Table 2.
Efficacy and Safety Outcomes of Nebulized Heparin for Smoke Inhalation Injury.
| Holt et al12 | Miller et al1 | Yip et al33 | Elsharnouby et al34 | Kashefi et al28 | McIntire et al26 | McGinn et al27 | Glas et al35 | |
|---|---|---|---|---|---|---|---|---|
| Efficacy outcomes | ||||||||
| Mortality | No difference, 24% vs 20% | Lower mortality in treatment group, 6% vs 43%, RR = 0.0055 (95% CI = 0.0314-0.02004) | No difference, 36.5% vs 54.5%, P = .32 | No difference, 4% vs 3%, P = .6 | No difference, 30% vs 25%, P = .72 | No difference in 28-day mortality, 2.8% vs 2.8%, P = 1 | No difference, 22.7% vs 23.1%, P = .99 | — |
| Hospital LOS (days) | No difference, 31 vs 31.9 | — | — | — | No difference, 15.3 vs 16.3, P = .8 | No difference, 17 vs 22, P = .195 | No difference, 9.0 vs 18.5, P = .093 | — |
| ICU LOS (days) | — | — | No difference, 6 vs 7, P = .86 | No difference, 19 vs 25, P = .17 | — | — | Shorter in treatment group, 5.5 vs 13, P = .033 | No difference in ICU-free days and alive at day 90, 71 vs 49, P = .73 |
| Duration of mechanical ventilation (days) | No difference, 18.2 vs 17.2, P = .76 | — | No difference, 5 vs 5, P = .63 | Shorter for treatment group, 11 vs 19, P = .037 | No difference, 8.5 vs 8.8, P = .9 | No difference, 7.0 vs 14.5, P = .60 Shorter duration in treatment group when patients who died or discharged on the ventilator excluded, 7 vs 14.5, P = .044 |
Shorter for treatment group, 3.0 vs 6.5, P = .022 Heparin associated with duration of mechanical ventilation in multivariable linear regression model (P = .039) |
No difference in ventilator-free days and alive at day 28, 16 vs 20, P = .62 |
| Pulmonary function | No difference in markers of oxygenation | Lower LIS, days 2-7 Lower lung resistance, days 2 and 4 Lower average hypoxemia score in first 7 days |
— | Lower LIS on days 5-7 | — | — | — | — |
| Safety outcomes | ||||||||
| Pneumonia | No difference, 63% vs 50%, P = .12 | — | No difference, 17.3% vs 18.2% | No difference, 27% vs 43%, P = .4 | Increased in treatment group, 45% vs 11%, P = .03 | No difference in VAP, 63.9% vs 72.2% | Increased in treatment group 18% vs 0%, P = .0376 | 28.5% vs 16.7%, No statistical analysis performed |
| Bleeding | — | — | No difference in PT or aPTT No difference in platelet trends |
No significant effect on coagulation parameters or platelet count No significant blood staining of bronchial secretions |
— | No difference in major bleeding: 5.6% vs 11.1%, P = .394 No difference in minor bleeding: 58.3% vs 52.8%, P = .635 |
— | No bleeds in either group One patient per group required blood transfusion for severe hemorrhage 7 and 13 days after last nebulization One patient in heparin group with aPTT >150 seconds aPTTs similar between groups; during nebulization: 36 vs 31 seconds After nebulization period: 33 vs 40 seconds |
| Other | No difference in unplanned reintubation, 14% vs 8%, |P = .20 | — | No difference in incidence of sepsis, 38.5% vs 63.6%, P = .18 No difference in incidence of ARDS, 23.1% vs 36.4%, P = .45 |
— | No difference in incidence of sepsis, 40% vs 33%, P = .7 No difference in incidence of ARDS, 15% vs 10%, P = 1 No documented complications directly attributed to administration of the protocol |
— | — | No HIT in either group One patient in the placebo group with ARDS Two patients in heparin group with ventilatory problems (high airway pressures) Feasibility: 127 of 429 heparin nebulizations withheld |
Abbreviations: aPTT, activated partial thromboplastin time; ARDS, acute respiratory distress syndrome; CI, confidence interval; HIT, heparin-induced thrombocytopenia; ICU, intensive care unit; LIS, lung injury score; LOS, length of stay; PT, prothrombin time; RR, relative risk; VAP, ventilator-associated pneumonia.