Antihypertensive Management — Zaib Un Nisa (67F, post-IVH)

Why the Current Regimen is Inadequate

• Prazosin (alpha-1 blocker) is not a first-line agent for hypertension in any major guideline (AHA/ACC, ESC, NICE). It lacks cardiovascular outcome data.
• It has no renoprotective benefit in CKD, no heart failure outcome benefit, and no specific post-stroke indication.
• Its short half-life causes significant BP variability, which is particularly dangerous post-ICH — BP variability independently worsens outcomes after intracerebral hemorrhage (Tanaka et al., Stroke 2014; de Havenon et al., Stroke 2018).
• BP of ~180/70 mmHg represents uncontrolled, isolated systolic hypertension — a major risk factor for recurrent hemorrhagic stroke.

BP Target for This Patient

Recommended Drug Strategy

1. ACE Inhibitor or ARB — FIRST PRIORITY

• Indications: CKD stage 4 (renoprotective, reduces proteinuria), DM2, HFpEF, hypertension, post-stroke
• Choice: Ramipril 2.5–5 mg OD OR Telmisartan 20–40 mg OD (if ACEi-intolerant)
• Caution: Monitor creatinine and K⁺ at 1–2 weeks; acceptable if creatinine rise <30% and K⁺ <5.5 mmol/L
• Note: Valsartan was held during admission due to AKI — check current eGFR before recommencing. If eGFR has stabilized, an ARB/ACEi should be restarted.

2. Calcium Channel Blocker (CCB) — ADD-ON

• Choice: Amlodipine 5 mg OD (titrate to 10 mg)
• Indications: Isolated systolic hypertension, post-stroke BP reduction, well-tolerated in CKD
• Has a long half-life — reduces BP variability (important post-ICH)
• Caution regarding aortic stenosis: CCBs are generally safe in aortic stenosis unless severe AS with low EF. She has HFpEF (preserved EF), so amlodipine is acceptable. Avoid verapamil/diltiazem due to negative inotropy + conduction effects.

3. Consider SGLT2 Inhibitor (for DM + HFpEF + CKD)

• Empagliflozin 10 mg OD or Dapagliflozin 10 mg OD
• Provides: HFpEF benefit (EMPEROR-Preserved, DELIVER trials), renal protection (EMPA-KIDNEY, DAPA-CKD), modest BP lowering (~3–5 mmHg SBP), cardiometabolic benefit
• Caution: eGFR must be ≥20 ml/min for dapagliflozin; ≥20 ml/min for empagliflozin. With CKD stage 4 (GFR 15–29), empagliflozin can still be used for its cardioprotective/renal effects even at lower eGFR — check current eGFR.
• Reduces recurrent CV events and hospitalizations in this phenotype.

4. Consider Low-dose Thiazide-like Diuretic or Loop Diuretic

• If she has fluid overload (HFpEF): Furosemide 20–40 mg OD
• Thiazide diuretics (e.g., indapamide 1.5 mg SR) are effective for isolated systolic hypertension and have post-stroke data (PROGRESS trial — perindopril + indapamide reduced recurrent stroke by 43%)
• However: In CKD stage 4, thiazides have reduced efficacy; loop diuretics preferred if diuresis is needed.

5. Discontinue or Deprioritize Prazosin

• Once effective agents are added and BP controlled, prazosin can be weaned off.
• If retained for any reason (e.g., urinary symptoms), it should not be the primary antihypertensive.

Practical Titration Sequence

Step 1 (Now):
- Restart ACEi/ARB if renal function allows (check BMP first)
  → Ramipril 2.5 mg OD or Telmisartan 20 mg OD
- Add Amlodipine 5 mg OD

Step 2 (2–4 weeks, if BP still >130/80):
- Up-titrate Amlodipine to 10 mg OD
- Up-titrate Ramipril to 5–10 mg OD / Telmisartan to 40–80 mg OD

Step 3 (If BP still not at target):
- Add Indapamide 1.5 mg SR OD (or furosemide if HF-related fluid overload)
- Introduce SGLT2i if eGFR permits

