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Epileptic Emergencies: Status Epilepticus in Canine Patients

Epileptic Emergencies: Status Epilepticus in Canine Patients
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Oriana D. Scislowicz, BS, LVT
CVCA Cardiac Care for Pets, Richmond, Virginia

Status epilepticus (SE) is characterized by epileptic seizures that continue for more than 5 minutes, or the occurrence of more than 1 seizure within a 5-minute period in which the human or animal does not return to “normal” in between seizures. Some seizures may last 20 to 30 minutes or longer.

The official definition—as defined by the International League Against Epilepsy—is a seizure that shows no clinical signs of arresting after a duration encompassing the great majority of seizures of that type in most patients, or recurrent seizures without resumption of baseline central nervous system function interictally.

Nearly 60% of epileptic dogs will—at some point in their lifetime—experience one or more SE events.1 The prognosis for dogs with SE is quite poor—up to 25% of affected dogs will not survive to hospital discharge.1 Moreover, the life span of epileptic patients with SE is drastically shortened compared with the life span of epileptic patients experiencing other types of epilepsy (ie, 3-year difference).2 Therefore, SE creates much concern among clinicians and pet owners alike.

SEIZURE TYPES

Cluster seizures may be a precursor of SE, and are defined as 2 or more seizures within 24 hours. However, they differ from SE because, during cluster seizures, patients regain consciousness, or return to baseline central nervous system function, between seizures.2

SE may be classified as either convulsive or nonconvulsive. Convulsive SE is the classic tonic-clonic seizure presentation, where first muscles stiffen, then the body begins to rhythmically jerk. SE is defined as nonconvulsive if patients do not regain consciousness within 30 minutes to an hour after a seizure, but are still experiencing subclinical cerebral seizure activity. Nonconvulsive SE is characterized by the presence of a stuporous, unresponsive state rather than active convulsions. Electroencephalography (EEG) may show epileptiform activity, even if the patient does not appear to be in a classic seizure-like state (Figures 1 and 2).

OLYMPUS DIGITAL CAMERA

FIGURE 1. Canine patient exhibiting seizure activity with tonic–clonic limb movements. Reproduced with permission from Chrisman CL. Neurology for the Small Animal Practitioner. Jackson, WY: Teton NewMedia, 2003.

 

2015_0506_TT_Status Epilepticus_Fig2

FIGURE 2. Seizures originate in the forebrain (cerebrum and diencephalon); the dots highlight these areas of the brain and suggest possible locations for lesions that might cause SE. Reproduced with permission from Chrisman CL. Neurology for the Small Animal Practitioner. Jackson, WY: Teton NewMedia, 2003.

 

PATHOPHYSIOLOGY

When seizures occur, functional abnormalities of neuronal cell membrane ion pumps (such as sodium-potassium ATPase and Ca2+ ATPase) cause an imbalance of the intracellular and extracellular concentrations of potassium and calcium, which leads to depolarization. Neurons become more excitable, which allows the seizure to spread more easily. When SE develops, excessive excitation occurs and inhibition, which would stop an isolated seizure event, fails.2

SE has 2 separate phases: early and late; then, the patient enters the maintenance or self-sustaining phase of seizure activity.

Typically, the early phase occurs in the first 30 minutes:

  • Stress-induced release of catecholamines causes cardiovascular effects—increased heart rate and systemic blood pressure, along with elevated left atrial and central venous pressure; arrhythmias are also common.
  • An increase in bronchial secretions and salivation, and a decrease in ventilation, can result in hypoxemia.
  • Increased muscle activity causes overheating and the patient becomes hyperthermic.

The late phase occurs during the latter portion of an SE event, after the 30-minute mark:

  • Respiratory compromise may occur due to neurogenic pulmonary edema, which is characterized by accumulation of pulmonary interstitial and alveolar fluid, most severe in the dorsocaudal lung fields, that is triggered by brain stem hypoxia. Aspiration of saliva and regurgitated gastric contents can also occur and contribute to respiratory complications. Consequently, hypoxia and hypercarbia may result.
  • Prolonged sympathetic nervous system stimulation and excessive release of catecholamines may damage cardiac myocytes, leading to impaired cardiac contractility. Decreased cardiac output is exacerbated by hypovolemia, resulting in hypotension, which decreases perfusion to the brain, myocardium, and viscera. Cardiac arrhythmias may result from acidemia, hypoxemia, electrolyte abnormalities, and sympathetic stimulation, further decreasing cardiac output.2
  • Poor kidney perfusion and rhabdomyolysis may result in acute kidney injury or acute renal failure.

