Higher Intensity Thromboprophylaxis Regimens and Pulmonary Embolism in Critically Ill Coronavirus Disease 2019 Patients.

OBJECTIVES: To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients. DESIGN: Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020. SETTING: ICU of an University Hospital in Belgium. PATIENTS AND INTERVENTIONS: Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin). MEASUREMENTS AND MAIN RESULTS: Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4-8 d) since ICU admission and 12 days (9-16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78-1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%-odds ratio 0.13 [0.02-0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24-3.26]; p = 0.99). CONCLUSIONS: In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.

Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.

BACKGROUND: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. METHODS: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. RESULTS: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. CONCLUSIONS: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Non-occlusive Mesenteric Ischemia as a Fatal Complication in Acute Pancreatitis: A Case Series.

BACKGROUND: Vascular complications of severe acute pancreatitis are well known and largely described unlike non-occlusive mesenteric ischemia, which is a rare and potentially fatal complication. Non-occlusive mesenteric ischemia is an acute mesenteric ischemia without thrombotic occlusion of blood vessels, poorly described as a complication of acute pancreatitis. METHODS: We retrospectively reviewed a prospectively maintained registry of all pancreatic diseases referred to our center from 2013 to 2018, in order to determine the causes of early death. We identified three patients who died within 48 h after hospital admission from severe acute pancreatitis complicated by irreversible non-occlusive mesenteric ischemia. Their clinical presentation, management, and outcomes were herein reported. RESULTS: Three consecutive patients with severe acute pancreatitis developed non-occlusive mesenteric ischemia within the first 5 days after onset of symptoms and died 48 h after non-occlusive mesenteric ischemia diagnosis despite optimal intensive care management and surgery, giving a prevalence of 3/609 (0.5%). Symptoms were unspecific with consequently potential delayed diagnosis and management. High doses of norepinephrine required for hemodynamic support (n = 3) potentially leading to splanchnic vessels vasoconstriction, transient hypotension (n = 3), and previous severe ischemic cardiomyopathy (n = 1) could be involved as precipitating factors of non-occlusive mesenteric ischemia. CONCLUSION: Non-occlusive mesenteric ischemia can be a fatal complication of acute pancreatitis but is also challenging to diagnose. Priority is to reestablish a splanchno-mesenteric perfusion flow. Surgery should be offered in case of treatment failure or deterioration but is still under debate in early stage, to interrupt the vicious circle of intestinal hypoperfusion and ischemia.

The impact of extracerebral organ failure on outcome of patients after cardiac arrest: an observational study from the ICON database.

BACKGROUND: We used data from a large international database to assess the incidence and impact of extracerebral organ dysfunction on prognosis of patients admitted after cardiac arrest (CA). METHODS: This was a sub-analysis of the Intensive Care Over Nations (ICON) database, which contains data from all adult patients admitted to one of 730 participating intensive care units (ICUs) in 84 countries from 8-18 May 2012, except admissions for routine postoperative surveillance. For this analysis, patients admitted after CA (defined as those with "post-anoxic coma" or "cardiac arrest" as the reason for ICU admission) were included. Data were collected daily in the ICU for a maximum of 28 days; patients were followed up for outcome data until death, hospital discharge, or a maximum of 60 days in-hospital. Favorable neurological outcome was defined as alive at hospital discharge with a last available neurological Sequential Organ Failure Assessment (SOFA) subscore of 0-2. RESULTS: Among the 469 patients admitted after CA, 250 (53 %) had had out-of-hospital CA; 210 (45 %) patients died in the ICU and 357 (76 %) had an unfavorable neurological outcome. Non-survivors had a higher incidence of renal (43 vs. 16 %), cardiovascular (56 vs. 45 %), and respiratory (62 vs. 48 %) failure on admission and during the ICU stay than survivors (all p < 0.05). Similar results were found for patients with unfavorable vs. favorable neurological outcomes. In multivariable analysis, independent predictors of ICU mortality were renal failure on admission, high admission Simplified Acute Physiology Score (SAPS) II, high maximum serum lactate levels within the first 24 h after ICU admission, and development of sepsis. Independent predictors of unfavorable neurological outcome were mechanical ventilation on admission, high admission SAPS II score, and neurological dysfunction on admission. CONCLUSIONS: In this multicenter cohort, extracerebral organ dysfunction was common in CA patients. Renal failure on admission was the only extracerebral organ dysfunction independently associated with higher ICU mortality.

