Mechanical Ventilation, Sedation and Neuromuscular Blockade Dr. Mohammad Aljawadi PharmD, Msc, PhD PHCL 478 Clinical Pharmacy Department College of Pharmacy.

Mechanical Ventilation, Sedation and Neuromuscular Blockade

Dr. Mohammad Aljawadi PharmD, Msc, PhD

PHCL 478

Clinical Pharmacy Department

College of Pharmacy

King Saud University

APRIL 2015

1

A disclaimer and an acknowledgment:

Part of these slides was prepared by

Dr. Rashid Amin Pharm D., BCPS

Clinical Pharmacy Specialist- Adult Critical Care

King Faisal Hospital & Research Centre

and have been used with his permission

2

Respiratory System Overview

http://en.wikipedia.org/wiki/Respiratory_system

3

Causes for Inadequate Ventilation and Respiratory Failure

4

First Steps

Oxygen Supplementation B2-Agonists Ipratropium Corticosteroids

5

First Steps

Oxygen Supplementations:

6

B2-Agonists

Stimulation of β2-adrenergic receptors causes bronchial and vascular smooth-muscle relaxation

Metered-dose inhaler or by intermittent or continuous nebulization

No role for long acting agents

7

Anticholinergic Agents

Ipratropium bromide competes with acetylcholine at the bronchial receptor site, resulting in bronchial smooth-muscle relaxation.

Metered-dose inhaler or by intermittent or continuous nebulization

More delayed onset of action than β2-agonists The addition of ipratropium to albuterol appears to have an

additive benefit in approximately 30% of asthma patients.

8

Corticosteroids The benefit from aggressive corticosteroid use in asthmatic patients

with ARF is well documented. Decrease β-receptor tachyphylaxis. Limited consensus exists on dosing schedules in asthma.

Doses of methylprednisolone of 80 mg/24 h have been as effective as >360 mg/24 hr. OR 1 mg/kg/24 h, adjusting as patient response dictates.

The intravenous and oral routes are equally effective. Routine use of inhalational agents is not recommended in the setting of acute

severe bronchospasm. Myopathies with moderate to high doses

9

10

If First Steps Fail then Mechanical Ventilation is the Way to Go

A ventilator is a device used to assist or replace the work of the respiratory system.

Mechanical Ventilation: Positive pressure ventilation

Air is pushed into the lungs Negative Pressure ventilation (Less used nowadays)

Air is sucked into the lungs

11

Mechanical Ventilation

Non-Invasive Noninvasive Positive Pressure Ventilation (mainly)

A form of mechanical ventilation that provides respiratory assistance without an invasive artificial airway

Invasive

12

Noninvasive Positive Pressure Ventilation

fear of having no escape or being closed-in

13

Noninvasive Positive Pressure Ventilation14

Invasive Mechanical Ventilation 15

THE IRON LUNG16

THE IRON LUNG17

18

Invasive Mechanical Ventilation

Endotracheal / Orotracheal tube Tracheostomy tube

19

Tracheostomy

Surgically created passage into the trachea for long term MV Do not necessitate any use of sedative drugs.

Inserted early: In patients with pre-existing severe respiratory disease Patients expected to be difficult to wean from mechanical

ventilation, i.e., patients with little muscular reserve.

Tracheostomy Advantages and Disadvantages

Advantages Reduced sedation requirement (greater

comfort than endotracheal intubation) Airway protection while unconscious Allows gradual weaning of ventilatory

support (reduced work of breathing) Enhanced communication (written or

phonation) Enhanced nursing care (mouth care and

mobility) Avoids laryngeal injury Can facilitate transfer to the ward Possibly reduces VAP (studies conflicting)

Disadvantages

Requirement for a surgical procedure with inherent risk of complications

Longterm benefit not shown (studies conflicting)

20

21

Ventilator Complications Pulmonary barotrauma

Pneumothorax (abnormal collection of air in the pleural space) Pneumomediastinum (air in chest cavity) Bronchopleural fistula (fistula between the pleural space and the lung)

Diaphragm atrophy Air embolism Motility of mucocilia in the airways

↑ Ventilator Associated pneumonia (VAP)

22

Weaning from mechanical ventilation When should we start thinking about weaning?

The day we intubate the patient (always plan ahead)

Should not be delayed unnecessarily, nor should it be done prematurely.

Patients should have their ventilation considered for withdrawal if they are able to support their own ventilation and oxygenation, and this should be assessed continuously.

