Psychotherapeutic Drugs Lecture 5 & 6 PDF

Psychotherapeutic Drugs Psychotherapeutic drugs are described for their effects of relieving symptoms of mental illness that include Schizophrenia Mania Depression Anxiety Drugs for these disorders are Palliative i.e. alleviate without curing Psychotherapeutic D...

Psychotherapeutic Drugs Psychotherapeutic drugs are described for their effects of relieving symptoms of mental illness that include Schizophrenia Mania Depression Anxiety Drugs for these disorders are Palliative i.e. alleviate without curing Psychotherapeutic Drugs These drugs are for major mental illnesses and not for trivial indications where simpler drugs do equally as well Commencing treatment Minimise side effects Allow gradual build up to an optimal dose Treatment May be long term or intermittent depending on the severity and type of condition Compliance Psychotherapeutic Drugs Many medically used drugs can produce psychiatric symptoms at therapeutic doses (rare) and when abused. Examples Depression Methydopa (Aldomet ®), Clonadine (Catapress®) and some beta blockers e.g. propanalol (Inderal®). Psychosis, euphoria, depression Corticosteriods e.g. Betemethasone (Celestone Chronodose® inj) Confusion disorientation, depression Atropine, Benztropine Antipsychotics Antipsychotics Used primarily in the management of psychotic disorders to ameliorate abnormal behaviour, thoughts and perceptions. These medications have sedating and tranquilising effects that make them useful in severely agitated or disturbed patients Antipsychotics Amisulphride (Solian®) Olanzapine (Zyprexa®) Aripiprazole (Abilify®) Paliperidone (Invega®) Chlorpromazine (Largactil®) Pericyazine (Neulactil®) Clozapine (Clopine®) Quetiapine (Seroquel®) Droperidol (Droleptan®) Risperidone (Risperdal®) Flupenthixol (Flunaxol®) Trifluperazine (Stelazine®) Fluphenazine (Modecate®) Ziprasidone (Zeldox®) Haloperidol (Serenace®) Zuclopenthixol (Clopixol®) Classification Traditionally antipsychotics have been classified as typical or 1st generation (older) or atypical or 2nd generation (newer) Not a useful classification as both groups Similar modes of action Similar side effect profiles Older medications were classified according to chemical structure, however not helpful for the newer antipsychotics In clinical practice – termed as high potency and low potency Mechanism of action Antipsychotic action involves blockade of CNS dopamine receptors in the mesolimbic pathways All effective antipsychotics block D2 receptors. The affinity for these receptors correlates with the effective dose of the drugs Mechanism of action Many antipsychotics also block serotonin 5HT2A and 5HT2C receptors and may antagonise other receptors α1 - adrenoreceptors Histamine H1 receptors This does not effect their efficacy in psychotic illness but can produce unwanted side effects Receptor affinities of some antipsychotics Note: some older FGA show some preference for D2 over D1 Some of the newer SGA agents are highly selective for D2 Indications Acute and chronic psychosis Acute mania & maintenance of bipolar disorder Organic psychosis (e.g. dementia – associated agitation) Severe behavioural disturbances in children Tourette's syndrome & other chorea's Some other indications Adjunct in anaesthesia e.g. Droperidol Adjunct in treatment of alcoholic hallucinations e.g. Haloperidol Intractable nausea & vomiting e.g. Haloperidol, Droperidol Intractable hiccup (if non-drug treatment fails) e.g. Chlorpromazine Common adverse effects All antipsychotics have Anticholinergic effects some degree of Blurred vision anticholinergic activity EXCEPT Dry Mouth Amisulphride Constipation Aripiprazole Paliperidone Urinary hesitance or retention Risperidone Ziprasidone Sedation Orthostatic hypotension – due to the blockade if the Alpha- receptors which may lead to syncope and falls EPSE *as with all medications there are individual differences in tolerability and occurrence of adverse effects Common adverse effects http://www.uspharmacist.com/content/c/10207/?t=alzheimer%27s_and_dementia,psychotropic_disorders Common adverse effects Extrapyramidal effects (EPSE) Acute dystonia Muscle spasm of face, neck, tongue, jaw and/or hands Hyperextension of the neck & trunk, arching of the back Can interfere with walking, talking or swallowing Dystonia's include Torticollis Carpopedal spasm Trismus Perioral spasm Oculogyric crisis Common adverse effects Drug induced Parkinsonism Similar to Parkinson’s Disease Shuffling gait Drooling Tremor Increased rigidity (cogwheel) or Bradykinesia Akinesia has also been reported Usually develops after week-months of treatment Usually reversible Treated with anticholinergics or using an alternative medication Common adverse effects Akathisia Motor restlessness Person feels unable to sit/stand still, feels urgent need to move, pace, rock or tap foot Can also present at apprehension, irritability & general uneasiness Often confused with worsening agitation More common in females Usually occurs 2-3 days (up to several weeks) after starting treatment and may subside spontaneously Common adverse effects Tardive Dyskinesia Characterised by abnormal movements of the mouth, face, tongue Lip smacking Tongue darting, licking movements Constant chewing movements Sucking Grunting Sometimes abnormal movements head, neck trunk or limbs May appear after medium to long term treatment May be irreversible/no cure Common adverse effects Endocrine effects More common in women Due to dopamine receptor blockade – leads to  prolactin release which may cause Gynecomastia Galactorrhoea Amenorrhoea Anovulation Impaired spermatogenesis  libido Impaired sexual arousal Impotence Anorgasmia Common adverse effects Effect due to hyperprolactinaemia Dose dependent Associated with all antipsychotic drugs except Aripiprazole Clozapine Quetiapine Hyperprolactinaemia more likely with Amisulphride Paliperidone Risperidone Typical antipsychotics Common adverse effects Weight Gain Most antipsychotics can cause weight gain Especially – Clozapine, Olanzapine and Quetiapine Less in – Amisulpride, Aripiprazole, Ziprasidone http://primarypsychiatry.com/augmentation-strategies-in-the-treatment-of-major-depressive-disorder/ Common adverse effects Metabolic Syndrome Schizophrenia and other mental illnesses are an independent risk factor for diabetes Most antipsychotics increase this risk Clozapine and Olanzapine are especially associated with Abnormal glucose tolerance  Serum lipids Infrequent or rare adverse effects Neuroleptic Malignant Syndrome Rare Coarse tremor Catatonia Potentially fatal Characterised by Fever (>38oC) Marked muscle rigidity Altered consciousness Autonomic instability (tachycardia, tachypnoea, urinary &faecal incontinence  serum creatine kinase concentrations and leucocytosis Infrequent or rare adverse effects ECG changes Some antipsychotics can prolong the QTc interval which can lead to life threatening arrhythmias (torsades de pointes) Especially: Amisulphride, Droperidol, Haloperidol, Ziprasidone Certain individuals are more susceptible Age/gender (female) Left ventricular failure Recent cardio conversion Electrolyte imbalances Hypomagnesaemia Hypokalaemia Hypocalcaemia Hepatic dysfunctions https://www.kg-ekgpress.com/ecg_web_brain_DEMO_-_chapter_7_-_qt_interval/ Pharmacokinetics Most antipsychotic drugs are Highly lipophilic Highly protein bound Relationship between plasma concentration and effect is highly variable – therefore need to tailor the dose 40% non response rate Some have erratic and unpredictable absorbency Diagram shows range of peak plasma concentrations v’s dosages in 14 patients Note: one patient showed no response Pharmacokinetics Most antipsychotic drugs enter foetal circulation and breast milk, therefore should be avoided in pregnancy Neonatal side effects include Dystonic reactions Sedation Withdrawal Most have long half lives (t1/2) Dosage forms Tablets Capsules Liquid preparations Depot injections Fluphenazine (Modecate®) Haloperidol (Haldol®) Fluphenthixol (Fluanxol Depot®) Zuclopenthixol; Zuclopenthixol Acetate (Clopixol Acuphase®) Zuclopenthixol deconoate (Clopixol depot®) Parenteral Haloperidol Droperidole (Droleptan®) Chlorpromazine (Largactil®) Dosage forms Clozapine Used in treatment of patients non responsive to, or intolerant of other antipsychotics Able to relieve +ve and –ve symptoms Antagonist at D1, D2, D4 and 5HT2 receptors Cancause profound orthostatic hypotension accompanied by cardiac or respiratory failure. Therefore need medical supervision & resuscitation facilities when started Clozapine Associate with severe side effects; Blood Dyscrasias Other side effects Hyperpyrexia (5%) Nausea and vomiting Drowsiness (40% of treated people) Tachycardia Hypersalivation (can cause aspiration pneumonia) Weight gain Seizures Priapism Clozapine Precautions; Parkinson’s disease Epilepsy Respiratory failure Hypothyroidism Shock Closed angle glaucoma, increase intraocular pressure, GI obstruction Urinary retention Low WCC or previous blood abnormality Elderly require lower starting doses Anticholinergic Drugs Anticholinergic Drugs Anticholinergic drugs can be used to treat a variety of conditions. Many different types of anticholinergic drug, but they all work by blocking the action of acetylcholine, a type of neurotransmitter. Blocking this neurotransmitter inhibits involuntary muscle movements and various bodily functions. Anticholinergics are regularly used in psychiatric practice to counteract the extrapyramidal symptoms secondary to antipsychotic drugs Some extrapyramidal side effects (e.g. drug induced Parkinsonism, akinesia, dystonia) may be decreased by anti-parkinsonian drugs with anticholinergic action Anticholinergic Drugs Anticholinergic drugs block muscarinic receptors & reduce relative excess of cholinergic activity that accompanies dopamine deficiency Drugs Include Benztropine Benzhexol Biperidin Orphenadrine Antidepressants Monoamine theory of depression States that depression is caused by functional deficit of monoamine transmitters at certain sites in the brain, while mania results from a functional excess Early observations found that Depletion of monoamines NA and 5HT in the neuronal synapses of the brain cause depression Drugs that ↑ the availability of these monoamines would be effective in relieving depression Monoamines & their metabolites are reduced in depressed patients *Interestingly, the direct biochemical effect of antidepressants is rapid BUT the antidepressant effects can take weeks to develop Antidepressants Monoamine theory of depression Tricyclic antidepressants (TCAs) Monoamine Oxidase Inhibitors (MAOIs) Selective Serotonin Reuptake Inhibitors (SSRIs) Other antidepressants Duloxetine (Cymbalta®) Mianserin (Lumin®) Mirtazapine (Avanza®) Moclobemide (Aurorix®) Reboxetine (Edronax®) Venlafaxine (Efexor®) Sites of action of antidepressants Selectivity of monoamine uptake inhibitors for Noradrenaline (NA) & Serotonin (5HT) Tricyclic antidepressants Mode of action: Block amine pump i.e. block the neuronal reuptake of noradrenaline and serotonin into presynaptic terminals. Also block other receptors Alpha1 adrenergic Histaminergic Cholinergic Serotonergic Tricyclic antidepressants Indications: Major depression Nocturnal enuresis, urge incontinence Adjunct in pain management ADHD (third line treatment) Migraine prophylaxis Clomipramine also indicated for Obsessive-compulsive disorder Cataplexy associated with narcolepsy Tricyclic antidepressants Common adverse effects these appear early by therapeutic response is usually delayed Anticholinergic effects Sedation Dry mouth Due to H1 block Blurred vision Tolerance develops with time  Lacrimation Orthostatic hypotension Constipation (esp. in elderly) Due to α1 block Urinary hesitance or retention Others  GI motility Loss of libido and other sexual side effects Anticholinergic delirium Tremor Confusion Dizziness Agitation Anxiety Common adverse effects - TCAs Infrequent adverse effects - TCAs Cardiovascular effects Slowed cardiac conduction Especially in high doses T wave inversion pr flattening Arrhythmias Sinus Tachycardia Others Hyperglycaemia Gynaecomastia in males Breast enlargement & galactorrhoea in females Manic episodes TCA Overdose Cardiovascular toxicity Leading cause of death in OD Death have occurred in children with low doses TCAs have a direct cardiac depressing action similar to class 1 antiarrhythmics Cardiac toxicity & hypotension – difficult to manage ECG QRS complex is prolonged QT interval is prolonged due to prolongation of the QRS complex Withdrawal Syndrome TCAsmust be withdrawn slowly to avoid discontinuation syndrome May develop Cholinergic rebound Runny nose Hypersalivation Diarrhoea Abdominal cramping Sleep disturbances Monoamine Oxidase Inhibitors (MAOI) Include Phenelzine (Nardil®) Tranylcypromine (Parnate®) Mode of action Bind irreversibly to monoamine oxidase (enzyme), responsible for the breakdown of the biogenic amine neurotransmitters; Noradreanline Dopamine Serotonin Monoamine Oxidase Inhibitors (MAOI) Indications: Major depression (2nd Line) Some anxiety disorders (including phobic and panic disorders (2nd Line) Common Adverse effects Orthostatic hypotension Weight gain Sleep disturbances (especially insomnia – not given after 3pm) Agitation Impotence Rare Hypertensive Crisis Monoamine Oxidase Inhibitors (MAOI) The most important side effect is HYPERTENSIVE CRISIS (which may result in death) A sudden paroxysmal rise in in BP may occur It is usually associated with foods containing tyramine (or some drug interactions) The metabolism of some amine drugs e.g. Sympathomimetic drugs, is inhibited by MAOIs; may lead to a dangerous rise in BP which may lead to intracranial bleeding and death. Sympathomimetics are found in many cough mixtures and decongestants including nasal drops Phenyephrine e.g. Demazin® Pseudoephedrine e.g. Sudafed® Dextromethophan e.g. Benadryl dry® Monoamine Oxidase Inhibitors (MAOI) Foods rich in tyramine may elicit the reaction Tryamine found in many foods (Particularly foods that contain aged proteins) Matured cheese Yeast extracts e.g. Vegemite Pods and broad beans Fermented or aged foods such as salami, pate, dried sausage Red wine, beer Sour cream Soy bean extracts e.g. Tofu Causes release of certain biogenic amines in the body Since MAOIs inhibit the breakdown of the amines →↑ BP →Death Danger of interaction persists 2-3 weeks after MAOI discontinued Monoamine Oxidase Inhibitors (MAOI) Moclobemide (Aurorix®) Competitively & reversibly inhibits monoamine oxidase Not related to other antidepressants Original MAOIs act non-selectively on MAO-A and MAO-B Irreversible inhibition Moclobemide is relatively selective for type A Monoamine oxidase Moclobemide  the metabolism of Noradrenaline, serotonin & dopamine   concentrations of these neurotransmitters. Moclobemide (Aurorix®) Indications Mood disorders, panic disorders and social phobia Advantages Not sedative Low tryamine diet not usually required Relatively nontoxic in overdose & less likely to cause sexual dysfunction than MAOIs Common side effects Nausea, dry mouth, constipation, diarrhoea, anxiety, restlessness, insomnia, dizziness & headache. Selective Serotonin Reuptake Inhibitors (SSRIs) Include Citalopram (Cipramil ®) Escitalopram (Lexapro®) Fluoxetine (Lovan®, Prozac®) Fluvoxamine (Faverin®, Luvox®) Paroxetine (Aropax®) Sertraline (Zoloft®) Mode of Action Selectively block the reuptake of serotonin into presynaptic terminals. Have little affinity for dopamine, acetylcholine, histamine or adreno-receptors Selective Serotonin Reuptake Inhibitors (SSRIs) Indications Mood disorders (Major Depression) Anxiety disorders (OCD, Panic disorder) Bulimia nervosa Premenstrual dysphoric disorder Common side effects