Shortening of the twitch stabilization period by tetanic stimulation in acceleromyography in infants, children and young adults (STSTS-Study): a prospective randomised, controlled trial.

Acceleromyography is characterised by an increase of the twitch response T1 (first twitch of the train-of-four [TOF]) during first 30 min of monitoring known as the staircase phenomenon. In adults the staircase phenomenon can be avoided by tetanic prestimulation. This study examined, if tetanic prestimulation eliminates the staircase phenomenon in children. After written informed consent, the neuromuscular function of 80 children, 10 in each age group (< 6 months, 6-12 months, 12-24 months, 2-3 years, 3-6 years, 6-12 years, 12-18 years, and ≥ 18 years) was measured on both arms simultaneously over 30 min under general anaesthesia. The ulnaris nerve was stimulated using the TOF technique every 15 s. The twitch response (T1, TOF ratio [TOFR]) was measured by acceleromyography. Before calibration, tetanic prestimmulation (50 Hz for 5 s) was administered to one randomly selected arm. The effect of tetanic prestimulation and age was analysed using general linear models based on the normalized T1 and TOFRs of both arms. Tetanic prestimulation significantly affected T1 values avoiding the staircase phenomenon (p < 0.0001). After 5.8 min [1.0-17.2 min] the normalized T1 values increased to 117% [102-147%] without prestimulation (p < 0.0001) independent of the age group (p = 0.539). The normalized TOFR was stable throughout the observation period of 30 min 100% [95-107%]. Infants (> 12 weeks), children, and young adults (< 18 years) develop similar characteristics of the staircase phenomenon than adults. Tetanic prestimulation prevents the staircase phenomenon in these age groups. The stability of the TOFR reading confirms its value to monitor neuromuscular function over time.Registration: The study was registered as NCT02552875 on Clinical Trials.gov on July 29, 2014.

In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats.

INTRODUCTION: Recent studies have shown that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may serve as important diagnostic and therapeutic targets in sepsis. Since polymorphonuclear neutrophils (PMNs) play a pivotal role in the early phase of sepsis, we evaluated the potential therapeutic effects of cholinesterase inhibitors on PMN functions during cecal ligation and puncture- (CLP-) induced sepsis and investigated the roles of AChE and BChE as inflammatory markers under standardized experimental conditions. METHODS: Sham surgery or CLP was performed in male Wistar rats (n = 60). Animals were randomized into four groups: physostigmine, 100 µg/kg; neostigmine, 75 µg/kg; 0.9% saline (control group); and sham group, each applied four times over 24 h. The levels of reactive oxygen species (ROS) production and CD11b/CD62l expression were quantified by flow cytometry at t = 0, 6, 15, 20, and 24 h. Blood gas analysis as well as AChE and BChE activity levels was measured by validated point-of-care measurements. Clinical scores and survival times were determined. RESULTS: CLP induced a significant increase in ROS production and CD11b upregulation by rat PMNs. Treatment with physostigmine or neostigmine significantly reduced ROS production and CD11b upregulation by PMNs 20 h after CLP induction. In physostigmine-treated animals, survival times were significantly improved compared to the control animals, but not in neostigmine-treated animals. While AChE activity significantly decreased in the control animals at t > 6 h, AChE activity did not change in the sham group. BChE activity decreased at t > 20 h in the control animals. CONCLUSION: While AChE activity may serve as an acute inflammatory marker, BChE activity shows a delayed decrease. Administration of centrally acting physostigmine in CLP-induced sepsis in rats has protective effects on PMN functions and improves survival times, which may be of interest in clinical practice.

The impact of obesity on pulmonary deterioration in patients undergoing robotic-assisted laparoscopic prostatectomy.