Once the patient reaches the maintenance or self-sustaining phase, a certain amount of neurologic damage has occurred and spontaneous resolution of the seizure becomes less likely. As SE progresses, hyperexcitable networks are enhanced and the seizure becomes more difficult to treat, garnering a poorer prognosis.

Clinical Approach

In patients with SE, the essential goals for the veterinary team are to:

  1. Stabilize the patient
  2. End seizure activity
  3. Correct adverse consequences of SE.

 

STABILIZATION: MEDICATIONS

Currently, there are no FDA-approved drugs specifically for SE in either human or veterinary patients. Instead, standard anticonvulsant and anesthetic drugs are used IV to end seizure activity.

Immediate Medical Therapy

As in most emergency situations, when a patient experiencing an SE episode is presented, the veterinary team should:

  • Place an IV catheter and begin administration of antiepileptic drugs (AEDs) (Table 1)
  • Provide oxygen by mask or flow-by administration.

It is critical to act quickly because neurologic damage continues to occur until seizure activity is ended.

At the time of IV catheter placement, it is beneficial to obtain a blood sample to perform an initial evaluation of blood glucose and electrolytes, which assists in ruling out a metabolic cause of seizures. Obtaining a packed cell volume/total solids is also ideal to help guide fluid therapy. A brief physical examination should evaluate airway patency, pulse quality, and rectal temperature.

Diazepam is typically administered via the IV route. If IV access is not possible, diazepam can be delivered rectally or intranasally, but it may have variable efficacy via these alternate routes. With regard to rectal administration, the presence of feces, extensive first-pass hepatic metabolism, ejection of the drug, and unpredictable absorption may contribute to lower efficacy.3

Effective vascular access must be established, if necessary, by surgical cut-down or by placement of an intraosseous catheter. If there is no response to IV diazepam after 1 to 2 doses, another AED may be chosen.

Levetiracetam is usually the next AED of choice and can be administered via IV, SC, or IM routes. This drug has less profound sedative effects than diazepam, and may be a better option for patients already in a dull state.2 Because levetiracetam is not metabolized by the liver, it is a safer drug for patients with hepatic compromise. However, it is excreted through the renal system, and patients with kidney disease may not be prime candidates for its use.

Lorazepam and midazolam are other options for AED therapy. Although more expensive, lorazepam tends to provide longer lasting seizure control compared with diazepam.

  • One or 2 initial IV dose(s) of lorazepam or midazolam is given and, if effective, can be followed by a constant rate infusion (CRI) in order to prevent recurrence of the seizure.1
  • Animals must be monitored for excessive cerebral depression while receiving CRIs of benzodiazepines, and the dose reduced over time to the minimum required to control seizures while maintaining a gag reflex.
  • Typically, patients are maintained on the CRI for 12 to 24 hours; then weaned off the CRI while being monitored carefully.

 

2015_0506_TT_Status Epilepticus_Table1

Ongoing Antiepileptic Drug Therapy
Once the patient is stabilized, long-term anticonvulsants can be initiated to prevent recurrence of seizure activity in the coming hours.

Phenobarbital is commonly used for long-term antiepileptic therapy, and it can be used IV for acute therapy of SE. However, it tends to cause significant cerebral depression and may cause hypotension and respiratory depression, necessitating monitoring of blood pressure and respiratory function. A loading dose of phenobarbital is calculated using this equation:

Body weight (kg) x 0.8 L/kg x desired phenobarbital serum concentration1

= Dose (mg) of phenobarbital to administer

The total calculated dose is divided into 4 to 6 aliquots, which are given no more than every 30 minutes. If the patient becomes excessively sedated, the subsequent aliquot can be skipped or delayed.

