Population kinetic/pharmacodynamic modelling of the haemodynamic effects of cafedrine/theodrenaline (Akrinor) under general anaesthesia.

AIMS: The 20:1 combination of cafedrine and theodrenaline (C/T) is widely used in Germany for the treatment of arterial hypotension. Since there is little knowledge about the impact of covariates on the effect, the aim was to develop a kinetic/pharmacodynamic covariate model describing mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) for 30 min after the administration of C/T. METHODS: Data of patients receiving C/T from the HYPOTENS study (NCT02893241, DRKS00010740) were analysed using nonlinear mixed-effects modelling techniques. RESULTS: Overall, 16 579 measurements from 315 patients were analysed. The combination of two kinetic compartments and a delayed effect model, coupled with distinct Emax models for HR, SBP and DBP, described the data best. The model included age, sex, body mass index (BMI), antihypertensive medication, American Society of Anaesthesiologists (ASA) physical status classification grade, baseline SBP at the time of hypotension and pre-surgery HR as covariates (all P < .001). A higher baseline SBP led to a lower absolute increase in MAP. Patients with higher age, higher BMI and lower ASA grade showed smaller increases in MAP. The initial increase was similar for male and female patients. The long-term effect was higher in women. Concomitant antihypertensive medication caused a delayed effect and a lower maximum MAP. The HR increased only slightly (median increase 2.6 bpm, P < .001). CONCLUSIONS: Seven covariates with an impact on the effect of C/T could be identified. The results will enable physicians to optimize the dose with respect to individual patients.

[Regional Anaesthesia in the Prehospital Setting]. / Regionalanästhesie in der präklinischen Notfallmedizin.

Pain is often the main symptom in trauma patients. Although peripheral nerve blocks (PNB) provide fast, safe, and adequate analgesia, they are currently only rarely used outside the perioperative setting. In Germany, intravenous analgesia with non-opioid analgesics (NOPA) and strong opioids is the main treatment concept for prehospital pain. However, the use of highly potent opioids can be associated with significant side effects, especially in emergency patients. Therefore, PNBs are used in many hospitals for the treatment of perioperative pain. As with perioperative use, the advantages of early PNB in the prehospital analgesic treatment of trauma patients are obvious, especially for elderly and multimorbid patients. Early prehospital PNB can also facilitate the reduction of dislocated fractures or dislocated joints as well as the technical rescue of trauma patients. Common geriatric fractures, such as proximal femur or humerus fractures, can be treated appropriately and adequately with PNB.In this article, we show which PNB procedures can be useful in prehospital patient care and which requirements should be met for their safe use. We also present a concept for assessing whether and to what extent the prehospital use of PNB is indicated and appropriate. The aim of this article is to draw attention to PNB as a possible part of prehospital care concepts for trauma patients and to discuss its prehospital use.

[Focused Transthoracic Echocardiography in the Perioperative Setting]. / Die fokussierte transthorakale Echokardiografie in der perioperativen Versorgung.

With focused transthoracic echocardiography (TTE) we rapidly and non-invasively receive up-to-date information on a patient's hemodynamic status. These can subsequently influence our therapy and thus our risk management. Postoperatively, TTE has proved its worth as an examination method in the recovery room and in the intensive care unit to promptly diagnose life-threatening causes of circulatory depression. Acute pathology such as a pericardial tamponade or fulminant pulmonary artery embolism can be detected quickly and thus possibly time-consuming transport to a CT can be avoided. Also, preoperatively, the use of TTE may be useful for assessing volume status, pumping function, or hemodynamically relevant heart defects. Especially in surgical interventions with a high perioperative risk of complications, these findings can be incorporated into a goal-directed therapy. Corresponding algorithms for enhanced hemodynamic monitoring and volume management already exist in many areas, but they are often not consistently implemented in the processes of their own clinic. In this article, we demonstrate the utility and relevance of TTE hemodynamic evaluation at every stage of patient care. We also present a possible algorithm for the care of critically ill patients, based on the main transthoracic and hemodynamic measurements. It is intended to provide assistance in the meaningful use of TTE in everyday clinical practice and especially for those on on-call duty.

Recovery and prediction of postoperative muscle power - is it still a problem?

