2998-(2) Diário da República, 1.ª série — N.º 114 — 14 de junho de 2012 PRESIDÊNCIA DO CONSELHO DE MINISTROS benefício recebido pelo trabalhador, correspondendo a uma forma descentralizada de incentivar novas contratações, Resolução do Conselho de Ministros n.º 51-A/2012 com baixos custos administrativos, e cuja concessão está condicionada à criação líquida d
Bardzo tanie apteki z dostawą w całej Polsce kupic levitra i ogromny wybór pigułek.
LayoutMedtronic Award Paper presented at CANN Conference, Halifax, N.S., June 2009
Intrathecal baclofen and pregnancy: Implications for clinical care
By Margo DeVries-Rizzo, Diny Warren, Gail Delaney, Simon Levin, Craig Campbell and Sandrine DeRibaupierre Abstract
Intrathecal baclofen use during pregnancy is rare. There are no Pregnancy in patients with intrathecal baclofen (ITB) pumps controlled studies of its use during pregnancy. A literaturesearch revealed only five reported cases of ITB use during is rare. To our knowledge, only five reported cases of pregnan- pregnancy. Four had implanted pumps and one of these cases cy exist in the literature. Thus, there is little experience to delivered two healthy infants while having an ITB pump inform health care practitioners about the maternal and fetal (Dalton et al., 2008; Delhaas & Verhagen, 1992; Munoz & safety of ITB or its efficacy throughout pregnancy. Marco, 2000; Roberts et al., 2003). One other case report exists There are no reports of a pregnant female with an implanted with ITB being delivered in bolus doses given once daily via an ITB pump having a spontaneous, vaginal delivery at term. As external catheter during the last trimester of pregnancy far as we know, this is the first case described in the literature. (Engrand et al., 2001). This accounts for six infants identified Additionally, current literature does not address clinical impli- in the literature born to females with ITB during pregnancy.
All cases reported in the literature required ITB for manage- This paper reviews literature to date and presents unique ment of spasticity. The four cases of implanted ITB pumps dur- aspects of our patient. It also discusses clinical implications for ing pregnancy were females aged 23 to 37. All cases with an treating a pregnant patient with an ITB pump. The intent of implanted ITB pump delivered prematurely (32 to 37 weeks ges- this paper is to advance our body of knowledge in caring for tation) by planned cesarean section. One female had her pump pregnant clients with ITB pumps and reassure families about implanted at 30 weeks gestation due to increasing spasticity and the safety and efficacy of this treatment. spasticity-related pain (Roberts et al., 2003). The remainingthree cases had their ITB pumps implanted 15 months to four Literature review
years prior to conception. Doses of ITB during gestation ranged Baclofen, a well-known antispasmodic and muscle relaxant, is from 140 ucg/d to 1400 ucg/d. One additional case was report- a common treatment for spasticity. This GABA agonist, more ed of a teenage primip with tetanus who required an external- commonly used as an oral agent, can be continuously delivered ized catheter for ITB bolus doses (250–1500 ucg once daily) who to the intrathecal space via a surgically implanted battery- had a 32-week neonate by spontaneous, vaginal delivery powered pump. Since its first use in 1983, its efficacy as an (Engrand et al., 2001). She received daily ITB boluses for 21 intrathecal preparation has been increasingly recognized.
days, which were discontinued eight days prior to delivery and Direct delivery and binding of the drug to spinal GABA replaced with an increase in intravenous diazepam.
receptors in much smaller doses than required orally results in Concern exists regarding ITB use during pregnancy given a marked reduction in systemic side effects (Albright, 1999).
