What clinical criteria define a sick‑day that warrants temporary discontinuation of renin‑angiotensin system blockers, diuretics, NSAIDs, SGLT2 inhibitors, and metformin?

Sick Day Criteria for Medication Discontinuation

A sick day requiring temporary medication discontinuation is defined by one or more new or worsening signs of volume depletion: vomiting or diarrhea causing significant fluid losses, anorexia or nausea reducing fluid intake significantly, new lightheadedness/dizziness/fainting (especially orthostatic), weight loss ≥3 kg in 2 days, or decreased urine output. 111

Core Triggering Symptoms

The 2023 international consensus guidelines achieved 100% agreement on the following sick day triggers 11:

• Vomiting or diarrhea resulting in significant fluid losses (100% consensus)
• Anorexia or nausea causing significant decrease in fluid intake (88% consensus)
• New orthostatic symptoms: lightheadedness, dizziness, or fainting, particularly with position changes (88% consensus)
• Acute weight loss: ≥3 kg over 2 days (83% consensus)
• Decreased urine output (75% consensus)

Critical distinction: These symptoms must be new or more frequent/severe than usual 11. Many patients with chronic disease experience baseline symptoms from their conditions or medications (e.g., nausea from GLP-1 receptor agonists), so the emphasis is on acute changes, particularly when fluid intake cannot keep pace with losses.

Red Flag Symptoms Requiring Immediate Healthcare Contact

The following severe symptoms warrant urgent contact with a healthcare provider rather than self-management 11:

• Reduced level of consciousness or new confusion (100% consensus)
• Vomiting >4 times in 12 hours or inability to keep fluids down (96% consensus)
• Low blood pressure: SBP <80 mmHg or drop of 20 mmHg in SBP/10 mmHg in DBP (92% consensus)
• Moderate or high ketones in patients taking SGLT2 inhibitors or insulin (91% consensus)
• Tachycardia: heart rate increase by 30 bpm (79% consensus)
• Fever: temperature >38°C (101°F) on 2 measurements (75% consensus)

Emergency services (911) should be sought for difficulty/rapid breathing or reduced consciousness 1.

Medications to Temporarily Stop

When sick day criteria are met, the following medications should be held 111:

Stop completely:

• SGLT2 inhibitors (96% consensus)
• NSAIDs (95% consensus)
• All diuretics: loop (95%), potassium-sparing (95%), thiazides/thiazide-like (90%)
• ACE inhibitors/ARBs (90% consensus)
• ARNI/sacubitril-valsartan (88% consensus)
• Metformin (86% consensus)
• Direct renin inhibitors/aliskiren (82% consensus)

Conditional management:

• Insulin/sulfonylureas/meglitinides: Hold ONLY if blood glucose is low; otherwise continue or increase by 10-20% if glucose elevated (96% consensus) 11

Do NOT routinely stop:

• GLP-1 receptor agonists (only 57% consensus—insufficient agreement due to long half-lives and lack of volume depletion risk) 1

Duration and Resumption

Hold medications for 111:

• Up to 3 days maximum (100% consensus)
• Until signs and symptoms resolve (88% consensus)

Resume medications 1:

• Within 24-48 hours of eating and drinking normally (95% consensus)
• For medications causing hypoglycemia: resume at usual doses as soon as symptoms improve and normal eating resumes (100% consensus)
• Seek healthcare assistance if symptoms persist >72 hours (100% consensus)

Self-Management Requirements

Sick day guidance is appropriate for self-management when 11:

• Absence of severe symptoms (96% consensus)
• Patient feels able to cope (92% consensus)
• Patient can maintain fluid intake (88% consensus)

Required self-monitoring actions 11:

• Patients on insulin: check blood glucose every 4-6 hours while awake (100% consensus)
• Patients on SGLT2 inhibitors, insulin, or ketogenic diets: check ketones (95% consensus)
• Increase fluid intake with limited caffeine; consider electrolyte replacement (92% consensus)

Common Pitfalls

Critical caveat: The metformin FDA label specifically warns about withholding during "restricted food and fluid intake" during surgical or other procedures due to increased risk of volume depletion, hypotension, and renal impairment 2. This directly supports sick day guidance for acute dehydrating illnesses.

Implementation barrier: Recent evidence shows that while 373 patients received sick day education, only 8 sick days were reported to healthcare providers, though telephone surveys revealed 12 additional unreported sick days occurred 3. This highlights that patient education alone is insufficient—involving caregivers and providing clear reporting mechanisms is essential.

Emerging controversy: Some experts question routine SGLT2 inhibitor discontinuation during illness, noting low DKA rates in cardiovascular outcome trials and potential loss of therapeutic benefits 4. However, the 2023 consensus guidelines with 96% expert agreement support temporary discontinuation 11, and this remains the current standard recommendation until further research clarifies optimal management.