In a patient admitted with severe Plasmodium falciparum malaria, what immediate antimalarial therapy should be initiated and what clinical and laboratory parameters need to be monitored?

Immediate Management of Severe Plasmodium falciparum Malaria

Start intravenous artesunate immediately at 2.4 mg/kg at 0,12, and 24 hours, then daily until oral intake is tolerated and parasitemia drops below 1%. 1, 2

Initial Antimalarial Therapy

First-Line Treatment

• Administer IV artesunate 2.4 mg/kg body weight at time zero, repeat at 12 hours, and again at 24 hours 1, 2
• Continue 2.4 mg/kg IV once daily after the first 24 hours until the patient can tolerate oral medication AND parasitemia has declined to <1% 1
• Do not delay treatment while awaiting confirmatory testing or transfer 2

Alternative if Artesunate Unavailable

• Use IV quinine dihydrochloride: 20 mg salt/kg loading dose over 4 hours, followed by 10 mg/kg over 4 hours starting 8 hours after initiation, then every 8 hours 1
• Switch to oral therapy after completing at least 48 hours of IV treatment 1

Transition to Oral Therapy

• Switch to oral artemisinin-based combination therapy (ACT) only when all of the following criteria are met: hemodynamically stable, conscious, able to tolerate oral intake, and parasitemia <1% 1, 2
• Administer a complete 3-day course of oral ACT (artemether-lumefantrine or dihydroartemisinin-piperaquine) regardless of how many days of IV artesunate were given 1, 2

Clinical Monitoring Parameters

Continuous ICU Monitoring

• Cardiac function and blood pressure 2
• Respiratory rate and oxygen saturation 2
• Urine output and renal function 2
• Neurological status using Glasgow Coma Scale 2

Frequent Laboratory Monitoring

• Blood glucose every 4 hours; treat presumptively with 50 mL of 50% IV dextrose if glucose <40 mg/dL or new neurological findings develop 2
• Plasma lactate and bicarbonate levels to assess acidosis 1, 2
• Parasitemia every 12 hours until it declines to <1%, then every 24 hours until negative 1, 2

Post-Treatment Surveillance

• Screen for post-artesunate delayed hemolysis (PADH) by checking hemoglobin, haptoglobin, and lactate dehydrogenase on days 7,14,21, and 28 after completing IV artesunate 1, 3
• PADH occurs in approximately 10–15% of patients and can develop up to 4 weeks post-treatment 1

Supportive Care Measures

Fluid Management

• Use restrictive fluid strategy to avoid pulmonary or cerebral edema without worsening kidney function 1, 2

Renal Protection

• Consider acetaminophen 1 gram every 6 hours for 72 hours for reno-protective effects in patients with acute kidney injury 1, 2

Infection Control

• Start empiric antibiotics only if bacterial co-infection is suspected, and continue only if blood cultures are positive 1, 2

Fever Management

• Use ibuprofen as the preferred antipyretic when renal function is normal, or paracetamol if renal impairment exists 1
• Tepid sponging can be used as a non-pharmacological approach 1

Critical Pitfalls to Avoid

• Do not stop IV artesunate after only three doses if the patient cannot yet tolerate oral intake; continue once-daily IV dosing until oral tolerance is achieved 1
• Do not switch to oral ACT while parasitemia remains ≥1%, as adequate parasite clearance has not been achieved 1
• Do not shorten the oral ACT regimen; a complete 3-day course is mandatory after IV artesunate cessation 1
• Do not use corticosteroids or exchange blood transfusion, as these have not been shown to improve outcomes and may be harmful 1, 2
• Do not delay PADH monitoring; systematic surveillance is required as hemolytic anemia can arise weeks after treatment 1, 3