ARDS Ở TRẺ EM ,ĐH Y DƯỢC TP HCM

bài giảng dành cho sinh viên y khoa, bác sĩ, sau đại học , ĐH Y DƯỢC TP HCM

ARDS

Acute respiratory distress syndrome

• Shock lung

• Da Nang Lung

• Traumatic wet lung

ĐỊNH NGHĨA

1 Acute lung injury — Acute lung injury (ALI)

• Acute onset

• Bilateral infiltrates consistent with pulmonary edema

• A ratio of the partial pressure of arterial oxygen to the fraction

of inspired oxygen (PaO2/FiO2) 201 and 300 mmHg, regardless

of the level of positive end-expiratory pressure (PEEP) The PaO2 is measured in mmHg and the FiO2 is expressed as a decimal between 0.21 and 1.00

• No clinical evidence for an elevated left atrial pressure If

measured, the pulmonary capillary wedge pressure is 18 mmHg

or less

- Acute respiratory distress syndrome — The

definition of ARDS is the same as ALI except that the

regardless of the level of PEEP

PaO2/FiO2 versus SpO2/FiO2

- To address this issue, use of the pulse oximetric

saturation (SpO2)/FiO2 ratio as a substitute was studied

• SpO2/FiO2 ratio of 235  PaO2/FiO2 ratio of 200

• SpO2/FiO2 ratio of 315  PaO2/FiO2 ratio of 300

• SpO2/FiO2 ratio of 201  PaO2/FiO2 ratio of 200,

SpO2/FiO2 ratio of 263  PaO2/FiO2 ratio of 300

- These findings suggest that the SpO2/FiO2 ratio may

be helpful when arterial blood cannot be obtained, although the PaO2/FiO2 ratio is preferred when available

Clinical Disorders Associated with the

Less common

Acute pancreatitis Cardiopulmonary bypass Transfusion-related TRALI Disseminated intravascular coagulation

Burns Head injury Drug overdose

Atabai K, Matthay MA Thorax 2000

Frutos-Vivar F, et al Curr Opin Crit Care 2004

The Problem: Lung Injury

Etiology In Children

Trauma 5%

Noninfectious Pneumonia 14%

Transfusion-related lung injury

(TRALI)

- ALI occurring during or within six hours after a

transfusion

• Anti-granulocyte antibodies

• Granulocyte Priming: his theory contends that

biologically active substances, such as lipids and cytokines contained within the transfusions, have the ability to prime the activity of granulocytes in the pulmonary vasculature, contributing to increased vascular permeability

• Two event hypothesis

ARDS mechanism of lung injury

- Activation of inflammatory mediators and

cellular components resulting in damage to capillary endothelial and alveolar epithelial cells

- Increased permeability of alveolar capillary

membrane

- Influx of protein rich edema fluid and

inflammatory cells into air spaces

- Dysfunction of surfactant

PATHOPHYSIOLOGY

- Q = K x [(Pmv - Ppmv) - rc (Π mv - Π pmv)]

• Q represents the net transvascular flow of fluid,

• K the permeability of the endothelial membrane,

• Pmv the hydrostatic pressure within the lumen of the microvessels,

• Ppmv the hydrostatic pressure in the perimicrovascular space, rc represents the reflection coefficient of the capillary barrier,

• Π mv the oncotic pressure in the circulation, and

• Π pmv the oncotic pressure in the perimicrovascular compartment

External forces applied on the lower lobes at end inspiration and end expiration in a patient in the supine position and mechanically ventilated with positive end-expiratory pressure

• Large blue arrows: Forces resulting from tidal ventilation

• Small blue arrows: Forces resulting from positive end-expiratory pressure (PEEP)

• Green arrows: forces exerted by the abdominal content and the heart on the lung

Rouby JJ, et al Anesthesiology 2004

Injury

Consequences

- Impaired gas exchange

- Decreased lung compliance

- Pulmonary hypertension

ARDS exudative and fibrotic phases

PROGNOSIS

- death during the initial three days was usually due

to the underlying cause of the ARDS [63]

- Later, most deaths were caused by nosocomial

infections and/or sepsis

- 16 percent of deaths were due to respiratory failure

Increased mortality among patients

with ARDS

- increased age,

- sepsis, failure of oxygenation to improve,

- more severe illness, steroid treatment prior to the

onset of ARDS,

- acidemia,

- transfusion of packed red cells certain biological

markers

Mechanical ventilation in acute respiratory distress syndrome

- LOW TIDAL VOLUME VENTILATION

- OPEN LUNG VENTILATION

- RECRUITMENT MANEUVER

Ventilator Goals

- Set the PEEP slightly higher than the lower inflection

point

- Lower tidal volume (generally < 6 mL/kg)

- Static peak pressure <40 cm H 2 0

- Wean oxygen to <60%

ARDS Network Low VT Trial

Patients with ALI/ARDS (NAECC definitions) of < 36 hours

Ventilator procedures

• Volume-assist-control mode

• RCT of 6 vs 12 ml/kg of predicted body weight PBW Tidal Volume

(PBW/Measured body weight = 0.83)

