Resuscitation

Chest compressions: The good, the bad and the ugly

Trygve Eftestøl — 2011-12-30

Where exactly is the chest compression, where does it begin, when does it end, how deep does it go and at what rate are they performed? In short – how good or bad is the chest compression? These are some of the questions researchers ask themselves repeatedly. As well as these data, we need to know the proportion of resuscitation time spent giving quality compressions, the ratio of interruptions and several other parameters and we need to evaluate the effect on survival. Considering the increasing capacity for data storage and growing repositories of resuscitation data one might also ask what proportion of valuable research time is spent in analysing compressions.

Ventilation pressure waveforms to detect oesophageal intubation – Do we need any more techniques?

Ed Morris — 2011-12-16

In this edition of Resuscitation Kalmar et al. present a novel method of detecting oesophageal intubation based on ventilation pressure waveforms. The arguments for tracheal intubation in emergency care, and the disastrous consequences of accidental intubation of the oesophagus, are well documented.

Extracorporeal life support for cardiac arrest due to pulmonary embolism: Further studies are needed

Claudio Sandroni, Vincenzo Palmieri — 2011-12-19

Until recently, cardiopulmonary resuscitation (CPR) has represented the only method to support life in cardiac arrest. During CPR, artificial circulation is produced by chest compression while pulmonary function is supported by positive pressure ventilation. Basic CPR techniques can be taught to everyone and used by everyone, which has enabled thousands of lives to be saved worldwide.

Prognostication after cardiac arrest: Time to change our approach

Mauro Oddo — 2011-12-19

Comprehensive post-resuscitation care and the implementation of therapeutic hypothermia (TH) have improved survival and neurological recovery in comatose victims of cardiac arrest (CA). Changes in the management of post-CA coma have also considerably modified outcome prognostication in a way that an increasing number of patients may awake from post-CA coma despite early clinical signs of severe secondary hypoxic–ischemic brain damage.

Use of ice-cold crystalloid for inducing mild therapeutic hypothermia following out-of-hospital cardiac arrest

N. Arulkumaran, R. Suleman, J. Ball — 2011-10-17

Abstract: Objective: Out of hospital cardiac arrest (OHCA) results in a significant mortality and neurological disability in survivors. The application of mild therapeutic hypothermia (MTH) to patients who have suffered an OHCA with a ventricular rhythm results in a significant reduction in mortality and neurological disability in survivors. The optimal timing of this intervention has not been clearly established; however there is emerging evidence to suggest that maximal benefit is gained from initiation at the earliest time point. Despite this, recent surveys have shown a considerable delay in initiating MTH, with variable uptake in emergency departments (EDs), where a number of impediments to delivery have been identified.Method: We have reviewed the literature to determine what are the barriers to the initiation of MTH in the ED. We also reviewed the literature on the use of ice-cold crystalloids as a practical, simple, effective, and safe method to induce MTH.Results: Among the several reasons, the perception of a lack of a practical method and logistical constraints are cited as common barriers. However, the available literature on the use of ice-cold crystalloids suggests that this is a safe and effective method of inducing MTH.Conclusion: ED staff need to be aware that the use of ice-cold fluids is an inexpensive, readily available and easy to perform method of inducing MTH in patients who suffer an out-of hospital cardiac arrest with a ventricular rhythm. We therefore suggest that ice-cold crystalloid is routinely stocked in emergency departments and, unless contraindicated, is used to induce MTH. Optimal post-resuscitation care also includes timely treatment of the cause of the OHCA and maintenance of MTH. Staff education and care bundles may help to facilitate optimal inter-departmental management of the patient.

Therapeutic hypothermia and prevention of acute kidney injury: A meta-analysis of randomized controlled trials

2011-10-07

Abstract: Background: Therapeutic hypothermia has been shown to reduce neurological morbidity and mortality in the setting of out-of-hospital cardiac arrest and may be beneficial following brain injury and cardiopulmonary bypass. We conducted a systematic review to ascertain the effect of therapeutic hypothermia on development of acute kidney injury (AKI) and mortality.Methods: We searched for randomized controlled trials in MEDLINE through February 2011. We included trials comparing hypothermia to normothermia that reported kidney-related outcomes including, development of AKI, dialysis requirement, changes in serum creatinine, and mortality. We performed Peto fixed-effect and random-effects model meta-analyses, and meta-regressions.Results: Nineteen trials reporting on 2218 patients were included; in the normothermia group, the weighted rate of AKI was 4.2%, dialysis requirement 3.7%, and mortality 10.8%. By meta-analysis, hypothermia was not associated with a lower odds of AKI (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.68, 1.51; P=0.95) or dialysis requirement (OR 0.81; 95% CI 0.30, 2.19; P=0.68); however, by meta-regression, a lower target cooling temperature was associated with a lower odds of AKI (P=0.01). Hypothermia was associated with lower mortality (OR 0.69; 95% CI 0.51, 0.92; P=0.01).Conclusions: In trials that ascertained kidney endpoints, therapeutic hypothermia prevented neither the development of AKI nor dialysis requirement, but was associated with lower mortality. Different definitions and rates of AKI, differences in mortality rates, and concerns about the optimal target cooling temperature preclude definitive conclusions.