reports that oral doses exceeding seven to 12 times the recom-mended human dose could be teratogenic in animal studies(Thomson Micromedex, 2008). Additionally, there is a lack of Le baclofen intrathécal et la grossesse :
controlled human studies. The manufacturer’s current recom- les implications pour les soins cliniques
mendation for oral baclofen use in pregnant women is restrict-ed for situations where the potential benefit justifies the poten- Résumé
tial risk to the fetus (Thomson Micromedex, 2008; Munoz & La grossesse chez des patientes avec une pompe à baclofen Marco, 2000). The Class C rating does not distinguish between intrathécal (BIT) est rare. À notre connaissance, seulement the levels of risk of the oral preparation as compared with the cinq cas rapportés de grossesse existent dans les écrits. Ainsi, il intrathecal solution. However, results indicate plasma baclofen y a peu d’expérience pour informer les professionnels de la levels in patients treated with intrathecal baclofen are often santé sur la sécurité maternelle et fœtale du BIT ou de son too low to be detected with routine testing methods, suggest- ing minimal systemic exposure and probably a lack of placen-tal transfer to the fetus (Albright, 1999).
Il n’y a pas de rapport d’accouchement vaginal, spontané, et àterme de femme enceinte avec une pompe implantée BIT. À To date, no problems have been identified for either the moth- notre connaissance, ceci est le premier cas décrit dans la er or the child in the reported cases with an ITB pump with littérature. De plus, les écrits courants n’adressent pas les continuous infusion (Dalton et al., 2008; Delhaas & Verhagen, implications cliniques pour ces patientes. 1992; Roberts et al., 2003). One case report exists where aneonate was reported to be hypotonic during the first few days Cet article fait la recension des écrits à ce jour et présente l’aspect of life. Although, in this case, the ITB boluses were changed to unique de notre patiente. Il discute aussi des implications intravenous diazepam at least one week prior to delivery, no cliniques dans le traitement de femmes enceintes avec une pompe etiology for the infant’s presentation is discussed in the article.
BIT. Le but de cet article est d’avancer notre corps de connaissance The neonate was discharged home nine days after delivery dans le soin de clientes enceintes avec une pompe BIT et rassurer with no follow-up report. Two infants were followed until 24 les familles sur la sécurité et l’efficacité de ce traitement. months of age and demonstrated normal development Canadian Journal of Neuroscience Nursing • Volume 31, Issue 3, 2009
(Munoz & Marco, 2000; Roberts et al.). To date, no evidence of The patient and her infant were discharged home on day three.
teratogenicity has been reported in pregnant females with ITB She remained on her prenatal ITB dose of 440 ucg/day. She was pumps (Dalton et al., 2008; Delhaas & Verhagen, 1992; noted to have slightly increased lower extremity tone during a Engrand et al., 2001; Munoz & Marco; Roberts et al.).
routine assessment six weeks after the birth of her infant and herITB dose was increased to 480 ucg/day. She remained on this dose until 12 months after delivery. In March 2009, she report- We report the first case of a young primip with an implanted ed a mild increase in spasticity in her lower extremities and her ITB pump who delivered a full-term, healthy infant by sponta- ITB dose was increased to 529 ucg/day. She remains on this dose neous vaginal delivery in 2008. The cognitively intact 18-year- and continues to be the primary caregiver for her infant. The old developed spastic diplegia after being diagnosed with trans- infant was followed for 15 months and demonstrated normal verse myelitis in 1995, at the age of six years. She had significant growth and development and no evidence of teratogenicity.
hypertonicity and spasticity of her lower extremities. She is pri-marily wheelchair dependent. She developed progressive lum- Clinical implications for practice
bar scoliosis in her early teenage years and had Luque spinal Intrathecal baclofen has been used since the mid 1980s (Penn instrumentation implanted in 2005 at the age of 16.
& Kroin, 1985). Although clinical management of patients withintrathecal baclofen pumps has been addressed in the litera- Oral baclofen had been tried at therapeutic dosages and was ture (Bhimani, 2008), none exists regarding clinical manage- unsuccessful. Regular physiotherapy was not preventing the ment of pregnant patients with intrathecal baclofen pumps.
development of contractures. An ITB trial was done and One recent case report highlighted the importance of a multi- demonstrated positive results. The ITB pump was implanted in disciplinary approach for a pregnant patient on oral baclofen February 2001, with the catheter tip placed at thoracic level 12.
to treat reflex sympathetic dystrophy (Moran et al., 2004).
