cns anatomy & physiology author: joe brierley may 2006 … · anatomy: • central nervous...

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CNS Anatomy & Physiology Author: Joe Brierley May 2006 Updated: Nicole Mettauer & Christine Pierce May 2007 Associated clinical guidelines/protocols:

• Head injury guideline • Status epilepticus guideline • Encephalitis guideline

Fundamental Knowledge: List of topics relevant to PIC that will have been covered in membership examinations. They will not be repeated here. Anatomy:

• Central nervous system anatomy – structural components of the brain, spinal cord, ascending and descending pathways, subarachnoid and extradural space

• CSF and its circulation • Cerebral and spinal cord blood supply. • The blood brain barrier. • Cranial nerve anatomy and distribution of innervation. • Sympathetic and parasympathetic nervous system • Dermatomes • Development of myelination

Physiology:

• Functions of nerve cells: action potentials, conduction and synaptic mechanism • Cerebral metabolism: preferred fuels • Developmental assessment • Physiology of the neuromuscular junction • Physiology of central neurotransmission • Autonomic nervous systems: functions and neurological reflexes. • Effect of sympathetic and parasympathetic blockade • Receptors for nociception • The blood brain barrier: causes of disruption • Pupillary changes • Fundoscopy • Motor examination

Disclaimer: The Great Ormond Street Paediatric Intensive Care Training Programme was developed in 2004 by the clinicians of that Institution, primarily for use within Great Ormond Street Hospital and the Children’s Acute Transport Service (CATS). The written information (known as Modules) only forms a part of the training programme. The modules are provided for teaching purposes only and are not designed to be any form of standard reference or textbook. The views expressed in the modules do not necessarily represent the views of all the clinicians at Great Ormond Street Hospital and CATS. The authors have made considerable efforts to ensure the information contained in the modules is accurate and up to date. The modules are updated annually. Users of these modules are strongly recommended to confirm that the information contained within them, especially drug doses, is correct by way of independent sources. The authors accept no responsibility for any inaccuracies, information perceived as misleading, or the success of any treatment regimen detailed in the modules. The text, pictures, images, graphics and other items provided in the modules are copyrighted by “Great Ormond Street Hospital” or as appropriate, by the other owners of the items. Copyright 2004-2005 Great Ormond Street Hospital. All rights reserved.

Great Ormond Street Hospital Modular ITU Training Programme 2006-2007


Information for Year 1 ITU Training (basic):

Year 1 ITU curriculum Physiology:

• Cerebral perfusion: range of autoregulation, causes of disruption of autoregulation. Effect of pH, CO2, hypoxia on cerebral perfusion.

• Diagnosis and management of syndromes causing electrolyte disturbances: SIADH, cerebral salt wasting syndrome and diabetes insipidus

• Assessment of mental status: GCS Investigations:

• CSF examination. Indications and contraindications for lumbar puncture in the ITU. Interpretation of results.

• EEG: recognize and know the significance of burst suppression, spike & wave, isoelectric. The typical findings in herpes encephalitis. Use of continuous EEG to guide drug dosing levels in induced barbiturate coma.

• Intracranial pressure monitoring.

Curriculum Notes for Year 1: Physiology Cerebral perfusion physiology The brain is only able to withstand very short periods of ishaemia. Thus cerebral blood flow must be maintained to ensure constant delivery of oxygen and glucose. Maintenance of cerebral blood flow (CBF) depends on a balance between intracranial pressure (ICP) and mean arterial blood pressure (MAP). Autoregulation ensures that CBF remains constant.

Intracranial Pressure Normal ICP values are estimated at 2-6 mmHg for infants and 3-7 mmHg for young children. The normal ICP for older children and adults is 0-10 mmHg. Intracranial hypertension (ICP) is defined as an ICP > 20 mmHg for more than 5 minutes. Signs and Symptoms of increasing Etiology of increased ICP based on acute intracranial pressure insult

(1)Macroux K. AACN Clinical Issues, 2005;16:212-213



High ICP will cause herniation of the brain, distortion and pressure on cranial nerves and vital neurological centres. Cerebral perfusion will be impeded. The principle constituents within the skull are brain (80%), blood (10%) and CSF (10%). The total volume is 1600ml. When there is an increase in any one of these components, one or more of the other components must decrease to keep the total volume the same. The blood and the CSF are the only compartments that can compensate. Therefore if intracranial pressure rises the CSF and blood volume will decrease until they can no longer compensate, at which point the ICP will increase.

The pressure changes within the skull are drawn in the classical curve Fig. 2 which indicates an increase in volume with little change in pressure until a certain point is reached when a further small change in volume results in a large increase in pressure: 1-2 compensation phase; 3-4 decompensation phase.

Walters F, Intracranial Pressure & Cerebral Blood Flow http://www.nda.ox.ac.uk/wfsa/index.htm

The volume of blood contained within the venous sinuses is reduced to a minimum as part of the compensatory process. However, should free flow of venous blood be impeded by a number of simple causes ( Table 1), then this increase in volume of the venous system in a critically swollen brain will lead to a rapid rise in ICP. In practice, it is imperative to ensure that when the patient is in the supine position that a head up tilt to a maximum of 30° is obtained. This improves venous drainage with minimal effect on arterial pressure [2]. Venous drainage is passive and thus maximised by ensuring there is no pressure on, or kinking, of the neck veins. In addition the higher the head, the greater the effect of gravity on the flow of venous blood. However, as the head is raised, the gravitational effect on the arterial pressure at the brain is also increased. This is a disadvantage as it reduces the pressure of blood perfusing the brain. The best compromise is the position described above of 30°.

