Higher Blood Pressure Targets Research Articles

Low Versus High Blood Pressure Targets in Critically Ill and Surgical Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Hypotension is associated with adverse outcomes in critically ill and perioperative patients. However, these assumptions are supported by observational studies. This meta-analysis of randomized controlled trials aims to compare the impact of lower versus higher blood pressure targets on mortality. We searched PubMed, Cochrane, and Scholar from inception to February 10, 2024. Randomized trials comparing lower versus higher blood pressure targets in the management of critically ill and perioperative settings. The primary outcome was all-cause mortality at the longest follow-up available. This review was registered in the Prospective International Register of Systematic Reviews, CRD42023452928. Of 2940 studies identified by the search string, 28 (12 in critically ill and 16 in perioperative settings) were included totaling 15,672 patients. Patients in the low blood pressure target group had lower mortality (23 studies included: 1019/7679 [13.3%] vs. 1103/7649 [14.4%]; relative risk 0.93; 95% CI, 0.87-0.99; p = 0.03; I2 = 0%). This corresponded to a 97.4% probability of any increase in mortality with a Bayesian approach. These findings were mainly driven by studies performed in the ICU setting and with treatment lasting more than 24 hours; however, the magnitude and direction of the results were similar in the majority of sensitivity analyses including the analysis restricted to low risk of bias studies. We also observed a lower rate of atrial fibrillation and fewer patients requiring transfusion in low-pressure target groups. No differences were found in the other secondary outcomes. Based on pooled randomized trial evidence, a lower compared with a higher blood pressure target results in a reduction of mortality, atrial fibrillation, and transfusion requirements. Lower blood pressure targets may be beneficial but there is ongoing uncertainty. However, the present meta-analysis does not confirm previous findings and recommendations. These results might inform future guidelines and promote the study of the concept of protective hemodynamics.

Combined effects of targeted blood pressure, oxygenation, and duration of device-based fever prevention after out-of-hospital cardiac arrest on 1-year survival: post hoc analysis of a randomized controlled trial

BackgroundThe “Blood Pressure and Oxygenation Targets in Post Resuscitation Care” (BOX) trial investigated whether a low versus high blood pressure target, a restrictive versus liberal oxygenation target, and a shorter versus longer duration of device-based fever prevention in comatose patients could improve outcomes. No differences in rates of discharge from hospital with severe disability or 90-day mortality were found. However, long-term effects and potential interaction of the interventions are unknown. Accordingly, the objective of this study is to investigate both individual and combined effects of the interventions on 1-year mortality rates.MethodsThe BOX trial was a randomized controlled two-center trial that assigned comatose resuscitated out-of-hospital cardiac arrest patients to the following three interventions at admission: A blood pressure target of either 63 mmHg or 77 mmHg; An arterial oxygenation target of 9–10 kPa or 13–14 kPa; Device-based fever prevention administered as an initial 24 h at 36 °C and then either 12 or 48 h at 37 °C; totaling 36 or 72 h of temperature control. Randomization occurred in parallel and simultaneously to all interventions. Patients were followed for the occurrence of death from all causes for 1 year. Analyzes were performed by Cox proportional models, and assessment of interactions was performed with the interventions stated as an interaction term.ResultsAnalysis for all three interventions included 789 patients. For the intervention of low compared to high blood pressure targets, 1-year mortality rates were 35% (138 of 396) and 36% (143 of 393), respectively, hazard ratio (HR) 0.92 (0.73–1.16) p = 0.47. For the restrictive compared to liberal oxygenation targets, 1-year mortality rates were 34% (135 of 394) and 37% (146 of 395), respectively, HR 0.92 (0.73–1.16) p = 0.46. For device-based fever prevention for a total of 36 compared to 72 h, 1-year mortality rates were 35% (139 of 393) and 36% (142 of 396), respectively, HR 0.98 (0.78–1.24) p = 0.89. There was no sign of interaction between the interventions, and accordingly, no combination of randomizations indicated differentiated treatment effects.ConclusionsThere was no difference in 1-year mortality rates for a low compared to high blood pressure target, a liberal compared to restrictive oxygenation target, or a longer compared to shorter duration of device-based fever prevention after cardiac arrest. No combination of the interventions affected these findings.Trial registration ClinicalTrials.gov NCT03141099, Registered 30 April 2017.

