Outcome after resuscitation using controlled rapid extracorporeal cooling to a brain temperature of 30 °C, 24 °C and 18 °C during cardiac arrest in pigs

Aim of the study

To identify the optimal level of hypothermia during cardiac arrest, just prior to resuscitation with an extracorporeal cooling system and without fluid overload, for neurological outcome at day 9 in pigs.

Methods

In a prospective randomised laboratory investigation, 24 female Large White pigs (31-38 kg) underwent ventricular-fibrillation cardiac arrest for 15 min, followed by 1 min, 3 min or 5 min (n = 8 per group) of 4 °C cooling with an extracorporeal cooling system via an aortic balloon catheter and resuscitation with cardiopulmonary bypass. Sixty minutes following induction of cardiac arrest, defibrillation attempts were started. Mild hypothermia (34.5 °C) and intensive care were continued for 20 h and final outcome was evaluated after 9 days.

Results

Brain temperature decreased from 38.5 °C to 30.4 ± 1.6 °C within 221 ± 81 s in the 1-min group; to 24.2 ± 4.6 °C within 375 ± 127 s in the 3-min group; and to 18.8 ± 4.0 °C within 450 ± 121 s in the 5-min group. Restoration of spontaneous circulation was achieved in seven (1-min group), six (3-min group) and six (5-min group) animals (p = 0.78), whereas survival to 9 days was only achieved in six, three and three animals in each group (p = 0.22), respectively.

Conclusions

An extracorporeal cooling system rapidly induced brain hypothermia following prolonged normovolaemic cardiac arrest in pigs. Difference in outcome was not statistically significant amongst the three groups with various levels of hypothermia (30 °C, 24 °C and 18 °C) during cardiac arrest prior to resuscitation; however, the animals with the least temperature reduction showed a trend to better survival at 9 days. Further studies are necessary to investigate optimised methods for induction, as well as level, of cerebral hypothermia.     

Rapid cooling of the heart with total liquid ventilation prevents transmural myocardial infarction following prolonged ischemia in rabbits

Study aim

Total liquid ventilation (TLV) with cooled perfluorocarbons has been demonstrated to induce an ultrafast cardioprotective cooling in rabbits. However, it remains unknown whether this technically challenging strategy would be actually more potent than a conventional external cooling after a prolonged ischemia inducing transmural myocardial infarction.

Methods

Anesthetized rabbits were randomly submitted to 60 min of coronary artery occlusion (CAO) under normothermic conditions (Control group, n = 7) or with cooling started at the 5th min of CAO (target left atrial temperature: 32 °C). Cooling procedures were either external cooling using cold blankets (EC group, n = 7) or ultrafast cooling initiated by 20 min of TLV (TLV group, n = 6). An additional group underwent a similar ultrafast cooling protocol started at the 20th min of CAO (TLV_delayed group, n = 6). After reperfusion, all hypothermic animals were rewarmed and infarct size was assessed after 4 h.

Results

In the EC group, the target temperature was reached only at 60 min of CAO whereas this time-interval was dramatically reduced to 15 and 25 min of CAO in TLV and TLV_delayed, respectively. Infarct sizes were significantly reduced in TLV and TLV_delayed but not in EC groups as compared to Control (45 ± 18%, 58 ± 5%, 78 ± 10% and 82 ± 7% of the risk zone, respectively). Similar significant differences were observed for the sizes of the no-reflow zones (15 ± 9%, 23 ± 8%, 49 ± 11% and 58 ± 13% of the risk zone, respectively).

Conclusion

Cooling induced by TLV afforded a potent cardioprotection and prevented transmural infarction following prolonged and severe ischemia, even when started later than a surface cooling in rabbits.     

