Target Mean Arterial Pressure Research Articles

Oxygen Delivery and Consumption in Patients Who Are Comatose After Out-of-Hospital Cardiac Arrest Are Affected by Blood Pressure Target.

In the management of patients resuscitated from out-of-hospital cardiac arrest, a primary goal is to restore sufficient oxygen delivery (DO2) to meet demands in oxygen consumption (VO2). This post hoc analysis of the BOX (Blood Pressure and Oxygen Targets) study included adult patients who were comatose and experienced out-of-hospital cardiac arrest from a presumed cardiac cause, who were randomized to a mean arterial blood pressure (MAP) target of 63 mm Hg (MAP63) or 77 mm Hg (MAP77) and a Restrictive PaO2 target of 9 to 10 kPa versus a Liberal target of 13 to 14 kPa in a 2×2 factorial design. A pulmonary artery catheter was inserted following randomization. DO2 and VO2 were calculated as: DO2=cardiac output × arterial oxygen content, and VO2= cardiac output × arteriovenous oxygen difference. Of 789 patients, 730 (92.5%) were included in this substudy. A total of 362 patients were randomized to MAP77, and 368 to MAP63, 368 to a liberal Pao2 target, and 362 to a restrictive target. At all prespecified time points, DO2 in MAP77 was higher compared with MAP63, with a cumulative treatment effect of 203 L (95% CI, 132-274) O2 after 36 hours. VO2 was higher in MAP77 after 36 hours, with a cumulative treatment effect of 21.9 L (95% CI, 5.8-38) O2, compared with the MAP63 group. Targeting a MAP of 77 mm Hg resulted in an overall increase in DO2 and a smaller increase in VO2 compared with a MAP target of 63 mm Hg. A higher Pao2 target did not result in any difference in DO2 or VO2.

Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol-SEPSIS-BRAIN.

Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

Hemodynamic management of acute kidney injury

Purpose of review To discuss the role of hemodynamic management in critically ill patients with acute kidney injury. Recent findings Acute kidney injury (AKI) may be associated with persistent alterations in renal perfusion, even when cardiac output and blood pressure are preserved. The effects of interventions aiming at increasing renal perfusion are best evaluated by renal Doppler or contrast enhance ultrasound. However, limited data have been acquired with these techniques and the essential of the literature is based on surrogates of renal function such as incidence of use of renal replacement therapy. Fluids may increase renal perfusion but their effects are quite unpredictable and can be dissociated from their impact on cardiac output and arterial pressure. Inotropes can also be used in selected conditions. At the de-escalation phase, fluid withdrawal should be considered. Safe fluid withdrawal may be achieved when applied in selected patients with preserved tissue perfusion presenting signs of fluid intolerance. When applied, stopping rules should be set. Dobutamine, milrinone and levosimendan increase renal perfusion in AKI associated with cardiac failure or after cardiac surgery. However, the impact of these agents in sepsis is not well defined. Regarding vasopressors, norepinephrine is the first-line vasopressor agent, but vasopressin derivative may limit the requirement of renal replacement therapy. Angiotensin has promising effects in a limited size post-Hoc analysis of a RCT, but these data need to be confirmed. While correction of severe hypotension is associated with improved renal perfusion and function, the optimal mean arterial pressure (MAP) target level remains undefined, Systematic increase in MAP results in variable changes in renal perfusion. It sounds reasonable to individualize MAP target, paying attention to central venous and intraabdominal pressures, as well as to the response to an increase in MAP. Summary Recent studies have refined the impact of the various hemodynamic interventions on renal perfusion and function in critically ill patients with AKI. Though several of these interventions improve renal perfusion, their impact on renal function is more variable.

Association between average mean arterial pressure and 30-day mortality in critically ill patients with sepsis and primary hypertension: a retrospective analysis