Nausea, diarrhoea, tremor, agitation, headache, sweating, insomnia, drowsiness, weight loss or gain, sexual dysfunction, rhinitis * Less cardiovascular, anticholinergic & sedating adverse effects than TCAs SSRI comparative information Selective Serotonin Reuptake Inhibitors (SSRIs) Serotonin Syndrome Serotonin toxicity due to  serotonin concentrations at synapse  hyper-stimulation of 5HT receptors Symptoms – a clinical triad of abnormalities Cognitive effects Mental confusion, hypomania, hallucinations, agitation Autonomic effects Fever, hypertension, tachycardia, nausea Somatic effects Muscle twitching, hyper-reflexia Serotonin Syndrome - (SSRIs) May occur if Changing antidepressants with inadequate ‘washout’ period High dose of single drug When more than one serotonergic agent used together Serotonin toxicity Warrants stopping implicated agent promptly May be serious Deaths have occurred Potential interactions Numerous and difficult to predict May inhibit liver cytochrome P450 enzyme that metabolises many drugs e.g. Fluoxetine inhibits CYP2D6 which effects the metabolism of metoprolol etc. Selective Serotonin Reuptake Inhibitors (SSRIs) Should not be given with reversible or irreversible MAOIs May cause serotonin toxicity If transferring from SSRI to reversible MAOI must let at least 5 half lives elapse before MAOI started Selective Serotonin Reuptake Inhibitors (SSRIs) Taper slowly over several weeks Symptoms of withdrawal Nausea Dizziness Anxiety Paraesthesia Agitation Sweating Tremor Confusion Electric shock like sensations Withdrawal symptoms more likely with Paroxetine & least likely with Fluoxetine Mianserin Indication - Major depression Tetracyclic antidepressant that shares most TCA properties Mode of action Antagonist α1-adrenergic H1 – histaminergic Serotonin receptors Has little anticholinergic effect Common side effects Sedation, dry mouth, dizziness, vertigo Can cause weight gain, blood dyscrasias (neutropenia, agranulocytosis) Mirtazapine (Avanza®, Mirtazon®) Indication - Major depression Closely related to Mianserin in structure so should be avoided in patients intolerant to Mianserin Mode of action Blocks post-synaptic serotonin 5HT2A, 5HT2c and 5HT3 receptors Blocks pre-synaptic central α2-adrenergic inhibitory receptors Common side effects Sedation, weakness, increased appetite, weight gain, peripheral oedema Reboxetine (Edronax®) Indication - Major depression Mode of action Inhibits noradrenaline reuptake Weakly inhibits serotonin reuptake Common side effects Urinary retention, insomnia, constipation, dry mouth, headache, paraesthesia,  in diastolic BP,  heart rate, sweating Venlafaxine (Efexor®) Indications - Major depression, generalised anxiety, social phobia, panic disorder Mode of action Inhibits serotonin and noradrenaline reuptake Common side effects Sweating, dizziness, anorexia, anxiety, nausea, rash, tremor, vomiting, hypertension More toxic than SSRIs in overdose – may cause arrhythmias, ECG changes & seizures, fatalities have occurred Adverse effects of Antidepressants Adverse effects of Antidepressants General Principles Evidence suggest that all are approximately equal in efficacy but response can vary markedly in patients First line drugs TCAs SSRIs Mirtazapine Moclobemide TCAs, MAOIs and Venlafaxine more toxic in overdose than other first line treatment TCAs & Mirtazapine often cause weight gain Some improvement in symptoms in 1-3 weeks but full antidepressant effect in 6-8 weeks Drugs used in Bipolar disorder Drugs used in Bipolar disorder Mood stabilisers Lithium Only specific anti-mania drug known Is drug of choice for treatment & prophylaxis of acute mania Carbamezepine, Sodium Valporate Antipsychotic drugs (may be used alone or in combination with BDZ) Note: Haloperidol, Zuclopenthixol, Olanzepine and Quetiapine approved for use in acute mania If patients unresponsive to drug treatment – electroconvulsive therapy may be useful Lithium – adverse effects Common Metallic taste Diarrhoea Epigastric discomfort Polyuria Weight gain Oedema Skin reactions e.g. acne Hypothyroidism Infrequent Nephrogenic diabetes insipidus with polydipsia and polyuria Rare Hyperthyroidism Lithium - Overdose Warning symptoms of lithium intoxication include; Extreme thirst, frequent urination, nausea and vomiting  anorexia Diarrhoea Drowsiness Ataxia Tinnitus Blurred vision Dysarthria Course tremor Treatment Not specific antidote for lithium poising Lithium treatment should be stopped and steps taken to reverse toxicity Serum levels monitored Lithium Cause of high blood levels Excessive dosage  lithium excretion  Sodium  Sodium loss – vomiting, diarrhoea, fever, Thiazide diuretics (e.g. chlorothiazide, hydrochlorothiazide) Dehydration Drug Interactions Blood levels or lithium are increased by; Thiazide diuretics, anti-inflammatory drugs and ACE inhibitors Blood levels are decreased by; Sodium salts (e.g. Sodium bicarbonate – found in indigestion medications e.g. Salvital, ural, citravescent) Hypnotics and Sedatives Hypnotics and Sedatives Medications to treat insomnia and anxiety Difficulty falling asleep or in staying asleep or disturbed sleep patterns → insufficient sleep Drug used to treat insomnia Hypnotics Anxiety may be due to A physical disorder (e.g. hyperthyroidism) or Use of legal or illicit drugs (e.g. corticosteroids, cocaine) Drugs used to treat symptoms of anxiety Anxiolytics (or sedatives) Sedatives & Hypnotics Examples Benzodiazepines Zolpidem Zopiclone Chloral hydrate Ethanol Barbiturates Sedationis a side effect of may drugs that are not general CNS depressants: Classical antipsychotics Antihistamines Gamma-Aminobutyric Acid (GABA) GABA is main inhibitory transmitter in brain Occurs fairly uniformly throughout brain tissue (very little in the peripheral tissues) Formed from glutamate by the enzyme glutamic acid decarboxylase (GAD) This enzyme is found only in GABA-synthesising neurons http://what-when-how.com/molecular-biology/gamma-aminobutyric-acid-gaba-molecular-biology/ Gamma-Aminobutyric Acid (GABA) Action of GABA is terminated mainly by uptake into the nerve terminals but also by deamination By GABA-transaminase (inhibited by Vigabatrin which is used in epilepsy) GABAA receptors are the target of a number of important centrally acting drugs including Benzodiazepine Barbiturate http://what-when-how.com/molecular-biology/gamma-aminobutyric-acid-gaba-molecular-biology/ Benzodiazepine – Mode of action Benzodiazepines Promote the binding of major inhibitory neurotransmitter GABA in the GABAA subtype of GABA receptors Bind with high affinity to an accessory site (Benzodiazepine BNZ receptor) on the GABAA receptor in such a way that they Promote the binding of GABA & Enhanced the GABA-induced ionic currents through the chloride channels http://www.arnoldgroup.org/Research-GABA%20Receptor.html Benzodiazepine – Mode of action Benzodiazepines appear to  the efficiency of GABA minergic synaptic inhibition by facilitating the frequency of opening of GABA-activated chloride ion channels Results in a  in the firing rate of critically important neurons in may regions of the brain. Benzodiazepines do not substitute for GABA i.e. they are not GABA-receptor agonist http://www.arnoldgroup.org/Research-GABA%20Receptor.html Benzodiazepines Indications Anxiety Insomnia Panic disorders Acute behavioural disturbance Seizures Muscle spasms Acute alcohol, barbiturate and benzodiazepine withdrawal Sedation procedures Comparative information Benzodiazepines can be categorised into different groups Very short acting (HL< 6 hours) Medium acting (12-24 hours) Midazolam (Hypnoval®)  Bromazepam (Lexotan®) Triazolam (Halcion®)  Lorazepam (Ativan®) Short acting (HL 6-12 hours) Long acting (HL > 24 hours) Alprazolam (Xanax®)  Clobazapam (Frisium®) Oxazepam (Murelax®,  Cloanazepam (Paxam®, Serepax®) Ribotril®) Temazepam (Normison®,  Diazepam (Valium®) Temaze®)  