Seizure Prophylaxis in Traumatic Head Injury Anthony Angelow, PhD(c), ACNPC, AGACNP-BC, CEN Associate Lecturer, Fitzgerald Health Education Associates Clinical practice Division of Trauma Surgery and Division of Hospital Medicine Cooper University Hospital, Camden, NJ Assistant Clinical Professor, College of Nursing and Health Professions Drexel University, Philadelphia, PA Disclosure No real or potential conflict of interest to disclose. No off-label, experimental or investigational use of drugs or devices will be presented. Fitzgerald Health Education Associates 2 Objectives At the end of the presentation, the participant will be able to: Describe the common types of traumatic head injury. Describe TBI severity based on physical exam and CT scan criteria. Objectives At the end of the presentation, the participant will be able to: (cont.) Identify the concepts of post-traumatic seizure. Discuss the purpose of PTS prophylaxis and the drugs use in PTS prophylactics. Fitzgerald Health Education Associates 3 Fitzgerald Health Education Associates 4 Additional references at end of presentation Traumatic Brain Injury Background TBI accounts for 1.1 million emergency department visits annually. 1:1,000 people are hospitalized for TBI each year. Source: Department of Surgical Education, Orlando Regional Medical Center (2012). Seizure prophylaxis in patients with traumatic brain injury. http://www.surgicalcriticalcare.net/guidelines/seizure%20prophylaxis %20in%20TBI.pdf Fitzgerald Health Education Associates 5 Fitzgerald Health Education Associates 6
Traumatic Brain Injury Background There are three main types of TBI to consider Subdural hematoma Subarachnoid hemorrhage Epidural hematoma Source: Department of Surgical Education, Orlando Regional Medical Center (2012). Seizure prophylaxis in patients with traumatic brain injury. http://www.surgicalcriticalcare.net/guidelines/seizure%20prophylaxis %20in%20TBI.pdf Dura Mater Subdural Hematoma Arachnoid Mater Image source: https://commons.wiki media.org/wiki/file:in tracranial_bleed_with _significant_midline_s hift.png Fitzgerald Health Education Associates 7 Fitzgerald Health Education Associates 8 Epidural Hematoma Subarachnoid Hemorrhage Skull Dura Mater Image source: https://commons.wiki media.org/wiki/file:t raumatic_acute_epid ual_hematoma.jpg Image source: https://commons.wik imedia.org/wiki/file: SubarachnoidP.png Fitzgerald Health Education Associates 9 Fitzgerald Health Education Associates 10 Severity of Traumatic Brain Injury TBI Sign/Symptom Prediction Rotterdam CT Classification Category Mild TBI Moderate TBI Severe TBI Sign/Symptom Prediction Criteria + LOC Amnesia <30 minutes Glasgow Coma Scale (GCS) 13 15 + LOC Amnesia 30 min 24 hrs Skull fracture GCS 9 12 Contusion or hematoma + LOC Amnesia >24 hours GCS 3 8 Source: Lamoureux J, Bajsarowicz P, Maleki M, & Marcoux, J. (2011). A critical look at phenytoin use for early post traumatic seizure prophylaxis. Canadian Journal of Neurology Science, 28(6), 896-901. Fitzgerald Health Education Associates 12
A CT scan derived metric used to predict outcome in patients with TBI, based on two main criteria Degree of swelling Presence and size of contusions/ hemorrhages Source: Saatman KE, Duhaime AC, Bullock R et al. (2008). Classification of traumatic brain injury for targeted therapies. Journal of Neurotrauma, 25(7), 719-38. doi: 10.1089/nue.2008.0586 Degree of swelling Midline shift Compression of basal cisterns Presence and size of contusions/hemorrhages High or mixed density lesions Source: Saatman KE, Duhaime AC, Bullock R et al. (2008). Classification of traumatic brain injury for targeted therapies. Journal of Neurotrauma, 25(7), 719-38. doi: 10.1089/nue.2008.0586 Fitzgerald Health Education Associates 13 Fitzgerald Health Education Associates 14 Diffuse Injury I Criteria Findings Degree of swelling Presence and size of contusions/hemorrhages No visible intracranial pathology seen on CT Source: Saatman KE, Duhaime AC, Bullock R et al. (2008). Classification of traumatic brain injury for targeted therapies. Journal of Neurotrauma, 25(7), 719-38. doi: 