Baclofen neurotoxicity in a patient with end-stage chronic renal failure
Neurotoxicidad por baclofeno en paciente con insuficiencia renal crónica terminal
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Teresa Compte-Jove, Cristina Gállego-Gil" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Pablo" "apellidos" => "Justo-Ávila" "email" => array:1 [ 0 => "nefrotortosa@grupsagessa.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "nombre" => "Luciemne" "apellidos" => "Fernández-Antuña" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "nombre" => "M. Teresa" "apellidos" => "Compte-Jove" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "nombre" => "Cristina" "apellidos" => "Gállego-Gil" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Sección de Nefrología, Hospital de la Santa Creu, Tortosa, Tarragona, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neurotoxicidad por baclofeno en paciente con insuficiencia renal crónica terminal" ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor,</span></p><p class="elsevierStylePara">Baclofen (4-beta-chlorophenyl-gamma-aminobutyric acid) is a muscle relaxant, used as an antispasmodic in diseases such as multiple sclerosis, medullary trauma and hiccups<span class="elsevierStyleSup">1,2</span>.</p><p class="elsevierStylePara">It is mainly excreted through the kidneys (69%-85%) and has a 2 to 6 hr. half life in healthy people. There is a high risk of neurotoxicity in patients with renal failure, especially if administered with <30ml/min glomerular filtration rate, causing episodes of unconsciousness<span class="elsevierStyleSup">3,4</span>.</p><p class="elsevierStylePara">Baclofen intoxication in dialysis patients is rare, with very diverse forms of clinical presentation<span class="elsevierStyleSup">5-9</span>.</p><p class="elsevierStylePara">We present the clinical case of a patient with baclofen-induced encephalopathy, with atypical clinical evolution; symptoms did not improve with haemodialysis and the patient went into complete remission following the drug’s discontinuation.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">CASE DESCRIPTION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">We present a 31-year-old patient with traumatic spinal injury at 20 and a history of repeated urinary infections related to neurogenic bladder (self-catheterisation) and episodes of urinary obstruction. In 2009 he was referred to the nephrology department due to stage 2 chronic kidney disease, with nephrotic-range proteinuria (1.3mg/dl creatinine, 20g/24h proteinuria). The patient refused renal biopsy and in the same year, he stopped attending nephrology consultations.</p><p class="elsevierStylePara">In January 2012 he started experiencing episodes of deteriorating levels of consciousness. Cranial computerised tomography and lumbar puncture were performed, both with normal results. Electroencephalogram showed diffuse slowing. At that time, creatinine was 3.3mg/dl. The clinical profile was suggested as secondary to urinary infection.</p><p class="elsevierStylePara">The same symptoms repeated in April 2012, accompanied by spatial and time disorientation. He presented a new episode in the same month, but this time with behavioural change (infantilism, nervousness, aggressiveness). Cerebral MRI was unremarkable. Following this episode, treatment with clonazepam was started.</p><p class="elsevierStylePara">In May 2012, due to end-stage renal failure analysis results and symptoms, haemodialysis was started using a temporary catheter in the right jugular vein.</p><p class="elsevierStylePara">Approximately once a month, in the first two hours after starting dialysis, the patient experienced episodes of reduced levels of consciousness and, at times, psychomotor agitation.