Goal-directed colloid versus crystalloid therapy and microcirculatory blood flow following ischemia/reperfusion.

OBJECTIVE: Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid - compared to crystalloid - therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury. METHODS: This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function. RESULTS: Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2-860.1) vs. 595.6 (496.3-694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2-592.1) vs. 442.1 (361.2-523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7-701.8) vs. 548.7 (444.0-653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid - compared to crystalloid - therapy also had less small intestinal, but not renal and hepatic, histopathological damage. CONCLUSIONS: Goal-directed isooncotic hydroxyethyl-starch colloid - compared to balanced isotonic crystalloid - therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.

Effect of thoracic epidural anesthesia on postoperative outcome in major liver surgery: a retrospective cohort study.

PURPOSE: Postoperative complications after major liver surgery are common. Thoracic epidural anesthesia may provide beneficial effects on postoperative outcome. We strove to compare postoperative outcomes in major liver surgery patients with and without thoracic epidural anesthesia. METHODS: This was a retrospective cohort study in a single university medical center. Patients undergoing elective major liver surgery between April 2012 and December 2016 were eligible for inclusion. We divided patients into two groups according to whether or not they had thoracic epidural anesthesia for major liver surgery. The primary outcome was postoperative hospital length of stay, i.e., from day of surgery until hospital discharge. Secondary outcomes included 30-day postoperative mortality and major postoperative complications. Additionally, we investigated the effect of thoracic epidural anesthesia on perioperative analgesia doses and the safety of thoracic epidural anesthesia. RESULTS: Of 328 patients included in this study, 177 (54.3%) received thoracic epidural anesthesia. There were no clinically important differences in postoperative hospital length of stay (11.0 [7.00-17.0] vs. 9.00 [7.00-14.0] days, p = 0.316, primary outcome), death (0.0 vs. 2.7%, p = 0.995), or the incidence of postoperative renal failure (0.6 vs. 0.0%, p = 0.99), sepsis (0.0 vs. 1.3%, p = 0.21), or pulmonary embolism (0.6 vs. 1.4%, p = 0.59) between patients with or without thoracic epidural anesthesia. Perioperative analgesia doses - including the intraoperative sufentanil dose (0.228 [0.170-0.332] vs. 0.405 [0.315-0.565] µg·kg-1·h-1, p < 0.0001) - were lower in patients with thoracic epidural anesthesia. No major thoracic epidural anesthesia-associated infections or bleedings occurred. CONCLUSION: This retrospective analysis suggests that thoracic epidural anesthesia does not reduce postoperative hospital length of stay in patients undergoing major liver surgery - but it may reduce perioperative analgesia doses. Thoracic epidural anesthesia was safe in this cohort of patients undergoing major liver surgery. These findings need to be confirmed in robust clinical trials.

In vivo evaluation of a new hybrid graft using retrograde visceral perfusion for thoracoabdominal aortic repair in an animal model.

Objectives: The SPIDER technique for hybrid thoracoabdominal aortic aneurysm repair can avoid thoracotomy and extracorporeal circulation. To improve technical feasibility and safety, the new Thoracoflo graft, consisting of a proximal stent graft connected to a 7-branched abdominal prosthesis, was evaluated in a pig model for technical feasibility testing, before implantation in humans. Methods: Retroperitoneal exposure of the infradiaphragmatic aorta, including visceral and renal arteries, was performed in 7 pigs (75-85 kg). One iliac branch was temporarily attached to the distal aorta to maintain retrograde visceral and antegrade iliac perfusion after deployment of the thoracic stent graft segment (SPIDER technique). The proximal stent-grafted segment was deployed in the thoracic aorta via direct aortic puncture over the wire without fluoroscopy. The graft was deaired before flow via the iliac side branch to the visceral and iliac arteries was established. Visceral, renal, and lumbar arteries were subsequently sutured to the corresponding side branches of the graft. Technical feasibility, operating and clamping time, blood flow, and tissue perfusion in the related organs were evaluated before implantation and after 3 and 6 hours using transit-time flow measurement and fluorescent microspheres. Final angiography or postprocedural computed tomography angiography were performed. Results: Over-the-wire graft deployment was successful in 6 animals without hemodynamic alteration (P = n.s.). In 1 pig, the proximal stent graft section migrated as the guidewire was not removed, as recommended, before release of the proximal fixation wire. Angiography and computed tomography scan confirmed successful graft implantation and transit-time flow measurement confirmed good visceral and iliac blood flow. Fluorescent microspheres confirmed good spinal cord perfusion. Conclusions: Over-the-wire implantation of the Thoracoflo graft using the SPIDER technique is feasible in a pig model. No fluoroscopy was required. For safe implantation, it is mandatory to follow the single steps of implantation.