Sepsis and hypertension pose significant health risks, yet the optimal mean arterial pressure (MAP) target for resuscitation remains uncertain. This study investigates the association between average MAP (a-MAP) within the initial 24 h of intensive care unit admission and clinical outcomes in patients with sepsis and primary hypertension using the Medical Information Mart for Intensive Care (MIMIC) IV database. Multivariable Cox regression assessed the association between a-MAP and 30-day mortality. Kaplan–Meier and log-rank analyses constructed survival curves, while restricted cubic splines (RCS) illustrated the nonlinear relationship between a-MAP and 30-day mortality. Subgroup analyses ensured robustness. The study involved 8,810 patients. Adjusted hazard ratios for 30-day mortality in the T1 group (< 73 mmHg) and T3 group (≥ 80 mmHg) compared to the T2 group (73–80 mmHg) were 1.25 (95% CI 1.09–1.43, P = 0.001) and 1.44 (95% CI 1.25–1.66, P < 0.001), respectively. RCS revealed a U-shaped relationship (non-linearity: P < 0.001). Kaplan–Meier curves demonstrated significant differences (P < 0.0001). Subgroup analysis showed no significant interactions. Maintaining an a-MAP of 73 to 80 mmHg may be associated with a reduction in 30-day mortality. Further validation through prospective randomized controlled trials is warranted.

Optimal target mean arterial pressure for patients with sepsis-associated encephalopathy: a retrospective cohort study

BackgroundSepsis-associated encephalopathy (SAE) patients often experience changes in intracranial pressure and impaired cerebral autoregulation. Mean arterial pressure (MAP) plays a crucial role in cerebral perfusion pressure, but its relationship with mortality in SAE patients remains unclear. This study aims to investigate the relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients, providing clinicians with the optimal MAP target.MethodsWe retrospectively collected clinical data of patients diagnosed with SAE on the first day of ICU admission from the MIMIC-IV (v2.2) database. Patients were divided into four groups based on MAP quartiles. Kruskal-Wallis H test and Chi-square test were used to compare clinical characteristics among the groups. Restricted cubic spline and segmented Cox regression models, both unadjusted and adjusted for multiple variables, were employed to elucidate the relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients and to identify the optimal MAP. Subgroup analyses were conducted to assess the stability of the results.ResultsA total of 3,816 SAE patients were included. The Q1 group had higher rates of acute kidney injury and vasoactive drug use on the first day of ICU admission compared to other groups (P < 0.01). The Q1 and Q4 groups had longer ICU and hospital stays (P < 0.01). The 28-day and in-hospital mortality rates were highest in the Q1 group and lowest in the Q3 group. Multivariable adjustment restricted cubic spline curves indicated a nonlinear relationship between MAP and mortality risk (P for nonlinearity < 0.05). The MAP ranges associated with HRs below 1 for 28-day and in-hospital mortality were 74.6–90.2 mmHg and 74.6–89.3 mmHg, respectively.The inflection point for mortality risk, determined by the minimum hazard ratio (HR), was identified at a MAP of 81.5 mmHg. The multivariable adjusted segmented Cox regression models showed that for MAP < 81.5 mmHg, an increase in MAP was associated with a decreased risk of 28-day and in-hospital mortality (P < 0.05). In Model 4, each 5 mmHg increase in MAP was associated with a 15% decrease in 28-day mortality risk (HR: 0.85, 95% CI: 0.79–0.91, p < 0.05) and a 14% decrease in in-hospital mortality risk (HR: 0.86, 95% CI: 0.80–0.93, p < 0.05). However, for MAP ≥ 81.5 mmHg, there was no significant association between MAP and mortality risk (P > 0.05). Subgroup analyses based on age, congestive heart failure, use of vasoactive drugs, and acute kidney injury showed consistent results across different subgroups.Subsequent analysis of SAE patients with septic shock also showed results similar to those of the original cohort.However, for comatose SAE patients (GCS ≤ 8), there was a negative correlation between MAP and the risk of 28-day and in-hospital mortality when MAP was < 81.5 mmHg, but a positive correlation when MAP was ≥ 81.5 mmHg in adjusted models 2 and 4.ConclusionThere is a nonlinear relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients. The optimal MAP target for SAE patients in clinical practice appears to be 81.5 mmHg.

