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eNeonatal Review VOLUME 8, ISSUE 11 Neonatal Abstinence Syndrome In this Issue... Neonatal abstinence syndrome (NAS) is a complex, commonly encountered clinical disorder that comprises a range of behavioral and physiologic signs. Affected infants have been exposed to a variety of drugs that, at the cellular level, induce tolerance and dependence, such that when the drug is discontinued, physical signs and symptoms of withdrawal occur. Exposure to these agents may take place either prenatally from maternal use or postnatally from therapeutic indications such as pain relief. Although several classes of drugs may cause NAS, analgesics (specifically, opioids) are the most common. NAS can be difficult to diagnose, quantify, and treat. Recent advances in our understanding of the complex neurochemical mechanisms involved have revealed novel approaches for treatment. Even with the advent of withdrawal scoring systems, treatment algorithms, and new approaches to pharmacologic management of NAS, there is still room for improvement in caring for narcotic-exposed neonates. In this issue, we review recent literature that addresses the broad range of prenatal illicit drug exposure triggering withdrawal symptoms to help clinicians more effectively implement appropriate treatment strategies. LEARNING OBJECTIVES After participating in this activity, the participant will demonstrate the ability to: Identify novel therapies for treating neonatal abstinence syndrome (NAS) Discuss the risk factors for and clinical presentations of selective serotonin reuptake inhibitor withdrawal in neonates Describe the spectrum of developmental outcomes among children who receive treatment for NAS IMPORTANT CME/CNE INFORMATION Program Begins Below accreditation statements This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Johns Hopkins University School of Medicine and the Institute for Johns Hopkins Nursing. The Johns Hopkins University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians. Nurses The Institute for Johns Hopkins Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Respiratory Therapists Respiratory therapists should visit this page to confirm that AMA PRA Category 1 Credit(s)™ are accepted toward fulfillment of RT requirements. credit designations Physicians eNewsletter: The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should only claim the credit commensurate with the extent of their participation in the activity. Podcasts: The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits(s)™Physicians should only claim the credit commensurate with the extent of their participation in the activity Nurses eNewsletter: This 1 contact hour educational activity is provided by The Institute for Johns Hopkins Nursing. Each newsletter carries a maximum of 1 contact hour or a total of 6 contact hours for the six newsletters in this program. Podcasts: This 0.5 contact hour educational activity is provided by The Institute for Johns Hopkins Nursing. Each podcast carries a maximum of 0.5 contact hour or total of 3 contact hours for the six podcasts in this program. To obtain contact hours, you must complete this Educational Activity and post-test by April 18, 2013. Respiratory Therapists For United States: Visit this page to confirm that your state will accept the CE Credits gained through this program. For Canada: Visit this page to confirm that your province will accept the CE Credits gained through this program. There are no prerequisites or fees associated with this activity. internet ce policy The Office of Continuing Medical Education (OCME) at the Johns Hopkins University School of Medicine and the Institute for Johns Hopkins Nursing are committed to protecting the privacy of its members and customers. Johns Hopkins maintains its Internet sites as an information resource and service for physicians, other health professionals and the public. Continuing Medical Education at the Johns Hopkins University School of Medicine and the Institute for Johns Hopkins Nursing will keep your personal and credit information confidential when you participate in a CE Internet-based program. Your information will never be given to anyone outside these institutions. CE collects only the information necessary to provide you with the service you request. Launch date September 2, 2010; activities expire two years from the date of each publication. disclaimer statement The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of the Johns Hopkins University School of Medicine or the Institute for Johns Hopkins Nursing name implies a review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients. The