Table 4.
Adverse effects of inhaled nitric oxide
| Author, year | Methaemoglobin and nitrogen dioxide concentrations | Other adverse effects |
|---|---|---|
| Day,w1 1997 | No known raised concentrations | None |
| Schwebel,w2 1997 | No methaemoglobinaemia | None |
| Dellinger,w3 1998 | Methaemoglobin concentration >5% (none >7%): NO 2.5% (3/120; 40 ppm, n=1; 80 ppm, n=2), control 2% (1/57); nitrogen dioxide level >3 ppm: NO 2.5% (3/120; all received 80 ppm), control: none | Renal function (“defined by adverse events”): NO 11% (13/120), control 9% (5/57); creatinine >177 µmol/l: NO 17% (20/120), control 13% (7/57). Adverse events “possibly” related to study gas: NO 3% (4/120: myopathy, agitation; abnormal liver enzymes; apnoea, lung haemorrhage, coagulopathy; renal dysfunction), control 2% (1/57: hypertension). All adverse events: no significant differences |
| Michael,w4 1998 | No methaemoglobinaemia | Bleeding. Blood transfusion: NO 5% (1/20), control 0/20. Intracranial hemorrhage after thrombolytic therapy: NO 5% (1/20), control 0/20 |
| Troncy,w5 1998 | No methaemoglobinaemia | Not reported |
| Dobyns,w6 1999 | Methaemoglobin concentration >5%: none; nitrogen dioxide concentration >2 ppm: none | No difference in “intensive care unit-dependent therapies”31 |
| Lundin,w7 1999 | Methaemoglobin concentration >5%: NO 1% (1/93), control 1% (1/87); median methaemoglobin concentrations over 30 days: NO 0.5%-1.2%, control 0.2%-1.0% (“overall lower” than in NO group) | Adverse events related to study gas: NO 1% (1/93: gastrointestinal bleeding), control 2% (2/87: coagulopathy, intracranial bleed). Renal function “abnormal”: NO 13% (12/93), control 5% (4/87). Renal replacement (incident cases): NO 27% (23/84), control 13% (10/79); risk ratio 2.16, 1.10 to 4.25. Creatinine >300 µmol/l without renal replacement (incident cases): NO 6% (5/80), control 3% (2/74). Other serious adverse events more common in NO group: circulatory failure: NO 31% (29/93), control 20% (17/87); encephalopathy: NO 3% (3/93), control none; sepsis: NO 8% (7/93), control, 3% (3/87). Other adverse events: no difference in incidence of raised total bilirubin, pneumothorax, or platelet, bleeding or clotting disorders or haemodynamic failure (definitions of haemodynamic v circulatory failure not given) |
| Payen,w8 1999 | Methaemoglobin concentrations reported as always acceptable and no different between groups | Renal replacement (incident cases): NO 37% (33/89), control 29% (26/90); risk ratio 1.28, 0.84 to 1.96. Bleeding: NO 6% (6/105), control 3% (3/98) |
| Mehta,w9 2001 | Methaemoglobin concentration >3%: none (concentration in 1/8 NO patients was 3.8% before therapy); nitrogen dioxide concentration >2 ppm: none | None |
| Gerlach,w10 2003 | No methaemoglobinaemia; no patients with increased nitrogen dioxide concentrations | No bleeding. No difference between groups in number of additional organ dysfunctions32 |
| Park,w11 2003 | No methaemoglobinaemia | None |
| Taylor,w12 2004 | Methaemoglobin concentration >5%: NO 0/192, control 0.005% (1/193); nitrogen dioxide concentration >2 ppm: none | All adverse events: no difference (NO, 630 events; control, 666 events). No difference in cardiovascular, gastrointestinal, endocrine, haematological, metabolic and nutritional, and neurological adverse events. Adverse events with different frequencies. Infections: NO 66 infections, control 41 infections. Respiratory: NO 51% (98/192), control 61% (118/193); pneumonia, pneumothorax, apnoea more common in control group. Renal function: creatinine ≥265 µmol/l: NO 6% (12/192), control 4% (8/193); creatinine ≥309 µmol/l: NO 5% (10/192), control 3% (6/193) |