CPR policies and the patient's best interests

Stuart McLennan — 2011-10-31

Abstract: Standard hospital CPR policies in many countries require CPR to be attempted on all patients having a cardiac arrest unless a Not-for-CPR order is in place. It has recently been shown that this approach is legally inappropriate in New Zealand. It appears that this argument may also potentially apply in other common law countries given the role that ‘best interests’ has in these jurisdictions in providing treatment to patients lacking decision-making capacity. Not-for-CPR orders provide an important and transparent mechanism for making advanced decisions regarding resuscitation. However, advanced planning is not always possible and it is legally inappropriate to require CPR to be performed when it is not in the patient's best interests. Notwithstanding the difficult practical balance that exists at the time of arrest between initiating CPR without delay or interruption for it to be effective for those whom CPR is in their best interests, and recognising as quickly as possible those patients for who CPR is not appropriate, it is argued that policies should be modified to allow clinicians to consider whether CPR is appropriate at time of arrest. Such a change may require ALS training to include a stronger emphasis on early recognition of patients for whom CPR is not in their best interests.

A new way to analyze resuscitation quality by reviewing automatic external defibrillator data

2011-11-07

Abstract: Aims: High quality cardiopulmonary resuscitation (CPR) plays an important role in survival of out-of-hospital cardiac arrests (OHCAs). We have developed an algorithm to automatically identify the quality of chest compressions from data retrieved from automatic external defibrillators (AEDs).Methods: Electrocardiographic (ECG) signals retrieved from AEDs were analyzed by a newly developed algorithm to identify fluctuations in CPR. The algorithm contained three steps. First, it decomposed the AED signals into several intrinsic mode fluctuations (IMFs) by empirical mode decomposition (EMD). Second, it identified the dominant IMFs that carried the chest compression signals and weighted the IMFs to both enhance the chest compression oscillations and filter the noise. Third, it calculated the autocorrelation function (ACF) of the reconstructed signals and tested their periodicity. Using this algorithm, several CPR quality indicators were automatically calculated minute-by-minute and compared with those derived by audio and visual review of AED data by experienced physicians.Results: A total of 77 (29 women, 48 men) OHCA patients were enrolled, and 351 one-min segments were analyzed. The results showed that the CPR quality parameters calculated from the algorithm were highly correlated with those from the manual review (all P<0.001). The limits of agreement by Bland–Altman analysis were acceptable for chest compression number, total flow time, and no flow time, but not for CPR rate. We also demonstrated that only 41.8±29.8% of time was spent in chest compressions and only 7.5±16.8% was spent in adequate chest compressions.Conclusion: Our results demonstrated that several indicators of CPR quality can be precisely and automatically determined by analyzing the ECG signals from AEDs using EMD and autocorrelograms.

A novel method to detect accidental oesophageal intubation based on ventilation pressure waveforms

Alain F. Kalmar, Anthony Absalom, Koenraad G. Monsieurs — 2011-10-31

Abstract: Background: Emergency endotracheal intubation results in accidental oesophageal intubation in up to 17% of patients. This is frequently undetected thereby adding to the morbidity and mortality. No current method to detect accidental oesophageal intubation in an emergency setting is both highly sensitive and specific. We hypothesized that, based on differences between the mechanical properties of the oesophagus and the trachea/lung, ventilation pressures could discriminate between tracheal and oesophageal intubation. Such a technique would potentially not suffer some of the limitations of current methods to detect oesophageal intubation in emergency conditions such as noisy environment (making clinical assessment difficult) or low/no flow states (reducing the applicability of capnometry). The aim of our study was thus to develop and assess a technique that may more rapidly and accurately differentiate oesophageal from tracheal intubation based on airway pressure gradients.Materials and methods: Forty adult patients undergoing elective surgery were included. In 20 patients the trachea was intubated with an endotracheal tube; in 20 patients the oesophagus was purposefully intubated using an Easytube® (Rüsh, Germany). In all patients, a thin air-filled catheter was inserted through the tube lumen until its tip was 1cm from the distal end, and connected to a pressure transducer. Pressure was recorded simultaneously from a second catheter at the proximal end of the tube. For the first three manual ventilations in each patient, a parameter (D) based on temporal (dP/dt) and spatial (dP/ds) pressure gradients (and reflecting flow divided by elastance) was calculated and evaluated for its ability to discriminate between oesophageal and tracheal intubation.Results and discussion: For all tracheal ventilations, D-values were >0.5 (range 0.6–47.9), while for all oesophageal ventilations D-values were <0.5 (range 0.0005–0.07).Conclusion: This technique has the potential to provide a diagnosis of failed intubation within seconds with high sensitivity and specificity.