Continuous intra-arterial versus intermittent oscillometric arterial pressure monitoring and hypotension during induction of anaesthesia: the AWAKE randomised trial.

BACKGROUND: Hypotension during induction of anaesthesia is associated with organ injury. Continuous arterial pressure monitoring might help reduce hypotension. We tested the hypothesis that continuous intra-arterial compared with intermittent oscillometric arterial pressure monitoring reduces hypotension during induction of anaesthesia in noncardiac surgery patients. METHODS: In this single-centre randomised trial, 242 noncardiac surgery patients in whom intra-arterial arterial pressure monitoring was planned were randomised to unblinded continuous intra-arterial or to intermittent oscillometric arterial pressure monitoring (with blinded intra-arterial arterial pressure monitoring) during induction of anaesthesia. The primary endpoint was the area under a mean arterial pressure (MAP) of 65 mm Hg within the first 15 min of induction of anaesthesia. Secondary endpoints included areas under MAP values of 60, 50, and 40 mm Hg and durations of MAP values <65, <60, <50, and <40 mm Hg. RESULTS: There were 224 subjects available for analysis. The median (25th-75th percentile) area under a MAP of 65 mm Hg was 15 (2-36) mm Hg • min in subjects assigned to continuous intra-arterial monitoring and 46 (7-111) mm Hg • min in subjects assigned to intermittent oscillometric monitoring (P<0.001). Subjects assigned to continuous intra-arterial monitoring had smaller areas under MAP values of 60, 50, and 40 mm Hg and shorter durations of MAP values <65, <60, <50, and <40 mm Hg than subjects assigned to intermittent oscillometric monitoring. CONCLUSION: Continuous intra-arterial arterial pressure monitoring reduces hypotension during induction of anaesthesia compared with intermittent oscillometric arterial pressure monitoring in noncardiac surgery patients. In patients for whom an arterial catheter is planned, clinicians might therefore consider inserting the arterial catheter before rather than after induction of anaesthesia. CLINICAL TRIALS REGISTRATION: NCT04894019.

Effects of fluids vs. vasopressors on spinal cord microperfusion in hemorrhagic shock induced ischemia/reperfusion.

OBJECTIVE: Spinal cord injury induced by ischemia/reperfusion is a devastating complication of aortic repair. Despite developments for prevention and treatment of spinal cord injury, incidence is still considerably high majorly impacting patient outcome. Microcirculation is paramount for tissue perfusion and oxygen supply and often dissociated from macrohemodynamic parameters used to guide resuscitation. Effects of fluids vs. vasopressors in the setting of hemodynamic resuscitation on spinal cord microperfusion are unknown. Aim of this study was to compare the effects of vasopressor and fluid resuscitation on spinal cord microperfusion in a translational acute pig model of hemorrhagic shock induced ischemia/reperfusion injury. METHODS: We designed this study as prospective randomized explorative large animal study. We induced hemorrhagic shock in 20 pigs as a model of global ischemia/reperfusion injury. We randomized animals to receive either fluid or vasopressor resuscitation. We measured spinal cord microperfusion using fluorescent microspheres as well as laser-Doppler probes. We monitored and analyzed macrohemodynamic parameters and cerebrospinal fluid pressure. RESULTS: Spinal cord microperfusion decreased following hemorrhagic shock induced ischemia/reperfusion injury. Both fluids and vasopressors sufficiently restored spinal cord microperfusion. There were no important changes between groups (percentage changes compared to baseline: fluids 14.0 (0.31-27.6) vs. vasopressors 24.3 (8.12-40.4), p = .340). However, cerebrospinal fluid pressure was higher in animals receiving fluid resuscitation (percentage changes compared to baseline: fluids 27.7 (12.6-42.8) vs. vasopressors -5.56 ((-19.8)-8.72), p = .003). Microcirculatory resuscitation was in line with improvements of macrohemodynamic parameters. CONCLUSIONS: Both, fluids and vasopressors, equally restored spinal cord microperfusion in a porcine acute model of hemorrhagic shock induced ischemia/reperfusion injury. However, significant differences in cerebrospinal fluid pressure following resuscitation were present. Future studies should evaluate these effects in perfusion disruption induced ischemia/reperfusion conditions of microcirculatory deterioration.

