Cynthia N. Steimle

Mortality is directly related to the duration of mechanical ventilation before the initiation of extracorporeal life support for severe respiratory failure

OBJECTIVE To investigate the relationship between the period of mechanical ventilation before extracorporeal life support and survival in patients with respiratory failure. DESIGN Retrospective review. SETTING Surgical intensive care unit at a university medical center. PATIENTS Thirty-six consecutive adult patients with severe respiratory failure managed with extracorporeal life support. INTERVENTIONS Extracorporeal life support was utilized in 36 acute respiratory failure adult patients with a variety of diagnoses and an estimated mortality rate of > 90%. Management protocols were followed before and during extracorporeal life support. The 36 patients were physiologically similar before extracorporeal life support was initiated: shunt of 48 +/- 17%; F10(2) of 1.0 +/- 0.1; peak inspiratory pressure of 56 +/- 16 cm H2O; positive end-expiratory pressure of 14 +/- 6 cm H2O; and respiratory rate of 23 +/- 10 breaths/ min. Ventilation was utilized for 1 to 17 days before extracorporeal life support. Typical lung rest settings during extracorporeal life support were F10(2) of 0.40, peak inspiratory pressure of 30 cm H2O, positive end-expiratory pressure of 10 cm H2O, and respiratory rate of 6 breaths/min. Death was almost always secondary to end-stage pulmonary failure. MEASUREMENTS AND MAIN RESULTS Survival (hospital discharge) in these 36 patients was inversely associated with the number of days of preextracorporeal life support ventilation, with a 50% mortality rate predicted by logistic regression after 5 days of mechanical ventilation. The overall survival rate was 18 (50.0%) of 36 patients. CONCLUSIONS In severe acute respiratory failure treated with lung rest and extracorporeal life support, a predicted 50% mortality rate was associated with 5 days of preextracorporeal life support mechanical ventilation.

Neutrophils are not necessary for ischemia-reperfusion lung injury

The role of neutrophils (PMNs) in ischemia-reperfusion injury after lung transplantation is unclear. If PMNs are involved in ischemia-reperfusion injury in the intact rat, then PMNs should sequester in the injured lung and PMN-depleted rats should develop less injury. Group A rats were treated with a rabbit anti-rat PMN antibody causing profound neutropenia (less than 100 PMNs/microL) and group B with control serum (greater than 2,000 PMNs/microL). Rats were anesthetized and left lung ischemia was sustained for 90 or 180 minutes by clamping the bronchus and the pulmonary artery and vein. Lung injury was quantified by the accumulation of radiolabeled (125I) albumin in ischemic left and nonischemic right lungs (cpm per gram of lung/cpm per gram of blood). Ischemia caused significant lung injury (p less than 0.05) in both PMN-depleted (albumin leak index: 90 min, 0.208; 180 min, 0.218) and nondepleted (90 min, 0.222; 180 min, 0.241) animals compared with nonischemic controls (depleted: 90 min, 0.050; 180 min, 0.100; nondepleted: 90 min, 0.063; 180 min, 0.101); microscopy also demonstrated lung injury. The injury was not associated with PMN sequestration as shown by light microscopy. Thus, we conclude that PMNs are not necessary for ischemia-reperfusion injury and PMN-depletion does not attenuate ischemia-reperfusion injury.

Extracorporeal life support for respiratory failure after multiple trauma

Respiratory failure may complicate multiple trauma and can add significant morbidity, mortality, and cost to the care of such patients. We used extracorporeal life support (ECLS) to treat 24 patients with multiple trauma who, after their injury, developed respiratory failure refractory to conventional ventilatory management. Injuries in these patients were the result of motor vehicle crashes (16 patients), pedestrian versus car collisions (3 patients), gunshots (2 patients), stabs (1 patient), and a recreational vehicle crash (1 patient). Patients were placed on venovenous or venoarterial ECLS, using continuous systemic anticoagulation with heparin, and percutaneous cannulation where possible. Average time on ECLS was 287 +/- 43 hours (12 +/- 1.8 days). The major complication was bleeding, which occurred in 75% of patients. Fifteen patients survived to be discharged from the hospital (63% survival). Early intervention (mechanical ventilation < or = 5 days prior to ECLS) was associated with good outcome. Despite risks of anticoagulation in patients with multiple injuries, ECLS can be life-saving in cases of respiratory failure refractory to conventional mechanical ventilation.

