Fundamentals of Critical Care

Fundamentals of Critical Care

Supporting pharmacists new to the critical care setting during the

COVID19 pandemic

Updated March 2020

www.ukclinicalpharmacy.org

Plan


Introduction

Sedation and muscle relaxants

Vasoactives

GI

Fluids

Haemofilter

General house keeping

You already know the basics!


Encompasses all other topics

Interpreting Lab results

Managing infection

Respiratory Disease

Care of surgical patients/

elderly/renal

Critical Care

The term critical care covers ‘ICU ’ (level 3) and ‘HDU’ (level 2)


Level 3Staffed with

1 nurse per patient

requiring 2 or more different organ support orrespiratory failure requiring

mechanical ventilation.

Level 2

1 nurse to 2 patients, receiving single organ support (e.g. post-surgical or on low dose

vasopressors such as noradrenaline)

Level 1Normal ward care – no organ support (may require IV or

oxygen by face mask)

Aims of Critical Care

• To preserve life and prevent, reverse or minimise damage to vital organs

• To optimise cardiovascularand respiratory function to maximise oxygen delivery to tissues


Monitoring in ICU

SIMPLE MORE COMPLEX

Respiratory rate Arterial line

Heart rate CVP line on central line

Blood pressure Oesophageal doppler

Temperature ECHO

Oxygen saturations ECG

Urine output


Lines

Central Line

➔ Inserted into a large vein in the patient

➔ Neck (jugular) vein➔ subclavian vein (the vein lying

beneath the collar bone)➔ femoral vein

(large vein in the groin)

Branches off into smaller lines (or lumens). This provides ports whereintravenous fluids, drugs and monitoringcan be attached. Each lumen can be treated as separate line when considering compatibilities

Arterial line

➔ Inserted into an artery (usually in the wrist or the groin)

It has 2 functions:

1. It is attached to a system to measure BP etc

2. It is set up to enable easy, frequent arterial blood sampling, with no stress to the patient.

There is a flush bag connected to the transducer setup is encased in a pressure cuff that constantly squeezes the bag. This allows the fluid from the flush bag to flow into the artery. This is important because without pressure from the flush, the arterial line tubing would fill with blood.


Ventilation

• Lots of different modes

• The higher the % oxygenused can estimate how sick patient is

• More invasive modes may require more sedation to tolerate


Methods of ventilation

Endotracheal tube (ETT)• Placed in through the mouth and

into the trachea• Can be very uncomfortable and the

patient is sedated to tolerate it

A tracheostomy

• An opening is made into the trachea allowing for ventilator support with minimal or no sedation.

• Useful if patient has excessive secretions during weaning

• Mouth care is easier

Disadvantages

• Bleeding• Communication

difficulties

Both methods can cause ventilator associated pneumonia


Sedation

• How sedated does a patient need to be?

– Awake? Unrousable? Aware?

• Beneficial practices to assess sedation

– Sedation breaks

– Sedation scoring

Example – Richmond Agitation Scale (RASS)

Patient sedated to a prescribed score

Score Description

+4 Combative, overtly combative or violent, immediate danger to staff.

+3 Very agitated, pulls on or removes tubes or catheters or is aggressive.

+2 Agitated, frequent non-purposeful movement or ventilator dyssynchrony.

+1 Restless, anxious or apprehensive but movements not aggressive or vigorous.

0 Alert and calm.

-1 Drowsy, but sustains more than 10 seconds awake, with eye opening in response to verbal command.

-2 Light sedation: Awakens briefly (less than 10 seconds) with eye contact to verbal command.

-3 Moderate sedation: Any movement, except eye contact, in response to command.