Table 1: Non-Pathological Causes of Raised ICP

Increased venous volume

Coughing Obstructed airway Head- down position Obstructed neck veins

Avoid Hypotonic IV solutions 5% dextrose, dextrose- saline, Hartmann's solution Cerebral oedema

Use 0.9% Normal saline

Increased CBF Anaesthetic drugs


Cerebral perfusion pressure (CPP) CPP = MAP − ICP MAP- mean arterial pressure, ICP- intracranial pressure Cerebral perfusion pressure (CPP) used as measure of adequacy of brain blood supply. Inadequate CPP has been shown to be a major factor in the poor outcome of patients with raised ICP. Target values in children are not well established but a level of <40mmHg should be avoided at any age. For adults a minimum target of 70mmHg is advised. At GOS the following minimum CPP values are recommended: Adequate CPP varies with age; 1m - 1y > 40mmHg 1y - 4y > 50mmHg 5y - 8y > 60mmHg 8y and over > 70mmHg



Adequate MAP varies with age; 1m - 1y 45 - 70mmHg 1y - 4y 50 - 100mmHg 5y - 12y 60 - 90mmHg 12y and over 65 - 95mmHg Cerebral blood flow (CBF) CBF is a function of the pressure drop across the cerebral circulation divided by the cerebral resistence, as predicted by Ohm’s law: CBF = (CAP − JVP) CAP- carotid artery pressure, JVP- jugular venous pressure

CVR CVR- cerebrovascular resistence

The normal cerebral blood flow in an adult is 50-70 ml 100g-1 min-1, and CBF of healthy children was found to be as high as 108 ml 100g-1 min-1. CBF <20 ml 100g-1 min-1 is usually indicative of cerebral ischemia and has been associated with poor neurological outcome. There are two essential facts to understand about cerebral blood flow. Firstly, in normal circumstances when the flow falls to less than 18-20ml 100g-1 min-1, physiological electrical function of the cell begins to fail. Secondly, an increase or decrease in CBF will cause an increase or decrease in cerebral arterial blood volume because of arterial dilatation or constriction. Thus, in a brain which is decompensated as a result of major intracranial pathology, increases or decreases in CBF will in turn lead to a significant rise or fall in ICP. The physiological factors which can alter CBF and hence ICP are listed in Table 2. There are also a number of drugs, which can induce arterial dilatation (e.g.volatile agents).

Table 2: Physiological Causes of Raised ICP

Hypoxia.Hypercapnia.

Pain.Low cerebral perfusion pressure.

Exaggerated hypertension.


Autoregulation CBF usually maintained at relatively constant level by cerebrovascular autoregulation of CVR over a wide range of CPP (MAP 50 mmHg to 150 mmHg). In traumatised or ischaemic brain CBF may become blood pressure dependent. Thus as arterial pressure rises so CBF will rise causing an increase in cerebral volume and increase in ICP. Similarly as pressure falls so CBF will also fall, reducing ICP, but also inducing an uncontrolled reduction in CBF.

However there is some data showing that following trauma autoregulation may still be functioning (2).

In this situation if CPP falls below the critical value, the patient will have inadequate cerebral perfusion. Autoregulation will cause cerebral vasodilatation leading to a rise in brain volume. This in turn will lead to a further rise in ICP and induce the vicious circle described by the vasodilatation cascade (fig 3a), which results in cerebral ischaemia.



This process can only be broken by increasing the blood pressure to raise CPP, inducing the vasoconstriction cascade (fig 3b). This explains why the maintenance of arterial blood pressure at adequate level by careful monitoring and rapid correction if it falls is so important.


Carbon dioxide (CO2) Carbon dioxide causes cerebral vasodilation. As the arterial tension of CO2 (fig 4) rises, CBF increases and when it is reduced vasoconstriction is induced.

Thus hyperventilation can lead to a mean reduction in intracranial pressure of about 50% within 2-30 minutes. When PaCO2 is less than 25 mmHg (3.3kPa) there is no further reduction in CBF. Therefore there is no advantage in inducing further hypocapnia as this will only shift the oxygen dissociation curve further to the left, making oxygen less available to the tissues. *


Acute hypocapnic vasoconstriction will only last for a relatively short time (5 h). While hypocapnia is maintained, there is a gradual increase in CBF towards control values leading which will lead to cerebral hyperaemia if the PaCO2 is returned rapidly to normal levels. When long term ventilation is required, normocapnis should be maintained. Chronic systemic hypertension Remember in chronic systemic hypertension (rare in children) ⇒ altered autoregulation setpoints

• SO rapid ↓ BP (even to ‘normal range’)can ⇒ can induce ischaemia in chronic HT

Diagnosis and management of syndromes causing electrolyte disturbances: SIADH, cerebral salt wasting syndrome and diabetes insipidus Hyponatremia is a common finding in patients with acute cerebral insults. The main differential diagnosis is between SIADH (syndrome of inappropriate antidiuretic hormone secretion) and CSW (cerebral salt wasting). Identical acute cerebral insults may cause either SIADH or CSW. The clinical and biochemical manifestations of both conditions can be virtually identical and the only discriminative feature is the status of extracellular volume (3). It tends to be expanded in SIADH and low in CSW. A practical approach of evaluating blood volume would be using either central venous pressure or radioisotope dilution techniques (not really clinically feasible).

