Second Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management.

The COVID-19 pandemic poses great challenges for healthcare workers around the world, including perioperative specialists. Previously, we provided a first overview of available literature on SARS-CoV-2 and COVID-19, relevant for anaesthetists and intensivists. In the current review, we provide an update of this topic, after a literature search current through May 2020. We discuss the evidence on perioperative risk for COVID-19 patients presenting for surgery, the risk of transmission of SARS-CoV-2 in the operating room, and the current literature on laboratory diagnostics. Furthermore, cardiovascular and nervous system involvement in COVID-19 are discussed, as well as considerations in diabetic patients. Lastly, the latest evidence on pharmacological treatment is summarised.

Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management.

When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.

European implementation of the "2014 ESC/ESA guideline on non-cardiac surgery: cardiovascular assessment and management".

BACKGROUND: Substandard implementation of a guideline is a major factor contributing to poor guideline adherence and has the potential to result in preventable patient harm. This study aims to quantify the uptake of the European guideline on non-cardiac surgery by European anesthetists. METHODS: This is a questionnaire-based cross-sectional study. Data was collected during Euroanaesthesia, the annual congresses of the Dutch Society of Anaesthesiology, European Association of Cardiothoracic Anaesthesiologists and European Society for Regional Anaesthesia and Pain Therapy in 2015. Primary endpoints were the implementation and knowledge scores derived from the questionnaires. RESULTS: The implementation score from 488 questionnaires was excellent in 4%, good in 14%, average in 22%, poor in 32% and very poor in 28% of the cases. The knowledge score was excellent in 1%, good in 27%, moderate in 49%, poor in 18% and very poor in 5% of the cases. CONCLUSIONS: Current implementation and knowledge of the guideline on non-cardiac surgery in Europe needs to be improved.

Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery.

BACKGROUND: The noble gas helium induces pre- and postconditioning in animals and humans. Volatile anesthetics induce cardioprotection in humans undergoing coronary artery bypass graft (CABG) surgery. We hypothesized that helium induces pre- and postconditioning in CABG-patients, affecting signaling molecules protein kinase C-epsilon (PKC-ε), p38 mitogen activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK-1/2) and heat shock protein 27 (HSP-27) within cardiac tissue, and reducing postoperative troponin levels. METHODS: After ethical approval and informed consent, 125 elective patients undergoing CABG surgery were randomised into this prospective, placebo controlled, investigator blinded, parallel arm single-centre study. Helium preconditioning (3 × 5 min of 70 % helium and 30 % oxygen) was applied before aortic cross clamping; postconditioning (15 min of helium) was applied before release of the aortic cross clamp. Signaling molecules were measured in right atrial appendix specimens. Troponin-T was measured at 4, 12, 24 and 48 h postoperatively. RESULTS: Baseline characteristics of all groups were similar. Helium preconditioning did not significantly alter the primary outcome (molecular levels of kinases PKC-ε and HSP-27, ratio of activated p38 MAPK or ERK ½). Postoperative troponin T was 11 arbitrary units [5, 31; area-under-the-curve (interquartile range)] for controls, and no statistically significant changes were observed after helium preconditioning [He-pre: 11 (6, 18)], helium postconditioning [He-post: 11 (8, 15)], helium pre- and postconditioning [He-PP: 14 (6, 20)] and after sevoflurane preconditioning [APC: 12 (8, 24), p = 0.13]. No adverse effects related to study treatment were observed in this study. CONCLUSIONS: No effect was observed of helium preconditioning, postconditioning or the combination thereof on activation of p38 MAPK, ERK 1/2 or levels of HSP27 and PKC-ε in the human heart. Helium pre- and postconditioning did not affect postoperative troponin release in patients undergoing CABG surgery. Clinical trial number Dutch trial register ( http://www.trialregister.nl/ ) number NTR1226.

[Cognitive aid for emergencies in the OR--AMC bundle helps ensure that no steps are left out]. / Cognitieve leidraad voor noodgevallen op de OK--AMC-bundel helpt om geen stappen te vergeten.

Crucial management steps in unexpected perioperative emergencies are frequently omitted by OR teams because of the suboptimal performance of the brain under stress.A cognitive aid is a tool that will help care providers to perform and speed up all the necessary management steps of a critical event. We have created a Dutch adaption of the Stanford Emergency Manual, a bundle of cognitive aids to manage a number of life threatening emergencies in the operating theatre. The effectiveness of these cognitive aids has been demonstrated in simulated emergencies. Their use has furthermore, been standard practice in other high-risk industries for many years. Further research should therefore mainly focus on the implementation and optimisation of these tools.

In vivo desflurane preconditioning evokes dynamic alterations of metabolic proteins in the heart--proteomic insights strengthen the link between bioenergetics and cardioprotection.

