Prophylactic norepinephrine infusion to treat hypotension after spinal anaesthesia during caesarean section: a meta-analysis.

BACKGROUND: Spinal anaesthesia is a common anaesthetic method for caesarean sections but often results in hypotension, posing potential risks to maternal and neonatal health. Norepinephrine, as a vasopressor, may be effective in preventing and treating this hypotension. This systematic review and meta-analysis aims to systematically evaluate the efficacy and safety of prophylactic norepinephrine infusion for the treatment of hypotension following spinal anaesthesia in caesarean sections. METHODS: Literature searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP databases for relevant studies on prophylactic administration of norepinephrine for the treatment of hypotension after spinal anaesthesia in caesarean delivery. Reference lists of included articles were also searched. The latest search update was on March 20, 2024. Meta-analysis was conducted using R software. The methods recommended by the Cochrane Handbook, Begge's and Egger's tests were used for risk of bias evaluation of the included literature. RESULTS: Nine studies were finally included in this study. The results showed that prophylactic administration of norepinephrine was superior to the control group in four aspects of treating hypotension after spinal anaesthesia in caesarean delivery: the incidence of hypotension was reduced [RR = 0.34, 95%CI (0.27-0.43), P < 0.01]; the incidence of severe hypotension was reduced [RR = 0.32, 95%CI (0.21-0.51), P < 0.01]; and maternal blood pressure was more stable with MDPE [MD = -5.00, 95%CI (-7.80--2.21), P = 0.06] and MDAPE [MD = 4.11, 95%CI (1.38-6.85), P < 0.05], the incidence of nausea and vomiting was reduced [RR = 0.52, 95%CI (0.35-0.77), P < 0.01]. On the other hand, the incidence of reactive hypertension was higher than the control group [RR = 3.58, 95%CI (1.94-6.58), P < 0.01]. There was no difference between the two groups in one aspects: newborn Apgar scores [MD = -0.01, 95%CI (-0.10-0.09, P = 0.85)]. CONCLUSION: Prophylactic administration of norepinephrine is effective in treating hypotension after spinal anaesthesia in caesarean delivery patients; however, it does not provide improved safety and carries a risk of inducing reactive hypertension.

Hypotension, or low blood pressure, after spinal anaesthesia can threaten the health of both mothers and their babies during caesarean sections. Norepinephrine is a drug that affects heart rate less and does not easily cross the placental barrier, which may reduce its potential negative effects on the baby. However, there are not many studies on using norepinephrine as a preventive measure. Our study systematically evaluated the use of prophylactic norepinephrine infusion to prevent hypotension in caesarean section patients. We found that it is effective in preventing low blood pressure but does not show improved safety and carries some risk of causing high pressure as a reaction.

A retrospective study of the effects of a vasopressor bolus on systolic slope (dP/dt) and dynamic arterial elastance (Eadyn).

BACKGROUND: To enhance the utility of functional hemodynamic monitoring, the variables systolic slope (dP/dt) and dynamic arterial elastance (Eadyn) are calculated by the Hypotension Prediction Index (HPI) Acumen® Software. This study was designed to characterize the effects of phenylephrine and ephedrine on dP/dt and Eadyn. METHODS: This was a retrospective, non-randomized analysis of data collected during two clinical studies. All patients required intra-operative controlled mechanical ventilation and had an indwelling radial artery catheter connected to an Acumen IQ sensor. Raw arterial pressure waveform data was downloaded from the patient monitor and all hemodynamic measurements were calculated off-line. The anesthetic record was reviewed for bolus administrations of either phenylephrine or ephedrine. Cardiovascular variables prior to drug administration were compared to those following vasopressor administrations. The primary outcome was the difference for dP/dt and Eadyn at baseline compared with the average after the bolus administration. All data sets demonstrated non-normal distributions so statistical analysis of paired and unpaired data followed the Wilcoxon matched pairs signed-rank test or Mann-Whitney U test, respectively. RESULTS: 201 doses of phenylephrine and 100 doses of ephedrine were analyzed. All data sets are reported as median [95% CI]. Mean arterial pressure (MAP) increased from 62 [54,68] to 78 [76,80] mmHg following phenylephrine and from 59 [55,62] to 80 [77,83] mmHg following ephedrine. Stroke volume and cardiac output both increased. Stroke volume variation and pulse pressure variation decreased. Both drugs produced significant increases in dP/dt, from 571 [531, 645] to 767 [733, 811] mmHg/sec for phenylephrine and from 537 [509, 596] to 848 [779, 930] mmHg/sec for ephedrine. No significant changes in Eadyn were observed. CONCLUSION: Bolus administration of phenylephrine or ephedrine increases dP/dt but does not change Eadyn. dP/dt demonstrates potential for predicting the inotropic response to phenylephrine or ephedrine, providing guidance for the most efficacious vasopressor when treating hypotension. TRIAL REGISTRATION: Data was collected from two protocols. The first was deemed to not require written, informed consent by the Institutional Review Board (IRB). The second was IRB-approved (Effect of Diastolic Dysfunction on Dynamic Cardiac Monitors) and registered on ClinicalTrials.gov (NCT04177225).

