1. Hemodynamic Support During Glycemic Excursions

Severe hyper- or hypoglycemia can precipitate volume shifts, osmotic diuresis, and vascular tone changes that lead to hypotension or end-organ hypoperfusion. Prompt assessment and tailored resuscitation are essential.

1.1 Fluid Resuscitation and Volume Status

In hyperglycemic emergencies (DKA, HHS):

• Initial bolus: Begin with 0.9% NaCl at 15–20 mL/kg over the first hour to rapidly expand intravascular volume.
• Fluid selection: Switch to a balanced crystalloid (e.g., Lactated Ringer’s) once hemodynamics stabilize to reduce the risk of hyperchloremic metabolic acidosis.
• Monitoring: Continuously assess urine output, hemodynamics, and dynamic indices of fluid responsiveness like passive leg raise or stroke volume variation.

Electrolyte Repletion:

• Potassium: If serum K⁺ is <5.3 mmol/L, replete aggressively before initiating insulin therapy. The goal is to maintain K⁺ ≥4.0 mmol/L to prevent life-threatening arrhythmias.
• Phosphate: For severe hypophosphatemia (<1.0 mg/dL), administer 20–45 mmol of potassium phosphate over 4 hours. Monitor levels closely to avoid over-repletion.
• Magnesium: Maintain serum Mg²⁺ ≥2 mg/dL to facilitate potassium repletion and ensure cardiac membrane stability.

1.2 Vasopressor Titration in Hypo- and Hyperglycemia

• First-line agent: Use norepinephrine for hypotension that is not responsive to initial fluid resuscitation. Consider adding vasopressin as a catecholamine-sparing agent in cases of refractory shock.
• DKA considerations: Be aware that insulin initiation can worsen hypotension through vasodilation. Ensure adequate vasopressor support is in place before starting or significantly increasing an insulin infusion.
• Hypoglycemia considerations: The endogenous catecholamine surge during a hypoglycemic event may cause transient hypertension or tachyarrhythmias. Anticipate the need for rapid vasopressor de-escalation after glucose correction.

2. Prevention of ICU-Related Complications

Dysglycemia augments the risk for common ICU complications, including venous thromboembolism (VTE) and stress-related mucosal bleeding. Prophylaxis must be individualized to balance the benefits against the risks of bleeding or infection.

2.1 VTE Prophylaxis: Dosing Adjustments in Dysglycemia

Hyperglycemia and diabetes create a prothrombotic state by potentiating coagulation and platelet activation. Pharmacologic prophylaxis is generally preferred.

• Preferred agent: Enoxaparin 40 mg subcutaneously once daily is a standard regimen. This should be reduced to 30 mg subcutaneously once daily if creatinine clearance (CrCl) is <30 mL/min.
• Obesity: In patients with a BMI ≥40 kg/m², consider weight-based dosing such as enoxaparin 0.5 mg/kg subcutaneously every 12 hours. Dosing should be guided by anti-Xa peak levels, with a target of 0.2–0.4 IU/mL.
• Mechanical prophylaxis: Intermittent pneumatic compression (IPC) devices should be used when pharmacologic anticoagulation is contraindicated due to active bleeding or high bleeding risk.

2.2 Stress Ulcer Prophylaxis and Enteral Nutrition Interplay

• High-risk indications: Prophylaxis is recommended for patients with major risk factors like mechanical ventilation >48 hours, coagulopathy, shock, or sepsis.
• Agent selection: Proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2-blockers) can be used. Avoid routine use in low-risk patients due to potential associations with C. difficile infection and pneumonia.
• Enteral nutrition: Initiating early enteral nutrition helps maintain gut mucosal integrity and may reduce the need for pharmacologic stress ulcer prophylaxis.

3. Management of Iatrogenic Complications

Intensive insulin therapy and the rapid correction of hyperglycemia can precipitate severe iatrogenic complications, primarily hypoglycemia and electrolyte disorders. Standardized protocols for detection and correction are vital for patient safety.

3.1 Insulin-Induced Hypoglycemia: Recognition and Treatment

Iatrogenic hypoglycemia is a common and dangerous complication of tight glycemic control. It is defined as a blood glucose (BG) <70 mg/dL, with severe hypoglycemia often defined as <40 mg/dL.

• Monitoring: Perform point-of-care BG checks every 1–2 hours during an insulin infusion and after any significant glucose-lowering event.
• Treatment: Follow a standardized protocol for rapid correction.

3.2 Electrolyte Disturbances: Monitoring and Replacement

Insulin therapy drives potassium, phosphate, and magnesium into the intracellular space, leading to potentially severe deficits in the serum. Proactive monitoring and repletion are critical.

4. Multidisciplinary Goals-of-Care and Invasive Therapy Considerations

Persistent, refractory dysglycemia in the context of critical illness may be a marker of irreversible multi-organ failure. Early and ongoing shared decision-making is crucial to align aggressive interventions with patient values and prognosis.

4.1 Shared Decision-Making in Persistent Dysglycemia

A collaborative approach is essential. Regularly engage the core ICU team, endocrinology, palliative care specialists, the patient (if able), and their family to discuss the clinical trajectory. Conversations should transparently address prognosis and the potential burdens versus benefits of escalating therapies (e.g., continuous renal replacement therapy [CRRT], extracorporeal membrane oxygenation [ECMO]).

4.2 Criteria for Parenteral Nutrition or Extracorporeal Support

4.3 Palliative Care Integration and Family Engagement

Early integration of palliative care can provide critical support for complex symptom management and help clarify goals of care, especially when refractory dysglycemia signals a high mortality risk. Structured, empathetic family meetings can help reduce the provision of non-beneficial interventions and ensure that care remains aligned with patient-centered outcomes.