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array:23 [ "pii" => "S0034935612000540" "issn" => "00349356" "doi" => "10.1016/j.redar.2012.02.021" "estado" => "S300" "fechaPublicacion" => "2012-02-01" "aid" => "35" "copyright" => "Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor" "copyrightAnyo" => "2012" "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Rev Esp Anestesiol Reanim. 2012;59:102-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1894 "formatos" => array:3 [ "EPUB" => 5 "HTML" => 1584 "PDF" => 305 ] ] "itemSiguiente" => array:18 [ "pii" => "S0034935612000552" "issn" => "00349356" "doi" => "10.1016/j.redar.2012.02.022" "estado" => "S300" "fechaPublicacion" => "2012-02-01" "aid" => "36" "copyright" => "Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "cita" => "Rev Esp Anestesiol Reanim. 2012;59:107-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1477 "formatos" => array:3 [ "EPUB" => 6 "HTML" => 1272 "PDF" => 199 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">CARTA AL DIRECTOR</span>" "titulo" => "Anestesia general en un pacientecon síndrome de Clarkson" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "107" "paginaFinal" => "108" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "General anaesthesia in a patient with Clarkson syndrome" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.L. Gómez Martínez, S. Pico Brezmes, M.J. Álvarez Arguello, A. Alonso Margüello" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.L." "apellidos" => "Gómez Martínez" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Pico Brezmes" ] 2 => array:2 [ "nombre" => "M.J." "apellidos" => "Álvarez Arguello" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Alonso Margüello" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935612000552?idApp=UINPBA00004N" "url" => "/00349356/0000005900000002/v1_201305031641/S0034935612000552/v1_201305031641/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0034935612000539" "issn" => "00349356" "doi" => "10.1016/j.redar.2012.02.020" "estado" => "S300" "fechaPublicacion" => "2012-02-01" "aid" => "34" "copyright" => "Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor" "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Rev Esp Anestesiol Reanim. 2012;59:98-101" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4419 "formatos" => array:3 [ "EPUB" => 5 "HTML" => 4112 "PDF" => 302 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">CASO CLÍNICO</span>" "titulo" => "Condrodisplasia punctata de Conradi-Hünermann: implicaciones anestésicas" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "98" "paginaFinal" => "101" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Conradi-Hünermann Chondrodysplasia punctata: anaesthetic implications" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Ventosa Fernández, E. Freire Vila, A. de la Iglesia López, S. Castro Aguiar" "autores" => array:4 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Ventosa Fernández" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Freire Vila" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "de la Iglesia López" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Castro Aguiar" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935612000539?idApp=UINPBA00004N" "url" => "/00349356/0000005900000002/v1_201305031641/S0034935612000539/v1_201305031641/es/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">CASO CLÍNICO</span>" "titulo" => "Anesthetic management of a patient diagnosed with CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy)" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "102" "paginaFinal" => "106" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "C.L. Errando, L. Navarro, M. Vila, M.A. Pallardó" "autores" => array:4 [ 0 => array:4 [ "nombre" => "C.L." "apellidos" => "Errando" "email" => array:1 [ 0 => "errando013@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Navarro" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Vila" ] 3 => array:2 [ "nombre" => "M.A." "apellidos" => "Pallardó" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Anestesiología, Reanimación y Tratamiento del Dolor, Consorcio Hospital General Universitario de Valencia, Valencia, España" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento anestésico de un paciente diagnosticado de CADASIL (arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía)" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0005">Introduction</span><p id="p0025" class="elsevierStylePara elsevierViewall">CADASIL is an inherited autosomal dominant progressive disorder that affects small arterial vessels. The disease is classified as a non-arteriosclerotic arteriopathy, and results in multiple cerebral subcortical infarcts with migraine, strokes, and white matter injuries with resultant dementia, cognitive impairment and other symptoms<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1-5</span></a>.