5.1 Sepsis, Septic Shock & Surviving Sepsis Guidelines

Q: A 68-year-old female is admitted to the intensive care unit with severe community-acquired pneumonia. Vital signs: blood pressure 78/42 mmHg (MAP 54 mmHg), heart rate 124 bpm, respiratory rate 28/min, and SpO2 91% on 4 L nasal cannula. Her laboratory results reveal a serum lactate of 4.6 mmol/L and an acute creatinine increase from baseline 0.8 mg/dL to 2.1 mg/dL. Her weight is 70 kg. Rapid intravenous fluid resuscitation with balanced crystalloids is initiated at 30 mL/kg. After 1,000 mL has infused over 25 minutes, her blood pressure remains 76/40 mmHg (MAP 52 mmHg). Which clinical action is the priority next step?

Initiate an intravenous infusion of norepinephrine immediately while continuing the crystalloid infusion and reassessing perfusion, with an initial MAP goal of 60–65 mmHg in this 68-year-old.. Surviving Sepsis Campaign guidelines emphasize that vasopressor therapy should be initiated immediately if the patient remains profoundly hypotensive during fluid resuscitation to prevent prolonged end-organ ischemia and cardiac arrest; clinicians should not wait until the entire 30 mL/kg fluid bolus is fully infused. Norepinephrine is first-line. At age 68, an initial MAP range of 60–65 mmHg is reasonable, with adjustment based on organ perfusion. Norepinephrine can be administered temporarily through a well-sited peripheral intravenous catheter in the upper extremity while central venous access is being established. Vasopressin is a second-line adjunct to norepinephrine, not a first-line monotherapy. IV corticosteroids may be considered in septic shock, commonly hydrocortisone 200 mg/day; they do not replace prompt norepinephrine and volume assessment in this profoundly hypotensive patient.

Q: A 72-year-old male with septic shock secondary to acute diverticulitis is intubated in the intensive care unit. He is currently receiving Lactated Ringer's solution, and norepinephrine is infusing at 0.35 mcg/kg/min with a current MAP of 60 mmHg. His serum lactate has increased from 3.2 mmol/L to 4.8 mmol/L over the past 4 hours. Central venous oxygen saturation (ScvO2) is 58%, and bedside echocardiography demonstrates a hyperdynamic left ventricle with an underfilled inferior vena cava. To restore vascular tone, reduce adrenergic exposure, and support end-organ perfusion, which pharmacologic escalation is indicated next?

Add a fixed-dose infusion of vasopressin at 0.03 units/min to reduce norepinephrine requirements and initiate intravenous hydrocortisone.. For septic shock with escalating norepinephrine requirements, SSC suggests adding vasopressin. A common adjunct regimen is a fixed 0.03 units/min infusion; the exact starting threshold and dosing follow clinical assessment and the local protocol. Vasopressin restores endogenous vascular tone by activating V1 receptors, mitigating relative vasopressin deficiency and significantly reducing norepinephrine dosage requirements, which reduces the risk of adrenergic-induced tachyarrhythmias and myocardial strain. IV corticosteroids are also reasonable to consider in this patient with ongoing septic shock; hydrocortisone 200 mg/day, as 50 mg IV every six hours or continuous infusion, is a common regimen. Consider dobutamine for cardiac dysfunction with persistent hypoperfusion despite adequate volume and arterial pressure. This patient has a hyperdynamic LV, so low ScvO2 alone does not justify an inotrope. Add vasopressin, consider hydrocortisone and continue reassessing volume and perfusion. Do not routinely give bicarbonate to improve hemodynamics in hypoperfusion-induced lactic acidemia. SSC suggests it for septic shock with pH <=7.2 and AKIN stage 2–3 AKI; those indications are not established here.

Q: An acute care nurse practitioner is evaluating a 64-year-old mechanically ventilated female with septic shock for dynamic fluid responsiveness following initial resuscitation. The patient is in sinus rhythm and sedated without spontaneous breathing efforts, receiving volume control ventilation with a tidal volume of 8 mL/kg predicted body weight. Invasive arterial monitoring demonstrates a pulse pressure variation (PPV) of 15%. Bedside capillary refill time measured on the index finger is 4.2 seconds. How should the nurse practitioner interpret these findings, and what is the most appropriate resuscitation decision?