Trials of spontaneous breathing

23

Factors which Lead to failed extubation

Underlying chronic cardiac or respiratory disease Time on ventilator Anything that contributes to muscle weakness:

High dose and prolonged use of steroids Neuromuscular blockade agents High dose opioids, benzodiazepines Insufficient caloric intake

24

Things to Remember

Every failed extubation and subsequent re-intubation has shown to increase mortality

Must have the followings: Cardiovascular stability No atelectasis (collapse or closure of the lung) Resolution of Pneumonia Good cough reflex Minimal tracheal secretions

25

Summary Mechanical ventilation can be life saving Start thinking about extubation from the day you intubate the patient Assess patient frequently by giving them Trials of spontaneous

breathing Be aware of complications such as Ventilator Associated Pneumonia,

pneumothorax etc.. Use non-invasive ventilation whenever possible Use the lowest doses and shortest duration of medications such as

steroids, opiods, benzodiazepine, and neuromuscular blockers.

SEDATION IN THE ICU26

Indication for Sedation in the ICU Many causes for anxiety:

Continuous audible alarms Poor lighting Interactions with medical and nursing staff Pain Immobility Interruptions in the normal sleep cycle.

Approximately 52% to 71% of all patients in the ICU may develop at least one episode of agitation.

Agitation can arise from anxiety, delirium, medications, pain, metabolic defects, hypoxia, and drug or alcohol withdrawal.

27

28

What We Know About ICU Agitation/Discomfort

Immediate sequelae of agitation: • Patient-ventilator dyssynchrony• Increased oxygen consumption • Self (and health care provider) injury• Family anxiety

Long-term sequelae: chronic anxiety disorders and post-traumatic stress disorder (PTSD)

29

Recall in the ICU

Some degree of recall occurs in up to 70% of ICU patients.• Anxiety, fear, pain, panic, agony, or nightmares reported in 90% of those who did have recall.

Potentially cruel:• Up to 36% recalled some aspect of paralysis.

Associated with PTSD in ARDS? • 41% risk of recall of two or more traumatic experiences.

Associated with PTSD in cardiac surgery

30

Appropriate Recall May be Important

Factual memories (even unpleasant ones) help to put ICU experience into perspective

Delusional memories risk panic attacks and PTSD

The optimal level of sedation for most patients is that which offers comfort while allowing for interaction with the environment.

31

Goals of Sedation in ICU Patient comfort and Control of pain Anxiolysis and amnesia Blunting adverse autonomic and hemodynamic responses Facilitate nursing management Facilitate mechanical ventilation Avoid self-extubation Reduce oxygen consumption The optimal level of sedation for most patients is that which offers comfort while

allowing for interaction with the environment.

32

Characteristics of an ideal sedation agents for the ICU

Lack of respiratory depression Analgesia, especially for surgical patients Rapid onset, titratable, with a short elimination

half-time Sedation with ease of orientation and arousability Anxiolytic Hemodynamic stability

33

The Challenges of ICU Sedation

Assessment of sedation Altered pharmacology Tolerance Delayed emergence Withdrawal Drug interaction

34

Correctable Causes of Agitation Full bladder Uncomfortable bed position Inadequate ventilator flow rates Mental illness Uremia Drug side effects Disorientation Sleep deprivation Noise Inability to communicate

35

Causes of Agitation Not to be Overlooked

Hypoxia Hypercarbia Hypoglycemia Endotracheal tube malposition Pneumothorax Myocardial ischemia Abdominal pain Drug and alcohol withdrawal

36

Daily Goal is Arousable, Comfortable Sedation

Sedation needs to be protocolized and titrated to goal: Lighten sedation to appropriate wakefulness daily. Effect of this strategy on outcomes:

One- to seven-day reduction in length of sedation and mechanical ventilation needs

50% reduction in tracheostomies Three-fold reduction in the need for diagnostic evaluation of

CNS

37

Assessment of Sedation

Many scales are used to assess the level of sedation and agitation of patients in ICU: Ramsay scale Riker Sedation-Agitation Scale Motor activity assessment scale Glasgow Coma Scale Richmond Agitation-Sedation Scale (RASS)

38

FYI

39

FYI

40

Riker Sedation-Agitation Scale FYI

41

FYI

42

Required

43

What Sedation Scales Do

Provide a semi-quantitative “score” Standardize treatment endpoints Allow review of efficacy of sedation Facilitate sedation studies Help to avoid over-sedation

44

What Sedation Scales Don’t Do

Assess anxiety Assess pain Assess sedation in paralyzed patients Predict outcome Agree with each other

45

Sedating/Analgesia Options

Rule out reversible causes of discomfort/anxiety such as hypoxemia, hypercarbia, and toxic/drug side effect.

