16.1 Mechanical Ventilation, Noninvasive Ventilation & High-Flow Oxygen: What the Pharmacist Must Know
Key Takeaways
Lung-protective ventilation uses a tidal volume of 6 mL/kg predicted body weight with a plateau pressure of 30 cm H2O or less, ideally with a driving pressure of 15 cm H2O or less.
Predicted body weight comes from height and sex, not actual weight: men 50 + 0.91 × (height in cm − 152.4) kg, and women 45.5 + 0.91 × (height in cm − 152.4) kg.
Noninvasive ventilation has its strongest evidence in hypercapnic COPD exacerbations (pH below 7.35) and cardiogenic pulmonary edema.
A high peak pressure with a normal plateau pressure means high airway resistance, such as bronchospasm, secretions or a kinked tube, rather than stiff lungs.
Aerosol delivery through a ventilator circuit needs the heat-moisture exchanger removed from between the nebulizer and the patient; vibrating mesh nebulizers deliver more drug than jet nebulizers.
16.1 Mechanical Ventilation, Noninvasive Ventilation & High-Flow Oxygen: What the Pharmacist Must Know
Note
Exam scope: 2025 outline subtopic 1B1 (Mechanical/Assisted Ventilation) within 1B, Medical Therapies and Devices (9% of the exam). Questions test how ventilator settings, oxygen devices and drug delivery interact with pharmacotherapy. Intubation drugs are covered in Chapter 4.
Oxygen Targets
Too much oxygen is not harmless. Hyperoxia causes absorption atelectasis and vasoconstriction, and may worsen outcomes after cardiac arrest and stroke. Common targets:
| Patient group | SpO2 target |
|---|---|
| Most acutely ill adults | About 92 to 96% (some guidelines use 94 to 98%) |
| Risk of hypercapnic failure (COPD, obesity hypoventilation, neuromuscular disease) | 88 to 92% |
| After return of spontaneous circulation | 90 to 98% (Section 2.4) |
High-Flow Nasal Cannula (HFNC)
HFNC delivers heated, humidified gas at up to 60 L/min with an FiO2 up to 1.0. It:
- Matches the patient's peak inspiratory flow, so the delivered FiO2 is reliable.
- Washes CO2 out of the upper airway dead space.
- Adds a small amount of positive airway pressure, roughly 1 cm H2O per 10 L/min with the mouth closed.
- Is more comfortable than a mask and lets the patient eat, talk and clear secretions.
In the FLORALI trial (2015), HFNC lowered 90-day mortality compared with standard oxygen or noninvasive ventilation in acute hypoxemic respiratory failure without hypercapnia. HFNC is also used for preoxygenation and apneic oxygenation during intubation (Section 4.1).
The ROX index = (SpO2/FiO2) ÷ respiratory rate. A value of 4.88 or higher at 2, 6 or 12 hours predicts HFNC success. Falling values signal the need to escalate.
Noninvasive Positive Pressure Ventilation (NIV)
CPAP gives one continuous pressure. Bilevel (BiPAP) gives a higher inspiratory pressure (IPAP) and a lower expiratory pressure (EPAP). The difference between them is the pressure support that increases tidal volume and removes CO2.
| Indication | Evidence | Typical starting settings |
|---|---|---|
| COPD exacerbation with hypercapnic acidosis (pH below 7.35, PaCO2 above 45 mmHg) | Strong (ERS/ATS 2017): lowers intubation and mortality | IPAP 10 to 12, EPAP 4 to 5 cm H2O, titrated |
| Cardiogenic pulmonary edema | Strong: CPAP or bilevel reduces intubation | CPAP 5 to 10 cm H2O |
| Immunocompromised hypoxemic failure, post-extubation in high-risk patients | Conditional | Individualized |
Contraindications: cardiac arrest or impending arrest, inability to protect the airway, uncontrolled vomiting, facial trauma or burns, recent upper GI or airway surgery, severe agitation, and hemodynamic instability.
Reassess blood gases after 1 to 2 hours. A rising PaCO2, falling pH or tiring patient means NIV is failing, and delayed intubation worsens outcomes.
