FRCPC Emergency
Medicine Exam Review
Course
Critical Care
Dr. Ian Ball
Dr. Chris Martin
Itinerary
Administration of Oxygen
NIPPV
Sepsis
Oxygen
Delivery
Dr. Christopher Martin
FRCPC ER/Critical Care
Director of Critical Care
RVH
Barrie Ontario
Nasal Prongs
• 1 lpm=24%
• 2 lpm=27%
• 3 lpm=30%
• 4lpm=33%
• 5 lpm=35%
• 6 lpm=38%
-O2 flow should be < 6 lpm
-Humidity not required for flows < 4 lpm
-O2 concentration will vary with patient
breathing pattern
Oxygen Mask
• Simple face mask
The volume of the face mask is 100-300 mL. It delivers an
FI,O2 of 40-60% at 5-10 L·min-1
• Venturi mask
A Venturi mask mixes oxygen with room air, creating highflow enriched oxygen of a settable concentration. It provides
an accurate and constant FI,O2. Typical FI,O2 delivery settings
are 24, 28, 31, 35 and 40% oxygen.
Nonrebreathing Mask
Nonrebreathing face mask with
reservoir and one-way valve
- indicated when an FI,O2 >40% is
required
- can deliver FI,O2 up to 90% at high
flow settings
- Oxygen flows into the reservoir at 810 L·min-
High-Flow Nasal Cannula
O2
• Flows ranging from 10-40 L·min• Warmed and saturated to full humidity
Non-Invasive
Postive Pressure
Ventilation
Dr. Christopher Martin
FRCPC ER/Critical Care
Director of Critical Care
RVH
Barrie Ontario
Non-Invasive Positive
Pressure Ventilation (NIPPV)
Continuous Spontaneous Ventilation
delivered though a sealed mask instead of
ETT
2 types
1) CPAP 2) BiPAP
PEEP - maintenance of positive airway
pressure after the completion of passive
exhalation
NIPPV
CPAP
Provides constant assistance through respiratory
cycle
BiPAP
Provides higher pressure during inspiration and a
lower level during expiration
Dr James Moffat http://www.nataliescasebook.com/tag/positive-airway-pressure-ventilation
Dr James Moffat http://www.nataliescasebook.com/tag/positive-airway-pressure-ventilation
NIPPV
Indications - Patients requiring ventilatory assistance
for reversible respiratory conditions who are not in
need of immediate ETT or have “Do Not Intubate”
orders
Contraindications
Need for intubation
Unable to protect airway
++ Vomiting / GI bleeding
Inability to clear secretions
Lack of Respiratory Drive
Hemodynamic Instability / Cardiac
Arrest
Facial Trauma
Diaphramatic Rupture
NIPPV
Best Evidence for Use is in patients with ACPE (Acute
Cardiogenic Pulmonary Edema) and COPD!
ACPE - Mulitiple trials show definitive improvement in physiology
and decreased intubation rates. Recent Cochrane database
shows mortality benefit.
COPD - Multiple meta-analysis show decrease intubation,
decrease hospital LOS and decrease mortality
in patients with SEVERE hypercarbic acute COPE
exacerbation.
NIPPV
Asthma - Weak evidence of benefit in small studies
Hypoxemic Respiratory Failure - ????
NIPPV
Practically Speaking…..
Can start off with BiPAP with a IPAP of 10cm H20 and an EPAP of
5cm H2O. In larger patients (with high BMI) may need high
pressures.
Fi02 can start at 50%. Titrate to Sa02 to 94 or greater in ACPE, 8892% in any chronic CO2 retaining COPD.
*Almost No patient needs an SaO2 of 100%
References
1) Rosen’s
2) Dr James Moffat, senior lecturer in physiology at St George's, University of London
http://www.nataliescasebook.com/tag/positive-airway-pressure-ventilation
3) Gray A, Goodacre S, Newby DE, Masson M, Sampson F, Nicholl J, 3CPO Trialists
Invasive ventilation in acute cardiogenic pulmonary edema.
N Engl J Med. 2008;359(2):142.
4) Vital FM, Ladeira MT, Atallah AN
Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary
oedema.
Cochrane Database Syst Rev. 2013;5:CD005351.
5) Ram FS, Picot J, Lightowler J, Wedzicha JA
Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of
chronic obstructive pulmonary disease.
