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proceedings from a special symposium on what would you do an audience interactive review of four clinical cases presented at the 52nd international respiratory congress of the american association for respiratory care december 2006 · las vegas nevada supported by an unrestricted educational grant from

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proceedings from a special symposium on what would you do an audience interactive review of four clinical cases presented at the 52nd international respiratory congress of the american association for respiratory care december 2006 · las vegas nevada 1 foreword dean r hess phd rrt faarc symposium chair pediatric acute respiratory distress syndrome ira m cheifetz md faarc adolescent with an asthma exacerbations timothy r myers bs rrt-nps hypoxic respiratory failure in a newborn steven m donn md exacerbation of chronic obstuctive pulmonary disease dean r hess phd rrt faarc instructions and questions for you to earn continuing respiratory care education crce contact hours 3 11 american association for respiratory care 9425 n macarthur blvd suite100 irving tx 75063-4706 www.aarc.org 19 ray masferrer rrt faarc editor 25 copyright © 2007 by the american association for respiratory care 31 continuing respiratory care education crce approved for 3 contact hours see page 31 for instructions.

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foreword what would you do an audience interactive review of four clinical cases dean r hess phd rrt faarc r disclosure drh does have a financial relationship with ino therapeutics es dean r hess phd rrt faarc associate professor of anesthesia harvard medical school assistant director of respiratory care massachusetts general hospital boston ma dhess@partners.org pir a t o ry ca 1 respiratory therapists are challenged every day to make important decisions in the care of their patients sometimes the questions we face have a clearly correct response but many times there is no clear-cut best response moreover the results of our actions bring additional questions this can be simulated in a non-clinical learning environment through use of an audience response system an audience response system allows an interactive program in which a clinical scenario is presented the audience responses are quickly tabulated and the presenter then discusses the responses with the audience such a program was presented as a breakfast symposium at the 52nd international respiratory congress of the american association for respiratory care on december 13 2006 at the las vegas hilton ira m cheifetz md faarc kicked off the program with a case of pediatric ards including the use of lung recruitment strategies and high frequency oscillatory ventilation this was followed by a case of an adolescent with an asthma exacerbation requiring use of continuous bronchodilators and heliox this case was presented by timothy r myers bs rrt-nps the program then moved to the neonatal icu for a case of hypoxic respiratory failure of the newborn presented by steven m donn md this case included the use of conventional ventilation and inhaled nitric oxide finally i presented a patient with copd exacerbation that included use of noninvasive ventilation aerosol bronchodilators and management of auto-peep this was a lively program that actively involved everyone in attendance herein are the proceedings of this symposium each of the faculty presents their clinical case in a very similar manner to how it was presented at the symposium the questions that were posed to the audience are provided verbatim along with the percentage of the audience who selected each option as you go through these proceedings you can consider the response you would choose and compare that to the responses of those who were present at the symposium the faculty is to be congratulated for making this a lively and informative program i would also like to thank ino therapeutics who supported the program with an unrestricted education grant i hope you will enjoy this program as much as we enjoyed putting it together ame r assoc an ia ic on ti re for

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pediatric acute respiratory distress syndrome ira m cheifetz md faarc introduction acute respiratory distress syndrome ards represents an acute lung injury characterized by pulmonary edema secondary to the disruption of the alveolar-capillary membrane hypoxemia and widespread infiltrates on a chest radiograph that can occur after a wide variety of pulmonary and nonpulmonary insults pulmonary edema in the absence of heart failure was initially described almost a century ago these conditions were originally known by the inciting injury rather than the overall clinical manifestation and included such names as shock lung noncardiogenic pulmonary edema and traumatic wet lung 1-2 in 1967 ashbaugh and colleagues 3 recognized ards as a constellation of pathophysiologic findings that were precipitated by a wide variety of insults highlighting ards as a final common pathway initiated by local or systemic insults definition in 1994 the american-european consensus conference on ards was charged to formally define this clinical entity table 1 provide uniformity and clarity in diagnosis and facilitate comparison of clinical investigations 4 the simplest clinical definition of ards is a diffuse hypoxemic acute lung injury radiographically there are bilateral areas of consolidation with air bronchograms table 1 the american-european consensus conference definition of acute respiratory distress syndrome.4 · acute onset of respiratory symptoms · frontal chest radiograph with bilateral infiltrates · pao2/fio2 200 mm hg · no clinical evidence of left atrial hypertension as defined by a pulmonary capillary wedge pressure less than 18 mm hg if measured that reflect alveolar filling and atelectasis clinically the patient demonstrates moderate to severe respiratory failure hypoxemia and decreased pulmonary compliance furthermore the consensus included a return from the use of adult respiratory distress syndrome back to acute respiratory distress syndrome to acknowledge that infants children and adults may be affected by the same pathophysiologic mechanisms 4 outcome mortality for patients requiring mechanical ventilation varies widely depending on the clinical condition requiring ventilatory support for otherwise healthy infants and children with acute self-limited conditions mortality rates approach 0 pediatric patients with severe ards may have mortality rates which range between 15 and 40 depending on the data reviewed mechanically ventilated patients with multiorgan system failure and/or severe immunodeficiency have a mortality rate which may approach 90 a recent report by flori and colleagues of 328 pediatric intensive care unit admissions for acute lung injury ali ards had a mortality rate of 22 5 this prospective evaluation additionally demonstrated disclosure imc does not have a financial relationship with ino therapeutics ira m cheifetz md faarc division chief and fellowship program director for pediatric critical care medicine and the medical director for the pediatric intensive care unit at duke children s hospital durham north carolina 3