Obesity affects respiratory and hemodynamic function in anesthetized patients. The aim of this study was to evaluate the influence of the body mass index (BMI) on pulmonary changes in a permanent 45° steep Trendelenburg position (STP) during robotic-assisted laparoscopic prostatectomy (RALP). 51 patients undergoing RALP under standardized anesthesia were included. Perioperative pulmonary function and oxygenation were measured in awake patients (T0), 20 min after the induction of anesthesia (T1), after insufflation of the abdomen in supine position (T2), after 30 min in STP (T3), when controlling Santorini's plexus in STP (T4), before awakening while supine (T5), and after 45 min in the recovery room (T6). Patient-specific and time-dependent factor on ventilation and predicted peak inspiratory pressure (PIP), driving pressure (Pdriv) and lung compliance (LC) in a linear regression model were calculated. PIP and Pdriv increased significantly after induction of capnoperitoneum (T2-4) (p < 0.0001). In univariate mixed effects models, BMI was found to be a significant predictor for PIP and Pdriv increase and LC decrease. Obese patients a BMI > 31 kg/m2 reached critical PIP values ≥ 35 cmH2O. Postoperative oxygenation represented by the PaO2/FiO2 ratio was significantly decreased compared to T0 (p < 0.0001). Obesity in combination with STP and capnoperitoneum during RALP has a profound effect on pulmonary function. Increased PIP and Pdriv and decreased LC are directly correlated with a high BMI. Changes in PIP, Pdriv and LC during RALP may be predicted in relation to patient's BMI for consideration in the preoperative setting. Trial registration number Z-2014-0387-6. Registered on 8 July 2014.

Platelet sequestration with a new-generation autotransfusion device.

BACKGROUND: Autologous platelet-rich plasma (PRP) can be used either to prevent platelets (PLTs) from lesions during extracorporeal circulation or for wound therapy, when processed into PLT gel. The aim of this study was to evaluate the PLT sequestration abilities of a new-generation autotransfusion device. STUDY DESIGN AND METHODS: In this experimental study the discontinuous, new-generation autotransfusion device XTRA was evaluated using fresh donor blood. The blood was processed in four different size bowls (X55, X125, X175, X225 [bowls' size in mL]) using the device's built-in "PLT sequestration program." PLT functionality was tested using aggregometry; for PLT activation, ß-thromboglobulin (ß-TG) and soluble P-selectin levels were determined. Cell damage was assessed by a morphology score and hypotonic shock response. Additionally, PLTs were tested after 6 hours to identify storage lesions. RESULTS: Platelet recovery in the PRP ranged from 39% to 64% and averaged 6.2-fold PLT enrichment as defined by the increase in PLT concentration. The preparation caused minimal cell damage and a decrease in cell function by only 10%, but a slight activation was observed amounting to 9% of the maximal ß-TG release. The efficiency of the preparation, represented by the PLT recovery rate, increased in a linear fashion with the increasing bowl sizes being tested. After 6 hours of storage the prepared PLTs showed an additional 9% loss in function, but only 4% decrease in viability. CONCLUSION: The autotransfusion device XTRA was capable of high-quality perioperative PRP preparation, and the bowl size was found to have an influence on the efficiency of the preparation.

Deep Brain Stimulation Surgery without Sedation.

BACKGROUND: Sedatives and opioids used during deep brain stimulation (DBS) surgery interfere with optimal target localization and add to side effects and risks, and thus should be minimized. OBJECTIVE: To retrospectively test the actual need for sedatives and opioids when cranial nerve blocks and specific therapeutic communication are applied. METHODS: In a case series, 64 consecutive patients treated with a strong rapport, constant contact, non-verbal communication and hypnotic suggestions, such as dissociation to a "safe place," reframing of disturbing noises and self-confirmation, were compared to 22 preceding patients under standard general anaesthesia or conscious sedation. RESULTS: With introduction of the protocol the need for sedation dropped from 100% in the control group to 5%, and from a mean dose of 444 mg to 40 mg in 3 patients. Remifentanil originally used in 100% of the patients in an average dose of 813 µg was reduced in the study group to 104 µg in 31% of patients. There were no haemodynamic reactions indicative of stress during incision, trepanation, electrode insertion and closure. CONCLUSION: With adequate therapeutic communication, patients do not require sedation and no or only low-dose opioid treatment during DBS surgery, leaving patients fully awake and competent during surgery and testing.

The impact of bowl size, program setup, and blood hematocrit on the performance of a discontinuous autotransfusion system.

