Vol. 22, No. 8 August 2000

Refereed Peer Review

FOCAL POINT 5The ideal pharmacologic
treatment of status epilepticus (SE) requires the use of an intravenous lipid-soluble anticonvulsant to rapidly attain and then maintain a therapeutic drug concentration in the brain.

Status Epilepticus: Patient Management and Pharmacologic Therapy*
University of Georgia

s Vital functions such as glucose metabolism, oxygenation, and temperature regulation should be monitored in patients with SE to prevent significant neurologic morbidity. s The drug used to treat SE should be determined by its ease of administration, time of onset, duration of effect, and extent of effects on cardiorespiratory function and level of consciousness. s A dangerous error that is commonly made when managing SE is to treat consecutive seizures with repeated doses of intravenous diazepam without treating the precipitating factors and without administering an adequate loading dose of a longer-acting antiepileptic drug.

Simon R. Platt, BVM&S, MRCVS John J. McDonnell, DVM, MS
ABSTRACT: Status epilepticus (SE) requires immediate treatment of the seizure activity to prevent the possibility of permanent brain damage. Intravenous drug therapy, most commonly achieved using diazepam, should be instituted without delay. Intravenous or intramuscular phenobarbital, often used in addition to a diazepam protocol, affords a longer period of seizure control. The use of multiple drugs in SE patients is limited by the onset of hypotension. Patients that do not respond to this pharmacologic approach are considered to be refractory; a more aggressive protocol involving intensive care will be required and, depending on the cause, may not be successful. This article addresses the systemic and pharmacologic management of SE.


tatus epilepticus (SE) is a medical emergency that requires immediate therapy to prevent severe cerebral damage.1–5 The management of SE involves prompt control of seizures as well as treatment of the systemic effects and underlying causes3 (Figure 1). The side effects of aggressive pharmacologic treatment should be recognized when determining a treatment plan. The first article in this series addressed the features and pathophysiology of SE. This paper discusses the antiepileptic drug (AED) therapies used to treat SE. A final article (see page 732) will discuss therapies for refractory patients and potential at-home treatment.

PATIENT MANAGEMENT Status epilepticus can be a danger to patients and can provide a treatment challenge for clinicians. Treatment can be divided into acute emergency management and rational drug administration. Emergency care is designed to prevent
*A companion article entitled “Status Epilepticus: Clinical Features and Pathophysiology” appeared in the July 2000 (Vol. 22 No. 7) issue of Compendium. A final installment in the series, entitled “Status Epilepticus: Managing Refractory Cases and Out-of-Hospital Patients,” can be found in this issue.

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Small Animal/Exotics

patient injury, whereas drug treatment is guided by its ability to limit morbidity resulting from systemic changes or from seizure-induced neuronal damage.6 The goal of immediate treatment is to stop the abnormal cerebral electrical activity associated with SE.3 The overall objectives in managing SE are to maintain vital functions at all times, identify and treat precipitating factors of SE, and administer an AED.7

Status Epilepticus


Significant impairment of airway, breathing, or circulation


IV glucose assessment

Urgent medical therapy 1) Intubate if necessary 2) Adequate venous access 3) IV glucose assessment 4) Temperature assessment 5) Pressors if necessary

for fluid and drug administration. Maintenance administration of IV isotonic saline, supplemented with potassium chloride, may be initiated. Other secondary metabolic complications (e.g., electrolyte imbalance) must be corrected.2,8

