Nicolas Segal

Potential negative effects of epinephrine on carotid blood flow and ETCO2 during active compression-decompression CPR utilizing an impedance threshold device.

OBJECTIVES This study examines the effects of IV epinephrine administration on carotid blood flow (CBF) and end tidal CO(2) (ETCO(2)) production in a swine model of active compression-decompression CPR with an impedance threshold device (ACD-CPR+ITD). METHODS Six female swine (32 ± 1 kg) were anesthetized, intubated and ventilated. Intracranial, thoracic aorta and right atrial pressures were measured via indwelling catheters. CBF was recorded. ETCO(2), SpO(2) and EKG were monitored. V-fib was induced and went untreated for 6 min. Three minutes each of standard CPR (STD), STD-CPR+impedance threshold device (ITD) and active compression-decompression (ACD)-CPR+ITD were performed. At minute 9 of the resuscitation, 40 μg/kg of IV Epinephrine was administered and ACD-CPR+ITD was continued for 1 min. Statistical analysis was performed with a paired t-test. p values of <0.05 were considered statistically significant and all values are reported in mmHg unless otherwise noted. RESULTS Aortic pressure, cerebral and coronary perfusion pressures increased from STD<STD+ITD<ACD-CPR+ITD (p<0.001). Epinephrine administered during ACD-CPR+ITD signficantly increased mean aortic pressure (29 ± 5 vs 42 ± 12, p = 0.01), cerebral perfusion pressure (12 ± 5 vs 22 ± 10, p = 0.01), and coronary perfusion pressure (8 ± 7 vs 17 ± 4, p = 0.02); however, mean CBF and ETCO(2) decreased (respectively 29 ± 15 vs 14 ± 7.0 ml/min, p = 0.03; 20 ± 7 vs 18 ± 6, p = 0.04). CONCLUSIONS In this model, administration of epinephrine during ACD-CPR+ITD significantly increased markers of macrocirculation, while significantly decreasing carotid blood flow and ETCO(2). This calls into question the ability of calculated perfusion pressures to accurately reflect oxygen delivery to end organs. The administration of epinephrine during ACD-CPR+ITD does not improve cerebral tissue perfusion.

Ischemic post-conditioning and vasodilator therapy during standard cardiopulmonary resuscitation to reduce cardiac and brain injury after prolonged untreated ventricular fibrillation

AIM OF THE STUDY We investigated the effects of ischemic postconditioning (IPC) with and without cardioprotective vasodilatory therapy (CVT) at the initiation of cardiopulmonary resuscitation (CPR) on cardio-cerebral function and 48-h survival. METHODS Prospective randomized animal study. Following 15 min of ventricular fibrillation, 42 Yorkshire farm pigs weighing an average of 34 ± 2 kg were randomized to receive standard CPR (SCPR, n=12), SCPR+IPC (n=10), SCPR+IPC+CVT (n=10), or SCPR+CVT (n=10). IPC was delivered during the first 3 min of CPR with 4 cycles of 20s of chest compressions followed by 20-s pauses. CVT consisted of intravenous sodium nitroprusside (2mg) and adenosine (24 mg) during the first minute of CPR. Epinephrine was given in all groups per standard protocol. A transthoracic echocardiogram was obtained on all survivors 1 and 4h post-ROSC. The brains were extracted after euthanasia at least 24h later to assess ischemic injury in 7 regions. Ischemic injury was graded on a 0-4 scale with (0=no injury to 4 ≥ 50% neural injury). The sum of the regional scores was reported as cerebral histological score (CHS). 48 h survival was reported. RESULTS Post-resuscitation left ventricular ejection (LVEF) fraction improved in SCPR+CVT, SCPR+IPC+CVT and SCPR+IPC groups compared to SCPR (59% ± 9%, 52% ± 14%, 52% ± 14% vs. 35% ± 11%, respectively, p<0.05). Only SCPR+IPC and SCPR+IPC+CVT, but not SCPR+CVT, had lower mean CHS compared to SCPR (5.8 ± 2.6, 2.8 ± 1.8 vs. 10 ± 2.1, respectively, p<0.01). The 48-h survival among SCPR+IPC, SCPR+CVT, SCPR+IPC+CVT and SCPR was 6/10, 3/10, 5/10 and 1/12, respectively (Cox regression p<0.01). CONCLUSIONS IPC and CVT during standard CPR improved post-resuscitation LVEF but only IPC was independently neuroprotective and improved 48-h survival after 15 min of untreated cardiac arrest in pigs.

Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17 min of untreated cardiac arrest

OBJECTIVE Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15min of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. METHODS Following 17min of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR+ITD+sevoflurane+P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. RESULTS Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48h), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48h). CONCLUSIONS Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17min of untreated cardiac arrest in pigs. All studies were performed with approval from the Institutional Animal Care Committee of the Minneapolis Medical Research Foundation (protocol #12-11).

Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest

PURPOSE OF THE STUDY To describe a new method of CPR that optimizes vital organ perfusion pressures and carotid blood flow. We tested the hypothesis that a combination of high dose sodium nitroprusside (SNP) as well as non-invasive devices and techniques known independently to enhance circulation would significantly improve carotid blood flow (CBF) and return of spontaneous circulation (ROSC) rates in a porcine model of cardiac arrest. METHODS 15 isofluorane anesthetized pigs (30±1 kg), after 6 min of untreated ventricular fibrillation, were subsequently randomized to receive either 15 min of standard CPR (S-CPR) (8 animals) or 5 min epochs of S-CPR followed by active compression-decompression (ACD)+inspiratory impedance threshold device (ITD) CPR followed by ACD+ITD+abdominal binding (AB) with 1mg of SNP administered at minutes 2, 7, 12 of CPR (7 animals). Primary endpoints were CBF and ROSC rates. ANOVA and Fishers exact test were used for comparisons. RESULTS/CONCLUSION There was significant improvement in the hemodynamic parameters in the SNP animals. ROSC was achieved in 7/7 animals that received SNP and in 2/8 in the S-CPR (p=0.007). CBF and end tidal CO(2) (ETCO(2)) were significantly higher in the ACD+ITD+AB+SNP (SNPeCPR) animals during CPR. Bolus doses of SNP, when used in conjunction with ACD+ITD+AB CPR, significantly improve CBF and ROSC rates compared to S-CPR.

Controlled pauses at the initiation of sodium nitroprusside- enhanced cardiopulmonary resuscitation facilitate neurological and cardiac recovery after 15 mins of untreated ventricular fibrillation

Objective: A multipronged approach to improve vital organ perfusion during cardiopulmonary resuscitation that includes sodium nitroprusside, active compression-decompression cardiopulmonary resuscitation, an impedance threshold device, and abdominal pressure (sodium nitroprusside-enhanced cardiopulmonary resuscitation) has been recently shown to increase coronary and cerebral perfusion pressures and higher rates of return of spontaneous circulation vs. standard cardiopulmonary resuscitation. To further reduce reperfusion injury during sodium nitroprusside-enhanced cardiopulmonary resuscitation, we investigated the addition of adenosine and four 20-sec controlled pauses spread throughout the first 3 mins of sodium nitroprusside-enhanced cardiopulmonary resuscitation. The primary study end point was 24-hr survival with favorable neurologic function after 15 mins of untreated ventricular fibrillation. Design: Randomized, prospective, blinded animal investigation. Setting: Preclinical animal laboratory. Subjects: Thirty-two female pigs (four groups of eight) 32 ± 2 kg. Interventions: After 15 mins of untreated ventricular fibrillation, isoflurane-anesthetized pigs received 5 mins of either standard car- diopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation + adenosine, or controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation + adenosine. After 4 mins of cardiopulmonary resuscitation, all animals received epinephrine (0.5 mg) and a defibrillation shock 1 min later. Sodium nitroprusside-enhanced cardiopulmonary resuscitation-treated animals received sodium nitroprusside (2 mg) after 1 min of cardiopulmonary resuscitation and 1 mg after 3 mins of cardiopulmonary resuscitation. After 1 min of sodium nitroprusside-enhanced cardiopulmonary resuscitation, adenosine (24 mg) was administered in two groups. Measurements and Main Results: A veterinarian blinded to the treatment assigned a cerebral performance category score of 1–5 (normal, slightly disabled, severely disabled but conscious, vegetative state, or dead, respectively) 24 hrs after return of spontaneous circulation. Sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation + adenosine, and controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation + adenosine resulted in a significantly higher 24-hr survival rate compared to standard cardiopulmonary resuscitation (7 of 8, 8 of 8, and 8 of 8 vs. 2 of 8, respectively p < .05). The mean cerebral performance category scores for standard cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation + adenosine, or controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation + adenosine were 4.6 ± 0.7, 3 ± 1.3, 2.5 ± 0.9, and 1.5 ± 0.9, respectively (p < .01 for controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation + adenosine compared to all other groups). Conclusions: Reducing reperfusion injury and maximizing circulation during cardiopulmonary resuscitation significantly improved functional neurologic recovery after 15 mins of untreated ventricular fibrillation. These results suggest that brain resuscitation after prolonged cardiac arrest is possible with novel, noninvasive approaches focused on reversing the mechanisms of tissue injury. (Crit Care Med 2012; 40:–7)

Deleterious Effects of Intra-arterial Administration of Particulate Steroids on Microvascular Perfusion in a Mouse Model