If the patient continues to seizure despite administration of benzodiazepines, levetiracetam, and phenobarbital, the following drugs can be added to therapy:

  • Fosphenytoin: Important to monitor for hypotension, arrhythmias, ataxia, and vomiting; a multicenter study is assessing the use and efficacy of this drug
  • Phenytoin: Administration should be slow to prevent cardiotoxicity and hypotension
  • Propofol: Often considered a last line of defense in patients with SE; those receiving this agent should be monitored closely for adverse blood pressure and respiratory effects
  • Ketamine: May have neuroprotective benefits and help end the maintenance, or self-sustaining, phase.2

 

Medical therapy at home

In some cases of SE, the client cannot bring the patient to the hospital quickly enough for management and must administer antiepileptic therapy at home prior to transport to the clinic. Note: For safety, clients should never give oral medications to an animal having seizure activity.

  • Recommended therapy for patients at home is a 1 mg/kg bolus of diazepam rectally Q 20 minutes, for a total of 4 or 5 doses after the second or third seizure.5
  • Many clients can be trained to administer rescue medications, such as midazolam, by IM injection prior to transport, with a more predictable response than that to rectally administered drugs. Note: Diazepam is not well absorbed when administered IM.
  • The attending neurologist may recommend that other maintenance AEDs, such as levetiracetam, phenobarbital, or zonisamide, be incorporated into the long-term seizure management protocol.
  • Ultimately, after 3 seizures within a 24-hour period, the client should bring the patient to the veterinary hospital for IV treatment and monitoring.

 

 STABILIZATION: FURTHER CARE 

The stabilization process involves many other elements in addition to control of seizure activity (Table 2).

2015_0506_TT_Status Epilepticus_Table2

Physiologic Concerns

Blood Pressure. Because hypertension, and then hypotension, is common in these patients and can worsen with addition of AEDs, monitor blood pressure at least every 1 to 2 hours while the patient is sedated, more frequently if it becomes abnormal, and maintain systolic blood pressure between 100 and 150 mm Hg.

Technicians should be aware of the Cushing’s reflex in these patients: if hypertension is noted alongside bradycardia, it raises concern for presence of high intracranial pressure. In hypotensive patients, hypertonic saline may be considered at 4 mL/kg over 10 minutes. Administer a balanced electrolyte replacement solution at a maintenance rate or, if needed to treat hypotension, at a higher rate.

Temperature. Patients often are hyperthermic, and body temperature should be regulated, if possible. If the patient has a temperature higher than 104°F, begin passive cooling, and monitor rectal temperature every 15 minutes; end cooling efforts once the patient’s temperature reaches 102°F. Hypothermia may occur in heavily sedated animals once seizure activity stops, and warming may be needed at that time.

Respiration. Patients with SE may be heavily sedated while receiving AED therapy and, therefore, have difficulty protecting their upper airways. Assess gag reflex every 15 to 20 minutes if the patient is unresponsive. If the gag reflex is insufficient or absent, it may be necessary to intubate these patients to help prevent and treat hypoxemia and protect the airway from aspiration. In intubated patients, carbon dioxide (CO2) should be monitored using end-tidal capnography or blood gases.

  • If CO2 levels exceed 45 mm Hg, discuss with the clinician placing the patient on a ventilator.
  • If CO2 levels exceed 60 mm Hg, immediately begin mechanical ventilation using an Ambubag.

Note: Nasal oxygen should not be administered because it may increase intracranial pressure.6 For conscious patients, a face mask, oxygen cage, or flow-by method can be used to administer oxygen. If patients are unconscious and have lost their gag reflex, oxygen is most safely and effectively provided via an endotracheal tube.

Oxygenation should be monitored by the arterial blood gas PaO2 or SaO2, which indicates the level of oxygen saturation of hemoglobin. Pulse oximetry can be monitored cageside as an additional continuous indicator of oxygenation levels.

Metabolic Abnormalities

Sodium abnormalities, along with hypocalcemia and hypoglycemia, can occur. During treatment of electrolyte imbalances, monitor heart rate and rhythm via electrocardiography, paying close attention to whether bradycardia is present. Cease treatment and contact a clinician if bradycardia occurs.

Sodium. Sodium should be corrected slowly to avoid contributing to neurologic deficits. In patients with hypernatremia, serum sodium levels should be lowered at a rate of 0.5 to 1 mEq/L/H, as cerebral edema may occur if plasma sodium levels change too quickly.

Administer hypotonic IV fluids to provide free water, diluting the high plasma sodium. If hypernatremia has existed more than 24 hours, perform correction at a slower rate. In rare cases of hyponatremia, 3% saline may be utilized, and the rate of correction should not exceed 0.5 mEq/L/H.

