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.

Ivabradine in Septic Shock: A Narrative Review.

In patients with septic shock, compensatory tachycardia initially serves to maintain adequate cardiac output and tissue oxygenation but may persist despite appropriate fluid and vasopressor resuscitation. This sustained elevation in heart rate and altered heart rate variability, indicative of autonomic dysfunction, is a well-established independent predictor of adverse outcomes in critical illness. Elevated heart rate exacerbates myocardial oxygen demand, reduces ventricular filling time, compromises coronary perfusion during diastole, and impairs the isovolumetric relaxation phase of the cardiac cycle, contributing to ventricular-arterial decoupling. This also leads to increased ventricular and atrial filling pressures, with a heightened risk of arrhythmias. Ivabradine, a highly selective inhibitor of the sinoatrial node's pacemaker current (If or "funny" current), mitigates heart rate by modulating diastolic depolarization slope without affecting contractility. By exerting a selective chronotropic effect devoid of negative inotropic properties, ivabradine shows potential for improving hemodynamics in septic shock patients with cardiac dysfunction. This review evaluates the plausible mechanisms and existing evidence regarding the utility of ivabradine in managing patients with septic shock.

Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

The Effects of Acetazolamide on Cerebral Hemodynamics in Adult Patients with an Acute Brain Injury: A Systematic Review.

BACKGROUND: Acetazolamide is a non-competitive inhibitor of carbonic anhydrase, an enzyme expressed in different cells of the central nervous system (CNS) and involved in the regulation of cerebral blood flow (CBF). The aim of this review was to understand the effects of acetazolamide on CBF, intracranial pressure (ICP) and brain tissue oxygenation (PbtO2) after an acute brain injury (ABI). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), we performed a comprehensive, computer-based, literature research on the PubMed platform to identify studies that have reported the effects on CBF, ICP, or PbtO2 of acetazolamide administered either for therapeutic or diagnostic purposes in patients with subarachnoid hemorrhage, intracerebral hemorrhage, traumatic brain injury, and hypoxic-ischemic encephalopathy. RESULTS: From the initial search, 3430 records were identified and, through data selection, 11 of them were included for the qualitative analysis. No data on the effect of acetazolamide on ICP or PbtO2 were found. Cerebral vasomotor reactivity (VMR-i.e., the changing in vascular tone due to a vasoactive substance) to acetazolamide tends to change during the evolution of ABI, with the nadir occurring during the subacute stage. Moreover, VMR reduction was correlated with clinical outcome. CONCLUSIONS: This systematic review showed that the available studies on the effects of acetazolamide on brain hemodynamics in patients with ABI are scarce. Further research is required to better understand the potential role of this drug in ABI patients.

Reliability of pulse pressure and stroke volume variation in assessing fluid responsiveness in the operating room: a metanalysis and a metaregression.

BACKGROUND: Pulse pressure and stroke volume variation (PPV and SVV) have been widely used in surgical patients as predictors of fluid challenge (FC) response. Several factors may affect the reliability of these indices in predicting fluid responsiveness, such as the position of the patient, the use of laparoscopy and the opening of the abdomen or the chest, combined FC characteristics, the tidal volume (Vt) and the type of anesthesia. METHODS: Systematic review and metanalysis of PPV and SVV use in surgical adult patients. The QUADAS-2 scale was used to assess the risk of bias of included studies. We adopted a metanalysis pooling of aggregate data from 5 subgroups of studies with random effects models using the common-effect inverse variance model. The area under the curve (AUC) of pooled receiving operating characteristics (ROC) curves was reported. A metaregression was performed using FC type, volume, and rate as independent variables. RESULTS: We selected 59 studies enrolling 2,947 patients, with a median of fluid responders of 55% (46-63). The pooled AUC for the PPV was 0.77 (0.73-0.80), with a mean threshold of 10.8 (10.6-11.0). The pooled AUC for the SVV was 0.76 (0.72-0.80), with a mean threshold of 12.1 (11.6-12.7); 19 studies (32.2%) reported the grey zone of PPV or SVV, with a median of 56% (40-62) and 57% (46-83) of patients included, respectively. In the different subgroups, the AUC and the best thresholds ranged from 0.69 and 0.81 and from 6.9 to 11.5% for the PPV, and from 0.73 to 0.79 and 9.9 to 10.8% for the SVV. A high Vt and the choice of colloids positively impacted on PPV performance, especially among patients with closed chest and abdomen, or in prone position. CONCLUSION: The overall performance of PPV and SVV in operating room in predicting fluid responsiveness is moderate, ranging close to an AUC of 0.80 only some subgroups of surgical patients. The grey zone of these dynamic indices is wide and should be carefully considered during the assessment of fluid responsiveness. A high Vt and the choice of colloids for the FC are factors potentially influencing PPV reliability. TRIAL REGISTRATION: PROSPERO (CRD42022379120), December 2022. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379120.