Institute for Johns Hopkins Nursing and the American Nurses Credentialing Center do not endorse the use of any commercial products discussed or displayed in conjunction with this educational activity. statement of responsibility The Johns Hopkins University School of Medicine and the Institute for Johns Hopkins Nursing take responsibility for the content, quality, and scientific integrity of this CE activity. intended audience This activity has been developed for neonatologists, NICU nurses, and respiratory therapists working with neonatal patients. There are no fees for this activity. There are no prerequisites to participate. Estimated time to complete activity: 1 hour. faculty disclosure As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine and the Institute for Johns Hopkins Nursing to require the disclosure of the existence of any relevant financial interest or any other relationship a faculty member or a provider has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The course director and planning committee reported the following: Christoph U. Lehmann, MD, has indicated a financial relationship of honoraria from Mead Johnson and Pediatrix. Dr. Lehmann is also the Editor-In-Chief of Applied Clinical Informatics Journal. He serves on the Board of Directors for the American Medical Informatics Association. Anthony Bilenki, MA, RRT, Edward E. Lawson, MD, Lawrence M. Nogee, MD and Mary Terhaar, DNSc, RN indicated they have no relevant financial relationships with any commercial supporters. Guest Author’s Disclosures Successful completion To successfully complete this activity, participants must read the content, and then link to the Johns Hopkins University School of Medicine's CME website or the Institute for Johns Hopkins Nursing to complete the post-test and evaluation. Once you receive a passing grade, you can access and print your certificate of credit. NOTE: if you have already registered for other Hopkins CME programs at the CME website simply enter the requested information when prompted. hardware & software requirements Pentium 800 processor or greater, Windows 98/NT/2000/XP or Mac OS 9/X, Microsoft Internet Explorer 5.5 or later, 56K Modem or better, Windows Media Player 9.0 or later, 128 MB of RAM Monitor settings: High color at 800 x 600 pixels, sound card and speakers, Adobe Acrobat Reader. IN THIS ISSUE COMMENTARY from our Guest Author SSRI EXPOSURE AND NEONATAL DISCONTINUATION SYNDROME ADVERSE NEURODEVELOPMENTAL OUTCOMES AMONG CHILDREN EXPOSED TO OPIATES IN UTERO EFFICACY AND SAFETY OF SUBLINGUAL BUPRENORPHINE FOR THE TREATMENT OF NAS ORAL CLONIDINE USED AS ADJUNCT THERAPY TO OPIOIDS FOR THE TREATMENT OF NAS Program Directors Edward E. Lawson, MD Professor of Pediatrics Johns Hopkins University School of Medicine Chief, Division of Neonatology Vice Chair, Department of Pediatrics Johns Hopkins Children’s Center Christoph U. Lehmann, MD Associate Professor Department of Pediatrics Division of Neonatology The Johns Hopkins University School of Medicine Lawrence M. Nogee, MD Professor Department of Pediatrics Division of Neonatology The Johns Hopkins University School of Medicine Mary Terhaar, DNSc, RN Assistant Professor Undergraduate Instruction The Johns Hopkins University School of Nursing Anthony Bilenki, MA, RRT Technical Director Respiratory Care Services Division of Anesthesiology and Critical Care Medicine The Johns Hopkins Hospital Baltimore, Maryland GUEST AUTHOR OF THE MONTH Commentary & Reviews Estelle Gauda, MD Professor of Pediatrics Department of Pediatrics The Johns Hopkins University School of Medicine Baltimore, Maryland Tamorah Lewis, MD Fellow Division of Neonatology The Johns Hopkins University School of Medicine Baltimore, Maryland Guest Faculty Disclosure Estelle Gauda, MD, and Tamorah Lewis, MD, have disclosed no relevant financial relationships with commercial entities. Program Directors’ Disclosures Unlabeled/Unapproved Uses The authors have indicated that there will be reference to the unapproved/unlabeled use of clonidine and buprenorphine.

Program Information CE Info Accreditation Credit Designations Intended Audience Learning Objectives Internet CME/CNE Policy Faculty Disclosure Disclaimer Statement Length of Activity 1 hour Physicians 1 contact hour Nurses Release Date April 19, 2011 Expiration Date April 18, 2013 TO ACCESS A POST-TEST Step 1. Review the CE Information and study the educational content. Step 2. Select a post-test link at the end of the newsletter. Step 3. Follow the instructions to access a post-test. Respiratory Therapists Please see the link at the end of this newsletter to confirm your state's acceptance of CE Credits.

