What is the step by step management of malaria in an Intensive Care Unit (ICU)?

Step-by-Step ICU Management of Severe Malaria

Immediate Recognition and Diagnosis

Severe malaria is a medical emergency requiring immediate ICU admission and treatment with intravenous artesunate without delay. 1

Confirm severe malaria if any of the following WHO criteria are present: 1

• Impaired consciousness or coma
• Multiple convulsions
• Prostration (inability to sit/stand)
• Acute respiratory distress or pulmonary edema
• Circulatory shock
• Acute kidney injury or renal failure
• Acidosis (pH <7.35 or bicarbonate <15 mmol/L)
• Hyperlactatemia (lactate >5 mmol/L)
• Severe anemia (hemoglobin <7 g/dL)
• Hypoglycemia (glucose <40 mg/dL)
• High parasitemia (>5% infected red cells)
• Jaundice with organ dysfunction
• Significant bleeding

Step 1: Initiate Antimalarial Treatment Immediately

Administer intravenous artesunate 2.4 mg/kg body weight at 0,12, and 24 hours, then daily until the patient can tolerate oral medication. 1, 2

• Artesunate provides faster parasite clearance and shorter ICU stays compared to quinine, with 34.7% reduction in mortality 2
• Do not delay treatment while awaiting transfer or confirmatory testing 3

If IV artesunate is unavailable, use IV quinine as second-line: 1

• Loading dose: 20 mg salt/kg over 4 hours
• Maintenance: 10 mg/kg over 4 hours, starting 8 hours after initiation, then every 8 hours
• If patient received quinine before admission, use 10 mg/kg loading dose instead 3

Step 2: Establish Continuous Physiological Monitoring

Monitor continuously in the ICU: 3, 1

• Cardiac function and blood pressure
• Respiratory rate and oxygen saturation
• Urine output and renal function
• Blood glucose every 4 hours (hypoglycemia risk with quinine) 3, 2
• Plasma lactate and bicarbonate levels
• Neurological status (Glasgow Coma Scale)

Step 3: Implement Restrictive Fluid Management

Use restrictive fluid strategy to avoid pulmonary or cerebral edema. 1

• Administer 5% dextrose with 1/2 normal saline as the preferred IV fluid 3
• Provide dextrose to prevent hypoglycemia while minimizing salt that can leak into pulmonary and cerebral tissues 3
• In volume-depleted patients, give fluids to maintain cardiac output and renal perfusion, but avoid fluid overload which precipitates pulmonary edema or ARDS 3
• Administer 10 mL/kg over 3 hours between quinine doses if using quinine 3

Step 4: Manage Hypoglycemia Aggressively

Monitor blood glucose closely and treat hypoglycemia presumptively if clinical deterioration occurs. 3

• Hypoglycemia is a major risk factor for fatal outcome, especially with quinine treatment 3, 2
• Treat with 50 mL of 50% IV dextrose if glucose <40 mg/dL or if new neurological findings develop 3
• Continue glucose monitoring every 4 hours throughout treatment

Step 5: Monitor Parasitemia Serially

Check peripheral blood parasitemia every 12 hours until it declines to <1%, then every 24 hours until negative. 3, 1

• An initial increase in parasite density within first 24 hours with quinine does not indicate treatment failure 3
• Expected 75% reduction by day 3 and negative result by day 7 3

Step 6: Manage Acute Kidney Injury

Consider acetaminophen 1 gram every 6 hours for 72 hours for reno-protective effects in patients with acute kidney injury. 3, 1

• This regimen demonstrated benefit in clinical trials in Bangladesh and P. knowlesi malaria 3
• Monitor renal function and urine output continuously

Step 7: Treat Severe Anemia

Transfuse packed red blood cells if: 3

• Hemoglobin <4 g/dL, OR
• Hemoglobin <6 g/dL with signs of heart failure (dyspnea, enlarging liver, gallop rhythm)

Step 8: Manage Fever

Control hyperpyrexia with antipyretics or tepid sponging. 1

• Use ibuprofen as preferred antipyretic when renal function is normal 1
• Use paracetamol if renal impairment present 3
• Tepid sponging with lukewarm water is an effective non-pharmacological approach 3, 1

Step 9: Treat Convulsions

If convulsions occur: 3

• Administer 0.2 mL/kg paraldehyde IM
• If convulsions recur, repeat paraldehyde
• If convulsions persist, give phenobarbitone 10 mg/kg IM

Perform lumbar puncture in patients with altered consciousness or repeated convulsions to rule out bacterial meningitis. 3

Step 10: Manage Bacterial Co-infection

Start empiric antibiotics only if bacterial co-infection is suspected, and continue only if blood cultures are positive. 3, 1

• Do not routinely administer antibiotics without clinical suspicion
• Obtain blood cultures before starting antibiotics

Step 11: Avoid Harmful Interventions

Do NOT administer: 3

• Corticosteroids (adverse effect on outcome in cerebral malaria) 3
• Exchange blood transfusion (no demonstrated benefit with artesunate availability) 3, 1

Step 12: Transition to Oral Therapy

Switch to oral artemisinin-based combination therapy (ACT) once the patient can tolerate oral medication and parasitemia has declined to <1%. 1

Preferred oral options: 1

• Dihydroartemisinin-piperaquine, OR
• Artemether-lumefantrine

Complete a full 3-day course of oral ACT after IV artesunate. 1

Step 13: Monitor for Post-Artesunate Delayed Hemolysis (PADH)

Check hemoglobin, haptoglobin, and lactate dehydrogenase levels at days 7,14,21, and 28 after artesunate treatment. 3, 1, 4

• PADH is a self-limiting episode of unexplained hemolysis that can occur after parasitologic cure 4
• Higher doses of artesunate increase risk 4
• Blood transfusion may be required in some cases 4

Step 14: Manage Treatment Failure

If parasitemia persists or recurs after 72 hours of appropriate therapy, switch to alternative antimalarial. 5

Second-line options: 5

• Atovaquone-proguanil (preferred for treatment failures) 5, 6
• Quinine sulfate plus doxycycline 5
• Quinine sulfate plus clindamycin (if doxycycline contraindicated) 5

Consider malabsorption as a cause before assuming true drug resistance. 5

Critical Pitfalls to Avoid

• Never delay artesunate while awaiting diagnostic confirmation - treat immediately on clinical suspicion 3, 1
• Avoid aggressive fluid resuscitation - this precipitates cerebral and pulmonary edema 3
• Do not use oral therapy for severe malaria - these patients require parenteral treatment 1
• Monitor for hypoglycemia vigilantly - it is easily missed and rapidly fatal 3
• Do not stop monitoring at discharge - PADH can occur weeks after treatment 3, 1, 4