Association of serum lactate and survival outcomes in patients undergoing therapeutic hypothermia after cardiac arrest

Introduction

Recent studies have suggested that serum lactate may serve as a marker to predict mortality after resuscitation from cardiac arrest (CA). The relationship between serum lactate and CA outcomes requires further characterization, especially among patients treated with therapeutic hypothermia (TH) and aggressive post-arrest care.

Methods

A retrospective analysis of patients resuscitated from non-traumatic CA at three urban U.S. hospitals was performed using an established internet-based post-arrest registry. Adult (≥18 years) patients resuscitated from CA and receiving TH treatment were included. Logistic regression analysis was used to adjust for potential confounders to survival outcomes. Survival to discharge served as the primary endpoint.

Results

A total of 199 post-CA patients treated with TH between 5/2005 and 11/2011 were included in this analysis. The mean age was 56.9 ± 16.5 years, 85/199 (42.7%) patients were female, and survival to discharge was attained in 84/199 (42.2%). While lower initial post-CA serum lactate levels were not associated with increased survival to discharge, subsequent lactate measurements were significantly associated with outcomes (24-h serum lactate levels in survivors vs. non-survivors, 2.7 ± 0.5 vs. 4.2 ± 0.4 mmol/L, p < 0.01). Multivariable logistic regression confirmed this relationship with survival to discharge (p < 0.01).

Conclusion

Lower serum lactate levels at 12 h and 24 h, but not initially following cardiac arrest, are associated with survival to hospital discharge after resuscitation from CA and TH treatment. Prospective investigation of serum lactate as a potential prognostic tool in CA is needed.     

Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome

Aim of the study

To investigate serum levels of glial fibrillary acidic protein (GFAP) for evaluation of neurological outcome in cardiac arrest (CA) patients and compare GFAP sensitivity and specificity to that of more studied biomarkers neuron-specific enolas (NSE) and S100B.

Method

A prospective observational study was performed in three hospitals in Sweden during 2008-2012. The participants were 125 CA patients treated with therapeutic hypothermia (TH) to 32-34 °C for 24 hours. Samples were collected from peripheral blood (n = 125) and the jugular bulb (n = 47) up to 108 hours post-CA. GFAP serum levels were quantified using a novel, fully automated immunochemical method. Other biomarkers investigated were NSE and S100B. Neurological outcome was assessed using the Cerebral Performance Categories scale (CPC) and dichotomized into good and poor outcome.

Results

GFAP predicted poor neurological outcome with 100% specificity and 14-23% sensitivity at 24, 48 and 72 hours post-CA. The corresponding values for NSE were 27-50% sensitivity and for S100B 21-30% sensitivity when specificity was set to 100%. A logistic regression with stepwise combination of the investigated biomarkers, GFAP, did not increase the ability to predict neurological outcome. No differences were found in GFAP, NSE and S100B levels when peripheral and jugular bulb blood samples were compared.

Conclusion

Serum GFAP increase in patients with poor outcome but did not show sufficient sensitivity to predict neurological outcome after CA. Both NSE and S100B were shown to be better predictors. The ability to predict neurological outcome did not increased when combining the three biomarkers.     

Low-dose nitroglycerine improves outcome after cardiac arrest in rats

Objective

The aim of this study was to evaluate the outcome of intravenously applied nitroglycerine (NTG, 1 μg kg⁻¹ min⁻¹ for 1 h) after resuscitation from an asphyxia cardiac arrest (ACA) insult. We hypothesized that NTG infused for 1 h after the return of spontaneous circulation (ROSC) would improve functional and neuro-morphological outcomes.

Methods

Adult rats were subjected to 8 min of ACA followed by resuscitation. There were three treatment groups: ACA, ACA + NTG and sham operated. Vital and blood parameters were monitored during the 1 h post-resuscitation intensive care phase. After survival times of 3, 6, 12, 24, 72 h and 7 days, the neurological deficit score (NDS) was measured. Histological evaluation of the hippocampus, cortex, the thalamic reticular nucleus and the caudate-putamen was performed 7 days post insult.

Results

We found that NTG (i) induced significantly higher initial MAP peaks; (ii) resulted in a less-pronounced elevation of heart rates after ROSC with significantly faster normalization to baseline levels; and (iii) influenced glucose metabolism, temporarily elevating blood glucose to non-physiological levels. Even so, NTG (iv) improved the neurological outcome and (v) reduced neurodegeneration, mainly in the hippocampal CA1 region. A significant NTG-associated decrease in blood pressure did not occur.