Intra-arrest selective brain cooling improves success of resuscitation in a porcine model of prolonged cardiac arrest

Aims of study

We have previously demonstrated that early intra-nasal cooling improved post-resuscitation neurological outcomes. The present study utilizing a porcine model of prolonged cardiac arrest investigated the effects of intra-nasal cooling initiated at the start of cardiopulmonary resuscitation (CPR) on resuscitation success. Our hypothesis was that rapid nasal cooling initiated during “low-flow” improves return of spontaneous resuscitation (ROSC).

Methods

In 16 domestic male pigs weighing 40 ± 3 kg, VF was electrically induced and untreated for 15 min. Animals were randomized to either head cooling or control. CPR was initiated and continued for 5 min before defibrillation was attempted. Coincident with starting CPR, the hypothermic group was cooled with a RhinoChill™ device which produces evaporative cooling in the nasal cavity of pigs. No cooling was administrated to control animals. If ROSC was not achieved after defibrillation, CPR was resumed for 1 min prior to the next defibrillation attempt until either successful resuscitation or for a total of 15 min.

Main results

Seven of eight animals in the hypothermic group (87.5%) and two of eight animals in control group (25%) (p = 0.04) were successfully resuscitated. At ROSC, brain temperature was increased from baseline by 0.3 °C in the control group, and decreased by 0.1 °C in the hypothermic animals. Pulmonary artery temperature was above baseline in both groups.

Conclusion

Intra-nasal cooling initiated at the start of CPR significantly improves the success of resuscitation in a porcine model of prolonged cardiac arrest. This may have occurred by preventing brain hyperthermia.     

Effects of ankle joint mobilizations in adults poststroke: a pilot study

Kluding PM, Santos M. Effects of ankle joint mobilizations in adults poststroke: a pilot study.

Objective

To compare the effect of 2 interventions on ankle mobility, ankle kinematics, and weight-bearing symmetry during functional activities in subjects with hemiparesis after a stroke.

Design

Randomized trial.

Setting

Academic medical center.

Participants

A convenience sample of 16 subjects with hemiparesis after stroke (mean age, 55.2y; mean time since stroke, 21.4mo).

Intervention

Subjects received 8 sessions over 4 weeks of either functional task practice combined with ankle joint mobilizations, or functional task practice only.

Main Outcome Measures

Changes in ankle range of motion (ROM) (not blinded), ankle kinematics during sit-to-stand (STS) and gait, and lower-extremity weight-bearing symmetry during STS and static standing.

Results

The combined intervention group gained 5.7°±3.1° in passive ankle ROM compared with 0.2°±2.6° in the functional practice only group (95% confidence interval [CI], 2.5-8.6; P<.01). No significant changes in ankle kinematics or weight bearing during static standing were noted in either group. The functional practice group decreased differences in weight bearing during STS by 9.5%±6.47%, whereas the combined intervention group increased this difference by 3.37%±5.29% (95% CI, 3.26-19.46; P=.01).

Conclusions

The increase in ankle motion did not improve joint kinematics and may have prevented improvement in weight-bearing symmetry.     

Comparison of non-calibrated pulse-contour analysis with continuous thermodilution for cardiac output assessment in patients with induced hypothermia after cardiac arrest

Aim

Induced mild hypothermia after cardiac arrest interferes with clinical assessment of the cardiovascular status of patients. In this situation, non-invasive cardiac output measurement could be useful. Unfortunately, arterial pulse contour is altered by temperature, and the performance of devices using arterial blood pressure contour analysis to derive cardiac output may be insufficient.

Methods

Mild hypothermia (32-34 °C) was induced in eight patients after out-of-hospital cardiac arrest and successful resuscitation. Cardiac output (CO) was measured simultaneously by continuous thermodilution using a pulmonary artery catheter and a cardiac output monitor (Vigilance II, Edwards Lifesciences) and by pulse contour analysis using an arterial line and the Vigileo monitor (Edwards Lifesciences) during both normothermia (>36 °C) and hypothermia. Continuous CO from both monitors was compared (Bland-Altman) and concordance of changes measured in consecutive 8-min intervals was measured.

