GC059 High Fever Low BP
A clinical scenario of high fever accompanied by low blood pressure, typically indicative of sepsis or septic shock resulting from a systemic inflammatory response to infection.
High Fever, Low Blood Pressure — Sepsis & Septic Shock
Big Idea: When a patient presents with high fever and low blood pressure, think sepsis and septic shock — a life-threatening condition where the body's dysregulated immune response to infection causes multi-organ dysfunction. This lecture, delivered by Dr. Chan Wai Ming (AICU, QMH), walks through the modern definition of sepsis (Sepsis-3), the hemodynamic profile of septic shock, the cascade of multi-organ dysfunction syndrome (MODS), and the evidence-based management principles from the Surviving Sepsis Campaign. Critically, it is a tour of landmark ICU trials — many of which were negative — that shaped current practice.
Learning Objectives (from slide 2):
- Definition of Sepsis (old SIRS concept → Sepsis-3)
- Multi-Organ Failure in sepsis
- Treatment of Sepsis — Surviving Sepsis Campaign Guidelines
- Targets of Resuscitation (EGDT and beyond)
- Use of Vasopressors (noradrenaline vs. dopamine, renal-dose dopamine debunked)
- Use of Fluids (crystalloid vs. colloid, balanced vs. NS, starch harm)
37.4% of ICU patients had sepsis in the 2002 European SOAP cohort reported in 2006. Hospital mortality was 24%. In a 2015–2016 Chinese ICU cohort reported by Xie et al., 33.9% of sepsis was hospital-acquired and 90-day mortality was 35.5%. [1]
Why this matters: sepsis is common and carries major mortality and post-ICU morbidity. The final lecture graphs use a historical US administrative dataset (2000–2007): coded severe-sepsis admissions rose from about 143 to 343 per 100,000 while in-hospital mortality fell from 39.6% to 27.3%; discharge to long-term care rose from 27% to 35% [1]. Changing coding, ascertainment, case mix and the now-retired term severe sepsis mean that these plots should not be treated as contemporary incidence estimates or as proof that treatment alone caused the mortality decline.
2. Definitions: From SIRS to Sepsis-3
SIRS = Systemic Inflammatory Response Syndrome — the systemic activation of the innate immune response to injury regardless of cause. [1]
SIRS criteria (for historical context):
- Temperature > 38°C or < 36°C
- Heart rate > 90 bpm
- Respiratory rate > 20 or PaCO₂ < 32 mmHg
- WBC > 12,000 or < 4,000 or > 10% bands
Problem with SIRS: Too sensitive, not specific. A patient running a marathon meets SIRS criteria. By 2001, the consensus moved away from requiring SIRS as obligatory for sepsis diagnosis.
"Definition after 2001: SIRS Not Obligatory" — Sepsis is the response of the body to infection, not simply inflammation. [1]
Infection is defined as a microbial phenomenon — the invasion of pathogens into normally sterile spaces (CNS, lung, pericardium) or pathological manifestations (abscess, endocarditis). [1]
Key lecture point:
"No commonly accepted serum marker of sepsis. Procalcitonin is promising but not the gold standard." [1]
Exam Trap
Don't write that procalcitonin definitively diagnoses sepsis. The lecture explicitly states it is NOT the gold standard. Use it as a supportive marker, not a diagnostic one.
Sepsis-3 Definition: "Life-threatening organ dysfunction caused by a dysregulated host response to infection." [1]
This is a conceptual shift: it's not just having an infection + inflammation. It's infection causing organ dysfunction through a dysregulated (not just activated) immune response.
Operationally, Sepsis-3 represents organ dysfunction as an acute SOFA-score increase of ≥2 points attributable to infection. This is a clinical construct: neither SOFA nor any biomarker substitutes for diagnostic judgement [8].
Septic Shock = subset of sepsis with circulatory AND cellular/metabolic dysfunction associated with higher risk of mortality. [1]
Clinical identification of septic shock (must know for exams):
A vasopressor requirement to maintain MAP ≥ 65 mmHg AND serum lactate > 2 mmol/L despite adequate volume resuscitation. [1,8]
| Concept | Definition | Key Discriminator |
|---|---|---|
| Sepsis | Life-threatening organ dysfunction from dysregulated host response to infection | Organ dysfunction is the hallmark |
| Septic Shock | Sepsis + need vasopressor for MAP ≥ 65 AND lactate > 2 mmol/L despite adequate fluids | Both hemodynamic AND metabolic criteria must be met |
High Yield
Septic shock requires both vasopressor dependence AND elevated lactate. If a patient needs noradrenaline but their lactate is 1.5 mmol/L, they technically do not meet Sepsis-3 criteria for septic shock. This is a common MCQ discriminator.