Conclusion

The effect of low-dosed NTG applied post-resuscitation appears to be neuroprotective, demonstrated by reduced hippocampal damage and a better NDS, even with temporarily elevated blood glucose to non-physiological levels. Thus, additional studies are needed to evaluate NTG-triggered mechanisms and optimized dosages before clinical translation should be considered.Animal study institutional protocol number: 42502-2-2-947-Uni-MD.     

Immature/total granulocyte ratio: A promising tool to assess the severity and the outcome of post-cardiac arrest syndrome

Background

The immature/total granulocyte (I/T-G) ratio increases during severe systemic inflammatory response syndrome. This study evaluated the I/T-G ratio as a predictor of poor outcome after out-of-hospital cardiac arrest (OHCA).

Methods

We conducted a pilot prospective cohort study of patients who were admitted in our intensive care unit (ICU) during a one-year period after post-OHCA resuscitation. I/T-G ratio measurements were obtained from blood samples collected on admission using flow cytometry and the outcomes were ICU mortality and post-cardiac arrest syndrome.

Results

Among the 130 patients (76% male, median age 54 [46–67] years), the median I/T-G ratio was 0.85 [0.42–1.98]%. The I/T-G ratio was poorly correlated with the SOFA score and lactate level on day 1 (r = 0.25, p = 0.005 and r = 0.5, p < 0.001, respectively). Patients with high I/T-G ratios were more likely to develop post-resuscitation shock (37% vs. 58%, p = 0.02). Patients dying from post-resuscitation shock had a higher I/T-G ratio than patients dying from neurological causes (2 [1–4]% vs. 1.2 [0.6–1.2]%, p = 0.02). The area under the ROC curve based on the I/T-G ratio was 0.82 for predicting ICU mortality.

Conclusion

The I/T-G ratio appears to be an accurate predictor of poor outcome. However, the added clinical value of this marker and the possible involvement of immature granulocytes in the pathophysiology of post-cardiac arrest syndrome remain to be investigated.     

The effect of percutaneous coronary intervention in patients suffering from ST-segment elevation myocardial infarction complicated by out-of-hospital cardiac arrest on 30 days survival

Aim of the study

To question the beneficial effects of the recommended early percutaneous coronary intervention (PCI) after out-of-hospital cardiac arrest on 30-day survival with favourable neurological outcome.

Methods

Prospectively collected data of 1277 out of hospital cardiac arrest patients between 2005 and 2010 from a registry at a tertiary care university hospital were used for a cohort study.

Results

In 494 (39%) arrest patients ST-segment elevation was identified in 249 (19%). Within 12 h after restoration of spontaneous circulation catheter laboratory investigations were initiated in 197 (79%) and PCI in 183 (93%) (78% got PCI in less than180 min). Adjustment for a cumulative time without chest compressions <2 min, initial shockable rhythm, cardiac arrest witnessed by healthcare professionals, and a higher core temperature at time of hospitalization reduced the effect of PCI on favourable neurological outcome at 30 days (OR 1.40; 95% CI, 0.53–3.7) compared to the univariate analysis (OR 2.52; 95% CI, 1.42–4.48).

Conclusion

This cohort study failed to demonstrate the beneficial effects of PCI as part of post-resuscitation care on 30-day survival with a favourable neurological outcome.     

The effects of adenocaine (adenosine and lidocaine) on early post-resuscitation cardiac and neurological dysfunction in a porcine model of cardiac arrest

Aim

Return of spontaneous circulation (ROSC) elicits ischaemia/reperfusion injury and myocardial dysfunction. The combination of adenosine and lidocaine (AL, adenocaine) has been shown to (1) inhibit neutrophil inflammatory activation and (2) improve left ventricular function after ischaemia. We hypothesized that resuscitation with adenocaine during early moments of cardiopulmonary resuscitation (CPR) attenuates leucocyte oxidant generation and myocardial dysfunction.