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that as in adults pneumonia sepsis and aspiration are the most common causes of ali and ards in children feasibility of clinical trials prospective randomized multicenter studies for pediatric mechanical ventilation and ards are limited for most clinical questions data are extrapolated from studies in the adult population the feasibility of performing clinical trials for pediatric ali and ards was investigated by the pediatric acute lung injury and sepsis investigator palisi network.6 6,403 total picu admissions across nine north american picus were screened for a pediatric acute lung injury ventilator weaning study only 1,096 mean 17.1 range across institutions 1224 of the infants and children screened for this study required mechanical ventilation for greater than 24 hours the incidence of ards was 5.7 in patients less than one year of age and 9.7 for those greater than one year of age 7.6 for the total population of these 1,096 patients 701 64.0 met an exclusion criteria common reasons for exclusion were upper airway obstruction cyanotic congenital heart disease restrictions on life support bone marrow transplantation and chronic ventilation thus only 395 6.2 of the total patients screened were eligible for enrollment this report helps to define the available population of infants and children eligible for multicenter ards trials additionally mortality in this population was very low 1.6 indicating that mechanical ventilation trials in pediatrics cannot use mortality as an end point unless the expected enrollment is extremely large clinical trials in critically ill infants and children are feasible but the study design must account for a heterogeneous population low mortality and short length of mechanical ventilation figure 1 chest radiograph at presentation case presentation a previously healthy eight year old girl presented to her pediatrician with a five day history of nasal congestion worsening cough and fever to 38.9ºc she was admitted to a local hospital for treatment of a right lower lobe pneumonia figure 1 despite antibiotic therapy with vancomycin and ceftriaxone the patient developed worsening tachypnea progressive infiltrate with an associated pleural effusion and decreasing oxygen saturations over the next 48 hours she was then transferred to the pediatric intensive care unit picu at a tertiary care institution on picu admission her vital signs included heart rate 170 beats/minute blood pressure 130/80 mm hg respiratory rate 60 breaths/minute and temperature 39.5ºc pulse oximetry revealed 92 saturation on nasal cannula oxygen at 3 l/min chest radiograph confirmed a right lower lobe pneumonia on physical assessment the child was awake alert and in moderate respiratory distress she had moderate subcostal retractions no supraclavicular retractions good air exchange except at the right base bilateral crackles right left she had a normal expiratory phase without any wheezing her cardiovascular exam revealed no murmur normal pulses and normal capillary refill she had no rashes or skin lesions her physical examination was otherwise unremarkable question 1 at this point what would be your most likely course of action a continue close observation 53 chose this option b initiate nasal cpap 20 chose this option figure 2 forest plot following subgroup analyses excluding chronic obstructive pulmonary disease and congestive heart failure patients of the pooled risk difference absolute risk reduction for the effect of noninvasive positive pressure ventilation on endotracheal intubation for patients with acute hypoxemic respiratory failure reference 7 4

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c initiate bilevel noninvasive ventilation 20 chose this option d intubate the patient 7 chose this option the majority of respondents chose to continue close observation this is a quite reasonable response as the patient is maintaining acceptable oxygenation however her work of breathing has significantly increased over a short period of time thus it would be reasonable to consider a trial of noninvasive ventilation in a meta-analysis by keenan et al 7 noninvasive ventilation was shown to reduce intubation rates but did not affect mortality in acute hypoxemic respiratory failure in adult patients figure 2 it should be noted that the use of noninvasive ventilation for hypoxemic respiratory failure for conditions beyond chronic obstructive pulmonary disease copd and cardiogenic pulmonary edema remains controversial the audience response to this question confirms the controversy as just under half of the respondents would have proceeded with some form of noninvasive ventilation in this patient bilevel noninvasive ventilation was chosen in an attempt to avoid endotracheal intubation the clinicians opted to be more aggressive in their management as opposed to continued observation given the relatively rapid progression of respiratory symptoms despite noninvasive ventilation the respiratory distress worsened the patient s fraction of inspired oxygen f io2 had increased to 0.60 via a non-rebreather mask at this point the patient was orally intubated with a 5.5 cuffed endotracheal tube without difficulty conventional mechanical ventilation was initiated question 2 what delivered tidal volume i.e as measured at the endotracheal tube would you choose initially a 4 ml/kg 22 chose this option b 6 ml/kg 61 chose this option c 8 ml/kg 13 chose this option d 10 ml/kg 4 chose this option there are no definitive data in the pediatric population to support one tidal volume target over another based on the response to this question the majority of respondents agreed with the landmark study by the ards network 8 this study clearly demonstrates that mortality for adult ards patients is significantly lower with a 6 ml/kg tidal volume figure 3 progression of the chest radiograph to ards than a 12 ml/kg tidal volume based on ideal body weight however the impressive results of this landmark study only relate to the two specific tidal volumes studied it remains unclear whether a tidal volume between 6 and 12 ml/kg or even less than 6 ml/kg may reduce mortality even further furthermore it remains uncertain whether the reduction in mortality was directly related to the lower tidal volume or an associated reduction in the plateau pressure although still unproven these results are likely to be applicable to children with acute lung injury and acute respiratory distress syndrome until a similar large-scale prospective randomized trial is accomplished in pediatrics it seems reasonable to proceed with lung protective ventilation strategies including a low tidal volume approach it is important to emphasize a significant difference between adult and pediatric patients studies in adult acute lung injury patients generally measure tidal volume at the ventilator however measuring delivered tidal volume at the ventilator does not account for the compliance of the ventilator circuit nor for uncontrolled variations in the circuit setup as well as changes in variables over time these variables are often negligible in adult patients but can be very significant in small pediatric patients a tidal volume measured with a pneumotachometer positioned between the endotracheal tube and the ventilator circuit has been demonstrated to be more reliable at indicating the tidal volume actually delivered to the patient s lungs 9-11 it should be noted that newer generation ventilations offer the ability to compensate for the compliance of the ventilator circuit and provide an estimate of the delivered tidal volume however this approach has not been formally studied in a large clinical trial 5

