Argipressin for prevention of blood loss during liver resection: a study protocol for a randomised, placebo-controlled, double-blinded trial (ARG-01).

INTRODUCTION: Liver resection carries a high risk for extensive bleeding and need for blood transfusions, which is associated with significant negative impact on outcome. In malignant disease, the most common indication for surgery, it also includes increased risk for recurrence of cancer. Argipressin decreases liver and portal blood flow and may have the potential to reduce bleeding during liver surgery, although this has not been explored. METHOD AND ANALYSIS: ARG-01 is a prospective, randomised, placebo-controlled, double-blinded study on 248 patients undergoing liver resection at Sahlgrenska University Hospital, Sweden. Patients will be randomised to one of two parallel groups, infusion of argipressin or normal saline administered peroperatively. The primary endpoint is peroperative blood loss. Secondary outcomes include need for blood transfusion, perioperative variables, length of hospital stay, the inflammatory response, organ damage markers and complications at 30 days. ETHICS AND DISSEMINATION: The study is enrolling patients since March 2022. The trial is approved by the Swedish Ethical Review Authority (Dnr 2021-03557) and the Swedish Medical Product Agency (Dnr 5.1-2021-90115). Results will be announced at scientific meetings and in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05293041 and EudraCT, 2021-001806-32.

Protein tau concentration in blood increases after SCUBA diving: an observational study.

PURPOSE: It is speculated that diving might be harmful to the nervous system. The aim of this study was to determine if established markers of neuronal injury were increased in the blood after diving. METHODS: Thirty-two divers performed two identical dives, 48 h apart, in a water-filled hyperbaric chamber pressurized to an equivalent of 42 m of sea water for 10 min. After one of the two dives, normobaric oxygen was breathed for 30 min, with air breathed after the other. Blood samples were obtained before and at 30-45 and 120 min after diving. Concentrations of glial fibrillary acidic, neurofilament light, and tau proteins were measured using single molecule array technology. Doppler ultrasound was used to detect venous gas emboli. RESULTS: Tau was significantly increased at 30-45 min after the second dive (p < 0.0098) and at 120 min after both dives (p < 0.0008/p < 0.0041). Comparison of matching samples showed that oxygen breathing after diving did not influence tau results. There was no correlation between tau concentrations and the presence of venous gas emboli. Glial fibrillary acidic protein was decreased 30-45 min after the first dive but at no other point. Neurofilament light concentrations did not change. CONCLUSIONS: Tau seems to be a promising marker of dive-related neuronal stress, which is independent of the presence of venous gas emboli. Future studies could validate these results and determine if there is a quantitative relationship between dive exposure and change in tau blood concentration.

Myocardial, renal and intestinal injury in liver resection surgery-A prospective observational pilot study.

BACKGROUND: Post-operative organ complications in liver resection surgery are not uncommon. This prospective observational pilot study was performed to evaluate the incidence, degree and timing of myocardial, renal and intestinal injury in patients undergoing liver resection surgery using the low central venous pressure (LCVP) technique and the Pringle manoeuvre. METHODS: Blood samples were obtained before, during and after elective liver resection until post-operative day (POD) 5. High-sensitive troponin T (hs-TnT), serum creatinine, urea, intestinal fatty acid binding protein (I-FABP), D-lactate, arterial lactate, portal lactate, amylase, as well as urine N-acetyl-ß-D-glucosaminidase (NAG) were analysed. Systemic haemodynamics were measured intraoperatively. RESULTS: Eighteen patients fulfilled the protocol. The Pringle manoeuvre was used in all but 1 patient. hs-TnT increased significantly over time (P < .001) and 5 patients (28%) developed myocardial injury. Five patients had a pre-operative elevation of hs-TnT, four of those developed myocardial injury. Serum creatinine increased significantly over time (P = .015). Acute kidney injury (AKI) occurred in 5 patients (28%), while NAG, as a marker of tubular injury, was not affected. I-FABP increased over time (P < .001) with a maximal 75% increase at 3 hours after resection. D-lactate was below detection level at all measuring points. CONCLUSIONS: In patients undergoing liver resection surgery, using LCVP technique and Pringle manoeuvre, myocardial injury was seen in approximately 30% of the patients post-operatively and almost 30% developed transient AKI in the early post-operative period with no tubular injury. Furthermore, a transient increase of the enterocyte damage marker I-FABP was demonstrated with no signs of gut barrier dysfunction.

Biomarkers of neuronal damage in saturation diving-a controlled observational study.

