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External ventricular drain

An external ventricular drain (EVD), also known as an external ventricular catheter, is a temporary neurosurgical device consisting of a small tube inserted into the brain's ventricles to drain excess cerebrospinal fluid (CSF), continuously monitor intracranial pressure (ICP), and for cerebrospinal fluid (CSF) sampling and analysis.^[1]^[2] It serves as a life-saving intervention in cases of acute hydrocephalus or elevated ICP, conditions often arising from subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), intraventricular hemorrhage (IVH), infections, brain tumors, or shunt malfunctions.^[2]^[3] EVD insertion is typically performed emergently by a neurosurgeon, often at the bedside in the intensive care unit or operating room, using a freehand technique at Kocher's point on the frontal skull (approximately 12 cm from the nasion and 3 cm lateral to the midline) to access the lateral ventricle.^[2]^[3] The procedure involves creating a burr hole in the skull, advancing a polyurethane catheter (usually no more than 7 cm deep toward the foramen of Monro), tunneling it subcutaneously, and connecting it to an external drainage system with a pressure transducer leveled to the foramen of Monro for accurate ICP measurement.^[1]^[3] Management strategies vary by underlying condition: continuous drainage (e.g., 10 mL/hour) is preferred in SAH and TBI to minimize complications like catheter clogging, while intermittent drainage may be used cautiously; CSF output is monitored (typically 100–300 mL/day), and the device is weaned gradually once ICP stabilizes to reduce dependency on permanent shunts.^[2] Despite its efficacy, EVD placement carries risks, including infection (0–27% incidence, rising with duration and CSF sampling), hemorrhage along the catheter tract (up to 12%), mechanical obstruction by blood clots or tissue, misplacement, and overdrainage leading to subdural hematomas.^[1]^[2]^[3] Operating room insertion and strict sterile protocols, such as antibiotic-impregnated catheters, help mitigate infection rates (e.g., 7.7% in OR vs. 13% in emergency settings).^[2] The device is removed once CSF dynamics normalize, often after several days to weeks, with complications potentially prolonging hospital stays and impacting prognosis.^[1]^[3]

Overview

Definition and Purpose

An external ventricular drain (EVD) is a temporary neurosurgical device designed to manage intracranial conditions by facilitating the drainage of cerebrospinal fluid (CSF) from the brain's ventricles. It consists of a thin, flexible catheter inserted into one of the brain's ventricles, typically the lateral ventricle, which is connected via tubing to an external collection system, such as a drainage bag or chamber. This setup often incorporates an intracranial pressure (ICP) transducer, zeroed to the level of the foramen of Monro, to enable continuous monitoring of ICP alongside fluid diversion.^[1]^[3] The physiological purpose of an EVD is to reduce elevated ICP, which can exceed 20 mmHg in critical scenarios, by draining excess CSF or blood, thereby mitigating the risk of brain herniation and supporting cerebral perfusion. Additionally, it permits diagnostic CSF sampling for analysis and therapeutic instillation of medications, such as tissue plasminogen activator, directly into the ventricular space. This multifunctional role makes the EVD essential in acute settings, including the management of hydrocephalus.^[1]^[3] External ventricular drainage was first described in 1744 by Claude-Nicolas Le Cat as a device for repeated drainage in the treatment of congenital hydrocephalus, with continuous external drainage developing in the early 20th century building on earlier pioneering efforts in ventricular access from the 18th and 19th centuries.^[4]^[2]^[5] In contrast to permanent internal shunts, such as ventriculoperitoneal devices that redirect CSF to the peritoneal cavity without external access, EVDs remain extracorporeal and adjustable, allowing precise control over drainage rates and real-time ICP assessment until the underlying issue resolves.^[4]^[5]^[3]

