Target Mean Arterial Pressure Research Articles

Lessons learned from kidney dysfunction : Preventing organ failure.

Acute kidney injury (AKI) is acommon and severe complication in patients in the intensive care unit with asignificant impact on patient's mortality and morbidity. Therefore renal protective therapy is very important in these severely ill patients. Several renal protective strategies have been postulated during recent decades, which came from pathophysiologic concepts and have been contradicted or changed during the last few years. So lessons had to be learned in AKI, leading to new, in many cases completely reversed preventive and therapeutic concepts which may also be important for protection in other organs. Most important for renal protection is the early identification of patients at risk for AKI or with acute kidney damage before renal function further deteriorates. Astage-based management of AKI comprises more general measures like discontinuation of the nephrotoxic agent but most importantly early hemodynamic stabilization. Recent research has contradicted that AKI is renal ischemia caused by vasoconstriction with consecutive tubular necrosis. In septic AKI, renal blood flow is even increased. Intrarenal vasodilation together with microcirculatory changes and redistribution of blood flow lead to adrop in glomerular filtration by functional changes. Accordingly it had to be learned that not vasodilators but vasoconstrictors are beneficial in AKI. Amean arterial blood pressure target of >65 mm Hg is often recommended but exact targets are not known, and patients with pre-existing hypertension even need higher perfusion pressure. Also the concept that fluid therapy is always beneficial for the kidney in shock states had to be revised. Avolume restrictive therapy with only balanced crystalloids is also becoming more important in AKI. Still no specific pharmacological therapy for renal protection is available. Inflammation and mitochondrial dysfunction appear to play asignificant role in AKI. Anti-inflammatory strategies are under investigation and may become more important for AKI prevention and therapy in the future. (This article is freely available.).

Premedication for Induced Hypotension in Functional Endoscopic Sinus Surgeries: Intravenous Dexmedetomidine Infusion vs Oral Metoprolol vs Placebo: A Comparative Study.

Background:Controlled hypotension has been used to reduce bleeding and the need for blood transfusions and provide a satisfactory bloodless surgical field. In this double-blind, randomized controlled trial, we are comparing intravenous (i.v.) dexmedetomidine infusion and oral metoprolol as a premedication for controlled hypotension in functional endoscopic sinus surgery (FESS) for evaluating surgical field visibility.Subjects and Methods:A total of 90 patients undergoing FESS were randomly divided into three groups of 30 each. Group A received intraoperative i.v. infusion of dexmedetomidine (loading 1 μg.kg−1 over 10 min followed by the maintenance of 0.2–0.5 μg.kg−1.h−1), Group B received oral metoprolol 50 mg on night and 2 h before surgery as a premedication, and Group C was taken as a control group and patients received oral placebo tablet as premedication and intraoperative normal saline infusion. General anesthesia was given using sevoflurane. Intraoperative target mean arterial blood pressure was set 55–65 mmHg. Various parameters were recorded and statistically compared.Results:The three groups were statistically comparable in demographics. Quality of surgical field was better in Group A compared to other two groups. Total blood loss was also less in Group A. The incidence of adverse reactions was more in Group A.Conclusion:Dexmedetomidine provides a better surgical field compared to oral metoprolol in FESS along with the desired hemodynamics with lesser blood loss and better outcome.

Controlled hypotension for FESS: A randomised double-blinded comparison of magnesium sulphate and dexmedetomidine.

Background and Aims:Intense bleeding during general anaesthesia (GA) is the major limitation during functional endoscopic sinus surgery (FESS). This study was aimed to compare the efficacy of dexmedetomidine and magnesium sulphate (MgSO4) for controlled hypotension in FESS.Methods:Sixty eight patients undergoing FESS were randomised to receive either dexmedetomidine 1 μg/kg over 10 min followed by infusion at 0.2 to 0.7 μg/kg/h (Group D) or MgSO4 40 mg/kg over 10 min followed by an infusion at 10 to 15 mg/kg/h (Group M). Anaesthesia and infusion rates for study drugs were maintained with sevoflurane to keep MAP between 60–70 mmHg throughout the surgery. The time to reach the target MAP, the number of patients requiring a minimum and maximum infusion doses of study drugs were noted.Results:The mean time to achieve target mean arterial pressure (MAP) was less in group D (10.59 ± 2.04) as compared with (21.32 ± 4.65 min) group M (P < 0.001). The target MAP was achieved between 5–15 min in 73.52% patients (Group D) with an infusion dose of 0.2–0.4 μg/kg/h of dexmedetomidine without the use of sevoflurane, while 82.35% patients in group M required 4% sevoflurane along with >12–15 mg/kg/hr infusion of MgSO4 to achieve target MAP in 10–20 min.Conclusion:Dexmedetomidine is superior to MgSO4 in achieving target MAP in lesser time with minimum infusion dose.

