肾上腺素与血管加压素对窒息性心脏骤停大鼠早期心肺复苏的影响

目的：比较肾上腺素与血管加压素对室息性心脏骤停大鼠早期心肺复苏的影响。方法：健康SI）夫鼠48只,体重200～250g,雌雄产拘,将大鼠随机分成4组（n=12）：正常对照组（C组）、模型组（M组）、肾上腺素组（E组）和血管加雎素组（V组）。M组、E组及V绀大鼠均经气管夹闭1min,建立窒息性心脏骤停模型。肖窒息时间达1min时,分别在常规心肺复苏前：c组和M组大鼠经股静脉注射生理盐水1m1。E组及V纰大鼠经股静脉分别注射肾上腺素0．04mg／kg及血管加压素0．4u／kg,H时开始胸外心脏按压及机械通气,观察自主循环恢复情况,5min无效则放弃复苏。自主循环恢复的大鼠连续监测心电和血压30min。记录在CPR30min内自主循环恢复情况及血流动力学;记录CPR30rain后,采用免疫组织化学法检测各组实验大鼠血清中肿瘤坏死因子-水平、白细胞介素6及白细胞介素10水平。结果：E、V组大鼠自主循环恢复率均显著高于M组（分别为73．4％．74．6％,和15．3％,P〈0．05）．E组大鼠自主循环恢复牢与V组比较差异无统计学意义（P〉0．05）;E、V组大鼠平均动脉压明显高于M绀大鼠（P〈0．05）,V组大鼠MAP高于E组大鼠。差异有统计学意义（P〈0．05）。M组大鼠血清中自细胞介素6及肿瘤坏死因子-水平与E、V组差异有统计学意义（P〈0．05）;E组大鼠m清中肿瘤坏死阔子-及白细胞介素-6水平高于V组（P〈0．05）。E组大鼠血清中白细胞介素-10水平低于V组（P〈0．05）。结论：肾卜腺素与血管加压素在窒息性心脏骤停大鼠早期心肺复苏过程中复苏成功牢无明显差异,但血管加乐素町维持大鼠复苏后平均动脉搓在相对较高水平;同时血管加压素可提高复苏后大鼠血清中抗炎因子水平。     

Brain tissue oxygen pressure and cerebral metabolism in an animal model of cardiac arrest and cardiopulmonary resuscitation

OBJECTIVE: Direct measurement of brain tissue oxygenation (PbtO2) is established during spontaneous circulation, but values of PbtO2 during and after cardiopulmonary resuscitation (CPR) are unknown. The purpose of this study was to investigate: (1) the time-course of PbtO2 in an established model of CPR, and (2) the changes of cerebral venous lactate and S-100B. METHODS: In 12 pigs (12-16 weeks, 35-45 kg), ventricular fibrillation (VF) was induced electrically during general anaesthesia. After 4 min of untreated VF, all animals were subjected to CPR (chest compression rate 100/min, FiO2 1.0) with vasopressor therapy after 7, 12, and 17 min (vasopressin 0.4, 0.4, and 0.8 U/kg, respectively). Defibrillation was performed after 22 min of cardiac arrest. After return of spontaneous circulation (ROSC), the pigs were observed for 1h. RESULTS: After initiation of VF, PbtO2 decreased compared to baseline (mean +/- SEM; 22 +/- 6 versus 2 +/- 1 mmHg after 4 min of VF; P < 0.05). During CPR, PbtO2 increased, and reached maximum values 8 min after start of CPR (25 +/- 7 mmHg; P < 0.05 versus no-flow). No further changes were seen until ROSC. Lactate, and S-100B increased during CPR compared to baseline (16 +/- 2 versus 85 +/- 8 mg/dl, and 0.46 +/- 0.05 versus 2.12 +/- 0.40 microg/l after 13 min of CPR, respectively; P < 0.001); lactate remained elevated, while S-100B returned to baseline after ROSC. CONCLUSIONS: Though PbtO2 returned to pre-arrest values during CPR, PbtO2 and cerebral lactate were lower than during post-arrest reperfusion with 100% oxygen, which reflected the cerebral low-flow state during CPR. The transient increase of S-100B may indicate a disturbance of the blood-brain-barrier.     

