CNS

Neuroimaging

***In the PICU, unless you are told otherwise, imaging should be ordered STAT***

1. Ultrasound: Grayscale images from ultrasound beam reflected off tissues, no ionizing radiation 

• Through anterior fontanelle → limitation 

• Can detect germinal matrix hemorrhage, ventricular size and severe white matter lesions.

• Poor at detecting parenchymal loss, extra-axial fluid, dural venous sinus thrombosis

2. CT: Ionizing radiation to produce digital computer reconstructed images based on tissue density 

• Good for bone, ventricular size, mass effect, cerebral edema, and blood (trauma). 

• Bone = highest density → soft tissue → water → fat → air

  • Acute blood = higher density than the brain parenchyma 

• Iodinated contrast - tests the integrity BBB

• Edema - loss of gray white differentiation several hours post insult. 

  • Can miss early infarcts (unmyelinated brains in kids)

• Blood - initially hyperdense and then evolves to isodense over the 1st week

3. MRI: High field strength magnet in combination with radiofrequency pulses to produce images based on nuclear resonance of H protons in tissues

• Most sensitive imaging for parenchyma, posterior fossa, brain stem, cerebellum, spinal cord

• Various MRI Sequences:

  • T1 - longitudinal relaxation of H proton (water is dark)

  • T2 - spin spin relaxation of the H proton (water is bright)

  • FLAIR (Fluid Attenuated Inversion Recovery) - CSF is rendered dark

  • GRE (Gradient Recalled Echo) - detection of hemorrhage with blood being hyperdense acutely (hard to detect < 12h from event)

  • DWI (Diffusion Weighted Imaging) - for acute cytotoxic injury

    • Sensitive to water motion → cytotoxic edema →  restriction of water (bright)

  • ADC (Apparent Diffusion Coefficient)- T2 “shine through” removed, looking at water movement

    • Will be dark when cytotoxic edema present

See this ICURE lecture for more information! 

CNS Drug Classes

Definitions

• Analgesia = treatment of pain

• Amnesia = sedatives that provide of hypnosis/dissociation

• Anxiolysis =  relive anxiety; minimal sedation 

Neuromuscular Blocking Agents

Critically ill children are subjected to painful procedures, medical devices, and an overall high-anxiety inducing environment in order to care for them.

Analgesia, amnesia, and anxiolysis are essential to help provide comfort as well as the highest quality care to these patients. 

Sometimes, neuromuscular blockade is needed to further facilitate medical care, and this is described below. 

Analgesia

• Pain Assessment – age-dependent pain scales monitored at least every 4 hours, more frequently if the patient is experiencing pain and not tolerating the associated tachycardia, hypertension

• Non-Opioid Analgesics are typically first line in the PICU. 

  • Practice opioid sparing measures when possible.

    • • • • Examples of appropriate opioid use: post-operative acute pain, trauma patients, invasive mechanical ventilation

  • Clarify with surgical service/PICU Fellow/Attending if NSAIDs are permitted

  • Typically, schedule non-opioid analgesics are scheduled to have steady state/baseline pain control.

  • It is important to reassess analgesia needs and discuss on daily rounds

• Subcutaneous lidocaine is phenomenal for local pain control for invasive procedures – use it! 

Opioids 

• bind to mu-receptors on the brain and spinal cord 

  • They are available in multiple formulations and can be delivered IN/IV/PO

  • Can be used intermittently, as a PCA or as a constant infusion 

• At RBC, please consult the Pediatric Pain Service for PCAs, any patient leaving the PICU on a weaning plan, or for any patient whose pain is difficult to manage

Sedation

• Analgesia alone may be insufficient for patients' to interact with medical interventions such as mechanical ventilation, non-invasive ventilation, CRRT/hemodialysis or ECMO.

• Use the State Behavior Scale (SBS) to target the level of sedation for patients (see below)

• When using medications:  generally, start low and go slow!

• Adequately address analgesia first and then increase sedation needs

Assessing Patient Sedation with SBS

This is one of the validated sedation assessments in pediatrics. The scale is -3 to +2, with -3 being the most sedated and +2 being the least sedation. 

The SBS scores should be reported on rounds and the goal for the depth of sedation for the day should be discussed on rounds. 