Impact of blood pressure targets on central hemodynamics during intensive care after out-of-hospital cardiac arrest

ObjectivesThe aim was to investigate the advanced hemodynamic effects of the two MAP-targets during intensive care on systemic hemodynamics in comatose patients after cardiac arrest. DesignSecondary analysis of a randomized controlled trial. SettingPrimary vasopressor used was per protocol norepinephrine. Hemodynamic monitoring was done with pulmonary artery catheters (PAC) and measurements were made on predefined time points. The primary endpoint of this substudy was the difference in cardiac index within 48 h from a repeated measurements-mixed model. Secondary endpoints included systemic vascular resistance index (SVRI), heart rate, and stroke volume index. PatientsComatose survivors after out-of-hospital cardiac arrest. InterventionsThe “Blood pressure and oxygenations targets after out-of-hospital cardiac arrest (BOX)”-trial was a randomized, controlled, double-blinded, multicenter-study comparing targeted mean arterial pressure (MAP) of 63 mmHg (MAP63) vs 77 mmHg (MAP77). Measurements and main resultsAmong 789 randomized patients, 730 (93%) patients were included in the hemodynamic substudy. From PAC-insertion (median 1 hours after ICU-admission) and the next 48 hours, the MAP77-group received significantly higher doses of norepinephrine (mean difference 0.09 µg/kg/min, 95% confidence interval (CI) 0.07–0.11, pgroup < 0.0001). Cardiac index was significantly increased (0.20 L/min/m2 (CI 0.12–0.28), pgroup < 0.0001) as was SVRI with an overall difference of (43 dynes m2/s/cm5 (CI 7–79); pgroup = 0.02). Heart rate was increased in the MAP77-group (4 beats/minute; CI 2–6, pgroup < 0.003), but stroke volume index was not (pgroup = 0.10). ConclusionsTargeted MAP at 77 mmHg compared to 63 mmHg resulted in a higher dose of norepinephrine, increased cardiac index and SVRI. Heart rate was also increased, but stroke volume index was not affected by a higher blood pressure target.

High versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: a study protocol for the HISTAP randomized clinical trial

BackgroundThe intraoperative period is often characterized by hemodynamic instability, and intraoperative hypotension is a common complication. The optimal mean arterial pressure (MAP) target in hypertensive patients is still not clear. We hereby describe the protocol and detailed statistical analysis plan for the high versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: the HISTAP randomized clinical trial. The HISTAP trial aims at addressing whether the use of a higher intraoperative MAP target in high-risk hypertensive surgical patients scheduled for elective abdominal surgery would improve postoperative outcomes, as compared to the standard and recommended perioperative MAP, by using a composite outcome including a 30-day mortality from surgical intervention and at least one major organ dysfunction or new onset of sepsis and septic shock occurring 7 days after surgery.MethodsThe HISTAP trial is an investigator-initiated, pragmatic, parallel-grouped, randomized, stratified, analyst-blinded trial with adequate allocation sequence generation, and allocation concealment. We will allocate 636 patients to a MAP target ≥ 80 mmHg (treatment group) or to a MAP target ≥65 mmHg (control group). The primary outcome is a composite outcome including a 30-day mortality from the operation and major organ complications. Secondary outcomes are mortality at 30 days, intensive care unit (ICU) length of stay, ICU readmission, Sequential Organ Failure Assessment (SOFA) scores recorded up to postoperative day 7, overall intraoperative fluid balance, vasopressors use, and the need for reoperation. An unadjusted χ2 test will be used for the primary outcome analysis. A Cox proportional hazards model will be used to adjust the association between the primary outcome and baseline covariates.ConclusionsThe HISTAP trial results will provide important evidence to guide clinicians’ choice regarding the intraoperative MAP target in high-risk hypertensive patients scheduled for elective abdominal surgery.

How do high blood pressure targets compare with low blood pressure targets for people undergoing cardiac surgery while on cardiopulmonary bypass?

How do high blood pressure targets compare with low blood pressure targets for people undergoing cardiac surgery while on cardiopulmonary bypass?

