The association of regional cerebral oximetry and neurologically intact survival in a porcine model of cardiac arrest.

Background: The objective of this study was to determine if regional cerebral oximetry (rSO2) assessed during CPR would be predictive of survival with favorable neurological function in a prolonged model of porcine cardiac arrest. This study also examined the relative predictive value of rSO2 and end-tidal carbon dioxide (ETCO2), separately and together. Methods: This study is a post-hoc analysis of data from a previously published study that compared conventional CPR (C-CPR) and automated head-up positioning CPR (AHUP-CPR). Following 10 min of untreated ventricular fibrillation, 14 pigs were treated with either C-CPR (C-CPR) or AHUP-CPR. rSO2, ETCO2, and other hemodynamic parameters were measured continuously. Pigs were defibrillated after 19 min of CPR. Neurological function was assessed 24 h later. Results: There were 7 pigs in the neurologically intact group and 7 pigs in the poor outcomes group. Within 6 min of starting CPR, the mean difference in rSO2 by 95% confidence intervals between the groups became statistically significant (p < 0.05). The receiver operating curve for rSO2 to predict survival with favorable neurological function reached a maximal area under the curve value after 6 min of CPR (1.0). The correlation coefficient between rSO2 and ETCO2 during CPR increased towards 1.0 over time. The combined predictive value of both parameters was similar to either parameter alone. Conclusion: Significantly higher rSO2 values were observed within less than 6 min after starting CPR in the pigs that survived versus those that died. rSO2 values were highly predictive of survival with favorable neurological function.

Improving post-cardiac arrest cerebral perfusion pressure by elevating the head and thorax.

AIM: The optimal head and thorax position after return of spontaneous circulation (ROSC) following cardiac arrest (CA) is unknown. This study examined whether head and thorax elevation post-ROSC is beneficial, in a porcine model. METHODS: Protocol A: 40 kg anesthetized pigs were positioned flat, after 7.75 min of untreated CA the heart and head were elevated 8 and 12 cm, respectively, above the horizontal plane, automated active compression decompression (ACD) plus impedance threshold device (ITD) CPR was started, and 2 min later the heart and head were elevated 10 and 22 cm, respectively, over 2 min to the highest head up position (HUP). After 30 min of CPR pigs were defibrillated and randomized 10 min later to four 5-min epochs of HUP or flat position. Multiple physiological parameters were measured. In Protocol B, after 6 min of untreated VF, pigs received 6 min of conventional CPR flat, and after ROSC were randomized HUP versus Flat as in Protocol A. The primary endpoint was cerebral perfusion pressure (CerPP). Multivariate analysis-of-variance (MANOVA) for repeated measures was used. Data were reported as mean ±â€¯SD. RESULTS: In Protocol A, intracranial pressure (ICP) (mmHg) was significantly lower post-ROSC with HUP (9.1 ±â€¯5.5) versus Flat (18.5 ±â€¯5.1) (p < 0.001). Conversely, CerPP was higher with HUP (62.5 ±â€¯19.9) versus Flat (53.2 ±â€¯19.1) (p = 0.004), respectively. Protocol A and B results comparing HUP versus Flat were similar. CONCLUSION: Post-ROSC head and thorax elevation in a porcine model of cardiac arrest resulted in higher CerPP and lower ICP values, regardless of VF duration or CPR method. IACUC PROTOCOL NUMBER: 19-09.

Controlled sequential elevation of the head and thorax combined with active compression decompression cardiopulmonary resuscitation and an impedance threshold device improves neurological survival in a porcine model of cardiac arrest.