COMMENTARY Maternal opiate use is a commonly encountered problem that is usually concentrated in major urban areas in the United States and abroad. The National Pregnancy and Health Survey, conducted from 1992 to 1993, estimated that 5.5% of women delivering live-born infants had used illicit drugs at some time during their pregnancies.1 In this survey of pregnant women in the United States, as many as one-fourth of those reporting illicit drug use had used heroin or other opioid analgesics within 30 days of the interview.2 Infants born to opiate-dependent mothers are at high risk for developing neonatal abstinence syndrome (NAS) after birth, and more than half of all neonates born to methadone-maintained mothers require treatment for the disorder. Clinical features of NAS include neurologic hyperexcitability, autonomic dysfunction, delayed growth, and abnormal sleep-wake cycling. The current standard of care for opiate-dependent pregnant women is enrollment in opioid maintenance treatment programs, the majority of which are methadone-based. Although a correlation between methadone exposure and severity of NAS has been suggested, methadone dose is not routinely predictive of occurrence or severity of withdrawal.3 Recently, buprenorphine, a semisynthetic opioid, has received approval for use as an alternative to methadone for treating maternal opioid dependency. A randomized, controlled trial showed that neonatal outcomes among infants whose mothers were treated with buprenorphine instead of methadone included significantly reduced length of treatment, decreased length of hospital stay, and reduced average dose of morphine required to manage NAS.4 Thus, buprenorphine may be an attractive alternative to methadone in the maternal population. Further, buprenorphine is well tolerated in infants and may thus be beneficial for those who require pharmacologic treatment for NAS. Standard treatment of NAS has shifted from sedatives, such as paregoric and phenobarbital, to opioid agonists, such as diluted tincture of opium (DTO), morphine, and methadone. A recent Cochrane review concluded that no one opiate is more effective than another in treating opiate withdrawal syndrome in infants, but when compared with such sedatives as midazolam and phenobarbitone, the use of opiates was associated with a lower risk of treatment failure.5 The results of a national survey6 reported that opioids are the most common first-line therapy for NAS secondary to narcotic (63% of respondents) or polydrug (52% of respondents) exposure, followed by phenobarbital (32% of respondents). The survey also demonstrated that only 54% of all neonatal intensive care units have a written policy for NAS management, and only 70% of respondents use an abstinence scoring system to direct pharmacologic therapy. Although opioids have become the drug of choice for treating NAS, the need for slow weaning and prolonged inpatient hospitalization renders alternate treatment options desirable. Two randomized trials that address the efficacy and safety of buprenorphine in neonates have been published.7,8 Another agent, clonidine, was recently shown to be effective in treating NAS, either as an adjunct to other sedative agents or as monotherapy.9-11 Both buprenorphine and clonidine are promising treatment options for more optimal pharmacologic therapy, based on the cellular mechanisms of NAS. Buprenorphine is a partial μ-opioid receptor agonist that has very strong binding affinity for the μ- and κ-opioid receptors. Clonidine is an α2-adrenergic receptor agonist, and μ-opioid and α2-adrenergic receptors are coexpressed on norepinephrine-containing neurons. Developmental outcomes of infants with NAS are confounded by numerous factors. For example, once inpatient therapy for NAS has been completed, infants of mothers compliant with prenatal treatment programs are often discharged home, while infants of noncompliant or untreated mothers are often placed temporarily into the social services system. Such a combination of social, economic, and other environmental factors makes the interpretation of long-term follow-up difficult. The wealth of data demonstrates that opiate-exposed children perform more poorly on developmental testing compared with their nonexposed peers12 and are at risk for poor ophthalmologic outcomes.13 Although it is not current practice, referral