BACKGROUND: Cell salvage is an essential element in the concept of blood management. Modern devices provide different bowl sizes and sensor-directed programs to optimally adjust to varying clinical situations. STUDY DESIGN AND METHODS: In an experimental performance study, the discontinuous autotransfusion device XTRA (LivaNova/Sorin) was evaluated using fresh donor blood anticoagulated with heparin 5 U/mL and adjusted to a hematocrit of 10% or 25%, representing orthopedic or cardiac surgery. Test blood was processed with the autotransfusion device XTRA in four different bowls (55 mL, 125 mL, 175 mL, and 225 mL) and in three different program modes (a standard program, an optimized program, and an emergency program). RESULTS: Processing speed increased with bowl size and with the emergency program (range, 6.4-29.8 mL red blood cells [RBCs]/min). The RBC recovery rate exceeded 90% for all bowls and programs except the 55-mL bowl with the emergency program. Plasma elimination exceeded 95% for all bowls and programs except the 225-mL bowl with the emergency and standard programs. Maximal RBC recovery (range, 94.7%-97.6%) and plasma elimination (range, 98.7%-99.5%) were obtained with the medium-sized bowls (125 mL and 175 mL) and the optimized program. Elimination rates for potassium or plasma free hemoglobin were consistently lower than for protein or albumin and were highest for heparin. CONCLUSIONS: Increased hematocrit and RBC recovery rates are obtained with the optimized program Popt with the discontinuous autotransfusion device. The emergency program Pem speeds up the process but leads to RBC loss and reduced plasma elimination rates; therefore, it should be restricted to emergency situations. All four different sized bowls have high performance. Plasma elimination is represented best by protein or albumin elimination rates.

Fat removal during cell salvage: an optimized program for a discontinuous autotransfusion device.

BACKGROUND: Fat in wound blood observed in orthopedic or cardiac surgery might pose a risk for fat embolism during blood salvage. Fat removal was optimized in the washing process. STUDY DESIGN AND METHODS: In an experimental study blood from fresh donations was adjusted to a hematocrit (Hct) of 25% and an admixture of 1.25% human tissue fat. This blood was processed with the cell salvage device XTRA in a modified program mode. Volumetric quantification of fat was performed after centrifugation of blood samples in Pasteur pipettes. From the volumes, the Hct levels and the concentrations of fat and other variables elimination rates and RBC recovery were calculated. RESULTS: Pretests showed wash volume, wash flow, and process interruptions affecting fat elimination. With the new optimized fat elimination program Pfat removal rate of fat increased to 98.5 ± 0.9% for the 225-mL bowl. The product had a mean Hct of 48.7 ± 1.2% and a RBC recovery rate of 93.5 ± 2.3%. The program conserved the high elimination rates for albumin, heparin, potassium, and free plasma hemoglobin (98.8, 99.3, 95.3, and 94.9%, respectively). Similar high fat removal was also observed with bowls of smaller size, namely, 98.1% for the 175-mL bowl and 98.2% for the 125- and the 55-mL bowls. With test blood of Hct 10% a mean fat elimination of 99.6 ± 01% was observed. CONCLUSIONS: A special program modification Pfat involving extra washing and RBC concentration steps significantly improves fat removal by the Latham bowl-based autotransfusion device XTRA, thus yielding results equivalent to the continuous cell salvage system.

Adenosine A2A and A2B Receptor Substantially Attenuate Ischemia/Reperfusion Injury in Septic rat Hearts.

