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In this randomized trial involving patients with traumatic brain injury and elevated intracranial pressure, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. In Europe, traumatic brain injury is the most common cause of permanent disability in people younger than 40 years of age, with the annual cost exceeding €33 billion (approximately $37.5 billion in U.S. dollars). 1 , 2 Recent statistics show a 21% increase in the incidence of traumatic brain injury during the past 5 years — three times greater than the increase in population. Despite this, management of traumatic brain injury has been underrepresented in medical research as compared with other health problems. 3 Consequently, there are few data to support the commonly used stage 2 interventions (Figure 1) for the management of . . .

This trial showed no significant difference in the percentage of patients who died or had severe disability or coma when higher or lower blood-pressure targets were used after an out-of-hospital cardiac arrest.

Background The StratosPHere 2 trial will evaluate the efficacy of hydroxychloroquine and phenylbutyrate in pulmonary arterial hypertension caused by mutations in BMPR2 by focussing on the novel biomarker and other endpoints including safety. Study design StratosPHere 2 is a three armed, placebo-controlled, phase 2 trial with two strata based on the mutation groups. It is response adaptive where the allocation of treatments follows a Bayesian response-adaptive randomisation algorithm. An expected number of 20 patients will be randomised in each stratum to one of the three arms containing hydroxychloroquine, phenylbutyrate and placebo. The primary outcome is a novel endpoint considering the change in the bone morphogenetic receptor type 2 (BMPR2). Method The final primary analysis on the efficacy of each active treatment against control is assessed using a one-sided nonparametric Wilcoxon test computed on the continuous biomarker data collected up to 8 weeks from the start of treatment. Discussion This manuscript presents the key elements of the StratosPHere 2 implementation and statistical analysis plan. This is submitted to the journal before the first interim analysis to preserve the scientific integrity under a response-adaptive design framework. The StratosPHere 2 trial closely follows published guidelines for the content of Statistical Analysis Plans in clinical trials. Trial registration The ISRCTN Registry ISRCTN10304915 (22/09/2023)

The close relationship between hypertension and dietary sodium intake is widely recognized and supported by several studies. A reduction in dietary sodium not only decreases the blood pressure and the incidence of hypertension, but is also associated with a reduction in morbidity and mortality from cardiovascular diseases. Prolonged modest reduction in salt intake induces a relevant fall in blood pressure in both hypertensive and normotensive individuals, irrespective of sex and ethnic group, with larger falls in systolic blood pressure for larger reductions in dietary salt. The high sodium intake and the increase in blood pressure levels are related to water retention, increase in systemic peripheral resistance, alterations in the endothelial function, changes in the structure and function of large elastic arteries, modification in sympathetic activity, and in the autonomic neuronal modulation of the cardiovascular system. In this review, we have focused on the effects of sodium intake on vascular hemodynamics and their implication in the pathogenesis of hypertension.

Purpose In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock. Methods We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60–65 mmHg) versus a higher (75–80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups. Results A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95 % CI 7–11). In the lower and higher MAP groups, we observed deviations on 12 versus 8 % of all days on vasopressors ( p  = 0.059). Risks of cardiac arrhythmias (20 versus 36 %, p  = 0.07) and hospital mortality (30 versus 33 %, p  = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60 %, p  = 0.03) but not in younger patients. Conclusions This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy.