Indications and Contraindications

External ventricular drains (EVDs) are primarily indicated for the management of acute hydrocephalus resulting from conditions such as subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), intraventricular hemorrhage (IVH), meningitis, or post-tumor resection.^[2]^[6] They are also used for therapeutic intracranial pressure (ICP) monitoring in comatose patients, particularly those with severe TBI and Glasgow Coma Scale scores of 3-8 accompanied by abnormal computed tomography findings.^[7]^[2] EVD placement is often lifesaving in emergency scenarios involving rapid ICP elevation, such as acute obstructive hydrocephalus following SAH or large-volume intracerebral hemorrhage (ICH) with IVH and neurological deterioration, where it facilitates immediate cerebrospinal fluid (CSF) diversion to alleviate pressure.^[8]^[7] In contrast, elective use occurs for controlled CSF diversion, such as intraoperative brain relaxation during procedures for posterior fossa tumors or to manage hydrocephalus from shunt malfunction.^[6]^[7] Contraindications to EVD insertion include uncorrectable coagulopathy, such as an international normalized ratio greater than 1.5 or concurrent use of anticoagulants or antiplatelet agents without reversal, due to heightened risk of hemorrhagic complications.^[7]^[9] Relative contraindications encompass significant midline shift on imaging, which may indicate herniation risk or inaccurate pressure readings, as well as superficial scalp infections at the proposed insertion site or systemic infections that could predispose to ventriculitis.^[2]^[6]^[7] These indications and contraindications are supported by guidelines from neurosurgical and neurocritical care societies, which emphasize EVD use for ICP exceeding 20 mmHg unresponsive to medical therapy, particularly in severe TBI where continuous CSF drainage improves ICP control (Level III evidence).^[7]^[2] The American Heart Association/American Stroke Association guidelines further recommend EVD for hydrocephalus in ICH/IVH with decreased consciousness to reduce mortality.^[8]

Placement Procedure

Preoperative Preparation

Preoperative preparation for external ventricular drain (EVD) insertion begins with a thorough patient assessment to evaluate suitability and minimize risks. This includes a detailed neurological examination to document baseline status, such as Glasgow Coma Scale (GCS) score and focal deficits, which helps guide urgency in cases of elevated intracranial pressure (ICP).^[10] Coagulation studies, including prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT), are essential to identify bleeding risks, with an acceptable INR range typically 1.2–1.6 for adults.^[11] Preoperative imaging via computed tomography (CT) or magnetic resonance imaging (MRI) is reviewed to confirm ventricular enlargement, assess midline shift, and identify optimal insertion sites, ensuring procedural precision.^[2] Risk mitigation strategies focus on correcting coagulopathies and preventing infections. Anticoagulants such as warfarin should be discontinued 5 days prior to elective insertion to allow INR normalization, while urgent cases may require reversal with vitamin K or prothrombin complex concentrate (PCC) to achieve therapeutic levels promptly.^[12] Prophylactic antibiotics, such as cefazolin, are administered as a single dose approximately 30 minutes before incision to reduce infection risk, particularly in operating room settings.^[11] Informed consent is obtained from the patient or surrogate, detailing procedure benefits and potential complications, even in emergencies where verbal consent may suffice initially.^[10] Patient positioning and site preparation follow standard protocols to facilitate safe access. The patient is placed supine with the head elevated 30 degrees in a neutral position to optimize venous drainage and reduce ICP, while the insertion site (typically Kocher's point) is shaved minimally and prepped with an antiseptic solution like chlorhexidine or povidone-iodine using sterile technique.^[2] Equipment setup involves selecting an appropriate catheter, such as polyurethane for ICP monitoring or antibiotic-impregnated variants (e.g., with minocycline and rifampin) to lower infection rates, alongside ensuring availability of guidance tools like ultrasound or neuronavigation if image-guided placement is planned.^[10]