INTRODUCTION: Mechanical and morphological ischemia and reperfusion (I/R) injury is reduced in septic hearts. The mechanism behind this "cardioprotection" is less well understood. As adenosine receptors play a major role for cardioprotection in non-septic hearts, we investigated the influence of adenosine receptors in a model of I/R in septic hearts. METHODS: SHAM operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats (n = 60). After 24 h of incubation, hearts were isolated and randomly assigned to a group with or without adenosine receptor (Ador) antagonists (SCH 58261 and MRS 1706) administered before reperfusion. Ischemia and reperfusion lasted for 40 min each. Cardiac function of the heart was determined by measuring left ventricular pressure (LVP). RESULTS: Before I/R, CLP hearts showed a significant mechanical left ventricular impairment (CLP: 63 ± 5 mmHg vs. SHAM: 104 ± 6 mmHg. After I/R, left ventricular function was significantly reduced in SHAM (24 ± 32 mmHg), but not in CLP hearts (65 ± 13 mmHg). mRNA expression for the AdorA2a and AdorA2b was significantly increased in CLP, but not in SHAM hearts. LVP of CLP hearts deteriorated when AdorA2a and AdorA2b were blocked. CONCLUSIONS: The morphological and functional I/R injury in septic animals is less pronounced compared to non-septic animals. By a combined blockade of AdorA2a and AdorA2b this "cardioprotective" effect is nearly abolished in septic hearts. This is the first study showing, that AdorA2a and AdorA2b may play an important role for a reduced functional I/R injury in the septic heart.

Fat removal during cell salvage: a comparison of four different cell salvage devices.

BACKGROUND: Fat embolism is a possible risk factor for pulmonic and cerebral dysfunction after orthopedic and heart surgery. It is unknown whether fat occasionally observed during cell salvage adds to the risk of fat embolism after retransfusion. We have examined the fat removal capacities of different cell salvage devices including discontinuous and a continuous system under various conditions. STUDY DESIGN AND METHODS: In an experimental study ABO-matched banked blood was adjusted to a hematocrit of 20%, and 1.25% of human fat was added. This blood was processed with the cell salvage devices XTRA and Electa, CATS, or Cell Saver 5 plus. Fat in the blood samples was quantified by volumetric measurement after centrifugation in Pasteur pipettes and by gravimetric measurement after extraction of fat in organic solvents and phase partition. Performance in fat removal was tested with different programs, bowl sizes, and additional filtration. RESULTS: The continuous system consistently showed a high fat removal rate of 99.8 ± 0.2%. Fat accumulated in the wash disposal, but not in the product. In the Latham bowl-based discontinuous systems, fat removal varied from 69.2 to 92.8 ± 4.4% depending on the program mode, but not on the bowl size. Additional filtration increased fat removal to 96.7 ± 2.2%, but also increased red blood cell loss. CONCLUSIONS: Fat contamination of wound blood can be detected by volumetric and gravimetric measurements. Continuous salvage systems remove fat to a higher extent than discontinuous systems. The fat removal capacities of discontinuous systems depend on the program mode and can be improved by filtration.

Processing of small volumes in blood salvage devices.

BACKGROUND: New technical developments such as a small Latham bowl, a continuous autotransfusion system, and a dynamic disk designed for postoperative autotransfusion raise hopes for a possible application of blood salvage in young children. However, the minimal blood volume for effective processing under clinically relevant conditions has yet to be determined. STUDY DESIGN AND METHODS: Fresh blood from volunteer donations adjusted to a hematocrit (Hct) of 10% was used to test ELECTA (Sorin) equipped with a 55-mL bowl, C.A.T.S (Fresenius) in the pediatric program mode, and OrthoPAT (Haemonetics). Twenty-milliliter portions of red blood cells (RBCs) were added and processed under various conditions, including clinically relevant first filling and intermittent emptying. RBC recovery and availability and plasma elimination were calculated from the Hct, free hemoglobin, and total protein. RESULTS: The main impediment to recovery and availability was the first filling. There, RBC recovery was significantly reduced, while it subsequently varied between 93 and 98%. To produce the first 30 mL of RBCs, ELECTA required 42 mL and C.A.T.S and OrthoPAT 62 mL owing to the dead space of the separation chamber or reservoir, respectively. RBC availability was much higher in subsequent processes, with only minimal differences between the three devices. They all consistently provided high plasma elimination rates. CONCLUSION: The continuous system showed no advantage over a small Latham bowl. From the results it can be calculated that the limit for feasible cell salvage at present is an infant of 6 months. All three devices are suitable for the processing of small volumes, but have the scope for further optimization.

Washing of banked blood by three different blood salvage devices.

