Effects of manganese superoxide dismutase on lung fluid balance after smoke inhalation.

There is evidence of increased oxygen free radical activity after smoke inhalation with and without concomitant burn injury. We determined the effects of manganese superoxide dismutase (Mn SOD) on lung fluid balance as measured by lung microvascular permeability coefficient (sigma), filtration coefficient (Kf), and lymph flow. Merino breed ewes (n = 6/group) were surgically prepared. The SOD group (SOD) received Mn SOD (9,000 U/kg) as an intravenous bolus and was insufflated with smoke. The control group (CON) received saline and smoke. sigma and Kf were determined 24 h before and 24 h after smoke injury. Lymph flow, arterial O2-to-inspired O2 fraction ratio, systemic hemodynamics, and pulmonary arterial and capillary pressures were measured. The sigma was significantly (P < 0.05) higher after smoke insufflation in SOD compared with CON (0.71 +/- 0.03 vs. 0.53 +/- 0.05). Kf was significantly lower after smoke insufflation in SOD compared with CON (0.038 +/- 0.010 vs. 0.061 +/- 0.010). Lymph flows were significantly lower during the 24 h after smoke insufflation in SOD compared with CON (33 +/- 7 vs. 55 +/- 8 ml/h at 24 h). Arterial O2-to-inspired O2 fraction ratio was significantly improved at 6 and 12 h after smoke insufflation in SOD compared with CON at the same time points. Mn SOD meliorates the lung microvascular permeability changes associated with smoke inhalation injury.

IVOX with gradual permissive hypercapnia: a new management technique for respiratory failure.

IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 +/- 4 mm Hg vs 51 +/- 3 mm Hg and 3.9 +/- 0.3 liters vs 8.4 +/- 0.5 liters (P < 0.05) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Complications of neonatal extracorporeal membrane oxygenation. Collective experience from the Extracorporeal Life Support Organization.

Since 1973, 7667 neonates have been treated with extracorporeal membrane oxygenation for severe respiratory failure and their cases reported to the Extracorporeal Life Support Organization Registry. The overall survival was 81% in these neonates, who were thought to have a survival of 20% without extracorporeal membrane oxygenation. A total of 4322 mechanical complications (0.56 +/- 0.84 per case) and 13,827 patient complications (1.80 +/- 2.12 per case) were reported overall. The most common mechanical complications included clots in the circuit (19%), cannula placement (9%), oxygenator failure (4%), and others (9%). Common patient complications included cardiopulmonary (43%), neurologic (35%), bleeding (35%), metabolic (32%), renal (25%), and renal (25%), and infectious (9%). From the initial experience to 1988 the average number of mechanical complications per case was 0.27 per case and this significantly increased during 1990 to 1992 to 0.75 per case (p < 0.05). Likewise, from 1973-1985 to 1988 the average patient complications per case were 1.44 per case and this significantly increased during 1990 to 1992 to 2.10 per case. During the same periods, patient survival significantly decreased from 84% (1973-1985 to 1988, n = 2463) to 80% (1990 to 1992, n = 4005). Venovenous double-lumen single cannula extracorporeal membrane oxygenation had a higher survival than venoarterial extracorporeal membrane oxygenation (91% versus 81%) and a lower rate of major neurologic complications. The incidence and survival with seizures (6% and 89% venovenous versus 13% and 61% venoarterial) or cerebral infarction (9% and 69% venovenous versus 14% and 46% venoarterial) was significantly lower with the venovenous method and appeared to have a substantial impact on overall survival. The correlation of patient complication rate and total complication rate with survival was highly significant, however, causality cannot be established. Explanations for the increase in complications, relative to a decrease in survival, despite a growing nationwide experience include (1) increased complexity of cases as many programs expand entry criteria (more premature infants, infants with grade 1 or 2 intracranial hemorrhage, and complex congenital diaphragmatic hernia), (2) a growing number of programs with fewer cases per program, yet greater accessibility, (3) less reluctance to report complications encountered during extracorporeal membrane oxygenation as group experience grows, and (4) changes in the Extracorporeal Life Support Organization data form to be more inclusive of more minor complications.

Complications of neonatal extracorporeal membrane oxygenation.

From 1973-1985 to 1988 the average patient complications per case were 1.44 per case and significantly increased during 1990 to 1992 to 2.10 per case (Figure 3). During the same periods patient survival significantly decreased from 84% (1973-1985 to 1988, n = 2463) to 80% (1990 to 1992, n = 4005) (Figure 4). The association between total complication rates and survival rate was examined by regression analysis (Table 5). The correlation of patient complication rate and total complication rate with survival is highly significant; however, causality cannot be established. When comparing different entry criteria (Table 2) for incidence of mechanical and patient complications, no significant differences are apparent. This is not surprising since each of the entry criteria were designed to identify the same patient population. When premature neonates (> 35 weeks) were placed on ECMO, 36% of them had intracranial haemorrhage (ICH) with 62% mortality while only 12% of the neonates < 35 weeks had ICH and a 49% mortality. Similar findings were noted with low birthweight neonates (< 2.2 kg), 28% had ICH with 64% mortality while only 12% of the neonates > 2.2 kg had ICH with a 50% mortality. Selection criteria remain problematic for a variety of reasons. They cannot be viewed as absolute because of variability between centres. What represents likely 80% mortality in one centre may not apply to another. Historical controls are misleading because changing respiratory therapy strategies make historical populations difficult to compare. Also, once an ECMO centre becomes established, a more challenging group of patients will be attracted than previously was the case. Further, a single entry criterion cannot be generalized for all entry diagnoses. Criteria for an 80% predicted mortality is probably not the same for MAS, CHN, PPHN, and sepsis. Subsequent patients registered in the Neonatal ECMO Registry of the Extracorporeal Life Support Organization will address these issues more thoroughly, as specific details of the pre-ECMO condition and therapeutic strategies are collected. This collective review should help to identify trends which require reassessment of technique or patient management.

S-(nitrocarbobenzoxy)glutathiones: potent competitive inhibitors of mammalian glyoxalase II.

Three potent competitive inhibitors of mammalian liver glyoxalase II, the S-(o-, m-, and p-nitrocarbobenzoxy)-glutathiones, have been synthesized and studied. The Ki values of the ortho, meta, and para isomers, as inhibitors of rat liver glyoxalase II, were 15, 9, and 6.5 microM, respectively. While showing marked competitive inhibition of glyoxalase II, the glutathione derivatives were almost inactive as inhibitors of glyoxalase I. For example, with the para isomer, [I]0.5 values for rat liver glyoxalase I and II were 925 and 12 microM, respectively. This is in marked contrast to other glyoxalase II competitive inhibitors, which in general are even more effective against glyoxalase I. The S-(o-, m-, and p-nitrocarbobenzoxy)glutathiones have found utility as affinity ligands for the purification of rat liver glyoxalase II and may well have use in the study of the glyoxalase enzymes in vivo.