Albumin and Cardioprotection in On-Pump Cardiac Surgery-A Post Hoc Analysis of a Randomized Trial.

OBJECTIVES: To study the quantitative potency of plasma albumin on cardioprotection in terms of creatinine kinase-myocardial band mass (CK-MBm) in on-pump cardiac surgery. DESIGN: Post hoc analysis of a double-blinded randomized clinical trial. SETTING: Single-center study in the Helsinki University Hospital. PARTICIPANTS: A total of 1,386 adult on-pump cardiac surgical patients. INTERVENTION: Administration of 4% albumin (n = 693) or Ringers acetate (n = 693) for cardiopulmonary bypass priming and volume replacement intraoperatively and postoperatively during the first 24 hours. MEASUREMENTS AND MAIN RESULTS: Albumin concentration was measured preoperatively and intraoperatively (after protamine administration), and CK-MBm on the first postoperative morning. Multivariate linear regression analyses were measured in the whole cohort and the Ringer group. Plasma albumin concentration did not differ between the groups preoperatively (Ringer v albumin: 38.3 ± 5.0 g/L v 38.6 ± 4.5 g/L; p = 0.171) but differed intraoperatively (29.5 ± 5.2 g/L v 41.5 ± 6.0 g/L; p < 0.001). Creatinine kinase-myocardial band mass was higher in the Ringer (32.0 ± 34.8 µg/L) than in the albumin group (24.3 ± 33.0 µg/L) (p < 0.001). Aortic cross-clamping time associated with CK-MBm in the whole cohort (standardized ß = 0.376 [95% CI 0.315-0.437], p < 0.001) and the Ringer group (ß = 0.363 [0.273-0.452]; p < 0.001). Albumin administration in the whole cohort (ß = -0.156 [-0.201 to -0.111]; p < 0.001) and high intraoperative albumin concentration in the Ringer group (ß = -0.07 [-0.140 to -0.003]; p = 0.04) associated with reduced CK-MBm. Compared with ischemia-induced increase in CK-MBm, albumin's potency to reduce CK-MBm was 41% in the whole cohort (ß-value ratio of -0.156/0.376) and 19% in the Ringer group (ß-value ratio of -0.07/0.363). CONCLUSION: Both endogenous and exogenous albumin appear to be cardioprotective regarding CK-MBm release in on-pump cardiac surgery.

The effect of higher or lower mean arterial pressure on kidney function after cardiac arrest: a post hoc analysis of the COMACARE and NEUROPROTECT trials.

BACKGROUND: We aimed to study the incidence of acute kidney injury (AKI) in out-of-hospital cardiac arrest (OHCA) patients treated according to low-normal or high-normal mean arterial pressure (MAP) targets. METHODS: A post hoc analysis of the COMACARE (NCT02698917) and Neuroprotect (NCT02541591) trials that randomized patients to lower or higher targets for the first 36 h of intensive care. Kidney function was defined using the Kidney Disease Improving Global Outcome (KDIGO) classification. We used Cox regression analysis to identify factors associated with AKI after OHCA. RESULTS: A total of 227 patients were included: 115 in the high-normal MAP group and 112 in the low-normal MAP group. Eighty-six (38%) patients developed AKI during the first five days; 40 in the high-normal MAP group and 46 in the low-normal MAP group (p = 0.51). The median creatinine and daily urine output were 85 µmol/l and 1730 mL/day in the high-normal MAP group and 87 µmol/l and 1560 mL/day in the low-normal MAP group. In a Cox regression model, independent AKI predictors were no bystander cardiopulmonary resuscitation (p < 0.01), non-shockable rhythm (p < 0.01), chronic hypertension (p = 0.03), and time to the return of spontaneous circulation (p < 0.01), whereas MAP target was not an independent predictor (p = 0.29). CONCLUSION: Any AKI occurred in four out of ten OHCA patients. We found no difference in the incidence of AKI between the patients treated with lower and those treated with higher MAP after CA. Higher age, non-shockable initial rhythm, and longer time to ROSC were associated with shorter time to AKI. CLINICAL TRIAL REGISTRATION: COMACARE (NCT02698917), NEUROPROTECT (NCT02541591).

