1. The document discusses the history and pathophysiology of acute respiratory distress syndrome (ARDS), including its original description in 1821 and formal naming/definition in 1967. 2. A key development was the use of mechanical ventilation in the 1950s, which extended patient survival from hours to days/weeks and allowed more time for recovery. 3. The role of the nuclear factor κB transcription factor and associated inflammatory cytokines and neutrophils in the pathogenesis of ARDS is described. Uncontrolled inflammation can lead to endothelial and epithelial damage in the lungs. 4. Progression of ARDS is discussed as either resolving or unresolving, with the latter associated with worse outcomes. Corticosteroids are

2. Topics to be covered.
1. When the ARDS first dIscovered
2. Patho physiology of ards and role of CS
3. When was the first use of steroid
started.
4. Current prospective .
5. doubble edege sword.

3. Introduction
 in 1821, in what was probably the first published scientific description,
Laennec described the gross pathology of the heart and lungs and
described idiopathic anasarca of the lungs; pulmonary edema without
heart failure in ―A Treatise on Diseases of the Chest‖
 By the 1950s, pulmonary edema had become a medical subject
heading by the National Library of Medicine; however, no distinction
was made at that time between cardiac and noncardiac causes.
 But what clearly moved ARDS from a nearly universally fatal form of
―double pneumonia‖ was the development of methods of establishing
secure airway access using tubes that could be attached to mechanical
ventilators to deliver adequate pulmonary distending pressures
 These techniques extended the lives of these patients from a few hours
to many days or even weeks—long enough to recover in some cases.
 Am. J. Respir. Crit. Care Med. October 1, 2005 vol. 172 no. 7 798-806

4.  For a period of time ARDS went by the name of inciting injuries (e.g., DaNang lung,
shock lung, post-traumatic lung, etc.).
 It wasn't until 1967, in a landmark article published in Lancet, that Ashbaugh,
Bigelow, Petty, and Levine first described the clinical entity that they called ―acute
respiratory distress in adults‖ .
 This article recognized for the first time that ARDS was a constellation of
pathophysiologic abnormalities common to a relatively large number of patients but
that were initiated by a wide variety of unrelated insultS…
 However, in 1971 Petty and Ashbaugh used the term ―adult‖ respiratory distress
syndrome in another publication, probably to address the perception of ARDS as an
adult version of the previously described infant respiratory distress syndrome
(IRDS).

5.  In 1992 the American European Consensus Conference
(AECC) was charged with developing a standardized
definition for ARDS to assist with clinical and epidemiologic
research.
 In 1994, the American-European Consensus Conference
(2) defined two pathogenetic pathways leading to ARDS as
a direct ("primary" or "pulmonary") insult, that directly
affects lung parenchyma, and an indirect ("secondary" or
"extrapulmonary") insult, that results from an acute
systemic inflammatory response
 Braz J Med Biol Res, February 2005, Volume 38(2) 147-159 (Review)

6. Berlin defination of ards jama -
2012
Timing Within 1 week of known clinical insult or new or worsening
of respiratory symptoms
Chest imaging b/l opacities not fully explained by effusion;lobar/lung collapse or
nodule
Origin of Respiratory failure not fully explained by cardiac failure or fluid
edema overload.need objective assement to exclude the hydrostatic
edema if no risk factor present.
oxygenation
mild 200mmhg <pao2/fio2,<300mmhg with peepor cpap .5cmh20
moderate 100mmhg <pao2/fio2,<200mmhg with peep > 5cmh20
severe pao2/fio2,<100mmhg with peep>5cmh20

7. Pathophysiology of ARDS
 Although the cellular and molecular basis of acute lung injury and ARDS remains an area
of active investigation,
 it appears that in ARDS, lung injury is caused by an imbalance of pro-inflammatory
and anti-inflammatory mediators.[4]
 The most proximate signals leading to uncontrolled activation of the acute inflammatory
response are not yet understood.
 However, nuclear factor κB (NF-κB), a transcription factor whose activation itself is
tightly regulated under normal conditions, has emerged as a likely candidate shifting the
balance in favor of a pro-inflammatory state.
 As early as 30 minutes after an acute insult, there is increased synthesis of interleukin-8
(IL-8), a potent neutrophil chemotactic and activating agent, by pulmonary macrophages.
Release of this and similar compounds, such as IL-1 and tumor necrosis factor (TNF),
leads to endothelial activation, and pulmonary microvascular sequestration and
activation of neutrophils.
 Neutrophils are thought to have an important role in the pathogenesis of ARDS.