SIADH

- Inappropriate elevation of ADH which causes free water retention Criteria for diagnosis

- hyponatraemia - low plasma osmolality with inappropriately high urine osmolality >100 mosmol/kg - urine to plasma osmolality ratio >1 - urine sodium excretion >20mmol/l - plasma renin activity suppressed - urine volume normal or decreased - body weight stable or increased - expanded extracellular volume → oliguria with or without weight gain indicates the diagnosis of SIADH → assess volume status with CVP measurements if CVL in situ



Treatment

- correction by fluid restriction - in symptomatic hyponatraemia partial correction by infusion of hypertonic 3% saline

at 1-2ml/kg/h (0.5 to 1 mmol/kg//h) for 2-3h - thereafter limit rate of correction to <0.5 mmol/l/h (12mmol/l/day)

CSW

- Salt-wasting is the primary defect with the ensuing volume depletion leading to a secondary rise in ADH release.

Criteria for diagnosis - hyponatraemia - low plasma osmolality with inappropriately high urine osmolality (as in SIADH) - urine sodium loss > 20 mmol/l (as in SIADH) - urine to plasma ratio >1 (as in SIADH) - plasma rennin high normal or raised - Urine volume normal or increased - body weight stable or decreased - extracellular fluid depletion → polyuria with or without weight loss indicates the diagnosis of CSW → assess volume status with CVP monitoring if CVL in situ

Treatment - Replace sodium and ECV deficit, but limit the rate of sodium correction to

<0.5mmol/l/h (NB In bold differences between SIADH and CSW)

Suggested approach for euvolemic hyponatraemic patients with CWS or SIADH

- Sodium supplementation and fluid maintenance - If no improvement or deterioration, assess ECV formally by CVP monitoring or

dilutional studies

Central DI After neurosurgery transient or permanent DI (diabetes insipidus) can ocurr. DI may coexist with SIADH or CSW.

- deficiency of ADH - leads to polyuria with excessive urine free water (in prescence of intact thirst

sensation this will induce excessive drinking) - fluid restriction will lead to hypernatraemic hypovolemia

Biochemical characteristics - high serum sodium and osmolality - inappropriately low urine osmolality compared to high plasma osmolality - urine to plasma osmolality ratio <1.5

Treatment - Desmopressin adjusted to clinical response - Vasopressin infusion titrated against plasma and urine biochemistry and urinary

output Hyponatraemia in patients with central DI can occur due to:

- water intoxication due to desmopressin over treatment - patients on anticonvulsants → readjust desmopressin dose - cortisol deficiency → start/adjust hydrocortisone treatment - diuretic therapy inducing sodium loss → stop diuretics and reassess - coexisting CWS ( urinary sodium >20 mmol/L) - different sources of sodium loss such as renal tubulopathy/ mineralcorticoid

deficiency/ non-renal sodium losses



Assessment of mental status: Glasgow Coma Scale (GCS) GCS scored between 3 and 15. Composed three parameters - Best Eye (4), Best Verbal (5), Best Motor Response (6): Modified GCS for infants and children (1)

GCS -11 essentially meaningless so get components ie E3V3M5 = GCS 11 GCS > 13 correlates with mild brain injury, 9 to 12 moderate and < 8 -severe brain injury(4).

Teasdale G., Jennett B., LANCET (ii) 81-83, 1974.

Investigations CSF examination. Indications and contraindications for lumbar puncture in the ITU. Interpretation of results. Contraindications-surround risk of coning and other side effects ie bleeding (5). The temporal relation between lumbar puncture (LP) and herniation strongly suggests that LP may cause herniation in some patients, and normal results on computed tomography do not mean that it is safe to do LP in a child with bacterial meningitis. It shows a retrospective, temporal association- but nothing else in literature convinces otherwise. More recent debate on when to do a lumbar puncture(6). Our practice NO LP if:

• Clinical suspicion of raised ICP/coma ie GCS at least 12-13, if not 15 • Hypotension/hypertension • Coagulopathy /thrombocytopenia • Abnormal neurology

Even if patient sedated consider local, and don’t forget post LP precautions. • CSF

- M,C +S, glucose, protein, +/- lactate - virological test → PCR and serology : see encephalitis guidelines - liase with ALL team for oncological tests

Acute bacterial meningitis

Viral meningitis und encephalitis Tuberculosis ADEM

Appearance turbid clear turbid or clear clear

Pressure (5-15 cm H2O) increased Normal or mildly increased Normal or mildly increased