Hospital-administered ECPR for out-of-hospital cardiac arrest: an observational cohort study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is a treatment method for refractory out-of-hospital cardiac arrest (OHCA) requiring a complex chain of care. METHODS: All cases of OHCA between 1 January 2016 and 31 December 2021 in the Helsinki University Hospital catchment area in which the ECPR protocol was activated were included in the study. The protocol involved patient transport from the emergency site with ongoing mechanical cardiopulmonary resuscitation (CPR) directly to the cardiac catheterisation laboratory where the implementation of extracorporeal membrane oxygenation (ECMO) was considered. Cases of hypothermic cardiac arrest were excluded. The main outcomes were the number of ECPR protocol activations, duration of prehospital and in-hospital time intervals, and whether the ECPR candidates were treated using ECMO or not. RESULTS: The prehospital ECPR protocol was activated in 73 cases of normothermic OHCA. The mean patient age (SD) was 54 (±11) years and 67 (91.8%) of them were male. The arrest was witnessed in 67 (91.8%) and initial rhythm was shockable in 61 (83.6%) cases. The median ambulance response time (IQR) was 9 (7-11) min. All patients received mechanical CPR, epinephrine and/or amiodarone. Seventy (95.9%) patients were endotracheally intubated. The median (IQR) highest prehospital end-tidal CO2 was 5.5 (4.0-6.9) kPa.A total of 37 (50.7%) patients were treated with venoarterial ECMO within a median (IQR) of 84 (71-105) min after the arrest. Thirteen (35.1%) of them survived to discharge and 11 (29.7%) with a cerebral performance category (CPC) 1-2. In those ECPR candidates who did not receive ECMO, 8 (22.2%) received permanent return of spontaneuous circulation during transport or immediately after hospital arrival and 6 (16.7%) survived to discharge with a CPC 1-2. CONCLUSIONS: Half of the ECPR protocol activations did not lead to ECMO treatment. However, every fourth ECPR candidate and every third patient who received ECMO-facilitated resuscitation at the hospital survived with a good neurological outcome.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Albumin Infusion and Blood Loss After Cardiac Surgery.

BACKGROUND: In the recent ALBICS (ALBumin In Cardiac Surgery) trial, 4% albumin used for cardiopulmonary bypass priming and volume replacement increased perioperative bleeding compared with Ringer acetate. In the present exploratory study, albumin-related bleeding was further characterized. METHODS: Ringer acetate and 4% albumin were compared in a randomized, double-blinded fashion in 1386 on-pump adult cardiac surgery patients. The study end points for bleeding were the Universal Definition of Perioperative Bleeding (UDPB) class and its components. RESULTS: The UDPB bleeding grades were higher in the albumin group than the Ringer group: "insignificant" (albumin vs Ringer: 47.5% vs 62.9%), "mild" (12.7% vs 8.9%), "moderate" (28.7% vs 24.4%), "severe" (10.2% vs 3.2%), and "massive" (0.9% vs. 0.6%; P < .001). Patients in the albumin group received red blood cells (45.2% vs 31.5%; odds ratio [OR], 1.80; 95% CI, 1.44-2.24; P < .001), platelets (33.3% vs 21.8%; OR, 1.79; 95% CI, 1.41-2.28; P < .001), and fibrinogen (5.6% vs 2.6%; OR, 2.24; 95% CI, 1.27-3.95; P < .05), and underwent resternotomy (5.3% vs 1.9%; OR, 2.95; 95% CI, 1.55-5.60, P < .001) more often than patients in the Ringer group. The strongest predictors of bleeding were albumin group allocation (OR, 2.18; 95% CI, 1.74-2.74) and complex (OR, 2.61; 95% CI, 2.02-3.37) and urgent surgery (OR, 1.63; 95% CI, 1.26-2.13). In interaction analysis, the effect of albumin on the risk of bleeding was stronger in patients on preoperative acetylsalicylic acid. CONCLUSIONS: Perioperative administration of albumin, compared with Ringer's acetate, resulted in increased blood loss and higher UDBP class. The magnitude of this effect was similar to the complexity and urgency of the surgery.

Effect of 4% Albumin Solution vs Ringer Acetate on Major Adverse Events in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass: A Randomized Clinical Trial.