Perfluorocarbon induced intra-arrest hypothermia does not improve survival in a swine model of asphyxial cardiac arrest

Background

Pulseless electrical activity is an important cause of cardiac arrest. Our purpose was to determine if induction of hypothermia with a cold perfluorocarbon-based total liquid ventilation (TLV) system would improve resuscitation success in a swine model of asphyxial cardiac arrest/PEA.

Methods

Twenty swine were randomly assigned to control (C, no ventilation, n = 11) or TLV with pre-cooled PFC (n = 9) groups. Asphyxia was induced by insertion of a stopper into the endotracheal tube, and continued in both groups until loss of aortic pulsations (LOAP) was reached, defined as a pulse pressure less than 2 mmHg. The TLV animals underwent asphyxial arrest for an additional 2 min after LOAP, followed by 3 min of hypothermia, prior to starting CPR. The C animals underwent 5 min of asphyxia beyond LOAP. Both groups then underwent CPR for at least 10 min. The endpoint was the resumption of spontaneous circulation maintained for 10 min.

Results

Seven of 9 animals achieved resumption of spontaneous circulation (ROSC) in the TLV group vs. 5 of 11 in the C group (p = 0.2). The mean pulmonary arterial temperature was lower in total liquid ventilation animals starting 4 min after induction of hypothermia (TLV 36.3 ± 0.2 °C vs. C 38.1 ± 0.2 °C, p < 0.0001). Arterial pO₂ was higher in total liquid ventilation animals at 2.5 min of CPR (TLV 76 ± 12 mmHg vs. C 44 ± 2 mmHg; p = 0.03).

Conclusion

Induction of moderate hypothermia using perfluorocarbon-based total liquid ventilation did not improve ROSC success in this model of asphyxial cardiac arrest.     

3:1 Compression to ventilation ratio versus continuous chest compression with asynchronous ventilation in a porcine model of neonatal resuscitation

Objective

In contrast to the resuscitation guidelines of children and adults, guidelines on neonatal resuscitation recommend synchronized 90 chest compressions with 30 manual inflations (3:1) per minute in newborn infants. The study aimed to determine if chest compression with asynchronous ventilation improves the recovery of bradycardic asphyxiated newborn piglets compared to 3:1 Compression:Ventilation cardiopulmonary resuscitation (CPR).

Intervention and measurements

Term newborn piglets (n = 8/group) were anesthetized, intubated, instrumented and exposed to 45-min normocapnic hypoxia followed by asphyxia. Protocolized resuscitation was initiated when heart rate decreased to 25% of baseline. Piglets were randomized to receive resuscitation with either 3:1 compressions to ventilations (3:1 C:V CPR group) or chest compressions with asynchronous ventilations (CCaV) or sham. Continuous respiratory parameters (Respironics NM3^®), cardiac output, mean systemic and pulmonary artery pressures, and regional blood flows were measured.

Main results

Piglets in 3:1 C:V CPR and CCaV CPR groups had similar time to return of spontaneous circulation, survival rates, hemodynamic and respiratory parameters during CPR. The systemic and regional hemodynamic recovery in the subsequent 4 h was similar in both groups and significantly lower compared to sham-operated piglets.

Conclusion

Newborn piglets resuscitated by CCaV had similar return of spontaneous circulation, survival, and hemodynamic recovery compared to those piglets resuscitated by 3:1 Compression:Ventilation ratio.     

Pulmonary arterial thermodilution, femoral arterial thermodilution and bioreactance cardiac output monitoring in a pediatric hemorrhagic hypovolemic shock model

Aim

Bioreactance is a new non-invasive method for cardiac output measurement (NICOM). There are no studies that have analysed the utility of this technique in a pediatric animal model of hemorrhagic shock.