Plasma sodium should be monitored initially every 2 to 4 hours, to ensure that the correction rate is appropriate and allow adjustment of fluid dose and rate, if necessary.

Calcium. Hypocalcemia can be treated by slow administration of 10% calcium gluconate, 0.5 to 1.5 mL/kg IV over 10 minutes.

Glucose. Hypoglycemia is often treated with slow administration of a bolus of 50% dextrose, 1 mL/kg diluted to 25%, over 15 minutes. To avoid adverse effects of hyperglycemia, such as contributing to neuronal injury, administer thiamine, 20 to 59 mg/animal IM, prior to administration of dextrose.2

Neurologic Protection

Protecting the brain during stabilization is vital, as SE can lead to such sequelae as cerebral edema, neuronal necrosis, and increased intracranial pressure.

  • Mannitol, 0.25 to 1 g/kg IV, can be administered over 20 minutes; then 15 minutes later, furosemide, 0.7 mg/kg IV, can be administered to help with diuresis. Furosemide may be avoided in hypotensive patients.
  • While the patient is resting, elevate the top half of the body (not just the head) 30° to help reduce intracranial pressure.
  • Avoid jugular blood collection and catheters, nasogastric tubes, and nasal oxygen catheters to decrease the risk for elevating intracranial pressure.
  • If intubation is necessary, administer IV lidocaine ahead of time to reduce the associated cough reflex.7

Additional Nursing Care

Other nursing care advised for patients with SE includes:

  • Recumbent patient care, padded cages, and rotation every 4 hours
  • Close monitoring of vitals, especially blood pressure, and weight
  • Lubrication of eyes and removal of secretions from the mouth, pharynx, and airway, if necessary
  • Placement of a urinary catheter, with urine output monitored every 4 hours
  • If needed, dexmedetomidine as a low-dose CRI to help relieve agitation and anxiety during the recovery period.

DIAGNOSTIC APPROACH

Once the patient is stabilized, further diagnostics, such as EEG and magnetic resonance imaging (MRI), may be pursued.

EEG should be considered the gold standard for diagnosis of patients with SE. In particular, it is useful for:

  • Determining whether emergency drug therapy is managing the seizure
  • Ascertaining whether the brain is continuing to actively seize even though the physical signs have resolved.

Patients in nonconvulsive SE—rather than presenting with a classic grand mal seizure—may instead present in a stuporous and/or unresponsive state or have subtle twitching. Additionally, when patients have received multiple drugs to control SE, as they awake, it may be difficult to distinguish recurrence of seizure activity from normal sedative recovery. Investigation with EEG can help better diagnose these patients and lead to correct treatment.

Diagnostic Imaging

MRI and computed tomography can help determine structural damage as a cause or consequence of seizure activity. On MRI, lesions can appear within the piriform/temporal lobes as a result of SE, but once a patient is seizure-free, they resolve within 10 days to 18 weeks.2

Laboratory Analysis

Blood analysis is also an important diagnostic tool in patients with SE.

  • In particular, blood analysis is key in evaluating glucose, sodium, and calcium levels.
  • SE, in general, may cause hypoxia and hypotension, resulting in elevated liver enzymes.
  • Patients experiencing convulsive SE may have increases in muscle enzymes.
  • Hypovolemia can lead to elevation of kidney values.
  • Onset of pneumonia can lead to changes in white blood cell count.
  • Blood analysis can also reveal metabolic disturbances that may have triggered SE activity.2

IN SUMMARY

Although SE cases can be intensive and difficult to manage, it is important for technicians and supportive veterinary team members to implement the necessary nursing care.

  • The excessive seizure activity itself can cause metabolic imbalances and harmful effects on intracranial pressure that must be closely managed.
  • Technical staff should understand the adverse effects and risks of certain AEDs, such as hypotension, excessive sedation, hypoxemia, and bradycardia.
  • Appropriate recumbent care, along with close monitoring of awareness level, gag reflex, blood pressure, oxygenation, and pupillary light reflexes, is necessary.

Successful outcomes for these patients often rely on top-notch, observant nursing care.