Noninvasive ventilation and survival in acute care settings: a comprehensive systematic review and metaanalysis of randomized controlled trials.

OBJECTIVE: Noninvasive ventilation is increasingly applied to prevent or treat acute respiratory failure, but its benefit on survival is still controversial for many indications. We performed a metaanalysis of randomized controlled trials focused on the effect of noninvasive ventilation on mortality. DATA SOURCES: BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials (updated December 31, 2013) were searched. STUDY SELECTION: We included all the randomized controlled trials published in the last 20 years performed in adults, reporting mortality, comparing noninvasive ventilation to any other treatment for prevention or treatment of acute respiratory failure or as a tool allowing an earlier extubation. Studies with unclear methodology, comparing two noninvasive ventilation modalities, or in palliative settings were excluded. DATA EXTRACTION: We extracted data on mortality, study design, population, clinical setting, comparator, and follow-up duration. DATA SYNTHESIS: Seventy-eight studies were analyzed. Noninvasive ventilation was associated with a reduction in mortality (12.6% in the noninvasive ventilation group vs 17.8% in the control arm; risk ratio=0.73 [0.66-0.81]; p<0.001; number needed to treat=19 with 7,365 patients included) at the longest available follow-up. Mortality was reduced when noninvasive ventilation was used to treat (14.2% vs 20.6%; risk ratio=0.72; p<0.001; number needed to treat=16, with survival improved in pulmonary edema, chronic obstructive pulmonary disease exacerbation, acute respiratory failure of mixed etiologies, and postoperative acute respiratory failure) or to prevent acute respiratory failure (5.3% vs 8.3%; risk ratio=0.64 [0.46-0.90]; number needed to treat=34, with survival improved in postextubation ICU patients), but not when used to facilitate an earlier extubation. Overall results were confirmed for hospital mortality. Patients randomized to noninvasive ventilation maintained the survival benefit even in studies allowing crossover of controls to noninvasive ventilation as rescue treatment. CONCLUSIONS: This comprehensive metaanalysis suggests that noninvasive ventilation improves survival in acute care settings. The benefit could be lost in some subgroups of patients if noninvasive ventilation is applied late as a rescue treatment. Whenever noninvasive ventilation is indicated, an early adoption should be promoted.

Democracy-based consensus in medicine.

BACKGROUND: High-quality evidence and derived guidelines, as typically published in major academic journals, are a major process that shapes physician decision-making worldwide. However, for many aspects of medical practice, there is a lack of High-quality evidence or an overload of somewhat contradictory low-quality information, which makes decision-making a difficult, uncertain, and unpredictable process. When the issues in question are important and evidence limited or controversial, the medical community seeks to establish common ground for "best practice" through consensus conferences and consensus statements or guidelines. Such consensus statements are seen as a useful tool to establish expert agreement, define the boundaries of acceptable practice, provide priorities for the research agenda, and obtain opinions from different countries and healthcare systems. This standard approach, however, can be criticized for being elitist, noninclusive, and poorly representative of the community of clinicians who will have to make decisions about the implementation of such recommendations. OBJECTIVE: Accordingly, the authors propose a new model based on a combination of a local core meeting (detailed review and expert input) followed by a worldwide web-based network assessment (democracy-based consensus). The authors already have applied this approach to develop consensus on all nonsurgical interventions that increase or reduce perioperative mortality in critically ill patients and in those with acute kidney injury. METHODS: The methodology was based on 5 sequential local and web-based steps. RESULTS: Both a panel of experts and a large number of professionals from all over the world were involved, giving birth to a new type of "democracy-based consensus." CONCLUSIONS: This new type of "democracy-based consensus" has the potential to increase grass-root clinician involvement, expand the reach to less-developed countries, provide a more global perspective on proposed interventions, and perhaps more importantly, increase awareness, ownership, and the statistical likelihood of subsequent implementation.