10.1089/nue.2008.0586 Diffuse Injury II Criteria Findings Degree of swelling Presence and size of contusions/hemorrhages Midline shift of 0 to 5 mm Basal cisterns remain visible No high or mixed density lesions >25 cm 3 Source: Saatman KE, Duhaime AC, Bullock R et al. (2008). Classification of traumatic brain injury for targeted therapies. Journal of Neurotrauma, 25(7), 719-38. doi: 10.1089/nue.2008.0586 Fitzgerald Health Education Associates 15 Fitzgerald Health Education Associates 16 Diffuse Injury III (Swelling) Criteria Findings Degree of swelling Presence and size of contusions/hemorrhages Midline shift of 0 to 5 mm Basal cisterns compressed or completely effaced No high or mixed density lesions >25 cm 3 Source: Saatman KE, Duhaime AC, Bullock R et al. (2008). Classification of traumatic brain injury for targeted therapies. Journal of Neurotrauma, 25(7),719-38. doi: 10.1089/nue.2008.0586 Diffuse Injury III (Shift) Criteria Findings Degree of swelling Presence and size of contusions/hemorrhages Midline shift >5 mm No high or mixed density lesions >25 cm 3 Source: Saatman KE, Duhaime AC, Bullock R et al. (2008). Classification of traumatic brain injury for targeted therapies. Journal of Neurotrauma, 25(7), 719-38. doi: 10.1089/nue.2008.0586 Fitzgerald Health Education Associates 17 Fitzgerald Health Education Associates 18
Diffuse Injury V Any lesion surgically evacuated Fitzgerald Health Education Associates Diffuse Injury VI High or mixed density lesions >25 cm 3 Source: Saatman KE, Duhaime AC, Bullock R et al. (2008). Classification of traumatic brain injury for targeted therapies. Journal of Neurotrauma, 25(7), 719-38. doi: 10.1089/nue.2008.0586 19 Rotterdam CT Classification Prognostic evaluation of patients admitted with acute TBI based on the following criteria Degree of basal cistern compression Degree of midline shift Epidural hematomas Intraventricular/subarachnoid blood Source: Maas AI, Hukkelhoven CW, Marshall LF et al. (2006). Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery, 57(6), 1173-82. Fitzgerald Health Education Associates 20 Rotterdam CT Classification Criteria Basal cisterns Midline shift Epidural mass lesion Intraventricular blood or traumatic SAH Normal Compressed Absent No shift Shift <5 mm Shift >5 mm Absent Present Absent Present Scoring 0 points 1 point 2 points 0 points 0 points 1 point 0 points 1 point 0 points 1 point Source: Maas AI, Hukkelhoven CW, Marshall LF et al. (2006). Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery, 57(6), 1173-82. Rotterdam CT Classification Score Risk of mortality 1 Point 0% 2 Points 7% 3 Points 16% 4 Points 26% 5 Points 53% 6 Points 61% Source: Maas AI, Hukkelhoven CW, Marshall LF et al. (2006). Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery, 57(6), 1173-82. Fitzgerald Health Education Associates 22 General Information Posttraumatic Seizure 275,000 people are hospitalized with TBI each year. 4% percent of all epilepsy cases are attributed to trauma. 13% of those cases are posttraumatic. Source: Diaz-Arrastia R, & Kenney K. (2014). Epidemiology of traumatic brain injury. Traumatic Brain Injury, 181 191. doi:10.1002/9781118656303.ch10 Fitzgerald Health Education Associates 24
General Risk Factors Alcoholism + LOC Age Focal neuro deficits Penetrating injuries Depressed skull Intracranial fractures hemorrhage Cerebral contusions Severity of injury Retained bone and Time of posttraumatic metal fragments amnesia Lesion location Source: Ritter AC, Wagner AK, Fabio A, et al. (2016). Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A traumatic brain injury model systems study. Epilepsia, 57(12), 1968-1977 Fitzgerald Health Education Associates 25 Risk Factors Biparietal contusions (66%) Dural penetration with bone and metal fragments (62.5%) Multiple intracranial operations (36.5%) Multiple subcortical contusions (33.4%) Source: Ritter AC, Wagner AK, Fabio A, et al. (2016). Incidence and risk factors of posttraumatic seizures following traumatic brain injury: a traumatic brain injury model systems study. Epilepsia, 57(12), 1968-1977 Fitzgerald Health Education Associates 26 Risk Factors Subdural hematoma with evacuation (27.8%) Midline shift greater than 5 mm (25.8%) Multiple or bilateral cortical contusions (25%) Source: Ritter AC, Wagner AK, Fabio A, et al. (2016). Incidence and risk factors of posttraumatic seizures following traumatic brain injury: a traumatic brain injury model systems study. Epilepsia, 57(12), 1968-1977 Why do they occur? The overall pathophysiologic process of PTS is largely unknown. Generally accepted that seizures occur secondary to stimulation of the brain tissue secondary to the injury. Source: Department of Surgical Education, Orlando Regional Medical Center (2012). Seizure prophylaxis in patients with traumatic brain injury. http://www.surgicalcriticalcare.net/guidelines/seizure%20prophylaxis %20in%20TBI.pdf Fitzgerald Health Education Associates 27 Fitzgerald Health Education Associates 28 Why do they occur? Early PTS occurs in 5 7% of the population. Most common 0 7 days after the injury Late PTS largely uncommon >7 days after the injury Early PTS is a main risk factor of developing late PTS. Seizure prophylaxis in patients with traumatic brain injury. Early PTS Risk Factors Depressed skull fracture and intracerebral hematoma requiring evacuation, subdural hematomas, and penetrating head injury PTS is not thought to occur in patients with mild TBI and normal head CT. Seizure prophylaxis in patients with traumatic brain injury. Fitzgerald Health Education Associates 29 Fitzgerald Health Education Associates 30
Early PTS Clinical Features 50% occur within the first 24 hours of head injury 25% occur within the first hour of head injury Most seizures presenting within the first 24 hours are generalized tonic-clonic. Source: Debenham S, Sabit B, Saluja RS, Lamoureux J, Bajsarowicz P, Maleki M, & Marcoux J. (2011). A Critical Look at Phenytoin Use for Early Post-Traumatic Seizure Prophylaxis. Canadian Journal of Neurological, 38(06), 896 901. doi:10.1017/s031716710001249x Early PTS Clinical Features 10% of patients with acute head injury develop status epilepticus Status epilepticus is often refractory to treatment and represents a high mortality rate. Source: Debenham S, Sabit B, Saluja RS, Lamoureux J, Bajsarowicz P, Maleki M, & Marcoux J. (2011). A Critical Look at Phenytoin Use for Early Post-Traumatic Seizure Prophylaxis. Canadian Journal of Neurological, 38(06), 896 901. doi:10.1017/s031716710001249x Fitzgerald Health Education Associates 31 Fitzgerald Health Education Associates 32 Early PTS Evaluation CT head without contrast Rebleeding Ischemia MRI brain More sensitive for posttraumatic intracranial abnormalities Source: Debenham S, Sabit B, Saluja RS, Lamoureux J, Bajsarowicz P, Maleki M, & Marcoux J. (2011). A Critical Look at Phenytoin Use for Early Post-Traumatic Seizure Prophylaxis. Canadian Journal of Neurological, 38(06), 896 901. doi:10.1017/s031716710001249x Evaluation/Prediction with Diagnostics EEG Clinical seizures are difficult to identify through observation or physical examination. TBI and sedative and neuromuscular blockade can mask seizure activity. Seizure prophylaxis in patients with traumatic brain injury Fitzgerald Health Education Associates 33 Fitzgerald Health Education Associates 34 Evaluation/Prediction with Diagnostics EEG (cont.) Routine use of EEG monitoring is encouraged but needs further study and evaluation. EEG abnormalities do not predict the risk or type of seizures. Seizure prophylaxis in patients with traumatic brain injury Evaluation/Prediction with Diagnostics CT CT scan findings and neurosurgical procedures performed were the most useful factors in identifying TBI patients at highest risk for late post traumatic seizures (moderate to severe TBI). Seizure prophylaxis in patients with traumatic brain injury Fitzgerald Health Education Associates 35 Fitzgerald Health Education Associates 36