Methods

A prospective study was performed using 9 immature Maryland pigs weighing 9 to 12 kg was performed. A Swan-Ganz catheter, a PiCCO catheter and 4 dual surface electrodes were placed at the four corners of the anterior thoracic body surface. Shock was induced by withdrawing a blood volume of 30 mL/kg, and then after, 30 mL/kg of Normal saline was administered. Seven simultaneous measurements of cardiac index (CI) were made by pulmonary artery thermodilution (PATD), Femoral artery thermodilution (FATD), and NICOM before, during, and after hypovolaemia and during and after volume expansion.

Results

The mean difference (bias) of differences (limits of agreement) between PATD and FATD was 0.84 (−1.87-3.51) L/min/1.77 m², between PATD and NICOM was 1.95 (−1.79-5.69) L/min/1.77 m², and between FATD and NICOM was 1.06 (−1.40-3.52) L/min/1.77 m². A moderate correlation was found between PATD and FATD (r = 0.43; P = 0.01), but no correlation was found between bioreactance and either PATD or FATD. Hypovolemia and volume expansion produced important significant differences in CI as measured by PATD and FATD, while the changes with bioreactance were small and non significant.

Conclusions

PATD and FATD measurements showed similar responses to hypovolemic shock and volume expansion. Bioreactance persistently underestimates the CI and is not significantly altered by either inducing hemorrhagic shock, or later, through volume expansion. Bioreactance is not a suitable method for monitoring the CI in pediatric hemorrhagic shock.     

Fluid therapy and acute kidney injury in cardiogenic shock after cardiac arrest

Aim of the study

It has recently been suggested that acute kidney injury (AKI) may strongly be influenced by post-resuscitation disease and cardiogenic shock (CS), and may not just be a consequence of cardiac arrest and time without spontaneous circulation. AKI also has been suggested as a strong independent predictor of in-hospital mortality. Therefore the present study aimed at investigating the effect of fluid management on the incidence of AKI in patients with cardiogenic shock after cardiac arrest treated by mild therapeutic hypothermia.

Methods

Fluid therapy and the incidence of acute kidney injury (AKI) was retrospectively reviewed in 51 patients with cardiogenic shock after cardiac arrest comparing patients with and without hemodynamic (PPV, SVV) and volumetric (ELWI, GEDI) monitoring.

Results

There was no significant difference in baseline or cardiac arrest characteristics between hemodynamic monitored patients and conventional monitored patients. 28 patients were monitored by standard monitoring, in 23 patients monitoring was complemented by a PICCO system. In the first 24 h of treatment the total amount of fluid was significantly higher in patients under PICCO monitoring compared to conventional monitoring (4375 ± 1285 ml vs. 5449 ± 1438 ml, p = 0.007). This was associated with a significant reduction in the incidence of AKI (RIFLE ‘I’/‘F’: PICCO-group: 1 (4.3%) vs. conventional group 8 (28.6%), p = 0.03).

Conclusion

The presented data suggest that volume therapy guided by volumetric (ELWI, GEDI) and arterial waveform derived variables (PPV, SVV) can reduce the incidence of AKI in patients with cardiogenic shock after cardiac arrest treated with mild therapeutic hypothermia.     

Extended series of cardiac compressions during CPR in a swine model of perinatal asphyxia

Background

The rationale for a compression to ventilation ratio of 3:1 in neonates with primary hypoxic, hypercapnic cardiac arrest is to emphasize the importance of ventilation; however, there are no published studies testing this approach against alternative methods. An extended series of cardiac compressions offers the theoretical advantage of improving coronary perfusion pressures and hence, we aimed to explore the impact of compression cycles of two different durations.

Materials and methods

Newborn swine (n = 32, age 12-36 h, weight 2.0-2.7 kg) were progressively asphyxiated until asystole occurred. Animals were randomized to receive compressions:ventilations 3:1 (n = 16) or 9:3 (n = 16). Return of spontaneous circulation (ROSC) was defined as a heart rate ≥100 beats min⁻¹.