From supporting notes [2]:
- RR ≥ 22/min
- sBP ≤ 100 mmHg
- Altered GCS
qSOFA was derived as a bedside risk prompt, not a diagnostic definition. A score ≥2 identified an infected cohort at higher risk of poor outcome, but it must not be used to rule sepsis in or out. The 2026 SSC recommends NEWS/NEWS2, MEWS or SIRS over qSOFA as a single in-hospital screening tool [7,8].
Slide 6 is a dense systems diagram rather than a linear “cytokine storm.” Its important visual message is a self-amplifying host-injury loop:
- Two danger inputs: microbial PAMPs (for example lipopolysaccharide) and host-cell DAMPs (for example HMGB1 released from injured tissue) activate pattern-recognition receptors.
- Parallel immune programmes: activated neutrophils and other innate cells release pro-inflammatory mediators (TNF-α, IL-1, IL-6 and HMGB1) while counter-regulatory IL-10/TGF-β pathways can produce clinically important immunosuppression. Sepsis can therefore combine hyperinflammation with impaired pathogen clearance.
- Endothelial barrier failure: glycocalyx and intercellular-junction disruption cause vasoplegia, vascular hyperpermeability, capillary leak and disordered microcirculatory flow. Coagulation activation and impaired oxygen use add “cytopathic” stress even when global cardiac output looks adequate.
- Cell and organ injury: apoptosis, necroptosis, pyroptosis and NET formation contribute to cardiomyopathy, encephalopathy and lung, kidney, liver, gut and coagulation dysfunction.
- Positive feedback: injured cells release more DAMPs, re-entering the loop and propagating MODS.
Why “dysregulated”? The simultaneous, spatially heterogeneous inflammatory and immunosuppressive responses explain why sepsis is a host-response syndrome, not simply pathogen burden or one circulating cytokine.
Septic shock is principally DISTRIBUTIVE shock — vasoplegia causes low SVR and hypotension, but the patient's phenotype may evolve or be mixed. [1]
| Parameter | Distributive | Cardiogenic | Hypovolemic | Obstructive |
|---|---|---|---|---|
| Blood Pressure | ↓ | ↓ | ↓ | ↓ |
| Cardiac Output | ↑ (initially) | ↓↓ | ↓ | ↓ |
| Preload | Variable/relatively low | ↑ | ↓↓ | Often ↑ upstream of obstruction |
| SVR (Afterload) | ↓↓↓ | ↑ | ↑ | ↑ |
| Extremities | Warm, flushed | Cold, clammy | Cold, clammy | Cold, clammy |
| Pulse pressure | Wide | Narrow | Narrow | Narrow |
The lecture's four-column haemodynamic figure depicts the classic early pattern: distributive shock has increased CO, reduced SVR and variable preload; cardiogenic, hypovolaemic and obstructive shock usually have reduced CO with raised SVR. This is a teaching model, not a guarantee at the bedside.
Why can CO be high in septic shock? The drop in SVR lowers afterload and tachycardia can raise cardiac output. But despite high CO, tissue perfusion may remain impaired because:
- Blood is maldistributed (pooling in dilated splanchnic beds)
- Microvascular dysfunction prevents oxygen extraction
- Capillary leak reduces effective circulating volume
Clinical Pearl
Warm extremities, bounding pulses and a wide pulse pressure support vasoplegia, but their absence does not exclude septic shock. Hypovolaemia, sepsis-induced myocardial dysfunction, pre-existing cardiac disease and obstructive pathology can coexist; reassess haemodynamics rather than assigning a permanently “warm/high-output” label.
