Neuromodulation: Technology at the Neural Interface Received: November 5, 2013
Revised: February 11, 2014
Accepted: February 13, 2014
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12191
Treatment of Severe Tetanus With Intrathecal Baclofen via Implantable Infusion Device: A Case Report Geraldine Dapul, MD*; Pritesh Patel, MD*; Tejpaul Pannu, MD†; Jay Meythaler, MD, JD* Objective: Severe tetanus remains a serious issue in less developed countries, leading to prolonged hospitalization due to prolonged neuromuscular contraction of muscles. We present a case of severe tetanus in the United States that was successfully managed with intrathecal baclofen. Case Report: A 42-year-old male without tetanus vaccination history presented to the emergency department with intractable jaw pain and worsening diffuse muscle contractures due to severe generalized tetanus requiring prolonged paralysis and ventilator support. After 14 days of continuous neuromuscular treatment with benzodiazepines, vecuronium, propofol, and magnesium sulfate, a baclofen pump trial was performed 14 days post-admission as an alternative to prolonged neuromuscular blockade. After demonstrable improvement in spasms and paroxysmal contractures due to intrathecal baclofen (ITB), a baclofen pump was implanted on hospital day 17. The catheter was threaded to T4 for maximal effect of intrathecal baclofen on the upper and lower extremities at an initial rate of 100 μg/day. ITB was titrated upward, the vecuronium was slowly weaned, and the patient was weaned off a ventilator by day 14 of ITB treatment. At an ITB dose of 450 μg/day, propofol was discontinued. ITB was continued over the next four weeks and eventually weaned over the next two weeks. The ITB pump was removed eight weeks after placement, and the patient was successfully discharged to home. Conclusion: Due to prolonged muscle weakness associated with long-term use of paralytic agents and sedation, early ITB trial and pump placement should be considered as an alternative in the treatment of severe tetanus to shorten length of stay and improve the functional outcome of the patient. Keywords: Intrathecal baclofen, severe tetanus Conflict of Interest: The authors reported no conflict of interest.
INTRODUCTION
CASE DESCRIPTION
The United States has seen a significant decline in tetanus cases since 1947, primarily due to immunization (1,2). Although on the decline, tetanus remains a serious issue in less developed countries, where access to intensive care facilities and proper care are quite limited. In developing countries, on the other hand, tetanus has still been found to affect those who are immune-compromised, IV drug users, and the elderly, as well as survivors of natural disasters (3,4). The mortality rate associated with tetanus can be as high as 50% in developing countries, along with prolonged hospitalizations, significant complications, and morbidity if not properly treated (1–5). Tetanus occurs after the spores of Clostridium tetani enter the host through open injuries. After inoculation, C. tetani germinates and produces tetanospasmin (tetanus toxin). The toxin reaches peripheral nerves and from there is carried via retrograde axonal transport to the central nervous system (CNS). Once it reaches the presynaptic nerve ending it cleaves membrane proteins involved in the neuroexocytosis of γ-aminobutyric acid (GABA) and glycine, causing disinhibition of excitatory impulses (6–8). Baclofen works as an agonist at presynaptic GABA-B receptors and has proven effective in reducing spasticity associated with spinal cord injury and traumatic brain injury (9–11).