Step 4:
- Wean and discontinue prazosin

Special Considerations in This Patient

Monitoring Plan

• Week 1–2: Renal function (Cr, K⁺, eGFR) after starting/restarting ACEi/ARB
• Monthly: BP (home readings ideally), renal function, blood glucose/HbA1c
• Quarterly: BMP, lipid panel (she has hyperlipidemia — ensure statin is on board)
• Echocardiogram: Reassess severity of aortic stenosis and EF — guides further management

Summary

1. ACEi or ARB (renoprotection, post-stroke BP reduction, DM)
2. Long-acting CCB (amlodipine) for sustained BP control with minimal variability
3. SGLT2 inhibitor given the triple overlap of DM + HFpEF + CKD
4. Diuretic as needed
5. Target SBP <130 mmHg to prevent recurrent hemorrhagic stroke

Insulin Regimen Review & Optimization

Problem 1: The Regimen Makes No Pharmacological Sense

• Insulin lispro 12 U OD — lispro is a rapid-acting insulin (onset 15 min, peak 30–90 min, duration 2–4 hours). Giving it once daily provides no meaningful basal coverage. It is not a basal insulin and should never be used as one.
• "Short-acting TDS" — presumably regular insulin (Actrapid/Humulin R) three times daily, likely with meals.

Problem 2: What She Actually Needs

Recommended Revised Regimen

Step 1 — Start Basal Insulin

• Insulin glargine (Lantus) 10 U SC at bedtime (or 0.1–0.2 U/kg/day)
  • For a typical 60–70 kg woman: start at 10–14 U at night
  • Titrate by 2 U every 3 days if fasting glucose >7 mmol/L (>126 mg/dL)
  • Target fasting glucose: 5–8 mmol/L
• Alternatively: Insulin degludec (Tresiba) — preferred if hypoglycemia is a concern (longer, flatter profile)

Step 2 — Bolus Insulin with Meals

• Insulin lispro (or aspart) before each main meal — keep the TDS short-acting but clarify it is a rapid-acting analogue
• Starting dose: 4–6 U per meal, titrate based on 2-hour post-meal glucose
• Target post-prandial glucose: <10 mmol/L (180 mg/dL)
• Important: She is PEG-fed — bolus insulin should be given relative to tube feed timing, not "meals." If feeds are continuous, a basal-only or basal-heavy regimen may be more appropriate. If bolus feeds TDS, give rapid-acting insulin with each feed.

Step 3 — Discontinue the Single Daily Lispro

Add-on Non-Insulin Therapy

SGLT2 Inhibitor — Strongly Recommended

• Empagliflozin 10 mg OD — proven benefit in HFpEF (EMPEROR-Preserved) and CKD (EMPA-KIDNEY) even at low eGFR
• Reduces HbA1c by ~0.5–1%, lowers SBP by 3–5 mmHg, reduces hospitalization for HF
• Can be used down to eGFR ≥20 ml/min for cardio/renal indication (even if glycemic efficacy is reduced)
• Given via PEG tube (tablet dispersible in water)

DPP-4 Inhibitor — Alternative if SGLT2i not tolerated

• Linagliptin 5 mg OD — no dose adjustment needed in CKD (unlike sitagliptin/alogliptin)
• Safe in CKD stage 4, neutral on HF outcomes
• Modest HbA1c reduction (~0.5–0.8%)
• Per guidelines (Medications for Blood Glucose Management in T2DM): DPP-4i are second-choice behind SGLT2i/GLP-1 RA in patients with CKD and HF, but useful when those are contraindicated or unavailable.

Blood Glucose Targets for This Patient

Strict glycemic control is less important than avoiding hypoglycemia in this patient. Hypoglycemia post-stroke causes secondary neurological injury and worsens outcomes. A slightly relaxed HbA1c target of 7.5–8% is appropriate.