BACKGROUND: The cardioprotective effect of anaesthetic preconditioning as measured by reduction of ischaemia-reperfusion (I/R) injury is a well described phenomenon. However little is known about the impact on the myocardial proteome. We therefore investigated proteome dynamics at different experimental time points of a preconditioning protocol. METHODS: Using an in vivo rat model of desflurane-induced preconditioning (DES-PC) cardiac tissue proteomes were analysed by a gel-based comparative approach. Treatment-dependent protein alterations were assessed by intra-group comparisons. Proteins were identified by mass-spectrometry. RESULTS: A total of 40 protein spots were altered during the 30-minutes lasting preconditioning protocol. None of the proteins was differentially regulated consistently at all experimental time points. Interestingly, 1) the repeated administration of desflurane mostly accounted for proteome alterations during DES-PC, 2) the majority of altered protein species showed a decrease in abundance, 3) these changes primarily affected metabolic proteins involved in NADH/NAD(+) redox balance, calcium homeostasis and acidosis and 4) protein alterations were not exclusively due to expression changes but also represented modifications of specific protein isoforms. CONCLUSION: DES-PC evokes dynamic alterations in the cardiac proteome which substantiate a tight regulation of bioenergetic proteins. Unique protein modifications may play a more important role in the preconditioning response.

Helium induces preconditioning in human endothelium in vivo.

AIMS: Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo. METHODS AND RESULTS: Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min. Endothelium-dependent and endothelium-independent responses were measured after cumulative dose-response infusion of acetylcholine and sodium nitroprusside, respectively, at baseline and after 15 min of reperfusion using strain-gauge, venous occlusion plethysmography. Helium preconditioning was applied by inhalation of helium (79% helium, 21% oxygen) either 15 min (helium early preconditioning [He-EPC]) or 24 h before I/R (helium late preconditioning). Additional measurements of He-EPC were done after blockade of endothelial nitric oxide synthase. Plasma levels of cytokines, adhesion molecules, and cell-derived microparticles were determined. Forearm I/R attenuated endothelium-dependent vasodilation (acetylcholine) with unaltered endothelium-independent response (sodium nitroprusside). Both He-EPC and helium late preconditioning attenuated I/R-induced endothelial dysfunction (max increase in forearm blood flow in response to acetylcholine after I/R was 180 ± 24% [mean ± SEM] without preconditioning, 573 ± 140% after He-EPC, and 290 ± 32% after helium late preconditioning). Protection of helium was comparable to ischemic preconditioning (max forearm blood flow 436 ± 38%) and was not abolished after endothelial nitric oxide synthase blockade. He-EPC did not affect plasma levels of cytokines, adhesion molecules, or microparticles. CONCLUSION: Helium is a nonanesthetic, nontoxic gas without hemodynamic side effects, which induces early and late preconditioning of human endothelium in vivo. Further studies have to investigate whether helium may be an instrument to induce endothelial preconditioning in patients with cardiovascular risk factors.

Helium-induced cardioprotection of healthy and hypertensive rat myocardium in vivo.

Helium protects healthy myocardium against ischemia/reperfusion injury by early and late preconditioning (EPC, LPC) and postconditioning (PostC). We investigated helium-induced PostC of the hypertensive heart and enhancement by addition of LPC and EPC. We also investigated involvement of signaling kinases glycogen synthase kinase 3 beta (GSK-3ß) and protein kinase C-epsilon (PKC-ε). To assess myocardial cell damage, we performed infarct size measurements in healthy Wistar Kyoto (WKY rats, n=8-9) and Spontaneous Hypertensive rats (SHR, n=8-9) subjected to 25 min ischemia and 120 min reperfusion. Rats inhaled 70% helium for 15 min after index ischemia (PostC), combined with 15 min helium 24h prior to index ischemia (LPC+PostC), a triple intervention with additional 3 short cycles of 5 min helium inhalation shortly before ischemia (EPC+LPC+PostC), or no further treatment. In WKY rats, PostC reduced infarct size from 46 ± 2% (mean ± S.E.M) in the control group to 29 ± 2%. LPC+PostC or EPC+LPC+PostC reduced infarct sizes to a similar extent (30 ± 3% and 32 ± 2% respectively). In SHR, EPC+LPC+PostC reduced infarct size from 53 ± 3% in control to 39 ± 3%, while PostC or LPC+PostC alone were not protective; infarct size 48 ± 4% and 44 ± 4%, respectively. Neither PostC in WKY rats nor EPC+LPC+PostC in SHR was associated with an increase in phosphorylation of GSK-3ß and PKC-ε after 15 min of reperfusion. Concluding, a triple intervention of helium conditioning results in cardioprotection in SHR, whereas a single intervention does not. In WKY rats, the triple intervention does not further augment protection. Helium conditioning is not associated with a mechanism involving GSK-3ß and PKC-ε.

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial).