Ibuprofen improves survival and neurologic outcome after resuscitation from cardiac arrest

Post-ischemic inflammatory changes in the central nervous system (CNS) following cardiac arrest and resuscitation are potentially responsible for ultimate survival and much of the neurologic damage, producing greater morbidity and mortality in successfully resuscitated patients. This study was undertaken to assess the non-steroidal anti-inflammatory agent, ibuprofen, in a controlled and monitored experimental model of canine cardiac arrest and resuscitation. With the investigator blinded as to the intervention, eight of 21 dogs were randomly assigned to receive ibuprofen as an i.v. bolus (10 mg/kg) and a 6-h i.v. infusion (5 mg/kg per h). The other 13 dogs received an equivalent volume of 0.9% NaCl to serve as controls. No statistically significant differences between the two groups were detected in any pre-arrest variables. All 21 dogs were successfully resuscitated. At 24 h, dogs receiving ibuprofen exhibited 100% survival, while control dogs exhibited only 54% survival (P = 0.03). The majority of deaths for the control group occurred within the first 6 h. Neurologic deficit scores were assigned at 1, 2, 6 and 24 h after resuscitation. A general trend occurred such that dogs treated with ibuprofen improved over time, while the control dogs remained severely impaired. A significant difference in neurologic deficit score was detected at 6 h (P = 0.01). At 24 h the ibuprofen group exhibited minimal neurologic deficit (5.9 +/- 3.2), and the control group exhibited significantly more severe neurologic impairment (52.2 +/- 13.0, P = 0.01). These results suggest that ibuprofen may be helpful in the pharmacologic management of cardiac arrest as a means of increasing survival and decreasing neurologic impairment.

A randomized prospective comparison of MALG with OKT3 for rescue therapy of acute myocardial rejection

A randomized prospective trial for rescue therapy from acute myocardial rejection was undertaken utilizing Minnesota antilymphoblastic globulin (n = 15) versus murine monoclonal anti-CD3 antibody therapy (OKT3) (n = 14). Patients included in the study had moderate rejection unresponsive to bolus high-dose steroid therapy, or moderate-to-severe rejection with hemodynamic instability. Analysis was performed using the t test and chi-square, significance was P less than 0.05. Patient age, sex, interval from transplant to treatment, and number of unresponsive patients vs. hemodynamically unstable patients were similar in both groups (P greater than 0.05). Initial resolution occurred in 9/15 MALG- vs. 14/14 OKT3-treated patients (P = 0.017). Secondary resolution following repeat treatment occurred in 5/6 remaining MALG patients, for a final resolution of 14/15 MALG vs. 14/14 OKT3 patients (P = NS). Rebound rejection was not significantly different (1/14 MALG vs. 4/13 OKT3). However, 7/14 OKT3-treated patients developed life-threatening infections (1 CMV pancreatitis, 2 CMV pneumonias, 1 systemic candidiasis, 3 CMV viremia) vs. 1/15 MALG-treated patients (CMV viremia) (P = 0.014). Death occurred in 4/14 OKT3- (infection) vs. 1/14 MALG- (rejection) treated patients (P = NS). There were no significant differences in the rate of resolution, rebound, infection, or outcome between unresponsive or hemodynamically unstable patients within either group. Although initial rescue is significantly better with OKT3, final resolution is the same in both groups. Since there was a significant incidence of life-threatening infections (7/14) leading to 4 deaths with OKT3 treatment, we recommend MALG for rescue therapy of refractory acute myocardial rejection if this immunosuppressive regimen is to be used.

Inotropic support for hemodynamic decompensation during acute myocardial transplant rejection

A LLOGENEIC orthotopic heart transplant rejection is common; however, associated acute hemodynamic decompensation at the time of rejection is rare. Improved immunosuppression and increased surveillance by serial endomyocardial biopsies are responsible for decreased mortality rates secondary to rejection.‘,’ However, those patients who do develop hemodynamic instability with rejection require immediate support until reversal of rejection (ie, immunologic rescue) can occur. This report reviews the technique used at the University of Michigan for support of patients with acute hemodynamic decompensation following cardiac rejection.