Sedation for NIV Intolerance
Anxiety and mask intolerance are common reasons NIV fails. Choose drugs that preserve respiratory drive:
- Dexmedetomidine 0.2 to 0.7 mcg/kg/h, usually without a loading dose to avoid bradycardia and hypotension.
- Small opioid doses, such as fentanyl 25 mcg, which can ease air hunger.
- Low-dose ketamine. In "delayed sequence intubation," a dissociative dose (about 1 mg/kg) lets a combative hypoxemic patient accept preoxygenation before paralysis.
- Avoid repeated benzodiazepine boluses, which depress respiratory drive and worsen hypercapnia.
Invasive Ventilation: Modes and Pressures
| Mode | Clinician sets | Patient-determined | Pharmacist relevance |
|---|---|---|---|
| Volume assist-control (most common in the ED) | Tidal volume, rate, PEEP, FiO2, flow | Airway pressures | Peak and plateau pressures reveal resistance or compliance problems |
| Pressure assist-control | Inspiratory pressure, rate, PEEP, FiO2 | Tidal volume | Tidal volume falls when bronchospasm or stiff lungs develop |
| Pressure-regulated volume control | Target tidal volume | Pressure adjusts breath to breath | Hides worsening compliance until pressures max out |
| Pressure support | Support pressure, PEEP | Rate and volume | Spontaneous breathing trials; heavy sedation causes apnea |
Reading the Pressures
| Pattern | Meaning | Common causes | Typical response |
|---|---|---|---|
| High peak, normal plateau | High airway resistance | Bronchospasm, secretions, biting or kinked tube | Bronchodilators, suctioning, bite block, sedation |
| High peak and high plateau | Low compliance | ARDS, pneumothorax, mainstem intubation, abdominal compartment syndrome, auto-PEEP | Treat the cause; check breath sounds and imaging |
| Sudden drop in pressures | Leak or disconnection | Cuff leak, circuit disconnect, extubation | Check the circuit and tube position |
Lung-Protective Ventilation
The ARDSNet strategy applies to ARDS and is a sensible default for almost every intubated ED patient:
- Tidal volume 6 mL/kg predicted body weight (PBW), range 4 to 8.
- Plateau pressure 30 cm H2O or less.
- Driving pressure (plateau minus PEEP) ideally 15 cm H2O or less.
- PEEP and FiO2 adjusted together using a table.
PBW depends only on height and sex:
- Men: 50 + 0.91 × (height in cm − 152.4) kg
- Women: 45.5 + 0.91 × (height in cm − 152.4) kg
Worked example: a man 175 cm tall has a PBW of 50 + 0.91 × 22.6 = 50 + 20.6 ≈ 70.6 kg. A tidal volume of 6 mL/kg is about 420 mL, whatever his actual weight. Using actual body weight in an obese patient produces injurious volumes.
A before-and-after ED quality program (LOV-ED, 2017) linked ED-initiated lung-protective ventilation with less ARDS and lower mortality. Early ventilator settings matter even when the patient boards in the ED.
ARDS Adjuncts (ATS 2024 Update)
- Prone positioning for at least 12 to 16 hours a day in moderate to severe ARDS (PaO2/FiO2 below 150), based on PROSEVA (2013).
- Neuromuscular blockade: suggested for early severe ARDS. The ROSE trial (2019) found no benefit from routine early cisatracurium with deep sedation compared with lighter sedation, so blockade is used selectively for refractory hypoxemia or dyssynchrony.
- Corticosteroids: suggested for ARDS in the 2024 ATS guideline.
- VV-ECMO: for selected patients with severe ARDS at experienced centers (Section 3.2).
Obstructive Disease on the Ventilator
In severe asthma or COPD, the danger is dynamic hyperinflation (auto-PEEP): the next breath starts before the last one has been exhaled.
- Use a low rate (about 10 to 12 breaths/min), tidal volume 6 to 8 mL/kg PBW and a high inspiratory flow to lengthen expiratory time (I:E ratio 1:4 or more).
