Vacuum-assisted closure versus on-demand relaparotomy in patients with secondary peritonitis-the VACOR trial: protocol for a randomised controlled trial.

BACKGROUND: Secondary peritonitis is a severe condition with a 20-32% reported mortality. The accepted treatment modalities are vacuum-assisted closure (VAC) or primary closure with relaparotomy on-demand (ROD). However, no randomised controlled trial has been completed to compare the two methods potential benefits and disadvantages. METHODS: This study will be a randomised controlled multicentre trial, including patients aged 18 years or older with purulent or faecal peritonitis confined to at least two of the four abdominal quadrants originating from the small intestine, colon, or rectum. Randomisation will be web-based to either primary closure with ROD or VAC in blocks of 2, 4, and 6. The primary endpoint is peritonitis-related complications within 30 or 90 days and one year after index operation. Secondary outcomes are comprehensive complication index (CCI) and mortality after 30 or 90 days and one year; quality of life assessment by (SF-36) after three and 12 months, the development of incisional hernia after 12 months assessed by clinical examination and CT-scanning and healthcare resource utilisation. With an estimated superiority of 15% in the primary outcome for VAC, 340 patients must be included. Hospitals in Denmark and Europe will be invited to participate. DISCUSSION: There is no robust evidence for choosing either open abdomen with VAC treatment or primary closure with relaparotomy on-demand in patients with secondary peritonitis. The present study has the potential to answer this important clinical question. TRIAL REGISTRATION: The study protocol has been registered at clinicaltrials.gov (NCT03932461). Protocol version 1.0, 9 January 2022.

Early laparoscopic cholecystectomy for acute cholecystitis is safe regardless of timing.

PURPOSE: The optimal timing for laparoscopic cholecystectomy for acute cholecystitis (AC) has not been resolved. In the revised Tokyo Guidelines from 2018 (TG18), early laparoscopic cholecystectomy (ELC) is recommended regardless of the duration of symptoms. The aim of this study was to evaluate the safety of ELC compared with delayed laparoscopic cholecystectomy (DLC) for AC. In addition, we assessed the perioperative outcomes after ELC based on duration of symptoms. METHODS: A retrospective cohort study of patients operated for acute calculous cholecystitis from January 1, 2017, to June 30, 2018, at Copenhagen University Hospital, Herlev. ELC was divided into three subgroups based on the duration of symptoms from onset to operation, ≤ 72 h, > 72-120 h, > 120 h. RESULTS: Two hundred twenty-two patients underwent ELC and 26 (10.5%) patients underwent DLC. We found no difference in mortality, morbidity, conversion rate, or bile duct injuries between DLC and ELC or in the subgroups based on duration of symptoms. We found significantly longer total hospital length of stay for patients with symptoms > 72 h (4.1-5.6 days) compared to ≤ 72 h (3.1 days) and the longest in DLC (9.9 days). Twenty-three percent of DLC needed an emergency operation in the waiting period with a high conversion rate (1/3). CONCLUSION: ELC for AC even beyond 5 days of symptoms is safe and not associated with increased complications. The duration of symptoms in AC is not an independent predictor and should not influence the surgeonsmsdecision to perform an ELC. Delaying cholecystectomy has a high failure rate.

[The surgical window for performing laparoscopic cholecystectomy may be extended to seven days after acute cholecystitis].

In Denmark, based on weak evidence from 2002, a surgical window of maximum four days after debut of symptoms has up till now been recommended. Based on 12 randomised controlled studies (RCTs) we conclude, that the surgical window may be extended to seven days. The main advantage is a significant reduction of total hospital stay and apparently without compromising safety. Unfortunately, evidence is based on mostly statistically underpowered RCTs of low or moderate methodological quality, and final conclusions on surgical results are still not possible.

Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation.

This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry). Cerebral and femoral venous blood flow was evaluated by transcranial Doppler ultrasound (CBF) and constant infusion thermodilution (FBF). With 3 participants lost to follow up (final n = 4♂, 3♀), hypoxia increased CBF and FBF (P = 0.041 vs. normoxia) with further elevations in FBF during exercise (P = 0.002 vs. rest). Cerebral and femoral ascorbate and α-tocopherol consumption (v < a) was accompanied by A•-/LOOH formation (v > a) and increased LDL oxidation during hypoxia (P < 0.043-0.049 vs. normoxia) implying free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = -0.397 to -0.459, P = 0.037-0.045) but unrelated to any reduction in PO2. These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O2 flux than to O2 tension.

Adaptive process triage system cannot identify patients with gastrointestinal perforation.