Dexmedetomidine versus labetalol for induced hypotension during functional endoscopic sinus surgery: a randomized, double-blind study

Background &amp; Objective: Functional endoscopic sinus surgery (FESS) is a surgical procedure for treating sinus diseases. Bleeding is a common concern during FESS, so maintaining hemodynamic stability and ensuring quality surgical field visibility is crucial for achieving the best outcomes. The present study compared the time taken to achieve target mean arterial pressure (MAP) when using dexmedetomidine or labetalol during FESS and assessed the quality of the surgical field to establish the better choice of the two. Methodology: The study was conducted as a prospective, randomized, double-blinded clinical study. Sixty patients classified as American Society of Anesthesiologists grade I or II, undergoing FESS under general anesthesia, were divided into two groups, each with 30 patients. Group D patients received dexmedetomidine and Group L received labetalol. The study aimed to maintain the mean arterial pressure (MAP) between 60-70 mmHg. The operative field visibility was assessed using the Fromme and Boezaart scoring system. Emergence time and postoperative first analgesic request time were also recorded. Results: The time taken to achieve target MAP (60-70 mmHg) was less in Group D (15.1 ± 0.2 min) than in Group L (18.2 ± 0.5 min), and it was statistically significant (P &lt; 0.05). Although insignificant, lower MAP were observed in the Group D than Group L. A significantly lower heart rate was observed at defined intervals in Group D than in Group L. The visibility of the surgical field in both groups has comparable results. The first analgesic request time was considerably longer in Group D (52.2 ± 1.9) compared to Group L (10.2 ± 2.1) (P &lt; 0.05). Conclusion: Dexmedetomidine provided better hemodynamic stability and operative field visibility than Labetalol during FESS. Abbreviations: FESS - Functional endoscopic sinus surgery; MAP - Mean arterial pressure; EtCO2 - end-tidal carbon dioxide Keywords: Dexmedetomidine; Labetalol; Controlled Hypotension; Mean Arterial Pressure Citation: Gupta S, Yadav I, Saxena A, Bagla RK, Nazir N. Dexmedetomidine versus labetalol for induced hypotension during functional endoscopic sinus surgery: a randomized, double-blind study. Anaesth. pain intensive care 2024;28(4):652−657; DOI: 10.35975/apic.v28i4.2507 Received: May 19, 2024; Reviewed: June 08, 2024; Accepted: June 08, 2024

Relevance of age and hypertension for blood pressure targets in comatose survivors of cardiac arrest: a BOX-trial sub-study.

To assess whether the optimal mean arterial blood pressure (MAP) target after out-of-hospital cardiac arrest (OHCA) is influenced by age and a history of arterial hypertension. A post hoc analysis of data from the Blood Pressure and Oxygenation Targets in Post Resuscitation Care trial. The trial included 789 comatose patients randomized to a MAP target of 63 or 77 mmHg. The primary outcome of this sub-study was 1-year all-cause mortality. Cox proportional hazards regression and restricted cubic splines were used to examine whether prevalent hypertension and age modified the effect of low vs. high MAP target on all-cause mortality. Of the 789 patients randomized, 393 were assigned to a high MAP target, and 396 to a low MAP target. Groups were well-balanced for mean age (high MAP target 63 ± 13 years vs. low 62 ± 14 years) and hypertension (45 vs. 47%, respectively). At 1 year, the primary outcome occurred in 143 patients (36%) with a high MAP target and 138 (35%) with a low MAP target. The risk of the primary outcome increased linearly with increasing age (P < 0.001). The effect of a high vs. low MAP target on the primary outcome was modified by age when tested continuously, potentially favouring a low MAP target in younger patients (P for interaction = 0.03). Prevalent hypertension did not modify the effect of a high vs. low MAP target on the primary outcome (P for interaction = 0.67). Among patients resuscitated after OHCA, older patients and those with a history of hypertension did not benefit from a high MAP target.

Perfusion index and mean arterial pressure after return of spontaneous circulation in out-of hospital cardiac arrest (OHCA) and their relationship with perfusion and survival