Percutaneous cardiopulmonary support in pulmonary embolism with cardiac arrest

2011-11-07

Abstract: Objective: To assess the role of percutaneous cardiopulmonary support (PCPS) for the resuscitation of patients with massive pulmonary embolism (PE) with circulatory collapse. We also compared outcomes for PCPS between patients with massive PE with circulatory collapse and patients with AMI with cardiogenic shock.Background: The effectiveness of PCPS for acute myocardial infarction (AMI) complicated with cardiogenic shock has been reported, but there are few reports on the use of PCPS for massive PE with circulatory collapse.Method: We studied 12 consecutive patients with massive PE and 16 patients with AMI, who required PCPS for resuscitation either during cardiopulmonary resuscitation (CPR) or after successful CPR.Results: Twelve patients with PE and 16 patients with AMI were identified. There were no differences in age, the Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) score at admission, rate of cardiac arrest on arrival, and time from first circulatory collapse to PCPS between the two groups. However, the proportion of men with PE (33%) was smaller than those with AMI (87%, p<0.05). The duration of PCPS was shorter in PE (38h) compared with AMI (83h, p=0.051) patients. The proportion of patients successfully weaned from PCPS (100% vs. 37.5%, p<0.01), survival rate at discharge (83.3% vs. 12.5%, p<0.001) and good neurological outcome (58.3% vs. 6.3%, p=0.004) was significantly higher for PE compared to AMI patients.Conclusion: In our small case series, percutaneous cardiopulmonary support (PCPS) had a life saving role in patients with massive PE and cardiac arrest. PCPS was also more effective in patients with massive PE with cardiac arrest than in patients with AMI and cardiac arrest.

Does therapeutic hypothermia benefit adult cardiac arrest patients presenting with non-shockable initial rhythms?: A systematic review and meta-analysis of randomized and non-randomized studies

2011-08-10

Abstract: Background: The benefit of therapeutic hypothermia (TH) for comatose adult patients with return of spontaneous circulation after cardiac arrest (CA) with non-shockable initial rhythms is uncertain. We evaluated whether TH reduces mortality and improves neurological outcome in comatose adults resuscitated from non-shockable CA.Methods: We searched PubMed, EMBASE, CENTRAL, and BIOSIS through March 2010, to identify studies using TH after non-shockable CA. Randomized and non-randomized studies (RS and NRS) comparing survival or neurological outcome in TH and standard care or normothermia were selected. We corresponded with authors to clarify data missing from published articles. Individual and pooled statistics were calculated as risk ratios (RRs) with 95% confidence interval (CI). Both fixed- and random-effects models were used for both meta-analyses.Findings: Two RS and twelve NRS were included in the meta-analysis and separately analyzed. The pooled RR for 6-month mortality of two RS was 0.85 (95% CI 0.65–1.11). The pooled RR for in-hospital mortality for 10 NRS was 0.84 (95% CI 0.78–0.92) and for poor neurological outcome on discharge was 0.95 (95% CI 0.90–1.01) in random-effects model. In subgroup analysis for the NRS with out-of-hospital CA, the pooled RR for in-hospital mortality was 0.86 (95% CI 0.76–0.99) and for the poor neurological outcome on discharge was 0.96 (95% CI 0.90–1.02). For the prospective NRS, the pooled RR for in-hospital mortality was 0.76 (95% CI 0.65–0.89) and for the poor neurological outcome on discharge was 0.96 (95% CI 0.90–1.02). Most of studies had substantial risks of bias and overall quality of evidence was very low.Interpretation: TH is associated with reduced in-hospital mortality for adults patients resuscitated from non-shockable CA. However, most of the studies had substantial risks of bias and quality of evidence was very low. Further high quality randomized clinical trials would confirm the actual benefit of TH in this population.

Serum matrix metalloproteinases in patients resuscitated from cardiac arrest. The association with therapeutic hypothermia

2011-08-19

Abstract: Aim: To study the systemic levels of matrix metalloproteinases (MMP) -7, -8 and -9 and their inhibitor TIMP-1 in cardiac arrest patients and the association with mild therapeutic hypothermia treatment on the serum concentration of these enzymes.Methods: MMP-7, -8 and -9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) were analysed in blood samples obtained from 51 patients resuscitated from cardiac arrest. The samples were taken at 24 and 48h from restoration of spontaneous circulation (ROSC). The biomarker levels were compared between patients (N=51) and healthy controls (N=10) and between patients who did (N=30) and patients who did not (N=21) receive mild therapeutic hypothermia.Results: MMP-7 (median 0.47ng/ml), MMP-8 (median 31.16ng/ml) and MMP-9 (median 253.00ng/ml) levels were elevated and TIMP-1 levels suppressed (median 78.50ng/ml) in cardiac arrest patients as compared with healthy controls at 24h from ROSC. Hypothermia treatment associated with attenuated elevation of MMP-9 (p=0.001) but not MMP-8 (p=0.02) or MMP-7 (p=0.69). Concentrations of MMPs -7, -8 and -9 correlated with the leukocyte count but not with C-reactive protein (CRP) or neurone-specific enolase (NSE) levels.Conclusion: We demonstrated that the systemic levels of MMP-7, -8 and -9 but not TIMP-1 are elevated in cardiac arrest patients in the 48h post-resuscitation period relative to the healthy controls. Patients who received therapeutic hypothermia had lower MMP-9 levels compared to non-hypothermia treated patients, which generates hypothesis about attenuation of inflammatory response by hypothermia treatment.