Cardiac dysfunction in patients affected by subarachnoid haemorrhage affects in-hospital mortality: A systematic review and metanalysis.

BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition with associated brain damage. Moreover, SAH is associated with a massive release of catecholamines, which may promote cardiac injury and dysfunction, possibly leading to haemodynamic instability, which in turn may influence a patient's outcome. OBJECTIVES: To study the prevalence of cardiac dysfunction (as assessed by echocardiography) in patients with SAH and its effect on clinical outcomes. DESIGN: Systematic review of observational studies. DATA SOURCES: We performed a systematic search over the last 20 years on MEDLINE and EMBASE databases. ELIGIBILITY CRITERIA: Studies reporting echocardiography findings in adult patients with SAH admitted to intensive care. Primary outcomes were in-hospital mortality and poor neurological outcome according to the presence or absence of cardiac dysfunction. RESULTS: We included a total of 23 studies (4 retrospective) enrolling 3511 patients. The cumulative frequency of cardiac dysfunction was 21% (725 patients), reported as regional wall motion abnormality in the vast majority of studies (63%). Due to the heterogeneity of clinical outcome data reporting, a quantitative analysis was carried out only for in-hospital mortality. Cardiac dysfunction was associated with a higher in-hospital mortality [odds ratio 2.69 (1.64 to 4.41); P  < 0.001; I2 = 63%]. The GRADE of evidence assessment resulted in very low certainty of evidence. CONCLUSION: About one in five patients with SAH develops cardiac dysfunction, which seems to be associated with higher in-hospital mortality. The consistency of cardiac and neurological data reporting is lacking, reducing the comparability of the studies in this field.

Pressure response to fluid challenge administration in hypotensive surgical patients: a post-hoc pharmacodynamic analysis of five datasets.

In this study we evaluated the effect of fluid challenge (FC) administration in elective surgical patients with low or normal blood pressure. Secondarily, we appraised the pharmacodynamic effect of FC in normotensive and hypotensive patients. We assessed five merged datasets of patients with a baseline mean arterial pressure (MAP) above or below 65 mmHg and assessed the changes of systolic, diastolic, mean and dicrotic arterial pressures, dynamic indexes of fluid responsiveness and arterial elastance over a 10-min infusion. The hemodynamic effect was assessed by considering the net area under the curve (AUC), the maximal percentage difference from baseline (dmax), the time when the maximal value was observed (tmax) and change from baseline at 5-min (d5) after FC end. A stroke volume index increase > 10% with respect to the baseline value after FC administration indicated fluid response. Two hundred-seventeen patients were analysed [102 (47.0%) fluid responders]. On average, FC restored a MAP [Formula: see text] 65 mmHg after 5 min. The AUCs and the dmax of pressure variables and arterial elastance of hypotensive patients were all significantly greater than normotensive patients. Pressure variables and arterial elastance changes in the hypotensive group were all significantly higher at d5 as compared to the normotensive group. In hypotensive patients, FC restores a MAP [Formula: see text] 65 mmHg after 5 min from infusion start. The hemodynamic profile of FC in hypotensive and normotensive patients is different; both the magnitude of pressure augmentation and duration is greater in the hypotensive group.

The Cardiac Power Index during Abdominal Open Aortic Surgery: Intraoperative Insights into the Cardiac Performance-A Retrospective Observational Analysis.