Abstract Funding Acknowledgements None. Background Current guidelines for post-cardiac arrest care recommend targeting mean arterial pressure (MAP) to restore adequate perfusion indicated by adequate urine output (UO) and normal or decreasing lactate, avoiding hypotension (MAP &amp;lt; 65 mmHg). The peripheral perfusion index (PI) is the ratio of the pulsatile blood flow to the non-pulsatile blood flow measured peripherally by a standard pulse-oximeter, and it represents a promising non-invasive tool to assess perfusion. The goal of this study is to assess whether prehospital PI and MAP measurements are associated with lactate clearance (LC), adequate UO and 30-days survival with good neurological outcome. Methods A retrospective analysis of prospectively collected data (January 2018 - March 2023) in two cardiac arrest registries located in Italy and Belgium was performed. PI was automatically and continuously measured by the manual monitor/defibrillator. The mean PI value of each minute after ROSC was extracted from the monitor data report and the mean value of 30 min of PI monitoring (MPI30) was calculated and categorized in tertiles (MPI30 T1-T3). The lowest prehospital value for MAP recording was considered. LC was defined by a serum lactate level &amp;lt;2 mmol/L at 6 hours. Inadequate UO was defined as &amp;lt; 0.5mL/kg/h averaged at 12 hours. Neurological outcome was assessed with the Cerebral Performance Category (CPC) at 30 days. Results Out of the 397 OHCA patients admitted to the ICU after ROSC enrolled over the study period 206 had a MPI30 value available and were included in this study; MAP value was available in 186 patients. In the subgroup of patients with hypotension, patients with MPI30 in T1 showed higher incidence of inadequate UO at 12 hours (78.9% vs 25.8%, p&amp;lt;0.001). At multivariable logistic regression, after adjusting for MAP, shockable rhythm, age, and dosage of adrenaline administered, MPI30 was independently associated with inadequate UO (OR 0.68, 95% CI 0.50-0.91, p=0.01). Patients with hypotension and MPI30 in T1 showed lower LC at 6h (15.8% vs 43.4%, p=0.02) when compared to the remaining population. At multivariable Cox proportional-hazard regression, after correction for shockable rhythm, age, and total amount of adrenaline administered, patients with hypotension and MPI30 in T1 showed lower survival with CPC 1-2 at 30 days (HR 2.61, 95% CI 1.52-4.51, p=&amp;lt;0.001) when compared to patients without hypotension or with hypotension but MPI30 in T2-T3. No difference in LC, adequate UO and survival with good neurological outcome was found between patients with hypotension and MPI30 in T2-T3 compared to patients without hypotension. Conclusion PI is a useful indicator of perfusion in patients with hypotension after OHCA. Patients with hypotension and reduced PI showed higher incidence of inadequate UO and lower incidence of LC, as well as association with lower survival at 30 days with CPC 1-2.Lactate clearenceSurvival at 30days with CPC 1-2

Impact of arginine-vasopressin on regional perfusions in a porcine model of post-resuscitation syndrome

BackgroundPost-cardiac arrest (CA) shock is associated with multiple organ failure, including acute kidney injury, and is the leading cause of early death among patient successfully resuscitated from CA. Arginine-vasopressin (AVP) may be an interesting therapeutic alternative or complement to noradrenaline (NAD) to both control shock and preserve regional, especially renal, organ perfusions. Methods18 swine (24–39 kg) were submitted to 14 min of ventricular fibrillation and cardio-pulmonary resuscitation. After return of spontaneous circulation (ROSC), animals randomly received either AVP, NAD or AVP-NAD combination for maintaining a targeted mean arterial pressure of 70 ± 5 mmHg for 6 h. Haemodynamic and biological parameters, including kidney function biomarkers and diuresis, were monitored throughout the follow-up. ResultsTargeted mean arterial pressure was successfully obtained in the NAD (n = 6) and the AVP-NAD (n = 6) groups, but not in the AVP group (n = 6), where 4 animals died. As compared to NAD alone, renal blood flow (2.9 ± 1.15 vs 4.36 ± 0.64 mL//kg/min in NAD and AVP-NAD groups) and diuresis were higher in the AVP-NAD group. This was associated with a reduction of carotid blood flow and a more severe metabolic acidosis during the first 3 h of follow-up in the AVP-NAD group as compared to NAD group. ConclusionCombination of AVP and NAD improved renal perfusion and diuresis but reduced carotid blood flow as compared to NAD alone in a porcine model of post-resuscitation syndrome. AVP alone failed to manage shock and led to mortality.