Flunitrazepam (Hypondorm®)  Nitrazepam (Aldorm®, Mogodon®) Benzodiazepines Withdrawal Symptoms Anxiety Insomnia Nightmares Irritability Dysphoria Sweating Hallucinations Tremors Tachycardia Hypertension Psychosis Seizures Benzodiazepines Withdrawal Symptoms Shorter acting BDZ are more likely to lead to acute withdrawal Symptoms High doses of BDZ used over a prolonged period can lead to more severe symptoms after discontinuation (agitation, depression, panic, & myalgia) Some symptoms May be similar to original complaint May continue for weeks/months BDZ best reserved for short term use 2 – 4 weeks Should be part of broader treatment plan Long term use can result in tolerance and dependence Drug seeking behaviour, craving etc. Drug interactions Additive CNS depression with drugs that act as CNS depressants; Alcohol Antihistamines Antidepressants Antipsychotics Opioid analgesics Benzodiazepine receptor antagonist In overdose BDZ → prolonged sleep, without serious depression of respiration or cardiovascular function When taken with other CNS depressants Can cause severe, sometimes life threatening respiratory depression Non-Benzodiazepine Anxiolytics Buspirone (Buspar®) Partial agonist at the 5HT1A receptor Indication - Anxiety Alternative where long term treatment is needed and BZD not desirable – less potential for dependence Concurrent use of BDZ  the efficacy of Buspirone Does not prevent BDZ withdrawal Optimal effect may take 2 weeks Common side effects – light headedness, dizziness, nausea, headaches, nervousness, excitement NOTE: Need to avoid grapefruit – may  risk side effects Non-Benzodiazepine Anxiolytics Zolpidem (Stilnox®) Indication – Short term treatment of insomnia Potentiates the inhibitory effect of GABA Is not a BDZ Adverse effects Common – diarrhoea Rare – paradoxical symptoms e.g. worsening insomnia, irritability, agitation Its Potential for tolerance, dependence or abuse is not clear Non-Benzodiazepine Anxiolytics Zopliclone (Imovane®, Imrest®) Indication – Short term treatment of insomnia Potentiates the inhibitory effect of GABA in the brain Adverse effects Common – taste disturbance (bitter), dry mouth Should be used short term Non-Benzodiazepine Anxiolytics Diphenhydramine (Snuzaid Gels®, Unisom®, Sleepgels®) Over the counter, 50mg nocte Injection of content of capsules (drug mis-users) may cause phelebitis, infection, more serious local effects Promathazine Doxylamine  Anticonvulsants (also known as antiepileptics) Anticonvulsants Anticonvulsants (Antiepileptic's) are used to control or prevent seizure disorders while minimising unwanted side-effects Aim for monotherapy (one medication) introduced slowly Trial and error (75% seizure free while 25% resistant) Desirable features highly effective with low toxicity long-acting and non-sedating not highly protein-bound inexpensive not resulting in tolerance Anticonvulsants Mechanism of action; Enhance GABA inhibition (e.g. benzodiazepines) or inhibit GABA transaminase (Vigabatrin, Tiagabine and Topiramate) Inhibit sodium channel function to stabilise the cell membrane (Phenytoin, Carbamazepine, Sodium Valproate and Lamotrigine) Inhibit calcium channel function or ‘calcium conductance’ (Ethosuximide) Raise brain levels of GABA (Gabapentin) Anticonvulsants Efficacy Different medications are more effective for treating specific seizures Anticonvulsants Side effects Behavioural and cognitive effects Anticonvulsants Other common side effects Depression of cardiovascular and respiratory system Enhance metabolism of Vitamin D – reduced bone mineral density Gastrointestinal effects Haematological effects Lithium NOTE: Long term use of lithium in therapeutic concentrations thought to cause histological and functional changes in kidney. Therefore should perform renal and thyroid function tests at baseline, then every 3-6 months Patient education Need to watch for signs of Lithium toxicity (e.g. extreme thirst and frequent urination, nausea and vomiting), especially during illness, excessive sweating or low fluid intake. If occurs – stop treatment STAT In general do not cease treatment abruptly – withdraw gradually to avoid relapse Take with food and consume more fluid (non-alcohol) during hot weather to avoid toxicity. Definition Head injury Broad category that may involve damage to other structures such as the scalp and skull Traumatic Brain Injury An insult to the brain caused by mechanical force. The spectrum of Intracranial Injury results from: Direct Forces = Object Striking or penetrating cranium Indirect Forces = Acceleration/Deceleration or Rotational Mechanism Traumatic brain injury The brain is susceptible to injury by trauma, ischemia, tumours, degenerative processes, and metabolic alterations. Brain injuries are classified as: Non-traumatic (i.e., stroke, infection, tumour, or seizure). Traumatic (i.e., epidural hematoma, subdural haematoma, concussion, or diffuse axonal injury) Brain damage can result from the effects of ischemia, excitatory amino acids, oedema, and increased intracranial pressure (ICP). Brain injuries can cause a change in the level of consciousness and alterations in cognition, motor, and sensory function Classification of Traumatic Brain Injury Blunt / Penetrating (Closed / Open) Severity Focal / Diffuse Primary / Secondary Brain injury Primary brain injury Primary damage resulting from these external forces Diffuse axonal injury Focal contusion Haematomas, or bleeding, in or around the brain Secondary brain injury Occurs hours or days after initial traumatic event. Injury may result from impairment or local decline in cerebral blood flow. Secondary brain injury Systemic and intracranial effects that follow the initial injury. Survival of severe brain injury is dependent on avoiding or minimizing the secondary insults to the brain. Systemic effects include: Hypotension/hypertension Hypoxia Anaemia CO2 changes Electrolyte/glucose/acid-base abnormalities Intracranial effects include: Ischemia Oedema Hydrocephalus Infection Seizure Haemorrhage Traumatic brain injury The brain is enclosed in the protective confines of the rigid bony skull. Although the skull generally affords protection to the soft tissues of the CNS from external forces, it also imposes risks as a source of injury from internal forces. The bony structures of the skull can induce traumatic and ischemic brain injuries when intracranial tissues increase in volume (swelling or bleeding) or shift (swelling or mechanical trauma). Fractures of the skull can compress sections of the nervous system and cause penetrating wounds Sequelae of Head Injury The prognosis for concussion (mild TBI) is generally good if appropriately managed. However, there are a variety of short – long-term sequelae. Second impact syndrome Post-concussion syndrome Post-traumatic epilepsy Sequelae of Head Injury Second Impact Syndrome Rare, Controversial entity Athlete who has sustained a mild concussion who subsequently suffers a second head injury before the symptoms from the first have resolved Patients subsequently develop rapid diffuse cerebral edema (within 2 min), increased ICP, and eventual herniation, coma, and death The first head injury is postulated to cause a disruption of the normal cerebral vascular autoregulation that causes increased cerebral blood flow, making the brain vulnerable to the second impact, when the rapid malignant swelling occurs Return-to-play guidelines have been developed to prevent this type of secondary injury Sequelae of Head Injury Post-Concussive Syndrome Constellation of symptoms that develops within 4 weeks of the injury and may persist for months (90% at 1 month, 25% at 1 year) Treatment is generally symptomatic Post-traumatic Epilepsy Seizure activity > 7 days from traumatic injury Head trauma is the cause of long-term epilepsy in 3% of patients with epilepsy Incidence is highest in patients with a compound skull