Influence of blood pressure on internal carotid artery blood flow during combined propofol-remifentanil and thoracic epidural anesthesia.

Background and Aims: Anesthesia often reduces mean arterial pressure (MAP) to a level that may compromise cerebral blood flow. We evaluated whether phenylephrine treatment of anesthesia-induced hypotension affects internal carotid artery (ICA) blood flow and whether anesthesia affects ICA flow and CO2 reactivity. Material and Methods: The study included twenty-seven patients (65 ± 11 years; mean ± SD) undergoing esophageal resection (n = 14), stomach resection (n = 12), or a gastroentero anastomosis (n = 1) during combined propofol-remifentanil and thoracic epidural anesthesia. Duplex ultrasound evaluated ICA blood flow. Evaluations were before and after induction of anesthesia, before and after the administration of phenylephrine as part of standard care to treat anesthesia-induced hypotension at a MAP below 60 mmHg, and the hypocapnic reactivity of ICA flow was determined before and during anesthesia. Results: Induction of anesthesia reduced MAP from 108 ± 12 to 66 ± 16 mmHg (P < 0.0001) and ICA flow from 340 ± 92 to 196 ± 52 mL/min (P < 0.0001). Phenylephrine was administered to 24 patients (0.1-0.2 mg) and elevated MAP from 53 ± 8 to 73 ± 8 mmHg (P = 0.0001) and ICA flow from 191 ± 43 to 218 ± 50 mL/min (P = 0.0276). Furthermore, anesthesia reduced the hypocapnic reactivity of ICA flow from 23 (18-33) to 14%/kPa (10-22; P = 0.0068). Conclusion: Combined propofol-remifentanil and thoracic epidural anesthesia affect ICA flow and CO2 reactivity. Phenylephrine partly restored ICA flow indicating that anesthesia-induced hypotension contributes to the reduction in ICA flow.

Internal carotid artery blood flow is enhanced by elevating blood pressure during combined propofol-remifentanil and thoracic epidural anaesthesia: A randomised cross-over trial.

BACKGROUND: Anaesthesia reduces mean arterial pressure (MAP), and to preserve organ perfusion, vasopressors are often used to maintain MAP above 60 mmHg. Cognitive dysfunction is common following major surgery and may relate to intra-operative cerebral hypoperfusion. OBJECTIVE: The aim of this study was to evaluate whether internal carotid artery (ICA) blood flow increases when MAP is kept higher than 60 mmHg using noradrenaline. DESIGN: A randomised, cross-over trial. SETTING: Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark, from December 2017 to April 2018. PATIENTS: Patients with median [IQR] age 71 [63 to 75] years underwent pancreaticoduodenectomy (n = 19), total pancreatic resection (n = 1) or gastro-entero anastomosis (n = 2) during combined propofol-remifentanil and thoracic epidural anaesthesia. INTERVENTION: MAP was maintained between 60 to 65, 70 to 75 and 80 to 85 mmHg, in a random order, by noradrenaline infusion at a stable level of anaesthesia. MAIN OUTCOME MEASURES: Primary outcome was change in ICA flow at MAP 60 to 65 vs. 80 to 85 mmHg. Secondary outcomes were change in ICA flow at MAP 60 to 65 vs. 70 to 75 and 70 to 75 vs. 80 to 85 mmHg. Duplex ultrasound evaluated ICA flow. RESULTS: A (mean ± SD) increase in MAP from 62 ±â€Š1 to 82 ±â€Š1 mmHg elevated ICA flow from 196 ±â€Š53 to 226 ±â€Š61 ml min (mean difference 31 ml min; 95% CI 19 to 42; P < 0.0001). An increase in MAP from 62 ±â€Š1 to 72 ±â€Š1 mmHg elevated ICA flow to 210 ±â€Š52 ml min (P = 0.0271) and ICA flow increased further (P = 0.0165) when MAP was elevated to 82 ±â€Š1 mmHg. CONCLUSION: During combined propofol-remifentanil and thoracic epidural anaesthesia, ICA flow increased by approximately 15% when the MAP was elevated from about 60 to 80 mmHg. Treatment of a reduction in MAP brought about by anaesthesia seems to enhance ICA flow. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03309917.