Methods

Pigs were randomized to: (1) sham (n = 7), (2) cardiac arrest (CA; n = 16), or 3) cardiac arrest + adenocaine (CA + AL; n = 12). After 7 min of electrically induced ventricular fibrillation, start of CPR was followed by infusion of saline (CA) or adenocaine (CA + AL) for 6 min. Haemodynamics, cardiodynamics (pressure–volume loops) and leucocyte superoxide anion generation were assessed. Neurological function was evaluated after 24 h by histology and neurological deficit score (0 = normal; 500 = brain dead).

Results

Rate of ROSC was comparable between groups: CA group 11/16 and CA + AL group 7/12 p = 0.57). Cardiac index transiently increased after ROSC in both groups. Left ventricular dysfunction demonstrated by a rightward shift of the intercept of end-systolic pressure–volume relations in CA was avoided in the CA + AL group. Leucocyte superoxide anion generation 2 h after ROSC was significantly attenuated in the CA + AL group compared to the CA group. Neurological deficit scores [CA: median: 17.5(IQR:0–75) and CA + AL: 35(IQR:15–150)] and histopathological damage were comparable in both groups (p = 0.37).

Conclusion

Infusion of adenocaine during early resuscitation from CA significantly improved early post-resuscitation cardiac function and attenuated leucocyte superoxide anion generation, without a change in post-ROSC neurological function. (IACUC protocol number 023-2009).     

Markers of intestinal injury are associated with endotoxemia in successfully resuscitated patients

Aims

Gut dysfunction is suspected to play a major role in the pathophysiology of post-resuscitation disease through an increase in intestinal permeability and endotoxin release. However this dysfunction often remains occult and is poorly investigated. The aim of this pilot study was to explore intestinal failure biomarkers in post-cardiac arrest patients and to correlate them with endotoxemia.

Methods

Following resuscitation after cardiac arrest, 21 patients were prospectively studied. Urinary intestinal fatty acid-binding protein (IFABP), which marks intestinal permeability, plasma citrulline, which reflects the functional enterocyte mass, and whole blood endotoxin were measured at admission, days 1–3 and 6. We explored the kinetics of release and the relationship between IFABP, citrulline and endotoxin values.

Results

IFABP was extremely high at admission and normalized at D3 (6668 pg/mL vs 39 pg/mL, p = 0.01). Lowest median of citrulline (N = 20–40 μmol/L) was attained at D2 (11 μmol/L at D2 vs 24 μmol/L at admission, p = 0.01) and tended to normalize at D6 (21 μmol/L). During ICU stay, 86% of patients presented a detectable endotoxemia. Highest endotoxin level was positively correlated with highest IFABP level (R² = 0.31, p = 0.01) and was inversely correlated with lowest plasma citrulline levels (R² = 0.55, p < 0.001). Endotoxin levels increased between admission and D2 in patients with post-resuscitation shock, whereas it decreases in patients with no shock (median +0.33 EU vs −0.19 EU, p = 0.03). Highest endotoxin level was positively correlated with D3 SOFA score (R² = 0.45, p = 0.004).

Conclusion

Biomarkers of intestinal injury are altered after cardiac arrest and are associated with endotoxemia. This could worsen post-resuscitation shock and organ failure.     

Erythropoietin improved initial resuscitation and increased survival after cardiac arrest in rats

Introduction

Recent data have demonstrated potent cardioprotective and neuroprotective effects of the application of growth hormones like erythropoietin (EPO) after focal cardiac or cerebral ischemia. In order to assess possible benefits regarding survival and resuscitation conditions, EPO was tested against placebo in a model of cardiac arrest in the rat.

Methods

Thirty-four male Wistar rats were randomized into two groups (EPO versus control; n = 17 per group). Under anesthesia, cardiac arrest was induced by asphyxia after neuromuscular blockade. After 6 min of global ischemia, animals were resuscitated by external chest compression combined with epinephrine administration. An intravenous bolus of recombinant human EPO (rhEPO, 3000 UI kg⁻¹ body weight, i.v.) or saline (in control group) was performed 15 min before cardiac arrest, by a blinded investigator. Restoration of spontaneous circulation (ROSC), survival at 1, 24, 48 and 72 h and hemodynamic changes after cardiac arrest were studied.

Results

Survival to 72 h was significantly improved in the EPO group (n = 15/17) compared to the control group (n = 7/17). All the EPO-treated rats were successfully resuscitated whereas only 13 of 17 control animals resuscitated. EPO-treated animals required a significantly smaller dose of epinephrine before resuscitation, compared to control rats. Time course of systolic arterial blood pressure after resuscitation revealed no significant differences between both groups.