fracture, intracranial hemorrhage, or presence of early acute symptomatic seizure (presence of all 3 factors increases risk by 50-80%) Cannot be prevented with prophylactic use of anticonvulsants Skull Fractures Skull Fracture = High Degree of Energy Classification: Location Pattern of fracture Open vs. Closed Location may indicate an underlying injury Depressed skull fracture - Often tear underlying dural tissue Fracture over pteryion - Middle Meningeal Artery = epidural haematoma Fracture over dural sinus - Subdural Hematoma Skull fracture increases the risk of intracranial bleeding Skull fractures A linear skull fracture is a break in the continuity of the bone. A comminuted skull fracture refers to a splintered or multiple fracture line. Compound fracture (Open fracture) When bone fragments are embedded into the brain tissue, the fracture is said to be depressed. A fracture of the bones that form the base of the skull is called a basilar skull fracture Fractures in young children Image source: http://caringforspecialneedskids.com/infant- skull-fracture/ Types of skull fractures Linear Fractures: The most common simple type. Seen in the temporal parietal region. Often accompanied by an overlying haematoma. They require no specific treatment and will heal well. A very small minority may develop into a "growing skull fracture" Types of skull fractures Depressed skull fractures May be seen with or without a cut on the scalp Part of the skull is actually sunken in from the trauma. If the inner part of the skull is pressed against the brain, surgical intervention is needed to help correct the deformity. Image source: http://slu.adam.com/content.aspx?prod uctId=617&pid=1&gid=000060 Types of skull fractures Basal skull Fractures: Serious type of skull fracture, involving a break at the base of the skull. These may be difficult to see radiologically, although the clinical suspicion should be high if "battle's sign" / "raccoon eyes" or a CSF leak is present. Types of skull fractures Diastatic Fractures: These are caused by the traumatic separation of the sutures most commonly lambdoidal. Growing Fractures: Seen in the toddler age group. Is generally "diastatic" and it grows as the brain herniates, through the torn dura up into the fracture site. Generally present some time after the initial injury, usually as a persistent swelling or pulsatile mass. There is almost always underlying parenchymal Head CT revealing an old brain damage, with associated neurological skull fracture with herniation of the underlying cortex in a symptoms. 14th month female Requires surgical repair of the dura. Image source: https://adc.bmj.com/content/101/Suppl_1/A193.2 Focal brain injury Coup/Contrecoup injury In a head injury, a coup injury occurs under the site of impact with an object, and a contrecoup injury occurs on the side opposite the area that was impacted. Focal injury at gray matter closest to the brain surface generates localized brain oedema and disruption of normal neurological function. Size of contusion defines the extent of the injury Concussion Symptoms can last for days, weeks, or even longer. Common symptoms after a concussive traumatic brain injury are headache, loss of memory (amnesia), and confusion. The amnesia usually involves forgetting the event that caused the concussion. Signs and symptoms of a concussion may include: Headache or a feeling of pressure in the head Temporary loss of consciousness Confusion or feeling as if in a fog Amnesia surrounding the traumatic event Dizziness or "seeing stars" Ringing in the ears Nausea Vomiting Slurred speech Delayed response to questions Appearing dazed Fatigue Haematomas Arise from vascular bleeding/injury Occur in various compartments depending on the location of the ruptured vessel Epidural, subdural and subarachnoid spaces and in the brain tissue itself (intracerebral haematoma). Haematomas Type Epidural Subdural Location Outer layers of the dura mater, Between dura mater & pia between the meninges & skull arachnoid mater. Increased risk in elderly and chronic alcohol use due to decreased brain volume Vessel involved Middle Meningeal Artery (36%) Bridging Veins Symptoms w/ LOC + Lucid Intervals followed Gradually increasing headache by deterioration and LOC again & confusion. Classic presentation = 47% of cases CT scan image Lenticular Shape on CT Hyperdense crescent shaped lesion Haematomas Epidural hematoma (EDH) Subdural hematomas (SDH) http://www.unipa.it/~sparacia/rimg/caso1.jpg Wikipedia Epidural (extradural) haematoma Usually occur in injury where the skull is fractured between in inner bones of the skull and the dura Usually from a tear of an artery (middle meningeal artery). Brief post-trauma LOC - followed by a lucid interval (may last a few hours), then rapid progression to unconsciousness Focal symptoms - Ipsilateral (same side) pupil dilatation and contralateral (opposite side) hemiparesis (from uncal herniation) Treatment Depends on location Surgical ligation Treatment aimed at reducing ICP Seizure control Subdural haematoma Develops between the dura and arachnoid (subdural space) as a result of a tear in small bridging veins that connect veins on the surface of the cortex to dural sinuses Subdural haematoma Classified according to an approximate time before the appearance of symptoms Acute - within 24 hours Subacute – 2 to 10 days Chronic – several weeks Acute subdural haematoma Acute subdural haematomas progress rapidly – high mortality due to secondary brain injury related to oedema and increased ICP. Presentation Similar to epidural haematoma except for no lucid interval. Treatment Depends on size Surgical evacuation Prevention of secondary brain injury (ICP, Oedema, Seizures etc.) Chronic Subdural Haematoma Presentation Generally occurs in the elderly- head trauma may seem minor Long-term alcohol use may be another risk factor Starts as acute SDH - small clot covered by membrane- dark fluid- like “motor oil” Symptoms (minor): headache, confusion; progress to seizures, hemiparesis & coma Treatment Evacuate clot Prevent and manage secondary brain injury Intracerebral haemorrhage Intracerebral haematoma bleeding into the brain tissue resulting from contusions or blood vessel injury (Craft et al, 2019) Single or multiple – any lobe of the brain (frontal and temporal lobes most common) Occur as a result of severe motion during traumatic head injury More frequent in older people, and chronic alcohol use (fragility of blood vessels) Signs and symptoms depend on size and location Increased ICP if large and encroaching vital structures Treatment can be medical or surgical Subarachnoid haemorrhage Disruption of subarachnoid vessels Common in moderate to severe brain injury Worse prognosis Twice as likely as other head injured patients to suffer death, persistent vegetative state or severe disability Image 2. http://www.virtualmedstudent.com/links/neurologic al/subarachnoid_hemorrhage.html Diffuse injuries Diffuse axonal injury -Widespread damage to the white matter. Results from shaking effect & associated with acceleration and deceleration injury. Ischemic brain injury from insufficient blood supply to the brain. Is the leading cause of secondary brain injury. Vascular injury usually causes death soon after injury. Swelling commonly seen after TBI can lead to increased cranial pressure Diffuse Axonal Injury Rotational Mechanism Widespread shearing strain at the deep cerebral white matter that disrupts normal axonal organization resulting in disruption of axonal fibers and myelin sheaths Generalized edema occurs after an injury, typically within 6 hours without any focal lesion on CT imaging Secondary Brain Injury Indirect result of injury. Arises from complications of injury Systemic or Intracranial processes that contribute to the primary brain injury cycle and result in greater tissue injury Ischemia Cerebral