Controversies in critical care

Dr. Balwinder Kaur Rekhi
Professor,
Department of Anaesthesiolgy
and Intensive care
GMC, Patiala

CONTROVERSIES in CRITICAL Care
Management

• The word controversy was coined from the Latin
controversia, as a composite of controversus – "turned
in an opposite direction," from contra – "against" – and
vertere – to turn, or versus (see verse), hence "to turn
against.
• Benford's law of controversy, claims that the less
factual information is available on a topic, the more
controversy can arise around that topic – and the more
facts are available, the less controversy can arise
• Controversies in critical are innumerable and never
ending
• From defintion of sepsis, to management of critical
illness, type of intervention and timing of intervention, to
end point of resuscitation

Controversies in management of
ARDS

Acute Respiratory Distress
Syndrome (ARDS)
It is an acute hypoxemic state caused by the
sudden development of diffuse injury to the
terminal respiratory units with exudative
pulmonary edema and is associated with very
high mortality.

• Advances in the knowledge of the pathophysiology of ARDS
and the prevention of further lung injury with lung-protective
therapy have led to dramatic improvements in patient survival.
• To date, rescue therapy has been found with the
 Use of high PEEP,
 Early NMB use, and
 Early and prolonged prone positioning for those with
severe ARDS.
 Referral to an expert center with ECMO capability
 The use of esophageal manometry to individually tailor
PEEP to transpulmonary pressure
 The use of iNO in severe ARDS
 The routine use of oscillatory ventilation
Despite these achievements, many questions still
remain as to how to best manage patients with the most
severe form of ARDS
Semin Respir Crit Care Med 2015;36:823–834.

Controversy in Ventilation Strategies

• It was thought that most of PEEP’s beneficial effects in ARDS
were due to its ability to increase functional residual capacity
through the recruitment of atelectatic alveoli.
• With the recognition of elevated lung interstitial pressures in
ARDS, the concept of using PEEP to improve lung compliance
began to take hold
• Higher PEEP levels are thought to generally improve
oxygenation and reduce VILI
• BUT may come at the cost of hemodynamic compromise in
the form of reduced cardiac preload and increased afterload on
the right ventricle

• Gattinoni et al in 1993 showed that incremental
levels of PEEP in ARDS patients resulted in
greater aeration of previously collapsed lung
regions.
• Amato et al found that a ventilator strategy that
included both lower tidal volumes and higher
levels of PEEP than conventional management
was associated with statistically significant
improvements in 28-day mortality, weaning
from mechanical ventilation, and incidence of
barotrauma.

• In 2008, Mercat and colleagues performed a multicenter RCT involving
767 patients with ALI named the Expiratory Pressure (EXPRESS) trial.
The interventions studied in this trial were a “minimal distention” ventilation
strategy using a PEEP of 5 to 9 cm H2O versus an “increased recruitment”
strategy that involved the titration of PEEP to achieve a plateau pressure
of 28 to 30 cm H2O.
• The EXPRESS trial again found that patients treated with higher levels of
PEEP achieved better oxygenation in terms of p:f ratio. The higher PEEP
group also had a higher number of ventilator-free days, organ failure–free
days, and better pulmonary compliance, and needed fewer rescue
therapies to assist with severe hypoxemia.
• There was no statistically significant difference seen between the
higher and lower PEEP groups with respect to 28-day mortality or in-
hospital mortality, although there did appear to be a trend toward
improved mortality for patients with ARDS (as compared with ALI as
defined by consensus criteria4) in the higher PEEP group upon post-hoc
analysis, suggesting that patients with more severe levels of hypoxemia
may benefit from higher PEEP to a greater degree than those with less
severe disease

• Secondary analyses and systematic reviews have found that
for patients with greater severity of disease as evidenced by
a p:f ratio less than 200, the use of higher PEEP appears to
be beneficial and has been associated with decreased
mortality.
• This finding may be explained by the concept that patients
with more severe ARDS have larger volumes of lung water
than their less ill counterparts, making their small airways
more susceptible to collapse and therefore available for
recruitment with PEEP.
• The use of higher PEEP in ARDS, however, does appear to
exhibit a threshold effect, as in patients with less severe
disease (p:f ratio 200–300) the use of higher PEEP strategies
has not been shown to result in improved survival and may be
associated with increased risk of harm.
• A better method of identifying patients who may benefit from
higher levels of PEEP is sorely needed.

SURVIVING SEPSIS CAMPAIGN 2016
• We suggest using higher PEEP over lower
PEEP in adult patients with sepsis-induced
moderate to severe ARDS(weak
recommendation, moderate quality of
evidence).
Intesive Care Med(2017)43:304-317

• Therefore, it is quite clear that nobody has the recipe
for some ideal PEEP setting that likely doesn’t exist.
We believe that in early full-blown ARDS the severity and
the recruitability suggest that values around 15 cmH2O
in severe patients, although non preventing the opening-
closing, are sufficient to keep open at least 70% of the
lung and to provide viable gas exchange. In moderate
ARDS, values around 10 cmH2O are indicated and in
mild ARDS even lower PEEP is more than adequate,
since the recruitability is extremely low
• Ann Transl Med 2017;5(14):288