A 42-year-old male with no prior vaccination history for tetanus presented to the emergency room with intractable jaw pain and trismus as well as total body muscle contractures. Seven days prior to admission, while repairing a roof, the patient contracted tetanus from a rusty nail. The patient was admitted to the ICU after worsening throat swelling, which prompted emergent intubation for airway protection and the initiation of vecuronium. The patient was diagnosed with tetanus. Subsequently, antibiotics, tetanus immunoglobulin, and tetanus toxoid were administered. Initially, the
* Department of Physical Medicine and Rehabilitation Oakwood, School of Medicine, Wayne State University, Dearborn, MI, USA † Department of Neurosurgery, Oakwood Hospital, Dearborn, MI, USA For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http:// www.wiley.com/bw/submit.asp?ref=1094-7159&site=1
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 791–793
791
www.neuromodulationjournal.com
Address correspondence to: Jay M. Meythaler, MD, JD, Department of Physical Medicine and Rehabilitation Oakwood, Wayne State University, School of Medicine, 18181 Oakwood Blvd., Dearborn, MI 48124, USA. Email: jmeythal@ med.wayne.edu
DAPUL ET AL. patient’s agitation and autonomic instability were treated with sedation using diazepam, propofol, and magnesium sulfate. However, the patient’s rigidity, trismus, and opisthotonos failed to resolve. A baclofen pump trial with a bolus dose of 50 μg was completed 14 days post-admission as an alternative to prolonged neuromuscular blockade. The patient’s spasms and paroxysmal contractures improved within two hours of the trial. A baclofen pump was implanted by neurosurgery 17 days post-admission. The catheter was inserted to T4 for maximal effect of the intrathecal baclofen (ITB) on the upper and lower extremities at an initial rate of 100 μg/ day. As the medication dosage was increased every day the vecuronium was slowly weaned. The weaning was not started until upper and lower extremity tone was 3/5 on the Ashworth scale, which was by day 3. The patient was weaned off vecuronium and off the ventilator by day 14 after starting ITB. To reduce painful spasms, increases in ITB pump infusion were made to a peak rate of 450 μg/ day by day 34, resulting in propofol cessation. However, the patient’s hospital course was complicated by C. difficile colitis that required laparoscopic loop ileostomy and subsequent small bowel resection and ileostomy takedown. After successful control of muscle rigidity and spasms, baclofen was then weaned over the next four weeks and eventually discontinued. At the end of the patient’s hospitalization, the ITB pump was removed, two months after its initial placement. The patient fully recovered from his tetanus as well as his hospital complications and was discharged to home. The patient had resultant painful joint contractures that responded to stretching and physical therapy over the next three months, during which he was treated as an outpatient. The patient resumed his normal life and at six months returned to his occupation.
DISCUSSION
792
This is only the second case report in the United States of use of an implantable pump with internalized catheter, versus an externalized catheter, for ITB delivery. The use of baclofen in cases of severe tetanus has been reported in Europe, Asia, Africa, and Australia in bolus form or via an external catheter (12–22). Only one other case has been documented in which severe tetanus was successfully treated via an implantable pump with internalized catheter for intrathecal delivery (23). Although tetanus rates have declined steadily, reaching an alltime low in 2009 (0.01 cases per 100,000), tetanus is still an international health problem, exclusively occurring in persons who are not vaccinated or are inadequately immunized (1,2). Prolonged neuromuscular blockade can result in profound weakness and complications. The use of subarachnoid infusions of baclofen for the treatment of severe spasticity in tetanus was first reported in 1986 (12). Numerous case reports have since been made on the success of treating generalized tetanus with ITB (9,13–20,22–24). ITB has been found to be an effective alternative method for improving mortality and morbidity of tetanus-affected individuals without compromising respiratory physiology and for controlling muscle activity (14,16). In 1996, Dressnandt and colleagues described four cases in which patients were administered ITB via an implanted spinal catheter that was connected to a subcutaneous port at the level of T9–T10. A programmable pump allows one to adjust and customize the dose of the medication. Despite the cost of implantation, the ability to www.neuromodulationjournal.com
