Pilot investigation of hypothermia in neonates receiving extracorporeal membrane oxygenation.

BACKGROUND: Infants requiring extracorporeal membrane oxygenation (ECMO) support represent a high risk group in terms of cerebral injury. Mild hypothermia both during and after cerebral hypoxic ischaemia appears to be a promising strategy for offering neuroprotection. OBJECTIVE: To investigate whether mild hypothermia was both feasible and safe in infants receiving ECMO as a prelude to any formal assessment of this approach in a randomised trial. METHODS: Twenty infants (body weight less than 5 kg) with severe cardiopulmonary insufficiency, referred for ECMO support at Glenfield Hospital, Leicester, were enrolled in this study. Twenty consecutive infants (compromising four groups of five) were studied. Baseline data were obtained from a control group who were run throughout their course at 37 degrees C. The patients in the next group were managed with a core temperature of 36 degrees C for the first 12 hours of their ECMO run, before being warmed up to 37 degrees C. After successful completion, the next group of five were cared for at 35 degrees C for the first 12 hours, and, there having been no previous complications, the final group were cared for at 34 degrees C for the first 12 hours. Patients were assessed clinically and biologically. In addition to routine laboratory tests, cytokines (interleukin 6, interleukin 8, tumour necrosis factor alpha, and C reactive protein) were measured and coagulation tests (D-dimer, thrombin-antithrombin III complex, plasmin-alpha(2)-antiplasmin complex) were performed serially for five days. RESULTS: There were no significant differences among the four groups in gestational age, birth weight, age at the time of ECMO, Apgar scores at one and five minutes, pH before cannulation, oxygenation index, duration of ECMO, and survival rate to discharge from hospital. No adverse effects of mild hypothermia were found on patient management during ECMO. Laboratory data for up to five days of ECMO also showed no difference among the four groups. CONCLUSION: Mild hypothermia (34 degrees C) for the initial 12 hours of an ECMO run is feasible.

Repeatability of cellular constituents and cytokine concentration in fluid obtained by non-bronchoscopic bronchoalveolar lavage of infants receiving extracorporeal oxygenation.

BACKGROUND: Since few studies have assessed the repeatability of non-bronchoscopic bronchoalveolar lavage (NB-BAL), we compared cellular counts and cytokine concentrations in fluid obtained by standardised NB-BAL from each side of 20 intubated infants receiving extracorporeal membrane oxygenation (ECMO). METHODS: Total cell counts were obtained from 95 paired lavages and 77 pairs were suitable for differential counts and measurement of cytokine concentrations. RESULTS: Moderate correlation was noted between the two sides for most cell types including total cell counts and percentages of neutrophils and macrophages (R=0.70-0.84) and for cytokine concentrations (IL-8 R=0.78, IL-6 R=0.75, TNF-alpha R=0.64, all p< or =0.001). Using Bland-Altman analysis the mean difference between the two sides approached zero for cellular constituents (total cell counts mean difference 1.7, limits of agreement -187.5 to +190.9 x 10(4)/ml; percentage neutrophils -3.9%, -41.5% to +33.6%; percentage macrophages 3.9%, -33.8% to +41.6%) but tended to be greater on the right for logarithmically transformed cytokine measurements (IL-8: left/right ratio 0.74, limits of agreement 0.12 to 5.45, IL-6: 0.93, 0.09 to 5.87, and TNF-alpha: 0.93, 0.27 to 3.16). Using linear regression with random effects to assess the variability, only the infant's age appeared to influence the cellular results but, for cytokines, only the volume retrieved affected the variability. The magnitude of the measurements, the underlying disease, the operator's experience, days on ECMO, or survival did not affect the variability. CONCLUSION: Measurements obtained by NB-BAL need to be interpreted with caution and strongly suggest that normalisation for the dilutional effects of saline is essential.

Spallation performance of extracorporeal membrane oxygenation tubing.

During the prolonged roller pump use of extracorporeal membrane oxygenation (ECMO), tubing wear generates spallation. The spallation performance of Tygon S-65-HL was measured and compared with a potential new ECMO tubing, LVA (Portex 800-500-575). Spallation was measured by on-line laser diode particle counting (HIAC) during simulated ECMO. The effects of differing levels of occlusion and pump speed were examined, as was the effect of spallation over time. The spallation produced by Tygon S-65-HL was less than that seen with LVA during 24 h of simulated ECMO (p < 0.001), and after 72 h had fallen almost to zero. Spallation with Tygon tubing increases with increasing pump speed and decreases over time. There appears to be only a weak correlation with occlusion, which is surprising. The spallation performance of Tygon S-65-HL was variable and under some conditions exceeded that of LVA. Overall, however, Tygon S-65-HL produced less spallation than LVA. Therefore, LVA cannot be recommended for clinical ECMO use.

Tubing failure during prolonged roller pump use: a laboratory study.

Little is known about the mechanical forces acting on extracorporeal circuit tubing with prolonged roller pump use during extracorporeal membrane oxygenation (ECMO). We examined the time to tubing rupture of three different materials during actual roller pump use, mean and standard deviation (SD) (SD shown in parentheses): Tygon (control) 243.7 h (175.4); LVA 121 h (14.3); and SRT 6.6 h (2.1). Failure times for both LVA and SRT were significantly different from the control (paired t-test, p = 0.02 and p < 0.001, respectively). The minimum failure times for Tygon and LVA were 99 and 101 h, respectively. We then examined Tygon under conditions of pure compression, demonstrating that even after 3.67 million compression cycles at full occlusion crack formation did not occur. If the tubing was over-occluded, cracks appeared within 24 h. Scanning electron microscopy of Tygon, which has been used during clinical ECMO, and the failure pattern during destruction testing demonstrate that shear stress and compression coexist during clinical ECMO. Use of under-occlusive pump settings could improve tubing life.

A porcine model of prolonged closed chest venovenous extracorporeal membrane oxygenation.

The sheep has been the standard laboratory animal for extracorporeal membrane oxygenation (ECMO) research for many years and has proven to be an invaluable and reliable model. However the coagulation system of the sheep is significantly different from humans. These differences make it difficult to investigate the coagulative and inflammatory response to ECMO in sheep. The pig has a very similar coagulation system to humans and therefore makes a more appropriate model. We describe a porcine model of prolonged (48 hours) closed chest venovenous (VV) ECMO that we developed to investigate the inflammatory and coagulative response to different ECMO tubing materials. This model could be used to investigate any aspect of venovenous ECMO.

Extracorporeal membrane oxygenation: potential for adults and children?

Extracorporeal membrane oxygenation is a proven therapy for severe neonatal respiratory failure. Extracorporeal membrane oxygenation for older children and adults who are failing to respond to maximal conventional therapy is more controversial, but survival figures of 50-80% can be obtained, in patients with an expected survival of 0-20% with conventional treatment.