An Individualized Low-Pneumoperitoneum-Pressure Strategy May Prevent a Reduction in Liver Perfusion during Colorectal Laparoscopic Surgery.

High intra-abdominal pressure (IAP) during laparoscopic surgery is associated with reduced splanchnic blood flow. It is uncertain whether a low IAP prevents this reduction. We assessed the effect of an individualized low-pneumoperitoneum-pressure strategy on liver perfusion. This was a single-center substudy of the multicenter 'Individualized Pneumoperitoneum Pressure in Colorectal Laparoscopic Surgery versus Standard Therapy II study' (IPPCollapse-II), a randomized clinical trial in which patients received an individualized low-pneumoperitoneum strategy (IPP) or a standard pneumoperitoneum strategy (SPP). Liver perfusion was indirectly assessed by the indocyanine green plasma disappearance rate (ICG-PDR) and the secondary endpoint was ICG retention rate after 15 min (R15) using pulse spectrophotometry. Multivariable beta regression was used to assess the association between group assignment and ICG-PDR and ICG-R15. All 29 patients from the participating center were included. Median IAP was 8 (25th-75th percentile: 8-10) versus 12 (12,12) mmHg, in IPP and SPP patients, respectively (p < 0.001). ICG-PDR was higher (OR 1.42, 95%-CI 1.10-1.82; p = 0.006) and PDR-R15 was lower in IPP patients compared with SPP patients (OR 0.46, 95%-CI 0.29-0.73; p = 0.001). During laparoscopic colorectal surgery, an individualized low pneumoperitoneum may prevent a reduction in liver perfusion.

Quantum Molecular Resonance Radiofrequency Disc Decompression and Percutaneous Microdiscectomy for Lumbar Radiculopathy.

Within the practice of pain management, one of the most commonly encountered events is low back pain. Lumbar radiculopathy (LR) is a pain syndrome caused by the compression or irritation of the nerve roots in the lower back due to lumbar disc herniation, vertebra degeneration, or foramen narrowing. Symptoms of LR include low back pain that propagates toward the legs, numbness, weakness, and loss of reflexes. The aim of this study is to assess the long-term effectiveness of quantum molecular resonance disc decompression and its combination with a percutaneous microdiscectomy using Grasper© forceps (QMRG) in patients with persistent lumbar radiculopathy (LR) in relation to patient physical stress status. The main outcome measures of this prospective observational study were DN4, NRS, ODI, SF12, PGI, CGI, and MOS Sleep Scale. An improvement 12 months post-intervention was observed in patients without physical stress, presenting better overall results. The mean change was over the minimal clinically important difference in 64.3% of outcome measures studied for the whole sample. QMRG appears to be an effective treatment option for LR, but a reduction in physical stress is needed to ensure long-term effectiveness.

Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

PURPOSE OF REVIEW: Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action. RECENT FINDINGS: We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects.

Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project.

Background: Opioid receptors are expressed not only by neural cells in the central nervous system, but also by many solid tumor cancer cells. Whether perioperative opioids given for analgesia after tumor resection surgery might inadvertently activate tumor cells, promoting recurrence or metastasis, remains controversial. We analysed large public gene repositories of solid tumors to investigate differences in opioid receptor expression between normal and tumor tissues and their association with long-term oncologic outcomes. Methods: We investigated the normalized gene expression of µ, κ, δ opioid receptors (MOR, KOR, DOR), Opioid Growth Factor (OGFR), and Toll-Like 4 (TLR4) receptors in normal and tumor samples from twelve solid tumor types. We carried out mixed multivariable logistic and Cox regression analysis on whether there was an association between these receptors' gene expression and the tissue where found, i.e., tumor or normal tissue. We also evaluated the association between tumor opioid receptor gene expression and patient disease-free interval (DFI) and overall survival (OS). Results: We retrieved 8,780 tissue samples, 5,852 from tumor and 2,928 from normal tissue, of which 2,252 were from the Genotype Tissue Expression Project (GTEx) and 672 from the Cancer Genome Atlas (TCGA) repository. The Odds Ratio (OR) [95%CI] for gene expression of the specific opioid receptors in the examined tumors varied: MOR: 0.74 [0.63-0.87], KOR: 1.27 [1.17-1.37], DOR: 1.66 [1.48-1.87], TLR4: 0.29 [0.26-0.32], OGFR: 2.39 [2.05-2.78]. After controlling all confounding variables, including age and cancer stage, there was no association between tumor opioid receptor expression and long-term oncologic outcomes. Conclusion: Opioid receptor gene expression varies between different solid tumor types. There was no association between tumor opioid receptor expression and recurrence. Understanding the significance of opioid receptor expression on tumor cells remains elusive.