Monocentric, Retrospective Study on Infectious Complications within One Year after Solid-Organ Transplantation at a Belgian University Hospital.

The epidemiology, diagnostic methods and management of infectious complications after solid-organ transplantation (SOT) are evolving. The aim of our study is to describe current infectious complications in the year following SOT and risk factors for their development and outcome. We conducted a retrospective study in adult SOT recipients in a Belgian university hospital between 2018 and 2019. We gathered demographic characteristics, comorbidities leading to transplantation, clinical, microbiological, surgery-specific and therapeutic data concerning infectious episodes, and survival status up to one year post-transplantation. Two-hundred-and-thirty-one SOT recipients were included (90 kidneys, 79 livers, 35 lungs, 19 hearts and 8 multiple organs). We observed 381 infections in 143 (62%) patients, due to bacteria (235 (62%)), viruses (67 (18%)), and fungi (32 (8%)). Patients presented a median of two (1-5) infections, and the first infection occurred during the first six months. Nineteen (8%) patients died, eleven (58%) due to infectious causes. Protective factors identified against developing infection were obesity [OR [IC]: 0.41 [0.19-0.89]; p = 0.025] and liver transplantation [OR [IC]: 0.21 [0.07-0.66]; p = 0.007]. Risk factors identified for developing an infection were lung transplantation [OR [IC]: 6.80 [1.17-39.36]; p = 0.032], CMV mismatch [OR [IC]: 3.53 [1.45-8.64]; p = 0.006] and neutropenia [OR [IC]: 2.87 [1.27-6.47]; p = 0.011]. Risk factors identified for death were inadequate cytomegalovirus prophylaxis, infection severity and absence of pneumococcal vaccination. Post-transplant infections were common. Addressing modifiable risk factors is crucial, such as pneumococcal vaccination.

Carbon Dioxide Targets in Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

Target values for arterial carbon dioxide tension (PaCO2) in extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) are unknown. We hypothesized that lower PaCO2 values on ECMO would be associated with lighter sedation. We used data from two independent patient cohorts with ARDS spending 1,177 days (discovery cohort, 69 patients) and 516 days (validation cohort, 70 patients) on ECMO and evaluated the associations between daily PaCO2, pH, and bicarbonate (HCO3) with sedation. Median PaCO2 was 41 (interquartile range [IQR] = 37-46) mm Hg and 41 (IQR = 37-45) mm Hg in the discovery and the validation cohort, respectively. Lower PaCO2 and higher pH but not bicarbonate (HCO3) served as significant predictors for reaching a Richmond Agitation Sedation Scale (RASS) target range of -2 to +1 (lightly sedated to restless). After multivariable adjustment for mortality, tracheostomy, prone positioning, vasoactive inotropic score, Simplified Acute Physiology Score (SAPS) II or Sequential Organ Failure Assessment (SOFA) Score and day on ECMO, only PaCO2 remained significantly associated with the RASS target range (adjusted odds ratio 1.1 [95% confidence interval (CI) = 1.01-1.21], p = 0.032 and 1.29 [95% CI = 1.1-1.51], p = 0.001 per mm Hg decrease in PaCO2 for the discovery and the validation cohort, respectively). A PaCO2 ≤40 mm Hg, as determined by the concordance probability method, was associated with a significantly increased probability of a sedation level within the RASS target range in both patient cohorts (adjusted odds ratio = 2.92 [95% CI = 1.17-7.24], p = 0.021 and 6.82 [95% CI = 1.50-31.0], p = 0.013 for the discovery and the validation cohort, respectively).

Ketone Bodies after Cardiac Arrest: A Narrative Review and the Rationale for Use.

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.