-4 Deep sedation: No response to voice, but any movement to physical stimulation

-5 Unarousable: No response to voice or physical stimulation


Indications for sedation


Reduce anxiety and distress

Alleviation of pain

Ventilation

Primary Therapy(reduce intracranial pressure, refractory status epilepticus)

During neuromuscular blockade

Sedation and analgesia

• Anaesthetic (propofol, midazolam etc)

• Analgesia (alfentanil, remifentanil, fentanyl, morphine etc)

• Most units have their standard and may use different if patient has allergies or contraindications

• May add another in if patient is difficult to sedate e.g. propofol + alfentanil + midazolam


Summary of Sedation Problems

• Accumulation can be a problem (delaying weaning and increasing complications)

• Some have detrimental effects on circulation, increasing inotrope (e.g. noradrenaline) requirement

• Tolerance and withdrawal

• Does not provide REM sleep


Propofol

• Intravenous anaesthetic. Mode of action unclear, potentiates glycine and GABA

• Dose = 1-4mg/kg/hr (practically 0-20mL/hr 1%) – max dose 4mg/Kg/hr


Advantages:– Short duration of action (starts and stops quickly)

• t1/2 is approximately 10 – 70 minutes– Good for assessing the patient e.g. head injury– Anti-tussive/reduces bronchospasm

Propofol

• Disadvantageso Causes hypotension

o High lipid load (1kcal/mL)

o No analgesic effects

o Tolerance

o Peanut allergy

o Propofol infusion syndrome

Propofol Infusion Syndrome Clinical features:

o Cardiomyopathy with acute cardiac failure.

o Metabolic acidosis, ↑↑K+

o Renal Failureo Hepatomegalyo Inhibition of free fatty acid entry into

mitochondria → failure of its metabolism.

KEEP DOSE BELOW 4mg/kg/hr


Midazolam

Advantages➢ Bolus rapid onset➢ Ease of administration➢ Stable in sodium chloride

and glucose

Disadvantages➢ No specific analgesic properties

➢ Prolonged duration of action in both hepatic and renal impairment

➢ Accumulation

➢ Dependence

• Half life 1-4 hours

• Metabolism - Liver

• 1,4 hydroxy midazolam- active metabolite cleared by kidney


Other sedatives

Ketamine• Blocks NMDA- receptors

• Lack of respiratory and cardiovascular depression

• Useful for anaesthesia in asthmatic patients

• Sympathetic agonist (↑ BP ↑HR ↑CO)

• Limitations: hallucinations, deliriumduring withdrawal

• Suggested dose range 1.0-2.5mg/kg/h

• Elimination half life 2-3 hours, renal excretion

Clonidine/Dexmedetomidine

• α2-adrenoreceptor agonists

• They are particularly useful if agitation is a feature or after withdrawal of benzodiazepines or opioids.

• Dex- shorter acting and easy to titrate

• Clonidine- enteral available


Alfentanil

• Synthetic opioid

• Peak effect after 2-3 mins

• Half-life 15-137 mins

• Not affected by renaldysfunction

• Metabolised by the liver

Advantages✔ Easy to administer

✔ Does not cause histamine release

✔ Less vasodilatation than with morphine

Very potent! Depending on patient metabolism 1mg of alfentanil is equivalent to 10-20mg of morphine


Disadvantages⮚ Potent respiratory depressant

Morphine• Half life 1-6 hours

Metabolism

• Morphine undergoes conjugation with glucuronide in the liver

• Metabolite is 40 times more potent, this is then excreted in urine and will accumulate in renal impairment

Advantages✔Excellent analgesic

✔ Inexpensive

✔Compatible with a range of drugs


Disadvantages⮚ Poor amnesic properties

⮚ Slow onset of action due to its slow distribution and relative lipid insolubility

Fentanyl

• Synthetic opioid

• 50-100x more potent than morphine

• Peak effect 30 mins

• Lipophilic - Short duration when given via bolus but long when given by continuous infusion

• Lack of emetic effect

• 80% plasma bound

• Hepatically metabolised to inactive and non toxic compounds, 8% urinary excretion

• Renal impairment - increase in half-life


Remifentanil• Very potent

• Rapid onset of less than 1 min

• Predictable offset of less than 10 mins

• Metabolised by non-specific blood and tissue esterases

• Less interpatient pharmacokinetic variability

• No bolus


Muscle Relaxants

▪ Routine paralysis is no longer recommended.

▪ Only indications

▪ Critical gas exchange- LIKE COVID 19 Patient

▪ Control of ICP

▪ Multiple trauma

▪ Must make sure well sedated

Atracurium• Hoffman elimination, Histamine

release

Rocuronium• Active metabolite of vecuronium

• Renally excreted, Rapid onset of action

• Less histamine

Cisatracurium• Cis-isomer of atracurium

• Minimal histamine release

• Less laudanosine production


Prone Position• Patient turns onto front or semi-

prone “swimming position”

• Used in resp failure and severe hypoxia despite optimisation of sedation, ventilation, neuromuscular blockade and fluid balance.

