Occasionally a patient treated with midazolam for conscious sedation may show a response opposite to that intended or expected. These paradoxical or disinhibition reactions can be difficult to control unless prepared for in advance.


Expected reaction to benzodiazepines: sedation and decreased anxiety


Paradoxical or disinhibition reactions:

(1) inconsolable crying

(2) excitation, combativeness, hostility, aggression, rage

(3) disorientation or hallucinations

(4) dysphoria or depression

(5) tachycardia

(6) agitation or restlessness


People reported to be at higher risk for a paradoxical reaction (although difficult to prove since reactions are so uncommon):

(1) extremes of age (very young or elderly)

(2) history of psychosis or other psychiatric disturbances

(3) history of violent behavior

(4) alcoholics

(5) genetic predisposition

(6) high preoperative anxiety


The differential diagnosis includes a number of conditions which should be evident if the patient is being properly monitored:

(1) improper dosing (too much or too little)

(2) improper administration

(3) hypoxemia or carbon dioxide retention

(4) cardiac event

(5) seizure activity


Using a higher dose of the benzodiazepine only worsens the syndrome.


Flumazenil is an imidazodiazepine, which is a class of benzodiazepines that are antagonists to the central effects of other benzodiazepines. It has been used successfully to control and reverse the paradoxical reactions. In addition, most patients remain sufficiently sedated to complete the procedure successfully.


Flumazenil is contraindicated in patients with benzodiazepine dependence since it can precipitate a withdrawal syndrome. If the dependence has not been reported, the withdrawal reaction may present as confusion or agitation after the flumazenil injection, rather than the expected reversal.


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