BACKGROUND: Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome. METHODS/DESIGN: This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditioning is applied at the arm by 3 cycles of 5 minutes of ischemia and reperfusion. Primary endpoint is the incidence AF in the first 72 hours after surgery, detected using a Holter-monitor. Secondary endpoints include length-of-stay on the intensive care unit and in-hospital, and the occurrence of major adverse cardiovascular events at 30 days, 3 months and 1 year.Based on an expected incidence in the control group of 27%, 195 patients per group are needed to detect with 80% power a reduction by 45% following either pre- or postconditioning, while allowing for a 10% dropout and at an alpha of 0.05. With the combined intervention expected to be stronger, we need 75 patients in this group to detect a reduction in incidence of AF of 60%. DISCUSSION: The RICO-trial (the effect of Remote Ischemic Conditioning on atrial fibrillation and Outcome) is a randomized controlled multicenter trial, designed to investigate whether remote ischemic pre- and/or post-conditioning of the arm reduce the incidence of AF following CABG surgery. TRIAL REGISTRATION: ClinicalTrials.gov under NCT01107184.

Effect of a comprehensive surgical safety system on patient outcomes.

BACKGROUND: Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses. Most surgical safety interventions have focused on the operating room. Since more than half of all surgical errors occur outside the operating room, it is likely that a more substantial improvement in outcomes can be achieved by targeting the entire surgical pathway. METHODS: We examined the effects on patient outcomes of a comprehensive, multidisciplinary surgical safety checklist, including items such as medication, marking of the operative side, and use of postoperative instructions. The checklist was implemented in six hospitals with high standards of care. All complications occurring during admission were documented prospectively. We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist, while accounting for potential confounders. Similar data were collected from a control group of five hospitals. RESULTS: In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation, the total number of complications per 100 patients decreased from 27.3 (95% confidence interval [CI], 25.9 to 28.7) to 16.7 (95% CI, 15.6 to 17.9), for an absolute risk reduction of 10.6 (95% CI, 8.7 to 12.4). The proportion of patients with one or more complications decreased from 15.4% to 10.6% (P<0.001). In-hospital mortality decreased from 1.5% (95% CI, 1.2 to 2.0) to 0.8% (95% CI, 0.6 to 1.1), for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). Outcomes did not change in the control hospitals. CONCLUSIONS: Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high standard of care. (Netherlands Trial Register number, NTR1943.).

Patient safety during anaesthesia: incorporation of the WHO safe surgery guidelines into clinical practice.

PURPOSE OF REVIEW: WHO makes clear recommendations on how to improve patient safety during surgical procedures by using the WHO Surgical Safety Checklist. We will review the scientific basis of these recommendations and the practical problems encountered during introduction. RECENT FINDINGS: Perioperative severe complications and death are a major health issue in both developed and developing countries. Nearly half of these complications can be avoided. The systematic use of checklists and structured preprocedural and postprocedural briefings like a time-out procedure reduces perioperative morbidity and mortality. A broader use of checklists to cover the whole surgical pathway gives additional benefit, further reducing perioperative morbidity and mortality.Introducing patient safety procedures can be met with some resistance from healthcare workers and is helped by an organization-wide safety policy and a systematic approach. SUMMARY: There is sufficient scientific evidence to make the use of checklists and structured perioperative briefings and debriefings mandatory for the broad spectrum of operative procedures.

Drugs mediating myocardial protection.

The occurrence of myocardial ischaemia will result in either reversible or irreversible myocardial dysfunction. Even when revascularization is successful, some reperfusion injury may occur that transiently impairs myocardial function. Therefore, treatment should not only be directed towards prompt restoration of myocardial blood flow but measures should also be taken to prevent or alleviate the consequences of myocardial reperfusion injury. Over the years, various strategies have been developed. The present contribution reviews a number of these strategies focusing on pharmacological treatments that have been developed to address myocardial reperfusion injury.

Update on inhalational anaesthetics.

PURPOSE OF REVIEW: Inhalational anaesthetic agents are a cornerstone in modern anaesthetic practice. The currently used compounds are very effective and have a good safety profile. In addition, it has been demonstrated that they possess organ-protective properties that might provide an additional tool in the treatment or prevention of the consequences of organ ischaemia-reperfusion injury or both. The present review summarizes some of the most recent findings on this subject. RECENT FINDINGS: The mechanisms underlying the organ-protective effects of inhalational anaesthetics continue to be further unravelled. The main challenge, however, is to determine the clinical importance of these protective effects and their potential benefits for patients. Initial observations in cardiac surgery are encouraging, and the first clinical studies on other organ systems are being published. Noble gases share these organ-protective properties and may provide an additional tool for this purpose both in situations in which anaesthesia is needed (xenon) or in cases in which anaesthesia is not necessary (helium). SUMMARY: In the experimental setting, inhalational anaesthetics have protective effects against ischaemia-reperfusion injury. Initial perioperative data suggest that these effects may also result into clinically relevant improved organ function. However, further research will be needed to reveal whether these organ-protective properties will ultimately translate into an improved short-term and long-term postoperative outcome.