hypoxia Hypotension Cerebral oedema Alternations in cerebral blood flow Raised ICP Herniation Hypercapnia Alterations in the release of neurotransmitters (Excitotoxicity) Hydrocephalus Image: https://www.barnesjewish.org/Newsroom/Publications/Innovate- Physician/Innovate-Trauma-Level-1/Winter-2013/Preventing-Secondary-Brain- Injury-in-the-Battlefield Secondary Brain Injury Systemic Insults Hypoxia (PaO2 < 60 mmHg) Mortality of TBI pts with hypoxia = doubled 40% of TBI ED patients exhibit hypoxia during the course Hypotension (SBP < 90 mmHg) Present in 33-35% of TBI patients Results from hemorrhagic shock, cardiac contusion, tension pneumothorax, etc. Hypotension → ↓Cerebral Perfusion→↑Cerebral Ischemia →↑Doubles Mortality Anemia Blood Loss (↓Oxygen Carrying Capacity) Secondary Brain Injury Systemic Insults - Continued Hypo/Hypercapnia Hyperventilation is commonly used in neurological patients to decrease elevated intracranial pressure Hypocapnia may be induced in order lower ICP by decreasing the Cerebral Blood Volume It induces cerebral arterial vasoconstriction However may cause regional ischemia Therefore -restrict to short-term use & restore normocapnia as soon as is feasible Zhang, Z., Guo, Q., & Wang, E. (2019). Secondary Brain Injury Other Systemic Insults Seizures Electrolyte Abnormalities Coagulopathy Infection Hyperthermia Iatrogenic (Under-resuscitation) Intracranial Insults Severe intracranial hypertension, cerebral oedema & presence of extra-axial lesions also worsens the outcome. Patient comorbidities also impact the extent of secondary injury such as patient age, other co-existing injuries and alcohol intoxication.  Cycle of ICP leading to reductions in cerebral contributes to decreases Increased perfusion ICP pressure Space occupying lesions Cerebral Hydrocephalus Cerebral hemorrhage blood flow exacerbates decreases Cerebral Perfusion oedema pressure manifests as decreases Blood flow to the Swelling affected area of the brain results in Infarction causes of brain Ischemia tissue From: Craft, Gordon & Tiziani (2012) leads to Brain injury Brain is protected by the rigid confines of the skull and the cushioning by cerebrospinal fluid (CSF). However brain is still vulnerable to injury Metabolic stability is maintained by: Blood brain barrier Autoregulatory mechanisms Hypoxic and ischemic brain injury The ability of cerebral circulation to deliver oxygen in sufficiently high concentrations to facilitate the metabolism of glucose and generate adenosine triphosphate (ATP) is essential to brain function  Hypoxia – deprivation of oxygen with maintained blood flow  Ischemia – greatly reduced or interrupted blood flow, thus reducing delivery of oxygen & glucose and removal of metabolic wastes. Focal V Global ischemia Focal ischemia Global ischemia Region of the brain is under Blood flow to entire brain is perfused (ischemia stroke) compromised. Collateral perfusion may to Inadequate to meet metabolic maintain a low level of metabolic needs. activity However, interruption delivery of Severe and prolonged ischemia glucose under anaerobic conditions leads to infarction or death of cells may lead to additional lactic acid of the brain. production and depletion of ATP stores. Reperfusion of injured tissue can lead to secondary brain injury. Global ischemic injury Neurological deficits vary widely. The symptoms of cerebral ischemia include: weakness in one arm or leg weakness in one entire side of the body weakness on both sides of the body dizziness, vertigo, double vision difficulty speaking slurred speech loss of coordination If the period of extensive: Coma, fixed dilated pupils, and abnormal posturing. May be a gradual improvement, but permanent deficits may persist. Excitotoxic Brain Injury Excitatory amino acids Some neurological disorders (stroke, hypoglycaemia, and trauma, Huntington’s, and Alzheimer's) are characterized by overstimulation of amino acids – particularly glutamate Excitotoxicity – excessive activity of excitatory neurotransmitters and receptor-mediated activity (receptor- operated ion channels)  Excitatory amino acids Glutamate The role of the glutamate–N -methyl-D -aspartate (NMDA) receptor in brain cell injury. Image: Porth, 2014 Normal Cerebral Autoregulation Cerebral Autoregulation Protective mechanism to maintain a tightly controlled environment where fluctuations in systemic arterial pressure or intracranial pressure do not have a large impact on cerebral blood flow. Maintained by intact blood brain barrier, a specialized set of endothelial cells with tight junctions. Disruption of the blood brain barrier by traumatic injury may impair normal cerebral autoregulation. Normal Cerebral Autoregulation Cranial Vault - fixed in size by outer rigid skull, it contains 80% brain tissue (consumes 20% of the body’s oxygen supply and 15% of cardiac output) 10% blood 10% Cerebrospinal fluid (CSF) The metabolic stability required by its electrically active cells is maintained by a number of regulatory mechanisms, including the blood-brain barrier and autoregulatory mechanisms that ensure adequate blood supply. Normal fluctuations occur with respiratory movements, coughing, and sneezing. Cerebral blood flow If blood pressure falls below 60mmHg, cerebral blood flow is compromised. Blood flow increases rapidly and overstretches the cerebral vessels. At least three metabolic factors affect cerebral blood flow: carbon dioxide, hydrogen ion, and oxygen concentration. Decreased oxygen concentration also increases cerebral blood flow. Decreased oxygen saturation increases cerebral blood flow, as does an increased carbon dioxide level. The body attempts to compensate by increasing blood flow to the area. Vascular autoregulation Multiple factors can initiate these vasodilation or vasoconstriction cascades Systemic arterial pressure Systemic blood volume Blood viscosity Oxygen level delivery Metabolism Hypo / hypercapnia Pharmacologic agents Increased Intracranial Pressure Increased ICP is a common pathway for brain injury from different types of insults and agents. ICP is the pressure within the intracranial cavity and is determined by. Pressure–volume relationships among the brain tissue, CSF, and blood in the intracranial cavity; Monro-Kellie hypothesis, which relates to reciprocal changes among the intracranial volumes; Compliance of the brain and its ability to buffer changes in intracranial volume. Excessive ICP can obstruct cerebral blood flow, destroy brain cells, displace brain tissue (herniation), and damage delicate brain structures. Intracranial pressure The pressure-volume relationship between ICP, the volume of CSF, blood, and brain tissue, and cerebral perfusion pressure (CPP) is known as the Monro-Kellie hypothesis. The Monro-Kellie hypothesis states that the cranial compartment is incompressible, and the volume inside the cranium is a fixed volume. The cranium and its constituents (blood, CSF, and brain tissue) create a state of volume equilibrium, such that any increase in the volume of one of the cranial constituents must be compensated by a decrease in volume of another. Increased Intracranial Pressure Medical emergency! Most frequent cause of death & disability after severe head injury Remember Monro-Kellie hypothesis. The body can temporarily compensate when the volume of one of components increases by shifting CSF or altering blood volume through vasoconstriction. If pressure is continuous, then unable to compensate. Normal ICP 5- 10 mmHg. https://www.ausmed.com.au/cpd/article s/increased-intracranial-pressure Increased ICP Limited cerebral blood flow due to decreased cerebral perfusion from increased pressure. Brain is being squeezed & which leads to ischemia Swelling and oedema (if not treated) will lead to herniation (displacement). When CPP falls too low the body will try to compensate by increasing systolic BP to increase blood flow to the