Negative drift of sedation depth in critically ill patients receiving constant minimum alveolar concentration of isoflurane, sevoflurane, or desflurane: a randomized controlled trial.

BACKGROUND: Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC's reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0-awake N_Index 100), might drift downward over time despite constant MAC values. METHODS: This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups. RESULTS: Thirty patients were recruited (female/male: 10/20, age 64 ± 11, Simplified Acute Physiology Score II 30 ± 10). In the first 24 h, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58 ± 0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index = 43 - 0.7·h (R2 = 0.76), showing a strong negative correlation between sedation's duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43-0.9, 45-0.8, and 43-0.4·h for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group. CONCLUSIONS: Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration. TRIAL REGISTRATION: NCT03860129.

Pain in children undergoing tonsillotomy with alternating ibuprofen and paracetamol - a prospective observational study.

BACKGROUND: The optimal pain therapy for children undergoing tonsillotomy remains unknown. Our aim was to evaluate a standard pain therapy including the alternating application of ibuprofen and paracetamol. METHODS: Pain intensity of 81 in-patients after tonsillotomy aged 2-12 years was evaluated three times daily (mean observation 3.85 days) using the Children's and Infants' Postoperative Pain Scale (CHIPPS) in children <5 years, or with the Faces Pain Scale-Revised (FPS-R) in older children. Parents completed the Parents' Postoperative Pain Measure (PPPM-D) in addition. Exceeding the cut-off value in one of the scores implied the indication for an opioid rescue medication (RM). Endpoints were number of children with indication for the RM, course of pain, concordance between pain scales, and adverse events. RESULTS: Overall, 45.7% of children needed the RM either in the recovery room or on the ward. The rate of children having an indication for RM on the ward was 30.9%. The highest proportion of affected children was identified on the day of surgery (32.1%). Most indications were detected with the PPPM-D only. A comparison with an earlier study showed less affected children compared to ibuprofen monotherapy on the day of surgery and the first postoperative day. Eleven children (13.6%) developed fever. CONCLUSION: Although our pain therapy concept was effective from postoperative day 1 onwards, it needs improvement for the day of surgery. The overall concordance between the PPPM-D and CHIPPS or FPS-R was low. Fever might be a confounder for the pain intensity measurement with the PPPM-D.

High dose ibuprofen as a monotherapy on an around-the-clock basis fails to control pain in children undergoing tonsil surgery: a prospective observational cohort study.

PURPOSE: The optimal pain management concept in children after tonsil surgery is controversial. Ibuprofen on an "around-the-clock" basis has been suggested to control postoperative pain sufficiently. Therefore, we established a standard scheme with weight-adapted recommended maximum ibuprofen dose. A reliable assessment of pain intensity can be performed with the Children's and Infants' Postoperative Pain Scale (CHIPPS) in children < 5 years, or with the Faces Pain Scale-Revised (FPS-R) in children aged ≥ 5 years. The Parents' Postoperative Pain Measure (PPPM-D) may be a useful tool for both age groups. We hypothesized that not more than 30% of the children would need an opioid rescue medication during their in-hospital stay and analyzed the consistency of the PPPM-D with other pain scales. METHODS: We included 158 in-patients aged 2-12 years. Ibuprofen was orally administered every 8 h. Three times daily, pain scores were assessed by CHIPPS or FPS-R, respectively. The PPPM-D was used in all children. Exceeding the cut-off value in one of the tools was regarded as relevant pain. RESULTS: A rescue medication was needed in 82.1% of children after tonsillectomy and 51.3% of children after tonsillotomy (P < 0.001). The cut-off value for relevant pain was mostly exceeded in the PPPM-D, but its overall concordance to the reference scales was low. CONCLUSION: High-dose ibuprofen "around-the-clock" is insufficient to control pain in children after tonsil surgery. Research is needed to find an optimal schema for management and assessment of postoperative pain.

Photoacoustic gas monitoring for anesthetic gas pollution measurements and its cross-sensitivity to alcoholic disinfectants.

