Critical care formulary

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Adrenaline

For use in Critical Care Areas for Adults only

Administer via central line only

MECHANISM OF ACTION:

  • Adrenaline exhibits primarily inotropic (beta-1) and vasodilator (beta-2) effects but some dose dependent vasopressor (alpha-1) effects are present at higher doses.
  • Half-life = 1 to 3 minutes.

USES:

  • Hypotension (second-line treatment for cardiogenic shock - after dobutamine).
  • Bradycardia with adverse signs (shock, syncope, myocardial ischaemia, heart failure) and/or risk of asystole which has not responded to atropine (if external pacing unavailable or unsuccessful).

CAUTIONS:

  • Hypotension due to uncorrected hypovolaemia.
  • Tachycardia and arrhythmias.
  • Narrow angle glaucoma.
  • Phaeochromocytoma.
  • Some brands contain sodium metabisulphite; caution if previous sensitivity.

PRESENTATION:

  • Ampoules containing 5mg in 5ml (1 in 1000).

ADMINISTRATION:

  • Dilute required volume of adrenaline with glucose 5% to total volume and administer via syringe pump (when preparing in a bag to give via volumetric infusion, withdraw equivalent volume before adding adrenaline).  The syringe must be clearly labelled.
  • Always start treatment using single strength preparation and titrate to response.  If the infusion is running at ≥10ml/hour, consider changing to a more concentrated preparation.
  • Inform pharmacy if running quad strength adrenaline to ensure sufficient stock available on ward.
  • Must be given via a dedicated port.

DOSE AND RATE:

  • Titrate dose to achieve clinical target.  The goal is to maintain an adequate blood pressure to ensure organ perfusion, and usually achieve a target mean arterial pressure (MAP) of 65 to 75 mmHg, as advised by the clinician.  Dose required should be guided by heart rate (HR), blood pressure (BP), cardiac output, presence of ectopic beats and urine output.
  • Infusions are usually started at 2 to 5ml/hour of single strength (80micrograms/ml), and titrated by increasing or reducing the infusion rate by 1ml/hour to achieve target MAP.
  • If dose is escalating rapidly, or dose required to achieve clinical target exceeds 0.3 micrograms/kg/minute (highlighted in red in the tables below) the doctor must be contacted to discuss further management.  Options include:
    • Addition of another therapy.
    • Sedation level reviewed (ICU only).
    • Cardiac Output Monitoring commenced (ICU only).
    • A new upper limit may be set.

To calculate dose in micrograms/kg/minute, use tables below or the following calculation:

Dose (micrograms/kg/minute) =

Rate (ml/hour) x Concentration (micrograms/ml)
Patient’s weight (kg) x 60

STABILITY

  • 24 hours.
  • Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidelines for switching over infusions or syringes.

EXTRAVASATION:

SIDE-EFFECTS:

  • Angina, tachycardia, arrhythmias and palpitations.
  • Hyperglycaemia.
  • Increased lactate.

MONITORING:

  • Ensure ECG and blood pressure monitoring is in place.  Invasive blood pressure monitoring is preferred as in hypoperfused or shock states with cool peripheries, non-invasive BP recordings are less reliable.
  • Pulse oximetry.
  • Monitor for tissue ischaemia or necrosis due to vasoconstriction.
  • Regular blood glucose monitoring.
  • Lactate.

BIBLIOGRAPHY:

  • Critical Care Group, UKCPA, Intensive Care Society. Standard Medication Concentrations for Continuous Infusions in Adult Critical Care [homepage on the internet]. London: National Health Service; 2020 [updated 2021 Sep 21; cited 21/12/2021]. Available from: https://medusa.wales.nhs.uk/docs/2020-12%20ICS%20standard%20concentrations%20list%20v4.1.pdf
  • National Health Service. Medusa: NHS Injectable Medicines Guide (online). Accessed via: https://medusa.wales.nhs.uk/ [accessed on 15/12/21]
  • Paw S, Shulman R. Handbook of Drugs in Intensive Care. An A-Z Guide. 6th Ed. Cambridge: Cambridge University Press; 2019.
  • Phillips B, Barton G, McKenzie C (editors in chief) Critical Illness (online). London: Pharmaceutical Press. Available at: www.medicinescomplete.com [accessed on 15/12/21]

Dobutamine - for central administration (5mg/ml)

For use in Critical Care Areas for Adults only.  Administer via central line – for peripheral administration see separate guideline.

MECHANISM OF ACTION:

  • Marked inotropic (beta-1) effects which increase heart rate and force of contraction.
  • Mild beta-2 and alpha-1 effects which decreases peripheral and pulmonary vascular resistance.
  • It does not have direct effects on renal blood flow, but may increase renal blood flow due to an increase in cardiac output.
  • Half-life = 2 to 3 minutes.

USES:

  • Hypotension in the absence of hypovolaemia (correct this first).
  • Cardiogenic shock.
  • Other low cardiac output states eg post myocardial infarction.

CAUTIONS:

  • Hypotension due to uncorrected hypovolaemia.
  • Ischaemic heart disease (due to the impact on myocardial oxygen demand).
  • Acute heart failure.
  • Arrhythmias or rapid AF (may increase ventricular response rate).
  • Marked obstruction of cardiac ejection eg idiopathic hypertrophic subaortic stenosis or hypertrophic obstructive cardiomyopathy.
  • Elderly.
  • Some brands contain sodium metabisulphite; caution if previous sensitivity.
  • If administered continuously for more than 72 hours, tachyphylaxis may occur, requiring a dose increase.
  • Contra-indicated in phaeochromocytoma.