Results

All animals except one in the 9:3 group achieved ROSC. One animal in the 3:1 group suffered bradycardia at baseline, and was excluded, leaving us with 15 animals in each group surviving to completion of protocol. Time to ROSC (median and interquartile range) was 150 s (115-180) vs. 148 s (116-195) for 3:1 and 9:3, respectively (P = 0.74). There were no differences in diastolic blood pressure during compression cycles or in markers of hypoxia and inflammation. The temporal changes in mean arterial blood pressure, heart rate, arterial blood gas parameters, and systemic and regional oxygen saturation were comparable between groups.

Conclusion

Neonatal pigs with asphyxia-induced cardiac arrest did not respond to a compression:ventilation ratio of 9:3 better than to 3:1. Future research should address if alternative compression:ventilation ratios offer advantages over the current gold standard of 3:1.     

The incidence and significance of bacteremia in out of hospital cardiac arrest

Background

The most common etiology of cardiac arrest is presumed of myocardial origin. Recent retrospective studies indicate that preexisting pneumonia, a form of sepsis, is frequent in patients who decompensate with abrupt cardiac arrest without preceding signs of septic shock, respiratory failure or severe metabolic disorders shortly after hospitalization. The contribution of pre-existing infection on pre and post cardiac arrest events remains unknown and has not been studied in a prospective fashion. We sought to examine the incidence of pre-existing infection in out-of hospital cardiac arrest (OHCA) and assess characteristics associated with bacteremia, the goal standard for presence of infection.

Methods and results

We prospectively observed 250 OHCA adult patients who presented to the Emergency Department (ED) between 2007 and 2009 to an urban academic teaching institution. Bacteremia was defined as one positive blood culture with non-skin flora bacteria or two positive blood cultures with skin flora bacteria. 77 met pre-defined exclusion criteria. Of the 173 OHCA adults, 65 (38%) were found to be bacteremic with asystole and PEA as the most common presenting rhythms. Mortality in the ED was significantly higher in bacteremic OHCA (75.4%) compared to non-bacteremic OHCA (60.2%, p < 0.05). After adjustment for potential confounders, predictive factors associated with bacteremic OHCA were lower initial arterial pH, higher lactate, WBC, BUN and creatinine.

Conclusions

Over one-third of OHCA adults were bacteremic upon presentation. These patients have greater hemodynamic instability and significantly increased short-term mortality. Further studies are warranted to address the epidemiology of infection as possible cause of cardiac arrest.     

Effects of cerebral hypoperfusion on bispectral index: A randomised, controlled animal experiment during haemorrhagic shock

Background

The aim of this porcine haemorrhagic shock model was to investigate the changes of bispectral index (BIS) after slow and fast recovery of cerebral perfusion, and its correlation with plasma propofol concentrations.

Methods

After Animal Investigational Committee approval, 16 pigs during propofol anaesthesia underwent a liver trauma with severe hypotension, and were randomly assigned to receive therapy for either slow recovery (fluid resuscitation; slow group; n = 8) or fast recovery of cerebral perfusion (vasopressor combined with hypertonic-saline-starch; fast group; n = 8), respectively. Cerebral perfusion pressure (CPP = MAP − ICP), cerebral tissue oxygenation index (TOI), BIS, and plasma concentrations of propofol and haemoglobin were measured at baseline (Pre-shock), haemodynamic decompensation (Shock), and 5 (Therapy) and 30 min (End) after therapy, respectively.

Results

CPP, TOI, and BIS decreased significantly during shock (pre-shock vs. shock, fast: CPP: 65 ± 14 vs. 15 ± 4 mm Hg; TOI: 64 ± 6 vs. 47 ± 7%; BIS 60 ± 5 vs. 9 ± 10; slow: CPP: 60 ± 12 vs. 13 ± 7 mm Hg; TOI: 68 ± 7 vs. 49 ± 7%; BIS 63 ± 5 vs. 13 ± 12; P < 0.05). In the fast group, CPP, TOI, and BIS increased after therapy compared to the slow group (Therapy, fast: CPP: 47 ± 15 mm Hg, TOI: 61 ± 7%, BIS: 47 ± 21; slow: CPP: 18 ± 9 mm Hg, TOI: 51 ± 5%, BIS: 21 ± 19; P < 0.05). Propofol and haemoglobin concentrations were comparable between groups throughout the resuscitation phase.