BACKGROUND: Real-time photoacoustic gas monitoring is used for personnel exposure and environmental monitoring, but its accuracy varies when organic solvents such as alcohol contaminate measurements. This is problematic for anesthetic gas measurements in hospitals, because most disinfectants contain alcohol, which could lead to false-high gas concentrations. We investigated the cross-sensitivities of the photoacoustic gas monitor Innova 1412 (AirTech Instruments, LumaSense, Denmark) against alcohols and alcoholic disinfectants while measuring sevoflurane, desflurane and isoflurane in a laboratory and in hospital during surgery. METHODS: 25 mL ethyl alcohol was distributed on a hotplate. An optical filter for isoflurane was used and the gas monitor measured the 'isoflurane' concentration for five minutes with the measuring probe fixed 30 cm above the hotplate. Then, 5 mL isoflurane was added vaporized via an Anesthetic Conserving Device (Sedana Medical, Uppsala, Sweden). After one-hour measurement, 25 mL isopropyl alcohol, N-propanol, and two alcoholic disinfectants were subsequently added, each in combination with 5 mL isoflurane. The same experiment was in turn performed for sevoflurane and desflurane. The practical impact of the cross-sensitivity was investigated on abdominal surgeons who were exposed intraoperatively to sevoflurane. A new approach to overcome the gas monitor's cross-sensitivity is presented. RESULTS: Cross-sensitivity was observed for all alcohols and its strength characteristic for the tested agent. Simultaneous uses of anesthetic gases and alcohols increased the concentrations and the recovery times significantly, especially while sevoflurane was utilized. Intraoperative measurements revealed mean and maximum sevoflurane concentrations of 0.61 ± 0.26 ppm and 15.27 ± 14.62 ppm. We replaced the cross-sensitivity peaks with the 10th percentile baseline of the anesthetic gas concentration. This reduced mean and maximum concentrations significantly by 37% (p < 0.001) and 86% (p < 0.001), respectively. CONCLUSION: Photoacoustic gas monitoring is useful to detect lowest anesthetic gases concentrations, but cross-sensitivity caused one third falsely high measured mean gas concentration. One possibility to eliminate these peaks is the recovery time-based baseline approach. Caution should be taken while measuring sevoflurane, since marked cross-sensitivity peaks are to be expected.

Comparison of perioperative strategies in ICD patients: The perioperative ICD management study (PIM study).

BACKGROUND: The prevalence of patients with implanted cardioverter defibrillators (ICDs) and the frequency of surgery on these patients are steadily on the rise. Guidelines recommend preoperative ICD reprogramming, although this is sometimes difficult in clinical practice. Placing a magnet on the ICD is a practical alternative and even no inactivation is possible in selected cases. METHODS: In this prospective observational study, we compared different perioperative ICD management strategies depending on the location of the surgery and the type of electrocautery used. Patients undergoing surgery above the umbilicus with monopolar electrocautery had their ICD therapy inactivated by reprogramming. When surgery below the navel or surgery above the navel with bipolar electrocautery was completed, ICD inactivation was performed using a magnet. No inactivation was performed on patients undergoing lower extremity surgery with bipolar electrocautery. Only ICD patients who were not pacemaker dependent were enrolled. After surgery, the ICDs were assessed regarding documented arrhythmias and parameters. RESULTS: Out of 101 patients included in this study, the ICD was preoperatively reprogrammed in 42 patients (41.6%), a magnet was used on 45 patients (44.5%), and ICDs were not deactivated at all in 14 patients (13.9%). No intraoperative electromagnetic interference was detected. Postoperative ICD analysis demonstrated no changes of preset parameters. CONCLUSIONS: All three tested ICD management strategies were proved safe in this study. Keeping the location of surgery and the type of electrocautery in mind, an intraoperative magnet or even no ICD deactivation at all could be feasible alternatives in surgery on patients with ICDs.

Inhaled anesthetic agent sedation in the ICU and trace gas concentrations: a review.