Conclusion

EPO, when administrated before cardiac arrest, improved initial resuscitation and increased the duration of post-resuscitation survival.     

Comparison of shock-first strategy and cardiopulmonary resuscitation-first strategy in a porcine model of prolonged cardiac arrest

Objective

The choice of a shock-first or a cardiopulmonary resuscitation (CPR)-first strategy in the treatment of prolonged cardiac arrest (CA) is still controversial. The purpose of this study was to compare the effects of these strategies on oxygen metabolism and resuscitation outcomes in a porcine model of 8 min CA.

Methods

Ventricular fibrillation (VF) was electrically induced. After 8 min of untreated VF, 24 male inbred Wu-Zhi-Shan miniature pigs were randomized to receive either defibrillation first (ID group) or chest compression first (IC group). In the ID group, a shock was delivered immediately. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly initiated at a rate of 100 compressions min⁻¹, and the compression-to-ventilation ratio was 30:2. If VF persisted after five cycles of CPR, a second defibrillation attempt was made. In the IC group, chest compressions were delivered first, followed by a shock.

Results

Hemodynamic variables, the VF waveform and blood gas analysis outcomes were recorded. Oxygen metabolism parameters and the amplitude spectrum area (AMSA) of the VF waveform were computed. There were no significant differences in the rate of ROSC and 24 h survival between two groups. The ID group had lower lactic acid levels, higher cardiac output, better oxygen consumption and better oxygen extraction ratio at 4 and 6 h after ROSC than the IC group.

Conclusions

In a porcine model of prolonged CA, the choice of a shock-first or CPR-first strategy did not affect the rate of ROSC and 24 h survival, but the shock-first strategy might result in better hemodynamic status and better oxygen metabolism than the CPR-first strategy at the first 6 h after ROSC.     

Cerebral tissue oxygen saturation during therapeutic hypothermia in post-cardiac arrest patients

Aim of the study

This observational study was performed to assess the cerebral tissue oxygen saturation during and after therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest.

Methods

We performed a prospective observational study on the cerebral tissue oxygen saturation (SctO₂) in post-cardiac arrest patients treated with therapeutic hypothermia (TH) between March 2011 and April 2012. SctO₂ (measured by near-infrared spectroscopy) was non-invasively and continuously measured in 28 post-cardiac arrest patients during hypothermia and active rewarming.

Results

At the start of mechanically induced TH, SctO₂ was 68% (65–72) and PaCO₂ was 47.2 mmHg (36.9 – 51.4). SctO₂ and PaCO₂ significantly decreased to 59% (57–64; p = 0.006) and 36.6 mmHg (33.9–44.7; p = 0.002), respectively, within the first 3 h of mechanically induced TH. Cerebral tissue oxygen saturation was significantly lower in non-survivors (n = 10) compared with survivors (n = 18) at 3 h after induction of hypothermia (p = 0.02) while the decrease in PaCO₂ was similar in both groups. During TH maintenance, SctO₂ gradually returned to baseline values (69% (63–72)) at 24 h, with no differences between survivors and non-survivors (p = 0.65). Carbon dioxide remained within the range of mild hypocapnia (32–38 mmHg) throughout the hypothermic period. During rewarming, SctO₂ further increased to 71% (67–78).

Conclusions

Induction of TH in comatose post-CA patients changes the balance between oxygen delivery and supply. The decrease in SctO₂ was less pronounced in patients surviving to hospital discharge.     

Emergency Department inter-hospital transfer for post-cardiac arrest care: Initial experience with implementation of a regional cardiac resuscitation center in the United States

Objective

The American Heart Association recently recommended regional cardiac resuscitation centers (CRCs) for post-resuscitation care following out-of-hospital cardiac arrest (OHCA). Our objective was to describe initial experience with CRC implementation.

Methods

Prospective observational study of consecutive post-resuscitation patients transferred from community Emergency Departments (EDs) to a CRC over 9 months. Transfer criteria were: OHCA, return of spontaneous circulation (ROSC), and comatose after ROSC. Incoming patients were received and stabilized in the ED of the CRC where advanced therapeutic hypothermia (TH) modalities were applied. Standardized post-resuscitation care included: ED evaluation for cardiac catheterization, TH (33–34 °C) for 24 h, 24 h/day critical care physician support, and evidence-based neurological prognostication. Prospective data collection utilized the Utstein template. The primary outcome was survival to hospital discharge with good neurological function [Cerebral Performance Category 1 or 2].