AED = antiepileptic drug; CO2 = carbon dioxide; CRI = constant rate infusion; EEG = electroencephalography; MRI = magnetic resonance imaging; PaO2 = partial pressure of oxygen; SaO2 = hemoglobin saturation with oxygen; SE = status epilepticus

References

  1. Rossmeisl JH. An update on the management of status epilepticus. Las Vegas, NV: Western Veterinary Conference Proceedings, 2013.
  2. Platt SR, Garosi L. Small Animal Neurological Emergencies. London: Manson Publishers/The Veterinary Press, 2012.
  3. Platt S. Benzodiazepines. In DeRisio L, Platt S (eds): Canine and Feline Epilepsy: Diagnosis and Management, 1st ed. Boston, MA: CABI, 2014, p 484.
  4. Dewey C. Seizures and narcolepsy. In: A Practical Guide to Canine and Feline Neurology, 2nd ed. Ames, Iowa: Wiley-Blackwell, 2008, p 248.
  5. Quesnel A. Emergency treatment of status epilepticus and cluster seizures in dogs and cats. Vancouver, British Columbia, Canada: WSAVA Congress Proceedings, 2001.
  6. Bach J. Seizures and status epilepticus. Kansas City, KS: Central Veterinary Conference Proceedings, 2011.
  7. Mariani CL. Treatment of cluster seizures and status epilepticus. Washington, DC: Central Veterinary Conference Proceedings, 2011.

 

 

Oriana D ScislowiczOriana D. Scislowicz, BS, LVT, is Team Leader of CVCA Cardiac Care for Pets, Richmond, Virginia. She currently serves on the editorial advisory board of Firstline, and has served on the executive board of the Virginia Association of Licensed Veterinary Technicians. Ms. Scislowicz writes for publications, such as NAVTA Journal, Firstline, VetTechLife, and Today’s Veterinary Practice. She received her BS in psychology from Virginia Commonwealth University and her AAS in veterinary technology from Blue Ridge Community College.

 

 

