Norepinephrine in Goal-Directed Fluid Therapy during General Anesthesia in Elderly Patients Undergoing Spinal Operation: Determining Effective Infusion Rate to Enhance Postoperative Functions

Background and Objective: Intraoperative hypotension is a common complication in general anesthesia that could result in different serious complications particularly in elderly patients. This Randomized Clinical Trial (RCT) aims to determine effective continuous infusion rate of norepinephrine to prevent intraoperative hypotension during spinal surgery under general anesthesia in elderly patients. Methods: This RCT was conducted on elderly patients (n= 108) undergoing general anesthesia for posterior lumbar spinal fusion. The patients were randomly divided into 0.030, 0.060, and 0.090 μg.kg-1.min-1 groups of norepinephrine infusion rates. The outcomes were assessed at entrance to operation room (T0), 15 mins after anesthesia induction (T1), 60 mins following surgery (T2), and immediately after surgery (T3). The intraoperative and postoperative complications and rehabilitation outcomes were comparatively assessed. Results: All three groups significantly reduced the incidence of delayed wound healing (0.030 vs. 0.060 vs. 0.090 μg.kg-1.min-1; 33.3% vs. 10% vs. 10%, P=0.024) and wound infection (26.7% vs. 6.7% vs. 6.7%, P=0.031). Intraoperative total fluid volume and colloids volume in the 0.030 group were significantly higher than 0.060 and 0.090 groups (P=0.005, P=0.003, and P=0.01, respectively). The 0.060 and 0.090 groups significantly increased mean-arterial-pressure than the 0.030 group at T2 and T3. Both 0.060 and 0.090 infusion rates significantly reduced intraoperative hypotension than 0.030 dosage (P=0.01 and P=0.003, respectively). The bradycardia incidence in the 0.090 group was significantly higher than the 0.030 (P=0.026) and 0.060 groups (P=0.038). The 0.060 group decreased the first intake by 1.4 hours (P=0.008) and first flatus by 1.1 hours (P=0.004) and postoperative hospital stay by 1 day (P=0.066). Conclusion: The 0.060 µg·kg-1·min-1 norepinephrine infusion combined with goal-directed fluid therapy exhibited adequate intraoperative management and postoperative outcomes.

Hyperspectral Imaging for the Evaluation of Microcirculatory Tissue Oxygenation and Perfusion Quality in Haemorrhagic Shock: A Porcine Study

Background: The ultimate goal of haemodynamic therapy is to improve microcirculatory tissue and organ perfusion. Hyperspectral imaging (HSI) has the potential to enable noninvasive microcirculatory monitoring at bedside. Methods: HSI (Tivita® Tissue System) measurements of tissue oxygenation, haemoglobin, and water content in the skin (ear) and kidney were evaluated in a double-hit porcine model of major abdominal surgery and haemorrhagic shock. Animals of the control group (n = 7) did not receive any resuscitation regime. The interventional groups were treated exclusively with either crystalloid (n = 8) or continuous norepinephrine infusion (n = 7). Results: Haemorrhagic shock led to a drop in tissue oxygenation parameters in all groups. These correlated with established indirect markers of tissue oxygenation. Fluid therapy restored tissue oxygenation parameters. Skin and kidney measurements correlated well. High dose norepinephrine therapy deteriorated tissue oxygenation. Tissue water content increased both in the skin and the kidney in response to fluid therapy. Conclusions: HSI detected dynamic changes in tissue oxygenation and perfusion quality during shock and was able to indicate resuscitation effectivity. The observed correlation between HSI skin and kidney measurements may offer an estimation of organ oxygenation impairment from skin monitoring. HSI microcirculatory monitoring could open up new opportunities for the guidance of haemodynamic management.