Background: The Cardiac Power Index (CPI) measures the rate of energy output generated by the heart and correlates this with in-hospital mortality due to cardiogenic shock. In open aortic surgery, both aortic clamping and unclamping expose the heart to abrupt variations of the left ventricle afterload, preload, and contractility, with possible hemodynamic impairment. We investigated how aortic-cross clamping (Ao-XC) and unclamping (Ao-UC) procedures affect the CPI during open aortic surgery. Methods: We retrospectively analyzed our surgical database of 67 patients submitted to open surgical aortic repair at Humanitas Research Hospital, Milan. Patients were monitored by an EV1000-FloTrac SystemTM (Edwards Lifescience, Irvine, CA, USA) beyond the standard intra-operative hemodynamic monitoring. The primary outcome was the variation of basal CPI after aortic clamping and unclamping. Secondary outcomes were variations of the cardiac index (CI), mean arterial pressure (MAP), heart rate, and lactate during aortic clamping and after unclamping. The CPI was computed as: (CI × MAP)/451. Results: The CPI changed significantly after aortic unclamping. CPI: basal = 0.39 ± 0.1 W/m2, after Ao-XC = 0.39 ± 0.1 W/m2, and after Ao-UC = 0.44 ± 0.2 W/m2, p < 0.05. The CI changed during both cross-clamping and unclamping (p < 0.0001), whilst the MAP and heart rate did not during any phase of the surgery. Five subjects (8.3%) needed inotropic support after cross-clamping. Their basal CPI was lower than the general population: 0.31 ± 0.11 W/m2 vs. 0.39 ± 0.1 W/m2. Conclusions: The CPI describes the adaptation of the cardiac function to the changes in preload, contractility, and afterload occurring during aortic cross-clamping and unclamping. It may be used to explore the cardiac performance in real-time and predict cardiac impairment in the intraoperative period in a minimally invasive way, similar to ventriculo-arterial coupling parameters.

Fluid challenge in critically ill patients receiving haemodynamic monitoring: a systematic review and comparison of two decades.

INTRODUCTION: Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000-2010 and 2011-2021. METHODS: We assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold. RESULTS: We included 124 studies, 32 (25.8%) published in 2000-2010 and 92 (74.2%) in 2011-2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011-2021 compared to the 2000-2010 period. CONCLUSIONS: In the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000-2010 decade, in 2011-2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.

Spinal anesthesia and hypotensive events in hip fracture surgical repair in elderly patients: a meta-analysis.

BACKGROUND: Spinal anesthesia (SA) is widely used for anesthetic management of patients undergoing hip surgery, and hypotension is the most common cardiovascular side effect of SA. This paper aims to assess the lowest effective dose of SA that reduces the occurrence of intraoperative hypotension in elderly patients scheduled for major lower limb orthopedic surgery. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) performed in elderly patients scheduled for surgical hip repair and a meta-analysis with meta-regression on the occurrence of hypotensive episodes at different effective doses of anesthetics. We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials registered. RESULTS: Our search retrieved 2085 titles, and after screening, 6 were finally included in both the qualitative and quantitative analysis, including 344 patients [15% (10-28) males], with a median (25th to 75th interquartile) age of 82 (80-85). The risk of bias assessment reported "low risk" for 5 (83.3%) and "some concerns" for 1 (16.7%) of the included RCTs. The low dose of SA of [mean 6.5 mg (1.9)] anesthetic was associated with a lower incidence of hypotension [OR = 0.09 (95%CI 0.04-0.21); p = 0.04; I2 = 56.9%], as compared to the high-dose of anesthetic [mean 10.5 mg (2.4)]. CONCLUSIONS: In the included studies of this meta-analysis, a mean dose of 6.5 mg of SA was effective in producing intraoperative comfort and motor block and associated with a lower incidence of hypotension as compared to a mean dose of 10.5 mg. TRIAL REGISTRATION: CRD42020193627.

Renal Resistive Index: Not Only for Kidney Clinics.

Renal Resistive Index (RRI) is a measurement of the resistance of the renal blood flow. A value higher than 0.70 is a marker of increased resistance and is correlated with kidney injury and its severity. Additionally, it may be associated with the mortality rate in the post-surgery population. In COVID-19 subjects, we found that high RRI has been associated with high levels of serum C-reactive protein, a marker of systemic inflammatory reaction syndrome. Finally, we propose RRI not only as a marker of kidney injury, but also as a tool to evaluate the course of critical illness.

Venous thromboembolism after total knee arthroplasty is associated with a worse functional outcome at one year.