Importance: In cardiac surgery, albumin solution may maintain hemodynamics better than crystalloids and reduce the decrease in platelet count and excessive fluid balance, but randomized trials are needed to compare the effectiveness of these approaches in reducing surgical complications. Objective: To assess whether 4% albumin solution compared with Ringer acetate as cardiopulmonary bypass prime and perioperative intravenous volume replacement solution reduces the incidence of major perioperative and postoperative complications in patients undergoing cardiac surgery. Design, Setting, and Participants: A randomized, double-blind, single-center clinical trial in a tertiary university hospital during 2017-2020 with 90-day follow-up postoperatively involving patients undergoing on-pump coronary artery bypass grafting; aortic, mitral, or tricuspid valve surgery; ascending aorta surgery without hypothermic circulatory arrest; and/or the maze procedure were randomly assigned to 2 study groups (last follow-up was April 13, 2020). Interventions: The patients received in a 1:1 ratio either 4% albumin solution (n = 693) or Ringer acetate solution (n = 693) as cardiopulmonary bypass priming and intravenous volume replacement intraoperatively and up to 24 hours postoperatively. Main Outcomes and Measures: The primary outcome was the number of patients with at least 1 major adverse event: death, myocardial injury, acute heart failure, resternotomy, stroke, arrhythmia, bleeding, infection, or acute kidney injury. Results: Among 1407 patients randomized, 1386 (99%; mean age, 65.4 [SD, 9.9] years; 1091 men [79%]; 295 women [21%]) completed the trial. Patients received a median of 2150 mL (IQR, 1598-2700 mL) of study fluid in the albumin group and 3298 mL (IQR, 2669-3500 mL) in the Ringer group. The number of patients with at least 1 major adverse event was 257 of 693 patients (37.1%) in the albumin group and 234 of 693 patients (33.8%) in the Ringer group (relative risk albumin/Ringer, 1.10; 95% CI, 0.95-1.27; P = .20), an absolute difference of 3.3 percentage points (95% CI, -1.7 to 8.4). The most common serious adverse events were pulmonary embolus (11 [1.6%] in the albumin group vs 8 [1.2%] in the Ringer group), postpericardiotomy syndrome (9 [1.3%] in both groups), and pleural effusion with intensive care unit or hospital readmission (7 [1.0%] in the albumin group vs 9 [1.3%] in the Ringer group). Conclusions and Relevance: Among patients undergoing cardiac surgery with cardiopulmonary bypass, treatment with 4% albumin solution for priming and perioperative intravenous volume replacement solution compared with Ringer acetate did not significantly reduce the risk of major adverse events over the following 90 days. These findings do not support the use of 4% albumin solution in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02560519.

Beta-blocker treatment in the critically ill: a systematic review and meta-analysis.

BACKGROUND: Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors and inotropes. Excessive adrenergic stress has been associated with organ dysfunction and higher mortality. ß-Blockers may reduce the adrenergic burden, but they may also compromise perfusion to vital organs thus worsening organ dysfunction. To assess the effect of treatment with ß-blockers in critically ill adults, we conducted a systematic review and meta-analysis of randomized controlled trials. MATERIALS AND METHODS: We conducted a search from three major databases: Ovid Medline, the Cochrane Central Register for Controlled Trials and Scopus database. Two independent reviewers screened, selected, and assessed the included articles according to prespecified eligibility criteria. We assessed risk of bias of eligible articles according to the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Sixteen randomized controlled trials comprising 2410 critically ill patients were included in the final review. A meta-analysis of 11 trials including 2103 patients showed a significant reduction in mortality in patients treated with ß-blockers compared to control (risk ratio 0.65, 95%CI 0.53-0.79; p < .0001). There was no significant difference in mean arterial pressure or vasopressor load. Quality of life, biventricular ejection fraction, blood lactate levels, cardiac biomarkers and mitochondrial function could not be included in meta-analysis due to heterogenous reporting of outcomes. CONCLUSIONS: In this systematic review we found that ß-blocker treatment reduced mortality in critical illness. Use of ß-blockers in critical illness thus appears safe after initial hemodynamic stabilization. High-quality RCT's are needed to answer the questions concerning optimal target group of patients, timing of ß-blocker treatment, choice of ß-blocker, and choice of physiological and hemodynamic parameters to target during ß-blocker treatment in critical illness.KEY MESSAGESA potential outcome benefit of ß-blocker treatment in critical illness exists according to the current review and meta-analysis. Administration of ß-blockers to resuscitated patients in the ICU seems safe in terms of hemodynamic stability and outcome, even during concomitant vasopressor administration. However, further studies, preferably large RCTs on ß-blocker treatment in the critically ill are needed to answer the questions concerning timing and choice of ß-blocker, patient selection, and optimal hemodynamic targets.

Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial.

BACKGROUND: Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. METHODS: A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0-12, 12-24, 24-48 h time-periods and integrated over 0-48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3-5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury. RESULTS: In 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0-48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [- 1.17 to 2.94] vs. - 2.71 95% CI [- 4.16 to - 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15-650] vs 20 IQR [13-199] pg/ml, p = 0.042). CONCLUSION: Impaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917 .

New-onset atrial fibrillation in the intensive care unit: Protocol for an international inception cohort study (AFIB-ICU).

INTRODUCTION: New-onset atrial fibrillation (NOAF) is frequently observed in critically ill patients and may be associated with prolonged hospital stay and increased mortality. Considerable variation exists in the reported frequencies of NOAF due to the lack of a standardised definition and detection method. Importantly, there are limited data on NOAF in the intensive care unit (ICU). Thus, we aim to provide contemporary epidemiological data on NOAF in the ICU. METHODS AND ANALYSIS: We have designed an international inception cohort study including at least 1,000 consecutive adult patients acutely admitted to the ICU without prior history of persistent or permanent AF. We will present data on the incidence, risk factors, used management strategies and outcomes of NOAF. We will register data daily during stay in the ICU for a maximum of 90 days after admission. The incidence of NOAF and management strategies used will be presented descriptively, and we will use Cox regression analyses including competing risk analyses to assess risk factors for NOAF and any association with 90-day mortality. CONCLUSION: The outlined international AFIB-ICU inception cohort study will provide contemporary data on the incidence, risk factors, used management strategies and outcomes of NOAF in adult ICU patients. ETHICS AND DISSEMINATION: This observational study poses no risk to the included patients. All participating sites will obtain relevant approvals according to national laws before patient enrollment. Funding sources will have no influence on data handling, analyses or writing of the manuscript. The study report(s) will be submitted to an international peer-reviewed journal.

The Association Between Arterial Oxygen Level and Outcome in Neurocritically Ill Patients is not Affected by Blood Pressure.

BACKGROUND: In neurocritically ill patients, one early mechanism behind secondary brain injury is low systemic blood pressure resulting in inadequate cerebral perfusion and consequent hypoxia. Intuitively, higher partial pressures of arterial oxygen (PaO2) could be protective in case of inadequate cerebral circulation related to hemodynamic instability. STUDY PURPOSE: We examined whether the association between PaO2 and mortality is different in patients with low compared to normal and high mean arterial pressure (MAP) in patients after various types of brain injury. METHODS: We screened the Finnish Intensive Care Consortium database for mechanically ventilated adult (≥ 18) brain injury patients treated in several tertiary intensive care units (ICUs) between 2003 and 2013. Admission diagnoses included traumatic brain injury, cardiac arrest, subarachnoid and intracranial hemorrhage, and acute ischemic stroke. The primary exposures of interest were PaO2 (recorded in connection with the lowest measured PaO2/fraction of inspired oxygen ratio) and the lowest MAP, recorded during the first 24 h in the ICU. PaO2 was grouped as follows: hypoxemia (< 8.2 kPa, the lowest 10th percentile), normoxemia (8.2-18.3 kPa), and hyperoxemia (> 18.3 kPa, the highest 10th percentile), and MAP was divided into equally sized tertiles (< 60, 60-68, and > 68 mmHg). The primary outcome was 1-year mortality. We tested the association between hyperoxemia, MAP, and mortality with a multivariable logistic regression model, including the PaO2, MAP, and interaction of PaO2*MAP, adjusting for age, admission diagnosis, premorbid physical performance, vasoactive use, intracranial pressure monitoring use, and disease severity. The relationship between predicted 1-year mortality and PaO2 was visualized with locally weighted scatterplot smoothing curves (Loess) for different MAP levels. RESULTS: From a total of 8290 patients, 3912 (47%) were dead at 1 year. PaO2 was not an independent predictor of mortality: the odds ratio (OR) for hyperoxemia was 1.16 (95% CI 0.85-1.59) and for hypoxemia 1.24 (95% CI 0.96-1.61) compared to normoxemia. Higher MAP predicted lower mortality: OR for MAP 60-68 mmHg was 0.73 (95% CI 0.64-0.84) and for MAP > 68 mmHg 0.80 (95% CI 0.69-0.92) compared to MAP < 60 mmHg. The interaction term PaO2*MAP was nonsignificant. In Loess visualization, the relationship between PaO2 and predicted mortality appeared similar in all MAP tertiles. CONCLUSIONS: During the first 24 h of ICU treatment in mechanically ventilated brain injured patients, the association between PaO2 and mortality was not different in patients with low compared to normal MAP.

