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This is a non-final version of an article published in final form in Lipcsey, Tenhunen, Pischke, Kuitunen, Flaatten, De Geer, Sjölin, Frithiof, Chew, Bendel, Kawati, Larsson, Mollnes, Tønnessen, Rubertsson. Endotoxin removal in septic shock with the Alteco LPS Adsorber was safe but showed no benefit compared to placebo in the double-blind randomized controlled trial - the Asset Study. Shock. 2020;54(2):224-231. Purpose: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed. Methods: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate 32 septic shock patients with abdominal or urogenital focus on LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS binding. The study treatment was initiated within 12 h of inclusion and given for 6 h daily on first 2 days. LPS was measured in all patients. Results: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups. Conclusions: In a small cohort of patients with presumed gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared with a sham device was seen when using a LPS adsorber in addition to standard care.

Background: In out-of-hospital cardiac arrest, chest compression–only cardiopulmonary resuscitation (CO-CPR) has emerged as an alternative to standard CPR (S-CPR), using both chest compressions and rescue breaths. Since 2010, CPR guidelines recommend CO-CPR for both untrained bystanders and trained bystanders unwilling to perform rescue breaths. The aim of this study was to describe changes in the rate and type of CPR performed before the arrival of emergency medical services (EMS) during 3 consecutive guideline periods in correlation to 30-day survival. Methods: All bystander-witnessed out-of-hospital cardiac arrests reported to the Swedish register for cardiopulmonary resuscitation in 2000 to 2017 were included. Nonwitnessed, EMS-witnessed, and rescue breath–only CPR cases were excluded. Patients were categorized as receivers of no CPR (NO-CPR), S-CPR, or CO-CPR before EMS arrival. Guideline periods 2000 to 2005, 2006 to 2010, and 2011 to 2017 were used for comparisons over time. The primary outcome was 30-day survival. Results: A total of 30 445 patients were included. The proportions of patients receiving CPR before EMS arrival changed from 40.8% in the first time period to 58.8% in the second period, and to 68.2% in the last period. S-CPR changed from 35.4% to 44.8% to 38.1%, and CO-CPR changed from 5.4% to 14.0% to 30.1%, respectively. Thirty-day survival changed from 3.9% to 6.0% to 7.1% in the NO-CPR group, from 9.4% to 12.5% to 16.2% in the S-CPR group, and from 8.0% to 11.5% to 14.3% in the CO-CPR group. For all time periods combined, the adjusted odds ratio for 30-day survival was 2.6 (95% CI, 2.4–2.9) for S-CPR and 2.0 (95% CI, 1.8–2.3) for CO-CPR, in comparison with NO-CPR. S-CPR was superior to CO-CPR (adjusted odds ratio, 1.2; 95% CI, 1.1–1.4). Conclusions: In this nationwide study of out-of-hospital cardiac arrest during 3 periods of different CPR guidelines, there was an almost a 2-fold higher rate of CPR before EMS arrival and a concomitant 6-fold higher rate of CO-CPR over time. Any type of CPR was associated with doubled survival rates in comparison with NO-CPR. These findings support continuous endorsement of CO-CPR as an option in future CPR guidelines because it is associated with higher CPR rates and overall survival in out-of-hospital cardiac arrest.