Opioid Receptor Expression in Colorectal Cancer: A Nested Matched Case-Control Study.

Background: There is growing interest in the possible effect of perioperative anesthetic management on the growth and spread of cancer. The impact of perioperative use of opioids on cancer recurrence remains controversial and an assessment cannot yet be established based on current publications. This study aimed to assess the differential expression of opioid receptors between healthy and tumor tissues in patients with stage II and III colorectal cancer undergoing elective surgery by immunohistochemistry (IHC). Methods: Propensity-score matched case-control study nested in a retrospective cohort of patients with stage II or III colorectal. The primary endpoint was the difference in µ-opioid receptor (MOR) expression measured by IHC between tumor and healthy tissue in subject with or without recurrence. Secondary endpoints were to evaluate the differences in Opioid Growth Factor Receptor (OGFR), cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) in the matched sample and from a from samples of colorectal cancer stored in the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression Project (GTEx). Results: There was a significant difference in MOR receptor (median 3 [intequartile range IQR: 1-3] and 0 [IQR: 0-2], P<0.001) and OGFR receptor (median 6 [IQR: 5-6] and 2 [IQR: 1-2], P<0.001) in tumor and control tissue respectively. However, there were no significant differences in cAMP nor PKA expression between both types of tissues and in expression in any of the analyzed variables by recurrence status. The MOR and OGFR expression data from TCGA database were similar to our sample size data with lower expression of MOR and higher expression of OGFR in tumoural samples with a skewed distribution for MOR expression in tumor tissue both in patients with and without recurrence. Conclusion: In patients with stage II and III colorectal cancer, overall expression of MOR and OGFR was significantly increased but was not different between previously matched patients with or without recurrence. No differences were found in the analyzed metabolic pathway of cAMP-PKA: These results were confirmed by an in silico analysis of samples from the TCGA-GTEx database.

Modeling intra-abdominal volume and respiratory driving pressure during pneumoperitoneum insufflation-a patient-level data meta-analysis.

During pneumoperitoneum, intra-abdominal pressure (IAP) is usually kept at 12-14 mmHg. There is no clinical benefit in IAP increments if they do not increase intra-abdominal volume IAV. We aimed to estimate IAV (ΔIAV) and respiratory driving pressure changes (ΔPRS) in relation to changes in IAP (ΔIAP). We carried out a patient-level meta-analysis of 204 adult patients with available data on IAV and ΔPRS during pneumoperitoneum from three trials assessing the effect of IAP on postoperative recovery and airway pressure during laparoscopic surgery under general anesthesia. The primary endpoint was ΔIAV, and the secondary endpoint was ΔPRS. The endpoints' response to ΔIAP was modeled using mixed multivariable Bayesian regression to estimate which mathematical function best fitted it. IAP values on the pressure-volume (PV) curve where the endpoint rate of change according to IAP decreased were identified. Abdomino-thoracic transmission (ATT) rate, that is, the rate ΔPRS change to ΔIAP was also estimated. The best-fitting function was sigmoid logistic and linear for IAV and ΔPRS response, respectively. Increments in IAV reached a plateau at 6.0 [95%CI 5.9-6.2] L. ΔIAV for each ΔIAP decreased at IAP ranging from 9.8 [95%CI 9.7-9.9] to 12.2 [12.0-12.3] mmHg. ATT rate was 0.65 [95%CI 0.62-0.68]. One mmHg of IAP raised ΔPRS 0.88 cmH2O. During pneumoperitoneum, IAP has a nonlinear relationship with IAV and a linear one with ΔPRS. IAP should be set below the point where IAV gains diminish.NEW & NOTEWORTHY We found that intra-abdominal volume changes related to intra-abdominal pressure increase reached a plateau with diminishing gains in commonly used pneumoperitoneum pressure ranges. We also found a linear relationship between intra-abdominal pressure and respiratory driving pressure, a known marker of postoperative pulmonary complications.