AIM OF THE STUDY: Controlled sequential elevation of the head and thorax (CSE) during active compression decompression (ACD) cardiopulmonary resuscitation (CPR) with an impedance threshold device (ITD) has been shown to increase cerebral perfusion pressure and cerebral blood flow in previous animal studies as compared to the traditional supine position. The potential for this novel bundled treatment strategy to improve survival with intact neurological function is unknown. METHODS: Female farm pigs were sedated, intubated, and anesthetized. Central arterial and venous access were continuously monitored. Regional brain tissue perfusion (CerO2) was also measured transcutaneous. Ventricular fibrillation (VF) was induced and untreated for 10 min. Pigs were randomized to (1) Conventional CPR (C-CPR) flat or (2) ACD + ITD CSE CPR that included 2 min of ACD + ITD with the head and heart first elevated 10 and 8 cm, and then gradual elevation over 2 min to 22 and 9 cm, respectively. After 19 min of CPR, pigs were defibrillated and recovered. A veterinarian blinded to the intervention assessed cerebral performance category (CPC) at 24 h. A neurologically intact outcome was defined as a CPC score of 1 or 2. Categorical outcomes were analyzed by Fisher's exact test and continuous outcomes with an unpaired student's t-test. RESULTS: In 16 animals, return of spontaneous circulation rate was 8/8 (100%) with ACD + ITD CSE and 3/8 (25%) for C-CPR (p = 0.026). For the primary outcome of neurologically intact survival, 6/8 (75%) pigs had a CPC score 1 or 2 with ACD + ITD CSE versus 1/8 (12.5%) with C-CPR (p = 0.04). Coronary perfusion pressure (mmHg, mean ±â€¯SD) was higher with CSE at 18 min (41 ±â€¯24 versus 10 ±â€¯5, p = 0.004). rSO2 (%, mean ±â€¯SD) and ETCO2 (mmHg, mean ±â€¯SD) values were higher at 18 min with CSE (32 ±â€¯9 versus 17 ±â€¯2, p = 0.01, and 55 mmHg ±â€¯10 versus 21 mmHg ±â€¯4, p < 0.001), respectively. CONCLUSIONS: The novel bundled resuscitation approach of CSE with ACD + ITD CPR increased favorable neurological survival versus C-CPR in a swine model of cardiac arrest.

Controlled progressive elevation rather than an optimal angle maximizes cerebral perfusion pressure during head up CPR in a swine model of cardiac arrest.

AIM OF THE STUDY: Elevation of the head and thorax (HUP) during cardiopulmonary resuscitation (CPR) has been shown to double brain blood flow with increased cerebral perfusion pressures (CerPP) after active compression-decompression (ACD) CPR with an impedance threshold device (ITD). However, the optimal angle for HUP CPR is unknown. METHODS: In Study A, different angles were assessed (20°, 30°, 40°), each randomized over 5-min periods of ACD + ITD CPR, after 8 min of untreated ventricular fibrillation in an anesthetized swine model. Based upon Study A, Study B was performed, where animals were randomized to 1 of 2 sequences: 20°, 30°, 40° or 40°, 30°, 20° with a similar protocol. The primary endpoint was CerPP for both studies. RESULTS: In Study A, no optimal HUP angle was observed in 18 pigs. CerPPs for 30° and 40° (mmHg, mean ±â€¯SD) were equivalent (44 ±â€¯22 and 47 ±â€¯26, p = 0.18). However, CerPP appeared higher when 40° HUP was performed during the last 5-min of CPR, suggestive of a sequence effect. For Study B, after 17 min of CPR, CerPP (mmHg) were higher with the 20°, 30°, 40° sequence: 60 ±â€¯17 versus 33 ±â€¯18 (p = 0.035). CONCLUSIONS: No optimal HUP CPR angle was observed. However, controlled progressive elevation of the head and thorax during CPR is more beneficial than an absolute angle or height to maximize CerPP. Further studies are needed to determine the optimal rate of rise during HUP ACD + ITD CPR. INSTITUTIONAL PROTOCOL NUMBER: 17-06.

Effect of controlled sequential elevation timing of the head and thorax during cardiopulmonary resuscitation on cerebral perfusion pressures in a porcine model of cardiac arrest.