What matters in shock? Flow or pressure?

Shock is a state of ‘acute circulatory failure’, the key feature of which is an inability for tissues and cells to get enough oxygen to meet their needs, ultimately resulting in cell death1. Shock can be classified as hypovolemic, cardiogenic, obstructive or distributive although many patients will have several types of shock simultaneously1. Although it is important to identify and treat the underlying cause of shock (e.g., antibiotics and source removal for septic shock; thrombolysis or embolectomy for massive pulmonary embolism causing obstructive shock1, hemodynamic support must be started immediately in all cases to provide a minimum perfusion pressure and prevent development or worsening of organ dysfunction. In this context, both “flow” and “pressure” are important components. Indeed, the arterial pressure is determined by blood flow and vascular tone, i.e., blood pressure = cardiac output x systemic vascular resistance. The essential aspects of shock resuscitation can be remembered using the simple VIP mnemonic: ventilate (ensure adequate oxygenation), infuse (provide adequate fluid resuscitation), and pump (administer vasoactive agents). Fluid administration should be guided by repeated fluid challenges so that patients receive enough fluid but not too much, as excess fluid can have multiple harmful effects. If hypotension is severe, vasopressors should be started early, at the same time as fluids, to increase systemic vascular resistance and thus arterial pressure. Prolonged periods of hypotension are associated with worse outcomes2. Importantly, although an initial mean arterial pressure (MAP) target of 65 mmHg may be a useful aim, this will not be optimal for all and target values should be adapted according to the individual patient, taking into account various factors including age and history of chronic hypertension. Indeed, if the MAP target is too low, resultant hypoperfusion may lead to cellular death and organ dysfunction, but a target that is too high may be associated with edema and excessive vasoconstriction as a result of higher amounts of fluid and vasoactive agents3, which may also impair organ function. Patients with circulatory shock must therefore be carefully monitored, including regular assessment of cardiac output, and treatment and targets adapted accordingly. Monitoring organ perfusion at the bedside is difficult without specific tools to assess the microcirculation. As such, we must generally rely on three “windows” that can indicate inadequate perfusion, i.e., impaired cutaneous perfusion, impaired renal function, and impaired mental status1. Plasma lactate levels can also be useful, with changes over time providing some indication of adequacy of tissue oxygenation. Although these changes are too slow to help acutely guide therapy, the trend can provide valuable information about patient status over time. If flow remains inadequate and there is no, or only a poor, response to fluids, an inotropic agent may be considered. Dobutamine is the inotrope of choice. In this context, measurement of mixed (SvO2) or central venous (ScvO2) oxygen saturation can help as it provides an indication of the balance between oxygen delivery and consumption, with low values ( < 70%) suggesting that increasing oxygen delivery could be beneficial4.

Assessment of Anesthesia Practice Patterns for Endovascular Therapy for Acute Ischemic Stroke: A Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Member Survey.