Effect of intraoperative personalized goal-directed hemodynamic management on acute myocardial injury in high-risk patients having major abdominal surgery: a post-hoc secondary analysis of a randomized clinical trial.

Acute myocardial injury is common after noncardiac surgery and associated with mortality. Impaired intraoperative cardiovascular dynamics are a risk factor for acute myocardial injury. Optimizing intraoperative cardiovascular dynamics may thus reduce acute myocardial injury. We aimed to investigate the effect of intraoperative personalized goal-directed hemodynamic management on the incidence of acute myocardial injury. We hypothesized that personalized goal-directed hemodynamic management reduces the incidence of acute myocardial injury compared to routine hemodynamic management in high-risk patients having major abdominal surgery. We performed a post-hoc secondary analysis of a randomized clinical trial including 180 high-risk major abdominal surgery patients that were randomized to personalized goal-directed hemodynamic management or routine hemodynamic management. We compared the incidences of acute myocardial injury-defined according to the Fourth Universal Definition of Myocardial Infarction (2018)-between patients randomized to personalized goal-directed hemodynamic management or routine hemodynamic management by calculating the relative and absolute risk reduction together with 95% Wald confidence intervals and P values. Acute myocardial injury occurred in 4 of 90 patients (4%) in the personalized goal-directed hemodynamic management group and in 12 of 90 patients (13%) in the routine hemodynamic management group (relative risk: 0.33, 95% confidence interval: 0.11 to 0.99, P = 0.036; absolute risk reduction: - 9%, 95% confidence interval: - 17% to - 0.68%, P = 0.034). In this post-hoc secondary analysis, intraoperative personalized goal-directed hemodynamic management reduced the incidence of acute myocardial injury compared to routine hemodynamic management in high-risk patients having major abdominal surgery. This needs to be confirmed in larger prospective trials.

Effectiveness of preoxygenation by conventional face mask versus non-invasive ventilation in morbidly obese patients: measurable by the oxygen-reserve index?

Preoxygenation is a crucial manoeuvre for patients' safety, particularly for morbidly obese patients due to their reduced pulmonary reserve and increased risk for difficult airway situations. The oxygen reserve index (ORI™) was recently introduced as a new parameter of multiple wavelength pulse oximetry and has been advocated to allow assessment of hyperoxia [quantified by the resulting arterial oxygen partial pressure (PaO2)]. This study investigates if ORI can be used to evaluate the impact of two different preoxygenation manoeuvres on the grade of hyperoxia. Two preoxygenation manoeuvres were sequentially evaluated in 41 morbidly obese patients: First, breathing 100% oxygen for 5 min via standard face mask. Second, after achieving a second baseline, 5 min of non-invasive ventilation (NIV) with 100% oxygen. The effect of preoxygenation on ORI compared to PaO2 was evaluated and whether differences in the two preoxygenation manoeuvres can be monitored by ORI. Overall correlation of PaO2 and ORI was significant (Spearman-Rho coefficient of correlation 0.818, p < 0.001). However, ORI could not differentiate between the two preoxygenation manoeuvres although the PaO2 values for NIV preoxygenation were significantly higher compared to standard preoxygenation (median 505 mmHg (M1) vs. 550 mmHg (M3); p < 0.0001). In contrast, ORI values did not differ significantly (median 0.39 (M1) vs. 0.38 (M3); p = 0.758). Absolute values of ORI cannot be used to assess effectiveness of a preoxygenation procedure in bariatric patients, mainly because its range of discrimination is considerably lower than the high ranges of PaO2 attained by adequate preoxygenation. Trial registration German Clinical Trials Register: DRKS00025023 (retrospectively registered on April 16th, 2021).

The impact of Enhanced Recovery after Surgery (ERAS) pathways with regard to perioperative outcome in patients with ovarian cancer.