The effect of increased positive end expiratory pressure on brain tissue oxygenation and intracranial pressure in acute brain injury patients.

Cerebral hypoxia is an important cause of secondary brain injury. Improving systemic oxygenation may increase brain tissue oxygenation (PbtO2). The effects of increased positive end-expiratory pressure (PEEP) on PbtO2 and intracranial pressure (ICP) needs to be further elucidated. This is a single center retrospective cohort study (2016-2021) conducted in a 34-bed Department of Intensive Care unit. All patients with acute brain injury under mechanical ventilation who were monitored with intracranial pressure and brain tissue oxygenation (PbtO2) catheters and underwent at least one PEEP increment were included in the study. Primary outcome was the rate of PbtO2 responders (increase in PbtO2 > 20% of baseline) after PEEP increase. ΔPEEP was defined as the difference between PEEP at 1 h and PEEP at baseline; similarly ΔPbtO2 was defined as the difference between PbtO2 at 1 h after PEEP incrementation and PbtO2 at baseline. We included 112 patients who underwent 295 episodes of PEEP increase. Overall, the median PEEP increased form 6 (IQR 5-8) to 10 (IQR 8-12) cmH2O (p = 0.001), the median PbtO2 increased from 21 (IQR 16-29) mmHg to 23 (IQR 18-30) mmHg (p = 0.001), while ICP remained unchanged [from 12 (7-18) mmHg to 12 (7-17) mmHg; p = 0.42]. Of 163 episode of PEEP increments with concomitant PbtO2 monitoring, 34 (21%) were PbtO2 responders. A lower baseline PbtO2 (OR 0.83 [0.73-0.96)]) was associated with the probability of being responder. ICP increased in 142/295 episodes of PEEP increments (58%); no baseline variable was able to identify this response. In PbtO2 responders there was a moderate positive correlation between ΔPbtO2 and ΔPEEP (r = 0.459 [95% CI 0.133-0.696]. The response in PbtO2 and ICP to PEEP elevations in brain injury patients is highly variable. Lower PbtO2 values at baseline could predict a significant increase in brain oxygenation after PEEP increase.

Safety and Effectiveness of Carbon Dioxide Removal CO2RESET Device in Critically Ill Patients.

BACKGROUND: In this retrospective study, we report the effectiveness and safety of a dedicated extracorporeal carbon dioxide removal (ECCO2R) device in critically ill patients. METHODS: Adult patients on mechanical ventilation due to acute respiratory distress syndrome (ARDS) or decompensated chronic obstructive pulmonary disease (dCOPD), who were treated with a dedicated ECCO2R device (CO2RESET, Eurosets, Medolla, Italy) in case of hypercapnic acidemia, were included. Repeated measurements of CO2 removal (VCO2) at baseline and 1, 12, and 24 h after the initiation of therapy were recorded. RESULTS: Over a three-year period, 11 patients received ECCO2R (median age 60 [43-72] years) 3 (2-39) days after ICU admission; nine patients had ARDS and two had dCOPD. Median baseline pH and PaCO2 levels were 7.27 (7.12-7.33) and 65 (50-84) mmHg, respectively. With a median ECCO2R blood flow of 800 (500-800) mL/min and maximum gas flow of 6 (2-14) L/min, the VCO2 at 12 h after ECCO2R initiation was 157 (58-183) mL/min. Tidal volume, respiratory rate, and driving pressure were significantly reduced over time. Few side effects were reported. CONCLUSIONS: In this study, a dedicated ECCO2R device provided a high VCO2 with a favorable risk profile.

Veno-arterial CO2 difference and respiratory quotient after cardiac arrest: An observational cohort study.

