Giovanni Babini

Effect of mild hypercapnia on outcome and histological injury in a porcine post cardiac arrest model

AIM OF THE STUDY To evaluate in an established porcine post cardiac arrest model the effect of a mild hypercapnic ventilatory strategy on outcome. METHODS The left anterior descending coronary artery was occluded in 14 pigs and ventricular fibrillation induced and left untreated for 12 min. Cardiopulmonary resuscitation was performed for 5 min prior to defibrillation. After resuscitation, pigs were assigned to either normocapnic (end-tidal carbon dioxide (EtCO2) target: 35-40 mmHg) or hypercapnic ventilation (EtCO2 45-50 mmHg). Hemodynamics was invasively measured and EtCO2 was monitored with an infrared capnometer. Blood gas analysis, serum neuron-specific enolase (NSE) and high sensitive cardiac troponin T (hs-cTnT) were assessed. Survival and functional recovery were evaluated up to 96 h. RESULTS Twelve pigs were successfully resuscitated and eight survived up to 96 h, with animals in the hypercapnic group showing trend towards a longer survival. EtCO2 and arterial partial pressure of CO2 were higher in the hypercapnic group compared to the normocapnic one (p < 0.01), during the 4-hour intervention. Hypercapnia was associated with higher mean arterial pressure compared to normocapnia (p < 0.05). No significant differences were observed in hs-cTnT and in NSE between groups, although the values tended to be lower in the hypercapnic one. Neuronal degeneration was lesser in the frontal cortex of hypercapnic animals compared to the normocapnic ones (p < 0.05). Neurological recovery was equivalent in the two groups. CONCLUSION Mild hypercapnia after resuscitation was associated with better arterial pressure and lesser neuronal degeneration in this model. Nevertheless, no corresponding improvements in neurological recovery were observed.

Blood pressure variability, heart functionality and left ventricular tissue alterations in a protocol of severe hemorrhagic shock and resuscitation

Autonomic control of blood pressure (BP) and heart rate (HR) is crucial during bleeding and hemorrhagic shock (HS) to compensate for hypotension and hypoxia. Previous works have observed that at the point of hemodynamic decompensation a marked suppression of BP and HR variability occurs, leading to irreversible shock. We hypothesized that recovery of the autonomic control may be decisive for effective resuscitation, along with restoration of mean BP. We computed cardiovascular indexes of baroreflex sensitivity and BP and HR variability by analyzing hemodynamic recordings collected from five pigs during a protocol of severe hemorrhage and resuscitation; three pigs were sham-treated controls. Moreover, we assessed the effects of severe hemorrhage on heart functionality by integrating the hemodynamic findings with measures of plasma high-sensitivity cardiac troponin T and metabolite concentrations in left ventricular (LV) tissue. Resuscitation was performed with fluids and norepinephrine and then by reinfusion of shed blood. After first resuscitation, mean BP reached the target value, but cardiovascular indexes were not fully restored, hinting at a partial recovery of the autonomic mechanisms. Moreover, cardiac troponins were still elevated, suggesting a persistent myocardial sufferance. After blood reinfusion all the indexes returned to baseline. In the harvested heart, LV metabolic profile confirmed the acute stress condition sensed by the cardiomyocytes. Variability indexes and baroreflex trends can be valuable tools to evaluate the severity of HS, and they may represent a more useful end point for resuscitation in combination with standard measures such as mean values and biological measures. NEW & NOTEWORTHY Autonomic control of blood pressure was highly impaired during hemorrhagic shock, and it was not completely recovered after resuscitation despite global restoration of mean pressures. Moreover, a persistent myocardial sufferance emerged from measured cardiac troponin T and metabolite concentrations of left ventricular tissue. We highlight the importance of combining global mean values and biological markers with measures of variability and autonomic control for a better characterization of the effectiveness of the resuscitation strategy.