quickly wean someone off of paralytic agents and the ventilator actually makes the treatment cost-effective. An internalized system may cost ∼$20,000, while the average cost per day in the ICU is close to $10,000. An implantable pump would decrease the duration over which sedation and paralytic agents would be required, minimizing the patient’s length of stay in our health care system. While this may change from locality to locality, more quickly transferring a patient out of the ICU is of benefit. Although ITB by external catheter has been found to be efficacious in controlling muscle rigidity and paroxysmal spasms in tetanus, it carries considerable infection risk. In a retrospective study performed by Santos et al. in 2004, 22 patients with severe tetanus received ITB after lumbar puncture was performed and a subarachnoid externalized catheter was placed (21). The success of the treatment was evident by the lower doses of sedatives and muscle relaxants used, as well as mechanical ventilation duration. However, one of the 22 patients developed meningitis from having an indwelling intrathecal catheter in spite of routine microbiologic studies of CSF studies completed on insertion, weekly, and upon removal. Seven patients had colonization of the catheter. Deibert et al. also reported bacterial meningitis after initial ITB trial via externalized lumbar catheter. However, implantation of a device that would administer ITB continuously was then performed to reduce the risk associated with external catheterization (23). In 1998, Deibert and colleagues were able to achieve adequate control of muscle spasms, dysautonomia, and respiratory instability by using an implantable, synchronized infusion device to administer baclofen (23). This method was first reported in a patient who initially failed treatment with oral antispasticity agents such as baclofen and intravenous benzodiazepine (23). The patient had responded positively to ITB via external delivery methods but unfortunately developed bacterial meningitis. Once ITB was instituted, this eliminated the need for prolonged mechanical ventilation, improved her mentation, and helped gain control of her tetanusinduced spasticity (23). In this case, it was decided to institute ITB delivery earlier in the course of illness via an implantable pump. ITB dosage needed to achieve successful control of rigidity, spasticity, and extubation has ranged from 1000 to 2000 μg per day (13,21,23). The therapeutic dose of ITB needed to control the effects of tetanus varies from patient to patient and largely rests on the severity of the disease. In this case the patient responded to only 450 μg per day, and this may be due to earlier initiation and/or the severity of the disease. The goal was to decrease the use of and dependence on these medications, avoid long-term sedation and mechanical ventilation, and reduce length of hospital stay. In spite of the internationally reported success of ITB, there have been cases reported in which ITB has been ineffective (22). In a 29-year-old intravenous and intramuscular drug abuser with severe spasms, non-depolarizing agents, magnesium, propofol, and midazolam were administered for spasticity management, but provided no successful control. ITB was then given, which also proved to be ineffective. The inefficacy, as reported by the authors, may have been due in part to subtherapeutic infusion and unfamiliarity with the medication. The patient had received an initial bolus dose of 250 μg followed by continuous infusion at a rate of 1000 μg for two days. Santos et al. also reported that one patient given intrathecal perfusion of baclofen at 3 mg/day did not achieve adequate control of all paroxysms and muscle rigidity in spite of the dose. It is not reported in either case whether catheter placement was confirmed (21,23). The lack of response also may be attributed to more inoculum present in the system, and the authors have speculated that it may be related to the patient’s drug addiction (21), although
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 791–793
ITB FOR TETANUS the mechanism of how drug addiction might interfere with the efficacy of ITB has never been clarified. Our patient treated with ITB via an implantable device was not reported to have any history of IV or IM drug use, nor did he exhibit clinical effects of hypotension, coma, areflexia, or respiratory depression associated with ITB administration. The fact that the patient was in an ICU allowed us to quickly increase the ITB without concerns over the complications of overdosage of ITB.
CONCLUSIONS Although severe tetanus remains an international health issue, effective and successful outcomes have been achieved by administering ITB. Externally placed catheters in the cerebrospinal fluid have been linked to increased infection, particularly at the time when they are placed (25–27), whereas bolus trials have shown very little risk (28). Placement of an intrathecal pump does involve some risk after the initial placement, but this drops precipitously with time (29). Considering the length of time patients require treatment, including through rehabilitation, an intrathecal pump is clearly preferable to an externally placed catheter for spinal delivery. Although symptomatic treatment with benzodiazepine and paralytic agents has been effective for the treatment of tetanus, prolonged muscle weakness has been associated with long-term use of these agents. Early ITB pump infusion should be considered as an alternative method that reduces the risks of infections such as meningitis. Most importantly, ITB reduces the need for prolonged sedation, use of neuromuscular blockade agents, and mechanical ventilatory requirements, thus shortening length of stay, improving overall morbidity and mortality associated with tetanus, and improving the functional outcome of the patient and potentially the costeffectiveness of the treatment.
Authorship Statements Drs. Dapul and Pritesh were the primary authors. Drs. Pritesh and Meythaler performed the initial clinical care on the patient. Dr. Pannu implanted the intrathecal pump surgically in the patient. Dr. Meythaler edited the paper after the preliminary draft and added substantial material to the discussion section due to his extensive intrathecal experience. Dr. Pannu contributed to the editing of the paper as well.
