CNS
Neuroimaging
***In the PICU, unless you are told otherwise, imaging should be ordered STAT***
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
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
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
Non-opioid Analgesics
Acetaminophen
Can cause hepatotoxicity
NSAIDS
Ibuprofen (Motrin)
Naproxen
Ketorolac (Toradol)
Can lead to GI bleed, nephrotoxicity, typically not used under 6 months of age.
Opioids / Narcotics
Act on mu-receptors in the CNS
All can cause respiratory depression
Morphine
Fentanyl
Shorter acting. Rapid administration can cause chest wall rigidity
Hydromorphone (Dilaudid)
Remifentanyl
Fastest acting, used in TBI to quickly remove for neuro exam
Oxycodone
Methadone
Longer duration of action, causes QTc prolongation
Naloxone
Reversal agent, used in low doses to prevent pruritus
Benzodiazepines
Lorazepam (Ativan)
Midazolam (Versed)
Short Half life
Used as continuous infusion or bolus dose
Diazepam (Diastat / Valium)
Clonazepam (Klonopin)
Longer halflife
Dissociative Anesthetic
Ketamine
Hemodynamically favorable, should not cause hypotension
Makes use of intrinsic catecholamines, therefore should use judiciously in patients with deplete catecholamine stores (chronic heart failure)
Sialagogue (causes sialorrhea)
Increases intraocular pressure
Useful for bronchospasm (critical asthma)
Can be used in patient with TBI
Usually develop nystagmus as starting to induce sedation
Etomidate
Binds GABA receptors to enhance GABA effect
Ultrashort acting - will wear off before paralytic during intubation
Hemodynamically favorable
Inhibits 11-beta-hydroxylase causing transient inhibition of adrenal steroid synthesis
General Anesthetic
Propofol
Can cause apnea / hypotension
Constituted in lipid emulsion
Avoid with soy / egg allergies
Avoid in patients with mitochondrial disease
Can cause urine to turn green (benign side effect)
Propofol infusion syndrome:
Life threatending, nearly exclusively fatal severe syndrome of metabolism failure caused by prolonged infusions of propofol, generally seen in pediatric patients
Metabolic acidosis, rhabdomyolysis, hyperlipidemia, lactic acidosis, renal failure, fever, tachycardia - leading to bradycardia, cardiovascular collapse and irreversible cardaic arrest
Monitor patients closely if requiring propofol infusions
Alpha-2 receptor Agonists
Dexmedetomidine
Used as continuous infusion for moderate sedation
Boluses should be run slowly over 20-30 minutes
Favorable respiratory profile
Decreases HR (causes rebound HTN, but sometimes hypotension)
Clonidine
Used for dexmedetomidine withdrawal
Helps with dysautonomia / neurogenic "storming"
Tizanidine (Tanaflex)
Guanfacine (Intuniv)
GABAergic
Gabapentin
Pregabalin (Lyrica)
Acamprosate
Barbituates
Phenobarbital
Pentobarbital
Longer half-life
causes hypotension, respiratory depression, myocardial depression
pharmacologically induced coma
Can check levels to evaluate if cleared from patient
Caution with feeding due to differential intestinal perfusion
Thiopental
Previously commonly used for induction prior to intubation
No longer available for use
Hypnotics
Chloral Hydrate
Active metabolite: Trichloroethanol
Only given enterally
Antipsychotics (agitation / Delirium)
Check periodic ECG for QT changes
Risperidone
Quetiapine (Seroquel)
Dosed enterally
Haloperidol
Given IV or IM
Olanzapine
Muscle Relaxants
Metaxalone (skelaxin)
Cyclobenzaprine (Flexeril, Amrix)
Tizanidine (Zanaflex)
Carisoprodol (vanadom)
Chlorzoxazone (Lorzone)
Methocarbamol (Robax)
Orphenadrine
Diazepam (Valium)
Baclofen
Topical NSAID (Voltaren), Lidocaine, Icy-hot, menthol, Ben-gay
Antiepileptics
Ativan/Versed
Keppra
Fosphenytoin
Phenobarbital
Valproic Acid
Anti-Nausea / Anti-emetic
Ondansetron (Zofran)
Granisetron (Kytril)
Lorazepam (Ativan)
Prochlorperazine (Compazine)
Phenothiazine antipsychotic
Aprepitant (Emend)
Neuromuscular Blocking Agents
Depolarizing
Succinylcholine
Rapid onset / Short duration of action (7-12 minutes)
Binds post-synaptic cholinergic receptors
Causes rapid depolarization, fasciculation and flaccid paralysis
Concern for hyperkalemia (avoid in burn, renal failure)
Malignant hyperthermia
Nondepolarizing
Rocuronium
Reverse with Neostigmine, Sugammadex (2-4mg/kg)
Vecuronium
Cisatracurium
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.