</p><p id="p0030" class="elsevierStylePara elsevierViewall">There is evidence that CADASIL is the consequence in most cases of a mutation in the <span class="elsevierStyleItalic">NOTCH3</span> gene located in the 19 chromosome (gene map locus 19p.13.2-p13.1 )<a class="elsevierStyleCrossRefs" href="#bb0015"><span class="elsevierStyleSup">3,5</span></a>. Almost all patients described are heterozygotic, meaning that homozigotic forms should be letal<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,5</span></a>.</p><p id="p0035" class="elsevierStylePara elsevierViewall">There are around 500 families affected worldwide<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>, mainly European, three of them in Spain<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a>.</p><p id="p0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">NOTCH3</span> gene codify for the Notch3 protein that is a membrane receptor that intervenes in cell differentiation during the embryonic development. It is involved in vascular vessel development and provides specialization to a vascular cell to be arterial, venous or capillary<a class="elsevierStyleCrossRefs" href="#bb0010"><span class="elsevierStyleSup">2,5</span></a>. The resulting Notch3 protein has a default in a cystein residual, changing its conformational aspect and inhibiting its receptor function<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,5</span></a>. In addition these proteins cannot be metabolized and accumulated in the membrane of the smooth muscle cells of the arterial wall<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,5</span></a>.</p><p id="p0045" class="elsevierStylePara elsevierViewall">Although it is a generalized arteriopathy involving small and medium sized arteries, it affects preferably the central nervous system<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,5</span></a>. Microscopy studies find a specific arteriopaty characterised by lumen stenosis due to the presence of non-amyloid granular osmiophilic material (GOM, nonatherosclerotic, nonamyloid arteriopathy), whose finding could be pathognomonic of the disease<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>, but this is controversial<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a>.</p><p id="p0050" class="elsevierStylePara elsevierViewall">The clinical features are derived from arterial stenosis at the vascular cerebral territory.</p><p id="p0055" class="elsevierStylePara elsevierViewall">CADASIL is considered a progressive disease and a clinical classification has been developed which correlates with MRI findings<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,5</span></a>. The disease is most likely to appear in individuals of around 45 years of age or younger, and consists of migraine attacks (MRI limited white matter alterations), subcortical ischemic strokes, neuropsychiatric symptoms (MRI coalescent white matter lesions and basal ganglia affected), and dementia with cognitive impairment (MRI diffuse leukoencephalopathy and basal ganglia with well defined injuries). As a general rule the patients can suffer from repeated ischemic strokes (84-87%), subcortical dementia with or without pseudobulbar palsy (31-60%), migraine with or without aura (22-38%), neuropsychyatric symptoms (20%), mood disturbances (20%), apathy (about 40%), epilepsy, hypoacusia, and learning retardation<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,5</span></a>. It should be pointed out that this disease is not a risk factor for ischemic cardiovascular events<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>. However, a recent study<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> suggest that cardiovascular risk factors, such as smoking and hypertension, might modulate the severity and development of clinical symptoms of CADASIL in the siblings with phenotype positive for the disease.</p><p id="p0060" class="elsevierStylePara elsevierViewall">The natural history is to a terminal stage within a mean of 25 years<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>, being the most frequent cause of death an ischemic stroke followed by bronchopneumonic complications<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>.</p><p id="p0065" class="elsevierStylePara elsevierViewall">Definitive diagnosis is the demonstration of the <span class="elsevierStyleItalic">NOTCH3</span> gene mutation or the finding of GOM deposition in the biopsy of the skin or small peripheral nerve arteries<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,2,5</span></a>.</p><p id="p0070" class="elsevierStylePara elsevierViewall">In this contribution we describe the anesthetic management of a patient diagnosed of CADASIL who was scheduled for prosthetic knee surgery.