Process trial s sc 2012

Critical care 1

Topic : Protocol based care for early septic shock trial May 2014

Surviving Sepsis Campaign 2012

Response of SSC to ProCESS

Dr. Ankur Gupta

J.L.N.Medical College,Ajmer

Why the need ??

ProCESS trial was conducted to determine whether the findings of EGDT Trial, in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, were generalizable and whether all aspects of the protocol were necessary.

METHODS

Study oversight

Multicenter, randomized trial at 31 hospitals in the United States.

Sites and Patients

Patients in the emergency department in whom-

• sepsis was suspected according to the treating physician,

• ≥ 18 years of age,

• who met ≥2 criteria for SIRS or refractory hypotension,

• serum lactate level of ≥4 mmol/liter .

Patients

Study duration - March 2008 through May 2013.

1341 patients for the analysis:

• 439 in the protocol based EGDT group,

• 446 in the protocol-based standard-therapy group

• 456 in the usual care group.

Study Interventions

Patients were randomly assigned, as 1:1:1

Protocol based EGDT group: The protocol prompted placement of a central venous catheter.

Protocol-based standard group set of 6-hour resuscitation instructions, but the components were less aggressive than those used for EGDT group.

Usual-care group, the bedside providers directed all care, with the study coordinator collecting data but not prompting any actions.

Outcome Measures

Primary outcome -- Rate of in-hospital death from any cause at 60 days.

Secondary outcomes -- Rate of death from any cause at 90 days and cumulative mortality at 90 days and 1 year.

Other outcomes –

• Duration of acute cardiovascular failure ,

• Acute respiratory failure,

• Acute renal failure,

• The duration of the stay in the hospital and ICU,

• Hospital discharge disposition

Statistical Analysis

• Analysis done according to the intention to-treat principle.

• For the primary outcome, design tested sequentially whether protocol-based resuscitation was superior to usual care and, if it was, whether protocol- based EGDT was superior to protocol-based standard therapy.

Resuscitation

• During the first 6 hours, the volume of IV fluids administered differed significantly among the groups (2.8 liters in the protocol-based EGDT group, 3.3 liters in the protocol-based standard-therapy group, and 2.3 liters in the usual care group (P<0.001).

• Patients in the protocol-based standard-therapy group received the greatest volume initially and overall, patients in the usual care group received the least volume of fluid, and patients in the protocol-based EGDT group received fluid at the most consistent rate.

• More patients in the two protocol-based groups than in the usual-care group received vasopressors

Outcomes

• By day 60, mortality was-

92 patients in the protocol based EGDT group(21.0%),

81 in the protocol based standard-therapy group (18.2%),

86 in the usual-care group (18.9%).

• There is no significant difference in 90-day mortality or in the time to death up to 90 days and 1 year

• The incidence of acute renal failure was higher in the protocol-based standard therapy group than in the other two groups (6.0% in the protocol-based standard-therapy group vs. 3.1% in the protocol-based EGDT group and 2.8% in the usual-care group, P = 0.04).

• The rate of admission to the intensive care unit was higher in the protocol-based EGDT group than in the other two groups.

• There were no significant differences in the incidence and duration of cardiovascular / respiratory failure,length of stay / the discharge disposition.

CONCLUSION

• No significant advantage, with respect to mortality or morbidity, of protocol-based resuscitation over bedside care that was provided according to the treating physician’s judgment.

• No significant benefit of the mandated use of central venous catheterization and central hemodynamic monitoring in all patients.

International Guidelines for Management of Severe Sepsis and

Septic Shock 2012

Initial Resuscitation and Infection Issues

Protocolized, quantitative resuscitation of patients with sepsis- induced tissue hypoperfusion (1C)

Goals during the first 6 hrs of resuscitation:

a) Central venous pressure (CVP) 8–12 mm Hg

b) Mean arterial pressure (MAP) ≥ 65 mm Hg

c) Urine output ≥ 0.5 mL/kg/hr

d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively

Diagnosis

Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins ) (1C)

Use of the 1,3 beta-D-glucan assay (2B), mannanand anti-mannan antibody assays (2C)

Imaging studies performed promptly to confirm a potential source of infection (UG).