AIMS: The primary aim of this study was to assess whether non-fatal postoperative venous thromboembolism (VTE) within six months of surgery influences the knee-specific functional outcome (Oxford Knee Score (OKS)) one year after total knee arthroplasty (TKA). Secondary aims were to assess whether non-fatal postoperative VTE influences generic health and patient satisfaction at this time. METHODS: A study of 2,393 TKAs was performed in 2,393 patients. Patient demographics, comorbidities, OKS, EuroQol five-dimension score (EQ-5D), and Forgotten Joint Score (FJS) were collected preoperatively and one year postoperatively. Overall patient satisfaction with their TKA was assessed at one year. Patients with VTE within six months of surgery were identified retrospectively and compared with those without. RESULTS: A total of 37 patients (1.5%) suffered a VTE and were significantly more likely to have associated comorbidities of stroke (p = 0.026), vascular disease (p = 0.026), and kidney disease (p = 0.026), but less likely to have diabetes (p = 0.046). In an unadjusted analysis, patients suffering a VTE had a significantly worse postoperative OKS (difference in mean (DIM) 4.8 (95% confidence interval (CI) 1.6 to 8.0); p = 0.004) and EQ-5D (DIM 0.146 (95% CI 0.059 to 0.233); p = 0.001) compared with patients without a VTE. After adjusting for confounding variables VTE remained a significant independent predictor associated with a worse postoperative OKS (DIM -5.4 (95% CI -8.4 to -2.4); p < 0.001), and EQ-5D score (DIM-0.169 (95% CI -0.251 to -0.087); p < 0.001). VTE was not independently associated with overall satisfaction after TKA (odds ratio 0.89 (95% CI 0.35 to 2.07); p = 0.717). CONCLUSION: Patients who had a VTE within six months of their TKA had clinically significantly worse knee-specific outcome (OKS) and general health (EQ-5D) scores one year postoperatively, but the overall satisfaction with their TKA was similar to those patients who did not have a VTE. Cite this article: Bone Joint J 2021;103-B(7):1254-1260.

COVID-19-related echocardiographic patterns of cardiovascular dysfunction in critically ill patients: A systematic review of the current literature.

PURPOSE: Coronavirus disease 2019 (COVID-19) infection may trigger a multi-systemic disease involving different organs. There has been growing interest regarding the harmful effects of COVID-19 on the cardiovascular system. This systematic review aims to systematically analyze papers reporting echocardiographic findings in hospitalized COVID-19 subjects. MATERIALS AND METHODS: We included prospective and retrospective studies reporting echocardiography data in >10 hospitalized adult subjects with COVID-19; from 1st February 2020 to 15th January 2021. RESULTS: The primary electronic search identified 1120 articles. Twenty-nine studies were finally included, enrolling 3944 subjects. Overall the studies included a median of 68.0% (45.5-100.0) of patients admitted to ICU. Ten studies (34.4%) were retrospective, and 20 (68.9%) single-centred. Overall enrolling 1367 subjects, three studies reported normal echocardiographic findings in 49 ± 18% of cases. Seven studies (24.1%) analyzed the association between echocardiographic findings and mortality, mostly related to right ventricular (RV) dysfunction. CONCLUSIONS: Data regarding the use of echocardiography on hospitalized, predominantly ICU, COVID-19 patients were retrieved from studies with heterogeneous designs, variable sample sizes, and severity scores. Normal echocardiographic findings were reported in about 50% of subjects, with LVEF usually not affected. Overall, RV dysfunction seems more likely associated with increased mortality. TRIAL REGISTRATION: CRD42020218439.

Perioperative liberal versus restrictive fluid strategies and postoperative outcomes: a systematic review and metanalysis on randomised-controlled trials in major abdominal elective surgery.

BACKGROUND: Postoperative complications impact on early and long-term patients' outcome. Appropriate perioperative fluid management is pivotal in this context; however, the most effective perioperative fluid management is still unclear. The enhanced recovery after surgery pathways recommend a perioperative zero-balance, whereas recent findings suggest a more liberal approach could be beneficial. We conducted this trial to address the impact of restrictive vs. liberal fluid approaches on overall postoperative complications and mortality. METHODS: Systematic review and meta-analysis, including randomised controlled trials (RCTs). We performed a systematic literature search using MEDLINE (via Ovid), EMBASE (via Ovid) and the Cochrane Controlled Clinical trials register databases, published from 1 January 2000 to 31 December 2019. We included RCTs enrolling adult patients undergoing elective abdominal surgery and comparing the use of restrictive/liberal approaches enrolling at least 15 patients in each subgroup. Studies involving cardiac, non-elective surgery, paediatric or obstetric surgeries were excluded. RESULTS: After full-text examination, the metanalysis finally included 18 studies and 5567 patients randomised to restrictive (2786 patients; 50.0%) or liberal approaches (2780 patients; 50.0%). We found no difference in the occurrence of severe postoperative complications between restrictive and liberal subgroups [risk difference (95% CI) = 0.009 (- 0.02; 0.04); p value = 0.62; I2 (95% CI) = 38.6% (0-66.9%)]. This result was confirmed also in the subgroup of five studies having a low overall risk of bias. The liberal approach was associated with lower overall renal major events, as compared to the restrictive [risk difference (95% CI) = 0.06 (0.02-0.09); p value = 0.001]. We found no difference in either early (p value = 0.33) or late (p value = 0.22) postoperative mortality between restrictive and liberal subgroups CONCLUSIONS: In major abdominal elective surgery perioperative, the choice between liberal or restrictive approach did not affect overall major postoperative complications or mortality. In a subgroup analysis, a liberal as compared to a restrictive perioperative fluid policy was associated with lower overall complication renal major events, as compared to the restrictive. TRIAL REGISTRATION: CRD42020218059; Registration: February 2020, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=218059 .

