PART 3 - DRUGS AND INFUSIONS

A. Policy

1. Patients admitted to the ICU must have a complete drug history documented:
a) Premorbid and current medications
*see pharmacy’s drug listing within the patient’s medical
records. b) Previous adverse drug reactions and allergies
*if known the basis for that
allergy. c) Note potential drug
interactions.
2. Charting of drugs and infusions is to be done by ICU medical
staff. a) Parent clinics must not write on the ICU flowchart.
b) Therapeutic changes suggested by the home team must be communicated to the
appropriate ICU medical staff for consideration prior to
charting.
3. All changes to drug and fluid orders must be written and signed for on the
flowchart. a) Nursing staff must be notified of such changes.
b) Verbal orders alone are neither sufficient nor legal.
4. All drugs, infusions and fluids are reviewed and transcribed at least daily.
5. Printed labels for commonly used infusions and drugs should be used where possible.
6. Standardisation of infusion concentrations is essential for the prevention of
drug errors. Infusion concentrations should not be changed (e.g. ‘double strength’)
from the protocols outlined below.
7. Vasoactive or hypertonic infusions (e.g. TPN) must be administered through a
dedicated lumen of a CVC or PICC.
8. Vasoactive infusions must not be used in the general wards, other than for patients
en route to ICU and who are being continuously monitored.
9. All antibiotics written on the ICU flowchart must also have an indication of either:
a) Date started and due date for review/completion,
or b) Duration and position in course, e.g. “Day 4/7”.
10. Patients cleared for discharge from ICU must have all appropriate drugs, infusions
and fluids prescribed on the standard hospital forms, prior to discharge.
Where appropriate, old drug charts should be re-written.
11. Patients discharged on TPN must have their details entered in the TPN folder (stored
in the Unit A office area).
12. Any changes to acute pain drug regimens in patients under the care of the Acute Pain
Service should be done in consultation with the Acute Pain Service.
13. Any proposed changes to specialty type drugs, e.g. immunosuppressives,
anticoagulants, antiplatelet agents, etc should be discussed with home teams.
B. Principles of Drug Prescription in Intensive Care

1. Drugs should be prescribed according to Unit protocols and

guidelines.
2. Critically ill patients have altered pharmacokinetics and pharmacodynamics, with
the potential for toxicity and drug interactions.
3. Where possible:
a) Use drugs that can be titrated or prescribed to an easily measured
endpoint. b) Use drugs that can be measured to monitor therapeutic drug
levels.
c) Avoid drugs with narrow therapeutic indices (e.g. digoxin,
theophylline), particularly in patients with associated hepatic or renal
dysfunction.
d) Cease a drug if there is no apparent benefit.
e) If two drugs are of equal efficacy, choose the cheaper drug as the cost of drugs in
ICU is significant.
4. Prescribe using generic drug names
only.
5. When there is a medication change (e.g. replacing an antibiotic for another,
alteration in drug dose, ceasing a drug) then some indication as to the reason behind
doing so should be made within the patient’s medical records or drug chart.
6. A Clinical Pharmacist conducts a daily review (Mon-Fri) of ICU drug
charting, attends grand ward-rounds and is available for consultation. This is an
invaluable service and should be utilized accordingly.

C. Cardiovascular
Drugs

1. Inotropes

Inotropes (specifically catecholamines) are frequently used in ICU. There are varied
prescription practices and preferences for these drugs, mostly based upon the reported
pharmacological effects of the different agents.