Second Generation of a Fast-track Liver Resection Programme.

BACKGROUND: Recent developments in perioperative pathophysiology and care have documented evidence-based, multimodal rehabilitation (fast-track) to hasten recovery and decrease morbidity and hospital stay in several major surgical procedures. The aim of this study was to investigate the effect over time of a modified previously published fast-track programme in unselected patients undergoing open or laparoscopic liver resection. METHODS: A prospective study includes the first 121 consecutive patients following an updated fast-track programme for liver resection. High-dose methylprednisolone was given to all patients before surgery, catheters and drains were systematically removed early, and patients were mobilized and started eating and drinking from the day of surgery. An opioid-sparing multimodal pain treatment was given for the first week. The discharge criteria were (1) pain sufficiently controlled by oral analgesics only; (2) patient comfortable with discharge; (3) no untreated complications. RESULTS: The median length of stay (LOS) for all patients was 4 days, with 2 days after laparoscopic vs. 4 days for open resections. The median LOS after major hepatectomies (≥3 segments) was 5 days. The readmission rate was 6% and the 30-day mortality zero. The LOS decreased compared to our first-generation fast-track programme with LOS 5 days. CONCLUSIONS: Fast-track principles for perioperative care and early discharge are safe even after major liver resection. The introduction of high-dose steroids preoperatively might have facilitated a shorter LOS. Routine discharge on POD 1 or 2 after laparoscopic resection and on POD 4 after open liver resection has proven to be feasible.

A reduced gastric corpus microvascular blood flow during Ivor-Lewis esophagectomy detected by laser speckle contrast imaging technique.

BACKGROUND: Reduced microvascular blood flow is related to anastomotic insufficiency following esophagectomy, emphasizing a need for intraoperative monitoring of the microcirculation. This study evaluated if laser speckle contrast imaging (LSCI) was able to detect intraoperative changes in gastric microcirculation. METHODS: Gastric microcirculation was assessed prior to and after reconstruction of gastric continuity in 25 consecutive patients operated for adenocarcinoma with open Ivor-Lewis esophagectomy while hemodynamic variables were recorded. RESULTS: During upper laparotomy, microcirculation at the corpus decreased by 25% from baseline to mobilization of the stomach (p = .008) and decreased further (to a total decrease of 40%) following gastric pull to the thorax (p = .013). On the other hand, microcirculation at the antrum did not change significantly after gastric mobilization (p = .091). The decrease in corpus microcirculation took place unrelated to central cardiovascular variables. CONCLUSION: Using LSCI technique, we identified a reduced microcirculation at the corpus area during open Ivor-Lewis esophagectomy. LSCI provides an option for real-time assessment of gastric microcirculation and could form basis for intraoperative stabilization of the microcirculation.

High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial.

BACKGROUND & AIMS: Acute liver failure (ALF) often results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh frozen plasma in case series improves systemic, cerebral and splanchnic parameters. METHODS: In this prospective, randomised, controlled, multicentre trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT; 90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary endpoint was liver transplantation-free survival during hospital stay. Secondary-endpoints included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken. RESULTS: For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP vs. 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI), 0.36-0.86; p=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; p=0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (p<0.001). CONCLUSIONS: Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction.

The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure.