Higher versus lower blood pressure targets after cardiac arrest: A meta-analysis of randomized controlled trials

A few mostly underpowered randomized controlled trials (RCTs) have been used to study the impact of blood pressure (BP) targets in out-of-hospital cardiac arrest (OHCA) patients. We aimed to perform an updated meta-analysis to compare the outcomes between the higher BP target and the lower BP target groups following OHCA. A systematic search was conducted on PubMed, Embase and the Cochrane Library until December 2022. We pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) using RevMan 5.4. Our search yielded four RCTs with a total of 1114 patients. Regarding our primary outcome of all-cause mortality, there was no significant difference between higher versus lower BP target goals in post-OHCA patients (OR 1.12, 95% CI: 0.86 to 1.45). Furthermore, there were no significant differences between the two groups in good neurological outcome, the incidence of arrhythmia, need for renal replacement therapy, and the levels of neuron-specific enolase at 48 h. The length of ICU stay of patients treated with the higher BP target was significantly lower but by a small margin. These findings do not support the use of a higher BP target but are subject to confirmation by large-scale RCTs investigating homogenous BP goals.

Relevance of age and hypertension for blood pressure targets in comatose survivors of cardiac arrest

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Novo Nordisk Foundation. Background Baseline arterial blood pressure (BP) is influenced by age. Therefore, age and previous hypertension may alter the appropriate BP target after out-of-hospital cardiac arrest (OHCA). Purpose To examine whether the optimal BP target after OHCA is affected by age and a history of arterial hypertension. Methods The Blood Pressure and Oxygenation Targets in Post Resuscitation Care (BOX) trial was a randomized, controlled, double-blind trial comprising 789 comatose patients ≥18 years of age, resuscitated after OHCA of presumed cardiac cause. Patients were randomized to a mean arterial BP target of either 63 mm Hg (low BP target group) or 77 mm Hg (high BP target group). The primary outcome was a composite of death from any cause or hospital discharge with severe cerebral disability within one year. The relationship between age or prevalent hypertension and clinical outcomes was evaluated using Cox proportional-hazards regression. Age was stratified into quartiles. We further determined if the effects of BP target varied across the age spectrum (and according to prevalent hypertension). Results Three-hundred and ninety-three patients were assigned to the high BP target group and 396 to the low BP target group. In all, 204 (25.9%), 201 (25.5%), 186 (23.6%), and 198 (25.1%) were ≤54, 55-64, 65-72, and ≥73 years. Mean age was similar between the two study groups (high BP target 63 ± 13 years versus low BP target 62 ± 14 years; P = 0.60). A total of 176 (45%) patients in the high BP target group and 186 (47%) patients in the low BP target group had known hypertension. At 90 days, 133 patients (34%) in the high BP target group and 127 patients (32%) in the low BP target group had experienced the primary outcome. The risk of the primary outcome increased with higher age (Figure 1). Hazard ratios of the primary outcome according to BP targets within each age quartile (with low BP target as reference) were as follows: ≤54: 1.71; 95% confidence interval [CI], 0.99 to 2.95; P = 0.054, 55-64: 0.92; 95% CI, 0.57 to 1.49; P = 0.73, 65-72: 1.12; 95% CI, 0.73 to 1.74; P = 0.59 and ≥73: 0.88; 95% CI, 0.60 to 1.27; P = 0.48 (Figure 2). The hazard ratio of the primary outcome was 0.99; 95% CI, 0.72 to 1.37; P = 0.97 in patients without prevalent hypertension, and 1.14; 95% CI, 0.83 to 1.54; P = 0.42 in patients with prevalent hypertension. Conclusions In patients resuscitated after OHCA, there was a significant association between age and the primary composite outcome of death, severe disability, or coma. The effect of BP target on the primary outcome did not appear to differ according to age groups or prevalent hypertension. Therefore, age and prevalent hypertension should not influence the choice of BP targets after OHCA.