PURPOSE: A prospective and controlled observational study was performed to determine if the central nervous system injury markers glial fibrillary acidic protein (GFAp), neurofilament light (NfL) and tau concentrations changed in response to a saturation dive. METHODS: The intervention group consisted of 14 submariners compressed to 401 kPa in a dry hyperbaric chamber. They remained pressurized for 36 h and were then decompressed over 70 h. A control group of 12 individuals was used. Blood samples were obtained from both groups before, during and after hyperbaric exposure, and from the intervention group after a further 25-26 h. RESULTS: There were no statistically significant changes in the concentrations of GFAp, NfL and tau in the intervention group. During hyperbaric exposure, GFAp decreased in the control group (mean/median - 15.1/ - 8.9 pg·mL-1, p < 0.01) and there was a significant difference in absolute change of GFAp and NfL between the groups (17.7 pg·mL-1, p = 0.02 and 2.34 pg·mL-1, p = 0.02, respectively). Albumin decreased in the control group (mean/median - 2.74 g/L/ - 0.95 g/L, p = 0.02), but there was no statistically significant difference in albumin levels between the groups. In the intervention group, haematocrit and mean haemoglobin values were slightly increased after hyperbaric exposure (mean/median 2.3%/1.5%, p = 0.02 and 4.9 g/L, p = 0.06, respectively). CONCLUSION: Hyperbaric exposure to 401 kPa for 36 h was not associated with significant increases in GFAp, NfL or tau concentrations. Albumin levels, changes in hydration or diurnal variation were unlikely to have confounded the results. Saturation exposure to 401 kPa seems to be a procedure not harmful to the central nervous system. TRIAL REGISTRATION: ClinicalTrials.gov NCT03192930.

Serum tau concentration after diving - an observational pilot study.

INTRODUCTION: Increased concentrations of tau protein are associated with medical conditions involving the central nervous system, such as Alzheimer's disease, traumatic brain injury and hypoxia. Diving, by way of an elevated ambient pressure, can affect the nervous system, however it is not known whether it causes a rise in tau protein levels in serum. A prospective observational pilot study was performed to investigate changes in tau protein concentrations in serum after diving and also determine their relationship, if any, to the amount of inert gas bubbling in the venous blood. METHODS: Subjects were 10 navy divers performing one or two dives per day, increasing in depth, over four days. Maximum dive depths ranged from 52-90 metres' sea water (msw). Air or trimix (nitrogen/oxygen/helium) was used as the breathing gas and the oxygen partial pressure did not exceed 160 kPa. Blood samples taken before the first and after the last dives were analyzed. Divers were monitored for the presence of venous gas emboli (VGE) at 10 to15 minute intervals for up to 120 minutes using precordial Doppler ultrasound. RESULTS: Median tau protein before diving was 0.200 pg·mL⁻¹ (range 0.100 to 1.10 pg·mL⁻¹) and after diving was 0.450 pg·mL⁻¹ (range 0.100 to 1.20 pg·mL⁻¹; P = 0.016). Glial fibrillary acidic protein and neurofilament light protein concentrations analyzed in the same assay did not change after diving. No correlation was found between serum tau protein concentration and the amount of VGE. CONCLUSION: Repeated diving to between 52-90 msw is associated with a statistically significant increase in serum tau protein concentration, which could indicate neuronal stress.

Cerebrospinal fluid markers of central nervous system injury in decompression illness - a case-controlled pilot study.

INTRODUCTION: Decompression sickness (DCS) may cause a wide variety of symptoms, including central nervous system (CNS) manifestations. The main objective of this study was to examine whether DCS is associated with neuronal injury, and whether DCS could result in altered amyloid metabolism. METHODS: Seven, male divers with DCS and seven age-matched controls were included in the study. All the divers were treated by recompression but the controls did not receive hyperbaric oxygen. Cerebrospinal fluid (CSF) samples were collected 7-10 days after the diving injury and at three months follow-up. CSF biomarkers of neuronal injury, astroglial Injury/activation, and a range of markers of amyloid ß (Aß) metabolism, as well as two proinflammatory interleukins, were analysed using immunochemical methods. RESULTS: There were no significant differences in the best-established CSF markers of neuronal injury, total tau (T-tau) and neurofilament light, between DCS patients and controls or between the two sampling time points. Also, there were no significant changes in the astroglial or amyloid (Aß)-related markers between DCS patients and controls. However, the only diver with CNS symptoms had the highest levels of CSF T-tau, Aß38, Aß40 and Aß42. CONCLUSION: The results of our study speak against subclinical CNS injury or induction of inflammation or amyloid build-up in the brain among the six DCS patients without neurological symptoms. Further research, including on divers with CNS DCS, is justified.

Pro-inflammatory cytokine release in rectal surgery: comparison between laparoscopic and open surgical techniques.

The objective of the present study was to investigate whether laparoscopic rectal surgery causes a less pronounced release of pro-inflammatory cytokines as compared to open surgical technique. Twenty-four consecutive patients undergoing rectal surgery due to cancer disease were included in a prospective and randomized trial. The patients were randomized to laparoscopic (n = 12) or open surgery (n = 12). Blood was sampled at five occasions; after induction of anesthesia before start of surgery, at 180, 360 min and 24 h after start of surgery and the last sample was taken in the late post-operative period 3-5 days after surgery. The levels of interleukin (IL)-1α, IL-6, IL-8, IL-10, tumor necrosis factor-α, C-reactive protein (CRP), white blood cells, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 were analyzed using multiplex sandwich enzyme-linked immunosorbent assay. There was a release of both pro- and anti-inflammatory cytokines during colorectal surgery. The release of IL-6, IL-10 and CRP was significantly lower in the laparoscopic group. Rectal surgery causes release of both pro- and anti-inflammatory cytokines. The inflammatory response is lower in laparoscopic rectal surgery as compared to conventional open surgery. Less tissue trauma in laparoscopic rectal surgery and/or less peri-operative bleeding in the laparoscopic cases leads to a lower degree of inflammatory response.