A Systematic Review and Meta-Analysis of the Timing of Vasopressor Therapy in Patients with Septic Shock: Assessing Clinical Outcomes and Implication

Background Septic shock, is associated with a high mortality rate and increased expenses. Currently, the first-line therapy for septic shock entails administering resuscitation fluids followed by infusing vasopressors when the blood pressure goal is not achieved. The recommended first-line vasopressor is norepinephrine, followed by vasopressin, epinephrine, angiotensin II, and dopamine. There is still a controversy on when each vasopressor should be administered. Therefore, we conducted this review to determine the impact and implications of vasopressor timing in septic shock patients. Methods PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar databases were comprehensively searched for potential studies until October 2023. The methodological quality and bias assessment of valid records was examined with the Newcastle Ottawa Scale and Cochrane’s risk of bias tool. Additionally, all the meta-analyses were performed with Review Manager software. Results Twelve articles were eligible for review and analysis. Pooled analyses of data from 7 of these studies demonstrated lower incidence of mortality and shorter duration to achieve target mean arterial pressure in the early vs. late epinephrine groups (OR:0.44; 95%CI: 0.35–0.55; p&lt;0.00001 and MD:-1.17; 95%CI:-2.00– -0.34; p=0.0006). However, the length of ICU stay didn’t differ between the early and late norepinephrine group (MD:0.55; 95%CI: -0.52–1.62; p=0.31). The subgroup analyses show that early vasopressin is associated with a decreased mortality than late administration (OR:0.60; 95%CI:0.41–0.90; p=0.01). Similarly, the pooled analysis has shown that early concomitant administration of vasopressin and norepinephrine is associated with a shorter duration to achieve target MAP than norepinephrine alone (MD:-3.15; 95%CI:-4.40– -1.90;p&lt;0.00001). Conclusion Early administration of norepinephrine has a mortality benefit and improves the duration taken to attain and sustain the goal MAP. Furthermore, early vasopressin possesses the potential to lower the fatality rate in individuals experiencing septic shock. However, further research is required to validate this finding.

Protocol for a Randomized Controlled Trial to Evaluate a Permissive Blood Pressure Target Versus Usual Care in Critically Ill Children with Hypotension (PRESSURE).

Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to evaluate the clinical and cost-effectiveness of a permissive mean arterial pressure (MAP) target of greater than a fifth centile for age compared with usual care. Pragmatic, open, multicenter, parallel-group randomized control trial (RCT) with integrated economic evaluation. Eighteen PICUs across the United Kingdom. Infants and children older than 37 weeks corrected gestational age to 16 years accepted to a participating PICU, on mechanical ventilation and receiving vasoactive drugs for hypotension. Adjustment of hemodynamic support to achieve a permissive MAP target greater than fifth centile for age during invasive mechanical ventilation. Randomization is 1:1 to a permissive MAP target or usual care, stratified by site and age group. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred until after randomization. The primary clinical outcome is a composite of death and days of ventilatory support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of BP and organ support, and discharge outcomes. This RCT received Health Research Authority approval (reference 289545), and a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee on May 10, 2021 (reference number 21/EE/0084). The trial is registered and has an International Standard RCT Number (reference 20609635). Trial findings will be disseminated in U.K. national and international conferences and in peer-reviewed journals.

Capillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study

BackgroundSeveral studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response.MethodsThirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80–85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions).ResultsCRT decreased significantly with both tests (from 5 [3.5–7.6] to 4 [2.4–5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3–5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin.ConclusionsOur findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.

Renin Levels and Angiotensin II Responsiveness in Vasopressor-Dependent Hypotension.

The relationship between renin levels, exposure to renin-angiotensin system (RAS) inhibitors, angiotensin II (ANGII) responsiveness, and outcome in patients with vasopressor-dependent vasodilatory hypotension is unknown. We conducted a single-center prospective observational study to explore whether recent RAS inhibitor exposure affected baseline renin levels, whether baseline renin levels predicted ANGII responsiveness, and whether renin levels at 24 hours were associated with clinical outcomes. An academic ICU in Melbourne, VIC, Australia. Forty critically ill adults who received ANGII as the primary agent for vasopressor-dependent vasodilatory hypotension who were included in the Acute Renal effects of Angiotensin II Management in Shock study. None. After multivariable adjustment, recent exposure to a RAS inhibitor was independently associated with a relative increase in baseline renin levels by 198% (95% CI, 36-552%). The peak amount of ANGII required to achieve target mean arterial pressure was independently associated with baseline renin level (increase by 46% per ten-fold increase; 95% CI, 8-98%). Higher renin levels at 24 hours after ANGII initiation were independently associated with fewer days alive and free of continuous renal replacement therapy (CRRT) (-7 d per ten-fold increase; 95% CI, -12 to -1). In patients with vasopressor-dependent vasodilatory hypotension, recent RAS inhibitor exposure was associated with higher baseline renin levels. Such higher renin levels were then associated with decreased ANGII responsiveness. Higher renin levels at 24 hours despite ANGII infusion were associated with fewer days alive and CRRT-free. These preliminary findings emphasize the importance of the RAS and the role of renin as a biomarker in patients with vasopressor-dependent vasodilatory hypotension.

