Influence of opioid analgesia type on circulating tumor cells in open colorectal cancer surgery (POACC-1): study protocol for a prospective randomized multicenter controlled trial.

BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.

Internal jugular vein collapsibility does not predict fluid responsiveness in spontaneously breathing patients after cardiac surgery.

PURPOSE: The objective of our study was to evaluate the diagnostic accuracy of internal jugular vein (IJV) collapsibility as a predictor of fluid responsiveness in spontaneously breathing patients after cardiac surgery. METHODS: In this prospective observational study, spontaneously breathing patients were enrolled on the first postoperative day after coronary artery bypass grafting. Hemodynamic data coupled with simultaneous ultrasound assessment of the IJV were collected at baseline and after passive leg raising test (PLR). Continuous cardiac index (CI), stroke volume (SV), and stroke volume variation (SVV) were assessed with FloTracTM/EV1000™. Fluid responsiveness was defined as an increase in CI ≥ 10% after PLR. We compared the differences in measured variables between fluid responders and non-responders and tested the ability of ultrasonographic IJV indices to predict fluid responsiveness. RESULTS: Fifty-four patients were included in the study. Seventeen (31.5%) were fluid responders. The responders demonstrated significantly lower inspiratory and expiratory diameters of the IJV at baseline, but IJV collapsibility was comparable (P = 0.7). Using the cut-off point of 20%, IJV collapsibility predicted fluid responsiveness with a sensitivity of 76.5% and specificity of 38.9%, ROC AUC 0.55. CONCLUSION: In spontaneously breathing patients after surgical coronary revascularisation, collapsibility of the internal jugular vein did not predict fluid responsiveness.

The diagnostic performance of CT pulmonary angiography in the detection of chronic thromboembolic pulmonary hypertension-systematic review and meta-analysis.

OBJECTIVES: To examine the diagnostic performance of CT of the pulmonary artery (CTPA) as a potential first-choice imaging modality in patients with pulmonary arterial hypertension and suspected chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: A systematic review and meta-analysis were conducted in accordance with the PRISMA reporting checklist. Six scientific databases and registers (PubMed, EMBASE, Scopus, Web of Science, Cochrane, ClinicalTrials.gov ) were searched for studies evaluating the diagnostic performance of CTPA in suspected CTEPH in adult patients. Results were pooled separately for studies based on the evaluation of the pulmonary artery and those that relied solely on changes in parenchymal perfusion. RESULTS: Ten single-center studies with 734 patients were eligible for pooling of the diagnostic performance of CTPA by evaluation of the pulmonary artery. The pooled sensitivity, specificity, PPV, NPV, accuracy, and diagnostic odds ratio (DOR) estimates for CTPA in the detection of CTEPH were 0.98, 0.99, 0.94, 1.00, 0.96, 0.96, and 292. Evaluation of perfusion changes yielded pooled estimates for sensitivity, specificity, PPV, NPV, accuracy, and DOR of 0.99, 0.84, 0.79, 0.98, 0.89, 0.89, and 98 across four studies with 278 patients. Scintigraphy, SPECT, digital subtraction angiography, right heart catheterization, pulmonary endarterectomy, and international guidelines were used to establish the diagnosis. CONCLUSION: CTPA has high sensitivity and specificity in the detection of CTEPH when the examination is evaluated by expert radiologists. Evaluation of parenchymal perfusion alone is associated with slightly lower specificity. Further research is needed to determine the diagnostic performance of CTPA in excluding CTEPH in general radiology departments. KEY POINTS: • CT pulmonary angiography (CTPA) is recommended in the diagnostic workup of chronic thromboembolic pulmonary hypertension (CTEPH). • CTPA has high sensitivity and specificity in the detection of CTEPH when evaluated by an expert radiologist. • Evaluation of changes in parenchymal perfusion alone is associated with slightly lower specificity. • Little is known about the diagnostic performance of CTPA in the detection of CTEPH in general radiology departments.

A bimodal pattern of the onset of COVID-19 related acute pancreatitis supports both the cytotoxic and immune-related pathogenesis - a systematic review.

