Relationships of Jugular Bulb Parameters with Cerebral Perfusion and Metabolism After Resuscitation from Cardiac Arrest: A Post-Hoc Analysis of Experimental Studies Using a Minipig Model.

BACKGROUND: Cerebral blood flow (CBF) decreases in the first few hours or days following resuscitation from cardiac arrest, increasing the risk of secondary cerebral injury. Using data from experimental studies performed in minipigs, we investigated the relationships of parameters derived from arterial and jugular bulb blood gas analyses and lactate levels (jugular bulb parameters), which have been used as indicators of cerebral perfusion and metabolism, with CBF and the cerebral lactate to creatine ratio measured with dynamic susceptibility contrast magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. METHODS: We retrospectively analyzed 36 sets of the following data obtained during the initial hours following resuscitation from cardiac arrest: percent of measured CBF relative to that at the prearrest baseline (%CBF), cerebral lactate to creatine ratio, and jugular bulb parameters, including jugular bulb oxygen saturation, jugular bulb lactate, arterial-jugular bulb oxygen content difference, cerebral extraction of oxygen, jugular bulb-arterial lactate content difference, lactate oxygen index, estimated respiratory quotient, and arterial-jugular bulb hydrogen ion content difference. Linear mixed-effects models were constructed to examine the effects of each jugular bulb parameter on the %CBF and cerebral lactate to creatine ratio. RESULTS: The arterial-jugular bulb oxygen content difference (P = 0.047) and cerebral extraction of oxygen (P = 0.030) had a significant linear relationship with %CBF, but they explained only 12.0% (95% confidence interval [CI] 0.002-0.371) and 14.2% (95% CI 0.005-0.396) of the total %CBF variance, respectively. The arterial-jugular bulb hydrogen ion content difference had a significant linear relationship with cerebral lactate to creatine ratio (P = 0.037) but explained only 13.8% (95% CI 0.003-0.412) of the total variance in the cerebral lactate to creatine ratio. None of the other jugular bulb parameters were related to the %CBF or cerebral lactate to creatine ratio. CONCLUSIONS: In conclusion, none of the jugular bulb parameters appeared to provide sufficient information on cerebral perfusion and metabolism in this setting.

Pralidoxime-Induced Potentiation of the Pressor Effect of Adrenaline and Hastened Successful Resuscitation by Pralidoxime in a Porcine Cardiac Arrest Model.

PURPOSE: Pralidoxime potentiated the pressor effect of adrenaline and facilitated restoration of spontaneous circulation (ROSC) after prolonged cardiac arrest. In this study, we hypothesised that pralidoxime would hasten ROSC in a model with a short duration of untreated ventricular fibrillation (VF). We also hypothesised that potentiation of the pressor effect of adrenaline by pralidoxime would not be accompanied by worsening of the adverse effects of adrenaline. METHODS: After 5 min of VF, 20 pigs randomly received either pralidoxime (40 mg/kg) or saline, in combination with adrenaline, during cardiopulmonary resuscitation (CPR). Coronary perfusion pressure (CPP) during CPR, and ease of resuscitation were compared between the groups. Additionally, haemodynamic data, severity of ventricular arrhythmias, and cerebral microcirculation were measured during the 1-h post-resuscitation period. Cerebral microcirculatory blood flow and brain tissue oxygen tension (PbtO2) were measured on parietal cortices exposed through burr holes. RESULTS: All animals achieved ROSC. The pralidoxime group had higher CPP during CPR (P = 0.014) and required a shorter duration of CPR (P = 0.024) and smaller number of adrenaline doses (P = 0.024). During the post-resuscitation period, heart rate increased over time in the control group, and decreased steadily in the pralidoxime group. No inter-group differences were observed in the incidences of ventricular arrhythmias, cerebral microcirculatory blood flow, and PbtO2. CONCLUSION: Pralidoxime improved CPP and hastened ROSC in a model with a short duration of untreated VF. The potentiation of the pressor effect of adrenaline was not accompanied by the worsening of the adverse effects of adrenaline.