Glucose <60 mg/dL
Yes No

MAINTAINING VITAL Administer 1) IV isotonic saline at FUNCTIONS 1) Intramuscular thiamine a maintenance rate Treatment must sometimes (vitamin B ), 50 mg 2) Complete blood count, 2) IV dextrose 50%, 500 chemistry, electrolytes be initiated before a diagnosmg/kg over 15 minutes plus toxicity screen tic evaluation can be made. Medical and neurologic examinations should be perNeurologic examination formed concomitant with patient management. The Figure 1—Patients that present in status epilepticus should initial care of patients with be considered to be in systemic crisis. Immediate assessment Temperature Regulation Hyperthermia, which can SE requires basic medical and stabilization are essential, as depicted in this flow diabe life threatening, can ocemergency measures, other- gram. (IV = intravenous) cur frequently during SE and wise known as the ABCs of even in humans represents a life support (i.e., airway, manifestation of the seizures rather than evidence of an breathing, circulation).3,8 infection.4,10 Hyperthermia should be treated promptly Oxygenation, Airway, and Acid–Base Status with passive cooling, especially if the body temperature Hypoxia may cause SE6 and must be corrected before exceeds 40˚C (104˚F).9 In some patients, temperature recovery can occur. Likewise, SE can also induce hypoxshould be monitored rectally, particularly if cooling ia.6 Airway management and respiratory monitoring in techniques are used. Passive cooling should be stopped patients with SE can be difficult. If possible, airway pawhen body temperature reaches 102˚F to prevent retency should be maintained while the patient remains bound hypothermia.9 unresponsive. Oxygen may be administered by using a PRINCIPLES OF DRUG TREATMENT nonrebreathing mask or an intranasal delivery system. The drug used in SE treatment can be determined by Arterial blood gas monitoring is extremely useful in its ease of administration, time of onset, duration of efpatients with SE because marked metabolic acidosis can fect, and minimal effects on cardiorespiratory function be prevalent during the convulsive episodes. Respiratoand level of consciousness.11–13 Unfortunately, no single ry acidosis or hypoxia detected on the blood gas analydrug is ideal.3,12 The rate of brain entry of a drug is disis should be treated immediately, whereas metabolic rectly proportional to the non–protein-bound drug acidosis may resolve after the physical manifestations of serum concentration, lipid solubility, and cerebral the convulsions subside. In experimental animal studblood flow.13 Therefore, SE can be treated by IV infuies, the severity of brain damage correlated best with sion (to obtain high serum concentration) of lipid-soluhypoxia, hypotension, and pyrexia as well as the durable AEDs. Drug volume of distribution increases with tion of the convulsive status.2,3,8 lipid solubility, and lipid-soluble drugs tend to redisIntravenous Access tribute out of the brain and serum and into body fat.13 A large intravenous (IV) catheter should be inserted To rapidly attain and then maintain a therapeutic

Glucose Metabolism Patients presenting with altered consciousness should be administered a bolus of IV glucose as soon as hypoglycemia is confirmed by routine blood tests. Thiamine (vitamin B1) should be administered immediately before the glucose (25 to 50 mg per animal IM) because it is an important cofactor in the aerobic metabolism of glucose.9


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Compendium August 2000

serum and brain concentration of drug, a loading dose sufficient to attain the desired concentration throughout the volume of distribution must be administered. The loading dose of a drug can be computed using the following equation: Loading dose (mg/kg) = Desired concentration (mg/L) × Volume of distribution (L/kg) Drug loading is therefore a passive process determined by volume of distribution and is independent of drug elimination kinetics. Intravenous drug treatment for SE should be initiated without delay11 based on the relationship between duration of SE and the extent of neurologic morbidity2; experimental animal models suggest that SE becomes progressively less responsive to treatment with diazepam.11,14 Anticonvulsants prevent the synchronization of related neurons and can be more effective when they act at more than one biochemical site.4

These AEDs, which can be effective at low doses, inhibit seizure activity induced by pentylenetetrazol and picrotoxin in animal models.16 Adverse effects of IV benzodiazepines include respiratory depression, hypotension, and impaired consciousness.3,16 However, it is believed that a low incidence of respiratory depression with benzodiazepines occurs because of the low density of binding sites in the brain stem.17 The dose of diazepam that causes respiratory arrest in patients may be difficult to determine.3,5

