Study on delay two-phase multiple organ dysfunction syndrome

OBJECTIVE: To study the injury factors, pathogenic process and clinical features of delay two-phase multiple organ dysfunction syndrome (MODS) in severe burned patients and to replicate a standardized animal model that would accurately imitate the clinical features of MODS. METHODS: Forty-five human patients with burn size larger than 30% total body surface area (TBSA) were analyzed. All of them underwent severe burn shock in early stage and sepsis in late stage. Thirty-two goats were randomly divided into three groups: 1) hemorrhagic shock (group H, n = 6); 2) endotoxemia (group E, n = 6); and 3) hemorrhagic shock plus endotoxemia (group M, n = 20). Hemorrhagic shock was produced according to the method of Wigger (6.7 kPa for an hour, 1 kPa = 7.5 mmHg). Endotoxin (E. coli O111 B4) was given via the portal vein 24 hours after the resuscitation of hemorrhagic shock, in a dose of 30 ng/kg/min for 5 consecutive days. During the observation period of 10 days, all animals were hemodynamically monitored, given standard metabolic support and due cardiac and pulmonary support according to human intensive care. RESULTS: All the patients showed burn shock at 1-3 days and hyperdynamic circulation, hypermetabolism and systemic inflammatory responses over two weeks post-injury. Thirteen cases were found to develop MODS according to the prevailing diagnostic criteria, and 10 of them died with a mortality of 77%. Eighteen animals died in group M with a mortality of 90%, 12 of the 18 developed MODS, with overall incidence of 60%. Most animals in group M showed changes similar to that observed in human cases. The experimentation proved that in the pathogenic process of MODS, there was a two-hit phenomenon in the dvelopment of the syndrome. To prevent the development of MODS, it therefore was imperative to blunt the first hit or the second hit, so that an excessive inflammatory response was alleviated. This postulation has been verified in the treatment of extensive burns. Two patients with burn extent reaching 100% TBSA survived with only mild acute respiratory distress syndrome (ARDS) and renal dysfunction after comprehensive treatment of burn shock, including adequate fluid resuscitation, drugs to remove oxygen free radicals, rapid restoration of pHi, and early extensive excision of burn eschars. CONCLUSION: Both in human patients or animal experimentation, the typical delay two-phase MODS is shown to be produced by two successive insults in the forms of hypovolemic shock and sepsis. This postulation is helpful in formulating the prevention and treatment modality of MODS.