Effect and safety of 4% albumin in the treatment of cardiac surgery patients: study protocol for the randomized, double-blind, clinical ALBICS (ALBumin In Cardiac Surgery) trial.

BACKGROUND: In cardiac surgery with cardiopulmonary bypass (CPB), large amounts of fluids are administered. CPB priming with crystalloid solution causes marked hemodilution and fluid extravasation. Colloid solutions may reduce fluid overload because they have a better volume expansion effect than crystalloids. The European Medicines Agency does not recommend the use of hydroxyethyl starch solutions (HES) due to harmful renal effects. Albumin solution does not impair blood coagulation but the findings on kidney function are conflicting. On the other hand, albumin may reduce endothelial glycocalyx destruction and decrease platelet count during CPB. No large randomized, double-blind, clinical trials have compared albumin solution to crystalloid solution in cardiac surgery. METHODS/DESIGN: In this single-center, double-blind, randomized controlled trial comprising 1386 adult cardiac surgery patients, 4% albumin solution will be compared to Ringer's acetate solution in CPB priming and volume replacement up to 3200 mL during surgery and the first 24 h of intensive care unit stay. The primary efficacy outcome is the number of patients with at least one major adverse event (MAE) during 90 postoperative days (all-cause death, acute myocardial injury, acute heart failure or low output syndrome, resternotomy, stroke, major arrhythmia, major bleeding, infection compromising post-procedural rehabilitation, acute kidney injury). Secondary outcomes are total number of MAEs, incidence of major adverse cardiac events (MACE; cardiac death, acute myocardial injury, acute heart failure, arrhythmia), amount of each type of blood product transfused (red blood cells, fresh frozen plasma, platelets), total fluid balance at the end of the intervention period, total measured blood loss, development of acute kidney injury, days alive without mechanical ventilation in 90 days, days alive outside intensive care unit at 90 days, days alive at home at 90 days, and 90-day mortality. DISCUSSION: The findings of this study will provide new evidence regarding efficacy and safety of albumin solution in adult patients undergoing cardiac surgery with CPB. TRIAL REGISTRATION: EudraCT (clinicaltrialsregister.eu) 2015-002556-27 Registered 11 Nov 2016 and ClinicalTrials.gov NCT02560519. Registered 25 Sept 2015.

Near-Infrared Spectroscopy in Adult Circulatory Shock: A Systematic Review.