Pharmacokinetics of micafungin in patients treated with extracorporeal membrane oxygenation: an observational prospective study. / Farmacocinética da micafungina em pacientes tratados com oxigenação por membrana extracorpórea: um estudo observacional prospectivo.

OBJECTIVE: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. METHODS: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. RESULTS: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. CONCLUSION: The pharmacokinetic parameters of micafungin were not significantly altered.

Farmacocinética da micafungina em pacientes tratados com oxigenação por membrana extracorpórea: um estudo observacional prospectivo / Pharmacokinetics of micafungin in patients treated with extracorporeal membrane oxygenation: an observational prospective study

RESUMO Objetivo: Determinar os níveis plasmáticos e o comportamento farmacocinético da micafungina em pacientes tratados com oxigenação por membrana extracorpórea. Métodos: As amostras foram colhidas por meio de pontos de acesso antes e depois da membrana, em dois hospitais espanhóis de nível terciário. Os momentos para o cálculo das curvas farmacocinéticas foram antes da administração do fármaco, e 1, 3, 5, 8, 18 e 24 horas após o início da infusão nos dias 1 e 4 de tratamento. Calcularam-se a área sob a curva, a depuração do fármaco, o volume de distribuição e a meia-vida plasmática por meio de análise farmacocinética não compartimental. Resultados: Os valores farmacocinéticos analisados no primeiro e quarto dias de tratamento não mostram qualquer diferença de concentração entre amostras colhidas antes da membrana e após a membrana, e o comportamento farmacocinético foi similar na vigência de diferentes falências de órgãos. A área sob a curva antes da membrana no dia 1 foi de 62,1 (IC95% 52,8 - 73,4) e a área sob a curva após a membrana nesse mesmo dia foi de 63,4 (IC95% 52,4 - 76,7), com p = 0,625. A área sob a curva antes da membrana no dia 4 foi de 102,4 (IC95% 84,7 - 142,8), enquanto a área sob a curva após a membrana nesse mesmo dia foi de 100,9 (IC95% 78,2 - 138,8), com p = 0,843. Conclusão: Os parâmetros farmacocinéticos da micafungina não foram alterados significantemente.

ABSTRACT Objective: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. Methods: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. Results: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. Conclusion: The pharmacokinetic parameters of micafungin were not significantly altered.

Intraabdominal Pressure Targeted Positive End-expiratory Pressure during Laparoscopic Surgery: An Open-label, Nonrandomized, Crossover, Clinical Trial.