Our goal for most patients is 0. 

Patients in shock or respiratory failure requiring deep sedation or paralysis for physiologic reasons, should have goal of lower than 0. 

SBS - 3 typically signifies paralysis or deeply induced coma

Neuromuscular Blockade (NMB)

• Used in conjunction with sedation to further decrease a patient's metabolic demand, help syncronize with life-saving medical equipment, or prevent movement to allow for medical treatment/healing

  • • • Examples: acute respiratory failure (ARDS), shock, severe traumatic brain injuries, cardiopulmonary collapse (heart failure), post-arrest care, sepsis, minimize patient induced edema to airway/tracheostomies, or after orthopeadic injury requiring immoblization

• ALWAYS sedate your patients and ensure pain control prior to paralysis. Ensure patient has appropriate ventilator support. 

• All patients should have ophthalmic ointment ordered q4h to prevent corneal abrasions

• Much of the neurological exam is lost while on NMB - consider EEG, daily NMB holiday to assess depending on clinical situation

  • • • PUPILLARY MUSCLES ARE NOT EFFECTED BY NMB - pupils should still be reactive 

• As with all therapies in the PICU, use for the shortest duration of time --> can cause critical illnes myopathy, delirium etc 

Delirium & Post-Intensive Care Syndrome (PICS)

●       Delirium - state of brain dysfunction characterized by decreased cognition and inattentiveness to the environment. Observed in 20 – 55% PICU patients, both medical and surgical populations

●       Symptoms - altered state of consciousness and decreased cognition

●       Types

○   Hyperactive - agitation, increased activity, inconsolable, purposeless movements

○   Hypoactive - lethargy, decreased activity -- often missed as patient is calm!

○   Mixed - cycles between hyperactive and hypoactive

●       Etiology: Many possible organic and iatrogenic causes.

●       Useful mnemonic = I WATCH DEATH 

○   I - infectious (Sepsis, PNA, meningitis etc)

○     W - withdrawal (from analgesia/sedatives)

○     A - acute metabolic disorder (acidosis, alkalosis, electrolyte abnormalities, renal/hepatic failure)

○     T - trauma

○     C - CNS pathology (seizures, CNS bleeds/stroke, hydrocephalus, encephalitis)

○     H - hypoxia

○   D - deficiencies (Vitamin 12, folate, niacin, thiamine)

○   E - endocrinopathies (glucose, cortisol, myxedema, hyperparathyroidism)

○   A - acute vascular (stroke, shock, arrhythmia, hypertensive encephalopathy, PRES)

○   T - toxins (prescription/illicit drugs, alcohol, other ingestions)

○   H - heavy metals (lead, mercury etc.)

●   Risk of delirium is associated with:

○   Benzodiazepine exposure

○   Untreated pain

○   Underlying neurocognitive dysfunction pre-hospitalization

●       Untreated delirium is associated with:

○   Increased PICU and hospital LOS

○   Decreased neurocognitive functioning

○   Long-term neurocognitive disability

●   Delirium screening performed using Cornell Assessment of Pediatric Delirium (CAPD)

○   Can only be done if patient’s SBS score > -2

○   CAPD > 9 or score increasing from baseline indicates possible delirium

Strategies for Managing Delirium

• Assess for treatable causes for agitation (I WATCH DEATH)

• Remove/minimize deliriogenic medications if possible

• Maximize normal sleep-wake cycles

• Maximize Noise reduction

• Create daily schedules with child life, PT, OT, family, RN etc.

• Consider psychiatric consult

• In some cases, treat with second generation anti-psychotics (risperidone)--> efficacy literature is lacking

https://pubmed.ncbi.nlm.nih.gov/32071582/ 

https://pubmed.ncbi.nlm.nih.gov/37082469/ 

• Treatment:

  • • • • Surgical Treatment

          • • Drain CSF with external ventricular device (EVD), a ventriculo-peritoneal shunt, or lumbar drain

            • Drain blood with craniotomy/craniectomy 

            • Tumor removal/debulking

            • Wash out of abscess 

        • Medical Treatment

          • • Hyperosmolar therapy 

            • Head of bed 30 degrees

            • Head midline

            • Neck straight and ensure that C-collar is not obstructing venous return

            • Monitor PaCO2 (CO2 governs cerebral blood flow) 

            • Antibiotics 

            • Anti-inflammatory (steroids) and/or anti-neoplastic (chemotherapy) medications 

Severe TBI Management

• TBI Classification: 

  • • Severe TBI = GCS <9; Moderate TBI = GCS 9-12; Mild TBI = GCS >12

In general the goal is to keep everything NORMAL

• Normothermia (use antipyretics, external cooling blanket) - AVOID FEVER!