Blood-pressure targets in comatose survivors of cardiac arrest with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention - a BOX sub-study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation. Background After successful resuscitation from out-of-hospital cardiac arrest (OHCA), patients who remain comatose often need hemodynamic support with vasoactive drugs in order to secure an adequate perfusion pressure to vital organs. However, evidence regarding specific blood-pressure targets is sparse, and patients with concomitant heart disease such as acute ST-elevation myocardial infarction (STEMI) might benefit from a lower afterload and lower doses of vasoactive drugs. Purpose To assess the impact of blood-pressure on biochemical infarct size in comatose survivors of OHCA with STEMI and, further, to investigate whether a high or low mean arterial blood-pressure target is superior in preventing death or severe brain injury. Methods The BOX study (n=789) is a randomized trial with a 2-by-2 factorial design which evaluated a double-blind intervention of a high (77 mmHg) versus a low (63 mmHg) mean arterial blood-pressure target in comatose survivors of OHCA of presumed cardiac cause. In this pre-specified sub-study we included patients who had an initial electrocardiogram with STEMI recorded after return of spontaneous circulation (ROSC). The primary outcome was creatine kinase (CK), creatine kinase MB (CKMB), and troponin T (TnT) levels measured at 48 hours as surrogate markers of infarct size. A secondary outcome was a composite of all-cause death within one year from admission or discharge from the hospital with a Cerebral Performance Category (CPC) of 3 to 4, indicating severe neurological disability or a comatose or vegetative state. Results A total of 350 patients were included. Mean time to ROSC was 21±13 minutes. The mean age was 63±12 years and approximately 4 out of 5 were male. The prevalence of relevant prior medical history was as follows; hypertension 42%, diabetes 12%, chronic ischemic heart disease 20%, percutaneous coronary intervention 11%, coronary artery bypass grafting 4%, and congestive heart failure 10%. Mean CK, CKMB and TnT measured at 48 hours did not differ between the two blood-pressure target groups (p=0.42, p=0.14 and p=0.65, respectively). Within one year, 138 patients (39%) had died or been discharged with a CPC of 3 to 4 with no difference found between high or low blood pressure targets (hazard ratio, 1.02; 95% CI, 0.73-1.43; p=0.9). Conclusion Targeting a high versus a low mean arterial blood-pressure in comatose survivors of OHCA with STEMI did not affect infarct size estimated by coronary biomarkers at 48 hours nor did it result in a significant difference in death or severe neurologic disability. Although not evaluating side effects, this study thus suggests that the use of pharmacologic circulatory support in post-resuscitation care can be limited.

Developments in Post-Resuscitation Care for Out-of-Hospital Cardiac Arrests in Adults-A Narrative Review.

This review focuses on current developments in post-resuscitation care for adults with an out-of-hospital cardiac arrest (OHCA). As the incidence of OHCA is high and with a low percentage of survival, it remains a challenge to treat those who survive the initial phase and regain spontaneous circulation. Early titration of oxygen in the out-of-hospital phase is not associated with increased survival and should be avoided. Once the patient is admitted, the oxygen fraction can be reduced. To maintain an adequate blood pressure and urine output, noradrenaline is the preferred agent over adrenaline. A higher blood pressure target is not associated with higher rates of good neurological survival. Early neuro-prognostication remains a challenge, and prognostication bundles should be used. Established bundles could be extended by novel biomarkers and methods in the upcoming years. Whole blood transcriptome analysis has shown to reliably predict neurological survival in two feasibility studies. This needs further investigation in larger cohorts.

High versus low blood pressure targets for cardiac surgery while on cardiopulmonary bypass.

Cardiac surgery is performed worldwide. Most types of cardiac surgery are performed using cardiopulmonary bypass (CPB). Cardiac surgery performed with CPB is associated with morbidities. CPB needs an extracorporeal circulation that replaces the heart and lungs, and performs circulation, ventilation, and oxygenation of the blood. The lower limit of mean blood pressure to maintain blood flow to vital organs increases in people with chronic hypertension. Because people undergoing cardiac surgery commonly have chronic hypertension, we hypothesised that maintaining a relatively high blood pressure improves desirable outcomes among the people undergoing cardiac surgery with CPB. To evaluate the benefits and harms of higher versus lower blood pressure targets during cardiac surgery with CPB. We used standard, extensive Cochrane search methods. The latest search of databases was November 2021 and trials registries in January 2020. We included randomised controlled trials (RCTs) comparing a higher blood pressure target (mean arterial pressure 65 mmHg or greater) with a lower blood pressure target (mean arterial pressure less than 65 mmHg) in adults undergoing cardiac surgery with CPB. We used standard Cochrane methods. Primary outcomes were 1. acute kidney injury, 2. cognitive deterioration, and 3. all-cause mortality. Secondary outcomes were 4. quality of life, 5. acute ischaemic stroke, 6. haemorrhagic stroke, 7. length of hospital stay, 8. renal replacement therapy, 9. delirium, 10. perioperative transfusion of blood products, and 11. perioperative myocardial infarction. We used GRADE to assess certainty of evidence. We included three RCTs with 737 people compared a higher blood pressure target with a lower blood pressure target during cardiac surgery with CPB. A high blood pressure target may result in little to no difference in acute kidney injury (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.81 to 2.08; I² = 72%; 2 studies, 487 participants; low-certainty evidence), cognitive deterioration (RR 0.82, 95% CI 0.45 to 1.50; I² = 0%; 2 studies, 389 participants; low-certainty evidence), and all-cause mortality (RR 1.33, 95% CI 0.30 to 5.90; I² = 49%; 3 studies, 737 participants; low-certainty evidence). No study reported haemorrhagic stroke. Although a high blood pressure target may increase the length of hospital stay slightly, we found no differences between a higher and a lower blood pressure target for the other secondary outcomes. We also identified one ongoing RCT which is comparing a higher versus a lower blood pressure target among the people who undergo cardiac surgery with CPB. A high blood pressure target may result in little to no difference in patient outcomes including acute kidney injury and mortality. Given the wide CIs, further studies are needed to confirm the efficacy of a higher blood pressure target among those who undergo cardiac surgery with CPB.