Assess comorbidities and potential side effects of drugs chosen.

Target irreversible etiologies of pain and agitation.

46

Strategies for Patient Comfort

Set treatment goal Quantitate sedation and pain Choose the right medication Use combined infusion Reevaluate need Treat withdrawal

Sedative Agents

Benzodiazepines Propofol Dexmedetomidine

47

Benzodiazepines

benzodiazepines bind γ-aminobutyric acid receptors results in the opening of a chloride channel, causing hyperpolarization and stabilization of the neuronal membrane

48

Benzodiazepines

Highly lipophilic Short onset (5 mins) Active metabolite

Desmethyldiazepam h1/2 of 50 to100 hours

Not recommended for ICU sedation

Highly lipophilic Short onset (5 mins) Shortest h1/2

Frequent administration Renal elimination Converted to α-hydroxymidazolam

(active) via CYP 3A4 Accumulation in RF and obese patients

due to high lipophilicity

Diazepam Midazolam

49

Benzodiazepines

Lorazepam is less lipophilic than the other benzodiazepines slower onset of action (5-20 minutes). Intermediate duration of action (6-8 hours)

Less frequent adminstration than midazolam. Lorazepam is eliminated by glucuronidation

no significant enzymatic drug interactions and it has no active metabolites.

50

51

PropofolPharmacology: GABA agonist

Pharmacokinetics/dynamics: onset 1 - 2 minutes, terminal half-life 6 hours, duration 10 minutes, hepatic metabolism

Benefits• Rapid onset and offset and easily titrated

• Hypnotic and antiemetic

• Can be used for intractable seizures and elevated intracranial pressure

Risks• Not reliably amnestic, especially at low doses

• NO analgesia!

• Hypotension

• Hypertriglyceridemia; lipid source (1.1 kcal/ml)

• Respiratory depression

• Propofol Infusion Syndrome

- Cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure

- Caution should be exercised at doses > 80 mcg/kg/min for more than 48 hours

- Particularly problematic when used simultaneously in patient receiving catecholamines and/or steroids

52

53

Propofol Dosing

3-5 g/kg/min antiemetic 5-20 g/kg/min anxiolytic 20-50 g/kg/min sedative hypnotic >100 g/kg/min anesthetic

54

55

DexmedetomidineAlpha-2-adrenergic agonist like clonidine but with much less imidazole activity

Has been shown to decrease the need for other sedation in postoperative ICU patients

Potentially useful while decreasing other sedatives to prevent withdrawal

Benefits• Does not cause respiratory depression

• Short-acting

• Produces sympatholysis which may be advantageous in certain patients such as postop cardiac surgery

Risks• No amnesia

• Small number of patients reported distress upon recollection of ICU period despite good sedation scores due to excessive awareness

• Bradycardia and hypotension can be excessive, necessitating drug cessation and other intervention

56

57

58

Dexmedetomidine (α-2 agonist)

Advantages: No respiratory depression Has sedative, anxiolytic and some analgesic properties Light sedation allows for it to be used as a bridge agent

Disadvantages: Can cause hypotension (especially with bolus dose) Expensive

59

60

Things to remember Overdose (prolonged infusion)

pK derived from healthy patients Drug interaction Individual variation

Delayed elimination Liver (Cp450) Kidney dysfunction Active metabolites

Quick onset and short t1/2 are desired characteristics for sedatives and analgesics (making midazolam and fentanyl a good choice)

Neuromuscular blocking agents (NMBA)61

62

Neuromuscular blocking agents (NMBA)

MOA: mimic acetylcholine as they bind with cholinergic receptors and block neuromuscular transmission at the neuromuscular junction causing paralysis.

63

Classification

Non-depolarizing blocking agents (majority) Rocuronium Vecuronium Pancuronium

Depolarizing blocking agents Succinyl-Choline

64

Clinical Use NMB are used adjunctively to anesthesia to produce paralysis,

firstly to paralyse the vocal cords, and permit intubation of the trachea, and secondly to optimize the surgical field by inhibiting spontaneous ventilation, and causing relaxation of skeletal muscles.

Because the appropriate dose of neuromuscular-blocking drug may paralyze muscles required for breathing (i.e., the diaphragm), mechanical ventilation should be available to maintain adequate respiration

65

Adverse effects

cause paralysis of the diaphragm facilitate histamine release, which causes hypotension,

flushing, and tachycardia Reversal

reversed with anticholinesterase inhibitors, neostigmine, and edrophonium.

Sugammadex is a newer drug for reversing neuromuscular block by rocuronium in general anesthesia.

66

Questions

67