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Clinical case</span><p id="p0075" class="elsevierStylePara elsevierViewall">A male 59-years-old patient, 90<span class="elsevierStyleHsp" style=""></span>kg, 171<span class="elsevierStyleHsp" style=""></span>cm, BMI 30, American Society of Anesthesiologists physical status III, was scheduled for left knee arthrodesis because of several postoperative infectious complications in the prosthetic knee.</p><p id="p0080" class="elsevierStylePara elsevierViewall">The patient was previously suspected to sustain Multiple Sclerosis but one year before was diagnosed of CADASIL. His past medical history included a familial history of neurologic disease. His father was diagnosed with multiple sclerosis and died of pneumonia at the age of 50. Furthermore one brother was genetically diagnosed of CADASIL, whereas other suffered seizures, and a sister had presented three vascular ischemic cerebral accidents. Several relatives in the father's lineage were known to sustain neuropsychiatric disorders.</p><p id="p0085" class="elsevierStylePara elsevierViewall">The patient suffered an ischemic cerebral vascular accident at the age of 39. At the age of 42 he was hospitalized because of severe migraine. Afterwards he presented two ischemic stroke events. After clinical suspicion, genetic analysis confirm the diagnosis of CADASIL because of the finding of a mutation c.213<span class="elsevierStyleHsp" style=""></span>G</p><p id="p0090" class="elsevierStylePara elsevierViewall">The patient was treated with antiplatelet drugs. Genetic counseling was recommended to his offsprings.</p><p id="p0095" class="elsevierStylePara elsevierViewall">He has been operated on for septoplasty, cholecystectomy, and apendicectomy, and orthopedic procedures included insertion of a right knee prosthesis, right ankle prosthesis and left knee prosthetic surgery. Five reoperations were needed in the latter case due to infection of the prosthetic material. Most surgical interventions were performed under general anesthesia, and a femoral nerve block was associated in the first left knee replacement surgery.</p><p id="p0100" class="elsevierStylePara elsevierViewall">The patient was progressively dependent for daily life, and showed dementia, apathy, mood changes and urinary incontinence. He received treatment with tamsulosine (alfa-adrenergic blocker for prostatic adenoma), soliphenacine (a urine tract spasmolytic), vitamin A, donepezil (an acetylcholine inhibitor for Alzheimer disease) and clopidogrel.</p><p id="p0105" class="elsevierStylePara elsevierViewall">Preanesthetic tests including blood analysis and coagulation profile (prothrombin time, partial thromboplastin time, INR, platelet count and bleeding time) were in normal range. Clopidogrel was withdrawn 7 days before surgery. Enoxaparin 40<span class="elsevierStyleHsp" style=""></span>mg/day was started at that time.</p><p id="p0110" class="elsevierStylePara elsevierViewall">A combined spinal-epidural anesthetic technique was chosen to perform surgery. Once in the operating room, the patient was noninvasively monitored (noninvasive arterial pressure, ECG, SpO<span class="elsevierStyleInf">2</span> and EtCO<span class="elsevierStyleInf">2</span> through nasal prongs). Oxygen 2<span class="elsevierStyleHsp" style=""></span>L/min was administered. An 18<span class="elsevierStyleHsp" style=""></span>G iv line was inserted and 1000<span class="elsevierStyleHsp" style=""></span>mL Ringer-lactate were perfused. Premedication consists of iv midazolam 3<span class="elsevierStyleHsp" style=""></span>mg. The anesthetic puncture was performed with the patient in the left lateral decubitus at the L3-L4 lumbar interspace. Hyperbaric bupivacaine 7.5<span class="elsevierStyleHsp" style=""></span>mg were injected and an epidural catheter inserted. The patient was led in this position for 10<span class="elsevierStyleHsp" style=""></span>min. A unilateral T8 sensory block level evaluated by pinprick was reached. Midazolam 1<span class="elsevierStyleHsp" style=""></span>mg iv boluses were used for sedation throughout the procedure (total dose 5<span class="elsevierStyleHsp" style=""></span>mg).</p><p id="p0115" class="elsevierStylePara elsevierViewall">Two episodes of slight decrease of arterial pressure (lowest mean arterial pressure 55<span class="elsevierStyleHsp" style=""></span>mmHg) occurred during surgery, which were treated with iv ephedrine 5<span class="elsevierStyleHsp" style=""></span>mg.