Morbidity and mortality in patients managed with high compared with low blood pressure targets during on-pump cardiac surgery: a systematic review and meta-analysis of randomized controlled trials.

Many believe that blood pressure management during cardiac surgery is associated with postoperative outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of high compared with low intraoperative blood pressure targets on postoperative morbidity and mortality in adults undergoing cardiac surgery on cardiopulmonary bypass (CPB). Our primary objective was to inform the design of a future large RCT. We searched MEDLINE, EMBASE, Web of Science, CINAHL, and CENTRAL for RCTs comparing high with low intraoperative blood pressure targets in adult patients undergoing any cardiac surgical procedure on CPB. We screened reference lists, grey literature, and conference proceedings. We included eight RCTs (N =1,116 participants); all examined the effect of blood pressure management only during the CPB. Trial definitions of high compared with low blood pressure varied and, in some, there was a discrepancy between the target and achieved mean arterial pressure. We observed no difference in delirium, cognitive decline, stroke, acute kidney injury, or mortality between high and low blood pressure targets (very-low to low quality evidence). Higher blood pressure targets may have increased the risk of requiring a blood transfusion (three trials; n = 456 participants; relative risk, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.01; moderate quality evidence) but this finding was based on a small number of trials. Individual trial definitions of high and low blood pressure targets varied, limiting inferences. The effect of high (compared with low) blood pressure targets on other morbidity and mortality after cardiac surgery remains unclear because of limitations with the body of existing evidence. Research to determine the optimal management of blood pressure during cardiac surgery is required. PROSPERO (CRD42020177376); registered: 5 July 2020.

Should Vasopressors Be Started Early in Septic Shock?

Sepsis can influence blood volume, its distribution, vascular tone, and cardiac function. Persistent hypotension or the need for vasopressors after volume resuscitation is part of the definition of septic shock. Since increased positive fluid balance has been associated with increased morbidity and mortality in sepsis, timing of vasopressors in the treatment of septic shock seems crucial. However, conclusive evidence on timing and sequence of interventions with the goal to restore tissue perfusion is lacking. The aim of this narrative review is to depict the pathophysiology of hypotension in sepsis, evaluate how common interventions to treat hypotension interfere with physiology, and to give a resume of the results from clinical studies focusing on targets and timing of vasopressor in sepsis. The majority of studies comparing early versus late administration of vasopressors in septic shock are rather small, single-center, and retrospective. The range of "early" is between 1 and 12 hours. The available studies suggest a mean arterial pressure of 60 to 65 mm Hg as a threshold for increased risk of morbidity and mortality, whereas higher blood pressure targets do not seem to add further benefits. The data, albeit mostly from observational studies, speak for combining vasopressors with fluids rather "early" in the treatment of septic shock (within a 0-3-hour window). Nevertheless, the optimal resuscitation strategy should take into account the source of infection, the pathophysiology, the time and clinical course preceding the diagnosis of sepsis, and also comorbidities and sepsis-induced organ dysfunction.

