Individualized blood pressure targets during postcardiac arrest intensive care

Purpose of review To discuss recent findings relevant to optimizing blood pressure targets in adult, postcardiac arrest (PCA) patients and whether to tailor these based on specific patient, cardiac arrest or treatment characteristics. Recent findings Observational data suggest that mean arterial pressure (MAP) below 65-75 mmHg in PCA patients is associated with worse outcome. A higher MAP could be beneficial in patients with chronic hypertension who more frequently have a right shift of the cerebral autoregulation curve. Two recent randomized pilot trials compared lower and higher MAP targets during PCA care and found no significant effect on biomarkers of neurological injury. The haemodynamic interventions in those studies did not use any cerebral perfusion endpoints beyond a static MAP targets during ICU stay. Individualized, dynamic MAP targets based on assessments of cerebral perfusion and tailored to the specifics of the patient, cardiac arrest circumstances and treatment responses may be more conducive to improved outcomes. Pilot data suggest that near infrared spectroscopy monitoring may be used to determine the cerebral autoregulatory capacity and an optimal MAP, but this approach is yet to be tested in clinical trials. Current evidence suggests targeting a MAP of at least 65-75 mmHg in PCA patients. Future studies should focus on whether certain patient groups could benefit from higher and dynamic MAP targets.Peer reviewe

Target temperature management following cardiac arrest : a systematic review and Bayesian meta-analysis

Background Temperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM. Methods Systematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 degrees C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI). Results In seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32-34 degrees C was 0.95 [95% CrI 0.78-1.09] for death and RR 0.93 [95% CrI 0.84-1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR >= 1) by TTM 32-34 degrees C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32-34 degrees C were the highest for an absolute risk reduction of 2-4% for death (28-53% chance) and unfavourable neurological outcome (63-78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome toPeer reviewe

In-hospital cardiac arrest in hospitals with mature rapid response systems - a multicentre, retrospective cohort study

Aim: To investigate in-hospital cardiac arrests (IHCAs) according to the Ustein template in hospitals with mature systems utilizing rapid response teams (RRTs), with a special reference to preceding RRT factors and factors associated with a favourable neurological outcome (cerebral performance category (CPC) 1-2) at hospital discharge. Methods: Multicentre, retrospective cohort study between 2017-2018 including two Finnish and one Australian university affiliated tertiary hospitals. Results: A total 309 IHCAs occurred with an incidence of 0.78 arrests per 1000 hospital admissions. The median age of the patients was 72 years, 63% were male and 73% had previously lived a fully independent life with a median Charlson comorbidity index of two. Before the IHCA, 16% of the patients had been reviewed by RRTs and 26% of the patients fulfilled RRT activation criteria in the preceding 8 h of the IHCA. Return of spontaneous circulation was achieved in 53% of the patients and 28% were discharged from hospital with CPC 1-2. In a multivariable model, younger age, no pre-arrest RRT criteria, arrest in normal work hours, witnessed arrest and shockable initial rhythm were independently associated with CPC 1-2 at hospital discharge. Conclusions: In hospitals with mature rapid response systems most IHCA patients live a fully independent life with low burden of comorbid diseases before their hospital admission, the IHCA incidence is low and outcome better than traditionally believed. Deterioration before IHCA is present in a significant number of patients and improved monitoring and earlier interventions may further improve outcomes.Peer reviewe

Afferent limb failure revisited - A retrospective, international, multicentre, cohort study of delayed rapid response team calls

Aim: The efficiency of rapid response teams (RRTs) is decreased by delays in activation of RRT (afferent limb failure, ALF). We categorized ALF by organ systems and investigated correlations with the vital signs subsequently observed by the RRT and associations with mortality. Methods: International, multicentre, retrospective cohort study including adult RRT patients without treatment limitations in 2017-2018 in one Australian and two Finnish tertiary hospitals. Results: A total of 5,568 RRT patients' first RRT activations were included. In 927 patients (17%) ALF was present within 4 h before the RRT call, most commonly for respiratory criteria (419 patients, 7.5%). In 3516 patients (63%) overall, and in 756 (82%) of ALF patients, the RRT observed abnormal vital signs upon arrival. The organ-specific ALF corresponded to the RRT observations in 52% of cases for respiratory criteria, in 60% for haemodynamic criteria, in 55% for neurological criteria and in 52% of cases for multiple organ criteria. Only ALF for respiratory criteria was associated with increased hospital mortality (OR 1.71, 95% CI 1.29-2.27), whereas all, except haemodynamic, criteria at the time of RRT review were associated with increased hospital mortality. Conclusions: Vital signs were rarely normal upon RRT arrival in patients with ALF, while organ-specific ALF corresponded to subsequent RRT observations in just over half of cases. Our results suggest that systems mandating timely responses to abnormal respiratory criteria in particular may have potential to improve deteriorating patient outcomes.Peer reviewe

