NEJM

1. RESTRICTION OF INTRAVENOUS FLUID IN ICU
PATIENTS WITH SEPTIC SHOCK
NEJM

2. Shock
● Shock is the clinical condition of organ dysfunction resulting from an
imbalance between cellular oxygen supply and demand
● Sepsis – a life threatening organ dysfunction caused by a dysregulated host
response to infection
● Septic shock – a subset of sepsis in which underlying circulatory and cellular /
metabolic abnormalities leads to substantially increased mortality risk

3. ● CRITERIA - Suspected( documented ) infection plus vasopressor therapy
needed to maintain mean arterial pressure at >65 mmHg and serum lactate >
2 mmol / l despite adequate fluid resuscitation

4. CLASSIFICATION OF SHOCK
1. Distributive
a. Septic shock
b. Pancreatitis
c. Severe burns
d. Anaphylactic shock
e. Neurogenic shock
f. Endocrine shock
Adrenal crisis
2. Cardiogenic
a. Myocardial infarction
b. Myocarditis
c. Arrhythmia
d. Valvular
i. Severe aortic valve insufficiency ii. Severe
mitral valve insufficiency

5. 3. Obstructive
a. Tension pneumothorax
b. Cardiac tamponade
c. Constrictive pericarditis
d. Pulmonary embolism
e. Aortic dissection
4. Hypovolemic
a. Hemorrhagic
i. Trauma
ii. Gl bleeding
iii. Ruptured ectopic pregnancy
b. Gl losses,BURNS,POLYURIA
C

7. Elements of Care in Sepsis and Septic Shock:
Sepsis and septic shock constitute an emergency, and treatment should begin right away.
Resuscitation with IV crystalloid fluid (30 mL/kg) should begin within the first 3 h.
Saline or balanced crystalloids are suggested for resuscitation.
The clinical examination does not clearly identify the diagnosis, hemodynamic assessments
(e.g., with focused cardiac ultrasound) can be considered.
In patients with elevated serum lactate levels, resuscitation should be guided toward normalizing
these levels when possible. In patients with septic shock requiring vasopressors, the
recommended target mean arterial pressure is 65 mmHg.
Hydroxyethyl starches and gelatins are not recommended.

8. Norepinephrine is recommended as the first-choice vasopressor.
Vasopressin should be used with the intent of reducing the norepinephrine dose.
The use of dopamine should be avoided except in specific situations-e.g., in those patients at
highest risk of tachyarrhythmias or relative bradycardia. Dobutamine use is suggested when
patients show persistent evidence of hypoperfusion despite adequate fluid loading and use of
vasopressors.
Red blood cell transfusion is recommended only when the hemoglobin concentration decreases
to <7.0 g/dL in the absence of acute myocardial infarction, severe hypoxemia, or acute
hemorrhage.

9. Infection Control
appropriate samples for microbiologic cultures should be obtained before antimicrobial therapy is started. antibiotics
should be initiated as soon as possible (within 1 h); specifically, empirical broad-spectrum therapy should be used to cover
all likely pathogens Antibiotic therapy should be narrowed once pathogens are identified and their sensitivities determined
and/or once clinical improvement is evident. If needed, source control should be undertaken as soon as is medically and
logistically possible.
Daily assessment for de-esclation of antimicrobial therapy should be conducted.

10. ● Respiratory Support
Atarget tidal volume of 6 mL/kg of predicted body weight (compared with 12 mL/kg in adult
patients) is recommended in sepsis-induced ARDS. A higher PEEP rather than a lower
PEEP is used in moderate to severe sepsis-induced ARDS.
Severe ARDS (Pao/Fio, <150 mmHg), prone positioning is recommended, and recruitment
maneuvers and/or neuromuscular blocking agents for 48 h are suggested. A conservative
fluid strategy should be used in sepsis-induced ARDS if there is no evidence of tissue
hypoperfusion.
Routine use of a pulmonary artery catheter is not recommended. Spontaneous breathing
trials should be used in mechanically ventilated patients who are ready for weaning

11. General Supportive Care
Patients requiring a vasopressor should have an arterial catheter placed as soon as Possible
Hydrocortisone is not suggested in septic shock if adequate fluids and vasopressor therapy can restore
hemodynamic stability. Continuous or intermittent sedation should be minimized in mechanically
ventilated sepsis patients, with titration targets used whenever possible.
insulin dosing initiated when two consecutive blood glucose levels are >180 mg/dL
Continuous or intermittent renal replacement therapy should be used in patients with sepsis and acute
kidney injury. Pharmacologic prophylaxis (unfractionated heparin or low-molecular-weight heparin)
against venous thromboembolism should be used in the absence of contraindications.
Stress ulcer prophylaxis should be given to patients with risk factors for gastrointestinal bleeding.