8. PATHOGENESIS OF ARDS

9. Role of NFKB GENE…..
 NF-κB (nuclear factor kappa-light-chain-enhancer of activated B
cells) is a protein complex that controls the transcription of DNA.
 NF-κB is found in almost all animal cell types and is involved in cellular
responses to stimuli such as stress cytokines,,Free radicals, oxidized
LDL and bacterial or viral antigens.
 NF-κB plays a key role in regulating the immune response to infection
(kappa light chains are critical components of immunoglobulins).
 Incorrect regulation of NF-κB has been linked to cancer, inflammatory
and autoimmune diseases, septic shock, viral infection, and improper
immune development.
Gilmore TD (2006). "Introduction to NF-κB: players, pathways,
perspectives". Oncogene 25 . PMID
Hayden MS, West AP, Ghosh S (October 2006). "NF-κB and the immune response". PMID.

10. Role of NFKB – conti….

11. 3- Histopathological stages of ARDS
it has been repeatedly shown that high levels of procollagen peptides
detected in early stages of ARDS and the degree of fibrosis per se can be
regarded as a key predictor of poor clinical outcome.

12. Activation and Regulation of Systemic
Inflammation in ARDS:
 Experimental and clinical evidence has demonstrated the cellular
mechanisms involved in activating and regulating inflammation
are contrasted between patients with resolving and unresolving
ARDS.
 In ARDS, down-regulation of systemic inflammation is essential to
restoring homeostasis, decreasing morbidity, and improving
survival.
 At the cellular level, patients with unresolving ARDS have
deficient glucocorticoid (GC)-mediated down-regulation of
inflammatory cytokine and chemokine transcription despite
elevated levels of circulating cortisol, a condition defined as
systemic inflammation-associated acquired GC RESISTANCE.
 Controll sydies shows; Prolonged low-to-moderate dose GC
therapy promotes the down-regulation of inflammatory cytokine
transcription at the cellular level. And consistently reported a
significant reduction in markers of systemic inflammation,
pulmonary and extrapulmonary organ dysfunction scores,
duration of mechanical ventilation, and ICU length of stay

13. Progression of ARDS: Resolving vs
Unresolving
 The lung injury score (LIS) quantifies the impaired respiratory physiology in
ARDS patients through the use of a 4-point score that is based on the level
1) positive end-expiratory pressure (PEEP),
2) the PaO2/FIO2 ratio,
3) the quasistatic lung compliance, and
4) the degree of infiltration seen on a chest radiograph
(1 point per quadrant of chest radiograph involved).
 Based on simple physiologic criteria, the evolution of ARDS can be divided
into resolving and unresolving based on achieving a 1-point reduction in LIS
by day 7.
 Daily measurement of LIS, MODS score, and CRP levels allow early
identification of non improvers.

14. Progression of ARDS conti….
Variables Resolving Unresolving
Onset of ARDS
Systemic inflammation* Moderate Exaggerated
HPA axis response Adequate Inadequate
Over time
Systemic inflammation Regulated Dysregulated
Cellularactivation/regulation of
GRα-driven NF-κB-driven
inflammation
Inflammation, markers Decreasing Persistent elevation
ACM permeability,mark. Decreasing Persistent elevation
Fibrogenesis, markers Decreasing Increasing
Lung repair (histology) Adaptive Maladaptive
Reduction in LIS ≥ 1 point by day 7 < 1 point by day 7
ICU mortality Low High
G. Umberto Meduri, MD, FCCP; Djillali Annane, MD, PhD; George P. Chrousos, MD;
Paul E. Marik, MD, FCCP; Scott E. Sinclair, MD, FCCP,chest-2009

