Gudrun Kunst - Academia.edu (original) (raw)
Papers by Gudrun Kunst
Anaesthesia
SummaryCardiac arrest in the peri‐operative period is rare but associated with significant morbid... more SummaryCardiac arrest in the peri‐operative period is rare but associated with significant morbidity and mortality. Current reporting systems do not capture many such events, so there is an incomplete understanding of incidence and outcomes. As peri‐operative cardiac arrest is rare, many hospitals may only see a small number of cases over long periods, and anaesthetists may not be involved in such cases for years. Therefore, a large‐scale prospective cohort is needed to gain a deep understanding of events leading up to cardiac arrest, management of the arrest itself and patient outcomes. Consequently, the Royal College of Anaesthetists chose peri‐operative cardiac arrest as the 7th National Audit Project topic. The study was open to all UK hospitals offering anaesthetic services and had a three‐part design. First, baseline surveys of all anaesthetic departments and anaesthetists in the UK, examining respondents' prior peri‐operative cardiac arrest experience, resuscitation train...
Trials, 2022
Background High-flow nasal therapy is a non-invasive form of respiratory support that delivers lo... more Background High-flow nasal therapy is a non-invasive form of respiratory support that delivers low-level, flow dependent positive airway pressure. The device can be better tolerated by patients than alternatives such as continuous positive airway pressure. The primary objective is to determine if prophylactic high-flow nasal therapy after tracheal extubation can result in an increase in the number of days alive and at home within the first 90 days after surgery, when compared with standard oxygen therapy. The co-primary objective is to estimate the incremental cost-effectiveness and cost-utility of high-flow nasal therapy vs standard oxygen therapy at 90 days, from the view-point of the public sector, the health service and patients. Methods This is an adaptive, multicentre, international parallel-group, randomised controlled trial with embedded cost-effectiveness analysis comparing the use of high-flow nasal therapy with control in patients at high risk of respiratory complications...
British Journal of Anaesthesia, 2022
Regional Anesthesia & Pain Medicine, 1995
Trials, 2021
Background Recent experimental evidence shows that sevoflurane can reduce the inflammatory respon... more Background Recent experimental evidence shows that sevoflurane can reduce the inflammatory response during cardiac surgery with cardiopulmonary bypass. However, this observation so far has not been assessed in an adequately powered randomized controlled trial. Methods We plan to include one hundred patients undergoing elective coronary artery bypass graft with cardiopulmonary bypass who will be randomized to receive either volatile anesthetics during cardiopulmonary bypass or total intravenous anesthesia. The primary endpoint of the study is to assess the inflammatory response during cardiopulmonary bypass by measuring PMN-elastase serum levels. Secondary endpoints include serum levels of other pro-inflammatory markers (IL-1β, IL-6, IL-8, TNFα), anti-inflammatory cytokines (TGFβ and IL-10), and microRNA expression in peripheral blood to achieve possible epigenetic mechanisms in this process. In addition clinical endpoints such as presence of major complications in the postoperative ...
Journal of Clinical Medicine, 2021
Acute kidney injury (AKI) is common after cardiac surgery. To date, there are no specific pharmac... more Acute kidney injury (AKI) is common after cardiac surgery. To date, there are no specific pharmacological therapies. In this review, we summarise the existing evidence for prevention and management of cardiac surgery-associated AKI and outline areas for future research. Preoperatively, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be withheld and nephrotoxins should be avoided to reduce the risk. Intraoperative strategies include goal-directed therapy with individualised blood pressure management and administration of balanced fluids, the use of circuits with biocompatible coatings, application of minimally invasive extracorporeal circulation, and lung protective ventilation. Postoperative management should be in accordance with current KDIGO AKI recommendations.
BMJ Open, 2020
IntroductionAcute kidney injury (AKI) is a frequent complication after cardiac surgery with adver... more IntroductionAcute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial.Methods and analysisWe plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to...
Journal of Cardiothoracic and Vascular Anesthesia, 2021
Neurocognitive dysfunction after cardiac surgery can present with diverse clinical phenotypes, wh... more Neurocognitive dysfunction after cardiac surgery can present with diverse clinical phenotypes, which include postoperative delirium, postoperative cognitive dysfunction, and stroke, and it presents a significant healthcare burden for both patients and providers. Neurologic monitoring during cardiac surgery includes several modalities assessing cerebral perfusion and oxygenation (near-infrared spectroscopy, transcranial Doppler and jugular venous bulb saturation monitoring) and those that measure cerebral function (processed and unprocessed electroencephalogram), reflecting an absence of a single, definitive neuromonitor. This narrative review briefly describes the technologic basis of these neuromonitoring modalities, before exploring their use in clinical practice, both as tools to predict neurocognitive dysfunction, and with a bundle of interventions designed to optimize cerebral oxygen supply, with the aim of reducing postoperative delirium and cognitive dysfunction following cardiac surgery.