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>Bahamas</option><option value='Bahrain' >Bahrain</option><option value='Bangladesh' >Bangladesh</option><option value='Barbados' >Barbados</option><option value='Belarus' >Belarus</option><option value='Belgium' >Belgium</option><option value='Belize' >Belize</option><option value='Benin' >Benin</option><option value='Bermuda' >Bermuda</option><option value='Bhutan' >Bhutan</option><option value='Bolivia' >Bolivia</option><option value='Bonaire, Sint Eustatius and Saba' >Bonaire, Sint Eustatius and Saba</option><option value='Bosnia and Herzegovina' >Bosnia and Herzegovina</option><option value='Botswana' >Botswana</option><option value='Bouvet Island' >Bouvet Island</option><option value='Brazil' >Brazil</option><option value='British Indian Ocean Territory' >British Indian Ocean Territory</option><option value='Brunei Darussalam' >Brunei Darussalam</option><option value='Bulgaria' >Bulgaria</option><option value='Burkina Faso' >Burkina Faso</option><option value='Burundi' >Burundi</option><option value='Cambodia' >Cambodia</option><option value='Cameroon' >Cameroon</option><option value='Canada' >Canada</option><option value='Cape Verde' >Cape Verde</option><option value='Cayman Islands' >Cayman Islands</option><option value='Central African Republic' >Central African Republic</option><option value='Chad' >Chad</option><option value='Chile' >Chile</option><option value='China' >China</option><option value='Christmas Island' >Christmas Island</option><option value='Cocos Islands' >Cocos Islands</option><option value='Colombia' >Colombia</option><option value='Comoros' >Comoros</option><option value='Congo, Democratic Republic of the' >Congo, Democratic Republic of the</option><option value='Congo, Republic of the' >Congo, Republic of the</option><option value='Cook Islands' >Cook Islands</option><option value='Costa Rica' >Costa Rica</option><option value='Côte d&#039;Ivoire' >Côte d&#039;Ivoire</option><option value='Croatia' >Croatia</option><option value='Cuba' >Cuba</option><option value='Curaçao' >Curaçao</option><option value='Cyprus' >Cyprus</option><option value='Czech Republic' >Czech Republic</option><option value='Denmark' >Denmark</option><option value='Djibouti' >Djibouti</option><option value='Dominica' >Dominica</option><option value='Dominican Republic' >Dominican Republic</option><option value='Ecuador' >Ecuador</option><option value='Egypt' >Egypt</option><option value='El Salvador' >El Salvador</option><option value='Equatorial Guinea' >Equatorial Guinea</option><option value='Eritrea' >Eritrea</option><option value='Estonia' >Estonia</option><option value='Eswatini (Swaziland)' >Eswatini (Swaziland)</option><option value='Ethiopia' >Ethiopia</option><option value='Falkland Islands' >Falkland Islands</option><option value='Faroe Islands' >Faroe Islands</option><option value='Fiji' >Fiji</option><option value='Finland' >Finland</option><option value='France' >France</option><option value='French Guiana' >French Guiana</option><option value='French Polynesia' >French Polynesia</option><option value='French Southern Territories' >French Southern Territories</option><option value='Gabon' >Gabon</option><option value='Gambia' >Gambia</option><option value='Georgia' >Georgia</option><option value='Germany' >Germany</option><option value='Ghana' >Ghana</option><option value='Gibraltar' >Gibraltar</option><option value='Greece' >Greece</option><option value='Greenland' >Greenland</option><option value='Grenada' >Grenada</option><option value='Guadeloupe' >Guadeloupe</option><option value='Guam' >Guam</option><option value='Guatemala' >Guatemala</option><option value='Guernsey' >Guernsey</option><option value='Guinea' >Guinea</option><option value='Guinea-Bissau' >Guinea-Bissau</option><option value='Guyana' >Guyana</option><option value='Haiti' >Haiti</option><option value='Heard and McDonald Islands' >Heard and McDonald Islands</option><option value='Holy See' >Holy See</option><option value='Honduras' >Honduras</option><option value='Hong Kong' >Hong Kong</option><option value='Hungary' >Hungary</option><option value='Iceland' >Iceland</option><option value='India' >India</option><option value='Indonesia' >Indonesia</option><option value='Iran' >Iran</option><option value='Iraq' >Iraq</option><option value='Ireland' >Ireland</option><option value='Isle of Man' >Isle of Man</option><option value='Israel' >Israel</option><option value='Italy' >Italy</option><option value='Jamaica' >Jamaica</option><option value='Japan' >Japan</option><option value='Jersey' >Jersey</option><option value='Jordan' >Jordan</option><option value='Kazakhstan' >Kazakhstan</option><option value='Kenya' >Kenya</option><option value='Kiribati' >Kiribati</option><option value='Kuwait' >Kuwait</option><option value='Kyrgyzstan' >Kyrgyzstan</option><option value='Lao People&#039;s Democratic Republic' >Lao People&#039;s Democratic Republic</option><option value='Latvia' >Latvia</option><option value='Lebanon' >Lebanon</option><option value='Lesotho' >Lesotho</option><option value='Liberia' >Liberia</option><option value='Libya' >Libya</option><option value='Liechtenstein' >Liechtenstein</option><option value='Lithuania' >Lithuania</option><option value='Luxembourg' >Luxembourg</option><option value='Macau' >Macau</option><option value='Macedonia' >Macedonia</option><option value='Madagascar' >Madagascar</option><option value='Malawi' >Malawi</option><option