Intracranial Physiology and Pathophysiology

• 1.
  

  Normally, cerebrovascular autoregulation ensures maintenance of constant blood flow to the brain during alterations in mean arterial blood pressure (BP). This system operates over a wide range of mean arterial pressures from 50 to 150 in adults, and as low as 20 to 60 mm Hg in the supine infant.

  
  
• 2.
  

  Cerebral blood flow (CBF) in infants and children (90 to 100 ml per 100 g/min) is greater than in adults (50 to 60 ml per 100 g/min). CBF varies directly with changes in PaCO ₂ between 20 and 80 mm Hg. CBF changes approximately 4% per mm Hg change in PaCO ₂ .

  
  
• 3.
  

  Vasodilation of normal reactive cerebral vessels reduces blood flow in areas that have lost autoregulation (e.g., AVMs, vascular tumors or areas of infection or trauma). This has been termed intracerebral steal.

  
  
• 4.
  

  Vasoconstriction of normal reactive cerebral vessels has the opposite effect (i.e., inverse intracerebral steal). Hence, hyperventilation as a means for rapidly reducing cerebral blood volume (ICP) is generally reserved for acute increases in ICP and not recommended for prolonged periods of time.

  
  
• 5.
  

  In older children, the total volume of the intracranial contents is fixed. However, any of its three constituents—blood, CSF, and brain tissue—can increase or decrease if compensated by an equal and opposite change in the volumes of the others (revised Munro-Kelly hypothesis).

  
  
• 6.
  

  Infants have a less rigid skull than older children; an increase in the contents may be accommodated to some extent by stretching of the dura, expansion of the fontanels, and separation of the suture lines. The ICP may be estimated by palpation of the fontanel.

  
  
• 7.
  

  The effect of a space-occupying lesion on ICP depends on its volume and rate of expansion and the rigidity of the skull. Initially, the lesion displaces CSF and/or venous blood from the skull, the sutures may separate in infants, and ICP increases slowly if at all. As expansion continues, compensation is no longer possible, and small increases in volume result in progressively larger increases in ICP. With a rapidly expanding lesion (i.e., intracranial bleeding), pressure increases rapidly from the outset.

Effects of Specific Anesthetic Drugs on Intracranial Physiology

• 1.
  

  All inhalation agents increase CBF and may increase ICP unless accompanied by mild hyperventilation (PaCO ₂ ∼ 30 to 35 mm Hg):

  
  
  
  
  • a.
    

    N ₂ O may cause a very small increase in CBF but has been used successfully in pediatric neurosurgery for many years. It may increase ICP if air is present within the cranium and in these circumstances is contraindicated.

    
    
  • b.
    

    The increase in CBF follows the order: desflurane > halothane > isoflurane > sevoflurane.

    
    
  • c.
    

    Cerebral autoregulation during changes in arterial BP is blunted as the concentrations of inhalational agents increase, but appears to be preserved at 1 MAC isoflurane and sevoflurane anesthesia. This emphasizes the importance of using moderate concentrations of potent inhalation agents; the CBF responses to changes in PaCO ₂ is retained. Moderate hypocarbia tends to modify or reverse the effects of agents that increase CBF (e.g., halothane, isoflurane, sevoflurane). Prior hypocapnia minimizes the increase in ICP with halothane. During isoflurane anesthesia, the CBF returns to control levels more rapidly with mild hyperventilation.

    
    
  • d.
    

    The CMRO ₂ is reduced by halothane, isoflurane, and sevoflurane. Isoflurane and sevoflurane at greater concentrations may even provide some cerebral protection against hypoxia/ischemia.

  
  
  
  
• 2.
  

  Intravenous anesthetic agents (with the notable exception of ketamine) either have no effect on CBF or decrease it, but if hypercarbia is present, these effects are reversed:

  
  
  
  
  • a.
    