Therapeutic hypothermia is associated with improved neurologic outcome and survival in cardiac arrest survivors of non-shockable rhythms

2011-08-22

Abstract: Background: Therapeutic hypothermia improves neurologic outcomes in patients resuscitated from cardiac arrest due to ventricular fibrillation. However, its role in patients with cardiac arrest due to non-shockable rhythms (pulseless electrical activity (PEA) and asystole) is unclear. We hypothesized that therapeutic hypothermia favorably impacts neurologic outcome and survival in patients resuscitated from cardiac arrest due to non-shockable rhythms.Methods: Retrospectively collected data on consecutive adult patients admitted to Hartford Hospital from 1/1/2004 to 11/1/2010 who survived a cardiac arrest due to PEA or asystole were analyzed. Patients who underwent therapeutic hypothermia (1/1/2007–11/1/2010) formed the hypothermia group while patients admitted prior to the institution of therapeutic hypothermia (1/1/2004–1/1/2007) at Hartford Hospital formed the control group. The primary end-point was measured using the Pittsburgh cerebral performance category (CPC) scale and patients were assessed for a good (CPC 1 and 2) or poor (CPC 3–5) neurological outcome prior to discharge from hospital. A secondary end-point was measured as survival at discharge from hospital.Results: Of 100 post-cardiac arrest patients included in the study, 15/52 (29%) patients in the hypothermia group had a good neurologic outcome as compared to 5/43 (10%) patients in the control group (P=0.021). On multivariate analysis, the odds ratio for good neurologic outcome and survival at discharge from the hospital with therapeutic hypothermia as compared to control were 4.35 (95% CI 1.10–17.24, P=0.04) and 5.65 (CI 1.66–19.23, P=0.006) respectively.Conclusion: Therapeutic hypothermia is associated with favorable neurologic outcome and survival in patients resuscitated after cardiac arrest due to non-shockable rhythms.

Relationship between blood, nasopharyngeal and urinary bladder temperature during intravascular cooling for therapeutic hypothermia after cardiac arrest

2011-09-09

Abstract: Objectives: Therapeutic hypothermia improves survival and neurological outcome in patients successfully resuscitated after cardiac arrest. Accurate temperature control during cooling is essential to prevent cooling-related side effects.Methods: Prospective observational study of 12 patients assessed during therapeutic hypothermia (32–34°C) achieved by intravascular cooling following cardiac arrest. Simultaneous temperature measurements were taken using a Swan–Ganz catheter (blood temperature BLT), nasopharyngeal probe (nasopharyngeal temperature NPT) and the urinary bladder catheter (urinary bladder temperature UBT). A total of 1728 measurements (144 measurements per patient) were recorded over a 48-h period and analyzed. Blood temperature was considered as the reference measurement.Results: Temperature profiles obtained from BLT, NPT and UBT compared with the use of analysis of variance did not differ significantly. Pearson correlation revealed that the correlation between BLT and NPT as well as BLT and UBT was statistically significant (r=0.96, p<0.001 and r=0.95, p<0.001, respectively). Bland–Altman analysis proved that the agreement between all measurements was satisfactory and the differences were not clinically important.Conclusions: In 12 post-cardiac arrest patients undergoing intravascular cooling, both nasopharyngeal and urinary bladder temperature measurements were similar to blood temperatures measured using a pulmonary artery catheter.

Circulating cell-free DNA levels correlate with postresuscitation survival rates in out-of-hospital cardiac arrest patients

2011-08-22

Abstract: Early prediction of prognosis is helpful in cardiac arrest patients. Plasma cell-free DNA, which increases rapidly after cell death, is a novel biomarker for the prognosis of critical ill patients. Changes in the plasma cell-free DNA level and its role for the early prognosis of cardiac arrest patients remain unclear. We prospectively enrolled adult out-of-hospital cardiac arrest (OHCA) patients with sustained return of spontaneous circulation. The resuscitation variables were recorded following the Utstein recommendation. The plasma cell-free DNA concentration was determined by quantitative real-time polymerase chain reaction assay of β-globin gene. A total of 42 patients were enrolled for the study. The plasma cell-free DNA level within 2h after cardiac arrest was higher in the non-survival group than the survival-to-discharge group (median level 1659.9g.e./mL vs. 1121.6g.e./mL, p=0.003 by non-parametric test). The plasma cell-free DNA level at 72h became no difference between these two groups. The optimal cutoff value of plasma cell-free DNA for predicting survival-to-discharge was 1170g.e./mL by ROC curve analysis (area under curve 0.752, p=0.010). A plasma cell-free DNA level higher than 1170g.e./mL and was an independent predictor for in-hospital mortality by multiple logistic regression analysis (adjusted odds ratio of 12.35, p=0.023) and was also associated with higher 90 day mortality (p=0.021 by log-rank test). In conclusion, the plasma cell-free DNA level increases during the early post-cardiac arrest phase and can be an early prognostic factor for OHCA patients.