Perioperative dobutamine infusion in an African lion (Panthera leo).

Laparoscopic ovariectomy under general anesthesia was planned in a 10-year-old, 146 kg, apparently healthy female African lion (Panthera leo). The lion was immobilized via intramuscular darts containing midazolam (0.033 mg/kg), medetomidine (50 µg/kg) and ketamine (2.5 mg/kg), and intubated using an endotracheal tube (16 mm internal diameter). The anesthesia was maintained using sevoflurane (0.9-2.1% end-tidal concentration), in combination with remifentanil (0.1 µg/kg/min) and ketamine (11 µg/kg/min) at a constant rate infusion (CRI), with Hartmann's solution (5 mL/kg/hr). Surgery was conducted with stable vital signs, but hypotension (mean arterial blood pressure 55 mmHg) developed, requiring dobutamine treatment. The hypotension was effectively controlled by adjusting dobutamine from 5 µg/kg/min to 0.2 to 0.3 µg/kg/min. This case suggests possibilities that dosages in this range can be clinically useful for peri-anesthetic hypotension in lions.

Effect of intravenous palonosetron on hypotension induced by spinal anesthesia for cesarean section: A randomized controlled trial.

BACKGROUND: The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section. METHODS: Fifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery. RESULTS: No significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 µg [interquartile range, 291.3-507.8 µg versus 428.0 µg [interquartile range, 305.0-507.0 µg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes. CONCLUSION: Prophylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section.

Norepinephrine weaning guided by the Hypotension Prediction Index in vasoplegic shock after cardiac surgery: protocol for a single-centre, open-label randomised controlled trial - the NORAHPI study.

INTRODUCTION: Norepinephrine (NE) is the first-line recommended vasopressor for restoring mean arterial pressure (MAP) in vasoplegic syndrome (vs) following cardiac surgery with cardiopulmonary bypass. However, solely focusing on target MAP values can lead to acute hypotension episodes during NE weaning. The Hypotension Prediction Index (HPI) is a machine learning algorithm embedded in the Acumen IQ device, capable of detecting hypotensive episodes before their clinical manifestation. This study evaluates the clinical benefits of an NE weaning strategy guided by the HPI. MATERIAL AND ANALYSIS: The Norahpi trial is a prospective, open-label, single-centre study that randomises 142 patients. Inclusion criteria encompass adult patients scheduled for on-pump cardiac surgery with postsurgical NE administration for vs patient randomisation occurs once they achieve haemodynamic stability (MAP>65 mm Hg) for at least 4 hours on NE. Patients will be allocated to the intervention group (n=71) or the control group (n=71). In the intervention group, the NE weaning protocol is based on MAP>65 mmHg and HPI<80 and solely on MAP>65 mm Hg in the control group. Successful NE weaning is defined as achieving NE weaning within 72 hours of inclusion. An intention-to-treat analysis will be performed. The primary endpoint will compare the duration of NE administration between the two groups. The secondary endpoints will include the prevalence, frequency and time of arterial hypotensive events monitored by the Acumen IQ device. Additionally, we will assess cumulative diuresis, the total dose of NE, and the number of protocol weaning failures. We also aim to evaluate the occurrence of postoperative complications, the length of stay and all-cause mortality at 30 days. ETHICS AND DISSEMINATION: Ethical approval has been secured from the Institutional Review Board (IRB) at the University Hospital of Amiens (IRB-ID:2023-A01058-37). The findings will be shared through peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05922982.