</p><p class="elsevierStylePara">The patient was evaluated in November 2012 by the Neurology and Psychiatry department, with no relevant findings. They diagnosed the condition as secondary to hypoxic metabolic encephalopathy.</p><p class="elsevierStylePara">Despite presenting correct KT and Kt/V, we increased the number of dialysis sessions to 4/week, without clinical improvement.</p><p class="elsevierStylePara">In January 2013, we decided to suspend treatment with baclofen (Lioresal<span class="elsevierStyleSup">®</span>), replacing it with tizanidine and diazepam. After two weeks of tizanidine treatment, the patient stopped the drug because of drowsiness and spasticity was controlled only with diazepam.</p><p class="elsevierStylePara">10 months after the drug’s discontinuation, the patient had not re-experienced neurological symptoms.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Spasticity is a classic symptom in spinal injury patients. Baclofen is widely used in these patients, despite their high risk of neurotoxicity, as a result of having reduced renal function due to neurogenic bladder. We also have to bear in mind that, on assessing serum creatinine levels, we overestimated the renal function due to a decrease in muscular mass<span class="elsevierStyleSup">10</span>.</p><p class="elsevierStylePara">Psychomotor agitation is a rare symptom of baclofen-induced encephalopathy. This encephalopathy usually manifests itself as a reduced level of consciousness. Our patient initially presented this symptom, since the same baclofen dose was used as in a patient with normal renal function. Following deterioration in renal function and the start of haemodialysis, the patient experienced the atypical symptom of psychomotor agitation.</p><p class="elsevierStylePara">In reviewing the literature, we observe that the pharmaco-dynamics of baclofen in dialysis patients is expressed as C = C<span class="elsevierStyleInf">0</span> + e<span class="elsevierStyleSup">Ket</span>, where Ke is dependent on the drug’s renal (Kr) and non-renal (Knr) metabolism. In dialysis patients, renal clearance is restricted to clearance during dialysis; thus Kr = Kd, where Kd = 0.291/h and Knr 0.045/h, therefore Ke = Kd + Knr = 0.336/h. Given the drug’s excretion, baclofen’s half life went from 15.5h in patients with stage 5 chronic renal failure not on dialysis to 2.06h in dialysis patients<span class="elsevierStyleSup">11-13</span>.</p><p class="elsevierStylePara">We suspect that this patient’s clinical symptoms can be attributed to a sudden suppression of baclofen levels in blood. It is worth noting that similar cases have been described in sudden withdrawals of this drug in patients with intrathecal perfusions.<span class="elsevierStyleSup">14,15</span></p><p class="elsevierStylePara">Despite no clear indications about baclofen in pharmacological guides, we do not recommend the use of this drug in dialysis patients.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article.</p>" "pdfFichero" => "P1-E572-S4663-A12320-EN.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Peces R, Navascués RA, Baltar J, Laurés AS, Alvarez-Grande J. 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Pediatr Emerg Care 2008;24(10):691-3. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19240673" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003400000004/v0_201502091609/X2013251414054225/v0_201502091609/en/main.assets" "Apartado" => array:4 [ "identificador" => "35437" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor - Brief Case Reports" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003400000004/v0_201502091609/X2013251414054225/v0_201502091609/en/P1-E572-S4663-A12320-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251414054225?idApp=UINPBA000064" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 2 | 5 |