BACKGROUND: Storage lesions in red blood cells (RBCs) lead to an accumulation of soluble contaminants that can compromise the patient. Organ failures, coagulopathies, and cardiovascular events including lethal cardiac arrest have been reported, especially with massive transfusion or in pediatric patients. Washing improves the quality of stored RBCs, and autotransfusion devices have been proposed for intraoperative processing, but these devices were designed for diluted wound blood, and limited data on their performance with RBCs are available. STUDY DESIGN AND METHODS: Three autotransfusion devices (Electa, Sorin; CATS, Fresenius; OrthoPAT, Haemonetics) differing in function of their centrifugation chambers were evaluated with RBCs at the end of their shelf life and with dilutions thereof. Elimination rates of potassium, plasma free hemoglobin, total protein, citrate, acid equivalents, and iomeprol added as a marker substance were analyzed, in addition to RBC recoveries. RESULTS: Product hematocrit (Hct) levels ranged between 54.8 and 72.6%. RBC recovery rates were between 62.7 and 95.0%, the lowest being with the OrthoPAT processing of undiluted RBCs. Plasma elimination rates increased with predilution and ranged from 46.6% to 99.5%, the lowest being with the CATS and undiluted RBCs. Washing did not change pH and buffering capacity of RBCs. CONCLUSION: Autotransfusion devices offer a practical and obviously economical option to wash banked RBCs intraoperatively to prevent hyperkalemia and other disturbances in massive transfusion or pediatric patients. Predilution improves elimination rates, especially in devices that produce high product Hct levels. With a Y-tubing the RBCs should bypass reservoir and vacuum, and the procedure should be guarded by a policy and procedure manual and a quality management system.

The use of the laryngeal tube disposable by paramedics during out-of-hospital cardiac arrest: a prospectively observational study (2008-2012).

SUMMARY: In the previous and the current guidelines of the European Resuscitation Council (ERC), endotracheal intubation (ETI), as an instrument for ventilation during resuscitation, was confirmed as less important for paramedics not trained in this method. For those, during resuscitation, the laryngeal tube is recommended by the ERC as a supraglottic airway device. The present study investigated prospectively the use of the laryngeal tube disposable (LT-D) by paramedics in prehospital emergency cases. METHODS: During a 42-month period (Sept 2008-Feb 2012), we prospectively registered all prehospital cardiac arrest situations in which the LT-D had been applied by paramedics (from one emergency medical service in Germany). RESULTS: During the defined period, 133 attempts, recorded on standardised data sheets, were enrolled into the investigation. Three were excluded from the study because of use during a trauma situation. Therefore, 130 patients were evaluated in this study. For this, the LT-D was used in 98% of all cases during resuscitation, and in about 2% of other emergencies (eg, trauma). With regard to resuscitation, adequate ventilation/oxygenation was described as possible in 83% of all included cases. In 66% of all cases, no problems concerning the insertion of the LT-D were described by the paramedics. No significant problems were reported in 93%. In 7% (n=9 cases), no insertion of the LT-D was possible. Instead of bag-mask-valve ventilation, the LT-D was used as a first-line airway device in about 66%. Between the two defined groups, no statistically significant differences were found (p>0.05). CONCLUSIONS: As an alternative airway device during resuscitation, recommended by the ERC in 2005 and 2010, the LT-D may enable ventilation rapidly and, as in most of our described cases, effectively. Additionally, by using the LT-D in a case of cardiac arrest, a reduced 'hands-off time' and, therefore, a high chest compression rate may be possible. Our investigation showed that the LT-D was often used as an alternative to bag-mask-ventilation and to ETI as well. However, we were able to describe more problems in the use of the LT-D than earlier investigations. Therefore, in future, more studies concerning the use of alternative airway devices in comparison with ETI and/or video-laryngoscopy seem to be necessary.

Effects of Individualised High Positive End-Expiratory Pressure and Crystalloid Administration on Postoperative Pulmonary Function in Patients Undergoing Robotic-Assisted Radical Prostatectomy: A Prospective Randomised Single-Blinded Pilot Study.

