# Ventilation and Supportive Care in Sepsis — SCCM/ESICM 2021

## Mechanical Ventilation in Sepsis-Induced ARDS

### Low Tidal Volume Ventilation

The SSC **recommends** using a **low tidal volume strategy of 6 mL/kg predicted body weight** (range 4-8 mL/kg PBW) over higher tidal volume ventilation (> 10 mL/kg PBW) for adults with sepsis-induced ARDS (Strong recommendation, High quality of evidence).

- The ARDSNet ARMA trial (2000) established that 6 mL/kg PBW ventilation reduces mortality compared to 12 mL/kg PBW (31% vs 39.8% mortality; p = 0.007).
- Target: **plateau pressure < 30 cmH2O**.
- Permissive hypercapnia may be required to maintain low tidal volumes.
- Predicted body weight (PBW) calculation:
  - **Males:** 50 + 2.3 x (height in inches - 60) kg
  - **Females:** 45.5 + 2.3 x (height in inches - 60) kg

### Plateau Pressure Limit

The SSC **recommends** targeting an upper limit for **plateau pressures of 30 cmH2O** over higher plateau pressures in adults with sepsis-induced ARDS (Strong recommendation, Moderate quality of evidence).

- If plateau pressure exceeds 30 cmH2O despite a tidal volume of 6 mL/kg PBW, reduce tidal volume further to 4 mL/kg PBW.
- Consider chest wall compliance in obese patients or those with abdominal compartment syndrome; elevated plateau pressure may reflect chest wall mechanics rather than lung overdistension.

### PEEP Strategy

The SSC **suggests** using a **higher PEEP strategy** over a lower PEEP strategy for adults with sepsis-induced moderate-to-severe ARDS (Weak recommendation, Moderate quality of evidence).

- Higher PEEP improves oxygenation and may reduce ventilator-induced lung injury in moderate-to-severe ARDS (PaO2/FiO2 < 200 mmHg).
- PEEP titration should use a systematic approach: FiO2/PEEP tables (ARDSNet), best compliance-guided PEEP, or oesophageal pressure-guided PEEP.
- Note: Individual-patient meta-analysis suggests benefit primarily in moderate-to-severe ARDS; in mild ARDS, higher PEEP may not improve outcomes and may cause haemodynamic compromise.

> **OpenMedicine Calculator:** `calculate_sofa` -- available via MCP for automated SOFA scoring. The respiratory component uses the PaO2/FiO2 ratio to grade respiratory dysfunction.

### Prone Positioning

The SSC **recommends** using **prone positioning for > 12 hours per day** for adults with sepsis-induced moderate-to-severe ARDS (Strong recommendation, Moderate quality of evidence).

- The PROSEVA trial demonstrated a significant mortality reduction with prone positioning >= 16 hours/day in severe ARDS (PaO2/FiO2 < 150 mmHg): 16% vs 32.8% mortality (p < 0.001).
- Prone positioning improves ventilation-perfusion matching, reduces ventilator-induced lung injury, and improves chest wall mechanics.
- Contraindications to prone positioning include: spinal instability, open abdominal wounds, haemodynamic instability requiring active intervention.
- Typical protocol: proning sessions of **16 hours** followed by **8 hours** supine.

### Recruitment Manoeuvres

The SSC **suggests against** routine use of **recruitment manoeuvres** in adults with sepsis-induced moderate-to-severe ARDS (Weak recommendation, Moderate quality of evidence).

- The ART trial demonstrated increased mortality with aggressive recruitment manoeuvres (incremental PEEP titration) compared with standard low-PEEP strategy.
- Recruitment manoeuvres may be considered on a case-by-case basis but should not be performed routinely.

### Neuromuscular Blocking Agents (NMBA)

The SSC **suggests against** routine use of continuous **NMBA infusion** for adults with sepsis-induced moderate-to-severe ARDS without refractory hypoxaemia (Weak recommendation, Moderate quality of evidence).

- The ROSE trial (re-evaluating cisatracurium in ARDS) showed no benefit of early continuous cisatracurium for 48 hours compared with a lighter sedation strategy.
- NMBA may still be considered for refractory hypoxaemia (PaO2/FiO2 < 150 despite optimised ventilation and prone positioning) or significant ventilator dyssynchrony.

## Blood Products

### Red Blood Cell Transfusion

The SSC **recommends** a **restrictive transfusion strategy** for adults with sepsis or septic shock (Strong recommendation, Moderate quality of evidence).

- Transfusion trigger: **haemoglobin < 7.0 g/dL** (< 70 g/L) in the absence of:
  - Acute myocardial ischaemia
  - Severe hypoxaemia
  - Acute haemorrhage
- The TRISS trial demonstrated that a restrictive strategy (trigger 7.0 g/dL) was non-inferior to a liberal strategy (trigger 9.0 g/dL) in septic shock patients.
- Target haemoglobin: **7.0-9.0 g/dL** after transfusion.

## Blood Glucose Management

The SSC **recommends** initiating insulin therapy at a glucose level of **>= 180 mg/dL (10 mmol/L)** (Strong recommendation, High quality of evidence).

- Target blood glucose range: **144-180 mg/dL (8-10 mmol/L)** after insulin initiation.
- The NICE-SUGAR trial demonstrated that intensive insulin therapy (target 81-108 mg/dL) was associated with increased mortality and severe hypoglycaemia compared with conventional control (target <= 180 mg/dL).
- Blood glucose should be monitored **every 1-2 hours** until stable, then every 4 hours.
- Avoid blood glucose levels < 70 mg/dL (hypoglycaemia); severe hypoglycaemia (< 40 mg/dL) is associated with increased mortality.