15. PATHWAY OF INHIBITION OF INFLAMATION BY
CORTICOSTEROIDS

16. Interaction Between Activated NF-κB and GRα in
ARDS
Longitudinal relation on natural logarithmic scales between mean levels of
nuclear NF-κB and nuclear GRα: resolving vs unresolving ARDS (left) and after
randomization to methylprednisolone vs placebo (right).
Activation and Regulation of Systemic Inflammation in ARDS: Rationale for Prolonged
Glucocorticoid TherapyFree .
G. Umberto Meduri, MD, FCCP; Djillali Annane, MD, PhD; George P. Chrousos, MD; Paul E. Marik, MD,
FCCP; Scott E. Sinclair, MD, FCCP,chest-2009

17. Corticosteroids for prevention of
ards
 ARDS develops after a variety of insults, including sepsis,
multiple trauma, pneumonia, aspiration of gastric
contents, and severe burns.
 Its pathogenesis includes immune-mediated injury
leading to loss of the alveolar-capillary barrier, injury to
the alveolar epithelium, an influx of neutrophils and
macrophages, and fibrin. These changes develop over
hours to a few days after the initiating event.
 Therefore, timely modulation of inflammation using
corticosteroids in these high-risk patients would be a
rational approach for prevention of ARDS and its
consequences.
 There are only a few trials on the role of corticosteroids as
immunomodulators to prevent development of ARDS in
high-risk patients, such as patients with severe
sepsis.However, results were not encouraging.

18. weigielt et al;1985;
 performed a randomized double-blind trial to determine the usefulness of early
methylprednisolone therapy for patients with pulmonary failure.
 selected 81 acutely ill, mechanically ventilated patients at high risk for adult respiratory
distress syndrome (ARDS).
 Thirty-nine patients received methylprednisolone, 30 mg/kg, every six hours for 48
hours; 42 patients received mannitol placebo.
 All patients were given a positive end-expiratory pressure of 5 cm H2O, monitored with
pulmonary artery catheters, and treated for their primary disease processes.
 Twenty-five steroid-treated patients (64%) and 14 placebo-treated patients (33%)
developed ARDS.
 Early infectious complications occurred in 30 steroid-treated patients (77%) and 18
placebo-treated patients (43%). There were no significant differences in factors
predisposing to ARDS, ventilatory requirements, or days of intensive care.
 These results do not support the use of methylprednisolone for ARDS. Steroids failed
to improve pulmonary function and were associated with an increased infection rate.
Intensive pulmonary and general supportive care remain the preferred therapy for
ARDS.

19. Bone et al;1987;
 In this study, 382 patients with sepsis were randomized
to receive either MP (30 mg/kg every 6 hours for 4
doses) or placebo.
 This study showed that there was a trend toward
increased incidence of ARDS in MP group (32%) as
compared with placebo (25%), though results were not
statistically significant.
 However, mortality at day-14 was significantly higher
(52% vs 22%; P = 0.005) in patients having received MP
as compared with placebo.
 Other studies also showed that prophylactic short
course high-dose corticosteroids were associated with
increased chances of developing ARDS and/or mortality

20. Trials of corticosteroids for prevention of ARDS
Authour Drug dosage No of pt OR P-
year developing (95%Ci) value
ards/total no pts%
Corticos Placebo
teroid group
group
2.36
Weigelt et Methylprednisolone 30 mg/kg 25/39 14/42
(1.14- 0.008
al. 1985 6 hourly for 48 hours (64.1) (33.3)
6.28)
Methylprednisolone 30 mg/kg 1.48 Not
Schein et 7/29 2/13
or Dexamethasone 6 mg/kg (0.48- menti
al. 1987 (24.1) (15.3)
single dose 4.44) oned
1.48
Bone et Methylprednisolone 30 mg/kg 50/152 38/152
(0.93- 0.10
al. 1987 6 hourly for 24 hours (32.9) (25)
2.34)
1.55 Not
Luce et Methylprednisolone 30 mg/kg 13/38 14/37
(0.44- signifi
al. 1988 6 hourly for 24 hours (34.2) (37.8)
2.32) cant

21. Prevention…
 It is important to note that in all these
studies, MP was used for a maximum
duration of 48 hours and its circulating half
life in ARDS patients varies from 3.8 to 7.2
hours; therefore, the effect of this drug will
diminish after 24 to 36 hours at the most.
 Above study shows, it leads to higher rates
of ARDS, increased infectious
complications, and mortality.