High Versus Normal Blood Pressure Targets in Relation to Right Ventricular Dysfunction After Cardiac Surgery: A Randomized Controlled Trial

Management of right ventricular (RV) dysfunction is challenging. Current practice predominantly is based on data from experimental and small uncontrolled studies and includes augmentation of blood pressure. However, whether such intervention is effective in the clinical setting of cardiac surgery is unknown. Randomized controlled trial. Single-center study in a tertiary teaching hospital. The study comprised 78 patients equipped with a pulmonary artery catheter (PAC), classified according to PAC-derived RV ejection fraction (RVEF); 44 patients had an RVEF of <20%, and 34 patients had an RVEF between ≥20% and <30%. Patients randomly were assigned to either a normal target group (mean arterial pressure 65 mmHg) or a high target group [mean arterial pressure 85 mmHg]). The primary end- point was the change in RVEF over a one-hour study period. There was no significant between-group difference in change of RVEF <20% (-1% [-3.3 to 1.8] in the normal-target group v 0.5% [-1 to 4] in the high-target group; p = 0.159). There was no significant between-group difference in change in RVEF 20%-to-30% (-1% [-3 to 0] in the normal-target group v 1% [-1 to 3] in the high-target group; p = 0.074). These results were in line with the simultaneous observation that echocardiographic variables of RV and left ventricular function also remained unaltered over time, irrespective of either baseline RVEF or treatment protocol. In a mixed cardiac surgery population with RV dysfunction, norepinephrine-mediated high blood pressure targets did not result in an increase in PAC-derived RVEF compared with normal blood pressure targets.

A randomised double-blind pilot trial comparing a mean arterial pressure target of 65 mm Hg versus 72 mm Hg after out-of-hospital cardiac arrest.

After resuscitation from out-of-hospital cardiac arrest, mean arterial pressure below 65 mm Hg is avoided with vasopressors. A higher blood-pressure target could potentially improve outcome. The aim of this pilot trial was to investigate the effect of a higher mean arterial pressure target on biomarkers of organ injury. This was a single-centre, double-blind trial of 50 consecutive, comatose out-of-hospital cardiac arrest patients randomly assigned in a 1:1 ratio to a mean arterial pressure target of 65 mm Hg (MAP65) or 72 mm Hg (MAP72). Modified blood pressure modules with a -10% offset were used, enabling a double-blind study design. End-points were biomarkers of organ injury including markers of endothelial integrity (soluble trombomodulin) brain damage (neuron-specific enolase) and renal function (estimated glomerular filtration rate). Mean arterial pressure was significantly higher in MAP72 with a mean difference of 5 mm Hg (pgroup=0.03). After 48 h, soluble trombomodulin (median (interquartile range)) was 8.2 (6.7-12.9) ng/ml and 8.3 (6.0-10.8) ng/ml (p=0.29), neuron-specific enolase was 20 (13-31 μg/l) and 18 (13-44 μg/l) p=0.79) and estimated glomerular filtration rate (mean (±standard deviation)) was 61±19 ml/min/1.73m2 and 48±22 ml/min/1.73 m2 (p=0.08) for the MAP72 and MAP65 groups, respectively. Renal replacement therapy was needed in eight patients (31%) in MAP65 and three patients (13%) in MAP72 (p=0.14). Double-blind allocation to different mean arterial pressure targets is feasible in comatose out-of-hospital cardiac arrest patients. A mean arterial pressure target of 72 mm Hg compared to 65 mm Hg did not result in improved biomarkers of organ injury. We observed a trend towards preserved renal function in the MAP72 group.

THE SAFETY AND EFFICACY OF HIGHER COMPARED TO LOWER INTRAOPERATIVE BLOOD PRESSURE IN ADULT PATIENTS UNDERGOING CARDIAC SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

The 2019 EACTS/EACTA/EBCP guidelines for the management of cardiopulmonary bypass (CPB) in adult cardiac surgery recommend maintaining mean arterial pressure (MAP) within a range of 50-80 mmHg. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of high vs. low blood pressure targets during CPB on morbidity and mortality in adult patients undergoing cardiac surgery.

High versus low blood pressure targets for cardiac surgery with cardiopulmonary bypass

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the benefits and harms of a higher versus lower blood pressure target during cardiac surgery with cardiopulmonary bypass (CPB).