Impact of therapeutic hypothermia during cardiopulmonary resuscitation on neurologic outcome: A systematic review and meta-analysis.

BACKGROUND: Therapeutic cooling initiated during cardiopulmonary resuscitation (intra arrest therapeutic hypothermia, IATH) provided diverging effect on neurological outcome of out-of-hospital cardiac arrest (OHCA) patients depending on the initial cardiac rhythm and the cooling methods used. METHODS: We performed a systematic search of PubMed, EMBASE and the CENTRAL databases using established Medical Subject Headings (MeSH) terms for IATH and OHCA. Only studies comparing IATH to standard in-hospital targeted temperature management (TTM) were selected. We used the revised Cochrane RoB-2 and the Newcastle-Ottawa scale tool to assess risk of bias of each study. Primary outcome was favorable neurological outcome (FO); secondary outcomes included return of spontaneous circulation (ROSC) rate and survival to hospital discharge. RESULTS: Out of 20,950 studies, 8 studies (n = 3493 patients, including 4 randomized trials, RCTs) were included in the final analysis. Compared to controls, the use of IATH was not associated with improved FO (OR 0.96 [95% CIs 0.68-1.37]; p = 0.84), increased ROSC rate (OR 1.11 [95% CIs 0.83-1.49]; p = 0.46) or survival (OR 0.91 [95% CIs 0.73-1.14]; p = 0.43). Significant heterogeneity among studies was observed for the analysis of ROSC rate (I2 = 69%). Trans-nasal evaporative cooling and cold fluids were explored in two RCTs each and no differences were observed on FO, event when only patients with an initial shockable rhythm were analyzed (OR 1.62 [95% CI 1.00-2.64]; p = 0.05]. CONCLUSIONS: In this meta-analysis, IATH was not associated with improved neurological outcome when compared to standard in-hospital TTM, based on very low certainty of evidence. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42019130322).

Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery.

BACKGROUND: Appropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients' hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid). RESULTS: The metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%, p value = 0.23 and 54.8% vs. 39.8%; p value = 0.09, respectively]. Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = - 0.10 (- 0.14, - 0.07); Chi2 = 30.97; p value < 0.0001], but not to a reduction of perioperative mortality [pooled risk difference (95%CI) = - 0.016 (- 0.0334; 0.0014); p value = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (p value = 0.52) nor cardiovascular (p value = 0.86) or pulmonary (p value = 0.14) or neurological (p value = 0.44) or infective (p value = 0.12) complications. CONCLUSIONS: Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality. TRIAL REGISTRATION: CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866.

Correlation Between Electroencephalography and Automated Pupillometry in Critically Ill Patients: A Pilot Study.

BACKGROUND: Electroencephalography (EEG) is widely used in the monitoring of critically ill comatose patients, but its interpretation is not straightforward. The aim of this study was to evaluate whether there is a correlation between EEG background pattern/reactivity to stimuli and automated pupillometry in critically ill patients. METHODS: Prospective assessment of pupillary changes to light stimulation was obtained using an automated pupillometry (NeuroLight Algiscan, ID-MED, Marseille, France) in 60 adult patients monitored with continuous EEG. The degree of encephalopathy and EEG reactivity were scored by 3 independent neurophysiologists blinded to the patient's history. The median values of baseline pupil size, pupillary constriction, constriction velocity, and latency were collected for both eyes. To assess sensitivity and specificity, we calculated areas under the receiver-operating characteristic curve. RESULTS: The degree of encephalopathy assessed by EEG was categorized as mild (42%), moderate (37%), severe (10%) or suppression-burst/suppression (12%); a total of 47/60 EEG recordings were classified as "reactive." There was a significant difference in pupillary size, constriction rate, and constriction velocity, but not latency, among the different EEG categories of encephalopathy. Similarly, reactive EEG tracings were associated with greater pupil size, pupillary constriction rate, and constriction velocity compared with nonreactive recordings; there were no significant differences in latency. Pupillary constriction rate values had an area under the curve of 0.83 to predict the presence of severe encephalopathy or suppression-burst/suppression, with a pupillary constriction rate of < 20% having a sensitivity of 85% and a specificity of 79%. CONCLUSIONS: Automated pupillometry can contribute to the assessment of cerebral dysfunction in critically ill patients.