Population kinetic/pharmacodynamic modelling of the haemodynamic effects of cafedrine/theodrenaline (Akrinor) under general anaesthesia.

AIMS: The 20:1 combination of cafedrine and theodrenaline (C/T) is widely used in Germany for the treatment of arterial hypotension. Since there is little knowledge about the impact of covariates on the effect, the aim was to develop a kinetic/pharmacodynamic covariate model describing mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) for 30 min after the administration of C/T. METHODS: Data of patients receiving C/T from the HYPOTENS study (NCT02893241, DRKS00010740) were analysed using nonlinear mixed-effects modelling techniques. RESULTS: Overall, 16 579 measurements from 315 patients were analysed. The combination of two kinetic compartments and a delayed effect model, coupled with distinct Emax models for HR, SBP and DBP, described the data best. The model included age, sex, body mass index (BMI), antihypertensive medication, American Society of Anaesthesiologists (ASA) physical status classification grade, baseline SBP at the time of hypotension and pre-surgery HR as covariates (all P < .001). A higher baseline SBP led to a lower absolute increase in MAP. Patients with higher age, higher BMI and lower ASA grade showed smaller increases in MAP. The initial increase was similar for male and female patients. The long-term effect was higher in women. Concomitant antihypertensive medication caused a delayed effect and a lower maximum MAP. The HR increased only slightly (median increase 2.6 bpm, P < .001). CONCLUSIONS: Seven covariates with an impact on the effect of C/T could be identified. The results will enable physicians to optimize the dose with respect to individual patients.

A Clinical Review of Vasopressors in Emergency Medicine.

BACKGROUND: Vasopressor medications raise blood pressure through vasoconstriction and are essential in reversing the hypotension seen in many critically ill patients. Previously, vasopressor administration was largely limited to continuous infusions through central venous access. OBJECTIVES OF THE REVIEW: This review addresses the clinical use of vasopressors in various shock states, including practical considerations and innovations in vasopressor administration. The focus is on the clinical administration of vasopressors across a range of shock states, including hypovolemic, distributive, cardiogenic, and obstructive shock. DISCUSSION: Criteria for starting vasopressors are not clearly defined, though early use may be beneficial. A number of physiologic factors affect the body's response to vasopressors, such as acidosis and adrenal insufficiency. Peripheral and push-dose administration of vasopressors are becoming more common. Distributive shock is characterized by inappropriate vasodilation and vasopressors play a crucial role in maintaining adequate blood pressure. The use of vasopressors is more controversial in hypovolemic shock, as the preferred treatment is correction of the volume deficit. Evidence for vasopressors is limited in cardiogenic shock. For obstructive shock, vasopressors can temporize a patient's blood pressure until definitive therapy can reverse the underlying cause. CONCLUSION: Across the categories of shock states, norepinephrine has wide applicability and is a reasonable first-line agent for shock of uncertain etiology. Keeping a broad differential when hypotension is refractory to vasopressors may help to identify adjunctive treatments in physiologic states that impair vasopressor effectiveness. Peripheral administration of vasopressors is safe and facilitates early administration, which may help to improve outcomes in some shock states.

Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

The current position of ß-blockers in hypertension: guidelines and clinical practice.

The benefits of improved clinical outcomes through blood pressure (BP) reduction have been proven in multiple clinical trials and meta-analyses. The new (2023) guideline from the European Society of Hypertension (ESH) includes ß-blockers within five main classes of antihypertensive agents suitable for initiation of antihypertensive pharmacotherapy and for combination with other antihypertensive agents. This is in contrast to the 2018 edition of ESH guidelines that recommended ß-blockers for use primarily in patients with compelling indications such as cardiovascular comorbidities, e.g. coronary heart disease, heart failure. This change was based on the fact that the magnitude of BP reduction is the most important factor for adverse cardiovascular outcomes, over and above the precise manner in which reduced BP is achieved. The ESH guideline also supports the use of ß-blockers for patients with resting heart rate (>80 bpm); high resting heart rate is a sign of sympathetic overactivity, an important driver of adverse cardiac remodelling in the setting of hypertension and heart failure. Hypertension management guidelines support for the use of combination therapies for almost all patients with hypertension, ideally within a single-pill combination to optimise adherence to therapy. Where a ß-blocker is prescribed, the inclusion of a dihydropyridine calcium channel blocker within a combination regimen is rational. These agents together reduce both peripheral and central BP, which epidemiological studies have shown is important for reducing the burden of premature morbidity and mortality associated with uncontrolled hypertension, especially strokes.

