Page 1727 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1196 PART 11: Special Problems in Critical Care

of the potential for unopposed α-adrenergic stimulation. In anticholin- short-acting and titratable agent such as nitroprusside, as hyperten-
ergic intoxication, physostigmine decreases heart rate by increasing ace- sion may be a precursor to drug-induced cardiovascular collapse (as in
tylcholine concentration at myoneural junctions; however, the potential MAOI toxicity). Phentolamine is effective in the setting of α-adrenergic
for physostigmine to worsen cardiac conduction disturbances precludes stimulation from phenylephrine, phenylpropanolamine, or cocaine.
its use in cyclic antidepressant overdose. Labetalol in carefully titrated doses is a third-line agent. Despite recent
Drugs such as cocaine, caffeine, and amphetamines cause ventricular research in the area, nonselective β-blockers are currently not recom-
arrhythmias through sympathomimetic effects. Membrane depressants mended particularly in cocaine-associated hypertension because they
such as cyclic antidepressants are arrhythmogenic by prolonging depo- may worsen α-adrenergic–induced hypertension. 11,12
larization and negative inotropy. Drugs that prolong the QT interval
procainamide, and disopyramide) may induce polymorphic ventricular ■ “COMA COCKTAIL”

(eg, amiodarone, astemizole, terfenadine, cyclic antidepressants, quinidine,
tachycardia or torsades de pointes. Drug-induced torsades de pointes A “cocktail” of oxygen, dextrose, thiamine, and naloxone should be
is treated by correction of risk factors (hypokalemia, hypomagnesemia, administered to patients with depressed mental status (see Table 124-1).
and hypoxemia), magnesium supplementation (even when serum con- These relatively innocuous drugs are helpful diagnostically and thera-
centrations are normal), and overdrive pacing by electrical stimulation peutically. Although not well supported in the literature, thiamine is
13
or isoproterenol. 6 administered to prevent Wernicke-Korsakoff syndrome. This disorder
Cardioversion or defibrillation is appropriate for pulseless patients is characterized by ocular disturbances (nystagmus and weak external
with drug-induced ventricular tachycardia (VT) or ventricular fibril- rectus muscles), ataxia, and deranged mental status (confusion,
lation (VF). Whether epinephrine should be used in the setting of apathy, drowsiness, and confabulation). Tachycardia, hypotension,
sympathomimetic-induced VT or VF is unknown; if used, the working electrocardiographic abnormalities, and cardiovascular collapse also
group of the AHA recommends increasing the interval between doses occur. Thiamine is particularly important in the nutritionally depleted
and avoidance of high-dose epinephrine. This group also recommends alcoholic receiving intravenous glucose. Glucose further depletes thiamine
6
more prolonged cardiopulmonary resuscitation (CPR) in poisoning and may precipitate or worsen Wernicke-Korsakoff syndrome. There are
cases because of case reports of good neurologic recovery after pro- no compelling data to support the practice of withholding dextrose until
longed CPR (eg, 3-5 hours). 6 thiamine has been administered in the hypoglycemic patient, although in
A variety of mechanisms are responsible for hypotension in drug alcoholic patients, it is recommended to at least give them concomitantly
overdose: hypovolemia, cardiac arrhythmias, systemic vasodilation, and if Wernicke-Korsakoff is suspected as the cause of coma. 13-15
myocardial depression. An initial strategy of rapid fluid administration A blood dipstick test can be used to detect severe hypoglycemia.
(eg, 1 L normal saline over 30 minutes) is appropriate in most cases, However, a normal value for glucose by dipstick does not exclude a low
although caution is warranted in the setting of pulmonary edema or serum level, thereby warranting treatment in all patients with normal or
poor cardiac contractility (eg, in verapamil overdose). Cardiac arrhyth- low values. If the dipstick reading is high, it is reasonable to wait for serum
mias and hypothermia should be corrected and antidotes administered confirmation of hyperglycemia. There is concern that overadministration
if appropriate. Hypotension refractory to the above measures should be of dextrose may cause harm by increasing serum osmolality or extending