The choice of general anesthesia (GA) or conscious sedation (CS) may impact neurological outcomes of patients undergoing endovascular therapy (EVT) for acute ischemic stroke (AIS). The aim of this survey was to describe the practice patterns of members of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) for anesthetic management of AIS. Following institutional review board approval, a 16-question online survey assessing anesthetic management of patients with AIS undergoing EVT was circulated to members of SNACC. A total of 76 SNACC members from 52 institutions and 11 countries completed the survey (12.5% response rate). Overall, 33% of institutions reported dedicated neuroanesthesia teams for EVT. Patients treated with GA ranged from 5% to 100% between centers. In total 51% and 49% of centers in the United States reported preferentially providing GA and CS, respectively, compared with 34% and 66%, respectively, in European centers. Reported anesthetic induction agents are propofol (64%), etomidate (4%) and either medication (33%). For maintenance of GA, volatile anesthetic is used more often (54%) than propofol (16%). There was wide variation in medications used for CS. Arterial catheter placement was reported by 75% and 43% of respondents for patients undergoing GA and CS, respectively. Systolic blood pressure >140 mm Hg was targeted by 35.7% of respondents, with others targeting mean arterial pressure within 10%, 20% or 30% of baseline values. Phenylephrine and norepinephrine were the most commonly used vasopressors. There is wide variation in anesthesia technique and hemodynamic management during EVT for AIS, and no consensus on the choice of, or preferred medications for, GA or CS, or target blood pressure and management of hypotension during the procedure.

The use of a machine-learning algorithm that predicts hypotension during surgery in combination with personalized treatment guidance: study protocol for a randomized clinical trial

BackgroundIntraoperative hypotension is associated with increased morbidity and mortality. Current treatment is mostly reactive. The Hypotension Prediction Index (HPI) algorithm is able to predict hypotension minutes before the blood pressure actually decreases. Internal and external validation of this algorithm has shown good sensitivity and specificity. We hypothesize that the use of this algorithm in combination with a personalized treatment protocol will reduce the time weighted average (TWA) in hypotension during surgery spent in hypotension intraoperatively.Methods/designWe aim to include 100 adult patients undergoing non-cardiac surgery with an anticipated duration of more than 2 h, necessitating the use of an arterial line, and an intraoperatively targeted mean arterial pressure (MAP) of > 65 mmHg. This study is divided into two parts; in phase A baseline TWA data from 40 patients will be collected prospectively. A device (HemoSphere) with HPI software will be connected but fully covered. Phase B is designed as a single-center, randomized controlled trial were 60 patients will be randomized with computer-generated blocks of four, six or eight, with an allocation ratio of 1:1. In the intervention arm the HemoSphere with HPI will be used to guide treatment; in the control arm the HemoSphere with HPI software will be connected but fully covered. The primary outcome is the TWA in hypotension during surgery.DiscussionThe aim of this trial is to explore whether the use of a machine-learning algorithm intraoperatively can result in less hypotension. To test this, the treating anesthesiologist will need to change treatment behavior from reactive to proactive.Trial registrationThis trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT03376347. The trial was submitted on 4 November 2017 and accepted for registration on 18 December 2017.

The efficacy of esmolol, remifentanil and nitroglycerin in controlled hypotension for functional endoscopic sinus surgery

IntroductionControlled hypotension is a reversible procedure in which the patient’s baseline mean arterial blood pressure is reduced by 30% and sustained at 60–70 mmHg during the procedure. It decreases blood loss and provides clear surgical field during the procedures. ObjectivesThe purpose of this study was to compare the efficacy of controlled hypotension agents esmolol, remifentanil, and nitroglycerin in functional endoscopic sinus surgery, in terms of hemodynamic changes and impact on the surgical efficiency. MethodsThe research was carried out as a cohort study. Patients who underwent functional endoscopic sinus surgery were randomized into 3 groups. Controlled hypotension was achieved with remifentanil (Group R), esmolol (Group E) and nitroglycerin (Group N). The efficacy of the drugs was tested by comparing the length of time with the targeted mean arterial pressure, the amount of anesthetics used, surgical field bleeding score and surgeon’s satisfaction. ResultsBetween May to December 2015, 60 patients were included and randomized equally into 3 different study groups. The median of the length of time with the targeted mean arterial pressure was shorter in the Group R when compared with Group E (p = 0.01) and Group N (p = 0.14). The amount of volatile anesthetics used was 25.0 mL (15–51), 43.0 mL (21–105) and 40.0 mL (26–97) in Groups R, E and N, respectively (p < 0.001). While there was more bleeding with nitroglycerin, surgical field bleeding scores were lower in Group R when compared with esmolol (p = 0.001) and nitroglycerin (p < 0.001). The analysis of surgeon’s satisfaction scores concluded that surgeons were more satisfied with the group R (100%), when compared with group E (60%) and group N (30%) (p < 0.001). ConclusionLess volatile agent, short time to achieve controlled hypotension, stable blood pressure, lower surgical field bleeding scores and larger length of time with the targeted mean arterial pressure were found as the advantages of Remifentanil. Less costly, efficiency of achieving the targeted median arterial pressure and less postoperative complications were the advantages of nitroglycerin. In functional endoscopic sinus surgery procedures, appropriate controlled hypotensive agents should be selected according to the patients’ characteristics and advantages/disadvantages of the drugs.