Influence of pre-course assessment using an emotionally activating stimulus with feedback: A pilot study in teaching Basic Life Support

2011-09-19

Abstract: Background: Cardiopulmonary resuscitation (CPR) mastery continues to challenge medical professionals. The purpose of this study was to determine if an emotional stimulus in combination with peer or expert feedback during pre-course assessment effects future performance in a single rescuer simulated cardiac arrest.Methods: First-year medical students (n=218) without previous medical knowledge were randomly assigned to one of the study groups and asked to take part in a pre-course assessment: Group 1: after applying an emotionally activating stimulus an expert (instructor) gave feedback on CPR performance (Ex). Group 2: after applying the same stimulus feedback was provided by a peer from the same group (Pe); Group 3: standard without feedback (S). Following pre-course assessment, all subjects received a standardized BLS-course, were tested after 1week and 6months later using single-rescuer-scenario, and were surveyed using standardized questionnaires (6-point-likert-scales: 1=completely agree, 6=completely disagree).Results: Participants exposed to stimulus demonstrated superior performance concerning compression depth after 6months independent of feedback-method (Ex: 65.85% [p=0.0003]; Pe: 57.50% [p=0.0076] vs. 21.43%). The expert- more than the peer-group was emotionally more activated in initial testing, Ex: 3.26±1.35 [p≤0.0001]; Pe: 3.73±1.53 [p=0.0319]; S: 4.25±1.37) and more inspired to think about CPR (Ex: 2.03±1.37 [p=0.0119]; Pe: 2.07±1.14 [p=0.0204]; S: 2.60±1.55). After 6months this activation effect was still detectable in the expert-group (p=0.0114).Conclusions: The emotional stimulus approach to BLS-training seems to impact the ability to provide adequate compression depth up to 6months after training. Furthermore, pre-course assessment helped to keep the participants involved beyond initial training.

The effectiveness of ERC advanced life support (ALS) provider courses for the retention of ALS knowledge

2011-10-03

Abstract: Purpose: Out-of-hospital emergency physicians in Austria need mandatory emergency physician training, followed by biennial refresher courses. Currently, both standardized ERC advanced life support (ALS) provider courses and conventional refresher courses are offered. This study aimed to compare the retention of ALS-knowledge of out-of-hospital emergency physicians depending on whether they had or had not participated in an ERC-ALS provider course since 2005.Methods: Participants (n=807) from 19 refresher courses for out-of-hospital emergency physicians answered eight multiple-choice questions (MCQ) about ALS based on the 2005 ERC guidelines. The pass score was 75% correct answers. A multivariate logistic regression analyzed differences in passing scores between those who had previously participated in an ERC-ALS provider course and those who had not. Age, gender, regularity of working as an out-of-hospital emergency physician and the self-reported number of real resuscitation efforts within the last 6months were entered as control variables.Results: Out-of-hospital emergency physicians who had previously attended an ERC-ALS provider course had a significantly higher chance of passing the MCQ test (OR=1.60, p=0.015). Younger age (OR=0.95, p<0.001), regular work as an out-of-hospital emergency physician (OR=2.66, p<0.001) and a higher number of self-reported resuscitations within the last 6months (OR=1.08, p=0.002) were also significant predictors of passing the test.Conclusion: Out-of-hospital emergency physicians that had attended an ERC-ALS provider course since 2005 had a higher retention of ALS knowledge compared to non-ERC-ALS course participants.

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

2011-08-01

Abstract: Aim of the study: Therapeutic hypothermia improves outcome after cardiac arrest. Dopamine D2 agonists and serotonin 5-HT1A 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 6min of cardiac arrest due to ventricular fibrillation. Following restoration of circulation, 1mg quinpirole, 1mg 8-OH-DPAT or vehicle were injected subcutaneously. Body temperature was monitored for 48h. 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.

