Safe intrathecal fluorescein use for identification of cerebrospinal fluid leaks: Case-report and perioperative algorithm description

Rev Esp Anestesiol Reanim. 2017;64(9):533---536

Revista Española de Anestesiología y Reanimación www.elsevier.es/redar

CASE REPORT

Safe intrathecal fluorescein use for identification of cerebrospinal fluid leaks: Case-report and perioperative algorithm description夽 M.Á. Rodríguez-Navarro ∗ , C. Díaz-Alejo, M.L. Padilla-del Rey, A.B. Alcaraz, P. González-Pérez, M. Benítez Departamento de Anestesiología y Reanimación, Hospital General Universitario Morales Meseguer, Murcia, Spain Received 28 November 2016; accepted 6 March 2017 Available online 10 September 2017

KEYWORDS Sodium fluorescein; Fistula; Cerebrospinal fluid; Natural orifice endoscopic surgery

Abstract Intrathecal injection of fluorescein is a method for repairing cerebrospinal fluid fistulas. The most frequent surgical procedure is endonasal endoscopy and the purpose of injecting this dye is to locate the fistula. The anaesthesiologists usually perform the puncture, therefore it is necessary to review this method and to specify some anaesthetic considerations such as correct dosing, safe management protocols and medical---legal aspects. In this case-report we describe the pre, intra and postoperative protocol of action implemented in our department that basically consists of: obtaining a specific consent, prior neurological/ophthalmologic assessment to rule out hypertension and brain damage, use of corticosteroids and previous antihistamines, choosing the correct dose and concentration of intrathecal sodium fluorescein (maximum 1 ml at a concentration of 5% diluted in 9 ml of cerebrospinal fluid) and close intra and postoperative monitoring. © 2017 Sociedad Espa˜ nola de Anestesiolog´ıa, Reanimaci´ on y Terap´ eutica del Dolor. Published by Elsevier Espa˜ na, S.L.U. All rights reserved.

夽 Please cite this article as: Rodríguez-Navarro MÁ, Díaz-Alejo C, Padilla-del Rey ML, Alcaraz AB, González-Pérez P, Benítez M. Uso seguro de fluoresceína intratecal en la localización de las fístulas de líquido cefalorraquídeo: descripción de un caso e implementación de un algoritmo perioperatorio. Rev Esp Anestesiol Reanim. 2017;64:533---536. ∗ Corresponding author. E-mail address: [email protected] (M.Á. Rodríguez-Navarro).

2341-1929/© 2017 Sociedad Espa˜ nola de Anestesiolog´ıa, Reanimaci´ on y Terap´ eutica del Dolor. Published by Elsevier Espa˜ na, S.L.U. All rights reserved.

534

PALABRAS CLAVE Fluoresceína de sodio; Fístula; Líquido cefalorraquídeo; Cirugía endoscópica por orificios naturales

M.Á. Rodríguez-Navarro et al.

Uso seguro de fluoresceína intratecal en la localización de las fístulas de líquido cefalorraquídeo: descripción de un caso e implementación de un algoritmo perioperatorio Resumen La inyección intratecal de fluoresceína es un método que se utiliza en las cirugías de reparación de fístulas de líquido cefalorraquídeo. El procedimiento quirúrgico más frecuente es la endoscopia endonasal y el propósito de la inyección de este colorante es la localización del área de la fístula. La participación en el proceso anestésico-quirúrgico del anestesiólogo (facultativo que habitualmente realiza la punción) hace indispensable la revisión de este método y la puntualización de algunas consideraciones anestésicas, como la correcta dosificación, el manejo de protocolos de administración seguros, aspectos médico-legales y relativos a la seguridad del paciente, que son claves. En este caso describimos el protocolo de actuación pre, intra y postoperatorio implementado en nuestro servicio y que básicamente consiste en: obtención de un consentimiento específico, la valoración neurológica/oftalmológica previa para descartar hipertensión y da˜ no cerebral, el uso de corticoides y antihistamínicos previos, elegir la dosis y concentración correcta de fluoresceína sódica intratecal (máximo de 1 ml a una concentración del 5%, diluida en 9 ml de líquido cefalorraquídeo) y un estrecho seguimiento intra y postoperatorio. © 2017 Sociedad Espa˜ nola de Anestesiolog´ıa, Reanimaci´ on y Terap´ eutica del Dolor. Publicado por Elsevier Espa˜ na, S.L.U. Todos los derechos reservados.