GCS Risk of late PTS 3 8 16.8% 9 12 24.3% 13 15 8% GCS vs. CT Evaluation Marshall criteria IV V VI Risk of late PTS Highest risk of developing late PTS Sources: Englander J, Bushnik T, Duong TT, Cifu DX, Zafonte R, Wright J, Bergman W. (2003). Analyzing risk factors for late posttraumatic seizures: A prospective, multicenter investigation. Archives of Physical Medicine and Rehabilitation, 84(3), 365 373. doi:10.1053/apmr.2003.50022 Debenham S, Sabit B, Saluja RS, Lamoureux J, Bajsarowicz P, Maleki M, & Marcoux J. (2011). A Critical Look at Phenytoin Use for Early Post-Traumatic Seizure Prophylaxis. Canadian Journal of Neurological, 38(06), 896 901. doi:10.1017/s031716710001249x Early PTS Management Patients with early seizures are often treated with anti-seizure pharmacotherapy secondary to Risk of status epilepticus Worsening of injury Recurrent seizures can increase cerebral blood flow increased ICP Seizure prophylaxis in patients with traumatic brain injury. Fitzgerald Health Education Associates 37 Fitzgerald Health Education Associates 38 Pharmacologic Prophylaxis Options studied for therapy Phenytoin (Dilantin ) Levetiracetam (Keppra ) Carbamazepine (Tegretol ) Valproate (Depakote ) Phenobarbital Phenytoin/phenobarbital Magnesium Seizure prophylaxis in patients with traumatic brain injury. Pharmacologic Agents Not Recommended in Seizure Prophylaxis Phenobarbital, phenytoin/phenobarbital, and magnesium Per multiple studies, these drugs are not acceptable for PTS prophylaxis. Risk of adverse effects/events is much higher than benefit. No clear benefit in outcome studies Source: Manaka, S. (1992). Cooperative Prospective Study on Posttraumatic Epilepsy: Risk Factors and the Effect of Prophylactic Anticonvulsant. Psychiatry and Clinical Neurosciences, 46(2), 311 315. doi:10.1111/j.1440-1819.1992.tb00865.x Fitzgerald Health Education Associates 39 Fitzgerald Health Education Associates 40 Valproate (Depakote ) Two Class I studies recommended against the use of valproate for early PTS prophylaxis in patients with severe TBI. No benefit over short-term phenytoin therapy Source: Temkin et al., 1999 Does not prevent the occurrence of PTS in outcome studies Source: Dikmen et al., 2000 Both studies showed increased mortality rates. Fitzgerald Health Education Associates 41 Carbamazepine (Tegretol ) One Class II study found a significantly lower rate of early seizures among 139 patients with severe TBI receiving carbamazepine prophylaxis. Started immediately after the injury Continued for 1 2 years Recommendation 1 year Need to monitor levels to keep therapeutic Seizure prophylaxis in patients with traumatic brain injury. Fitzgerald Health Education Associates 42
Phenytoin (Dilantin ) Preferred Two Class I studies assessed the efficacy of phenytoin for PTS prophylaxis in patients with severe TBI. Significantly lower rate of early PTS Rate of reported early seizures significantly decreased Has the best available data Seizure prophylaxis in patients with traumatic brain injury. Fitzgerald Health Education Associates 43 Phenytoin (Dilantin ) Preferred Dosing 17 mg/kg IV loading dose over 20 minutes 100 mg IV or PO, three times daily for 7 days Serum levels 97% have levels in or above the therapeutic range on day #1 and 57% remained in range for 1 week. Source: Phenytoin sodium injection (Dilantin ) [prescribing information]. New York, NY: Pfizer Inc.; November 2017 Fitzgerald Health Education Associates 44 Phenytoin (Dilantin ) Preferred Serum levels Total phenytoin 10 20 mg/l (15 mg/l) Free phenytoin 1 to 2.5 mg/l Toxicity >30 mg/l (toxic) >100 mg/l (lethal) Source: Phenytoin sodium injection (Dilantin ) [prescribing information]. New York, NY: Pfizer Inc.; November 2017 Phenytoin (Dilantin ) Preferred Major Adverse Effects Cardiovascular Mainly with IV administration CNS Dermatologic Endocrine and metabolic GI GU Hematologic/ oncologic Immunologic Ophthalmic Source: Phenytoin sodium injection (Dilantin ) [prescribing information]. New York, NY: Pfizer Inc.; November 2017 Fitzgerald Health Education Associates 45 Fitzgerald Health Education Associates 46 Phenytoin (Dilantin ) Preferred Contraindications Hypersensitivity Hx of acute hepatotoxicity related to phenytoin Source: Phenytoin sodium injection (Dilantin ) [prescribing information]. New York, NY: Pfizer Inc.; November 2017 Phenytoin (Dilantin ) Preferred Contraindications (cont.) IV specific Sinus bradycardia Sinoatrial block 2 nd and 3 rd degree heart block Adams-stokes syndrome Multiple drug interactions Source: Phenytoin sodium injection (Dilantin ) [prescribing information]. New York, NY: Pfizer Inc.; November 2017 Fitzgerald Health Education Associates 47 Fitzgerald Health Education Associates 48
