Sunday, April 22, 2012

Management of Status Epilepticus (PART 2)

MANAGEMENT OF TONIC- CLONIC  SE:(1,2)
Time from initiation
of observation and
treatment (min)          Procedure
=================================================
        0                         Assesss cardiorespiratory function
                                   as the presence of tonic clonic sta
                                   tus is verified.If ensure of diagnosis
                                   observe one tonic-clonic attack and
                                   verify the presence of unconcious
                                   ness after the end of the tonic clo
                                   nic attack.Insert oral airway and ad
                                   minister 02,if necessary.Insert an in
                                   travenous catheter.Draw venous 
                                   blood to determine anticonvulsant
                                   levels,glucose,BUN,electrolytes,and
                                   complete blood count stat.Draw ar
                                   terial blood for stat pH,PO2,PCO2,
                                   HCO3-.Monitor respiration,blood 
                                   pressure,and electrocardiograph.
                                   If possible monitor encephalograph.


        5                         Start iv infusion with NS contain- 
                                   ing with B complex. Give a bolus    
                                   injection of 50 ml of 50% glucose.


     10                          Infuse 1 mg lorazepam over 5 mi  
                                  nutes also give fosphenytoin to a
                                  total of 17 mg/kg(level >20 mcg
                                  per ml). If hypotension develops
                                  slow infusion rate.Phenytoin 50
                                  mg/ml in propyleneglycol may be
                                  placed in a 100 ml volume control
                                  set and diluted with normal saline.     
                                  the rate of infusion should be 
                                  watched. Alternatively phenytoin  
                                  may be injected slowly by iv.


    20                         If seizures persist give 1mg lorazepam 
                                 intravenously.


    30                         If seizures persist consider pseudo 
                                seizures if no CNS infection or   
                                trauma.Otherwise, phenobarbital 20 
                                mg/kg iv no faster than 100 mg/min  
                                until seizures stop or to a loading of 20 
                                mg/kg(level > 40 mcg/ml).


  60                          If seizure continue, general anesthesia  
                               with pentobarbital is instituted.


120                          If SE continue a neurologist and 
                               anesthesiologist with expertise in SE    
                               should be consulted. Advice from a 
                               regional epilepsy center on the 
                               management of intractable SE also 
                               should be sought Push pentobarbital      
                               until seizures stop or hypotension 
                               arises.With cessation of seizures if
                               still twitching assess EEG to rule out
                               subtle SE.


Generalized convulsive SE is considered a neurologic emergency.
Treatment to secure the airway, provide oxygen,and maintain circulation must be initiated within the first fiew minutes to prevent complications such as hypoxaemia,
systemic hypertension,tachydysrythmia.


Protocols for the treatment of convulsive SE remain somewhat individualized by institution and specialty.
Recent trends have pushed aggressive treatment beginning as soon as 10 minutes into continuous convulsive state. 
In practice this intervention can rarely be effected except in hospital. One of many approaches to control SE is shown as mention above. 
This protocol reflects the current widespread use of lorazepam titrated to effect (0,03 to 0,22 mg/kg) as a subtitute for diazepam.
Parke Davis has withdrawn phenytoin(Dilantin) in favor of the prodrug fosphenytoin(Cerebyx).This a water soluble preparation with pH of 9 is converted in 15 minutes to the active drug phenytoin by tissue phosphatases. It is equally as effective as phenytoin but without complications of the propyleneglycol solvent and higher alkalinity (pH 12).
It can be delivered intramuscularly and more stable in the iv form but it can also precipitate hypotension if adminis-
tered too rapidly.


Phenobarbital as alternative drug when seizure persist after lorazepam. Physicians are using thiopental much earlier in the treatment of SE when phenobarbital is not available.
When phenytoin and phenobarbital are ineffective, a benzodiazepine is often suggested. Midazolam and diazepam have a shorter onset time than lorazepam although lorazepam generally has a longer duration of action with a lower likelihood of severe respiratory depression making it the preferred agent of some clinicians.