    Thiopental reduces ICP and therefore is an ideal induction agent in neurosurgery. It does not prevent an increase in BP and ICP during laryngoscopy and intubation; these may, however, be attenuated by prior administration of lidocaine (1 to 1.5 mg/kg IV) and an opioid (e.g., fentanyl 2 to 5 µg/kg).

    
    
  • b.
    

    Propofol reduces CBF and CMRO ₂ , preserves autoregulation, and may offer some cerebral protection. Induction doses (3 mg/kg) may cause mild hypotension but also more effectively blunt the cardiovascular responses to laryngoscopy and intubation.

    
    
  • c.
    

    Remifentanil, fentanyl and sufentanil have little effect on CBF provided that ventilation is maintained. Autoregulation and the cerebrovascular response to PaCO ₂ are also maintained. Alfentanil has been demonstrated to increase CSF pressure in children with cerebral tumors.

    
    
  • d.
    

    Ketamine increases CBF and CMRO ₂ ; CSF pressure is increased. This drug should not be used in neurosurgical patients with raised ICP.

    
    
  • e.
    

    Midazolam and diazepam decrease CBF, CMRO ₂ , and ICP and may control seizures. Flumazenil, which antagonizes benzodiazepines, also antagonizes their effects on CBF and ICP. The latter should be used with caution.

  
  
  
  
• 3.
  

  Nondepolarizing muscle relaxants have no direct effect on CBF. (Vasodilation resulting from histamine release after atracurium is a possible exception.) The duration of action of vecuronium and rocuronium may be reduced in children taking chronic anti-seizure medications.

  
  
• 4.
  

  Succinylcholine may transiently and very slightly increase CBF and ICP in children with space-occupying lesions; this response may be attenuated by prior administration of a small dose of a nondepolarizing muscle relaxant. Hyperkalemia has been reported after succinylcholine was given to children with cerebral trauma and other central nervous system diseases, including paraplegia, encephalitis, and subarachnoid hemorrhage.

  
  
• 5.
  

  Sodium nitroprusside, nitroglycerin, adenosine, and the calcium channel-blocking drugs impair cerebral autoregulation and may increase CBF and ICP.

  
  
• 6.
  

  Dexamethasone (0.15 mg/kg IV to a maximum of 8 mg) may decrease focal cerebral edema in response to surgical trauma of brain tissue.

  
  
• 7.
  

  If an independent vasodilator effect is absent, drugs that decrease neuronal function decrease CBF (such as thiopental).

  
  
• 8.
  

  Drugs that increase neuronal function increase CBF (such as ketamine).

  
  
• 9.
  

  Somatosensory evoked potentials (SSEPs), to monitor brain or spinal cord function, are attenuated by inhalational anesthetics if these agents are given in more than minimal concentrations. Nitrous oxide, propofol, opioids, and muscle relaxants have little effect on SSEPs.

  
  
• 10.
  

  Motor evoked potentials (MEPs), to monitor brain and spinal cord function, are much more sensitive to the presence of inhalational anesthetics than SSEPs. Although the requirements for MEP monitoring varies among neurophysiology groups, in general nitrous oxide is completely avoided, as are muscle relaxants; inhalational agents are limited to 0.5 MAC. Propofol, alpha-2 agonists, benzodiazepines and opioids do not significantly compromise MEP monitoring.

Premedication

Children with increased ICP should not receive excessive doses of drugs that depress ventilation, prolong recovery, or hamper postoperative assessment. Therefore, with one exception (see later discussion), do not give heavy sedative premedication to those undergoing craniotomy. If IV access has not been established, topical local anesthetic will facilitate pain-free insertion. Some children may benefit from a small dose of midazolam to calm them before surgery, but they should be closely observed. Children with normal ICP who are undergoing elective or noncranial surgery (e.g., laminectomy) may be given the usual dose of oral midazolam before anesthesia.

Induction of Anesthesia

Management during induction of anesthesia should aim to minimize changes in ICP and fluctuations in arterial and venous pressures.