PURPOSE: To characterize venous-arterial CO2 difference (ΔpCO2) and the respiratory quotient (RQ) in post cardiac arrest patients and evaluate the association between these parameters and patient outcome. MATERIALS AND METHODS: Data were obtained retrospectively from post cardiac arrest patients admitted between 2007 and 2016 to a medical intensive care unit. Comatose, adult patients in whom arterial and venous blood gas analyses were concomitantly performed in the first 24 h were included. Patients were grouped according to the time-point of sampling; 0-6, 6-12 and 12-24 h after admission. RESULTS: 308 patients were included; 174 (56%) died before ICU discharge and 212 (69%) had an unfavorable neurologic outcome. RQ was associated with ICU mortality (OR:1.09 (95%CI: 1.04-1.14; p < 0.01)), although not with neurological outcome. ΔpCO2 was negatively associated with both ICU mortality (OR: 0.92 (95%CI: 0.86-0.99; p = 0.02)) and poor neurologic outcome (adjusted OR: 0.93 (95%CI: 0.87-0.99; p = 0.02)). ΔpCO2 predicted an elevated RQ; a ΔpCO2 above 8.5 mmHg identified a high RQ with reasonable sensitivity and specificity. CONCLUSIONS: RQ was associated with ICU mortality and ΔpCO2 identified elevated RQ in the early phase after cardiac arrest. However, ΔpCO2 were negatively associated with both ICU mortality and neurologic outcome.

Validation of Prognostic Scores in Extracorporeal Life Support: A Multi-Centric Retrospective Study.

Multiple prognostic scores have been developed for both veno-arterial (VA) and veno-venous (VV) extracorporeal membrane oxygenation (ECMO), mostly in single-center cohorts. The aim of this study was to compare and validate different prediction scores in a large multicenter ECMO-population. METHODS: Data from five ECMO centers included 300 patients on VA and 329 on VV ECMO support (March 2008 to November 2016). Different prognostic scores were compared between survivors and non-survivors: APACHE II, SOFA, SAPS II in all patients; SAVE, modified SAVE and MELD-XI in VA ECMO; RESP, PRESET, ROCH and PRESERVE in VV ECMO. Model performance was compared using receiver-operating-curve analysis and assessment of model calibration. Survival was assessed at intensive care unit discharge. RESULTS: The main indication for VA ECMO was cardiogenic shock; overall survival was 51%. ICU survivors had higher Glasgow Coma Scale scores and pH, required cardiopulmonary resuscitation (CPR) less frequently, had lower lactate levels and shorter ventilation time pre-ECMO at baseline. The best discrimination between survivors and non-survivors was observed with the SAPS II score (area under the curve [AUC] of 0.73 (95% CI 0.67-0.78)). The main indication for VV ECMO was pneumonia; overall survival was 60%. Lower PaCO2, higher pH, lower lactate and lesser need for CPR were observed among survivors. The best discrimination between survivors and non-survivors was observed with the PRESET score (AUC 0.66 (95% CI 0.60-0.72)). CONCLUSION: The prognostic performance of most scores was moderate in ECMO patients. The use of such scores to decide about ECMO implementation in potential candidates should be discouraged.

Epidural analgesia improves outcome in cardiac surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: The authors conducted a review of randomized studies to determine whether there were any advantages for clinically relevant outcomes by adding epidural analgesia in patients undergoing cardiac surgery under general anesthesia. DESIGN: Meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 2366 patients from 33 randomized trials. INTERVENTIONS: None. DATA SOURCES AND STUDY SELECTION: PubMed, BioMedCentral, CENTRAL, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings were searched (updated January 2008) for randomized trials that compared general anesthesia with an anesthetic plan including general anesthesia and epidural analgesia in cardiac surgery. Two independent reviewers appraised study quality, with divergences resolved by consensus. Overall analysis showed that epidural analgesia reduced the risk of the composite endpoint mortality and myocardial infarction (30/1125 [2.7%] in the epidural group v 64/1241 [5.2%] in the control arm, odds ratio [OR] = 0.61 [0.40-0.95], p = 0.03 number needed to treat [NNT] = 40), the risk of acute renal failure (35/590 [5.9%] in the epidural group v 54/618 [8.7%] in the control arm, OR = 0.56 [0.34-0.93], p = 0.02, NNT = 36), and the time of mechanical ventilation (weighted mean differences = -2.48 hours [-2.64, -2.32], p < 0.001). CONCLUSIONS: This analysis suggested that epidural analgesia on top of general anesthesia reduced the incidence of perioperative acute renal failure, the time on mechanical ventilation, and the composite endpoint of mortality and myocardial infarction in patients undergoing cardiac surgery.

