The Sepsis Six protocol (oxygen, blood cultures, IV antibiotics, IV fluids, serum lactate, urine output monitoring) has robust evidence for mortality reduction in septic shock — a landmark 2015 UK Sepsis Trust audit showed that completing all six elements within 1 hour of sepsis recognition reduced mortality from approximately 40% to 20%. The key primary care action is calling 999 first, then initiating what can be done before the ambulance arrives: high-flow oxygen, IV access if available, blood cultures (one aerobic + one anaerobic set), and IV or IM broad-spectrum antibiotics. The 7% per-hour mortality increase for delayed antibiotics in septic shock is one of the most compelling statistics in emergency medicine. Addisonian crisis is frequently missed in primary care because: (1) the patient may not know they have Addison's (up to 30% of Addisonian crises are the presenting event); (2) the symptoms (fatigue, nausea, vomiting, abdominal pain, confusion) are non-specific; and (3) the BP may be only marginally low before deterioration. The electrolyte pattern (hyponatraemia + hyperkalaemia) combined with postural hypotension and hyperpigmentation in an unwell patient is pathognomonic. The safe action: give hydrocortisone 100 mg IM and call 999 — if the patient does not have Addison's, hydrocortisone 100 mg is not harmful. If they do and you do not give it, they may die.

The sildenafil (and all PDE5 inhibitors) + nitrate combination is the most dangerous drug-drug interaction in common primary care prescribing — both drugs independently cause vasodilatation and BP reduction (PDE5 inhibitors prevent cGMP breakdown → smooth muscle relaxation; nitrates directly release nitric oxide → cGMP-mediated vasodilation), and in combination can cause catastrophic hypotension resulting in syncope, MI, and death. This combination is absolutely contraindicated regardless of timing — the interaction can persist for up to 24 hours after sildenafil use. GPs prescribing nitrates must ask about sildenafil use; GPs prescribing sildenafil must check for nitrate use (including GTN spray kept for angina relief). The STOPP (Screening Tool of Older People's Prescriptions) criteria specifically identifies alpha-1 receptor blockers (tamsulosin, doxazosin) in patients prone to falls as inappropriate due to orthostatic hypotension risk — in an elderly patient presenting with falls, reviewing and stopping or reducing alpha-1 blockers is often the highest-yield single medication intervention.

The orthostatic BP measurement technique is one of the most commonly performed incorrectly — many clinicians measure a single standing BP immediately after the patient stands, without the prerequisite 5 minutes of supine rest. This misses the classical orthostatic pattern (which develops over 1–3 minutes as venous pooling accumulates) and produces false-negative results. The correct protocol takes 10 minutes but is the only reliable way to detect orthostatic hypotension. The absence of a compensatory tachycardia on standing is as diagnostically important as the BP drop itself — in normal orthostasis, HR rises by 10–20 bpm to compensate for reduced cardiac filling. Absence of this HR increase in the context of a significant BP drop indicates autonomic failure (the baroreflex arc is broken), pointing specifically to neurogenic causes: Multiple System Atrophy, pure autonomic failure, diabetic cardiac autonomic neuropathy, or Parkinson's disease with autonomic involvement. This finding should always trigger neurology referral.

Multiple System Atrophy (MSA) is a crucial diagnosis to recognise presenting as orthostatic hypotension — it is a progressive neurodegenerative disease causing autonomic failure (orthostatic hypotension, urinary dysfunction, erectile dysfunction, constipation) combined with parkinsonism and/or cerebellar ataxia. The key distinguishing feature from Parkinson's disease: MSA autonomic failure causes orthostatic hypotension without compensatory tachycardia because the entire sympathetic efferent system degenerates (not just the dopaminergic nigrostriatal pathway). In contrast, Parkinson's disease has variable and often mild orthostatic hypotension with partial HR compensation. Any patient with Parkinsonism + severe orthostatic hypotension (SBP drop >30 mmHg) + urinary dysfunction = MSA until neurology assessment proves otherwise. MSA has a significantly worse prognosis than PD (median survival 7–9 years from symptom onset) — patients deserve accurate diagnosis and appropriate support.