Insertion Technique

The insertion of an external ventricular drain (EVD) typically occurs at Kocher's point on the non-dominant frontal lobe, located approximately 2-3 cm lateral to the midline and 1-2 cm anterior to the coronal suture, or equivalently 11 cm posterior to the nasion along the midline and then 2.5-3 cm lateral, to target the frontal horn of the ipsilateral lateral ventricle.^[13]^[14] This freehand approach relies on surface landmarks, such as the midpupillary line and tragus, with the patient's head positioned supine and elevated 30-45 degrees to facilitate access and minimize venous bleeding.^[3]^[15] The procedure begins with local anesthesia and mild sedation administered at the entry site, following sterile preparation that may include prophylactic antibiotics as outlined in preoperative protocols. A 3-4 cm linear skin incision is made at Kocher's point, followed by dissection through the galea and scraping of the periosteum to expose the bone. A burr hole is then drilled using a twist drill, Hudson brace, or craniotome with saline irrigation to penetrate the cranium, taking care to avoid dural sinus injury.^[14]^[3] A cruciate dural incision is performed to access the brain parenchyma, often with a small cortisectomy to create a pathway. The ventricular catheter, primed with saline and equipped with a stylet, is inserted perpendicular to the skull surface at a depth of 5-7 cm, directed toward the medial canthus of the ipsilateral eye and 1-2 cm anterior to the tragus to reach the foramen of Monro; if initial passage fails, the trajectory may be adjusted slightly medially on a second attempt.^[15]^[14] Once ventricular entry is suspected, the stylet is removed to check for cerebrospinal fluid (CSF) backflow, and the catheter is advanced an additional 1-2 cm if flow is confirmed. The catheter is then tunneled subcutaneously for 3-4 cm, secured with non-absorbable sutures at the exit site, and connected to a closed drainage system via a three-way stopcock.^[3]^[15] Guidance during insertion is most commonly freehand, utilizing anatomical landmarks, which carries a misplacement risk of 10-40% depending on ventricular size and operator experience, with accuracy rates around 70-83% for optimal tip positioning in the frontal horn.^[16]^[15] In cases of distorted anatomy, such as small or shifted ventricles, advanced methods improve precision: ultrasound provides real-time visualization for trajectory adjustment, CT stereotaxy or neuronavigation offers preoperative planning and intraoperative tracking to reduce passes needed, endoscopy allows direct ventricular visualization, and emerging technologies such as augmented reality systems (e.g., using Microsoft HoloLens) have shown promise in further enhancing precision as of 2025.^[3]^[16]^[17] Intraoperative confirmation of correct placement relies primarily on immediate CSF return upon stylet withdrawal, indicating ventricular puncture, followed by transduction of opening intracranial pressure (ICP) through the connected system to verify functionality.^[14]^[3] If flow is absent or questionable, fluoroscopy or portable CT may be used for real-time imaging to assess tip position, though postoperative CT remains the gold standard for final verification.^[15]

Postoperative Management

Monitoring and Care

Following placement of an external ventricular drain (EVD), continuous intracranial pressure (ICP) monitoring is essential to guide management and prevent secondary brain injury. The transducer is zeroed at the level of the Foramen of Monro, approximated by the external auditory meatus in the supine patient, using a leveling device such as a Carpenter's level or laser to ensure accurate readings. ICP waveforms are interpreted to assess compliance: normal patterns feature three peaks (P1 as the sharpest percussion wave, P2 reflecting intracranial compliance, and P3 as the dicrotic notch), while elevated P2 amplitude or loss of pulsatility may indicate rising ICP or dysfunction. The target ICP is typically maintained below 20-25 mmHg, with drainage initiated if thresholds are exceeded for more than 5 minutes.^[3]^[2] Drainage management involves adjusting the height of the collection system, often set at 10-20 cm H₂O above the external auditory meatus to control cerebrospinal fluid (CSF) outflow and avoid over- or under-drainage. Common modes include continuous drainage (e.g., at 10 mL/hour), intermittent drainage (opened for symptoms or elevated ICP), or ICP-triggered release, selected based on the underlying pathology such as traumatic brain injury or subarachnoid hemorrhage. Daily CSF output is tracked, with typical drained volumes ranging from 100-300 mL per day in many patients; excessive output (>20 mL/hour) prompts evaluation for overdrainage, while minimal output suggests possible obstruction.^[2] Nursing protocols emphasize infection prevention and system integrity through sterile dressing changes at the insertion site every 48-72 hours or if soiled, using aseptic technique to minimize ventriculitis risk. CSF sampling for cell count, glucose, and culture is limited to fewer than three times per week, performed via the proximal port with slow aspiration (≤1 mL/min) and strict sterility to avoid contamination. If clogging is suspected, gentle irrigation with less than 2 mL of sterile saline may be attempted under physician guidance, but only if ICP is stable.^[3] Patient care focuses on positioning and activity to optimize ICP control, including head elevation to 30 degrees to promote venous outflow while maintaining EVD height. Valsalva maneuvers, such as straining or coughing, are avoided by using stool softeners and suctioning as needed to prevent acute ICP spikes. Signs of EVD dysfunction, including absent drainage, suddenly rising ICP, or altered waveform, require immediate notification of the neurosurgical team for troubleshooting.^[3]^[2]