PURPOSE: Major surgery for ovarian cancer is associated with significant morbidity. Recently, guidelines for perioperative care in gynecologic oncology with a structured "Enhanced Recovery after Surgery (ERAS)" program were presented. Our aim was to evaluate if implementation of ERAS reduces postoperative complications in patients undergoing extensive cytoreductive surgery for ovarian cancer. METHODS: 134 patients with ovarian cancer (FIGO I-IV) were included. 47 patients were prospectively studied after implementation of a mandatory ERAS protocol (ERAS group) and compared to 87 patients that were treated before implementation (pre-ERAS group). Primary endpoints of this study were the effects of the ERAS protocol on postoperative complications and length of stay in hospital. RESULTS: Preoperative and surgical data were comparable in both groups. Only the POSSUM score was higher in the ERAS group (11.8% vs. 9.3%, p < 0.001), indicating a higher surgical risk in the ERAS group. Total number of postoperative complications (ERAS: 29.8% vs. pre-ERAS: 52.8%, p = 0.011), and length of hospital stay (ERAS: 11 (6-23) vs pre-ERAS: 13 (6-50) days; p < 0.001) differed significantly. A lower fraction of patients of the ERAS group (87.2%) needed postoperative admission to the ICU compared to the pre-ERAS group (97.7%), p = 0.022). Mortality within the ERAS group was 0% vs. 3.4% (p = 0.552) in the pre-ERAS group. CONCLUSION: The implementation of a mandatory ERAS protocol was associated with a lower rate of postoperative complications and a reduced length of stay in hospital. If ERAS has influence on long-term outcome needs to be further evaluated.

Assessing volume responsiveness using right ventricular dynamic indicators of preload.

PURPOSE: Dynamic indicators of preload currently only do reflect preload requirements of the left ventricle. To date, no dynamic indicators of right ventricular preload have been established. The aim of this study was to calculate dynamic indicators of right ventricular preload and assess their ability to predict ventricular volume responsiveness. MATERIALS AND METHODS: The study was designed as experimental trial in 20 anaesthetized pigs. Micro-tip catheters and ultrasonic flow probes were used as experimental reference to enable measurement of right ventricular stroke volume and pulse pressure. Hypovolemia was induced (withdrawal of blood 20 ml/kg) and thereafter three volume-loading steps were performed. ROC analysis was performed to assess the ability of dynamic right ventricular parameters to predict volume response. RESULTS: ROC analysis revealed an area under the curve (AUC) of 0.82 (CI 95% 0.73-0.89; p < 0.001) for right ventricular stroke volume variation (SVVRV), an AUC of 0.72 (CI 95% 0.53-0.85; p = 0.02) for pulmonary artery pulse pressure variation (PPVPA) and an AUC of 0.66 (CI 95% 0.51-0.79; p = 0.04) for pulmonary artery systolic pressure variation (SPVPA). CONCLUSIONS: In our experimental animal setting, calculating dynamic indicators of right ventricular preload is possible and appears promising in predicting volume responsiveness.

The use of pulse pressure variation for predicting impairment of microcirculatory blood flow.

Dynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg-1 bodyweight-1. Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia-reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min-1) 1.68 (1.02-2.35) versus 2.84 (2.15-3.53), p = 0.002, mean arterial pressure (mmHg) 29.89 (21.65-38.12) versus 52.34 (43.55-61.14), p < 0.001, pulse pressure variation (%) 24.84 (17.45-32.22) versus 9.59 (1.68-17.49), p = 0.004, mean Flux (p.u.) 414.95 (295.18-534.72) versus 327.21 (206.95-447.48), p = 0.006. Receiver operating characteristic analysis revealed an area under the curve of 0.88 (CI 95% 0.73-1.00; p value < 0.001) for pulse pressure variation for predicting a decrease of microcirculatory blood flow. The results of our study show that pulse pressure variation does have the potential to predict decreases of intestinal microcirculatory blood flow due to volume-load after ischemia/reperfusion-injury. This should encourage further translational research and might help to prevent microcirculatory impairment due to excessive fluid resuscitation and to guide fluid therapy in the future.

Real-Time Assessment of Spinal Cord Microperfusion in a Porcine Model of Ischemia/Reperfusion.