| 2024 October | 39 | 58 | 97 |
| 2024 September | 57 | 35 | 92 |
| 2024 August | 55 | 102 | 157 |
| 2024 July | 56 | 41 | 97 |
| 2024 June | 93 | 55 | 148 |
| 2024 May | 65 | 39 | 104 |
| 2024 April | 60 | 43 | 103 |
| 2024 March | 33 | 24 | 57 |
| 2024 February | 35 | 35 | 70 |
| 2024 January | 33 | 24 | 57 |
| 2023 December | 43 | 34 | 77 |
| 2023 November | 62 | 48 | 110 |
| 2023 October | 43 | 26 | 69 |
| 2023 September | 46 | 29 | 75 |
| 2023 August | 41 | 25 | 66 |
| 2023 July | 53 | 49 | 102 |
| 2023 June | 70 | 37 | 107 |
| 2023 May | 93 | 38 | 131 |
| 2023 April | 86 | 32 | 118 |
| 2023 March | 88 | 26 | 114 |
| 2023 February | 62 | 27 | 89 |
| 2023 January | 65 | 35 | 100 |
| 2022 December | 39 | 40 | 79 |
| 2022 November | 45 | 40 | 85 |
| 2022 October | 57 | 53 | 110 |
| 2022 September | 40 | 33 | 73 |
| 2022 August | 47 | 52 | 99 |
| 2022 July | 45 | 46 | 91 |
| 2022 June | 43 | 39 | 82 |
| 2022 May | 55 | 32 | 87 |
| 2022 April | 59 | 49 | 108 |
| 2022 March | 56 | 38 | 94 |
| 2022 February | 55 | 46 | 101 |
| 2022 January | 66 | 24 | 90 |
| 2021 December | 54 | 43 | 97 |
| 2021 November | 47 | 29 | 76 |
| 2021 October | 56 | 44 | 100 |
| 2021 September | 45 | 36 | 81 |
| 2021 August | 38 | 45 | 83 |
| 2021 July | 35 | 35 | 70 |
| 2021 June | 35 | 25 | 60 |
| 2021 May | 47 | 33 | 80 |
| 2021 April | 125 | 82 | 207 |
| 2021 March | 82 | 36 | 118 |
| 2021 February | 75 | 38 | 113 |
| 2021 January | 62 | 30 | 92 |
| 2020 December | 55 | 21 | 76 |
| 2020 November | 38 | 13 | 51 |
| 2020 October | 41 | 16 | 57 |
| 2020 September | 49 | 7 | 56 |
| 2020 August | 56 | 14 | 70 |
| 2020 July | 58 | 19 | 77 |
| 2020 June | 44 | 14 | 58 |
| 2020 May | 63 | 10 | 73 |
| 2020 April | 57 | 15 | 72 |
| 2020 March | 44 | 13 | 57 |
| 2020 February | 69 | 19 | 88 |
| 2020 January | 98 | 13 | 111 |
| 2019 December | 98 | 26 | 124 |
| 2019 November | 66 | 26 | 92 |
| 2019 October | 56 | 17 | 73 |
| 2019 September | 104 | 32 | 136 |
| 2019 August | 88 | 19 | 107 |
| 2019 July | 77 | 25 | 102 |
| 2019 June | 76 | 23 | 99 |
| 2019 May | 80 | 22 | 102 |
| 2019 April | 111 | 49 | 160 |
| 2019 March | 68 | 20 | 88 |
| 2019 February | 49 | 22 | 71 |
| 2019 January | 66 | 31 | 97 |
| 2018 December | 94 | 46 | 140 |
| 2018 November | 106 | 19 | 125 |
| 2018 October | 76 | 12 | 88 |
| 2018 September | 91 | 19 | 110 |
| 2018 August | 50 | 18 | 68 |
| 2018 July | 71 | 13 | 84 |
| 2018 June | 60 | 22 | 82 |
| 2018 May | 60 | 21 | 81 |
| 2018 April | 82 | 9 | 91 |
| 2018 March | 80 | 7 | 87 |
| 2018 February | 51 | 7 | 58 |
| 2018 January | 74 | 9 | 83 |
| 2017 December | 68 | 10 | 78 |
| 2017 November | 73 | 12 | 85 |
| 2017 October | 57 | 7 | 64 |
| 2017 September | 57 | 9 | 66 |
| 2017 August | 67 | 16 | 83 |
| 2017 July | 61 | 13 | 74 |
| 2017 June | 55 | 20 | 75 |
| 2017 May | 65 | 13 | 78 |
| 2017 April | 66 | 13 | 79 |
| 2017 March | 38 | 6 | 44 |
| 2017 February | 45 | 12 | 57 |
| 2017 January | 33 | 11 | 44 |
| 2016 December | 77 | 8 | 85 |
| 2016 November | 131 | 8 | 139 |
| 2016 October | 112 | 12 | 124 |
| 2016 September | 166 | 3 | 169 |
| 2016 August | 220 | 4 | 224 |
| 2016 July | 233 | 9 | 242 |
| 2016 June | 166 | 0 | 166 |
| 2016 May | 167 | 0 | 167 |
| 2016 April | 172 | 0 | 172 |
| 2016 March | 113 | 0 | 113 |
| 2016 February | 117 | 0 | 117 |
| 2016 January | 124 | 0 | 124 |
| 2015 December | 126 | 0 | 126 |
| 2015 November | 97 | 0 | 97 |
| 2015 October | 116 | 0 | 116 |
| 2015 September | 102 | 0 | 102 |
| 2015 August | 85 | 0 | 85 |
| 2015 July | 123 | 0 | 123 |
| 2015 June | 46 | 0 | 46 |
| 2015 May | 83 | 0 | 83 |
| 2015 April | 15 | 0 | 15 |
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