There is a growing interest in the use of volatile anesthetics for inhalational sedation of adult critically ill patients in the ICU. Its safety and efficacy has been demonstrated in various studies and technical equipment such as the anaesthetic conserving device (AnaConDa™; Sedana Medical, Uppsala, Sweden) or the MIRUS™ system (Pall Medical, Dreieich, Germany) have significantly simplified the application of volatile anesthetics in the ICU. However, the personnel's exposure to waste anesthetic gas during daily work is possibly disadvantageous, because there is still uncertainty about potential health risks. The fact that average threshold limit concentrations for isoflurane, sevoflurane and desflurane either differ significantly between countries or are not even defined at all, leads to raising concerns among ICU staff. In this review, benefits, risks, and technical aspects of inhalational sedation in the ICU are discussed. Further, the potential health effects of occupational long-term low-concentration agent exposure, the staffs' exposure levels in clinical practice, and strategies to minimize the individual gas exposure are reviewed.

Use of the MIRUS™ system for general anaesthesia during surgery: a comparison of isoflurane, sevoflurane and desflurane.

The MIRUS™ system enables automated end-expired control of volatile anaesthetics. The device is positioned between the Y-piece of the breathing system and the patient's airway. The system has been tested in vitro and to provide sedation in the ICU with end-expired concentrations up to 0.5 MAC. We describe its performance in a clinical setting with concentrations up to 1.0 MAC. In 63 ASA II-III patients undergoing elective hip or knee replacement surgery, the MIRUS™ was set to keep the end-expired desflurane, sevoflurane, or isoflurane concentration at 1 MAC while ventilating the patient with the PB-840 ICU ventilator. After 1 h, the ventilation mode was switched from controlled to support mode. Time to 0.5 and 1 MAC, agent usage, and emergence times, work of breathing, and feasibility were assessed. In 60 out of 63 patients 1.0 MAC could be reached and remained constant during surgery. Gas consumption was as follows: desflurane (41.7 ± 7.9 ml h-1), sevoflurane (24.3 ± 4.8 ml h-1) and isoflurane (11.2 ± 3.3 ml h-1). Extubation was faster after desflurane use (min:sec): desflurane 5:27 ± 1:59; sevoflurane 6:19 ± 2:56; and isoflurane 9:31 ± 6:04. The support mode was well tolerated. The MIRUS™ system reliable delivers 1.0 MAC of the modern inhaled agents, both during mechanical ventilation and spontaneous (assisted) breathing. Agent usage is highest with desflurane (highest MAC) but results in the fastest emergence. Trial registry number: Clinical Trials Registry, ref.: NCT0234509.

[Need of analgetics in children aged 2-12 years after tonsil surgery]. / Analgetikabedarf bei Kindern im Alter zwischen 2 und 12 Jahren nach Tonsillenoperationen.

OBJECTIVE: Tonsil surgery is one of the most painful operations in childhood. The Children's and Infants' Postoperative Pain Scale (CHIPPS), the Faces Pain Scale-Revised (FPS-R) and the little-known German version of the parents' postoperative pain measure (PPPM-D) are age-appropriate measures. Children undergoing intracapsular tonsillectomy (TO) or extracapsular tonsillectomy (TE) received the non-opioids ibuprofen (IBU) and paracetamol (PCM) on a "as needed"-basis requested by parents. A pain service checked pain scales and applied piritramide as rescue medication (RM) if required. Objective was evalution of sufficient analgesia. Endpoints were number of patients (PAT) needing the RM, doses of requested non-opioids, consistency of indications in different pain scales and correlation between pain and efficacy of the premedication or duration of the intervention. MATERIAL/METHODS: 3 measures were carried out daily: CHIPPS for PAT ≤ 4 years old, FPS-R from the age of 5. Parents completed the PPPM-D. Exceeding a cut-off score of 4 in CHIPPS or FPS-R or 6 in PPPM-D was rated as indication for RM. RESULTS: We included 68 PAT in an interim analysis. Mean daily doses of non-opioids within the first 3 postoperative days were as follows: PAT undergoing TE got 14,1-16,3 mg/Kg IBU and 4,2-12,4 mg/Kg PCM. PAT undergoing TO got 10,8-14,7 mg/Kg IBU and 5,2-8,8 mg/Kg PCM. On 212 visits PAT required RM, but 121 times it was detected in the PPPM-D only. After exclusion of potentially false-positive results remained 67 % PAT after TE and 48 % PAT after TO with at least 1 indication for RM. The study was terminated due to the high need for RM. CONCLUSIONS: The need of non-opioids was underrated. Combining the PPPM-D with established measures may improve the postoperative pain therapy.