PRESENTATION:

  • 250mg in 50ml (5000micrograms in 1ml) vials.

ADMINISTRATION:

  • For central administration use the ready diluted preparation (250mg in 50ml) to provide a concentration of 5000micrograms in 1ml.
  • Administer via a syringe pump.

DOSE AND RATE:

  • Dobutamine should be titrated to the cardiac indices set by the clinician.  Dose required should be guided by HR, BP, cardiac output, presence of ectopic beats and urine output.  In particular, patients receiving dobutamine should be monitored closely for tachyarrhythmias.
  • The dose should be adjusted according to clinical response but would normally be kept in the range 2·5 to 10 micrograms/kg/minute, increasing to 20micrograms/kg/minute if needed.
  • Doses above 10 micrograms/kg/minute should rarely be required.
  • Adjust rate of dobutamine infusion to clinical effect with caution in obese patients.
  • Do not allow infusion to run out.  Prepare a new syringe or infusion before the previous one finishes.  Refer to local nursing guidelines for switching over infusions or syringes.  In clinically unstable patients, double-pumping may be required when switching over syringes; discuss with consultant. 
  • Must be given via a dedicated port.
  • On discontinuation, reduce dose slowly rather than abruptly stopping.

To calculate dose in micrograms/kg/minute, use table below or the following calculation:

Dose (micrograms/kg/minute) =

Rate (ml/hour) x Concentration (micrograms/ml)
Patient’s weight (kg) x 60

STABILITY:

  • 24 hours.
  • Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidelines for switching over infusions or syringes.

EXTRAVASATION:

SIDE EFFECTS:

  • Hypotension.
  • At higher doses, tachyarrhythmias.
  • Alterations in serum potassium.

MONITORING:

  • Ensure ECG and blood pressure monitoring is in place. Invasive blood pressure monitoring is preferred as in hypoperfused or shock states with cool peripheries, non-invasive BP recordings are less reliable.
  • Daily electrolytes (especially potassium and magnesium) and fluid balance.

OTHER INFORMATION:

  • Solutions may have a pink discolouration which may become darker with time, resulting from a slight oxidation of the drug.  There is no significant loss of drug potency within the recommended storage time for solutions of the drug.

BIBLIOGRAPHY:

Critical Care Group, UKCPA, Intensive Care Society. Standard Medication Concentrations for Continuous Infusions in Adult Critical Care [homepage on the internet]. London: National Health Service; 2020 [updated 2020 December; cited 01/03/2022]. Available from: https://medusa.wales.nhs.uk/docs/2020-12%20ICS%20standard%20concentrations%20list%20v4.1.pdf

Hameln. Electronic Medicines Compendium: Dobutamine 5 mg/ml, solution for infusion [homepage on the internet]. London: Datapharm; 2021 [updated 2021 December 10; cited 01/03/2022]. Available from: https://www.medicines.org.uk/emc/product/6462/smpc

Joint Formulary Committee. Dobutamine. In: Joint Formulary Committee. British National Formulary. [BNF online]. London: BMJ Group and Pharmaceutical Press; 2020 [updated 2020 Aug 11; 01/03/2022]. Available from: https://www.medicinescomplete.com/#/content/bnf/_829952202?hspl=dobutamine

National Health Service. Medusa: NHS Injectable Medicines Guide: Dobutamine [homepage on the intranet]. London: National Health Service; 2021 [updated 2021 Dec 11; cited 01/03/2022] Available from: https://medusa.wales.nhs.uk/IVGuideDisplayNewFormat.asp

Paw S, Shulman R. Handbook of Drugs in Intensive Care. An A-Z Guide. 6th Ed. Cambridge: Cambridge University Press; 2019.

 

Dobutamine – for peripheral administration (1mg/ml)

For use in Critical Care Areas for Adults Only.  Administer via peripheral line – for central administration see separate guideline.

MECHANISM OF ACTION:

  • Marked inotropic (beta-1) effects which increase heart rate and force of contraction.
  • Mild beta-2 and alpha-1 effects which decreases peripheral and pulmonary vascular resistance.
  • It does not have direct effects on renal blood flow, but may increase renal blood flow due to an increase in cardiac output.
  • Half-life = 2 to 3 minutes.

USES:

  • Hypotension in the absence of hypovolaemia (correct this first).
  • Cardiogenic shock.
  • Other low cardiac output states eg post myocardial infarction.

CAUTIONS:

  • Hypotension due to uncorrected hypovolaemia.
  • Ischaemic heart disease (due to the impact on myocardial oxygen demand).
  • Acute heart failure.
  • Arrhythmias or rapid AF (may increase ventricular response rate).
  • Marked obstruction of cardiac ejection eg idiopathic hypertrophic subaortic stenosis or hypertrophic obstructive cardiomyopathy.
  • Elderly.
  • Some brands contain sodium metabisulphite; caution if previous sensitivity.
  • If administered continuously for more than 72 hours, tachyphylaxis may occur, requiring a dose increase.
  • Contra-indicated in phaeochromocytoma.

