Rainer Hofmockel

Reversal of Rocuronium-induced Neuromuscular Blockade with Sugammadex in Pediatric and Adult Surgical Patients

Background:Sugammadex reverses neuromuscular blockade by chemical encapsulation of rocuronium. This phase IIIA study explored efficacy and safety of sugammadex in infants (28 days to 23 months), children (2–11 yr), adolescents (12–17 yr), and adults (18–65 yr). Methods:Anesthetized patients (American Society of Anesthesiologists class 1–2) received 0.6 mg/kg rocuronium and were randomized to receive sugammadex (0.5, 1.0, 2.0, or 4.0 mg/kg) or placebo at reappearance of T2. Neuromuscular monitoring was performed using acceleromyography. Primary endpoint was time from sugammadex/placebo administration to recovery of the train-of-four ratio to 0.9. Adverse events and electrocardiograms were recorded, and blood samples were collected for safety and determination of sugammadex and rocuronium plasma concentrations. Results:A dose-response relation was demonstrated in children (n = 22), adolescents (n = 28), and adults (n = 26), but not infants because of the small sample size (n = 8). After placebo, median recovery time of train-of-four to 0.9 was 21.0, 19.0, 23.4, and 28.5 min in infants, children, adolescents, and adults, respectively. After 2.0 mg/kg sugammadex train-of-four 0.9 was attained in 0.6, 1.2, 1.1, and 1.2 min, respectively. The sugammadex plasma concentrations were similar for the children, adolescent, and adult age groups across the dose range. Sugammadex was well tolerated: No reoccurrence of blockade, inadequate reversal, significant QT prolongation, or other abnormalities were observed. Conclusions:Sugammadex is a new reversal agent that rapidly, effectively, safely, and with similar recovery times reverses rocuronium-induced neuromuscular blockade in children, adolescents, adults, and the small number of infants studied.

Comparison of invasive and less-invasive techniques of cardiac output measurement under different haemodynamic conditions in a pig model.

Background and objective: Despite the introduction of various less‐invasive concepts of cardiac output measurement, pulmonary arterial thermodilution is still the most common measurement technique. Methods: This prospective controlled study was designed to compare different methods of cardiac output measurement simultaneously. Pulmonary arterial thermodilution, transpulmonary thermodilution (PiCCO™), trans‐oesophageal echo‐Doppler probe (HemoSonic™) and partial carbon dioxide rebreathing technique (NICO™ monitor) were evaluated against a peri‐aortic transit‐time flow‐probe as reference method in a clinically relevant animal model. After approval from the Local Ethics Committee on Animal Research, the investigations were conducted in nine anesthetized domestic pigs. Systemic haemodynamics were modulated systematically by the application of catecholamines, caval occlusion and exsanguination. Statistical analysis was performed with Bland‐Altman and linear regression. Results: A total of 366 paired cardiac output measurements were carried out at a reference cardiac output between 0.5 and 7 L min−1. The correlation coefficients for pulmonary arterial and transpulmonary thermodilution against reference were 0.93 and 0.95, for trans‐oesophageal Doppler and partial rebreathing technique 0.84 and 0.77. Pulmonary arterial thermodilution and transpulmonary thermodilution showed comparable bias and limits of agreement. Where HemoSonic™ showed an overestimation of cardiac output at a higher precision, NICO™ overestimated low and underestimated higher cardiac output values. Conclusions: Our data suggest that pulmonary arterial thermodilution and PiCCO™ may be interchangeably used for cardiac output measurement even under acute haemodynamic changes. The method described by Bland and Altman demonstrated an overestimation of cardiac output for both thermodilution methods. HemoSonic™ and NICO™ offer non‐invasive alternatives and complementary monitoring tools in numerous clinical situations. Trend monitoring and haemodynamic optimizing can be applied sufficiently, when absolute measures are judged critically in a clinical context. The use of the NICO™ system seems to be limited during acute circulatory changes.

Design and implementation of a control system reflecting the level of analgesia during general anesthesia.