Driving pressure in ARDS
• Recent studies have shown that ventilatory
strategies with use of low tidal volume(Vt) and
higher PEEP may be insufficient to prevent
ventilator induced lung injury in ARDS patients.
• Controversy arises in best way to titrate Vt -:
IBW, body surface area, lung size, airway
pressures, etc
• Amato et al* showed that driving pressure as
opposed to Vt and PEEP best correlated with
survival in ARDS.
*(Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M,
Talmor D, Mercat A, et al. Driving pressure and survival in the acute respiratory distress syndrome.
N Engl J Med. 2015;372(8):747–55. doi: 10.1056/NEJMsa1410639)

• Driving pressure (DP) is the difference between
the airway pressure at the end of inspiration
(plateau pressure, Ppl) and PEEP.
• Static compliance of the respiratory system (CRS)
is the quotient between Vt and driving pressure.
DP=Ppl−PEEP
CRS = Vt /(Ppl−PEEP) = Vt/DP
DP=Vt/CRS
• Thus, driving pressure represents the Vt corrected
for the patient’s CRS .
• So DP is a safety limit to adjust Vt in a better way
& hence decreased dynamic strain during
mechanical ventilation.

• Driving pressure during mechanical ventilation is
directly related to stress forces in the lung.
• Using driving pressure as a safety limit may be a
better way to adjust Vt in order to decrease
cyclic or dynamic strain during mechanical
ventilation and might better protect the lungs in
patients with more severe lung injury and low
end-expiratory lung volumes

Bugedo et al. Critical Care (2017) 21:199

CLINICAL EVIDENCE
*Amato MB, Meade MO, Slutsky AS,
Brochard L, Costa EL, Schoenfeld
DA,Stewart TE, Briel M, Talmor D, Mercat
A, et al. Driving pressure and survivalin the
acute respiratory distress syndrome. N Engl
J Med.2015;372(8):747–55.
20. Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM,
et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107–16.
21. Guerin C, Reignier J, Richard JC, Beuret P,Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, et al.
Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159–68.
22. Guerin C, Papazian L, Reignier J, Ayzac L, Loundou A, Forel JM, investigators of the A, Proseva T. Effect of driving
pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials.
Crit Care. 2016;20(1):384

*Serpa Neto A, Schmidt M, Azevedo LC, Bein T, Brochard L, Beutel G,Combes A, Costa EL, Hodgson C,
Lindskov C, et al. Associations between ventilator settings during extracorporeal membrane
oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome:
a pooled individual patient data analysis: mechanical
ventilation during ECMO. Intensive Care Med. 2016;42(11):1672–84.

Marker of severity
A high driving pressure is strongly associated with
higher mortality.
Higher driving pressures were an independent
factor associated with cor pulmonale.
Driving pressure ≥18 cm H2O, a PaO2:FiO2 ratio
<150 mmHg, and a PaCO2 ≥ 48 mmHg have been
reported to promote RV failure in patients with
ARDS caused by pneumonia

BUT
• Evidence is rather weak to support a firm
recommendation to target driving pressure as a
primary goal in mechanically ventilated patients.
• Driving pressure should be used as a
compliment to, and not a substitute for Vt
• Adjusting ventilatory support with traditional
protective parameters, Vt 6–8 mL/kg IBW and
moderate PEEP levels, and adjusting them
according to driving pressure, which should
ideally be below 15 cm H2O may prove useful
for ARDS patients

• Potential mechanisms for the putative benefits of prone
positioning include
• improvements in ventilation : perfusion matching,
• more effective regional ventilation patterns, and
• reduced compression of the small airways from the
chest wall and the heart.
• Patients in the prone positioning found to have better
oxygenation in terms of p:f ratio as well as lower airway
plateau pressures and PEEP requirements . But despite this,
patients in the prone group did not experience significantly
reduced ICU or in-hospital Mortality
• Patients in the prone position experience higher rates of
complications including need for increased sedation or
paralysis, airway obstruction, loss of venous access, and
endotracheal tube displacement.

• To date, there has only been a single RCT*, The
Proning Severe ARDS Patients (PROSEVA) study
group led by Guérin in 2013, that has shown a
significant mortality benefit, in patients treated in
the prone position for roughly 16 consecutive hours a
day. The large mortality benefit seen in this study,
when combined with the relative lack of complications
suggests that center expertise in this technique is a
major factor in its success.
• At present, the available data suggest that early
prone positioning may provide benefit as rescue
therapy to those with severe hypoxemia,
• A significant risk of positioning-related
complications will have to be taken into account
when weighing the risk to benefit ratio for each patient,
especially for centers less experienced in this
technique.

SURVIVING SEPSIS CAMPAIGN:2016
We recommend using prone over supine
position in adult patients with sepsis-induced
ARDS and a Pao2 /Fio2 ratio < 150 (strong
recommendation, moderate quality of
evidence)

EXTRACORPOREAL MEMBRANE
OXYGENATION

• The use of this high-risk and resource-intensive technique in
the treatment of severe ARDS lies in the potential opportunity
for almost complete lung rest and complete avoidance of
VILI, allowing for resolution of extreme pulmonary disease
while providing adequate gas exchange extracorporeally.
• There has only been one RCT that has shown a significant
benefit to transferring patients with severe ARDS for
consideration for ECMO at an experienced facility.
• The findings from this trial and the favorable reported survival
rates from ELSO and the German ARDSnet groups suggest
that ECMO can be safely utilized as a rescue therapy for
patients with severe ARDS, though careful selection of
patients with reversible disease and without significant
comorbidities should be performed.
• Those who do not meet these criteria have shown to have
poor survival despite ECMO therapy.