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the patient was initially ventilated in the pressure control/pressure support mode with a set rate of 24 breaths/minute a peak inspiratory pressure pip of 30 cm h 2 o to deliver a tidal volume of 6.5 ml/kg a positive end-expiratory pressure peep of 12 cm h 2 o and an f io2 of 0.60 the resultant arterial blood gas was ph 7.3 p aco2 55 mm hg and p ao2 65 mm hg the oxygenation index oi was 15 and p ao2 /f io2 was 140 mm hg the significant progression of the chest radiograph to ards is displayed in figure 3 question 3 which of the following interventions is supported by the medical literature to improve outcomes for pediatric acute lung injury a inhaled nitric oxide 28 chose this option b prone positioning 46 chose this option c heliox 16 chose this option d surfactant administration 10 chose this option pediatric studies have demonstrated improved oxygenation with prone positioning and the administration of inhaled nitric oxide however no study has demonstrated improved survival with either therapy for acute lung injury 12-15 previous studies using heliox for ards have been based on acute physiology end points and have generally been laboratory studies the effect of heliox on outcome for pediatric ards has not been studied of the choices listed the only intervention which is supported by the published medical literature for pediatric acute lung injury is exogenous surfactant administration 16 hospital mortality was significantly lower for pediatric patients with acute lung injury who were treated with surfactant as compared to those who received placebo 19 vs 36 p 0.03 before exogenous surfactant could be administered the child decompensated the f io2 was increased to 1.0 and the peep to 12 cm h 2 o while the s po2 decreased to 90 question 4 what would you do now a continue conventional ventilation with a further increase in peep 13 chose this option b transition to high frequency oscillatory ventilation 73 chose this option c call for the extracorporeal membrane oxygenation ecmo team/transfer to an ecmo center 13 chose this option d watch the clock and hope your replacement arrives early 1 chose this option luckily 99 of the respondents opted to proceed with a therapy rather than waiting for their replacement to arrive despite the lack of a definitive study that compares high frequency oscillatory ventilation hfov to low tidal volume lung protective conventional ventilation hfov remains a standard approach to pediatric ali/ards hfov continues to be routinely used in pediatrics based on physiology pathophysiology tremendous clinical experience and extrapolation of data from the neonatal and adult populations high frequency ventilation is low tidal volume ventilation taken to the extreme it should be noted that continued conventional ventilation with an increase in peep and a low tidal volume lung protective strategy with conventional ventilation is supported by the ards network data 8 17 additionally transfer to a center with an extracorporeal membrane oxygenation ecmo program is a very reasonable approach at this point the patient was transitioned to hfov with the following settings mean airway pressure 25 cm h 2 o amplitude 40 cm h 2 o frequency 9 hertz and f io2 0.60 the resultant arterial blood gas was ph 7.22 p aco2 70 mm hg and p ao2 70 mm hg question 5 what is the goal arterial oxygen saturation sao2 for your patient a 95 7 chose this option b 90 ­ 94 42 chose this option c 85 ­ 89 48 chose this option d 80 ­ 84 3 chose this option e whatever the physician orders 0 chose this option the adverse effects of high fraction of inspired oxygen have been widely reported clinicians have struggled for many years to define the ideal balance between inspired oxygen levels and acceptable arterial oxygen saturation however when asked what is an acceptable oxygen saturation one is hard pressed to find a definitive answer as indicated by the audience s response to this question permissive hypoxemia is a concept that follows from permissive hypercapnia it is a strategy that allows the arterial oxygen saturation to be less than normal in an attempt to minimize the amount of artificial support provided to the lungs it must be noted that this concept is predominantly based 6