PRESENTATION:

  • 250mg in 20ml ampoules OR 250mg in 50ml vials.

ADMINISTRATION:

  • For peripheral administration prepare a concentration of 1000 micrograms in 1ml.
  • Use 250mg in 20ml ampoule or 250mg in 50ml vial.
  • Withdraw equivalent volume from a 250ml bag of glucose 5% or sodium chloride 0.9% (20ml if using 250mg in 20ml, or 50ml if using 250mg in 50ml) and add the 250mg dobutamine to prepare a 1000micrograms in 1ml solution and administer via a volumetric pump.
  • Use a large peripheral vein.

Dobutamine (peripheral)

250ml bag via volumetric pump

Prescribe

250mg in 250ml

Drug dose to be added

250mg in 20ml OR 250mg in 50ml

Diluent to be added

Glucose 5% (preferred) or sodium chloride 0.9%

Withdraw equivalent volume from bag of glucose 5% or sodium chloride 0.9% before adding dobutamine i.e. remove 20ml if using 250mg in 20ml, or 50ml if using 250mg in 50ml

Final volume

250ml

Final concentration

1000 micrograms/ml

DOSE AND RATE:

  • Dobutamine should be titrated to the cardiac indices set by the clinician.  Dose required should be guided by heart rate (HR), blood pressure (BP), cardiac output, presence of ectopic beats and urine output.  In particular, patients receiving dobutamine should be monitored closely for tachyarrhythmias.
  • The dose should be adjusted according to clinical response but would normally be kept in the range 2·5 to 10 micrograms/kg/minute, increasing to 20micrograms/kg/minute if needed.
  • Doses above 10 micrograms/kg/minute should rarely be required.
  • Adjust rate of dobutamine infusion to clinical effect with caution in obese patients.
  • Do not allow infusion to run out.  Prepare a new syringe or infusion before the previous one finishes.  Refer to local nursing guidelines for switching over infusions or syringes.  In clinically unstable patients, double-pumping may be required when switching over syringes; discuss with consultant.
  • Must be given via a dedicated port.
  • On discontinuation, reduce dose slowly with close monitoring of BP, rather than abruptly stopping.

To calculate dose in micrograms/kg/minute, use table below or the following calculation:

Dose (micrograms/kg/minute) =

Rate (ml/hour) x Concentration (micrograms/ml)
Patient’s weight (kg) x 60

STABILITY:

  • 24 hours.
  • Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidelines for switching over infusions or syringes.

EXTRAVASATION:

  • The infusion has a low pH and extravasation is likely to cause venous irritation and tissue damage.  Use a large peripheral vein with monitoring for phlebitis.  Resite catheter at first signs of inflammation.

SIDE EFFECTS:

  • Hypotension.
  • At higher doses, tachyarrhythmias.
  • Alterations in serum potassium.

 MONITORING:

  • Ensure ECG and blood pressure monitoring is in place.  Invasive blood pressure monitoring is preferred as in hypoperfused or shock states with cool peripheries, non-invasive BP recordings are less reliable.
  • Daily electrolytes (especially potassium and magnesium) and fluid balance.

OTHER INFORMATION:

  • Solutions may have a pink discolouration which may become darker with time, resulting from a slight oxidation of the drug.  There is no significant loss of drug potency within the recommended storage time for solutions of the drug.

BIBLIOGRAPHY:

Critical Care Group, UKCPA, Intensive Care Society. Standard Medication Concentrations for Continuous Infusions in Adult Critical Care [homepage on the internet]. London: National Health Service; 2020 [updated 2020 December; cited 01/03/2022]. Available from: https://medusa.wales.nhs.uk/docs/2020-12%20ICS%20standard%20concentrations%20list%20v4.1.pdf

Hameln. Electronic Medicines Compendium: Dobutamine 5 mg/ml, solution for infusion [homepage on the internet]. London: Datapharm; 2021 [updated 2021 December 10; cited 01/03/2022]. Available from: https://www.medicines.org.uk/emc/product/6462/smpc

Joint Formulary Committee. Dobutamine. In: Joint Formulary Committee. British National Formulary. [BNF online]. London: BMJ Group and Pharmaceutical Press; 2020 [updated 2020 Aug 11; 01/03/2022]. Available from: https://www.medicinescomplete.com/#/content/bnf/_829952202?hspl=dobutamine

National Health Service. Medusa: NHS Injectable Medicines Guide: Dobutamine [homepage on the intranet]. London: National Health Service; 2021 [updated 2021 Dec 11; cited 01/03/2022] Available from: https://medusa.wales.nhs.uk/IVGuideDisplayNewFormat.asp

Paw S, Shulman R. Handbook of Drugs in Intensive Care. An A-Z Guide. 6th Ed. Cambridge: Cambridge University Press; 2019.

Isoprenaline hydrochloride

For use in Critical Care Areas for adults only.  Administer via a large peripheral vein or central line (*caution – different strengths*).

MECHANISM OF ACTION:

  • Stimulates beta-1 and beta-2 adrenoceptors producing an increase in cardiac output by increasing heart rate and myocardial contractility.
  • Half-life = 2.5 to 5 minutes.

USES:

  • For bradycardia in patients with adverse signs (systemic hypotension, signs of cerebral hypoperfusion, progressive heart failure, angina, or life-threatening ventricular arrhythmias) and/or risk of asystole which has not responded to atropine, until temporary or permanent pacing can be initiated.

