Faculty Bibliography

Advances in resuscitation science have indicated that, contrary to perception, death by cardiorespiratory criteria can no longer be considered a specific moment but rather a potentially reversible process that occurs after any severe illness or accident causes the heart, lungs, and brain to stop functioning. The resultant loss of vital signs of life (and life processes) is used to declare a specific time of death by physicians globally. When medical attempts are made to reverse this process, it is commonly referred to as cardiac arrest; however, when these attempts do not succeed or when attempts are not made, it is called death by cardiorespiratory criteria. Thus, biologically speaking, cardiac arrest and death by cardiorespiratory criteria are synonymous. While resuscitation science has provided novel opportunities to reverse death by cardiorespiratory criteria and treat the potentially devastating consequences of the resultant postresuscitation syndrome, it has also inadvertently provided intriguing insights into the likely mental and cognitive experience of death. Recollections reported by millions of people in relation to death, so-called out-of-body experiences (OBEs) or near-death experiences (NDEs), are often-discussed phenomena that are frequently considered hallucinatory or illusory in nature; however, objective studies on these experiences are limited. To date, many consistent themes corresponding to the likely experience of death have emerged, and studies have indicated that the scientifically imprecise terms of NDE and OBE may not be sufficient to describe the actual experience of death. While much remains to be discovered, the recalled experience surrounding death merits a genuine scientific investigation without prejudice.

Breakthroughs in emergency medicine have enabled science to halt and even reverse death. However, these advances have inadvertently led science into a domain that has traditionally been the purview of theology and philosophy. Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion that included emergency medicine experts Lance B. Becker and Sam Parnia, and neurosurgeon Stephan A. Mayer; they discussed recent discoveries and emerging technologies in resuscitation science and the ethical dilemmas they sometimes confront during medical crises. The following is an edited transcript of the discussion from October 9, 2013, 7:00-8:30 PM, at the New York Academy of Sciences in New York City.

For millennia, human beings have wondered what happens after death. What is the first-person experience of dying and being brought back to life? Technological advances in resuscitation science have now added an intriguing new chapter to the literature of out-of-body or near-death experiences by eliciting detailed and vivid accounts of those who have approached the threshold of death. Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion that included neurologist Kevin Nelson, neuropsychiatrist Peter Fenwick, emergency medicine expert Sam Parnia, and orthopedic surgeon and drowning survivor Mary Neal; they share some remarkable stories and discuss how they analyze such experiences in light of their own backgrounds and training. The following is an edited transcript of the discussion from December 11, 2013, 7:00-8:30 PM, at the New York Academy of Sciences in New York City.

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.