The child's behavior during inhalational induction and its impact on the anesthesiologist's sevoflurane exposure.

BACKGROUND: Sevoflurane is commonly used for inhalational inductions in children, but the personnel's exposure to it is potentially harmful. Guidance to reduce gas pollution refers mainly to technical aspects, but the impact of the child's behavior has not yet been studied. AIMS: The purpose of this study was to determine how child behavior, according to the Frankl Behavioral Scale, affects the amount of waste sevoflurane in anesthesiologists' breathing zones. METHODS: Sixty-eight children aged 36-96 months undergoing elective ENT surgery were recruited for this prospective, observational investigation. After oral midazolam premedication (0.5 mg/kg body weight), patients obtained sevoflurane using a facemask with an inspiratory concentration of 8 Vol.% in 100% oxygen (flow 10 L/min). Ventilation was manually supported and a venous catheter was placed. The inspiratory sevoflurane concentration was reduced, and remifentanil and propofol were administered before the facemask was removed and a cuffed tracheal tube inserted. The child's behavior toward the operating room personnel during induction was evaluated by the anesthesiologist (Frankl Behavioral Scale: 1-2 = negative behavior, 3-4 = positive behavior). During induction mean (c¯mean) and maximum (c¯max), sevoflurane concentrations were determined in the anesthesiologist's breathing zone by continuous photoacoustic gas monitoring. RESULTS: Mean and maximum sevoflurane concentrations were c¯mean = 4.38 ± 4.02 p.p.m and c¯max = 70.06 ± 61.08 p.p.m in patients with positive behaviors and sufficient premedications and c¯mean = 12.63 ± 8.66 p.p.m and c¯max = 242.86 ± 139.91 p.p.m in children with negative behaviors and insufficient premedications (c¯mean: P < .001; c¯max: P < .001). CONCLUSION: Negative behavior was accompanied by significantly higher mean and maximum sevoflurane concentrations in the anesthesiologist's breathing zone compared with children with positive attitudes. Consequently, the status of premedication influences the amount of sevoflurane pollution in the air of operating rooms.

Occupational Chronic Sevoflurane Exposure in the Everyday Reality of the Anesthesia Workplace.

BACKGROUND: Although sevoflurane is one of the most commonly used volatile anesthetics in clinical practice, anesthesiologists are hardly aware of their individual occupational chronic sevoflurane exposure. Therefore, we studied sevoflurane concentrations in the anesthesiologists' breathing zones, depending on the kind of induction for general anesthesia, the used airway device, and the type of airflow system in the operating room. Furthermore, sevoflurane baselines and typical peaks during general anesthesia were determined. METHODS: Measurements were performed with the LumaSense Photoacoustic Gas Monitor. As we detected the gas monitor's cross-sensitivity reactions between sevoflurane and disinfectants, regression lines for customarily used disinfectants during surgery (Cutasept®, Octeniderm®) and their alcoholic components were initially analyzed. Hospital sevoflurane concentrations were thereafter measured during elective surgery in 119 patients. The amount of inhaled sevoflurane by anesthesiologists was estimated according to mVA = cVA × V × t × ρVA aer. RESULTS: Induction of general anesthesia stopped after tracheal intubation with the patient's expiratory sevoflurane concentration of 1.5%. Thereby, inhalational inductions (INH) caused higher sevoflurane concentrations than IV inductions (mean [SD]: (Equation is included in full-text article.)[ppm] INH 2.43 ± 1.91 versus IV 0.62 ± 0.33, P < 0.001; mVA [mg] INH 1.95 ± 1.54 versus IV 0.30 ± 0.22, P < 0.001). The use of laryngeal mask airway (LMA™) led to generally higher sevoflurane concentrations in the anesthesiologists' breathing zones than tracheal tubes ((Equation is included in full-text article.)[ppm] tube 0.37 ± 0.16 versus LMA™ 0.79 ± 0.53, P = 0.009; (Equation is included in full-text article.)[ppm] tube 1.91 ± 0.91 versus LMA™ 2.91 ± 1.81, P = 0.057; mVA [mg] tube 1.47 ± 0.64 versus LMA™ 2.73 ± 1.81, P = 0.019). Sevoflurane concentrations were trended higher during surgery in operating rooms with turbulent flow (TF) air-conditioning systems compared with laminar flow (LF) air-conditioning systems ((Equation is included in full-text article.)[ppm] TF 0.29 ± 0.12 versus LF 0.13 ± 0.06, P = 0.012; mVA [mg/h] TF 1.16 ± 0.50 versus LF 0.51 ± 0.25, P = 0.007). CONCLUSIONS: Anesthesiologists are chronically exposed to trace concentrations of sevoflurane during work. Inhalational inductions, LMA™, and TF air-conditioning systems in particular are associated with higher sevoflurane exposure. However, the amount of inhaled sevoflurane per day was lower than expected, perhaps because concentrations in previous measurements could be overestimated (10%-15%) because of the cross-sensitivity reaction.

