruction 1364 (1.9) 77 (2.3) 341 (3.9) 45 (6.8) <.001 Snoring 1220 (1.7) 60 (1.8) 297 (3.4) 39 (5.9) <.001 Laryngospasm 229 (0.3) 16 (0.5) 63 (0.7) 6 (0.9) <.001 Apnea > 15 s 605 (0.9) 24 (0.7) 94 (1.1) 9 (1.4) .054 Any airway-related 4433 (6.3) 304 (9.1) 1258 (14.6) 146 (22.2) <.001 adverse event Adverse events not directly related to the airway Agitation 213 (0.3) 13 (0.4) 25 (0.3) 1 (0.2) .295 Intravenous-related 268 (0.4) 12 (0.4) 46 (0.5) 4 (0.6) .043 problem Unexpected change 241 (0.3) 6 (0.2) 15 (0.2) 3 (0.5) .026 in heart rate and/ or blood pressure >30% Procedure not 168 (0.2) 13 (0.4) 60 (0.7) 14 (2.1) <.001 completed because of a problem with sedation Vomiting 174 (0.3) 7 (0.2) 15 (0.2) 3 (0.5) .373 Aspiration 11 (0.02) 1 (0.03) 2 (0.02) 0 (0.0) .868 Unplanned admission 16 (0.02) 1 (0.03) 6 (0.07) 0 (0.0) .097 Unable to sedate 78 (0.1) 4 (0.1) 21 (0.2) 3 (0.5) .001 Emergency call to 15 (0.02) 2 (0.06) 1 (0.01) 0 (0.0) .423 anesthesia Myoclonus 62 (0.1) 0 (0.0) 8 (0.1) 2 (0.3) .087 Data are presented as n (%).

22.2% for those with current URI outcomes for which odds ratios are based on the characteristics and with thick and/or green secretions. depicted include all individual AAEs, timing of their URI. Because the event Adverse events not directly related occurrence of any AAE, occurrence "procedure unable to be completed to the airway were less likely to of any non-AAE, and procedure due to problem with sedation" was demonstrate a statistically significant not complete because of a problem strongly associated with URI status, relationship with URI status. related to sedation. Recent URI and because this outcome could be and current URI with thick and/or plausibly related to the occurrence of Rates of AI by URI status are green secretions demonstrated a AAEs, we chose to include it in Fig 1. provided in Table 5. Like AAEs, statistically significant association most AIs increased from no URI to with 7 of 10 AAEs when compared ‍Figure 2 provides a forest plot recent URI, to current URI with thin with no URI. Current URI with of the odds ratios for the various and/or clear secretions, and then to thin and/or clear secretions AIs based on URI status by using current URI with thick and/or green demonstrated a statistically no URI as the referent from the secretions. significant association with 8 of 10 multivariable logistic regression ‍Figure 1 provides a forest plot of the AAEs when compared with no URI. model that controlled for the same odds ratios for adverse events based For a number of the AAEs, confidence characteristics as the model used to on URI status by using no URI as intervals of odds ratios for URI with create Fig 1. As with AAEs, there were the referent from the multivariable thick and/or green secretions and statistically significant differences logistic regression model that URI with thin and/or clear secretions between the odds ratios for various controlled for a multitude of patient did not overlap, indicating differences AIs based on the characteristics and and procedure characteristics. The in the odds ratios for various AAEs timing of their URI. Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 140, number 1, July 2017 5 TABLE 5 AI by URI Status No URI (n = 70 830) Recent URI (n = 3354) Current URI With Clear Current URI With Thick P Secretion (n = 8649) Secretion (n = 658) None 19 846 (28.0) 780 (23.3) 1838 (21.3) 116 (17.6) <.001 Bag-mask ventilation 1087 (1.5) 65 (1.9) 205 (2.4) 29 (4.4) <.001 CPAP 1330 (1.9) 83 (2.5) 273 (3.2) 38 (5.8) <.001 Endotracheal tube 127 (0.2) 1 (0.0) 21 (0.2) 4 (0.6) .006 Jaw thrust or chin lift 5712 (8.1) 247 (7.4) 956 (11.1) 118 (17.9) <.001 Nasotracheal tube 41 (0.1) 1 (0.0) 13 (0.2) 1 (0.2) .011 Nasopharyngeal airway 564 (0.8) 41 (1.2) 189 (2.2) 22 (3.3) <.001 Mask or NC Oxygen blowby 48 160 (68.0) 2428 (72.4) 6381 (73.8) 503 (76.4) <.001 Oral airway 558 (0.8) 19 (0.6) 145 (1.7) 26 (4.0) <.001 Repositioning 13 835 (19.5) 610 (18.2) 2479 (28.7) 192 (29.2) <.001 Suction 2629 (3.7) 250 (7.5) 725 (8.4) 106 (16.1) <.001 Supraglottic or LMA 141 (0.2) 5 (0.2) 30 (0.4) 9 (1.4) <.001 Other 184 (0.3) 15 (0.5) 34 (0.4) 6 (0.9) .001 Data are presented as n (%). CPAP, continuous positive airway pressure; LMA, laryngeal mask airway; NC, nasal cannula.