5. Multi-Organ Dysfunction Syndrome (MODS)
MODS is the clinical expression of sepsis-associated organ dysfunction. The term severe sepsis belonged to older definitions and is redundant under Sepsis-3. [8]
| Organ System | Pathology | Clinical Manifestation |
|---|---|---|
| CVS | Vasoplegia ± sepsis-induced myocardial dysfunction | Hypotension; CO may be high, normal or low |
| Respiratory | ARDS | Type I respiratory failure |
| Renal | Multifactorial AKI/acute tubular injury | Oliguric or non-oliguric AKI |
| Blood | DIC | ↓ Platelets, bleeding |
| GI | Multi-factorial | GI bleeding, ileus |
| Liver | Multi-factorial | Jaundice |
| CNS | Septic Encephalopathy | Encephalopathy, confusion |
| Peripheral NS | Critical Illness Polyneuropathy | Weakness, ventilator weaning failure |
ARDS = Non-cardiogenic pulmonary oedema, Type I failure, low lung compliance. [1]
Why does ARDS happen in sepsis? Inflammatory mediators damage the alveolar-capillary membrane → protein-rich fluid leaks into alveoli → impairs gas exchange → refractory hypoxemia. The lungs become stiff (low compliance) because fluid-filled alveoli resist inflation.
Reading the lecture radiograph (slide 11): there are diffuse bilateral air-space opacities rather than a single lobar opacity, illustrating the imaging distribution expected in ARDS. Imaging alone is not diagnostic: bilateral opacities must be integrated with acute timing, oxygenation and exclusion of hydrostatic oedema.
ARDS Berlin Definition (2012) — Know this table cold:
| Feature | Criteria |
|---|---|
| Timing | Within 1 week of known clinical insult or new respiratory symptoms |
| Chest Imaging | Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules |
| Origin of edema | Not fully explained by cardiac failure or fluid overload; need objective assessment if no risk factor |
| Mild | 200 < PaO₂/FiO₂ ≤ 300 mmHg with PEEP or CPAP ≥ 5 cmH₂O |
| Moderate | 100 < PaO₂/FiO₂ ≤ 200 mmHg with PEEP ≥ 5 cmH₂O |
| Severe | PaO₂/FiO₂ ≤ 100 mmHg with PEEP ≥ 5 cmH₂O |
Historical vs. Current Definition
The older 1994 American-European definition used PAWP < 18 mmHg to help exclude hydrostatic oedema and called PaO₂/FiO₂ ≤300 “acute lung injury.” Berlin 2012 dropped both the wedge-pressure threshold and the term “ALI.” The 2024 Global ARDS Definition now expands Berlin by allowing HFNO ≥30 L/min, SpO₂/FiO₂ ≤315 when SpO₂ ≤97%, and lung ultrasound for bilateral loss of aeration; it also provides a resource-variable category. The Berlin severity table remains important for interpreting the lecture and many exams, but it is no longer the newest consensus framework [10].
The lecture diagram presents the historical RIFLE criteria (ADQI 2004) [1]:
| Stage | GFR Criteria | Urine Output |
|---|---|---|
| Risk | ↑Cr × 1.5 or ↓GFR > 25% | < 0.5 mL/kg/hr × 6 hrs |
| Injury | ↑Cr × 2 or ↓GFR > 50% | < 0.5 mL/kg/hr × 12 hrs |
| Failure | ↑Cr × 3 or ↓GFR > 75% or Cr ≥354 μmol/L | < 0.3 mL/kg/hr × 24 hrs or anuria × 12 hrs |
| Loss | Persistent ARF > 4 weeks | — |
| ESRD | End-stage > 3 months | — |
For current diagnosis and staging, use KDIGO, which integrates creatinine and urine-output criteria [9]:
| KDIGO stage | Serum creatinine | Urine output |
|---|---|---|
| 1 | 1.5–1.9 × baseline or rise ≥26.5 μmol/L (0.3 mg/dL) | < 0.5 mL/kg/h for 6–12 h |
| 2 | 2.0–2.9 × baseline | < 0.5 mL/kg/h for ≥12 h |
| 3 | ≥3 × baseline, or ≥353.6 μmol/L (4.0 mg/dL), or renal replacement therapy | < 0.3 mL/kg/h for ≥24 h or anuria ≥12 h |
Sepsis-associated AKI is multifactorial: altered macro- and microcirculation, inflammation, endothelial/tubular injury, nephrotoxins and obstruction can contribute. “ATN from hypoperfusion” is therefore too narrow, and AKI may be non-oliguric.
6. Treatment of Sepsis — Lecture Evidence and Current SSC 2026
The slides summarize SSC 2021. The SSC 2026 adult guideline now supersedes it; the sections below retain the lecture's landmark trials while labelling the current recommendations [7].
