Sepsis and Septic Shock: Comprehensive Management Guide
Definition and Recognition
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, clinically identified by an acute increase in the SOFA score of 2 points or more. 1
- Septic shock is a subset of sepsis characterized by persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg and serum lactate >2 mmol/L (>18 mg/dL) despite adequate volume resuscitation 1
- Use the qSOFA criteria for bedside screening in suspected infection: Glasgow Coma Score ≤14, systolic blood pressure ≤100 mmHg, and respiratory rate ≥22/min 1
- Sepsis and septic shock are medical emergencies requiring immediate treatment—do not delay resuscitation 1, 2
Initial Resuscitation (First 3 Hours)
Fluid Resuscitation
Administer at least 30 mL/kg of intravenous crystalloid within the first 3 hours of sepsis-induced hypoperfusion, either before or concurrent with vasopressor initiation. 1, 3
- Balanced crystalloids (lactated Ringer's or Plasma-Lyte) are preferred over normal saline to reduce hyperchloremic metabolic acidosis 3
- This 30 mL/kg is a minimum target, not a ceiling—most patients will require additional volume 3
- Continue fluid challenges as long as hemodynamic parameters improve, using dynamic variables (pulse-pressure variation, stroke-volume variation, passive leg raise) or static signs (MAP, heart rate, mental status, urine output, skin perfusion) 1, 3
- Stop fluids when no improvement occurs, signs of fluid overload develop, or hemodynamic parameters stabilize 3
Common Pitfall: Do not delay resuscitation due to concerns about fluid overload in patients with heart failure—the standard 30 mL/kg bolus applies even to those with reduced ejection fraction 4
Albumin Supplementation
- Add albumin when large volumes of crystalloids (several liters) are required, especially in oncotic deficit or prolonged shock 3, 4
Fluids to Avoid
- Never use hydroxyethyl starch solutions—they increase mortality and acute kidney injury risk 3, 4
- Avoid gelatin solutions when crystalloids are available 3
Antimicrobial Therapy
Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, then administer broad-spectrum antimicrobials within the first hour of septic shock recognition. 1, 4
- Do not delay antibiotics >45 minutes for culture collection 1
- Reassess the antimicrobial regimen daily to narrow spectrum or discontinue 3
- Consider procalcitonin levels to guide duration or stop empiric therapy in patients with limited clinical evidence of infection 3
Vasopressor Management
First-Line: Norepinephrine
Initiate norepinephrine as the mandatory first-line vasopressor when hypotension persists after adequate fluid resuscitation, targeting MAP ≥65 mmHg. 1, 5, 3
- Start at 0.05–0.1 µg/kg/min (≈5–10 µg/min for a 70 kg adult) via central venous access 5
- Place an arterial catheter for continuous blood pressure monitoring as soon as practical 1, 5
- For chronic hypertension: Target MAP of 70–85 mmHg to reduce need for renal replacement therapy 5
Why norepinephrine? It reduces 28-day mortality by 11% absolute risk reduction compared to dopamine (NNT=9) and causes 53% fewer supraventricular arrhythmias and 65% fewer ventricular arrhythmias 5
Second-Line: Vasopressin
Add vasopressin at a fixed dose of 0.03 units/min when norepinephrine reaches 0.1–0.25 µg/kg/min and MAP remains <65 mmHg. 5
- Vasopressin must always be added to norepinephrine—never use as monotherapy 5
- Do not exceed 0.03–0.04 units/min except as salvage therapy—higher doses cause cardiac, digital, and splanchnic ischemia 5
- Vasopressin preferentially constricts the efferent arteriole, producing higher glomerular filtration and better urine output than norepinephrine alone 5
Third-Line: Epinephrine
Add epinephrine starting at 0.05 µg/kg/min (titrate up to 0.3 µg/kg/min) when MAP cannot be achieved with norepinephrine plus vasopressin. 5
- For a 70 kg patient, maximum dose is 21 µg/min 5
- Epinephrine causes transient lactic acidosis through β₂-adrenergic stimulation, interfering with lactate clearance as a resuscitation endpoint 5
Inotropic Support: Dobutamine
Add dobutamine 2.5–20 µg/kg/min when MAP is adequate (≥65 mmHg) but signs of tissue hypoperfusion persist, particularly with myocardial dysfunction. 5, 4
- Indications: elevated lactate, low urine output, altered mental status, cold extremities, or documented low cardiac output 5
- Discontinue dobutamine when cardiac output is adequate or elevated, as it may worsen hypotension through vasodilation and increase arrhythmia risk 5
Agents to Avoid