Journal of Cardiothoracic and Vascular Anesthesia, 2020
Journal of Cardiothoracic and Vascular Anesthesia, 2019
European Journal of Cardio-Thoracic Surgery, 2019
Anesthesia & Analgesia, 2018
BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse... more BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considere...
Journal of Cardiothoracic and Vascular Anesthesia, 2017
Contemporary clinical trials, Aug 19, 2017
There is initial evidence that the use of volatile anesthetics can reduce the postoperative relea... more There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small Randomized Controlled Trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. Tertiary and University hospitals. Patients (n=10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-d...
Basic research in cardiology, 2015
Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagn... more Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagnosis of early, and recurrent, acute myocardial infarction. Cardiac myosin-binding protein C (cMyC) is a similarly cardiac-restricted protein that may have different release/clearance kinetics. Using novel antibodies raised against the cardiac-specific N-terminus of cMyC, we used confocal microscopy, immunoblotting and immunoassay to document its location and release. In rodents, we demonstrate rapid release of cMyC using in vitro and in vivo models of acute myocardial infarction. In patients, with ST elevation myocardial infarction (STEMI, n = 20), undergoing therapeutic ablation of septal hypertrophy (TASH, n = 20) or having coronary artery bypass surgery (CABG, n = 20), serum was collected prospectively and frequently. cMyC appears in the serum as full-length and fragmented protein. Compared to cTnT measured using a contemporary high-sensitivity commercial assay, cMyC peaks earlier (ST...
Journal of Cardiothoracic and Vascular Anesthesia, 2000
To determine sex hormone-binding globulin (SHBG) and osteocalcin (OC) levels in patients undergoi... more To determine sex hormone-binding globulin (SHBG) and osteocalcin (OC) levels in patients undergoing coronary artery bypass graft surgery to clarify the status of peripheral thyroid metabolism and to correlate SHBG and OC with thyroid hormones and adverse postoperative events. Prospective study. University medical center. Fifty randomly selected patients undergoing coronary artery bypass graft surgery. On the morning of surgery before induction of anesthesia; 30 minutes after cross-clamping of the aorta; 2 hours and 6 hours after aortic cross-clamp removal; and on the first, second, third, and seventh postoperative mornings, blood samples were drawn and analyzed for OC, SHBG, triiodothyronine (tT3), free T3 (fT3), thyroxine (tT4), free T4 (fT4), thyroid-stimulating hormone, and thyroid-binding globulin. Adverse postoperative events were recorded. Mean tT3 and fT3 decreased on average by 35% and 18% but remained within the normal range perioperatively. Similarly, mean SHBG and OC remained within the normal range. More than half of the patients investigated (60%) had OC concentrations below the normal range. Patients with pathologically decreased tT3 (n = 6) and tT4 (n = 16) intraoperatively and postoperatively had SHBG and OC concentrations similar to those in patients with normal tT3 and tT4 levels. Patients with postoperative complications had significantly lower OC levels preoperatively and on the first postoperative morning than those with an uneventful postoperative recovery. Despite significant intraoperative and postoperative decreases in levels of thyroid hormones, low T3 syndrome was rare in this patient population. Unchanged concentrations of SHBG and OC in patients with pathologically decreased tT3 or tT4 suggest normal local thyroid exposure at the tissue sites in these patients. OC may act as a predictor for postoperative outcome.
Clinical Research in Cardiology, 2011
Circulation Research, 2006
Myosin binding protein-C (MyBP-C) is a poorly understood component of the thick filament in stria... more Myosin binding protein-C (MyBP-C) is a poorly understood component of the thick filament in striated muscle sarcomeres. Its C terminus binds tightly to myosin, whereas the N terminus contains binding sites for myosin S2 and possibly for the thin filament. To study the role of the N-terminal domains of cardiac MyBP-C (cMyBP-C), we added human N-terminal peptide fragments to human and rodent skinned ventricular myocytes. At concentrations >10 μmol/L, the N-terminal C0C2 peptide activated force production in the absence of calcium (pCa 9). Force at the optimal concentration (80 μmol/L) of C0C2 was ≈60% of that in maximal Ca 2+ (pCa 4.5), but the rate constant of tension redevelopment ( k tr ) matched or exceeded (by up to 80%) that produced by Ca 2+ alone. Experiments using different N-terminal peptides suggested that this activating effect of C0C2 resulted from binding by the pro/ala-rich C0-C1 linker region, rather than the terminal C0 domain. At a lower concentration (1 μmol/L), ...
