Reactions Weekly | 2021
Multiple drugs
Abstract
Lack of efficacy and cardiac arrest: 10 case reports In an observational and retrospective study conducted at Necker-Enfants Malades University Hospital, Paris, France between January 2016 and February 2017, ten patients (5 boys and 5 girls) aged 5.9-17.9 years were described, who exhibited lack of efficacy during treatment with sildenafil and bosentan along with epoprostenol or treprostinil for idiopathic pulmonary arterial hypertension (PAH). In addition, two of them developed cardiac arrest (CA) during treatment with etomidate, ketamine, propofol, sevoflurane, midazolam or sufentanil for anaesthesia [not all routes stated]. The 13.3-year-old girl (patient 1) who exhibited lack of efficacy during treatment with sildenafil, bosentan and epoprostenol: The girl, who had been diagnosed with PAH at the age of 11 years, started receiving sildenafil 60 mg/day, bosentan 125 mg/day and epoprostenol 20 ng/kg/min. At the age of 13.3 years, she presented with progressive symptoms despite treatment with sildenafil, bosentan and epoprostenol (lack of efficacy). Hence, she underwent percutaneous reverse Potts shunt under anaesthesia. After 4 days of ICU, she was discharged from hospital. The 17.9-year-old girl (patient 2) who exhibited lack of efficacy during treatment with sildenafil, bosentan and treprostinil: The girl, who had been diagnosed with PAH at the age of 12 years, started receiving sildenafil 60 mg/day, bosentan 250 mg/day and treprostinil 20 ng/kg/min. At the age of 17.9 years, she presented with progressive symptoms despite treatment with sildenafil, bosentan and treprostinil (lack of efficacy). Hence, she underwent percutaneous reverse Potts shunt under anaesthesia. After 5 days of ICU, she was discharged from hospital. The 9.6-year-old girl (patient 3) who exhibited lack of efficacy during treatment with sildenafil, bosentan and treprostinil. She also developed CA during treatment with etomidate, midazolam and propofol: The girl, who had been diagnosed with PAH at the age of 0.1 years, started receiving sildenafil 120 mg/day, bosentan 125 mg/day and treprostinil 30 ng/kg/min. At the age of 9.6 years, she presented with progressive symptoms despite treatment with sildenafil, bosentan and treprostinil (lack of efficacy). Hence, she underwent percutaneous reverse Potts shunt under anaesthesia. The anaesthesia was induced with etomidate 0.4 mg/kg and midazolam 0.05 mg/kg, and was maintained with IV propofol 1–2 μg/mL. She was also administered with atracurium besilate and nitric oxide. However, subsequently she developed atrial tachycardia, extreme cyanosis due to atrial septal defect and intervascular haematoma as procedural complications. Moreover, she developed CA due to anaesthetic agents. Therefore, she was started on extracorporeal life support. After 2 days of ICU, she died due to cerebral haemorrhage. The 8.7-year-old boy (patient 4) who exhibited lack of efficacy during treatment with sildenafil, bosentan and epoprostenol: The boy, who had been diagnosed with PAH at the age of 4.5 years, started receiving sildenafil 60 mg/day, bosentan 144 mg/day and epoprostenol 14 ng/kg/min. At the age of 8.7 years, he presented with progressive symptoms despite treatment with sildenafil, bosentan and epoprostenol (lack of efficacy). Hence, he underwent percutaneous reverse Potts shunt under anaesthesia. After 1 day of ICU, he was discharged from hospital. The 5.9-year-old girl (patient 5) who exhibited lack of efficacy during treatment with sildenafil, bosentan and treprostinil. She also developed CA during treatment with ketamine, sevoflurane, sufentanil and midazolam: The girl, who had been diagnosed with PAH at the age of 0.4 years, started receiving sildenafil 60 mg/day, bosentan 64 mg/day and treprostinil 31 ng/kg/min. At the age of 5.9 years, she presented with progressive symptoms despite treatment with sildenafil, bosentan and treprostinil (lack of efficacy). Hence, she underwent percutaneous reverse Potts shunt under anaesthesia. The anaesthesia was induced with ketamine 1 mg/kg, sevoflurane 5% and sufentanil 0.2 μg/kg, and maintained with midazolam 0.1 mg/kg/h and sufentanil 0.2 μg/kg/h. She was also administered with atracurium besilate and rocuronium bromide. At induction, she developed first cardiac arrest. She also developed multiple radiofrequency perforations, sheath exchange and intervascular haematoma as procedural complications. After sheath exchange, she developed second cardiac arrest. Therefore, she was started on extracorporeal life support. After 11 days of ICU, she died due to irreversible brain damage. The 10.8-year-old boy (patient 6) who exhibited lack of efficacy during treatment with sildenafil, bosentan and treprostinil. The boy, who had been diagnosed with PAH at the age of 9 years, started receiving sildenafil 120 mg/day, bosentan 112 mg/day and treprostinil 35 ng/kg/min. At the age of 10.8 years, he presented with progressive symptoms despite treatment with sildenafil, bosentan and treprostinil (lack of efficacy). Hence, he underwent percutaneous reverse Potts shunt under anaesthesia. After 3 days of ICU, he was discharged from hospital. The 14.3-year-old boy (patient 7) who exhibited lack of efficacy during treatment with sildenafil, bosentan and epoprostenol. The boy, who had been diagnosed with PAH at the age of 13.9 years, started receiving sildenafil 40 mg/day, bosentan 250 mg/day and epoprostenol 42 ng/kg/min. At the age of 14.3 years, he presented with progressive symptoms despite treatment with sildenafil, bosentan and epoprostenol (lack of efficacy). Hence, he underwent percutaneous reverse Potts shunt under anaesthesia. After 31 days of ICU, he died due to septic shock and acute respiratory distress syndrome. The 8.9-year-old boy (patient 8) who exhibited lack of efficacy during treatment with sildenafil, bosentan and epoprostenol. The boy, who had been diagnosed with PAH, started receiving sildenafil 60 mg/day, bosentan 64 mg/day and epoprostenol 40 ng/kg/min. However, he presented with progressive symptoms despite treatment with sildenafil, bosentan and epoprostenol (lack of efficacy). Hence, he underwent percutaneous reverse Potts shunt under anaesthesia. After 3 days of ICU, he was discharged from hospital. The 12.5-year-old girl (patient 9) who exhibited lack of efficacy during treatment with sildenafil, bosentan and treprostinil. The girl, who had been diagnosed with PAH, started receiving sildenafil 60 mg/day, bosentan 125 mg/day and treprostinil 35 ng/kg/min. However, she presented with progressive symptoms despite treatment with sildenafil, bosentan and treprostinil (lack of efficacy). Hence, she underwent percutaneous reverse Potts shunt under anaesthesia. After 5 days of ICU, she was discharged from hospital. This report involves a 8.5-year-old boy (patient 10) who exhibited lack of efficacy during treatment with sildenafil, bosentan and treprostinil. The boy, who had been diagnosed with PAH at the age of 8 years, started receiving sildenafil 60 mg/day, bosentan 96 mg/day and treprostinil 29 ng/kg/min. At the age of 8.5 years, he presented with progressive symptoms despite treatment with sildenafil, bosentan and treprostinil (lack of efficacy). Hence, he underwent percutaneous reverse Potts shunt under anaesthesia. After 1 day of ICU, he was discharged from hospital.