• More common in COVID patients

Pharmaceutical Implications

Eye, lip and skin care

May need longer infusion lines

Absorption of feed more difficult

More at risk of transient arrythmia-ensure electrolytes within range


Vasoactive agents


VASOPRESSOR – a drug which causes

contraction of muscular tissue in capillaries and

arteries

INOTROPE - a drug that affects myocardial

contractility positive / negative

CHRONOTROPE - a drug that affects the

myocardial contractionrate

all have short half-lives ~ 2minutes and must be

administered by infusion for prolonged effect

stable plasma concentrations are

achieved within 10-15 minutes

Haemodynamic values

● Cardiac output (CO): amount of blood

ejected from the heart into systemic

circulation each minute

○ *Normal = 4-8 L/min

● Cardiac index (CI): CO adjusted for BSA

○ *Normal = 2.5-4 L/min

● Stroke volume (SV): amount of blood

ejected from the heart into systemic

circulation with each contraction

○ SV = CO (mls) / HR

○ *Normal = 60-130 / beat

• MAP= CO x SVR

• CO= HR x SV

• SVR=Systemic vascular resistance


Summary of ActionsReceptor Site Effect Drug with predominate

agonist effect

Adrenaline receptor affinity (Dose dependant)

α1 Arterial Vasculature

Vasoconstriction NoradrenalineMetaraminol, Phenylephrine

++

V1 Vascular smooth muscle

Vasoconstriction VasopressinTerlipressin

β1 Heart ↑myocardial contractility↑heart rate

Dobutamine +++

β2 Lungs, blood vessels

BronchodilationVasodilation

++

Phosphodiesterase III inhibitors in cardiac and smooth muscle

Mycocardial diastolic relaxation

MilrinoneEnoximone


Drug delivery - Gut

• If the gut works use it!

– For both nutrition and drugs

• Post GI surgery may be nil by mouth

• Non-ventilated patients may be fine to swallow tablets normally

• Ventilated patients will normally have an NG tube

• Ask whether the patient is absorbing feed


Drugs via NG tube

• Avoid MR/EC preparation– Can change to ‘normal release’ if possible &

amend frequency

• Consider safety for staff

– finasteride

• Liquids – watch bioavailability

• Patches

• Alternative drugs for same condition/same class

– Often anaesthetists looking after patients that aren’t familiar with every day drugs


Gastric stasis

• Some patients in shock/sepsis may have gastric stasis.

• Also called ileus• Opiates also slow peristalsis• Won’t absorb feed• Drug absorption likely to be impaired• Treat with prokinetics

– low dose erythromycin IV 125mg-250mg BD

– Metoclopramide IV 10mg TDS


Blood Glucose

• In critically ill patients there is impaired hepatocyte response to insulin which correlates with increased risk of death

• Hypoglycaemia associated with worse outcomes.

• Hyperglycaemia (due to insulin resistance) is common in the critically ill patient (inc. non diabetics)

• All patients should have HbA1C checked on admission

• REVIEW all oral agents- check policy & resource section of www.saferinsulin.org

Consider implications of poor SC absorption

Further reading www.saferinsulin.org


4 phases of IV Fluid Therapy

Hoste et al 2014

IV Fluid Therapy

Fluid overload big problem in COVID

patients

Only give small boluses in

resuscitation phase

Consider all COVID patients fluid

restricted


(CALORIES HELP TO DEAL WITH ELECTROLYTES NORMALLY)

DAILY REQUIREMENTS (GIFTASUP Guidance)

Water 25-35 ml/kg (30)

Sodium Approx. 1 mmol/kg

Potassium Approx. 1 mmol/kg

Calories Minimum 400 calories (i.e. 100g glucose)


Methods of RRT

⚫Haemofiltration (Usually continuous venous-venousso called CVVH)

⚫MOST COMMON FORM ⚫Dialysis⚪ Diffusion

⚪ Rarely ever (never) used on its own

⚪ Sudden big shifts in fluids/electrolytes make haemodynamically unstablepatients difficult to manage

