In vitro norepinephrine significantly activates isolated platelets from healthy volunteers and critically ill patients following severe traumatic brain injury

INTRODUCTION: Norepinephrine, regularly used to increase systemic arterial blood pressure and thus improve cerebral perfusion following severe traumatic brain injury (TBI), may activate platelets. This, in turn, could promote microthrombosis formation and induce additional brain damage. METHODS: The objective of this study was to investigate the influence of norepinephrine on platelets isolated from healthy volunteers and TBI patients during the first two post-traumatic weeks. A total of 18 female and 18 male healthy volunteers of different age groups were recruited, while 11 critically ill TBI patients admitted consecutively to our intensive care unit were studied. Arterial and jugular venous platelets were isolated from norepinephrine-receiving TBI patients; peripheral venous platelets were studied in healthy volunteers. Concentration-dependent functional alterations of isolated platelets were analyzed by flow cytometry, assessing changes in surface P-selectin expression and platelet-derived microparticles before and after in vitro stimulation with norepinephrine ranging from 10 nM to 100 microM. The thrombin receptor-activating peptide (TRAP) served as a positive control. RESULTS: During the first week following TBI, norepinephrine-mediated stimulation of isolated platelets was significantly reduced compared with volunteers (control). In the second week, the number of P-selectin- and microparticle-positive platelets was significantly decreased by 60% compared with the first week and compared with volunteers. This, however, was associated with a significantly increased susceptibility to norepinephrine-mediated stimulation, exceeding changes observed in volunteers and TBI patients during the first week. This pronounced norepinephrine-induced responsiveness coincided with increased arterio-jugular venous difference in platelets, reflecting intracerebral adherence and signs of cerebral deterioration reflected by elevated intracranial pressure and reduced jugular venous oxygen saturation. CONCLUSION: Clinically infused norepinephrine might influence platelets, possibly promoting microthrombosis formation. In vitro stimulation revealed a concentration- and time-dependent differential level of norepinephrine-mediated platelet activation, possibly reflecting changes in receptor expression and function. Whether norepinephrine should be avoided in the second post-traumatic week and whether norepinephrine-stimulated platelets might induce additional brain damage warrant further investigations

Current trends in vena cava reconstructive techniques with major liver resection: a systematic review

Purpose: Historically, invasion of the inferior vena cava (IVC) represented advanced and often unresectable hepatic disease. With surgical and anesthetic innovations, IVC resection and reconstruction have become feasible in selected patients. This review assesses technical variations in reconstructive techniques and post-operative management. Methods: A comprehensive literature search was performed according to PRISMA. Inclusion criteria were (i) peer-reviewed articles in English; (ii) at least three cases; (iii) hepatic IVC resection and reconstruction (January 2015-March 2020). Primary outcomes were reconstructive technique, anti-thrombotic regimen, post-operative IVC patency, and infection. Secondary outcomes included post-operative complications and malignant disease survival. Results: Fourteen articles were included allowing for investigation of 351 individual patients. Analysis demonstrated significant heterogeneity in surgical reconstructive technique, anti-thrombotic management, and post-operative monitoring of patency. There was increased utilization of ex vivo approaches and decreased use of venovenous bypass compared with previously published reviews. Conclusion: This review of literature published between 2015 and 2020 reveals persistent heterogeneity of hepatic IVC reconstructive techniques and peri-operative management. Increased utilization of ex vivo approaches and decreased use of venovenous bypass point towards improved operative techniques, peri-operative management, and anesthesia. In order to gain evidence for consensus on management, a registry would be beneficial

Assessing the Value of Prehabilitation in Patients Undergoing Colorectal Surgery According to the Enhanced Recovery After Surgery (ERAS) Pathway for the Improvement of Postoperative Outcomes: Protocol for a Randomized Controlled Trial

A key element in the postoperative phase of the standardized Enhanced Recovery After Surgery (ERAS) treatment pathways is mobilization. Currently, there are no recommendations in the ERAS guidelines for preoperative physical activity. Patients undergoing major surgery are prone to functional decline due to the impairment of muscle, cardiorespiratory, and neurological function as a response to surgical stress. It has been shown that preoperative physical training reduces postoperative complications. To date, there are limited studies that investigate preoperative physical training combined with ERAS

ALPPS Offers a Better Chance of Complete Resection in Patients with Primarily Unresectable Liver Tumors Compared with Conventional-Staged Hepatectomies: Results of a Multicenter Analysis