Evaluating the clinical and cost-effectiveness of permissive hypotension in critically ill patients aged 65 years or over with vasodilatory hypotension: Protocol for the 65 randomised clinical trial

Vasodilatory shock is common in critically ill patients and vasopressors are a mainstay of therapy. A meta-analysis suggested that use of a higher, as opposed to a lower, mean arterial pressure target to guide titration of vasopressor therapy, could be associated with a higher risk of death in older critically ill patients. The 65 trial is a pragmatic, multi-centre, parallel-group, open-label, randomised clinical trial of permissive hypotension (a mean arterial pressure target of 60–65 mmHg during vasopressor therapy) versus usual care in critically ill patients aged 65 years or over with vasodilatory hypotension. The trial is conducted in 2600 patients from 65 United Kingdom adult, general critical care units. The primary outcome is all-cause mortality at 90 days. An economic evaluation is embedded. The 65 trial received favourable ethical opinion from the South Central – Oxford C Research Ethics Committee and approval from the Health Research Authority. The results will be presented at national and international conferences and published in peer-reviewed medical journals. Trial registration: ISRCTN10580502

Initial Experience of Spinal Cord Perfusion Pressure Goals in Lieu of Mean Arterial Pressure Goals in Acute Traumatic Spinal Cord Injury at a United States Level I Trauma Center: A Transforming Research and Clinical Knowledge-Spinal Cord Injury Study

Abstract INTRODUCTION Management of traumatic spinal cord injury (SCI) includes urgent decompression and decreasing secondary injury through blood pressure augmentation. Mean arterial pressure (MAP) targets have been the standard of care for decades, however recent clinical trial data have demonstrated the relationship between spinal cord perfusion pressure (SCPP) and neurologic recovery. These data led to implementation of a novel standard of care protocol at our institution focused on SCPP, in lieu of MAP goals. We provide the initial experience of implementation of protocolized SCPP goals for acute SCI at a US level I trauma center. METHODS Starting December 2017, all moderate/severe blunt SCI patients at our institution presenting &lt; 24 h of injury received lumbar subarachnoid drain placement (LSAD) for intraspinal pressure (ISP) and SCPP monitoring in the neurological intensive care unit (NICU), and were included in the Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI) data registry. This is known as the SCPP Protocol, and comprises standard care at our institution. SCPPs were monitored for 5 d with goal = 65 mmHg achieved through intravenous fluids and vasopressor support. American Spinal Injury Association Impairment Scale (AIS) grades were assessed at admission and day 7. RESULTS In 15 patients enrolled to date, age was 60.5 ± 17.0 yr and 46.7% were = 65. Injury level was 93.3% cervical and 6.7% thoracic. Admission AIS were 20.0%/20.0%/26.7%/33.3% for A/B/C/D, respectively. A total of 14 patients underwent surgical decompression with time to surgery 8.8 ± 7.1 h and 71.4% &lt; 12 h. Hospital length of stay (LOS) was 14.7 ± 8.3 d. NICU LOS was 11.5 ± 8.9 d. No patient had lumbar drain-related complications. Seven patients had respiratory complications and 1 expired after family transitioned to comfort care. AIS grade improvement of 1 occurred in one-third of patients (2 AIS = B, 3 AIS = C). CONCLUSION In our initial experience of 15 patients with acute traumatic SCI, standardized SCPP goal-directed care through lumbar ISP monitoring for the first 5 d postinjury was feasible and without SCPP-related complications.