Cochrane Database Syst Rev. 2004
6) Lim WJ, Mohammed Akram R, Carson KV, Mysore S, Labiszewski NA, Wedzicha JA, Rowe BH, Smith BJ
Non -invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of
asthma.
Cochrane Database Syst Rev. 2012;12:CD004360
SEPSIS
Dr. Christopher Martin
FRCPC ER/Critical Care
Director of Critical Care
RVH
Barrie Ontario
Sepsis
Definition
Sepsis is a state of malignant inflammation in
response to infection. This process overwhelms the
regulatory system, disrupts homeostasis and can cause
severe tissue damage.
Ali H Al-Khafaji -http://emedicine.medscape.com/article/169640-overview
Sepsis
SIRS >2 of the following
Temp <36oC or >38oC
RR >20 or PaCO2 <32mmHg
HR >90
WBC <4 or >12 or >10% bands
Sepsis = Infection (probable OR documented) + SIRS
Severe Sepsis = Sepsis + End Organ Dysfunction
Septic Shock = Severe Sepsis plue hypotension
Risk Factors
Elderly
Comorbidities
HIV
Chemo
Other Immune
suppressants
Indwelling
devices/catheters
Splenectomy
CAP
Genetics
Diabetes
Epidemiology
Incidence in US is 5/100000 <65 and 26/100000 >65
1400 people die from sepsis worldwide each day
Best mortality rates in RTCs around 20%
Prospective observational study of 12 Canadian
community and teaching hospitals found mortality of
severe sepsis >38%
STEMI
Severe Sepsis/
Septic Shock
30 day mortality
-13% - medical
therapy
- 7 % - fibrinolytic
therapy
- 4% - PCI
In hospital mortality
At best 20% (20-46%)
Pathophysiology
1) Pathogen detected by host immune cells and bind to them
2) Cytokines released by macrophages and neutrophils
activate both pro-inflammatory (IL-1, IL-8, TNF- alpha) and
anti-inflammatory (IL-6, IL-10) mediators
3) Dysregulation of mediators results in cellular hypoxia, and
tissue injury
4) Activation of Clotting Cascade (pro-coagulant state
5) Instability of Vascular Tone and microvascular dysfunction
Rosen’s 8th edition
Organ Dysfunction
Nervous System
- Altered Sensorium (Septic Encephalopathy) common.
- Multifactorial (Endotoxin, altered perfusion, dyfunction
of BBB, drugs, hepatic/renal failure)
- Critical Illness polymyopathy
Organ Dysfunction
Cardiovascular
Hypotension due to:
1) Diffuse vasodilation (distributive shock). Mediated by
Oxide (NO) as well as Vasopressin suppression.
prostacyclin, Nitric
2) Increased “third spacing” of fluid due to increased vascular permeability
3) Myocardial depression (after an initial period of hyper dynamic cardiac
output
Microvascular Dysfunction - decrease in the number and function
of capillaries as well as endothelial dysfunction
Organ Dysfunction
Pulmonary
Lungs are early victims of inflammation
- Neutrophil invasion and endothelial injury cause surfactant
dysfunction and pulmonary oedema
- Monocyte infiltration leads to fibrosis and ARDS
- Right to Left Shunt and hypoxemia
Organ Dysfunction
Gastrointestinal
Endothelial dysfunction disrupts gut barrier leading to
translocation of bacteria/endotoxin
Ileus from hypo perfusion
Organ Dysfunction
Renal
Sepsis often accompanied by AKI
- ATN due to hypoperfusion/hypoxemia, cytokine, direct renal
vasoconstriction, neutrophil activation
- Likelihood of death increased significantly in sepsis
complicated by renal failure.
Organ Dysfunction
Endocrine
Absolute/relative adrenal insufficiency
Heme
Pathologic activation of extrinsic clotting cascade
- May result in consumption of essential factors and DIC
- May result in fibrin deposition and microvascular thrombi =
decreased tissue perfusion
Sepsis - Diagnosis
1st need to Identify that a patient HAS SEVERE SEPSIS!