OBJECTIVES: To review clinical and laboratory findings in patients with SARS-Cov-2 (COVID-19) related acute pancreatitis. METHODS: This systematic review was based on a database search for articles of COVID-19 related acute pancreatitis in adult patients with confirmed COVID-19 infection that included age, gender, presenting symptoms, the onset of symptoms, laboratory values, imaging findings and exclusion of common causes of pancreatitis. RESULTS: Altogether 35 articles comprising 37 patients were included. Acute pancreatitis was the first presentation of COVID-19 in 43% of patients, concurrent with general or respiratory symptoms in 14% of patients or delayed after general or pulmonary symptoms by an average of 10 ± 5 d (range, 1 - 19 d) in 43% of patients. Serum amylase and lipase levels were elevated in 87% and 100% of patients. In 50% and 84%, amylase and lipase levels exceeded three-fold the upper normal limit. Pancreatic necrosis was reported in 6% of patients and in 12% of patients, the pancreas appeared normal. Three patients died. CONCLUSIONS: We conclude that the bi-modal pattern of the onset of symptoms supports both the cytotoxic and the immune-related pathogenesis of the pancreatic injury. Acute pancreatitis may be the first symptom of COVID-19 infection. Necrosis of the pancreas is rare.

Extracorporeal Oxygenation Techniques in Adult Critical Airway Obstruction: A Review.

Extracorporeal life support has been increasingly utilized in different clinical settings to manage either critical respiratory or heart failure. Complex airway surgery with significant or even total perioperative airway obstruction represents an indication for this technique to prevent/overcome a critical period of severe hypoxaemia, hypoventilation, and/or apnea. This review summarizes the current published scientific evidence on the utility of extracorporeal respiratory support in airway obstruction associated with hypoxaemia, describes the available methods, their clinical indications, and possible limitations. Extracorporeal membrane oxygenation using veno-arterial or veno-venous mode is most commonly employed in such scenarios caused by endoluminal, external, or combined obstruction of the trachea and main bronchi.

Snakebite Envenoming by Sochurek's Saw-scaled Viper Echis Carinatus Sochureki.

A snake breeder, 47-years-old man, was bitten by the saw-scaled viper (Echis carinatus sochureki). After admission to Toxinology Centre, within 1.5 h, laboratory evaluation showed clotting times prolonged to non-measurable values, afibrinogenaemia, significantly elevated D-dimers, haemolysis and myoglobin elevation. Currently unavailable antivenom was urgently imported and administered within 10 hours. In 24 hours, oligoanuric acute kidney injury (AKI) and mild acute respiratory distress syndrome (ARDS) developed. Despite administration of 10 vials of urgently imported Polyvalent Snake Antivenom Saudi Arabia, the venom-induced consumption coagulopathy (VICC) and AKI persisted. Another ten vials of antivenom were imported from abroad. VICC slowly subsided during the antivenom treatment and disappeared after administration of total 20 vials during 5 day period. No signs of haemorrhage were present during treatment. After resolving VICC, patient was transferred to Department of Nephrology for persisting AKI and requirement for haemodialysis. AKI completely resolved after 20 days. Despite rather timed administration of appropriate antivenom, VICC and AKI developed and the quantity of 20 vials was needed to cease acute symptoms of systemic envenoming. The course illustrates low immunogenicity of the venom haemocoagulation components and thus higher requirements of the antivenom in similar cases.

Severe Snakebite Envenoming in Intensive Care.

Snakebites by exotic venomous snakes can cause serious or even life-threatening envenoming. In Europe and North America most victims are breeders, with a few snakebites from wild native American rattlesnakes. The envenomed victims may present in organ and/or system failure with muscle paralysis, respiratory failure, circulatory instability, acute kidney injury, severe coagulation disorder, and local disability - compartment syndrome and necrosis. Best managed by close collaboration between clinical toxicology and intensive care, most severe envenomings are managed primarily by intensive care physicians. Due to the low incidence of severe envenoming, the clinical course and correct management of these cases are not intrinsically familiar to most physicians. This review article summarizes the clinical syndromes caused by severe envenoming and the therapeutic options available in the intensive care setting.

