The accuracy of Pleth Variability Index for directed fluid optimization in donors in living donor liver transplantation

Background Fluid management strongly affects hepatic resection and aims to reduce intraoperative bleeding during living donation. The Pleth Variability Index (PVI) is a tool to assess the fluid responsiveness from the pulse oximeter waveform; we evaluated the efficacy and accuracy of finger PVI compared to pulse pressure variation (PPV) from arterial waveform in predicting the fluid response in donor hepatectomy patients with the guide of non-invasive cardiac output (CO) measurements. We recruited forty patients who were candidates for right lobe hepatectomy for liver transplantation under conventional general anesthesia methods. During periods of intraoperative hypovolemia not affected by surgical manipulation, PVI, PPV, and CO were recorded then compared with definitive values after fluid bolus administration of 3–5 ml/kg aiming to give a 10% increase in CO which classified the patients into responders and non-responders. Results Both PPV and PVI showed a significant drop after fluid bolus dose (P < 0.001) leading to an increase of the CO (P < 0.0001), and the area under the curve was 0.934, 0.842 (95% confidence interval, 0.809 to 0.988, 0.692 to 0.938) and the standard error was 0.0336, 0.124, respectively. Pairwise comparison of PPV and PVI showed non-significant predictive value between the two variables (P = 0.4605); the difference between the two areas was 0.0921 (SE 0125 and 95% CI − 0.152 to 0.337). Conclusions PVI is an unreliable indicator for fluid response in low-risk donors undergoing right lobe hepatectomy compared to PPV. We need further studies with unbiased PVI monitors in order to implement a non-invasive and safe method for fluid responsiveness.

Goji Berry (Lycium barbarum) Supplementation during Pregnancy Influences Insulin Sensitivity in Rabbit Does but Not in Their Offspring

This study investigated the effects of Goji berry (Lycium barbarum) dietary supplementation during pregnancy on insulin sensitivity of rabbit does and their offspring. Starting from two months before the artificial insemination, 75 New Zealand White does were fed only commercial standard diet (C) or supplemented with 1% (G1) and 3% (G3) of Goji berries. Their offspring received a standard diet but kept the nomenclature of the mother’s group. Fasting and intravenous glucose tolerance test-derived indices were estimated at 21 days of pregnancy on rabbit does and at 90 days of age on the offspring. No difference was found in the fasting indices, while the diet modulated the response to glucose load of rabbit does. In particular, G3 group had the lowest glucose concentrations 5 min after the bolus administration (p < 0.05) and, as a result, differed in the parameters calculated during the elimination phase such as the elimination rate constant (Kel), the half-life of the exogenous glucose load (t1/2), and apparent volume of distribution (Vd; for all, p < 0.05). The high dose of Goji supplementation could thus enhance the first-phase glucose-induced insulin secretion. Findings on the offspring were inconsistent and therefore a long-term effect of Goji supplementation during pregnancy could not be demonstrated. Further study on the effect of Goji on the secretory pathway of insulin could clarify its hypoglycaemic action, while different protocols are needed to investigate its potential effects on foetal programming.

Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion

BackgroundSanguinate, a bovine PEGylated carboxyhemoglobin-based oxygen carrier with vasodilatory, oncotic and anti-inflammatory properties designed to release oxygen in hypoxic tissue, was tested to determine if it improves infarct volume, collateral recruitment and blood flow to the ischemic core in hyperacute middle cerebral artery occlusion (MCAO).MethodsUnder an IACUC approved protocol, 14 mongrel dogs underwent endovascular permanent MCAO. Seven received Sanguinate (8 mL/kg) intravenously over 10 min starting 30 min following MCAO and seven received a similar volume of normal saline. Relative cerebral blood flow (rCBF) was assessed using neutron-activated microspheres prior to MCAO, 30 min following MCAO and 30 min following intervention. Pial collateral recruitment was scored and measured by arterial arrival time (AAT) immediately prior to post-MCAO microsphere injection. Diffusion-weighted 3T MRI was used to assess infarct volume approximately 2 hours after MCAO.ResultsMean infarct volumes for control and Sanguinate-treated subjects were 4739 mm3 and 2585 mm3 (p=0.0443; r2=0.687), respectively. Following intervention, rCBF values were 0.340 for controls and 0.715 in the Sanguinate group (r2=0.536; p=0.0064). Pial collateral scores improved only in Sanguinate-treated subjects and AAT decreased by a mean of 0.314 s in treated subjects and increased by a mean of 0.438 s in controls (p<0.0276).ConclusionPreliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.

Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery

Background Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated. Methods This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus. Results Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min–1 · m–2 (95% CI, 0.11 to 0.29; P &lt; 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P &lt; 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of –1.5 (–2 to –1; P &lt; 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of –0.03 (–0.07 to 0.02) mmHg, P = 0.229). Conclusions There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

1106. Evaluation of Penetration of Cefiderocol into Cerebrospinal Fluid Using a Rat Meningitis Model

Background Central nervous system (CNS) infections caused by Gram-negative bacteria (GNB) are sometimes hard to treat due to antibiotic resistance and difficulty with penetration into cerebrospinal fluid (CSF). Cefiderocol (CFDC) which was approved by the FDA and the EMA in 2019 to 2020 is a siderophore cephalosporin with potent activity against various GNB including carbapenem-resistant strains. In this study, we evaluated the penetration of CFDC into CSF using a rat meningitis model. Methods To induce meningitis, the anesthetized immunocompetent rats were infected by intracisternal inoculation of a bacterial suspension of 8.7×101 CFU of E. coli SR200138. 200 mg/kg or 50 mg/kg of CFDC was administered via tail vein bolus injection to uninfected rats (n=4/sampling point) and rats with meningitis (n=4/sampling point) 24 hours after infection. CSF was collected by cisternal puncture and blood was collected from heart. The samplings were performed 0.25, 0.5, 1, 3, and 5 hours after dosing. The concentrations of CFDC in plasma and CSF for individuals were determined by LC/MS/MS. PK parameters for the average values in plasma and CSF were calculated. Results CFDC concentration and the PK parameters are shown in Figure and Table, respectively. The penetration of CFDC from plasma to CSF was observed in both uninfected and meningitis groups, and the penetration rates increased in the rats withs meningitis (AUCCSF/AUCplasma: 0.149-0.183) compared with the uninfected rats (AUCCSF/AUCplasma: 0.0508-0.0588). The penetration rates of CFDC in the meningitis were comparable to those of piperacillin, cefepime, and meropenem in human (0.32, 0.103, and 0.39 in strongly inflamed meninges, respectively) [1]. In both groups, elimination of CFDC from CSF was slower compared with that from plasma as seen with other β-lactam antibiotics such as meropenem, suggesting that T&gt; MIC, an indicator that correlates with the efficacy of β-lactams, may be higher in CSF [2]. Table. PK Parameters of Cefiderocol after Intravenous Bolus Administration in Uninfected Rats and Rats with Meningitis Figure. Concentrations of Cefiderocol after Intravenous Bolus Administration in Uninfected Rats and Rats with Meningitis Conclusion It was confirmed that CFDC penetrates into CSF from plasma in a rat model and the penetration rate was increased 3-fold in meningitis. References 1. Nau, R. et al. Clin Microbiol Rev. 2010 Oct;23(4):858–883. 2. Nau, R. et al. Antimicrob Agents Chemother. 1998 Aug;42(8):2012–2016. Disclosures Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Sachi Kanazawa, PhD, Shionogi & Co., Ltd. (Employee) Naoki Kohira, PhD, Shionogi & Co., Ltd. (Employee) Yuki Aoe, BS, Shionogi TechnoAdvance Research Co., Ltd. (Employee) Atsushi Morimoto, n/a, Shionogi TechnoAdvance Research Co., Ltd. (Employee) Kana Horiuchi, MPharm, Shionogi & Co., Ltd. (Employee) Yuji Inoue, MPharm, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi (Employee)

The improvement of cardiac multispiral computed tomography protocol for planning interventional arrhythmia management

Purpose. The study aimed at the comparison of computed tomography (СT) contrast enhancement (CE) protocols for optimal visualization of cardiac chambers, evaluation of their impact on results of non-invasive superficial cardiac mapping.Methods. The study included 93 patients with heart rhythm disorders in whom catheter ablation of arrhythmia was planned. Noninvasive cardiac mapping for arrhythmia localization was performed and included multichannel ECG-registration and CT with intravenous СE (1st group - monophasic (50 patients), 2nd group - split-bolus (18 patients), 3rd group - with pre-bolus (25 patients). Qualitative and quantitative (measurement of mean blood attenuation in four chambers, calculation of ventricular-myocardial [VM] contrast-to-noise ratio VM-LV и VM-RV for the left ventricle [LV] and right ventricle [RV], respectively) parameters were compared between the groups. Fusion of ECG and CT data was carried out a semi-automatic mode with a non-invasive imaging complex.Results. Regardless of CE technique, sufficient and homogeneous contrast attenuation was obtained for the left atrium (LA) and LV (mean blood attenuation in LA more than 278 HU, LV 250 HU, VM-LV 0,582). In most cases, the enhancement of the right heart was insufficient with the monophasic protocol; the average CT density was lower than 200 HU, VM-RV 0,256. The split-bolus protocol improved visualization of the right atrium (RA) and RV (blood density in RA 258HU, RV 227HU, VMRV 0,541); however, there was a heterogeneity of the RA cavity due to artifacts from the superior vena cava (VC) and unenhanced blood from the inferior VC. Pre-bolus administration increased the contrast ratio between RA myocardium and blood due to the improvement of blood CT density in the inferior VC (blood density 294 HU). The quality of RV CE was similar to 2nd group (blood density 264 HU, VM-RV 0,565).Conclusion. The split-bolus and with pre-bolus CE protocols improve visualization of the RV, supporting the high-level enhancement of the left heart. The protocol with a pre-bolus is preferable for exact differentiation of the right atrial endocardial contour.