a) General principles:
i) Defence of BP in the critically ill forms the basis of haemodynamic
resuscitation and organ perfusion.
 Must be interpreted in the context of the patient’s pre-morbid BP
 Particularly in renovascular hypertension or cerebrovascular disease.
ii) Hypovolaemia is the most common cause of hypotension and low cardiac
output in ICU and must be assiduously monitored and corrected.
iii) The main indications for the use of inotropes are to increase
myocardial contractility, heart rate and/or vascular tone.
iv) The use of inotropes requires regular haemodynamic monitoring:
 Arterial line and CVC are mandatory
 Where indicated - PAC, PiCCO, Vigileo CO or ultrasound.
v) No single inotrope (or mixture) has been shown to be superior to another.
vi) There is marked inter-individual variation in the response to inotropes:
  Pre-existing chronic illness, genetic variation
 Co-administration of other drugs
 Qualitative and quantitative changes in adrenergic receptor kinetics.
vii) Prolonged exposure to catecholamine infusions can produce adrenergic
receptor down-regulation and tachyphylaxis.
b) Catecholamines
i) Receptor effects may be unpredictable, however, in general:
 -adrenergic effects predominate at low doses, and
 -adrenergic effects at higher doses.
ii) It is impossible to predict the dose range for an individual patient.
iii) Prescription on a body weight basis (µg/kg/min) is of little clinical utility.
iv) Infusions should be started at a low rate (3-5 µg/min) and titrated to a set
clinical response, e.g. MAP (not systolic)
v) There is no well established maximal dose.
vi) Regular assessment should be made of both global (pH, lactate) and
regional effects (urine output/creatinine clearance, limb perfusion).
c) Phosphodiesterase inhibitors (milrinone)
i) Inhibition of PDE3 increases intracellular cAMP and calcium, causing:
 an increase in myocardial contractility
 systemic and pulmonary vasodilatation, and
 improved diastolic relaxation (lusitropy)
ii) Any resultant hypotension (due to systemic vasodilatation) usually
responds with the addition of a vasopressor (e.g. noradrenaline).
iii) Phosphodiesterase inhibitors have longer half-lives than catecholamines,
are less titratable and their half-life is prolonged with renal failure.

Table: Cardiovascular Effects of Catecholamines

1 effects 2 effects 1 effects 2 effects

 Chronotropy  Inotropy  Inotropy  Inotropy
Agent  Dromotropy Vasodilatation
 Inotropy Bronchodilatation Vasoconstriction Vasoconstriction
 glucose/lactate

Adrenaline
Noradrenaline  effects predominate at low dose  effects predominate at high dose
Dopamine
Dobutamine + + (+) -
Isoprenaline + (+) - -
+ = strong effect (+) mild effect - = no effect
 Table: Inotropic Agents Used in ICU
Agent Standard Infusion
Noradrenaline 6 mg / 100 ml 5% dextrose
(ml/hr = µg/min)
Adrenaline 6 mg / 100 ml 5% dextrose
(ml/hr = µg/min)
Dobutamine 500 mg / 100 ml 5% dextrose
(ml/hr approx µg/kg/min)
Dopamine 400 mg / 100ml 5% dextrose
(ml/hr approx µg/kg/min)
Isoprenaline 6 mg / 100 ml 5% dextrose
(ml/hr = µg/min)
Levosimendan 12.5 mg / 250 mL 5% dextrose
Loading dose: 6-12µg/kg/10min
Infusion: 0.05-0.2 µg/kg/min
NB: Loading dose may cause
marked hypotension, may be
omitted or reduced.
Milrinone 10mg / 100 ml 5% dextrose
Loading dose: 50µg/kg/20 min
Infusion: 0.5 µg/kg/min*
*Standard milrinone prescription for 70 kg patient:
2. Vasopressor agents
a) General principles
i) Vasopressors usually act directly on the peripheral vasculature and
are primarily used to acutely elevate BP
ii) The most common cause of hypotension in ICU patients is
hypovolaemia. iii) Pressor agents should not be used as an alternative to
fluid resuscitation.
b) Indications (in ICU)
i) Tissue infiltration with local anaesthesia
ii) Topically prior to nasal intubation
Uses
 First line drug in septic shock
 Maintenance of blood pressure
 Cardiopulmonary resuscitation
 Acute severe asthma
 Anaphylaxis
 Cardiogenic shock
 Maintenance of blood pressure
 Medical pacing
 Primarily a vasodilator, weak inotropic action
 Traditionally used in cardiogenic shock or low
output, high afterload states or when filling
pressures high
 Often used in combination with noradrenaline
 Maintenance of blood pressure
 No advantage over adrenaline/noradrenaline
 “Renal dose” dopamine is not used
 Endocrine side effects
 Vasodilator, chronotrope (rarely used)
 Symptomatic bradycardia
 Calcium sensitizer
 Increases myocardial contractility in an oxygen
efficient manner and dilates coronary and systemic
vessels
 Role in Intensive Care not established
 Cardiogenic shock due to diastolic failure
 Pulmonary hypertension following valve
replacement
 Catecholamine induced down regulation
Loading dose: 3500 µg = 35 ml over 20 minutes
Maintenance: 2100 µg/hr = 20 ml/hr.
 iii) Hypotension following sympathetic block (e.g. epidural anaesthesia)
iv) Hypotension refractory to large doses of catecholamines (vasoplegia):
 Consider relative hypoadrenalism
 Consider use of vasopressin
c) Complications
i) Rebound hypertension
ii) Vagal reflex bradycardia
iii) Tachyphylaxis