Weaning and Removal

The weaning process for an external ventricular drain (EVD) involves systematically reducing cerebrospinal fluid (CSF) drainage to assess the patient's ability to maintain normal intracranial pressure (ICP) without ongoing intervention, typically once the underlying condition has stabilized. Two primary strategies are employed: gradual weaning and rapid closure. In gradual weaning, the drainage height is incrementally raised by 5 cm every 24 hours until reaching 20-25 cm H₂O, followed by a clamping trial of 24-48 hours, during which ICP, neurological status, and symptoms such as headache are closely monitored to ensure stability.^[18]^[19] Alternatively, rapid closure entails immediate clamping of the EVD for 24 hours, with monitoring for any signs of hydrocephalus or ICP elevation exceeding 20 mmHg for more than 5 minutes; this approach may shorten hospital length of stay but carries a higher risk of failure in some cohorts.^[20]^[21] During these trials, parameters such as ICP trends and clinical examination, as established in routine postoperative monitoring, guide decisions to proceed or reopen drainage. Removal criteria emphasize sustained stability to minimize risks of recurrence. The EVD is considered for removal when ICP remains below 15-20 mmHg for 24-48 hours, daily CSF output is less than 250 mL, CSF is non-bloody, the neurological examination is stable (e.g., no deterioration in Glasgow Coma Scale), and imaging confirms resolution of hydrocephalus without ventricular enlargement.^[19]^[22] Additionally, the underlying etiology, such as subarachnoid hemorrhage or trauma, must be resolving, with no active infection present; coagulopathy should be corrected prior to discontinuation.^[7] Failure of weaning trials, indicated by ICP rise, clinical worsening, or new hydrocephalus on computed tomography (CT), necessitates reopening the drain or alternative interventions. The removal technique is typically performed at the bedside by a neurosurgeon or trained neurocritical care provider under sterile conditions to reduce infection risk. Sutures securing the catheter are cut, and the device is gently withdrawn in a straight trajectory while applying countertraction to the skin to prevent tract disruption; the incision is then closed with sutures or staples.^[1] Immediately following removal, a head CT is obtained to evaluate for hemorrhage or ventricular changes, ensuring early detection of any adverse effects.^[22] If chronic CSF diversion is required after EVD removal, transition to a permanent ventriculoperitoneal (VP) shunt may be indicated for ongoing hydrocephalus management, with placement often delayed until infection is ruled out. In select cases, a temporary lumbar drain can serve as a bridge during this period, allowing further assessment of CSF dynamics before committing to a shunt.^[2] These transitions are individualized based on imaging and clinical response to weaning.

Complications

Hemorrhagic Complications

Hemorrhagic complications associated with external ventricular drains (EVDs) primarily include intraparenchymal hemorrhage along the catheter tract, subdural or epidural hematomas, and intraventricular bleeding. Intraparenchymal hemorrhage, often resulting from vessel puncture during insertion, occurs in 10-34% of cases, though clinically significant events are less frequent at approximately 5-10%. Subdural and epidural hematomas may arise from catheter migration or overdrainage, with reported incidences varying from 1-5% in retrospective series. Intraventricular bleeding is rarer but can occur if subependymal vessels are disrupted, contributing to overall hemorrhage rates of up to 33% when including minor events detected on routine imaging.^[23]^[24]^[25] Key risk factors for these hemorrhagic events encompass coagulopathy, such as thrombocytopenia (platelet count <100,000/μL) or elevated INR (>1.5), uncontrolled hypertension, and procedural elements like multiple catheter passes during insertion. Patients with underlying cerebrovascular disease or intracerebral hemorrhage exhibit higher rates, up to 39%, compared to other cohorts. Additionally, EVD removal carries a separate risk of hemorrhage in 7.8-22.5% of cases, often due to tract disruption.^[24]^[25]^[26]^[27] Diagnosis typically involves serial computed tomography (CT) scans immediately post-insertion and at 24-48 hours, or sooner if neurological deterioration occurs, to identify new hemorrhages and assess for mass effect or hydrocephalus progression. Management strategies depend on hemorrhage size and symptoms: minor tract bleeds often require only observation and supportive care, while coagulopathy is addressed with reversal agents such as fresh frozen plasma (FFP) for INR correction or platelet transfusions. Significant hematomas causing mass effect or midline shift necessitate urgent surgical evacuation, potentially via craniotomy, alongside temporary cessation of drainage if feasible.^[28]^[29]^[24] Prevention focuses on preoperative optimization of coagulation parameters, aiming for platelet counts >100,000/μL and INR <1.5, and controlling blood pressure to systolic levels below 160 mmHg. Image-guided techniques, such as frameless stereotaxy or ultrasound, reduce vessel injury risk by minimizing blind passes, with studies showing lower hemorrhage rates compared to freehand methods. Limiting insertion attempts to one or two and selecting optimal trajectories further mitigates risks during placement.^[9]^[24]^[26]