Results

Twenty-seven patients transferred from 11 different hospitals were included. The majority (21/27 [78%]) had arrest characteristics suggesting poor prognosis for survival (i.e. asystole/pulseless electrical activity initial rhythm, absence of bystander cardiopulmonary resuscitation, or an unwitnessed cardiac arrest). The median (IQR) time from transfer initiation to reaching TH target temperature was 7 (5–13) h. Ten (37%) patients survived to hospital discharge, and of these 9/10 (90% of survivors, 33% of all patients) had good neurological function.

Conclusions

Despite a high proportion of patients with cardiac arrest characteristics suggesting poor prognosis for survival, we found that one-third of CRC transfers survived with good neurological function. Further research to determine if regional CRCs improve outcomes after cardiac arrest is warranted.     

Reduced in-hospital survival rates of out-of-hospital cardiac arrest victims with obstructive pulmonary disease

Aim

Out-of-hospital cardiac arrest (OHCA) due to sustained ventricular tachycardia/fibrillation (VT/VF) is common and often lethal. Patient's co-morbidities may determine survival after OHCA, and be instrumental in post-resuscitation care, but are poorly studied. We aimed to study whether patients with obstructive pulmonary disease (OPD) have a lower survival rate after OHCA than non-OPD patients.

Methods

We performed a community-based cohort study of 1172 patients with non-traumatic OHCA with ECG-documented VT/VF between 2005 and 2008. We compared survival to Emergency Room (ER), to hospital admission, to hospital discharge, and at 30 days after OHCA, of OPD-patients and non-OPD patients, using logistic regression analysis. We also compared 30-day survival of patients who were admitted to hospital, using multivariate logistic regression analysis.

Results

OPD patients (n = 178) and non-OPD patients (n = 994) had comparable survival to ER (75% vs. 78%, OR 0.9 [95% CI: 0.6–1.3]) and to hospital admission (56% vs. 57%, OR 1.0 [0.7–1.4]). However, survival to hospital discharge was significantly lower among OPD patients (21% vs. 33%, OR 0.6 [0.4–0.9]). Multivariate regression analysis among patients who were admitted to hospital (OPD: n = 100, no OPD: n = 561) revealed that OPD was an independent determinant of reduced 30-day survival rate (39% vs. 59%, adjusted OR 0.6 [0.4–1.0, p = 0.035]).

Conclusion

OPD-patients had lower survival rates after OHCA than non-OPD patients. Survival to ER and to hospital admission was not different between both groups. However, among OHCA victims who survived to hospital admission, OPD was an independent determinant of reduced 30-day survival rate.     

Post-resuscitation electrocardiograms,acute coronary findings and in-hospital prognosis of survivors of out-of-hospital cardiac arrest

Background

Identification of acute coronary lesions amenable to urgent intervention in survivors of out-of-hospital cardiac arrest is crucial. We aimed to compare the clinical and electrocardiographic characteristics to urgent coronary findings, and to analyze in-hospital prognosis of these patients.

Methods

From January 2005 to December 2012 we retrospectively identified consecutive patients resuscitated from out-of-hospital cardiac arrest, and analyzed the clinical characteristics, post-resuscitation electrocardiogram and coronary angiogram of those who underwent emergent angiography. Mortality and neurologic status at discharge were also assessed.

Results

Patients with ST-elevation more frequently had obstructive coronary artery disease (89% vs. 51%, p < 0.001) or acute coronary occlusions (83% vs. 8%, p < 0.001) than patients without ST-elevation. Independent predictors of an acute coronary occlusion were chest pain before arrest (OR 0.16, 95% CI 0.04–0.7, p = 0.01), a shockable initial rhythm (OR 0.16, 95% CI 0.03–0.9, p = 0.03), and ST-elevation on the post-resuscitation electrocardiogram (OR 0.02, 95% CI 0.004–0.13, p < 0.001). Survival with favorable neurologic recovery at discharge was 59%. Independent predictors of mortality or unfavorable neurological outcome at discharge were absence of basic life support (OR 0.2, 95% CI 0.06–0.9, p = 0.04), prolonged resuscitation time (OR 0.9, 95% CI 0.8–0.9, p = 0.01), and necessity of vasopressors (OR 14.8, 95% CI 3.3–65.4, p = 0.001).