CONTRA-INDICATIONS:

  • Recent MI – may increase myocardial oxygen demand.
  • Do not give at the same time as adrenaline.
  • Ventricular arrhythmias or tachyarrhythmias.
  • Heart block due to digoxin toxicity.
  • Angina – may exacerbate.

CAUTIONS:

  • Phaeochromocytoma.
  • Hypotension due to uncorrected hypovolaemia.
  • Hyperthyroidism.

PRESENTATION:

  • Isoprenaline hydrochloride 1mg in 5ml ampoules.
  • Stored in refrigerator.

ADMINISTRATION:

For peripheral administration (4 micrograms per ml):

  • Add 2mg (10ml) to 500ml glucose 5% (withdraw 10ml from bag before adding Isoprenaline) to prepare a 4 microgram per ml solution.
  • Glucose 5% is the preferred diluent but sodium chloride 0.9% may be used if there are concerns around hyperglycaemia.
  • Administer via a volumetric pump via a large peripheral vein.

For central administration (40 micrograms per ml)

  • Dilute 2mg (10ml) to 50ml with glucose 5% to prepare a 40 microgram per ml solution.
  • Administer via syringe pump.

Isoprenaline

Peripheral Administration

(volumetric infusion)

Central Administration (syringe pump)

Prescribe

2mg in 500ml

2mg in 50ml

Drug dose to be added

2mg in 10ml (2 ampoules)

2mg in 10ml (2 ampoules)

Diluent to be added

490ml glucose 5%

(withdraw 10ml from 500ml bag glucose 5% before adding isoprenaline)

*Sodium chloride 0.9% may be used if concerns around hyperglycaemia*

40ml glucose 5%

Final volume

500ml

50ml

Final concentration

4micrograms/ml

40micrograms/ml

DOSE AND RATE:

  • Usual dose is 1 to 5 micrograms/minute.
  • Commence at 1 microgram/minute and titrate upwards at intervals of 2 to 3 minutes until an adequate heart rate is achieved (50 to 60 beats per minute or target set by medical team).  Discuss with medical staff before increasing rate further if side-effects such as hypotension or arrhythmias occur.

Dose (micrograms/minute)

Rate (ml/hour)

4 micrograms/ml solution

PERIPHERAL ADMINISTRATION

Rate (ml/hour)

40 micrograms/ml solution

CENTRAL ADMINISTRATION

1

15

1.5

2

30

3.0

3

45

4.5

4

60

6.0

5

75

7.5

STABILITY:

  • 24 hours.
  • Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidelines for switching over infusions or syringes.

EXTRAVASATION:

  • The infusion has a low pH and extravasation is likely to cause venous irritation and tissue damage.  If given peripherally, use a large vein with monitoring for phlebitis.  Resite catheter at first signs of inflammation.
  • Please refer to NHS Highland Extravasation Protocol on intranet. 

 SIDE-EFFECTS:

  • Tachycardia and arrhythmias.
  • Angina.

 MONITORING:

  • Continuous ECG and blood pressure monitoring.
  • Renal function and urine output/fluid balance.

BIBLIOGRAPHY:

National Health Service. Medusa: NHS Injectable Medicines Guide (online). Accessed via: https://medusa.wales.nhs.uk/ [accessed on 31/01/22]

Macure Pharma UK Ltd. Electronic Medicines Compendium: Isoprenaline Macure 0.2mg/ml concentrate for solution for infusion [homepage on the internet]. London: Datapharm; 2021 [updated 2021 May 17; cited 04/02/22]. Available from: Isoprenaline Macure 0.2mg/ml concentrate for solution for infusion - Summary of Product Characteristics (SmPC) - (emc) (medicines.org.uk).

Paw S, Shulman R. Handbook of Drugs in Intensive Care. An A-Z Guide. 6th Ed. Cambridge: Cambridge University Press; 2019.

 

Metaraminol

For use in Critical Care Areas for Adults only.  Administer via syringe pump via central line or a large peripheral vein.

MECHANISM OF ACTION:

  • Metaraminol exhibits marked vasopressor (alpha-1) as well as positive inotropic (beta) effects.

USES:

  • Severe hypotension associated with low peripheral resistance eg in sepsis (correct hypovolaemia first).

CAUTIONS:

  • Hypotension due to uncorrected hypovolaemia.
  • Tachycardia or reflex bradycardia.
  • Cardiac arrhythmias.
  • Sustained use can result in cumulative effects that persist even when therapy is discontinued.
  • Some brands contain sodium metabisulphite; caution if previous sensitivity.

PRESENTATION:

  • Pre-filled syringe: 2.5mg/5ml (0.5ml/ml).
  • Ampoule: 10mg/1ml.

ADMINISTRATION:

For IV Injection (bolus) [EMERGENCY USE ONLY]:

  • Use the pre-filled syringe.

For Infusion:

  • Dilute 5ml (50mg) of metaraminol to 50ml with glucose 5% or sodium chloride 0.9% to provide a concentration of 1mg/ml.
  • Administer infusion via a syringe driver via central line (use a dedicated port) or a large peripheral vein.
  • When stopping the infusion, reduce the rate of infusion gradually. Abrupt withdrawal can cause acute hypotension.
  • Note this concentration of 1mg/ml differs from the NHS Injectable Medicines Guide (Medusa) but has been historically used in NHS Highland and agreed locally with consultants.

