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Inhaled nitric oxide no better than placebo for cerebral malaria
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Inhaled nitric oxide was deemed a safe adjuvant therapy for pediatric cerebral malaria, but it did not increase plasma angiopoietin-1 levels at 48 hours, according to recent study data.
Cerebral malaria has a 20% mortality rate and causes long-term neurological problems in 10% to 24% of survivors, Julie Mwanga-Amumpaire, MD, of the Epicentre Mbarara Research Center in Uganda, and colleagues wrote. Inhaled nitric oxide may help reduce inflammation and thus improve results.
In a randomized open-label, phase 2 trial, Mwanga-Amumpaire and colleagues assigned 92 children with cerebral malaria either inhaled nitric oxide (n = 46) or nitrogen (n = 46) for at least 48 hours. These treatments were an adjunct therapy to IV artesunate. Patients were aged 2 months to 12 years and treated at Mbarara Regional Referral Hospital Pediatric Ward and Holy Innocents Children’s Hospital. There were no differences in baseline characteristics between groups.
The researchers monitored patients’ vital signs — including transcutaneous pulse oxygen saturation, methemoglobin, hemoglobin levels and pulse rate — and coma scores every 2 hours during treatment. There were no differences between groups, the researchers wrote. Plasma angiopoietin-1 levels increased in both groups; however, these levels were similar at 48 hours. Although plasma Ang-2 and cytokine levels decreased 48 hours after treatment, there was no difference between groups. Blood methemoglobin and plasma nitrate increased in patients treated with nitric oxide.
The trial was too small to detect a reduction in mortality or neurological impairment, the investigators wrote. Within 7 days after enrollment, seven patients in the nitrogen group died vs. four in the nitric oxide group. The incidence of neurological sequelae was 12%, which coincided with rates reported in other studies in sub-Saharan Africa.
“We believe [nitric oxide] treatment to be safe because the mortality rate in our study was low, breathing [nitric oxide] did not increase the incidence of neurological sequelae, mean methemoglobin levels remained low (4.1% + 0.4%) and the number of patients affected by serious adverse events and adverse events were similar in both groups,” the researchers wrote.
A larger trial measuring cell-free hemoglobin and right heart pressures to evaluate pulmonary vasoconstriction, is needed to determine if inhaled nitric oxide will improve survival rates in children with cerebral malaria, the researchers wrote. – by Colleen Owens
Disclosure: Mwanga-Amumpaire reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.
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