Juxtarenal Mycotic Aneurysm as a Complication of Acute Exacerbation of Chronic Cholecystitis Treated by Resection and Replacement by a Fresh Allograft.

We present a case of a female patient with infectious (mycotic) juxtarenal abdominal aneurysm with atypical symptoms beginning as acute exacerbation of chronic cholecystitis. Apart from common antibiotic treatment, the patient successfully underwent resection of the diseased segment and replacement by a fresh allograft in order to reduce the risk of infection of the graft, but with the need of subsequent life-long immunosuppressive therapy. Perioperative monitoring of the spinal cord by near infrared spectroscopy was used to identify possible spinal ischemia. The choice of the fresh allograft was based on our experience supported by review of the literature.

The i-gel Supraglottic Airway as a Conduit for Fibreoptic Tracheal Intubation - A Randomized Comparison with the Single-use Intubating Laryngeal Mask Airway and CTrach Laryngeal Mask in Patients with Predicted Difficult Laryngoscopy.

Fibreoptic intubation through a supraglottic airway is an alternative plan for airway management in difficult or failed laryngoscopy. The aim of this study was to compare three supraglottic airways as conduits in patients with at least one predictor for difficult laryngoscopy. The i-gel was compared with the single-use intubating laryngeal mask airway (sILMA) and CTrach laryngeal mask in 120 adult patients scheduled for elective surgeries under general anaesthesia using a prospective, randomized and single-blinded design. Primary outcome was success rate of tracheal intubation through the device, while secondary outcomes were times required for device insertion and tracheal tube placement, fibreoptic scores and the incidence of perioperative complications and postoperative complaints. The success rates showed no statistical difference between devices (i-gel 100%, CTrach 97.5%, ILMA 95%). Insertion time was shortest for the i-gel (12.4 s) compared with ILMA (19.3 s) and CTrach (24.4 s). Intubation time was shorter in the i-gel group (29.4 s) in comparison with the CTrach (39.8 s, p<0.05) and sILMA (51.9 s, p<0.001) groups. Best fibreoptic scores were observed also in the i-gel group. In total, 24 patients (20%) presented with difficult laryngoscopy. The i-gel showed significantly shorter times for insertion and fibreoptic intubation than the other two devices in this group. No difference was observed in the incidence of postoperative complaints. The i-gel is a suitable alternative to the sILMA and CTrach for fibrescope-guided tracheal intubation. Shorter insertion and intubation times with the i-gel may provide advantage in case of difficult oxygenation.

Neonatal effect of remifentanil in general anaesthesia for caesarean section: a randomized trial.

BACKGROUND: Remifentanil has been suggested for its short duration of action to replace standard opioids for induction of general anaesthesia in caesarean section. While the stabilizing effect of remifentanil on maternal circulation has been confirmed, its effect on postnatal adaptation remains unclear, as currently published studies are not powered sufficiently to detect any clinical effect of remifentanil on the newborn. METHODS: Using a double-blinded randomized design, a total of 151 parturients undergoing caesarean delivery under general anaesthesia were randomized into two groups--76 patients received a bolus of remifentanil prior to induction, while 75 patients were assigned to the control group. Remifentanil 1 µg/kg was administered 30 seconds before the standard induction of general anaesthesia. The primary outcome measure was an assessment of neonatal adaptation using the Apgar score, while secondary outcomes included the need for respiratory support after delivery and differences in umbilical blood gas analysis (Astrup). RESULTS: The incidence of lower Apgar scores between 0 and 7 was significantly higher in the remifentanil group at one minute (25% vs. 9.3% of newborns, p = 0.017); whilst at five minutes and later no Apgar score differences were observed. There was no difference in the need for moderate (nasal CPAP) or intensive (intubation) respiratory support, but significantly more neonates in the remifentanil group required tactile stimulation for breathing support (21% vs. 7% of newborns, p = 0.017). There was no difference in the parameters from umbilical cord blood gas analysis between the groups. CONCLUSION: At a dose of 1 µg/kg, remifentanil prior to induction of general anaesthesia increases the risk of neonatal respiratory depression during first minutes after caesarean delivery but duration of clinical symptoms is short. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01550640.