A practical approach to the use of targeted temperature management after cardiac arrest.

Among comatose survivors after cardiac arrest, target temperature management (TTM) is considered the most effective treatment to reduce the consequences of postanoxic brain injury. Several international guidelines have thus incorporated TTM in the management of the postresuscitation phase. However, despite extremely promising results in animal models and in randomized trials including selected patient cohorts, TTM benefits on neurological outcome have been questioned. Moreover, TTM potential side effects have raised some concerns on its wide application in all cardiac arrest patients in different healthcare systems. There is indeed still relatively large uncertainty concerning some practical aspects related to TTM application, such as: A) how to select patients who will benefit the most from TTM; B) the optimal time to initiate TTM; C) the best target temperature; D) the most effective methods to provide TTM; E) the length of the cooling phase; and F) the optimal rewarming rate and fever control strategies. The purpose of this manuscript is to review and discuss the most recent advances in TTM use after cardiac arrest and to give some proposals on how to deal with all these relevant practical questions.

Oxygen and carbon dioxide levels in patients after cardiac arrest.

BACKGROUND: The relationship of PaO2 and PaCO2 levels with outcome after cardiac arrest (CA) is controversial. Few studies have analysed both PaO2 and PaCO2 in this setting and the overall exposure to different PaO2 and PaCO2 levels has not been taken into account. METHODS: We reviewed blood gas data obtained within the first 24 h from all comatose adult patients who were admitted to the intensive care unit after successful resuscitation from CA. Exposure times to different PaO2 and PaCO2 thresholds were reported as areas under the curve (AUC) and the time above these thresholds was then calculated. The primary outcome measure was neurological outcome assessed using the Cerebral Performance Category (CPC) score at 3 months. An unfavourable outcome was defined as a CPC of 3-5 and a favourable outcome as a CPC of 1-2. RESULTS: A total of 356 patients were studied, with a median number of 9 [6-11] blood gas measurements within the first 24 h after admission. The highest and lowest PaO2 and PaCO2 were similar in patients with unfavourable and favourable neurological outcomes. There were no differences in the AUCs or times over different thresholds of PaO2 and PaCO2 in the two groups. In a multivariable analysis, high blood lactate concentrations on admission, presence of shock and a non-shockable initial rhythm were significantly associated with unfavourable outcome. CONCLUSIONS: There was no association between exposure to various levels of PaO2 and PaCO2 and neurological outcome after cardiac arrest.

Low hemoglobin and venous saturation levels are associated with poor neurological outcomes after cardiac arrest.

INTRODUCTION: Hemoglobin (Hb) is a main determinant of tissue oxygen delivery and anemia could be particularly harmful in post-anoxic brain injury. The aim of this study was to evaluate the association of Hb and venous Hb oxygen saturation (SvO2/ScvO2) with long-term neurological outcome in patients admitted after cardiac arrest (CA). METHODS: Analysis of adult CA patients admitted to the Department of Intensive Care of the Erasme University Hospital (Brussels, Belgium) over 9 years. We retrieved all data concerning CA characteristics as well as Hb during the first 48 h since injury as well as the need for red blood cells transfusions (RBCT). Minimum Hb and Hb oxygen saturation values were recorded. Neurological outcome was evaluated 3 months after CA. Unfavorable neurological outcome (UO) was defined as a Cerebral Performance Categories (CPC) score of 3-5. RESULTS: We treated 414 patients patients with CA, including 231 (56%) out-of-hospital cardiac arrest (OHCA) and 158 (38%) with an initial shockable rhythm. Median Hb concentration on admission was 12.0 [9.9-13.7] g/dL and the lowest Hb concentration was 10.0 [8.1-11.0] g/dL; 127 patients (31%) received at least one RBCT. Hb oxygen saturation on admission was 67 [59-74]%, while the lowest value was 60 [53-68]%. Low Hb and Hb oxygen saturation values were independently associated with UO; the optimal cut-off to predict UO was <9.9 g/dL and <60%, respectively. CONCLUSIONS: Low hemoglobin values and low values of oxygen venous saturation are significantly associated with unfavorable neurological outcome in adult patients resuscitated from cardiac arrest.