• Severe ARDS is often accompanied by significant disruptions in
ventilation–perfusion (V/Q) matching, resulting from increased
extravascular lung water and exacerbated by the limited ability of
positive pressure ventilation to reach smaller airways in the
dependent lung regions.
• The use of inhaled pulmonary vasodilators such as inhaled nitric
oxide (iNO) in ARDS is centered on the ability to dilate the
pulmonary vasculature in the areas that are being adequately
ventilated but poorly perfused, thus optimizing V/Q matching.
Studies have suggested a role of NO in limiting inflammation as
well.
• In multiple RCTs, patients receiving iNO group experienced
improvements in oxygenation over the first 4 hours of treatment
and improved oxygenation index over the first 4 days of
treatment, but these findings did not translate into a reduction in
mortality or to an increase in ventilator-free days.

• Additionally, analysis of the use of iNO in the adult
population revealed a significant increase in the risk
of renal failure defined as need for renal replacement
therapy, new raised creatinine concentration (>300
μmol/L), or raised creatinine concentration (>177 μmol/L
or >265 μmol/L).
• To date, the theoretical benefit of using iNO to optimize
V/Q matching in patients with ARDS has not translated
into more than a transient improvement in
oxygenation.
• At this point, the routine use of iNO in adults with ARDS
cannot be recommended, and its use as primary rescue
therapy for severe ARDS should not be expected to
significantly improve survival

HIGH-FREQUENCY OSCILLATORY
VENTILATION

• The specialized technique of high-frequency oscillatory
ventilation (HFOV) involves the delivery of very small tidal
volumes at high respiratory rates (3 and 15 Hz, which is 180–
900 breaths/minute).
• The use in ARDS is the potential to mitigate VILI through the
use of very small tidal volumes and relatively constant
mean airway pressures.
• EARLIER trials conducted without the use of lung-
protective ventilation in the control groups found that HFOV
was associated with a significant mortality benefit.
• BUT, in two large RCTs, published in 2013, there was no
difference in ICU mortality or the number of ventilator-
free days with the early routine use of HFOV in
moderate/severe ARDS and an increase in mortality when
compared with a lung-protective high-PEEP strategy

• Patients in the HFOV group were treated with muscle
relaxants for a mean of 12 hours longer than the control
group, and there was the longer use of sedatives and
vasopressors in this group as well.
• SURVIVING SEPSIS CAMPAIGN: 2016 - We
recommend against using high-frequency oscillatory
ventilation (HFOV) in adult patients with sepsis-induced
ARDS (strong recommendation, moderate quality of
evidence)

Why Corticosteroids ?
• Corticosteroids are a group of natural and synthetic
analogues of hormones secreted by the hypothalamic-
pituitary-adrenocortical axis.
• Corticosteroids are
• Anti-inflammatory
• Anti-fibrotic
• Immuno-modulator agent
• Considering the fact that inflammation is central to
the pathogenesis of ARDS, corticosteroids would
be a logical choice in the management.
blockade of
transcription of
various cytokines,
chemokines, cell
adhesion
molecules, and
complement
factors responsible
for development of
ARDS.

Preventive Role ?
• In a study by Weigelt et al., Methyl
Prednisolone(MP) given as 30 mg/kg IV every
6 hours for 48 hours did not prevent ARDS
but was associated with increased incidence
of infectious complications.

• In another study by Bone et al., MP (30 mg/kg every 6
hours for 4 doses) showed a trend toward increased
incidence of ARDS in MP group.
• Thus corticosteroids have no role in prevention of
ARDS in high-risk patients. On the contrary, it leads
to higher rates of ARDS, increased infectious
complications, and mortality.
• It was also found that short duration & high doses
might have been responsible for the negative results.
Corticostertoids and ARDS: lung INDIA
2011

Steroids as Therapeutic? YES
EARLY<14 days
• Study by Meduri et al., however, showed that prolonged corticosteroids
use loading dose of 1 mg/kg followed by
Infusion of 1 mg/kg/day from day 1 to day 14
Then 0.5 mg/kg/day from day 15 to day 21
Followed by 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 was associated with significantly decreased ICU mortality
(20.6% VS 42.9% ). Patients were enrolled within 72 hours of entry to the
study, thereby insuring corticosteroids early in the course of disease.
• 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)

Steroids as Therapeutic? No
Early (<14days)
In a large trial by ARDSnet, Methyl Prednisolone
2 mg/kg bolus in first 24 hrs
followed by 0.5 mg/kg every 6 hours for 14 days
Then 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 in the placebo and
in MP group.

Late (>14days) Therapeutic Role ?
• Persistent ARDS at later stages is characterized by
more of fibrosis than cellular inflammation.
• Late initiation of corticosteroids was associated with
a 50% failure rate.
• In ARDSnet trial, corticosteroids use was
associated with increased mortality and
neuromuscular weakness.
• These results suggest that corticosteroid use in late
stage of ARDS probably have negative effect on
final outcome.