- Accept hypercapnia (permissive hypercapnia) as long as pH stays above about 7.15 to 7.20.
- Measure auto-PEEP with an expiratory hold.
- If a ventilated asthmatic suddenly becomes hypotensive, disconnect the circuit and let the chest deflate. Then reassess for tension pneumothorax.
Continue in-line bronchodilators, IV magnesium, systemic corticosteroids and, when needed, ketamine as a bronchodilating sedative (Section 7.2).
Inhaled Pulmonary Vasodilators
Inhaled nitric oxide (5 to 20 ppm) and inhaled epoprostenol (about 0.01 to 0.05 mcg/kg/min) dilate vessels only in ventilated lung units. They improve oxygenation and offload a failing right ventricle (massive PE, pulmonary hypertension) but have not reduced mortality in ARDS. Precautions:
- Abrupt withdrawal of nitric oxide causes rebound pulmonary hypertension; wean gradually.
- Nitric oxide can cause methemoglobinemia and forms nitrogen dioxide.
- Epoprostenol's sticky glycine buffer can jam the ventilator's expiratory valve, so the expiratory filter must be changed regularly.
Drug Delivery Through Ventilator Circuits
| Device | Placement and technique | Key points |
|---|---|---|
| Metered-dose inhaler with in-line spacer | Inspiratory limb near the Y-piece; actuate at the start of inspiration | Doses often need to be higher than in spontaneously breathing patients |
| Jet nebulizer | Inspiratory limb, often placed upstream toward the ventilator | Adds gas flow that changes delivered tidal volume and triggering |
| Vibrating mesh nebulizer | Inspiratory limb | Adds no gas flow and delivers more drug than a jet nebulizer |
Important
A heat-moisture exchanger (HME) traps aerosol. Remove it, or use a circuit that bypasses it, during aerosol treatments, and replace it afterward. Place a filter on the expiratory limb to protect the ventilator from drug deposits.
Aerosols can also be given during NIV (nebulizer between the exhalation port and the mask) and through HFNC (vibrating mesh in-line).
Sedation and analgesia for intubated patients follow the "analgesia first, light sedation" approach in Section 4.3. Two ventilator-specific points are worth remembering. Propofol supplies about 1.1 kcal/mL as lipid, so check triglycerides with prolonged infusions. Deep sedation started in the ED tends to carry over into the ICU.
A 175-cm, 128-kg man is intubated for pneumonia with hypoxemia. Using lung-protective ventilation at 6 mL/kg, which initial tidal volume is most appropriate?
About 420 mL, based on predicted body weight
About 770 mL, based on actual body weight
About 300 mL, the lowest volume that limits barotrauma
About 560 mL, based on adjusted body weight
Thirty minutes after intubation for severe asthma, a patient on volume assist-control has a peak inspiratory pressure of 52 cm H2O and a plateau pressure of 21 cm H2O. Breath sounds are equal with diffuse wheezing. What does this pattern most likely indicate?
A right mainstem intubation
Low lung compliance from evolving ARDS
Tension pneumothorax on the left
High airway resistance from bronchospasm
A 68-year-old woman with COPD is alert but tiring. Her venous gas shows pH 7.27 and PCO2 72 mmHg, and SpO2 is 86% on 2 L/min. She can protect her airway and is not vomiting. What is the best respiratory support?
High-flow oxygen by non-rebreather mask titrated to SpO2 98 to 100%
Immediate rapid sequence intubation before any trial of other support
Nasal cannula at 6 L/min with a single dose of lorazepam for anxiety
Bilevel noninvasive ventilation, reassessed with a blood gas in 1 to 2 hours
A ventilated patient is receiving albuterol by jet nebulizer with little effect on wheezing. Which circuit practice most likely reduces the delivered dose?
Switching from the jet nebulizer to a vibrating mesh nebulizer
Placing the nebulizer in the inspiratory limb rather than the expiratory limb
Adding a filter to the expiratory limb to protect the ventilator
Leaving the heat-moisture exchanger between the nebulizer and the patient
Sections you finish are checked off in the contents.