Spinal cord injury is a devastating complication of aortic repair. Despite developments for the prevention and treatment of spinal cord injury, its incidence is still considerably high and therefore, influences patient outcome. Microcirculation plays a key role in tissue perfusion and oxygen supply and is often dissociated from macrohemodynamics. Thus, direct evaluation of spinal cord microcirculation is essential for the development of microcirculation-targeted therapies and the evaluation of existing approaches in regard to spinal cord microcirculation. However, most of the methods do not provide real-time assessment of spinal cord microcirculation. The aim of this study is to describe a standardized protocol for real-time spinal cord microcirculatory evaluation using laser-Doppler needle probes directly inserted in the spinal cord. We used a porcine model of ischemia/reperfusion to induce deterioration of the spinal cord microcirculation. In addition, a fluorescent microsphere injection technique was used. Initially, animals were anesthetized and mechanically ventilated. Thereafter, laser-Doppler needle probe insertion was performed, followed by the placement of cerebrospinal fluid drainage. A median sternotomy was performed for exposure of the descending aorta to perform aortic cross-clamping. Ischemia/reperfusion was induced by supra-celiac aortic cross-clamping for a total of 48 min, followed by reperfusion and hemodynamic stabilization. Laser-Doppler Flux was performed in parallel with macrohemodynamic evaluation. In addition, automated cerebrospinal fluid drainage was used to maintain a stable cerebrospinal pressure. After completion of the protocol, animals were sacrificed, and the spinal cord was harvested for histopathological and microsphere analysis. The protocol reveals the feasibility of spinal cord microperfusion measurements using laser-Doppler probes and shows a marked decrease during ischemia as well as recovery after reperfusion. Results showed comparable behavior to fluorescent microsphere evaluation. In conclusion, this new protocol might provide a useful large animal model for future studies using real-time spinal cord microperfusion assessment in ischemia/reperfusion conditions.

Detrimental effects of cerebrospinal fluid pressure elevation on spinal cord perfusion: first-time direct detection in a large animal model.

OBJECTIVES: Cerebrospinal fluid (CSF) drainage is routinely utilized to mitigate perioperative and postoperative spinal cord ischaemia in open and endovascular thoraco-abdominal aortic aneurysm repair to prevent permanent paraplegia. Clinical decision-making in the vulnerable perioperative period, however, is still based on limited clinical and experimental data. Our aim was to investigate the isolated effect of CSF pressure elevation on spinal cord perfusion in an established large animal model. METHODS: Ten juvenile pigs with normal (native) arterial inflow (patent segmental arteries and collaterals) underwent iatrogenic CSF pressure elevation (×2, ×3, ×4 from their individual baseline pressure). Each pressure level was maintained for 30 min to mimic clinical response time. After the quadrupling of CSF pressure, the dural sac was slowly depressurized against gravity allowing CSF pressure to passively return to baseline values. Measurements were taken 30 and 60 min after normalization, and microspheres for regional blood flow analysis were injected at each time point. RESULTS: Spinal cord perfusion decreased significantly at all mid-thoracic to lumbar cord segments at the doubling of CSF pressure and declined to values <53% compared to baseline when pressure was quadrupled. Normalizing CSF pressure led to an intense hyperperfusion of up to 186% at the cervical level and 151% within the lumbar region. CONCLUSIONS: CSF pressure elevation results in a relevant impairment of spinal cord blood supply. Close perioperative and postoperative monitoring of CSF pressure is crucial for maintaining sufficient spinal cord perfusion. Radical and rapid withdrawal of CSF is followed by significant hyperperfusion in all spinal cord segments and may lead to 'drainage-related' iatrogenic reperfusion injury-aggravating the risk of delayed spinal cord injury-and should therefore be avoided.

Guiding Opioid Administration by 3 Different Analgesia Nociception Monitoring Indices During General Anesthesia Alters Intraoperative Sufentanil Consumption and Stress Hormone Release: A Randomized Controlled Pilot Study.

