Rationale and design of a large trial of perioperative ketamine for prevention of chronic post-surgical pain.

Background: Chronic post-surgical pain (CPSP) is recognised as one of the most common and debilitating complications of major surgery. Progression from acute to chronic pain after surgery involves sensitisation of central nervous system pathways with the N-methyl-D-aspartate (NMDA) receptor having a central role. Ketamine is a potent, non-selective NMDA antagonist commonly used for management of acute postoperative pain.

The safety of nitrous oxide: glass half-full or half-empty?

A systematic review of clinical trials confirms that including nitrous oxide in the gas mixture for general anaesthesia has minor short-term benefits and does not impact most patient safety outcomes. However, no risk-benefit analysis of nitrous oxide should ignore its known environmental effects. If continued nitrous oxide use is supported, strategies to minimise and monitor the contribution of medical nitrous oxide to global warming are vital.

Effects of N O elimination on the elimination of second gases in a two-step mathematical model of heterogeneous gas exchange.

We have investigated the elimination of inert gases in the lung during the elimination of nitrous oxide (N O) using a two-step mathematical model that allows the contribution from net gas volume expansion, which occurs in Step 2, to be separated from other factors. When a second inert gas is used in addition to N O, the effect on that gas appears as an extra volume of the gas eliminated in association with the dilution produced by N O washout in Step 2. We first considered the effect of elimination in a single gas-exchanging unit under steady-state conditions and then extended our analysis to a lung having a log-normal distribution of ventilation and perfusion.

A modal definition of ideal alveolar oxygen.

In the three-compartment model of lung ventilation-perfusion heterogeneity (VA/Q scatter), both Bohr dead space and shunt equations require values for central "ideal" compartment O and CO partial pressures. However, the ideal alveolar gas equation most accurately calculates mixed (ideal and alveolar dead space) PAO . A novel "modal" definition has been validated for ideal alveolar CO partial pressure, at the VA/Q ratio in a lung distribution where CO elimination is maximal.

The relationship between study findings and publication outcome in anesthesia research following implementation of mandatory trial registration: A systematic review of publication bias.

Previously, we reviewed 1052 randomized-controlled trial abstracts presented at the American Society of Anesthesiologists annual meetings from 2001-2004. We found significant positive publication bias in the period examined, with the odds ratio for abstracts with positive results proceeding to journal publication over those with null results being 2.01 [95% confidence interval: 1.

Postoperative Pulmonary Complications in the ENIGMA II Trial: A Post Hoc Analysis.

Background: Nitrous oxide promotes absorption atelectasis in poorly ventilated lung segments at high inspired concentrations. The Evaluation of Nitrous oxide In the Gas Mixture for Anesthesia (ENIGMA) trial found a higher incidence of postoperative pulmonary complications and wound sepsis with nitrous oxide anesthesia in major surgery compared to a fraction of inspired oxygen of 0.8 without nitrous oxide.

Postoperative anaemia and patient-centred outcomes after major abdominal surgery: a retrospective cohort study.

Background: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown.

Methods: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery.

Trial registration of abstracts from the American Society of Anesthesiologists Meetings 2010-2016: A review of prospective trial registration and selective outcome reporting.

Mandatory prospective trial registration was introduced in 2005 to reduce publication bias and selective outcome reporting. In this study, we measured the proportion of prospective trial registration in randomized controlled trials in the anesthesia literature after this introduction, discrepancies between these trial protocols and subsequent publications, the association between being prospectively registered and reporting positive or negative results, and between being prospectively registered and achieving publication. We reviewed all abstracts from the American Society of Anesthesiologists annual meetings between 2010-2016 and included randomized controlled trials in humans.

Inclusion, characteristics, and outcomes of male and female participants in large international perioperative studies.

Background: We compared baseline characteristics and outcomes and evaluated the subgroup effects of randomised interventions by sex in males and females in large international perioperative trials.

Methods: Nine randomised trials and two cohort studies recruiting adult patients, conducted between 1995 and 2020, were included. Baseline characteristics and outcomes common to six or more studies were evaluated.

Intraoperative low tidal volume ventilation and the risk of ICD-10 coded delirium and the use for antipsychotic medications.

Background: Low tidal volume (V) ventilation and its associated increase in arterial carbon dioxide (PaCO) may affect postoperative neurologic function. We aimed to test the hypothesis that intraoperative low V ventilation affect the incidence of postoperative ICD-10 coded delirium and/or the need for antipsychotic medications.