Cardioprotective effect of therapeutic hypothermia at 34°C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model

Toshiaki Mochizuki, Shuchun Yu, Takasumi Katoh, Katsunori Aoki, Shigehito Sato — 2011-08-29

Abstract: Aim: Therapeutic hypothermia (TH) is widely used as a cardioprotective treatment for cardiac arrest. TH at 30–32°C during ischaemia and reperfusion has a cardioprotective effect. The aims of the study were to examine whether TH at 34°C with late induction (immediately after the start of reperfusion) has a cardioprotective effect and to determine if this effect is mediated by nitric oxide (NO) and phosphatidylinositol 3′-kinase (PI3K).Methods: Langendorff perfusion of Sprague–Dawley rat hearts was initiated at 75mmHg at 37°C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n=7): control group; ischaemia group, with 34°C TH during ischaemia for 30min and reperfusion for 180min; reperfusion group, with 34°C TH induced solely during the reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound.Results: TH reduced the left ventricle infarct size from 54.2±14.8% of the control group to 11.9±6.3% (ischaemia group, p<0.001) and to 23.5±10.5% (reperfusion group, p<0.001). l-NAME, LY294002, and wortmannin reversed the cardioprotective effect of TH induced during reperfusion to 42.5±10.6% (p=0.009), 40.9±4.1% (p=0.021), and 51.9±13.0% (p<0.001), respectively. Circulatory temperatures reached 34°C within 5min in all groups subjected to TH.Conclusions: TH of 34°C showed a cardioprotective effect even with late initiation of cooling during reperfusion. The effect was mediated by NO and PI3K.

Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion

2011-08-08

Abstract: Objectives: Acute lung injury (ALI) can develop during the course of many clinical conditions, and is associated with significant morbidity and mortality. Valproic acid (VPA), a well-known anti-epileptic drug, has been shown to have anti-oxidant and anti-inflammatory effects in various ischemia/reperfusion (I/R) models. The purpose of this study was to investigate whether VPA could affect survival and development of ALI in a rat model of intestinal I/R.Methods: Two experiments were performed. Experiment I: Male Sprague-Dawley rats (250–300g) were subjected to intestinal ischemia (1h) and reperfusion (3h). They were randomized into 2 groups (n=7 per group) 30min after ischemia: Vehicle (Veh) and VPA (300mg/kg, IV). Primary end-point for this study was survival over 4h from the start of ischemia. Experiment II: The histological and biochemical effects of VPA treatment on lungs were examined 3h (1h ischemia+2h reperfusion) after intestinal I/R injury (Veh vs. VPA, n=9 per group). An objective histological score was used to grade the degree of ALI. Enzyme linked immunosorbent assay (ELISA) was performed to measure serum levels of interleukins (IL-6 and 10), and lung tissue of cytokine-induced neutrophil chemoattractant (CINC) and myeloperoxidase (MPO). In addition, the activity of 8-isoprostane was analyzed for pulmonary oxidative damage.Results: In Experiment I, 4-h survival rate was significantly higher in VPA treated animals compared to Veh animals (71.4% vs. 14.3%, p=0.006). In Experiment II, ALI was apparent in all of the Veh group animals. Treatment with VPA prevented the development of ALI, with a reduction in the histological score (3.4±0.3 vs. 5.3±0.6, p=0.025). Moreover, compared to the Veh control group the animals from the VPA group displayed decreased serum levels of IL-6 (952±213pg/ml vs. 7709±1990pg/ml, p=0.011), and lung tissue concentrations of CINC (1188±28pg/ml vs. 1298±27pg/ml, p<0.05), MPO activity (368±23ng/ml vs. 490±29ng/ml, p<0.05) and 8-isoprostane levels (1495±221pg/ml vs. 2191±177pg/ml, p<0.05).Conclusion: VPA treatment improves survival and attenuates ALI in a rat model of intestinal I/R injury, at least in part, through its anti-oxidant and anti-inflammatory effects.

Effects of n-propyl gallate on neuronal survival after forebrain ischemia in rats

2011-08-01

Abstract: The aim of the study: The present study was conducted to assess the effects of intraperitoneal administration of n-propyl gallate (PG) on hippocampal neuronal survival after forebrain ischemia.Methods: Forty male Sprague-Dawley rats were randomly assigned to one of 6 groups. Animals in the PG-I-10, PG-I-8 and PG-S groups received intraperitoneal injection of PG (100mg/kg) 72, 48, 24h and 30min before severe (10min) or moderate (8min) ischemia or sham operation, respectively, while animals in the V-I-10, V-I-8 and V-S groups received the vehicle (10% DMSO) in the same manner. Forebrain ischemia was produced by bilateral carotid occlusion combined with hypotension (35mmHg) under isoflurane anesthesia. Animals were killed 7 days after reperfusion. Histological assessments were performed using hematoxylin and eosin staining. In separate groups of animals that received PG or vehicle, m-RNA levels of hypoxia-inducible factor 1α (HIF-1α), erythropoietin (EPO) and vascular endothelial growth factor (VEGF) were measured using the reverse transcription-PCR protocol.Results: The number of normal neurons was significantly higher in the PG-I-8 group compared with that in the V-I-8 group, whereas it was similar between the PG-I-10 and V-I-10 groups. Animals that received PG had significantly higher levels of HIF-1α, EPO and VEGF expression compared with those that received vehicle.Conclusion: The results indicated that intraperitoneal administration of PG may have neuroprotective effects in a model of moderate, but not severe, forebrain ischemia in rats.