22. Prevention conti….
Therefore, we strongly argue against
prophylactic use of corticosteroids in
seriously ill patients who are prone to
develop ARDS.
It is evident from these clinical trials that
corticosteroids have no role in prevention
of ARDS in high-risk patients

23.  Animal studies have shown that in acute
lung injury, prolonged corticosteroids
were shown to be effective in reducing
edema and collagen deposition in lung,
while premature withdrawal rapidly
negated these positive effects.

24.  Hetsberg et al; In a rat model of butylated-hydroxytoluene-
induced ARDS, the timing of corticosteroid administration had
strikingly different effects.
Early administration of steroids resulted in increased
collagen deposition, increased lung damage, and inhibition of
type II pneumocyte proliferation. Late administration, on the
other hand, prevented excessive collagen deposition.
 Systemic methylprednisolone or dexamethasone at doses of 20
or 4 mg kg-/day. respectively, improved pulmonary inflammation
and mechanics in animals with acute lung injury.
 Volpe et al; On this basis, dexamethasone (a single dose of 2.5
mg/kg) significantly reduced inflammatory cell protein content in
bronchoalveolar lavage fluid (BALF), and improved lung
compliance 24 h after injury induced by oleic acid .

25.  Kuwabara and co-workers (39),
showed that prophylactic treatment with methylprednisolone (60 mg /kg 30
min before oleic acid infusion, followed by continuous infusion until the end
of the experiments) did not attenuate oleic acid-induced acute lung injury or
the increased level of phospholipase A2 activity, leukotriene B4 and
thromboxane B2 in the BALF, but greatly reduced IL-8
 Corticosteroid at a dose of 10 mg/kg, starting on day 5 after the infection
with reovirus 1/L, and given daily until the end of the time course of the
disease, also did not attenuate the infiltration of inflammatory leukocytes,
did not suppress key cytokine/chemokine expression, and did not inhibit the
development of fibrotic changes in the lungs
 Therefore, one may argue that in addition to short duration, high
doses might have been responsible for the negative results.

26.  Hesterberg TW, Last JA. Ozone-induced acute pulmonary fibrosis in
rats.Prevention of increased rates of collagen synthesis by
methylprednisolone. Am Rev Respir Dis. 1981;123:47–52.
 Kuwabara K, Furue S, Tomita Y et al. (2001). Effect of methylprednisolone
on phospholipase A2 activity and lung surfactant degradation in acute lung
injury in rats. European Journal of Pharmacology, 433: 209-216.
 London L, Majeski E, Altman-Hamamdzic S, Enockson C, Paintlia MK,
Harley RA & London SD (2002). Respiratory Reovirus 1/L induction of
diffuse alveolar damage: pulmonary fibrosis is not modulated by
corticosteroids in acute respiratory distress syndrome in rats. Clinical
Immunology, 103: 284-295.
 Volpe BT, Lin W & Thrall RS (1994). Effect of intratracheal dexamethasone
on oleic acid-induced lung injury in the rat. Chest, 106: 583-587

27.  This seems a plausible explanation for the
negative results observed in earlier studies with
short course of high-dose MP.
Furthermore, it may be noticed that all these
studies have used high doses of MP for prevention
of ARDS.
 However, we have seen that the low-dose
corticosteroids are useful in other critical illnesses
such as septic shock.

28. CORTICOSTEROIDS FOR THE TREATMENT OF
ARDS
 Based on above results, researchers tried
prolonged course of corticosteroids in patients with
established ARDS at various stages, that is, early
(<14 days of onset of ARDS) and late phases
(after 14 days of onset of ARDS).
 1) Corticosteroids in early ards
 2) Corticosteroids in late ards.