Early single session of hyperbaric oxygen therapy mitigates renal apoptosis in lipopolysaccharides-induced endotoxemia in rats.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a prominent sepsis complication, often resulting in adverse clinical outcomes. Hyperbaric oxygen therapy (HBOT), known for its anti-inflammatory characteristics, antioxidant effects, and ability to deliver high oxygen tension to hypo-perfused tissues, offers potential benefits for SA-AKI. This study investigated whether HBOT improved renal injury in sepsis and elucidated its underlying mechanisms. Methods: A lipopolysaccharide (LPS)-induced endotoxemia model was established using 8-week-old C57BL/6 mice. Thirty minutes post-LPS administration, a group of mice underwent HBOT at a 2.5 atmospheric pressure absolute with 100% oxygen for 60 minutes. After 24 hours, all mice were euthanized for measurements. Results: Our results demonstrated that HBOT effectively mitigated renal tubular cell apoptosis. Additionally, HBOT significantly reduced phosphorylated p53 proteins and cytochrome C levels, suggesting that HBOT may attenuate renal apoptosis by impeding p53 activation and cytochrome C release. Notably, HBOT preserved manganese-dependent levels of superoxide dismutase, an antioxidant enzyme, compared to the LPS group. Furthermore, transforming growth factor beta (TGF-ß)/Smad4 and alpha smooth muscle actin expressions were significantly reduced in the LPS + HBOT group. Conclusion: An early single session of HBOT exhibited renoprotective effects in LPS-induced endotoxemia mice models by suppressing p53 activation and cytochrome C levels to mitigate apoptosis. The observed TGF-ß decrease, downstream Smad expression reduction, and antioxidant capacity preservation following HBOT may contribute to these effects.

Assessment of the Effects of Sodium Nitroprusside Administered Via Intracranial Subdural Catheters on the Cerebral Blood Flow and Lactate Using Dynamic Susceptibility Contrast Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy in a Pig Cardiac Arrest Model.

Background Cerebral blood flow (CBF) is impaired in the early phase after return of spontaneous circulation. Sodium nitroprusside (SNP) administration via intracranial subdural catheters improves cerebral cortical microcirculation. We determined whether the SNP treatment improves CBF in the subcortical tissue and evaluated the effects of this treatment on cerebral lactate. Methods and Results Sixty minutes after return of spontaneous circulation following 14 minutes of untreated cardiac arrest, 14 minipigs randomly received 4 mg SNP or saline via intracranial subdural catheters. CBF was measured in regions of interest within the cerebrum and thalamus using dynamic susceptibility contrast-magnetic resonance imaging. After return of spontaneous circulation, CBF was expressed as a percentage of the baseline value. In the saline group, the %CBF in the regions of interest within the cerebrum remained at approximately 50% until 3.5 hours after return of spontaneous circulation, whereas %CBF in the thalamic regions of interest recovered to approximately 73% at this time point. The percentages of the baseline values in the cortical gray matter and subcortical white matter were higher in the SNP group (group effect P=0.026 and 0.025, respectively) but not in the thalamus. The cerebral lactate/creatine ratio measured using magnetic resonance spectroscopy increased over time in the saline group but not in the SNP group (group-time interaction P=0.035). The thalamic lactate/creatine ratio was similar in the 2 groups. Conclusions SNP administered via intracranial subdural catheters improved CBF not only in the cortical gray matter but also in the subcortical white matter. The CBF improvement by SNP was accompanied by a decrease in cerebral lactate.

Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model.