AIM: Controlled sequential elevation of the head and thorax (CSE) during active compression-decompression (ACD) CPR with an impedance threshold device (ITD) augments cerebral (CerPP) and coronary (CorPP) perfusion pressures. The optimal CSE is unknown. METHODS: After 8 minutes of untreated VF, 40 kg anesthetized female pigs were positioned on a customized head and thorax elevation device (CED). After 2 min of automated ACD + ITD-16 CPR to 'prime the system', 12 pigs were randomized to CSE to the highest CED position over 4-min or 10-min. The primary outcome was CerPP after 7 minutes of CPR. Secondarily, 24-sec (without a priming step) and 2-min CSE times were similarly tested (n = 6 group) in a non-randomized order. Values expressed as mean ±â€¯SD. RESULTS: After 7 min of CPR, CerPPs were significantly higher in the 4-min vs 10-min CSE groups (53 ±â€¯14.4 vs 38.5 ±â€¯3.6 mmHg respectively, p = 0.03) whereas CorPP trended higher. The 4-min CSE group achieved 50% of baseline (50% BL) CerPP faster than the 10-min group (2.5 ±â€¯1.2 vs 6 ±â€¯3.1 minutes, p = 0.03). CerPP values in the 2-min and 4-min CSE groups were significantly higher than in the 24-sec group. With CSE, CerPPs and CorPPs increased over time in all groups. CONCLUSIONS: By optimizing controlled sequential elevation timing, CerPP values achieved 50% of baseline within less than 2.5 minutes and >80% of baseline after 7 minutes of CPR. This novel CPR approach rapidly restored CerPPs to near normal values non-invasively and without vasopressors.

Supraglottic airway devices variably develop negative intrathoracic pressures: A prospective cross-over study of cardiopulmonary resuscitation in human cadavers.

AIM OF THE STUDY: Negative intrathoracic pressure (ITP) during the decompression phase of cardiopulmonary resuscitation (CPR) is essential to refill the heart, increase cardiac output, maintain cerebral and coronary perfusion pressures, and improve survival. In order to generate negative ITP, an airway seal is necessary. We tested the hypothesis that some supraglottic airway (SGA) devices do not seal the airway as well the standard endotracheal tube (ETT). METHODS: Airway pressures (AP) were measured as a surrogate for ITP in seven recently deceased human cadavers of varying body habitus. Conventional manual, automated, and active compression-decompression CPR were performed with and without an impedance threshold device (ITD) in supine and Head Up positions. Positive pressure ventilation was delivered by an ETT and 5 SGA devices tested in a randomized order in this prospective cross-over designed study. The primary outcome was comparisons of decompression AP between all groups. RESULTS: An ITD was required to generate significantly lower negative ITP during the decompression phase of all methods of CPR. SGAs varied in their ability to support negative ITP. CONCLUSION: In a human cadaver model, the ability to generate negative intrathoracic pressures varied with different SGAs and an ITD regardless of the body position or CPR method. Differences in SGAs devices should be strongly considered when trying to optimize cardiac arrest outcomes, as some SGAs do not consistently develop a seal or negative intrathoracic pressure with multiple different CPR methods and devices.

Consistent head up cardiopulmonary resuscitation haemodynamics are observed across porcine and human cadaver translational models.

AIM: The objectives were: 1) replicate key elements of Head Up (HUP) cardiopulmonary resuscitation (CPR) physiology in a traditional swine model of ventricular fibrillation (VF), 2) compare HUP CPR physiology in pig cadavers (PC) to the VF model 3) develop a new human cadaver (HC) CPR model, and 4) assess HUP CPR in HC. METHODS: Nine female pigs were intubated, and anesthetized. Venous, arterial, and intracranial access were obtained. After 6 min of VF, CPR was performed for 2 min epochs as follows: Standard (S)-CPR supine (SUP), Active compression decompression (ACD) CPR + impedance threshold device (ITD-16) CPR SUP, then ACD + ITD HUP CPR. The same sequence was performed in PC 3 h later. In 9 HC, similar vascular and intracranial access were obtained and CPR performed for 1 min epochs using the same sequence as above. RESULTS: The mean cerebral perfusion pressure (CerPP, mmHg) was 14.5 ±â€¯6 for ACD + ITD SUP and 28.7 ±â€¯10 for ACD + ITD HUP (p = .007) in VF, -3.6 ±â€¯5 for ACD + ITD SUP and 7.8 ±â€¯9 for ACD + ITD HUP (p = .007) in PC, and 1.3 ±â€¯4 for ACD + ITD SUP and 11.3 ±â€¯5 for ACD + ITD HUP (p = .007) in HC. Mean systolic and diastolic intracranial pressures (ICP) (mmHg) were significantly lower in the ACD + ITD HUP group versus the ACD + ITD SUP group in all three CPR models. CONCLUSION: HUP CPR decreased ICP while increasing CerPP in pigs in VF as well as in PC and HC CPR models. This first-time demonstration of HUP CPR physiology in humans provides important implications for future resuscitation research and treatment.