How to Cite this Article: Dapul G., Patel P., Pannu T., Meythaler J. 2014. Treatment of Severe Tetanus With Intrathecal Baclofen via Implantable Infusion Device: A Case Report. Neuromodulation 2014; 17: 791–793
REFERENCES 1. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccinepreventable diseases: the pink book: course textbook, 12th ed. Atlanta: CDC, 2012. 2. Tiwari T, Clark TA, Messonnier NE, Thomas CG. Tetanus surveillance—United States, 2001–2008. MMWR Morb Mortal Wkly Rep 2011;60:365–367. 3. Afshar M, Raju M, Ansell D, Bleck TP. Narrative review: tetanus—a health threat after natural disasters in developing countries. Ann Intern Med 2011;154:329–335. 4. Centers for Disease Control and Prevention. Tetanus among injecting-drug users— California 1997. MMWR Morb Mortal Wkly Rep 1998;47:149–151. 5. Rushdy AA, White JM, Ramsay ME, Crowcroft NS. Tetanus in England and Wales, 1984–2000. Epidemiol Infect 2003;130:71–77. 6. Brook I. Current concepts in the management of Clostridium tetani infection. Expert Rev Anti Infect Ther 2008;6:327–336. 7. Lalli G, Gschmeissner S, Schiavo G. Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons. J Cell Sci 2003;116:4639–4650. 8. Farrar JJ, Yen LM, Cook T et al. Tetanus. J Neurol Neurosurg Psychiatry 2000;69:292– 301. 9. Penn RD, Savoy SM, Corcos DM et al. Intrathecal baclofen for severe spinal spasticity. N Engl J Med 1989;320:1517–1522. 10. Meythaler JM, Steers WD, Tuel SM, Cross LL, Haworth CS. Continuous intrathecal baclofen in spinal cord spasticity: a prospective study. Am J Phys Med Rehabil 1992;71:321–327. 11. Lazorthes Y, Sallerin-Caute B, Verdie J, Bastide R, Carillo J. Chronic intrathecal baclofen administration for control of severe spasticity. J Neurosurg 1990;72:393– 402. 12. Muller H, Borner U, Zierski J, Hempelmann G. Intrathecal baclofen in tetanus. Lancet 1986;1:317–318. 13. Muller H, Borner U, Zierski J, Hempelmann G. Intrathecal baclofen for treatment of tetanus-induced spasticity. Anesthesiology 1987;66:76–79. 14. Saissy JM, Demaziere J, Viris M et al. Treatment of severe tetanus by intrathecal injections of baclofen without artificial ventilation. Intensive Care Med 1992;18:241– 244. 15. Brock H, Moosbauer W, Gabriel C, Necek S, Bidal D. Treatment of severe tetanus by continuous intrathecal infusion of baclofen. J Neurol Neurosurg Psychiatry 1995;59:193–194. 16. Dressnandt J, Kontanzer A, Weinzierl FX, Pfab R, Klingelhofer J. Intrathecal baclofen in tetanus: four cases and a review of reported cases. Intensive Care Med 1997;23:896–902. 17. Francois B, Clavel M, Desachy A, Vignon P, Salle JY, Gastinne H. Continuous intrathecal injection of baclofen in generalized tetanus. Presse Med 1997;26:1045–1047. 18. Engrand N, Guerot E, Rouamba A, Vilain G. The efficacy of intrathecal baclofen in severe tetanus. Anesthesiology 1999;90:1773–1776. 19. Boots RJ, Lipman J, O’Callaghan J, Scott P, Fraser J. The treatment of tetanus with intrathecal baclofen. Anaesth Intensive Care 2000;28:438–442. 20. Trampitsch E, Krumpholz R, Likar R, Other M, Gulle D. Continuous intrathecal administration of baclofen in severe tetanus. Anasthesiol Intensivmed Notfallmed Schmerzther 2000;35:532–533. 21. Santos ML, Mota-Miranda A, Alves-Pereira A, Gomes A, Correia J, Marcal N. Intrathecal baclofen for the treatment of tetanus. Clin Infect Dis 2004;38:321–328. 22. Thomas RM, Bellamy MC. Tetanus in a subcutaneous drug abuser: ineffectiveness of intrathecal baclofen. Anaesth Intensive Care 2006;34:811–815. 23. Deibert E, Bhardwaj A, Staats P, Ulatowski JA. Chronic intrathecal baclofen administration for the treatment of severe generalized tetanus via a synchronized infusion pump. Neuromodulation 1998;1:2–5. 24. Solsona M, Miro G, Yebenes JC, Balanzo X, Almirall J, Mauri M. Tetanus treated with continuous baclofen intrathecal perfusion. Med Intensiva 2007;31:204–206. 25. Lozier AP, Sciacca RR, Romagnoli MF, Connolly ES. Ventriculostomy-related infections: a critical review of the literature. Neurosurgery 2002;51:170–182. 26. Paramore CG, Turner DA. Relative risks of ventriculostomy infection and morbidity. Acta Neurochir (Wien) 1994;127:79–84. 27. Aprili D, Bandschapp O, Rochlitz C, Urwyler A, Ruppen W. Serious complications associated with external intrathecal catheters used in cancer pain patients. Anesthesiology 2009;111:1346–1355. 28. Meythaler JM, Guin-Renfroe S, Brunner RC, Johnson A, Hadley MN. Intrathecal baclofen for spastic hypertonia from stroke. Stroke 2001;32:2099–2109. 29. Fjelstad AB, Hommelstad J, Sorteberg A. Infections related to intrathecal baclofen therapy in children and adults: frequency and risk factors. J Neurosurg Pediatr 2009;4:487–493.