Methods: This is a post-hoc analysis of a large randomized controlled trial evaluating low vs.

Gas Phase Diffusion Does Not Limit Lung Volatile Anesthetic Uptake Rate.

Background: Inefficiency of lung gas exchange during general anesthesia is reflected in alveolar (end-tidal) to arterial (end-tidal-arterial) partial pressure gradients for inhaled gases, resulting in an increase in alveolar deadspace. Ventilation-perfusion mismatch is the main contributor to this, but it is unclear what contribution arises from diffusion limitation in the gas phase down the respiratory tree (longitudinal stratification) or at the alveolar-capillary barrier, especially for gases of high molecular weight such as volatile anesthetics.

Methods: The contribution of longitudinal stratification was examined by comparison of end-tidal-arterial partial pressure gradients for two inhaled gases with similar blood solubility but different molecular weights: desflurane and nitrous oxide, administered together at 2 to 3% and 10 to 15% inspired concentration (FiG), respectively, in 17 anesthetized ventilated patients undergoing cardiac surgery before cardiopulmonary bypass.

Methylomic and transcriptomic characterization of postoperative systemic inflammatory dysregulation.

In this study, we define and validate a state of postoperative systemic inflammatory dysregulation (PSID) based on postoperative phenotypic extremes of plasma C-reactive protein concentration following major abdominal surgery. PSID manifested clinically with significantly higher rates of sepsis, complications, longer hospital stays and poorer short, and long-term outcomes. We hypothesized that PSID will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression.

Effects of an open lung ventilatory strategy on lung gas exchange during laparoscopic surgery.

In general anaesthesia, early collapse of poorly ventilated lung segments with low alveolar ventilation-perfusion ratios occurs and may lead to postoperative pulmonary complications after abdominal surgery. An 'open lung' ventilation strategy involves lung recruitment followed by 'individualised' positive end-expiratory pressure titrated to maintain recruitment of low alveolar ventilation-perfusion ratio lung segments. There are limited data in laparoscopic surgery on the effects of this on pulmonary gas exchange.

Sugammadex, neostigmine and postoperative pulmonary complications: an international randomised feasibility and pilot trial.

Background: Sugammadex reduces residual neuromuscular blockade after anaesthesia, potentially preventing postoperative pulmonary complications. However, definitive evidence is lacking. We therefore conducted a feasibility and pilot trial for a large randomised controlled trial of sugammadex, neostigmine, and postoperative pulmonary complications.

Ideal alveolar gas defined by modal gas exchange in ventilation-perfusion distributions.

Under the three-compartment model of ventilation-perfusion ([Formula: see text]) scatter, Bohr-Enghoff calculation of alveolar deadspace fraction (VDA/VA) uses arterial CO partial pressure measurement as an approximation of "ideal" alveolar CO ( [Formula: see text]). However, this simplistic model suffers from several inconsistencies. Modeling of realistic physiological distributions of [Formula: see text] and [Formula: see text] instead suggests an alternative concept of "ideal" alveolar gas at the [Formula: see text] ratio where uptake or elimination rate of a gas is maximal.

Ventilatory parameters measured during a physiological study of simulated powered air-purifying respirator failure in healthy volunteers.

Powered air-purifying respirators (PAPR) are a high level of respiratory personal protective equipment. Like all mechanical devices, they are vulnerable to failure. The precise physiological consequences of failure in live subjects have not previously been reported.

Effect of fluid strategy on stroke volume, cardiac output, and fluid responsiveness in adult patients undergoing major abdominal surgery: a sub-study of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial.

Background: We designed a prospective sub-study of the larger Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial to measure differences in stroke volume and other haemodynamic parameters at the end of the intraoperative fluid protocols. The haemodynamic effects of the two fluid regimens may increase our understanding of the observed perioperative outcomes.

Methods: Stroke volume and cardiac output were measured with both an oesophageal Doppler ultrasound monitor and arterial pressure waveform analysis.

End-tidal to Arterial Gradients and Alveolar Deadspace for Anesthetic Agents.

Background: According to the "three-compartment" model of ventilation-perfusion ((Equation is included in full-text article.)) inequality, increased (Equation is included in full-text article.)scatter in the lung under general anesthesia is reflected in increased alveolar deadspace fraction (VDA/VA) customarily measured using end-tidal to arterial (A-a) partial pressure gradients for carbon dioxide.