Anaesthesia
SummaryCardiac arrest in the peri‐operative period is rare but associated with significant morbid... more SummaryCardiac arrest in the peri‐operative period is rare but associated with significant morbidity and mortality. Current reporting systems do not capture many such events, so there is an incomplete understanding of incidence and outcomes. As peri‐operative cardiac arrest is rare, many hospitals may only see a small number of cases over long periods, and anaesthetists may not be involved in such cases for years. Therefore, a large‐scale prospective cohort is needed to gain a deep understanding of events leading up to cardiac arrest, management of the arrest itself and patient outcomes. Consequently, the Royal College of Anaesthetists chose peri‐operative cardiac arrest as the 7th National Audit Project topic. The study was open to all UK hospitals offering anaesthetic services and had a three‐part design. First, baseline surveys of all anaesthetic departments and anaesthetists in the UK, examining respondents' prior peri‐operative cardiac arrest experience, resuscitation train...
Trials, 2022
Background High-flow nasal therapy is a non-invasive form of respiratory support that delivers lo... more Background High-flow nasal therapy is a non-invasive form of respiratory support that delivers low-level, flow dependent positive airway pressure. The device can be better tolerated by patients than alternatives such as continuous positive airway pressure. The primary objective is to determine if prophylactic high-flow nasal therapy after tracheal extubation can result in an increase in the number of days alive and at home within the first 90 days after surgery, when compared with standard oxygen therapy. The co-primary objective is to estimate the incremental cost-effectiveness and cost-utility of high-flow nasal therapy vs standard oxygen therapy at 90 days, from the view-point of the public sector, the health service and patients. Methods This is an adaptive, multicentre, international parallel-group, randomised controlled trial with embedded cost-effectiveness analysis comparing the use of high-flow nasal therapy with control in patients at high risk of respiratory complications...
British Journal of Anaesthesia, 2022
Regional Anesthesia & Pain Medicine, 1995
Trials, 2021
Background Recent experimental evidence shows that sevoflurane can reduce the inflammatory respon... more Background Recent experimental evidence shows that sevoflurane can reduce the inflammatory response during cardiac surgery with cardiopulmonary bypass. However, this observation so far has not been assessed in an adequately powered randomized controlled trial. Methods We plan to include one hundred patients undergoing elective coronary artery bypass graft with cardiopulmonary bypass who will be randomized to receive either volatile anesthetics during cardiopulmonary bypass or total intravenous anesthesia. The primary endpoint of the study is to assess the inflammatory response during cardiopulmonary bypass by measuring PMN-elastase serum levels. Secondary endpoints include serum levels of other pro-inflammatory markers (IL-1β, IL-6, IL-8, TNFα), anti-inflammatory cytokines (TGFβ and IL-10), and microRNA expression in peripheral blood to achieve possible epigenetic mechanisms in this process. In addition clinical endpoints such as presence of major complications in the postoperative ...
Journal of Clinical Medicine, 2021
Acute kidney injury (AKI) is common after cardiac surgery. To date, there are no specific pharmac... more Acute kidney injury (AKI) is common after cardiac surgery. To date, there are no specific pharmacological therapies. In this review, we summarise the existing evidence for prevention and management of cardiac surgery-associated AKI and outline areas for future research. Preoperatively, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be withheld and nephrotoxins should be avoided to reduce the risk. Intraoperative strategies include goal-directed therapy with individualised blood pressure management and administration of balanced fluids, the use of circuits with biocompatible coatings, application of minimally invasive extracorporeal circulation, and lung protective ventilation. Postoperative management should be in accordance with current KDIGO AKI recommendations.
BMJ Open, 2020
IntroductionAcute kidney injury (AKI) is a frequent complication after cardiac surgery with adver... more IntroductionAcute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial.Methods and analysisWe plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to...
Journal of Cardiothoracic and Vascular Anesthesia, 2021
Neurocognitive dysfunction after cardiac surgery can present with diverse clinical phenotypes, wh... more Neurocognitive dysfunction after cardiac surgery can present with diverse clinical phenotypes, which include postoperative delirium, postoperative cognitive dysfunction, and stroke, and it presents a significant healthcare burden for both patients and providers. Neurologic monitoring during cardiac surgery includes several modalities assessing cerebral perfusion and oxygenation (near-infrared spectroscopy, transcranial Doppler and jugular venous bulb saturation monitoring) and those that measure cerebral function (processed and unprocessed electroencephalogram), reflecting an absence of a single, definitive neuromonitor. This narrative review briefly describes the technologic basis of these neuromonitoring modalities, before exploring their use in clinical practice, both as tools to predict neurocognitive dysfunction, and with a bundle of interventions designed to optimize cerebral oxygen supply, with the aim of reducing postoperative delirium and cognitive dysfunction following cardiac surgery.