BACKGROUND: Pneumoperitoneum for laparoscopic surgery is associated with a rise of driving pressure. The authors aimed to assess the effects of positive end-expiratory pressure (PEEP) on driving pressure at varying intraabdominal pressure levels. It was hypothesized that PEEP attenuates pneumoperitoneum-related rises in driving pressure. METHODS: Open-label, nonrandomized, crossover, clinical trial in patients undergoing laparoscopic cholecystectomy. "Targeted PEEP" (2 cm H2O above intraabdominal pressure) was compared with "standard PEEP" (5 cm H2O), with respect to the transpulmonary and respiratory system driving pressure at three predefined intraabdominal pressure levels, and each patient was ventilated with two levels of PEEP at the three intraabdominal pressure levels in the same sequence. The primary outcome was the difference in transpulmonary driving pressure between targeted PEEP and standard PEEP at the three levels of intraabdominal pressure. RESULTS: Thirty patients were included and analyzed. Targeted PEEP was 10, 14, and 17 cm H2O at intraabdominal pressure of 8, 12, and 15 mmHg, respectively. Compared to standard PEEP, targeted PEEP resulted in lower median transpulmonary driving pressure at intraabdominal pressure of 8 mmHg (7 [5 to 8] vs. 9 [7 to 11] cm H2O; P = 0.010; difference 2 [95% CI 0.5 to 4 cm H2O]); 12 mmHg (7 [4 to 9] vs.10 [7 to 12] cm H2O; P = 0.002; difference 3 [1 to 5] cm H2O); and 15 mmHg (7 [6 to 9] vs.12 [8 to 15] cm H2O; P < 0.001; difference 4 [2 to 6] cm H2O). The effects of targeted PEEP compared to standard PEEP on respiratory system driving pressure were comparable to the effects on transpulmonary driving pressure, though respiratory system driving pressure was higher than transpulmonary driving pressure at all intraabdominal pressure levels. CONCLUSIONS: Transpulmonary driving pressure rises with an increase in intraabdominal pressure, an effect that can be counterbalanced by targeted PEEP. Future studies have to elucidate which combination of PEEP and intraabdominal pressure is best in term of clinical outcomes.

Mu Opioid Receptor 1 (MOR-1) Expression in Colorectal Cancer and Oncological Long-Term Outcomes: A Five-Year Retrospective Longitudinal Cohort Study.

Preclinical evidence has shown increased expression of mu opioid receptor 1 (MOR-1) in colorectal cancer although its association with disease-free and overall survival (DFS and OS) has not been investigated. We hypothesized that MOR-1 was overexpressed in tumor samples compared to normal tissue and this was associated with decreased DFS and OS. We carried out a retrospective study assessing the association of MOR-1 tumor expression with long-term outcomes by immunohistochemistry in normal and tumor samples from 174 colorectal cancer patients. The primary endpoint was five years of DFS. Secondary endpoints were five years of OS, the difference in MOR-1 expression between normal and tumor tissue and the occurrence of postoperative complications. Multivariable Cox regression showed no significant association between MOR-1 expression and DFS (HR 0.791, 95% CI 0.603-1.039, p = 0.092). MOR-1 expression was higher in tumor tissue compared to non-tumor tissue. No associations were found between MOR-1 expression and OS or postoperative complications. These findings suggest that although MOR-1 is over-expressed in colorectal cancer samples there is no association to increased risk of recurrence or mortality. Future studies are warranted to elucidate the role of cancer stage, genetic polymorphism, and quantitative assessment of MOR-1 over-expression on long-term outcomes in colorectal cancer.

A multifaceted individualized pneumoperitoneum strategy for laparoscopic colorectal surgery: a multicenter observational feasibility study.

BACKGROUND: While guidelines for laparoscopic abdominal surgery advise using the lowest possible intra-abdominal pressure, commonly a standard pressure is used. We evaluated the feasibility of a predefined multifaceted individualized pneumoperitoneum strategy aiming at the lowest possible intra-abdominal pressure during laparoscopic colorectal surgery. METHODS: Multicenter prospective study in patients scheduled for laparoscopic colorectal surgery. The strategy consisted of ventilation with low tidal volume, a modified lithotomy position, deep neuromuscular blockade, pre-stretching of the abdominal wall, and individualized intra-abdominal pressure titration; the effect was blindly evaluated by the surgeon. The primary endpoint was the proportion of surgical procedures completed at each individualized intra-abdominal pressure level. Secondary endpoints were the respiratory system driving pressure, and the estimated volume of insufflated CO2 gas needed to perform the surgical procedure. RESULTS: Ninety-two patients were enrolled in the study. Fourteen cases were converted to open surgery for reasons not related to the strategy. The intervention was feasible in all patients and well-accepted by all surgeons. In 61 out of 78 patients (78%), surgery was performed and completed at the lowest possible IAP, 8 mmHg. In 17 patients, IAP was raised up to 12 mmHg. The relationship between IAP and driving pressure was almost linear. The mean estimated intra-abdominal CO2 volume at which surgery was performed was 3.2 L. CONCLUSION: A multifaceted individualized pneumoperitoneum strategy during laparoscopic colorectal surgery was feasible and resulted in an adequate working space in most patients at lower intra-abdominal pressure and lower respiratory driving pressure. ClinicalTrials.gov (Trial Identifier: NCT03000465).

