44 year old male is admitted to the hospital after he fell and broke his hip while shoveling snow out of his driveway. He has no significant past history and is duly taken to the OR for a hip pin, which he tolerates well. About 48 hours into his recovery he progressively develops restlessness that active agitation. Some lorazepam is prescribed. However, he does not improve. The nursing staff finally call you at 0300 after the orthopod refuses to talk on the phone about the patient anymore.
You arrive and evaluate the patient: He is in constant motion, pulling at restraints, cursing loudly, screaming. You glance through the chart and note that he is receiving 2 mg of lorazepam every 2 hours IM on a PRN schedule and he has received the medication every two hours for the last 10 hours. As you observe, he breaks out of an arm restraint, restraint grabs the nearest nurse and bangs her head against the bed frame. After she is pried away, the head nurse eyes you suspiciously and demands to know what your plan is.
Vital Signs:
What's going on here and what are you going to do about it?
Comment 1: Delirium tremens is a severe neuronal hyperexcitation syndrome following abrupt cessation of alcohol consumption. It is not uncommon for patients to enter DT after unexpected hospitalization- cutting them off from their supply, as it were. It can happen any time during a hospitalization. Frequently, their spouse is unaware of their drinking until numerous bottles are found hidden around the house. Withdrawal symptomatology results from a compensatory increase in activity of excitatory neuronal mechanisms (upregulation) involving the neurotransmitters norepinephrine, dopamine, the N-methyl-D-aspartate (NMDA) receptor and diminished activity (downregulation) of the inhibitory receptors GABA-A, and alpha-2 adrenoceptors after prolonged depression of CNS by ethanol. Once developed, delirium tremens is manifested by an unpredictable and volatile course frequently unappreciated by clinicians. In the past, a relatively high mortality resulted from cardiovascular collapse after inadequate treatment in non-monitored areas. This patient has all the classic manifestations of alcohol withdrawal cum delirium tremens, an agitation syndrome of a life threatening nature. This is an acute psychosis and acute catecholamine storm at the same time and the results can be frightening.
Here's the pathophysiology of what's going on here:
This patient is in DEEP trouble.
Normally, the mainstay of treatment involves substitution therapy. Withdrawal symptoms only occur following the rapid cessation of CNS active drugs having a short duration of action (alcohol). Accordingly, withdrawal symptoms can be ameliorated with similar but longer acting depressant drugs, allowing the withdrawal period to be effectively lengthened and attenuated and avoiding rapid neuronal upregulation. But there is a catch. Dependence on alcohol extends to other similar CNS depressants as well (cross dependence). Tolerance to alcohol also occurs as a result of the body's ability to effectively deactivate the drug as a consequence of repeated exposure. Tolerance to cross dependent drugs occurs as well. Accordingly, exceedingly high doses of replacement depressants such as benzodiazepines are frequently required to equal the various pharmacodynamic effects of alcohol (cross tolerance). The depressive properties of these drugs become hemodynamically apparent before the withdrawal symptoms are completely controlled.
This patient has received exceedingly high doses of the benzodiazepine lorazepam (lorazepam) as well as a relatively high dose of haloperidol, and IS STILL NOT CONTROLLED. There is evidence of hemodynamic suppression (rapid, shallow ventilations, fluctuating SaO2). This patient is in SERIOUS trouble and likely to sleep unto death if intervention is not rapid and effective. What do you think is the right thing to do at this point?
Although cheap, and effective in the short term, alcohol infusions exacerbate organ toxicity and do nothing to get the patient detoxified from alcohol, their primary problem. Switching to benzodiazepine "dependence" is much easier for the next guy down the line to deal with, and much less toxic side effects.
Here's how I would deal with this patient and why: The point of diminishing returns from cross dependent benzodiazepines has already been reached, and the patient is now languishing in never-land between hemodynamic/ventilatory suppression and control of his disease process. Addition of more benzos will exacerbate untoward side effects in equal proportion to beneficial therapeutic effects.
There are two life threatening processes here and one urgent process:
Suspended animation using musculoskeletal paralytic agents, and numerous selective agents will effectively stop increased oxygen consumption and the effects of muscular hyperactivity on end organs as well as the end organ effect of catecholamine storm. However, it must be remembered that underneath paralysis lies unprotected cerebral function. In the past, sedation has been titrated under paralysis until tachycardia and hypertension normalize, suggesting that patient comfort has been achieved. However, this patient is also on titrated beta antagonists so all bets are now off and the visual/objective clues of adequacy of sedation are nil. Therefore, we attach a computer interpreted cerebral function monitor at the bedside to monitor the effects of sedatives on brain function AND also monitor the cerebral response to external stimuli as well, insuring that the patient is still responding appropriately under sedation. The effects of DT boil off in a day or so and the therapeutic treatment is de-titrated on the basis of monitoring evidence.