Faculty Bibliography

BACKGROUND: One of the major causes of death and neurological injury after cardiac arrest is delayed ischemia combined with oxygen free radical mediated reperfusion injury. Consequently determining the optimal balance between oxygen delivery and uptake in the brain using a reliable non-invasive monitoring system during the post-resuscitation period is of importance. In this observational study, we evaluated the feasibility of using cerebral oximetry during the post-resuscitation period in order to identify changes in regional cerebral oxygen saturation (rSO2) and its association with survival to discharge. METHODS: 21 consecutive patients admitted to the intensive care units following cardiac arrest had cerebral oximetry monitoring carried out for 48 h. Mean rSO2 values were collected during the first 24h and then again during the subsequent 24-48 h of the post-resuscitation period. RESULTS: 43% (n=9) patients survived to hospital discharge and 57% (n=12) died. Amongst all patients the median (IQR) rSO2% was 65.5% (62.6-68.2) in the first 24-h following ROSC and increased to 72.1% (64.6-73.7) (p=0.11) in the subsequent 24-48 h. The median (IQR) rSO2% during the first 24 h in patients who survived to discharge compared to those who did not survive were significantly higher 68.2% (66.0-71.0) vs. 62.9% (56.5-66.0), p=0.01). During the subsequent 24-48 h period, while a difference in the rSO2 between survivors and non-survivors was noted, this did not achieve statistical significance (median (IQR): 73.7 (70.2-74.0) vs. 66.5 (58.2-72.1), p=0.11). CONCLUSIONS: Our study indicates that the use of cerebral oximetry is feasible during the post resuscitation period after cardiac arrest. Further studies are needed to determine whether cerebral oximetry may be used as a novel non-invasive monitoring system to evaluate changes in the balance between cerebral oxygen delivery and uptake during the post-resuscitation period.

OBJECTIVE: A major hurdle limiting the ability to improve the quality of resuscitation has been the lack of a noninvasive real-time detection system capable of monitoring the quality of cerebral and other organ perfusion, as well as oxygen delivery during cardiopulmonary resuscitation. Here, we report on a novel system of cerebral perfusion targeted resuscitation. DESIGN: An observational study evaluating the role of cerebral oximetry (Equanox; Nonin, Plymouth, MI, and Invos; Covidien, Mansfield, MA) as a real-time marker of cerebral perfusion and oxygen delivery together with the impact of an automated mechanical chest compression system (Life Stat; Michigan Instruments, Grand Rapids, MI) on oxygen delivery and return of spontaneous circulation following in-hospital cardiac arrest. SETTING: Tertiary medical center. PATIENTS: In-hospital cardiac arrest patients (n = 34). MAIN RESULTS: Cerebral oximetry provided real-time information regarding the quality of perfusion and oxygen delivery. The use of automated mechanical chest compression device (n = 12) was associated with higher regional cerebral oxygen saturation compared with manual chest compression device (n = 22) (53.1% +/- 23.4% vs 24% +/- 25%, p = 0.002). There was a significant difference in mean regional cerebral oxygen saturation (median % +/- interquartile range) in patients who achieved return of spontaneous circulation (n = 15) compared with those without return of spontaneous circulation (n = 19) (47.4% +/- 21.4% vs 23% +/- 18.42%, p < 0.001). After controlling for patients achieving return of spontaneous circulation or not, significantly higher mean regional cerebral oxygen saturation levels during cardiopulmonary resuscitation were observed in patients who were resuscitated using automated mechanical chest compression device (p < 0.001). CONCLUSIONS: The integration of cerebral oximetry into cardiac arrest resuscitation provides a novel noninvasive method to determine the quality of cerebral perfusion and oxygen delivery to the brain. The use of automated mechanical chest compression device during in-hospital cardiac arrest may lead to improved oxygen delivery and organ perfusion.