Tromboelastometría: ¿determinación centralizada en el laboratorio o prueba a la cabecera del paciente? Experiencia en nuestro hospital como test centralizado / Thromboelastometry: centralized test in the laboratory or point of care testing? Experience in our hospital as centralized test

Introducción. La tromboelastografía es la herramienta que permite medir in vitro las propiedades viscoelásticas de la sangre de una manera dinámica y global, integrando las diferentes fases de la coagulación y fibrinólisis. Existen en el mercado dos dispositivos semiautomatizados: el tromboelastograma y el tromboelastómetro rotacional. Material y métodos. Se ha realizado un estudio observacional descriptivo retrospectivo de las solicitudes de tromboelastometría en nuestro hospital desde la implementación del protocolo con la técnica centralizada desde el laboratorio. Se ha evaluado el número de solicitudes, los servicios peticionarios y el grado de cumplimentación de la petición al laboratorio. Así mismo, hemos realizado una encuesta de satisfacción dirigida al personal facultativo del Servicio de Anestesia y Reanimación. El periodo estudiado fue de julio del 2012 a enero del 2016. Resultados. Desde el establecimiento del protocolo hasta la actualidad se ha producido un incremento y una consolidación de la técnica de tromboelastometría en nuestro hospital. La mayor parte de las solicitudes proceden de los Servicios de Anestesia y Reanimación (36,5%) y Angiología y Cirugía Cardiovascular (30,1%). En cuanto a la encuesta de satisfacción, los resultados obtenidos muestran una aceptación positiva por parte de los facultativos tanto con el protocolo como con los tiempos de respuesta obtenidos. Conclusiones. Estableciendo un protocolo elaborado y consensuado entre el laboratorio y los servicios solicitantes, podemos garantizar el estricto cumplimiento del mismo y que los tiempos de respuesta difieran poco de los obtenidos cuando esta técnica se realiza en la cabecera del paciente, permitiendo así dar un servicio global a todo el hospital (AU)

Introduction. Thromboelastography is the tool that allows in vitro measurement of the viscoelastic properties of the blood in a dynamic and comprehensive way, integrating the different phases of coagulation and fibrinolysis. There are two semi-automated devices on the market: the thromboelastogram and the rotational thromboelastometry analyzer. Material and methods. We have conducted a descriptive observatory retrospective study of the thromboelastography requests in our hospital after the implementation of the protocol. It has been evaluated the number of petitions, the petitioners services and the degree of filling of the application laboratory. Likewise, we have performed a satisfaction survey aimed at the medical staff of the Anesthesia and Resuscitation Service. The studied period was from July 2012 until January 2016. Results. From the protocol introduction in our hospital has been produced an increase and a consolidation of the thromboelastography. Most of the requests came from the Anesthesia and Resuscitation Service (36.5%) and Angiology and Cardiovascular Surgery Service (30.1%). As for the satisfaction survey, the results show a positive acceptance by the medical staff both of the protocol as of the response times obtained. Conclusions. By establishing a protocol elaborated and agreed between the laboratory and the requesting departments, we can guarantee the strict compliance of the same and that the response times only differ a little from the obtained ones when this technique is realized as point of care testing, providing a global service to the whole hospital (AU)