Metaraminol continuous infusion

Syringe Pump

Prescribe

50mg in 50ml

Drug dose to be added

50mg in 5ml

Diluent to be added

45ml glucose 5% or sodium chloride 0.9%

Final volume

50ml

Final concentration

1mg/ml

DOSE AND RATE:

For IV Injection (bolus) [EMERGENCY USE ONLY]:

  • 1 to 2ml (0.5 to 1mg) can be given as a rescue bolus in an emergency while infusion is being prepared.  The effect begins approximately 1 minute after IV bolus.

For Infusion:

  • Start with a low infusion rate (commonly in the range of 3 to 5ml/hour but lower rates may be required for elderly/frail patients) then dose titrated to achieve clinical target (blood pressure or mean arterial pressure [MAP]).  The infusion rate should normally be kept within the range 0.5 to 10ml/hour (0.5 to10mg/hour)
  • If dose is escalating rapidly or if clinical target is not being met, the doctor must be contacted to discuss further management.  Options Include:
    • Fluid resuscitation.
    • Switch to alternative therapies as appropriate such as noradrenaline if there is a central line (CVC) in place.
    • If necessary consult ICU staff.

 STABILITY:

  • 24 hours.
  • Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidance for switching over infusions or syringes.
  • Due to duration of action of metaraminol of 20 to 60 minutes, double pumping is not required when changing over syringes.

 EXTRAVASATION:

  • This medicine has a low pH and may cause venous irritation and tissue damage in cases of extravasation.  Resite catheter at first signs of inflammation.
  • Please refer to NHS Highland Extravasation Protocol on intranet. 

SIDE EFFECTS:

  • Bradycardia (reflex to the increase in blood pressure).
  • Arrhythmias.
  • Peripheral ischaemia.
  • Headaches.

MONITORING:

  • Ensure ECG and blood pressure monitoring is in place.  Invasive blood pressure monitoring is preferred as in hypoperfused or shock states with cool peripheries, non invasive BP recordings are less reliable.

ADDITIONAL INFORMATION:

  • Metaraminol has a longer duration of action than noradrenaline so an excessive vasopressor response may cause prolonged rise in blood pressure.
  • Metaraminol is the vasopressor of choice where only peripheral access is available.  If central access is available consider switching to noradrenaline.

BIBLIOGRAPHY:

Flexipharm Austrading Limited. Electronic Medicines Compendium: Metaraminol 10mg/ml Solution for Injection/Infusion [homepage on the internet]. London: Datapharm; 2021 [updated 2021 May 6; cited 16/12/21]. Available from: https://www.medicines.org.uk/emc/product/12493/smpc

Intensive Care Society. Guidance For: The use of Vasopressor Agents by Peripheral Intravenous Infusion in Adult Critical Care Patients [homepage on the intranet]. London: Intensive Care Society; 2020 [updated 2020; cited 16/12/21]. Available from: https://medusa.wales.nhs.uk/Docs/Peripheral_Vasopressor_guide_fianl.pdf

Joint Formulary Committee. Metaraminol. In: Joint Formulary Committee. British National Formulary. [BNF online]. London: BMJ Group and Pharmaceutical Press; 2020 [updated 2020 April 28; cited 2021 Dec 16]. Available from: https://www.medicinescomplete.com/#/content/bnf/_807506645?hspl=metaraminol

National Health Service. Medusa: NHS Injectable Medicines Guide: Metaraminol [homepage on the intranet]. London: National Health Service; 2021 [updated 2021 Sep 15; cited 16/12/21] Available from: https://medusa.wales.nhs.uk/  

Torbay & South Devon NHS Foundation Trust. Electronic Medicines Compendium: Metaraminol 10mg/ml Solution for Injection/Infusion [homepage on the internet]. London: Datapharm; 2016 [updated 2016 July 22; cited 16/12/21]. Available from: https://www.medicines.org.uk/emc/product/7111/smpc

Milrinone

For use in Critical Care Areas for Adults only.  Administer preferably via central line (low pH).

MECHANISM OF ACTION:

  • Positive inotrope and vasodilator, with little chronotropic activity.
  • Selectively inhibits PEAK III cAMP phosphodiesterase isoenzyme in cardiac and vascular tissue, leading to an increase in intracellular ionised calcium and contractile force in cardiac muscle.  This activity results in left ventricular afterload reduction, with an increase in cardiac output and reduction in total peripheral resistance.
  • Half-life approximately 50 minutes in healthy volunteers; 1.7 to 2.7 hours in cardiac failure and up to 3.2 hours in renal impairment.

USES:

  • Short-term treatment of severe congestive cardiac failure unresponsive to conventional maintenance therapy (not immediately after myocardial infarction).
  • Acute heart failure including low output states.
  • The use of milrinone in critical care is complicated by its long half-life (2 to 4 hours, prolonged in renal impairment), and adverse effects such as systemic hypotension. 

CONTRA-INDICATIONS:

  • Severe aortic or pulmonary valve disease, or hypertrophic subaortic stenosis.  A drug with inotropic/vasodilator properties may aggravate outflow obstruction.
  • Severe hypovolaemia.