PHARMACOLOGIC THERAPY Benzodiazepines Because the benzodiazepines (diazepam, lorazepam, midazolam, and clonazepam) are potent, fast-acting AEDs, these drugs (particularly diazepam) are the preferred initial therapy in SE.3,4,11,15 However, none of the benzodiazepines are effective for long-term control of SE.15 This widely used class of sedative/tranquilizer and anxiolytic agents differs greatly in course of timing and central effects.15 These differences may be related to their pharmacokinetics,15 especially their central nervous system (CNS) distribution, which has been related to the drugs’ lipophilicity and plasma protein binding.15 The lipophilicity of these compounds determines their rapid brain penetration after IV administration.15 Although penetration is rapid, distribution equilibrium among all regions takes longer.15 Their primary pharmacologic actions are probably related to a benzodiazepine-receptor–mediated enhancement of γ-aminobutyric acid (GABA) -ergic transmission, both pre- and postsynaptically.4,5,11,16,17 Benzodiazepines do not seem to alter the synthesis, release, or metabolism of GABA but rather potentiate its action at the receptor.17 The resultant augmented flow of chloride ions into cells decreases the cell’s ability to initiate an action potential.17 At higher concentrations, benzodiazepines also limit sustained repetitive neuronal firing in a manner similar to that of carbamazepine and phenytoin; this effect may be relevant to their mechanism of action in SE.11 Benzodiazepines seem to prevent the spread of seizure rather than suppress the focus.16 In animal screening tests, benzodiazepines have shown a broad spectrum of anticonvulsant activity.16

Diazepam Classified as a Schedule IV drug under the 1970 Controlled Substances Act, diazepam is not approved for animal use by the FDA4; however, it remains the drug of choice for the treatment of SE in dogs and cats.4 The major metabolites of diazepam, nordiazepam (desmethyldiazepam) and oxazepam, have up to 33% of the activity of the parent drug.4 Although the halflife of diazepam is 3.2 hours in dogs, the half-lives of the metabolites (up to 5.2 hours in the case of oxazepam) are slightly longer.18 With its relatively brief duration of action, diazepam is not a definitive therapy for SE. Because IV diazepam produces transiently high serum and brain concentrations, however, the drug can be useful in therapy. Because SE may end spontaneously, IV diazepam should not be administered to patients presenting in a postictal state unless another seizure occurs. In treating dogs and cats, diazepam has been recommended at a dose of 0.5 to 1.0 mg/kg IV, up to a maximum dose of 20 mg.4,19 This dose can be repeated to effect or twice within 2 hours.4 Constant-rate infusions of diazepam have been advocated in human and veterinary patients.4 The recommended dose is 2 to 5 mg/ hour in 5% dextrose in water.4 Continuous diazepam infusions have been shown to be an effective modality to control refractory SE in children and have been associated with a reduced need for ventilatory and vasopressor support.5 If diazepam does not control the seizures, the use of phenobarbital should be considered. Probably the most dangerous error commonly made in SE management is to treat consecutive seizures with repeated doses of IV diazepam without administering an adequate loading dose of a longer-acting AED. Patients will continue to have seizures, toxic concentrations of diazepam or diazepam metabolites will accumulate, and serious morbidity may result from diazepam overdosage. In some patients, administration of IV diazepam may not be possible. The drug can be given intramuscularly (IM), although absorption is not predictable.4 Rectal administration of diazepam may be considered initially at a dose of 0.5 to 2.0 mg/kg depending on whether


Compendium August 2000

Small Animal/Exotics

the animal was being treated with phenobarbital before the onset of SE.4,9 The higher dose may be necessary in dogs receiving long-term phenobarbital therapy.20 In untreated dogs, a per-rectum (PR) diazepam dose of 1 mg/kg resulted in a mean time to peak plasma concentration of 14.3 minutes.9 The peak concentration was 474 µg/L; plasma benzodiazepine concentrations greater than 300 µg/L were needed to provide anticonvulsant action in the dog’s brain.9

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We invite you to impart your clinical knowledge by discussing your interesting cases, unusual presentations, or procedures for clinical solutions for the following features:

Midazolam Midazolam is a recently developed water-soluble benzodiazepine of the group of 1,2-annelated benzodiazepines.21 The water solubility allows midazolam to be packaged without the use of such diluents as propylene glycol, thus decreasing venous and IM irritation.17 At physiologic pH, midazolam becomes extremely lipophilic, enabling a rapid onset of action.17 Like other benzodiazepines, midazolam is biotransformed by hepatic microsomal oxidation followed by glucuronide conjugation.17 Alpha-hydroxy-midazolam, the primary metabolite after hydroxylation, is pharmacologically active and has sedative properties equivalent to those of midazolam in humans, although only low levels of this metabolite could be detected after IV or IM administration of midazolam to dogs.17,22 All the metabolites are rapidly excreted in human urine, but in dogs a more predominant extrarenal excretion is suggested, probably through the bile.22 In dogs, the elimination half-life of these metabolites is 11 minutes.22 Midazolam has been shown to have a wide margin of safety and a broad therapeutic index12; therefore, it can diffuse rapidly across the capillary wall into the CNS and can be mixed with saline or glucose solutions.21 The mean plasma elimination half-life in dogs was 53 to 77 minutes following IV administration.22 Midazolam has a significant antiepileptic effect in humans proven to be caused by GABAA receptor stimulation3,23 and has been shown to be more effective and safer for the control of seizures than comparable doses of diazepam.17,21 A recent study in humans demonstrated the beneficial effects of an IV midazolam infusion in 11 of 12 patients with refractory SE.21 Data that relate concentrations of venous midazolam to anticonvulsant effects in humans or in animals are not yet available, although the anticonvulsant effect of midazolam has been documented in experimental animal models.17,21 Unlike diazepam, with erratic and incomplete IM absorption, midazolam is rapidly absorbed following IM injection, with a high bioavailability, an early onset of sedation, and early clinical effects.17 Peak plasma concentration in dogs after IM administration occurred within 15 minutes, and a mean elimination half-life of

isoning rn on a Rat Po Unexpected Tu
I.M., ., Dipl. A.C.V. Brooks, D.V.M . By Marjory on, D.V.M and Jeff Jacobs


A detailed account of a clinical dilemma takes readers from specific patient presentation through the steps leading to the ultimate diagnosis in 1000-1500 words.


was examd male Beagle, r-old, neutere Conugsy, a four-yea n of the rat poison hour of ingestio l placement ined within one d of subconjunctiva treatment consiste peroxide to induce trac® . Initial oral hydrogen and 30 mL of vomited a large of apomorphine therapy, Mugsy Addiresponse to this the rat bait. vomiting. In identified as gaslue material d charcoal by amount of green-b mL of activate nt included 200 neously (SC). tional treatme 2.5 mg/kg subcuta supply of and vitamin K1 with a 10-day tric intubation ed to his owners Mugsy was discharg 24 hours orally. K1 50 mg every vitamin
ry blood chemist nation. All


for PT determi PT at recheck hours later limits. The because corwithin normal d for 48 hours ted finding values were tion was schedule , an unexpec confirm K deficiency A recheck examina vitamin K regimen to was 65.9 seconds al PT due to vitamin initiating an ion of the owners reportrection of abnorm 48 hours of after complet Although his within 24 to and Mugsy coagulopathy. should resolve K1 as directed resolution of K1. of dose of vitamin persistent prolongation had given vitamin re to rat poison, clotting appropriate ed that they y the cause of nity for reexposu additional vitamin assay was markedl To determine had no opportu PT and whether bin time (PT) finding in the sent for more prothrom : 9.5-12.5). This clotting time time in the a sample was was needed, 57 seconds (normal d that his early preblood was drawn K therapy prolonged at it appeare ed analyses. Whole part 3.8 percent ion prevent ted because detailed coagulat anticoagulant (one was unexpec vomiting had , howand the productive citrate ide. Contrac centrifuged, directly into sentation with blood) and dose of rodentic to a vetpoison. parts a toxic cold packs a long-acting citrate to nine absorption of shipped on Coagulation s bromadiolone, at the same vitamin K1 plasma was supernatant (Comparative ever, contain e laboratory University, therefore resumed ory, Cornell erinary referenc Treatment was tic Laborat two weeks. completion Section, Diagnos dosage for another recheck, 48 hours after d ed and York). d of activate At Mugsy’s next was still markedly prolong Ithaca, New ion panel consiste thrombin sample. A , the PT The initial coagulattime (aPTT), PT, and of vitamin K1 g from the previous al vitaplastin TCT screenin unchanged partial thrombo aPTT and essentially submitted, parenter were (TCT). The ry profile was and the owners clotting time blood chemist 48 50 mg SC, given and recheck min K1 was vitamin K1 August 2000 resume oral instructed to