Correlation of end tidal carbon dioxide, amplitude spectrum area, and coronary perfusion pressure in a porcine model of cardiac arrest.

Amplitude Spectrum Area (AMSA) values during ventricular fibrillation (VF) correlate with myocardial energy stores and predict defibrillation success. By contrast, end tidal CO2 (ETCO2) values provide a noninvasive assessment of coronary perfusion pressure and myocardial perfusion during cardiopulmonary resuscitation (CPR). Given the importance of the timing of defibrillation shock delivery on clinical outcome, we tested the hypothesis that AMSA and ETCO2 correlate with each other and can be used interchangably to correlate with myocardial perfusion in an animal laboratory preclinical, randomized, prospective investigation. After 6 min of untreated VF, 12 female pigs (32 ± 1 Kg), isoflurane anesthetized pigs received sequentially 3 min periods of standard (S) CPR, S-CPR+ an impedance threshold device (ITD), and then active compression decompression (ACD) + ITD CPR Hemodynamic, AMSA, and ETCO2 measurements were made with each method of CPR The Spearman correlation and Friedman tests were used to compare hemodynamic parameters. ETCO2, AMSA, coronary perfusion pressure, cerebral perfusion pressure were lowest with STD CPR, increased with STD CPR + ITD and highest with ACD CPR + ITD Further analysis demonstrated a positive correlation between AMSA and ETCO2 (r = 0.37, P = 0.025) and between AMSA and key hemodynamic parameters (P < 0.05). This study established a moderate positive correlation between ETCO2 and AMSA These findings provide the physiological basis for developing and testing a novel noninvasive method that utilizes either ETCO2 alone or the combination of ETCO2 and AMSA to predict when defibrillation might be successful.

Head and thorax elevation during active compression decompression cardiopulmonary resuscitation with an impedance threshold device improves cerebral perfusion in a swine model of prolonged cardiac arrest.

AIM OF THE STUDY: As most cardiopulmonary resuscitation (CPR) efforts last longer than 15min, the aim of this study was to compare brain blood flow between the Head Up (HUP) and supine (SUP) body positions during a prolonged CPR effort of 15min, using active compression-decompression (ACD) CPR and impedance threshold device (ITD) in a swine model of cardiac arrest. METHODS: Ventricular fibrillation (VF) was induced in anesthetized pigs. After 8min of untreated VF followed by 2min of ACD-CPR+ITD in the SUP position, pigs were randomized to 18min of continuous ACD-CPR+ITD in either a 30° HUP or SUP position. Microspheres were injected before VF and then 5 and 15min after start of CPR. RESULTS: The mean blood flow (ml/min/g, mean±SD) to the brain after 15min of CPR was 0.42±0.05 in the HUP group (n=8) and 0.21±0.04 SUP (n=10), respectively, (p<0.01). The HUP group also had statistically significantly lower intracranial pressures and higher calculated cerebral perfusion pressures after 5, 15, 19 (before adrenaline) and 20 (after adrenaline) minutes of HUT versus SUP CPR. CONCLUSIONS: After prolonged ACD-CPR+ITD in the HUP position, brain blood flow was 2-fold higher versus the SUP position. These positive findings provide strong pre-clinical support to proceed with a clinical evaluation of elevation of the head and thorax during ACD-CPR+ITD in humans in cardiac arrest.

Evaluation of the Boussignac Cardiac arrest device (B-card) during cardiopulmonary resuscitation in an animal model.