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© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 791–793
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Revised: February 11, 2014
Accepted: February 13, 2014
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12191
Treatment of Severe Tetanus With Intrathecal Baclofen via Implantable Infusion Device: A Case Report Geraldine Dapul, MD*; Pritesh Patel, MD*; Tejpaul Pannu, MD†; Jay Meythaler, MD, JD* Objective: Severe tetanus remains a serious issue in less developed countries, leading to prolonged hospitalization due to prolonged neuromuscular contraction of muscles. We present a case of severe tetanus in the United States that was successfully managed with intrathecal baclofen. Case Report: A 42-year-old male without tetanus vaccination history presented to the emergency department with intractable jaw pain and worsening diffuse muscle contractures due to severe generalized tetanus requiring prolonged paralysis and ventilator support. After 14 days of continuous neuromuscular treatment with benzodiazepines, vecuronium, propofol, and magnesium sulfate, a baclofen pump trial was performed 14 days post-admission as an alternative to prolonged neuromuscular blockade. After demonstrable improvement in spasms and paroxysmal contractures due to intrathecal baclofen (ITB), a baclofen pump was implanted on hospital day 17. The catheter was threaded to T4 for maximal effect of intrathecal baclofen on the upper and lower extremities at an initial rate of 100 μg/day. ITB was titrated upward, the vecuronium was slowly weaned, and the patient was weaned off a ventilator by day 14 of ITB treatment. At an ITB dose of 450 μg/day, propofol was discontinued. ITB was continued over the next four weeks and eventually weaned over the next two weeks. The ITB pump was removed eight weeks after placement, and the patient was successfully discharged to home. Conclusion: Due to prolonged muscle weakness associated with long-term use of paralytic agents and sedation, early ITB trial and pump placement should be considered as an alternative in the treatment of severe tetanus to shorten length of stay and improve the functional outcome of the patient. Keywords: Intrathecal baclofen, severe tetanus Conflict of Interest: The authors reported no conflict of interest.
INTRODUCTION
CASE DESCRIPTION
The United States has seen a significant decline in tetanus cases since 1947, primarily due to immunization (1,2). Although on the decline, tetanus remains a serious issue in less developed countries, where access to intensive care facilities and proper care are quite limited. In developing countries, on the other hand, tetanus has still been found to affect those who are immune-compromised, IV drug users, and the elderly, as well as survivors of natural disasters (3,4). The mortality rate associated with tetanus can be as high as 50% in developing countries, along with prolonged hospitalizations, significant complications, and morbidity if not properly treated (1–5). Tetanus occurs after the spores of Clostridium tetani enter the host through open injuries. After inoculation, C. tetani germinates and produces tetanospasmin (tetanus toxin). The toxin reaches peripheral nerves and from there is carried via retrograde axonal transport to the central nervous system (CNS). Once it reaches the presynaptic nerve ending it cleaves membrane proteins involved in the neuroexocytosis of γ-aminobutyric acid (GABA) and glycine, causing disinhibition of excitatory impulses (6–8). Baclofen works as an agonist at presynaptic GABA-B receptors and has proven effective in reducing spasticity associated with spinal cord injury and traumatic brain injury (9–11).