Cell count > 1000/mm3 < 1000/mm3 50-1500/mm3 < 300/mm3

Predominant cell type polymorphs mononuclear mononuclear mononuclear

Glucose (% plasma glucose) < 50% > 50% < 30% > 60%

Lactate > 3,5 mmol/l < 3,5 mmo/l > 3,5 mmol/l < 3,5 mmol/l

Protein > 1000 mg/l < 1000 mg/l > 1000 mg/l < 1000 mg/l

Sheldon L, cerebrospinal fluid analysis in CNS infection, http://www.utdol.com/utd/login.do



EEG: burst suppression, spike & wave, isoelectric, herpes encephalitis. Use of continuous EEG to guide drug dosing levels in induced barbiturate coma. EEG linked to cerebral metabolism, so highly sensitive indicator of cerebral dysfunction. 4 main uses on PICU:

1. Diagnosis 2. CNS monitoring 3. Therapy guidance 4. Prognosis

1. Diagnosis • EEG assists diagnosis in encephalopathic or comatose patients. Distinguishes

apparent coma from psychogenic coma (eyes firmly shut, resistant to opening with normal motor tone and reflexes) or locked-in syndrome (total paralysis below the level of the 3rd nerve nuclei usually due to infarction of the ventral pons and efferent motor tracks). In psychogenic coma and locked-in syndrome the EEG has normal awake pattern.

• Helps define depth and cause of toxic-metabolic encephalopathies and may indicate specific aetiology

• e.g excessive fast activity in sedative-hypnotics overdose • triphasic waves in hepatic dysfunction or less commonly in renal failure and

anoxia • Herpes Simplex encephalitis - characteristic periodic sharp waves localized to

temporal lobe if early EEG. Paroxysmal lateral epileptiform discharges are pathognomonic for HSV encephalitis.

• Useful in identification of non-convulsive status eg if cause of acute confusional state/coma not apparent and no clinical seizures

2. Monitoring CNS

• EEG useful CNS monitor if clinical assessment not easy. It detects potential injuries at reversible stage – EEG is very sensitive to ischaemia/hypoxia and can show neuronal dysfunction at reversible point, furthermore localizes pathology.

• Abnormalities occur if CBF drops to 20-25 ml/100 g/min. As cell death occurs below 12 ml/100 g/min. EEG used in carotid/cardiac surgery to warn of critical drops in cerebral perfusion. Used in ICU with acute intracranial ischaemia/haemorrhage in which CBF precarious.

• EEG -increasing role in ICU as need to monitor CNS recognized, but complex. Methods for simplifying -include digital EEG, compressed spectral analysis, single channels EEG and topographic brain mapping -allow simplification of vast amount of complex data, easily retrieved, and rapidly reviewed even by non-neurologists! (ie us)

• Expert supervision readily available as multitude of pitfalls limit data validity. Digitalized real-time EEG best meets the current logistical challenges of ICU. Data can easily be remotely transmitted, in real-time to neurophysiology.

3. Guide therapy

• In status epilepticus EEG monitoring may help avoid under-treatment→ metabolic acidosis, rhabdomyolysis and neuronal death overtreatment → respiratory failure and CVS collapse

• Critically ill children have involuntary/semi-purposeful movements (tremors, myoclonus, spasms, and posturing) which mimic seizures and EEG can distinguish.

• EEG guidance required for barbiturate-induced "burst suppression" coma for refractory intracranial hypertension.

burst suppression is a high amplitude EEG pattern with intervening low amplitude activity.

burst suppression reduces cerebral metabolism and has cerebral protective effect 4. Establishing a prognosis

• Cortical and subcortical integrity can be assessed. Normal/near-normal EEG suggests favorable outcome Sleep activity/reactivity to stimuli - generally favorable indicators



Isoelectric pattern or burst suppression pattern -grave significance • Very sensitive to clinical deterioration – limited by lack of specificity

Hypothermia/sedative medications can mimic grave prognostic pattern Prognostic value ⇑ if

- aetiology known - EEG performed - at least six hours after injury - sedative medications minimal - abnormalities persist on serial recordings