So....
• Corticosteroids have not shown clear cut
benefit in prevention and late phase of ARDS.
• However, there is silver lining in the
management of EARLY ARDS using these
agents.

• ICU may experience higher infection rates due to
the severity of illness and frequent use of invasive
devices such as intravenous catheters, feeding
tubes, airways, etc.
• The practice of using protective footwear before
entering the intensive care units (ICU) is enforced
with the assumption that it lower the incidence
of bacterial floor colonization.
• It is also assumed that it may lower the chances of
infections caused due to failures in
decontamination and aseptic techniques

• Using personal protective equipment
– provides physical barrier between micro-organisms and the
wearer.
– prevent microorganisms from contaminating hands, eyes,
clothing, hair and shoes; thus preventing transmission to other
patients and staff
• Personal protective equipment includes: Gloves,
protective eye wear, Masks, Apro Gown, Shoe covers
and a Cap / Haircover
• BUT, The physical barrier has never been proven to
decrease the risk or incidence of surgical site
infections, or to decrease the bacterial counts of the
operating room floors

Earlier studies have shown that the use of barrier nursing and
protective measures by the staff in ICU will reduce the incidence
of infections due to reduced contamination.

In related studies, With the use of shoe covers no
significant difference was found in infections rate, length
of icu stay, mortality and no significant impact on
bacterial contamination of floors

THEREFORE…
• Personal protective equipment reduces but does not completely
eliminate the risk of acquiring an infection
• Staff must also be aware that use of personal protective equipment
does not replace the need to follow basic infection control measures
such as hand hygiene.
• Personal protective equipment should be chosen in accordance with
the risk of exposure.
• Also the rates of infection were more with shoe covers in a study, this
was probably due to the fact that individuals while putting on the
shoe covers the shoes contaminated their hands and thus
further transmitted the infection.
• It requires more studies to be carried out involving aspects such as
shoe change practices, restricted access, etc.; so that definite policies
can be laid down for infection control in critical care patients
Pak J Med Sci 2014 Vol. 30 No. 2

Early versus late tracheostomy for
critically ill patients.
• Long-term mechanical ventilation is the most
common situation for which tracheostomy is
indicated for patients in intensive care units (ICUs).
• 'Early’ (<10 days)and 'late' tracheostomies (>10
days)are two categories of the timing of
tracheostomy.
• Evidence on the advantages attributed to early
versus late tracheostomy is somewhat
conflicting and controversial but includes
shorter hospital stays and lower mortality rates

• Cochrane Central Register of Controlled Trials
(CENTRAL) (2013)
• (1977 participants) Showed lower mortality rates
in the early as compared with the late
tracheostomy group.
• Divergent results were reported on the time
spent on mechanical ventilation and no
differences were noted for pneumonia, but the
probability of discharge from the ICU was
higher at day 28 in the early tracheostomy
group

The main justifications used for early tracheostomy
placement is that:
Tracheostomy is far better tolerated than
endotracheal intubation.
Placing the tracheostomy might therefore allow a
reduction in sedative use which in turn might
translate into a shorter time in a critical care unit,
and in the hospital.

TracMan Randomized Trial
• Of 1032 eligible patients, Of the 455 patients assigned
to early tracheostomy, 91%received a tracheostomy
and of 454 assigned to late tracheostomy, 44%
received a tracheostomy.
Conclusions and Relevance
• Tracheostomy within 4 days of critical care admission
was not associated with an improvement in 30-day.
• A subsequent systematic review of the literature and
meta-analysis suggested that early tracheostomy
placement reduced the duration of mechanical
ventilation and hospital stay.

• Another literature from Pubmed CINAHL Embase web
of science 2013 suggested that early tracheostomy is
not associated with lower mortality in the ICU than
late or no tracheostomy.
• Might be associated with lower incidence of
Pneumonia, a finding that questions presence
practice of delaying tracheostomy beyond first week.
• Nevertheless the scarcity of a beneficial effect on long
term mortality and the potential complication
associated need careful consideration thus further
study focusing on long term outcome are needed.

RENAL REPLACEMENT THERAPY:
EARLY VS LATE

Early vs late RRT in critically ill patients :
A controversy
• Acute kidney injury (AKI) is a common yet
potentially fatal complication of illnesses among
50% of critically ill patients admitted to the
intensive care unit (ICU)
• AKI carries increased risk of morbidity and
mortality
• Although renal replacement therapy (RRT)
remains the primary supportive management
strategy for patients with severe AKI, but the
critical decision is when to initiate RRT.

Definition of early versus late RRT
initiation
The terms early and late RRT are subjective and
there is no referance definition, but in studies
,early RRT is taken as:
• Immediately after randomization.
• RRT started in less than 12 hours of admission
to ICU
• Serum BUN > 70 mg/dl or Creatinine > 7 mg/dl
• Within 8 hours of diagnosis of stage 2 AKI
(ELLAN TRIAL)

WHY Earlier initiation of RRT?
• A better control of fluid and electrolyte
imbalance
• Superior acid base homeostasis
• Removal of uremic base
• Prevention of subsequent complication
attributable to AKI
• Earlier RRT could potentially limit the kidney-
specifc and remote organ injuries due to fluid
overload, electrolyte imbalance, and systemic
inflammation

YES Early RRT ?
• Systematic review suggests that early institution
of RRT in critical ill pts. with AKI may have a
measureable benefit on survival . However,
existing evidence is based on mostly smaller
studies with important difference in design &
quality, and only two randomised trials.
Karvellas et al. Critical care 2011

Early RRT in post surgical patients
• Early initiation of RRT for patients with AKI after
cardiac surgery showed improved mortality
• Postoperative fluid overload in the surgical ICU is
very common, and these patients may benefit from
the earlier removal of excessive fluid by RRT
• Surgical patients often suffer from single organ
failure and extensive preoperative evaluation and
optimization has been done in these patients which
contributes to better outcomes in these patients

BUT
Earlier RRT may also expose the patients to
• increased risks of haemodynamic instability
• Anticoagulation induced bleeding
• Blood stream infection
• Even inflammatory or oxidative stress
induced by the dialyzer membranes.