A 42-year-old male with no prior vaccination history for tetanus presented to the emergency room with intractable jaw pain and trismus as well as total body muscle contractures. Seven days prior to admission, while repairing a roof, the patient contracted tetanus from a rusty nail. The patient was admitted to the ICU after worsening throat swelling, which prompted emergent intubation for airway protection and the initiation of vecuronium. The patient was diagnosed with tetanus. Subsequently, antibiotics, tetanus immunoglobulin, and tetanus toxoid were administered. Initially, the
* Department of Physical Medicine and Rehabilitation Oakwood, School of Medicine, Wayne State University, Dearborn, MI, USA † Department of Neurosurgery, Oakwood Hospital, Dearborn, MI, USA For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http:// www.wiley.com/bw/submit.asp?ref=1094-7159&site=1
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 791–793
791
www.neuromodulationjournal.com
Address correspondence to: Jay M. Meythaler, MD, JD, Department of Physical Medicine and Rehabilitation Oakwood, Wayne State University, School of Medicine, 18181 Oakwood Blvd., Dearborn, MI 48124, USA. Email: jmeythal@ med.wayne.edu
DAPUL ET AL. patient’s agitation and autonomic instability were treated with sedation using diazepam, propofol, and magnesium sulfate. However, the patient’s rigidity, trismus, and opisthotonos failed to resolve. A baclofen pump trial with a bolus dose of 50 μg was completed 14 days post-admission as an alternative to prolonged neuromuscular blockade. The patient’s spasms and paroxysmal contractures improved within two hours of the trial. A baclofen pump was implanted by neurosurgery 17 days post-admission. The catheter was inserted to T4 for maximal effect of the intrathecal baclofen (ITB) on the upper and lower extremities at an initial rate of 100 μg/ day. As the medication dosage was increased every day the vecuronium was slowly weaned. The weaning was not started until upper and lower extremity tone was 3/5 on the Ashworth scale, which was by day 3. The patient was weaned off vecuronium and off the ventilator by day 14 after starting ITB. To reduce painful spasms, increases in ITB pump infusion were made to a peak rate of 450 μg/ day by day 34, resulting in propofol cessation. However, the patient’s hospital course was complicated by C. difficile colitis that required laparoscopic loop ileostomy and subsequent small bowel resection and ileostomy takedown. After successful control of muscle rigidity and spasms, baclofen was then weaned over the next four weeks and eventually discontinued. At the end of the patient’s hospitalization, the ITB pump was removed, two months after its initial placement. The patient fully recovered from his tetanus as well as his hospital complications and was discharged to home. The patient had resultant painful joint contractures that responded to stretching and physical therapy over the next three months, during which he was treated as an outpatient. The patient resumed his normal life and at six months returned to his occupation.
DISCUSSION
792
This is only the second case report in the United States of use of an implantable pump with internalized catheter, versus an externalized catheter, for ITB delivery. The use of baclofen in cases of severe tetanus has been reported in Europe, Asia, Africa, and Australia in bolus form or via an external catheter (12–22). Only one other case has been documented in which severe tetanus was successfully treated via an implantable pump with internalized catheter for intrathecal delivery (23). Although tetanus rates have declined steadily, reaching an alltime low in 2009 (0.01 cases per 100,000), tetanus is still an international health problem, exclusively occurring in persons who are not vaccinated or are inadequately immunized (1,2). Prolonged neuromuscular blockade can result in profound weakness and complications. The use of subarachnoid infusions of baclofen for the treatment of severe spasticity in tetanus was first reported in 1986 (12). Numerous case reports have since been made on the success of treating generalized tetanus with ITB (9,13–20,22–24). ITB has been found to be an effective alternative method for improving mortality and morbidity of tetanus-affected individuals without compromising respiratory physiology and for controlling muscle activity (14,16). In 1996, Dressnandt and colleagues described four cases in which patients were administered ITB via an implanted spinal catheter that was connected to a subcutaneous port at the level of T9–T10. A programmable pump allows one to adjust and customize the dose of the medication. Despite the cost of implantation, the ability to www.neuromodulationjournal.com
quickly wean someone off of paralytic agents and the ventilator actually makes the treatment cost-effective. An internalized system may cost ∼$20,000, while the average cost per day in the ICU is close to $10,000. An implantable pump would decrease the duration over which sedation and paralytic agents would be required, minimizing the patient’s length of stay in our health care system. While this may change from locality to locality, more quickly transferring a patient out of the ICU is of benefit. Although ITB by external catheter has been found to be efficacious in controlling muscle rigidity and paroxysmal spasms in tetanus, it carries considerable infection risk. In a retrospective study performed by Santos et al. in 2004, 22 patients with severe tetanus received ITB after lumbar puncture was performed and a subarachnoid externalized catheter was placed (21). The success of the treatment was evident by the lower doses of sedatives and muscle relaxants used, as well as mechanical