Shortly after pump implantation, the patient reported dramatic Additional literature suggests a multidisciplinary approach improvement in lower limb tone and ability to perform activities works best for obstetric management of the pregnant patient of daily living, including increased ease with self-catheteriza- with a spinal cord injury (Pereira, 2003). This section will focus tion. She also experienced decreased pain at night, as a result of on some of the unique challenges we faced with our pregnant decreased muscle spasms. Her caregivers also noted improve- patient with an ITB pump. We present collaborative-care rec- ment with assistance with ADLs. Elective reimplantation of the ommendations since no standards of practice exist to date.
pump, due to battery depletion, was done in April 2006 in con-junction with scoliosis surgery revision. In May 2006, she devel- Multidisciplinary team
oped right femoral vein thrombosis, which was managed with Our pediatric intrathecal baclofen program is affiliated with a subcutaneous low-molecular-weight heparin for six months.
larger citywide adult baclofen program. This group encom- Etiology for the DVT was not felt to be related to the ITB passes multidisciplinary teams from two major health care pump. In March 2007, prior to her pregnancy, she developed centres located across several hospital sites within the city.
a DVT in her left leg secondary to immobility. Once again she Primary members are nurses, neurology nurse practitioners, was placed on low-molecular-weight heparin and continued neurologists, physiatrists, neurosurgeons, physiotherapists, with this treatment throughout pregnancy. After delivery she social workers and psychologists. The multidisciplinary, was placed on an oral antithrombolytic agent indefinitely.
across-the-lifespan mandate is designed to facilitate collabora-tion resulting in improved patient care and education. This The patient became pregnant in mid-2007 at the age of 18. At team approach facilitates discussion of interesting cases and the start of the pregnancy, the patient was on an intrathecal transitioning of pediatric patients to the adult setting to baclofen dose of 375 ucg/day. No increased spasticity was noted enhance seamless health care. At the age of 18, patients are during the early part of her first trimester. During the fourth transitioned to the adult spinal cord injury (SCI) program. The month of gestation, a mild increase in tone and urine retention pediatric team continues to provide clinical support and liais- was noted during routine assessment and the ITB dosage was es with the adult program until the patients are fully trans- increased to 400 ucg/day. By the fifth month of gestation, urine ferred. This multidisciplinary perspective and approach retention had improved and was being managed with intermit- addresses the biopsychosocial needs unique to this population.
tent catheterizations. However, spasticity had increased in herlower extremities and her ITB dosage was increased to 440 However, given the paucity of literature and our patient’s etiol- ucg/day. She was managed on this dose for the remainder of her ogy, including several comorbidities, a broader multidiscipli- pregnancy and initial postpartum period. The patient reported nary team including several sub-specialties was implemented that although her spasticity increased during pregnancy and she within the first trimester. Thus, the development of a multidis- required dose adjustments of ITB, the spasticity never signifi- ciplinary team is essential early in the pregnancy to address the cantly impaired her ability to perform activities of daily living.
unique and evolving needs of these patients. It allows for a pre-ventative, proactive approach and anticipates the need for reac- Unassisted labour occurred at 38 weeks gestation and a healthy tive care when necessary. It is essential for the patients and their male infant was born by spontaneous vaginal delivery. The families to be well informed early in the pregnancy and include intrapartum period was complicated by a urinary tract infec- them as an integral part of the decision-making process.
tion and intravenous antibiotics were required in the immedi-ate postpartum period. No significant changes in spasms or Prenatal care
spasticity were noted. The patient was able to participate inthe care of her infant on the first day of delivery and success- Our patient was referred to a gynecologist for a prenatal assess- ment in her first trimester. Her underlying SCI and comorbidi- Volume 31, Issue 3, 2009 • Canadian Journal of Neuroscience Nursing
ties, which included hip dysplasia, necessitated an assessment Although our case demonstrates a spontaneous vaginal delivery for risks associated with preterm labour, increased risks for is possible, a labour plan that includes consideration of a caesar- infection and increased risks for operative delivery. In addition ian section is recommended. The obstetrician has to be aware of to routine pregnancy investigations, close monitoring occurred the position of the pump in order to plan the C-section, if nec- on a regular basis with decreasing intervals prior to delivery.
essary. Usually the pump is inserted higher and more laterallythan the C-section incision and, therefore, should not interfere.