PEG Tube Feeding Considerations

• If on continuous feeds: use basal insulin only (glargine/degludec) + correction doses; avoid fixed-dose pre-meal bolus
• If on intermittent bolus feeds TDS: give rapid-acting insulin with each feed bolus
• Hold rapid-acting insulin if feed is delayed or stopped — risk of hypoglycemia
• Monitor glucose every 6 hours initially

Summary of Changes

Revised Assessment: Lantus (Glargine) 12 U OD + Lispro TDS

What She Has Now

Why 12 U Glargine is Likely Insufficient

• Standard basal insulin starting dose: 0.1–0.2 U/kg/day
  • At 65 kg: 6.5–13 U → 12 U is at the lower end of the starting range, not a therapeutic maintenance dose
• For uncontrolled T2DM already on basal-bolus, the basal requirement is typically 0.3–0.5 U/kg/day
  • At 65 kg: that's ~20–35 U of glargine
• 12 U is essentially a starting/initiation dose — it has likely never been titrated up

Basal Insulin Titration Protocol

• Review and adjust every 3 days
• No ceiling until fasting glucose is consistently at target (6–8 mmol/L)
• Most T2DM patients on basal-bolus end up needing 30–60 U/day of glargine

Bolus Lispro — What to Check

• Fixed low dose not titrated to meal size or post-prandial glucose
• Not being given appropriately relative to PEG feeds (as discussed previously)

The "Basal First" Diagnostic Step

Practical Plan

1. Titrate glargine upward — increase by 2–4 U every 3 days based on fasting glucose, targeting 6–8 mmol/L. Most patients will need 25–40 U before fasting glucose is controlled.
2. Check lispro dose — if not documented, start at 4–6 U per feed/meal and titrate by 2-hourly post-feed glucose.
3. Add Empagliflozin 10 mg OD — provides independent glycemic, cardiac, and renal benefit on top of insulin (check current eGFR first).
4. Monitor for hypoglycemia — especially important post-IVH; if any fasting glucose <5 mmol/L, reduce glargine before increasing it further.
5. HbA1c target: 7.5–8% — do not push for tight control given her neurological status and hypoglycemia risk.

Bottom Line

Medication Restart Review

1. Lasix 40 mg (Furosemide) — ✅ RESTART

• She has HFpEF, hypertension, and CKD stage 4 — all indications for a loop diuretic
• Furosemide remains effective even at low eGFR (unlike thiazides)
• Helps with volume status in HFpEF and contributes to BP lowering
• Dose: 40 mg OD — reasonable starting point; can titrate to 40 mg BD if fluid overloaded
• Monitor: renal function, electrolytes (K⁺, Na⁺) at 1–2 weeks — loop diuretics cause hypokalemia, which is dangerous in a post-stroke patient
• Via PEG: furosemide oral solution or crushed tablet is acceptable

2. Diovan 80 mg (Valsartan) — ✅ RESTART, WITH CAUTION

• She has hypertension, CKD stage 4, DM2, HFpEF — all strong indications for an ARB
• Valsartan was held during admission due to AKI — now that she is stable at home, it should be restarted
• Critical prerequisite: Check creatinine, eGFR, and potassium before restarting
  • If eGFR has returned to baseline (CKD stage 4 = 15–29 ml/min) → restart at 40–80 mg OD
  • If K⁺ >5.5 mmol/L → hold until corrected (especially as she is also on furosemide which paradoxically may help K⁺ balance)
• Recheck renal function and K⁺ 1–2 weeks after restarting
• This is also the most important drug for secondary stroke prevention via BP control
• Consider uptitrating to 160 mg OD once tolerated, given her BP is 180/70

3. Dexlansoprazole 60 mg (Dolgina / Dexilant) — ⚠️ RESTART BUT RATIONALIZE

• She has a PEG tube — PPI use is reasonable to prevent stress/tube-related gastropathy
• However, two brands of the same drug (Dolgina and Dexilant) are present — she should only be on one
• Dose: Dexlansoprazole 30–60 mg OD via PEG — capsules can be opened and granules administered directly through the tube (do not crush the granules)
• Reassess whether long-term PPI is still needed — if no active GI indication, step down to 30 mg or switch to a cheaper PPI (omeprazole 20 mg OD)

4. Zyloric 100 mg (Allopurinol) — ⚠️ RESTART WITH DOSE ADJUSTMENT

• Presumably prescribed for gout or hyperuricemia, likely in the context of CKD (uric acid rises with declining GFR)
• Allopurinol is generally safe in CKD but requires dose reduction:

• At CKD stage 4 (eGFR 15–29), 100 mg OD is acceptable but should not be increased without monitoring
• Check uric acid level before restarting — if normal, question whether it is still needed
• Caution: Allopurinol + furosemide together increases risk of allopurinol toxicity (furosemide competes for renal tubular secretion and raises urate) — monitor closely

Summary Table

What is Still Missing From Her Regimen

Prazosin — Stop It

Why Prazosin Was Likely Started

Reasons to Stop It in This Patient

1. Valsartan + Furosemide + Amlodipine (to be added) are superior replacements

• These three agents together will provide adequate, evidence-based BP control
• There is no residual role for prazosin once this combination is in place

2. Significant hypotension and fall risk

• Prazosin causes postural/orthostatic hypotension — especially the first-dose effect and with concurrent use of furosemide and valsartan
• This patient is post-IVH, post-craniotomy, with right-sided weakness requiring rehabilitation
• A fall could be catastrophic — recurrent ICH, fracture, further neurological injury
• Loop diuretics + ARB + alpha-blocker together is a high-risk combination for syncope

3. No cardiovascular outcome benefit

• Prazosin has no proven benefit in reducing stroke, MI, heart failure hospitalization, or renal progression
• The ALLHAT trial demonstrated that alpha-blockers (doxazosin) were inferior to thiazide diuretics for cardiovascular outcomes in hypertension — the doxazosin arm was stopped early due to increased heart failure events

4. Not appropriate in HFpEF

• Peripheral vasodilation from alpha-blockade can cause reflex tachycardia, which is poorly tolerated in aortic stenosis
• No benefit in heart failure management

5. BP variability

• Short half-life of prazosin causes fluctuating BP throughout the day
• As discussed, BP variability post-ICH independently worsens neurological outcomes

The Only Reason to Keep It

Transition Plan

Corrected Stance on Valsartan Restart

• Her kidneys had already adapted to the ARB at her baseline CKD stage 4 eGFR
• There is no need to treat it as a new prescription requiring pre-checks
• The valsartan was only held temporarily during admission because of the acute-on-chronic kidney injury (creatinine peaked at 1.95 mg/dL) — a standard precaution during AKI
• Now that she is stable and back home, she can simply resume her previous dose

What You Still Should Do — But Routinely, Not as a Gate

Practical Instruction

Restart valsartan 80 mg OD now — no need to wait for bloods. Check renal function and electrolytes at the next clinic visit as routine monitoring, not as a prerequisite.

Furosemide 40 mg — Restart Without Hesitation

• Her kidneys were already functioning at CKD stage 4 on furosemide chronically
• She tolerated it at baseline
• It was part of her established regimen for HFpEF + hypertension
• No reason to withhold it now that she is stable at home

One Practical Point — Timing with Valsartan

• Furosemide causes volume depletion → can amplify the hypotensive effect of valsartan
• This is not a reason to delay either drug, but give a practical instruction to the family/carer:

Take furosemide in the morning and valsartan at any consistent time daily. Ensure she is well hydrated via PEG feeds — do not restrict fluids excessively.

Summary — Restart Order

Furosemide — OD is Sufficient

• She is stable at home, not acutely fluid overloaded
• Her primary indication is chronic HFpEF management and hypertension — not acute decompensation
• In CKD stage 4, the kidneys still respond adequately to once-daily furosemide at this dose
• BD dosing (40 mg BD = 80 mg/day) is reserved for:
  • Acute decompensated heart failure
  • Resistant fluid overload (leg swelling, pulmonary congestion)
  • Inadequate response to OD

If she develops leg swelling, breathlessness, or signs of fluid overload → step up to 40 mg BD at that point

Valsartan — OD is Sufficient, But Consider Uptitration

• 320 mg OD is the maximum licensed dose for hypertension
• In HFpEF the target dose in trials (Val-HeFT) was 160 mg BD — so BD dosing has a role specifically if HF is the primary indication and BP tolerates it