12. a study conducted by T S Meyhoff et al and article published on june 17 th 2022
has been reviewed here

13. What They Did:
• Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in the Intensive Care (CLASSIC)
31 ICUs in Denmark, Norway, Sweden Switzerland, Italy, the Czech Republic, the United Kingdom and Belgium
Patients with septic shock in the ICU randomized to:
Restricted IV Fluids At least 1L (Given in 250 to 500mL boluses)
Could only give fluids under certain circumstances:
• Severe hypoperfusion
• Defined as a plasma lactate 24mmol/L
MAP <50mmHg despite infusion of vasopressor Or ionotropes
• Urinary output <0.1mL/kg/hr during 1st 2 hours after randomization
Fluid losses (Gl or drains)
Dehydration or electrolyte deficiency if enteral route contraindicated
Ensure a total daily fluid intake of 1L including fluids with medication and nutrition if
enteral route contraindicated

14. • Standard IV Fluids: Standard IV fluid therapy
• No upper limit was set for the amount of IV fluids
• Could only give fluids under any of the following 3 conditions:
• As long as patient had improved hemodynamic factors
Replace expected or observed losses or to correct dehydration or electrolyte derangements
• Maintenance fluids
• Enteral/oral fluids, nutrition (enteral or parenteral), and fluid used as a medium for administration of
meds were allowed in both groups
Albumin only used following abdominal paracentesis

15. Outcomes:
• Primary: Death from any cause within god after randomization
Secondary:
• Serious Adverse Events (Cerebral, cardiac, intestinal, or limb ischemic events OR a
new episode of severe kidney injury)
Number of days alive without life support (circulatory support, invasive mechanical
ventilation, or renal replacement therapy) at god
• Number of days alive and out of the hospital at god

16. Inclusion:
• Adults (218 years of age)
In the ICU
• Had septic shock (Defined as a suspected or confirmed infection, a plasma lactate level of 22mmol/L. receipt of ongoing infusion of a vasopressor
or inotropic agent, and receipt of at least 1L of IV fluids in 24 hours before screening)
• Onset of shock within 12hrs before screening
Exclusion:
• Septic shock >12hrs
. No consent
Life-threatening bleeding
• Acute burn injury involving >10% of body surface area
Pregnant

17. Results
1554 patients enrolled
• 1545 (99.4%) of patients enrolled had data available for primary outcome
Median age: 70 years
Median time from ICU admission to randomization: 3hrs
Median predicted god mortality 40%
Admission from ED/Prehospital 39%
Primary focus of infection GI (37%), Pulmonary (27%) and Urine (16%)
⚫ Median volume of IV fluids 24hrs prior to randomization =3100mL
• Use of systemic glucocorticoid: 28%
• Use of respiratory support =50%
Median Fluids Received (Excluding fluids administered with meds and nutrition):
Restricted IV Fluids: 1798mL (Range: 500 to 4366mL)
Standard IV Fluids: 3811mL (Range: 1861 to 6762mL)
Median Cumulative Volume of All Fluids Given in ICU:
• Restricted IV Fluids: 10.433mL
Standard IV Fluids: 12.747mL

18. • Death within god of Randomization (Primary Outcome):
• Restricted IV Fluids: 42.3%
• Standard IV Fluids: 42.1%
• Adjusted Absolute Difference: 0.1%; 95% CI 04.7 to 4.9: p = 0.96
Findings consistent after risk factors at baseline adjustment, per-protocol analysis (This is important due to the imbalance in protocol violations),
and predefined subgroup analyses
• Serious Adverse Events:
• Restricted IV Fluids: 29.4%
• Standard IV Fluids: 30.8%
Adjusted Absolute Difference: -1.7%; 99% CI -7.7 to 4.3: p = 0.46
At god after randomization number of days alive without life support and days alive and out of the hospital were similar in the two groups

19. METHODS
>18 Years of age who wer in ICU and had SEPTIC SHOCK
1. Suspected or confirmed infection
2. plasma lactate (2 mmol per liter/ 18 mg per dl)
3. ongoing vasopressor or inotropic agent
4. atleast 1 liter of IV fluids in 24 hours
total -1554 patients with 770 into restricted fluid group and 784 in standard fluid group

20. RESTRICTED fluid group
intravenous fluid should be given if the patient had severe hypoperfusion
1. plasma lactate (>4 mmol per liter / 36 mg per dl)
2. MAP below 50 mm hg ,despite infusion of vasopressor or inotropic agent
3. Urine output less then 0.1 ml/kg/hr during first 2 hours
4. iv fluids given to replace fluid loses (git loss,dehydration,electrolyte
deficiency)
STANDARD FLUID GROUP - NO RESTRICTION OF IV FLUIDS

21. RESULTS
● During the 90 day trial period the median cumulative volume of IV
fluids,excluding fluid administrated through medications and nutrition was
● 1798 ml in restrictive fluid group ( cumulative volume-10433 ml)
● 3811 in standard fluid group (cumulative volume 12747 ml)