Early Use of Norepinephrine Improves Survival in Septic Shock: Earlier than Early

The timing of initiation of Norepinephrine (NEP) in septic shock is controversial. We evaluated the impact of early NEP simultaneously with fluids in those patients. We randomized 101 patients admitted to the emergency department with septic shock to early NEP simultaneously with IV fluids (early group) or after failed fluids trial (late group). The primary outcome was the in-hospital survival while the secondary outcomes were the time to target mean arterial pressure (MAP) of 65mmHg, lactate clearance and resuscitation volumes. There was no significant difference between the two groups regarding the baseline characteristics. NEP infusion started after 25 (20-30) and 120 (120-180) min in the early and late groups (p=0.000). MAP of 65mmHg was achieved faster in the early group (2 [1-3.5] h vs. 3 [2-4.75] h, p=0.003). Serum lactate was decreased by 37.8 (24-49%) and 22.2 (3.3-38%) in both groups respectively (p=0.005). Patients with early NEP were resuscitated by significantly lower volume of fluids (25 [18.8-28.7] mL/kg vs. 32.5 [24.4-34.6] mL/kg) in the early and late groups (p=0.000). The early group had survival rate of 71.9% compared to 45.5% in the late group (p=0.007). NEP started after 30 (20-120min) in survivors vs. 120 (30-165min) in non-survivors (p=0.013). We concluded that early Norepinephrine in septic shock might cause earlier restoration of blood pressure, better lactate clearance and improve in-hospital survival.

Posterior Reversible Encephalopathy Syndrome as a Complication of Induced Hypertension in Subarachnoid Hemorrhage: A Case-Control Study

Induced hypertension (IH) remains the mainstay of medical management for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). However, raising blood pressure above normal levels may be associated with systemic and neurological complications, of which posterior reversible encephalopathy syndrome (PRES) has been increasingly recognized. To ascertain the frequency and predisposing factors for PRES during IH therapy. We identified 68 patients treated with IH from 345 SAH patients over a 3-yr period. PRES was diagnosed based on clinical suspicion, confirmed by imaging. We extracted additional data on IH, including baseline and highest target mean arterial pressure (MAP), comparing PRES to IH-treated controls. Five patients were diagnosed with PRES at median 6.6 d (range 1-8 d) from vasopressor initiation. All presented with lethargy, 3 had new focal deficits, and 1 had a seizure. Although baseline MAP (prior to DCI) did not differ between cases and controls, both MAP immediately prior to IH (112 vs 90) and highest MAP targeted were greater (140 vs 120 mm Hg, both P<.01). Magnitude of MAP elevation was greater (54 vs 34 above baseline, P=.004) while degree of IH was not (37 vs 38 above pre-IH MAP). All 4 surviving PRES patients had complete resolution with IH discontinuation. PRES was diagnosed in 7% of SAH patients undergoing IH therapy, most often when MAP was raised well above baseline to levels that exceed traditional autoregulatory thresholds. High suspicion for this reversible disorder appears warranted in the face of unexplained neurological deterioration during aggressive IH.

Evaluating the clinical and cost-effectiveness of permissive hypotension in critically ill patients aged 65 years or over with vasodilatory hypotension: Statistical and Health Economic Analysis Plan for the 65 trial

The 65 trial is a pragmatic, multicentre, parallel-group, open-label, randomised clinical trial of permissive hypotension (targeting a mean arterial pressure target of 60–65 mmHg during vasopressor therapy) versus usual care in critically ill patients aged 65 years or over with vasodilatory hypotension. The trial will recruit 2600 patients from 65 United Kingdom adult general critical care units. The primary outcome is all-cause mortality at 90 days. An economic evaluation is embedded. This paper describes the proposed statistical and health economic analysis for the 65 trial.

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.

Effect of Targeting Mean Arterial Pressure During Cardiopulmonary Bypass by Monitoring Cerebral Autoregulation on Postsurgical Delirium Among Older Patients