Purpose To determine the in vivo effects of several particulate steroids on microvascular perfusion by using intravital microscopy in a mice model and to investigate the in vitro interactions between these particulate steroids and red blood cells (RBCs). Materials and Methods The study was conducted in agreement with the guidelines of the National Committee of Ethic Reflection on Animal Experimentation. By using intravital microscopy of mouse cremaster muscle, the in vivo effects of several particulate steroids on microvascular perfusion were assessed. Four to five mice were allocated to each of the following treatment groups: saline solution, dexamethasone sodium phosphate, a nonparticulate steroid, and the particulate steroids cortivazol, methylprednisolone, triamcinolone, and prednisolone. By using in vitro blood microcinematography and electron microscopy, the interactions between these steroids and human RBCs were studied. All results were analyzed by using nonparametric tests. Results With prednisolone, methylprednisolone, or triamcinolone, blood flow was rapidly and completely stopped in all the arterioles and venules (median RBC velocity in first-order arterioles, 5 minutes after administration was zero for these three groups) compared with a limited effect in mice treated with saline, dexamethasone, and cortivazol (20.3, 21.3, and 27.5 mm/sec, respectively; P < .003). This effect was associated with a large decrease in the functional capillary density (4.21, 0, and 0 capillaries per millimeter for methylprednisolone, triamcinolone, or prednisolone, respectively, vs 21.0, 21.4, and 19.1 capillaries per millimeter in mice treated with saline, dexamethasone, and cortivazol, respectively; P < .003). This was because of the rapid formation of RBC aggregates. However, no change in microvascular perfusion was associated with administration of cortivazol or dexamethasone. In vitro experiments confirmed the formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs with the same steroids. Conclusion Several particulate steroids have an immediate and massive effect on microvascular perfusion because of formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs. (©) RSNA, 2016 Online supplemental material is available for this article.

Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models.

Objective:Sodium nitroprusside-enhanced cardiopulmonary resuscitation consists of active compression-decompression, an impedance threshold device, abdominal binding, and large intravenous doses of sodium nitroprusside. We hypothesize that sodium nitroprusside-enhanced cardiopulmonary resuscitation will significantly increase carotid blood flow and return of spontaneous circulation compared to standard cardiopulmonary resuscitation after prolonged ventricular fibrillation and pulseless electrical activity cardiac arrest. Design:Prospective randomized animal study. Setting:Hennepin County Medical Center Animal Laboratory. Subjects:Forty Yorkshire female farm-bred pigs weighing 32 ± 2 kg. Interventions:In protocol A, 24 isoflurane-anesthetized pigs underwent 15 mins of untreated ventricular fibrillation and were subsequently randomized to receive standard cardiopulmonary resuscitation (n = 6), active compression-decompression cardiopulmonary resuscitation + impedance threshold device (n = 6), or sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 12) for up to 15 mins. First defibrillation was attempted at minute 6 of cardiopulmonary resuscitation. In protocol B, a separate group of 16 pigs underwent 10 mins of untreated ventricular fibrillation followed by 3 mins of chest compression only cardiopulmonary resuscitation followed by countershock-induced pulseless electrical activity, after which animals were randomized to standard cardiopulmonary resuscitation (n = 8) or sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 8). Measurements and Main Results:The primary end point was carotid blood flow during cardiopulmonary resuscitation and return of spontaneous circulation. Secondary end points included end-tidal CO2 as well as coronary and cerebral perfusion pressure. After prolonged untreated ventricular fibrillation, sodium nitroprusside-enhanced cardiopulmonary resuscitation demonstrated superior rates of return of spontaneous circulation when compared to standard cardiopulmonary resuscitation and active compression-decompression cardiopulmonary resuscitation + impedance threshold device (12 of 12, 0 of 6, and 0 of 6 respectively, p < .01). In animals with pulseless electrical activity, sodium nitroprusside-enhanced cardiopulmonary resuscitation increased return of spontaneous circulation rates when compared to standard cardiopulmonary resuscitation. In both groups, carotid blood flow, coronary perfusion pressure, cerebral perfusion pressure, and end-tidal CO2 were increased with sodium nitroprusside-enhanced cardiopulmonary resuscitation. Conclusions:In pigs, sodium nitroprusside-enhanced cardiopulmonary resuscitation significantly increased return of spontaneous circulation rates, as well as carotid blood flow and end-tidal CO2, when compared to standard cardiopulmonary resuscitation or active compression-decompression cardiopulmonary resuscitation + impedance threshold device.

Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation.

