Define septic shock, SIRS and MODS. Discuss the etiopathogenesis, investigations and treatment

SIRS (ACCP/SCCM 1992) = two or more of: temperature > 38°C or < 36°C; heart rate > 90/min; respiratory rate > 20/min or PaCO < 32 mmHg; total leucocyte count > 12,000/µL or < 4,000/µL or > 10% band forms. It is non-specific 2 — pancreatitis, burns, trauma and surgery also produce SIRS.

Septic shock = a subset of sepsis with circulatory, cellular and metabolic abnormalities profound enough to increase mortality substantially. Clinically: vasopressors needed to maintain MAP ‡ 65 mmHg AND lactate > 2 mmol/L despite adequate fluid resuscitation. Hospital mortality exceeds 40%.

MODS = progressive but potentially reversible dysfunction of two or more organ systems arising from an acute insult, such that homeostasis cannot be maintained without intervention. Primary MODS results directly from the insult; secondary MODS develops later as a consequence of the host response.

SOFA score grades six systems 0–4 each: respiratory (PaO /FiO ), coagulation (platelets), hepatic (bilirubin), 2 2 cardiovascular (MAP/vasopressor dose), CNS (Glasgow Coma Scale) and renal (creatinine/urine output). A rise of ‡ 2 points defines sepsis.

Trigger: PAMPs (lipopolysaccharide, peptidoglycan, flagellin) and DAMPs (mitochondrial DNA, HMGB1, histones released from injured cells) are recognised by Toll-like receptors on monocytes and endothelium.

Hyperinflammatory limb: TLR ligation activates NF-kB and the inflammasome, releasing TNF-a, IL-1b, IL-6 and IL-8 — the ‘cytokine storm’ that produces fever, capillary leak and myocardial depression.

Endothelial injury: shedding of the endothelial glycocalyx, loss of tight junctions and upregulated adhesion molecules cause capillary leak, tissue oedema and microcirculatory failure, with maldistribution of flow despite a normal or high cardiac output.

Vasoplegia: induction of iNOS generates excess nitric oxide; ATP-sensitive potassium channels open and vasopressin stores are depleted, producing catecholamine-resistant vasodilatation.

Coagulopathy: monocyte and endothelial tissue factor expression drives thrombin generation, while the natural anticoagulants (antithrombin, protein C, protein S) are consumed and fibrinolysis is suppressed by PAI-1 — giving microvascular thrombosis with simultaneous bleeding, i.e. DIC.

The paradox of DIC (Pathy's Ch. 23): the clinical picture is one of bleeding, while morbidity and mortality result from organ damage due to microvascular thrombosis — AKI and ARDS. Recognising and treating the underlying cause matters far more than replacing factors; giving factors and platelets without treating the cause simply provides more substrate for thrombosis.

Cellular/mitochondrial dysfunction: nitric-oxide-mediated inhibition of the respiratory chain produces cytopathic hypoxia — oxygen is delivered but cannot be utilised, hence lactate rises despite adequate perfusion.

Immunoparalysis (compensatory anti-inflammatory response): lymphocyte and dendritic-cell apoptosis, reduced monocyte HLA-DR expression, IL-10 excess — responsible for late deaths from secondary and opportunistic infection and for viral reactivation (CMV, HSV).

Why the elderly do worse: inflammaging gives a raised baseline IL-6 and TNF-a; immunosenescence impairs pathogen clearance; reduced cardiac, renal, respiratory and cerebral reserve means a small insult exhausts compensation; and polypharmacy (beta-blockers masking tachycardia, ACE inhibitors and diuretics worsening hypotension, NSAIDs precipitating AKI) blunts both the response and its recognition.

Confirm and grade organ dysfunction: haemogram, serum lactate and repeat lactate, ABG (metabolic acidosis, raised anion gap, PaO /FiO ratio), creatinine and urine output, bilirubin and transaminases, GCS.

DIC screen (Pathy's, Table 23): APTT prolonged > 10 s beyond normal; PT prolonged > 5 s; thrombin time prolonged > 10 s; fibrinogen usually < 1 g/L; platelets usually < 50,000/µL; D-dimer > 1000 ng/mL. Serial trends matter more than a single set.

Microbiology: two sets of blood cultures before antibiotics, urine, sputum/endotracheal aspirate, pus, CSF; pathogen-specific rapid molecular tests on a case-by-case basis.

Source imaging: chest radiograph, ultrasound abdomen and chest (chest ultrasound is particularly suitable in the geriatric patient), CT abdomen/thorax, echocardiography. Biomarkers — CRP, procalcitonin (better for de-escalation than initiation) — support but never replace clinical judgement.

Resuscitation: 30 mL/kg balanced crystalloid in the first 3 hours for hypoperfusion, then individualised; noradrenaline first-line, started peripherally if necessary; vasopressin added on escalation; adrenaline third; dobutamine added if there is myocardial dysfunction with persistent hypoperfusion despite adequate filling.

Anti-infective therapy and source control as in Q1 — immediate broad-spectrum antibiotics in shock, ideally within one hour, and source control ideally within 6 hours.

Organ support: lung-protective ventilation at 6 mL/kg ideal body weight with plateau pressure £ 30 cmH O in 2 ARDS, higher PEEP in moderate-to-severe ARDS, prone positioning > 12 h/day; renal replacement therapy only for definite indications; sodium bicarbonate only if pH £ 7.2 with AKIN stage 2–3.

Treatment of DIC: treat the cause; transfuse only if bleeding or before a procedure — platelets if < 50,000/µL with bleeding, fresh frozen plasma for prolonged PT/APTT, cryoprecipitate or fibrinogen concentrate if fibrinogen < 1 g/L. In the chronic/thrombotic form (malignancy-associated), low-molecular-weight heparin is the treatment of choice, with DOACs a recognised alternative; warfarin is notoriously difficult in this setting.

Adjuncts and de-escalation: IV hydrocortisone in vasopressor-dependent shock; stress-ulcer prophylaxis with a PPI if risk factors; LMWH thromboprophylaxis; early enteral nutrition; active fluid removal with diuretics after the acute resuscitation phase; daily review for antimicrobial de-escalation and for the shortest effective duration.