Diazepam is the fastest onzet (1-3 minutes) and hystoricaly was the treatment of choice because is known as the fastest  medication to terminate seizures. However because of its lipholicity diazepam has a very short duration in CNS (10-20 min). For this reason lorazepam has replaced diazepam as the drug of choice. Its onset in only slower (2-3 min) but its anticonvulsant action typically last for more than 4 hours.
Diazepam has been reported to be effective rectally, and midazolam to be effective intramuscularly and intranasally in children.
If seizures continue to be refractory to treatment with the previously noted drugs, pentobarbital  usually can be used some times thiopental.


Alternatively,volatile anesthetics can also be used. 
Intravenous valproate (depakene) is now available which being tried in refractory status. Any of the other non iv formulated AEDs can be administered via nasogastric tube.
Propofol has been used in ambulances for patient refractory to iv benzodiazepine, given in 30 mg boluses every 30 seconds until the seizure are terminated.There may be a future role for alpha 2 agonist therapy as such drugs become clinically available. 
Dexmedetomidine confered brain protection in an animal
seizure model.


Other protocol for tonic clonic generalized SE based on stage :


Stage             General measures            AEDs  Usual route of adm
Premonitory   Continued neurolo           Diazepam 10mg iv bolus                                                                
                     gic observation,dia         max 5mg/min
                     agnostic SE by ob           Lorazepam 4mg iv bolus                                       
                     serving continued           max 2mg/min                                                    
                     seizure activity of          Midazolam 5mg iv bolus                                                                                               
                     one additional sei           max 4m/min 
                     zure.                             Paraldehyde 5- 10 ml in
                                                         5- 1 ml water or oil
                                                         by rectal First line


Early              Ensure adequate           Diazepam 10mg iv bls
(0-30 mins)     cardiorespiratory          Lorazepam 4- 8mg iv
                     function,iv line,ad-             
                     minister 02,initiate      Second line
                     regular ECG,and BP      Midazolam  5-10 mg iv
                     monitoring,draw         Phenytoin 15-18 mg/kg
                     blood for emergen-     iv loading                  
                     cy investigations,in-    dose(max.               
                     tubation may be          50mg/min.
                     considered.                Paraldehyde solution 4%                                        
                                                      in saline,50-100ml/h                                                                                  
                                                      iv solution
                                                      Lidocaine:iv bolus and
                                                      short infusion.


Established     Set second iv line         First line                 
                     (large veins)admi-        Phenytoin repeate                        
                     nister thiamine 100       7mg /kg iv.                                
                     mg iv and glucose         Phenobarbital                                    
                     D50W-50 ml iv,           10-20 mg/kg iv         
                     treat acidosis,estab      loading dose                                         
                     lished etiology,admis-  (<100mg/m)
                     sion to ICU,intubation   second line        
                     ICU,intubation has to    Diazepam iv infusion       
                     be considered,EEG/     Midazolam iv infusion
                     ECG monitoring.          Paradeldehyde iv infusion


Refractory   Full anesthesia needed    First line
(>120 min)   EEG/ECG monitoring,ar-  Pentobarbital iv/infus
                   terial line,initiate pres-   Propofol iv/infusion           
                   sor therapy when requi-        
                   red monitoring of AEDs    Second line
                   levels intracranial pres-    Isoflurane inhalation      
                   sure monitoring where 
                   appropriate.


In a patient who is actively seizing a lateral position may help prevent aspiration.The choice of iv fluids should include normal saline if phenytoin will be used because phenytoin will precipitate in glucose containing solution 


After 8 mg of lorazepam if seizures have not been aborted
use of another anticonvulsant medication is indicated.
If benzodizepine are effecive in seizure control further seizures need to be prevented with a long acting anticonvulsant.


A loading dose of phenytoin is 18-20 mg /kg ,even at the recomended rate of administration (50mg/min),hypotension is the most common side effect and mandates decreasing the infusion rate.


to be continued

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