AIM OF THE STUDY: The purpose of this study was to examine continuous oxygen insufflation (COI) in a swine model of cardiac arrest. The primary hypothesis was COI during standard CPR (S-CPR) should result in higher intrathoracic pressure (ITP) during chest compression and lower ITP during decompression versus S-CPR alone. These changes with COI were hypothesized to improve hemodynamics. The second hypothesis was that changes in ITP with S-CPR+COI would result in superior hemodynamics compared with active compression decompression (ACD) + impedance threshold device (ITD) CPR, as this method primarily lowers ITP during chest decompression. METHODS: After 6min of untreated ventricular fibrillation, S-CPR was initiated in 8 female swine for 4min, then 3min of S-CPR+COI, then 3min of ACD+ITD CPR, then 3min of S-CPR+COI. ITP and hemodynamics were continuously monitored. RESULTS: During S-CPR+COI, ITP was always positive during the CPR compression and decompression phases. ITP compression values with S-CPR+COI versus S-CPR alone were 5.5±3 versus 0.2±2 (p<0.001) and decompression values were 2.8±2 versus -1.3±2 (p<0.001), respectively. With S-CPR+COI versus ACD+ITD the ITP compression values were 5.5±3 versus 1.5±2 (p<0.01) and decompression values were 2.8±2 versus -4.7±3 (p<0.001), respectively. CONCLUSION: COI during S-CPR created a continuous positive pressure in the airway during both the compression and decompression phase of CPR. At no point in time did COI generate a negative intrathoracic pressures during CPR in this swine model of cardiac arrest.

Chest compliance is altered by static compression and decompression as revealed by changes in anteroposterior chest height during CPR using the ResQPUMP in a human cadaver model.

INTRODUCTION: Chest compliance plays a fundamental role in the generation of circulation during cardiopulmonary resuscitation (CPR). To study potential changes in chest compliance over time, anterior posterior (AP) chest height measurements were performed on newly deceased (never frozen) human cadavers during CPR before and after 5min of automated CPR. We tested the hypothesis that after 5min of CPR chest compliance would be significantly increased. METHODS: Static compression (30, 40, and 50kg) and decompression forces (-10, -15kg) were applied with a manual ACD-CPR device (ResQPUMP, ZOLL) before and after 5min of automated CPR. Lateral chest x-rays were obtained with multiple reference markers to assess changes in AP distance. RESULTS: In 9 cadavers, changes (mean±SD) in the AP distance (cm) during the applied forces were 2.1±1.2 for a compression force of 30kg, 2.9±1.3 for 40kg, 4.3±1.0 for 50kg, 1.0±0.8 for a decompression force of -10kg and 1.8±0.6 for -15kg. After 5min of automated CPR, AP excursion distances were significantly greater (p<0.05). AP distance increased to 3.7±1.4 for a compression force of 30kg, 4.9±1.6 for 40kg, 6.3±1.9 for 50kg, 2.3±0.9 for -10kg of lift and 2.7±1.1 for -15kg of lift. CONCLUSIONS: These data demonstrate chest compliance increases significantly over time as demonstrated by the significant increase in the measured AP distance after 5min of CPR. These findings suggest that adjustments in compression and decompression forces may be needed to optimize CPR over time.

Reperfusion injury protection during Basic Life Support improves circulation and survival outcomes in a porcine model of prolonged cardiac arrest.