CAUTIONS:

  • The use of inotropic agents such as milrinone during the acute phase of a myocardial infarction may lead to an undesirable increase in myocardial oxygen consumption.  Milrinone is not recommended immediately following MI.
  • Supraventricular and ventricular arrhythmias have been observed.  Ensure electrolyte derangements are corrected.
  • Shortened AV node conduction can lead to increased ventricular rate in patients with uncontrolled atrial fibrillation or flutter.  Consideration should be given to ceasing milrinone treatment if rate cannot be controlled with cardiac glycosides or other drugs.
  • Improvement in cardiac output with resultant diuresis may necessitate a reduction in the dose of any diuretics co-prescribed.
  • Potassium loss due to excessive diuresis may pre-dispose patients to arrhythmias.  Potassium should be monitored closely and hypokalaemia corrected.
  • Dose reduction required in renal impairment (see below).

PRESENTATION:

  • Ampoules containing 10mg in 10ml.

ADMINISTRATION:

*Loading dose is not usually given due to risk of hypotension. Discuss with consultant*

Loading Dose

Administer loading dose by IV injection:

  • Dilute the volume required for the loading dose (50micrograms/kg) to 10ml or 20ml of glucose 5% or sodium chloride 0.9% and give over 10 minutes.

Continuous infusion

  • Prepare a 50ml solution containing milrinone 200 microgram/ml by diluting 10ml of milrinone 10mg/10ml with 40ml of glucose 5% (preferred) or sodium chloride 0.9%.
  • Prescribe 10mg in 50ml, final concentration 200 micrograms/ml.
  • Must be given via a dedicated port.

Milrinone continuous infusion

50ml syringe via syringe pump

Prescribe

10mg in 50ml

Drug dose to be added

10mg in 10ml

Diluent to be added

40ml glucose 5% (preferred) or sodium chloride 0.9%

Final volume

50ml

Final concentration

200 micrograms/ml

DOSE AND RATE:

Loading dose (if indicated, see above):

  • 50 micrograms/kg.

Continuous infusion:

  • Licensed dose: 0.375 to 0.75 micrograms/kg/minute in normal renal function.  Adjust according to haemodynamic response.  In practice, many units start at lower rates.  See table below.
  • Consider dosing according to adjusted body-weight in patients who are morbidly obese or over 120kg: mdcalc.com/ideal-body-weight-adjusted-body-weight.
  • Dose needs to be adjusted for renal impairment due to risk of accumulation and hypotension.  Note that eGFR is not applicable in AKI, use acute changes in renal function (eg urine output) to help guide dose adjustments.  Start at lower end of dosing range and adjust according to haemodynamic response.
  • Wean infusion slowly (over at least 2 to 4 hours), monitoring for clinical signs of inadequate cardiac output.
  • Usual duration of therapy: 48 to 72 hours, maximum 5 days.

To calculate dose in micrograms/kg/minute, use table below or the following calculation:

Dose (micrograms/kg/minute) =

Rate (ml/hour) x Concentration (micrograms/ml)
Patient’s weight (kg) x 60

STABILITY:

  • 24 hours.
  • Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidance for switching over infusions or syringes.

EXTRAVASATION:

  • Milrinone has a low pH and extravasation is likely to cause venous irritation and tissue damage.  If given peripherally, use a large vein with monitoring for phlebitis.  Resite catheter at first signs of inflammation.
  • Please refer to NHS Highland Extravasation Protocol on intranet.  

SIDE EFFECTS:

  • Supraventricular and ventricular arrhythmias have been observed.  The infusion should be stopped if arrhythmias develop.
  • Milrinone may induce hypotension as a result of vasodilatory activity.  The rate of infusion should be reduced, or infusion stopped, if patients show excessive reduction in blood pressure.
  • Mild thrombocytopenia.                                                                                       

MONITORING:                                                                                                 

  • ECG monitoring.
  • Fluid balance.
  • Renal function.
  • Electrolytes (especially potassium).

BIBLIOGRAPHY:

National Health Service. Medusa: NHS Injectable Medicines Guide (online). Accessed via: https://medusa.wales.nhs.uk/ [accessed on 31/01/2022]

Paw S, Shulman R. Handbook of Drugs in Intensive Care. An A-Z Guide. 6th Ed. Cambridge: Cambridge University Press; 2019.

Phillips B, Barton G, McKenzie C (editors in chief) Critical Illness (online). London: Pharmaceutical Press. Available at: www.medicinescomplete.com [accessed on 31/12/2022

Wockhardt UK Ltd. Electronic Medicines Compendium: Milrinone 1mg/ml solution for injection/infusion. [homepage on the internet]. London: Datapharm; 2022 [updated 2019 Jun 18; cited 31/01/22]. Available from: Milrinone 1mg/ml Solution for injection/infusion - Summary of Product Characteristics (SmPC) - (emc) (medicines.org.uk)

Noradrenaline

For use in Critical Care Areas for Adults only.  Administer via central line only.

MECHANISM OF ACTION:

  • Noradrenaline exhibits marked inotropic (beta-1) and vasopressor (alpha-1) effects.
  • Half-life = 2.5 to 5 minutes.

USES:

  • Hypotension in the absence of hypovolaemia (correct this first) eg in sepsis where there is low peripheral resistance.
  • May be used as an alternative inotrope to adrenaline in cardiogenic shock eg in post-resuscitation phase.

