Regulatory Challenges for the Resuscitation Outcomes Consortium

Tisherman, Samuel A.; Powell, Judy; Schmidt, Terri A.; Aufderheide, Tom P.; Kudenchuk, Peter J.; Spence, Julie; Climer, Dixie; Kelly, Donna; Marcantonio, Angela; Brown, Todd B.; Sopko, George; Kerber, Richard E.; Sugarman, Jeremy; Hoyt, David B.

doi:10.1161/circulationaha.107.764084

Cited by 31 publications

(29 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…95,96 This has proven to be a challenge for research involving patients in cardiac arrest because research interventions must frequently be implemented at a time when it is impossible to obtain consent. 97,98 After much public discussion and in recognition of the value of this type of human research, the United States government, through the Food and Drug Administration and the National Institutes of Health, adopted regulations that allow an exception for the need to obtain informed consent in certain limited circumstances. 99 These exceptions to informed consent for research enrollment apply only if the following conditions are met:…”

Section: Ethics and Privacy Issues Related To Resuscitation Researchmentioning

confidence: 99%

Part 3: Ethics

Morrison¹,

Kierzek²,

Diekema³

et al. 2010

Circulation

222

161

View full text Add to dashboard Cite

Section: Ethics and Privacy Issues Related To Resuscitation Researchmentioning

confidence: 99%

Part 3: Ethics

Morrison¹,

Kierzek²,

Diekema³

et al. 2010

Circulation

222

161

View full text Add to dashboard Cite

“…brain; sodium chloride; sheep; conscious; saline; shock SEVERE HEMORRHAGE IS A LEADING cause of death and morbidity (30). Hypertonic saline solutions are frequently used for resuscitation in states of shock, having beneficial cardiovascular effects comprising improved cardiac output (CO), blood pressure, and regional blood flows (32) and leading to prompt restoration of oxygen delivery.…”

mentioning

confidence: 99%

Hypertonic sodium resuscitation after hemorrhage improves hemodynamic function by stimulating cardiac, but not renal, sympathetic nerve activity

Frithiof

Ramchandra

Hood

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Frithiof R, Ramchandra R, Hood SG, May CN. Hypertonic sodium resuscitation after hemorrhage improves hemodynamic function by stimulating cardiac, but not renal, sympathetic nerve activity. Am J Physiol Heart Circ Physiol 300: H685-H692, 2011. First published December 10, 2010 doi:10.1152/ajpheart.00930.2010.-Small volume hypertonic saline resuscitation can be beneficial for treating hemorrhagic shock, but the mechanism remains poorly defined. We investigated the effects of hemorrhagic resuscitation with hypertonic saline on cardiac (CSNA) and renal sympathetic nerve activity (RSNA) and the resulting cardiovascular consequences. Studies were performed on conscious sheep instrumented with cardiac (n ϭ 7) and renal (n ϭ 6) sympathetic nerve recording electrodes and a pulmonary artery flow probe. Hemorrhage (20 ml/kg over 20 min) caused hypotension and tachycardia followed by bradycardia, reduced cardiac output, and abolition of CSNA and RSNA. Resuscitation with intravenous hypertonic saline (1.2 mol/l at 2 ml/kg) caused rapid, dramatic increases in mean arterial pressure, heart rate, and CSNA, but had no effect on RSNA. In contrast, isotonic saline resuscitation (12 ml/kg) had a much delayed and smaller effect on CSNA, less effect on mean arterial pressure, no effect on heart rate, but stimulated RSNA, although the plasma volume expansion was similar. Intracarotid infusion of hypertonic saline (1 ml/min bilaterally, n ϭ 5) caused similar changes to intravenous administration, indicating a cerebral component to the effects of hypertonic saline. In further experiments, contractility (maximum change in pressure over time), heart rate, and cardiac output increased significantly more with intravenous hypertonic saline (2 ml/kg) than with Gelofusine (6 ml/kg) after hemorrhage; the effects of hypertonic saline were attenuated by the ␤-receptor antagonist propranolol (n ϭ 6). These results demonstrate a novel neural mechanism for the effects of hypertonic saline resuscitation, comprising cerebral stimulation of CSNA by sodium chloride to improve cardiac output by increasing cardiac contractility and rate and inhibition of RSNA. brain; sodium chloride; sheep; conscious; saline; shock SEVERE HEMORRHAGE IS A LEADING cause of death and morbidity (30). Hypertonic saline solutions are frequently used for resuscitation in states of shock, having beneficial cardiovascular effects comprising improved cardiac output (CO), blood pressure, and regional blood flows (32) and leading to prompt restoration of oxygen delivery. Plasma volume expansion, caused by cellular dehydration via an osmotic gradient, partly accounts for these effects. There is, however, evidence that hypertonic saline has important additional actions to increase cardiac function, as similar increases in plasma volume by other fluids cause less improvement in CO (2). Studies investigating the direct effects of elevated osmolality/sodium levels on the heart have rendered inconclusive results, showing increased, decreased, or no effect on cardiac performance (5,10,13,2...

show abstract

“…19 In some studies, an exception from informed consent can permit patient enrollment following community consultation, in which investigators meet with members of the community to explain the proposed study and to listen to any concerns raised. Examples of studies exempted from informed consent include those sponsored by the Resuscitation Outcomes Consortium 20 and the ProTECT3 study, a Phase III clinical trial of progesterone for treatment of acute traumatic brain injury. 21 However, this is a long and labor-intensive process.…”

Section: Challenges For Research In the Emergency Settingmentioning

confidence: 99%