Comparison between epidural and intravenous analgesia effects on disease-free survival after colorectal cancer surgery: a randomised multicentre controlled trial.

BACKGROUND: Thoracic epidural analgesia (TEA) has been suggested to improve survival after curative surgery for colorectal cancer compared with systemic opioid analgesia. The evidence, exclusively based on retrospective studies, is contradictory. METHODS: In this prospective, multicentre study, patients scheduled for elective colorectal cancer surgery between June 2011 and May 2017 were randomised to TEA or patient-controlled i.v. analgesia (PCA) with morphine. The primary endpoint was disease-free survival at 5 yr after surgery. Secondary outcomes were postoperative pain, complications, length of stay (LOS) at the hospital, and first return to intended oncologic therapy (RIOT). RESULTS: We enrolled 221 (110 TEA and 111 PCA) patients in the study, and 180 (89 TEA and 91 PCA) were included in the primary outcome. Disease-free survival at 5 yr was 76% in the TEA group and 69% in the PCA group; unadjusted hazard ratio (HR): 1.31 (95% confidence interval [CI]: 0.74-2.32), P=0.35; adjusted HR: 1.19 (95% CI: 0.61-2.31), P=0.61. Patients in the TEA group had significantly better pain relief during the first 24 h, but not thereafter, in open and minimally invasive procedures. There were no differences in postoperative complications, LOS, or RIOT between the groups. CONCLUSIONS: There was no significant difference between the TEA and PCA groups in disease-free survival at 5 yr in patients undergoing surgery for colorectal cancer. Other than a reduction in postoperative pain during the first 24 h after surgery, no other differences were found between TEA compared with i.v. PCA with morphine.

A high risk of sleep apnea is associated with less postoperative cognitive dysfunction after intravenous anesthesia: results of an observational pilot study.

BACKGROUND: The obstructive sleep apnea syndrome (OSAS) is characterized by temporary cerebral hypoxia which can cause cognitive dysfunction. On the other hand, hypoxia induced neurocognitive deficits are detectable after general anesthesia. The objective of this study was to evaluate the impact of a high risk of OSAS on the postoperative cognitive dysfunction after intravenous anesthesia. METHODS: In this single center trial between June 2012 and June 2013 43 patients aged 55 to 80 years with an estimated hospital stay of at least 3 days undergoing surgery were enrolled. Patients were screened for a high risk of OSAS using the STOP-BANG test. The cognitive function was assessed using a neuropsychological test battery, including the DemTect test for cognitive impairment and the RMBT test for memory, the day before surgery and within 36 h after extubation. RESULTS: Twenty-two of the 43 analyzed patients were identified as patients with a high risk of OSAS. Preoperatively, OSAS patients showed a significant worse performance only for the DemTect (p = 0.0043). However, when comparing pre- and postoperative test results, the OSAS patients did not show a significant loss in any test but significantly improved in RMBT test, whereas the control group showed a significant worse performance in three of eight tests. In five tests, we found a significant difference between the two groups with respect to the change from pre- to postoperative cognitive function. CONCLUSION: Patients with a high risk of OSAS showed a less impairment of memory function and work memory performance after intravenous anesthesia. This might be explained by a beneficial effect of intrinsic hypoxic preconditioning in these patients.

Effects of propofol/remifentanil-based total intravenous anesthesia versus sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-ß and prognosis after breast cancer surgery: a prospective, randomized and controlled study.