Delirium occurs in up to 52% of patients after cardiac surgery and may result from changes in cerebral perfusion. Using intraoperative cerebral autoregulation monitoring to individualize and optimize cerebral perfusion may be a useful strategy to reduce the incidence of delirium after cardiac surgery. To determine whether targeting mean arterial pressure during cardiopulmonary bypass (CPB) using cerebral autoregulation monitoring reduces the incidence of delirium compared with usual care. This randomized clinical trial nested within a larger trial enrolled patients older than 55 years who underwent nonemergency cardiac surgery at a single US academic medical center between October 11, 2012, and May 10, 2016, and had a high risk for neurologic complications. Patients, physicians, and outcome assessors were masked to the assigned intervention. A total of 2764 patients were screened, and 199 were eligible for analysis in this study. In the intervention group, the patient's lower limit of cerebral autoregulation was identified during surgery before CPB. On CPB, the patient's mean arterial pressure was targeted to be greater than that patient's lower limit of autoregulation. In the control group, mean arterial pressure targets were determined according to institutional practice. The main outcome was any incidence of delirium on postoperative days 1 through 4, as adjudicated by a consensus expert panel. Among the 199 participants in this study, mean (SD) age was 70.3 (7.5) years and 150 (75.4%) were male. One hundred sixty-two (81.4%) were white, 26 (13.1%) were black, and 11 (5.5%) were of other race. Of 103 patients randomized to usual care, 94 were analyzed, and of 102 patients randomized to the intervention 105 were analyzed. Excluding 5 patients with coma, delirium occurred in 48 of the 91 patients (53%) in the usual care group compared with 39 of the 103 patients (38%) in the intervention group (P = .04). The odds of delirium were reduced by 45% in patients randomized to the autoregulation group (odds ratio, 0.55; 95% CI, 0.31-0.97; P = .04). The results of this study suggest that optimizing mean arterial pressure to be greater than the individual patient's lower limit of cerebral autoregulation during CPB may reduce the incidence of delirium after cardiac surgery, but further study is needed. ClinicalTrials.gov identifier: NCT00981474.

Effects of mean arterial pressure on arousal in sedated ventilated patients with septic shock: a SEPSISPAM post hoc exploratory study

BackgroundIt is unknown whether the recommended mean arterial pressure (MAP) target of 65 mmHg during initial resuscitation of septic shock is sufficient to maintain cerebral perfusion. Thus, we tested the hypothesis that a higher MAP target in patients with septic shock may improve level of arousal.MethodsWe performed a post hoc exploratory analysis of the SEPSISPAM trial, which assessed the effect of a “high-target” level of MAP (80–85 mmHg) versus the recommended “low-target” MAP (65–70 mm Hg) on mortality in patients with septic shock. Among the 776 patients originally recruited in SEPSISPAM trial, we selected those who were mechanically ventilated and sedated and with available evaluation of arousal level assessed by the Richmond Agitation and Sedation Scale (RASS).ResultsWe restricted our analysis to the period in which patients were treated with vasoactive drugs. Cumulative sedative drugs were assessed daily. A total of 532 patients were included in this study: 253 (47.6%) in the low-target group and 279 (52.4%) in the high-target group. Daily cumulative sedative drugs were similar in both groups. Compared to the low-target group, minimal and maximal RASS were significantly higher in the high-target group at day 2, 4 and 5. Furthermore, in order to consider the fact that multiple measures were done for each patient and to consider the global effect of time on these measures, we used a mixed linear regression and multivariate models: we confirmed that maximal RASS values were significantly higher in the high-target group.ConclusionIn patients with septic shock who were mechanically ventilated and sedated, resuscitation with MAP target between 80 and 85 mmHg was associated with higher arousal level as compared to a MAP target between 65 and 70 mmHg.

Angiotensin II (Giapreza): A Distinct Mechanism for the Treatment of Vasodilatory Shock.

Septic shock, a form of vasodilatory shock associated with high morbidity and mortality, requires early and effective therapy to improve patient outcomes. Current management of septic shock includes the use of intravenous fluids, catecholamines, and vasopressin for hemodynamic support to ensure adequate perfusion. Despite these interventions, hospital mortality rates are still greater than 40%. Practitioners are continuously faced with cases of refractory shock that are associated with poor clinical outcomes. In December of 2017, the Food and Drug Administration approved the first synthetic human angiotensin II, a potent vasoconstrictor, to increase blood pressure in adults with septic or other distributive shock. This approval was based (ATHOS) on the results from the Angiotensin II for the Treatment of High Output Shock study. In this randomized, double-blind, placebo-controlled trial, patients in the angiotensin II group achieved higher rates of target mean arterial pressure and had lower catecholamine requirements in the first 3 hours of therapy compared with patients in the placebo group. There was no significant difference in the 28-day mortality. Safety issues including the risk of thromboembolic events, infection, and delirium have made clinicians cautious in adopting angiotensin II into practice. Ongoing studies are needed to more clearly define the role of this agent and its utility in the management of shock.