treated with vasopressors. Dopamine (5-20 µg/kg/min by continuous IV ischemic stroke, but this has not been well supported in the literature. 13
infusion) stimulates α-, β-, and dopaminergic receptors to increase heart Naloxone is an opioid antagonist with no opioid agonist properties.
rate, blood pressure, and cardiac output in most patients. In patients It can rapidly reverse opioid-induced coma, hypotension, respiratory
with tachyarrhythmias or ventricular fibrillation, agents with weak β - depression, and analgesia. Naloxone is traditionally administered
16
1
activity (norepinephrine) or no β-receptor activity (phenylephrine) are intravenously, intramuscularly, or subcutaneously; although use of
preferred. Norepinephrine and phenylephrine are preferred in cyclic nebulized and intranasal naloxone has been studied. 17,18 Initial low
antidepressant overdose because cyclic antidepressants deplete presyn- doses (0.4 mg IV or 0.8 mg IM or SC) are preferred to avoid symptoms
aptic catecholamine stores, limiting the effectiveness of dopamine. 8-10 In of severe withdrawal in patients with chronic opioid dependence or in
contrast, in the presence of cocaine, dopamine and other vasopressors patients with accompanying stimulant use. 6
may trigger an exaggerated response caused by inhibition of catechol- The goal is to restore airway reflexes and adequate ventilation, not
amine reuptake; in the presence of monoamine oxidase inhibitors an complete arousal. Abrupt withdrawal may increase the risk of arrhyth-
19
exaggerated response occurs because of inhibition of catecholamine mias, agitation, and acute pulmonary edema. If naloxone does not pro-
degradation. An enhanced hypertensive response to phenylephrine can duce a clinical response after 2 to 3 minutes, an additional 1 to 2 mg IV
occur in anticholinergic overdose because anticholinergics interfere may be administered to a total dose of 6 to 10 mg. In general, a lack
with phenylephrine-induced reflex bradycardia. Vasopressor agents of response to 6 to 10 mg of naloxone is required to exclude opioid
should not be used in the setting of ergot derivative toxicity because of toxicity. Even higher doses may be required to antagonize the effects of
the potential for severe and sustained vasoconstriction. longer acting and synthetic opioids such as meperidine, propoxyphene,
2
Hypertension with tachycardia occurs in the setting of (1) sympa- and methadone. Continuing naloxone beyond a total dose of 10 mg is
thomimetic drugs (amphetamines, cocaine, lysergic acid diethylamide reasonable if there is a suspicion of opioid overdose and a partial
[LSD], marijuana, monoamine oxidase inhibitors, and phencyclidine response has been achieved.
[PCP]); (2) anticholinergics (antihistamines, atropine, cyclic antidepres- In general, opioid antagonism occurs within minutes of naloxone admin-
sants, and phenothiazines); and (3) withdrawal from nicotine, alcohol, istration and has a serum half-life of 30 to 80 minutes. The effects of nalox-
and sedative-hypnotics. Hypertension with reflex bradycardia occurs one do not last as long as those of heroin or methadone, so repeat boluses
in ergot derivative, methoxamine, phenylephrine, and phenylpropanol- may be required to maintain an adequate clinical response. Alternatively, a
amine toxicity. continuous naloxone infusion may be started (0.4-0.8 mg/h, or two-thirds of
Treatment of hypertension depends on the chronicity and severity the initial dose needed to achieve a response per hour IV).
of hypertension and on the response to initial supportive efforts (eg, Consider flumazenil if benzodiazepine overdose is highly suspected
agitated patients often respond well to benzodiazepines alone). When or confirmed and benzodiazepines have not been prescribed for a poten-
hypertension is severe in chronically hypertensive patients, lowering tially life-threatening condition (such as status epilepticus or raised
diastolic blood pressure by 20% or to approximately 100 to 110 mm Hg intracranial pressure). In the setting of long-term benzodiazepine use,
is recommended. In the absence of prior hypertension, diastolic blood flumazenil may result in severe withdrawal or seizures. 20,21 In a rat model
pressure may be lowered safely into the normal range. Drug-induced of combined cocaine-diazepam poisoning, flumazenil precipitated
hypertension refractory to benzodiazepines should be treated with a seizures and increased mortality. 22

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