</p><p id="p0120" class="elsevierStylePara elsevierViewall">After the two-hour-long operation, the patient remained 4 hours in the postanesthesia care unit without any hemodynamic disturbances, nausea or vomiting. Intravenous paracetamol 1<span class="elsevierStyleHsp" style=""></span>g and dexketoprofen trometamol 50<span class="elsevierStyleHsp" style=""></span>mg were administered. The epidural catheter was tested with lidocaine 2% 60<span class="elsevierStyleHsp" style=""></span>mg. After 20<span class="elsevierStyleHsp" style=""></span>min an additional 5<span class="elsevierStyleHsp" style=""></span>ml bolus of 2% lidocaine was administered and an infusion of levobupivacaine 0.125% with fentanyl 2<span class="elsevierStyleHsp" style=""></span>μg/mL in an elastomeric pump was started at a rate of 5<span class="elsevierStyleHsp" style=""></span>mL/h (VAS 2/10). Six hours later, the rate was increased to 7<span class="elsevierStyleHsp" style=""></span>mL/h because of insufficient analgesia (VAS 4/10). The catheter was accidentally withdrawn after 24<span class="elsevierStyleHsp" style=""></span>h, and intravenous analgesia was maintained. The patient was discharged home at 5th postoperative day. Clopidogrel was reintroduced 48<span class="elsevierStyleHsp" style=""></span>h after surgery and LMWH were maintained for one week. No other incidences were reported until evaluation at the 30th postoperative day.</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Discussion</span><p id="p0125" class="elsevierStylePara elsevierViewall">We describe the uneventful anesthetic management of a patient with CADASIL.</p><p id="p0130" class="elsevierStylePara elsevierViewall">There is insuficient available information about the anesthetic management of patients with this disease. Maintenance of arterial pressure-cerebral perfusion pressure could be important in order to achieve adequate cerebral perfusion, as the cerebral arteries are mainly affected, and some studies indicate that the neuronal injury is secondary to chronic reduction of cerebral blood flow<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,5</span></a>. These concepts are indirectly supported from studies in patients with occlusive cerebrovascular diseases<a class="elsevierStyleCrossRefs" href="#bb0035"><span class="elsevierStyleSup">7,8</span></a>, and with Moyamoya disease, a rare progressive occlusive vascular disease that manifests as vascular ischemia<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a>. Moreover, it should be taken into account that post-stroke nervous system physiologic changes (impaired cerebral autoregulation, increased permeability of the blood-brain-barrier, and loss of CO<span class="elsevierStyleInf">2</span> responsiveness) can persist for several weeks<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a>.</p><p id="p0135" class="elsevierStylePara elsevierViewall">In fact there is no formal contraindication to use regional anesthetic techniques including the neuraxial ones, as in the case of patients with occlusive strokes<a class="elsevierStyleCrossRefs" href="#bb0035"><span class="elsevierStyleSup">7,9</span></a>. In carotid surgery for acquired aterosclerotic carotid artery stenosis, local and regional anesthesia had their own advantages and disadvantages<a class="elsevierStyleCrossRefs" href="#bb0050"><span class="elsevierStyleSup">10,11</span></a>, but general anesthesia frequently induces marked hypotensive responses<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a>.</p><p id="p0140" class="elsevierStylePara elsevierViewall">In our patient only the treatment with clopidogrel could prevent the use of neuraxial techniques<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a>, but this drug was withdrawn seven days before surgery as recommended.</p><p id="p0145" class="elsevierStylePara elsevierViewall">CADASIL is a genetically determined disease that can be classified among the dementias of vascular origin. It is the most common cause of inherited stroke and vascular cognitive impairment in adults<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>, but the genotypephenotype correlations are not uniform among patients<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a>. The differential diagnosis and recommended diagnostic procedures had been previously extensively reported<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,2</span></a>. To date, are two types of this disease have been described: the dominant autosomal form (CADASIL)<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a>, and the recessive autosomal form (CARASIL)<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a>. The diagnostic criteria are depicted in table <a class="elsevierStyleCrossRef" href="#t0005">1</a>. The clinical and MRI features are significantly different from <span class="elsevierStyleItalic">NOTCH3</span> negative forms<a class="elsevierStyleCrossRefs" href="#bb0025"><span class="elsevierStyleSup">5,14,15</span></a>.