Although a theoretical risk exists regarding thrombotic compli-cations in pregnant patients with a chronic SCI, there is little Spasticity
evidence to support this. Additionally, no evidence exists to sug-gest patients with ITB pumps have an increased risk of DVTs.
In the five ITB cases reported to date, three patients required Our patient was followed closely by hematology specialists and no increases of ITB (Munoz & Marco, 2000; Dalton et al., 2008).
maintained on thrombosis prophylaxis due to her pre-existing One patient required a 14% increase (Delhaas & Verhagen, 1992) DVT. However, current antithrombotic recommendations for while another patient with an ITB pump, implanted at 30 weeks each case are to be evaluated individually (Pereira, 2003).
gestation due to increasing spasticity, required a 250% increase(Roberts et al., 2003). Our patient required a 17% increase during Although pregnancies in patients with SCI present interesting her pregnancy, but did not experience any significant impact of challenges attributed to loss of autonomic control below the spasticity or spasms on her ADLs or bladder and bowel function.
level of the spinal cord lesion, current evidence suggests that She also experienced no side effects to increases in ITB baclofen.
most patients with an SCI will have successful deliveries atterm. There is also no increased risk for post-term delivery Increased spasticity during pregnancy may result from multi- (Pereira, 2003). Literature on pregnant patients with ITB ple etiologies. In addition to the underlying neuromuscular pumps suggests pre-term delivery has been planned rather disorder, the pregnancy, bladder and bowel changes, alter- than allowing the pregnancy to go to term (Delhaas & ations in skin integrity and seating issues may exacerbate spas- Verhagen, 1992; Munoz & Marco, 2000; Roberts et al., 2003).
ticity. Close evaluation of multiple etiologies and their impact Our patient did receive an assessment with the pre-admission on the patient and their ability to perform ADLs is essential.
clinic in case a caesarian section would be required and a ITB therapy is well known to decrease spasticity and spasms comprehensive labour plan was established.
and improve patient’s abilities to perform activities of daily liv-ing (Bhimani, 2008). It is important to include assessments Intrathecal baclofen pump
using validated tools, such as the Ashworth Scale (Ashworth, Since the pump is implanted subcutaneously and above the 1964), as well as taking the patient’s perspective into account abdominal muscle, there should be no interference with the when evaluating spasticity and its impact on ADLs during expanding uterus or abdominal organs (Medtronic, 2004).
pregnancy. ITB dosages should be adjusted to facilitate contin- Although the pump may appear more prominent as the abdom- ued independence both before and after the birth of the infant.
inal girth expands, there should be no risk for pump dehiscence.
Assessments for devices and equipment required to facilitate Health care practitioners may find accessing the ITB pump actu- independence with ADLs and infant care need to be addressed ally becomes easier due to its prominence. However, the grow- early in the pregnancy to ensure availability of resources.
ing abdomen may interfere with restraints and devices requiredfor mobility and adjustments to seating may be required.
No literature exists describing tubing disconnections or pump Effects of ITB on bladder function are unknown. Alterations in migration during pregnancy. Extra tubing length is routinely function are primarily attributed to the underlying etiology for implanted at the time of pump implantation and looped behind the spasticity. Genitourinary complications are well recognized the pump to allow for expansion changes associated with weight in patients with underlying SCI and asymptomatic urinary tract gain and growth. Therefore, issues with pump tubing must be
infections occur in a high number of pregnant patients with kept in mind during the expansion of the abdomen, though no SCI (Pereira, 2003). Our patient required an increase in the fre- specific monitoring is required. Our patient experienced no quency of intermittent catheterizations during the initial part difficulties with the implanted ITB pump or pump tubing.
of her first trimester and the latter part of her third trimester.
