ANTICHOLINERGIC  TOXIDROMES

 

  • Included in this category: Antihistaminic, Phenothiazines, TCA,  Antiparkinsonians.
     
  • Anticholinergics have two receptors: Muscarinic that predominate in brain  and Nicotinic that predominate  in spine. The blocking of these receptors will result in following S & S:

     BRAIN                      PERIPHERY

    Agitation                                 

    Arrhythmia* 

    Ataxia                                     

    ¯ GI motility*

    Anxiety                                   

    Hyperthermia  

    Confusion        

    ¯ Salivation

    Coma                                    

    Urinary  Retention*

    Mydriasis*                                 

    Dry Skin 

    Respi. Failure

    		 

    Audit/Visual hallucinations*  

    		 
                                                                   





     






    Thus S&S can be summarized as : hot (hyperthermia), blind (mydriasis), dry (dry skin), red and mad (agitation). The * indicates the most common presentations.

Diagnosis:

  1. Dx is based on clinical grounds and common clues are suggested by  asterix (*). To avoid  confusion  with sympatomimetics, the presence of dry skin and bowel sounds are suggestive of anticholinergic.
     
  2. EKG most commonly shows sinus tachycardia. Prolonged QRS and BBB (L or R) are also commonly found, especially in TCA OD. EKG changes seen with TCA are: ST and T wave changes, prolonged QT (40msec ) and QRS, AV blocks ,  R axis deviation (-ve lead I and +ve  aVR), sinus tachy, ventricular arrhythmias, PEA(EMD). QRS of >160msec heralds malignant arrhythmia.

Treatment:

  1. ABC
     
  2. Activated  Charcoal & Lavage : Both because of ¯ GI motility and enterohepatic circulation of  these drugs  both  AC (50-100mg) and Lavage can be used for several hrs after ingestion.
     
  3. SZ: generally treated with usual measures. In case of TCA OD, SZ is observed in < 10% and are generally of  2 min duration. Commonly  seen when QRS is > 0.1sec (100msec). SZ  can aggravate TCA toxicity by creating acidemic milieu. Treatment of SZ is: Benzo( may interfere with further neuro assessments), Alkalinization  (this is only to protect heart against the acidic environment  created by seizure), Phenytoin.
     
  4. Hyperthermia: this could be 2ry to anticholinergic properties or in case of certain medications  2ry to dystonic reaction, NMS. Common methods  to bring the temperature  down are used (cooling blankets, ice).
     
  5. Hypertension: generally is transient and not high enough to be aggressively treated.
     
  6. Hypotension:  in case of TCA is an ominous sign and represents myocardial depression 2ry to-blockade.  Alkalinization (see below) is 1st  line of treatment to be tried in conjunction with NS IVF and Trendelenburg. Since in TCA OD we have blockade of dopa and cathecolamine depletion, if above measures do not work  neither  Dopamine  nor Dobutamine would be useful as vasopressors and Norepinephrine (Levophed) is used instead.
     
  7. Arrhythmias: generally standard antiarrhythmics are used. Special consideration  in case of TCA where class IA (quinidine, procainamide) must be avoided.
     
    1. Sinus tachy- no treatment
       
    2. SVT, Conduction defect, Ventricular arrhythmia- alkalinization Lidocaine Physostigmine.  The latter only ab extremes if at all.

Therapeutic tools to achieve the treatment are summarized below:

  1. ALKALINIZATION:  This is achieved by  HYPERVENTILATION  with intubation and with NaHCO3 @ a dose of 1-5 mEq/kg. These modalities are titrated  to serum/urine pH of 7.45 -7.5. By altering pH  one changes the ratio between ionized and nonionezd  drug making  it more difficult for ionized drug to penetrate the cell membrane. Thus, the drug remains in ECF and is excreted via kidney more easily. Since hypokalemia occurs with alkalinization,  if not corrected alkaline urine will not be produced. Other complications of alkalinization   therapy are : a) paradoxical CSF acidosis  b) peripheral hypoxia due to L shift of  OX saturation curve.
     
  2. PHYSOSTIGMINE :0.5 -2mg IV over 2min  repeated q20-30 min prn. This medication lost its popularity. It is a short acting cholinergic that reverses the  anticholinergic effects of TCA. It has very narrow therapeutic / toxic ratio and can give cholinergic crisis, SZ, worsen AV conduction , produce cardiac arrest.
     
  3. HEMOPERFUSION WITH ACTIVATED CHARCOAL : even if this modality works it is not very useful in case of TCA OD since the majority is tissue bound.

Disposition:

  1. Pt can be DC after 6 hrs of observation if no symptoms have developed, if last AC is administered, and in cases of TCA OD psychiatry consult is obtained. All major complications occur within 24 hr period and most of them in first few hours.

 

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