Detection and distribution of opioid peptide receptors in porcine myocardial tissue.

There is growing evidence that opioid peptide receptors (OPRs) play an important role in cardiovascular function. Many studies have been conducted in swine, in view of their anatomic and physiologic similarities to humans. Until now, the presence and particularly distribution of OPRs has been unclear. Porcine myocardial tissue was obtained from both the left and right atria and ventricles. Expression of mRNA for µ-, δ- and κ-OPR was determined by reverse transcription PCR. OPR proteins were detected by Western blot, distribution and cellular location were identified using immunohistochemistry. Homogenous expression of mRNA and protein for δ- and κ-OPRs were demonstrated in all porcine myocardial tissue tested, whereas expression of µ-OPR mRNA was not demonstrated in any of the tissues tested. This study demonstrates the expression of δ- and κ-OPRs in porcine myocardial tissue. No differences in distribution of δ- and κ-OPRs were found between the four heart cavities. Modulation of cardiac function by δ- and κ-OPR agonists or antagonists is therefore possible, while µ-OPR-mediated direct cardiac effects appear unlikely, due to nonexpression of the receptor. This study demonstrates that porcine studies can further elucidate the role of OPRs in cardiac (patho-)physiology.

Effects of liberal vs. conventional volume regimen on pulmonary function in posterior scoliosis surgery.

BACKGROUND: We observed an increased rate of pulmonary complications (hypoxemia, pulmonary edema, re-intubation) in some patients after posterior spinal fusion, though standardized intraoperative volume regimens for major surgery were used. Therefore, we focused on the effects of two different standardized fluid regimens (liberal vs. conventional) as well as on two different types of postoperative pain management (thoracic epidural catheter vs. intravenous analgesia) concerning pulmonary function in patients undergoing posterior spinal fusion. METHODS: 23 patients received a conventional intraoperative fluid management (crystalloids 5.5 ml/kg/h), whereas 22 patients obtained a liberal regimen (crystalloids approximately 11 ml/kg/h) during surgery. After surgery a thoracic epidural catheter was used in 29 patients, whereas 16 patients got a conventional intravenous analgesia. Regarding pulmonary outcome, the re-intubation rate, the postoperative oxygen saturations as well as delivery volumes and retention times of pleural drainages were evaluated. RESULTS: Patients with conventional intraoperative fluid management had a less frequent reintubation rate (p = 0.015), better postoperative oxygen saturations (p = 0.043) and lower delivery volumes of pleural drainages (p = 0.027) compared to those patients with liberal volume regimen. Patients with thoracic epidural catheter had improved oxygen saturations on pulse oximetry at the first day after surgery (p < 0.001) and lower delivery volumes of pleural drainages than patients with intravenous analgesia (p = 0.008). CONCLUSIONS: The combination of a more restrictive fluid management (better pulmonary oxygen uptake and ventilation, less pulmonary edema) and a thoracic epidural catheter (sympatholysis, pain management) in posterior spinal fusion may be advantageous as both factors can improve pulmonary outcome.

Anesthetic gas consumption with target-controlled administration versus a semi-closed circle system with automatic end-tidal concentration control in an artificial lung model.