Results

Mean cardiac output was 3.9 ± 1.2 l/min during hypothermia and 6.1 ± 2.6 l/min during normothermia (p < 0.001). During hypothermia (normothermia), bias was 0.23 (0.77) l/min, precision (1 SD) was 0.6 (0.72) l/min, and the limits of agreement were −1.06 to 1.51 (−0.64 to 2.18) l/min, corresponding to a percentage error of ±34% (±24%). Concordance of directional CO changes >10% was 53.9% in hypothermia and 51.4% in normothermia.

Conclusion

Induced hypothermia was not associated with increased bias or limits of agreement for the comparison of Vigileo and continuous thermodilution, but percentage error was high during normothermia and increased further during hypothermia. Less than 50% of clinically relevant CO changes during hypothermia were concordant.     

Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest

Background

The platelet inhibitor clopidogrel is administered to patients treated with therapeutic hypothermia following cardiac arrest due to acute coronary syndromes. Interactions with proton pump inhibitors and genetics are factors with a known potential to attenuate the platelet inhibition of clopidogrel. In patients treated with therapeutic hypothermia, reduced gastrointestinal function and hypothermia may also reduce the effect of clopidogrel. To investigate the net platelet inhibition of clopidogrel, we have measured the platelet reactivity index in patients treated with therapeutic hypothermia.

Methods and results

Twenty-five Caucasian patients treated with clopidogrel and therapeutic hypothermia were prospectively included. Therapeutic hypothermia was defined as 33-34 °C and delivered for 24 h. Clopidogrel loading doses (300-600 mg) were administered enterally the day of admission and followed by 75 mg daily. Blood samples were collected on day 1 (n = 25) and day 3 (n = 16). The samples were analysed for inhibition by clopidogrel with a vasodilator stimulated phosphoprotein phosphorylation kit. On day 1 and day 3, platelet reactivity index was 0.77 ± 0.09 and 0.57 ± 0.16, respectively. The number of patients with a satisfactory antiplatelet effect (defined as platelet reactivity index <0.5) were 0 (0%) and 5 (31%), respectively.

Conclusion

In patients treated with therapeutic hypothermia after cardiac arrest, the effect of clopidogrel on platelets was virtually nonexistent on day 1 after administration, with some improvement on day 3.     

Facilitation of hypothermia by quinpirole and 8-OH-DPAT in a rat model of cardiac arrest

Aim of the study

Therapeutic hypothermia improves outcome after cardiac arrest. Dopamine D₂ agonists and serotonin 5-HT_1A agonists lower body temperature by decreasing the set-point. We investigated the effect of these drugs on temperature and cerebral recovery of rats after cardiac arrest.

Methods

Male Wistar-Han rats were subjected to 6 min of cardiac arrest due to ventricular fibrillation. Following restoration of circulation, 1 mg quinpirole, 1 mg 8-OH-DPAT or vehicle were injected subcutaneously. Body temperature was monitored for 48 h. One additional group was kept normothermic. Animals were neurologically tested by a tape removal test. After 7 days, histology of hippocampal CA-1 sector was analysed with Nissl and TUNEL staining.

Results

Rats became spontaneously hypothermic after cardiac arrest. Induction of hypothermia was facilitated by both quinpirole (−0.033 ± 0.008 °C/min) and 8-OH-DPAT (−0.029 ± 0.010 °C/min) when compared to vehicle (−0.020 ± 0.005 °C/min). Total ‘dose’ of hypothermia (area under the curve) was not different. All animals showed a neurological deficit, which improved with time; after 7 days, test results of the normothermic group (30 [11-88] s) still tended to be worse than those of the hypothermic groups (vehicle 8 [6-14] s, quinpirole 9 [4-17] s, 8-OH-DPAT 10 [8-22] s). There were no clear differences in Nissl or TUNEL histology after 7 days.

Conclusion

Both quinpirole and 8-OH-DPAT led to faster induction of hypothermia. However, the outcome was not different from spontaneous hypothermia, probably because the total ‘dose’ of hypothermia was not influenced.     