</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0150" class="elsevierStylePara elsevierViewall">There is no specific treatment for this disease<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,14</span></a>. Drugs acting in the microcirculation as pentoxifilin are recommended, as are antiplatelet drugs. However the anticoagulants can be sometimes contraindicated because some patients develop cerebral hemorrhage in advanced forms of the disease<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1,5</span></a>, and in cases where hypertension coexists<a class="elsevierStyleCrossRefs" href="#bb0025"><span class="elsevierStyleSup">5,6</span></a>. Acetazolamide is recomended mainly for migraine attacks<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>. Although there is no relation with increased cardiovascular risk in patients with CADASIL<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>, the disease advance is more rapid if cardiovascular risk factors such hypertension or smoke habit appear<a class="elsevierStyleCrossRefs" href="#bb0025"><span class="elsevierStyleSup">5,6</span></a>.</p><p id="p0155" class="elsevierStylePara elsevierViewall">In a PubMed search we have found only one case related to the anesthetic management of CADASIL<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>. It should be highlighted that, from a pathophysiologic point of view, the perioperative management should avoid cerebral ischemic events, and this is obtained by means of adequate vascular cerebral perfusion including maintenance of systemic arterial pressure between the limits of cerebral autoregulation, and prevention of hypovolemia by iv fluid infusion<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>. There are no studies related to the vasopressor drugs of choice, but, in theory, vasopressors of direct mechanism of action might be preferred<a class="elsevierStyleCrossRefs" href="#bb0025"><span class="elsevierStyleSup">5,15</span></a>. For the patient discussed here, we chose ephedrine, an indirect sympathomimetic agent that showed adequate hemodynamic effect without adverse responses in this case.</p><p id="p0160" class="elsevierStylePara elsevierViewall">In the case general anesthesia was used, normocapnia should be maintained because vascular cerebral reactivity to both hyper and hypocapnia seemed to be obtunded in these patients<a class="elsevierStyleCrossRefs" href="#bb0035"><span class="elsevierStyleSup">7,8,15</span></a>. We observe EtCO<span class="elsevierStyleInf">2</span> in normal range throughout the operation.</p><p id="p0165" class="elsevierStylePara elsevierViewall">If a hypertensive event is detected, vasodilators such as nimodipine are best indicated<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>.</p><p id="p0170" class="elsevierStylePara elsevierViewall">A different approach should be taken in the case of chronic hypertension, since chronic hypoperfusion is a putative risk of anti-hypertensive drugs<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>. Moreover statins are used if hypercholesterolemia exists<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>.</p><p id="p0175" class="elsevierStylePara elsevierViewall">In order to prevent obstruction of the cerebral venous drainage, it is recommended<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> to maintain the head elevated 30°.</p><p id="p0180" class="elsevierStylePara elsevierViewall">Regarding direct neural toxicity of local anesthetic drugs, there is no contraindication of loco-regional anesthesia because no clinical peripheral nerve involvement has been described<a class="elsevierStyleCrossRefs" href="#bb0070"><span class="elsevierStyleSup">14,15</span></a>. Neuraxial techniques can be used as well, but it should be considered that arterial pressure should be maintained within normal limits<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>. It could be discussed whether a continuous peripheral nerve block (i.e. femoral nerve block) could have been preferable to a neuraxial block for postoperative analgesia<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> both for efectiveness and lower incidence of adverse effects. In addition, the mental status of this patient could have limited the use of a PCA device or VAS evaluation, but it has been demonstrated that postoperative delirium does not affect the correct pain evaluation or PCA use<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a>.</p><p id="p0185" class="elsevierStylePara elsevierViewall">These patients are usually under antiplatelet drug therapy, so, if an urgent surgery is indicated, a balanced risk-benefit decision should be taken. We chose a neuraxial technique because antiplatelet drugs were withdrawn for more than seven days<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a>. However in this type of patients, antiplatelet drugs should be replaced for other drug acting on the coagulation cascade in order to avoid ischemic events. Moreover, they should be considered high risk patients for deep vein thrombosis and thromboembolic disease<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a>.