The use of automated pupillometry to assess cerebral autoregulation: a retrospective study.

BACKGROUND: Critically ill patients are at high risk of developing neurological complications. Among all the potential aetiologies, brain hypoperfusion has been advocated as one of the potential mechanisms. Impairment of cerebral autoregulation (CAR) can result in brain hypoperfusion. However, assessment of CAR is difficult at bedside. We aimed to evaluate whether the automated pupillometer might be able to detect impaired CAR in critically ill patients. METHODS: We included 92 patients in this retrospective observational study; 52 were septic. CAR was assessed using the Mxa index, which is the correlation index between continuous recording of cerebral blood flow velocities using the transcranial Doppler and invasive arterial blood pressure over 8 ± 2 min. Impaired CAR was defined as an Mxa > 0.3. Automated pupillometer (Neuroptics, Irvine, CA, USA) was used to assess the pupillary light reflex concomitantly to the CAR assessment. RESULTS: The median Mxa was 0.33 in the whole cohort (0.33 in septic patients and 0.31 in the non-septic patients; p = 0.77). A total of 51 (55%) patients showed impaired CAR, 28 (54%) in the septic group and 23 (58%) in the non-septic group. We found a statistically significant although weak correlation between Mxa and the Neurologic Pupil Index (r 2 = 0.04; p = 0.048) in the whole cohort as in septic patients (r 2 = 0.11; p = 0.026); no correlation was observed in non-septic patients and for other pupillometry-derived variables. CONCLUSIONS: Automated pupillometry cannot predict CAR indices such as Mxa in a heterogeneous population of critically ill patients.

Mortality and Implant Survival With Simultaneous and Staged Bilateral Total Hip Arthroplasty: Experience From the Australian Orthopedic Association National Joint Replacement Registry.

BACKGROUND: Total hip arthroplasty (THA) is an effective procedure for relieving pain and restoring function in osteoarthritis. A significant proportion of patients have severe disease bilaterally. Consensus regarding safety and selection of patients for simultaneous bilateral THA or the optimal timing for staged THA has not been reached. The aim of this study is to compare rates, causes of revision, and 30-day mortality between simultaneous and staged bilateral THA using data from the Australian Orthopedic National Joint Replacement Registry. METHODS: Data for 12,359 bilateral THA procedures were collected from September, 1999 to December, 2017. Rates and causes of revision and 30-day mortality were obtained for simultaneous bilateral and staged procedures with intervals of 1 day-6 weeks, 6 weeks-3 months, and 3 months-6 months. Yearly cumulative percent revision or cumulative percent survival with 95% confidence intervals calculated by the Kaplan-Meier method, and adjusted hazard ratios were used for comparisons. RESULTS: Thirty-day mortality is lower in patients who have bilateral procedures within 6 months, regardless of timing, than those who have unilateral procedures (0.06% vs 0.18%). Staged bilateral THA had a significantly lower mortality than simultaneous bilateral THA (odds ratio 0.175, 95% confidence interval = 0.04-0.78, P = .022). When separate time intervals were compared, no significant differences were seen. Bilateral 6 week-3 months has a higher rate of revision from 1.5 years-2years compared with same day bilaterals (hazard ratio = 2.39, 95% confidence interval = 1.12, 5.09, P = .024). There were no other significant differences in the rate of revision between groups. The most common reasons for revision were fracture, loosening, and infection. Simultaneous bilateral procedures have a significantly higher rate of revision for fracture compared with staging 3-6 months (hazard ratio = 1.96 [1.27, 3.03], P = .002). CONCLUSION: This study demonstrates that bilateral THA has a low mortality rate regardless of time interval between procedures. Simultaneous and staged bilateral THA have similar rates of revision.

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.