to neurodevelopmental follow-up based on narcotic exposure alone should be considered for optimal developmental outcomes. Pharmacologic treatment of depression is a common practice, and it is becoming more common for mothers to be treated with antidepressants during pregnancy. As a result, a new type of abstinence syndrome has emerged, known as “neonatal behavioral syndrome.”14 Evidence to date demonstrates that this poor neonatal adaptation following in utero antidepressant (mainly selective serotonin reuptake inhibitor [SSRI] and serotonin norepinephrine reuptake inhibitor [SNRI]) exposure can be treated with close observation and supportive care.14 Commentary References 1. National Institutes of Health. National Institute on Drug Abuse (NIDA). Drug use during pregnancy Accessed March 3, 2011. 2. Finkelstein N, Kennedy C, Thomas K, Kearns M. Gender-Specific Substance Abuse Treatment. Alexandria, VA: National Women's Resource Center for the Prevention and Treatment of Alcohol, Tobacco, and Other Drug Abuse and Mental Illness; 1997. 3. Thajam D, Atkinson DE, Sibley CP, Lavender T. Is neonatal abstinence syndrome related to the amount of opiate used? J Obstet Gynecol Neonatal Nurs. 2010;39(5):503-509. 4. Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010;363(24):2320-2331. 5. Osborn DA, Jeffery HE, Cole MJ. Opiate treatment for opiate withdrawal in newborn infants. Cochrane Database Syst Rev. 2010;(10):CD002059. 6. Sarkar S, Donn SM. Management of neonatal abstinence syndrome in neonatal intensive care units: a national survey. J Perinatol. 2006; 26(1):15-17. 7. Kraft WK, Gibson E, Dysart K, et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. 2008;122(3):e601-e607. 8. Kraft WK, Dysart K, Greenspan JS, Gibson E, Kaltenbach K, Ehrlich ME. Revised dose schema of sublingual buprenorphine in the treatment of the neonatal opioid abstinence syndrome. Addiction. 2011; 106(3):574-580. 9. Agthe AG, Kim GR, Mathias KB, et al. Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial. Pediatrics. 2009;123(5):e849-e856. 10. Hoder EL, Leckman JF, Poulsen J, et al. Clonidine treatment of neonatal narcotic abstinence syndrome. Psychiatry Res. 1984;13(3): 243-251. 11. Esmaeili A, Keinhorst AK, Schuster T, Beske F, Schlösser R, Bastanier C. Treatment of neonatal abstinence syndrome with clonidine and chloral hydrate. Acta Paediatr. 2010;99(2):209-214. 12. Hunt RW, Tzioumi D, Collins E, Jeffery HE. Adverse neurodevelopmental outcome of infants exposed to opiate in-utero. Early Hum Dev. 2008;84(1):29-35. 13. Hamilton R, McGlone L, MacKinnon JR, Russell HC, Bradnam MS, Mactier H. Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy. Br J Ophthalmol. 2010;94(6):696-700. 14. Moses-Kolko EL, Bogen D, Perel J, et al. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA. 2005;293(19):2372-2383. back to top

SSRI EXPOSURE AND NEONATAL DISCONTINUATION SYNDROME Oberlander TF, Misri S, Fitzgerald CE, Kostaras X, Rurak D, Riggs W. Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry. 2004;65(2):230-237. View Journal Abstract View Full Article In a prospective cohort study, Oberlander and colleagues evaluated 2 cohorts (N=46) of infants exposed to either an SSRI alone (fluoxetine, paroxetine, or sertraline) or an SSRI in combination with clonazepam during pregnancy. The investigators compared these infants with a control cohort of 23 nonexposed neonates. The children were examined by pediatricians for any abnormal symptoms, including jitteriness, tachypnea, hypoglycemia, lethargy, weak/absent cry, desaturations, or other symptoms considered to be of concern by the infant's nurse Overall, 30% of the exposed infants exhibited symptoms of poor neonatal adaptation, compared with 9% of the control infants. In the SSRI-only group, 25% of exposed neonates exhibited symptoms; in the SSRI-plus-clonazepam group, 39% of exposed neonates exhibited symptoms. Symptoms typically included mild respiratory distress and hypotonia. Developmental outcomes using Bayley scoring at 2 months and 8 months of age did not differ between symptomatic and asymptomatic infants. Maternal drug levels during the third trimester and at birth, as well as infant drug levels from cord blood and serum on day 2 of life, were obtained. When paroxetine was combined with clonazepam, symptomatic infants had significantly higher paroxetine levels compared