</p><p id="p0190" class="elsevierStylePara elsevierViewall">For postoperative analgesia nonsteroidal antiinflammatory drugs and paracetamol can be used<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>. Opioids can be indicated but respiratory depression leading to hypercapnia should be taken into account. Intravenous tramadol 1<span class="elsevierStyleHsp" style=""></span>mg/kg has been used because it has no effect in cranial pressure neither in cerebral perfusion<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>.</p><p id="p0195" class="elsevierStylePara elsevierViewall">In the case described in the anesthetic literature of CADASIL general anesthesia was indicated for an urgent laparotomy because Falopian tube torsion. In this case anesthetic maintenance was with halogenated drugs, and surgery and recovery were both uneventful<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>.</p><p id="p0200" class="elsevierStylePara elsevierViewall">In conclusion, we describe the anesthetic management of a patient with CADASIL whose knee prosthetic surgery was performed under combined spinal-epidural anesthesia. We outline the need of maintain adequate cerebral perfusion in patients with this type of hereditary arteriopathy.</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Conflicts of interests</span><p id="p0205" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "xres114052" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec101370" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres114051" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec101369" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "s0010" "titulo" => "Clinical case" ] 6 => array:2 [ "identificador" => "s0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "s0020" "titulo" => "Conflicts of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-05-26" "fechaAceptado" => "2012-02-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec101370" "palabras" => array:5 [ 0 => "CADASIL" 1 => "Rare diseases" 2 => "Regional anesthesia" 3 => "Combined spinal epidural anesthesia" 4 => "Neurologic diseases" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec101369" "palabras" => array:5 [ 0 => "CADASIL" 1 => "Enfermedades poco frecuentes" 2 => "Anestesia regional" 3 => "Anestesia combinada epidural-subaracnoidea" 4 => "Enfermedades neurológicas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leu–koencephalopathy) is an infrequent inherited disease that could have anesthetic implica–tions. However these have rarely been reported. We present a male patient previously diagnosed with CADASIL, who had suffered an ischemic vascular cerebral accident with a MRI compatible with leukoencephalopathy, and who was dependent for daily activities, and sustained dementia, mood alterations, apathy, and urine incontinence. He had famil–ial antecedents of psychiatric symptoms and ischemic stroke events in several relatives including his father, two brothers and one sister. He was scheduled for arthrodesis of the left knee because of multiple infectious complications of prosthetic knee surgery. He was under clopidogrel treatment which was withdrawn seven days before surgery. The pro–cedure was performed under combined spinal-epidural anesthesia, intraoperative seda–tion with midazolam, and postoperative multimodal analgesia including epidural patient controlled analgesia. The perioperative management was uneventful and we outline the adequacy of managing these patients under regional anesthesia and analgesia, as these permit to maintain hemodynamic stability leading to adequate cerebral perfusion, key to avoid an increase in the effects of the chronic arteriopathy patients with CADASIL sustain</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">CADASIL (arteriopatía cerebral autosómica dominante, con infartos subcorticales y leu–coencefalopatía) es una enfermedad hereditaria poco frecuente que puede tener impli–caciones anestesiológicas, escasamente comunicadas. Presentamos el caso de un varón, previamente diagnosticado de CADASIL, que había sufrido un accidente cerebrovascular isquémico, con resonancia magnética compatible con leucoencefalopatía, y estaba muy limitado para las actividades diarias, con demencia, alteraciones del comportamiento, apatía e incontinencia urinaria. Entre sus antecedentes familiares, había varios parientes con síntomas psiquiátricos y accidentes cerebrovasculares, como su padre, dos hermanos y una hermana. Programado para artrodesis de la rodilla izquierda por complicaciones infecciosas tras cirugía de prótesis de rodilla, estaba tomando clopidogrel, que había sus–pendido 7días antes. Se empleó anestesia combinada epidural-subaracnoidea y sedación intraoperatoria con midazolam, así como analgesia multimodal en el postoperatorio que incluyó analgesia epidural. No hubo incidencias notables. La anestesia y la analgesia epi–durales permitieron mantener la estabilidad hemodinámica para una perfusión cerebral adecuada, clave para no empeorar los efectos de la arteriopatía crónica en la CADASIL.