29. Author, Drug/dosage No. death/total no. OR (95% P
Year patients with CI) valu
ARDS (%) e
Corticogro PLACEBOgr
oup
up
Bernard 0.75
Methylprednisolone 30 mg/kg 30/50 31/49
et al. (0.4- 0.74
IV 6 hourly for 24 hours. (60) (63.2)
1987 1.57)
Meduri
Protocol-based IV 2/16 5/8 0.41
et al. 0.03
methylprednisolonea. (12.5) (62.5) (0.06-99)
1998
Hydrocortisone 50 mg IV 6
Annane 0.35
hourly and 9-alpha 33/62 50/67
et al. (0.15- 0.16
fludrocortisone once a day for (53) (75)
2006 0.82)
7 days.
Steinber 0.84
Protocol-based IV 26/89 26/91
g et al. (0.40- 1.00
methylprednisoloneb. (29.2) (28.5)
2006 1.60)
Meduri 0.53
Protocol-based IV 15/63 12/28
et al. (0.21- 0.03
methylprednisolonec. (23.8) (42.8)
2007 1.21)

30.  aLoading dose of 2 mg/kg; then 2 mg/kg/d from day 1 to
day 14, 1 mg/kg/d from day 15 to day 21, 0.5 mg/kg/d
from day 22 to day 28, 0.25 mg/kg/d on days 29 and 30,
and 0.125 mg/kg/d on days 31 and 32. In patients who
were extubated prior to day14, treatment was advanced
to day 15 of drug therapy and tapered according to
schedule
 bLoading dose of 2 mg/kg of predicted body weight
followed by 0.5 mg/kg 6 hourly for 14 days; 0.5 mg/kg 12
hourly for 7 days; and then tapering of the dose
 cLoading dose of 1 mg/kg followed by an infusion of 1
mg/kg/d from day 1 to day 14, 0.5 mg/kg/d from day 15 to
day 21, 0.25 mg/kg/d from day 22 to day 25, and 0.125
mg/kg/d from day 26 to day 28. In patients who were
extubated between days 1 and 14 were advanced to day
15 of drug therapy and tapered according to schedule

31.  In all these studies, mortality (at various intervals during
therapy) was taken as main outcome to document benefit of
the therapy. Other clinically important parameters which have
been studied were
organ dysfunction score,
lung injury score, oxygenation,
duration of mechanical ventilation, and
duration of ICU stay.
Bernard et al.
tried short course of high-dose MP (30 mg/kg body weight
every six hours for 24 hours) in 50 patients with ARDS.This
study demonstrated insignificant beneficial effects of MP, such
as reduced 45-day mortality (60% vs 63%) and increased
chance of reversal of ARDS (39% vs 36%) as compared with
placebo (P = 0.07)

32.  Meduri et al.,
however, showed that prolonged corticosteroids
use (a loading dose of 1 mg/kg, followed by an
infusion of 1 mg/kg/day from day 1 to day 14, 0.5
mg/kg/day from day 15 to day 21, 0.25 mg/kg/day
from day 22 to day 25, and 0.125 mg/kg/day from
day 26 to day 28) in early ARDS ,
patients were enrolled within 72 hours of entry to
the study, thereby insuring corticosteroids early in
the course of disease,associated with significant
decrease in I.C.U motrality(20.6% vs 42.9%).

33.  large trial by ARDS clinical trial network (ARDSnet),
consisting of 180 patients with ARDS (both early [73%] and late
[27%]), showed that
MP (2 mg/kg bolus in first 24 hours, followed by a dose of 0.5 mg/kg
every 6 hours for 14 days, 0.5 mg/kg every 12 hours for 7 days, and
then tapering over 4 days) has no survival benefits.
It showed that in patients with early ARDS (enrolled 7-13 days after
onset of ARDS), there were no significant differences in 60-day
mortality (36% vs 27%; P = 0.26) in the placebo and in MP group.
Similar results were seen at 180-day with mortality of 31.9 and 31.5%
in the placebo and MP group, respectively.
Other workers have also shown that corticosteroids use have no
statistically significant mortality benefits in patients with ARDS.

