Second edition

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Respiratory failure, as may be seen in pneumonia or
decompensated chronic obstructive pulmonary disease
(COPD), generally produces a delirium when the P aO 2 falls
below 50 mmHg; CO 2 levels are not as reliable a guide in
this regard: although acute rises to 70 mmHg may be associated
with delirium, levels of 90 mmHg or more may be
tolerated if reached gradually. In cases where the delirium is
secondary to elevated CO 2 levels, patients may appear
intoxicated, a phenomenon that accounts for the old term
for this condition, namely ‘CO 2 narcosis’.
Obstructive sleep apnea may be accompanied by delirium,
not only during nocturnal awakenings, but also while
the patient is awake during the day, and this appears to be
particularly common in stroke patients early in their
recovery (Sandberg et al. 2001). Although the mechanism
underlying the daytime delirium is not clear, it is probably
related to nocturnal hypoxemia and hypercarbia.
Hyponatremia, most commonly seen, in hospital settings
at least, as part of the syndrome of inappropriate
antidiuretic hormone (ADH) secretion, generally is not
associated with delirium until the sodium level falls to
120 mEq/L; although gradually developing falls to this level
may be tolerated, falls below 110 mEq/L are generally
symptomatic.
Hypernatremia, typically seen in the setting of dehydration,
may, if of acute onset, cause a delirium when the
sodium level reaches 160 mEq/L; gradual rises are better
tolerated, and some patients may not experience delirium
even with levels of 170 mEq/L.
Hypoglycemia may cause autonomic symptoms, such
as anxiety, tremor, and diaphoresis, but these may or may
not be present in cases of hypoglycemia-associated delirium;
in any case, cognitive dysfunction generally does not
appear until the blood glucose level falls below 50 mg/dL,
or lower, if the fall is gradual.
Hyperglycemia of sufficient degree to cause delirium is
generally only found in either diabetic ketoacidosis or the
hyperglycemic, hyperosmolar, non-ketotic syndrome. In
diabetic ketoacidosis delirium may appear with blood glucose
levels in the range of 300 to 700 mg/dL, whereas in the
hyperglycemic, hyperosmolar, non-ketotic syndrome the
range associated with cognitive dysfunction is higher, from
600 mg/dL up to an astounding 2000 mg/dL.
Hypocalcemia of sufficient degree to cause delirium is
generally associated with muscle cramping and tetany.
Acute falls to 8 mg/dL may cause symptoms, whereas gradual
falls to 6 mg/dL may be well tolerated.
Hypercalcemia is typically associated with nausea, vomiting,
constipation, and abdominal pain; delirium may
supervene when the level rises above 16 mg/dL.
Hypomagnesemia typically does not cause symptoms
until the level falls below 1.2 mg/dL; given that magnesium
is required for the release of parathyroid hormone, there is
often an associated hypocalcemia.
Hypermagnesemia, generally occurring only with
increased magnesium intake in the presence of renal failure,
may cause delirium at a level of 6 mg/dL if reached
5.3 Delirium 179
acutely, whereas levels as high as 18 mg/dL may be tolerated
if reached very gradually.
Systemic effects of infection
Although an association between sepsis and delirium is
well known, it is perhaps not as well appreciated that less
severe infections can also cause delirium. This is especially
the case in the elderly, as for example in the case of pneumonia
or even uncomplicated urinary tract infections.
Indeed, in the author’s experience, several cases of urinary
tract infection have presented with delirium. In all likelihood,
the delirium is mediated by cytokines (Reichenberg
et al. 2001).
Vitamin deficiencies
Of the vitamin deficiencies seen in malnourished patients,
two are typified by delirium: namely Wernicke’s
encephalopathy and encephalopathic pellagra.
Wernicke’s encephalopathy, occurring secondary to thiamine
deficiency, although most commonly seen in alcoholics,
may occur secondary to thiamine deficiency of any
cause, including fasting (Frantzen 1966), prolonged vomiting
(as in post-gastric restriction surgery [Abarbanel et al.
1987; Paulson et al. 1985]), or prolonged intravenous feeding
without adequate thiamine supplementation (Vortmeyer
et al. 1992). Although most of us were taught to look for the
classic ‘triad’ of delirium, ataxia, and nystagmus, this combination
is, in fact, the exception (Cravioto et al. 1961), and
most patients with Wernicke’s encephalopathy present with
delirium alone (Harper et al. 1986). The recognition of this
syndrome is critical: treated promptly, patients may survive
without sequelae; untreated, or with delayed treatment,
patients may recover but be left with a permanent
Korsakoff’s syndrome (Malamud and Skillicorn 1956).
Pellagra, due to niacin deficiency, occurs in two forms.
The chronic form is characterized by the classic ‘three Ds’
of dementia, dermatitis, and diarrhea. By contrast, the
acute, ‘encephalopathic’ form is marked by delirium, mild
parkinsonism, and dysarthria.
SUBSTANCE WITHDRAWAL DELIRIUM
Withdrawal from alcohol, benzodiazepines, or barbiturates
may produce a syndrome of delirium accompanied
by autonomic signs such as postural tremor, diaphoresis,
and tachycardia. This diagnosis, sadly, is often missed.
Alcoholics in delirium tremens may deny using alcohol to
excess, and their relatives are often complicit in this denial,
and the same holds true for those abusing benzodiazepines
or barbiturates. Both benzodiazepines and barbiturates
may also be taken in high doses for therapeutic reasons,
and when writing admission orders it is not uncommon
for physicians not to order these home medications, even
although aware of them, on the belief that they are ‘not
needed’.
Gamma hydroxybutyrate is now available on prescription
for treatment of cataplexy, but it is not appreciated by