Non-paroxysmal junctional tachycardia complicating disseminated intravascular coagulation during massive surgical hemorrhage: A case report.

RATIONALE: Non-paroxysmal junctional tachycardia (NPJT) is a self-limiting supraventricular tachycardia associated with primary heart disease, cardiac surgery, digitalis toxicity, and metabolic or electrolyte imbalances. However, NPJT caused enhanced normal automaticity even in the absence of structural heart disease can be fatal if not managed properly. PATIENT CONCERNS: A 74-year-old hypertensive female patient was scheduled for transureteroureterostomy and right ureteroneocystostomy under general anesthesia. DIAGNOSIS: The patient developed NPJT without visible P wave and severe hypotension due to adrenergic stimulation in response to massive hemorrhage during surgery. INTERVENTIONS: NPJT with hypotension was initially converted to sinus rhythm with normotension with administration of adenosine and esmolol. However uncontrolled surgical hemorrhage and administration of large dose of vasopressors eventually perpetuated NPJT refractory to antiarrhythmic drugs. OUTCOMES: Despite intravenous fluid resuscitation and massive transfusion, the patient was deteriorated hemodynamically due to uncontrolled bleeding and persistent NPJT, which resulted in hypovolemic shock and fatal disseminated intravascular coagulation (DIC). LESSONS: NPJT can occur by enhanced automaticity due to increased catecholamine during severe surgical hemorrhage. Although NPJT is generally self-limiting, it can be refractory to antiarrhythmic agents and accelerate hypotension if the surgical bleeding is uncontrolled. Therefore, aggressive management of the primary pathologic condition is crucial for the management of NPJT and hemodynamic collapse even in the absence of structural heart disease.

Outcomes of Vasopressin-Receptor Agonists Versus Norepinephrine in Adults With Perioperative Hypotension: A Systematic Review.

Consensus statements recommend the use of norepinephrine and/or vasopressin for hypotension in cardiac surgery. However, there is a paucity of data among other surgical subgroups and vasopressin analogs. Therefore, the authors conducted a systematic review of randomized controlled trials (RCTs) to compare vasopressin-receptor agonists with norepinephrine for hypotension among those undergoing surgery with general anesthesia. This review was registered prospectively (CRD42022316328). Literature searches were conducted by a medical librarian to November 28, 2023, across MEDLINE, EMBASE, CENTRAL, and Web of Science. The authors included RCTs enrolling adults (≥18 years of age) undergoing any surgery under general anesthesia who developed perioperative hypotension and comparing vasopressin receptor agonists with norepinephrine. The risk of bias was assessed by the Cochrane risk of bias tool for randomized trials (RoB-2). Thirteen (N = 719) RCTs were included, of which 8 (n = 585) enrolled patients undergoing cardiac surgery. Five trials compared norepinephrine with vasopressin, 4 trials with terlipressin, 1 trial with ornipressin, and the other 3 trials used vasopressin as adjuvant therapy. There was no significant difference in all-cause mortality. Among patients with vasoplegic shock after cardiac surgery, vasopressin was associated with significantly lower intensive care unit (N = 385; 2 trials; mean 100.8 v 175.2 hours, p < 0.005; median 120 [IQR 96-168] v 144 [96-216] hours, p = 0.007) and hospital lengths of stay, as well as fewer cases of acute kidney injury and atrial fibrillation compared with norepinephrine. One trial also found that terlipressin was associated with a significantly lower incidence of acute kidney injury versus norepinephrine overall. Vasopressin and norepinephrine restored mean arterial blood pressure with no significant differences; however, the use of vasopressin with norepinephrine was associated with significantly higher mean arterial blood pressure versus norepinephrine alone. Further high-quality trials are needed to determine pooled treatment effects, especially among noncardiac surgical patients and those treated with vasopressin analogs.