Antimicrobial Therapy

Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis (1B).

Antimicrobial regimen should be reassessed daily for potential de-escalation (1B).

Source Control

A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible (1C).

Hemodynamic Support and Adjunctive Therapy

Fluid Therapy of Severe Sepsis

Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (1B).

Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (1B).

Fluid Therapy of Severe Sepsis

Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent).

More rapid administration and greater amounts of fluid may be needed in some patients (1C).

Vasopressors

Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg (1C).

Norepinephrine as the first choice vasopressor(1B).

Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (2B).

Mechanical Ventilation of Sepsis-Induced ARDS

Target a TV of 6 mL/kg predicted body weight in patients with sepsis-induced ARDS ( 1A vs. 12 mL/kg).

Plateau pressures upper limit goal for plateau pressures in a passively inflated lung be ≤30 cm H2O (1B).

PEEP be applied to avoid alveolar collapse at end expiration (atelectotrauma) (1B).

Mechanical Ventilation of Sepsis-Induced ARDS

Head of the bed elevated to 30-45 degrees to limit aspiration (1B).

A conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypoperfusion (1C).

Mechanical Ventilation of Sepsis-Induced ARDS

weaning protocol be in place when patients satisfy the following criteria: a) arousableb) hemodynamically stable (without vasopressoragents)c) no new potentially serious conditions;d) low ventilatory and end-expiratory pressure requirements and e) low Fio2 requirements which can be safely delivered with a face mask or nasal cannula.

If the spontaneous breathing trial is successful, consideration should be given for extubation (1A).

Sedation, Analgesia, and Neuromuscular Blockade

Continuous or intermittent sedation be minimized in ventilated sepsis patients (1B).

Neuromuscular blocking agents (NMBAs) be avoided if possible in the septic patient without ARDS. If NMBAs must be maintained, either intermittent bolus as required or continuous infusion with train-of-four monitoring (1C)

Glucose Control

Commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL ,targeting an upper blood glucose ≤180 mg/dL (1A).

Blood glucose values be monitored every 1–2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter (1C).

Deep Vein Thrombosis Prophylaxis

Patients with severe sepsis receive daily pharmaco prophylaxis (1B), with subcutaneous low-molecular weight heparin (LMWH) or UFH.

If creatinine clearance is <30 mL/min, use dalteparin (1A) or another form of LMWH that has a low degree of renal metabolism (2C) or UFH (1A).

Stress Ulcer Prophylaxis

Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to patients with severe sepsis/septic shock who have bleeding risk factors (1B).

Setting Goals of Care

Discuss goals of care and prognosis with patients and families (1B).

Incorporate goals of care into treatment and end-of-life care planning, utilizing palliative care principles where appropriate (1B).

SURVIVING SEPSIS CAMPAIGN BUNDLES

TO BE COMPLETED WITHIN 3 HOURS:1) Measure lactate level2) Obtain blood cultures prior to administration of antibiotics3) Administer broad spectrum antibiotics4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L

TO BE COMPLETED WITHIN 6 HOURS:5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) 65 mm Hg6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate 4 mmol/L (36 mg/dL):- Measure central venous pressure (CVP)*- Measure central venous oxygen saturation (ScvO2)*7) Remeasure lactate if initial lactate was elevated*

*Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate.

Surviving Sepsis Campaign Responds to ProCESS Trial

(1) The ProCESS trial reflects the consensus that early diagnosis of septic shock is essential. Notably, all groups in the study received on average more than 2 liters of fluid prior to randomization and more than 75% received antibiotics prior to randomization--both elements of the 3-hour Surviving Sepsis Campaign bundle.

(2) ProCESS does not address the protocolizedmanagement of patients with severe sepsis without septic shock, a group of patients for whom early detection and treatment remain critical.

Further, the ProCESS results have no impact on the 3-hour bundle

(3) The 18% mortality rate in the “usual care” arm of ProCESS illustrates a dramatic change in the management and outcomes of patients with septic shock.

In comparison, septic shock mortality was 46.5% in the 2001 early goal-directed therapy trial by Rivers.