Dilantin
                                ========

þ Dilantin Toxicity
 - nystagmus generally starts at 20 mcg/ml
 - ataxia generally starts at 30 mcg/ml
 - but nystagmus doesn't reliably precede ataxia or lethargy
   [Tintinalli, 3rd ed. p 564.]
 - see also IV Loading and Toxicity, below.

þ Therapeutic range:
 - 10-20 mcg/ml
 - (may need to go up to 25)

þ IV Loading and Toxicity
 - IV Dilantin dose 18-20 mg/kg (1 g for average adult)
 - Average 16 mg/kg in:
   [Crawford RE, et al.  IV phenytoin in acute treatment of seizures.
   Neurology 29(11):1474, 1979.]
   A study of 139 patients.  Only side effect when given at 50mg/min was
   dose-related hypotension that responded to slowing infusion.  Conclude
   18mg/kg is safe and effective and results in level of about 23mcg/ml.  Note
   that unless pre-administration level was > 20 should have no toxic side
   effect. 1/3 of patients had "therapeutic" dilantin levels but seizures were
   still controlled by loading and reaching so-called "toxic" levels.  Mean
   level in those who stopped sezing was 26mcg/ml.
 - What if doesn't respond to 18mg/kg?  Go up to 25/kg before starting another
   agent (also per Dr. James Roberts, In Focus, Emergency Medicine News
   May 1991 page 22.)
 - give no faster than 50 mg/min (1mg/kg/min in kids)
 - Quick-and-Dirty: 500mg/50cc NS.  Set pump to 240cc/hr; will give 40mg/min.
   (Carducci et al. Ann Emerg Med 13(11):1027, 1984.)
 - must be given in saline.
 - side effects of IV loading:
  + expected side effects of loading include ataxia, blurred vision, and
    nystagmus.
  + more severe side effects mostly due to the propylene glycol diluent
  + more severe side effects include coma, seizures, circulatory collapse,
    ventricular arrhythmias, cardiac nodal depression, hypotension,
    hyperosmolality, hemolysis, and lactate-associated metabolic acidosis.
    [Tintinalli, 3rd ed. p 563]

þ Extravasation of IV Dilantin
 - Extravasation causes skin necrosis which can lead to compartment syndrome,
   gangrene, amputation and death.  The fatality rate of phenytoin
   extravasation exceeds that of overdose with oral phenytoin.
   [Tintinalli 3rd ed. p 564.]

þ What if seizing and already on Dilantin?
 - Give half a loading dose per Dr. James Roberts, In Focus,
   Emergency Medicine News May 1991 page 22.

þ Oral loading:
  -(Osborn NH, et al.  Single dose oral phenytoin loading.  Ann Emerg Med
   16(4):407,1988.)  18 mg/kg to 44 patients resulted in only 64% with
   therapeutic levels, though none had any more seizures in the 24 hours after
   the loading (maybe they just have infrequent seizures)
  -(Evens et al.  Am J Hosp. Pharm 37(2):232, 1980)  900 mg given to 6
   volunteers; only 2 developed therapeutic levels.
  -(Record et al.  Ann Neurol. 5(3):268, 1979)  19mg/kg over 6-12 hours in 2-4
   divided doses:  low therapeutic levels (11) in 18-24 hours.

þ May need to wait 6-8 hours from therapeutic serum levels to achieve
  appropriate CNS levels.

þ Wait for 30-40 minutes after end of IV load to check serum levels, to allow
  redistribution.

þ Dilantin excretion is variable:  a fast constant-rate excretion that is easily
  overloaded; at higher loads, excretion is slower and concentration-related.

þ "Following an 18 mg/kg load, levels should stay therapeutic for 18-24 hours"
  (Jim Roberts, M.D., Emergency Medicine News, May 1991)

þ Kids may develop a type of dystonic-type reaction (Clin Ped 24(8):467,1985)
  from Dilantin loading.