Randomized Double-Blinded Comparison of Intermittent Boluses Phenylephrine and Norepinephrine for the Treatment of Postspinal Hypotension in Patients with Severe Pre-Eclampsia During Cesarean Section.

Background: Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section. Methods: A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness. Results: No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups. Conclusion: A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.

Provider Experience With the Use of Ketamine for Refractory Status Epilepticus.

OBJECTIVE: Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE. METHODS: A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated. RESULTS: There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use. CONCLUSIONS: Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.

Efficacy and safety of esketamine combined with propofol for curative endoscopic resection in colorectum: a prospective, randomized controlled trial.

BACKGROUND: Curative endoscopic resection is widely used to treat colonic polyps and early stage cancers. The anesthetic strategy commonly involves the use of propofol combined with a small dose of opioids for sedation. Adverse respiratory or cardiovascular events such as hypotension often occur when attempting to achieve the necessary level of sedation. Several studies have suggested its advantages owing to the anesthetic, analgesic, and sympathomimetic properties of esketamine. However, there are no reports on curative colorectal endoscopic resection. We designed this randomized controlled trial to assess the efficacy and safety of esketamine combined with propofol for sedation in patients undergoing curative colorectal endoscopic resection. METHODS: A total of 166 patients who underwent curative colorectal endoscopic resection were randomly assigned to groups A (propofol + fentanyl) or E (propofol + esketamine). Ideal sedation was assessed using the MOAA/S scale and was achieved using TCI-propofol with different doses of fentanyl and esketamine. The propofol consumption and vasoactive drug dosages were recorded. Sedation-related times, adverse events, and satisfaction were recorded. RESULTS: Of the 160 patients, the total propofol consumption was significantly lower in group E (n = 81) (300 mg) than in group A (n = 79) (350 mg). Hypotension and bradycardia were significantly lower in Group E than in Group A. The groups showed no significant differences in other adverse events, induction time, recovery time, or patient or endoscopist satisfaction. CONCLUSION: Compared to fentanyl, esketamine helps decrease propofol consumption and increases cardiovascular stability during curative colorectal endoscopic resection in American Society of Anesthesiologists Class I-III patients without affecting anesthesia, patient and endoscopist satisfaction, or other adverse events. TRIAL REGISTRATION: The study was retrospectively registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; registration number: ChiCTR2300069014 on 03/03/2023).

A new potential therapeutic approach for ALS: A case report with NGS analysis.

RATIONALE: Amyotrophic lateral sclerosis (ALS) poses a significant clinical challenge due to its rapid progression and limited treatment options, often leading to deadly outcomes. Looking for effective therapeutic interventions is critical to improve patient outcomes in ALS. PATIENT CONCERNS: The patient, a 75-year-old East Asian male, manifested an insidious onset of right-hand weakness advancing with dysarthria. Comprehensive Next-generation sequencing analysis identified variants in specific genes consistent with ALS diagnosis. DIAGNOSES: ALS diagnosis is based on El Escorial diagnostic criteria. INTERVENTIONS: This study introduces a novel therapeutic approach using artificial intelligence phenotypic response surface (AI-PRS) technology to customize personalized drug-dose combinations for ALS. The patient underwent a series of phases of AI-PRS-assisted trials, initially incorporating a 4-drug combination of Ibudilast, Riluzole, Tamoxifen, and Ropinirole. Biomarkers and regular clinical assessments, including nerve conduction velocity, F-wave, H-reflex, electromyography, and motor unit action potential, were monitored to comprehensively evaluate treatment efficacy. OUTCOMES: Neurophysiological assessments supported the ALS diagnosis and revealed the co-presence of diabetic polyneuropathy. Hypotension during the trial necessitated an adaptation to a 2-drug combinational trial (ibudilast and riluzole). Disease progression assessment shifted exclusively to clinical tests of muscle strength, aligning with the patient's well-being. LESSONS: The study raises the significance of personalized therapeutic strategies in ALS by AI-PRS. It also emphasizes the adaptability of interventions based on patient-specific responses. The encountered hypotension incident highlights the importance of attentive monitoring and personalized adjustments in treatment plans. The described therapy using AI-PRS, offering personalized drug-dose combinations technology is a potential approach in treating ALS. The promising outcomes warrant further evaluation in clinical trials for searching a personalized, more effective combinational treatment for ALS patients.