The falls-hypotension linkage is a NICE quality standard — orthostatic hypotension is one of the most prevalent modifiable fall risk factors in community-dwelling elderly patients (present in approximately 20% of those over 65). NICE NG147 (Falls in older people, 2019) requires that all older patients presenting with falls have an assessment for postural hypotension including lying-to-standing BP measurement. GPs should incorporate this measurement into every fall assessment. The multifactorial falls intervention (STOPP medication review + physiotherapy gait and balance + OT home hazard assessment + vision check + vitamin D/calcium) reduces fall rate by approximately 30–40% in at-risk patients. The medication review is often the highest-yield intervention — removing one antihypertensive, diuretic, or alpha-blocker from a polypharmacy elderly patient can be transformative for falls frequency and quality of life.

Fludrocortisone for neurogenic orthostatic hypotension requires careful supine BP monitoring — while fludrocortisone raises plasma volume and improves standing BP (desired), it simultaneously raises supine BP (potentially harmful in patients with cardiac disease or pre-existing hypertension). The target: eliminate symptomatic standing hypotension while maintaining supine systolic BP below 150–160 mmHg. If supine hypertension develops on fludrocortisone, the dose should be reduced and midodrine considered as an alternative (midodrine has a shorter duration of action and can be timed to avoid overnight supine hypertension — patients should not take it within 4 hours of bedtime). The Jordan 1999 RCT cold-water-before-meals finding: 480 ml of cold water ingested 15 minutes before a meal increased standing BP by approximately 20 mmHg for 45–60 minutes in elderly patients with post-prandial hypotension, via a sympathetic nervous system reflex triggered by gastric distension with cold fluid. This is entirely free, safe, has no contraindications, and specifically targets the post-prandial period.

Midodrine is available in the UK (licensed as Gutron) and is listed in the BNF for symptomatic orthostatic hypotension. It is the preferred second-line agent after fludrocortisone in neurogenic OH because it acts peripherally (alpha-1 agonist on peripheral vasculature) without CNS stimulation, and its shorter duration of action (3–4 hours per dose) allows dosing to be timed to waking hours, avoiding overnight supine hypertension. GPs may initiate midodrine following a specialist recommendation or for patients with clearly established neurogenic OH who have failed or cannot tolerate fludrocortisone. The three-times-daily dosing schedule should be planned around the patient's activity: typically on waking, mid-morning, and early afternoon — never in the evening. The clinical goal is symptomatic improvement in standing tolerance and reduction in fall frequency, not a specific BP target.

Head-of-bed elevation is a counter-intuitive but evidence-based intervention that most patients have not heard of — the mechanism is that sleeping with the head elevated 10–15 degrees causes mild volume redistribution overnight (reduced renal perfusion → renin-angiotensin activation → aldosterone release → sodium retention → expanded plasma volume by morning). This effect is specific to whole-body tilt (head AND torso elevated together) — using extra pillows only flexes the cervical spine without the haemodynamic benefit. Studies in autonomic failure patients show morning orthostatic BP improves by approximately 10–15 mmHg with consistent head-of-bed elevation. The practical instruction: place 10–15 cm blocks (wooden blocks, thick books, commercially available bed risers) under the two legs at the HEAD end of the bed only, tilting the entire mattress. Document that the patient has been instructed in this technique and understands the distinction from using extra pillows.

The Addison's sick day rules education is the highest-priority recurring safety message for any patient with adrenal insufficiency — adrenal crisis (acute cortisol deficiency during physical stress) is potentially fatal and almost entirely preventable with appropriate dose adjustment. The key failure mode: patients forget their sick day rules, or their family/partner does not know about them, and when the patient becomes too unwell to take oral steroids or loses consciousness, no one gives the IM injection. Prevention: (1) teach the rules at EVERY primary care encounter (not just at diagnosis); (2) ensure a family member or carer is trained in IM hydrocortisone administration; (3) check at each annual review that the IM kit is in date and the patient is carrying their emergency card; (4) add 'Addisonian — sick day rules education given' as a coded alert in the patient record to ensure every clinician who sees the patient reinforces this. Approximately 5–10% of Addison's patients require hospital admission for adrenal crisis each year — better sick day rules education would prevent the majority.