Treatment with beta-hydroxybutyrate and melatonin is associated with improved survival in a porcine model of hemorrhagic shock

2011-08-22

Abstract: Introduction: The neuroprotective ketone β-hydroxybutyrate (BHB) and the antioxidant melatonin have been found at elevated levels in hibernating mammals. Previous studies in rat models of hemorrhagic shock have suggested a benefit. We compared infusion of 4M BHB and 43mM melatonin (BHB/M) to 4M sodium chloride and 20% DMSO (control solution) to evaluate for potential benefits in porcine hemorrhagic shock.Methods: Hemorrhagic shock was induced to obtain systolic blood pressures <50mmHg for 60min. Pigs were treated with a bolus of either BHB/M (n=9) or control solution (n=8) followed by 4-h infusion of the either BHB/M or control solution. All animals were then resuscitated for 20h after shock. Physiological data were continually recorded, and blood samples were taken at intervals throughout the experiment. Serum samples were analyzed via high resolution NMR for metabolomic response.Results: BHB/M treatment significantly increased 24-h survival time when compared to treatment with control solution (100% versus 62%; p=0.050), with a trend toward decreased volume of resuscitative fluid administered to animals receiving BHB/M. BHB/M-treated animals had lower base deficit and higher oxygen consumption when compared to animals receiving control solution. Serum metabolite profiles revealed increases in β-hydroxybutyrate (BHB), succinate, 2-oxovalerate and adipate with BHB/M treatment as compared with animals treated with control infusion.Conclusion: Infusion of BHB/M conferred a survival benefit over infusion of control solution in hemorrhagic shock. BHB and its products of metabolism are identified in serum of animals subjected to shock and treated with BHB/M. Further preclinical studies are needed to clarify the mechanisms of action of this promising treatment strategy.

Clinically plausible hyperventilation does not exert adverse hemodynamic effects during CPR but markedly reduces end-tidal PCO2

2011-08-19

Abstract: Aims: Ventilation at high respiratory rates is considered detrimental during CPR because it may increase intrathoracic pressure limiting venous return and forward blood flow generation. We examined whether ventilation at high, yet clinically plausible, tidal volumes could also be detrimental, and further examined effects on end-tidal pCO2 (PETCO2).Methods: Sixteen domestic pigs were randomized to one of four ventilatory patterns representing two levels of respiratory rate (min−1) and two levels of tidal volume (ml/kg); i.e., 10/6, 10/18, 33/6, and 33/18 during chest compression after 8min of untreated VF.Results: Data (mmHg, mean±SD) are presented in the order listed above. Ventilation at 33/18 prompted higher airway pressures (p<0.05) and persistent expiratory airway flow (p<0.05) before breath delivery demonstrating air trapping. The right atrial pressure during chest decompression showed a statistically insignificant increase with increasing minute-volume (7±4, 10±3, 12±1, and 13±3; p=0.055); however, neither the coronary perfusion pressure (23±1, 17±6, 18±6, and 21±2; NS) nor the cerebral perfusion pressure (32±3, 23±8, 30±12, and 31±3; NS) was statistically different. Yet, increasing minute-volume reduced the PETCO2 demonstrating a high dependency on tidal volumes delivered at currently recommended respiratory rates.Conclusions: Increasing respiratory rate and tidal volume up to a minute-volume 10-fold higher than currently recommended had no adverse hemodynamic effects during CPR but reduced PETCO2 suggesting that ventilation at controlled rate and volume could enhance the precision with which PETCO2 reflects CPR quality, predicts return of circulation, and serve to guide optimization of resuscitation interventions.

Neurologic recovery after therapeutic hypothermia in patients with post-cardiac arrest myoclonus

2011-10-03

Abstract: Early myoclonus in comatose survivors of cardiac arrest, even when it is not myoclonic status epilepticus (MSE), is considered a sign of severe global brain ischemia and has been associated with high rates of mortality and poor neurologic outcomes. We report on three survivors of primary circulatory cardiac arrests who had good neurologic outcomes (two patients with a CPC score=1 and one patient with a CPC score=2) after mild therapeutic hypothermia, despite exhibiting massive myoclonus within the first 4h after return of spontaneous circulation. The concept that early myoclonus heralds a uniformly poor prognosis may need to be reconsidered in the era of post-cardiac arrest mild therapeutic hypothermia.

Basic life support – Becoming more complex

Peter Paal, Elisabeth Gruber, Hermann Brugger, Gabriel Putzer — 2011-11-03

We read with interest the article of Adelborg et al. where lifeguards performed single rescuer cardiopulmonary resuscitation (CPR) in a simulated manikin scenario. Mouth-to-mouth ventilation resulted in reduced interruptions of chest compressions and a higher proportion of effective ventilations when compared to mouth-to-mask or bag-valve mask ventilation. The authors concluded that in this simulated single rescuer scenario CPR quality improved with mouth-to-mouth when compared to mouth-to-mask and bag-valve mask ventilation.