LACTATE
Sepsis - Diagnosis
•
A good history and physical best chance to find
source
Respiratory > GI > GU > STI > Bacteremia > Gyne > MSK
•
Labs - CBC, LUC, Coags, LFTs, VBG, Lactate, Trop,
CK
•
Micro - Blood cultures x2, Urine, Sputum (Blood
cultures before ABX as long as <45min delay)
•
Imagine studies ASAP to confirm source
Sepsis - Treatment
Early Antibiotics
- (SSCM <1hr to effective Abx)
- 1 or more drugs that have activity against al likely pathogens
(bacterial/viral/fungal)
- Must penetrate in adequate concentrations into tissues presumed to
be the source
- Combination empiric treatment for neutropenic patients, difficult to
treat/resistant organisms (P. aeruginosa, Acinetobacter)
•
Source Control
- Use least traumatic
means possible (drain
intraabdominal
abscess vs open I+D)
Sepsis - Treatment
Stabilize Respiration
- Supplemental Oxygen
- Intubation and Mechanical Ventilation may be required for
airway protection, hypoxemia or fatigue from increased work of
breathing
Sepsis - Treatment
Circulation - FLUID THERAPY
- Aggressive IV crystalloid resuscitation key to treating
hypotension/hypoperfusion of sepsis.
- SCCM recommends minimum 30mL/kg
- EGDT study patients received 5L of crystaloid in first 6 hrs, PROCESS
2.3-3.3L
- RL or NS …. No benefit to Albumin ($$$)
- NO Hydroxyethyl Starch!!! (Voluven, Pentaspan). Increased risk of
requiring RRT and increased mortality.
Sepsis - Treatment
Circulation - Vasopressors
- Used in those hypotensive despite adequate fluid resuscitation or
those who develop pulmonary edema
- SCCM 1) initially target a mean of 65mmHg
2) Norepinephrine > Vasopressin > Epinephrine
- SEPSISPAM. NEJM 2014. No difference between patients in septic
shock randomized to MAP target of 65-70mmHG vs. 85-90mmHg
•
Circulation - Inotropes
- SCCM - Trial of dobutamine if ongoing signs of hypo perfusion despite
adequate intravascular volume and adequate MAP
Sepsis - Treatment
Circulation - Corticosteroids
SCCM - If adequate fluid resuscitation and vasopressor therapy
unable to restore hemodynamic stability, IV hydrocortisone 50mg IV
q6h
- Stress doses also required if patients on chronic steroid therapy
- Also, new role in CAP…
Sepsis - Treatment
Additional Therapies - RBC Transfusions
EGDT - transfusion target HCT of 30%
SCCM - transfusion target 70g/L
TRISS trial NEJM 2014;371(15):1381-91. NO difference
in 90 day mortality between ICU patients in septic shock
transfused to target of 70 g/L vs. 90 g/L.
Protocol Guided Quantitative
Resuscitation - Early Goal Directed
Therapy
NEJM 2001:345: 1368-1377
Single centre randomized trial of 263 patients
presenting to ED with Severe Sepsis/Septic Shock
Rivers et al. NEJM 2001;345:1368-1377
Rivers et al. NEJM 2001;345:1368-1377
Rivers et al. NEJM 2001;345:1368-1377
Rivers et al. NEJM 2001;345:1368-1377
2014 - The death of EGDT?
ARISE. NEJM 2014;371(16): 1496-506
ProCESS. NEJM 2014;370: 1683-93
A Randomized Trial of Protocol-Based
Care for Early Septic Shock
The ProCESS Investigators
1341 patients with severe sepsis/septic shock
randomized to 1 of 3 groups
1) EGDT
2) Protocol Based Standard Therapy
3) Usual Care
No difference in 60 day mortality between the 3 groups
Protocol-Based
EGDT
Rivers et al.
NEJM 2001;
345:1368-1377
Protocol-Based
Standard Therapy
ProCESS Investigators.
NEJM 2014;370:1683-93
No difference in 60
day mortality (18.221%) between the 3
groups
Sepsis Summary
Go looking for it, especially in at risk populations
Early antibiotics and source control key
Although Protocol-Based Quantitative Resuscitation
non superior, Aggressive fluid resusciation still
required
References
1) Ali H Al-Khafaji, Sat Sharma, Gregg Eschun
http://emedicine.medscape.com/article/169640-overview
2) C. M. Martin et al., “A Prospective, Observational Registry of Patients With Severe Sepsis: The Canadian Sepsis
Treatment and Response Registry,” Critical Care Medicine 37, 1 (2009): pp. 81–88
3) http://www.sccm.org/Documents/SSC-Guidelines.pdf
4) Uptodate
5)Rivers et al. Early Goal Directed Therapy in the Treatment of Severe Sepsis. NEJM 2001;345:1368-1377.