## Venous Thromboembolism (VTE) Prophylaxis

The SSC **recommends** using pharmacological VTE prophylaxis unless contraindicated (e.g., active bleeding, recent intracranial haemorrhage, severe thrombocytopenia) (Strong recommendation, Moderate quality of evidence).

- The SSC **recommends** using **low-molecular-weight heparin (LMWH) over unfractionated heparin (UFH)** for VTE prophylaxis (Strong recommendation, Moderate quality of evidence).
  - LMWH: e.g., enoxaparin 40 mg subcutaneously once daily.
  - UFH: 5,000 units subcutaneously every 8-12 hours (alternative when LMWH is contraindicated, e.g., CrCl < 30 mL/min).
- **Mechanical prophylaxis** (intermittent pneumatic compression devices) should be used when pharmacological prophylaxis is contraindicated.
- The SSC **suggests against** combining pharmacological and mechanical prophylaxis routinely (Weak recommendation, Low quality of evidence).

## Stress Ulcer Prophylaxis

The SSC **suggests** providing stress ulcer prophylaxis for adults with sepsis or septic shock who have **risk factors for gastrointestinal bleeding** (Weak recommendation, Moderate quality of evidence).

- Risk factors for GI bleeding include: coagulopathy, mechanical ventilation > 48 hours, history of GI ulceration or bleeding, concurrent use of anticoagulants or corticosteroids, hepatic failure, AKI.
- Agents: **proton pump inhibitors (PPIs)** or **H2-receptor antagonists (H2RAs)** are both acceptable.
  - PPI: e.g., pantoprazole 40 mg IV once daily.
  - H2RA: e.g., famotidine 20 mg IV every 12 hours.
- The SUP-ICU trial demonstrated that pantoprazole reduced clinically important GI bleeding in ICU patients at highest risk.
- The SSC **suggests against** stress ulcer prophylaxis in patients **without** risk factors for GI bleeding.

## Nutrition

The SSC **suggests** initiating **early enteral nutrition** (within 72 hours) over parenteral nutrition or no nutrition in adults with sepsis or septic shock who can be fed enterally (Weak recommendation, Very Low quality of evidence).

- Early trophic/hypocaloric enteral feeding is preferred over early full enteral feeding in the initial phase.
- **Parenteral nutrition (TPN)** should not be initiated in the first 7 days if enteral nutrition is feasible.
- Avoid supplemental parenteral nutrition early (first 7 days of ICU stay); the EPaNIC trial showed worse outcomes with early supplemental PN.
- Gastric residual volume monitoring is not required routinely; the NUTRIREA-2 trial showed no benefit of routine monitoring.

## Renal Replacement Therapy

### Continuous vs Intermittent

The SSC **suggests** using either **continuous or intermittent renal replacement therapy (RRT)** for adults with sepsis or septic shock and AKI who require RRT (Weak recommendation, Low quality of evidence).

- Continuous RRT (CRRT) may be preferred in haemodynamically unstable patients due to slower solute and fluid removal.
- Intermittent haemodialysis is appropriate in haemodynamically stable patients and may be more practical in resource-limited settings.

### Against Routine Early RRT

The SSC **suggests against** initiating renal replacement therapy in adults with sepsis or septic shock and AKI **without definitive indications** for RRT (Weak recommendation, Moderate quality of evidence).

- Definitive indications for RRT include: refractory hyperkalaemia, refractory metabolic acidosis, refractory fluid overload, and uraemic complications (encephalopathy, pericarditis).
- The STARRT-AKI and AKIKI trials demonstrated no benefit to early RRT initiation in the absence of definitive indications.
- A "watchful waiting" approach is recommended, with close monitoring for the development of definitive RRT indications.

## Long-Term Outcomes and Discharge Planning

The SSC 2021 guideline introduces **12 new recommendations** addressing post-sepsis care and long-term outcomes.

### Strong Recommendations

- **Screen** for economic and social support needs (including housing, nutritional, financial, and spiritual support).
- Use **shared decision-making** in post-ICU and hospital discharge planning.
- **Reconcile medications** at ICU and hospital discharge.
- Include **sepsis-specific information** in both written and verbal discharge summaries, including information about sepsis diagnosis, its potential sequelae, and follow-up plans.
- Provide **follow-up assessment** for physical, cognitive, and emotional problems after hospital discharge.

### Weak Recommendations

- Referral to **peer support groups**.
- Structured **handoff processes** at care transitions.
- **Critical care transition programmes** for patients being transferred out of ICU.
- Referral to **post-critical illness and post-hospital rehabilitation programmes**.

## Limitations

- Many supportive care recommendations (nutrition, blood products, VTE prophylaxis, stress ulcer prophylaxis) are not specific to sepsis and draw from general critical care guidelines. The SSC acknowledges this overlap and reduced the number of recommendations in these domains compared to prior guidelines.
- Ventilation recommendations are primarily derived from ARDS trials, not sepsis-specific ventilation studies.
- The optimal timing for RRT initiation in sepsis-associated AKI continues to be debated; evidence is evolving.
- Long-term outcome recommendations are new and based largely on expert consensus and observational data; prospective validation is needed.
- Blood glucose targets are based on a single large RCT (NICE-SUGAR); optimal glucose control in subpopulations (e.g., diabetic ICU patients) remains an area of active investigation.