• Plateau pressure  30 vs  50 cmH 2 O

• Ventilator rate setting 6-35 (breaths/min) to achieve a pH goal

of 7.3 to 7.45

• I/E ratio:1.1 to 1.3

• Oxygenation goal: PaO 2 55 - 80 mmHg/SpO 2 88 - 95%

• Allowable combination of FiO 2 and PEEP:

Days after Randomization

Lower tidal volumes

Survival Discharge Traditional tidal values

Survival Discharge

ARDS Network N Engl J Med 2000

ARDS Network:

Main Outcome Variables

ARDS Network N Engl J Med 2000

Low Vt Traditional Vt p Value

Death before discharge home and

breathing without assistance (%)

No of days without failure of

nonpulmonary organs or systems,

days 1 to 28

15  11 12  11 0.006

V T ~ 6 ml/kg

PEEP ~13-16

V T ~12 ml/kg

Amato M, et al N Engl J Med 1998

Significant prognostic factors responsible of the ventilatory treatment effect:

• APACHE II score

• Mean PEEP during the first 36 hours (with a protective effect)

• Driving pressures (PPLAT - PEEP) during the first 36 hours

NIH-NHLBI ARDS Network: Hypothesis

In patients with ALI/ARDS (NAECC definitions) of < 36 hours who receive mechanical ventilation with a V T of 6 ml/kg of PBW, higher PEEP may improve clinical outcomes

NHLBI ARDS Clinical Trials Network N Engl J Med 2004

NIH-NHLBI ARDS Network

Patients with ALI/ARDS (NAECC definitions) of < 36 hours

• Oxygenation goal: PaO 2 55 - 80 mmHg/SpO 2 88 - 95%

• Allowable combination of FiO 2 and PEEP:

Low PEEP FiO 2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0

PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 18-24 High PEEP FiO 2 0.3 0.3 0.4 0.4 0.5 0.5 0.5-0.8 0.8 0.9 1.0

PEEP 12 14 14 16 16 18 20 22 22 22-24

• The trial was stopped early after the second interim analysis (n = 549

on the basis of the specified futility stopping rule)

NHLBI ARDS Clinical Trials Network N Engl J Med 2004

HFOV Gas Transport

1 Direct alveolar ventilation

2 Mixing of high frequency ventilation

Bouchut et al: High-frequency Oscillatory Ventilation, Anesthesiology v 100 April 2004 1007-1015

Bouchout et al: High-frequency Oscillatory Ventilation, Anesthesiology vol 100, April 2004 1007-1015

Conclusion

- No significant differences in mortality, morbidity,

hemodynamics, oxygenation failure, ventilation failure, barotrauma or mucus plugging between groups

- HFO equivalent to CMV in managing ARDS

Derdek AJRCCM 2002:166:801

ARDS- “Mechanical” Therapies

Non-ventilatory-based Strategies

in the Management of ARDS/ALI

Fluid and hemodynamic management Inhaled nitric oxide

Prone position ventilation Steroids

Other drug therapy

Fluid management

- conservative strategy of fluid management

Inhaled Nitric Oxide

Physiology of inhaled nitric oxide therapy

• Selective pulmonary vasodilatation (decreases arterial and venous

resistances)

• Decreases pulmonary capillary pressure

• Selective vasodilatation of ventilated lung areas

• Bronchodilator action

• Inhibition of neutrophil adhesion

• Protects against tissue injury by neutrophil oxidants

Steudel W, et al Anesthesiology 1999

Effects of Inhaled Nitric Oxide in Patients with Acute Respiratory Distress Syndrome:

Results of a Randomized Phase II Trial

In patients with documented ARDS, iNO at 1.25, 5, 20, 40, or 80 ppm:

• Is associated with a significant improvement in oxygenation compared with

placebo over the first four hours of treatment An improvement in oxygenation index was observed over the first four days

of the change were similar in each of the inhaled NO dose groups

• Appears to be well tolerated in doses between 1.25 to 40 ppm

• Although these concentrations appear to be safe, it would be prudent to more

closely monitor NO 2 concentrations, and methemoglobin

• There are trends in decreasing the intensity of mechanical ventilation needed to maintain adequate oxygenation and improved patient benefit at 5 ppm inhaled

NO

Dellinger RP et al., Crit Care Med 1998

Low-dose Inhaled Nitric Oxide in Patients

with Acute Lung Injury:

A Randomized Controlled Trial

In patients with documented ARDS and severe acute lung injury (PaO 2 /FiO 2  250) but without sepsis or other organ system failure, iNO

at 5 ppm:

• Induces short-term improvements in oxygenation with a 20%

increase in PaO 2 that were maintained only during 24 - 48 hours

• Does not improve clinical outcomes or mortality

These data do not support the routine use of inhaled nitric oxide in the treatment of acute lung injury or ARDS

Inhaled nitric oxide may be considered (Grade C recommendation) as a salvage therapy in acute lung injury or ARDS patients who continue to have life threatening hypoxemia despite optimization of conventional mechanical ventilator support

Taylor RW, et al JAMA 2004

Effect of Prolonged Methylprednisolone

in Unresolving ARDS

Rationale: Within seven days of the onset of ARDS, many patients exhibit a new phase of their disease marked by fibrotic lung disease or fibrosing alveolitis with alveolar collagen and fibronectin accumulation

Patient selection: Severe ARDS/  7 days of mechanical ventilation with an LIS  2.5/No evidence

of untreated infection

Treatment protocol: Methylprednisolone

In patients with unresolving ARDS, prolonged administration of methylprednisolone was associated with improvement in lung injury and MODS scores and reduced mortality

Meduri GU et al., JAMA 1998

Corticosteroid Therapy in ARDS:

Better late than never?