Infectious Complications

Infectious complications associated with external ventricular drains (EVDs) primarily manifest as ventriculitis or meningitis, with reported incidence rates ranging from 2% to 36%, and a median of approximately 11% across multiple studies.^[30] These infections are often caused by gram-positive organisms, particularly coagulase-negative staphylococci such as Staphylococcus epidermidis and Staphylococcus aureus, though gram-negative bacilli like Pseudomonas aeruginosa and fungi such as Candida species can also occur.^[31] The risk increases with prolonged EVD duration exceeding 5-7 days, cerebrospinal fluid (CSF) leaks, frequent CSF sampling or catheter manipulation, and use of non-antimicrobial-impregnated catheters.^[30] Additional factors include intraventricular hemorrhage, prior systemic infections, and bilateral EVD placement.^[30] Diagnosis relies on a combination of clinical signs and laboratory findings from CSF analysis obtained via the EVD. Common clinical indicators include new-onset fever, meningismus, and worsening neurological status, while CSF evaluation typically shows pleocytosis with white blood cell counts greater than 10 cells/mm³, glucose levels below 40 mg/dL, elevated protein, and positive microbial cultures confirming the pathogen.^[32] Cultures should be held for at least 10 days to detect slow-growing organisms like Propionibacterium acnes, and supportive tests such as CSF lactate may aid in cases with equivocal findings.^[31] Management involves prompt EVD removal to eliminate the nidus of infection, particularly in cases involving biofilms, followed by temporary replacement if ongoing drainage is needed.^[30] Empiric intravenous antibiotics, such as vancomycin combined with an anti-pseudomonal beta-lactam (e.g., cefepime or meropenem), are initiated, targeting vancomycin trough levels of 15-20 μg/mL, with therapy tailored to culture susceptibilities and continued for 10-14 days or up to 21 days for gram-negative infections.^[31] Intraventricular administration of antibiotics like vancomycin (5-20 mg daily) may be considered for severe or refractory cases, with the drain clamped briefly post-infusion.^[32] Prevention strategies emphasize antimicrobial-impregnated EVD catheters, which reduce infection risk by approximately 40-50% compared to standard catheters, alongside strict adherence to sterile insertion and handling protocols, care bundles from the Neurocritical Care Society, and minimizing EVD duration through early weaning when clinically feasible.^[30] Periprocedural systemic antibiotics are recommended to further mitigate initial colonization risks.^[31]