brain. BUT this makes things worse. At this point, arteries will dilate due to the retention of carbon dioxide. Causes more blood flow to the brain BUT will compress veins and limit blood flow to the heart. Therefore leads to more swelling and a further increase in ICP. Signs & Symptoms of Increased ICP Changes to the mental state Restlessness, confusion, difficulty following instructions. Changes to consciousness - Unconscious LATE sign. Seizures Headache Changes to optic & oculomotor nerve may cause, papilledema, changes to pupil size & response Emesis (vomiting) without nausea projectile Deterioration of motor function Posturing. Decerebrate or decorticate posturing or flaccid Reflex positive Babinski (toe fan out…abnormal) Cushing’s Triad: LATE SIGN…herniation of the brain stem Rising systolic pressure Widening pulse pressure Bradycardia Cushing’s Triad Cushing’s Triad = Acute entity is seen in severely head injured patients with significant increased intracranial pressure and impending herniation. Seen when increased ICP decreases the cerebral blood flow significantly. A response is triggered that increases arterial pressure in order to overcome the increased ICP Characterized by: Progressive Hypertension Bradycardia Irregular or impaired respiratory pattern Image: https://www.pinterest.com.au/pin/374291419013800228/  Increased Intracranial Pressure Maintain or control cerebral perfusion Increase Decrease rates (CPP) and control ICP in ICP CPP Decrease cerebral edema, lower volume of CSF, or decrease cerebral blood flow. (Farrell & Dempsey, 2013) Increase in edema Decrease & pressure CBF on tissue Increased Ischemia Nursing Interventions Focus on preventing further increased ICP and monitoring ICP (if a monitoring device is inserted). Position head of the bed: 30 to 45 degree Prevent HYPOXIA and HYPERCAPNIA When blood oxygen levels drop or carbon dioxide levels increase, vasodilation occurs and this increases intracranial pressure. Monitor blood gases, oxygen level, suctioning as needed only (no longer than 15 seconds…increase ICP) hyper-oxygenated before and after. Mechanical ventilation to keep PaCO2 low 30-35. Vasoconstriction helps decrease ICP by decreasing blood flow. Nursing Interventions Monitor and manage fever A high temp increases ICP, cerebral blood flow & metabolic needs of the patient. Keep patient cool (reduces metabolic needs) but prevent shivering, (increases metabolic needs & ICP) Monitor systems Glasgow Coma Scale Neuro obs Monitor ICP (ventriculostomy (external ventricular drain). Avoid straining activities. (vomiting, coughing, sneezing, stressful activities, agitation) Unconscious patient care Treatments Barbiturates Decrease brain metabolism which decreases ICP Vasopressors/IV fluids or antihypertensives Maintain SBP greater than 90 but less than 150. Anticonvulsants Hyperosmotic drugs to manage oedema Mannitol Must be done carefully and watch BP & renal functioning. Loop diuretics Corticosteroids Intracranial Monitoring Indications Severe TBI with GCS < 9 with abnormal CT scan. Intubated patients with moderate or severe head injury with significant intracranial findings on CT Brain Herniation Excessive ICP can obstruct cerebral blood flow, destroy brain cells, displace brain tissue (herniation), and damage delicate brain structures. Protrusion (herniation) of brain tissue through one of the rigid intracranial barriers (tentorial notch, falx cerebri, foramen magnum). Brain herniation is classified based on the structure through which tissue is herniated: Brain Herniation Signs and Symptoms Abnormal posturing - a characteristic positioning of the limbs indicative of severe brain damage Low level of consciousness (GCS 3-5) One or both pupils may be dilated and fail to constrict in response to light. Vomiting can also occur due to compression of the vomiting center in the medulla oblongata Cerebral oedema Increased brain tissue volume secondary to abnormal fluid accumulation May or may not increase ICP Impact on the brain depends on the compensatory mechanisms Two types - vasogenic and cytotoxic edema Treatment Conservative if no increase in ICP Localized edema often responds to corticosteroids or osmotic diuretics Cerebral Oedema Cytotoxic Oedema Vasogenic edema Actual swelling of the brain cells, When the integrity of the blood increasing intracellular fluid brain barrier is disrupted Impaired function of allowing fluid to escape into the sodium/potassium pump extracellular fluid surrounding brain cells - usually in white Inadequate removal of matter. anaerobic metabolites e.g. lactic acid, results in extracellular Occurs in tumors, prolonged acidosis ischemia, haemorrhage and brain injuries Cell membrane rupture damages neighboring cells - leads to stupor, coma or cerebral infarction Cerebral oedema  Hydrocephalus Abnormal increase in CSF volume in any part of the ventricular system Due to decreased absorption or overproduction of CSF Two types Communicating Noncommunicating Porth, C. M. (2008). (2005). Pathophysiology: Concepts of altered health states (8th (7th ed.). Communicating hydrocephalus Occurs when full communication occurs between the ventricles and subarachnoid space Caused by overproduction of CSF (rarely), defective absorption of CSF (most often), or venous drainage insufficiency (occasionally). http://emedicine.medscape.com/article/1135286-overview Noncommunicating hydrocephalus Occurs when CSF flow is obstructed within the ventricular system or in its outlets to the arachnoid space, resulting in impairment of the CSF from the ventricular to the subarachnoid space. Commonly caused by obstruction by a lesion Image shows Horizonatal section of the brain from a patient who died of a brain tumour that obstructed the aqueduct of Sylvius shows marked dilation of the lateral ventricles. Head Injury in children Head injury is the leading cause of death in children > 1 year of age Head injury is the 3rd most common cause of death in children Ratio of head injury, boys to girls is 2:1 Ratio of fatal head injury, boys to girls is 4:1. (PCH, 2018) Infants: commonly due to falls from heights, e.g.. from a bed, couch, pram, change table, or downstairs. School-aged children, sporting activities (Luckhoff & Starr, 2010) Head Injury in children Newborns Delivery head injury Caused by head compression and traction through Intracranial haemorrhages the birth canal (vaginal delivery) with obstetric Cephalic hematoma instruments. Subgaleal haematoma A low birth weight and hypoxemia are risk factors (extracranial) for intracranial haemorrhage. Infants Accidental head injury Caused by inappropriate childcare practices. Abusive Head Trauma If mechanism of injury is not clear, careful consideration for diagnosis of child abuse is required. Toddlers & Accidental head injury Caused by accidents increase as children develop school motor ability. children With increase in use of child safety seats, the severity of injury and the mortality has dropped. Pedestrian injury also increases in this age group. Adolescents Bicycle and motorcycle-related Awareness of prevention must be raised. accidents Trainers and players those involved in contact Sports-related head injuries sports - require education about concussion. Injury characteristics according to age and development. Table from Araki, T., Yokota, H., & Morita, A. (2016). Pediatric traumatic brain injury: characteristic features, diagnosis, and management. Neurologia medico-chirurgica Head injury in children A child's behavior and symptoms after a head injury depend upon the type and extent of the injury. The most common signs and symptoms include: Lacerations Scalp swelling LOC Return to play Headache Children and adolescents who have sustained a concussion are at risk for a serious or even fatal Vomiting complication if they have a second head injury within a short time after the first injury. e.g.., second