Therapeutic hypothermia after cardiac arrest - cerebral perfusion and metabolism during upper and lower threshold normocapnia

Background

During cardiac arrest and after successful resuscitation a continuum of ischaemia-reperfusion injury develops. Mild hypothermia exerts protective effects in the postresuscitation phase but also alters CO₂ production and solubility, which may lead to deleterious effects if overlooked when adjusting the ventilation of the resuscitated patient. Using a multimodality approach, the effects of different carbaemic states on cerebral perfusion and metabolism were evaluated during therapeutic hypothermia.

Methods

Eight comatose survivors of prehospital cardiac arrest were cooled to 33 °C for 24 h and underwent a 60 min phase of interventional lower threshold normocapnia according to temperature non-corrected pCO₂ (4.2 kPa) and higher threshold normocapnia according to corrected pCO₂ (6.0 kPa) in a random order. Prior to, during and after each phase, cerebral perfusion and metabolites via a microdialysis catheter were measured.

Results

During upper-threshold pCO₂, an increase in middle cerebral artery mean flow velocity (MFV) and jugular bulb oxygen saturation (jSvO₂) were observed with a concomitant decrease in cerebral lactate concentration. Lower threshold normocapnia was associated with a decrease in MFV in most patients. In all patients jSvO₂ decreased but no change in cerebral lactate was observed. In seven patients jSvO₂ decreased below 55%. These changes were not reflected to intracranial pressure or cerebral oximetry.

Conclusions

During induced hypothermia, lower threshold normocapnia was associated with decreased cerebral perfusion/oxygenation but not reflected to interstitial metabolites. Upper threshold pCO₂ increased cerebral perfusion and reduced cerebral lactate. Vigilance over the ventilatory and CO₂ analysis regimen is mandatory during mild hypothermia.     

Changes in interleukin-10 mRNA expression are predictive for 9-day survival of pigs in an emergency preservation and resuscitation model

Aim of the study

This study aimed at evaluating (I) the impact of different intra-arrest hypothermia levels on the expression of selected cytokines and (II) their prognostic value for 9-day survival.

Methods

Female Large White pigs (n = 21, 31-38 kg) were subjected to 15 min of ventricular fibrillation, followed by intra-arrest cardiopulmonary bypass cooling for 1, 3, or 5 min achieving brain temperatures (Tbr) of 30.4 ± 1.6, 24.2 ± 4.6 and 18.8 ± 4.0 °C. After 40 min of controlled rewarming, pigs were defibrillated and kept at Tbr of 34.5 °C for 20 h, survival was for 9 days. Plasma samples were analysed for interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 levels by ELISA. Total RNA out of peripheral blood mononuclear cells was analysed by real-time PCR for IL-1, IL-2, IL-4, IL-10, TNF-α, interferon-γ, inducible NO synthase, and heme oxygenase-1 gene expressions.

Results

Plasma IL-6 and TNF-α levels significantly (p = 0.0001 and 0.0003) increased in all animals within 1 h after resuscitation with no significant differences between groups. Pigs surviving exhibited a decrease in IL-10 expression between baseline and intra-arrest values as compared to non-surviving animals, which showed a slight increase (p = 0.0078). ROC curve analysis revealed that changes in IL-10 expression had a good prognostic power for survival to day 9 (area under the curve = 0.882).

Conclusion

The systemic inflammatory response syndrome after cardiac arrest was reflected by a remarkable increase of plasma IL-6 and TNF-α levels. Intra-arrest hypothermia levels did not influence the expression of selected cytokines. As prognostic marker for survival IL-10 was identified with decreasing mRNA levels during cardiac arrest in survivors.     

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.     

Early coronary revascularization improves 24 h survival and neurological function after ischemic cardiac arrest. A randomized animal study

Background

Survival after out-of-hospital cardiac arrest (OHCA) remains poor. Acute coronary obstruction is a major cause of OHCA. We hypothesize that early coronary reperfusion will improve 24 h-survival and neurological outcomes.

