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B:ticioii
Clinical Notes (not core)
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Common problems in the ITU include:
septic shock
haemorrhagic shock
cardiogenic shock
Common co-morbidities:
cardiac failure
(chronic) hypertension
diabetes (mellitus)
Problems of Drug Dosage
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Oedema
Patients are often oedematous (e.g., from septic shock
or cardiac failure). Volume of distribution is increased for
hydrophilic drugs (e.g., vancomycin) but not for protein-bound
or tissue-bound drugs (e.g., digoxin). Need to titrate drug dose
against effect or against plasma concentration. Sudden changes
in plasma concentration may result from sudden shifts in fluid
into or out of oedematous areas.
Perfusion
Some tissues may be underperfused if blood pressure remains
low, affecting the volume of distribution of drugs. Slight changes
in blood pressure, or use of pressor agents, may produce
sudden shifts of blood into previously-underperfused tissue.
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Reduction of perfusion of the liver may result from cor pulmonale
and right heart failure, slowing the rate of elimination of all
drugs. Renal failure may similarly result in reduction in the rate
of elimination of a drug or of its (potentially toxic) metabolites.
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Prothrombotic state
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Patients aie at iisk of thiombosis because of:
hypovolaemia
immobility
inammation
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Activated Protein C (APC)
Antithiombotic and anti-inammatoiy. Inactivates factois
Va and VIII, ieducing pioduction of thiombin. Tiombin is
pioinammatoiy, piocoagulant and antibiinolytic; so APC
might bieak the ciicle of inammation and thiombosis
ieinfoicing one anothei. There is some evidence that exogenous
APC improves survival in ITU patients, though the conclusions are
still disputed.
Side-eect: bleeding.
Heparins
Advantage: shoit-acting, easily titiated against coagulation
tests. Low-molecular-weight heparins (extracts of the active site)
reduce the risk of auto-immune disorders after heparin therapy
(such as heparin-induced thrombocytopaenia).
Inammation
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Use of immunosuppressants is controversial because the
inflammatory process often works in the patients favour, for
example in septic shock.
Corticosteroids
Steioids can be used to suppiess inammation in patients who
aie not septic, oi in patients in whom inammatoiy oedema
poses a specic pioblem (e.g., iaised intiacianial piessuie).
Activated Protein C
APC has some anti-inammatoiy eect, as noted above.
Hypotension
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Septic shock iesults fiom vasodilation as a by-pioduct
of the inammatoiy piocess. Peiipheiies aie waim and
well-peifused (because of vasodilation); but the patient is
hypotensive, with a compensatoiy high heait iate (and a iisk
of caidiac ischaemia). It is a foim of distributive shock: the
patient is not (necessaiily) shoit of uid, but capillaiy leaks
and loss of piotein into the tissues cause movement of uid
out of the ciiculating compaitment.
Cardiogenic shock iesults fiom a fall in caidiac output
(usually sudden and piofound, ofen following a myocaidial
infaiction). Peiipheiies aie usually cold, because of compen-
satoiy vasoconstiiction. Heait iate is high. Oedema may
be piesent behind the failing chambei, and the JVP may be
elevated.
Hypovolaemic shock iesults fiom low ciiculating volume, foi
example following haemoiihage. Peiipheiies aie cold; heait
iate is high; theie is no oedema and no elevation of the JVP.
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Tiee diugs aie commonly used in an attempt to maintain
tissue peifusion:
noiepinephiine (at low doses as a continuous infusion), foi
vasoconstiiction
dobutamine (or dopamine), as a beta-1 agonist, to inciease
caidiac output
vasopiessin (ADH), as a vasoconstiictoi, to ieduce
noiadienaline doses
Gastric protection
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High levels of coiticosteioids, secieted as pait of the stiess
iesponse, lead to incieased gastiic acid secietion and
decieased mucosal piotection. ITU patients aie usually
fed intiavenously iathei than oially, so missing out on the
bueiing eect of food in the stomach. Tey aie pione to
develop gastiic ulcei.
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Omeprazole (proton-pump inhibitor) and ranitidine (H
2
antagonist) are used to reduce gastric acid secretion.
Sedation
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Patients develop chronic depression after physical recovery.
The syndrome appears to be more severe, and more persistent,
in patients who have been constantly sedated during their time
in the ITU.
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Hypnotic-based sedation (e.g., piopofol; benzodiazepines
such as diazepam) is usually longei-lasting, and associated
with longei post-ITU depiession and othei psychiatiic
pioblems, than analgesia-based sedation (e.g., remifentanil).
Lung Injury
Lung injury may result from infection or shock, or from the use
of high tidal volumes in mechanical ventilators.
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Activated Protein C
APC and other anti-inflammatory drugs have been reported to
reduce the rate of lung injury.
Nitric Oxide
Inhaled nitiic oxide is used to tieat ARDS. Te eect is to
cause vasodilation of those capillaiies that aie paiticipating
in gas exchange, so impioving the ventilation-peifusion
matching.
P.D.D. 3/11
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