EVIDENCE BASED MEDICINE

(CASE OF SEVERE ARDS)

DR PRIYADHARSHINI R
RESIDENT, DNB CCM
EVIDENCE BASED MEDICINE
term EBM - 1990 by Gordon Guyatt of McMaster University
the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patient

aim - to integrate the experience of the clinician, the values of the patient, and the best available scientific information to
guide decision-making about clinical management
describe an approach to teaching the practice of medicine and improving decisions by individual physicians about individual
patients
OUR CASE
45/m c/o fever - 6 days, admitted else where, scrub IgM +
Worsening dyspnea- 3 days, ABG - type 1 respiratory failure, cxr - b/l infiltrates , echo - normal
scrub ARDS
Initiated on NIV later intubated, put on ventilator in v/o worsening pf ratio (110)
On same day, despite peep titration and lttv, pf ratio dropped further (83) - proned after placing lines

Berlin Definition. JAMA 2012; 307(23): 2526 - 2533

WHY ARDS?

associated with significant mortality

estimates from a multicenter, international cohort study - 3022 patients with ARDS- overall rate of death in
hospital - 40 %
Mortality and severity; mild - 35% , moderate - 40%, severe - 46%
Numerous studies suggest - survival has improved over time
ex. an observational study of 2451 in ARDSNet randomized trials - fall in mortality from 35 to 26 percent
between 1996 and 2005.
 COVID ARDS

LATELY,
Several retrospective studies- mortality from COVID-19-ARDS

Mortality driven by the presence of severe ARDS - 12 to 78 % (25 to 50 %)

Limited data - no difference in mortality between COVID-19-ARDS and non-COVID-19 ARDS 

CURRENT EVIDENCE

5,159 ARDS

mortality rate decreased from 35.4% 1996 to 28.3% in 2013.

lower risk of death as compared to those enrolled before 2000.

significant trends of declines in daily fluid balance, tidal volume, and plateau pressure and an increase in PEEP over the 17 years

improvement in mortality rate in critically ill patients enrolled in ARDS Network trials - decreased tidal volume, plateau pressure,
and daily fluid balance and increased PEEP
 atelectrauma Cyclic
SUPPORTIVE CARE WITH MV -
CORNERSTONE OF ARDS closing and reopening
MANAGEMENT of alveoli, Alveolar
barotrauma high shear stress-related
THE MOST IMPORTANT injury, Heterogeneous
ADVANCEMENT IN ARDS RESEARCH - inflation
nature of lung aeration
MV CAN ITSELF AGGRAVATE / CAUSE transpulmonary
LUNG DAMAGE BY A VARIETY OF pressures in ARDS
MECHANISMS - VENTILATOR
INDUCED LUNG INJURY (VILI)

VILI biotrauma mechanical

forces trigger complex
array of inflammatory
volutrauma Increased alveolar
mediators - local /
wall stress (stretch) by high
SIRS - propagating
tidal volume Parenchymal
injury to non-
injury - Gross physical
pulmonary organs -
disruption, Stretch-responsive
inflammatory pathways MODS and death
TREATMENT GUIDELINES (NICE)

►  Lung protective ventilation: tidal volume (Vt).

►  Corticosteroids.
►  PEEP.
►  Prone ventilation .
 Fluid strategy.
►  Neuromuscular blocking agents (NMBA).
►  High-frequency oscillation ventilation (HFOV).
►  Inhaled vasodilators (iNO)
►  ECMO.
►  ECCO2R.
 LTTV

PICO question
In mechanically ventilated adult patients with ARDS, do lower tidal volumes compared with
higher, conventional tidal volumes affect survival and other related outcomes?
LUNG PROTECTIVE VENTILATION

Low TV 6ml/kg
Pplat < 30cm H2O
Optimal peep

Amato
ARDS NET- -NEJM 1998;342:1301–1308
NEJM 2000; 338:347–
354
ARDSNET 2000
Included 861 patients with early ALI/ARDS (within 36 hrs)
Randomized traditional tidal volume (12 mL/kg ideal weight) or lower tidal volume (6
mL/kg ideal weight), ACMV, Pplat <30 vs <50 PEEP >5 (SpO2 >88%)
Primary endpoint (death before discharge or breathing without assistance) was reduced with
low tidal volumes
Lower tidal volume - reduction in 28-day breathing without assistance, ventilator-free days,
and non-pulmonary organ failures
mortality benefit
 PEEP

PICO question
In adult patients with ARDS, does mechanical ventilation with higher PEEP, compared with
standard (lower) PEEP improve survival, and selected outcomes?
HIGH PEEP VS LOW PEEP - ALVEOLI

549 intubated patients with early ADS (< 36 h), P:F ratio < 300.
Randomized to "high" PEEP or "low" PEEP according to Fi02 and PEEP titration table.
low tidal volume ventilation (6 mL/kg), pplat ≤ 30 cmH20, Pa02 55 - 80, SpO2 88 - 95%.
Primary endpoint (in-hospital mortality) was not different between high and low PEEP
no difference in ventilator-free days, ICU-free days, incidence of barotrauma, days without organ failures, or plasma levels of
inflammatory markers.
mean PEEP on days 1 to 4 was higher with the high PEEP group. The high PEEP group had slightly better PF ratios, higher
compliance, and higher plateau pressures.
Blood gas values (pH, PaCO2, Pa02) were very similar
SETTING PEEP

Determine if the patient has recruitable lung units

Increase PEEP from 5 cm H2O to 15 H2O
Observe response in compliance
If the patient responds favorably use the higher-PEEP table, if there is minimal or no response
use the lower-PEEP table
DRIVING PRESSURE (PPLAT - PEEP)

ΔP was most strongly associated with survival.