Comparison of bolus administration effects of lidocaine on preventing tourniquet-induced hypertension in patients undergoing general anesthesia: a randomized controlled trial

Background: This study assessed the effect of a single bolus administration of lidocaine on the prevention of tourniquet-induced hypertension (TIH) and compared the effect of lidocaine to that of ketamine in patients undergoing general anesthesia.Methods: This randomized, controlled, double-blind study included 75 patients who underwent lower limb surgery using a tourniquet. The patients were administered lidocaine (1.5 mg/kg, n = 25), ketamine (0.2 mg/kg, n = 25) or placebo (n = 25). The study drugs were administered intravenously 10 min before tourniquet inflation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured before tourniquet inflation, after tourniquet inflation for 60 min at 10 min intervals, and immediately after tourniquet deflation. The incidence of TIH, defined as an increase of 30% or more in SBP or DBP during tourniquet inflation, was also recorded.Results: SBP, DBP, and HR increased significantly over time in the control group compared to those in the lidocaine and ketamine groups for 60 min after tourniquet inflation (P < 0.001, P < 0.001, and P = 0.007, respectively). The incidence of TIH was significantly lower in the lidocaine (n = 4, 16%) and ketamine (n = 3, 12%) group than in the control group (n = 14, 56%) (P = 0.001). Conclusion: Single-bolus lidocaine effectively attenuated blood pressure increase due to tourniquet inflation, with an effect comparable to that of bolus ketamine.

Paradoxical and Retrograde Air Embolism from Pressurized Peripheral Bolus

Introduction. Cerebral air embolism is a rare, yet serious neurological occurrence with unclear incidence and prevalence. Here, we present a case of fatal cerebral arterial and venous cerebral gas embolism in a patient with infective endocarditis and known large right-to-left shunt and severe tricuspid regurgitation following pressurized fluid bolus administration. Case Presentation. A 32-year-old female was admitted to the medical intensive care unit from a long-term acute care facility with acute on chronic respiratory failure. Her medical history was significant for intravenous heroin and cocaine abuse, methicillin-sensitive Staphylococcus aureus tricuspid valve infective endocarditis on vancomycin, patent foramen ovale, septic pulmonary embolism with cavitation, tracheostomy with chronic ventilator dependence, multifocal cerebral infarction, hepatitis C, nephrolithiasis, anxiety, and depression. After intravenous fluid administration, she became unresponsive with roving gaze, sluggish pupils, and hypotensive requiring vasopressors. CT of the brain showed diffuse arterial and venous cerebral air embolism secondary to accidental air administration from fluid bolus. Magnetic resonance imaging of the brain showed diffuse global anoxic injury and flattening of the globe at the optic nerve insertion. Given poor prognosis, her family chose comfort measures and she died. Conclusions. Fatal cerebral air embolism can occur through peripheral intravenous routes when the lines are inadequately primed and fluids administered with pressure. Caution must be exercised in patients with right-to-left shunting as air may gain access to systemic circulation.

Physiologic Effects of Instilled and Aerosolized Surfactant Using a Breath-Synchronized Nebulizer on Surfactant-Deficient Rabbits

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would have similar efficacy and safety as instilled surfactant. Juvenile rabbits (1.50 ± 0.20 kg, n = 17) were sedated, anesthetized, intubated, and surfactant was depleted via lung lavage on mechanical ventilation. Subjects were randomized to receive standard dose liquid instillation via catheter (n = 5); low dose surfactant (n = 5) and standard dose surfactant (n = 5) via aerosol; and descriptive controls (no treatment, n = 2). Peridosing events, disease severity and gas exchange, were recorded every 30 min for 3 h following surfactant administration. Direct-Instillation group had higher incidence for peridosing events than aerosol. Standard dose liquid and aerosol groups had greater PaO2 from pre-treatment baseline following surfactant (p < 0.05) with greater ventilation efficiency with aerosol (p < 0.05). Our study showed similar improvement in oxygenation response with greater ventilation efficiency with aerosol than liquid bolus administration at the same dose with fewer peridosing events. Breath-synchronized aerosol via nebulizer has potential as a safe, effective, and economical alternative to bolus liquid surfactant instillation.