Abstract 274: Identifying the Optimal Cerebral Perfusion Pressure Following Hypoxic-Ischemic Brain Injury

Introduction: The optimal cerebral perfusion pressure (CPP) following hypoxic-ischemic brain injury (HIBI) is currently unknown. We retrospectively analyzed intracranial monitoring data from a cohort of patients with HIBI to identify a threshold level for CPP that optimizes cerebrovascular pressure reactivity (a surrogate for CA) while limiting the risk of intracranial hypertension and brain tissue hypoxia. Hypothesis: We hypothesized that higher CPP values would be associated with improved cerebrovascular pressure reactivity. Methods: ICP, brain tissue oxygen (P bt O 2 ), MAP, and CPP (defined as MAP - ICP) were recorded continuously and time synchronized for all patients using a bedside monitor (CNS Monitor, Moberg Research). Pressure Reactivity Index (PRx) was calculated as the time varying correlation between MAP and ICP over 5 min intervals updated every minute. The degree of CA impairment (defined as % time PRx &gt; 0.2) was plotted against MAP and CPP, respectively. The relationships between ICP and P bt O 2 versus CPP, as well as ICP and P bt O 2 versus % time PRx &gt; 0.2, were similarly calculated. Results: We analyzed 37 patients (33 cardiac arrest, 4 prolonged hypoxia) with HIBI who underwent intracranial neuromonitoring over a 3 year period. Lower CPP values were associated with higher degrees of CA impairment. The cumulative burden of elevated PRx was significantly lower for CPP values above a cutoff of 85 mmHg compared to lower CPP values (p &lt; 0.001, Wilcoxon rank sum test). A similar cutoff for MAP could not be identified, although lower MAP values were also associated with greater CA impairment. Intracranial hypertension (ICP &gt; 20 mmHg) and brain hypoxia (P bt O2 &lt; 20 mmHg) were both associated with CA impairment (p &lt; 0.001 and p &lt; 0.001, respectively, Wilcoxon rank sum test). Conclusions: Higher CPP and MAP values appear to be associated with improved CA after HIBI. Given that CA impairment is associated with both intracranial hypertension and brain hypoxia, our work reaffirms the notion that higher blood pressure targets may improve outcome after HIBI. The identification of a distinct CPP cutoff for CA optimization suggests that targeting CPP instead of MAP may be advantageous, although further work is required to clarify this issue.

Design paper of the \u201cBlood pressure targets in post-resuscitation care and bedside monitoring of cerebral energy state: a randomized clinical trial\u201d

BackgroundNeurological injuries remain the leading cause of death in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Adequate blood pressure is of paramount importance to optimize cerebral perfusion and to minimize secondary brain injury. Markers measuring global cerebral ischemia caused by cardiac arrest and consecutive resuscitation and reflecting the metabolic variations after successful resuscitation are needed to assist a more individualized post-resuscitation care. Currently, no technique is available for bedside evaluation of global cerebral energy state, and until now blood pressure targets have been based on limited clinical evidence. Recent experimental and clinical studies indicate that it might be possible to evaluate cerebral oxidative metabolism from measuring the lactate-to-pyruvate (LP) ratio of the draining venous blood. In this study, jugular bulb microdialysis and immediate bedside biochemical analysis are introduced as new diagnostic tools to evaluate the effect of higher mean arterial blood pressure on global cerebral metabolism and the degree of cellular damage after OHCA.Methods/designThis is a single-center, randomized, double-blinded, superiority trial. Sixty unconscious patients with sustained return of spontaneous circulation after OHCA will be randomly assigned in a one-to-one fashion to low (63 mm Hg) or high (77 mm Hg) mean arterial blood pressure target. The primary end-point will be a difference in mean LP ratio within 48 h between blood pressure groups. Secondary end-points are (1) association between LP ratio and all-cause intensive care unit (ICU) mortality and (2) association between LP ratio and survival to hospital discharge with poor neurological function.DiscussionMarkers measuring cerebral ischemia caused by cardiac arrest and consecutive resuscitation and reflecting the metabolic changes after successful resuscitation are urgently needed to enable a more personalized post-resuscitation care and prognostication. Jugular bulb microdialysis may provide a reliable global estimate of cerebral metabolic state and can be implemented as an entirely new and less invasive diagnostic tool for ICU patients after OHCA and has implications for early prognosis and treatment.Trial registrationClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03095742). Registered March 30, 2017.

Blood pressure targets for hypertension in older adults.