OBJECTIVES: Robotic-assisted laparoscopic prostatectomy (RALP) is typically conducted in steep Trendelenburg position (STP). The aim of the study was to evaluate whether crystalloid administration and individual management of positive end-expiratory pressure (PEEP) improve peri- and post-operative pulmonary function in patients undergoing RALP. DESIGN: Prospective randomised single-centre single-blinded explorative study. SETTING: Patients were either allocated to a standard PEEP (5 cmH2O) group or an individualised high PEEP group. Furthermore, each group was divided into a liberal and a restrictive crystalloid group (8 vs. 4 mL/kg/h predicted body weight). Individualised PEEP levels were determined by means of preoperative recruitment manoeuvre and PEEP titration in STP. PARTICIPANTS: Informed consent was obtained from 98 patients scheduled for elective RALP. INTERVENTIONS: The following intraoperative parameters were analysed in each of the four study groups: ventilation setting (peak inspiratory pressure [PIP], plateau pressure, driving pressure [Pdriv], lung compliance [LC] and mechanical power [MP]) and postoperative pulmonary function (bed-side spirometry). The spirometric parameters Tiffeneau index (FEV1/FVC ratio) and mean forced expiratory flow (FEF25-75) were measured pre- and post-operatively. Data are shown as mean ± standard deviation (SD), and groups were compared with ANOVA. A p-value of <0.05 was considered significant. RESULTS: The two individualised high PEEP groups (mean PEEP 15.5 [±1.71 cmH2O]) showed intraoperative significantly higher PIP, plateau pressure and MP levels but significantly decreased Pdriv and increased LC. On the first and second postoperative day, patients with individualised high PEEP levels had a significantly higher mean Tiffeneau index and FEF25-75. Perioperative oxygenation and ventilation and postoperative spirometric parameters were not influenced by restrictive or liberal crystalloid infusion in either of the two respective PEEP groups. CONCLUSIONS: Individualised high PEEP levels (≥14 cmH2O) during RALP improved intraoperative blood oxygenation and resulted in more lung-protective ventilation. Furthermore, postoperative pulmonary function was improved for up to 48 h after surgery in the sum of the two individualised high PEEP groups. Restrictive crystalloid infusion during RALP seemed to have no effect on peri- and post-operative oxygenation and pulmonary function.

Cell Salvage at the ICU.

Patient Blood Management (PBM) is a patient-centered, systemic and evidence-based approach. Its target is to manage and to preserve the patient's own blood. The aim of PBM is to improve patient safety. As indicated by several meta-analyses in a systematic literature search, the cell salvage technique is an efficient method to reduce the demand for allogeneic banked blood. Therefore, cell salvage is an important tool in PBM. Cell salvage is widely used in orthopedic-, trauma-, cardiac-, vascular and transplant surgery. Especially in cases of severe bleeding cell salvage adds significant value for blood supply. In cardiac and orthopedic surgery, the postoperative use for selected patients at the intensive care unit is feasible and can be implemented well in practice. Since the retransfusion of unwashed shed blood should be avoided due to multiple side effects and low quality, cell salvage can be used to reduce postoperative anemia with autologous blood of high quality. Implementing quality management, compliance with hygienic standards as well as training and education of staff, it is a cost-efficient method to reduce allogeneic blood transfusion. The following article will discuss the possibilities, legal aspects, implementation and costs of using cell salvage devices in an intensive care unit.

Cell Salvage During Liver Transplantation for Hepatocellular Carcinoma: A Retrospective Analysis of Tumor Recurrence Following Irradiation of the Salvaged Blood.