Background Postischemic cerebral hypoperfusion has been indicated as an important contributing factor to secondary cerebral injury after cardiac arrest. We evaluated the effects of sodium nitroprusside administered via a subdural intracranial catheter on the microcirculation, oxygenation, and electrocortical activity of the cerebral cortex in the early postresuscitation period using a pig model of cardiac arrest. Methods and Results Twenty-nine pigs were resuscitated with closed cardiopulmonary resuscitation after 14 minutes of untreated ventricular fibrillation. Thirty minutes after restoration of spontaneous circulation, 24 pigs randomly received either 4 mg of sodium nitroprusside (IT-SNP group) or saline placebo (IT-saline group) via subdural intracranial catheters and were observed for 5 hours. The same dose of sodium nitroprusside was administered intravenously in another 5 pigs. Compared with the IT-saline group, the IT-SNP group had larger areas under the curve for tissue oxygen tension and percent changes of arteriole diameter and number of perfused microvessels from baseline (all P<0.05) monitored on the cerebral cortex during the 5-hour period, without severe hemodynamic instability. This group also showed faster recovery of electrocortical activity measured using amplitude-integrated electroencephalography. Repeated-measures analysis of variance revealed significant group-time interactions for these parameters. Intravenously administered sodium nitroprusside caused profound hypotension but did not appear to increase the cerebral parameters. Conclusions Sodium nitroprusside administered via a subdural intracranial catheter increased post-restoration of spontaneous circulation cerebral cortical microcirculation and oxygenation and hastened electrocortical activity recovery in a pig model of cardiac arrest. Further studies are required to determine its impact on the long-term neurologic outcomes.

Effect of Epinephrine Administered during Cardiopulmonary Resuscitation on Cerebral Oxygenation after Restoration of Spontaneous Circulation in a Swine Model with a Clinically Relevant Duration of Untreated Cardiac Arrest.

Severe neurological impairment was more prevalent in cardiac arrest survivors who were administered epinephrine than in those administered placebo in a randomized clinical trial; short-term reduction of brain tissue O2 tension (PbtO2) after epinephrine administration in swine following a short duration of untreated cardiac arrest has also been reported. We investigated the effects of epinephrine administered during cardiopulmonary resuscitation (CPR) on cerebral oxygenation after restoration of spontaneous circulation (ROSC) in a swine model with a clinically relevant duration of untreated cardiac arrest. After 7 min of ventricular fibrillation, 24 pigs randomly received either epinephrine or saline placebo during CPR. Parietal cortex measurements during 60-min post-resuscitation period showed that the area under the curve (AUC) for PbtO2 was smaller in the epinephrine group than in the placebo group during the initial 10-min period and subsequent 50-min period (both p < 0.05). The AUC for number of perfused cerebral capillaries was smaller in the epinephrine group during the initial 10-min period (p = 0.005), but not during the subsequent 50-min period. In conclusion, epinephrine administered during CPR reduced PbtO2 for longer than 10 min following ROSC in a swine model with a clinically relevant duration of untreated cardiac arrest.

Pralidoxime improves the hemodynamics and survival of rats with peritonitis-induced sepsis.

Several studies have suggested that sympathetic overstimulation causes deleterious effects in septic shock. A previous study suggested that pralidoxime exerted a pressor effect through a mechanism unrelated to the sympathetic nervous system; this effect was buffered by the vasodepressor action of pralidoxime mediated through sympathoinhibition. In this study, we explored the effects of pralidoxime on hemodynamics and survival in rats with peritonitis-induced sepsis. This study consisted of two sub-studies: survival and hemodynamic studies. In the survival study, 66 rats, which survived for 10 hours after cecal ligation and puncture (CLP), randomly received saline placebo, pralidoxime, or norepinephrine treatment and were monitored for up to 24 hours. In the hemodynamic study, 44 rats were randomly assigned to sham, CLP-saline placebo, CLP-pralidoxime, or CLP-norepinephrine groups, and hemodynamic measurements were performed using a conductance catheter placed in the left ventricle. In the survival study, 6 (27.2%), 15 (68.1%), and 5 (22.7%) animals survived the entire 24-hour monitoring period in the saline, pralidoxime, and norepinephrine groups, respectively (log-rank test P = 0.006). In the hemodynamic study, pralidoxime but not norepinephrine increased end-diastolic volume (P <0.001), stroke volume (P = 0.002), cardiac output (P = 0.003), mean arterial pressure (P = 0.041), and stroke work (P <0.001). The pressor effect of norepinephrine was short-lived, such that by 60 minutes after the initiation of norepinephrine infusion, it no longer had any significant effect on mean arterial pressure. In addition, norepinephrine significantly increased heart rate (P <0.001) and the ratio of arterial elastance to ventricular end-systolic elastance (P = 0.010), but pralidoxime did not. In conclusion, pralidoxime improved the hemodynamics and 24-hour survival rate in rats with peritonitis-induced sepsis, but norepinephrine did not.