Background: No practical tool quantitates the risk of circulatory-etiology death (CED) immediately after successful cardiopulmonary resuscitation in patients without ST-segment–elevation myocardial infarction. We developed and validated a prediction model to rapidly determine that risk and facilitate triage to individualized treatment pathways. Methods: With the use of INTCAR (International Cardiac Arrest Registry), an 87-question data set representing 44 centers in the United States and Europe, patients were classified as having had CED or a combined end point of neurological-etiology death or survival. Demographics and clinical factors were modeled in a derivation cohort, and backward stepwise logistic regression was used to identify factors independently associated with CED. We demonstrated model performance using area under the curve and the Hosmer-Lemeshow test in the derivation and validation cohorts, and assigned a simplified point-scoring system. Results: Among 638 patients in the derivation cohort, 121 (18.9%) had CED. The final model included preexisting coronary artery disease (odds ratio [OR], 2.86; confidence interval [CI], 1.83–4.49; P ≤0.001), nonshockable rhythm (OR, 1.75; CI, 1.10–2.77; P=0.017), initial ejection fractionP =0.002), shock at presentation (OR, 2.27; CI, 1.42–3.62; P25 minutes (OR, 1.42; CI, 0.90–2.23; P=0.13). The derivation model area under the curve was 0.73, and Hosmer-Lemeshow test P=0.47. Outcomes were similar in the 318-patient validation cohort (area under the curve 0.68, Hosmer-Lemeshow test P=0.41). When assigned a point for each associated factor in the derivation model, the average predicted versus observed probability of CED with a CREST score (coronary artery disease, initial heart rhythm, low ejection fraction, shock at the time of admission, and ischemic time >25 minutes) of 0 to 5 was: 7.1% versus 10.2%, 9.5% versus 11%, 22.5% versus 19.6%, 32.4% versus 29.6%, 38.5% versus 30%, and 55.7% versus 50%. Conclusions: The CREST model stratified patients immediately after resuscitation according to risk of a circulatory-etiology death. The tool may allow for estimation of circulatory risk and improve the triage of survivors of cardiac arrest without ST-segment–elevation myocardial infarction at the point of care.

The aim of this review is to update and discuss the use of mechanical chest compression devices in treatment of cardiac arrest.Three recently published large multicenter randomized trials have not been able to show any improved outcome in adult out-of-hospital cardiac arrest patients when compared with manual chest compressions.Mechanical chest compression devices have been developed to better deliver uninterrupted chest compressions of good quality. Prospective large randomized studies have not been able to prove a better outcome compared to manual chest compressions; however, latest guidelines support their use when high-quality manual chest compressions cannot be delivered. Mechanical chest compressions can also be preferred during transportation, in the cath-lab and as a bridge to more invasive support like extracorporeal membrane oxygenation.

To evaluate the outcomes of cardiac arrest survivors with myoclonus receiving modern postresuscitation care.

Despite a lack of randomized trials, practice guidelines recommend that mild induced hypothermia be considered for comatose survivors of in-hospital cardiac arrest. This study describes the safety, feasibility, and outcomes of mild induced hypothermia treatment following in-hospital cardiac arrest.Prospective, observational, registry-based study.Forty-six critical care facilities in eight countries in Europe and the United States reporting in the Hypothermia Network Registry and the International Cardiac Arrest Registry.A total of 663 patients with in-hospital cardiac arrest and treated with mild induced hypothermia were included between January 2004 and February 2012.None.A cerebral performance category of 1 or 2 was considered a good outcome. At hospital discharge 41% of patients had a good outcome. At median 6-month follow-up, 34% had a good outcome. Among in-hospital deaths, 52% were of cardiac causes and 44% of cerebral cause. A higher initial body temperature was associated with reduced odds of a good outcome (odds ratio, 0.79; 95% CI, 0.68-0.92). Adverse events were common; bleeding requiring transfusion (odds ratio, 0.56; 95% CI, 0.31-1.00) and sepsis (odds ratio, 0.52; 95% CI, 0.30-0.91) were associated with reduced odds for a good outcome.In this registry study of an in-hospital cardiac arrest population treated with mild induced hypothermia, we found a 41% good outcome at hospital discharge and 34% at follow-up. Infectious complications occurred in 43% of cases, and 11% of patients required a transfusion for bleeding. The majority of deaths were of cardiac origin.

Objective Representatives of five international critical care societies convened topic specialists and a nonexpert jury to review, assess, and report on studies of targeted temperature management and to provide clinical recommendations. Data sources Questions were allocated to experts who reviewed their areas, made formal presentations, and responded to questions. Jurors also performed independent searches. Sources used for consensus derived exclusively from peer-reviewed reports of human and animal studies. Study selection Question-specific studies were selected from literature searches; jurors independently determined the relevance of each study included in the synthesis. Conclusions and recommendations 1) The jury opines that the term "targeted temperature management" replace "therapeutic hypothermia." 2) The jury opines that descriptors (e.g., "mild") be replaced with explicit targeted temperature management profiles. 3) The jury opines that each report of a targeted temperature management trial enumerate the physiologic effects anticipated by the investigators and actually observed and/or measured in subjects in each arm of the trial as a strategy for increasing knowledge of the dose/duration/response characteristics of temperature management. This enumeration should be kept separate from the body of the report, be organized by body systems, and be made without assertions about the impact of any specific effect on the clinical outcome. 4) The jury STRONGLY RECOMMENDS targeted temperature management to a target of 32°C-34°C as the preferred treatment (vs. unstructured temperature management) of out-of-hospital adult cardiac arrest victims with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular tachycardia and still unconscious after restoration of spontaneous circulation (strong recommendation, moderate quality of evidence). 5) The jury WEAKLY RECOMMENDS the use of targeted temperature management to 33°C-35.5°C (vs. less structured management) in the treatment of term newborns who sustained asphyxia and exhibit acidosis and/or encephalopathy (weak recommendation, moderate quality of evidence).