Introduction Nasal cerebrospinal fluid (CSF) fistula repair has come a long way from the surgical technique involving craniotomy and its associated complications. Nowadays, the most widely used surgical procedure is endonasal endoscopy, and the fistula is located by intrathecal injection of fluorescein. The injection is usually administered by an anaesthesiologist, and it is therefore important that all such specialists are familiar with this procedure and are aware of the correct dose of anaesthesia to be administered, safe anaesthesia protocols, and patient safety or legal considerations. All these aspects will be described in the following case study.

Case study We present the case of a 67-year-old patient, 68 kg in weight, scheduled for endonasal endoscopic surgery for CSF rhinorrhoea with suspicion of CSF fistula after mild head injury. Her relevant history included allergy to metamizole and some fruits, no allergy to latex, Crohn’s disease, fibromyalgia, lumbociatalgia, chronic headaches and sleep apnoea syndrome under treatment with a continuous positive airway pressure mask. In order to accurately pinpoint the location of the fistula and repair it, specialists from the Department of Otorhinolaryngology suggested instilling intrathecal fluorescein prior to the surgical procedure. The same specialists ordered a pre-surgical neurological/ophthalmological evaluation and a complete examination of the fundus of the eye. We obtained consent for the surgery, the anaesthesia technique, and obtained specific consent for the off-label use of intrathecal fluorescein. In the operating room, the patient was monitored with continuous electrocardiography, non-invasive blood

pressure and pulse oximetry. She was premedicated with intravenous midazolam (0.05 mg/kg), dexamethasone 0.1 mg/kg and 5 mg dexchlorpheniramine. Then, with the patient in the side-lying position, lateral lumbar puncture in the L3---L4 space was performed using a 25 G needle, and 1 ml of 5% fluorescein (50 mg) diluted in 9 ml of CSF was administered at a rate of approximately 0.1 ml/min (10 min). Immediately after the puncture, the patient was placed prone and in the Trendelenburg position. After monitoring the patient’s vital signs and clinical status for 45 min, general anaesthesia was administered with propofol (2.2 mg/kg) and rocuronium (0.8 mg/kg), and hypnosis was maintained with variable-dose propofol to achieve a bispectral index of between 45 and 50. Analgesia was administered with fentanyl 200 mg, dexketoprofen 50 mg and morphine chloride 5 mg. In view of the small size of the suspected fistula, endonasal endoscopy was chosen instead of other more aggressive surgeries usually reserved for larger defects. Nasal endoscopy revealed a puncture with drainage of fluorescein-stained CSF (Fig. 1), which was then covered with fascia lata and mucoperiosteum from the turbinate. The surgery lasted 100 min and was uneventful. The patient was awakened and extubated in the operating room before transfer to the post anaesthesia care unit for postoperative monitoring. She reported transient occipital headache at 2 postoperative hours, which responded to intravenous treatment with paracetamol 1 g and tramadol 50 mg. At 24 h, the nasal packing was removed and the patient was discharged home after 2 days, with no complications.

Discussion The diagnosis of CSF fistula can be established by signs of continuous or intermittent rhinorrhoea. The cause is usually puncture of the arachnoid and dura mater, often associated

Safe intrathecal fluorescein use: Algorithm

Figure 1 Endoscopic view of the leak point and drainage of cerebrospinal fluid from the fistula.

with a bone defect. Communication between the dura mater and the upper airway can lead to serious infections (meningitis, encephalitis, etc.). The aetiology can vary, although CSF fistula is most frequently spontaneous, and is usually located in the cribous lamina.1,2 Fistula repair has evolved since the first reported case in 1926,3 when the procedure of choice was craniotomy with its concomitant high morbidity. More recently, endoscopic methods have become the gold standard, achieving a success rate of between 60% and 100%. Fluorescein stain is widely used, mainly in ophthalmology, and is therefore readily available for any procedures in this field. In endoscopic CSF fistula repair, it is mainly used to stain the CSF released through the fistula, enabling it to be easily identified during a physical or endoscopic examination. Thus, the puncture can be repaired once the CSF leak site causing the rhinolokorrhea has been located.4,5 To be suitable for surgical use, fluorescein must be prepared by the Pharmacy Service to ensure it is free from germs