AIM OF STUDY Sodium nitroprusside-enhanced CPR, or SNPeCPR, consists of active compression-decompression CPR with an impedance threshold device, abdominal compression, and intravenous sodium nitroprusside (SNP). We hypothesize that SNPeCPR will improve post resuscitation left ventricular function and neurological function compared to standard (S) CPR after 15 min of untreated ventricular fibrillation in a porcine model of cardiac arrest. METHODS Pigs (n = 22) anesthetized with isoflurane underwent 15 min of untreated ventricular fibrillation, were then randomized to 6 min of S-CPR (n = 11) or SNPeCPR (n = 11) followed by defibrillation. The primary endpoints were neurologic function as measured by cerebral performance category (CPC) score and left ventricular ejection fraction. RESULTS SNPeCPR increased 24-hour survival rates compared to S-CPR (10/11 versus 5/11, p = 0.03) and improved neurological function (CPC score 2.5 ± 1, versus 3.8 ± 0.4, respectively, p = 0.004). Left ventricular ejection fractions at 1, 4 and 24 hours after defibrillation were 72 ± 11, 57 ± 11.4 and 64 ± 11 with SNPeCPR versus 29 ± 10, 30 ± 17 and 39 ± 6 with S-CPR, respectively (p < 0.01 for all). CONCLUSIONS In this pig model, after 15 min of untreated ventricular fibrillation, SNPeCPR significantly improved 24-hour survival rates, neurologic function and prevented post-resuscitation left ventricular dysfunction compared to S-CPR.

Intrathoracic pressure regulation during cardiopulmonary resuscitation: A feasibility case-series !

AIM OF THE STUDY Intrathoracic pressure regulation (IPR) is a novel, noninvasive therapy intended to increase cardiac output and blood pressure in hypotensive states by generating a negative end expiratory pressure of -12 cm H2O between positive pressure ventilations. In this first feasibility case-series, we tested the hypothesis that IPR improves End tidal (ET) CO2 during cardiopulmonary resuscitation (CPR). ETCO2 was used as a surrogate measure for circulation. METHODS All patients were treated initially with manual CPR and an impedance threshold device (ITD). When IPR-trained medics arrived on scene the ITD was removed and an IPR device (CirQLATOR™) was attached to the patients advanced airway (intervention group). The IPR device lowered airway pressures to -9 mmHg after each positive pressure ventilation for the duration of the expiratory phase. ETCO2, was measured using a capnometer incorporated into the defibrillator system (LifePak™). Values are expressed as mean ± SEM. Results were compared using paired and unpaired Students t test. p values of <0.05 were considered statistically significant. RESULTS ETCO2 values in 11 patients in the case series were compared pre and during IPR therapy and also compared to 74 patients in the control group not treated with the new IPR device. ETCO2 values increased from an average of 21 ± 1 mmHg immediately before IPR application to an average value of 32 ± 5 mmHg and to a maximum value of 45 ± 5mmHg during IPR treatment (p<0.001). In the control group ETCO2 values did not change significantly. Return of spontaneous circulation (ROSC) rates were 46% (34/74) with standard CPR and ITD versus 73% (8/11) with standard CPR and the IPR device (p<0.001). CONCLUSIONS ETCO2 levels and ROSC rates were significantly higher in the study intervention group. These findings demonstrate that during CPR circulation may be significantly augmented by generation of a negative end expiratory pressure between each breath.

Accuracy of a feedback device for cardiopulmonary resuscitation on a dental chair

Background Conflicting studies exist about the effectiveness of cardiopulmonary resuscitation (CPR) on a dental chair. In some situations, dental surgeons are obliged to perform CPR with the patient on the chair. Feedback devices are supposed to guide the compression depth in order to improve the quality of CPR, but some devices are based on an accelerometer that can theoretically report erroneous results because of the lack of rigidity of a dental chair. Objective The aim of this study was to evaluate the accuracy of these devices to guide chest compressions on a dental chair. Methods A prospective, randomised, crossover, equivalence/non-inferiority study was conducted to compare the values of compression depths provided by the feedback device (Real CPR Help®, delivered by Zoll© Medical Corporation, Chelmsford, MA, USA) with the real measurements provided by the manikin (Resusci Anne® Advanced SkillTrainer, Laerdal Medical AS©, Norway). Chest-compression-only CPR was performed by 15 Basic Life Support instructors who carried out two rounds of continuous CPR for 2 min each. Data were analysed with a correlation test, a Bland–Altman method and a Wilcoxon test. Statistical significance was defined as p<0.05. Results A significant difference was found between the mean depths of compression measured by the feedback device and the manikin on a dental chair and on the floor (p<0.0001). The feedback device overestimated the depth of chest compressions, and Bland–Altman analysis demonstrated poor agreement. Conclusion This study indicates that feedback devices with accelerometer technology are not sufficiently reliable to ensure adequate chest compression on dental chairs.