6) Perner, A et al. Hydroxyethyl Starch 130/0.42 versus Ringer's Acetate in Severe Sepsis. NEJM 2012, 367:124-134
7) Asfar et al. High versus Low Blood-Pressure Target in Patients with Septic Shock. NEJM 2014;370:1583-93
8) Holst et al. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock. NEJM 2014;371(15):1381-91.
9) Process Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock. NEJM 2014;370: 1683-93
Critical Care
Ventilation and Vasoactive Medications
Ian Ball MD FACEP FCCP FRCPC
Assistant Professor, Division of Critical Care Med, Western University
Topics
Standard ventilation
Ventilating the asthmatic
ARDS
Vasoactive Medication Selection (VICE)
Case 1
34 yo male in a “romantic tragedy”
Ingests 30 tablets of Midazolam 5mg
HD stable
GCS 3
already intubated and decontaminated appropriately
Your colleague asks for help with ventilation
How to Set a Ventilator?
Rate (breaths per minute)
Tidal volume (generally described in cc/kg)
Inspiratory : expiratory ratio
Peep
Pressure control / volume control /combinations
Mode
Other important ventilator
concepts for review
Peak pressure
Plateau pressure
Pressure-volume loops
End inspiratory hold
End expiratory hold
Case
26 yo female
Known asthma
Ventolin and inhaled steroids
URTI symptoms x 4 days
Abrupt worsening this am
O/E
125, 135/86, 96% room air, bg 7.2, 36.8,
Working very hard to breathe
Not much to hear on auscultation
7.36 / 40 / 26
Receiving continuous Ventolin
Prednisone 50mg PO already administered
Other Medical Therapies?
Ipratropium (Atrovent)
Magnesium
Ketamine 34,35
Heliox 36-41
Epinephrine
Volatile anesthetics 42-44
ECMO 45-46
What About NIV?
Little experience
Sparse literature
Potential Benefits of NIV
Decreased work of breathing
Decrease auto-Peep 16
Improved V/Q matching 17
May improve bronchodilator delivery 18,19
May recruit collapsed alveoli 20
Literature
NIV is supported by two observational trials 21,22
And two randomized trials 23,24
Absolute Contraindications
Need for immediate intubation
Decreased LOC
Excess secretions
Abnormal facial anatomy precluding mask fitting
Relative contraindications
Hemodynamic instability
Severe hypoxemia and /or hypercapnia
Poor patient cooperation
Severe agitation
Lack of trained or experienced staff
Ventilator Strategies
Titrate FiO2 to correct hypoxemia
Low respiratory rate
Low i:e
Low tidal volume
Optimal Peep is controversial 27-30
High inspiratory flow
15
Minute ventilation?
Respiratory rate x tidal volume
Differential Diagnosis of
Hypoxemia?
V/Q mismatch
Hypoventilation
Shunts (pulmonary or cardiac)
Hemoglobinopathies
Diffusion problems
A-a gradient and its
significance
A-a gradient= pAO2-paO2 = Alveolar – arterial
pAO2= FiO2 (Patm-PH2O) – PCO2 / 0.8
= 0.21 (760-47) - PCO2 / 0.8
= 150 - 5/4 PCO2
Normal A-a is 5-10 but increases by 1 per decade of age
How to calculate oxygen
delivery
O2 content = 1.39 x Hgb x O2 saturation + 0.003 PaO2
DO2 = O2 content x Q
Q= cardiac output = HR x Stroke volume
Stroke volume dependent on: preload / afterload /
contractility
Vasopressors and Inotropes in
Canadian Emergency
Departments (VICE)
VICE
No guidelines for which vasoactive medication to use
Surprisingly little evidence
VICE worked with the Caep standards committee and
CJEM
Vasopressors
Systemic vasoconstriction (afterload effect)
Pulmonary vasoconstriction (right sided afterload
effect)
Inotropes
Increase inotropy (increase cardiac workload)
Increase chronotropy (increase cardiac workload +
decrease coronary perfusion)
Dopamine and Epinephrine increase rate of dysrhythmias
Side Effects
Dopamine increases the risk of tachyarrhythmia
compared to norepinephrine47 (Grade A)
Dopamine use in septic shock increases mortality
compared to norepinephrine (Gr B)
Vasopressin may cause cellular ischemia and skin
necrosis (Grade C)
Kaplan–Meier Curves for 28-Day Survival in
the Intention-to-Treat Population.
