Frusemide
INDICATIONS
Diuretic used in settings such as:
fluid overload; ARDS; congestive heart failure; AKI; Hypercalcaemia (requires
rehydration first)
PRESENTATION AND ADMINISTRATION
PO:
Tablets:
Diurin 40mg tablets (off white), Diurin 500mg tablets (off white)
Oral Solution:
Lasix oral solution 10mg/ml
IV:
IV formulations available are:
1. Frusemide injection 20mg/2ml solution
2. Lasix high dose infusion 250mg in 25ml with 1000mg of mannitol as a stabilising
agent
Administer doses of up to 80mg by slow IV injection over 2-5 minutes
For infusion doses of up to 5mg/hr use low dose infusion mixture of 40mg in 40ml of
compatible IV fluid; for infusion doses of greater than 5mg/hr use high dose infusion
mixture with undiluted Lasix high dose infusion (ie 250mg in 25ml or 500mg in 50ml)
Rate of infusion should not exceed 4mg/min
Compatible with the following IV fluids:
Normal saline, Hartmanns
Note: glucose solutions are unsuitable
Store at room temperature; protect from light
Dilutions in compatible IV fluid are stable for 24 hours at room temperature – discard
if not used within 24 hours. Do not use if solutions have a yellow colour or contain
crystal deposits
DOSAGE
PO:
Usual dosage from 10mg daily to 80mg three times a day
IV:
Dosage is highly individualised. 5mg may be sufficient to cause significant diuresis in
the frusemide naïve patient. Doses of 100mg/hr by infusion may be required in those
with significant renal impairment.
Renal failure and renal replacement therapy
Dose in renal impairment [GFR (ml/min)]
<10: dose as in normal renal function; increased doses may be required
10-20: dose as in normal renal function; increased doses may be required
>20-50: dose as in normal renal function
Dose in renal replacement therapy
CAPD: not indicated
HD: not indicated
CVVHDF: rarely indicated; increased doses may be required
Paediatrics
IV/ PO:
Usually, 0.5-1mg/kg 6 hourly to four times a day.
IV infusion: 50mg/kg in 50ml of normal saline at 0.1-1 mg/kg/hr (i.e 0.1-1ml/hr)
CLINICAL PHARMACOLOGY
Frusemide is a potent diuretic that inhibits the absorption of sodium and chloride in the
proximal and distal tubules and the loop of Henle
PHARMACOKINETICS
Absorption:
Poor oral bioavailability (possibly due to the poor solubility of the compound, site-
specific absorption, presystemic metabolism and/or other unknown
mechanisms). Diuretic effect onset is within 1 hour following oral administration and
the peak effect occurs within 1-2h. The duration of action is 4-6h (up to 8h).
Following IV administration diuresis occurs within 30 min and duration of action is~ 2h.
Distribution: highly bound to plasma proteins, almost exclusively to albumin. Although
the drug is insoluble in water and favours partitioning into fatty tissue, the high degree
of plasma protein binding restricts the apparent volume of distribution at steady-state
to values within a multiple of 2 to 5 times the plasma volume
Metabolism: a small fraction is metabolised by the liver
Elimination: 2/3 renal (by both glomerular filtration and proximal tubular secretion), 1/3
biliary (as faeces)
DRUG INTERACTIONS
Frusemide may increase the ototoxic potential of aminoglycoside antibiotics, especially
in the presence of impaired renal function. Except in life-threatening situations, avoid
this combination.
Lithium generally should not be given with diuretics because they reduce lithium’s renal
clearance and add a high risk of lithium toxicity.
Allergy to sulfa drugs
ADVERSE REACTIONS
Gastrointestinal System Reactions:
Pancreatitis, jaundice (intrahepatic cholestatic juandice), anorexia, oral and gastric
irritation, cramping, diarrhea, constipation, nausea, and vomiting.
Systemic Hypersensitivity Reactions:
Systemic vasculitis, interstitial nephritis, and necrotizing angiitis.
Central Nervous System Reactions:
Tinnitus and hearing loss, paresthesias, vertigo, dizziness, headache, blurred vision,
and xanthopsia.
Hematologic Reactions:
Aplastic anemia (rare), thrombocytopenia, agranulocytosis (rare), hemolytic anemia,
leukopenia, and anemia.
Dermatologic-Hypersensitivity Reactions:
Exfoliative dermatitis, erythema multiforme, purpura, photosensitivity, urticaria, rash,
and pruritus.
Cardiovascular Reaction:
Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or
narcotics.
Other Reactions:
Hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weaknesses, restlessness,
urinary bladder spasm, thrombophlebitis, and fever.
EVIDENCE
The primary role of diuretics in the critically ill is in adjusting overall fluid
balance. ARDSNet investigators found that a conservative strategy of fluid
management (due to fluid restriction and/or diuretics) improved lung function and
shortened the duration of mechanical ventilation and intensivecare without increasing
nonpulmonary-organ failures.
In critically ill patients with acute renal failure, there is no evidence to suggest that the
use of loop diuretics reduces mortality, reduces length of ICU or hospital stay, or
increases the recovery of renal function.
Co-administration of albumin with furosemide may help overcome diuretic resistance in
hypoalbuminemic patients (modest effect suggested in meta-analysis)
Furosemide by continuous infusion in the recovery phase of hemofiltration-dependent
acute kidney failure did increase urinary volume and sodium excretion but did not lead
to a shorter duration of renal failure or more frequent renal recovery.
1 2 3 4 5 Rule
Simple table to calculate metabolic compensation in respiratory acidosis and alkalosis
(aka the 1-2-3-4-5 rule)
Simple calculation to predict changes in HCO3– from PaCO2
HCO3
(Baseline 24 mmol/L)
Every 10 mmHg change in PaCO2 ACUTE CHRONIC
from baseline 40 mmHg
↑PaCO2 1 4
↓PaCO2 2 5
Approach to interpreting Acid-base disturbance
Is the patient Acidemic or Alkalemic
Identify the primary Acidbase disorder by evaluating HCO3 and PaCO2
What is the [HCO3]
o Elevated------Metabolic alkalosis if alkalotic
o Decreased ---- Metabolic acidosis if acidotic
What is the PaCO2
o Elevated ---Respiratory acidosis if acidotic
o Decreased --- Respiratory alkalosis if alkalotic
What is the anion gap (to determine etiology of Metabolic acidosis)
What is the bicarbonate gap (to evaluate mixed disorders)
Is the degree of compensation what you expect (appropriate)?