Reply to Letter: Basic Life Support-becoming more complex

Kasper Adelborg, Christian Dalgas, Erik Lerkevang Grove, Bo Løfgren — 2011-11-03

We appreciate the letter by Paal et al. in response to our recent paper. The main finding of our study was that mouth-to-mouth ventilation reduces interruptions in chest compressions and results in a higher proportion of effective ventilations compared to mouth-to-pocket mask ventilation and bag-valve-mask ventilation. Mouth-to-mouth ventilation resulted in improved quality of cardiopulmonary resuscitation (CPR).

Heart fatty acid binding protein and myoglobin do not improve early rule out of acute myocardial infarction when highly sensitive troponin assays are used

Sally Aldous, Chris Pemberton, Richard Troughton, Martin Than, A. Mark Richards — 2011-11-04

In the August issue of Resuscitation, Body et al. concluded that a combination of heart fatty acid binding protein (hFABP) and cardiac troponin could rule out acute myocardial infarction (AMI) with a sensitivity of 82.2% overall and 96.9% in low risk patients. hFABP has previously been shown to be an early marker of myocardial damage but is unsuitable as a test for patients presenting >6h from onset of symptoms due to rapid renal clearance. However, the troponin assays used in the above paper for adjudication (Roche troponin T) and as an index test (Alere troponin I) and in previous publications have been relatively insensitive assays.

Reply to Letter: Still FABP-ulous even with a more sensitive troponin assay

Richard Body, Simon Carley, Kevin Mackway-Jones — 2011-11-10

We welcome the thoughtful response by Aldous et al. to our recent publication in Resuscitation and the presentation of some new evidence with regard to this fascinating biomarker. We agree that the analytical characteristics of the Alere troponin I assay (with particular regard to precision) do not compare favourably with some of the other contemporary assays. The advantages of the Alere troponin I and heart fatty acid binding protein (H-FABP) assays are their availability as automated immunoassays for use at the point of care. This enables a more rapid turnaround time, which is ideal for use in the emergency department. Alere has recently developed a more sensitive troponin I assay, which warrants prospective evaluation.

Animations for teaching the recognition of cardiac arrest

Jasmeet Soar, John Parry — 2011-11-23

Rescuers often fail to recognize cardiac arrest. This causes a delay in starting cardiopulmonary resuscitation (CPR) and this decreases the victim's chances of survival. A common reason for not starting CPR is the presence of a period of agonal breathing (gasping) after the heart stops. This is often mistaken for normal breathing. Training rescuers to recognize the signs of cardiac arrest using inanimate manikins is difficult. The use of video clips from actual arrests raises ethical issues about consent, and trainees may also find these real videos disturbing. Actors role playing cardiac arrest victims are not always realistic. Animation offers an alternative approach to teaching the recognition of cardiac arrest. A project by second and third year students at the Bristol School of Animation, University of the West of England in which students worked individually or in teams resulted in four short video clips that can be viewed at: http://www.youtube.com/user/ResusCouncilUK#p/u

Response to letter of Sloth and Blaivas entitled “The future of cardiopulmonary resuscitation: What if a TEE probe could shock, sense and pace?” [Resuscitation 82 (2011) 1253]

Richard E. Kerber — 2011-10-24

Drs. Sloth and Blaivas state: “A small inexpensive TEE probe capable of sensing, pacing and defibrillating in an ideal location just behind the heart could be used in multiple care settings, including pre-hospital ones…this would result in significant improvement in the management of cardiopulmonary resuscitation in a variety of settings.” We agree with this suggestion and wish to point out that such a TEE probe with the capability of delivering a cardioverting or defibrillating shock has already been designed and initial clinical experience with patients undergoing cardioversion of atrial fibrillation has been gained . In addition, we have suggested that a sheath could be designed containing the necessary connecting wires and electrodes into which any TEE probe could be inserted, thereby making a usable combined instrument without permanently altering the probe.

Metabolic dysfunction in the post-resuscitation heart

Luca Siracusano, Viviana Girasole — 2011-11-03

We read with great interest the article by Fang et al. about the ultrastructural changes observed in the myocardium of rats submitted to ventricular fibrillation and cardiopulmonary resuscitation (CPR).

Corrigendum to “A sternal accelerometer does not impair hemodynamics during piglet CPR” [Resuscitation 82 (9) (2011) 1231–1234]

2011-08-24

The authors regret that Table 1 was reproduced twice as both Tables 1 and 2 in the above article. The authors would like to apologise for any inconvenience caused. The correct appears below.

Erratum to “Pauses during CPR—Are breaks hindering our efforts?” [Resuscitation 82 (2011) 1379–1380]

Patrick Braun, Volker Wenzel — 2011-11-30

The recent editorial ‘Pauses during CPR—Are breaks hindering our efforts?’ indicated incorrectly that the study by Hoppu and colleagues was undertaken in Helsinki. In fact, this research was undertaken in Turku and Tampere and was not connected with Helsinki. I apologise to these authors for overlooking this error and for any offence caused.Jerry NolanEditor-in-Chief