Each hour of delay in antimicrobial therapy over the ensuing 6 hours was associated with an average decrease in survival of 7.6% per hour. — Kumar et al., retrospective 1989–2004 septic-shock cohort [1]
Current Antibiotic-Timing Framework
Do not convert the Kumar association into a universal causal “7.6% mortality per hour” rule. SSC 2026 recommends antimicrobials immediately, ideally within 1 hour, for probable/definite sepsis without shock and for possible, probable or definite septic shock. For possible sepsis without shock, perform a rapid time-limited investigation and treat within 3 hours if infection concern persists; with low infection likelihood and no shock, close observation without immediate antibiotics is reasonable. Obtain blood cultures as soon as possible and ideally first, but urgent treatment should proceed in parallel—not wait for results. Procalcitonin should not determine whether antibiotics are started [7].
Use crystalloids first; SSC 2026 conditionally favours balanced crystalloids over 0.9% saline during initial resuscitation. [7]
Key Trials on Fluid Choice:
| Trial | Design | Key Finding |
|---|---|---|
| SAFE Study (NEJM 2004) | 4% albumin vs. normal saline, multicentre RCT | No difference in D28 mortality: 20.9% vs. 21.1% (p=0.87) |
| CHEST (NEJM 2012) | 6% HES (Voluven) vs. NS | No survival benefit; MORE renal failure with HES (RR 1.21, p=0.04) |
| 6S Trial (NEJM 2012) | 6% HES (Tetraspan) vs. Ringer's acetate | Higher D90 mortality with HES (51% vs. 43%, p=0.03); MORE renal failure (RR 1.35, p=0.04) |
| Hammond meta-analysis (NEJM Evidence 2022) | Balanced crystalloids vs. NS, 6 trials, n=34,450 | CIs crossed no effect: mortality RR 0.96 (0.91–1.01), AKI RR 0.96 (0.89–1.02), RRT RR 0.95 (0.81–1.11) |
Bottom line from the lecture:
For starch-based colloids: No survival benefits, More Renal Failure. [1]
Balanced solutions reduce chloride load and the tendency to hyperchloraemic acidosis, but “balanced” does not mean that every infusion is literally pH-neutral or outcome-superior in every patient. [1,7]
Why is Hyperchloremia a Concern?
Normal saline has 154 mmol/L chloride (versus about 100 mmol/L in plasma) and a strong-ion difference of zero, so large volumes can produce hyperchloraemic metabolic acidosis; renal perfusion effects are biologically plausible but AKI is not inevitable. In the slide's 2022 meta-analysis, confidence intervals crossed no effect for mortality, AKI and RRT. SSC 2026 nonetheless conditionally prefers balanced crystalloids for initial resuscitation (except that 0.9% saline is suggested with traumatic brain injury) [1,7].
Current fluid hierarchy: use crystalloid first; do not use hydroxyethyl starch, and avoid gelatin. SSC 2026 suggests crystalloid alone rather than routine supplemental albumin, while allowing albumin selectively after large crystalloid volumes or in cirrhosis (avoid it in traumatic brain injury). For sepsis-induced hypoperfusion or septic shock, SSC still suggests at least 30 mL/kg in the first 3 hours, but explicitly requires individualisation and frequent reassessment. Thereafter, use dynamic response to passive leg raise or a small bolus rather than static CVP alone; either liberal or restrictive strategies may be chosen after the initial volume based on patient factors [7].
Comparison of Common IV Solutions (from lecture slide 26):
| Component | Plasma | NS (0.9% NaCl) | Ringer's Lactate | Plasmalyte | Gelofusine |
|---|---|---|---|---|---|
| Na⁺ | 140 | 154 | 130 | 140 | 154 |
| K⁺ | ~4 | 0 | 4 | 5 | 0 |
| Cl⁻ | 100 | 154 | 109 | 98 | 125 |
| Ca²⁺ | 2.2 | 0 | 1.5 | 0 | 0 |
| HCO₃⁻ | 24 | 0 | 0 | 0 | 0 |
| Lactate | 1 | 0 | 28 | 0 | 0 |
| Acetate | 0 | 0 | 0 | 27 | 0 |
| Gluconate | 0 | 0 | 0 | 23 | 0 |
6.4 Vasopressors
Preferred vasopressor: Noradrenaline [1]
| Receptor | Action | Dopamine | Dobutamine | Adrenaline | Noradrenaline |
|---|---|---|---|---|---|
| α₁ | Vasoconstriction | ++ (high dose) | 0 | +++ | ++++ |
| β₁ | ↑ Cardiac Output | + (low dose) | +++ | +++ | ++ |
Inotropes (e.g., dobutamine) increase cardiac output but cause peripheral vasodilation and may DROP blood pressure. [1]
The slide lists noradrenaline, high-dose dopamine, phenylephrine and vasopressin as pressors, but this is not a list of equivalent routine choices.