To study the effects of high-dose epinephrine, compared with standard-dose epinephrine, on the dynamics of superficial cortical cerebral blood flow as well as global cerebral oxygenation during experimental cardiopulmonary resuscitation. We hypothesized that high-dose epinephrine might be unable to improve cerebral blood flow during cardiopulmonary resuscitation as compared with standard-dose epinephrine.Randomized controlled study.University hospital research laboratory.A total of 20 male anesthetized piglets.Ventricular fibrillation was induced. A nonintervention interval of 8 mins was followed by open-chest cardiopulmonary resuscitation. The animals were randomized to receive repeated bolus injections of either 20 microg/kg (standard-dose group, n = 10) or 200 microg/kg (high-dose group, n = 10) of epinephrine.Focal cortical cerebral blood flow was measured continuously by using laser Doppler flowmetry. The duration of blood flow increase was significantly shorter in the high-dose group after the second dose of epinephrine. In the high-dose group there was also a consistent tendency for lower peak levels and shorter duration of flow increase in response to repeated bolus doses of epinephrine. Cerebral oxygen extraction ratio was significantly lower in the high-dose group after administration of epinephrine.Repeated bolus doses of epinephrine 200 microg/kg, as compared with 20 microg/kg, do not improve superficial cortical cerebral blood flow during experimental open-chest cardiopulmonary resuscitation. High-dose epinephrine appears to induce vasoconstriction of cortical cerebral blood vessels resulting in redistribution of blood flow from superficial cortex. This might be one explanation for the failure of high-dose epinephrine to improve overall outcome in clinical trials.

To evaluate the blood flow and perfusion pressure differences observed during open- vs. closed-chest cardiopulmonary resuscitation (CPR), including the effects of epinephrine and sodium bicarbonate administration.Prospective, randomized, controlled trial.Experimental animal laboratory in a university hospital.A total of 35 anesthetized piglets.After tracheostomy and insertion of arterial, right atrial, and pulmonary arterial catheters, thoracotomy was performed with placement of a pulmonary arterial flow probe and left atrial catheter. Ventricular fibrillation was induced and followed by 15 mins of either open-chest (n = 14) or closed-chest (n = 21) CPR. A 4-min infusion of 50 mmol of sodium bicarbonate or saline was added at the start of CPR. After 8 mins of CPR, 0.5 mg of epinephrine was given intravenously, and after 15 mins, direct current (DC) shocks were used to revert the heart to sinus rhythm.Blood flow was studied using transit-time ultrasound flowmetry. In an extended group, intrathoracic pressure was measured for calculation of transmural pressure. Before epinephrine administration, mean pulmonary arterial flow (cardiac output) was reduced: a) during closed-chest CPR relatively more than pulmonary perfusion pressure but in proportion to systemic perfusion pressure; b) during open-chest CPR relatively less than pulmonary perfusion pressure but still in proportion to systemic perfusion pressure. Epinephrine administration temporarily increased systemic perfusion pressure during both closed- and open-chest CPR but temporarily decreased pulmonary perfusion pressure only during closed-chest CPR. After epinephrine administration, cardiac output temporarily decreased during both closed-and open-chest CPR.Open-chest CPR resulted in better cardiac output and systemic perfusion pressure than closed-chest CPR. However, cardiac output values obtained with both methods were much lower than previously reported. After epinephrine administration, cardiac output became extremely low with both methods.

To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.Prospective parallel-grouped placebo-controlled randomized interventional experimental study.University research unit.Healthy pigs.The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 microg endotoxin x kg x h for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-alpha (TNF-alpha) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-alpha concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-alpha peak or later will have very little or no effect on TNF-alpha-mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.