High-dose corticosteroids in early ARDS

infection

is needed to clearly demonstrate a survival advantage that outweighs the potential risks

ARDS/Appropriate time window for corticosteroid administration, between early acute injury and established postagressive fibrosis

Kopp R et al., Intensive Care Med 2002 Brun-Buisson C and Brochard L, JAMA 1998

Effects of Prolonged Steroids in

• Methylprednisolone 2 mg/kg/day x 4 days,

tapered over 1 month Meduri et al, JAMA 280:159, 1998

Steroids in Unresolving ARDS

- By day 10, steroids improved:

• Lung injury/MOD scores

• Static lung compliance

- 24 patients enrolled; study stopped due

to survival difference

Meduri et al, JAMA, 1998

Steroids in Unresolving ARDS

0 10

Hospital survival

Steroid Placebo

Related Studies

- 4 trials of high-dose, short-course for early ARDS

failed to show survival improvement

- Small case series suggest benefit of moderate-dose

in persistent ARDS

- A 24-patients trial: moderate-dose improve lung

function and survival for ARDS 7 or more days

Related studies

- High-dose increase the risk of secondary infections?

- Hyperglycemia, poor wound healing, psychosis,

pancreatitis, prolonged muscle weakness, impaired function status

NHLBI ARDS Clinical Trials Network

- 180 patients from 1997 to 2003

- 7 to 28 days after onset of ARDS

- PaO2:FIO2 less than 200

- Protocol of methylprednisolone given

1 Single dose of 2mg/kg predicted BW

2 0.5mg/kg Q6H for 14 days

3 0.5mg/kg Q12H for 7 days

4 Tapering

Results

- No difference in 60-day or 180-day hospital mortality

rate, in days in ICU or hospitalization

- Steroid group had more ventilator-free days, more

improvement in PaO2:FiO2, improved compliance, higher serum glucose level, lower suspected or probable pneumonia

Discussion

- Routinely use of steroids in ARDS patient is

- Increased mortality rate if Initiation 2 or

- Improve cardiopulmonary physiology, increase ventilator-free days, ICU-free days, and shock-free days

- Not increase infection, but may increase risk

of neuromyopathy

Other Drug Therapy

Prostaglandin E1 (PGE1) (pulmonary vasodilatation and inflammatory effects on neutrophils/macrophages)

anti-Aerosolized prostacyclin (PGI2) (selective pulmonary vasodilatation of ventilated lung areas)

Almitrine (selective pulmonary vasoconstrictor of nonventilated lung areas)

Surfactant (prevents alveolar collapse and protects against intrapulmonary injury and infection)

Antioxidants (protect the lung from free oxygen radical production)

Partial liquid ventilation (recruitment of collapsed areas and inflammatory effect)

anti-Anti-inflammatory drugs (Ibuprofen - ketoconazole)

No recommendation can be made for their use - Rescue modality in the patient with refractory hypoxia?

Prone Positioning in ARDS

Prone Positioning in ARDS

- Theory: let gravity improve matching

perfusion to better ventilated areas

- Improvement immediate

- Uncertain effect on outcome

Prone Positioning in Adult ARDS

Prone Positioning

Limits the expansion of cephalic and parasternal lung regions

Relieves the cardia and abdominal compression exerted on the lower lobes

Makes regional ventilation/perfusion ratios and chest elastance more uniform

Facilitates drainage of secretions

Potentiates the beneficial effect of recruitment maneuvers

 Life-threatening circulatory shock

 Increased intracranial pressure

Prone Positioning

Main complications

 Facial and periorbital edema

 Pressure sores

 Accidental loss-displacement of the endotracheal tube, thoracic or

abdominal drains, and central venous catheters

 Airway obstruction

 Hypotension

 Arrythmias

 Vomiting

- Corticosteroids have not been proven to increase

survival among all patients with fibroproliferative ARDS However, the effect of corticosteroids may be related to the duration of disease prior to the initiation of therapy and the dose used

- Additional studies are necessary to determine

whether there is a role for corticosteroids in the management of ARDS

Recommendations in Practice

Principle of precaution

Limited VT 6 mL/kg PBW to avoid alveolar distension

End-inspiratory plateau pressure < 30 - 32 cm H 2 O

Adequte end-expiratory lung volumes utilizing PEEP and higher mean airway pressures to minimize atelectrauma and improve oxygenation

Consider recruitment maneuvers

Avoid oxygen toxicity: FiO 2 < 0.7 whenever possible

Monitor hemodynamics, mechanics, and gas exchange

Address deficits of intravascular volume

Prioritize patient comfort and safety