BACKGROUND: Diesel exhaust is associated with cardiovascular and respiratory mortality and morbidity. Acute exposure leads to increased IL-8 expression and airway neutrophilia, however the mechanism of this response is unknown. OBJECTIVES: As cigarette smoke-induced IL-8 expression by epithelial cells involves transactivation of the epidermal growth factor receptor (EGFR), we studied the effects of diesel exhaust particles (DEP) on IL-8 release and the role of the EGFR. METHODS: Primary bronchial epithelial cells (PBEC) were exposed to DEPs or carbon black. IL-8 and EGFR ligand expression (transforming growth factor alpha (TGFalpha), heparin-binding EGF-like growth factor, and amphiregulin (AR)) were assessed by quantitative RT-PCR and ELISA. RESULTS: DEP, but not carbon black, caused a dose-dependent increase in mitogen-activated protein kinase (MAPK) activation and IL-8 expression, however above 50 mug/ml there was an increase in cytotoxicity. At 50 mug/ml, DEPs stimulated transcription and release of IL-8 and EGFR ligands. IL-8 release was blocked by EGFR neutralizing antibodies, an EGFR-selective tyrosine kinase inhibitor and by the metalloprotease inhibitor, GM6001, which blocks EGFR ligand shedding. Neutralizing antibodies to AR, TGFalpha and heparin-binding (HB)-EGF reduced DEP-induced IL-8 by >50%. Conclusion Expression of IL-8 in response to DEPs is dependent on EGFR activation and that autocrine production of EGFR ligands makes a substantial contribution to this response. CAPSULE SUMMARY: This study identifies a mechanism whereby diesel particles stimulates IL-8 release from bronchial epithelial cells. This mechanism may help to explain the recruitment of neutrophils into the airways of people exposed to particulate air pollution.

BACKGROUND: Non-invasive monitoring of cerebral perfusion and oxygen delivery during cardiac arrest is not routinely utilized during cardiac arrest resuscitation. The objective of this study was to investigate the feasibility of using cerebral oximetry during cardiac arrest and to determine the relationship between regional cerebral oxygen saturation (rSO2) with return of spontaneous circulation (ROSC) in shockable (VF/VT) and non-shockable (PEA/asystole) types of cardiac arrest. METHODS: Cerebral oximetry was applied to 50 in-hospital and out-of-hospital cardiac arrest patients. RESULTS: Overall, 52% (n=26) achieved ROSC and 48% (n=24) did not achieve ROSC. There was a significant difference in mean+/-SD rSO2% in patients who achieved ROSC compared to those who did not (47.2+/-10.7% vs. 31.7+/-12.8%, p<0.0001). This difference was observed during asystole (median rSO2 (IQR) ROSC versus no ROSC: 45.0% (35.1-48.8) vs. 24.9% (20.5-32.9), p<0.002) and PEA (50.6% (46.7-57.5) vs. 31.6% (18.8-43.3), p=0.02), but not in the VF/VT subgroup (43.7% (41.1-54.7) vs. 42.8% (34.9-45.0), p=0.63). Furthermore, it was noted that no subjects with a mean rSO2<30% achieved ROSC. CONCLUSIONS: Cerebral oximetry may have a role as a real-time, non-invasive predictor of ROSC during cardiac arrest. The main utility of rSO2 in determining ROSC appears to apply to asystole and PEA subgroups of cardiac arrest, rather than VF/VT. This observation may reflect the different physiological factors involved in recovery from PEA/asytole compared to VF/VT. Whereas in VF/VT, successful defibrillation is of prime importance, however in PEA and asytole achieving ROSC is more likely to be related to the quality of oxygen delivery. Furthermore, a persistently low rSO2 <30% in spite of optimal resuscitation methods may indicate futility of resuscitation efforts.

INTRODUCTION: Hypothermia improves neurologic recovery compared to normothermia after resuscitation from out-of-hospital ventricular fibrillation, but may or may not be beneficial for patients resuscitated from in-hospital cardiac arrest. Therefore, we evaluated the effect of induced hypothermia in a large cohort of patients with in-hospital cardiac arrest. METHODS: Retrospective analysis of multi-center prospective cohort of patients with in-hospital cardiac arrest enrolled in an ongoing quality improvement project. Included were adults with a pulseless event in an in-patient hospital ward of a participating institution who achieved restoration of spontaneous circulation between 2000 and 2009. The exposure of interest was induced hypothermia. The primary outcome was survival to discharge. The secondary outcome was neurological status at discharge. Analyses evaluated all eligible patients; those with a shockable rhythm; or those with endotracheal tube inserted after resuscitation; and the effect of no hypothermia versus hypothermia (lowest temperature>32 degrees C but