The use of volatile anesthetics as sedatives in the intensive care unit is relevant to the patient's outcome. We compared anesthetic gas consumption of the conventional semi-closed Aisys CSTM with the MIRUSTM system, which is the first anesthetic gas reflector system that can administer desflurane in addition to isoflurane and sevoflurane. We connected an artificial lung model to either a MIRUSTM system and a Puritan BennettTM 840 ventilator or an Aisys CSTM anesthesia machine. We found that consumption of 0.5% isoflurane, which corresponds to the target concentration 0.5 MAC, was averaged to 2 mL/h in the MIRUSTM system, which is identical to the Aisys CSTM at a fresh gas flow (FGF) of 1.0 L/min. MIRUSTM consumption of 1% sevoflurane was averaged to 10 mL/h, which corresponds to 8.4 mL/h at FGF 2.5 L/min. The MIRUSTM system consumed 3% or 4% desflurane at an average of 13.0 mL/h or 21.3 mL/h, which is between the consumption at 1.0 L/min and 2.5 L/min FGF. Thus, the MIRUSTM system can effectively deliver volatile anesthetics in clinically relevant concentrations in a similar rate as a conventional circular breathing system at FGFs between 1.0 L/min and 2.5 L/min.

Spontaneous breathing for managing analgesia during balanced anesthesia with remifentanil and desflurane: a prospective, single center randomized controlled trial.

The main goal of anesthesiology is to achieve the best level of analgesia and a fast recovery of consciousness following anesthesia. The preservation of spontaneous breathing during general anesthesia with anesthetic gases is practiced by many anesthetists. However, very few studies have dealt with these positive properties of volatile anesthetics such as sevoflurane or desflurane. Remifentanil is a very short half-life opiate that combines sufficient intra-operative analgesia with a fast post-operative recovery time. We tested the hypothesis that spontaneous breathing can reduce overdosing with remifentanil during desflurane anesthesia. In this prospective, single center, multiple anesthetist study, 30 patients were randomized into two groups (volume-controlled ventilation mode and spontaneous breathing). The spontaneous breathing group showed a significantly lower post-operative pain level than the volume-controlled ventilation mode group. Furthermore, less remifentanil as well as less piritramide was needed in the spontaneous breathing group compared with volume-controlled ventilation mode. It was possible to achieve spontaneous breathing in all patients with 0.6 minimum alveolar concentration desflurane, in order to control the remifentanil rate and prevent an overdose. All spontaneous breathing patients had low intra- and post-operative pain levels and the need for analgesics was equal to or lower than that in the volume-controlled ventilation mode group. By reducing the intra-operative amount of opiates, both the post-operative pain and the amount of post-operative analgesia required can be reduced. A balanced anesthesia with spontaneous intra-operative breathing is needed to determine the required amount of opiates. This study was approved by the Ethic Committee of the Ruhr-University of Bochum (approval No. 2435) in September, 2004.

Extracorporeal membrane oxygenation and inhaled sedation in coronavirus disease 2019-related acute respiratory distress syndrome.

Coronavirus disease 2019 (COVID-19) related acute respiratory distress syndrome (ARDS) is a severe complication of infection with severe acute respiratory syndrome coronavirus 2, and the primary cause of death in the current pandemic. Critically ill patients often undergo extracorporeal membrane oxygenation (ECMO) therapy as the last resort over an extended period. ECMO therapy requires sedation of the patient, which is usually achieved by intravenous administration of sedatives. The shortage of intravenous sedative drugs due to the ongoing pandemic, and attempts to improve treatment outcome for COVID-19 patients, drove the application of inhaled sedation as a promising alternative for sedation during ECMO therapy. Administration of volatile anesthetics requires an appropriate delivery. Commercially available ones are the anesthetic gas reflection systems AnaConDa® and MIRUSTM, and each should be combined with a gas scavenging system. In this review, we describe respiratory management in COVID-19 patients and the procedures for inhaled sedation during ECMO therapy of COVID-19 related ARDS. We focus particularly on the technical details of administration of volatile anesthetics. Furthermore, we describe the advantages of inhaled sedation and volatile anesthetics, and we discuss the limitations as well as the requirements for safe application in the clinical setting.