Abstract Introduction: Measuring and ensuring an adequate level of analgesia in patients are of increasing interest in the area of automated drug delivery during general anesthesia. Therefore, the aim of this investigation was to develop a control system that may reflect the intraoperative analgesia value. Our hypothesis was that a feedback controller could be applied in clinical practice safely and at an adequate quality of analgesia. The purpose of this study was to evaluate the practical feasibility of such a system in a clinical setting. Methods: The control system for the level of analgesia described in this paper relies on a parameter combination of heart rate variability (HRV), heart rate (HR), and blood pressure (mean arterial pressure, MAP), which serve as input variables for an expert system. For this fuzzy system, the experience of the participating anesthesiologists was translated into a set of fuzzy rules. In a pilot trial, the control system for automated titration of remifentanil, a short-acting opioid, was tested combined with a closed-loop propofol infusion system for hypnosis. Ten adult patients (4 women, 6 men), aged 22–52 years (median, 45 years; range, 29–49 years), with an American Society of Anesthesiologists physical status class I or II and who were scheduled for elective trauma surgery in a supine position were enrolled in this prospective trial. The precision of the system was calculated using internationally defined performance parameters. Results: There was no human intervention necessary during the computer-controlled administration of propofol and remifentanil, and operating conditions were satisfactory in all patients. All patients assessed the quality of anesthesia as “good” to “very good”. Median performance error, median absolute performance error, and wobble for HR and MAP during maintenance of anesthesia were -8.98 (5.32), 10.08 (4.17), and 2.68 (1.29) and -4.51 (12.73), 13.63 (2.27), and 3.90 (2.08) [mean (SD)], respectively. Conclusion: The control system, reflecting the level of analgesia during general anesthesia designed and evaluated in this study, allows for a clinically practical, nearly fully automated infusion of an opioid during medium-length surgical procedures with acceptable technical requirements and an adequate precision.

Automatic drug delivery in anesthesia: From the beginning until now

The main goals of general anesthesia are adequate hypnosis, analgesia and maintenance of vital functions. For some special kinds of operations neuromuscular block is essential. Furthermore the patient safety and cost reduction as a case of minimized drug consumption and shortened postoperative recovery phases are part of the main issues to motivate automation in anesthesia. Since the beginning of the eighties engineers and physician are working together in the field of the development of closed-loop systems for drug delivery. The work gives a short overview about the development of the automation in drug delivery systems over the last years without the claim of completeness and expressed the much more vision.

Comparison of heart rate variability response in children undergoing elective endotracheal intubation with and without neuromuscular blockade: a randomized controlled trial

The routine use of neuromuscular blocking drugs (NMBD) for endotracheal intubation in children is the subject of much controversy. The analysis of heart rate variability (HRV) can reveal information about the functional state of the autonomic nervous system (ANS).

Automatic drug delivery in anesthesia - the design of an anesthesia assistant system ⋆

Abstract The main goals of general anesthesia are adequate hypnosis, analgesia and maintenance of vital functions. For a number of surgical procedures neuromuscular block is essential. Furthermore patient safety and cost reduction as minimized drug consumption and shortened post-operative recovery are main issues and motivation of automation efforts in anesthesia. Since the beginning of the eighties engineers and physician are working together in the field of the development of closed-loop systems for drug delivery. The work gives only a short overview about the development of the automation in drug delivery systems over the last years without the claim of completeness and expressed the much more vision. In the final stage, the designed control system, the so called “Rostocker assistant system for anesthesia control (RAN)” should be fitted out with the possibility to control four different drugs automatically. Currently the multiple-input multiple-output (MIMO) control of the depth of hypnosis and neuromuscular blockade is realized as well as the closed-loop control of deep hypotension. A pilot study for the closed-loop control of analgesia is currently running. The paper points some general remarks and the designed MIMO-system for controlling the depth of hypnosis and the neuromuscular blockade

Monitoring the stress response during general anaesthesia

The major objectives of anaesthetists in the operating theatre are to maintain the hypnosis, the relaxation, the analgesia, and the vital functions during the operation. The aim of this paper is to present an overview of new developments regarding monitoring and control of stress response during general anaesthesia. The applicability of the main parameters to monitor the adequacy of analgesia online will be discussed. Different models based on pharmacokinetic and pharmacodynamic effects in particular the opioid remifentanil and the hypnotic propofol were developed. The response of these anaesthetics on heart rate, different parameters of the heart rate variability and the bispectral index during induction of general anaesthesia were studied. Starting from these models, control strategies in analgesia have been discussed. The developed environment for the assistant system for anaesthesia at the University of Rostock is presented.