• Normotension - do NOT allow hypotension

  • •   Tolerate hypertension based on your Cerebral Perfusion Pressure (CPP) goals

• Appropriate oxygenation - do NOT allow hypoxia, avoid hyperoxia; SpO2 92-97%, PaO2 80-120

• Normoglycemic - not < 100 and not > 250

• Avoid acidosis

• Avoid hypercarbia goals;  PaCO2 35-40

• Maintain Normal ICP (<20)

• Place EEG for seizures, consider AED prophylactically - Seizure avoidance is critical

• Monitor Pupillary changes closely

• Hyperosmolarity; generally sodium 145 -160 (Avoid allowing sodium to drop below 140 or 145)

  • • See medications below

When using Mannitol as hyperosmolar therapy, important to calculate osmolar gap to prevent mannitol toxicity

• Osmolar gap = measured serum osmolality (lab value) - calculated osmolality (equation below) < 20 (to give more Mannitol)  

• Serum Osmolality= 2(Na) + glucose/18 + BUN/2.8  

• Alternative equation: Osmolality = 1.86 (Na + K) + BUN/2.8 + glucose/18 + 10

TBI guidelines here

Other steps in medical management are: 

• Intubation: airway protection and to control oxygenation/ventilation

• Head Positioning: HOB to 30 degrees, head midline. Optimizes blood flow both in AND out of brain

• Intracranial pressure monitors: ICP goal <20

  • • • Intraparenchymal fiberoptic pressure monitors (bolts): continuous ICP monitoring

      • External Ventricular Drains (EVDs): can measure ICP or drain CSF

      • Brief spikes in ICP are normal w/ pain/agitation/suctioning

• Cerebral Perfusion Pressure: CPP = MAP - ICP
  ***Can increase MAP or decrease ICP to maintain goal CPP***

  • • • • Estimate of brain perfusion

        • Goal CPP >40 for infants

        • Goal CPP >50-60 for older children

• Sedation/Analgesia:

  • • • Bolus sedation/analgesia as needed if ICP > 20 (if hemodynamically stable)

      • Minimize stimulation (from family, environment, medical staff)

      • Consider neuromuscular blockade 

      • Consider pentobarbital coma if other medications are not effective enough for ICP control

• Hyperventilation for increased ICP:

  • • • Acute increased ICP situations, not for chronic management 

      • Alkalosis decreases cerebral blood flow which decreases ICP 

• Monitor pituitary function

  • • • Brain injury can cause pituitary dysfunction

      • Can lead to secondary adrenal insufficiency, hypothyroid

      • Phases of ADH secretion - SIADH through diabetes insipidus (often can go through different phases)

      • Consider cerebral salt wasting in a patient with hyponatremia who has brisk urine output and urine has high Na concentration 

        • Also be aware that often patients auto-diurese due to previous fluid overload and salt loading

Decompressive Craniotomy

●   Most aggressive and invasive form of decompression

●   Removal of skull to allow brain to swell outwards

●      Current literature shows that while lowering ICP, this may not ultimately improve  neurological outcomes. Review article here. 

Management: 

• ABCs! Ensure airway is intact, patient is breathing and that they maintain spontaneous circulation

• Make sure patient is in a safe environment 

• First line: Benzodiazepines (Lorazepam, Diazepam, Midazolam) 

• Second line: Fosphenytoin, Levetiracetam (Keppra), Phenobarbital

• Third line: Propofol, Midazolam (versed) infusion, pentobarbital 

***see dosing chart from UpToDate

***RBC has a status epilepticus protocol - please see link in "Available Resources" Tab

• Continuous EEG is essential for monitoring 

• Many medications have side effect of respiratory depression and thus will need intubation/mechanical support until seizures are under control

• Will likely need neuroimaging