SBS Scale
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
Additional Sedatives
Weaning Analgesia & Sedation:
Most of the analgesic and sedative medications we use lead to tolerance, defined as an increased dose needed to obtain the same clinical effect and subsequent dependence. Therefore, we observe iatrogenic withdrawal syndromes (IWS) in patients when the medications are discontinued abruptly. IWS is less common/rate if patietn was on medications for </= 5 days of use.
IWS Assessment:
WAT-1 assessment tool is used to assess for withdrawal from benzodiazepines and opioids
A WAT > 3 indicates withdrawal
Withdrawal/weaning plans should be discussed AT LEAST 24h prior to starting to desire to wean medications on rounds.
Signs of Opioid-associated IWS
CNS hyperactivity (difficulty sleeping, irritability, inconsolability)
Autonomic dysfunction (fever, diaphoresis, tremulousness)
GI symptoms (feeding difficulty, emesis, diarrhea)
Signs of Benzodiazepine-associated IWS
CNS hyperactivity, autonomic dysfunction
Signs of Dexmedetomidine-associated IWS:
agitation, hypertension, tachycardia
Weaning Strategies
A weaning protocol exists in the PICU with an EMR order set and incorporates the following:
Uses a validated IWS assessment tool (WAT-1) and report scores on daily rounds
Wean no more than 25% daily
Avoid weaning multiple drugs at once (eg. alternate weans or get completely off one then wean the next drug)
Transition to intermittent longer lasting PO/IV medications to wean off infusions
Use breakthrough doses of shorter-acting drugs to treat withdrawal symptoms
Please ask the PICU fellow/Pharmacist for help ordering these
Consult Pain Team when patient transferred to the floor prior if not completed wean
WAT-1 Scoring Rubric
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
CAPD Tool:
Each patient should be assessed once per shift by their bedside nurse. Documented in EMR.
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/
Brain physiology:
Autoregulation = under normal conditions, blood flow to the brain will be constant over a wide range of blood pressures and Oxygen levels
Severe brain injury will cause loss of autoregulation and can make it difficult to ensure appropriate blood flow to the brain
CO2 levels very tightly control the vascular tone of cerebral blood vessels and therefore requires tight control in the setting of a brain injury
Hyperventilation (low CO2) causes constriction of the cerebral vessels - decreased blood flow to the brain
Hypoventilation (high CO2) causes dilation of the cerebral vessels - increased blood flow to the brain
Cerebral Autoregulation with PaO2, PaCo2, and MAP over various SBP
Cerebral blood flow and vascular reactivity
Increased Intracranial Pressure (ICP)/Traumatic Brain Injury (TBI) Management
**Please see TBI/head trauma protocol for orders/RBC PICU management**
Causes of increased ICP: head trauma, tumors, CNS infections, hydrocephalus, intracranial bleeding, idiopathic
Signs/symptoms: headaches, visual changes, unexplained mental status change, cranial nerve deficits, pupillary dilation, and Cushing’s triad (late finding)
Cushing’s triad (HTN, bradycardia, irregular breathing)
Do not wait for imaging confirmation to treat if strong clinical suspicion
Pathophysiology: Monro-Kellie Doctrine - because of the fixed intracranial space due to the skull, any increase in brain parenchyma, blood volume or CSF volume will cause an increase in pressure (Boyle's law, where pressure = 1/ volume)
Monro-Kellie Doctrine
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
Intracranial pressure waveforms:
P1 = pressure wave, transmission of the arterial systolic pressure from choroid plexus to the ventricle
P2 = Tidal wave, correlates with brain tissue compliance. Poor compliance = high P2
P3 = Dicrotic wave, follows the dicrotic notch (closure of aortic valve)
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.
Status Epilepticus
Definition: Per the International League Against Epilepsy "a condition resulting either form the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonted seizures (after time point 1). Long term consequences if not treated by time point 2 like neuronal death, injury and alteration of the neuronal networks"
~ > 5 mins or 3 episodes in an hour without returning to baseline
Causes: infection, tumor, electrolyte disturbances, toxic ingestion, trauma, intracranial bleeding, cerebral edema, primary epileptic disorder, anatomic structural abnormality, hydrocephalus, acute liver failure, genetic syndrome, hypoxia
Pathophysiology: (expand to see)
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