Intracranial pressure monitoring Current ICP devices can be placed in either epidural, subdural, subarachnoid, intra-parenchymal or intraventricular location. Intraventricular drains are considered to be the “gold standard” for measuring ICP and have to be placed surgically into the ventricular system and affixed to a drainage bag and pressure transducer. These ventricular catheters enable therapeutic CSF drainange in event of intracranial hypertension and instillation of selected medication (e.g. antibiotics or thrombolytic agents). There is a risk infection (10%) and a small risk of haemorrhage during placement. Our current standard is subarachnoid bolt- the main reason being that these devices are very easy to place and have a low risk of infection and haemorrhage. The bolt is a hollow screw that goes through the skull abutting the dura. The dural membrane is perforated allowing CSF to fill the bolt, and their pressures to become equal. Then the closed fluid tubing transmits the pressure in this space. These devices are less accurate than intraventricular drains and may be prone to errors including ICP underestimation, misplacement of the screw and occlusion by debris. Exhaustive review attached (7) Basis of most of what we term ‘Neuro-ICU’ evidence base is not absolute Full series on Neuro PICU in Peds CCM (8) And selected papers referenced below. Other sources of information: Websites Brain trauma foundation:-http://www.braintrauma.org/ Peds CCM file book is great resource: http://pedsccm.wustl.edu/FILE-CABINET/File_cab_index.html http://bmj.bmjjournals.com/cgi/content/full/316/7136/1015 Brasher W, Elevated intracranial pressure in children. :Available online at: http://www.uptodate.com. Walters F, Intracranial Pressure and Cerebral Blood Flow , © World Federation of Societies of Anaesthesiologists: http://www.nda.ox.ac.uk/wfsa/index.htm References. (1) Macroux K, Management of increased intracranial pressure in the critically ill child with an acute neurological injury, AACN Clinical Issues, 2005;16:212-213 (2) Bourma GJ, Muizelaar JP, Handoh K & Marmarou A. Blood pressure and intracranial pressure – volume dynamics in severe head injury: relationship with cerebral blood flow. J Neurosurgery 1992; 77: 15-19 (3) Management of hyponatraemia in patients with acute cerebral insults. Albanese et al. Arch Dis Child 2001;85:246–251 (4) Teasdale G., Jennett B., LANCET (ii) 81-83, 1974. (5) Rennick G, Shann F, de Campo J. Cerebral herniation during bacterial meningitis in children. BMJ. 1993 Apr 10;306(6883):953-5 (6) Riordan and Cant . Archives of Disease in Childhood 2002;87:235-237 (7) Jun et al Neurological Research. 2003 (8) Pediatr Crit Care Med 2003 Vol. 4, No. 3 (Suppl.), (9) Chapter 5. Indications for intracranial pressure monitoring in pediatric patients with severe traumatic brain injury (10). Chapter 7. Intracranial pressure monitoring technology. IBID



Information for Year 2 ITU Training (advanced):

Year 2 ITU curriculum Physiology:

• Drugs affecting cerebrovascular resistance/dilation- α-adrenergic drugs have little effect.

Investigations:

• SSEVP & BAEVP: Indications and prognostic significance. • EMG and bulbar EMG: Indications and interpretation • Cerebral blood flow – angiography, SPECT scans, jugular venous saturations.

Indications, limitations and complications.

Curriculum Notes for Year 2: Physiology Drugs affecting cerebrovascular resistance/dilation - α-adrenergic drugs have little effect.

ITU drugs Inhalational Agents Anaesthetic agents reduce neuronal function and so depress metabolic demands. This mechanism reduces CBF. On the other hand volatile anaesthetic agents cause direct cerebral vasodilatation. The overall effect therefore is a rise in CBF. The consequence is an increase in arterial volume and increase in brain volume and therefore ICP rises. Two other physiological mechanisms may influence ICP when using volatile agents. Firstly the normal autoregulatory mechanism is gradually abolished as the concentration of the volatile agent is increased, CBF becoming blood pressure dependent. Thus as blood pressure rises, CBF increases and cerebral vasodilation occurs. In contrast when blood pressure falls, there is no mechanism to sustain flow by reducing cerebrovascular resistance (fig 2).

Effect of a progressively increased dose of a volatile anaesthetic agent on CBF autoregulation.


Secondly the volatile agents also affect the CO2-CBF relationship, the curve being shifted to the left. Hypocapnia is still able to reduce cerebral blood flow and therefore to oppose the vasodilation. However if CO2 is allowed to rise, there is a much more rapid increase in CBF (fig 3).

Effects of anaesthetic agents on the CBF-CO2 response curve. Curves indicate the effects of carbon dioxide (CO2) and volatile agents. The slope of the thin line indicates that CBF-CO2 sensitivity is increased with agents, which increase CBF, such as volatile agents.




Halothane and Isoflurane • ⇑ CBF - dose-dependent manner due to vasodilatation, extent related to cerebral

metabolic state pre-administration • ⇑ CBF seen cf. nitrous oxide, which in its own right ⇑ CBF • Regional differences

• halothane predominantly ⇑ neocortical CBF • isoflurane ⇑ subcortical CBF

• In a dose-dependent manner a reduction of cerebral autoregulation and CO2 reactivity (however cerebral autoregulation is maintained < 1 MAC)

• In prescence of cerebral swelling these agents produce rises in ICP!! Isoflurane is used in neuroanaesthsia despite increasing ICP due to its ability to reduce cerebral metabolic rate and as it causes less vasodilation than other volatile agents. By hyperventilating to induce hypocapnia you can prevent some of the vasodilatory effects. Sevoflurane

• Newer volatile agent • CBF effects very similar to isoflurane, although slightly less vasodilation • Autoregulation in humans maintained up to 1.5 MAC • Rapid recovery following surgery due to low blood:gas solubility

Nitrous Oxide

• used as carrier gas and for its analgesic effects • causes signigicant increase in CBF acting synergistically with volatile agents • increase in CBF in combination with volatile agent is greater than simply increasing

volatile agent to provide same MAC • direct acting potent cerebral vasodilator mechanism • does not alter cerebral metabolism

Intravenous Agents

• Dose-dependent ⇓ CBF coupled with reduction in cerebral metabolism (exception ketamine)

• Once maximal suppression of metabolism occurs, no further reduction in CBF occurs Barbiturates

• Barbiturates reduce CBF and cerebral metabolism ⇒ maximal 50% reduction ⇒ leads to fall in ICP which is used therapeutically

• remember that barbiturates cause hypotension which will lead to fall in CPP • CO2 reactivity maintained but quantitatively ⇓ cf. awake response • Cerebral autoregulation maintained intact • Mechanism ⇓ CBF not fully understood -In vitro studies

- low doses - vasoconstrictor and vasodilator - higher doses -vasodilation, mechanism endothelium independent - ? membrane changes → altered agonist affinity and/or changes Ca influx

Opioids.