Optimal Cerebral Perfusion Pressure Guided by Brain Oxygen Pressure Measurement

Background: Although increasing cerebral perfusion pressure (CPP) is commonly accepted to improve brain tissue oxygen pressure (PbtO2), it remains unclear whether recommended CPP targets (i. e., >60 mmHg) would result in adequate brain oxygenation in brain injured patients. The aim of this study was to identify the target of CPP associated with normal brain oxygenation.Methods: Prospectively collected data including patients suffering from acute brain injury and monitored with PbtO2, in whom daily CPP challenge using vasopressors was performed. Initial CPP target was >60 mmHg; norepinephrine infusion was modified to have an increase in CPP of at least 10 mmHg at two different steps above the baseline values. Whenever possible, the same CPP challenge was performed for the following days, for a maximum of 5 days. CPP “responders” were patients with a relative increase in PbtO2 from baseline values > 20%.Results: A total of 53 patients were included. On the first day of assessment, CPP was progressively increased from 73 (70–76) to 83 (80–86), and 92 (90–96) mmHg, which resulted into a significant PbtO2 increase [from 20 (17–23) mmHg to 22 (20–24) mmHg and 24 (22–26) mmHg, respectively; p < 0.001]. Median CPP value corresponding to PbtO2 values > 20 mmHg was 79 (74–87) mmHg, with 2 (4%) patients who never achieved such target. Similar results of CPP targets were observed the following days. A total of 25 (47%) were PbtO2 responders during the CPP challenge on day 1, in particular if low PbtO2 was observed at baseline.Conclusions: PbtO2 monitoring can be an effective way to individualize CPP values to avoid tissue hypoxia. Low PbtO2 values at baseline can identify the responders to the CPP challenge.

Effect of heart rate control with amiodarone infusion on hemodynamic and clinical outcomes in septic shock patients with tachycardia: a prospective, single-arm clinical study

Background Keeping the heart rate within the normal range has improved the survival of septic shock patients. Amiodarone could target the underlying pathophysiology of sepsis-induced tachycardia. This study aimed to determine whether amiodarone is effective in controlling the heart rate in critically ill patients with septic shock and sustained tachycardia who were receiving vasopressor. Methods In this prospective, single-arm cohort study, 46 patients with septic shock and tachycardia were enrolled to receive a loading dose of amiodarone 150 mg, then continuous infusion of 1 mg/min. The primary outcome was the ability of amiodarone in rate control lower than 95 beats per minute (BPM) and maintaining it during 24-h study period. We also recorded the effect of amiodarone on hemodynamic indices as the secondary outcomes. Results The results of the present study indicated a significant decrease in HR in septic shock patients for amiodarone, from 121.0 (116.5, 140.0) at baseline to 91.5(89.3, 108.0) at the end of the study period (p < 0.001). During the study period, a total of 26 (56.52%) of patients achieved the target heart rate lower than 95 BPM and maintained it during study period. Amiodarone decreased HR by 22.8 ± 13.7. While receiving amiodarone infusion, the values for heart rate, mean arterial pressure, cardiac index, norepinephrine infusion rate, and stroke volume index changed significantly between amiodarone initiation and 24-h follow-up (P < 0.001). Amiodarone was well tolerated, because this anti-arrhythmic agent did not increase the need for vasopressor and none of the patients experienced episodes of refractory hypotension. Conclusion This study showed that amiodarone infusion successfully reduced the heart rate in sepsis-induced tachycardia. The patients had improved hemodynamic state as indicated by an increase in cardiac index and SVI.

The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study

Background: Hypotension commonly occurs with spinal anesthesia during cesarean delivery. Norepinephrine is an alternative to phenylephrine which can be used to prevent or treat hypotension, with better maintained cardiac output and less bradycardia. However, an appropriate initial prophylactic infusion dose of norepinephrine remains unclear. The aim of this study was to describe the dose-response relationship of prophylactic norepinephrine infusion during cesarean delivery under combined spinal-epidural anesthesia.Methods: We performed a prospective, randomized, double-blinded dose-finding study. One hundred patients undergoing elective cesarean delivery were randomly assigned to receive an infusion of norepinephrine at 0, 0.025, 0.05, 0.075 or 0.1 μg/kg/min initiated immediately after intrathecal injection of 10 mg bupivacaine combined with 5 µg sufentanil. An effective dose was considered when there was no hypotension (systolic blood pressure &lt; 90 mm Hg or &lt; 80% of baseline) during the time period from injection of intrathecal local anesthetic to delivery of the neonate. The primary aim was to determine the dose-response relationship of norepinephrine to prevent spinal anesthesia-induced hypotension. The median effective dose (ED50) and 95% effective dose (ED95) for norepinephrine were calculated utilizing probit analysis.Results: The proportion of patients with hypotension was 80, 70, 40, 15 and 5% at norepinephrine doses of 0, 0.025, 0.05, 0.075 and 0.1 μg/kg/min, respectively. The ED50 and ED95 were 0.042 (95% CI, 0.025–0.053) µg/kg/min and 0.097 (95% CI, 0.081–0.134) µg/kg/min, respectively. There were no differences in the Apgar scores (p = 0.685) or umbilical arterial pH (p = 0.485) measurements of the newborns among the treatment groups.Conclusion: A norepinephrine infusion of 0.1 μg/kg/min as an initial starting dose was effective for the prevention of spinal-induced hypotension.