The 2023 AO Spine-Praxis Guidelines in Acute Spinal Cord Injury: What Have We Learned? What Are the Critical Knowledge Gaps and Barriers to Implementation?

Narrative summary of the 2023 AO Spine-Praxis clinical practice guidelines for management in acute spinal cord injury (SCI). The objective of this article is to summarize the key findings of the clinical practice guidelines for the optimal management of traumatic and intraoperative SCI (ISCI). This article will also highlight potential knowledge translation opportunities for each recommendation and discuss important knowledge gaps and areas of future research. Systematic reviews were conducted according to accepted methodological standards to evaluate the current body of evidence and inform the guideline development process. The summarized evidence was reviewed by a multidisciplinary guidelines development group that consisted of international multidisciplinary stakeholders. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of the evidence for each critical outcome and the "evidence to recommendation" framework was used to formulate the final recommendations. The key recommendations regarding the timing of surgical decompression, hemodynamic management, and the prevention, diagnosis, and management of ISCI are summarized. While a strong recommendation was made for early surgery, further prospective research is required to define what constitutes sufficient surgical decompression, examine the role of ultra-early surgery, and assess the impact of early surgery in different SCI phenotypes, including central cord syndrome. Furthermore, additional investigation is required to evaluate the impact of mean arterial blood pressure targets on neurological recovery and to determine the utility of spinal cord perfusion pressure measurements. Finally, there is a need to examine the role of neuroprotective agents for the treatment of ISCI and to prospectively validate the new AO Spine-Praxis care pathway for the prevention, diagnosis, and management of ISCI. To optimize the translation of these guidelines into practice, important barriers to their implementation, particularly in underserved areas, need to be explored. Ultimately, these recommendations will help to establish more personalized approaches to care for SCI patients. The recommendations from the 2023 AO Spine-Praxis guidelines not only highlight the current best practice in the management of SCI, but reveal critical knowledge gaps and barriers to implementation that will help to guide further research efforts in SCI.

Comparison of Clonidine versus Esmolol in Controlled Hypotension in Patients Undergoing FESS Surgery

Background: FESS has its share of complications which can be a challenge for both the surgeon as well the anesthetist and achieving a bloodless surgical field is essential So the principle of controlled hypotension can be used to combat this issue.&#x0D; Methods: A hospital-based randomized comparative interventional study was conducted on 60 patients to compare Clonidine (2mcg/kg in 10 ml of saline over 10 minutes before induction followed by an infusion of 1mcg/kg/hr during maintenance) and Esmolol (1mg/kg in 10 ml of saline over 10 minutes before induction followed by an infusion of 1mg/kg/hr during maintenance) to assess and compare the hypotensive properties of both the drugs.&#x0D; Results: After the induction of anesthesia, there was a significant difference in the mean heart rate, and mean arterial pressure between the two groups throughout the intraoperative period (p-value &lt; 0.05). Both groups achieved a target mean arterial pressure (MAP) of 65-70 mmHg and improved surgical field quality.&#x0D; Conclusion: This study concluded that clonidine and esmolol both provide hemodynamic stability and a better surgical field in functional endoscopic sinus surgery (FESS). Clonidine also helps in achieving postoperative sedation and analgesia.

Traumatic cervical spinal cord injury: Comparison of two different blood pressure targets on neurological recovery.