34. These conflicting conclusions may be a result of differences in
characteristics of study cohort and treatment protocol of these
studies.
 Meduri ET AL;
1) This study may be criticized for poor matching between two
groups as incidence of catecholamine-dependent shock in placebo
group was nearly twice as compared with corticosteroids group
(46.4% vs 23.8%).
There is enough evidence that vasopressor use is an independent
predictor of mortality and might have contributed to increased
mortality in placebo group.
2) Second limitation of this study is that a significant percentage of
control patients crossed over to receive open-label MP; however,
data were analyzed as intention to treat analysis.
Intention to treat analysis is meant for larger trials but when same is
applied to the smaller trials, the results may be biased by protocol
violation and per protocol analysis is the best method.

35. In ARDSnet trial,
1) There was poor matching for age, gender, pneumonia,
trauma, serum creatinine, APACHE III, compliance, and
lung injury score. All these factors can affect the final
outcome.
2) in ARDSnet trial, there was rapid tapering of
corticosteroids, as compare with cohort studied by Meduri
et al. which might have contributed to increased mortality in
this trial.
3)Another important difference between these two trials is
the timing of administration of corticosteroids.

36. In ARDSnet trial corticosteroids were used during unresolving or
persistent ARDS (less than 14 day).
However, pathological ARDS has been classified as
―early‖ (from 1-7 days after onset),
―early persistent‖ (days 7-14), and
―late persistent‖ (>14 days).
Conceptually, corticosteroids administration should be more
effective during exudative phase (early phase).
Unfortunately, clinically, it is difficult to identify different phases of ARDS
without lung biopsy; however, its role in clinical practice is yet to be
defined.

37. There are many clinical parameters which are important contributors to the
morbidity associated with ARDS, such as
organ dysfunction score, lung injury score, oxygenation, duration of
mechanical ventilation, and ICU stay, as these have significant effect on the
cost of treatment.
Therefore, the effect of corticosteroids on these parameters would be
important consideration for its use in ARDS.
ARDSnet trial showed that
MP increased the number of ventilator-free days (14.1 days vs 23.6 days, P =
0.006)
Meduri et al. showed that corticosteroids use leads to significant reduction in
number days of ICU stay (7 vs 14.5 days; P = 0.007).
Similar findings has been reported by various other studies.
Length of ICU stay is an important factor which uses lots of resources.
The corticosteroids have been shown to reduce disease severity scores,
namely, the multiple organ dysfunction syndrome score and lung
injury score. These agents also improve oxygenation (PaO2/FIO2
ratios).

38. Corticosteroids in late ARDS
 Persistent ARDS at later stages is characterized by
more of fibrosis than cellular inflammation; therefore,
corticosteroid effect is expected to be different.
 It has been observed that there is significant
association between late initiation corticosteroids and
failure to improve, with 50% failure rate (P = 0.04).
 In ARDSnet trial in patients with late ARDS (LATE
STEROID RESCUE STUDY –LASRS enrolled 13 days
after onset of ARDS), corticosteroids use was
associated with increased mortality (35% vs 8%; P =
0.02) and neuromuscular weakness.
These results suggest that corticosteroid use in late stage
of ARDS probably have negative effect on final
outcome.

39. Adverse effect of
corticosteroids
 ARDSnet trial showed that rate of new
infections was lower in patients receiving MP
(22.4%) as compared with placebo (32.9%),
though results were not statistically significant
(P = 0.14).
 Meduri et al. reported similar infection rate in
both the groups and no GI bleed.
 Annane et al. showed that rates of
superinfection (13% vs 12%), GI bleed (2% vs
6%), and psychiatric disorders were similar in
both placebo and corticosteroids group

40.  Hyperglycemia was observed in ARDSnet trial with
MP group having significantly higher glucose.
 Meduri et al. have shown that patients requiring
insulin to treat hyperglycemia were similar (71.4%
vs 64.3%) with MP and placebo.
 ARDSnet trial reported similar incidence of
neuromuscular weakness in both placebo and
treatment arm (24% vs 29%). However, serious
neuromuscular weakness was observed in 9
patients, all were in MP group (P = 0.001)
 Meduri et al. showed similar incidence of
neuromuscular weakness (6.4% vs 3.6%) in
patients treated with MP as compared with
placebo.