INTRODUCTION: Adaptive process triage (ADAPT) is a triage tool developed to assess the severity and address the priority of emergency patients. In 2009-2011, ADAPT was the most frequently used triage system in Denmark. Until now, no Danish triage system has been evaluated based on a selective group of patients in need of acute abdominal surgery. Gastrointestinal perforation (GIP) is acknowledged as one of the surgical conditions with the highest mortality rates. The aim of this study was to evaluate whether ADAPT can identify patients with GIP. METHODS: All abdominal emergency laparoscopies and laparotomies performed over a one-year period at Herlev Hospital, Denmark, were included. Patient data and triage levels were collected from medical records. We defined patients suspected of less severe surgical illness as green-yellow and patients suspected of severe/life-threatening illness as orange-red. RESULTS: A total of 803 patients with a known triage level were identified: 47% green, 38% yellow, 13% orange and 2% red. Of these patients, 136 were identified with a GIP. The negative predictive value was 83.2% (95% confidence interval: 80.1-85.7), meaning that one out of six abdominal surgery patients triaged as green or yellow had a GIP that was not identified by the triage system. CONCLUSION: ADAPT is incapable of identifying one of the most critically ill patient groups in need of emergency abdominal surgery. FUNDING: none. TRIAL REGISTRATION: HEH-2013-034 I-Suite: 02336.

Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia.

BACKGROUND: The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish their relative contribution in vivo, we quantified arterial-venous concentration gradients across the human cerebral and femoral circulation at rest and during exercise, an ideal model system characterized by physiological extremes of O2 tension and blood flow. METHODS: Ten healthy participants (5 men, 5 women) aged 24±4 (mean±SD) years old were randomly assigned to a normoxic (21% O2) and hypoxic (10% O2) trial with measurements performed at rest and after 30 minutes of cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled simultaneously from the brachial artery and internal jugular and femoral veins with plasma and RBC nitric oxide metabolites measured by tri-iodide reductive chemiluminescence. Blood flow was determined by transcranial Doppler ultrasound (cerebral blood flow) and constant infusion thermodilution (femoral blood flow) with net exchange calculated via the Fick principle. RESULTS: Hypoxia was associated with a mild increase in both cerebral blood flow and femoral blood flow (P<0.05 versus normoxia) with further, more pronounced increases observed in femoral blood flow during exercise (P<0.05 versus rest) in proportion to the reduction in RBC oxygenation (r=0.680-0.769, P<0.001). Plasma gradients reflecting consumption (arterial>venous; P<0.05) were accompanied by RBC iron nitrosylhemoglobin formation (venous>arterial; P<0.05) at rest in normoxia, during hypoxia (P<0.05 versus normoxia), and especially during exercise (P<0.05 versus rest), with the most pronounced gradients observed across the bioenergetically more active, hypoxemic, and acidotic femoral circulation (P<0.05 versus cerebral). In contrast, we failed to observe any gradients consistent with RBC SNO-Hb consumption and corresponding delivery of plasma S-nitrosothiols (P>0.05). CONCLUSIONS: These findings suggest that hypoxia and, to a far greater extent, exercise independently promote arterial-venous delivery gradients of intravascular nitric oxide, with deoxyhemoglobin-mediated reduction identified as the dominant mechanism underlying hypoxic vasodilation.

Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain.

Lactate is shuttled between organs, as demonstrated in the Cori cycle. Although the brain releases lactate at rest, during physical exercise there is a cerebral uptake of lactate. Here, we evaluated the cerebral lactate uptake and release in hypoxia, during exercise and when the two interventions were combined. We measured cerebral lactate turnover via a tracer dilution method ([1-(13)C]lactate), using arterial to right internal jugular venous differences in 9 healthy individuals (5 males and 4 females), at rest and during 30 min of submaximal exercise in normoxia and hypoxia (F(i)o(2) 10%, arterial oxygen saturation 72 ± 10%, mean ± sd). Whole-body lactate turnover increased 3.5-fold and 9-fold at two workloads in normoxia and 18-fold during exercise in hypoxia. Although middle cerebral artery mean flow velocity increased during exercise in hypoxia, calculated cerebral mitochondrial oxygen tension decreased by 13 mmHg (P<0.001). At the same time, cerebral lactate release increased from 0.15 ± 0.1 to 0.8 ± 0.6 mmol min(-1) (P<0.05), corresponding to ∼10% of cerebral energy consumption. Concurrently, cerebral lactate uptake was 1.0 ± 0.9 mmol min(-1) (P<0.05), of which 57 ± 9% was oxidized, demonstrating that lactate oxidation may account for up to ∼33% of the energy substrate used by the brain. These results support the existence of a cell-cell lactate shuttle that may involve neurons and astrocytes.