1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality, even
in patients receiving “protective” plateau pressures and V T.
Individual changes in VT or PEEP randomisation - not independently associated with survival; they
were associated only if they were among the changes that led to reductions in ΔP
 PRONE VENTILATION

Improves V/Q match

Better gas exchange
Improves FRC
Better oxygenation
Decreases VILI
Early prolonged proning improves survival & more MV free
days
PROSEVA

466 patients with early (< 36 h)

Prone - at least 16h/ day, stopped once oxygenation criteria improved (Pa02:Fi02 >=150 mmHg with PEEP <=0, FiO2 <= 60%)
28-day mortality was significantly lower with prone, 90-day mortality was also reduced
On average, prone done 4+4 sessions lasting for 17‡3 hrs ( 73% of the time spent on a ventilator)
Importantly, all ICUs included in this trial had at least five years of proning experience. Given the complexity and resources
required for proning, this is a potential issue for external validity.
The mortality reduction of >50% in severe ARDS seems "too good to be true" -- many clinicians are awaiting further studies,
but for the time being, these results are difficult to ignore.
ENTERAL FEEDING IN PRONE VENTILATED PATIENTS

Mean days under EN in the supine position were significantly higher > in PP - no significant differences in GRV
adjusted per day of EN, diet volume ratio.
No significant differences in high GR events per day of EN, vomiting per day, or diet regurgitation per day of EN
feasible, safe, not associated with increased risk of GI complications, can be continued when a patient is turned
from supine to prone position or vice versa
results indicate that patients with a clinically significant GRV in one position are likely to have a clinically
significant GRV in the other
Nutritional delivery of calories and proteins in prone position is comparable to that in supine position.
Larger studies needed to confirm these findings
CHEST TUBES - ICD- DURING PRONING
RRT IN PRONE VENTILATED PATIENTS

Patients with venous cannulae for ECMO or CRRT can be safely placed in the prone position.
Flow rates are maintained in this position.
Potential cannula complications of ECMO and CRRT are not a contraindication to prone positioning in severely ill
patients.
STEROIDS IN ARDS - MEDURI PROTOCOL

n= 91, ARDS < 72h, randomized to MPS or placebo

Dosing: 1 mg/kg loading dose, then 1 mg/kg/day (days 0-14), then 0.5 mg/kg/day (days 15-21), then 0.25 mg/kg/day (days 22-25), then 0.125
mg/kg/day (days 26-28).
Primary endpoints: improvement in lung injury score (LIS) after 7 days of treatment
MPS - higher incidence of extubation or LIS improvement at day 7, more patients breathing without assistance
MPS - fewer days of mechanical ventilation, reduction in ICU LOS and greater ICU survival
Hospital length of stay and hospital mortality were non-significantly improved with MPS.
NEUROMUSCULAR BLOCKADE

PICO question
In adults with ARDS, does the use of NMBA, compared with standard care, affect survival
and selected outcomes?
 MC RCT (20 French centers) – n = 340.

improved the adjusted 90-day survival

Reduced mechanical ventilator days
Less organ failure
No increase in CIPN
 Retrospective review of 73 pts with ARDS in a SICU

Extended use of NMB was not associated with increased mortality

FLUID MANAGEMENT

PICO question
In adults with ARDS, does the use of a conservative fluid strategy, compared with a liberal
fluid strategy or standard care, affect survival or selected outcomes?
FLUID MANAGEMENT

.
a meta-analysis of 11 randomised trials (2051 patients)
.
Decreased ICU LOS
.
Increased ventilator free days
.
No significant difference in mortality

Silversides JA. ICM 2016; 43(2): 155 - 170

FACTT

Included 1,000 patients with early-onset ALI/ADS (within 48 hrs)

Primary endpoint (60-day mortality) was not different between groups
Conservative management had more 28-day ventilator-free days and 28-day ICU-free days
Conservative strategy has higher incidence of metabolic alkalosis (serum bicarbonate > 40 mEq/L) and
electrolyte imbalances (serum sodium > 150 mEq/L, potassium < 3 mEg/ L)

N Engl J Med. 2006;354(24):2564-75.

BACK TO OUR CASE

Worsening pf - proned
1st proning - 30 hours - better gas exchange ( pH, pCO2, pf ratio, with driving pressure guided lttv
), feeding continued, maintained on conservative fluid management, steroids and NMB
2nd proning - 24 hours - better gas exchange, fio2 requirements well reduced
Extubated on day 6, later shifted out of ICU and discharged
POINTS TO PONDER

Based on these enough evidences we can still safely manage ARDS with
1. Lung protective ventilation (acc. to ARDSNET)
2. conservative fluid therapy,
3. Protocoled steroid usage, NMB
4. RT feeding the patient on PP
5. Also, HD can safely be done on prone ventilated patients with no cannula related issues and chest
tubes can still be left in situ and taken care of on prone ventilated patients
 REFERENCES
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THANK YOU