BACKGROUND: Vascular endothelial growth factor (VEGF) and transforming growth factor-ß (TGF-ß) have been involved in tumor growth and metastasis. Sevoflurane may promote angiogenesis, whereas propofol can present an anti-angiogenic effect. In this study, we compared the effects of propofol/remifentanil-based total intravenous anesthesia (TIVA) and sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-ß, as well as recurrence- free survival (RFS) rates in the patients undergoing breast cancer surgery. METHODS: Eighty female patients undergoing breast cancer resection were enrolled and randomized to receive either sevoflurane-based inhalational anesthesia (SEV group) or propofol/remifentanil-based TIVA (TIVA group). The serum concentrations of VEGF-C and TGF-ß before and 24 h after surgery were measured and RFS rates over a two-year follow-up were analyzed in both groups. The postoperative pain scores assessed using a visual analogue scale (VAS) and the use of perioperative opioids were also evaluated. RESULTS: Although VAS scores at 2 h and 24 h after surgery were comparable between the two groups, there were more patients receiving postoperative fentanyl in the TIVA group (16[40%]) compared with the SEV group (6[15%], p = 0.023). VEGF-C serum concentrations increased after surgery from 105 (87-193) pg/ml to174 (111-281) pg/ml in the SEV group (P = 0.009), but remained almost unchanged in the TIVA group with 134 (80-205) pg/ml vs.140(92-250) pg/ml(P = 0.402). The preoperative to postoperative change for VEGF-C of the SEV group (50 pg/ml) was significantly higher than that of the TIVA group (12 pg/ml) with a difference of 46 (- 11-113) pg/ml (P = 0.008). There were also no significant differences in the preoperative and postoperative TGF-ß concentrations between the two groups. The two-year RFS rates were 78% and 95% in the SEV and TIVA groups (P = 0.221), respectively. CONCLUSION: In comparison with sevoflurane-based inhalational anesthesia, propofol/remifentanil -based total intravenous anesthesia can effectively inhibit the release of VEGF-C induced by breast surgery, but didn't seem to be beneficial in the short-term recurrence rate of breast cancer. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1800017910 . Retrospectively Registered (Date of registration: August 20, 2018).

Inhalational versus Intravenous Induction of Anesthesia in Children with a High Risk of Perioperative Respiratory Adverse Events: A Randomized Controlled Trial.

BACKGROUND: Limited evidence suggests that children have a lower incidence of perioperative respiratory adverse events when intravenous propofol is used compared with inhalational sevoflurane for the anesthesia induction. Limiting these events can improve recovery time as well as decreasing surgery waitlists and healthcare costs. This single center open-label randomized controlled trial assessed the impact of the anesthesia induction technique on the occurrence of perioperative respiratory adverse events in children at high risk of those events. METHODS: Children (N = 300; 0 to 8 yr) with at least two clinically relevant risk factors for perioperative respiratory adverse events and deemed suitable for either technique of anesthesia induction were recruited and randomized to either intravenous propofol or inhalational sevoflurane. The primary outcome was the difference in the rate of occurrence of perioperative respiratory adverse events between children receiving intravenous induction and those receiving inhalation induction of anesthesia. RESULTS: Children receiving intravenous propofol were significantly less likely to experience perioperative respiratory adverse events compared with those who received inhalational sevoflurane after adjusting for age, sex, American Society of Anesthesiologists physical status and weight (perioperative respiratory adverse event: 39/149 [26%] vs. 64/149 [43%], relative risk [RR]: 1.7, 95% CI: 1.2 to 2.3, P = 0.002, respiratory adverse events at induction: 16/149 [11%] vs. 47/149 [32%], RR: 3.06, 95% CI: 1.8 to 5. 2, P < 0.001). CONCLUSIONS: Where clinically appropriate, anesthesiologists should consider using an intravenous propofol induction technique in children who are at high risk of experiencing perioperative respiratory adverse events. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B725.

Inflamación y anestesia, ¿hay algo nuevo? / Inflammation and anesthesia, is there anything new?

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Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia.