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While the course of therapy is often clear-cut, some patients present true challenges to medical skills. In 1000-1500 words, these cases describe the steps that eventually lead to case resolution.

Intussuscep tio In a Yearlin n g
By Linnea Lentz, D.V.M.

eau, a 15-mont h-old colt, had been colicky for about when the owners four hours called the referring and no other veterinarian. The abnormalidescribed as mild, colic was ties. An initial and Beau was treated IV injection with 10 cc Banamin ® nixine) administe of xylazine appeared e (flured intravenously to (IV), 10 cc of control the pain approximately 1 dipyrone IV, and for only 20 ⁄2 gallon of mineral minutes before oil administered a second tube. Within the via nasogastric dose was necessary. hour, Beau was again colicky and Rectal University of Minneso was referred to the palpation revealed ta. many
Initial Treatme nt on Referra l Clinical signs on presentation included profuse sweating, numerous attempts to lie down, and a distended abdomen. Physical examination revealed a pulse of 84 beats per minute, decreased gastrointe stinal motility in all four quadrants , slightly toxic mucous membran es, a capillary refill time of 2.5 seconds (normal: 1-2), and a normal temperature. Blood work revealed a packed cell volume of 48 percent (normal: 32-48), total protein of 7.2 g/dL (normal: 5.7-7.9),
August 2000


distended loops of small testine. After placemen int of a nasogastric reflux were obtained. tube, 6-7 L of Abdominocentesis results were normal. Because of the severity of the colic, the small intestinal distention , and nasogastr ic reflux, we recommended explorato ry laparotomy to diagnose the cause of the colt’s colic. The owners quickly agreed, and preoperative antibiotic potassium penicillin s, including 22,000 units/kg IV and Gentocin (gentamicin) 6.6 mg/kg IV, were administered before preparing the colt for surgery. During surgery, a jejunocec al intussuscep-➔
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is Canine Hemipares J

, D.V.M. By Donivan Hudgins

Some case presentations are so confounding that both diagnosis and therapy are perplexing. Often, a patient may return again and again with continuously changing signs. Word count: 1000-2000.

had been normal, activity levels old, 29were current asmine, a four-yearand vaccinations Retrievhepatitis, lepkg, spayed Golden for distemper, nza, parto the clinic er, was presented tosporosis, parainflue irus, Lyme of lameness. for sudden onset vovirus, coronoav found a stray The owner had disease, and rabies. and susgiven Solu The patient was goat in the backyard ® (prednisolone) may have goat pected that the Delta Cortef On presentausly (IV) and butted Jasmine. 100 mg intraveno 2.5 cc inambulatory was tion, the dog amoxicillin injectable uncoordinated, The owner was but obviously tramuscularly. n revealed the provide cage rest and observatio instructed to and return deficit was in primary walking over the weekend dog’s condition the right rear leg. Monday if the ion re. Physical examinat had not improved week, Jasre of 101.6˚F, The following vealed a temperatu es, capilto improve, and pink mucous membran (normal: mine appeared she did have of 1 sec lary refill time whatever problems heart and Over the next 1-2 sec), normal seemed subtle. sign of pain. The weeks, her problungs, and no two to three but not as prodid knuckle over, right rear foot lems recurred the propriobefore, and indicating decreased indicatnounced as that the dog pinch ception, but toe owner reported were intact. to her deficits. ed sensory nerves seemed to adjust next few weeks, of the affected Temperatures Then, over the no different of coördination foot and leg were Jasmine’s lack other three feet than that of the seemed to worsen. and flexion 21, Jasmine On October and legs. Extension for examinahip joints were of the stifle and was re-presented reflex on on a leash normal, but patellar tion. When followed appeared exaggerated, the right was in the lawn, Jasmine ated, with upper motor which suggested to be very uncoördin Appetite and neuron disease.
August 2000