Envenoming by Crotalid Snake Chinese Moccasin Agkistrodon Acutus Bite - A Case Report.

Although the bites caused by snakes from former Agkistrodon family in the areas of occurrence are not rare and even have certain epidemiologic importance, in case of envenoming by Deinagkistrodon acutus the clinical studies and case reports are very sporadic. This case report describes the envenoming of a private snake breeder bitten by young Chinese moccasin Deinagkistrodon acutus to the thumb of his left hand. He sought for a medical help immediately after snakebite. Patient presented with a local oedema on the affected limb, extending up to the half of the forearm. Laboratory examinations showed serious haemostatic disturbance with defibrination syndrome, immeasurably prolonged clotting times and extreme elevation of D-dimers. No other obvious clinical symptoms were present. Fibrinogen and fresh frozen plasma were administered because the antivenom was not available immediately. The specific antivenom was urgently imported 22 hours after the bite and administered at a dose of two vials three times until laboratory haemocoagulation parameters returned back to physiological values.

Airway management evolution - in a search for an ideal extraglottic airway device.

Extraglottic airway devices (EADs) are commonly used equipment for airway maintenance during elective procedures under general anaesthesia. They may be used also in other indications such as conduit for tracheal intubation or rescue airway device in prehospital medicine. Current classifications of the EADs lack systematic approach and therefore classification according to the sealing sites and sealing mechanisms is suggested in this review article. Modern EADs are disposable, latex-free devices made of plastic materials most commonly from polyvinylchloride (PVC). The bowl of uncuffed sealers is manufactured from different materials such as thermoplastic elastomers or ethylene-vinyl-acetate co-polymer. EADs create various physical forces exerted on the adjacent tissues which may contribute to different sealing characteristic of particular device or to variable incidence of postoperative complications. Desired features of an ideal EAD involve easy insertion, high insertion success rate even by inexperienced users, protection against aspiration of gastric contents and low incidence of postoperative complications such as sore throat, hoarseness, cough or swallowing difficulties.

Common viper bites in the Czech Republic - epidemiological and clinical aspects during 15 year period (1999-2013).

The aim of this study was to analyse most important epidemiological and clinical aspects of registered snakebites caused by a native common European viper Vipera berus in the Czech Republic over a period of 15 years (1999–2013). Data have been collected retrospectively from a database of the Toxinology Centre belonging to the General University Hospital in Prague. In total, 191 cases of snakebites caused by common viper were registered during the study period. Systemic envenoming occurred in 49 (25.7%) patients, local envenoming without systemic symptoms was recorded in 91 (47.6%) and asymptomatic dry bites were seen in 51 (26.7%) cases, respectively. Twenty-four patients (12.6% of all bites) were treated with administration of antivenom. None of the victims died as a result of snakebite during the observation period. Native viper snakes usually did not cause serious harm to the patients, with the exception of children. Antivenom should be administered in all cases with systemic manifestations, in children even with serious local affection and administered as soon as possible. Envenomed patients should be admitted to the hospital and treated at least under supervision of specialists with experience in snakebite treatment, who can indicate and provide administration of the antivenom.

Vancomycin loading dose individualization in a population of obese patients undergoing haemodialysis based on population pharmacokinetic model.

This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2-52.9 kg/m2 were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6-84.2) L and 0.86 (0.79-0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50-60, 60-70, 70-80, 80-85 and >85 kg, respectively.

Ultrasound imaging of the infraorbital foramen and simulation of the ultrasound-guided infraorbital nerve block using a skull model.