Conclusions

In a haemorrhagic shock scenario, therapies with different impact on cerebral perfusion resulted in differing changes of BIS values, while plasma propofol and haemoglobin concentrations were comparable during the resuscitation phase; this suggests that BIS may also have reflected changes of cerebral perfusion.     

Levosimendan improves postresuscitation outcomes in a rat model of CPR

In this study we sought to determine whether a calcium sensitizer, levosimendan, would have a more favorable effect on postresuscitation myocardial function and, consequently, postresuscitation survival than beta-adrenergic dobutamine. The extreme decrease in survival before hospital discharge of resuscitated victims is attributed, in part, to postresuscitation myocardial failure, and dobutamine has been recommended for the management of postresuscitation myocardial failure. We studied a total of 15 animals. Ventricular fibrillation was induced in Sprague-Dawley rats weighing 450 to 550 g. Cardiopulmonary resuscitation (CPR), including chest compressions and mechanical ventilation, was begun after 8 minutes of untreated cardiac arrest. Electrical defibrillation was attempted after 6 minutes of CPR. Each animal was resuscitated. Animals were randomized to undergo treatment with levosimendan, dobutamine, or saline-solution placebo. These agents were administered 10 minutes after the return of spontaneous circulation. Levosimendan was administered in a loading dose of 12 microg kg(-1) over a 10-minute period, followed by infusion of 0.3 microg kg(-1) min(-1) over the next 230 minutes. Dobutamine was continuously infused at a dosage of 3 microg kg(-1) min(-1). Saline-solution placebo was administered in the same volume and over the same amount of time as levosimendan. Levosimendan and dobutamine produced comparable increases in cardiac output and rate of left-ventricular pressure increase. However, administration of levosimendan resulted in lower heart rates and lesser increases in left ventricular diastolic pressure compared with both dobutamine and placebo. The duration of postresuscitation survival was significantly greater with levosimendan (16 +/- 2 hours), intermediate with dobutamine (11 +/- 2 hours) and least with saline-solution placebo (8 +/- 1 hour). Levosimendan and dobutamine both improved postresuscitation myocardial function. However, levosimendan produced more favorable postresuscitation myocardial function and increased the duration of postresuscitation survival.     

Early adrenaline administration does not improve circulatory recovery during resuscitation from severe asphyxia in newborn piglets

Aim of the study

To investigate the effects of early intravenous adrenaline administration on circulatory recovery, cerebral reoxygenation, and plasma catecholamine concentrations, after severe asphyxia-induced bradycardia and hypotension.

Methods

One-day-old piglets were left in apnoea until heart rate and mean arterial pressure were less than 50 min⁻¹ and 25 mmHg, respectively. They randomly received adrenaline, 10 μg kg⁻¹ (n = 16) or placebo (n = 15) and were resuscitated with air ventilation and, when needed, closed-chest cardiac massage (CCCM). Eight not asphyxiated animals served as time controls.

Results

CCCM was required in 13 piglets given adrenaline and in 13 given placebo. Time to return of spontaneous circulation was: 72 (66–85) s vs. 77 (64–178) s [median (quartile range)] (p = 0.35). Time until cerebral regional oxygen saturation (CrSO₂) had increased to 30% was 86 (79–152) s vs. 126 (88–309) s (p = 0.30). The two groups did not differ significantly in CrSO₂, heart rate, arterial pressure, right common carotid artery blood flow, or number of survivors: 13 vs. 11 animals. Plasma concentration of adrenaline, 2.5 min after resuming ventilation, was 498 (268–868) nmol l⁻¹vs. 114 (80–306) nmol l⁻¹ (p = 0.01). Corresponding noradrenaline concentrations were 1799 (1058–4182) nmol l⁻¹vs. 1385 (696–3118) nmol l⁻¹ (ns). In the time controls, the concentrations were 0.4 (0.2–0.6) nmol l⁻¹ of adrenaline and 1.8 (1.3–2.4) nmol l⁻¹ of noradrenaline.