The findings support fluid responsiveness with persistent peripheral hypoperfusion; give a cautious balanced-crystalloid challenge while monitoring the response.. With sinus rhythm, passive controlled ventilation and tidal volume 8 mL/kg predicted body weight, PPV 15% supports fluid responsiveness. The prolonged CRT of 4.2 seconds supports persistent peripheral hypoperfusion, but CRT is an adjunct to other perfusion measures. ANDROMEDA-SHOCK tested a CRT-guided resuscitation strategy; it did not establish CRT as a definitive diagnostic test or show a significant 28-day mortality reduction. A cautious 250–500 mL balanced-crystalloid challenge with reassessment of stroke volume/cardiac output, CRT and signs of overload is appropriate. PPV alone does not diagnose RV failure. Abnormal CRT does not justify abruptly stopping vasopressors, and static CVP alone does not predict the cardiac-output response to fluid.

Key Takeaways

Sepsis is defined under Sepsis-3 as life-threatening organ dysfunction caused by a dysregulated host response to infection, clinically identified by an acute increase in the Sequential Organ Failure Assessment (SOFA) score of 2 or more points.
Septic shock represents a subset of sepsis characterized by persistent hypotension requiring vasopressors to maintain a mean arterial pressure (MAP) >= 65 mmHg AND a serum lactate > 2 mmol/L despite adequate fluid resuscitation.
Begin sepsis treatment immediately: obtain lactate and cultures promptly, give antibiotics ideally within one hour for shock or probable/definite sepsis, and reassess perfusion. For possible sepsis without shock, rapidly investigate and treat within three hours if concern persists. Initial fluids and vasopressors depend on hypoperfusion and response.
Norepinephrine is first-line. Start with MAP around 65 mmHg for most adults and 60–65 mmHg as an initial range in adults aged 65 or older. Add vasopressin with escalating norepinephrine and consider epinephrine if pressure remains inadequate.
Consider IV corticosteroids in septic shock; hydrocortisone 200 mg/day is a common regimen. A particular norepinephrine dose is not a universal requirement. Use dynamic fluid responsiveness and capillary refill alongside other perfusion measures to guide resuscitation.

Last updated: November 2026

5.1 Sepsis, Septic Shock & Surviving Sepsis Guidelines

Clinical Scenario: A 68-year-old female presents to the ICU with severe community-acquired pneumonia. Vital signs: BP 78/42 mmHg (MAP 54 mmHg), HR 124 bpm, RR 28/min, SpO2 91% on 4 L nasal cannula, and temp 39.1°C. Laboratory results demonstrate serum lactate 4.6 mmol/L, WBC 18,400/mcL with 16% bands, and acute creatinine increase from baseline 0.8 to 2.1 mg/dL.

Sepsis-3 Definitions & Screening Paradigms

The Sepsis-3 consensus definitions established organ injury as the cornerstone of sepsis pathology:

Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection, clinically defined by an acute increase in total Sequential Organ Failure Assessment (SOFA) score of >= 2 points attributable to infection. Baseline SOFA is assumed zero unless preexisting acute or chronic organ dysfunction is known.
Septic Shock: A subset of sepsis with profound circulatory and cellular/metabolic abnormalities. Identified by persisting hypotension requiring vasopressors to maintain MAP >= 65 mmHg AND serum lactate > 2 mmol/L (18 mg/dL) despite adequate volume resuscitation.

Screening: SIRS vs. qSOFA vs. NEWS

SIRS: Requires >= 2 criteria: temperature >38°C or <36°C; HR >90/min; RR >20/min or PaCO2 <32 mmHg; WBC >12,000 or <4,000/mcL or >10% immature bands. Highly sensitive but lacks specificity for infection or organ failure.
qSOFA: Bedside score of 1 point each for altered mental status (GCS <15), SBP <=100 mmHg, and RR >=22/min. A score >= 2 flags higher risk of poor outcomes. However, the Surviving Sepsis Campaign (SSC) recommends against qSOFA as a single screening tool due to poor sensitivity for early sepsis.
NEWS / MEWS: SSC recommends NEWS, NEWS2, MEWS or SIRS over qSOFA alone for hospital screening. Screening supports early recognition and does not establish the diagnosis.