Gentle preoxygenation followed by an intravenous induction using thiopental or propofol, and then a muscle relaxant to facilitate tracheal intubation and ensure optimal ventilation, is preferred. Lidocaine (1 to 1.5 mg/kg IV) and fentanyl (2 to 5 µg/kg) may be given 3 minutes before intubation to minimize changes in ICP associated with laryngoscopy and tracheal intubation.

Anesthesia for children with vascular anomalies should be induced as above but should then be deepened with an inhalation agent using gentle controlled ventilation to prevent hypercapnia. The blood pressure during induction is carefully monitored to prevent hypertension.

Some children undergoing emergency surgery have a full stomach and should have a rapid sequence induction using succinylcholine or high-dose rocuronium (1.2 mg/kg) with all precautions to prevent regurgitation and aspiration.

For surgery in the prone position, for small infants, and for any procedure that entails changes in position, a nasotracheal tube is preferred. (An orotracheal tube may kink in the prone patient or become dislodged if saliva loosens the adhesive tape; a nasotracheal tube is easier to secure firmly and accurately in the infant). Alternately, in older children use a reinforced oral tube, secure this firmly using tape and benzoin, and limit drooling with glycopyrrolate and a soft throat pack in the mouth. Be alert and always check ventilation bilaterally after the child is positioned; remember that flexion of the head (as in posterior fossa surgery) pushes the tip of the tracheal tube towards the carina whereas extension pulls the tracheal tube cephalad. ( N.B. To prevent an endobronchial intubation after positioning prone, flex the neck after the tube is taped but while the child is still supine. If wheezing or an endobronchial intubation is detected, withdraw the tube and retape.)

Sudden preoperative apnea may occur in neurosurgical patients awaiting operation and may indicate acutely increased ICP. If this occurs, hyperventilate the lungs with 100% oxygen and advise the surgeon to tap the CSF immediately.

Maintenance

Inhalational anesthetics may increase CBF; therefore they should be used in the smallest concentrations compatible with adequate anesthesia and should be accompanied by muscle relaxant drugs and mild-moderate hyperventilation. Otherwise, N ₂ O together with short-acting opioids (e.g., fentanyl, remifentanil, sufentanil), which ensure rapid postoperative recovery, may be preferred. Deep anesthesia is unnecessary. Propofol infusions may be a useful alternative in some children, particularly toward the end of a prolonged procedure when other drugs have been discontinued to provide for rapid emergence.

Ventilation

Controlled hyperventilation is used to decrease brain bulk and ICP during intracranial surgery and to improve the quality of cerebral arteriograms during neuroradiology. A PaCO ₂ approximately 30 to 35 mm Hg is preferred during controlled ventilation.

Monitoring

The child should be monitored as follows:

• 1.
  

  Esophageal stethoscope, pulse oximeter, automated BP cuff.

  
  
• 2.
  

  Continuous recording of body temperature (esophageal or rectal).

  
  
• 3.
  

  ECG.

  
  
• 4.
  

  PetCO ₂ monitor; this is useful both as a guide to the adequacy of ventilation and as a means of detecting air embolism.

  
  
• 5.
  

  For major neurosurgery, arterial and central venous access should be considered. Arterial access is useful to assess rapid fluctuations in blood pressure because of traction on neural tissues, blood loss or air embolism and for laboratory testing. Central venous access will help assure a stable circulating blood volume, provide a means for administering vasoactive drugs (dilator or inotrope) and provide a possible means for aspirating embolized air. Central venous access is best sited in the subclavian (or femoral) vein to prevent misleading readings and occluding neck/intracranial veins. Rapid blood transfusions should not be given into CVP lines in small infants as cold, hyperkalemic blood may lead to cardiac arrest.

  
  
• 6.
  

  Measurement of urinary output via catheter, during all major neurosurgery and if diuretics will be given.

  
  
• 7.
  