Methods

Total occlusion of the mid LAD was induced by balloon inflation in 27 pigs. After 5 min, VF was induced and left untreated for 8 min. If return of spontaneous circulation (ROSC) was achieved within 15 min (21/27 animals) of cardiopulmonary resuscitation (CPR), animals were randomized to a total of either 45 min (group A) or 4 h (group B) of LAD occlusion. Animals without ROSC after 15 min of CPR were classified as refractory VF (group C). In those pigs, CPR was continued up to 45 min of total LAD occlusion at which point reperfusion was achieved. CPR was continued until ROSC or another 10 min of CPR had been performed. Primary endpoints for groups A and B were 24-h survival and cerebral performance category (CPC). Primary endpoint for group C was ROSC before or after reperfusion.

Results

Early compared to late reperfusion improved survival (10/11 versus 4/10, p = 0.02), mean CPC (1.4 ± 0.7 versus 2.5 ± 0.6, p = 0.017), LVEF (43 ± 13 versus 32 ± 9%, p = 0.01), troponin I (37 ± 28 versus 99 ± 12, p = 0.005) and CK-MB (11 ± 4 versus 20.1 ± 5, p = 0.031) at 24-h after ROSC. ROSC was achieved in 4/6 animals only after reperfusion in group C.

Conclusions

Early reperfusion after ischemic cardiac arrest improved 24 h survival rate and neurological function. In animals with refractory VF, reperfusion was necessary to achieve ROSC.     

Cold saline infusion and ice packs alone are effective in inducing and maintaining therapeutic hypothermia after cardiac arrest

Aim of the study

Hypothermia treatment with cold intravenous infusion and ice packs after cardiac arrest has been described and used in clinical practice. We hypothesised that with this method a target temperature of 32-34 °C could be achieved and maintained during treatment and that rewarming could be controlled.

Materials and methods

Thirty-eight patients treated with hypothermia after cardiac arrest were included in this prospective observational study. The patients were cooled with 4 °C intravenous saline infusion combined with ice packs applied in the groins, axillae, and along the neck. Hypothermia treatment was maintained for 26 h after cardiac arrest. It was estimated that passive rewarming would occur over a period of 8 h. Body temperature was monitored continuously and recorded every 15 min up to 44 h after cardiac arrest.

Results

All patients reached the target temperature interval of 32-34 °C within 279 ± 185 min from cardiac arrest and 216 ± 177 min from induction of cooling. In nine patients the temperature dropped to below 32 °C during a period of 15 min up to 2.5 h, with the lowest (nadir) temperature of 31.3 °C in one of the patients. The target temperature was maintained by periodically applying ice packs on the patients. Passive rewarming started 26 h after cardiac arrest and continued for 8 ± 3 h. Rebound hyperthermia (>38 °C) occurred in eight patients 44 h after cardiac arrest.

Conclusions

Intravenous cold saline infusion combined with ice packs is effective in inducing and maintaining therapeutic hypothermia, with good temperature control even during rewarming.     

Effect of therapeutic hypothermia vs δ-opioid receptor agonist on post resuscitation myocardial function in a rat model of CPR

Aim

This study is to compare the effect of the δ-opioid receptor agonist, d-Ala²-d-Leu⁵ enkephalin (DADLE) with normothermic control and therapeutic hypothermia on post resuscitation myocardial function and 72-h survival in a rat model of cardiac arrest and resuscitation.

Methods

Ventricular fibrillation (VF) was induced in 15 male Sprague-Dawley rats. After 8 min of untreated VF, cardiopulmonary resuscitation was performed for 8 min before defibrillation. Animals were randomized to three groups of five: (a) normothermia; (b) hypothermia (32 °C); and (c) normothermia with DADLE intravenous infusion (1 mg/kg h⁻¹). Hypothermia and drug infusion were started after successful defibrillation. Myocardial functions, including cardiac output (CO), left ventricular ejection fraction (LVEF), and myocardial performance index (MPI) were measured echocardiographically together with duration of survival.