⚫Haemodiafiltration⚪ A combination of the two

⚫Continuous vs intermittent


Dialysis Filtration

⚫Diffusion

⚫Moves down a concentrationgradient across a semi-permeable membrane

⚫<5,000 daltons (500-2,000)

⚫Convection

⚫Pressure gradient drives water and molecules through a highly permeable membrane

⚫ <30-40,000 daltons (10,000-30,000)

Dialysis compared to CVVH


Considerations

Composition of replacement fluid • All the potassium that is removed should soon become level in replacement fluid

• If remains high- check input or likely cell death releasing potassium

• No phosphate in replacement fluid-look to replace- regular phosphate Sandoz before gets too low and requires IV

• Set amount of fluid removed and replacement fluid added before blood

returned to patient.

Anticoagulation often required-Check local policy and recommended

plan with DVT prophylaxis


Doses during filtration

• Ask “what harm I am going to do if give too much

• “What harm if give too little”• Check reason for filtration

– Sepsis, don’t reduce antibiotic doses

• Avoid renal toxic drugs• Some doses may be higher

– Fluconazole• Renal Handbook only good for

pharmacokinetics

Drug Clearance Likely

• Small water soluble molecules

• Lower levels of protein binding

• Smaller Volume of Distribution


TPN

• TPN is not an emergency drug so should not be started out of hours.

• Check for local guidelines and advice


Delirium

Very common in crit care. Patients are screened daily• Types: Hyperactive -Restless, agitated, hyper vigilant, paranoid,

hallucinations, aggressive, combative

• Hypoactive: Lethargic, short attention span, withdrawn, apathetic

• Mixed: combination

• Non-pharmacological

Multi-component interventions may be helpful

• Pharmacological

• Atypical antipsychotic (Quetiapine, Olanzapine, Risperidone)

• Typical antipsychotics (Haloperidol)


Directly deliriogenic drugsAnalgesics

CodeineFentanyl

MorphinePethidine

Cardiovascular agentsAtenololDigoxin

DopamineLidocaine

CorticosteroidsDexamethasoneHydrocortisone

Prednisolone

AntidepressantsAmitriptyline

Paroxetine

AntipsychoticsChlorpromazine

Hypnotic agentsChlordiazepoxide

Diazepam

AnticonvulsantsPhenytoin

Phenobarbitone

AntimuscarinicsAtropineHyoscine

Miscellaneous agentsFurosemideRanitidine

AntihistamineChlorphenamine

Promethazine

AntiemeticsProchlorperazine


Everyday considerations

• Stress ulcer prophylaxis if not being fed

• Infection prevention

• Bowel management

• Electrolytes

• Eye/mouth hygiene


Step down patients


Meds rec on step down

Considering stopping crit care meds- omeprazole, amiodarone, antipsychotics, inhalers

Consider restarting usual meds but only if needed

Summary points


Don’t be afraid of critical care, you know lots of info already

Drugs which are unusual to you are familiar to critical care staff, and often titrated against response

Route is important. Can be IV via either peripheral line or central line (check out how many lumens) but also NG, PO, rectal, etc.

Just as important to stop drugs as start them

In COVID patients, avoid unneccessary fluid, low dose steroidsconsidered

Never be afraid to ask

Daily checklist

Organ system Issue

General Meds rec, U&Es, coag, interactions, allergies, co- morbidities (including alcohol and smoking)

CVS BP meds, pump failure, fluid balance

GI Feeding (ideally enteral), bowels, blood glucose, prokinetic, stress ulcer

Renal urine output, urea/creatinine, dose adjustments, CVVH

CNS Sedative or analgesic effects, previous meds, tolerance and withdrawal

Infection Micro (including route and choice), steroids

Liver LFTs (abnormal in sepsis), drug interactions

Haem Clotting, DVT prophylaxis

Administration Available stock, instructions on safe admin, compatibilities


Useful resources

• SPC

• Other pharmacists – UKCPA Message board

• Renal drug handbook – only for pharmacokinetics

• UKCPA guidance e.g. minimum volumes, dosing in

extremes of bodyweight, compatibility

• ToxBase

• Medusa

• UpToDate


Acknowledgements


Emma Boxall, Specialist Critical Care PharmacistGreg Barton, Specialist Pharmacist Critical Care and Burns

Fundamentals of Critical Care

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