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the active extrusion of sodium from neurons and the decrease of the spread of nerve impulses to other Diazepam 0.5 mg/kg neurons.4 As this drug deIV/PR presses motor areas of the cortex without affecting No the sensory areas, a stabiWait 20—60 seconds lizing effect occurs without causing general CNS depression.25 Yes Go to refractory Seizures More than 1—2 mg/kg Although phenytoin is status protocol persist diazepam given? used to treat SE in humans, Yes IV injection can cause seNo Yes vere hypotension in dogs Repeated Yes and IM absorption is extwice No Lorazepam tremely variable. IM injecLorazepam is not as lipidtion of phenytoin can also Start phenobarbital load Seizures Wait 15—30 soluble as is diazepam; in aniresult in adverse local reac2 mg/kg IV/IM persist? minutes mals, brain and cerebrospinal tions caused by precipitafluid concentrations of lortion at the site, including (i) Consider the cause azepam rise at a slower rate soft tissue sloughing.4,15 (ii) Assess the need for No maintenance of The half-life of phenythan do those of diazepam afanticonvulsant treatment toin in dogs is variable and ter IV injection.11 Pilot studies on the use of lorazepam 0.2 Figure 2—Initial pharmacologic treatment of patients in gen- can be as short as 3.65 mg/kg IV and 0.5 to 1.0 mg/ eralized tonic–clonic status epilepticus. (IM = intramuscular; hours after an 11 mg/kg IV kg PR in normal dogs suggest- IV = intravenous; PR = per rectum) dose.26 In cats, phenytoin can have an effective duraed that the drug may not be tion of up to 108 hours, acceptable for PR administrawhereby this may be related to the decreased ability to tion because of an extensive first-pass effect.24 However, lorazepam can reach therapeutic blood concentrations conjugate the compound to glucuronic acid.4 24 when administered IV. Lorazepam is being evaluated Fosphenytoin in normal dogs by one of the authors (S. P.) for its poFosphenytoin sodium (Cerebyx®; Parke-Davis) is a tential use in an intranasal dosing regimen. At present, phospate ester prodrug of phenytoin developed as a rethere are no data on the use of lorazepam in clinical finement of parenteral phenytoin. After administration, studies. phenytoin is cleaved from the prodrug by phosphatases Clonazepam in the bloodstream and several other organs.27 However, Compared with diazepam, tolerance to the IV adfosphenytoin is freely soluble in aqueous solutions and ministration of clonazepam develops more slowly.4 An rapidly absorbed by the IM route.27 Fosphenytoin has IV dose of 0.05 to 0.2 mg/kg may have a comparably no known antiepileptic action before conversion.27 To the authors’ knowledge, there are no veterinary studies longer-lasting effect than that of diazepam, but no IV using this drug clinically as an AED. preparation is available in the United States.
Generalized Tonic—Clonic Status Epilepticus

56 minutes was demonstrated with a bioavailability of more than 90%.22 These properties may support the use of IM midazolam for the treatment of SE. A human-approved midazolam injectable product (Versed; Roche Laboratories, Nutley, NJ) is available, but at present there are no approved veterinary midazolam preparations. A poorly documented dose for cats and dogs is 0.066 to 0.22 mg/kg IM or IV.19

Phenytoin Sodium (Diphenylhydantoin) Although approved by the FDA to treat seizure activity in dogs, phenytoin (Dilantin®; Parke-Davis) is not very efficacious. 4 This AED, which is a hydantoin derivative, is a five-membered ring structure lacking a C=O group in comparison with the barbiturates.4 Synaptic junctions that normally allow nerve impulses to be transmitted at lower thresholds are stabilized by phenytoin.4 The effect of this drug seems to be caused by