Levetiracetam (Keppra ) Safe and efficacious in preventing early PTS One recent prospective randomized, single blinded study of 52 patients (Class II) compared IV levetiracetam with IV phenytoin in patients with severe TBI. Source: Szaflarski JP, Sangha KS, Lindsell CJ, 7 Shutter LA. (2010). Prospective, randomized, single-blinded comparative trial, of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Journal of Neuro Critical Care, 12(1), 165-172 Levetiracetam (Keppra ) Patients treated with levetiracetam experienced better long-term outcomes than those on phenytoin. Source: Szaflarski JP, Sangha KS, Lindsell CJ, 7 Shutter LA. (2010). Prospective, randomized, single-blinded comparative trial, of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Journal of Neuro Critical Care, 12(1), 165-172 Fitzgerald Health Education Associates 49 Fitzgerald Health Education Associates 50 Levetiracetam (Keppra ) Dosing Loading dose of 20 mg/kg IV Maintenance dose of 1000 mg IV every 12 hrs May be adjusted as needed for therapeutic effect up to 1500 mg every 12 hrs Source: Szaflarski JP, Sangha KS, Lindsell CJ, 7 Shutter LA. (2010). Prospective, randomized, single-blinded comparative trial, of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Journal of Neuro Critical Care, 12(1), 165-172 Levetiracetam (Keppra ) Adverse effects Cardiovascular CNS GI Contraindications None, renally dosed Source: Levetiracetam in Sodium Chloride Injection [prescribing information]. Rockford, IL: Mylan Institutional; December 2015. Fitzgerald Health Education Associates 51 Fitzgerald Health Education Associates 52 Levetiracetam (Keppra ) Drug-drug interactions Food interactions Decreases absorption Source: Levetiracetam in Sodium Chloride Injection [prescribing information]. Rockford, IL: Mylan Institutional; December 2015. Cost Analysis A cost minimization analysis of phenytoin vs. levetiracetam for routine pharmacoprophylaxis Superiority of phenytoin over levetiracetam Source: Department of Surgical Education, Orlando Regional Medical Center (2012). Seizure prophylaxis in patients with traumatic brain injury. http://www.surgicalcriticalcare.net/guidelines/seizure%20prophylaxis% 20in%20TBI.pdf Fitzgerald Health Education Associates 53 Fitzgerald Health Education Associates 54
Cost Analysis A cost minimization analysis (cont.) Institutional Mean cost per patient $151.24 vs. $411.85 and patient Patient Mean cost $2,302.58 vs. $3,498.40 Source: Department of Surgical Education, Orlando Regional Medical Center (2012). Seizure prophylaxis in patients with traumatic brain injury. http://www.surgicalcriticalcare.net/guidelines/seizure%20prophyl axis%20in%20tbi.pdf Summary Early PTS occurs from the time of injury up to 7 days post injury. Prophylaxis of PTS shows benefit in preventing long-term PTS/epilepsy. No benefit in prophylaxis for late PTS Fitzgerald Health Education Associates 55 Fitzgerald Health Education Associates 56 Summary Phenytoin is the preferred agent to early PTS prophylaxis. Levetiracetam has also shown benefit in early PTS prophylaxis. Questions? Fitzgerald Health Education Associates 57 Fitzgerald Health Education Associates 58 Debenham S, Sabit B, Saluja RS, Lamoureux J, Bajsarowicz P, Maleki M, & Marcoux J. (2011). A Critical Look at Phenytoin Use for Early Post-Traumatic Seizure Prophylaxis. Canadian Journal of Neurological, 38(06), 896 901. doi:10.1017/s031716710001249x Fitzgerald Health Education Associates 59 Department of Surgical Education, Orlando Regional Medical Center (2012). Seizure prophylaxis in patients with traumatic brain injury. http://www.surgicalcriticalcare.net/guidelines/ Seizure%20prophylaxis%20in%20TBI.pdf Diaz-Arrastia R, & Kenney K. (2014). Epidemiology of traumatic brain injury. Traumatic Brain Injury, 181 191. doi:10.1002/9781118656303.ch10 Fitzgerald Health Education Associates 60