value='Malaysia' >Malaysia</option><option value='Maldives' >Maldives</option><option value='Mali' >Mali</option><option value='Malta' >Malta</option><option value='Marshall Islands' >Marshall Islands</option><option value='Martinique' >Martinique</option><option value='Mauritania' >Mauritania</option><option value='Mauritius' >Mauritius</option><option value='Mayotte' >Mayotte</option><option value='Mexico' >Mexico</option><option value='Micronesia' >Micronesia</option><option value='Moldova' >Moldova</option><option value='Monaco' >Monaco</option><option value='Mongolia' >Mongolia</option><option value='Montenegro' >Montenegro</option><option value='Montserrat' >Montserrat</option><option value='Morocco' >Morocco</option><option value='Mozambique' >Mozambique</option><option value='Myanmar' >Myanmar</option><option value='Namibia' >Namibia</option><option value='Nauru' >Nauru</option><option value='Nepal' >Nepal</option><option value='Netherlands' >Netherlands</option><option value='New Caledonia' >New Caledonia</option><option value='New Zealand' >New Zealand</option><option value='Nicaragua' >Nicaragua</option><option value='Niger' >Niger</option><option value='Nigeria' >Nigeria</option><option value='Niue' >Niue</option><option value='Norfolk Island' >Norfolk Island</option><option value='North Korea' >North Korea</option><option value='Northern Mariana Islands' >Northern Mariana Islands</option><option value='Norway' >Norway</option><option value='Oman' >Oman</option><option value='Pakistan' >Pakistan</option><option value='Palau' >Palau</option><option value='Palestine, State of' >Palestine, State of</option><option value='Panama' >Panama</option><option value='Papua New Guinea' >Papua New Guinea</option><option value='Paraguay' >Paraguay</option><option value='Peru' >Peru</option><option value='Philippines' >Philippines</option><option value='Pitcairn' >Pitcairn</option><option value='Poland' >Poland</option><option value='Portugal' >Portugal</option><option value='Puerto Rico' >Puerto Rico</option><option value='Qatar' >Qatar</option><option value='Réunion' >Réunion</option><option value='Romania' >Romania</option><option value='Russia' >Russia</option><option value='Rwanda' >Rwanda</option><option value='Saint Barthélemy' >Saint Barthélemy</option><option value='Saint Helena' >Saint Helena</option><option value='Saint Kitts and Nevis' >Saint Kitts and Nevis</option><option value='Saint Lucia' >Saint Lucia</option><option value='Saint Martin' >Saint Martin</option><option value='Saint Pierre and Miquelon' >Saint Pierre and Miquelon</option><option value='Saint Vincent and the Grenadines' >Saint Vincent and the Grenadines</option><option value='Samoa' >Samoa</option><option value='San Marino' >San Marino</option><option value='Sao Tome and Principe' >Sao Tome and Principe</option><option value='Saudi Arabia' >Saudi Arabia</option><option value='Senegal' >Senegal</option><option value='Serbia' >Serbia</option><option value='Seychelles' >Seychelles</option><option value='Sierra Leone' >Sierra Leone</option><option value='Singapore' >Singapore</option><option value='Sint Maarten' >Sint Maarten</option><option value='Slovakia' >Slovakia</option><option value='Slovenia' >Slovenia</option><option value='Solomon Islands' >Solomon Islands</option><option value='Somalia' >Somalia</option><option value='South Africa' >South Africa</option><option value='South Georgia' >South Georgia</option><option value='South Korea' >South Korea</option><option value='South Sudan' >South Sudan</option><option value='Spain' >Spain</option><option value='Sri Lanka' >Sri Lanka</option><option value='Sudan' >Sudan</option><option value='Suriname' >Suriname</option><option value='Svalbard and Jan Mayen Islands' >Svalbard and Jan Mayen Islands</option><option value='Sweden' >Sweden</option><option value='Switzerland' >Switzerland</option><option value='Syria' >Syria</option><option value='Taiwan' >Taiwan</option><option value='Tajikistan' >Tajikistan</option><option value='Tanzania' >Tanzania</option><option value='Thailand' >Thailand</option><option value='Timor-Leste' >Timor-Leste</option><option value='Togo' >Togo</option><option value='Tokelau' >Tokelau</option><option value='Tonga' >Tonga</option><option value='Trinidad and Tobago' >Trinidad and Tobago</option><option value='Tunisia' >Tunisia</option><option value='Turkey' >Turkey</option><option value='Turkmenistan' >Turkmenistan</option><option value='Turks and Caicos Islands' >Turks and Caicos Islands</option><option value='Tuvalu' >Tuvalu</option><option value='Uganda' >Uganda</option><option value='Ukraine' >Ukraine</option><option value='United Arab Emirates' >United Arab Emirates</option><option value='United Kingdom' >United Kingdom</option><option value='United States' >United States</option><option value='Uruguay' >Uruguay</option><option value='US Minor Outlying Islands' >US Minor Outlying Islands</option><option value='Uzbekistan' >Uzbekistan</option><option value='Vanuatu' >Vanuatu</option><option value='Venezuela' >Venezuela</option><option value='Vietnam' >Vietnam</option><option value='Virgin Islands, British' >Virgin Islands, British</option><option value='Virgin Islands, U.S.' >Virgin Islands, U.S.</option><option value='Wallis and Futuna' >Wallis and Futuna</option><option value='Western Sahara' >Western Sahara</option><option value='Yemen' >Yemen</option><option value='Zambia' >Zambia</option><option value='Zimbabwe' 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