Discrimination between the presence and absence of spontaneous circulation using smartphone seismocardiography: A preliminary investigation.

BACKGROUND: Seismocardiography measures the vibrations produced by the beating heart using an accelerometer sensor placed on the chest. We evaluated the ability of smartphone seismocardiography to distinguish between the presence and absence of spontaneous circulation. METHODS: Seismocardiography signals were obtained using a smartphone placed on the sternum in a convenience sample of 60 adult patients (30 comatose patients with spontaneous circulation and 30 deceased patients). The maximum, minimum, and standard deviation (SD) of acceleration values for head-to-foot, right-to-left, and dorsoventral axes and the three axis-root mean square (RMS) of the acceleration signals were calculated. Blinded observers (n = 156) were each asked to determine the presence or absence of spontaneous circulation based on seismocardiography video clips for each of the 60 patients. RESULTS: The seismocardiography revealed periodic large positive peaks in the patients with spontaneous circulation, which were absent in the patients without spontaneous circulation. For each of the four output measurements (three independent axes plus the three-axis RMS), the acceleration maxima and SD were significantly higher and the minima significantly lower in the patients with spontaneous circulation than in those without spontaneous circulation (all P < 0.001 except the minimum of three axis-RMS results [P = 0.009]). The observers accurately identified the seismocardiography signals from patients without spontaneous circulation, with a sensitivity of 97.6% (95% confidence interval, 97.0%-98.2%) and a specificity of 98.4% (95% confidence interval, 97.8%-99.0%). CONCLUSIONS: In conclusion, blinded observers accurately distinguished between seismocardiography signals from patients with and without spontaneous circulation.

Relationship of common hemodynamic and respiratory target parameters with brain tissue oxygen tension in the absence of hypoxemia or hypotension after cardiac arrest: A post-hoc analysis of an experimental study using a pig model.

Brain tissue oxygen tension (PbtO2)-guided care, a therapeutic strategy to treat or prevent cerebral hypoxia through modifying determinants of cerebral oxygen delivery, including arterial oxygen tension (PaO2), end-tidal carbon dioxide (ETCO2), and mean arterial pressure (MAP), has recently been introduced. Studies have reported that cerebral hypoxia occurs after cardiac arrest in the absence of hypoxemia or hypotension. To obtain preliminary information on the degree to which PbtO2 is responsive to changes in the common target variables for PbtO2-guided care in conditions without hypoxemia or hypotension, we investigated the relationships between the common target variables for PbtO2-guided care and PbtO2 using data from an experimental study in which the animals did not experience hypoxemia or hypotension after resuscitation. We retrospectively analyzed 170 sets of MAP, ETCO2, PaO2, PbtO2, and cerebral microcirculation parameters obtained during the 60-min post-resuscitation period in 10 pigs resuscitated from ventricular fibrillation cardiac arrest. PbtO2 and cerebral microcirculation parameters were measured on parietal cortices exposed through burr holes. Multiple linear mixed effect models were used to test the independent effects of each variable on PbtO2. Despite the absence of arterial hypoxemia or hypotension, seven (70%) animals experienced cerebral hypoxia (defined as PbtO2 <20 mmHg). Linear mixed effect models revealed that neither MAP nor ETCO2 were related to PbtO2. PaO2 had a significant linear relationship with PbtO2 after adjusting for significant covariates (P = 0.030), but it could explain only 17.5% of the total PbtO2 variance (semi-partial R2 = 0.175; 95% confidence interval, 0.086-0.282). In conclusion, MAP and ETCO2 were not significantly related to PbtO2 in animals without hypoxemia or hypotension during the early post-resuscitation period. PaO2 had a significant linear association with PbtO2, but its ability to explain PbtO2 variance was small.