De Backer D et al. N Engl J Med 2010;362:779-789.
Side effects (Cont’d)
Epinephrine increases “metabolic abnormalities”
compared to norepinephrine (Grade A)
Epinephrine increases “metabolic abnormalities”
compared to norepinephrine-dobutamine in
cardiogenic shock without acute cardiac ischemia
(Grade B)
Case 1
56 yo male
Obese, smoker, htn, DM
To ED with 2 hrs retrosternal CP, diaphoresis
78/42, 118 sinus, 96% rm air, 36.2
Extremities are cool
Vasoactive Agent of Choice for
Cardiogenic Shock?
Norepinephrine (Strong)
Vasopressor + Inotrope for
Cardiogenic Shock?
Norepinephrine + Dobutamine (conditional)
Dobutamine
Synthetic beta agonist
5-15 ug/kg/min
Pure inotrope
Variable blood pressure response
May cause tachycardia, arrhythmias
Milrinone is other option
Case 2
26 yo drunk driver
•
(male, of course)
Single vehicle MVC into post
138, 68/42, 96%, 36.6, 34
Mentating, describes diffuse abd pain
How to manage his hemodynamic status?
What vasoactive medication
for hypovolemic shock?
Routine vasopressor use in hypovolemic shock is not
recommended (conditional)
Case 3
86 yo male with productive cough and progressive “feeling unwell”
Otherwise healthy
116 sinus, 82/56, 90% on FiO2 0.8
Crackles on right side
How much fluid?
Which vasoactive agent?
Norepinephrine
Endogenous catecholamine
Alpha effect >>> beta effect
Start at 5 ug / min
Little tachycardic response
Levophed --- Leave ‘em Dead??
Best Vasoactive Medication
for Sepsis?
Norepinephrine (strong)
Last Case
26 yo female with peanut allergy
Eating thai food, but being careful…..
76/52, 122, covered in urticaria
First and most important treatment?
Case 2
What induction agent if you need to intubate?
What is Epi’s role in ACE inhibitor induced
angioedema?
Anaphylaxis?
Epinephrine!!! (strong)
Start with 0.3-0.5 mg IM
My practice --- start central line + infusion if
second IM dose is required….
Route of Vasoactive
Medication Administration?
By central venous catheter (conditional)
Take-home VICE
Dopamine is NEVER first line
Epinephrine is only first for anaphylaxis
The era of “aggressive” crystalloid resuscitation in sepsis
or trauma are OVER!
No agent is safer than any other peripherally
ARDS—Berlin definition
Formerly the Europeen-American Consensus
Definition (1994)
2011 ATS, Europeen Society of CCM, Society of
CCM met
Mild PaO2/FiO2 ratio 200-300
Moderate P/F ratio 100-200
Severe P/F ratio < 100
Berlin Derivation
•
Evaluated respiratory system compliance
(<40mL/cmH2O), radiographic burden, expired
volumes (<10L/min), Peep (>10 cm H2O)
Mortalities of 27%, 32%, 45%
Improved area under the ROC compared to Europeen
Consensus Definition
Treatments
Out: nitric oxide, steroids, HFO
In: prone positioning, ECMO
Questions?
References
15. Ball IM. The critically ill asthmatic. Handbook of ICU Therapy, 3rd edition. Cambridge University Press2015. 416-427.
16. Manser R, Reid D, Abramson M. Corticosteroids for acute severe asthma in hospitalized patients. Cochrane
Database Syst Rev 2000;2.
17. Tokioka H, Saito S, Saeki S,et al. The effect of pressure support ventilation on auto-PEEP in a patient with asthma.
Chest 1992;101:285-286.