with similarly exposed asymptomatic infants (P<.05). The maternal dose of clonazepam was significantly higher during pregnancy and at delivery among symptomatic infants compared with asymptomatic infants. Many children who were assessed underwent sepsis evaluations, all of which were negative. All symptoms resolved within 48 hours of life, and length of hospital stay did not differ between infants with and without symptoms. Of note, no differences were observed in growth parameters, gestational age at birth, or rate of congenital anomalies between the exposed and nonexposed cohorts. The investigators concluded that infants with prenatal exposure to SSRI antidepressants alone or in combination with the benzodiazepine clonazepam have an increased incidence of poor neonatal adaptation, which is particularly true among infants of mothers with high maternal SSRI levels and of those taking high doses of clonazepam in the third trimester. Respiratory distress was the most prominent symptom, and all infants who exhibited this spectrum of symptoms received a heightened level of observation and removal from couplet care. The authors recommended the avoidance of polypharmacy for the treatment of maternal depression and anxiety, whenever possible, indicating that if a benzodiazepine is required, a taper in the third trimester is recommended in an effort to reduce neonatal symptoms. Maternal drug levels during pregnancy and at the time of delivery may help to stratify infants to risk for postnatal symptoms. back to top

ADVERSE NEURODEVELOPMENTAL OUTCOMES AMONG CHILDREN EXPOSED TO OPIATES IN UTERO Hunt RW, Tzioumi D, Collins E, Jeffery HE. Adverse neurodevelopmental outcome of infants exposed to opiate in-utero. Early Hum Dev. 2008;84(1):29-35. View Journal Abstract View Full Article The authors reviewed the literature  and identified a total of 14 studies (from 1966 to 2005),that  involved 629 opiate-exposed infants who were followed for developmental progress between 2 months and 10 years of age. All of the studies were case series or case-control in design. The results of the studies were stratified by number of cases (<50 vs. >50 cases) and percentage retention (although no studies were excluded for lack of retention at follow-up). Opiate-exposed infants consistently exhibited evidence of neurodevelopmental impairment, regardless of their age at testing or the tool used to compare these children with unexposed controls. The authors also conducted their own case-control study, between May 1979 and January 1984, enrolled a total of 133 known opiate-dependent infants (mothers were compliant patients in a methadone program). A total of 103 nonopiate-exposed controls were recruited from the antenatal clinic during the same time period. The mothers were matched for age, height, race, and prior obstetric history. Developmental assessments were conducted in the child's home at the ages of 18 months and 36 months. Of the exposed infants, 56% had received pharmacologic treatment for NAS. Many of the opiate-exposed infants were discharged to foster care; the overall rate of follow-up was 59% at 18 months and 50% at 3 years. Opiate-exposed infants had significantly lower scores on all assessment tools used (the Bayley Scales of Infant Development and Vineland Social Maturity Scale at 18 months; the Stanford-Binet Intelligence Scales, McCarthy Motor Scale, Vineland Social Maturity Scale, and Reynell Expressive Language Scale and Verbal Comprehension Scale at 36 months), except for the Bayley psychomotor developmental index (PDI). Of note, although the PDI was not statistically significant at 18 months, significantly lower scores were reported (P<.05) on the McCarthy Motor Scale in opiate-exposed children at 3 years of age. The authors noted that the children for whom they had data were the ones with a home environment conducive to follow-up. They speculated that children who were lost to follow-up more than likely had less stable home environments and predicted that these infants would also have performed less well on the neurodevelopmental assessments. Thus, every effort should be made to follow opiate-exposed children longitudinally for developmental abnormalities, so that in utero effects can be minimized and outcomes can be optimized. back to top