Norepinephrine versus phenylephrine on cerebral tissue oxygen saturation during prophylactic infusion to prevent spinal hypotension for Caesarean birth.

BACKGROUND: Phenylephrine may cause a reduction in maternal cerebral tissue oxygen saturation (SctO2) during Caesarean birth to prevent spinal hypotension; however, the effect of norepinephrine has not been assessed. We hypothesized that norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth. METHODS: We conducted a randomized, double-blind, controlled study. Sixty patients were randomly assigned to prophylactic norepinephrine or phenylephrine to maintain blood pressure during spinal anesthesia for Caesarean birth. SctO2, systolic blood pressure, and heart rate were recorded. The primary outcome was the incidence of a 10% reduction of intraoperative SctO2 from baseline or more during Caesarean birth. RESULTS: The norepinephrine group had a lower incidence of more than 10% reduction of intraoperative SctO2 from baseline than that of the phenylephrine group (13.3% vs 40.0%, P = .02). The change in SctO2 after 5 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-3.4 ±â€…4.7 vs -6.2 ±â€…5.6, P = .04). The change in SctO2 after 10 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-2.5 ±â€…4.4 vs -5.4 ±â€…4.6, P = .006). The norepinephrine group showed greater left- and right-SctO2 values than the phenylephrine group at 5 to 10 minutes. However, the change in systolic blood pressure was comparable between the 2 groups. CONCLUSION: Norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth. However, the changes in clinical outcomes caused by differences in SctO2 between the 2 medications warrant further studies.

Efficacy of Sacubitril-Valsartan on Survival and Cardiac Remodeling in Hypotensive Heart Failure With Reduced Ejection Fraction: A Multicenter Study.

OBJECTIVE: To investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor-neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials. PATIENTS AND METHODS: In this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis. RESULTS: Diverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting. CONCLUSION: Patients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting.

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

OBJECTIVES: 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. DESIGN: 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. SETTING: An academic ICU in Melbourne, VIC, Australia. PATIENTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

Comparative Study Between Dexmedetomidine with Bupivacaine and Bupivacaine Alone in Erector Spinae Plane Block for Postoperative Pain Control of Posterior Lumbosacral Spine Fixation Surgeries: A Randomized Controlled Trial.

Background: As posterior lumbosacral spine fixation surgeries are common spine procedures done nowadays due to different causes and mostly accompanied with moderate-to-severe postoperative pain, so should find effective postoperative analgesia for these patients. This study aimed to observe analgesic effect of dexmedetomidine combined with bupivacaine versus bupivacaine alone for erector spinae plane block ESPB for postoperative pain control of posterior lumbosacral spine fixation surgeries. Methods: Double-blind randomized controlled study including 90 patients who were randomly allocated into 3 groups (30 patients for each): Dexmedetomidine combined with bupivacaine (DB group), bupivacaine (B group), and saline (control) (S group). US-guided ESPB was performed preoperatively bilaterally in all patients of the 3 groups. All patients received intravenous patient-controlled postoperative analgesia with morphine and 1 gm intravenous paracetamol every 8 hours. Primary clinical outcomes were active (while mobilization) and passive (at rest) visual analog scale (VAS) pain score at first 24 hours measured every 2 hours, opioid consumption (number of PCA presses), and need for rescue analgesia. Other clinical outcomes included active and passive VAS pain score at second 24 hours, measured every 4 hours, opioid consumption, need for rescue analgesia, postoperative opioid side effects, and intraoperative dexmedetomidine side effects as bradycardia and hypotension. Results: Active and passive VAS pain scores, postoperative opioid consumption, need for rescue analgesia, and postoperative opioid side effects were significantly lower in DB group when compared to other groups (B and S groups). There were no additional intraoperative dexmedetomidine side effects as bradycardia and hypotension. The estimated effect-size r was -0.58 and Cohen's d was -1.46. Conclusion: Addition of dexmedetomidine to bupivacaine 0.25% in ESPB for postoperative pain control in patients of posterior lumbosacral spine fixation surgeries resulted in lower active and passive VAS pain scores, decreased postoperative opioid consumption, need for rescue analgesia and postoperative opioid side effects without additional intraoperative dexmedetomidine side effects. Clinicaltrialsgov Identifier: NCT05590234.