Early RRT in septic patients
• In septic patients, earlier RRT was not found to
be associated with improvement in mortality
or RRT dependence
• In these patients,sepsis associated AKI due to
intrinsic renal lesions is only one part of the
puzzle
• Often mortality in these patients correlates with
various sepsis-induced inflammatory tissue
damage and multiorgan failure

WHY later initiation of RRT?
• It may allow more time for hemodynamic
optimization prior to RRT
• It may avoid the need for RRT and its
associated complications

• In CURRENT SYSTEMATIC review of 9 RCT
including 1627 critically ill pts., no significant survival
benefits found in pts. who underwent earlier versus
later RRT.
• Furthermore, 30-, 60-, & 90- day mortality, dialysis
dependence, & LOS in the hospital or ICU were not
lower in pts. who underwent earlier RRT in
comparison with those who underwent later RRT.
The optimal timing of RRT initiation still remains
debatable
Annals of Intensive Care:Lai et al.(2017) 7:38

• Metabolic acidosis is common in critically ill
patients
• Along with case specific treatment, improvement
of tissue perfusion and supportive measures such
as mechanical ventilation and renal-
replacement therapy are the cornerstones of
severe metabolic acidaemia management in
critically ill patients
• Because an acidotic cellular environment can
cause cellular dysfunction, intravenous sodium
bicarbonate administration to increase the pH
may be beneficial

Pathophysiology of severe metabolic
acidosis

Sodium bicarbonate treatment had no effect on the primary
composite outcome (ie, mortality by day 28 or the presence
of at least one organ failure at day 7),but decreased the need
for renal-replacement therapy.
registered with ClinicalTrials.gov, number NCT02476253

• Whether sodium bicarbonate infusion is
beneficial, ineffective, or indeed harmful to
patients with severe metabolic acidaemia
remains controversial
• Early sodium bicarbonate infusion have
bought time to avoid or delay the initiation
of CRRT therapy.
• Sodium bicarbonate counterbalances the
deleterious consequences of severe
acidosis on myocardial contractility,
systemic vasodilatation, tissue perfusion, or
cellular function

BUT…….
• Sodium bicarbonate infusion is associated
with metabolic side-effects such as
hypernatraemia, hypocalcaemia, and
metabolic alkalosis
• The reluctance to use sodium bicarbonate for
the treatment might be related to the absence
of cardiovascular effects and potential side-
effects like intracellular acidification due to
the accumulation of carbon dioxide and the
risk of hypocalcaemia.

Surviving sepsis guidelines:2016
Suggest against the use of sodium
bicarbonate therapy to improve hemodynamics
or to reduce vasopressor requirements in
patients with hypoperfusion-induced lactic
acidemia with pH ≥ 7.15 (weak recommendation,
moderate quality of evidence).

• Sedation is a critical component in the management
of the mechanically ventilated patient.
• Achieving adequate but not excessive sedation in
critically ill, mechanically ventilated patients is a
complex process.
• Although pharmacotherapy remains the mainstay for
the prevention and treatment of pain, anxiety, and
delirium (PAD) in the intensive care unit (ICU), Drugs
once thought to have a pharmacologically desirable
profile in reducing PAD have been shown to have
either little benefit, OR potential for significant risk
associated with any benefit, or in some cases, the
potential to worsen patient outcome.
*Jacobi et al. Critical Care Med 2002;30:119-41

LIGHT VERSUS DEEP SEDATION
• ICU patients frequently exhibit unpredictable
pharmacology with accumulation of drug in tissue
stores, renal and hepatic dysfunction, drug-drug
interactions, hypoproteinemia, and shock
• DEEP SEDATION may cause delayed emergence,
respiratory depression, hypotension, bradycardia,
increased protein break down, muscle atrophy,
venous stasis, pressure injury, increased cost.
• Post traumatic stress disorder (PTSD) in ICU
survivors is associated with increased sedative use,
and maintaining deeper levels of sedation is
associated with a higher incidence of delusional
memories in these patients.

• Maintaining a light level of sedation in patients with
underlying agitation may improve both short- and long
term outcomes in mechanically ventilated adults
• Increased patient alertness in the ICU facilitates patient
participation in early physical and occupational therapy,
leading to less delirium, fewer ventilator days, and
improved functional status after hospital discharge.
• BUT, The strategy of maintaining lighter sedation levels
may be associated with increased physiological stress
(e.g., increased catecholamine levels, increased oxygen
consumption)

• There are several sedation strategies to direct
sedative administration, including daily
interruption of sedation and protocolized
sedation titration algorithms.
• The goal of both of these approaches is to
reduce overall patient exposure to
“excessive” sedation, and either approach
can be applied to patients receiving either
sedative infusions or intermittent IV bolus
dosing.