Hypotension and Hypocapnia During General Anesthesia in Piglets: Study of S100b as an Acute Biomarker for Cerebral Tissue Injury.

Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA. Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery. Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001). S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported.

High versus low mean arterial pressures in hepatorenal syndrome: A randomized controlled pilot trial

There is controversy regarding the mean arterial pressure (MAP) goals that should be targeted in the treatment of hepatorenal syndrome (HRS.) We conducted a study to assess different MAP targets in HRS in the intensive care unit (ICU). Materials and methodsThis is a prospective randomized controlled pilot trial. ICU patients had target mean arterial pressure (MAP) ≥ 85 mmHg (control arm) or 65–70 mmHg (study arm). Urine output and serum creatinine were trended and recorded. ResultsA total of 18 patients were enrolled. The day four urine output in the high and low MAP group was 1194 (SD = 1249) mL/24 h and 920 (SD = 812) mL/24 h, respectively. The difference in day four – day one urine output was −689 (SD = 1684) mL/24 h and 272 (SD = 582) mL/24 h for the high and low MAP groups. The difference in serum creatinine at day four – day one was −0.54 (SD = 0.63) mg/dL and − 0.77 (SD = 1.14) mg/dL in the high and low MAP groups, respectively. ConclusionIn this study, we failed to prove non-inferiority between a low and high target MAP in patients with HRS.Trial registration: This trial was registered with and approved by the University of Louisville Internal Review Board and hospital research review committees (IRB # 14.1190). The trial was registered with ClinicalTrials.gov (ID # NCT02789150). The IRB committee roster 7/21/2014–2/26/2015 is registered with IORG (IORG # IORG0000147; OMB # 0990–0279) and is available at http://louisville.edu/research/humansubjects/about-the-irb/rosters/RosterEffective20140721thru20150226.pdf

Norepinephrine and Vasopressin Compared With Norepinephrine and Epinephrine in Adults With Septic Shock.

Background: The optimal adjuvant vasopressor to norepinephrine in septic shock remains controversial. Objective: To compare durations of shock-free survival between adjuvant vasopressin and epinephrine. Methods: A retrospective, single-center, matched cohort study of adults with septic shock refractory to norepinephrine was conducted. Patients receiving norepinephrine not at target mean arterial pressure (MAP; 65 mm Hg) were initiated on vasopressin or epinephrine to raise MAP to target. Vasopressin-exposed patients were matched to epinephrine-exposed patients using propensity scores. Mortality outcomes were examined using multivariable Poisson regression with robust variance estimation. Results: Of 166 patients, 96 (entire cohort) were included in the propensity score-matched cohort. Shock-free survival durations in the first 7 days were similar between epinephrine- and vasopressin-exposed patients in the matched cohort (median = 13.2 hours, interquartile range [IQR] = 0-121.0, vs median = 41.3 hours, IQR = 0-125.9; P = 0.51). Seven- and 28-day mortality rates were similar in the matched cohort (7-day: 47.9% vs 39.6%, P = 0.35; 28-day: 56.3% vs 58.3%, P = 0.84). Mortality rates were similar between epinephrine- and vasopressin-exposed patients in propensity score-matched regression models with and without adjustments at 7 (relative risk [RR] = 1.28, 95% CI = 0.92-1.79; RR = 1.21, 95% CI = 0.81-1.81) and 28 days (RR = 1.04, 95% CI = 0.81-1.34; RR = 0.96, 95% CI = 0.69-1.34). Conclusion and Relevance: Shock-free survival durations were similar in matched epinephrine- and vasopressin-exposed groups. Adjuvant epinephrine or vasopressin alongside norepinephrine to raise MAP to target requires further investigation.