BACKGROUND: Circulatory shock affects every third patient in intensive care units and is associated with high mortality. Near-infrared spectroscopy (NIRS) could serve as a means for monitoring tissue perfusion in circulatory shock. PURPOSE: To assess the evidence of NIRS monitoring in circulatory shock, we conducted a systematic review of the literature. METHODS: The study protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO). We searched PubMed, Ovid MEDLINE, Scopus, and EBM Reviews databases. The reference lists of included articles, last volumes of key journals, and NIRS monitor manufacturers' webpages were searched manually. Two reviewers independently selected included studies. The quality of studies was assessed. The qualitative synthesis was guided by 3 questions: First, does NIRS monitoring improve patient-centered outcomes in adult circulatory shock patient? Second, do NIRS-derived parameters predict patient-centered outcomes, such as mortality and organ dysfunction, and third, does NIRS monitoring give additional information to guide treatment decisions? MAIN RESULTS: Eighteen observational studies with 927 patients were included. Because of considerable clinical heterogeneity of the data, we were not able to perform a meta-analysis. Also, due to lack of randomized controlled trials, the first review question could not be answered. Based on the current review, baseline tissue oxygen saturation (StO2) however seems to predict mortality and identify patients with most severe forms of circulatory shock. CONCLUSIONS: Near-infrared spectroscopy-derived StO2 can predict mortality in circulatory shock, but high-quality data on the impact of NIRS monitoring are lacking. Furthermore, the marked heterogeneity of the studies makes combining the results of individual studies difficult. Standardization of methodology and clinical randomized trials are needed before wider clinical use.

Cerebrovascular autoregulation following cardiac arrest: Protocol for a post hoc analysis of the randomised COMACARE pilot trial.

BACKGROUND: Approximately two-thirds of the mortality following out of hospital cardiac arrest is related to devastating neurological injury. Previous small cohort studies have reported an impaired cerebrovascular autoregulation following cardiac arrest, but no studies have assessed the impact of differences in oxygen and carbon dioxide tensions in addition to mean arterial pressure management. METHODS: This is a protocol and statistical analysis plan to assess the correlation between changes in cerebral tissue oxygenation and arterial pressure as measure of cerebrovascular autoregulation, the tissue oxygenation index, in patients following out of hospital cardiac arrest and in healthy volunteers. The COMACARE study included 120 comatose survivors of out of hospital cardiac arrest admitted to ICU and managed with low-normal or high-normal targets for mean arterial pressure, arterial oxygen and carbon dioxide partial pressures. In addition, 102 healthy volunteers have been investigated as a reference group for the tissue oxygenation index. In both cohorts, the cerebral tissue oxygenation was measured by near infrared spectroscopy. CONCLUSIONS: Cerebrovascular autoregulation is critical to maintain homoeostatic brain perfusion. This study of changes in autoregulation following out of hospital cardiac arrest over the first 48 hours, as compared to data from healthy volunteers, will generate important physiological information that may guide the rationale and design of interventional studies.

Near-infrared spectroscopy after out-of-hospital cardiac arrest.

BACKGROUND: Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO2) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients. METHODS: We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO2 in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO2 and serum NSE concentrations and the association between rSO2 and good (CPC 1-2) and poor (CPC 3-5) neurological outcome. RESULTS: The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4-25.0) µg/l in patients with good neurological outcome and 35.2 (22.6-95.8) µg/l in those with poor outcome, p < 0.001. We found no significant correlation between median rSO2 and NSE at 48 h, rs = - 0.08, p = 0.392. The median (IQR) rSO2 during the first 36 h of intensive care was 70.0% (63.5-77.0%) in patients with good outcome and 71.8% (63.3-74.0%) in patients with poor outcome, p = 0.943. There was no significant association between rSO2 over time and neurological outcome. In a binary logistic regression model, rSO2 was not a statistically significant predictor of good neurological outcome (odds ratio 0.99, 95% confidence interval 0.94-1.04, p = 0.635). CONCLUSIONS: We found no association between cerebral oxygenation measured with NIRS and NSE concentrations or outcome in patients resuscitated from OHCA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.

Early Lactate Values After Out-of-Hospital Cardiac Arrest: Associations With One-Year Outcome.