BACKGROUND & AIMS: Patients with acute liver failure have a disturbed amino acid metabolism and a compromised oxidative metabolism in the brain. A limited number of clinically neuroprotective interventions are available. This study aimed at assessing the effect of fractionated plasma separation and adsorption (FPSA), an extracorporeal liver support system, on cerebral amino acids and lactate to pyruvate ratio. METHODS: Seven patients with acute liver failure and high risk of intracranial hypertension were included for cerebral microdialysis and intracranial pressure monitoring. Microdialysate, arterial blood, and venous blood from the jugular bulb were sampled, before and after an FPSA session, and the content of nineteen amino acids, lactate, and pyruvate was determined. RESULTS: The total amino acid concentration in arterial plasma was not significantly reduced by FPSA (11.2 mM (3.0-26.0 mM) vs. 9.7 mM (2.7-13.6 mM); median with range). The total amino acid content in the microdialysate was 5.6 mM both before and after FPSA and no change in glutamine content was observed in plasma or microdialysate. The content of aromatic amino acids in arterial plasma, but not in microdialysate, was marginally reduced (p<0.05). Arterial lactate concentration and lactate to pyruvate ratio in the microdialysate did not change following FPSA. CONCLUSIONS: One single treatment session with FPSA had a marginal effect on plasma amino acid composition. We found minimal changes in the amino acids content in the microdialysate, and the lactate to pyruvate ratio was unaffected.

Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure.

BACKGROUND & AIMS: The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively). METHODS: In 17 patients (aged 18-60 years) with acute liver failure and severe hyperammonemia (182 ± 36 µM (mean ± SD)), cerebral microdialysis was performed, and ICP and CPP were monitored. Microdialysate concentrations of hypoxanthine, inosine, lactate, and pyruvate were measured. RESULTS: The hypoxanthine concentration was 23.0 ± 12 µM in early samples and 11.7 ± 6.8 µM in late samples (normal level ~2.0 µM). The inosine concentration was 7.2 ± 7.1 µM and 2.8 ± 1.6 µM, and the LP ratio was 55.8 ± 21.6 and 45.6 ± 20.8, respectively (normal level ~18). Hypoxanthine correlated significantly to LP ratio (r(2)=0.40, p<0.01) while inosine did not. The purine levels and L/P ratio did not correlate to ICP or CPP, nor did they differ between patients with high ICP (>20 mmHg, n=9) and patients without (n=8). CONCLUSIONS: This study shows that the high cerebral LP ratio correlates to the hypoxanthine level in patients with acute liver failure. However, these metabolic alterations were not related to the development of intracranial hypertension.

[Anaesthesia in connection with liver transplantation]. / Anaestesi i forbindelse med levertransplantation.

The anaesthetic plan for liver transplantation focuses on maintaining central blood volume and thereby cerebral oxygenation. Normovolaemia represents a central blood volume that establishes a maximal venous oxygen saturation, and a value of 85% (78-90%) is maintained during the operation by administration of blood components. Treatment quality is expressed as a maintained central blood volume evaluated by transthoratic electrical impedance and a stable cerebral oxygenation (71% (67-82%)) as determined by near-infrared spectroscopy.

Effect of Prometheus liver assist system on systemic hemodynamics in patients with cirrhosis: a randomized controlled study.

AIM: To evaluate treatment safety and hemodynamic changes during a single 6-h treatment with the Prometheus liver assist system in a randomized, controlled study. METHODS: Twenty-four patients were randomized to either the study group or to one of two control groups: Fractionated Plasma Separation Adsorption and Dialysis, Prometheus system (Study group; n = 8); Molecular Adsorbent Recirculation System (MARS) (Control group 1, n = 8); or hemodialysis (Control group 2; n = 8). All patients included in the study had decompensated cirrhosis at the time of the inclusion into the study. Circulatory changes were monitored with a Swan-Ganz catheter and bilirubin and creatinine were monitored as measures of protein-bound and water-soluble toxins. RESULTS: Systemic hemodynamics did not differ between treatment and control groups apart from an increase in arterial pressure in the MARS group (P = 0.008). No adverse effects were observed in any of the groups. Creatinine levels significantly decreased in the MARS group (P = 0.03) and hemodialysis group (P = 0.04). Platelet count deceased in the Prometheus group (P = 0.04). CONCLUSION: Extra-corporal liver support with Prometheus is proven to be safe in patients with endstage liver disease but does not exert the beneficial effects on arterial pressure as seen in the MARS group.

Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure.