impact syndrome. Seizures If suspected of having a concussion should be removed from play (e.g., if Concussion playing a team sport) and monitored for signs of brain injury. Patient education: Head injury in children and adolescents (Beyond the Basics) - UpToDate Assessment of head injury - Children Examination CNS  Full neurological examination. Head Penetrating injury Depressed skull fracture Investigations Large bruising or swelling X-ray skull Panda eyes CT spine Battles sign Bloods Fundi Papilloedema not seen acutely Retinal haemorrhage in NAI Pupillary reaction - equal, reactive, size https://pch.health.wa.gov.au/For-health-professionals/Emergency-Department- Guidelines/Head-injury Assessment of head injury - Children Mild head injury Moderate head injury Severe head injury 95% of HI are mild GCS 9-13 GCS < 9 GCS 14-15 AVPU = V AVPU = P or U AVPU = A 3 or more vomits Seizures No LOC Brief seizure after head injury Focal neurological deficit Normal neurological Amnesia of event Raised ICP examination LOC < 5 mines Penetrating head injury Large scalp laceration, bruise or abrasion (> 5cm in < 1 year old) Drowsy Features of basal skull fracture Blood behind tympanic membrane CSF leak from ear/nose Raccoon eyes Battles sign Open or depressed skull fracture High energy mechanisms https://pch.health.wa.gov.au/For-health-professionals/Emergency-Department-Guidelines/Head-injury Head injury in the elderly Evaluation and diagnosis of TBI are challenging in older persons, especially those with pre-existing dementia or cognitive disorders. A pre-existing alteration in consciousness may confuse the diagnosis. Common symptoms of brain injury—such as balance impairment, depression, and cognitive deficits—may be misattributed to other causes, especially when elderly patients experience a non-witnessed fall The frequent use of anticoagulants for comorbid conditions leads to an increased risk of haemorrhage, even with low-velocity head trauma. High suspicion for intracranial haemorrhage Some patients may present days or weeks after trauma, such as may occur with subdural haemorrhage. Filer, W., & Harris, M. (2015). Falls and traumatic brain injury among older adults. North Carolina medical journal, 76(2), 111-114. Assessment Glasgow Coma Scale Originally designed for measure 6 hours after injury to provide long-term prognostic information about mortality and disability Now, standardized to measure 30 min after injury and repetitive measurements throughout patient’s stay Should be performed after adequate resuscitation b/c scale is sensitive to hypotension, hypoxia, intoxication, and pharmacologic interventions Current Classification GCS 14-15 - Mild Head Injury GCS 9-13 - Moderate Head Injury GCS < 9 - Severe Head Injury Assessment Neurologic Exam Pupillary Size + Reactivity Fixed Dilated Pupil - Ipsilateral Intracranial Hematoma Bilateral Fixed + Dilated - Poor Brain Perfusion, bilateral Uncas herniation or severe hypoxia Indicative of very poor neurological outcome Neurological Posturing Decorticate Posturing - Upper extremity flexion with lower extremity extension Cortical Injury above the midbrain Image: http://prehospitalresearch.eu/?p Decerebrate Posturing - Arm extension and internal rotation =1683 with wrist flexion Indicative of brainstem injury Very poor predictor of outcome Mild head injury Clinical features- Signs and symptoms (early/late) Signs and Symptoms of Head Injury Cognitive Somatic Affective Confusion Headache Emotional Lability Anterograde amnesia Fatigue Irritability Retrograde amnesia Disequilibrium Sadness Loss of consciousness Dizziness Disorientation Nausea/vomiting Feeling “zoned out” Visual disturbances Feeling “foggy” Photophobia Vacant stare Phonophobia Inability to focus Difficulty sleeping Delayed verbal/motor Ringing of the ears response Slurred or incoherent speech Excessive Drowsiness Mild Head Injury Management Symptomatic treatment and prevention of secondary injury Appropriate management depends on an assessment of the risk of neurological decompensation and risk factors for intracranial haematoma. Risk factors for intracranial haematoma Coagulopathy, Drug/Alcohol Intoxication, Previous neurosurgical procedures, Pre-trauma epilepsy, or older age (> 60 y/o) Low-risk patients can be d/c with instructions –if GCS is normal, neuro- exam is normal, normal CT & no predisposition bleeding. All patients with mild traumatic brain injury should be observed for 24 hours after that injury (either inpatient or outpatient). Don’t have to keep the patient awake. Mild Head Injury Management Discharge Instructions Warning Signs after Appropriate follow-up instructions should be Discharge provided both verbally and written Inability to awaken the patient instructions. Decreased/ Altered mental No need to awaken the patient every 2 hours status Severe or worsening headache Patients who return to ED due to persistent Somnolence or confusion symptoms should undergo careful repeat Restlessness, Unsteadiness neurological evaluation but little data supports repeat CT Scanning Seizure activity Visual difficulties “Return to play” guidelines Change in behavior Return to sporting activities in a step-wise Vomiting, fever, neck stiffness fashion Urinary or bowel incontinence Should not return to sporting events if they Weakness or numbness are still symptomatic Moderate/ Severe Head Injury Moderate Severe GCS = 9-13 GCS < 9 Early aggressive treatment is required with airway control, resuscitation, admission to ICU setting Outcome is poor with mortality as high as 60% Clinical presentation varies widely Exam typically with abnormal exam, often evidence of external trauma, abnormal Specialized Subset = “Talk and Die pupillary exam and neurological deficits Syndrome” Cushing’s Triad Moderate/ Severe Head Injury Management General Principles All moderate and severe head injured patients should undergo CT imaging Stabilisation and prevention of secondary insults is the mainstay of treatment Airway Management Prevention of hypoxia and hypoventilation key to preventing secondary insults Patients with GCS < 9, should have endotracheal airway placed Special attention should be paid to maintaining cervical spinal immobilisation Moderate /Severe Head Injury Management Haemodynamic Assessment Hypotension (SBP < 90) should be aggressively treated as a significant cause of the worse outcome Rarely, hypotension is due to head injury itself & other traumatic injuries should be investigated Treatment of hypotension is directed at the maintenance of cerebral perfusion Hypotonic fluids are contraindicated Typically isotonic fluids are used (NS) Prevention of secondary brain injury by avoiding hypoxemia (O2 saturation 90 PaCO2 35-40 Systolic BP > 90 Head up 30° Nursing interventions and management Summary Supportive care Prevention of secondary brain juries Restore homeostasis. Mild TBI - serial neurological exams may be required for the first few days, with neurology follow-up. Moderate TBI- serial exams and cardiovascular monitoring may be required for close observation. Severe TBI - serial exams & Cardiovascular monitoring Intracranial monitoring EEGs for potential seizure activity Hickman, R., Alfes, C. M., & Fitzpatrick, J. (Eds.). (2018). Nursing interventions and management Outcome goals Stabilisation of primary injury Minimise secondary brain injury Protect airway and adequate ventilation Minimise metabolic needs of the brain Maintain nutritional support Seizure precautions Mean arterial pressure sufficient to provide cerebral perfusion (CPP = 60– 70 mmHg) ICPs maintained within normal limits Normoglycemia, fever prevention, and normocarbia. Anticholinergic Drugs Peripheral side effects Dryness of the mouth Urinary hesitancy / constipation worsened Dilation of pupils Worsening of glaucoma Central side effects Dizziness Euphoria Hallucinations Delirium (important in elderly)