535 and toxic substances. The ophthalmologic solution should not be used, and a preparation with a concentration suitable for intrathecal administration should be chosen instead (although this is an off-label use of the drug, and therefore specific informed consent must be obtained after explaining the possible adverse effects).1 The technique is not risk-free.5,6 Important side effects have been described, the most frequent being headache, followed by nausea, vomiting, high body temperature, dizziness and neck pain. Other less frequent, but serious, side effects include epileptic seizures, myelopathy and neurological damage. Intrathecal injection of fluorescein in patients with a history of hydrocephalus, spinal stenosis, neurological damage with cerebral oedema or epilepsy should be contraindicated or performed with the utmost care. Jacob et al.6 reported case of a patient who presented status epilepticus after administration of fluorescein. In that case, the dye was administered using an intrathecal catheter with the patient under general anaesthesia, and seizures persisted for 24 h. Sevoflurane and benzodiazepines were used intraoperatively, but the authors reported that residual tremor and small spasms (attributed to possible direct neurological toxicity) persisted for 3 days after surgery. The aetiology of fluorescein-induced side effects is unclear, and the solvent using in the solution, a direct toxic effect, meningeal irritation, and neuroactivation of the central nervous system have all been implicated. The differential diagnosis includes aseptic, or even infectious, meningitis, since the onset of symptoms may be immediate or delayed up to 12 h. As already noted, side effects are usually mild and resolve without sequelae in 7---10 days. Some authors have suggest avoiding as far as possible the use of muscle relaxants during surgery, since they may mask or prevent the early diagnosis of tremors and epilepsy, thus delaying treatment.6 With regard to anaesthesia, the complications associated with lumbar puncture include some symptoms or syndromes that are also found in ‘‘post-fluorescein injection syndrome’’, so it is important to establish an early differential diagnosis between both entities, for example, between

Table 1 Protocolo de actuación perioperatoria del manejo de la fluoresceína intratecal en la cirugía por endoscopia endonasal de fístulas de líquido cefalorraquídeo. Protocol for intrathecal fluorescein injection for the Department of Anaesthesiology 1. All patients with suspected cerebrospinal fluid fistula should be referred to the ophthalmologist/neurologist to rule out endocranial hypertension, in addition to the conventional pre-anaesthesia workup. 2. The intrathecal injection of 5% fluorescein is not included in the package insert: therefore, it is important to explain the procedure and risks to the patients and request their SPECIFIC INFORMED CONSENT, in addition to obtaining consent for regional subarachnoid anaesthesia and general anaesthesia 3. Patients should be premedicated with dexamethasone 0.1 mg/kg and dexchlorpheniramine 5 mg. 4. Confirm that the dye used is suitable for intrathecal injection (do not use the ophthalmology solution) a. Prepare the appropriate volume and concentration (0.1 ml/kg) with a maximum of 1 ml of 5% fluorescein (dilute to 10 ml with CSF) b. Observe strict asepsis throughout the extraction, preparation and injection of the drug c. To avoid complications, perform a very slow (ideally 10 min) intrathecal injection at the level of L3---L4 d. Place the patient in the Trendelenburg position e. Closely monitor and observe the patient at all times 5. After 45 min, proceed with general anaesthesia 6. Perform a full neurological examination on waking up and before discharge home.

536 suspicion of epidural haematoma or secondary paralysis due to meningeal irritation, meningitis or CSF hypotension syndrome.7 Intrathecal instillation of the dye in the awake patient makes it is easier to identify symptoms and correctly determine their origin. On the basis of the above, the prevention of adverse effects associated with intrathecal fluorescein injection appears to depend on several factors that can be controlled by creating a protocol and procedure algorithm (Table 1): pre-surgical neurological/ophthalmological assessment, pre-surgical use of corticosteroids and antihistamines, and administration of the correct dose and concentration of the drug at the correct rate.1,8---10 After a review of the literature, we decided that to avoid or reduce the incidence of morbidity and mortality, up to 1 ml of 5% intrathecal sodium fluorescein (diluted up to 10 ml with 9 ml of CSF obtained at the time of the puncture) should be administered at a dose of 0.1 ml/kg. This was the dose used in the case presented here most studies propose doses of less than 10 mg (other authors propose 0.1 ml of 10% fluorescein diluted in 9.9 ml CSF).10

Conclusions The case presented here, together with further experience acquired in the technique, shows that injection of intrathecal fluorescein is not without its risks, and care must be taken in preparing the solution and using the appropriate concentration of fluorescein in CSF. Anaesthesiologist must be aware of the medical algorithm and the possible complications associated with the technique.

Ethical disclosures Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study. Confidentiality of data. The authors declare that they have followed the protocols implemented in their place of work regarding the use of patient data in publications. Right to privacy and informed consent. The authors declare that no patient data appears in this article.

M.Á. Rodríguez-Navarro et al.

Conflict of interests The authors declare they have no conflicts of interest.

Acknowledgments We thank Dr. José Luis Sánchez-Ortega for his participation in the implementation of the protocol and his interest in keeping the department up to date in the most current and relevant publications in the field of anaesthesiology.

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