Results

The 72-h survival was significantly greater in the hypothermic group than in both DADLE and normothermic group (p = 0.02). However, the survival time of the DADLE treated animals was significantly longer than that of the normothermia group (51.8 ± 18.9 vs 18.8 ± 10.1 h, p < 0.01). DADLE group showed significantly better CO (PR 60 min, p = 0.049), better LVEF (PR 60 min, p = 0.044; PR 240 min, p < 0.001) and lower MPI (PR 60 min, p = 0.043; PR 240 min, p = 0.045) than normothermic group. Hypothermia group also showed significantly better CO (PR 60 min, p = 0.044; PR 240 min, p = 0.007), better LVEF (PR 60 min, p = 0.001; PR 240 min, p < 0.001) and lower MPI (PR 60 min, p = 0.003; PR 240 min, p = 0.012) than the normothermic group.

Conclusions

DADLE attenuated post resuscitation myocardial dysfunction and increased short term survival time. However, the 72-h survival in the DADLE group was less than that in the hypothermia group.     

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.     

Vasopressin for cardiac arrest: meta-analysis of randomized controlled trials

Background

Prior meta-analyses-reported results of randomised controlled trials (RCTs) published between 1997 and 2004 failed to show any vasopressin-related benefit in cardiac arrest. Based on new RCT-data and a hypothesis of a potentially increased vasoconstricting efficacy of vasopressin, we sought to determine whether the cumulative, current evidence supports or refutes an overall and/or selective benefit for vasopressin regarding sustained restoration of spontaneous circulation (ROSC), long-term survival, and neurological outcome.

Methods

Two reviewers independently searched PubMed, EMBASE, and Cochrane Database for RCTs assigning adults with cardiac arrest to treatment with a vasopressin-containing regimen (vasopressin-group) vs adrenaline (epinephrine) alone (control-group) and reporting on long-term outcomes. Data from 4475 patients in 6 high-methodological quality RCTs were analyzed. Subgroup analyses were conducted according to initial cardiac rhythm and time from collapse to drug administration (T_DRUG) < 20 min.

Results

Vasopressin vs. control did not improve overall rates of sustained ROSC, long-term survival, or favourable neurological outcome. However, in asystole, vasopressin vs. control was associated with higher long-term survival {odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.04-3.12, P = 0.04}. In asystolic patients of RCTs with average T_DRUG < 20 min, vasopressin vs. control increased the rates of sustained ROSC (data available from 2 RCTs; OR = 1.70, 95% CI = 1.17-2.47, P = 0.005) and long-term survival (data available from 3 RCTs; OR = 2.84, 95% CI = 1.19-6.79, P = 0.02).

Conclusions

Vasopressin use in the resuscitation of cardiac arrest patients is not associated with any overall benefit or harm. However, vasopressin may improve the long-term survival of asystolic patients, especially when average T_DRUG is <20 min.     

Reducing the duration of 100% oxygen ventilation in the early reperfusion period after cardiopulmonary resuscitation decreases striatal brain damage

Purpose

Previous data indicate that 100% O₂ ventilation during early reperfusion after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) increases neuronal death. However, current guidelines encourage the use of 100% O₂ during resuscitation and for an undefined period thereafter. We retrospectively analyzed data from a porcine CA model and hypothesized that prolonged hyperoxic reperfusion would be associated with increased neurohistopathological damage and impaired neurological recovery.

Methods

Fifteen male pigs underwent 8 min of CA and 5 min of CPR. After resuscitation animals were ventilated with either 100% oxygen for 60 min (hyperoxia; n = 8) or 10 min (normoxia; n = 7). Physiological variables were obtained at baseline and 10, 60 and 240 min after resuscitation. Daily functional performance was assessed using an established neurocognitive test in parallel to a neurological deficit score (NDS). On day 5, brains of the re-anaesthetized pigs were harvested for neurohistopathological analyses.