BACKGROUND: Previous studies have shown associations between high admission serum lactate, lower lactate clearance, and increased short-term mortality after out-hospital cardiac arrest (OHCA). We studied whether lactate levels predict long- term outcome after OHCA. METHODS: We included 458 OHCA patients with lactate measurements during intensive care unit (ICU) stay from the prospective FINNRESUSCI study. We evaluated thresholds for time-weighted (TW) mean lactate values for the first 24, 48, and 72 h. We analyzed lactate clearance and used multivariate regression to assess the prognostic value of the different measurement time points. RESULTS: The admission lactate (median [IQR] 3.06 [2.68-3.44] mmol/L vs 4.76 [4.29-5.23] mmol/L) and the last measured lactate (0.98 [0.90-1.06] mmol/L vs 2.40 [2.03-2.78] mmol/L) were higher in non-survivors than in survivors, as were the lowest (0.73 [0.67-0.79] mmol/L vs 1.83 [1.52-2.14] mmol/L) and the highest (3.44 [3.05-3.83] mmol/L vs 5.25 [4.76-5.74] mmol/L) lactate values (all P < 0.001). Time-weighted mean lactate values for the first 24, 48, 72, and for the entire ICU stay were lower in patients with good outcome (P < 0.001). In multivariate backward regression models, time-weighted mean lactate for the entire ICU stay (OR 1.41 per mmol/L, CI 95% 1.08-1.86, P = 0.013) and the last measured lactate in the ICU (OR 2.16 per mmol/L, CI 95% 1.47-3.18, P < 0.001) were independent predictors of poor 1-year outcome. CONCLUSIONS: In the present study time-weighted mean lactate values for the entire ICU stay, and the last measured lactate value in the ICU, but not admission lactate or lactate clearance were independent predictors of poor 1-year outcome.

Efficacy and safety of intravenous esmolol for cardiac protection in non-cardiac surgery. A systematic review and meta-analysis.

Haemodynamic instability predisposes patients to cardiac complications in non-cardiac surgery. Esmolol, a short-acting cardioselective beta-adrenergic blocker might be efficient in perioperative cardiac protection, but could affect other vital organs, such as the kidneys, and post-discharge survival. We performed a systematic review on the use of esmolol for perioperative cardiac protection. We searched PubMed, Ovid Medline and Cochrane Central Register for Controlled trials. Eligible randomized controlled studies (RCTs) reported a perioperative esmolol intervention with at least one of the primary (major cardiac or renal complications during the first 30 postoperative days) or secondary (postoperative adverse effects and all-cause mortality) outcomes. We included 196 adult patients from three RCTs. Esmolol significantly reduced postoperative myocardial ischaemia, RR =0.43 [95% confidence interval, CI: 0.21-0.88], p = .02. No association with clinically significant bradycardia and hypotension compared to patients receiving control treatment could be confirmed (RR =7.4 [95% CI: 0.29-139.81], p = .18 and RR =2.21 [95% CI: 0.34-14.36], p = .41, respectively). No differences regarding other outcomes were observed. No study reported postoperative renal outcomes. Esmolol seems promising for the prevention of perioperative myocardial ischaemia. However, the association with bradycardia and hypotension remains unclear. Randomized trials investigating the effect of ß1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted. Key messages Short-acting cardioselective esmolol seems efficient in the prevention of perioperative myocardial ischaemia. The possibly increased risk of bradycardia and hypotension with short-acting intravenous beta blockade could not be confirmed or refuted by available data. Future adequately powered trials investigating the effect of ß1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted.

Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial.

PURPOSE: We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury. METHODS: In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 23 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65-75 mmHg) vs. high-normal (80-100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest. RESULTS: We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p < 0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2-34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6-30.9 µg/L) in the high-normal MAP group, p = 0.522. We found no differences in the secondary outcomes. CONCLUSIONS: Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.

Lower heart rate is associated with good one-year outcome in post-resuscitation patients.

BACKGROUND: Optimal hemodynamic goals in post-resuscitation patients are not clear. Previous studies have reported an association between lower heart rate and good outcome in patients receiving targeted temperature management (TTM) after out-of-hospital cardiac arrest. METHODS: We analyzed heart rate (HR) and outcome data of 504 post-resuscitation patients from the prospectively collected database of the FINNRESUSCI study. One-year neurologic outcome was dichotomized by the Cerebral Performance Category (CPC) to good (1-2) or poor (3-5). RESULTS: Of 504 patients, 40.1% (202/504) had good and 59.9% (302/ 504) had poor one-year neurologic outcome. Patients with good outcome had lower time-weighted mean HR during the first 48 h in the ICU (69.2 bpm [59.2-75.1] vs. 76.6 bpm [65.72-89.6], p < 0.001) and the first 72 h in the ICU (71.2 bpm [65.0-79.0] vs. 77.1 bpm [69.1-90.1, p < 0.001]). The percentage of HR registrations below HR threshold values (60, 80 and 100 bpm) were higher for patients with good neurologic outcome, p < 0.001 for all. Lower time-weighted HR for 0-48 h and 0-72 h, and a higher percentage of HR recordings below threshold values were independently associated with good neurological one-year outcome (p < 0.05 for all). When TTM and non-TTM patients were analyzed separately, HR parameters were independently associated with one-year neurologic outcome only in non-TTM patients. CONCLUSION: Lower heart rate was independently associated with good neurologic outcome. Whether HR in post-resuscitation patients is a prognostic indicator or an important variable to be targeted by treatment, needs to be assessed in future prospective controlled clinical trials.