Journal of Cardiothoracic and Vascular Anesthesia, 2020
Journal of Cardiothoracic and Vascular Anesthesia, 2019
European Journal of Cardio-Thoracic Surgery, 2019
Anesthesia & Analgesia, 2018
BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse... more BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considere...
Journal of Cardiothoracic and Vascular Anesthesia, 2017
Contemporary clinical trials, Aug 19, 2017
There is initial evidence that the use of volatile anesthetics can reduce the postoperative relea... more There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small Randomized Controlled Trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. Tertiary and University hospitals. Patients (n=10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-d...
Basic research in cardiology, 2015
Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagn... more Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagnosis of early, and recurrent, acute myocardial infarction. Cardiac myosin-binding protein C (cMyC) is a similarly cardiac-restricted protein that may have different release/clearance kinetics. Using novel antibodies raised against the cardiac-specific N-terminus of cMyC, we used confocal microscopy, immunoblotting and immunoassay to document its location and release. In rodents, we demonstrate rapid release of cMyC using in vitro and in vivo models of acute myocardial infarction. In patients, with ST elevation myocardial infarction (STEMI, n = 20), undergoing therapeutic ablation of septal hypertrophy (TASH, n = 20) or having coronary artery bypass surgery (CABG, n = 20), serum was collected prospectively and frequently. cMyC appears in the serum as full-length and fragmented protein. Compared to cTnT measured using a contemporary high-sensitivity commercial assay, cMyC peaks earlier (ST...
Journal of Cardiothoracic and Vascular Anesthesia, 2000
To determine sex hormone-binding globulin (SHBG) and osteocalcin (OC) levels in patients undergoi... more To determine sex hormone-binding globulin (SHBG) and osteocalcin (OC) levels in patients undergoing coronary artery bypass graft surgery to clarify the status of peripheral thyroid metabolism and to correlate SHBG and OC with thyroid hormones and adverse postoperative events. Prospective study. University medical center. Fifty randomly selected patients undergoing coronary artery bypass graft surgery. On the morning of surgery before induction of anesthesia; 30 minutes after cross-clamping of the aorta; 2 hours and 6 hours after aortic cross-clamp removal; and on the first, second, third, and seventh postoperative mornings, blood samples were drawn and analyzed for OC, SHBG, triiodothyronine (tT3), free T3 (fT3), thyroxine (tT4), free T4 (fT4), thyroid-stimulating hormone, and thyroid-binding globulin. Adverse postoperative events were recorded. Mean tT3 and fT3 decreased on average by 35% and 18% but remained within the normal range perioperatively. Similarly, mean SHBG and OC remained within the normal range. More than half of the patients investigated (60%) had OC concentrations below the normal range. Patients with pathologically decreased tT3 (n = 6) and tT4 (n = 16) intraoperatively and postoperatively had SHBG and OC concentrations similar to those in patients with normal tT3 and tT4 levels. Patients with postoperative complications had significantly lower OC levels preoperatively and on the first postoperative morning than those with an uneventful postoperative recovery. Despite significant intraoperative and postoperative decreases in levels of thyroid hormones, low T3 syndrome was rare in this patient population. Unchanged concentrations of SHBG and OC in patients with pathologically decreased tT3 or tT4 suggest normal local thyroid exposure at the tissue sites in these patients. OC may act as a predictor for postoperative outcome.
Clinical Research in Cardiology, 2011
Circulation Research, 2006
Myosin binding protein-C (MyBP-C) is a poorly understood component of the thick filament in stria... more Myosin binding protein-C (MyBP-C) is a poorly understood component of the thick filament in striated muscle sarcomeres. Its C terminus binds tightly to myosin, whereas the N terminus contains binding sites for myosin S2 and possibly for the thin filament. To study the role of the N-terminal domains of cardiac MyBP-C (cMyBP-C), we added human N-terminal peptide fragments to human and rodent skinned ventricular myocytes. At concentrations >10 μmol/L, the N-terminal C0C2 peptide activated force production in the absence of calcium (pCa 9). Force at the optimal concentration (80 μmol/L) of C0C2 was ≈60% of that in maximal Ca 2+ (pCa 4.5), but the rate constant of tension redevelopment ( k tr ) matched or exceeded (by up to 80%) that produced by Ca 2+ alone. Experiments using different N-terminal peptides suggested that this activating effect of C0C2 resulted from binding by the pro/ala-rich C0-C1 linker region, rather than the terminal C0 domain. At a lower concentration (1 μmol/L), ...