EFFICACY AND SAFETY OF SUBLINGUAL BUPRENORPHINE FOR THE TREATMENT OF NAS Kraft WK, Gibson E, Dysart K, et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. 2008;122(3):e601-e607. View Journal Abstract View Full Article Kraft WK, Dysart K, Greenspan JS, Gibson E, Kaltenbach K, Ehrlich ME. Revised dose schema of sublingual buprenorphine in the treatment of the neonatal opioid abstinence syndrome. Addiction. 2011;106(3):574-580. View Journal Abstract View Full Article Kraft and colleagues conducted a randomized, open-label, prospective pilot study investigating the safety and efficacy of sublingual buprenorphine in neonates with NAS. A total of 26 infants born to mothers in methadone maintenance who required pharmacologic therapy for NAS were randomized to either sublingual buprenorphine or DTO treatment. Sublingual buprenorphine was formulated from the injectable solution and administered in aliquots of <0.5 mL. A pacifier was used to decrease immediate swallowing among the infants. Sublingual buprenorphine, initiated at 13 μg /kg/day divided into 3 doses and escalated per protocol to a maximum dose of 39 μg /kg/day, was effective as monotherapy in controlling NAS. The mean length of treatment in the DTO group was 32 ± 16 days (mean ± standard deviation), compared with 22 ± 11 days in the buprenorphine group (P=.077). Mean length of hospital stay was 38 ±16 days and 27 ± 11 days, respectively, in the DTO and buprenorphine groups (P=.068). Overall, 3 infants in the buprenorphine arm and 1 infant in the DTO arm received additional phenobarbital because of failure to control NAS symptoms once the maximum protocol dose had been reached. Buprenorphine serum levels were lower than those reported for adults with adequate control of opioid withdrawal symptoms. In a subsequent randomized, open-label, prospective study designed to determine the optimal dosage of buprenorphine for treating NAS, buprenorphine 15.9 μg /kg/day escalated to a dose of 60 μg /kg/day was compared with oral morphine treatment. Buprenorphine-treated infants had a 40% shorter length of treatment (23 vs. 38 days; P=.01) and a 24% shorter length of hospital stay (32 days vs. 42 days; P=.05), compared with the oral morphine-treated group. Buprenorphine administered at the higher dosages was well tolerated. back to top

ORAL CLONIDINE USED AS ADJUNCT THERAPY TO OPIOIDS FOR THE TREATMENT OF NAS Agthe AG, Kim GR, Mathias KB, et al. Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial. Pediatrics. 2009;123(5):e849-e856. View Journal Abstract View Full Article This report by Agthe and associates used a blinded, prospective, randomized, placebo-controlled protocol to investigate the efficacy of oral clonidine as adjunct therapy to DTO for treating NAS. In this study, 80 infants were randomized to either oral clonidine plus DTO or placebo plus DTO for treating NAS secondary to in utero opiate exposure (heroin or methadone). The epidural formulation of clonidine 1 μg /kg every 4 hours was administered enterally. Infants at risk for NAS were monitored using modified Finnegan scores (MFSs) and started on treatment if they had consecutive MFSs ≥9. Escalation and de-escalation of DTO were algorithm-driven and based on MFS values. The infants’ clonidine dose remained the same throughout treatment course. The median length of therapy was 27% shorter in the clonidine group than in the placebo group (11 vs. 15 days, respectively; P=.02). The average daily DTO dose/kg was also lower in the clonidine group. Treatment failure occurred in 12.5% of patients in the placebo group vs. none in the clonidine group. Infants exposed to methadone had an average length of therapy that was 3 times that of infants exposed to heroin alone (15 days vs. 5 days, respectively; P=.005). Treatment with clonidine 1 μg /kg every 4 hours was not associated with hypertension, hypotension, bradycardia, or desaturations. This publication reports on the first placebo-controlled trial to show that clonidine, an α2-adrenergic agonist, used as adjunct therapy for treating NAS is narcotic-sparing, shortens the duration of therapy, and prevents treatment failure. back to top		TO COMPLETE A POST-TEST Step 1. Click on the link to download instructions for the posttest and evaluation. Respiratory Therapists Visit this page to confirm that your state will accept the CE Credits gained through this program.

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