Effects of different target blood pressure resuscitation on peripheral blood inflammatory factors and hemodynamics in patients with traumatic hemorrhagic shock

To investigate the target blood pressure level of restrictive fluid resuscitation in patients with traumatic hemorrhagic shock. Sixty patients with traumatic hemorrhagic shock admitted to the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2018 were enrolled. All patients were resuscitated with sodium acetate ringer solution after admission. According to the difference of mean arterial pressure (MAP) target, the patients were divided into low MAP (60 mmHg ≤ MAP < 65 mmHg, 1 mmHg = 0.133 kPa), middle MAP (65 mmHg ≤ MAP < 70 mmHg) and high MAP (70 mmHg ≤ MAP < 75 mmHg) groups by random number table using the admission order with 20 patients in each group. Those who failed to reach the target MAP after 30-minute resuscitation were excluded and supplementary cases were deferred. The restrictive fluid resuscitation phase was divided into three phases: before fluid resuscitation, liquid resuscitation for 30 minutes and 60 minutes. The most suitable resuscitation blood pressure level was further speculated by monitoring the inflammatory markers and hemodynamics in different periods in each group of patients. Pearson correlation analysis was used to detect the correlation of variables. Before fluid resuscitation, there was no significant difference in hemodynamics or expressions of serum cytokines among the three groups. Three groups of patients were resuscitated for 30 minutes to achieve the target blood pressure level and maintain 30 minutes. With the prolongation of fluid resuscitation time, the central venous pressure (CVP), cardiac output (CO) and cardiac index (CI) were increased slowly in the three groups, and reached a steady state at about 30 minutes after resuscitation, especially in the high MAP group and the middle MAP group. The expressions of serum inflammatory factors in the three groups were gradually increased with the prolongation of fluid resuscitation time. Compared with the low MAP group and the high MAP group, after 30 minutes of resuscitation the middle MAP group was superior to the other two groups in inhibiting the expressions of pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and promoting anti-inflammatory factors IL-10 [TNF-α mRNA (2-ΔΔCt): 0.21±0.13 vs. 0.69±0.34, 0.57±0.35; IL-6 mRNA (2-ΔΔCt): 0.35±0.31 vs. 0.72±0.39, 0.59±0.42; IL-10 mRNA (2-ΔΔCt): 1.25±0.81 vs. 0.61±0.46, 0.82±0.53; all P < 0.05], but there was no significant difference in promoting the expression of IL-4 mRNA among three groups. At 60 minutes of resuscitation, compared with the low MAP group and the high MAP group, the middle MAP group could significantly inhibit the expressions of TNF-α, IL-6 and promote IL-10 [TNF-α mRNA (2-ΔΔCt): 0.72±0.35 vs. 1.05±0.54, 1.03±0.49; IL-6 mRNA (2-ΔΔCt): 0.57±0.50 vs. 1.27±0.72, 1.01±0.64; IL-10 mRNA (2-ΔΔCt): 1.41±0.90 vs. 0.81±0.48, 0.94±0.61; all P < 0.05]. Compared with the high MAP group, the middle MAP group had significant differences in promoting the expression of IL-4 mRNA (2-ΔΔCt: 1.32±0.62 vs. 0.91±0.60, P < 0.05). There was no significant difference in serum cytokine expressions at different time points of resuscitation between the low MAP group and the high MAP group (all P > 0.05). Correlation analysis showed that there was a strong linear correlation between MAP and mRNA expressions of TNF-α, IL-6, IL-10 in the middle MAP group (r value was 0.766, 0.719, 0.692, respectively, all P < 0.01), but had no correlation with IL-4 (r = 0.361, P = 0.059). Fitting linear regression analysis showed an increase in 1 mmHg per MAP, the expression of TNF-α mRNA increased by 0.027 [95% confidence interval (95%CI) = 0.023-0.031, P < 0.001], IL-6 mRNA increased by 0.021 (95%CI = 0.017-0.024, P < 0.001), and IL-10 mRNA increased by 0.049 (95%CI = 0.041-0.058, P < 0.001). When patients with traumatic hemorrhagic shock received restrict fluid resuscitation at MAP of 65-70 mmHg, the effect of reducing systemic inflammatory response and improving hemodynamics is better than the target MAP at 60-65 mmHg or 70-75 mmHg. It is suggested that 65-70 mmHg may be an ideal target MAP level for restrictive fluid resuscitation.