Barbiturates Phenobarbital is a safe, inexpensive drug that may be administered orally, IV, or IM. Like diazepam, phenobarbital is classified as a Schedule IV drug. Phenobarbital increases the threshold required for seizure discharge and acts to decrease the spread of the discharge to neighboring neurons.4 The actions of this drug are primarily caused by the enhancement of the inhibitory effects of GABA postsynaptically.8 Some inhibition of


Compendium August 2000

Small Animal/Exotics

glutamate activity and the flux of calcium across the neuronal membranes also occurs.25 Distribution of phenobarbital to the CNS may take up to 30 minutes because of weaker lipophilicity compared with diazepam.4 Practitioners must consider the time of onset when treating animals that are still exhibiting generalized seizure activity. The recommended loading dose is 12 to 24 mg/kg IV if immediate therapeutic concentrations are desired.4 Alternatively, the initial dose can be 2 mg/kg IV, repeated every 20 to 30 minutes to effect and to a maximum 24-hour dose of 24 mg/kg4 (Figure 2). The serum concentrations of phenobarbital will rise by approximately 5 µg/ml for each 3 mg/kg administered IV.4 The parenteral form can also be given IM, which is recommended if diazepam has already been administered, thereby avoiding the potentiation of profound respiratory and cardiovascular depression. 4 Phenobarbital, especially when administered after a benzodiazepine, may have depressant effects on respiratory drive, level of consciousness, and blood pressure, which may complicate management of SE patients.8 For these reasons, tracheal intubation may be necessary during IV administration of phenobarbital.

Your comprehensive guide to diagnostic ultrasonography
Nautrup and Tobias


Potassium bromide Potassium bromide (KBr) is a recommended maintenance AED in dogs.4 The half-life of KBr after oral administration is approximately 25 days, which has precluded its use in SE.4 Recent studies have established that KBr is well absorbed after PR administration, with an estimated bioavailability of 57.7% and a mean halflife of 20.4 days.28 For a more rapid effect than that obtained with oral maintenance dosing regimens, a PR loading protocol has been devised.28 Intrarectal administration may be preferred in patients that are heavily sedated from prior diazepam and phenobarbital administration. A loading dose for KBr (600 mg/kg) can be administered over a 24-hour period as 6 PR boluses (100 mg/kg every 4 hours).28 The side effects from this regimen may be transient diarrhea and sedation. SUMMARY The goal of treatment for patients exhibiting SE is rapid cessation of the seizure activity. Practitioners must have a knowledge and understanding of the available AED therapies and a step-wise plan for their use. Misuse of these drugs in an already cerebrally compromised patient can create management problems and may be fatal. AEDs administered in emergent situations, even if used correctly, will suppress the patient’s respiratory and cardiovascular systems, necessitating constant and close monitoring.