Procalcitonin and Presepsin as Prognostic Markers After Out-of-Hospital Cardiac Arrest.

BACKGROUND: Patients resuscitated from cardiac arrest commonly develop an inflammatory response called post-cardiac arrest syndrome that clinically resembles septic shock.Procalcitonin and presepsin are associated with inflammation. We hypothesized that these biomarkers reflect the severity of post-cardiac arrest syndrome and predict short-term hemodynamical instability and long-term neurological outcome after cardiac arrest. METHODS: As a subcohort analysis of a prospective, observational, multicenter study "FINNRESUSCI," we obtained plasma from 277 intensive care unit (ICU) patients treated following out-of-hospital cardiac arrest (OHCA). Procalcitonin and presepsin levels were measured 0 to 6 h from ICU admission and 24, 48, and 96 h thereafter. We defined poor outcome as a 12-month Cerebral Performance Category of 3 to 5. We tested statistical associations between biomarkers and hemodynamical parameters and outcome with regression models. RESULTS: Plasma procalcitonin had best predictive value for 12-month poor outcome at 96 h (AUC 0.76; 95% CI 0.68-0.83) and presepsin at ICU admission (AUC 0.72; 95% CI 0.65-0.78). Elevated procalcitonin concentration at ICU admission predicted unstable hemodynamics in the following 48 h in a linear regression model. In a multivariate logistic regression model with clinical variables, only procalcitonin at 96 h had independent prognostic value for poor 12-month neurological outcome. CONCLUSIONS: Elevated procalcitonin is associated with hemodynamical instability and worsened long-term outcome in OHCA patients. The association is not strong enough for it to be used as a single predictor. Presepsin did not provide clinically relevant information for risk stratification after OHCA.

Epicardial delivery of autologous atrial appendage micrografts during coronary artery bypass surgery-safety and feasibility study.

BACKGROUND: The atrial appendages are a tissue reservoir for cardiac stem cells. During on-pump coronary artery bypass graft (CABG) surgery, part of the right atrial appendage can be excised upon insertion of the right atrial cannula of the heart-lung machine. In the operating room, the removed tissue can be easily cut into micrografts for transplantation. This trial aims to assess the safety and feasibility of epicardial transplantation of atrial appendage micrografts in patients undergoing CABG surgery. METHODS/DESIGN: Autologous cardiac micrografts are made from leftover right atrial appendage during CABG of 6 patients. Atrial appendage is mechanically processed to micrografts consisting of atrial appendage-derived cells (AADCs) and their extracellular matrix (ECM). The micrografts are epicardially transplanted in a fibrin gel and covered with a tissue-engineered ECM sheet. Parameters including echocardiography-reflecting cardiac insufficiency-are studied pre- and post-operatively as well as at 3 and 6 months of the follow-up. Cardiac functional magnetic resonance imaging is performed preoperatively and at 6-month follow-up. The primary outcome measures are patient safety in terms of hemodynamic and cardiac function over time and feasibility of therapy administration in a clinical setting. Secondary outcome measures are left ventricular wall thickness, change in the amount of myocardial scar tissue, changes in left ventricular ejection fraction, plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, New York Heart Association class, days in hospital, and changes in the quality of life. Twenty patients undergoing routine CAGB surgery will be recruited to serve as a control group. DISCUSSION: This study aims to address the surgical feasibility and patient safety of epicardially delivered atrial appendage micrografts during CABG surgery. Delivery of autologous micrografts and AADCs has potential applications for cell and cell-based gene therapies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02672163. Date of registration: 02.02.2016.