DAILY INTERRUPTION OF SEDATIVE
INFUSION
• Daily interruption of continuous sedation infusions has been
shown to decrease the number of days of mechanical
ventilation, duration of ICU length of stay (LOS). It also
improves daily assessment of the neurological status of
patients undergoing mechanical ventilation. BUT, it was noted
that patients who were managed with both the hourly protocol
and daily interruption received higher mean doses of both
midazolam and fentanyl and required more benzodiazepine
“as needed” intravenous (IV) boluses, and nurses reported
that their workload was greater
• The concerns also include fear of precipitating psychologic
distress, myocardial ischemia, or drug and alcohol
withdrawal syndromes.
• Therefore, DIS creates a conundrum; it may potentially be
protective as a means to achieve awakening with an
increased likelihood of patient recall, or it may risk
further psychologic distress resulting from the nature of
the abrupt changes in level of consciousness.

• The recent “no sedation” study using morphine as the
primary opioid reported significant benefits such as more
days without requiring mechanical ventilation, and
shorter stays in both the ICU and the hospital.
• A 2-year follow-up of a subset of patients from this study
revealed no increases in the risk of long-term
psychological sequelae such as depression and
posttraumatic stress disorder.
• Interestingly, another subset analysis reported patients in
the morphine only group had increases in urine output
and fewer patients with renal impairment

• We recommend that continuous or
intermittent sedation be minimized in
mechanically ventilated sepsis patients,
targeting specific titration end points
(BPS).

• Nutrition support in critically ill adults has progress over the
years due to innovations in nutrition delivery techniques and
practices
• •Nutrition Support
–Preserve lean body mass
–Maintain immune function
–Avert metabolic complications
• Consensus is that the prefer route of nutrition is via the oral or
enteral route due to enhancement in patient outcomes
• Nutrition administered to the gut has beneficial effects,
including
– stimulating secretion of brush border enzymes,
– preserving epithelial tight cell junctions,
– enhancing immune function,
– preserving intestinal epithelium,
– mucosal mass and microvilli height and
– preventing bacterial translocation

EARLY VERSUS LATE NUTRITION
• The definition of ‘early’ has not been consistent
throughout trials. Although early nutrition is often
defined as initiating some form of nutrition within
48 h of critical illness.
• But, in recent meta-analyses, ‘early’ was defined as
the initiation of nutrition within 24 h of critical illness.
• It is unclear whether nutrition given within 24 h
will be more or less beneficial than that given
between 24 and 48 h or even later.
• Curr Opin Gastroenterol. 2014 March ; 30(2): 178–181

ENTRAL Vs PARENTRAL
• Fears about precipitating bowel ischemia
in the patient with shock, gastric residual
volumes, aspiration, ileus and obtaining
enteral access are probably the largest
obstructions to immediate enteral nutrition.
• These possible complications of enteral
nutrition, coupled with the inability to
achieve full caloric needs in many
patients, the use of parenteral nutrition
became a widespread practice in many
ICUs.

• BUT, Initiation of parenteral nutrition to meet the caloric needs
of a patient not met by enteral nutrition remains Controversial
• The EpaNIC trial attempted to answer this question by
comparing the use of early (day 2) versus late supplemental
parenteral nutrition (day 8) in a heterogeneous group of
critically ill adult patients.
• Although rates of death in the ICU and hospital and overall
survival at 90 days did not differ between groups, the late
parenteral nutrition group experienced a 6.3% relative
increase in the likelihood of being discharged from the ICU
alive, equalling a 1-day shorter median ICU length of stay.
• Patients in the late parenteral nutrition group also acquired
fewer new infections, spent less time on the ventilator
and on dialysis.
• It demonstrated that the addition of parenteral nutrition within
the first 48 h in patients only able to tolerate hypocaloric
enteral nutrition is detrimental compared with delayed
initiation of supplemental parenteral nutrition

• A recent observational study found that early use
of parenteral nutrition may be beneficial if the
patient could not receive enteral nutrition.
• However, a large randomized trial in critically ill
patients in which enteral nutrition was
contraindicated failed to demonstrate significant
benefit of protocolized early initiation of parenteral
nutrition compared with standard care
• Patients started on early parenteral nutrition did
experience 0.5 fewer days of mechanical
ventilation, but the clinical significance of this
remains questionable

LOW DOSE TROPHIC Vs FULL
CALORIE
• Although it is well accepted that some enteral nutrition is better than
no enteral nutrition, the appropriate amount of calories provided
to patients has been a topic of significant debate.
• Two large studies attempted to answer this question by comparing
early low dose trophic feeds (10 ml/h) versus early full calorie feeds
(25 ml/h with an increase every 6 h until full caloric needs met) for
the first 6 days of mechanical ventilation.The results of these studies
found no significant difference in clinical outcomes, including
days alive and off the ventilator, out of the ICU or survival,
between either arms of the study.
• Not surprisingly, there were more gastrointestinal intolerances in
the full feeding arm in both studies, but not severe enough to
warrant protocol changes or other significant interventions.
• At both 6-month and 1-year follow ups after their illnesses,
researchers found no significant differences between the low-dose
trophic feeding group versus the full dose feeding group in any
meaningful clinical outcome, including cognitive and muscle strength
measurements

• We recommend against the administration of early
parenteral nutrition alone or parenteral nutrition in
combination with enteral feedings (but rather initiate
early enteral nutrition) in critically ill patients with sepsis
or septic shock who can be fed enterally (strong
recommendation, moderate quality of evidence).
• We recommend against the administration of
parenteral nutrition alone or In combination with enteral
feeds (but rather to initiate IV glucose and advance
enteral feeds as tolerated) over the first 7 days in
critically ill patients with sepsis or septic shock for whom
early enteral feeding is not feasible (strong
recommendation, moderate quality of evidence).