Why noradrenaline is preferred:
- Potent α₁ agonist → restores SVR (the primary problem in distributive shock)
- Some β₁ activity → maintains cardiac output
- Less arrhythmogenic than dopamine
SOAP II (NEJM 2010) — Dopamine vs. Noradrenaline:
| Dopamine | Noradrenaline | P value | |
|---|---|---|---|
| N | 858 | 821 | |
| D28 Mortality | 52.5% | 48.5% | 0.10 (NS) |
| Arrhythmias | 24.1% | 12.4% | < 0.001 |
| Discontinued for arrhythmias | 6.1% | 1.6% | < 0.001 |
No difference in D28 survival. Dopamine group had MORE patients discontinued for arrhythmias. [1]
Subgroup analysis: In cardiogenic shock, dopamine was associated with HIGHER mortality (p=0.03). [1]
High Yield
Noradrenaline is the recommended first-line vasopressor for septic shock. If its dose is escalating, add vasopressin; if MAP remains inadequate on both, add adrenaline. In unstable shock, pressors may begin concurrently with initial fluid, and peripheral noradrenaline can be started rather than waiting for central access. Dopamine is not routine because it causes more arrhythmias. The apparent excess mortality in SOAP II's cardiogenic subgroup was a subgroup signal, not proof that dopamine is uniquely “worse in cardiogenic shock” [1,7].
ANZIC Trial (Lancet 2000) — "Renal-Dose" Dopamine:
Dopamine 2 μg/kg/min vs. placebo in ICU patients at risk of renal failure: NO difference in peak creatinine, need for RRT, ICU/hospital stay, or mortality. [1]
"Renal Dose" Dopamine is OUT. [1]
Exam Trap
If an MCQ asks about "low-dose dopamine for renal protection," the answer is that it does NOT work. The ANZIC trial debunked this practice. Never recommend renal-dose dopamine.
NOT NECESSARY to target supranormal cardiac output (Class 1B recommendation). [1]
If cardiac dysfunction causes persistent hypoperfusion despite adequate volume status and arterial pressure, SSC 2026 suggests an inotrope: add dobutamine to noradrenaline or use adrenaline alone. Dobutamine is not a substitute for the pressor needed to maintain MAP [7].
Historical Rivers EGDT targets (2001)—learn the trial, not a current fixed protocol: [1]
| Target | Value |
|---|---|
| Central Venous Pressure | 8–12 mmHg |
| Mean Arterial Pressure | > 65 mmHg |
| Urine Output | > 0.5 mL/kg/hr |
| Central Venous O₂ Saturation (ScvO₂) | > 70% |
| Mixed Venous O₂ Saturation (SvO₂) | > 65% (if PA catheter used) |
EGDT — Rivers (NEJM 2001):
| EGDT | Control | P | |
|---|---|---|---|
| N | 130 | 133 | |
| D28 Mortality | 33.3% | 49.2% | 0.01 |
| D60 Mortality | 44.3% | 56.9% | 0.03 |
This single-centre trial reported lower mortality with protocolised resuscitation. The lecture's forest plot then shows ProCESS, ARISE and ProMISe clustered around no effect (pooled OR about 1.01, 95% CI 0.88–1.16): later multicentre usual-care pathways achieved similar outcomes without compulsory CVP/ScvO₂ targets. Current practice keeps the urgency but uses individualised, repeatedly reassessed resuscitation—initial MAP around 65 mmHg, serial lactate interpreted in context, capillary refill and dynamic fluid responsiveness—rather than a rigid EGDT bundle [7].