ventilation duration. However, one of the 22 patients developed meningitis from having an indwelling intrathecal catheter in spite of routine microbiologic studies of CSF studies completed on insertion, weekly, and upon removal. Seven patients had colonization of the catheter. Deibert et al. also reported bacterial meningitis after initial ITB trial via externalized lumbar catheter. However, implantation of a device that would administer ITB continuously was then performed to reduce the risk associated with external catheterization (23). In 1998, Deibert and colleagues were able to achieve adequate control of muscle spasms, dysautonomia, and respiratory instability by using an implantable, synchronized infusion device to administer baclofen (23). This method was first reported in a patient who initially failed treatment with oral antispasticity agents such as baclofen and intravenous benzodiazepine (23). The patient had responded positively to ITB via external delivery methods but unfortunately developed bacterial meningitis. Once ITB was instituted, this eliminated the need for prolonged mechanical ventilation, improved her mentation, and helped gain control of her tetanusinduced spasticity (23). In this case, it was decided to institute ITB delivery earlier in the course of illness via an implantable pump. ITB dosage needed to achieve successful control of rigidity, spasticity, and extubation has ranged from 1000 to 2000 μg per day (13,21,23). The therapeutic dose of ITB needed to control the effects of tetanus varies from patient to patient and largely rests on the severity of the disease. In this case the patient responded to only 450 μg per day, and this may be due to earlier initiation and/or the severity of the disease. The goal was to decrease the use of and dependence on these medications, avoid long-term sedation and mechanical ventilation, and reduce length of hospital stay. In spite of the internationally reported success of ITB, there have been cases reported in which ITB has been ineffective (22). In a 29-year-old intravenous and intramuscular drug abuser with severe spasms, non-depolarizing agents, magnesium, propofol, and midazolam were administered for spasticity management, but provided no successful control. ITB was then given, which also proved to be ineffective. The inefficacy, as reported by the authors, may have been due in part to subtherapeutic infusion and unfamiliarity with the medication. The patient had received an initial bolus dose of 250 μg followed by continuous infusion at a rate of 1000 μg for two days. Santos et al. also reported that one patient given intrathecal perfusion of baclofen at 3 mg/day did not achieve adequate control of all paroxysms and muscle rigidity in spite of the dose. It is not reported in either case whether catheter placement was confirmed (21,23). The lack of response also may be attributed to more inoculum present in the system, and the authors have speculated that it may be related to the patient’s drug addiction (21), although
© 2014 International Neuromodulation Society
Neuromodulation 2014; 17: 791–793
ITB FOR TETANUS the mechanism of how drug addiction might interfere with the efficacy of ITB has never been clarified. Our patient treated with ITB via an implantable device was not reported to have any history of IV or IM drug use, nor did he exhibit clinical effects of hypotension, coma, areflexia, or respiratory depression associated with ITB administration. The fact that the patient was in an ICU allowed us to quickly increase the ITB without concerns over the complications of overdosage of ITB.
CONCLUSIONS Although severe tetanus remains an international health issue, effective and successful outcomes have been achieved by administering ITB. Externally placed catheters in the cerebrospinal fluid have been linked to increased infection, particularly at the time when they are placed (25–27), whereas bolus trials have shown very little risk (28). Placement of an intrathecal pump does involve some risk after the initial placement, but this drops precipitously with time (29). Considering the length of time patients require treatment, including through rehabilitation, an intrathecal pump is clearly preferable to an externally placed catheter for spinal delivery. Although symptomatic treatment with benzodiazepine and paralytic agents has been effective for the treatment of tetanus, prolonged muscle weakness has been associated with long-term use of these agents. Early ITB pump infusion should be considered as an alternative method that reduces the risks of infections such as meningitis. Most importantly, ITB reduces the need for prolonged sedation, use of neuromuscular blockade agents, and mechanical ventilatory requirements, thus shortening length of stay, improving overall morbidity and mortality associated with tetanus, and improving the functional outcome of the patient and potentially the costeffectiveness of the treatment.
Authorship Statements Drs. Dapul and Pritesh were the primary authors. Drs. Pritesh and Meythaler performed the initial clinical care on the patient. Dr. Pannu implanted the intrathecal pump surgically in the patient. Dr. Meythaler edited the paper after the preliminary draft and added substantial material to the discussion section due to his extensive intrathecal experience. Dr. Pannu contributed to the editing of the paper as well.
How to Cite this Article: Dapul G., Patel P., Pannu T., Meythaler J. 2014. Treatment of Severe Tetanus With Intrathecal Baclofen via Implantable Infusion Device: A Case Report. Neuromodulation 2014; 17: 791–793
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Neuromodulation 2014; 17: 791–793
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