Conclusions

Most patients with ST-elevation on the post-resuscitation electrocardiogram had an acute coronary occlusion, as opposed to patients without ST-elevation. Absence of basic life support, prolonged resuscitation time and use of vasopressors were independent predictors of worse in-hospital outcome.     

Post-resuscitation myocardial microcirculatory dysfunction is ameliorated with eptifibatide

Background

The post-cardiac arrest syndrome includes a decline in myocardial microcirculation function. Inhibition of the platelet IIb/IIIa glycoprotein receptor has improved myocardial microvascular function post-percutaneous coronary intervention. Therefore, we evaluated such inhibition with eptifibatide for its effect on myocardial microcirculation function post-cardiac arrest and resuscitation.

Methods

Four groups of swine were studied in a prospective, randomized, blinded, placebo-controlled protocol including; eptifibatide administered during CPR (Group 1, n = 5), after resuscitation (Group 2, n = 4), during and after resuscitation (Group 3, n = 5), or placebo (Group 4, n = 10). CPR was initiated following 12 min of untreated VF. Those successfully resuscitated were studied during a 4-h post-resuscitation period. Coronary flow reserve, a measure of microcirculation function (in the absence of coronary obstruction), as well as parameters of left ventricular systolic and diastolic function, were measured pre-arrest and serially post-resuscitation.

Results

Coronary flow reserve was preserved during the post-resuscitation period, indicating normal microcirculatory function in the eptifibatide-treated animals, but not in the placebo-treated group. However, LV function declined equally in both groups during the first 4 h after cardiac arrest.

Conclusion

Inhibition of platelet IIb/IIIa glycoprotein receptors with eptifibatide post-resuscitation prevented myocardial microcirculation dysfunction. Left ventricular dysfunction post-resuscitation was not improved with eptifibatide, and perhaps transiently worse at 30 min post-resuscitation. Post-cardiac arrest ventricular dysfunction may require a multi-modality treatment strategy for successful prevention or amelioration.     

Incidence and factors associated with cardiac arrest complicating emergency airway management

Objective

Cardiac arrest (CA) is a rare but recognized complication of emergency airway management. Our aim was to measure the incidence of peri-intubation CA during emergency intubation and identify factors associated with this complication.

Methods

Retrospective cohort study of emergency endotracheal intubations performed in a large, urban emergency department over a one-year period. Patients were included if they were >18 years old and not in CA prior to intubation. Multiple logistic regression modeling was used to define factors independently associated with CA.

Results

A total 542 patients underwent emergency intubation during the study period and 410 met inclusion criteria for this study. CA occurred in 17/410 (4.2%) at a median of 6 min post-intubation. Nearly two-thirds of CA events occurred within 10 min of drug induction; early peri-intubation CA rate 2.4% (95% CI: 1.3–4.5%). Pulseless electrical activity was the initial rhythm in the majority of cases. More than half of CA events were successfully resuscitated but CA was associated with increased odds of hospital death (OR 14.8; 95% CI: 4.2–52). Pre-intubation hemodynamic and oximetry variables were associated with CA. CA was more common in patients experiencing pre intubation hypotension (12% vs 3%; p < 0.002). Pre RSI shock index (SI) and weight were independently associated with CA.

Conclusions

In this series, 1 in 25 emergency intubations was associated with the complication of CA. Peri-intubation CA is associated with increased mortality. Pre-intubation patient characteristics are associated with this complication.     

Awakening after cardiac arrest and post resuscitation hypothermia: Are we pulling the plug too early?

Background

Time to awakening after out-of-hospital cardiac arrest (OHCA) and post-resuscitation therapeutic hypothermia (TH) varies widely. We examined the time interval from when comatose OHCA patients were rewarmed to 37 °C to when they showed definitive signs of neurological recovery and tried to identify potential predictors of awakening.

Methods

With IRB approval, a retrospective case study was performed in OHCA patients who were comatose upon presentation to a community hospital during 2006–2010. They were treated with TH (target of 33 °C) for 24 h, rewarmed, and discharged alive. Comatose patients were generally treated medically after TH for at least 48 h before any decision to withdraw supportive care was made. Pre-hospital TH was not used. Data are expressed as medians and interquartile range.