BACKGROUND: This pilot study investigated the effect of sufentanil titration by 3 different analgesia monitoring devices or clinical signs during general anesthesia. METHODS: Forty-eight patients undergoing radical retropubic prostatectomy with sevoflurane/sufentanil anesthesia were randomly assigned into 4 groups and received sufentanil guided either by 1 of 3 analgesia monitoring devices (Surgical Pleth Index [SPI], Pupillary Pain Index [PPI], Nociception Level [NoL]) or by clinical judgment (control). The primary end point was intraoperative sufentanil consumption. Adrenocorticotropic hormone (ACTH) and cortisol were measured at 4 time points during the day of surgery. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests and by mixed model and area under the curve (AUC) analyses for group comparisons and time effects of stress hormones. RESULTS: The total amount of sufentanil administration (µg·kg·minute·10) differed between the groups (median [quartiles]: control = 5.6 [4.4-6.4], SPI = 7.2 [4.8-8.4], PPI = 2.0 [1.8-2.9], NoL = 3.8 [3.3-5.1]; PPI versus SPI, -5.1 [-6.6 to -1.3], P < .001; NoL versus SPI, -3.0 [-5.2 to 0.2], P = .024; control versus SPI, -1.6 [-3.7 to 1.7], P = .128; NoL versus PPI, 1.7 [0.6-3.4], P < .001; control versus PPI, 3.4 [2.0-4.6], P < .001; control versus NoL, 1.6 [-0.2 to 3.3], P = .017) (Hodges-Lehmann estimator [99% confidence interval {CI}], P values). The AUC analysis indicated differences among groups in cumulative ACTH levels (ng·liter·minute, natural logarithm (ln)-transformed data) of NoL versus PPI (-1.079 [-1.950 to -0.208], P = .001) and PPI versus SPI (1.192 [0.317-2.068], P= .001), as well as differences in cortisol levels (µg·liter·minute) for PPI versus SPI (46,710 [21,145-72,274], P < .001), NoL versus SPI (27,645 [3163-52,126], P = .003), and control versus SPI (31,824 [6974-56,675], P = .001) (differences in means [99% CI], P value). Secondary end points (postoperative recovery, pain level, and analgesia medication) showed no differences. CONCLUSIONS: The type of analgesia nociception monitoring affected the total amount of sufentanil administered. Lower sufentanil doses in the PPI group were associated with an increased endocrine stress response. Titration by SPI caused no opioid reduction compared to the control but was associated with a reduced endocrine stress response.

Sonographic real-time imaging of tissue perfusion in a porcine haemorrhagic shock model.

Injection of fluorescence-labelled microspheres (FMs) in pigs allows only the postmortem determination of organ perfusion. Colour duplex ultrasound (CDU) and contrast-enhanced ultrasound were established as techniques for real-time imaging of tissue perfusion in a porcine haemorrhagic shock model. Haemorrhagic shock was provoked in nine domestic pigs by taking at least 15% of the calculated blood volume. Ultrasound examinations were performed with a Hitachi HI VISION Ascendus. SonoVue was injected for contrast-enhanced ultrasound. Monitoring of the resistive index and time-to-peak ratio enabled quantification of tissue perfusion in vivo during the entire study, allowing real-time differentiation of animals with systemic shock versus failing shock effect. Postmortem analyses of injected FMs confirmed the sonographic in vivo results. Determination of the resistive index and time-to-peak ratio by CDU and contrast-enhanced ultrasound allowed real-time monitoring of tissue perfusion. Effects of haemorrhagic shock and therapeutic approaches related to organ perfusion can be observed live and in vivo.

Distribution of Air Embolization During TEVAR Depends on Landing Zone: Insights From a Pulsatile Flow Model.

Purpose: To analyze the distribution of air bubbles in the supra-aortic vessels during thoracic stent-graft deployment in zones 2 and 3 in an aortic flow model. Materials and Methods: Ten identical, investigational, tubular, thoracic stent-grafts were deployed in a glass aortic flow model with a type I arch: 5 in zone 2 and 5 in zone 3. A pulsatile pump generated a flow of 5 L/min with systolic and diastolic pressures (±5%) of 105 and 70 mm Hg, respectively. The flow rates (±5%) were 300 mL/min in the subclavian arteries, 220 mL/min in the vertebral arteries, and 400 mL/min in the common carotid arteries (CCAs). The total amounts of air released in each supra-aortic branch and in the aorta were recorded. Results: The mean amounts of air measured were 0.82±0.23 mL in the zone-2 group and 0.94±0.28 mL in the zone-3 group (p=0.49). In the zone-2 group compared with zone 3, the amounts of released air were greater in the right subclavian artery (0.07±0.02 vs 0.02±0.02 mL, p<0.01) and right CCA (0.30±0.8 vs 0.18±07 mL, p=0.04). There were no differences between the groups concerning the mean amounts of air measured in the right vertebral and all left-side supra-aortic branches. The amount of air released in the descending aorta was significantly higher in the zone-3 group vs the zone-2 group (0.48±0.12 vs 0.13±0.08 mL, p<0.01). Small bubbles were observed continuously during deployment, whereas large bubbles appeared more commonly during deployment of the proximal stent-graft end and after proximal release of the stent-graft. Conclusion: Air is released into all supra-aortic branches and the descending aorta during deployment of tubular thoracic stent-grafts in zones 2 and 3 in an aortic flow model. Higher amounts of air were observed in right-side supra-aortic branches during deployment in zone 2, whereas significantly greater amounts of air were observed in the descending aorta during deployment in zone 3.

