Background: Perioperative red blood cell (RBC) transfusion is associated with poor outcomes in liver surgery. Hypovolemic phlebotomy (HP) is a novel intervention hypothesized to decrease transfusion requirements. The objective of this study was to examine this hypothesis.Methods: Consecutive patients who underwent liver resection at one institution (2010)(2011)(2012)(2013)(2014)(2015)(2016) were included. Factors found to be predictive of transfusion on univariate analysis and those previously published were modeled using multivariate logistic regression. Results: A total of 361 patients underwent liver resection (50% major). HP was performed in 45 patients. Phlebotomized patients had a greater proportion of primary malignancy (31% vs 18%) and major resection (84% vs 45%). Blood loss was significantly lower with phlebotomy in major resections (400 vs 700 mL). Nadir central venous pressure was significantly lower with HP (2.5 vs 5 cm H 2 O). On multivariate logistic regression, HP (OR 0.20, 95% CI 0.068-0.57, p = 0.0029), major liver resection (OR 2.91, 95% CI 1.64-5.18, p = 0.0003), preoperative hemoglobin < 125 g/L (OR 6.02, 95% CI 3.44-10.56, p < 0.0001), and underlying liver disease (OR 2.24, 95% CI 1.27-3.95, p = 0.0051) were significantly associated with perioperative RBC transfusion. Conclusion: Hypovolemic phlebotomy appears to be strongly associated with a reduction in RBC transfusion requirements in liver resection, independent of other known risk factors.

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Background: Major liver resection is associated with blood loss and transfusion. Observational data suggest that hypovolaemic phlebotomy can reduce these risks. This feasibility RCT compared hypovolaemic phlebotomy with the standard of care, to inform a future multicentre trial.Methods: Patients undergoing major liver resections were enrolled between June 2016 and January 2018. Randomization was done during surgery and the surgeons were blinded to the group allocation. For hypovolaemic phlebotomy, 7-10 ml per kg whole blood was removed, without intravenous fluid replacement. Co-primary outcomes were feasibility and estimated blood loss (EBL).Results: A total of 62 patients were randomized to hypovolaemic phlebotomy (31) or standard care (31), at a rate of 3⋅1 patients per month, thus meeting the co-primary feasibility endpoint. The median EBL difference was −111 ml (P = 0⋅456). Among patients at high risk of transfusion, the median EBL difference was −448 ml (P = 0⋅069). Secondary feasibility endpoints were met: enrolment, blinding and target phlebotomy (mean(s.d.) 7⋅6(1⋅9) ml per kg). Blinded surgeons perceived that parenchymal resection was easier with hypovolaemic phlebotomy than standard care (16 of 31 versus 10 of 31 respectively), and guessed that hypovolaemic phlebotomy was being used with an accuracy of 65 per cent (20 of 31). There was no significant difference in overall complications (10 of 31 versus 15 of 31 patients), major complications or transfusion. Among those at high risk, transfusion was required in two of 15 versus three of nine patients (P = 0⋅326).Conclusion: Endpoints were met successfully, but no difference in EBL was found in this feasibility study. A multicentre trial (PRICE-2) powered to identify a difference in perioperative blood transfusion is justified. Registration number: NCT02548910 (http://www.clinicaltrials.gov).