Sickle Cell Anemia: Conclusions from a Forensic Case Report of a Young African Woman Who Died After Anesthesia

A 20-year old African woman underwent anesthesia for interruption of an unwanted pregnancy. As a consequence of the anesthesia, she went into coma because of an as yet unknown and untested homozygotic state of sickle cell anemia. Her vital functions were maintained for more than 1 year by intensive medicine, but she died finally in multiorgan failure and aspiration pneumonia. Because of the complications under anesthesia and the missing preanesthetic test for hemoglobinopathy, autopsy was conducted in the forensic medicine department and not in the department of pathology. The sickle cell disease was diagnosed by electrophoresis of the blood, by molecular detection of mutation in the hemoglobin gene, as well as by postmortem light and electron microscopy. Sickle cells were found in capillaries of brain, liver, lung, bone marrow, and spleen. Electrophoretic analysis revealed 80.2% HbS in addition to 3.2% HbA2 and 16.6% HbF, whereas no HbA0 could be detected in blood, confirming the homozygosity of sickle cell anemia. Because of sickle cell crisis, occluded blood vessels, and severe brain cortex necrosis, the patient died in spite of reanimation and intensive medicine. This case demonstrates that it is still important to realize the possibility of this disease and diagnostic obstacles even in regions where its manifestation is not endemic, as in Northern and Central Europe.

A surgical technique for a terminal intracranial hypertension model in pigs

The life-threatening effects of intracranial hypertension on brain perfusion and cerebral metabolism are the subject of current research in different animal models. The purpose of this study was to describe an efficient, reliable and inexpensive surgical method for temporary elevation of intracranial pressure (ICP) in acutely instrumented pigs in a research setting. Therefore, a balloon catheter was inserted into the left lateral ventricle and an ICP sensor was placed in the parenchyma of the right cerebral hemisphere. Ten acutely instrumented pigs were studied while under deep terminal general anaesthesia. The step-by-step inflation of the intraventricular balloon allows one to achieve the desired ICP up to 46 mmHg and maintain it at this level. ICP values ranged from a median of 2 (1–2) mmHg to 43 (29–45) mmHg. To the authors’ knowledge, this is the first detailed description of a minimally invasive surgical technique for temporary ICP elevation in pigs via stepwise inflation of an intraventricular balloon.

A fuzzy system for regulation of the analgesic remifentanil during general anaesthesia

During the last decade, the research group Anaesthesia Control at the University of Rostock (Germany) developed an assistant system to support anaesthetists in the operating theatre. The main objectives during general anaesthesia are appropriate hypnosis, analgesia, relaxation, and stable vital functions. The development of our controllers for hypnosis and relaxation were completed in the last years. The systems were established in the clinical routine in the university hospital. Until now there exists no standard method to measure the state of analgesia or stress response of the patient. In this paper a fuzzy approach is presented to control the application of the analgesic drug remifentanil based on the expert knowledge of anaesthetists. The anaesthetists monitor vital parameters for example arterial blood pressure and heart rate to apply the analgesic drug. Additionally, the heart rate variability was involved as input for the fuzzy analgesia system, which is realized with two controllers, one active at a time. The main controller regulates the continuous rate of remifentanil based on the change in the mean arterial blood pressure, the heart rate and its standard deviation. The second controller calculates a bolus amount of remifentanil based on the absolute values of input parameters, if the heart rate is higher than 90 bpm. Both fuzzy controllers are Mamdani inference systems. The usual time regime for general anaesthesia as well as the minimal and maximal dosage of remifentanil are regarded in the system. The development options of the systems and the first results by controller simulations are discussed.