CAUTIONS:

  • Some brands contain sodium metabisulphite; caution if previous sensitivity.
  • Caution in patients taking monoamine oxidase inhibitors, tricyclic antidepressants and linezolid due to risk of hypertension and arrhythmias.

PRESENTATION

  • Ready-to-use vials containing 4mg in 50ml (single strength).
  • Ready-to-use vials containing 8mg in 50ml (double strength).
  • Ampoules containing 4mg in 4ml.  Use only for preparing quad strength noradrenaline.

ADMINISTRATION:

  • Use ready-to-use preparations wherever possible. Use caution when selecting strength.
  • Always start treatment using single strength preparation and titrate to response. If the infusion is running at 10ml/hour, consider changing to a more concentrated preparation.
  • If ready-to-use preparations unavailable, or preparing quad strength noradrenaline (16mg in 50ml, 320 micrograms/ml), dilute required volume of noradrenaline with glucose 5% to total volume and administer via syringe pump or volumetric infusion.
    • Only use quad strength for patients requiring high infusion rates.  Ready-to-use preparations are safer.
    • For patients on high rates of quad strength noradrenaline, consider preparing in 100ml bag and giving via a volumetric pump.
    • Inform pharmacy if using quad strength noradrenaline to ensure sufficient stocks available on unit.
  • Must be given via a dedicated port.

Noradrenaline

Single strength

 

Double strength

Quad strength

Syringe pump

Syringe pump

Syringe pump

Volumetric infusion

Prescribe

4mg in 50ml

8mg in 50ml

16mg in 50ml

32mg in 100ml

Ready-to-use preparation available

Yes – use if available

If not available follow instructions below

Yes – use if available

If not available follow instructions below

No – prepare on ward

Drug dose to be added

4mg in 4ml

8mg in 8ml

16mg in 16ml

32mg in 32ml

Diluent to be added

46ml glucose 5%

42ml glucose 5%

34ml glucose 5%

68ml glucose 5%

(Withdraw 32ml glucose 5% from 100ml bag)

Final volume

50ml

50ml

50ml

100ml

Final concentration

80micrograms/ml

 

160micrograms/ml

 

320micrograms/ml

 

 DOSE AND RATE:

  • Titrate dose to achieve clinical target.
  • The goal is to maintain an adequate blood pressure to ensure organ perfusion, and usually targeting a mean arterial pressure (MAP) of 65 to 75mmHg or target set by Consultant looking after patient.  Dose required should be guided by heart rate (HR), blood pressure (BP), cardiac output, presence of ectopic beats and urine output.
  • Infusions are usually started at 2 to 5ml/hour, and titrated by increasing or reducing the infusion rate by 1ml/hour to achieve target MAP.
  • When stopping the infusion, reduce the rate of infusion gradually.  Abrupt withdrawal can cause acute hypotension.
  • If dose is escalating rapidly, or dose required to achieve clinical target exceeds 0.4 micrograms/kg/minute (highlighted in red in tables below) the doctor must be contacted to discuss further management.  Options include:
    • Addition of another therapy.
    • Sedation level reviewed (ICU only).
    • Cardiac output monitoring commenced (ICU only).
    • Use of hydrocortisone IV 50mg four times daily (in patients with sepsis).
    • A new upper limit may be set.

To calculate dose in micrograms/kg/minute, use tables below, NHS Injectable Medicines Guide (Medusa) for example calculations or the following calculation:

Dose (micrograms/kg/minute) =

Rate (ml/hour) x Concentration (micrograms/ml)
Patient’s weight (kg) x 60

STABILITY:

  • 24 hours.
  • Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidelines for switching over infusions or syringes.

EXTRAVASATION:

SIDE-EFFECTS

  • Bradycardia (as a reflex to the increase in blood pressure).
  • Arrhythmias.
  • Ischaemia – peripheral, myocardial, renal or mesenteric.

MONITORING:

  • Ensure ECG and blood pressure monitoring is in place.  Invasive blood pressure monitoring is preferred as in hypoperfused or shock states with cool peripheries, non-invasive BP recordings are less reliable.
  • Renal function and urine output.
  • Monitor for tissue ischaemia or necrosis due to vasoconstriction.

BIBLIOGRAPHY:

Critical Care Group, UKCPA, Intensive Care Society. Standard Medication Concentrations for Continuous Infusions in Adult Critical Care [homepage on the internet]. London: National Health Service; 2020 [updated 2021 Sep 21; cited 21/12/2021]. Available from: https://medusa.wales.nhs.uk/docs/2020-12%20ICS%20standard%20concentrations%20list%20v4.1.pdf

National Health Service. Medusa: NHS Injectable Medicines Guide (online). Accessed via: https://medusa.wales.nhs.uk/ [accessed on 31/01/22]

Paw S, Shulman R. Handbook of Drugs in Intensive Care. An A-Z Guide. 6th Ed. Cambridge: Cambridge University Press; 2019.

Phillips B, Barton G, McKenzie C (editors in chief) Critical Illness (online). London: Pharmaceutical Press. Available at: www.medicinescomplete.com [accessed on 15/12/21]

 

Vasopressin (argipressin) for septic shock

For use in Critical Care Areas for Adults only.  Administer preferably via a central line.