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on physiology as data in the medical literature are very limited permissive hypoxemia as an approach to acute lung injury remains controversial in the clinical setting the goal is to optimize oxygen delivery while minimizing toxicity of the therapy ie mechanical ventilation it is essential when allowing low oxygen saturations that tissue oxygen delivery again not necessarily p ao2 and s ao2 be optimized to all vital organs and tissues the strategy of permissive hypoxemia requires close monitoring of the balance between oxygen delivery and oxygen consumption the only resolution to the controversy surrounding permissive hypoxemia will come with a prospective randomized controlled trial comparing two different arterial oxygenation ranges possibly 82-86 vs 88-92 in pediatric and adult patients with acute lung injury and acute respiratory distress syndrome at this point any debate can be based only on physiology and pathophysiology question 6 do you routinely use recruitment ie sustained inflation maneuvers for your pediatric ali/ards patients a yes 50 chose this option b no 50 chose this option the use of recruitment ie sustained inflation maneuvers for adult and pediatric patients with acute lung injury acute respiratory distress syndrome remains extremely controversial the goal of a recruitment maneuver is to bring the lung to total lung capacity in an attempt to maximize alveolar recruitment and then move down the deflation limb of the pressure-volume curve to an appropriate peep to prevent de-recruitment table 2 general approach to the management of the pediatric patient with ards · · · · use a low tidal volume 6 ml/kg lung protective strategy for pediatric patients with ali and ards use sufficient peep to keep the lungs open keeping in mind that excessive peep is not necessary better consider exogenous surfactant early in the course of mechanical ventilation for pediatric ali and ards maintain a safe level of oxygenation consider permissive hypoxemia ­ keeping in mind that this approach has not been systematically studied generally allow for permissive hypercapnia except in the presence of reactive vascular beds ie traumatic brain injury with intracranial hypertension close cardiorespiratory monitoring of the balance between oxygen delivery and oxygen consumption as well as end organ function the members of the audience who responded to this question were evenly split on this issue it is interesting to note that when the same question was asked of a panel of experts at a r espiratory c are journal conference in october 2006 published in may 2007 only three of 12 experts felt that recruitment maneuvers should be routinely performed in the adult ards population the bottom line is that there are no outcome data available in the adult or the pediatric populations question 7 what is the goal paco2 for your patient a 50 ­ 60 mm hg 22 chose this option b 60 ­ 70 mm hg 15 chose this option c 70 ­ 80 mm hg 4 chose this option d 80 ­ 100 mm hg 1 chose this option e any paco2 as long as the ph is acceptable 58 chose this option a logical consequence of low tidal volume ventilation is hypercapnia limiting the peak inspiratory pressure by reducing the tidal volume may decrease minute ventilation and result in hypercapnia the exact degree of respiratory acidosis that can be safely tolerated remains controversial however most undesirable effects related to respiratory acidosis are minor and reversible when the ph is greater than approximately 7.20 18 thus as confirmed by the audience response clinical care is increasingly moving in the direction of accepting any p aco2 as long as the ph is acceptable it must be stressed that such an approach would not be advocated in patients with reactive vascular beds such as significant traumatic brain injury with intracranial hypertension it should be noted that a cochrane review of the large multicenter low tidal volume studies of ards was unable to reach a definitive conclusion on the implications of permissive hypercapnia 19 this review noted several confounding variables on the role of permissive hypercapnia in the management of acute lung injury the published low tidal volume studies were not designed to address the specific question of hypercapnia however the medical literature seems to support the beneficial role of permissive hypercapnia in ali/ards limited evidence does suggest that low-volume pressure-limited ventilation with permissive hypercapnia may improve outcome in both adults and pediatric patients with ards 20-22 in a ten year study milberg et al reported a positive association between permissive hypercapnia and out · · 7