BACKGROUND: In the postoperative period, immediate recovery of muscular power is essential for patient safety, but this can be affected by anaesthetic drugs, opioids and neuromuscular blocking agents (NMBA). In this cohort study, we evaluated anaesthetic and patient-related factors contributing to reduced postoperative muscle power and pulse oximetric saturation. METHODS: We prospectively observed 615 patients scheduled for minor surgery. Premedication, general anaesthesia and respiratory settings were standardized according to standard operating procedures (SOP). If NMBAs were administered, neuromuscular monitoring was applied to establish a Train of four (TOF)-Ratio of >0.9 before extubation. After achieving a modified fast track score > 10 at 4 time points up to 2 h postoperatively, we measured pulse oximetric saturation and also static and dynamic muscle power, using a high precision digital force gauge. Loss of muscle power in relation to the individual preoperative baseline value was analysed in relation to patient and anaesthesia-related factors using the T-test, simple and multiple stepwise regression analysis. RESULTS: Despite having achieved a TOF ratio of >0.9 a decrease in postoperative muscle power was detectable in most patients and correlated with reduced postoperative pulse oximetric saturation. Independent contributing factors were use of neuromuscular blocking agents (p < 0.001), female gender (p = 0.001), TIVA (p = 0.018) and duration of anaesthesia >120 min (p = 0.019). CONCLUSION: Significant loss of muscle power and reduced pulse oximetric saturation are often present despite a TOF-Ratio > 0.9. Gender differences are also significant. A modified fast track score > 10 failed to predict recovery of muscle power in most patients. TRIAL REGISTRATION: German Clinical Trial Register DRKS-ID DRKS00006032 ; Registered: 2014/04/03.

A randomized open label, parallel-group study to evaluate the hemodynamic effects of Cafedrine/Theodrenaline vs Noradrenaline in the treatment of intraoperative hypotension after induction of general anesthesia: the "HERO" study design and rationale.

OBJECTIVE: Intraoperative arterial hypotension (IOH) is associated with poor patient outcome. This study aims to compare the hemodynamic effects of Cafedrine/Theodrenaline (C/T) and Noradrenaline (NA) for the treatment of hypotension in patients who develop IOH after anesthesia induction. RESEARCH DESIGN AND METHODS: This is a national, randomized, parallel-group, multicenter, and open-label study. Adult patients (≥50 years, ASA-classification III-IV) who undergo elective surgery will be included. When IOH (MAP <70 mmHg) develops, C/T or NA will be given as a bolus injection ("bolus phase", 0-20 min after initial application) and subsequently as continuous infusion ("infusion phase", 21-40 min after initial application) to achieve MAP = 90 mmHg. Hemodynamic data are captured in real time by advanced hemodynamic monitoring. RESULTS: Primary endpoints, i.e. the treatment-related difference in average mean arterial pressure (MAP) during the "infusion phase" and the treatment-related difference in average cardiac index during the "bolus phase" are assessed (fixed-sequence method). Non-inferiority of C/T compared to NA in achieving 90 mmHg (MAP) when applied as continuous infusion is hypothesized. In addition, superiority of C/T over NA, applied as bolus injection, in increasing cardiac index is postulated. It is estimated that 172 patients are required to establish statistical significance with a power of 90%. After adjusting for ineligibility and dropout rate, 220 patients will be screened. CONCLUSION: This clinical trial will yield evidence for marketing authorization of C/T applied as continuous infusion. Additionally, the effects of C/T compared to NA on cardiac index will be assessed. First results of the "HERO"-study are expected in 2024. DRKS identifier: DRKS00028589. EudraCT identifier: 2021-001954-76.

Intraoperative hypotension when using hypotension prediction index software during major noncardiac surgery: a European multicentre prospective observational registry (EU HYPROTECT).

Background: Intraoperative hypotension is associated with organ injury. Current intraoperative arterial pressure management is mainly reactive. Predictive haemodynamic monitoring may help clinicians reduce intraoperative hypotension. The Acumen™ Hypotension Prediction Index software (HPI-software) (Edwards Lifesciences, Irvine, CA, USA) was developed to predict hypotension. We built up the European multicentre, prospective, observational EU HYPROTECT Registry to describe the incidence, duration, and severity of intraoperative hypotension when using HPI-software monitoring in patients having noncardiac surgery. Methods: We enrolled 749 patients having elective major noncardiac surgery in 12 medical centres in five European countries. Patients were monitored using the HPI-software. We quantified hypotension using the time-weighted average MAP <65 mm Hg (primary endpoint), the proportion of patients with at least one ≥1 min episode of a MAP <65 mm Hg, the number of ≥1 min episodes of a MAP <65 mm Hg, and duration patients spent below a MAP of 65 mm Hg. Results: We included 702 patients in the final analysis. The median time-weighted average MAP <65 mm Hg was 0.03 (0.00-0.20) mm Hg. In addition, 285 patients (41%) had no ≥1 min episode of a MAP <65 mm Hg; 417 patients (59%) had at least one. The median number of ≥1 min episodes of a MAP <65 mm Hg was 1 (0-3). Patients spent a median of 2 (0-9) min below a MAP of 65 mm Hg. Conclusions: The median time-weighted average MAP <65 mm Hg was very low in patients in this registry. This suggests that using HPI-software monitoring may help reduce the duration and severity of intraoperative hypotension in patients having noncardiac surgery.