• Low doses -little effect on CBF if CO2 is not allowed to rise. • ⇑ doses result small ⇓ CBF ? secondary to ↓ metabolic rate. • Autoregulation remains intact, therefore with ↓ BP, vasodilation occurs to maintain

CBF and this ⇑ CBF and thus ICP. • ? accounts for controversy RE opioids ⇑ ICP

Excellent review of all this at (1)



Investigations

SSEVP & BAEVP: Indications and prognostic significance

SSEPs (somatosensory evoked potentials)

• series of potentials recorded from brainstem and cerebral cortex after peripheral nerve stimulation eg median. Assesses larger portion of nervous system cf BAER, negligibly affected by sedatives.

• Greater prognostic cf BAER's - assess both brainstem and cortical function. Absent bilateral cortical SSEP's is reliable marker of widespread cortical necrosis; excellent prognostic test for persistent vegetative state.

• Normal SSEP's -reassuring + encourage aggressive treatment cf normal BAER's (not predictive)

BAEVPs (brain auditory evoked potentials)

• Collection of waveforms produced by central auditory pathway - highly resistant to sedation and neuromuscular block.

• Limited prognosis role as only assess central auditory pathway, not cortical function so in severe cortical injury you can get normal BAER's.

• Must have normal peripheral auditory pathway! • All other settings absent BAER's indicate severe structural brainstem pathology and

strong prediction of a poor outcome.

Summary SSEPs best overall predictor of outcome while motor and pupillary responses have advantages in some specific areas. Routine SSEP’s should be considered in prediction of outcome of severely brain-injured patients.(2) Prediction of neurological outcome Reliable and early prediction difficult yet vital especially with HIE

• Aim – to distinguish hopeless cases (ICU is expensive and futile) from where aggressive treatment may ⇒ reasonable outcome.

• Ideal predictor - objective, reproducible, non-invasive, portable, independent of therapies, and be accurate with negligible false negatives.

⇒ EEG and evoked potentials have many of these attributes EMG and bulbar EMG: Indications + interpretation

• Electromyography (EMG) is the clinical study of the electrical activity of muscle fibers individually and collectively. The desired goal of EMG analysis is the characterization of a disease process as neurogenic or myopathic, or normal. This electrical activity is recorded via surface or needle electrodes and is evaluated during needle insertion, rest (spontaneous activity), and during periods of voluntary muscle contraction.

• Neuropathic disorders: fewer voluntary motor units available to respond to central drive. The surviving motor units are larger than normal, hence the amplitude ⇑.

• Myopathic disorder: total number of units same, but the force generated by individual motor unit is reduced, so that more motor units must be activated and motor unit firing rate must be increased in order to produce constant force level. Overall pattern similar to normal, but amplitude ⇓.

• EMG possesses great clinical value in the diagnostic work-up of symptoms such as weakness, and for the diagnosis and prognosis of neurogenic disorders and myopathies.

• EMG used in children with Guillan-Barré



Electromyography

1. At rest (spontaneous activity): a. fibrilations, b. positive sharp waves, c. fasiculation. 2. Slight effort (motor unit potentials): d. giant polyphasic, e. BSAPS (brief-small-abundant polyphasic). 3. Strong effort (interference pattern): f. full, g. reduced units, h. reduced amplitude.

Horowitz S, Electormyographie http://www.utdol.com/utd/login.do Suspicion of the below -indications for EMG -for review with interpretation see:- REF 3

(3) Basil and Jones. Neuromuscular Problems of the Critically Ill Neonate and Child Seminars in Pediatric Neurology. Vol11:2, 2004, 147-168- Review of PICU muscle weakness/ critical illness neuropathy, a problem we see, but fortunately rarely - Muscle weakness in critically ill children. REF 4



Cerebral blood flow – angiography, SPECT scans, jugular venous oxygenation saturations. Indications, limitations and complications • Resting cerebral blood flow (CBF) approximately 50ml/100g brain tissue/min • Neuronal dysfunction and injury occur as CBF decreases • Brain critically dependent on continuous delivery of oxygen and glucose to sustain

aerobic energy production Angiography • qualitative assessment of the presence and adequacy of CBF and the patency of cerebral

blood vessels • Contrast angiography — Angiography is usually performed as digital subtraction angio-

graphy (DSA). • CT and MR angiography (CTA, MRA)— noninvasive tests that are useful for the same

indications as contrast angiography. A major advantage of CTA over conventional contrast angiography is the speed and ease by which it can be obtained, often immediately after diagnostic head CT.