Table: Vasopressors

Agent Standard Infusion / Dose Uses

Metaraminol 10mg / 10ml 5% dex: titrate
Ephedrine 30mg / 10ml 5% dex: titrate
Vasopressin 20units/20ml 5%dex:
1.8mls/hrs (0.03u/min)
 Potent short acting vasoconstrictor
 Synthetic indirect sympathomimetic.
 Commonly used in anaesthesia, little
benefit over adrenaline.
 Noradrenaline resistant hypotension.
 May be useful in septic shock and post
cardiac bypass for catecholamine
resistant hypotension

3. Antihypertensive agents

a) General principles
i) The most common cause of hypertension in ICU patients is sympathetic
drive due to pain, agitation, drug withdrawal or delirium. These should be
treated with adequate sedation, anxiolytics and/or analgesia.
ii) Patients in the recovery phase of acute renal failure are often hypertensive.
This usually represents the resetting of endogenous neurohumoral
mechanisms and as such does not routinely require treatment.
iii) Hypertension following an intracranial event (haemorrhagic or ischaemic)
is common and the underlying mechanism dictates therapy. A high BP
may be tolerated in ischaemic stroke, c.f. the setting of SAH with an
unclipped aneurysm, where treatment would be paramount.
iv) Target therapy should be titrated against the patient’s premorbid BP.
v) In the absence of adverse effects, the maximal therapeutic dose of a
selected agent should be used prior to commencing a second or third agent.
b) Indications
i) Acute
 Perioperative control of BP in “at risk” patients.
 Hypertensive crisis (malignant hypertension)
 Pre-eclampsia / eclampsia
 Phaeochromocytoma
 Untreated aneurysm or vascular injury,
e.g. intracranial aneurysm, ruptured/dissected aorta ii) Other
indications for vasodilators
 Reduction of afterload in CCF or valvular disease
 Adjunct to passive warming in hypothermia iii) Chronic
 Sustained essential hypertension
 Ischaemic heart disease
 Cerebrovascular disease
c) Complications – are many, but in relation to ICU patients:
i) Hypotension
 First-dose effect / especially in hypovolaemia ii) Reflex
tachycardia
iii) Tachyphylaxis
iv) Pulmonary vasodilatation  shunt and hypoxaemia v) Cyanide
toxicity (SNP)
vi) Angioedema – especially ACEI
vii) Deterioration in renal function viii) Electrolyte
disturbances