Use of MIRUS™ for MAC-driven application of isoflurane, sevoflurane, and desflurane in postoperative ICU patients: a randomized controlled trial.

BACKGROUND: The MIRUS™ (TIM, Koblenz, Germany) is an electronical gas delivery system, which offers an automated MAC (minimal alveolar concentration)-driven application of isoflurane, sevoflurane, or desflurane, and can be used for sedation in the intensive care unit. We investigated its consumption of volatile anesthetics at 0.5 MAC (primary endpoint) and the corresponding costs. Secondary endpoints were the technical feasibility to reach and control the MAC automatically, the depth of sedation at 0.5 MAC, and awakening times. Mechanically ventilated and sedated patients after major surgery were enrolled. Upon arrival in the intensive care unit, patients obtained intravenous propofol sedation for at least 1 h to collect ventilation and blood gas parameters, before they were switched to inhalational sedation using MIRUS™ with isoflurane, sevoflurane, or desflurane. After a minimum of 2 h, inhalational sedation was stopped, and awakening times were recorded. A multivariate electroencephalogram and the Richmond Agitation Sedation Scale (RASS) were used to assess the depth of sedation. Vital signs, ventilation parameters, gas consumption, MAC, and expiratory gas concentrations were continuously recorded. RESULTS: Thirty patients obtained inhalational sedation for 18:08 [14:46-21:34] [median 1st-3rd quartiles] hours. The MAC was 0.58 [0.50-0.64], resulting in a Narcotrend Index of 37.1 [30.9-42.4] and a RASS of - 3.0 [- 4.0 to (- 3.0)]. The median gas consumption was significantly lowest for isoflurane ([ml h-1]: isoflurane: 3.97 [3.61-5.70]; sevoflurane: 8.91 [6.32-13.76]; and desflurane: 25.88 [20.38-30.82]; p < 0.001). This corresponds to average costs of 0.39 € h-1 for isoflurane, 2.14 € h-1 for sevoflurane, and 7.54 € h-1 for desflurane. Awakening times (eye opening [min]: isoflurane: 9:48 [4:15-20:18]; sevoflurane: 3:45 [0:30-6:30]; desflurane: 2:00 [1:00-6:30]; p = 0.043) and time to extubation ([min]: isoflurane: 10:10 [8:00-20:30]; sevoflurane: 7:30 [4:37-14:22]; desflurane: 3:00 [3:00-6:00]; p = 0.007) were significantly shortest for desflurane. CONCLUSIONS: A target-controlled, MAC-driven automated application of volatile anesthetics is technically feasible and enables an adequate depth of sedation. Gas consumption was highest for desflurane, which is also the most expensive volatile anesthetic. Although awakening times were shortest, the actual time saving of a few minutes might be negligible for most patients in the intensive care unit. Thus, using desflurane seems not rational from an economic perspective. Trial registration Clinical Trials Registry (ref.: NCT03860129). Registered 24 September 2018-Retrospectively registered.

Chest compression quality management and return of spontaneous circulation: a matched-pair registry study.

AIMS: Investigating the effects of any intervention during cardiac arrest remains difficult. The ROSC after cardiac arrest score was introduced to facilitate comparison of rates of return of spontaneous circulation (ROSC) between different ambulance services. To study the influence of chest compression quality management (including training, real-time feedback devices, and debriefing) in comparison with conventional cardiopulmonary resuscitation (CPR), a matched-pair analysis was conducted using data from the German Resuscitation Registry, with the calculated ROSC after cardiac arrest score as the baseline. METHODS AND RESULTS: Matching for independent ROSC after cardiac arrest score variables yielded 319 matched cases from the study period (January 2007-March 2011). The score predicted a 45% ROSC rate for the matched pairs. The observed ROSC increased significantly with chest compression quality management, to 52% (P=0.013; 95% CI, 46-57%). No significant differences were seen in the conventional CPR group (47%; 95% CI, 42-53%). The difference between the observed ROSC rates was not statistically significant. CONCLUSIONS: Chest compression quality management leads to significantly higher ROSC rates than those predicted by the prognostic score (ROSC after cardiac arrest score). Matched-pair analysis shows that with conventional CPR, the observed ROSC rate was not significantly different from the predicted rate. Analysis shows a trend toward a higher ROSC rate for chest compression quality management in comparison with conventional CPR. It is unclear whether a single aspect of chest compression quality management or the combination of training, real-time feedback, and debriefing contributed to this result.