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comes 23 data from a laboratory model of ischemia-reperfusion acute lung injury indicate that hypercapnic acidosis is protective and that buffering of the hypercapnic acidosis attenuates its protective effects 24 after five days of high frequency oscillatory ventilation the patient was converted to conventional ventilation she then extubated five days later to nasal cannula oxygen and was transferred to the wards she was subsequently discharged without oxygen or medications and without any apparent sequelae summary the medical literature addressing the therapeutic options for pediatric acute respiratory distress syndrome has advanced dramatically over the past several years table 2 during this time many changes have occurred and continue to occur inhaled nitric oxide and prone positioning have been demonstrated to have no affect on outcome on the other hand exogenous surfactant administration has been shown to reduce mortality high frequency ventilation remains a standard of care despite limited current pediatric data and this approach is based on physiology and tremendous clinical experience data in the pediatric population are completely void on the subjects of low tidal volume ventilation recruitment maneuvers permissive hypoxemia and permissive hypercapnia when data are lacking in the pediatric population it seems reasonable to attempt to extrapolate data from adult ards/ali patients although this approach remains controversial more randomized controlled trials are clearly needed to answer the many questions that continue to face pediatric clinicians future clinical investigations in both the adult and pediatric arenas are likely to study combined therapeutic strategies as opposed to focusing on discovering the single magic bullet references 1 fackler jc et al acute respiratory distress syndrome in rogers mc editor textbook of pediatric intensive care baltimore williams wilkins 1996 2 bernard gr acute respiratory distress syndrome a historical perspective am j respir crit care med 2005;172:798-806 3 ashbaugh dg bigelow db petty tl levine be acute respiratory distress in adults lancet 1967;2:319-323 4 bernard gr artigas a brigham kl carlet j falke k hudson l lamy m legall jr morris a spragg r the american-european consensus conference on ards am j respir crit care med 1994;149:818-824 5 flori hr glidden dv rutherford gw matthay ma pediatric acute lung injury prospective evaluation of risk factors associated with mortality am j respir crit care med 2005;171;995-1001 6 randolph ag meert kl o neil me hanson jh luckett pm arnold jh gedeit rg cox pn roberts js venkataraman st forbes pw cheifetz im for the pediatric acute lung injury and sepsis investigator s palisi network the feasibility of conducting clinical trials in infants and children with acute respiratory failure am j resp crit care med 2003;167:13341340 7 keenan sp sinuff t cook dj hill ns does noninvasive positive pressure ventilation improve outcome in acute hypoxemic respiratory failure a systematic review crit care med 2004;3212 2516-2523 8 ards network ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome n engl j med 2000;34218 1301-1308 9 castle ra dunne cj mok q wade am stocks j accuracy of displayed tidal volume in the pediatric intensive care unit crit care med 2002;3911 2566-2574 10 cannon ml cornell j tripp-hamel ds gentile ma hubble cl meliones jn cheifetz im tidal volume measurements in infants should be obtained with a pneumotachometer located at the endotracheal tube am j resp crit care med 2000;1626 2109-2112 11 chow lc vanderhal a raber j sola a are tidal volume measurements in neonatal pressure-controlled ventilation accurate pediatr pulmonol 2002;34:196-202 12 dobyns el cornfield dn anas ng fortenberry jd tasker rc lynch a liu p eells pl griebel j baier m kinsella jp abman sh multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure j pediatr 1999;134:406412 13 dobyns el anas ng fortenberry jd deshpande j cornfield dn tasker rc liu p eells pl griebel j kinsella jp abman sh interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics crit care med 2002;30:2425-2429 14 abman sh griebel jl parker dk schmidt jm swanton d kinsella jp acute effects of inhaled nitric oxide in children with severe hypoxemic respiratory failure j pediatr 1994;124:881888 15 curley ma hibberd pl fineman ld wypij d shih mc thompson je grant mj barr fe cvijanovich nz sorce l luckett pm matthay ma arnold jh effect of prone positioning on clinical outcomes in children with acute lung injury a randomized clinical trial jama 2005;294:229-237 16 willson df thomas nj markovitz bp bauman la dicarlo jv pon s jacobs br jefferson ls conaway mr egan ea effect of exogenous surfactant calfactant in pediatric acute lung injury a randomized controlled trial jama 2005;293:470476 17 brower rg lanken pn macintyre n matthay ma morris a ancukiewicz m schoenfeld d thompson bt higher versus 8

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lower positive end-expiratory pressure in patients with acute respiratory distress syndrome new eng j med 2004;351:327336 18 feihl f perret c permissive hypercapnia how permissive should we be am j respir crit care med 1994;150 17221737 19 petrucci n iacovelli w ventilation with lower tidal volumes versus traditional tidal volumes for acute lung injury and acute respiratory distress syndrome cochrane database of systematic reviews most recent update february 25 2004 20 fackler jc et al ecmo for ards stopping a randomized clinical trial am j respir crit care med 1997;155:a504 21 hickling kg henderson sj jackson r low mortality associated with low volume pressure-limited ventilation with permis sive hypercapnia in severe adult respiratory distress syndrome intensive care med 1990;16:372-377 22 hickling kg walsh j henderson s jackson r low mortality rate in adult respiratory distress syndrome using low-volume pressure-limited ventilation with permissive hypercapnia a prospective study crit care med 1994;22:1568-1578 23 milberg ja davis dr steinberg kp hudson ld improved survival in patients with acute respiratory distress syndrome jama 1995;273:306-309 24 laffey jg engelberts d kavanagh bp buffering hypercapnic acidosis worsens acute lung injury am j resp crit care med 2000;161:141-146 ame r n associ a ca i on ti r es pir a t o ry ca re for 9