Conclusion

The high endogenous catecholamine levels, especially those of noradrenaline, may explain why early administered adrenaline did not significantly improve resuscitation outcome.     

Effects of recombinant-hemoglobin solutions rHb2.0 and rHb1.1 on blood pressure, intestinal blood flow, and gut oxygenation in a rat model of hemorrhagic shock

The vasoconstriction induced by hemoglobin-based oxygen carriers (HBOCs), mainly a result of nitric oxide (NO) scavenging, until now has limited the application of HBOCs as resuscitation fluids. In this study, we tested the hypothesis that the new modified recombinant-hemoglobin solution rHb2.0, with a 20 to 30 times lesser NO-scavenging rate, would minimize vasoconstriction without adverse effects on microvascular oxygenation. Responses were compared with those to rHb1.1, a recombinant-hemoglobin solution with a wild-type NO-scavenging rate, as well as an oncotically matched albumin solution. In a fixed-pressure (40 mm Hg) rat model of hemorrhagic shock and resuscitation, rHb2.0 and albumin both restored mean arterial pressure (MAP) to baseline values, whereas rHb1.1 increased MAP to 27% above the baseline value. Mesenteric vascular resistance after resuscitation with rHb2.0 was 57% less than that with rHb1.1. rHb2.0 was found to have 55% greater intestinal oxygen delivery (Do2int ) and resulted in a 27% lower oxygen-extraction rate than did rHb1.1 after resuscitation. Intestinal microvascular Po2 , determined on the basis of oxygen-dependent quenching of palladium-porphyrin phosphorescence, revealed no difference between rHb2.0 and rHb1.1. The findings of this study confirm that the well-known pressure effect of HBOCs is caused by their effect on the NO-scavenging rate; recombinant modification of this rate did not increase MAP during resuscitation compared with baseline values. Although systemic vasoconstriction was absent, intestinal vasoconstriction almost negligible, and Do2int greater after resuscitation with rHb2.0, the effect of rHb2.0 on pH, base-excess and microvascular Po2 levels after resuscitation were comparable to those achieved with the use of the albumin solution.     

The neuroprotective effects of intraperitoneal injection of hydrogen in rabbits with cardiac arrest

Objective

The purpose of this study was to investigate the neuroprotective effects of intraperitoneal injection of hydrogen (H₂) in rabbits with cardiac arrest (CA).

Methods

A rabbit model of CA was established by the delivery of alternating current between the esophagus and chest wall to induce ventricular fibrillation. Before CA, the animals were randomly divided into four groups: a sham group (no CA), a CA group, a CA + low dose (10 ml/kg) H₂ group (CA + H₂ group 1), and a CA + high dose (20 ml/kg) H₂ group (CA + H₂ group 2). In the first experiment, animals were observed for 72 h after the restoration of spontaneous circulation (ROSC). The neurological scores were assessed at 24, 48 and 72 h after ROSC. The rabbits that survived until 72 h were sacrificed using an overdose of anesthetic, and the brain tissues were collected and Nissl-stained to observe nerve cell damage in the hippocampal CA1 area. In addition, TUNEL assay was performed to detect apoptosis. In the second experiment, animals were observed for 6 h after ROSC. Blood samples and brain hippocampal tissues were collected, and differences in oxidative stress indicators were compared among the four groups.

Results

Intraperitoneal injection of H₂ improved the 72-h survival rate and neurological scores, reduced neuronal injury and inhibited neuronal apoptosis. Intraperitoneal injection of H₂ reduced oxidative stress indicators in the plasma and hippocampal tissues and enhanced antioxidant enzyme activity. No significant difference was observed between the two CA groups treated with different doses of H₂.

Conclusions

Intraperitoneal injection of H₂ is a novel hydrogen administration method and can reduce cerebral ischemia-reperfusion injury and improve the prognosis of cardiopulmonary cerebral resuscitation in a rabbit model of CA.