SEPSISPAM Study (NEJM 2014):
| MAP 65–70 mmHg | MAP 80–85 mmHg | ||
|---|---|---|---|
| N | 388 | 388 | |
| D28 Mortality | 34.0% | 36.6% | p=0.57 (NS) |
| New AF | 2.8% | 6.7% | p=0.02 |
| RRT in chronic HT patients | 42.2% | 31.7% | p=0.046 |
The slide's time-series graph confirms that the protocol produced sustained separation: achieved MAP was roughly 73–78 mmHg in the lower-target group and 85–87 mmHg in the higher-target group over the first 5 days. The neutral primary outcome therefore was not explained by failure to separate blood pressure.
A higher blood pressure target (80–85) was not associated with better overall survival and caused more atrial fibrillation. The lower RRT rate in participants with chronic hypertension was a subgroup finding [1].
Clinical Nuance
SSC 2026 recommends an initial MAP target of 65 mmHg (a practical range around it) rather than a universally higher target, and conditionally suggests 60–65 mmHg initially for adults aged ≥65. Chronic hypertension and organ-perfusion response may inform later individualisation, but SEPSISPAM does not mandate 80–85 mmHg for every hypertensive patient [7].
Lactate clearance is associated with better prognosis in sepsis. RR of death with lactate clearance = 0.38 (95% CI 0.29–0.50). [1]
| Population | Sensitivity | Specificity |
|---|---|---|
| All patients | 0.75 (0.58–0.87) | 0.72 (0.61–0.90) |
| ICU only | 0.83 (0.67–0.92) | 0.67 (0.59–0.75) |
Why lactate matters: Lactate rises in sepsis due to:
- Tissue hypoperfusion → anaerobic metabolism
- Impaired lactate clearance by the liver
- Catecholamine-driven aerobic glycolysis
Serial lactate helps track risk and response, but lactate is not a direct tissue-oxygen meter. A fall is reassuring; persistence may reflect hypoperfusion, adrenergic aerobic glycolysis, impaired hepatic clearance, drugs such as adrenaline or another process. SSC 2026 suggests serial measurements plus capillary refill, explicitly warning against continuing fluid simply until lactate normalises [7].
Initiate insulin when glucose is ≥10 mmol/L (180 mg/dL); do NOT target normoglycaemia with intensive insulin. [1,7]
| Trial | Protocol | Key Finding |
|---|---|---|
| Van den Berghe (NEJM 2001) | Surgical ICU, tight glucose (4.4–6.0) vs. control (10–11) | ↓ ICU mortality with tight control (4.6% vs. 8.0%, p=0.04) |
| NICE-SUGAR (NEJM 2009) | Multicentre, tight glucose (4.5–6.0) vs. < 10 | ↑ D90 mortality with tight control (27.5% vs. 24.9%, p=0.02); severe hypoglycemia 6.8% vs. 0.5% |
"Tight Glucose Control Could Be Harmful!" [1]
The Van den Berghe study was single-centre and predominantly surgical. The much larger NICE-SUGAR trial (medical and surgical ICUs) found higher mortality and much more severe hypoglycaemia with tight control. SSC 2026 recommends starting insulin at ≥10 mmol/L; this is an initiation threshold, not a command to drive glucose to normal [7].
Appropriate ventilatory strategy, appropriate use of renal replacement therapy, appropriate nutritional protocol. [1]
These are broad categories. The key principles:
- ARDS: tidal volume about 6 mL/kg ideal/predicted body weight and plateau pressure ≤30 cmH₂O; prone for > 12 hours/day in moderate–severe ARDS [7]
- RRT: use for a definitive indication, not merely because AKI is present; either continuous or intermittent modality is acceptable [7]
- Corticosteroid: SSC 2026 conditionally suggests IV corticosteroids for septic shock [7]
- Nutrition: early enteral nutrition within 72 hours when feasible [7]
The lecture concludes with a powerful table [1]:
| Study | Reference | Result |
|---|---|---|
| ANZICS Renal Dose Dopamine | Lancet 2000 | Negative |
| Albumin Study (SAFE) | NEJM 2004 | No overall mortality difference vs saline |
| VASST (NE vs. Vasopressin) | NEJM 2008 | No overall mortality difference from adding vasopressin |
| CORTICUS (Steroids) | NEJM 2008 | No mortality benefit in that trial; faster shock reversal |
| NICE-SUGAR | NEJM 2009 | Intensive group WORSE |
| SOAP II (Dop vs. NE) | NEJM 2010 | No significant mortality difference; dopamine caused more arrhythmias |
| PROWESS-SHOCK (Activated Protein C) | NEJM 2012 | Negative |
| 6S Study (HES vs. Ringer's) | NEJM 2012 | Starch WORSE |
"Specific drugs to modulate the process of sepsis in favour of survival is still lacking." [1]
Exam Intelligence
“Negative” does not mean “never use the class.” The trials helped reject renal-dose dopamine, hydroxyethyl starch, drotrecogin alfa and tight glucose control. Albumin remains a selective option, vasopressin is a recommended add-on to escalating noradrenaline, and current SSC guidance conditionally supports IV corticosteroids in septic shock [7].