Results

At baseline there were no differences in hemodynamics and neurological status between groups. Post-arrest only PaO₂, as a result of the different inspired oxygen fractions, was significantly higher in the hyperoxia group.There was a numerical trend towards improved clinical recovery in both the NDS and the neurocognitive testing for animals exposed to 10 min of 100% oxygen. However, hyperoxic animals showed a significantly greater degree of necrotic neurons and perivascular inflammation in the striatum in comparison to normoxic animals.

Conclusion

In this retrospective analysis prolonged hyperoxia after CA aggravated necrotic brain damage and perivascular inflammation in the striatum of pigs.     

Comparison of sudden cardiac arrest resuscitation performance data obtained from in-hospital incident chart review and in situ high-fidelity medical simulation

Introduction

High-fidelity medical simulation of sudden cardiac arrest (SCA) presents an opportunity for systematic probing of in-hospital resuscitation systems. Investigators developed and implemented the SimCode program to evaluate simulation's ability to generate meaningful data for system safety analysis and determine concordance of observed results with institutional quality data.

Methods

Resuscitation response performance data were collected during in situ SCA simulations on hospital medical floors. SimCode dataset was compared with chart review-based dataset of actual (live) in-hospital resuscitation system performance for SCA events of similar acuity and complexity.

Results

135 hospital personnel participated in nine SimCode resuscitations between 2006 and 2008. Resuscitation teams arrived at 2.5 ± 1.3 min (mean ± SD) after resuscitation initiation, started bag-valve-mask ventilation by 2.8 ± 0.5 min, and completed endotracheal intubations at 11.3 ± 4.0 min. CPR was performed within 3.1 ± 2.3 min; arrhythmia recognition occurred by 4.9 ± 2.1 min, defibrillation at 6.8 ± 2.4 min. Chart review data for 168 live in-hospital SCA events during a contemporaneous period were extracted from institutional database. CPR and defibrillation occurred later during SimCodes than reported by chart review, i.e., live: 0.9 ± 2.3 min (p < 0.01) and 2.1 ± 4.1 min (p < 0.01), respectively. Chart review noted fewer problems with CPR performance (simulated: 43% proper CPR vs. live: 98%, p < 0.01). Potential causes of discrepancies between resuscitation response datasets included sample size and data limitations, simulation fidelity, unmatched SCA scenario pools, and dissimilar determination of SCA response performance by complementary reviewing methodologies.

Conclusion

On-site simulations successfully generated SCA response measurements for comparison with live resuscitation chart review data. Continued research may refine simulation's role in quality initiatives, clarify methodologic discrepancies and improve SCA response.     

Early selective trans-nasal cooling during CPR improves success of resuscitation in a porcine model of prolonged pulseless electrical activity cardiac arrest

Aim of study

In the present study, we investigated trans-nasal cooling in settings of pulseless electrical activity (PEA). We hypothesized that early trans-nasal cooling during CPR improves outcomes when cardiac arrest is associated with PEA.

Methods

Ventricular fibrillation (VF) was electrically induced in 16 domestic male pigs weighing 40 ± 3 kg. After 14 min of untreated VF, PEA was induced following delivery of one or more electrical shocks. One min after onset of PEA, CPR was started, including chest compression and ventilation. Each animal received 5 min of CPR prior to defibrillation attempt. CPR and resuscitation efforts were discontinued at 15 min unless return to spontaneous circulation was achieved. In 8 animals, selective trans-nasal cooling was begun coincident with start of CPR and 8 randomized controls were identically treated except for trans-nasal cooling. Mean aortic pressure was continuously measured together with aortic and right atrial pressure and nasal, body and right jugular vein temperatures. Coronary perfusion pressure (CPP) was computed from measured data.