MECHANISM OF ACTION:

  • Vasopressin, also known as argipressin, is antidiuretic hormone, an endogenous peptide hormone released by the pituitary gland.
  • It is a vasoconstrictor and its mechanism of action includes binding to V1 receptors on vascular smooth muscle to increase arterial blood pressure.
  • Vasopressin plays a minimal role in blood pressure regulation in normotensive states.  In vasodilatory shock, administration may correct a relative endogenous vasopressin deficiency that develops when endogenous secretory stores become depleted.  It works synergistically with catecholamines and is commonly used as a noradrenaline sparing agent in septic shock.
  • Half-life = 10 to 20 minutes.

USES:

  • In resistant septic shock, where noradrenaline dose has reached 0.5 micrograms/kg/minute, with the aim of increasing the mean arterial pressure (MAP) or reducing noradrenaline requirements.  Consider also use of corticosteroids.
  • Vasopressin should not be used as the first-line or sole agent in the management of septic shock.  Noradrenaline remains the first-line vasopressor as per Surviving Sepsis Guidelines.
  • Use in organ donation – see separate guideline.

 CAUTIONS:

  • Vascular disease, particularly of the coronary arteries but also peripheral vascular disease.  Monitor for signs of ischaemia (see below).
  • Avoid fluid overload.  Caution in conditions exacerbated by fluid overload eg heart failure, asthma and epilepsy.
  • Patients with arrhythmias and those at risk of prolonged QTc interval.
  • Low cardiac output states.
  • Bradycardia.
  • Intravascular depletion (correct hypovolaemia).

PRESENTATION:

  • Ampoules containing argipressin (synthetic vasopressin) 20 units in 1ml.
  • Stored in refrigerator.

ADMINISTRATION:

  • Dilute one ampoule (20 units) to 50ml with glucose 5% to produce a concentration of 0.4 units per ml.

Vasopressin

50ml syringe via syringe pump

Prescribe

20 units in 50ml

Drug dose to be added

20 units in 1ml (1 ampoule)

Diluent to be added

49ml glucose 5%

Final volume

50ml

Final concentration

0.4 units/ml

 DOSE AND RATE:

  • Usual starting dose is 0.03 units/minute = 1.8 units per hour as per Surviving Sepsis Guidelines.
  • The dose may be titrated between 0.6 units per hour and 2.4 units per hour.
  • Doses above 2.4 units per hour must be discussed with the Consultant Intensivist.  Higher doses have been associated with cardiac, digital and splanchnic ischaemia and cardiac arrhythmias, particularly if QTc prolonged.
  • As the patient’s condition improves, the vasopressin must be weaned down slowly and stopped before the noradrenaline is stopped.  Consider stopping vasopressin when noradrenaline requirements <0.25 micrograms/kg/minute.  Reduce infusion by half every 30 minutes until 0.6 units per hour (1.5ml/hour) is reached, then stop.

Dose

0.6 units/hour

1.2 units/hour

Usual starting dose:

1.8 units/hour

2.4 units/hour

Rate (0.4 units/ml)

1.5ml/hour

3ml/hour

4.5ml/hour

6ml/hour

STABILITY:

  • 24 hours.
  • Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidelines for switching over infusions or syringes.
  • However due to the half-life of vasopressin of 10 to 20 minutes, double pumping is not required when changing over syringes.

EXTRAVASATION:

  • The infusion has a low pH and extravasation is likely to cause venous irritation and tissue damage.  If given peripherally, use a large vein with monitoring for phlebitis.  Resite catheter at first signs of inflammation.
  • Please refer to NHS Highland Extravasation Protocol on intranet.  

SIDE EFFECTS:

  • Reduced cardiac output, chest pain due to angina, cardiac arrest.
  • Fluid retention with resulting hyponatraemia.
  • Peripheral ischaemia and gangrene.
  • Nausea and vomiting, diarrhoea.
  • Bronchospasm.

MONITORING:

  • Ensure ECG and blood pressure monitoring is in place. Invasive blood pressure monitoring is preferred as in hypoperfused or shock states with cool peripheries, non-invasive BP recordings are less reliable.
  • Renal function and urine output/fluid balance.
  • Monitor for signs of peripheral ischaemia.

BIBLIOGRAPHY:

Critical Care Group, UKCPA, Intensive Care Society. Standard Medication Concentrations for Continuous Infusions in Adult Critical Care [homepage on the internet]. London: National Health Service; 2020 [updated 2021 Sep 21; cited 21/12/2021]. Available from: https://medusa.wales.nhs.uk/docs/2020-12%20ICS%20standard%20concentrations%20list%20v4.1.pdf

Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith C et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine. 2021; 49 (11): e1063-1143.

National Health Service. Medusa: NHS Injectable Medicines Guide (online). Accessed via: https://medusa.wales.nhs.uk/ [accessed on 31/01/22]

Paw S, Shulman R. Handbook of Drugs in Intensive Care. An A-Z Guide. 6th Ed. Cambridge: Cambridge University Press; 2019.

Phillips B, Barton G, McKenzie C (editors in chief) Critical Illness (online). London: Pharmaceutical Press. Available at: www.medicinescomplete.com [accessed on 15/12/21]

Last reviewed: 30 June 2022

Next review: 30 December 2022

Author(s): Jane Wylie

Version: 1.0

Approved By: Critical Care Formulary Development Group

Reviewer Name(s): Jane Wylie