1. Sepsis is a complicated immune process of the body in response to infection. [1]
2. Early recognition of sepsis and effective antimicrobial therapy are important. [1]
3. Treatments that work theoretically need to be validated in RCTs. [1]
4. Specific drugs to modulate the process of sepsis in favour of survival is still lacking. [1]
9. Integration with Related Material
- 2024 SAQ Q11 [3]: A 65-year-old with cough, high fever, SOB, confusion, hypotension, ABG showing mixed acidosis with lactate 4.5 → classic septic shock from pneumonia. Expected answers: identify acid-base disturbance, investigations within 1 hour (blood cultures, lactate), and 5 management steps (O₂, IV fluids, blood cultures, empirical antibiotics, vasopressors).
- 2023 Minicase Case 3 [4]: S. aureus bacteremia → deterioration with T 41°C, warm extremities, BP 85/45 → septic shock. Asked for airway management, diagnosis of hemodynamic condition (septic shock), and 5 acute management points.
- 2021 Minicase Case 2 [5]: Acute cholecystitis with BP 95/50, HR 120 → asked about causes of hemodynamic instability (sepsis + hypovolemia) and pathophysiology.
Neutropenic fever → septic shock is the most feared complication. ANC < 500 + fever = empirical broad-spectrum antibiotics within 1 hour. Same urgency as Kumar et al. data.
Post-op sepsis management follows the same SSC principles. Source control may involve returning to OT.
High Yield Summary
- Sepsis-3
- Life-threatening organ dysfunction from dysregulated host response to infection.
- Septic shock = vasopressor needed for MAP ≥ 65 + lactate > 2 after fluids.
- Shock type: principally distributive (↓SVR); CO and peripheral temperature vary with time and mixed physiology.
- MODS: CVS (vasoplegia ± myocardial dysfunction), respiratory (ARDS), renal (multifactorial AKI), blood (DIC), GI (ileus/bleed), liver (jaundice), CNS (encephalopathy), PNS (ICU-acquired weakness).
- Current treatment: urgent likelihood-based antibiotics and source control; individualised crystalloid with dynamic reassessment; noradrenaline first; initial MAP about 65; serial lactate in context plus capillary refill; avoid starch/gelatin and tight glucose control [7].
- Landmark “negative studies” rejected rigid EGDT targets, renal-dose dopamine, HES, drotrecogin alfa and intensive insulin—not all colloids, steroids or vasopressin in every context.
Active Recall - High Fever Low BP
[1] Lecture slides: GC 059. High fever low BP.pdf (slides 1–40) [2] Senior notes: Ryan Ho Critical Care.pdf (pp. 15, 21–22) [3] Past papers: 2024 Fourth Summative SAQ.pdf (Q11, p.12) [4] Past papers: 2023 Fourth Summative Minicase.pdf (Case 3, pp.23–25) [5] Past papers: 2021 Fourth Summative Minicase.pdf (Case 2, pp.14–17) [6] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1329 — neutropenic fever) [7] Society of Critical Care Medicine & European Society of Intensive Care Medicine. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Intensive Care Med. 2026. [8] Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801–810. [9] Kidney Disease: Improving Global Outcomes. Clinical Practice Guideline for Acute Kidney Injury. 2012. (The 2027 update was still a public-review draft at the time of this note.) [10] Matthay MA, et al. A New Global Definition of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2024;209:37–47.
GC058 High Blood Pressure
High blood pressure (hypertension) is a chronic cardiovascular condition defined by persistently elevated systemic arterial pressure, typically ≥140/90 mmHg, that increases the risk of end-organ damage to the heart, brain, kidneys, and vasculature.
GC060 High White Cell Count
Leukocytosis is an elevation of the total white blood cell count above the normal range (typically > 11,000/μL), indicating infection, inflammation, stress, or hematologic malignancy.