Dopamine is strongly contraindicated as first-line therapy—it increases absolute mortality by 11% and causes significantly more arrhythmias than norepinephrine. 5
- Reserve dopamine only for highly selected patients with bradycardia and low arrhythmia risk 5
- Low-dose dopamine for renal protection is ineffective (Grade 1A recommendation against use) 5, 3
Phenylephrine is not recommended except in three specific situations: (1) norepinephrine-induced serious arrhythmias, (2) documented high cardiac output with persistent hypotension, or (3) salvage therapy when all other agents have failed 5
Hemodynamic Monitoring and Targets
Blood Pressure Targets
- Initial MAP target: ≥65 mmHg for most patients 1, 5
- Restoring MAP to ≥65 mmHg re-establishes renal perfusion pressure above the autoregulatory threshold 5
- Higher MAP targets (85 mmHg) do not improve renal function, urine output, or lactate clearance in most patients and show no mortality benefit (34% vs 36.6% at 28 days) 5
Tissue Perfusion Markers (Assess Every 2–4 Hours)
Monitor beyond MAP—assess tissue perfusion using lactate clearance, urine output ≥0.5 mL/kg/h, mental status, skin perfusion, and capillary refill. 5, 3
- Obtain baseline lactate and repeat within 6 hours if elevated; aim for normalization 5, 3
- Target urine output ≥0.5 mL/kg/h as primary bedside indicator of renal perfusion 5
- Perform bedside echocardiography to assess cardiac output, ventricular function, and filling pressures—this distinguishes vasodilatory shock (high CO, low SVR) from cardiogenic shock (low CO, high SVR) 5
Dynamic vs. Static Variables
- Prefer dynamic variables (pulse-pressure variation, stroke-volume variation) over static pressures (CVP) to predict fluid responsiveness 1, 3
- CVP alone is unreliable for predicting fluid responsiveness, particularly in the 8–12 mmHg range 3
Source Control
Rapidly identify or exclude an anatomic source requiring emergent control and intervene as soon as feasible, ideally within 12 hours. 3
- Prefer the least physiologically invasive effective intervention (e.g., percutaneous drainage rather than open surgery) 3
- Promptly remove intravascular access devices that may be the infection source after establishing alternative access 3
Adjunctive Therapies for Refractory Shock
Corticosteroids
Administer hydrocortisone 200 mg/day IV for shock reversal if hypotension remains refractory to vasopressors after at least 4 hours of high-dose therapy. 5, 2
Angiotensin II
- In profound hypotension unresponsive to standard catecholamines, Angiotensin II can achieve rapid resuscitation by increasing systemic vascular resistance while preserving cardiac output 5
Practical Titration Algorithm
- After initial 30 mL/kg crystalloid bolus, if MAP <65 mmHg → start norepinephrine at 0.05–0.1 µg/kg/min 5
- Titrate norepinephrine to keep MAP ≥65 mmHg (or 70–85 mmHg in chronic hypertension) 5
- When norepinephrine reaches 0.1–0.25 µg/kg/min and MAP remains <65 mmHg → add vasopressin 0.03 units/min (fixed dose) 5
- If MAP still inadequate → add epinephrine starting at 0.05 µg/kg/min, titrating up to 0.3 µg/kg/min 5
- If MAP adequate but hypoperfusion persists → add dobutamine 2.5–20 µg/kg/min to improve cardiac output 5
- If refractory after ≥4 hours → add hydrocortisone 200 mg/day IV 5
Special Populations
Patients with Heart Failure (Reduced Ejection Fraction)
- Apply the standard 30 mL/kg crystalloid bolus even in chronic systolic heart failure (EF <40%)—withholding fluids is not evidence-based 4
- Norepinephrine has the most favorable cardiac safety profile in heart-failure patients 4
- Dobutamine is indicated when myocardial dysfunction with low cardiac output persists despite adequate MAP 4
Patients with Chronic Hypertension
- Target MAP 70–85 mmHg instead of 65 mmHg to lower incidence of renal replacement therapy 5
Critical Pitfalls to Avoid
- Do not delay vasopressors while pursuing aggressive fluid resuscitation in severe hypotension—early vasopressor use is appropriate when diastolic BP is critically low 5
- Do not rely solely on MAP numbers—tissue perfusion markers are equally critical for safe management 5
- Do not use dopamine for renal protection—it provides no benefit and is strongly contraindicated 5, 3
- Do not exceed vasopressin 0.03–0.04 units/min—higher doses cause end-organ ischemia without hemodynamic benefit 5
- Do not use phenylephrine as first-line therapy—it may raise BP on the monitor while worsening tissue perfusion 5
- Do not adopt a "maintenance-fluid" mindset—active, repeated resuscitation guided by hemodynamic response is required 3