Results

The 89 patients treated with TH in this analysis were divided into three groups based upon the time between rewarming to 37 °C and regaining consciousness. The 69 patients that regained consciousness in ≤48 h after rewarming were termed “early-awakeners”. Ten patients regained consciousness 48–72 h after rewarming and were termed “intermediate-awakeners”. Ten patients remained comatose and apneic >72 h after rewarming but eventually regained consciousness; they were termed “late-awakeners”. The ages for the early, intermediate and late awakeners were 56 [49,65], 62 [48,74], and 58 [55,65] years, respectively. Nearly 67% were male. Following rewarming, the time required to regain consciousness for the early, intermediate and late awakeners was 9 [2,18] (range 0–47), 60.5 [56,64.5] (range 49–71), and 126 [104,151] h (range 73–259), respectively. Within 90 days of hospital admission, favorable neurological function based on a Cerebral Performance Category (CPC) score of 1 or 2 was reported in 67/69 early, 10/10 intermediate, and 8/10 late awakeners.

Conclusion

Following OHCA and TH, arbitrary withdrawal of life support <48 h after rewarming may prematurely terminate life in many patients with the potential for full neurological recovery. Additional clinical markers that correlate with late awakening are needed to better determine when withdrawal of support is appropriate in OHCA patients who remain comatose >48 h after rewarming.     

Effect of moderate hyperventilation and induced hypertension on cerebral tissue oxygenation after cardiac arrest and therapeutic hypothermia

Aim

Improving cerebral perfusion is an essential component of post-resuscitation care after cardiac arrest (CA), however precise recommendations in this setting are limited. We aimed to examine the effect of moderate hyperventilation (HV) and induced hypertension (IH) on non-invasive cerebral tissue oxygenation (SctO₂) in patients with coma after CA monitored with near-infrared spectroscopy (NIRS) during therapeutic hypothermia (TH).

Methods

Prospective pilot study including comatose patients successfully resuscitated from out-of-hospital CA treated with TH, monitored with NIRS. Dynamic changes of SctO₂ upon HV and IH were analyzed during the stable TH maintenance phase. HV was induced by decreasing PaCO₂ from ∼40 to ∼30 mmHg, at stable mean arterial blood pressure (MAP ∼ 70 mmHg). IH was obtained by increasing MAP from ∼70 to ∼90 mmHg with noradrenaline.

Results

Ten patients (mean age 69 years; mean time to ROSC 19 min) were studied. Following HV, a significant reduction of SctO₂ was observed (baseline 74.7 ± 4.3% vs. 69.0 ± 4.2% at the end of HV test, p < 0.001, paired t-test). In contrast, IH was not associated with changes in SctO₂ (baseline 73.6 ± 3.5% vs. 74.1 ± 3.8% at the end of IH test, p = 0.24).

Conclusions

Moderate hyperventilation was associated with a significant reduction in SctO₂, while increasing MAP to supra-normal levels with vasopressors had no effect on cerebral tissue oxygenation. Our study suggests that maintenance of strictly normal PaCO₂ levels and MAP targets of 70 mmHg may provide optimal cerebral perfusion during TH in comatose CA patients.     

Survival after avalanche-induced cardiac arrest

Aim

Criteria to prolong resuscitation after cardiac arrest (CA) induced by complete avalanche burial are critical since profound hypothermia could be involved. We sought parameters associated with survival in a cohort of victims of complete avalanche burial.

Methods

Retrospective observational study of patients suffering CA on-scene after avalanche burial in the Northern French Alps between 1994 and 2013. Criteria associated with survival at discharge from the intensive care unit (ICU) were collected on scene and upon admission to Level-1 trauma center. Neurological outcome was assessed at 3 months using cerebral performance category score.

Results

Forty-eight patients were studied. They were buried for a median time of 43 min (25–76 min; 25–75th percentiles) and had a pre-hospital body core temperature of 28.0 °C (26.0–30.7). Eighteen patients (37.5%) had pre-hospital return of spontaneous circulation and 30 had refractory CA. Rewarming of 21 patients (43.7%) was performed using extracorporeal life support. Eight patients (16.7%) survived and were discharged from the ICU, three (6.3%) had favorable neurological outcome at 3 months. Pre-hospital parameters associated with survival were the presence of an air pocket and rescue collapse. On admission, survivors had lower serum potassium concentrations than non-survivors: 3.2 mmol/L (2.7–4.0) versus 5.6 mmol/L (4.2–8.0), respectively (P < 0.01). They also had normal values for prothrombin and activated partial thromboplastin compared to non-survivors.