Dikmen SS, Machamer JE, Winn HR, Anderson GD, & Temkin NR. (2000). Neuropsychological effects of valproate in traumatic brain injury : A randomized trial. Neurology, 54(4), 895 902. Lamoureux J, Bajsarowicz P, Maleki M, & Marcoux J. (2011). A critical look a phenytoin use for early post traumatic seizure prophylaxis. Canadian Journal of Neurology Science, 28(6), 896-901. Fitzgerald Health Education Associates 61 Levetiracetam in Sodium Chloride Injection [prescribing information]. Rockford, IL: Mylan Institutional; December 2015. Maas AI, Hukkelhoven CW, Marshall LF et al. (2006). Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery, 57(6), 1173-82. Fitzgerald Health Education Associates 62 Manaka, S. (1992). Cooperative Prospective Study on Posttraumatic Epilepsy: Risk Factors and the Effect of Prophylactic Anticonvulsant. Psychiatry and Clinical Neurosciences, 46(2), 311 315. doi:10.1111/j.1440-1819.1992.tb00865.x Phenytoin sodium injection (Dilantin ) [prescribing information]. New York, NY: Pfizer Inc.; November 2017 Fitzgerald Health Education Associates 63 Ritter AC, Wagner AK, Fabio A, et al. (2016). Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A traumatic brain injury model systems study. Epilepsia, 57(12), 1968-1977 Saatman KE, Duhaime AC, Bullock R et al. (2008). Classification of traumatic brain injury for targeted therapies. Journal of Neurotrauma, 25(7), 719-38. doi: 10.1089/nue.2008.0586 Fitzgerald Health Education Associates 64 Szaflarski JP, Sangha KS, Lindsell CJ, 7 Shutter LA. (2010). Prospective, randomized, single-blinded comparative trial, of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Journal of Neuro Critical Care, 12(1), 165-172 Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, & Winn HR. (1990). A Randomized, Double-Blind Study of Phenytoin for the Prevention of Post- Traumatic Seizures. New England Journal of Medicine, 323(8), 497 502. doi:10.1056/nejm199008233230801 Fitzgerald Health Education Associates 65 Fitzgerald Health Education Associates 66
Temkin NR, Dikmen SS, Anderson GD, Wilensky AJ, Holmes MD, Cohen W, et al. (1999). Valproate therapy for prevention of posttraumatic seizures: a randomized trial. Journal of Neurosurgery, 91(4), 593 600. doi:10.3171/jns.1999.91.4.0593 End of Presentation Thank you for your time and attention. Anthony Angelow, PhD(c), ACNPC, AGACNP-BC, CEN www.fhea.com anthony@fhea.com Fitzgerald Health Education Associates 67 Fitzgerald Health Education Associates 68 Copyright Notice Images/Illustrations: Unless otherwise noted, all images/ illustrations are from open sources, such as the CDC or Wikipedia or property of FHEA or author. All websites listed active at the time of publication. Copyright by Fitzgerald Health Education Associates All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording or any information storage and retrieval system, without permission from Fitzgerald Health Education Associates Requests for permission to make copies of any part of the work should be mailed to: Fitzgerald Health Education Associates 85 Flagship Drive North Andover, MA 01845-6184 Fitzgerald Health Education Associates 69 Fitzgerald Health Education Associates 70 Statement of Liability The information in this program has been thoroughly researched and checked for accuracy. However, clinical practice and techniques are a dynamic process and new information becomes available daily. Prudent practice dictates that the clinician consult further sources prior to applying information obtained from this program, whether in printed, visual or verbal form. Fitzgerald Health Education Associates disclaims any liability, loss, injury or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents of this presentation. Fitzgerald Health Education Associates 85 Flagship Drive North Andover, MA 01845-6154 978.794.8366 Fax-978.794.2455 Website: fhea.com Learning & Testing Center: fhea.com/npexpert www.facebook.com/fitzgeraldhealth @npcert Fitzgerald Health Education Associates 71 Fitzgerald Health Education Associates 72