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adolescent with an asthma exacerbation timothy r myers bs rrt-nps asthma is a chronic inflammatory disease with periodic episodes of airway hyperreactivity and airflow obstruction despite multiple advances in the understanding management and medications of the disease it is the most common chronic condition of childhood while it is estimated that the prevalence of asthma affects approximately 7.3 of the american population that percentage is even higher for children under the age of 18 with approximately 8.7 of the us population currently having asthma.1 it is estimated that asthma currently affects 20.5 million americans approximately of which a third 6.2 million are children under the age of 18 yrs.1 while the prevalence of asthma is almost threefold higher in the adult population data on emergency department utilization for asthma exacerbation management are vastly different in 2002 there were 1.9 million visits to emergency departments ed for asthma or 67 per 10,000 people.1 children aged 0 to 17 yrs had an ed visit rate of 100 per 10,000 asthmatics contrasted to 24 ed visit per 10,000 adults the ed visit rate was highest among children aged 0-4 years at 162 per 10,000 the ed visit rate for blacks was 380 higher than that for whites and 6 higher for females than for males asthma can exacerbate at anytime in any patient regardless of disease severity or disease control a study by fuhlbrigge et al2 further displays the fact that asthmatics of all severity have exacerbations this retrospective cohort study of 13,842 children over 15 years from 6 different states in the u.s evaluated the potential relationship between fev1 and asthma attacks figure 1 percentage of children experiencing an asthma exacerbation in the past year by either self or parental report stratified by predicted percentage of the forced expiratory value in 1 second fev1 j allergy clin immunol 2001 107:61-67 disclosure trm does not have a financial relationship with ino therapeutics timothy myers bs rrt-nps director of the diagnostic and asthma centers and the department of respiratory care at rainbow babies children s hospital in cleveland ohio fuhlbrigge and colleagues documented a strong association between a decrease in fev1 and the risk of an asthma exacerbation however the data figure 1 also showed exacerbations occur in asthmatics of all severities including approximately a third 33 of the mild asthmatics fev1 between 80-100 and approximately 25 of those with a normal fev1 100 predicted in fact this study s data compliments an earlier data set demonstrating the unpredictability of asthma by robertson et al.3 in this pediatric cohort of 51 patients who suffered death from an asthma exacerbation approximately 1/3 fell into each level of chronic asthma severity mild moderate and severe the national heart lung and blood institutes nhlbi asthma guidelines identify four essential components of asthma management.4 one of these four components is the pharmacologic management of asthma and is divided into chronic daily controller medications and rescue medications for asthma exacerbations the asthma guidelines from the expert panel describe three very specific goals for emergency department management of acute exacerbations correction of significant hypox 11

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emia rapid reversal of airflow obstruction and reduction of likelihood of reoccurrence case summary darin is a 17-year-old adolescent transferred by the emergency medical service to the ed for treatment of an acute asthma exacerbation during a high school football game he is a known asthmatic and had a positive exercise challenge test demonstrating exercise induced bronchospasm 3 years ago pharmacy registries document 6 to 8 refills of albuterol per year but no history of filled prescriptions for inhaled corticosteroids for the past 6 months he has not been hospitalized for an exacerbation of his asthma in the past year but has appeared twice in the ed during that time with an asthma exacerbation he also has a history of 2 prior admissions in the past 5 years to the pediatric intensive care unit for severe status asthmaticus after participating in athletic activities prior to his arrival to the ed darin received 2 albuterol treatments 2.5 milligrams mg each by the ems rescue squad upon arrival his heart rate is 170 beats/minute and his blood pressure is 160/85 mm hg he has labored breathing at a rate of 24 breaths/minute with moderate intercostal and substernal retractions his spo2 is 90 breathing room air auscultation reveals inaudible to muffled air exchange bilaterally through all lung regions he refuses to perform a peak flow due to his shortness of breath question 1 the frontline treatment option should be a beta-agonists 14 chose this option b beta-agonists combined with an anticholinergic 55 chose this option c systemic corticosteroids 20 chose this option d inhaled corticosteroids 4 chose this option e intubation 7 chose this option it is determined that darin is in the midst of a severe asthma exacerbation and is placed on a pediatric asthma assess and treat protocol that calls for beta-agonist treatments at a dose of 2.5 mg every 20 min due to the fact that he has experienced a severe exacerbation and has already received 2 beta-agonists treatments in route the pediatric asthma team will provide a nebulized albuterol treatment in combination with 500 micrograms µg of ipratropium bromide the rationale is that the combination of a beta-agonists and an anti-cholinergic provides a better combined effect in moderate to severe airflow obstruction than either of these drugs independently in one of the earliest trials of a combination therapy approach garrett et al5 demonstrated that a single dose of nebulized combivent provided additional bron figure 2 effect of ipratroprium on hospitalization rate among children 2 ­ 18 years of age with asthma note that the benefit is in those with a severe exacerbation data from qureshi f pestian j davis p et al effect of nebulized ipratropium on the hospitalization rates of children with asthma n engl j med 1998 339:1030-1035 chodilation over salbutamol alone in acute asthma this was most beneficial for patients who received inhaled beta-agonist prior to presentation to the ed qureshi et al6 reported a significant improvement in pulmonary function over 120 minutes in children with severe asthma who were given nebulized ipratropium combined with albuterol and oral steroids compared with children who received standard therapy in a follow-up study qureshi et al7 reported a significant decrease in the hospitalization rate with combination therapy among children 2 ­ 18 years of age with a severe exacerbation of asthma figure 2 plotnick et al8 concluded that adding multiple doses of anticholinergics to beta2-agonists was safe improves lung function and avoided hospital admission in 1 of 11 such treated patients the available evidence only supports multiple doses in school aged children and adolescents with severe asthma lane et al9 conducted a meta-analysis and concluded that adding ipratropium bromide to salbutamol in the treatment of acute asthma produces a small improvement in lung function and reduces the need for additional treatment subsequent asthma exacerbations and hospitalizations plotnick et al10 concluded that the addition of a single dose of inhaled anticholinergic agent to beta2-agonists improves lung function but does not prevent hospital admission this review did not identify any beneficial effects of anticholinergic agents in children with non-severe asthma the most recent meta-analysis by rodrigo et al11 strongly suggests that the addition of multiple doses of anticholinergics to albuterol decreases hospitalizations in both adults and children and improves spirometric values in adults and children after 60 to 120 minutes of treatment after receiving a nebulizer treatment with a combination of ipratropium bromide and albuterol darin has a heart rate of 180 beats/minute and blood pressure of 160/80 mm hg his respiratory rate is 20 breaths minute and labored and his spo2 is 90 breathing room air moderate intercostal and substernal retractions con 12