The characteristics of patients with bilateral absent evoked potentials after post-anoxic brain damage: A multicentric cohort study.

OBJECTIVES: Patients with bilateral absence of cortical response (N20ABS) to somatosensory evoked potentials (SSEPs) have poor neurological outcome after cardiac arrest (CA). However, SSEPs are not available in all centers. The aim of this study was to identify predictors of N20ABS. METHODS: Retrospective analysis of institutional databases (2008-2015) in three ICUs including all adult admitted comatose patients undergoing SSEPs between 48 and 72 h after CA. We collected clinical (i.e. absence of pupillary reflexes, PLR, myoclonus and absent or posturing motor response and myoclonus on day 2-3), electroencephalographic (EEG; i.e. unreactive to painful stimuli; presence of a highly malignant patterns, such as burst-suppression or flat tracings) findings during the first 48 h, and the highest NSE levels on the first 3 days after CA. Unfavorable neurological outcome (UO) was assessed at 3 months using the Cerebral Performance Categories of 3-5. RESULTS: We studied 532 patients with SSEPs, including 143 (27%) without N20ABS; UO was observed in 334 (63%) patients. Median time to SSEPs was 72 [48-72] h after CA. No patient with absent PLR and myoclonus during the ICU stay had N20 present; similar results were observed with the combination of absent PLR, myoclonus and any EEG pattern (i.e. unreactive or highly malignant). Similar results were observed in the subgroup of patients where NSE was available (n = 303). In a multivariate logistic regression, non-cardiac etiology of arrest, unreactive EEG to painful stimuli, absence of pupillary reflexes and posturing motor response, were independent predictors of N20ABS. When available, the highest NSE was also an independent predictor of N20ABS. CONCLUSIONS: Clinical and EEG findings predicting patients with N20ABS, confirm that N20ABS reflects a severe and permanent cerebral damage after CA.

Acute liver dysfunction after cardiac arrest.

Few data are available regarding hypoxic hepatitis (HH) and acute liver failure (ALF) in patients resuscitated from cardiac arrest (CA). The aim of this study was to describe the occurrence of these complications and their association with outcome. All adult patients admitted to the Department of Intensive Care following CA were considered for inclusion in this retrospective study. Exclusion criteria were early death (<24 hours) or missing biological data. We retrieved data concerning CA characteristics and markers of liver function. ALF was defined as a bilirubin >1.2 mg/dL and an international normalized ratio ≥1.5. HH was defined as an aminotransferase level >1000 IU/L. Neurological outcome was assessed at 3 months and an unfavourable neurological outcome was defined as a Cerebral Performance Categories (CPC) score of 3-5. A total of 374 patients (age 62 [52-74] years; 242 male) were included. ALF developed in 208 patients (56%) and HH in 27 (7%); 24 patients developed both conditions. Patients with HH had higher mortality (89% vs. 51% vs. 45%, respectively) and greater rates of unfavourable neurological outcome (93% vs. 60% vs. 59%, respectively) compared to those with ALF without HH (n = 184) and those without ALF or HH (n = 163; p = 0.03). Unwitnessed arrest, non-shockable initial rhythm, lack of bystander cardiopulmonary resuscitation, high adrenaline doses and the development of acute kidney injury were independent predictors of unfavourable neurological outcome; HH (OR: 16.276 [95% CIs: 2.625-81.345; p = 0.003), but not ALF, was also a significant risk-factor for unfavourable outcome. Although ALF occurs frequently after CA, HH is a rare complication. Only HH is significantly associated with poor neurological outcome in this setting.