OBJECTIVE: Ischemic postconditioning (PC) using three intentional pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. We hypothesized PC, performed during basic life support (BLS) in the absence of epinephrine, would reduce reperfusion injury and enhance 24h functional recovery. DESIGN: Prospective animal investigation. SETTING: Animal laboratory SUBJECTS: Female farm pigs (n=46, 39±1kg). INTERVENTIONS: Protocol A: After 12min of ventricular fibrillation (VF), 28 pigs were randomized to four groups: (A) Standard CPR (SCPR), (B) active compression-decompression CPR with an impedance threshold device (ACD-ITD), (C) SCPR+PC (SCPR+PC) and (D) ACD-ITD CPR+PC. Protocol B: After 15min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD+PC. The BLS duration was 2.75min in Protocol A and 5min in Protocol B. Following BLS, up to three shocks were delivered. Without return of spontaneous circulation (ROSC), CPR was resumed and epi (0.5mg) and defibrillation delivered. The primary end point was survival without major adverse events. Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean±SEM. MEASUREMENTS AND MAIN RESULTS: Protocol A: ACD-ITD+PC (group D) improved coronary perfusion pressure after 3min of BLS versus the three other groups (28±6, 35±7, 23±5 and 47±7 for groups A, B, C, D respectively, p=0.05). There were no significant differences in 24h survival between groups. PROTOCOL B: LVEF 4h post ROSC was significantly higher with ACD-ITD+PC vs ACD-ITD alone (52.5±3% vs. 37.5±6.6%, p=0.045). Survival rates were significantly higher with ACD-ITD+PC vs. ACD-ITD alone (p=0.027). CONCLUSIONS: BLS using ACD-ITD+PC reduced post resuscitation cardiac dysfunction and improved functional recovery after prolonged untreated VF in pigs. PROTOCOL NUMBER: 12-11.

The Effect of Head Up Cardiopulmonary Resuscitation on Cerebral and Systemic Hemodynamics.

AIM: Chest compressions during cardiopulmonary resuscitation (CPR) increase arterial and venous pressures, delivering simultaneous bidirectional high-pressure compression waves to the brain. We hypothesized that this may be detrimental and could be partially overcome by elevation of the head during CPR. MEASUREMENTS: Female Yorkshire farm pigs (n=30) were sedated, intubated, anesthetized, and placed on a table able to elevate the head 30° (15cm) (HUP) and the heart 10° (4cm) or remain in the supine (SUP) flat position during CPR. After 8minutes of untreated ventricular fibrillation and 2minutes of SUP CPR, pigs were randomized to HUP or SUP CPR for 20 more minutes. In Group A, pigs were randomized after 2minutes of flat automated conventional (C) CPR to HUP (n=7) or SUP (n=7) C-CPR. In Group B, pigs were randomized after 2minutes of automated active compression decompression (ACD) CPR plus an impedance threshold device (ITD) SUP CPR to either HUP (n=8) or SUP (n=8). RESULTS: The primary outcome of the study was difference in CerPP (mmHg) between the HUP and SUP positions within groups. After 22minutes of CPR, CerPP was 6±3mmHg in the HUP versus -5±3 in the SUP (p=0.016) in Group A, and 51±8 versus 20±5 (p=0.006) in Group B. Coronary perfusion pressures after 22minutes were HUP 6±2 vs SUP 3±2 (p=0.283) in Group A and HUP 32±5 vs SUP 19±5, (p=0.074) in Group B. In Group B, 6/8 pigs were resuscitated in both positions. No pigs were resuscitated in Group A. CONCLUSIONS: The HUP position in both C-CPR and ACD+ITD CPR significantly improved CerPP. This simple maneuver has the potential to improve neurological outcomes after cardiac arrest.

Tilting for perfusion: head-up position during cardiopulmonary resuscitation improves brain flow in a porcine model of cardiac arrest.

INTRODUCTION: Cerebral perfusion is compromised during cardiopulmonary resuscitation (CPR). We hypothesized that beneficial effects of gravity on the venous circulation during CPR performed in the head-up tilt (HUT) position would improve cerebral perfusion compared with supine or head-down tilt (HDT). METHODS: Twenty-two pigs were sedated, intubated, anesthetized, paralyzed and placed on a tilt table. After 6min of untreated ventricular fibrillation (VF) CPR was performed on 14 pigs for 3min with an automated CPR device called LUCAS (L) plus an impedance threshold device (ITD), followed by 5min of L-CPR+ITD at 0° supine, 5min at 30° HUT, and then 5min at 30° HDT. Microspheres were used to measure organ blood flow in 8 pigs. L-CPR+ITD was performed on 8 additional pigs at 0°, 20°, 30°, 40°, and 50° HUT. RESULTS: Coronary perfusion pressure was 19±2mmHg at 0° vs. 30±3 at 30° HUT (p<0.001) and 10±3 at 30° HDT (p<0.001). Cerebral perfusion pressure was 19±3 at 0° vs. 35±3 at 30° HUT (p<0.001) and 4±4 at 30° HDT (p<0.001). Brain-blood flow was 0.19±0.04mlmin(-1)g(-1) at 0° vs. 0.27±0.04 at 30° HUT (p=0.01) and 0.14±0.06 at 30° HDT (p=0.16). Heart blood flow was not significantly different between interventions. With 0, 10, 20, 30, 40 and 50° HUT, ICP values were 21±2, 16±2, 10±2, 5±2, 0±2, -5±2 respectively, (p<0.001), CerPP increased linearly (p=0.001), and CPP remained constant. CONCLUSION: During CPR, HDT decreased brain flow whereas HUT significantly lowered ICP and improved cerebral perfusion. Further studies are warranted to explore this new resuscitation concept.

Sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitates intra-arrest therapeutic hypothermia in a porcine model of prolonged ventricular fibrillation.

OBJECTIVES: The aim of this study was to assess the effect of sodium nitroprusside-enhanced cardiopulmonary resuscitation on heat exchange during surface cooling. We hypothesized that sodium nitroprusside-enhanced cardiopulmonary resuscitation would decrease the time required to reach brain temperature less than 35°C compared to active compression-decompression plus impedance threshold device cardiopulmonary resuscitation alone, in the setting of intra-cardiopulmonary resuscitation cooling. We further hypothesized that the addition of epinephrine during sodium nitroprusside-enhanced cardiopulmonary resuscitation would mitigate heat exchange. DESIGN: Prospective randomized animal investigation. SETTING: Preclinical animal laboratory. SUBJECTS: Female farm pigs (n=28). INTERVENTIONS: After 10 minutes of untreated ventricular fibrillation, animals were randomized to three different protocols: sodium nitroprusside-enhanced cardiopulmonary resuscitation (n=8), sodium nitroprusside-enhanced cardiopulmonary resuscitation plus epinephrine (n=10), and active compression-decompression plus impedance threshold device alone (control, n=10). All animals received surface cooling at the initiation of cardiopulmonary resuscitation. Sodium nitroprusside-enhanced cardiopulmonary resuscitation included active compression-decompression plus impedance threshold device plus abdominal binding and 2 mg of sodium nitroprusside at 1, 4, and 8 minutes of cardiopulmonary resuscitation. No epinephrine was used during cardiopulmonary resuscitation in the sodium nitroprusside-enhanced cardiopulmonary resuscitation group. Control and sodium nitroprusside-enhanced cardiopulmonary resuscitation plus epinephrine groups received 0.5 mg of epinephrine at 4.5 and 9 minutes of cardiopulmonary resuscitation. Defibrillation occurred after 10 minutes of cardiopulmonary resuscitation. After return of spontaneous circulation, an Arctic Sun (Medivance, Louiseville, CO) was applied at maximum cooling on all animals. The primary endpoint was the time required to reach brain temperature less than 35°C beginning from the time of cardiopulmonary resuscitation initiation. Data are presented as mean±SEM. MEASUREMENTS AND MAIN RESULTS: The time required to reach a brain temperature of 35°C was decreased with sodium nitroprusside-enhanced cardiopulmonary resuscitation versus control or sodium nitroprusside-enhanced cardiopulmonary resuscitation plus epinephrine (24±6 min, 63±8 min, and 50±9 min, respectively; p=0.005). Carotid blood flow was higher during cardiopulmonary resuscitation in the sodium nitroprusside-enhanced cardiopulmonary resuscitation group (83±15 mL/min vs 26±7 mL/min and 35±5 mL/min in the control and sodium nitroprusside-enhanced cardiopulmonary resuscitation plus epinephrine groups, respectively; p=0.001). CONCLUSIONS: This study demonstrates that sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitates intra-cardiopulmonary resuscitation hypothermia. The addition of epinephrine to sodium nitroprusside-enhanced cardiopulmonary resuscitation during cardiopulmonary resuscitation reduced its improvement in heat exchange.