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Adapted and modified from Navarro et al<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CADASIL probable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Symptoms starting under the age of 50Two or more of the following clinical events:<ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">•</span><p id="p0005" class="elsevierStylePara elsevierViewall">Stroke-like episodes with permanent neurologic sequelae</p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">•</span><p id="p0010" class="elsevierStylePara elsevierViewall">Migraine</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">•</span><p id="p0015" class="elsevierStylePara elsevierViewall">Major affective disorder</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">•</span><p id="p0020" class="elsevierStylePara elsevierViewall">Subcortical dementia</p></li></ul>Absence of cardiovascular risk factorsAutosomal dominant inheritanceMRI with white matter alterations without subcortical infarcts \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CADASIL possible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disease delayed ><span class="elsevierStyleHsp" style=""></span>50 years oldStroke-like episodes without sequelaeMinor affective disorderGlobal dementiaMinor cardiovascular risk factorsUnknown or incomplete inheritanceMRI with atypic white matter alterations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CADASIL definitive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">NOTCH 3</span> gene mutation demonstrationPathologic demonstration of small vessels artheriopathy with GOM deposition \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exclusion criteria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age of starting ><span class="elsevierStyleHsp" style=""></span>70 years oldSevere arterial hypertension or hypertensive disease complicated with cardiac or systemic alterationsAbsence of hereditary transmissionMRI normal at ><span class="elsevierStyleHsp" style=""></span>35 years old \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab202002.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Diagnostic criteria of CADASIL</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." 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Bousser" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "CADASIL. Lancet Neurol" "fecha" => "2009" "volumen" => "8" "paginaInicial" => "643" "paginaFinal" => "653" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bb0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P. Adib-Samii" 1 => "G. Brice" 2 => "R.J. Martin" 3 => "H.S. Markus" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Study in 200 consecutively recruited individuals. Stroke" "fecha" => "2010" "volumen" => "41" "paginaInicial" => "630" "paginaFinal" => "634" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bb0035" "etiqueta" => "7." 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Reg Anesth Pain Med" "fecha" => "2010" "volumen" => "35" "paginaInicial" => "64" "paginaFinal" => "101" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20052816" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bb0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CARASIL [updated Oct 4, 2009; cited March 3, 2010]. Available from: <a class="elsevierStyleInterRef" href="http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi%3Fcmd=entry%26id=600142">http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?cmd=entry&id=600142</a>." ] ] ] 13 => array:3 [ "identificador" => "bb0070" "etiqueta" => "14." 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Tsai" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/ALN.0b013e3181acf7e6" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology" "fecha" => "2009" "volumen" => "111" "paginaInicial" => "625" "paginaFinal" => "631" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19672166" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00349356/0000005900000002/v1_201305031641/S0034935612000540/v1_201305031641/en/main.assets" "Apartado" => array:4 [ "identificador" => "7575" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Casos clínicos" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/00349356/0000005900000002/v1_201305031641/S0034935612000540/v1_201305031641/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935612000540?idApp=UINPBA00004N" ]