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tinue to be present breath sounds remain inaudible to muffled bilaterally through all lung regions darin remains unable to perform a peak flow due to his shortness of breath question 2 what is the next treatment option a beta-agonists 16 chose this option b oxygen 16 chose this option c systemic corticosteroids 53 chose this option d inhaled corticosteroids 9 chose this option e intubation 6 chose this option the most appropriate intervention is to administer methylprednisolone at the recommended dose of 2 mg/kg to a maximum dose of 60 mg for patients over 30 kg the general recommendation from the naepp is that oral steroids should be given to patients with moderate-to-severe exacerbations who fail to respond promptly and completely to an initial inhaled beta2-agonist and patients admitted to the hospital within 20 to 60 minutes of initial treatment two systematic reviews reported that systemic corticosteroids at the start of an exacerbation reduce the rates of admission and relapse and the need for additional beta2-agonists without increasing adverse effects.12 13 in patients taking oral steroids long term a supplemental dose should be administered even if the exacerbation is mild onset of action of steroids is typically at or greater than 4 hours.12,14,15 the naepp guidelines recommend that infants and children be given oral steroids early in the course of an asthma exacerbation within 20 to 60 minutes of treatment initiation oral prednisone is usually preferred to intravenous methylprednisolone because it is less invasive and the effects are equivalent.16,17 in a randomized control trial barnett et al randomized 49 children to receive 2 mg/kg methylprednisolone orally or 2 mg/kg methylprednisolone intravenously 30 minutes after the initial treatment with nebulized albuterol.18 four hours after treatment the groups had similar respiratory rates oxygen saturation pulmonary index scores ages 18 months to 6 years and fev1 ages 7 18 years eleven of 23 patients in the oral methylprednisolone group 48 and 13 of 26 patients in the intravenous methylprednisolone group 50 were admitted to the hospital p 0.88 after receiving a 60-mg dose of oral methylprednisolone darin has a heart rate of 150 beats/minute and blood pressure of 180/70 mm hg his breathing continues to be labored at a rate of 28 breaths/minute with moderate intercostal and substernal retractions spo2 is 89 breathing room air breath sounds remain inaudible to muffled bilaterally through all lung regions arterial blood gas results demonstrate the following values ph 7.42 paco2 33 mm hg and pao2 65 mm hg darin remains unable to perform a peak flow due to his shortness of breath question 3 what is the next option a beta-agonists 4 chose this option b intubation 7 chose this option c systemic corticosteroids 0 chose this option d large volume nebulizer with continuous betaagonists 43 chose this option e heliox 46 chose this option there is academic and clinical debate of the use of continuous versus intermittent nebulization of beta-agonists only one systematic review of randomized controlled trials has addressed this subject.19 in the 6 studies included in the review 393 adults with asthma exacerbations there were no significant differences in pulmonary function measures between the 2 delivery methods after 1 2 or 3 hours of treatment at treatment conclusion continuous nebulization resulted in a significant decrease in both heart rate and serum potassium levels compared to intermittent therapy there were no differences in hospital admission rates between groups the reviewers concluded that based on the systematic review there was no difference in treatment delivered by either continuous or intermittent nebulization for the treatment of acute adult asthma there have been 3 trials supportive of continuous nebulizer therapy rudnitsky et al reported that a subgroup of 69 of 99 severe asthmatics had a significant increase in peak flow at 120 minutes and a significant decrease in hospital admissions for continuous aerosol delivery compared with as intermittent delivery.20 another trial of 165 patients with asthma compared 4 regimens of salbutamol in a factorial design.21 patients were allocated into high 1.5 mg versus standard 0.5 mg doses of albuterol and continuous versus as needed delivery they reported significant improvement in fev1 measured at 2 hours in both high and standard doses of continuous therapy compared to intermittent therapy at like dosing strategies a smaller study of 38 patients reported a significant increase in fev1 in severely obstructed exacerbations with continuous therapy.22 while there was no overall improvement in fev1 between continuous and intermittent therapy the subgroup of more severe patients lower initial fev1 showed a significant improvement in fev1 these studies suggest that continuous nebulization is safe at least as effective as intermittent nebulization and may be more effective in patients with the most severely impaired pulmonary function after continuous nebulization for 1.5 hours darin has a heart rate of 80 beats/minute and blood pressure of 180/100 mm hg breathing is labored at 20 breaths/minute and he has moderate intercostal and substernal retractions spo2 is 92 while breathing 13