Discussion

14 URIs are ubiquitous in children. Therefore, it is not surprising that children with active or recent URIs will present for therapeutic or diagnostic procedures facilitated by procedural sedation. Given the high prevalence of URIs in childhood, a generalized decision to cancel or delay a sedation and procedure because of a URI would have an enormous impact on the ability to accomplish needed tests and procedures in this patient population. The deferral or delay of a procedure could adversely affect outcomes for children undergoing cancer treatment or other time-sensitive procedures. Even if it would not affect patient FIGURE 1 health, the blanket cancellation of A forest plot of odds ratios from multivariable logistic regression model for AAEs by URI status (no current or recent URI as reference). procedures for all children with URIs would lead to costly logistical problems for parents and medical centers alike. Understanding the URIs are associated with AAEs do not indicate that anesthesia is potential risks and complications of during general anesthesia in contraindicated. Whether children providing sedation to a child with children. Investigators in the field are at the same risk (or greater) for an active or recent URI is necessary of anesthesia have defined AAE AAEs during procedural sedation to assist practitioners in developing to include specific events such as during an uncomplicated URI is an optimal sedation plan or in oxygen desaturation,– laryngospasm, uncertain. There is limited data in 18 the decision to defer a procedure. bronchospasm,5,6, 15 17 coughing, and breath- this area of practice. Grunwell et al Appreciation of the rate and nature holding. ‍ ‍ ‍ Review of this data performed a retrospective case- of AAEs and AIs associated with URIs has led to the conclusion that when control evaluation of children who will allow appropriate counseling the URI is not associated with fever had failed procedural sedation in a of patients and families concerning or any lower respiratory tract or single institution. Eighty-three cases the risk versus benefit of procedural systemic symptoms the majority of of failed sedation between January sedation. these AAEs are minor in nature and 2007 and December 2011 were Downloaded from www.aappublications.org/news by guest on October 1, 2021 6 Mallory et al thick and/or green secretions were more likely to experience airway obstruction, oxygen desaturation, snoring, secretions requiring suction, wheezing, or the occurrence of any AAE than those children with URI characterized by thin and/or clear secretions. Children with a recent URI (within 2 weeks of the procedure, but not with active symptoms at the time of the procedure) were more likely to experience airway obstruction, oxygen desaturation, cough that interfered with the procedure, secretions requiring suctioning, stridor, emergent AI, wheezing, and any AAE than those children who did not have a URI. There was no increased risk of a non-AAE for either children with a current or a FIGURE 2 recent URI when compared with A forest plot of odds ratios from multivariable logistic regression model for AIs by URI status (no children without a URI. Our use of current or recent URI as reference). multivariable regression analyses to account for variables characterizing demographics, underlying medical problems, procedures, sedative compared with a convenience sample character of the URI is an important medications, and adjunctive of 523 successful sedation cases determinant of risk for AAEs. medications, which could between January 2011 and February Children with a current URI were independently impact AAEs, failed 2011. Thirteen patient characteristics more likely to experience airway to show any effect of these factors and comorbidities were subsequently obstruction, oxygen desaturation, and strengthens the validity of the analyzed for possible association snoring, cough that interfered with association between URI and AAEs with failed sedation. After regression the procedure, secretions requiring as well as AIs during procedural analysis, the presence of URI, suctioning, laryngospasm, stridor, sedation. obstructive sleep apnea or snoring, wheezing, any AAE, or an inability ASA classification III, and older to complete the procedure because It is interesting to note that the age were likely to predict sedation of a sedation related problem than odds ratios were higher for patients failure. However, the presence of a those children who did not have a with a current URI versus a recent URI alone was a poor predictor of URI. Children with URI were also URI for all AAEs except for the need whether a child would fail sedation. more likely to receive AIs, including for an emergent AI and apnea. Our Furthermore, no correlation intubation. However, they do findings are similar but distinct between the presence of URI and the not appear to have a statistically when compared with those in the nature of any AAE could be made in significant increased risk of apnea 17 anesthesia literature in which this study. or need for emergent AIs when AAEs are noted to be significantly compared with those without We are aware of no prior studies increased over baseline for the URI. This implies that intubation, that have examined the relationship 2 weeks after the resolution of a in the few cases that it was used, between current or recent patient URI. Subtle differences in these was likely an intended part of URI and AAEs during pediatric findings are likely because of the the sedation plan. And for almost procedural sedation. Our data more invasive airway management all patients who were intubated, demonstrate that both current and that is associated with general the sedation provider was an recent URI symptoms in children anesthesia versus procedural intensivist or anesthesiologist. 