Background: Portal vein occlusion to increase the size of the future liver remnant (FLR) is well established, using portal vein ligation (PVL) or embolization (PVE) followed by resection 4-8weeks later. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL and complete parenchymal transection, followed by hepatectomy within 1-2weeks. ALPPS has been recently introduced but remains controversial. We compare the ability of ALPPS versus PVE or PVL for complete tumor resection. Methods: A retrospective review of all patients undergoing ALPPS or conventional staged hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and 2012 was performed. Patients with primary liver tumors and liver metastases were included. Primary endpoint was complete tumor resection. Secondary endpoints include 90-day mortality, complications, FLR increase, time to resection, and tumor recurrence. Results: Forty-eight patients with ALPPS were compared with 83 patients with conventional-staged hepatectomies. Eighty-three percent (40/48 patients) of ALPPS patients achieved complete resection compared with 66% (55/83 patients) in PVE/PVL (odds ratio 3.34, p=0.027). Ninety-day mortality in ALPPS and PVE/PVL was 15 and 6%, respectively (p=0.2). Extrapolated growth rate was 11 times higher in ALPPS (34.8cc/day; interquartile range (IQR) 26-49) compared with PVE/PVL (3cc/day; IQR2-6; p=0.001). Tumor recurrence at 1year was 54 versus 52% for ALPPS and PVE/PVL, respectively (p=0.7). Conclusions: This study provides evidence that ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors at the cost of a high mortality. The technique is promising but should currently not be used outside of studies and registries

ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors compared with conventional-staged hepatectomies: results of a multicenter analysis

BACKGROUND: Portal vein occlusion to increase the size of the future liver remnant (FLR) is well established, using portal vein ligation (PVL) or embolization (PVE) followed by resection 4-8 weeks later. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL and complete parenchymal transection, followed by hepatectomy within 1-2 weeks. ALPPS has been recently introduced but remains controversial. We compare the ability of ALPPS versus PVE or PVL for complete tumor resection. METHODS: A retrospective review of all patients undergoing ALPPS or conventional staged hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and 2012 was performed. Patients with primary liver tumors and liver metastases were included. Primary endpoint was complete tumor resection. Secondary endpoints include 90-day mortality, complications, FLR increase, time to resection, and tumor recurrence. RESULTS: Forty-eight patients with ALPPS were compared with 83 patients with conventional-staged hepatectomies. Eighty-three percent (40/48 patients) of ALPPS patients achieved complete resection compared with 66 % (55/83 patients) in PVE/PVL (odds ratio 3.34, p = 0.027). Ninety-day mortality in ALPPS and PVE/PVL was 15 and 6 %, respectively (p = 0.2). Extrapolated growth rate was 11 times higher in ALPPS (34.8 cc/day; interquartile range (IQR) 26-49) compared with PVE/PVL (3 cc/day; IQR2-6; p = 0.001). Tumor recurrence at 1 year was 54 versus 52 % for ALPPS and PVE/PVL, respectively (p = 0.7). CONCLUSIONS: This study provides evidence that ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors at the cost of a high mortality. The technique is promising but should currently not be used outside of studies and registries

Exercise Improves Outcomes of Surgery on Fatty Liver in Mice: A Novel Effect Mediated by the AMPK Pathway.

OBJECTIVE To investigate whether exercise improves outcomes of surgery on fatty liver, and whether pharmacological approaches can substitute exercising programs. SUMMARY OF BACKGROUND DATA Steatosis is the hepatic manifestation of the metabolic syndrome, and decreases the liver's ability to handle inflammatory stress or to regenerate after tissue loss. Exercise activates adenosine monophosphate-activated kinase (AMPK) and mitigates steatosis; however, its impact on ischemia-reperfusion injury and regeneration is unknown. METHODS We used a mouse model of simple, diet-induced steatosis and assessed the impact of exercise on metabolic parameters, ischemia-reperfusion injury and regeneration after hepatectomy. The same parameters were evaluated after treatment of mice with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Mice on a control diet served as age-matched controls. RESULTS A 4-week-exercising program reversed steatosis, lowered insulin levels, and improved glucose tolerance. Exercise markedly enhanced the ischemic tolerance and the regenerative capacity of fatty liver. Replacing exercise with AICAR was sufficient to replicate the above benefits. Both exercise and AICAR improved survival after extended hepatectomy in mice challenged with a Western diet, indicating protection from resection-induced liver failure. CONCLUSIONS Exercise efficiently counteracts the metabolic, ischemic, and regenerative deficits of fatty liver. AICAR acts as an exercise mimetic in settings of fatty liver disease, an important finding given the compliance issues associated with exercise. Exercising, or its substitution through AICAR, may provide a feasible strategy to negate the hepatic consequences of energy-rich diet, and has the potential to extend the application of liver surgery if confirmed in humans

Pheochromocytoma crisis

KEY CLINICAL MESSAGE: Adrenergic crisis induced by a pheochromocytoma leads to life-threatening catecholamine-induced hemodynamic disturbances. Successful treatment of a pheochromocytoma crisis demands prompt diagnosis, vigorous pharmacological therapy and emergent tumor removal, if the patient continues to deteriorate