Results

Six of eight animals were resuscitated after early trans-nasal cooling, while only one untreated control was resuscitated (p = 0.012). Nasal, body and jugular vein temperatures decreased after cooling. At PC (precordial compression) 5 min, the cooled group recorded a higher CPP (25 ± 5 mmHg) than the non-cooled group (15 ± 4 mmHg, p = 0.001).

Conclusion

When selective trans-nasal cooling was initiated during CPR in the animal model of prolonged cardiac arrest with PEA, CPP was higher and the likelihood of return of spontaneous circulation was improved.     

Body temperature effects on lung injury in ventilated preterm lambs

Aims

Mechanical ventilation causes lung injury in premature infants. Hypothermia may protect against and hyperthermia may augment lung injury. We tested the effects of hypo- and hyperthermia on ventilation induced acute lung injury in preterm lambs.

Methods

Twin sheep fetuses at 128 d GA (term 150 d) were surgically delivered and randomized to unventilated control (UVC), normothermia (38-39 °C) without lung injury (NTNI), or to 1 of 3 injurious ventilation groups: hypothermic (33-34 °C, LT), normothermic (38-39 °C, NT) or hyperthermic (40-41 °C, HT). NT, LT and HT groups had 15 min of injurious ventilation (PEEP 0 cmH₂O, V_T escalation to 15 mL/kg) following delivery and prior to surfactant. The animals were then gently ventilated (PEEP 5 cmH₂O, V_T 7.5 mL/kg) for 2 h 45 min. NTNI lambs received surfactant at birth prior to gentle ventilation. The lambs were then euthanized, and bronchoalveolar lavage (BAL) fluid and lung tissue were used to evaluate lung injury, inflammatory cell counts, inflammatory markers and cytokine mRNA.

Results

Target temperatures were achieved by 15 min of age and maintained for 3 h. All ventilated groups had increased BAL protein, lung inflammation and increased cytokine mRNA. HT animals developed acidosis, premature death, pneumothoraces, impaired lung function and increased inflammatory mRNA expression. LT animals remained clinically stable without pneumothoraces or death, had improved ventilatory efficiency and trended toward lower inflammatory mRNA expression than NT animals.

Conclusion

Hyperthermia exacerbated ventilator induced lung injury, while hypothermia may protect against lung injury in the preterm lamb.     

Severe QTc prolongation under mild hypothermia treatment and incidence of arrhythmias after cardiac arrest--a prospective study in 34 survivors with continuous Holter ECG

Background

Mild hypothermia treatment (32-34 °C) in survivors after cardiac arrest (CA) is clearly recommended by the current guidelines. The effects of cooling procedure towards QT interval have not been evaluated so far outside of case series. In a prospective study 34 consecutive survivors after cardiac arrest were continuously monitored with Holter ECG over the first 48 h.

Patients and methods

A total of 34 patients were analysed and received mild therapeutic hypothermia treatment (MTH) according to the current guidelines and irrespective of the initial rhythm. At admission to hospital and in the field in case of OHCA, a 12-lead ECG was performed in all patients.

Results

During cooling the incidence of ventricular tachycardia was low (8.8%) and in none of the patients Torsade de pointes occurred. The QTc interval was within normal range at first patient contact with EMS in the field (440.00 ms; IQR 424.25-476.75; n = 17) but during hypothermia treatment the QTc interval was significantly prolonged at 33 °C after 24 h of cooling (564.47 ms; IQR 512.41-590.00; p = 0.0001; n = 34) and decreased after end of hypothermia to baseline levels (476.74 ms; 448.71-494.97; p = 0.15).

Conclusion

The QTc interval was found to be significantly prolonged during MTH treatment, and some severe prolongations >670 ms were observed, without a higher incidence of life-threatening arrhythmias, especially no Torsade des pointes were detected. However, routine and frequent ECG recording with respect to the QTc interval should become part of any hypothermia standard operation protocol and should be recommended by official guidelines.