Melatonin treatment of pigs with acute pancreatitis reduces inflammatory reaction of pancreatic tissue and enhances fitness score of pigs: experimental research.

Background: Severe acute pancreatitis is associated with high morbidity and mortality. Melatonin is known as the activator of antioxidant enzymes. The main purpose of this study was to evaluate the clinical effect of melatonin treatment in a pig model with induced acute pancreatitis. Methods: In this study, acute pancreatitis was induced in 38 German domestic pigs (German Hybrid). After induction of acute pancreatitis, 18 animals were treated with melatonin. Intraoperative clinical data, postoperative blood parameters, fitness, and Porcine Well-being (PWB) score, and post-mortal histopathological data were analyzed in both study groups. Results: The matching procedure created two groups (melatonin group and control group) which were very similar. The fitness and PWB score were postoperative significantly enhanced in the melatonin group as compared to the control group (p = 0.005 and p = 0.003). Additionally, histological analysis revealed that acinar necrosis, fat tissue necrosis, and edema were significantly reduced in the melatonin group as compared to the non-melatonin group (p = 0.025, p = 0.003, and p = 0.028). Conclusions: Pigs, which were treated with melatonin, were characterized by higher fitness and PWB scores than those of the control group. Moreover, melatonin treatment reduces the acinar necrosis, fat tissue necrosis, and edema of pancreatic tissue. Thus, melatonin might be a useful therapeutic option in severe acute pancreatitis.

Assessment of central hemodynamic effects of phenylephrine: an animal experiment.

Phenylephrine is an α1-adrenergic receptor agonist widely used to treat perioperative hypotension. Its other hemodynamic effects, in particular on preload and contractility, remain controversial. We, therefore, investigated the effect of continuously applied phenylephrine on central hemodynamics in eight mechanically ventilated domestic pigs. Mean arterial pressure (MAP) was increased in steps by 50%, and 100% using phenylephrine. Besides stroke volume (SV), cardiac output (CO), and MAP, mean systemic vascular resistance (SVR) and dynamic arterial elastance (Eadyn) were assessed for characterization of afterload. Changes in preload were assessed by central venous pressure (CVP), global end-diastolic volume (GEDV), mean systemic filling pressure analog (Pmsfa), pulse pressure variation (PPV), and stroke volume variation (SVV). Further, cardiac function index (CFI), global ejection fraction and dPmax were measured as markers of preload dependent contractility. MAP, SV, and CO significantly increased following both interventions, as did SVR. In contrast, Eadyn did not show significant changes. Although the volumetric preload variable GEDV increased after the first step of phenylephrine, this was not reflected by significant changes in CVP or Pmsfa. CFI and dPmax significantly increased after both steps. Phenylephrine does not only affect cardiac afterload, but also increases effective preload. In contrast to CVP and Pmsfa, this effect can be monitored by GEDV. Further, phenylephrine affects contractility.

Air Embolism During TEVAR: Liquid Perfluorocarbon Absorbs Carbon Dioxide in a Combined Flushing Technique and Decreases the Amount of Gas Released From Thoracic Stent-Grafts During Deployment in an Experimental Setting.