To determine the appropriate mean arterial pressure (MAP) control level for elderly patients with hypertension during the perioperative period. A prospective, randomized study. Three teaching hospitals in China. Six hundred seventy-eight elderly patients with chronic hypertension undergoing major gastrointestinal surgery. Patients were randomly allocated to three groups and the target MAP level was strictly controlled to one of three levels: level I (65-79mmHg), level II (80-95mmHg), or level III (96-110mmHg). The primary outcome was acute kidney injury (AKI) (50% or 0.3mg·dL increase in creatinine level) during the first 7 postoperative days. The secondary outcomes were perioperative adverse complications. Moreover, vasoactive agents were observed during surgery. The overall incidence of postoperative AKI was 10.9% (71/648). AKI occurred significantly less often in patients with level II MAP control (6.3%;13/206) than in patients with level I (13.5%; 31/230) and level III (12.9%; 27/210) (P<0.001) MAP control. Level II was associated with lower incidences of hospital-acquired pneumonia (6.7%; 14/206; P=0.014) and admission to the intensive care unit (ICU) (4.4%; 9/206; P=0.015) and with shorter length of stay in the ICU (P=0.025) when compared with level I and level III. Use of norepinephrine, phenylephrine, and nitroglycerin was significantly higher for patients with level III MAP control than for patients with level I and level II MAP control (P=0.001). For elderly hypertensive patients, controlling intraoperative MAP levels to 80 to 95mmHg can reduce postoperative AKI after major abdominal surgery.

Normal mean pulmonary arterial pressure (mPAP) is 14.0 ± 3.3 mm Hg (mean ± SD). The prognostic relevance of mildly elevated mPAP not fulfilling the definition of pulmonary hypertension (PH; mPAP ≥ 25 mm Hg) has not been prospectively evaluated in a real-world setting. To assess the association of resting mPAP with all-cause mortality in a retrospective and a prospective cohort of patients with unexplained dyspnea and/or at risk of PH. Prognostic cutoffs were calculated by means of 1) classification and regression tree (CART) analysis without any preset thresholds, and 2) preset thresholds on the basis of literature data defining mPAP as lower-normal (≤mean + 1 SD), upper-normal (between mean + 1 SD and mean + 2 SD), borderline (between mean + 2 SD and 25 mm Hg), and manifest PH (≥25 mm Hg). We performed univariate and multivariate survival analysis adjusted for age and comorbidities. We enrolled 547 patients, of whom 137, 56, 64, and 290 presented with lower-normal, upper-normal, or borderline mPAP, and manifest PH, respectively. The CART analysis on mPAP discriminated three prognostic groups: mPAP less than 17 mm Hg, 17 to 26 mm Hg, and greater than 26 mm Hg, with significantly decreasing survival. The univariate analysis on the basis of preset thresholds showed that upper-normal mPAP, borderline mPAP, and manifest PH were significantly associated with poor survival compared with lower-normal mPAP. In the multivariate model, considering age and comorbidities, only borderline mPAP (hazard ratio, 2.37; 95% confidence interval, 1.14-4.97; P = 0.022) and manifest PH (hazard ratio, 5.05; 95% confidence interval, 2.79-9.12; P < 0.001) were significantly associated with poor survival. In patients at risk for PH and/or with unexplained dyspnea, CART analysis detects prognostic thresholds at a resting mPAP of 17 mm Hg and 26 mm Hg, and values between 20 mm Hg and 25 mm Hg represent an independent predictor of poor survival. Clinical trial registered with www.clinicaltrials.gov (NCT 01607502).

We compared the immediate and sustained effects of 500 mL of crystalloid administered at slow (333 mL/h) versus fast rates (999 mL/h) on mean arterial pressure (MAP) in critically ill patients. Hemodynamic variables were collected immediately before and every 30 min up to 60 min after the end of the infusion. The primary outcome was the adjusted difference in MAP. We included 146 patients (slow rate: 71, fast rate: 75). One hour after the end of the infusion, there was no difference in the overall mean marginal effect on MAP between the groups [1.9 mmHg (95 % CI: −1.5 to 5.3 mmHg), p = 0.27] or on the perfusion parameters. Similarly, no difference was found in the immediate effect after 90 min [overall marginal effect: 1.1 mmHg (95 % CI: −2.3 to 4.6 mmHg); p = 0.52]. In patients with cardiac output (CO) monitoring, there was an increase in CO in the fast rate group (overall mean marginal effect: 1.78 L/min (95 % CI: 0.08 to 3.48 L/min); p = 0.04). In critically ill patients, crystalloid infusion at both fast and slow rates did not lead to immediate or sustained differences in MAP. However, fast infusion may result in a greater increase in CO. •Crystalloid infusion at both fast and slow rates did not result in immediate or sustained differences in MAP mean arterial pressure•Fast fluid infusion appears to increase central venous pressure more prominently compared to slow infusion rates•Fast infusion may result in a greater increase in cardiac output, although perfusion parameters did not differ between groups