Table: Antihypertensive & Vasodilator Agents

Agent Infusion & Dose Uses

Glyceryl 30mg / 100ml 5%D  Mainly venodilation:
trinitrate (GTN) (non PVC bottle and giving set)  Useful in cardiac ischaemia
Range 2-25 ml/hr  Less predictable control of BP than SNP
First line drug in RAH ICU  Tachyphylaxis develops within 24-48hr
Can be given topically. will need additional agents for persistent BP
Sodium 50mg / 250 ml 5%D  Rapid control of hypertensive crises.
nitroprusside Range 3-40 ml/hr  Tachyphylaxis and metabolic acidosis may imply
(SNP) cyanide toxicity (total dose > 1.5mg/kg/24 hrs)
Phentolamine 10mg / 10ml 5%D: titrate  Pure -blockade, short acting antihypertensive
Hydralazine 5-10 mg as bolus  Short to medium term IV agent.
20-40 mg 6-8 hourly  Often use with -blockers to control reflex tachycardia
 Useful in renovascular hypertension

Table: Antiarrhythmic Agents

Agent Infusion & Dose Uses

Amiodarone Acute use:  Rapid AF / flutter or MAT
900mg / 250ml 5%D:  Monomorphic ventricular tachycardia
 Generally does not suppress contractility
Load 100ml / 1 hr (5mg/kg)  Can cause acute hypotension if given too rapidly
Infuse 10 ml/h for 24-48 hrs  Less proarrhythmic than most other drugs
(15mg/kg/day)  Causes QTc, but rarely Torsade de pointes
 Renal excretion is minimal – no need to change dose
Bolus Dose 150- in renal failure
300mg  Long term side-effects rare in short-term use.
 Interference with digoxin kinetics and assay.
Chronic:  Interference with thyroid function tests.
200-400 mg IV/oral daily
Magnesium 5-10 mmol IV slow bolus  Acts principally as a calcium blocker
Infuse at 2-5 mmol/hr. 2.4g MgSO4  Useful in SVT and Torsade de pointes
= 10 mmol Mg++
Verapamil 5-10 mg IV slow bolus
Digoxin Loading dose: 0.5-1 mg IV.
Maintenance: 62.5-250 µg IV/day
Levels: 0.6–1.0 mmol/l
Metoprolol 1-2 mg IV bolus (up to 10 mg)
25-100 mg oral bd
Sotolol 10-80 mg IV slow bolus
(10-15 min)
Adenosine 6-12 mg IV push
Lignocaine 0.4% solution = 4mg/ml :
60 ml/hr (4mg/min) for 1-2 hrs
45 ml/hr for 2-4 hrs
30 ml/hr for 2-4 hrs
Flecanaide 1 mg/kg slow IV push
100 mg oral BD (max of
300 mg/day)
Phenytoin 15 mg/kg loading / 1 hr
300 mg/day
(level 40-80 mmol/l)
 Conversion atrial flutter  SR
 SVT
 Ventricular rate control in rapid AF (usually 2nd line to
amiodarone in critically ill)
 Narrow therapeutic index esp in renal failure and
metabolic abnormalities ( K+, Mg, PO4, alkalosis)
 Proarrhythmic potential high in critically ill patients
 Minimal inotropic effect in critically ill patients
 Hypokalaemia potentiates effects
 Used in high sympathetic drive states : neurogenic
hypertension, hyperthyroidism
 Control of reflex tachycardia with vasodilators
 Caution in poor LV function, asthma
 Mainly hepatic metabolism
 Class III and -blocking actions
 Supraventricular tachyarrhythmias
Conversion AF/flutter  SR
 Low pro-arrhythmic potential
 Diagnosis / conversion of SVT
 2nd line drug after amiodarone
 Sustained, recurrent VT
 No longer routinely used for prophylaxis for VT
 VF resistant to defibrillation (now questioned)
 Potent negative inotrope, pro-convulsant
 SVT
 AV nodal re-entrant tachycardia
 WPW
 Ventricular dysrythmias
 Digoxin toxicity
 Tricyclic induced malignant arrhythmias