Current Surviving Sepsis Campaign Initial Management

Sepsis and septic shock are emergencies; begin treatment and resuscitation immediately:

Measure Lactate and Reassess Perfusion: Obtain lactate promptly and follow serial values with examination, urine output and capillary refill. Elevated lactate has multiple causes; do not keep giving fluid solely to normalize it.
Obtain Cultures Promptly: Collect blood cultures, ideally before antimicrobials, without substantially delaying urgent treatment.
Give Appropriate IV Antimicrobials: For possible/probable/definite septic shock or probable/definite sepsis, administer immediately, ideally within one hour. For possible sepsis without shock, investigate rapidly and give antibiotics within three hours if infection remains a concern; monitor closely if antibiotics are deferred for low infection likelihood.
Resuscitate with Crystalloid: SSC suggests at least 30 mL/kg within three hours for sepsis-induced hypoperfusion or shock. Prefer balanced crystalloid, individualize volume and reassess frequently for benefit and overload.
Start Vasopressors for Persistent or Severe Hypotension: Do not wait for the entire fluid dose or central access when shock is profound. Start norepinephrine while reassessing volume and organ perfusion.
Address the Source: Evaluate promptly for a source that needs drainage, debridement or removal. When source control is required, aim to achieve it within six hours of diagnosis.

Vasoactive Escalation & Hemodynamic Protocols

Agent	Receptor Targets	Clinical Action	Dosing & Escalation Rules
Norepinephrine	Potent $\alpha_1$ , modest $\beta_1$	Vasoconstriction, increases venous return and preload	First-line vasopressor; initial MAP about 65 mmHg; SSC suggests 60–65 mmHg in adults >=65 years. Individualize using perfusion and treatment effects.
Vasopressin	Pure $V_1$ vascular	Restores vascular tone in relative vasopressin deficiency	Adjunct to escalating norepinephrine; commonly 0.03 units/min as a fixed dose; follow the local dosing protocol and monitor ischemic effects
Epinephrine	Potent $\alpha_1$ , $\beta_1$ , $\beta_2$	Pronounced vasoconstriction and inotropy	Third-line vasopressor; titrate 0.01–0.5 mcg/kg/min; transiently raises lactate via $\beta_2$ glycolysis
Dobutamine	Potent $\beta_1$ , mild $\beta_2$	Positive inotropy and modest afterload reduction	Inotrope of choice; titrate 2.5–20 mcg/kg/min for persistent hypoperfusion with septic cardiomyopathy
Hydrocortisone	Glucocorticoid / mineralocorticoid	Supports vascular responsiveness	Consider in septic shock; hydrocortisone 200 mg/day IV (50 mg q6h or continuous infusion) is common; individualize timing

Dynamic Fluid Responsiveness & Capillary Refill

Static parameters (CVP, PCWP) fail to predict fluid responsiveness. Resuscitation must utilize dynamic measures of cardiopulmonary interaction:

Pulse Pressure Variation (PPV) & Stroke Volume Variation (SVV): Valid in controlled mechanical ventilation without spontaneous breathing efforts, tidal volumes >= 8 mL/kg PBW, and sinus rhythm. A PPV or SVV > 12–13% predicts volume responsiveness.
Passive Leg Raise (PLR) Test: Reversibly shifts ~300–500 mL of autologous venous blood into the thorax. A prompt rise in measured cardiac output or stroke volume of about 10% or more supports fluid responsiveness. The test can be useful with spontaneous breathing or arrhythmia when PPV is unreliable.
Capillary Refill Time (ANDROMEDA-SHOCK Trial): In ANDROMEDA-SHOCK, targeting CRT <=3 seconds reduced organ dysfunction at 72 hours but did not significantly reduce 28-day mortality compared with lactate-guided resuscitation. Use CRT as an adjunct to other perfusion measures.

Fever of Unknown Origin

Classic FUO in an immunocompetent adult is fever of at least 38.3°C on several occasions over at least three weeks without an explanation after an appropriate minimum diagnostic evaluation. It is different from the first unexplained fever during an acute ICU illness. Reassess travel, exposures, medications, implanted devices, examination findings and noninfectious causes such as malignancy or inflammatory disease. Initial testing includes blood counts, chemistries, inflammatory markers, blood/urine evaluation and appropriate chest/abdominal imaging; pursue clue-directed microbiology, tissue sampling or advanced imaging when unrevealing. The duration criterion never justifies delaying evaluation or sepsis treatment in an acutely unstable patient.

High-Yield Board Exam Traps & Clinical Pearls

Vasopressor Delay Trap: Never withhold vasopressors while awaiting completion of 30 mL/kg fluid infusion in severe hypotension (MAP <55 mmHg). Initiate peripheral norepinephrine immediately to protect coronary perfusion.
Vasopressin Dosing Trap: A fixed dose of 0.03 units/min is common, but dosing and titration follow the local protocol. Higher doses increase ischemic risk; monitor perfusion and individualize withdrawal of vasopressors.
Epinephrine Lactate Trap: Increasing lactate during epinephrine infusion frequently reflects non-ischemic hepatic and skeletal muscle beta-2 glycogenolysis rather than failing resuscitation.
Corticosteroid Selection Trap: Hydrocortisone 200 mg/day IV is a common septic shock regimen. Hydrocortisone plus enteral fludrocortisone is another studied regimen; fludrocortisone alone is not a substitute. Do not use cosyntropin testing to select patients for shock treatment.