PURPOSE: Infraorbital nerve block is used for intraoperative and postoperative analgesia in nasal and oral surgery procedures, as well as in the chronic pain settings. Ultrasound guidance has not been described in the literature. The aim of the study was to assess the quality of ultrasound imaging of the infraorbital foramen and develop an "in-plane" technique of the block using a skull model. METHODS: The infraorbital foramina were assessed on five skull models immersed in the water bath. Ultrasound-guided simulation of an in-plane infraorbital nerve block was then performed. Slightly curved needle was placed close to the foramina and its visibility was recorded. Success rate and time to locate infraorbital foramina, success rate and time to insert the needle close to the foramina under ultrasound and correlation between the ultrasound and caliper measurements were evaluated and recorded. Data for the left and right foramen were compared. RESULTS: The infraorbital foramina were successfully located using ultrasound in all 20 cases. Simulation of infraorbital nerve block was also successful in all measurements. The time difference between locating or simulating blockade of the left and right infraorbital foramina was not statistically significant. Correlation between ultrasound measurement and direct measurement using a caliper was satisfactory for the distances between the inferior orbital rim and the inferior margin of the infraorbital foramen but poor for the distances between the lower rim of the orbit and the superior margin of the foramen. CONCLUSIONS: This experimental study suggests that the infraorbital foramen is easily located using ultrasound and an "in-plane" ultrasound-guided technique for infraorbital nerve blockade is feasible on the model.

A Prospective Comparative Study of Laryngeal Glottic View Using the Vie Scope® versus Standard Macintosh Laryngoscope in Morbidly Obese Patients.

Background: The visualization of the glottis may be inadequate in morbidly obese patients when a standard Macintosh blade laryngoscope (MCL) is used. The Vie Scope® (VS) is a novel type laryngoscope consisting of a straight, enclosed, illuminated tube that offers intubation via a bougie using the paraglossal technique. In this prospective, nonrandomized comparative study, we tested the research hypothesis that the VS may improve visualization of the glottic larynx in comparison to the MCL. Materials and Methods: After obtaining institutional ethics committee approval, 60 morbidly obese patients (BMI >40 kg/m2) undergoing elective non-head and neck surgery were included in the study. After induction of general anesthesia (GA), the glottic visualization was performed using the two laryngoscopes in succession, first MCL size 3 or 4 followed by the VS and was assessed using the modified Cormack-Lehane scale. Tracheal intubation was performed using the VS The first pass intubation success and the total success rate was recorded only for the VS Intubation time was not measured because of the paired study design. Results and Discussion: Mean demographic data included: age 41.9±8.2 years, height 171.2±10.2 cm, weight 129.9±21.6 kg, BMI 44.95±3.85 kg/m2. Using MCL, Cormack-Lehane grade 1 was observed in 36 (60%) cases; grade 2 in 7/60 (11.6%); grade 3 in 13/60 (21.7%); and grade 4 in 4/60 (6.7%). Poor laryngeal views represented by grades 3 and 4 were observed in 28.4% of patients with the MCL. Grades obtained with the VS were all grade 1 (100%). The first attempt intubation success was in 58/60 (96.7%) with the VS. No complications were observed. Conclusion: The Vie Scope® laryngoscope, using the paraglossal technique of tracheal intubation, significantly improves visualization of the vocal cords in morbidly obese patients compared to the standard Macintosh laryngoscope.

Using the national electronic prescription system to determine the primary non-adherence to medication in the Czech Republic.

The primary medication non-adherence occurs when a patient does not collect his or her newly prescribed medication. Various studies give estimates that this occurs between 0.2 percent and 74 percent. Recently, this topic has been researched by analyzing data in national electronic prescription systems. The database of the Czech electronic prescription system was used to obtain the number of all prescriptions issued and collected in 2021 for fifty particular substances (associated with six medication groups). Additionally, a similar query was performed with an additional criterion that the same substance had not been prescribed within the last 365 days. The data were obtained separately in five age categories. The total number of prescriptions analyzed in this study was over 21 million, which represents almost 30 percent of all prescriptions issued in the Czech Republic in 2021. The primary medication non-adherence in the selected substances was 4.56 percent, which negatively correlates (rxy = 0.707) with the age of a patient. There is a higher primary non-adherence in the Psychoanaleptics and Lipid modifying medication groups than in the whole studied sample (p < 0.05). Lipid-modifying medication group and several other particular substances showed a larger difference between primary non-adherence and overall non-adherence, indicating issues in the initiation of these drugs. The results of our study are following earlier studies with similar methodologies from other countries. However, the difference between primary non-adherence and overall non-adherence had not been observed in other studies before. The electronic prescription system proved to be a valuable tool for conducting this type of research.