BACKGROUND: Orthotopic liver transplantation (OLT) is the treatment option for early-stage hepatocellular carcinoma (HCC). OLT is often associated with high blood loss, requiring blood transfusion. Retransfusion of autologous blood is a key part of blood conservation. There are, however, concerns that the retransfusion of salvaged blood might cause the spread of cancer cells and induce metastasis. Irradiation of salvaged blood before retransfusion eliminates viable cancer cells. Here, we analyzed the incidence of tumor recurrence in patients with HCC undergoing OLT who received irradiated cell-salvaged blood during transplant surgery. METHODS: We retrospectively analyzed patients undergoing OLT for HCC between 2002 and 2018 at our center. We compared the tumour recurrence in patients who received no retransfusion of autologous blood with patients who received autologous blood with or without preceding irradiation of the blood. RESULTS: Fifty-one (40 male, 11 female) patients were included in the analysis; 10 patients developed tumor recurrence within a time period of 2.45 ± 2.0 years. Statistical analysis revealed that there was no significant difference in tumor recurrence between patients who received autologous blood with or without irradiation. CONCLUSION: Intraoperative transfusion of cell-salvaged blood did not increase tumor recurrence rates. Cell salvage should be used in liver transplantation of HCC patients as part of a blood conservation strategy. The effect of blood irradiation on tumor recurrence could not be definitively evaluated.

Does cerebral near-infrared spectroscopy (NIRS) help to predict futile cannulation in extracorporeal cardiopulmonary resuscitation (ECPR)?

AIM OF THE STUDY: Extracorporeal cardiopulmonary resuscitation (ECPR) is an evolving technique to improve cardiopulmonary resuscitation (CPR) outcomes. Identifying a readily available tool helpful for predicting patient's outcome is warranted. The aim of the study was to evaluate the capability of cranial near-infrared spectroscopy (cNIRS) to identify non-survivors or patients with unfavorable neurologic outcome prior to cannulation for ECPR to avoid futile cannulations. METHODS: Retrospective analysis (2015-2021) of 97 patients requiring ECPR due to cardiac arrest with prior cNIRS measurement, which was performed immediately after ECPR team arrived on scene. Lowest possible regional cerebral oxygen saturation (rSO2) is 15%. RESULTS: Mortality was 72.1% (70/97). Survivors showed in 88.9% (24/27) good neurological outcome (Cerebral Performance Category (CPC) 1 + 2). rSO2 = 15% (11/97) prior to cannulation was only found in non-survivors. Among survivors, initial rSO2 was not associated with neurological outcome. Non-shockable initial rhythm was associated with higher mortality (44/50). In survivors, time to ECPR was shorter (p = 0.006), and initial lactate was significantly lower, whereas initial pH and hemoglobin levels were higher (p = 0.001). Survivors and those with favorable neurological outcome showed lower maximal NSE levels in the first 72 hours (p < 0.001; p = 0.041). CONCLUSION: In our patient cohort, rSO2 = 15% immediately prior to cannulation for ECPR did not result in any survivors, thus might be a marker for futile cannulation in ECPR. Higher rSO2 values were not associated with favorable neurologic outcome. Lower initial lactate and lower maximal NSE within the first 72 h after arrest were associated with favorable outcome.

Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model.

BACKGROUND: Sepsis is a leading cause of morbidity and mortality worldwide. Many patients suffering from sepsis are treated on intensive care units and many of them require mechanical ventilation under sedation or general anesthesia. Propofol, a drug used for these purposes, is known to interact with polymorphonuclear granulocytes (PMNs). Therefore, the aim of this study was to investigate the influence of propofol on PMN functions after experimental Gram-negative induced sepsis using lipopolysaccharide (LPS) stimulation. METHODS: A total of 34 granulocyte-enriched samples were collected from healthy subjects. PMNs were isolated by density gradient centrifugation and incubated simultaneously with either 6 µg/mL or 60 µg/mL propofol, or none (control). Additionally, the experimental sepsis samples were incubated with either 40 pg/mL or 400 pg/mL LPS. Live cell imaging was conducted in order to observe granulocyte chemotactic migration, ROS production, and NETosis. Flow cytometry was used to analyze viability and antigen expression. RESULTS: Propofol led to significantly reduced PMN track length (p < 0.001) and track speed (p < 0.014) after LPS-induced sepsis in a dose-dependent manner. NETosis (p = 0.018) and ROS production (p = 0.039) were accelerated by propofol without LPS incubation, indicating improved immune function. Propofol also ameliorated LPS-induced increased NETosis and ROS-production. Antigen expression for CD11b, CD62l and CD66b was unaffected by propofol. CONCLUSION: Propofol improves LPS-induced exaggerated PMN activation in an ex vivo model. Beneficial effects due to restored immune function in septic patients might be possible, but needs further investigation.