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1. Maytal J, Shinnar S, Moshe SL, et al: Low morbidity and mortality of status epilepticus in children. Pediatrics 83(3): 323–331, 1989. 2. Harrison AM, Lugo RA, Schunk JE: Treatment of convulsive status epilepticus with propofol: Case report. Pediatr Emerg Care 13(6):420–422, 1997. 3. Cascino GD: Generalized convulsive status epilepticus. Mayo Clin Proc 71:787–792, 1996. 4. Boothe DM: Anticonvulsant therapy in small animals. Vet Clin North Am Small Anim Pract 28(2):411–448, 1998. 5. Singhi S: Refractory status epilepticus in children: Role of continuous diazepam infusion. J Child Neurol 13(1):23–26, 1998. 6. Singhal PC, Chugh KS, Gulati DR: Myoglobinuria and renal failure after status epilepticus. Neurology 28(2):200–201, 1978. 7. Kiessling M, Hossman KA, Kleihues P: Pulmonary edema during bicuculline-induced seizures in rats. Exp Neurol 74(2): 430–438, 1981. 8. Cruz J: Neurologic and Neurosurgical Emergencies. Philadelphia, WB Saunders Co, 1998, pp 51–88. 9. Podell M: Seizures in dogs. Vet Clin North Am Small Anim Pract 26(4):779–809, 1996. 10. Hauser WA: Status epilepticus: Epidemiologic considerations. Neurology 40(Suppl 2):9–13, 1990. 11. Lowenstein DH, Alldredge BK: Status epilepticus. N Engl J Med 338 (14):970–976, 1998. 12. Walsh GO, Delgado-Escueta AV: Status epilepticus. Neurol Clin 11(4):835–853, 1993. 13. Ropper AH: Neurological and Neurosurgical Intensive Care. New York, Raven Press, 1993, pp 383–410. 14. Treiman DM: Generalized convulsive status epilepticus, in Engel J, Pedley TA (eds): Epilepsy: A Comprehensive Textbook. Philadelphia, Lippincott-Raven, 1997, pp 669–680. 15. Van der Kleijn E, Baars AM, Vree TB, et al: Clinical pharmacokinetics of drugs used in the treatment of status epilepticus. Adv Neurol 34(2):421–430, 1983. 16. Trieman DM: Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus. Epilepsia 30(Suppl 2):4–10, 1989. 17. Nordt SP, Clark RF: Midazolam: A review of therapeutic uses and toxicity. J Emerg Med 15(3):357–365, 1997. 18. Klotz U, Antonin KH, Bieck PR: Pharmacokinetic profiles of diazepam in man, dog, rabbit, guinea pig and rat. J Phar-

macol Exp Ther 199(1):67–73, 1976. 19. Plumb DC: Veterinary Drug Handbook, ed 3. White Bear Lake, MN, Pharma Vet Publishing, 1999. 20. Wagner SO, Sams RA, Podell M: Chronic phenobarbital therapy reduces plasma benzodiazepine concentrations after intravenous and rectal administration of diazepam in the dog. J Vet Pharmacol Ther 21(5):335–341, 1998. 21. Koul RL, Aithala GR, Chacko A, et al: Continuous midazolam infusion as treatment of status epilepticus. Arch Dis Child 76(5):445–448, 1997. 22. Court MH, Greenblatt DJ: Pharmacokinetics and preliminary observations of behavioral changes following administration of midazolam to dogs. J Vet Pharmacol Ther 15(4): 343–350, 1992. 23. Scott RC, Besag FMC, Boyd SG: Buccal absorption of midazolam: Pharmacokinetics and EEG pharmacodynamics. Epilepsia 39(3):290–294, 1998. 24. Podell M, Wagner SO, Sams RA: Lorazepam concentrations in plasma following its intravenous and rectal administration in dogs. J Vet Pharmacol Ther 21(2):158–160, 1998. 25. McNamara JD: Drugs effective in the therapy of epilepsies, in Hardmoan JG, Limbird LE (eds): Goodman and Gilman’s the Pharmacological Basis of Therapeutics. New York, McGraw-Hill, 1996, pp 461–485. 26. Sanders JE, Yeary RAL: Serum concentrations of orally administered diphenylhydantoin in dogs. JAVMA 172(2): 153–155, 1978. 27. Morton LD, Rizkallah E, Pellock JM: New drug therapy for acute seizure management. Semin Pediatr Neurol 4(4):51– 63, 1997. 28. Dewey CW, Ducote JM, Coates JR, et al: Intrarectally administered potassium bromide loading in normal dogs. Proc 17th ACVIM Forum, Abstract 213:745, 1999.

About the Authors
When this article was submitted for publication, Drs. Platt and McDonnell were affiliated with the Department of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens. Dr. Platt is now affiliated with The Animal Health Trust, Centre for Small Animal Studies, Suffolk, England. Dr. McDonnell is affiliated with the Veterinary Medical Center, Tufts University, North Grafton, Massachusetts. Both are Diplomates of the American College of Veterinary Internal Medicine (Neurology).

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