Mechanical Complications

Mechanical complications of external ventricular drains (EVDs) encompass hardware-related failures that disrupt cerebrospinal fluid (CSF) drainage or accurate intracranial pressure (ICP) monitoring, potentially leading to inadequate hydrocephalus management or elevated ICP. The most prevalent types include catheter obstruction, migration or malposition, and disconnection or kinking of the external tubing system. Obstruction, reported in 19-47% of cases, typically arises from blood clots, cellular debris, or tissue fragments accumulating within the catheter lumen, compromising patency and necessitating intervention to prevent acute neurological deterioration.^[33] Migration or malposition occurs in approximately 7-17% of insertions, often resulting from patient movement or inadequate initial securing, which positions the catheter tip outside the ventricular space and impairs CSF outflow.^[34] Disconnection or kinking of the tubing, though less quantified, can stem from mechanical stress or improper assembly, further hindering system functionality.^[3] Diagnosis of these complications relies on clinical signs such as absence or reduction of CSF drip from the drainage chamber, lack of pulsatile CSF meniscus, or fluctuating and dampened ICP waveforms on monitoring devices, indicating potential blockage or misalignment.^[3] If initial troubleshooting fails to restore flow, confirmatory imaging via computed tomography (CT) or plain head X-ray is essential to assess catheter position relative to the ventricles, with CT preferred for its superior visualization of tip placement and any associated shifts.^[34] These diagnostic steps allow for prompt differentiation from other issues, ensuring targeted resolution without unnecessary procedures. Management prioritizes minimally invasive corrections to restore function rapidly. For suspected obstruction, gentle irrigation with 0.5-2 mL of preservative-free sterile normal saline can dislodge debris, performed cautiously by trained personnel to avoid over-pressurization.^[3] Migration or malposition may require bedside repositioning under sterile conditions or surgical adjustment, while kinking or disconnection involves straightening the tubing, reconnecting components, or verifying the drainage height relative to the external auditory meatus to optimize gravitational flow.^[34] Persistent failures, such as no output after 24 hours of troubleshooting, warrant complete EVD replacement to mitigate risks of prolonged underdrainage.^[34] Prevention of mechanical complications emphasizes meticulous technique and ongoing vigilance. Secure fixation using bolted or tunneled EVD systems reduces migration and dislodgement rates compared to traditional methods, with suturing or adhesive dressings applied immediately post-insertion to stabilize the catheter.^[34] Regular patency assessments, including hourly checks of CSF output and ICP trends, enable early detection of issues, while incorporating filtered drainage systems like the LiquoGuard device minimizes debris ingress and maintains consistent flow.^[34] These strategies, when combined with staff education on proper handling, significantly lower the overall incidence of hardware failures.^[3]

Neurological Complications

Neurological complications associated with external ventricular drain (EVD) placement primarily involve alterations in brain function due to pressure imbalances or direct tissue disruption, excluding hemorrhagic and infectious etiologies. These include brain herniation, seizures, and focal neurological deficits, which can significantly impact patient outcomes if not promptly identified and addressed.^[3] Brain herniation may result from rapid overdrainage, which creates excessive negative intracranial pressure gradients, or from malposition of the EVD catheter, potentially causing transtentorial or upward herniation syndromes. In patients with obstructive hydrocephalus from posterior fossa lesions, upward herniation has been observed post-ventriculostomy, emphasizing the need for cautious cerebrospinal fluid (CSF) drainage to mitigate this risk. Seizures may occur following EVD insertion, often due to cortical irritation along the catheter tract or exacerbation of underlying brain pathology. Focal neurological deficits, such as hemiparesis or hemichorea-hemiballismus, can arise from malpositioned catheters causing direct neuronal injury, as evidenced by lesions along the EVD tract on imaging.^[35]^[36] Key risk factors for these complications include overdrainage, such as setting the drainage system too low, which can lead to subdural hygroma formation through excessive CSF removal and brain sagging. Pre-existing cerebral edema further heightens vulnerability by altering intracranial compliance, making the brain more susceptible to pressure shifts during EVD use. Overdrainage may also contribute to hematoma development, as explored in the context of hemorrhagic complications.^[37] Diagnosis relies on vigilant monitoring of clinical neurological changes, including altered mental status, pupillary abnormalities, or motor asymmetries indicative of herniation. Electroencephalography (EEG) is essential for detecting subclinical seizures, particularly in comatose patients where clinical signs may be obscured. Serial neurological examinations and imaging, such as computed tomography (CT), help confirm malposition or evolving deficits by visualizing catheter trajectory and brain shift.^[38]^[2] Management focuses on reversing the underlying mechanism while supporting neurological stability. Slow weaning of the EVD, typically by incremental height adjustments, prevents rebound intracranial pressure elevation that could worsen herniation. For seizures, prompt initiation of anticonvulsants such as levetiracetam is recommended, given its efficacy in controlling post-procedural and traumatic seizures with a favorable safety profile. Suspected herniation due to malposition necessitates urgent catheter repositioning or replacement under imaging guidance to restore proper drainage and alleviate pressure gradients.^[39]^[35] Prevention strategies emphasize controlled CSF drainage rates, generally limited to 15-20 mL per hour to avoid excessive negative pressure, combined with regular leveling of the drain at the patient's external auditory canal or mid-tragus. Frequent neurological checks, at least every 1-2 hours initially, enable early detection of subtle changes, allowing timely interventions to avert progression to severe deficits.^[37]^[2]

References

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