Controversy exists whether blood pressure augmentation therapy benefits patients suffering from spinal cord injury (SCI). This retrospective comparative study was designed to assess the impact of two different mean arterial pressure (MAP) targets (85-90 mmHg vs. 65-85 mmHg) on neurological recovery after traumatic cervical SCI. Fifty-one adult patients with traumatic cervical SCI were retrospectively divided into two groups according to their intensive care unit (ICU) MAP targets: 85-90 mmHg (higher MAP group, n = 32) and 65-85 mmHg (lower MAP group, n = 19). Invasive MAP measurements were stored as 2-min median values for 3-7 days. The severity of SCI (AIS grade and neurological level) was evaluated upon ICU stay and during rehabilitation. Neurological recovery was correlated with individual mean MAP values and with the proportion of MAP values ≥85 mmHg upon the first 3 days (3d-MAP%≥85 ). The initial AIS grades were A 29.4%, B 17.6%, C 31.4%, and D 21.6%. AIS grade improved in 24 patients (47.1%). During ICU care, 82.0% and 36.8% of the measured MAP values reached ≥85 mmHg in the higher and the lower MAP groups, respectively (p < .001). The medians of individual mean MAP values were different between the groups (90.2 mmHg vs. 81.4 mmHg, p < .001). Similarly, 3d-MAP%≥85 was higher in the higher MAP group (85.6% vs. 50.0%, p < .001). However, neurological recovery was not different between the groups, nor did it correlate with individual mean MAP values or 3d-MAP%≥85 . The currently recommended MAP target of 85-90 mmHg was not associated with improved outcomes compared to a lower target in patients with traumatic cervical SCI in this cohort.

Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol.

One of the most important components of sepsis management is hemodynamic restoration. If the target mean arterial pressure (MAP) is not obtained, the first recommendation is for volume expansion, and the second is for norepinephrine (NE). We describe the methodology of a randomized multicenter trial aiming to assess the hypothesis that low-dose NE given early in adult patients with sepsis will provide better control of shock within 6 hours from therapy starting compared to standard care. This trial includes ICU septic patients in whom MAP decrease below 65 mmHg to be randomized into 2 groups: early NE-group versus standard care-group. The patient's attending clinician will determine how much volume expansion is necessary to meet the target of a MAP > 65 mm Hg. If this target not achieved, after at least 30 ml/kg and guided by the available indices of fluid responsiveness, NE will be used in a usual way. The latter must follow a consensual schedule elaborated by the investigating centers. Parameters to be taken at inclusion and at H6 are: lactates, cardiac ultrasound parameters (stroke volume (SV), cardiac output (CO), E/E' ratio), and P/F ratio. MAP and diuresis are recorded hourly. Our primary outcome is the shock control defined as a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours) within 6 hours. Secondary outcomes: Decrease in serum lactate> 10% from baseline within 6 hours, the received fluid volume within 6 hours, variation of CO and E/E', and 28 days-Mortality. The study is ongoing and aims to include at least 100 patients per arm. This study is likely to contribute to support the indication of early initiation of NE with the aim to restrict fluid intake in septic patients. (ClinicalTrials.gov ID: NCT05836272).

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.

Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Research Algorithms.

The efficacy of our current approach to incorporating intracranial pressure (ICP) data into pediatric severe traumatic brain injury (sTBI) management is incompletely understood, lacking data from multicenter, prospective, randomized studies. The National Institutes of Health-supported Benchmark Evidence from Latin America-Treatment of Raised Intracranial Pressure-Pediatrics trial will compare outcomes from pediatric sTBI of a management protocol based on ICP monitoring vs 1 based on imaging and clinical examination without monitoring. Because no applicable comprehensive management algorithms for either cohort are available, it was necessary to develop them. A consensus conference involving the 21 intensivists and neurosurgeons from the 8 trial sites used Delphi-based methodology to formulate management algorithms for both study cohorts. We included recommendations from the latest Brain Trauma Foundation pediatric sTBI guidelines and the consensus-based adult algorithms (Seattle International Brain Injury Consensus Conference/Consensus Revised Imaging and Clinical Examination) wherever relevant. We used a consensus threshold of 80%. We developed comprehensive management algorithms for monitored and nonmonitored cohort children with sTBI. We defined suspected intracranial hypertension for the nonmonitored group, set minimum number and timing of computed tomography scans, specified minimal age-adjusted mean arterial pressure and cerebral perfusion pressure targets, defined clinical neuroworsening, described minimal requisites for intensive care unit management, produced tiered management algorithms for both groups, and listed treatments not routinely used. We will study these protocols in the Benchmark Evidence from Latin America-Treatment of Raised Intracranial Pressure-Pediatrics trial in low- and middle-income countries. Second, we present them here for consideration as prototype pediatric sTBI management algorithms in the absence of published alternatives, acknowledging their limited evidentiary status. Therefore, herein, we describe our study design only, not recommended treatment protocols.