17 are associated with an increased sedation. Airway hyper-reactivity risk of specific AAEs during Furthermore, our data indicate that in association with a viral infection pediatric procedural sedation. the character of secretions matters: diminishes with resolution of the Furthermore, it appears that the children with URIs characterized by infection, but the increased odds Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 140, number 1, July 2017 7 for an emergent AI in the recent found an increase in adverse out a particular AAE. Twenty-one URI group highlights the need for events associated with use of percent of database entries ongoing vigilance during procedural anticholinergics19 in conjunction with during the study period could not sedation in this 2-week period after ketamine. Our data indicate the be used because of URI status or a URI. need for additional study regarding other data elements not being the need for adding anticholinergics recorded, which may have caused As with any study that includes tens when sedating children with URIs. a selection bias. Unfortunately, of thousands of patients, we found subgroup analysis is not possible statistical significance in some AAE The large number of patients with this database model. subcategories in which the absolute available for analysis because of Additionally, we are not able to difference in incidence is relatively our multicenter approach is an comment on the number of patients small. For example, although the important strength of this study. who may have presented for difference in laryngospasm between Our study incorporated specific sedation only to have been turned those with a URI (0.7%) and questions about the presence of a away because of the severity of without a URI (0.3%) is statistically URI to our existing prospectively URI symptoms. It is possible that significant, the clinical significance collected database for the duration our selection of patients with URIs may not be of great concern to the of the study period. These focused represents a group with milder sedation provider. On the other questions allow for identification symptoms. We also recognize that hand, the consistency of the increase of patients with current and the centers involved in the PSRC in risk between the different URI recent URI. It is likely that our are willing to devote significant categories is noteworthy, as is identification of patients with a time and effort to this quality the cumulative adverse event rate, current URI is more accurate than improvement project and, as which was found to be over 15% in those with a recent URI, which such, may be higher performance those with a URI and 6.3% in those is the reason they are present in systems than average. The data without. a greater number. On the other presented here may not reflect data Notable demographic findings hand, those identified as having that would be collected from all include an older age for patients had a recent infection are almost centers around the United States or with no recent or current URI certainly accurately identified. internationally where procedural who undergo sedation. It is likely Furthermore, complications were sedation care is provided for that older patients have already specifically defined a priori for children. developed an immunity to many consistency in data collection. Our Conclusions of the viruses that cause URI results reflect the effect of URIs symptoms. Medication utilization on AAEs across various pediatric also differed for patients with a procedural sedation programs, URIs are common in children who current URI versus no URI, with institutions, provider types, present for procedural sedation. current URI patients receiving and medication regimens. Thus, Based on the results of this large more propofol and less ketamine our results should be minimally database study, children with current and narcotic. This may be because impacted by individual center effect URIs have an increased occurrence of the increased frequency of URI and applicable to many current of some AAEs and AIs. Among those in patients who were sedated for pediatric procedural sedation children with current URI, there is MRI compared with those who practices. an increased rate of some AAEs and underwent a painful procedure. The AIs for those with thick and/or green ease of titration and rapid offset Previous reports from the PSRC secretions compared with those of propofol would be desirable have outlined7,12 the limitations of our with thin and/or clear secretions. in patients with an active URI, database. ‍ This is a retrospective Despite the statistically significant as would avoiding the sialorrhea analysis of prospectively collected relationships that we found, the rates associated with ketamine. data and has all the inherent of major AAEs such as laryngospasm, Anticholinergic medications were difficulties associated with aspiration, emergent AI, unplanned also more commonly used in observational data. Blinding and admission and emergent call for patients with a current URI than randomization are not possible, anesthesia all remained <1% those without a URI, although and although definitions of the regardless of URI status. In many the impact of this practice on various AAEs are provided with instances, the increased rate of decreasing AAEs is uncertain. A the database entry tool, there AAEs and AIs that we document ’ meta-analysis of ketamine use may be some variation in various reaches statistical significance, but for pediatric procedural sedation providers threshold for calling is of questionable clinical relevance. Downloaded from www.aappublications.org/news by guest on October 1, 2021 8 Mallory et al Abbreviations Similar to the data that has been without whom this project would produced concerning general not have been completed. The anesthesia, our data supports the PSRC database is maintained as a AAE: airway adverse event general safety of procedural sedation core function of and with funding AI: airway intervention in children with URIs. from the Society for Pediatric ASA: American Society of Anesthesiology Acknowledgments Sedation. URI: upper respiratory infection PSRC: Pediatric Sedation The authors wish to recognize Susan Research Consortium The authors recognize the members Gallagher for her contributions to NPO: nil per os of the Society for Pediatric Sedation this project. Address correspondence to Michael D. Mallory, MD, MPH, Emergency Medicine, Children’s Healthcare of Atlanta at Scottish Rite, 2133 Kodiak Drive, Atlanta, GA 30345. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2017 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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Downloaded from www.aappublications.org/news by guest on October 1, 2021 10 Mallory et al Upper Respiratory Infections and Airway Adverse Events in Pediatric Procedural Sedation Michael D. Mallory, Curtis Travers, Courtney E. McCracken, James Hertzog and Joseph P. Cravero Pediatrics originally published online June 29, 2017;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2017/06/27/peds.2 017-0009 References This article cites 18 articles, 1 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2017/06/27/peds.2 017-0009#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Emergency Medicine http://www.aappublications.org/cgi/collection/emergency_medicine_ sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on October 1, 2021 Upper Respiratory Infections and Airway Adverse Events in Pediatric Procedural Sedation Michael D. Mallory, Curtis Travers, Courtney E. McCracken, James Hertzog and Joseph P. Cravero Pediatrics originally published online June 29, 2017;

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