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Sepsis Resuscitation and Vasoactive Escalation Algorithm

Test Your Knowledge

A 68-year-old female is admitted to the intensive care unit with severe community-acquired pneumonia. Vital signs: blood pressure 78/42 mmHg (MAP 54 mmHg), heart rate 124 bpm, respiratory rate 28/min, and SpO2 91% on 4 L nasal cannula. Her laboratory results reveal a serum lactate of 4.6 mmol/L and an acute creatinine increase from baseline 0.8 mg/dL to 2.1 mg/dL. Her weight is 70 kg. Rapid intravenous fluid resuscitation with balanced crystalloids is initiated at 30 mL/kg. After 1,000 mL has infused over 25 minutes, her blood pressure remains 76/40 mmHg (MAP 52 mmHg). Which clinical action is the priority next step?

Withhold vasoactive infusions until the full 2,100 mL balanced crystalloid bolus completes infusion over the next 2 hours.

Initiate an intravenous infusion of norepinephrine immediately while continuing the crystalloid infusion and reassessing perfusion, with an initial MAP goal of 60–65 mmHg in this 68-year-old.

Administer an immediate intravenous bolus of 50 mg hydrocortisone to reverse suspected acute corticosteroid insufficiency.

Initiate an intravenous infusion of vasopressin at 0.03 units/min as the initial first-line monotherapy for septic shock.

Test Your Knowledge

A 72-year-old male with septic shock secondary to acute diverticulitis is intubated in the intensive care unit. He is currently receiving Lactated Ringer's solution, and norepinephrine is infusing at 0.35 mcg/kg/min with a current MAP of 60 mmHg. His serum lactate has increased from 3.2 mmol/L to 4.8 mmol/L over the past 4 hours. Central venous oxygen saturation (ScvO2) is 58%, and bedside echocardiography demonstrates a hyperdynamic left ventricle with an underfilled inferior vena cava. To restore vascular tone, reduce adrenergic exposure, and support end-organ perfusion, which pharmacologic escalation is indicated next?

Initiate dobutamine at 15 mcg/kg/min to increase cardiac contractility.

Increase norepinephrine to 0.70 mcg/kg/min and titrate upward without adding adjunctive agents.

Administer intravenous sodium bicarbonate 8.4% boluses to improve catecholamine receptor responsiveness.

Add a fixed-dose infusion of vasopressin at 0.03 units/min to reduce norepinephrine requirements and initiate intravenous hydrocortisone.

Test Your Knowledge

An acute care nurse practitioner is evaluating a 64-year-old mechanically ventilated female with septic shock for dynamic fluid responsiveness following initial resuscitation. The patient is in sinus rhythm and sedated without spontaneous breathing efforts, receiving volume control ventilation with a tidal volume of 8 mL/kg predicted body weight. Invasive arterial monitoring demonstrates a pulse pressure variation (PPV) of 15%. Bedside capillary refill time measured on the index finger is 4.2 seconds. How should the nurse practitioner interpret these findings, and what is the most appropriate resuscitation decision?

The findings support fluid responsiveness with persistent peripheral hypoperfusion; give a cautious balanced-crystalloid challenge while monitoring the response.

The elevated pulse pressure variation indicates severe right ventricular failure; fluid administration is strictly contraindicated and inotropes must be started immediately.

The capillary refill time demonstrates adequate peripheral perfusion; discontinue vasopressors immediately to prevent peripheral gangrene.

Dynamic arterial parameters are invalid in mechanically ventilated patients without spontaneous breathing; rely on static central venous pressure to guide all further fluid administration.

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5.2 Differentiation & Resuscitation of Non-Septic Shock States

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5.1 Sepsis, Septic Shock & Surviving Sepsis Guidelines

Key Takeaways

5.1 Sepsis, Septic Shock & Surviving Sepsis Guidelines

Sepsis-3 Definitions & Screening Paradigms

Screening: SIRS vs. qSOFA vs. NEWS

Current Surviving Sepsis Campaign Initial Management

Vasoactive Escalation & Hemodynamic Protocols

Dynamic Fluid Responsiveness & Capillary Refill

Fever of Unknown Origin

High-Yield Board Exam Traps & Clinical Pearls