  A precordial Doppler flowmeter should be used for operations when air embolism is a danger. This includes those performed with the child in the sitting or head-up position and all major cranial reconstructions (including cranioplasty for craniosynostosis). The Doppler probe should be placed over the right atrium (second right interspace adjacent to the sternum).

  
  
• 8.
  

  If neurophysiologic monitoring is planned (SSEPs, MEPs), or EEGs, ensure that the anesthetic prescription is consistent with producing optimal signals. Important considerations are:

  
  
  
  
  • a.
    

    The depth of anesthesia should remain constant if sequential recordings are to be compared. Ventilation (PaCO ₂ ) and oxygenation should remain constant.

    
    
  • b.
    

    Body temperature should remain constant.

    
    
  • c.
    

    Opioids do not affect neurophysiologic monitoring.

    
    
  • d.
    

    Nitrous oxide has little effect on latency of SSEPs but depresses the amplitude; it is contraindicated for MEPs.

    
    
  • e.
    

    Inhalational anesthetics generally increase latency and depress amplitude of SSEPs; they are limited to ≤ 0.5 MAC for MEPs.

    
    
  • f.
    

    Propofol, ketamine, midazolam, and α ₂ -agonists exert little effect.

    
    

    In practice, a prescription using 0.5 MAC of an inhalational agent in an oxygen/air mixture, an opioid infusion (remifentanil or sufentanil), midazolam, and a propofol infusion provides acceptable conditions for monitoring both SSEPs and MEPs. For SSEPs, muscle relaxants may also be used, whereas for MEPs, muscle relaxants must be avoided after tracheal intubation. We prefer succinylcholine, or cis-atracurium for tracheal intubation when MEPs are planned. If remifentanil is used, be certain to administer a long-acting opioid to control postoperative pain before discontinuing the remifentanil.

  
  

Strategies for Intravenous Fluid Therapy

A very reliable intravenous cannula is essential for children undergoing neurosurgery; at least 22- or 20-gauge cannulas for infants and 18-gauge or larger cannulas for older children. Small infants undergoing major surgery should have at least two large and well-secured IV routes. (Exsanguination during neurosurgery in small infants happens!)

Control of ICP and Reduction of Brain Volume

Most important in the conduct of neuroanesthesia is to ensure that the surgeon has absolutely optimal intracranial operating conditions. This can be ensured as follows:

• 1.
  

  Prevent any episodes of hypoventilation or hypoxemia, coughing or straining, during induction of anesthesia.

  
  
• 2.
  

  Provide a clear, unobstructed airway at all times as increases in intrathoracic and airway pressures are directly transmitted to the CNS. The largest tracheal tube that will pass easily should be used. It should be positioned so that there is no possibility of kinking or compression. Reinforced tubes should be used where applicable. Monitor airway pressures.

  
  
• 3.
  

  Provide mild hyperventilation to a PaCO ₂ of approximately 30 to 35 mm Hg.

  
  
• 4.
  

  A slight head-up tilt is preferred (15°). The veins in the neck should be totally unobstructed, avoid significant neck rotation.

  
  
• 5.
  

  Administer furosemide 0.5 mg/kg IV followed by mannitol 20% (0.5 to 1 g/kg) infused over 20 to 30 minutes as the skull is being opened (or as requested by the neurosurgeon).

After administering a diuretic, the schedule of fluid therapy also depends on the urine output. When urine volume equals 10% of the estimated blood volume (EBV), further urine losses are replaced (volume for volume) with normal saline. Alternatively, fluid administration can be guided by the CVP; maintaining a constant CVP generally indicates a stable circulating blood volume. Subsequently, serum electrolyte determinations should be made to exclude abnormalities and guide replacement.