Conclusions

Our findings indicate that survival after avalanche burial and on-scene CA is rarely associated with favorable neurological outcome. Among criteria associated with survival, normal blood coagulation on admission warrants further investigation.     

Serum procalcitonin as a marker of post-cardiac arrest syndrome and long-term neurological recovery,but not of early-onset infections,in comatose post-anoxic patients treated with therapeutic hypothermia

Objective

To examine the relationship of early serum procalcitonin (PCT) levels with the severity of post-cardiac arrest syndrome (PCAS), long-term neurological recovery and the risk of early-onset infections in patients with coma after cardiac arrest (CA) treated with therapeutic hypothermia (TH).

Methods

A prospective cohort of adult comatose CA patients treated with TH (33 °C, for 24 h) admitted to the medical/surgical intensive care unit, Lausanne University Hospital, was studied. Serum PCT was measured early after CA, at two time-points (days 1 and 2). The SOFA score was used to quantify the severity of PCAS. Diagnosis of early-onset infections (within the first 7 days of ICU stay) was made after review of clinical, radiological and microbiological data. Neurological recovery at 3 months was assessed with Cerebral Performance Categories (CPC), and was dichotomized as favorable (CPC 1–2) vs. unfavorable (CPC 3–5).

Results

From December 2009 to April 2012, 100 patients (median age 64 [interquartile range 55–73] years, median time from collapse to ROSC 20 [11–30] min) were studied. Peak PCT correlated with SOFA score at day 1 (Spearman's R = 0.44, p < 0.0001) and was associated with neurological recovery at 3 months (peak PCT 1.08 [0.35–4.45] ng/ml in patients with CPC 1–2 vs. 3.07 [0.89–9.99] ng/ml in those with CPC 3–5, p = 0.01). Peak PCT did not differ significantly between patients with early-onset vs. no infections (2.14 [0.49–6.74] vs. 1.53 [0.46–5.38] ng/ml, p = 0.49).

Conclusions

Early elevations of serum PCT levels correlate with the severity of PCAS and are associated with worse neurological recovery after CA and TH. In contrast, elevated serum PCT did not correlate with early-onset infections in this setting.     

Post-resuscitation intestinal microcirculation: Its relationship with sublingual microcirculation and the severity of post-resuscitation syndrome

Objective

Post-resuscitation syndrome has been recognized as one of the major causes of the poor outcomes of cardiopulmonary resuscitation. The aims of this study were to investigate the intestinal microcirculatory changes following cardiopulmonary resuscitation and relate those changes to sublingual microcirculation and the severity of post-resuscitation syndrome as measured by myocardial function and serum inflammatory cytokine levels.

Methods

Twenty-five rats were randomized into three groups: (1) short duration of cardiac arrest (n = 10): ventricular fibrillation (VF) was untreated for 4 min prior to 6 min of cardiopulmonary resuscitation (CPR); (2) long duration of cardiac arrest (n = 10): VF was untreated for 8 min followed by 8 min of CPR; (3) sham control group (n = 5): a sham operation was performed without VF induction and CPR. Intestinal and sublingual microcirculatory blood flow was visualized by a sidestream dark-field (SDF) imaging device at baseline and 1, 2, 4, 6, 8 h post-resuscitation. Myocardial function was measured by echocardiography and serum cytokine levels (TNF-α and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Both intestinal and sublingual microcirculatory blood flow decreased significantly with increasing duration of cardiac arrest and resuscitation. The decreases in intestinal microcirculatory blood flow were closely correlated with the reductions of sublingual microcirculatory blood flow (perfused small vessels density: r = 0.772, p < 0.01; microcirculatory flow index: r = 0.821, p < 0.01). The decreased microcirculatory blood flow was closely correlated with weakened myocardial function and elevated inflammatory cytokine levels.

Conclusions

The severity of post-resuscitation intestinal microcirculatory dysfunction is closely correlated with that of myocardial function and inflammatory cytokine levels. The measurement of sublingual microcirculation reflects changes of intestinal microcirculation and may therefore provide a new option for post-resuscitation monitoring.