The etiology for this was unclear. During the latter part of her Regularly scheduled clinical assessments of response to ITB are first trimester she was noted to have an asymptomatic UTI for recommended. Spasticity has been noted to increase with preg- which she was treated and then placed on antibiotic prophylax- nancy (Dalton et al., 2008; Roberts et al., 2003), so it is important is. She presented during labour, febrile and with an unrecog- to differentiate between evolving spasticity related to pregnancy nized UTI. We recommend very close monitoring for evidence and other health conditions versus mechanical complications,such as tubing dislodgement, disconnection or pump malfunc- of lower and upper urinary tract infections in pregnant patients tion. Observance of presentation of acuity of symptoms is with an ITB pump who have a neurogenic bladder regardless of important. Mechanical complications need to be included in etiology, and are performing self-catheterizations.
the differential diagnosis when acute changes in spasticity pres-ent. If concerns exist regarding catheter placement or mechan- Intrapartum issues
ical delivery of ITB, a bolus can be programmed and effective- One identified risk of pregnant patients with SCI is that of ness observed within the clinical setting. This method of eval- unrecognized contractions, which may result in an unattended uation would be recommended initially over x-ray examination delivery. Our patient has some preserved sensation and was to avoid unnecessary radiation exposure.
able to recognize subtle contractions. It is important to provide Canadian Journal of Neuroscience Nursing • Volume 31, Issue 3, 2009
education regarding recognizing sympathetic nervous system effects on the infant post-natally. It also suggests a pregnant symptoms such as increased spasticity, shortness of breath and female with an ITB pump, who has spinal instrumentation leg or abdominal spasms as a probable indication of labour.
and a previous history of DVT, is able to have a spontaneous However, this needs to be differentiated from symptoms of ITB vaginal delivery at term. A multidisciplinary approach that withdrawal. We recommend patients be taught uterine palpa- integrates preventative and proactive care into the health tion techniques, how to time contractions and to be aware of care spectrum is recommended. Additionally, patient and their baseline pulse, blood pressure and temperature readings.
family involvement in the health care decision-making Postpartum
Plasma baclofen levels are essentially undetectable in both About the authors
children and adults receiving therapeutic chronic intrathecal Margo DeVries-Rizzo, BScN, MScN, RN(EC), Nurse baclofen infusion dosages (Albright, 1999). There have been Practitioner, Pediatric Neurology at Children’s Hospital, no adverse events or signs and symptoms of withdrawal relat- London Health Sciences Centre, Adjunct Assistant Professor, ed to intrathecal baclofen reported in newborns of women Faculty of Health Sciences, University of Western Ontario. with a chronic intrathecal baclofen pump (Dalton et al., 2008; Diny Warren, RN, CCRN, recently retired clinic nurse from Delhaas, 1992; Munoz & Marco, 2000; Roberts et al., 2003).
Evidence does exist for close monitoring of infants born to Spinal-Cord Injury (SCI) Program, Parkwood Hospital, St. mothers on oral baclofen since plasma concentrations are higher and signs and symptoms of baclofen withdrawal may Gail Delaney, MD, Associate Professor, Department of occur. Possible prophylactic therapy of these infants in the ini- Physical Medicine and Rehabilitation, University of Western tial neonatal period may be warranted (Moran et al., 2004).
Ontario, works in the Spinal Cord Injury Program, Parkwood Our patient’s infant was closely monitored and demonstrated Hospital, St. Joseph’s Health Care. no evidence of baclofen withdrawal or teratogenicity. Thepatient was encouraged to participate in her infant’s care and Simon Levin, MD, FRCPC, Consultant Pediatric Neurologist, establish breastfeeding early in the initial postpartum period.