• Possible indications for angiography include: Evaluation of pediatric stroke. Diagnosis of vasculitis. Confirmation of large vessel stenosis that may require antithrombotic therapy for the

prevention of recurrent stroke or transient ischemic attacks. Evaluation of the vascular anatomy prior to neurosurgery or endovascular

neurointerventional therapy. • Data regarding the incidence of complications during cerebral angiography in children are

limited, but suggest that the complication rate is very low. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) provide functional assessment of the CNS mapping of brain metabolism and function.

• SPECT uses gamma ray emitting radioisotopes and a gamma camera to record data that

a computer uses to construct two- or three-dimensional images of active tissue regions. When applied to neuroimaging, SPECT relies on an injection of radioactive tracer, which is rapidly taken up by the brain but does not redistribute, e.g 99mTc labeled HMPAO (hexamethylpropylene amine oxime) and ECD (ethyl cysteinate dimer)⇒ uptake is nearly 100% within 30 to 60 seconds, reflecting cerebral blood flow (CBF) at the time of injection

• Measures regional CBF and cerebral blood volume by labelling plasma or RBCs, resolution in range of 1 cm. Not absolute quantification but available clinically + allows scanning every 2 hr

• Xenon 133 study ⇒ SPECT of inhaled or intravenous Xenon 133 used to map quantitative regional cerebral flow. Cerebral blood flow can be measured quantitatively from clearance of Xenon 133 which is rapidly cleared from brain.

• PET ⇒ detection and tomographic imaging of dual-photon positron emitting radionuclides

serves as a functional imaging modality. PET neuroimaging is based on the assumption that areas of high radioactive uptake are associated with brain activity. The flow of blood to different parts of the brain, which is believed to be correlated with brain activity, is measured using radioactive tracers, such as 15-oxygen (15-O), 18-fluorothymidine (18-F) or fluorodeoxyglucose (FDG). For practical reasons, FDG is the preferred tracer.

• PET measures regional CBF, CBV, pH, and cerebral O2 and glucose consumption. Resolution 4 mm → absolute quantification cf SPECT. PET expensive, not readily available

• Indications for SPECT and PET

Focus localization in refractory childhood epilepsy Assessment of tumor progression versus treatment effects in CNS neoplasia Evaluation of occlusive cerebrovascular disease for surgical revascularization Diagnosis of brain death



Assessment of CSF kinetics (eg, in hydrocephalus or CSF leaks) Spinal column screening (skeletal SPECT) in the evaluation of occult trauma (eg,

stress fracture), infection (eg, discitis or osteomyelitis), and neoplastic processes (eg, osteoid osteoma)

Our current standard is cerebral perfusion (SPECT) scan – often used to confirm suspicion of severe injury i.e this image of cerebral perfusion scan showing no flow, consistent with ‘brain death’ further neuroimaging modalities: Xenon-enhanced CT Xenon inhaled for 5 min then sequential CT scans. CBF is quantitated by integrating build-up of xenon within tissue and arterial blood by CT enhancement. Clears quickly rpt after 20 mins Magnetic Resonance Imaging (MRI) Extremely sensitive measure of tissue water movements and cerebral perfusion. Injection of paramagnetic contrast and arterial spin labelling → CBV, CBF and mean transit time. Spatial and temporal resolution accurate -MR increasingly used for diagnosis +follow up Transcranial Doppler Sonography (TCD) Noninvasively and continuously measures cerebral blood flow velocity (cm/s) in major basal cerebral arteries. Absolute cerebral blood flow cannot be inferred flow spectra closely reflect (relative) changes in CBF regardless of status of CBF autoregulation or cerebral metabolism. TCD used to measure changes in CBF post head injury, to detect cerebral emboli during cardiac or neurovascular surgery, and to monitor cerebral vasospasm after subarachnoid haemorrhage. Laser Doppler Flowmetry Measures relative changes in blood flow (arbitrary units). Used to assess autoregulation, CO2 reactivity, and effects of retractor pressure or ICP of tissue flow. Invasive-needs craniotomy and exposure of brain/spinal cord to place probe on neuronal tissue surface. Changes in probe position and movement artifacts ⇒ deviations from true organ blood flow. So must maintain probe in constant position. Thermal Measurement Systems Type 1) Monitors CBF - heated thermistors on cortical surface. Heat conducted into surrounding tissue dissipates at rate related to tissue perfusion. Useful for dynamic assessments during neurosurgery. Type 2) Double indicator dilution -bedside monitoring of CBF cf standard thermodilution techniques Jugular venous oxygenation saturation (SjVO2 ) monitoring SjVO2 assesses the adequacy of CBF related to cerebral metabolic demand. SjVO2 is a measurement of the oxygen saturation in the jugular vein after cerebral perfusion has occurred. The jugular mixed venous saturation is compared to the arterial oxygenation saturation ⇒ the arteriovenous oxygen content difference (AVDO2) is the caculated. Physiology The Fick equation describes the relationship between cerebral blood flow (CBF), arterial oxygen content (CaO2), venous oxygen content (CjO2) and cerebral metabolic rate for oxygen (CMRO2): ⇒ CMRO2 = CBF x (CaO2 - CjO2) ⇒CMRO2 = CBF x 1.34 x Hb (SaO2-SjO2) (assuming dissolved oxygen is negligible) ⇒ SjO2 ∝ CBF/CMRO2 (assuming Hb and SaO2 are constant)



thus SjO2 is predominantly dependent on SaO2, CMRO2 and CBF. if CMRO2 increases without increase in CBF, the A-vO2 difference rises in conjunction

with cerebral O2 extraction ⇒ decrease O2 content/saturation in internal juglar veins (IJV), as virtually all blood from brain drains into IJV

if Hb and arterial saturation remain constant, the SjVO2 indicates cerebral O2 demand