Current guidelines for the care of patients with acute spinal cord injuries (SCIs) recommend maintaining mean arterial pressure (MAP) values of 85–90 mm Hg for 7 days after an acute SCI however, little evidence supports this recommendation. We sought to better inform the relationship between MAP values and neurological recovery. A computer system automatically collected and stored q1 min physiological data from intensive care unit monitors on patients with SCI over a 6-year period. Data for 100 patients with acute SCI were collected. 74 of these patients had American Spinal Injury Association Impairment Scale (AIS) grades determined by physical examination on admission and at time of hospital discharge. Average MAP values as well as the proportion of MAP values below thresholds were explored for values from 120 mm Hg to 40 mm Hg in 1 mm Hg increments; the relationship between these measures and outcome was explored at various time points up to 30 days from the time of injury. A total of 994,875 q1 min arterial line blood pressure measurements were recorded for the included patients amid 1,688,194 min of recorded intensive care observations. A large proportion of measures were below 85 mm Hg despite generally acceptable average MAP values. Higher average MAP values correlated with improved recovery in the first 2–3 days after SCI while the proportion of MAP values below the accepted threshold of 85 mm Hg seemed a stronger correlate, decreasing in strength over the first 5–7 days after injury. This study provides strong evidence supporting a correlation between MAP values and neurological recovery. It does not, however, provide evidence of a causal relationship. Duration of hypotension may be more important than average MAP. It provides support for the notion of MAP thresholds in SCI recovery, and the highest MAP values correlated with the greatest degree of neurological recovery. The results are concordant with current guidelines in suggesting that MAP thresholds >85 mm Hg may be appropriate after acute SCI.

We hypothesize that personalized perioperative blood pressure management maintaining intraoperative mean arterial pressure (MAP) above the preoperative mean nighttime MAP reduces perfusion-related organ injury compared to maintaining intraoperative MAP above 65 mmHg in patients having major non-cardiac surgery. Before testing this hypothesis in a large-scale trial, we performed this bicentric pilot trial to determine a) if performing preoperative automated nighttime blood pressure monitoring to calculate personalized intraoperative MAP targets is feasible; b) in what proportion of patients the preoperative mean nighttime MAP clinically meaningfully differs from a MAP of 65 mmHg; and c) if maintaining intraoperative MAP above the preoperative mean nighttime MAP is feasible in patients having major non-cardiac surgery. Bicentric pilot randomized trial. University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and RWTH Aachen University Hospital, Aachen, Germany. Patients ≥ 45 years old having major non-cardiac surgery. Personalized blood pressure management. Proportion of patients in whom preoperative automated nighttime blood pressure monitoring was possible; proportion of patients in whom the preoperative mean nighttime MAP clinically meaningfully differed from a MAP of 65 mmHg (difference > ±10 mmHg); intraoperative time-weighted average MAP below the preoperative mean nighttime MAP. We enrolled 105 patients and randomized 98 patients. In 98 patients (93 %), preoperative automated nighttime blood pressure monitoring was possible. In 83 patients (85 %), the preoperative mean nighttime MAP clinically meaningfully differed from a MAP of 65 mmHg. The median time-weighted average MAP below the preoperative mean nighttime MAP was 3.29 (1.64, 6.82) mmHg in patients assigned to personalized blood pressure management. It seems feasible to determine the effect of personalized perioperative blood pressure management maintaining intraoperative MAP above the preoperative mean nighttime MAP on postoperative complications in a large multicenter trial. [Display omitted] •Optimal blood pressure targets during surgery remain unknown.•Individual nighttime mean arterial pressure (MAP) may be a reasonable blood pressure target.•Performing preoperative automated blood pressure monitoring is feasible.•Nighttime MAP meaningfully differs from a MAP of 65 mmHg in most patients.•Targeting nighttime MAP during surgery is feasible.