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30 oxygen by facemask breath sounds remain inaudible to muffled through all lung regions a repeat arterial blood gas reveals ph 7.36 paco2 42 mm hg and pao2 60 mm hg he is unable to perform a peak flow due to his shortness of breath the examination and assessment is categorized as a partial to incomplete response by nih guidelines4 and dictates that further treatment is required question 4 your next option a beta-agonists 4 chose this option b intubation 7 chose this option c large volume nebulizer with continuous betaagonists 43 chose this option d heliox 46 chose this option although use of heliox in the management of exacerbations of pediatric asthma is relatively common strong evidence to support its use has not been well documented in large randomized controlled trials.23 barach24 first described the therapeutic use of heliox 1934 for treatment of upper airway obstruction and asthma exacerbation helium is an odorless tasteless non-explosive non-combustible inert gas it is approximately 1/7 the density of nitrogen and as a result produces a more laminar flow through a partially obstructed airway bronchial smooth muscle constriction results in restricted gas flow and hypothetically positions heliox as an alternative treatment strategy for asthma exacerbations the 2002 update issued by the national asthma education and prevention program25 naepp highlights the potential benefits of heliox in the treatment of asthma exacerbations especially as an alternative to intubation for therapeutic use helium is combined with oxygen to produce heliox heliox administered to spontaneously breathing patients is most efficacious when delivered through a closed-system typical clinical administration consists of a facemask and reservoir bag or a non-rebreather mask frequently a y-piece attachment is placed between the mask and the reservoir figure 3 example of a setup for continuous aerosol therapy using a nebulizer non-rebreather and a y-piece bag to add a nebulizer for concurrent beta-agonist administration figure 3 this type of delivery system needs to be continuously supplied with a flow of 12 to 15 l/min to maintain reservoir bag inflation which requires 2 to 5 h-sized cylinders per day heliox can be combined with aerosol delivery hess et al evaluated the performance of nebulizers powered with heliox or oxygen.26 the study evaluated conventional hudson micro-mist hudson respiratory care temucula ca and continuous miniheart vortran medical technology sacramento ca nebulizers with 5 mg or 10 mg doses of albuterol 5 ml total fill volume powered with various flows of heliox or traditional gases they concluded that the use of heliox to power a nebulizer affects both the inhaled mass of medication and the size of the aerosol particles and that the set flow should be increased when a heliox powered nebulizer is used the efficacy of early implementation of 80:20 heliox for clinical improvement in 18 children 6 months to 16 years with status asthmaticus was evaluated by kudukis et al in a double-blind randomized controlled trial.27 ten children were randomized to heliox and 8 children were randomized to control gas all children received continuous beta agonists and intravenously administered methylprednisolone within 15 minutes of heliox administration decreases in pulsus paradoxus and dyspnea index score were noted heliox also resulted in a significant increase in peak flow they concluded that the early use of heliox for children with status asthmaticus relieves dyspnea and improves the work of breathing in a late intervention study carter et al28 evaluated the use of heliox to improve pulmonary function status relieve dyspnea sensation or decrease a clinical symptom score in 11 children hospitalized with status asthmaticus in a double-blind prospective randomized controlled trial patients received nebulized albuterol 5 mg every 1 to 4 hours and intravenous corticosteroids for a minimum of 6 hours before study entry patients were randomized to either 70:30 heliox or 30 oxygen for 15 minutes prior to crossover to the other treatment arm for 15 minutes there were significant improvements in peak flow and midexpiratory flow fef25­75 with heliox but no difference in clinical or dyspnea scores or in fev1 or fvc between groups the authors also noted that heliox provided the least benefit in the patients that were determined to have the worst airflow obstruction unlike the kudukis study,27 this was an inpatient study where the children were treated with conventional therapy before heliox administration the authors concluded that use of heliox in the management of pediatric status asthmaticus did not benefit these children during its short-term utilization however one could argue that administering heliox may serve as a bridge between arrival in the emer 14

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gency department and onset of conventional therapy effectiveness kim et al29 investigated the effectiveness of a heliox 70 30 versus 100 oxygen driven continuous aerosol delivery in the treatment of children with asthma and moderate to severe exacerbations in a randomized controlled single-blind trial children between the ages 2 to 18 years visiting the ed with a pulmonary index pi score of 8 were enrolled when a study investigator was available convenience sample after 20 minutes of 5 mg of inhaled albuterol via face mask from a large volume oxygen-driven nebulizer and a dose of oral steroids patients were randomly assigned to receive continuously nebulized albuterol 15 mg/hour either with heliox or oxygen for 60 minutes followed by 500 µg of ipratropium bromide over 5 minutes heliox produced a significant pi improvement after 125 minutes of therapy that was sustained at 150 180 and 240 minutes a significantly higher discharge rate from the emergency department in <12 hours was also demonstrated for the group randomized to heliox they concluded that in children presenting to the ed with moderate to severe asthma exacerbation continuously nebulized albuterol delivered by heliox was associated with a greater degree of clinical improvement compared with that delivered by oxygen rivera et al30 compared the initial response to albuterol nebulized with heliox versus control in a prospective blinded randomized controlled trial in children presenting to a pediatric emergency department for the treatment of moderately severe asthma potential enrollees were selected when the two investigators were available convenience sample after receiving 1 hour of conventional therapy 3 treatments of a 2.5 mg dose of aerosolized albuterol and 2 mg/kg intravenous methylprednisolone patients were randomized to re figure 4 sample of pediatric asthma assess and treat protocol from rainbow babies children s hospital page 1 of 4 showing the first 2 of 4 phases 15

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