Effects of Different Doses of Pralidoxime Administered During Cardiopulmonary Resuscitation and the Role of α-Adrenergic Receptors in Its Pressor Action.

Background We previously reported that pralidoxime facilitated restoration of spontaneous circulation by potentiating the pressor effect of epinephrine. We determined the optimal dose of pralidoxime during cardiopulmonary resuscitation and evaluated the involvement of α-adrenoceptors in its pressor action. Methods and Results Forty-four pigs randomly received 1 of 3 doses of pralidoxime (40, 80, or 120 mg/kg) or saline placebo during cardiopulmonary resuscitation, including epinephrine administration. Pralidoxime at 40 mg/kg produced the highest coronary perfusion pressure, whereas 120 mg/kg of pralidoxime produced the lowest coronary perfusion pressure. Restoration of spontaneous circulation was attained in 4 (36.4%), 11 (100%), 9 (81.8%), and 3 (27.3%) animals in the saline, 40, 80, and 120 mg/kg groups, respectively (P<0.001). In 49 rats, arterial pressure response to 40 mg/kg of pralidoxime was determined after saline, guanethidine, phenoxybenzamine, or phentolamine pretreatment, and the response to 200 mg/kg pf pralidoxime was determined after saline, propranolol, or phentolamine pretreatment. Pralidoxime at 40 mg/kg elicited a pressor response. Phenoxybenzamine completely inhibited the pressor response, but guanethidine and phentolamine did not. The pressor response of pralidoxime was even greater after guanethidine or phentolamine pretreatment. Pralidoxime at 200 mg/kg produced an initial vasodepressor response followed by a delayed pressor response. Unlike propranolol, phentolamine eliminated the initial vasodepressor response. Conclusions Pralidoxime at 40 mg/kg administered with epinephrine improved restoration of spontaneous circulation rate by increasing coronary perfusion pressure in a pig model of cardiac arrest, whereas 120 mg/kg did not improve coronary perfusion pressure or restoration of spontaneous circulation rate. The pressor effect of pralidoxime was unrelated to α-adrenoceptors and buffered by its vasodepressor action mediated by sympathoinhibition.

Ion shift index as a promising prognostic indicator in adult patients resuscitated from cardiac arrest.

BACKGROUND: Several studies reported that disturbances in cellular ion homeostasis occur following ischaemia, the magnitude of which was proportional to illness severity. The changes in serum electrolyte levels following ischaemia were minor compared with the changes in ion concentrations in the extracellular fluid. To amplify the serum electrolyte changes, we devised a new index (ion shift index), which could be calculated using commonly measured serum electrolyte levels, and explored its prognostic value in adult cardiac arrest patients. METHODS: This retrospective observational study included adult cardiac arrest survivors treated at a tertiary university hospital between January 2014 and December 2017. Using the first available serum electrolyte levels, the ion shift index was calculated as follows: ion shift index = (potassium + phosphate + magnesium) / calcium. The primary outcome was poor outcome at hospital discharge (cerebral performance categories 3-5). RESULTS: The area under the receiver operating characteristic curve (AUC) of ion shift index for predicting poor outcome was 0.878 (95% confidence interval [CI], 0.849-0.907). The AUC of ion shift index was greater than those of individual electrolytes (all p < 0.001). In multivariate analysis, higher ion shift index levels were independently associated with poor outcome (odds ratio, 2.916; 95% CI, 1.798-4.730; p < 0.001). The AUC of multivariate model including ion shift index was greater than that of multivariate model after excluding ion shift index (p = 0.007). CONCLUSIONS: Our results suggest that the ion shift index can be helpful in the early prognostication of adult cardiac arrest patients.