Potential Impact of Local Anesthetics Inducing Granulocyte Arrest and Altering Immune Functions on Perioperative Outcome.

INTRODUCTION: Local anesthetics (LAs) are frequently used during anesthesia; however, they may influence granulocyte function which in turn could modify immune responses in the perioperative period. Therefore, the aim of this study was to investigate the impact of clinically used doses of bupivacaine and lidocaine on granulocyte function with regard to migration, reactive oxygen species (ROS) production, neutrophil extracellular traps (NETosis) formation, and viability. METHODS: A total of 38 granulocyte-enriched samples from healthy subjects were obtained by whole blood lysis. Polymorphonuclear neutrophil (PMN) samples were incubated simultaneously with different concentrations of either bupivacaine (0.03-3.16 mmol/L) or lidocaine (0.007-14.21 mmol/L), or without drug (control). Live cell imaging was conducted in order to observe granulocyte chemotaxis, migration, ROS production, and NETosis. Flow cytometry was used to analyze viability and antigen expression. RESULTS: The track length (TL) of PMNs exposed to bupivacaine concentrations of 0.16 mmol/L and above significantly decreased compared to the control. Low concentrations of lidocaine were associated with slight but significant increases in TL, whereas this changed with concentrations above 1.4 mmol/L, showing a significant decrease in TL. PMN incubated with bupivacaine concentrations of 1.58 mmol/L and above or lidocaine concentrations of at least 3.6 mmol/L showed no migration or chemotaxis at all. Time to onset of maximal ROS production and time for half-maximal NETosis decreased in a dose-dependent manner for both substances. Equipotency in NETosis induction was reached by bupivacaine (1.1 mmol/L) at significantly lower concentrations than lidocaine (7.96 mmol/L). Cell viability and oxidative burst were unaffected by LAs. CONCLUSION: Local anesthetics in clinically used doses ameliorate granulocyte defense mechanisms, thus indicating their potentially decisive effect during the perioperative period.

Time-Dependent Negative Effects of Verbal and Non-verbal Suggestions in Surgical Patients-A Study on Arm Muscle Strength.

INTRODUCTION: The medical environment is full of suggestions that affect patients and their healing. Most of them inadvertently are negative, thus evoking nocebo effects. Recently, we have reported on the effect of such verbal and non-verbal suggestions as well as alternative formulations on maximal muscular arm strength in healthy volunteers. In the present study, we tested the same suggestions in patients at two time points to evaluate nocebo effects in a clinical situation and the impact of the approaching surgery date. METHODS: In 45 patients, maximal muscular strength during arm abduction was measured by dynamometry of the deltoid muscle group. One test was several days before and the second on the evening before surgery. Baseline values were compared to the performance after exposure to 18 verbal and non-verbal suggestions. The sequence of presumably negative and positive suggestions was randomized for each patient in order to avoid cumulation effects of immediate succession of two negatives. State anxiety was evaluated at both time points, and suggestibility was measured after surgery. RESULTS: Strong and statistically significant weakening effects were observed with all presumed negative suggestions from daily clinical practice including words of encouragement (91.4% of baseline), evaluation of symptoms (89.0%), announcement of a medical intervention (82.8%), a negative memory (86.5%), expectation of an uncertain future (82.8%), and non-verbal signals (87.7-92.2%). In contrast, alternative formulations did not interfere with muscular performance in most cases. A more pronounced effect was observed in the test repeated closer to the date of surgery, accompanied by a 15% higher anxiety level. The increase in anxiety correlated slightly with stronger weakening effects of suggestions, as did suggestibility. CONCLUSIONS: Negative suggestions cause a decrease in arm muscle strength, i.e., a "weakening" of the patient. This effect is enhanced by an increase in anxiety as the time of treatment, like surgery, approaches. The reaction can be avoided by alternative formulations. These nocebo effects that are objectively measured and quantified by a decrease in arm muscle strength are more pronounced in patients, i.e., in a clinical situation, than in healthy volunteers.