AIM: Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate-pyruvate ratio is associated with a rise in the glutamine concentration and ICP. PATIENTS AND METHODS: In 13 patients with ALF (8F/5M; median age 46 (range 18-66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion pressure (CPP). RESULTS: The cerebral glutamine concentration was 4,396 (1,011-9,712) microM, lactate 2.15 (1.1-4.45) mM, and pyruvate 101 (43-255) microM. The lactate-pyruvate ratio was 21 (16-40), ICP 20 (2-28) mmHg, and CPP 72 (56-115) mmHg. Cerebral glutamine concentration correlated with the lactate-pyruvate ratio (r = 0.89, P < 0.05). Also the ICP, but not CPP, correlated to the lactate-pyruvate ratio (r = 0.64, P < 0.05). CONCLUSION: ICP and the cerebral glutamine concentration in patients with ALF correlate to the lactate-pyruvate ratio. Since CPP was sufficient in all patients the rise in lactate-pyruvate ratio indicates that accumulation of glutamine compromises mitochondrial function and causes intracranial hypertension.

Comparison of terlipressin and noradrenalin on cerebral perfusion, intracranial pressure and cerebral extracellular concentrations of lactate and pyruvate in patients with acute liver failure in need of inotropic support.

BACKGROUND/AIMS: Volume expansion and inotropic support with catecholamines are sometimes insufficient to ensure adequate blood pressure and cerebral perfusion in acute liver failure (ALF). The aim of this study was to determine if terlipressin increases cerebral perfusion, cerebral concentration of lactate and intracranial pressure (ICP), and to compare the effect with that of noradrenalin (NA). METHODS: Ten patients (median age 42.5 yr; range 15-66; 5 women) who needed inotropic support and had an ICP and a cerebral microdialysis catheter placed had concomitant recording of cerebral perfusion pressure (CPP), cerebral perfusion (using transcranial Doppler sonography (V(mean))) and ICP. Also cerebral extracellular concentration of lactate ([lactate]ec) and pyruvate ([pyruvate]ec) was collected before and after an increase in the NA infusion rate and/or i.v.-injection of 1mg terlipressin. RESULTS: Both NA and terlipressin increased CPP and V(mean) (p<0.01). Also ICP increased during NA infusion (p<0.01) but not after terlipressin. The cerebral [lactate]ec decreased after terlipressin injection from 2.34 (1.52-8.38) to 1.99 (0.03-4.83)mmol/l (p=0.027) but not during NA infusion (2.83 (1.53-7.11)mmol/l). The [lactate]ec to [pyruvate]ec ratio remained unchanged in both the NA group (20.7 (13.2-40.0)) and terlipressin group (22.2 (10.5-30.0)). CONCLUSIONS: This study shows that terlipressin increases CPP and cerebral perfusion with little influence upon ICP and cerebral [lactate]ec in ALF patients. These findings indicate that terlipressin may be valuable, as an additive treatment to NA infusion to secure brain viability.

Erythropoietin in the cerebrospinal fluid of patients with aneurysmal subarachnoid haemorrhage originates from the brain.

Recent years' research has revealed a specific, neuroprotective erythropoietin (EPO) system in the central nervous system (CNS) that is upregulated by hypoxia. The presence and dynamics of EPO in the cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage (SAH) has not been investigated. We collected a total of 83 corresponding serum and CSF samples from 18 patients with aneurysmal SAH and compared the concentrations of EPO with those of blood-derived markers of blood-brain barrier function (albumin, transferrin, alpha(2)-macroglobulin) and with those of proteins with well-known CNS synthesis (prealbumin, apolipoprotein E). The EPO concentration in CSF was 0.93 (0.82) mU/ml (median and inter-quartile range). Nine patients presented CSF-EPO values above 1 mU/ml. CSF levels did not correlate with serum concentrations and were independent of blood-brain barrier integrity suggesting a synthesis in CNS rather than a blood-derived origin. Furthermore, the median CSF:serum ratio (Q(protein)) of EPO was similar to those of prealbumin and apolipoprotein E, and much higher than those of albumin, transferrin and alpha(2)-macroglobulin. When the Q(protein) of all proteins were plotted against Q(albumin), EPO showed dynamics similar to CNS-derived proteins. Our data indicate that EPO in the CSF of patients with aneurysmal SAH originates mainly from the CNS.