Children’s Hospital, London Health Sciences Centre,Associate Professor, Department of Pediatrics and Clinical Currently, no literature is available to suggest ITB is contraindi- Neurosciences, Schulich School of Medicine and Dentistry, cated with breastfeeding. Given that plasma levels are largely undetectable, our patient chose to breastfeed her infant forthree-and-a-half months. No adverse effects were noted on Sandrine De Ribaupierre, MD, Pediatric Neurosurgeon, London multiple assessments, such as neurological or growth and devel- Health Sciences Centre, Assistant Professor, Schulich School of opmental issues. Additionally, the literature reports no adverse Medicine and Dentistry, University of Western Ontario. developmental effects in healthy infants born to patients withITB pumps (Dalton et al., 2008; Delhaas, 1992; Munoz & Marco, Craig Campbell, MD, MSc, FRCPC, Pediatric Neurologist at 2000; Roberts et al., 2003). Our patient’s son is exceeding his Children’s Hospital, London Health Sciences Centre, Assistant developmental milestones at the age of 15 months, lending addi- Professor, Department of Pediatrics, Clinical Neurological tional support that ITB does not adversely affect development.
Sciences and Epidemiology, Schulich School of Medicine andDentistry, University of Western Ontario. Conclusion
Comments or requests for further information may be Our case lends support for the safety and efficacy of ITB dur- directed via e-mail to [email protected]
ing the intrapartum period and the impression of lack of side References
Albright, L. (1999). Plasma baclofen levels in children Moran, L.R., Almeida, P.G., Worden, S., & Huttner, K.M.
receiving continuous intrathecal baclofen infusion. Journal of Child
(2004). Intrauterine baclofen exposure: A multidisciplinary approach.
Neurology, 14, 408–409.
Pediatrics, 114(2), 267–269.
Ashworth B. (1964). Preliminary trial of carisoprodol in Munoz, C., & Marco, D. (2000). Pregnancy outcome in a multiple sclerosis. Practitioner, 192, 540–542.
woman exposed to continuous intrathecal baclofen infusion. The
Bhimani, R. (2008). Intrathecal baclofen therapy in adults and Annals of Pharmacotherapy, 34, 956.
guideline for clinical nursing care. Rehabilitation Nursing, 33(3),
Penn, R.D., & Kroin, J.S. (1985). Continuous intrathecal baclofen for severe spasticity. Lancet, 2, 125–7.
Dalton, C.M., Keenan, E., Jarrett, L., Buckley, L., & Stevenson, Pereira, L. (2003). Obstetric management of the patient with V. (2008). The safety of baclofen in pregnancy: Intrathecal therapy in spinal cord injury. Obstetrical and Gynecological Survey, 58(10),
multiple sclerosis. Multiple Sclerosis, 14, 571–572.
Delhaas, E.M., & Verhagen, J. (1992). Pregnancy in a Roberts, A.G., Graves, C.R., Konrad, P.E., Groomes, T.E., quadriplegic patient treated with continuous intrathecal baclofen Pfister, A.A., Damian, M.M., et al. (2003). Intrathecal baclofen pump infusion to manage her severe spasticity. Case report. Paraplegia,
implantation during pregnancy. Neurology, 61, 1156–1157.
Thomson Micromedex. (2008). MICROMEDEX® Healthcare
Engrand, J., Van de Perre, P., Vilain, G., & Benhamou, D.
Series. Retrieved from http://www.thomsonhc.com/hcs/librarian/
(2001). European Journal of Anaesthesiology, 18, 261–263.
ND_T/HCS/ND_PR/Main/CS/AA49FA/DUPLICATIONSHIELDSY Medtronic. (2004). Synchromed II Programmable Infusion
NC/08487B/ND_PG/PRIH/ND_B/HCS/ND_P/Main/PFPUI/NXY1 System, Clinical Reference Guide. Minneapolis, MN.
RO2Hxw8IG/PFDefaultActionId/hcs.main.KeywordSearch.Search Volume 31, Issue 3, 2009 • Canadian Journal of Neuroscience Nursing
Data and Safety Monitoring During Randomized Controlled Trials of Nursing Interventions Nancy T. Artinian ▼ Erika Sivarajan Froelicher ▼ Background: Principal investigators have a responsibility to ensure and maintain the scientific integrity of their research studies and to protect the safety of the partici-pants. Data and safety monitoring is required for all types of c