• We suggest the early initiation of enteral
feeding rather than a complete fast or only IV
glucose in critically ill patients with sepsis or
septic shock who can be fed enterally (weak
recommendation, low quality of evidence).
• We suggest either early trophic/hypocaloric
or early full enteral feeding in critically ill
patients with sepsis or septic shock; if
trophic/hypocaloric feeding is the initial strategy,
then feeds should be advanced according to
patient tolerance (weak recommendation,
moderate quality of evidence).

DEFINITION OF SEPSIS
• International consensus conference (1992)
defined
Sepsis as a subgroup of SIRS when infection
was determined to be the cause of inflammatory
process.

Findings from a new retrospective study by
Kaukonen et al published in the New England
Journal of Medicine (2015), challanged these
definitions as of the 109663 patients identified
with organ failure and infection, 13278 (12.1% )
did not meet the two SIRS criteria.

Surviving Sepsis Campaign guidelines
published in 2012 define sepsis as
“ The presence ( probably or documented ) of
infection together with systemic manifestations
of infection.”

Sepsis is now defined as life threatening organ
dysfunction caused by a dysregulated host
response to infection.
Septic shock is a subset of sepsis with circulatory
and cellular/metabolic dysfunction associated
with a higher risk of mortality.
*Intensive Care Med(2017) 43:304-377

The new sepsis definitions shift emphasis from
SIRS to organ dysfunction. They use the
Sequential Organ Failure Assessment (SOFA)
score as a simple, tested method of quantifying
organ dysfunction.
SSC: International guidelines for management of
sepsis & septic shock: 2016

• Vasopressor-dependent hypotension and
increased lactate levels are required in the
absence of hypovolemia to diagnose septic
shock.
• The new sepsis definitions also propose QUICK
SOFA (qSOFA) criteria (>2 of hypotention,
tachypnoea, and /or altered mental status) for
efficient bedside screening to identify potentially
infected pts. at risk for poor outcomes in out-of-
hospital , emergency dept. and general ward
settings.

BUT
The emphasis on organ dysfunction may lead to
delays in identifying serious infections before
they progress to organ dysfunction.
Furthermore, the SOFA score has primarily
been used as a research tool and is
unfamiliar to many clinicians.

System-based Approaches to sepsis
Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New
England Journal of Medicine, 345(19), 1368–1377.

EGDT RESUSCITATION
 Begin at onset of hypotension or lactate >
4mmol/l
 Do not delay while awaiting ICU admission
 Initial bolus is 30 ml/kg crystalloid

System-based Approaches to sepsis
Early-Goal Directed Therapy
INCLUSION = SEPSIS AND [BP < 90 after fluid OR Lactate > 4]
CVP 8-12 Fluids CVP 8-12
MAP > 65 Vasopressors MAP > 65
Transfusions
Dobutamine
ScvO2 > 70%
49% mortality 33% mortality
Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., et al.
(2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New
England Journal of Medicine, 345(19), 1368–1377.
Control Intervention EGDT

CONTROVERSY
• Severe Sepsis and Septic Shock Trials (ProCESS, ARISE,
ProMISe):
Between 2014 and 2015, 3 independent, multicenter, randomized
controlled trials evaluated early goal-directed therapy (EGDT) in
severe sepsis and septic shock: Protocolized Care for Early
SepticShock (ProCESS) from the United States; Australasian
Resuscitation in Sepsis Evaluation (ARISE), and Protocolised
Management in Sepsis (ProMISe) in the United Kingdom. All 3 trials
confirmed that there was no survival benefit of EGDT compared
to usual resuscitation.
• PMID: 28284298 DOI: 10.1016/j.ccc.2016.12.004

• It has been well established that there is no
relationship between the CVP and intravascular
volume and no relationship between the CVP
and fluid responsiveness. Consequently, I
believe that the CVP should not be used to
guide fluid therapy.
Marik PE, Chest 2014

CONCLUSION
• All one can derive from these trials are :-
• CVP is not mandatory but if central line is in place
you can use it.
• EGDT: does not increase mortality or morbidity.
• You cannot say that EGDT is dead , but sepsis
care is more aggressive. ( GLOBAL SEPSIS
ALLIANCE CRITICAL CARE EMERGENCY
MED.)