Lower limit of normal range thought to be about 50-54% with an upper limit of 75% As with all global measures of cerebral oxygenation a normal SjO2 does not exclude localized areas of cerebral ischaemia with associated areas of luxury perfusion. Interpretation

Normal SjVO2 is 55- 70% SjVO2 <55% indicates cerebral hypoperfusion SjVO2 <40% indicates cerebral ischaemia

Low SjO2 Increased brain oxygen extraction as a result of

Systemic arterial hypoxia Low CBF from hypotension, vasospasm or intracranial hypertension

Increased brain metabolic requirements due to: Pyrexia Fits (may be subclinical)

Increased SjO2 Hyperaemia Failure of oxygen extraction Grossly reduced cerebral blood flow due to high ICP with shunting of arterial blood

(pre-terminal event) Clinical uses • Part of multi-modality monitoring of brain injured patients • As a guide during hyperventilation

Although hyperventilation reduces intracranial pressure it is important that this does not occur at the expense of cerebral ischaemia. The PaCO2 at which this occurs varies between patients depending on cerebral perfusion pressure, baseline PaCO2 and other factors

Complications • Carotid artery puncture (1-4.5%) • Thrombosis (incidence of subclinical thrombosis may be as high as 40%) • Haematoma formation • Raised ICP (rare) • Infection

Catheter placement Positioned the patient horizontally or slightly head down. ICP kept < 20 mmHg. IJV cannulated in cephaled direction, either distally between SCM heads or more proximally at level of cricoid. Fibreoptic catheter advanced to jugular bulb (about 12-15cm in adults), at level of mastoid process.

Important correct position obtained to limit contamination from extra cerebral blood (3% of blood in jugular BUT there are anecdotal reports of far greater contamination).

Catheter should sit as close to roof of the jugular bulb as possible. Even 2 cm difference can → 10% contamination. Rises exponentially as tip withdrawn further.

Position of tip confirmed with Xray



• Lateral neck Xray: tip should be above disc of C1/C2 and as close to skull base as possible

• AP neck Xray -tip cranial to line extending from atlanto-occipital joint space and caudal to lower margin of orbit. Tip also lies cranial to a line connecting tips of mastoid processes.

Newer version-cf continuous SCVO2 catheters for early goal therapy in sepsis- Continuous SCVO2 in the neuro ICU – a brief review. REF 8 Near-infrared spectroscopy (NIRS) This technology utilizes light in the near infrared range to determine cerebral oxygenation, blood flow, and metabolic status of the brain. The instrument consists of fiberoptic bundles or optodes placed either on opposite sides of the head or close together at acute angles. Light enters the head through one optode and a fraction of the photons are captured by a second optode and conveyed to a measuring device. Multiple light emitters and detectors can also be placed in a headband to provide tomographic imaging of the brain. The method is based on the fact that light in the near infrared range (700 to 1000 nm) can pass through skin, bone, and other tissues relatively easily, especially in the neonatal head. It utilizes the characteristic absorption bands of oxygenated and deoxygenated hemoglobin, and the mitochondrial enzyme cytochrome oxidase (or cytochrome aa3). Cytochrome oxidase is the terminal member of the mitochondrial respiratory chain, and is necessary for conversion of ADP to ATP. It has a very high affinity for oxygen in both neonate and adult, thus reduction of cytochrome oxidase occurs only after oxygen saturation falls to very low levels and the majority of hemoglobin is deoxygenated. NIRS can provide useful information about the global as well as focal metabolic status of the brain. It can provide an early diagnosis, even within a few hours of life, of cerebral blood flow increases, energy metabolism decreases, and brain functional activity. NIRS imaging is be sensitive enough to image regional changes and gray and white matter differences in the premature and full term infant. Other sources of information: Websites http://www.nda.ox.ac.uk/wfsa/html/u09/u09_019.htm http://www.uptodate.com. References. (1)Walters FJM. Neuropharmacology - ICP and Cerebral Blood Flow. Update in Anaesthesia 1998; 9:7 (2). Carter BG, Butt W. A prospective study of outcome predictors after severe brain injury in children. Intensive Care Med. 2005 Jun;31(6):840-845: (3) Basil and Jones. Neuromuscular Problems of the Critically Ill Neonate and Child. Seminars in Pediatric Neurology. Vol11:2, 2004, 147-168- (4) Banwell et al. NEUROLOGY 2003;61:1779–82 (5) P Barnes,J Hunter. Approach to neuroimaging in children Available online (6)Friedman et al. Techniques of intraoperative cerebral blood flow measurement. (7) Neurosurg Focus 9 (5):Article 4, (8) White and Baker. CAN J ANESTH 2002 / 49: 6 / pp 623–629

cns anatomy & physiology author: joe brierley may 2006 … · anatomy: • central nervous...

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