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.Peer reviewe

The impact of blood pressure targets on venous return physiology during post cardiac arrest care

Background: Venous return (VR) physiology may be elucidated using a calculated mean systemic filling pressure analogue (Pmsa) that reflects the stressed intravascular volume. The aim of this study was to explore differences in VR physiological variables with the hypothesis that vasopressor therapy targeting a higher mean arterial pressure (MAP) would associate with an increased volume state. This would be important to appreciate the intravascular volume effect of an intervention that traditionally is judged by the pressure response alone. Methods: This exploratory study used data from the BOX trial that investigated a higher (MAP of 77 mmHg, MAP77) versus a lower (63 mmHg, MAP63) blood pressure target during intensive care of survivors from out-of-hospital cardiac arrest. Data from 730 patients (MAP63, n = 362 and MAP77, n = 368) were used to calculate Pmsa, the driving pressure for VR (VRdP, the difference between Pmsa and central venous pressure [CVP]), the resistance to venous return (RVR, the VRdP divided by the cardiac output [CO]) and heart efficiency (Eh, the VRdP divided by Pmsa). Linear mixed models were used to evaluate longitudinal haemodynamic data captured from admission to the intensive care unit and over 36 h. Results: The Pmsa was consistently higher in the MAP77 group (p &lt;.03) while the CVP was not statistically different. The greater Pmsa translated into a progressively increasing VRdP (p &lt;.0001) and thus an increased CO (p &lt;.001). Similar stroke volumes in both groups meant that CO was maintained by an increased heart rate in MAP77 (p &lt;.001). The RVR was higher in MAP77 (p &lt;.04) but gradually decreased in both groups, while the Eh was similar overall. Conclusion: In conclusion, a higher MAP target effectively increased the stressed intravascular volume to sustain a higher CO. Editorial Comment: This post-hoc analysis of the BOX trial explores VR physiology and how it is influenced by the use of various doses of noradrenaline and dopamine. A higher blood pressure target appears to increase VR by increasing the stressed intravascular volume. This results in an increase in the CO. These findings are important given the worry about the effect of a higher afterload on cardiac function.</p

Level of sedation in critically ill adult patients : a protocol for a systematic review with meta-analysis and trial sequential analysis

Publisher Copyright: © 2022 BMJ Publishing Group. All rights reserved.Introduction It is standard of care to provide sedation to critically ill patients to reduce anxiety, discomfort and promote tolerance of mechanical ventilation. Given that sedatives can have differing effects based on a variety of patient and pharmacological characteristics, treatment approaches are largely based on targeting the level of sedation. The benefits of differing levels of sedation must be balanced against potential adverse effects including haemodynamic instability, causing delirium, delaying awakening and prolonging the time of mechanical ventilation and intensive care stay. This systematic review with meta-analysis aims to investigate the current evidence and compare the effects of differing sedation levels in adult critically ill patients. Methods and analyses We will conduct a systematic review based on searches of preidentified major medical databases (eg, MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify trials meeting inclusion criteria. We will include randomised clinical trials comparing any degree of sedation with no sedation and lighter sedation with deeper sedation for critically ill patients admitted to the intensive care unit. We will include aggregate data meta-analyses and trial sequential analyses. Risk of bias will be assessed with domains based on the Cochrane risk of bias tool. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed using Grades of Recommendations, Assessment, Development and Evaluation. Ethics and dissemination No formal approval or review of ethics is required as individual patient data will not be included. This systematic review has the potential to highlight (1) whether one should believe sedation to be beneficial, harmful or neither in critically ill adults; (2) the existing knowledge gaps and (3) whether the recommendations from guidelines and daily clinical practice are supported by current evidence. These results will be disseminated through publication in a peer-reviewed journal.Peer reviewe

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.Peer reviewe

Interactions in the 2x2x2 factorial randomised clinical STEPCARE trial and the potential effects on conclusions : a protocol for a simulation study

Background: Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2x2x2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest. Methods: By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all- cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errors Discussion: This protocol for a simulation study will inform the design of a 2x2x2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results.Peer reviewe