GLYCEMIC CONTROL IN
CRITICALLY ILL PATIENTS?-
A CONTROVERSY

In-hospitalMortalityRate
(%)
New
Hyperglycemia
Known
Diabetes
Normoglycemia
P<0.01
P<0.01
MORTALITY IN ICU PATIENTS
Umpierrez GE, et al. J Clin Endocrinol
Metab. 2002;87:978-982

Stress Hyperglycemia
• Hyperglycemia occurs frequently in critically ill
patients,including in patients with previously
known or unrecognised type 1 or 2 diabetes
mellitus,or in those with normoglycemia
(STRESS HYPERGLYCEMIA). In trials of
intensive glucose control, over 98% of patients
in ICUs will have a blood glucose recorded
above the upper limit for normal for fasting.*
• *NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in
critically ill patients. N Engl J Med 2009; 360:1346-9; PMID:19318385.

Strict Glycemic Control(SGC)
OR
Tight glycemic control(tgc)
Maintainence of the blood glucose level in the range
of 80-110 mg/dl with help of Dose variable and
Intensive Insulin Therapy(IIT)

The concept of strict glycemic control
was introduced by Van den Burghe
• In twelve months period, in Surgical ICU
• In the patients enrolled in the study (N=1548)
• With intensive insulin therapy (IIT) when the
blood glucose levels were maintained < 110 mg/
dl
The conventional group had 1.74 times more mortality
IIT patients had 34% reduction in mortality,
46% reduction in sepsis,
41% reduction in dialysis,
50% reduction in the blood transfusion
44% reduction in polyneuropathy.

Building Evidence
• This was followed by few encouraging studies by
• • Lazar et al.
• • Juvela et al.
• • Krinsley et al.
• Which were supporting the use of IIT orstrict or tight
control of glucose improving the outcomes.
*Lazar HL, Chipkin SR, Fitzgerald CA, et al. Tight glycemic control in diabetic coronary artery bypass graft patients improves
perioperative outcomes and decreases recurrent ischemic events. Circulation. 2004; 109: 1497–1502.
• Juvela S, Siironen J, Kuhmonen J. Hyperglycemia, excess weight, and history of hypertension as risk factors for poor
outcome and
cerebral infarction after aneurysmal subarachnoid hemorrhage J of Neurosurgery 2005;102(6 ) :998-1003
• Krinsley JS et al. Effect of an intensive glucose management protocol on the mortality of criticall illadult patients. Mayo
Clinics
Proceedings 2004; 79: 992-1000.

Beginning of Conflict
Then Van den Burghe et al. came back again in 2006,
• “IIT and understanding it’s impact in medical ICU
patients”
• Could not convincingly prove significant reduction in,
in-hospital mortality
• 40% in conventional treatment vs. 37.7% in IIT group,
(p=0.33)
The saving grace was
• significant reduction in morbidity by prevention of new kidney
injury
• earlier ventilator weaning
• so logically earlier ICU and hospital discharge.
This led to serious introspection, debates & further trials.
Van den Berghe G, Woulters P, Hermans G, et al. Intensive Insulin Therapy in the medical ICU. N.Eng.J.
Med 2006,354(5): 449-61.

Crescendo of Conflict
• To put to rest all these controversies, NIH
funded a study from 2003-2008
• It appeared that TGC had 25% higher
mortality
• The study was voluntarily discontinued
• Welch HG. Schwartz LM, Woloshin S. Over diagnosed, making people sick in the pursuit of
health. Publishers:Beacon Press, Massachusetts, c 2011.

Final Straw that broke camel’s back
NICE-SUGAR study (Normoglycemia In Intensive Care
Evaluation-Survival Using Glucose Algorithm Regulation
study)
• Published in 2009,
• 38 tertiary hospitals and 4 community hospitals,
• 6030 patient evaluable in the period of 5 years
(December 2004-November 2008)
• Again the groups were Intensive vs. Conventional;
i.e. 81 to 108 mg per dl vs. <180 mg per dl glucose levels
were the targets
• The patients were randomized but not blinded
• The mean age was 60 years with equal distribution by
gender and Apache II scoring of 21 in each group.
• NICE-SUGAR Study: Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Intensive versus conventional glucose
control in critically ill patients.N Engl J Med 2009, 360:1283-1297.

NICE SUGAR STUDY……….
Results were very revealing:
• Mortality at 90 days was 27.5% in IIT group
vs. 24.9% in conventional group (CT)
(Odds Ratio- O.R. 1.14, p=0.02)
• Mortality at 28 days was 22.3% in IIT group
vs. 20.8% in CT ( O.R. 1.09, p=0.17)
• Location of death in ICU
65.9% in IIT vs. 66.3% in CT
In-hospital 26.9% IIT vs. 26.2% CT

 Blood glucose target: 140-180 mg/dL
 In selected critical;ly ill patients with hyperglucemia
(such as post cabg and uncomplicated surgical
procedures), blood glucose target:110-140mg/dl
 Intravenous insulin infusion prefered
 Hypoglycemia
 Reassess the regimen if blood glucose level is <100
mg/dL
 Modify the regimen if blood glucose level is <70
mg/Dl.Cessation of insulin infusion and management
of hypoglycemia should be ensured.Moghissi ES, et al. Endocr Pract. 2009;15:353-369

पुस्तकस्था तु या विद्या परहस्तगतं धनं।
काययकाले समुत्पन्ने न सा विद्या न तद् धनं॥
The knowledge which is residing in the book and the
money which is in possession of someone else are of
no use if during the time of need they don't serve their
purpose.

Controversies in critical care

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