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Purpose: The dissimilar pharmacokinetic properties of cisatracurium (CIS) and rocuronium (ROC) predict different potential for drug cumulation when these drugs are administered by continuous infusion. A study was therefore undertaken to compare cumulation potential of CIS and ROC during surgical procedures of relatively long duration (2-4 hr). Methods: Sufentanil/propofol-N 2 O anesthesia was administered to 40 ASA I and II adults. In a double-blind protocol, patients were randomly allocated to receive a continuous iv infusion of either CIS or ROC, titrated in progressive increments or decrements as required to achieve and maintain 95 ± 5% depression of the T1 response of the adductor pollicis muscle, using a Datex NMT-100 Relaxograph EMG monitor applied at the wrist. At the end of surgery, 60 µg·kg -1 neostigmine plus 15 µg·kg -1 atropine were administered for reversal. Results: The duration of infusion was 104 ± 33 min in group CIS and 110 ± 23 min in group ROC (P=NS). In both groups, a progressive decrease in potency-adjusted infusion rates was observed after 30 min, then stabilized beyond 60 min. When allowing for an initial period of stabilization, mean potency-adjusted infusion requirements were: CIS 0.81 ± 0.02 µg·kg -1 ·min -1 and ROC 5.58 ± 1.94 µg·kg -1 ·min -1 . There were no differences between groups at any time with regard to potency-adjusted infusion requirements necessary to maintain 90-99% block (P=NS). However, drug costs/hr for maintenance of neuromuscular block were less with CIS ($3.57 ± 0.09) than with ROC ($6.03 ± 0.27), P < 0.001. Conclusion: When adjusted to equipotency, infusion requirements of CIS and ROC vary at similar rates during general anesthesia. Despite pharmacokinetic differences, neither drug demonstrates cumulation for infusion lasting up to 3.5 hr.Objectif : Les propriétés pharmacocinétiques différentes du cisatracurium (CIS) et du rocuronium (ROC) laissent présager un potentiel différent d'accumulation lorsqu'on les administre en perfusion continue. Une étude a donc été menée pour comparer le potentiel d'accumulation de CIS et de ROC pendant des interventions chirurgicales de durée relativement longue (2-4 h). Méthode : Une anesthésie à base de sufentanil/propofol-N 2 O a été administrée à 40 adultes d'état physique ASA I et II. Selon un protocole à double insu, les patients ont été répartis de façon aléatoire et ont reçu une perfusion iv continue de CIS ou de ROC en doses progressives ou dégressives comme l'exigent la réalisation et le maintien d'une dépression de 95 ± 5 % de la réponse à T1 du muscle adducteur du pouce, en utilisant un moniteur Datex NMT-100 Relaxograph EMG appliqué au poignet. À la fin de l'opération, 60 µg·kg -1 de néostigmine et 15 µg·kg -1 d'atropine ont été administrés pour renverser le bloc. Résultats : La perfusion a duré 104 ± 33 min dans le groupe CIS et 110 ± 23 min dans le groupe ROC (P=NS). Dans les deux groupes, une baisse progressive des vitesses de perfusion ajustée en fonction de la puissance a été observée après 30 min, puis stabilisée a...

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Background: At least 1 in 6 COVID-19 patients admitted to hospital and receiving supplemental oxygen will die of complications. More than 50% of patients with COVID-19 that receive invasive treatment such as mechanical ventilation will die in hospital. Such impacts overwhelm the limited intensive care unit resources and may lead to further deaths given inadequate access to care. Hyperbaric oxygen therapy (HBOT) is defined as breathing 100% oxygen at a pressure higher than 1.4 atmosphere absolute (ATA). HBOT is safe, including for lungs, when administered by experienced teams and is routinely administrated for a number of approved indications. Preliminary clinical evidence suggests clinical improvement when hypoxemic COVID-19 patients are treated with HBOT. Objective: We aim to determine the effectiveness of HBOT for improving oxygenation, morbidity, and mortality among hypoxemic COVID-19 patients. Methods and analysis: This trial is a sequential Bayesian Parallel-group, individually Randomized, Open, Blinded Endpoint controlled trial. Admitted hypoxemic COVID-19 patients who require supplemental oxygen (without high flow and mechanical ventilation) to maintain a satisfying tissue oxygenation will be eligible to participate. The anticipated sample size of 234 patients is informed by data from a treatment trial of COVID patients recently published. The intervention group will receive one HBOT per day at 2.0 ATA for 75 minutes. Daily HBOT will be administered until either the patient does not require any oxygen supplementation or requires any type of mechanical ventilation or high flow oxygenation until day 28 post-randomization. Patients in the control group will receive the current standard of care treatment (no HBOT). The primary outcome of this trial will be the 7-level COVID ordinal outcomes scale assessed on Day 7 post-randomization. Secondary outcomes will include: (a) clinical outcomes (length of hospital stay, days with oxygen supplementation, oxygen flow values to obtain a saturation by pulse oximetry ≥90%, intensive care admission and length of stay, days on invasive mechanical ventilation or high flow oxygen, sleep quality, fatigue, major thrombotic events, the 7-level COVID ordinal outcomes scale on Day 28; mortality, safety); (b) biological outcomes (plasma inflammatory markers); and (c) health system outcomes (cost of care and cost-effectiveness). Predetermined inclusion/exclusion criteria have been specified. The analytical approach for the primary outcome will use a Bayesian proportional odds ordinal logistic semiparametric model. The primary analysis will be by intention-to-treat. Bayesian posterior probabilities will be calculated every 20 patients to assess accumulating evidence for benefit or harm. A planned subgroup analysis will be performed for pre-specified variables known to impact COVID-19 prognosis and/or HBOT (biologic sex and age). Discussion: Based on the mortality rate and substantial burden of COVID-19 on the healthcare system, it is imperative that solutions be found. HBOT is a non-invasive and low-risk intervention when contraindications are respected. The established safety and relatively low cost of providing HBOT along with its potential to improve the prognosis of severe COVID-19 patients make this intervention worth studying, despite the current limited number of HBOT centres. If this trial finds that HBOT significantly improves outcome and prevents further deterioration leading to critical care for severe COVID-19 patients, practice will change internationally. If no benefit is found from the intervention, then the current standard of care (no HBOT) will be supported by level I evidence.