18. Broux R, Foidart G, Mendes P,et al. Use of PEEP in management of life-threatening status asthmaticus: a method for
the recovery of appropriate ventilation-perfusion ratio. Appl Cardioplum Pathophysiol 1991;4:79-83.
19. Pollack CV Jr, Fleisch KB, Dowsey K. Treatment of acute bronchospasm with beta-adrenergic agonist aerosols
delivered by a nasal BiPap circuit. Ann Emerg Med 1995;26:552-557.
20. Brandao DC, Lima VM, Filho VG, et al. Reversal of bronchial obstruction with bi-level positive airway pressure and
nebulization in patients with acute asthma. J Asthma 2009;46:356-361.
21. Sorksky A, Klinowski E, Ilgyev E, Mizrachi A, Miller A, Ben Yehuda TM, Shpirer I, Leonov Y. Noninvasive positive
pressure ventilation in acute asthmatic attack. Eur Respir Rev 2010;19:115,39-45.
References
22. Meduri GU, Cook TR, Turner RE, et al. Noninvasive positive pressure ventilation in status asthmaticus. Chest 1996;110:767774.
23. Fernandez MM, Villagra A, Blanch L, et al. Non-invasive mechanical ventilation in status asthmaticus. Intensive Care Med
2001;27:486-492.
24. Soroksky A, Stav D, Shpirer I. A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway pressure in
acute asthmatic attack. Chest 2003;123:1018-1025.
34. Silverman RA, Osborn H, Runge J, Gallagher EJ, Chiang W, Feldman J, Gaeta T, Freeman K, Levin B, Mancherje N, et al. IV
magnesium sulfate in the treatment of acute severe asthma: a multicenter randomized controlled trial. Chest 2002;122:489-497.
35. Sarma V. use of Ketamine in acute severe asthma. Acta Anaesthesiol Scand. 1992;36:106-107.
36. Hemmingsen C, Nielsen PK, Odorico J. Ketamine in the treatment of bronchospasm during mechanical ventilation. Am J
Emerg Med. 1994;12:417-420.
37. Schaeffer EM, Pohlman A, Morgan S, Hall JB. Oxygenation in status asthmaticus improves during ventilation with heliumoxygen. Crit Care Med. 1999;27:2666-2670.
References
38. Gluck EH, Onorato DJ, Castriotta R. Helium-oxygen mixtures in intubated patients with status asthmaticus and
respiratory acidosis. Chest.1990;98:693-698.
39. Henderson SO, Acharya P, Kilaghbian T,Perez J, Korn CS, Chan LS. Use of heliox-driven nebulizer therapy in the
treatment of acute asthma. Ann Emerg Med. 1999;33:141-146.
40. Tassaux D, Jolliet P, Roeseler J, Chevrolet JC. Effects of helium-oxygen on intrinsic Positive end-expiratory pressure
in intubated and mechanically ventilated patients with severe chronic obstructive pulmonary disease. Crit Care Med.
2000;28:2721-2728.
41. Kass JE, Terregino CA. The effect of heliox in acute severe asthma: a randomized controlled trial. Chest.
1999;116:296-300.
42. Ho AMH, Lee A, Karmakar MK, Dion PW, Chung DC, Contardi LH. Heliox vs air–oxygen mixtures for the treatment of
patients with acute asthma: a systematic overview. Chest 2003; 123(3): 882–90.
43. Otte RW, Fireman P. Isoflurane anesthesia for the treatment of refractory status asthmaticus. Ann Allergy.
1991;66:305-309.
References
44. Maltais F, Sovilj M, Gottfried SB. Respiratory mechanics in status asthmaticus. Effects of inhalational
anesthesia. Chest. 1994;116:296-300.
45. Rooke GA, Choi JH, Bishop M. The effect of isoflurane, halothane, sevoflurane, and thiopental / nitrous oxide
on respiratory system resistance after tracheal intubation. Anesthesiol. 1997;86:1294-1299
46. Kukita I, Okamoto K, Sato T, Shibata Y, Taki K, Kurose M, Terasaki H, Kohrogi H, Ando M. Emergency
extracorporeal life support for patients with near-fatal status asthmaticus. Am J Emerg Med. 1997;15:566-569.
47. De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur C, Defrance P,
Gottignies P, M.D., Vincent J-L for the SOAP II Investigators N Engl J Med 2010; 362:779-789