Cine and tagged magnetic resonance imaging in short-term stunned versus necrotic myocardium.

We investigated the potential of Cine and 2D Tagged Cardiac Magnetic Resonance (CMR) Imaging to distinguish stunned from necrotic left ventricular (LV) myocardium in the early postischemic phase in an open-chest animal model (N = 12). Reversible and permanent occlusion of the LAD coronary artery resulted in global LV dysfunction in both groups without significant differences. LAD perfused segments revealed significant higher values for end systolic wall thickening (ESWT) and percentual systolic wall thickening in animals with stunned myocardium. Analysis of strain parameters showed significant regional differences (maximal principal strain lambda1, deviation angle beta) between postischemic and remote myocardium within both groups, however results were not significantly different comparing animals with stunned myocardium to animals with myocardial necrosis. In conclusion, at rest neither global LV functional nor regional strain parameters derived from Cine and 2D Tagged CMR Imaging can distinguish animals with short-term stunned myocardium from respective animals with necrotic myocardium. Diagnostic value of ESWT is limited due to the spatial resolution of the gradient-echo sequence used.

Arteriovenous carboxyhemoglobin difference in critical illness: fiction or fact?

It is still unclear whether the paradoxical arteriovenous carboxyhemoglobin (COHb) difference found in critical illness is due to increased COHb production by the lung, or whether this gradient is caused by technical artifacts using spectrophotometry. In healthy and matched endotoxemic sheep, blood gases were analyzed with a standard ABL 625 and the updated version, an ABL 725. The latter one was accurately calibrated for COHb wavelengths (SAT 100) to eliminate the FCOHb dependency on oxygen tension. All endotoxemic sheep exhibited a hypotensive-hyperdynamic circulation and a pulmonary hypertension. Interestingly, arteriovenous COHb difference occurred in both healthy and endotoxemic sheep (P<0.001 each). Arterial and central venous COHb concentrations determined with the ABL 625 were significantly lower than those measured with the ABL 725 (P<0.001 each). We conclude that (a) arteriovenous COHb difference per se does not reflect critical illness and (b) measurements with an ABL 625 underestimate COHb concentrations.

Short-term administration of ethanol does not affect functional recovery from myocardial stunning in awake dogs.

UNLABELLED: Chronic ingestion of small doses of ethanol protects the myocardium from ischemic damage. It was demonstrated that short-term administration of ethanol (SAE) enhances the recovery of stunned myocardium in acutely instrumented, anesthetized dogs. It is unclear whether this beneficial effect of SAE also occurs in awake dogs. Therefore, we investigated the effects of SAE on regional myocardial stunning in awake dogs. Thirty-six dogs were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure, left systolic ventricular contactility (dP/dt(max)) and diastolic ventricular function (dP/dt(min)), and regional myocardial wall-thickening fraction (WTF). Occluders around the left anterior descending (LAD) artery allowed the induction of reversible ischemia in the LAD-perfused myocardium. The dogs were assigned to one of three groups that differed in the dose of ethanol administered in the ethanol experiment (I, 0.125 g/kg [n = 12]; II, 0.25 g/kg [n = 12]; III, 0.5 g/kg [n = 12]). In each group, the dogs underwent two ischemic episodes (randomized crossover fashion; separate days): 10 min of LAD occlusion after the application of ethanol IV over 30 min (ethanol group) and without ethanol (control). WTF and hemodynamic variables were measured at baseline and at predetermined time points until complete recovery of myocardial stunning occurred. LAD-ischemia led to a significant decrease of LAD-WTF in all groups. There was no difference in WTF and hemodynamic variables with or without SAE during reperfusion. We conclude that SAE (0.125 g/kg, 0.25 g/kg, and 0.5 g/kg) does not significantly affect myocardial stunning in conscious dogs. IMPLICATIONS: In contrast to previous experiments in anesthetized dogs, short-term administration of ethanol does not alter myocardial stunning in conscious dogs.