86 Haemodynamic effects of the enteral administration of tranexamic acid in an experimental model of haemorrhagic shock

Aim Systemic proteolysis has been proposed as part of the complex pathologic events occurring during haemorrhagic shock (HS). Hypoperfusion may increase permeability of the gut mucosa, promoting intestinal proteases translocation into the circulation and multiorgan failure (‘autodigestion hypothesis’).1 The interruption of this cascade of events may improve systemic perfusion and organ functions. Method The present study investigated the effects of the enteral administration of a protease inhibitor, i.e. tranexamic acid (TXA), on hemodynamics in a porcine model of controlled severe acute bleeding, fluid resuscitation and blood transfusion. Six animals underwent HS without any treatment while five animals were treated with enteral TXA. Results Baseline measurements were similar in both HS and TXA groups. Both groups showed a significant reduction in mean arterial pressure (MAP) after bleeding compared to baseline values, however at the end of the fluid resuscitation MAP was significantly higher in the TXA group (62.67±13.17 vs 92.20±22.35 mmHg, p<0.01). Echocardiographic stroke volume (SV) and left ventricle ejection fraction (LVEF) were higher in the TXA group at the end of both fluid resuscitation and blood transfusion phases (SV: 32.42±5.83 vs 45.23%±13.76% and 35.11±14.62 vs 43.68%±13.92%, p not significant; LVEF: 65.9±5.3 vs 77.8%±4.7%, p=0.05 and 61.5±8.2 vs 76.3%±4.3%, p<0.01). No significant differences were observed in mixed venous saturation (SvO2) and lactate levels, despite SvO2 remained higher in the TXA group throughout the experiment except at baseline. Conclusion In this experimental model of HS the enteral administration of TXA was associated with a global improvement in hemodynamics; however, only small benefits were observed on mixed venous saturation and lactate levels. Reference . Schmid-Schönbein GW. 2008landis award lecture. Inflammation and the autodigestion hypothesis. Microcirculation 2009;16(4):289–306. Conflict of interest None Funding None

Epinephrine for resuscitation: A century of use and decades of doubts. Let’s look to the real physiological response, now!

Despite major efforts to standardize cardiopulmonary resusitation (CPR), including dose and timing of vasopressor and nti-arrhythmic drugs, average survival rate after cardiac arrest CA) remains poor, with a large variation all over the world and with he majority of patients dying before hospital discharge due to the ost-CA syndrome. Most prominent is the impaired neurological unction caused by ischemic brain injury.1 Among the interventions to improve outcome of CA, the first is he capability to potentially reestablish some cardiac output and rgan blood flows by CPR, such to account for tissue oxygen delivry and reduce the ischemic injury to the vital organs.2 To this xtent, the concept of the “chain of survival” addresses the priorities ery well, through its four links: (1) calling for emergency medial assistance; (2) (bystander-initiated) basic life support; (3) early efibrillation; and (4) advanced life support (ALS).3 Accordingly, ithin the ALS link, an important role is played by the pharmaologic treatment, and more specifically by epinephrine, routinely dministered to augment circulation during CPR.2 Nevertheless, vidence has clearly demonstrated that the addition of the fourth ink to a system with the first 3 links of the chain of survival already ell optimized does not improve survival.4 Poor outcomes have also raised concerns on the optimal harmacologic approach during CPR.2 Indeed, there is no clincal demonstration of survival benefits from administration of pinephrine, while doubts that such a drug may worsen longerm outcome and neurological recovery have been raised over the ears.2 Primary vasopressor efficacy of epinephrine is due to its lpha-adrenergic actions. However, epinephrine also acts as potent eta-adrenergic agonist, increasing oxygen utilization and failing o improve the balance between oxygen supply/demand.5 Thereore, epinephrine might ensure increases in coronary perfusion ressures and, consequently, in return of spontaneous circulaion (ROSC), but may concurrently lead to a more severe ischemic nsult to the heart and probably to the brain.6,7 In addition, all he randomized controlled trials and observational studies as well s retrospective registry analyses and meta-analyses, agree on he association between epinephrine and higher rates of ROSC nd survival to hospital admission compared to placebo, with o difference and/or a potentially reduced likelihood of being

The Prone Position in the Treatment of Patients with ARDS: Problems and Real Utility

Prone positioning is a life-saving treatment used in ARDS patients in order to improve oxygenation and reduce lung injury due to mechanical ventilation. The beneficial effects of this procedure are the result of complex mechanisms that cooperate in improving gas exchange and in reducing global “stress” and “strain” of the lung. Prone positioning seems to be more effective in extrapulmonary form of ARDS, where the main feature of the disease is represented by compression atelectasis in dependent lung regions caused by the gain in lung weight due to pulmonary edema. To date, it is recommended in ARDS patients that maintain a PaO2/FiO2 ratio lower than 150 mmHg even after optimization of mechanical ventilation. However, only the patients who react to prone positioning with a decrease in PaCO2 show a real benefit in terms of survival rate. The relationship between improvement in gas exchange and patient outcome still remains unclear. This is not a maneuver free of complications, and it is important to balance risks and benefits associated with the procedure. An expert team is required to safely prone the patient and to reduce the incidence of adverse effects.