Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA. We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality. Our search identified 6886 studies; 22 studies (n = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75–0.96]; p = 0.008) but not mortality (OR 0.88 [95% CIs 0.62–1.25]; p = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs. Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).

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.

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 (I_f 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.

In patients with acute illness, compensatory tachycardia initially serves to maintain adequate cardiac output, oxygen delivery and tissue oxygenation but may persist despite appropriate fluid and vasopressor resuscitation or may be secondary to inotropic therapy. Sustained tachycardia is a predictor of adverse outcomes in critical illness. Ivabradine, a highly selective inhibitor of the sinoatrial node's pacemaker current (If or "funny" current), mitigates tachycardia by modulating diastolic depolarization slope without affecting contractility. To report the existing evidence on the use of ivabradine in critically ill patients and assess its effect on rate control. A systematic literature search was performed up to May 2024 in the MEDLINE/PubMed®, Cochrane Controlled Clinical Trial register, EMBASE® and Scopus® databases. The search included: P- only original studies conducted in humans admitted to the Intensive Care Unit (ICU); I – when ivabradine administration was tested; C – in presence or absence of a control group; O – for any outcome; S – including case reports, randomized and observational trials, published in English in peer-reviewed journals. After the first screening, 39 studies were assessed for eligibility on a total of 682 records identified. Among those, 29 were excluded; 10 studies (4 randomized controlled trial, 5 case report/series, 1 prospective observational), including a total of 243 patients, were included in the qualitative analysis, 6 studies were included in the quantitative analysis. The use of ivabradine resulted in a pooled mean heart rate reduction of 18.70 [12.70–24.80] bpm (p < 0.01) without a significant decrease in cardiac index (p = 0.59). A significant reduction of noradrenaline dose was reported in one study (-0.134 mcg/kg/min; 95% CI -0.172 to -0.012; p = 0.027). In addition, the combination of dobutamine with ivabradine has been reported to optimize dobutamine inotropic action, while mitigating its positive chronotropic effects, resulting in a more efficient cardiac cycle and improved hemodynamics. Ivabradine may be a useful alternative to beta-blocker in the management of inappropriate sinus tachycardia. Yet, evidence is limited and inconsistent. Larger randomized trials are needed to investigate the potential benefits or hazards of ivabradine use on hemodynamics and long-term outcomes.