Eight out of 10 major antihypertensive trials in older adults attempted to achieve a target systolic blood pressure (BP) less than 160 mmHg. Collectively these trials demonstrated benefit for treatment, as compared to no treatment, for an older adult with BP greater than 160 mmHg. However an even lower BP target of less than 140 mmHg is commonly applied to all age groups. At the present time it is not known whether a lower or higher BP target is associated with better cardiovascular outcomes in older adults. To assess the effects of a higher (less than 150 to 160/95 to 105 mmHg) BP target compared to the lower BP target of less than 140/90 mmHg in hypertensive adults 65 years of age or older. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Hypertension Specialised Register, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We also contacted authors of relevant papers regarding further published and unpublished work. Randomised trials, of at least one year's duration, conducted on hypertensive adults aged 65 years or older, which report the effect on mortality and morbidity of a higher systolic or diastolic BP treatment target (whether ambulatory, home, or office measurements) in the range of systolic BP less than 150 to 160 mmHg or diastolic BP less than 95 to 105 mmHg as compared to a lower BP treatment target of less than 140/90 mmHg or lower. Two authors independently screened and selected trials for inclusion, assessed risk of bias, and extracted data. We combined data for dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI) and for continuous outcomes we used mean difference (MD). Primary outcomes were all-cause mortality, stroke, institutionalisation, and cardiovascular serious adverse events. Secondary outcomes included cardiovascular mortality, non-cardiovascular mortality, unplanned hospitalisation, each component of cardiovascular serious adverse events separately (including cerebrovascular disease, cardiac disease, vascular disease, and renal failure), total serious adverse events, total minor adverse events, withdrawals due to adverse effects, systolic BP achieved, and diastolic BP achieved. We found and included three unblinded randomised trials in 8221 older adults (mean age 74.8 years), in which higher BP targets of less than 150/90 mmHg (two trials) and less than 160/90 mmHg (one trial) were compared to a lower target of less than 140/90 mmHg. Treatment to the two different BP targets over two to four years failed to produce a difference in any of our primary outcomes, including all-cause mortality (RR 1.24 95% CI 0.99 to 1.54), stroke (RR 1.25 95% CI 0.94 to 1.67) and total cardiovascular serious adverse events (RR 1.19 95% CI 0.98 to 1.45). However, the 95% confidence intervals of these outcomes suggest the lower BP target is probably not worse, and might offer a clinically important benefit. We judged all comparisons to be based on low-quality evidence. Data on adverse effects were not available from all trials and not different, including total serious adverse events, total minor adverse events, and withdrawals due to adverse effects. At the present time there is insufficient evidence to know whether a higher BP target (less than150 to 160/95 to 105 mmHg) or a lower BP target (less than 140/90 mmHg) is better for older adults with high BP. Additional good-quality trials assessing BP targets in this population are needed.

A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension.

Clinicians must balance the risks from hypotension with the potential adverse effects of vasopressors. Experts have recommended a mean arterial pressure (MAP) target of at least 65 mmHg, and higher in older patients and in patients with chronic hypertension or atherosclerosis. We conducted a systematic review of randomized-controlled trials comparing higher vs lower blood pressure targets for vasopressor therapy administered to hypotensive critically ill patients. We searched MEDLINE®, EMBASE™, and the Cochrane Central Register of Controlled Trials for studies of higher vs lower blood pressure targets for vasopressor therapy in critically ill hypotensive adult patients. Two reviewers independently assessed trial eligibility based on titles and abstracts, and they then selected full-text reports. Outcomes, subgroups, and analyses were prespecified. We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the overall confidence in the estimates of intervention effects. Of 8001 citations, we retrieved 57 full-text articles and ultimately included two randomized-controlled trials (894 patients). Higher blood pressure targets were not associated with lower mortality (relative risk [RR], 1.05; 95% confidence interval [CI], 0.90 to 1.23; P = 0.54), and neither age (P = 0.17) nor chronic hypertension (P = 0.32) modified the overall effect. Nevertheless, higher blood pressure targets were associated with a greater risk of new-onset supraventricular cardiac arrhythmia (RR, 2.08; 95% CI, 1.28 to 3.38; P < 0.01). Current evidence does not support a MAP target > 70 mmHg in hypotensive critically ill adult patients requiring vasopressor therapy.