Blood Replacement

Because blood loss during neurosurgery cannot be measured accurately, it must be gauged clinically from observation of the amount of bleeding and measurement of the child’s cardiovascular indices. The systolic BP must be monitored as it is the most valuable guide to volume status; fluid replacement should maintain it at 60 mm Hg in infants and 70 to 80 mm Hg in older children. ( N.B. The latter may lose up to 20% of EBV without a significant decrease in blood pressure). When surgery is complete but before the dura is closed, sufficient colloid or crystalloid are given to return the arterial pressure to the preblood loss level. The decision to transfuse blood is based on determination of the hematocrit together with clinical judgment of the blood losses occurring in relation to the allowable blood loss.

If a major blood transfusion has occurred, particularly in small infants, serum Ca ⁺⁺ may decrease. Hypotension unresponsive to further volume replacement should be treated with parenteral calcium gluconate or chloride. Assess coagulation indices and replace clotting factors as indicated.

Controlled Hypotensive Techniques

Controlled hypotensive anesthesia is rarely used in children but may be indicated for resection of a large AVM or aneurysm. An arterial line is essential if controlled hypotension is planned. A safe range of mean arterial pressure in the supine position is 50 to 65 mm Hg in children up to 10 years of age and 70 to 75 mm Hg in older children. If the child is positioned head-up, the arterial transducer must be zeroed at the level of the head so as to accurately reflect cerebral perfusion pressure.

Air Embolism

Air embolism is a particular hazard when surgery is performed with the child in the sitting position, but it may also occur when the child is prone or supine if the head is elevated. It is relatively common during craniosynostosis surgery and has also occurred during laminectomy. Air may be drawn in rapidly if a venous sinus is entered, or it may trickle in through veins within the bone. Air embolism detected by Doppler ultrasonography has a similar incidence in children and in adults, but is more likely to produce cardiovascular instability in children.

Embolism most often occurs during opening of the skull, but may also occur at the time of skin closure when the skin clips are removed. The signs, in order of decreasing sensitivity, include:

• 1.
  

  Changes in Doppler ultrasound over the precordium or appearance on transesophageal echocardiogram

  
  
• 2.
  

  Sudden decrease in EtCO ₂ (or increase in end-tidal nitrogen level)

  
  
• 3.
  

  Hypotension

  
  
• 4.
  

  Change in heart sounds (windmill murmur or muffled/muted heart tones)

Early diagnosis and rapid therapy are required to prevent a serious outcome.

• 1.
  

  Inform the surgeon, who will compress and/or flood the wound with saline to prevent the entrainment of further air.

  
  
• 2.
  

  Lower the head; this increases the venous pressure at the wound and augments venous return from the legs. If the child is prone but in a head holding device thought should be given to covering the wound, releasing the head and turning the child supine so as to be able to perform chest compressions if needed.

  
  
• 3.
  

  Compress the jugular veins in the neck.

  
  
• 4.
  

  Ventilate with 100% O ₂ , discontinue N ₂ O to prevent further expansion of air emboli within the bloodstream, and add 5 to 10 cm H ₂ O PEEP.

  
  
• 5.
  

  Attempt to aspirate air via the central venous catheter; this is successful in fewer than 60% of cases.

  
  
• 6.
  

  Initiate cardiopulmonary resuscitation and other measures (e.g., inotropes) as required. N. B. measureable expired carbon dioxide indicates the adequacy of chest compressions.

Postoperative Considerations

All children should be fully recovered from the effects of anesthetic drugs and awake at completion of the procedure. Extubation should be smooth, without coughing or bucking; this can be facilitated by giving lidocaine 1.5 mg/kg IV. If the child remains unresponsive or respirations are depressed, leave the endotracheal tube in place and control ventilation until the cause is determined. After some major neurosurgery, it may be preferable to continue controlled ventilation into the postoperative period and extubate the trachea later, particularly if the surgery was in proximity to structures that control ventilation.

Postoperative nursing care should include routine monitoring of neurologic signs. The fluid status should be carefully monitored because regulatory mechanisms (i.e., antidiuretic hormone levels) may be altered after craniotomy. Often a brief CT scan is performed immediately postoperatively to assess the success of the surgical procedure.