PURPOSE: To investigate the influence of flushing thoracic stent-grafts with carbon dioxide and perfluorocarbon on the amount of gas released during stent-graft deployment in thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Ten TX2 ProForm thoracic stent-grafts were deployed into a water-filled container with a curved plastic pipe and flushed sequentially with carbon dioxide, 20 mL of liquid perfluorocarbon (PFC), and 60 mL of saline. Released gas was measured using a calibrated setup. The volume of released gas was compared with the results of an earlier published reference group, in which identical stent-grafts were flushed with 60 mL saline alone as recommended in the instructions for use. RESULTS: The average amount of gas released in the test group was 0.076 mL, significantly lower (p<0.001) than the mean 0.79 mL of gas released in the reference group. Big bubbles appearing at the tip of the sheath when deployment was started were seen in all grafts of the reference group but in only 2 of the test group stent-grafts. Small bubbles were less frequent in the test group. CONCLUSION: The amount of gas released from thoracic stent-grafts during deployment can be influenced by different flushing techniques. The use of PFC in addition to the carbon dioxide flushing technique reduces the volume of gas released during deployment of tubular thoracic stent-grafts to a few microliters. This significant effect is presumably based on the high solubility of carbon dioxide in perfluorocarbon and could be a potential future approach to lower the risk of cerebral injury and stroke from air embolism during TEVAR.

Volume Based Resuscitation and Intestinal Microcirculation after Ischaemia/Reperfusion Injury: Results of an Exploratory Aortic Clamping Study in Pigs.

OBJECTIVES: In the presence of ischaemia/reperfusion (I/R) induced endothelial injury, volume administration may not correlate with increased microcirculation. The aim of this study was to evaluate intestinal microcirculation after standardised sequential volume loading in an animal model of I/R injury following supracoeliac aortic clamping. METHODS: This was a prospective exploratory pilot animal study. Intestinal I/R injury was induced in eight pigs during experimental thoraco-abdominal aortic repair. After 6 h of I/R, microcirculatory blood flow (mFlux, measured in the ileum using direct laser speckle contrast imaging) and macrohaemodynamic parameters (using trans-cardiopulmonary thermodilution) were measured and measurements were repeated after each of four sequential volume loading steps (VLS1 - 4). Each load was administered over 5 min followed by another 5 min for equilibration. RESULTS: All animals survived until after VLS4. After 6 h of I/R cardiac output (CO) (p < .001) and mFlux (p < .001) had both decreased. CO increased again after VLS1 (p < .001) and VLS2 (p = .036), whereas mFlux did not change. In contrast, mFlux further decreased after VLS3 (p < .01) and VLS4 (p < .001), whereas CO did not change anymore. Extravascular lung water continued to increase after VLS2 (p = .046) and VLS4 (p = .049). CONCLUSIONS: I/R leads to impaired intestinal microcirculation, which was not restored by volume administration in spite of improved CO. In contrast, further volume administration exceeding preload reserves was associated with additional decreases in the intestinal microcirculation. The potentially negative effect of excessive volume resuscitation after I/R injury should encourage further translational research.

Invasive Hemodynamic Monitoring of Aortic and Pulmonary Artery Hemodynamics in a Large Animal Model of ARDS.

One of the leading causes of morbidity and mortality in patients with heart failure is right ventricular (RV) dysfunction, especially if it is due to pulmonary hypertension. For a better understanding and treatment of this disease, precise hemodynamic monitoring of left and right ventricular parameters is important. For this reason, it is essential to establish experimental pig models of cardiac hemodynamics and measurements for research purpose. This article shows the induction of ARDS by using oleic acid (OA) and consequent right ventricular dysfunction, as well as the instrumentation of the pigs and the data acquisition process that is needed to assess hemodynamic parameters. To achieve right ventricular dysfunction, we used oleic acid (OA) to cause ARDS and accompanied this with pulmonary artery hypertension (PAH). With this model of PAH and consecutive right ventricular dysfunction, many hemodynamic parameters can be measured, and right ventricular volume load can be detected. All vital parameters, including respiratory rate (RR), heart rate (HR) and body temperature were recorded throughout the whole experiment. Hemodynamic parameters including femoral artery pressure (FAP), aortic pressure (AP), right ventricular pressure (peak systolic, end systolic and end diastolic right ventricular pressure), central venous pressure (CVP), pulmonary artery pressure (PAP) and left arterial pressure (LAP) were measured as well as perfusion parameters including ascending aortic flow (AAF) and pulmonary artery flow (PAF). Hemodynamic measurements were performed using transcardiopulmonary thermodilution to provide cardiac output (CO). Furthermore, the PiCCO2 system (Pulse Contour Cardiac Output System 2) was used to receive parameters such as stroke volume variance (SVV), pulse pressure variance (PPV), as well as extravascular lung water (EVLW) and global end-diastolic volume (GEDV). Our monitoring procedure is suitable for detecting right ventricular dysfunction and monitoring hemodynamic findings before and after volume administration.