Bottom Line

Insulin Regimen Assessment: Glargine 14 U OD + Lispro 8 U TDS

Total Daily Dose (TDD)

The Problem — Basal:Bolus Ratio is Off

• The basal is relatively underdosed compared to the bolus
• This means fasting and overnight glucose will be poorly controlled
• High fasting glucose then drives high glucose all day regardless of how much bolus is given

What to Do

Step 1 — Titrate Glargine Based on Fasting Glucose

• Adjust every 3 days
• Expected final glargine dose: likely 20–30 U OD before fasting glucose is controlled
• Do not keep increasing lispro to compensate for high fasting glucose — fix the basal first

Step 2 — Review Lispro Once Fasting is Controlled

• 8 U TDS is a reasonable starting bolus dose — may need to go to 10–12 U TDS
• Titrate each meal dose independently if glucose patterns differ by meal

PEG Feed Consideration

• Confirm feeds are given TDS as bolus feeds — if so, lispro timing is correct (give just before or at time of each feed)
• If feeds are continuous, lispro TDS is less appropriate — switch to corrections only with basal-heavy regimen
• Never give lispro if a feed is delayed or stopped — hypoglycemia risk

Glucose Monitoring Schedule

Summary

Continuous PEG Feeding + RBS >200 mg/dL at 6am

What the 6am High Sugar Tells You

• Overnight glucose while feed is running
• Primarily driven by inadequate basal insulin (glargine)
• Glargine is not covering the continuous glucose load from the feed overnight

Lispro TDS is Inappropriate for Continuous Feeding

• Lispro is a rapid-acting insulin designed to cover discrete meal glucose spikes
• On continuous 24-hour feeding, there are no meal spikes — glucose load is constant and spread evenly
• Giving lispro TDS creates unpredictable peaks and troughs — risk of hypoglycemia between doses and inadequate coverage at other times
• Lispro TDS should be stopped

Correct Insulin Strategy for Continuous 24-Hour PEG Feeding

The Principle

Continuous feed = continuous glucose load → needs continuous/basal coverage, not bolus spikes

Recommended Regimen

1. Glargine — Increase and Split

• This replaces the single 14 U OD dose
• More physiological for continuous feeding
• Titrate total daily dose upward based on glucose readings
• Alternatively keep OD but increase to 20–24 U if BD not feasible

2. Stop Lispro TDS — Replace with Correction Doses Only

• Check glucose every 6 hours (6am, 12pm, 6pm, 12am)
• Give correction lispro only when needed based on the scale above
• This replaces fixed TDS lispro

3. What to Do if Feed is Interrupted

If feed stops or is interrupted for any reason → reduce glargine by 20–30% immediately and monitor glucose every 2 hours

Titration Going Forward

Target Glucose on Continuous Feeds

Summary of Changes

⚠️ ACUTE EMERGENCY — Hypotension + Anuria

Immediate Actions — Do Right Now

1. CALL EMERGENCY SERVICES IMMEDIATELY

2. While Waiting for Ambulance

• Furosemide — do not give next dose
• Valsartan — hold
• Prazosin — hold
• Amlodipine — hold (if already started)

3. Position

• Lay her flat — elevate legs slightly if no respiratory distress
• If breathless — sit her up (may indicate acute pulmonary oedema)

4. Check Immediately at Home if Possible

Differential Diagnosis — What is Causing This?

In Hospital — Expected Management

• IV fluid challenge: 250 ml Normal Saline bolus over 15–30 min (cautiously given HFpEF and AS)
• Urinary catheter: confirm true anuria vs urinary retention (common post-stroke)
• Urgent bloods: FBC, renal function, electrolytes, lactate, blood cultures, glucose
• ECG + troponin: rule out acute MI
• Urgent renal review: AKI on CKD
• CT brain: if any change in neurology — rule out rebleed
• Hold all antihypertensives and diuretics until haemodynamically stable

Critical Point

The combination of restarting furosemide + valsartan together in a CKD stage 4 patient who may not have been adequately hydrated via PEG feeds is the most likely cause of this acute decompensation — aggressive volume depletion leading to pre-renal AKI and hypotension.