41.  A recent meta-analysis has shown that there
was no difference in the incidence of
infection, neuromyopathy, GI bleeding, and
life-threatening complications, such as major
organ failure (heart, kidney, and liver),
between corticosteroid and placebo group.
Tang BM, Craig JC, Eslick GD, Seppelt I, McLean AS. Use of corticosteroids
in acute lung injury and acute respiratory distress syndrome: A systematic
.
review and meta-analysis. Crit Care Med 2009;37:1594–603.[PubMed]

42. Corticosteroid use current view.
 Methylprednisolone-induced down-regulation of systemic
inflammation was associated with significant improvement in
pulmonary and extrapulmonary organ dysfunction and
reduction in duration of mechanical ventilation and ICU
length of stay.
Methylprednisolone infusion in early severe ARDS: results of a
randomized controlled trial.
Meduri GU, Golden E Freire AX, Taylor E,, Zaman M, Carson SJ
GibsonM, Umberger R,chest-2009

43. Admistration of glucocorticoids
I.C.U PROTOCOL,ISCCM.
 Wigh the risk and benefits of individual
patients.
 It should be avoided in patients with
active infection.
 It is used in 2weeks of onset.
 Dose should be 1mg/kg bolus followed
by 1mg/kg/day infusion.
 Use only when paralytic agents are
discontinued.

44.  Response is seen in 5 days ,if there is
no response it may discontinued.
 If favorabel response continue for 14
days or until extubation..there after half
the dose for 7 days and then stop.
 The safety profile proven including no
added risk of infection.

45. Exclusion criteria for steroids
treatment.
 Clinical evidence of active untreated infection.
 A known undrained abcess or a known
intravascular nidus of infection. A bacterial
infection being treated with std antibiotic regimen
with exception of above.
 Disseminated fungal infection even if being
treated.
 Age <13 year
 Pregnancy
 Burns requiring skin grafting
 Patien with AIDS or AIDS defining illness.
 malignancy or other chronic disease for which 6
month mortality is estimated 50%

46. Summary
 Despite sound physiological basis, corticosteroids have not
shown clear cut benefit in management of ARDS.
 It is clear from the available data that these agents have no role
in prevention and late phase of ARDS and there is silver lining
in the management of early ARDS using these agents.
 There is distinct advantage of corticosteroids in improving organ
function score, lung injury score, and oxygenation which result
in reduction in duration of mechanical ventilation requirement
and ICU stay, although only few tudy showed mortality benefits.
 Heterogeneity of the conditions causing ARDS may be the
reason for the lack of uniformity in the results.
 More studies are required to have convincing data regarding
corticosteroid use in early ARDS before any definitive treatment
recommendation.
 Future trials with corticosteroids may be designed in such way
to make this cohort as homogenous as possible, so that we can
identify the patients who will be benefited with such therapy.

47.  Activation and Regulation of Systemic Inflammation in ARDS:
Rationale for Prolonged Glucocorticoid TherapyFree To ViewG.
Umberto Meduri, MD, FCCP; Djillali Annane, MD, PhD; George P. Chrousos, MD;
Paul E. Marik, MD, FCCP; Scott E. Sinclair, MD, FCCP
 Activation and Regulation of Systemic Inflammation in ARDS: Rationale for
Prolonged Glucocorticoid TherapyFree To ViewG. Umberto Meduri, MD, FCCP;
Djillali Annane, MD, PhD; George P. Chrousos, MD; Paul E. Marik, MD, FCCP; Scott E.
Sinclair, MD, FCCP.lungindia april 2009
 .lung inflamation in ardsfriend and foe NEJMcorticosteroids in ards : a review of
treatment and prevention evidence. G.c khillani ,vijay hadda may 2011..
 Corticosteroids in prevention and treatment of ards in adult meta analysis.BMJ.
 Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent
literature.Meduri GU, Marik PEChrousos GP Pastores SM Arlt W, Beishuizen A Bokhari F Zaloga G
AnnanD

48. Thank you.