This study describes the pharmacodynamic interaction between propofol and remifentanil. Sixty patients who were scheduled for elective surgery under general anaesthesia (30 males/30 females) were enrolled. Patients were randomly allocated to receive one of 15 combinations of drug levels. Baseline electroencephalograms (EEGs) were recorded for 5 minutes prior to administering the drugs. Patients received a target-controlled infusion at one of four predefined doses of propofol (high, 3 µg/mL; medium, 1.5 µg/mL; low, 0.5 µg/mL; or no drug) and of remifentanil (high, 6 or 8 ng/mL; medium, 4 ng/mL; low, 2 ng/mL; or no drug). The occurrence of muscle rigidity, apnoea, and loss of consciousness (LOC) was monitored, and EEGs were recorded during the drug administration phase. Electroencephalographic approximate entropy (ApEn) and temporal linear mode complexity (TLMC) parameters at baseline and under steady state conditions were calculated off-line. Response surfaces were developed to map the interaction between propofol and remifentanil to the probability of occurrence for quantal responses (muscle rigidity, apnoea, LOC) and ApEn and TLMC measurements. Model parameters were estimated using non-linear mixed effects modelling. The response surface revealed infra-additive and synergistic effects for muscle rigidity and apnoea, respectively. The effects of the combined drugs on LOC and EEG parameters (eg, ApEn and TLMC) were additive. The C50 estimates of remifentanil (ng/mL) and propofol (µg/mL) were 9.11 and 130 000 for muscle rigidity, 8.99 and 6.26 for apnoea, 13.9 and 3.04 for LOC, 23.4 and 10.4 for ApEn, and 14.8 and 6.51 for TLMC, respectively. The probability of occurrence for muscle rigidity declined when propofol was combined with remifentanil.

Anaesthesia in Cancer Surgery: Can it Affect Cancer Survival?

Surgical removal of a tumor may, ironically, unleash prometastatic effects that enhance cancer recurrence and metastatic disease. The patient's physiologic response to the surgical trauma may increase tumor cell growth and invasiveness while diminishing the immune system's ability to eliminate residual disease. At the same time anaesthetic drugs used to accomplish the surgery may also have important effects on cancer cells and the immune system. Those combined effects potentially lead to sooner recurrence of local or metastatic cancer, and, ultimately, decreased survival. This review explores current research on the influences of surgery and anaesthesia on tumor cells, the immune system, and cancer recurrence. Although a substantial body of evidence sheds much light on the nature of these processes and is at times suggestive of how they might be relevant in clinical practice that literature also reveals a foundation of data that remain largely preclinical with as yet insufficient human study to support clinical recommendations. The tantalizing possibility that anaesthetic care of the surgical oncology patient might affect long term oncologic outcome remains unproven speculation, awaiting prospective human study.

Total intravenous anesthesia will supercede inhalational anesthesia in pediatric anesthetic practice.

Inhalational anesthesia has dominated the practice of pediatric anesthesia. However, as the introduction of agents such as propofol, short-acting opioids, midazolam, and dexmedetomidine a monumental change has occurred. With increasing use, the overwhelming advantages of total intravenous anesthesia (TIVA) have emerged and driven change in practice. These advantages, outlined in this review, will justify why TIVA will supercede inhalational anesthesia in future pediatric anesthetic practice.

Are postoperative behavioural changes after adenotonsillectomy in children influenced by the type of anaesthesia?: A randomised clinical study.

BACKGROUND: Negative postoperative behavioural changes (NPOBCs) are very frequent in children after surgery and general anaesthesia. If they persist, emotional and cognitive development may be affected significantly. OBJECTIVE: To assess whether the choice of different anaesthetic techniques for adenotonsillectomy may impact upon the incidence of NPOBC in repeated measurements. DESIGN: A randomised, controlled, parallel-group trial. SETTING: University Hospital Split, Croatia. PATIENTS: Sixty-four children (aged 6 to 12 years, ASA 1 to 2) undergoing adenotonsillectomy assigned into one of two groups: sevoflurane (S) (n = 32) or total intravenous anaesthesia (TIVA) (n = 32). INTERVENTIONS: Permuted-block randomisation with random block sizes of 4, 6 and 8, administering anaesthesia, and evaluation of NPOBC with the Post Hospitalization Behavior Questionnaire (PHBQ: 27 items describing six subscales). The PHBQ was filled out by parents at postoperative days (POD) 1, 3, 7 and 14, and 6 months after surgery. MAIN OUTCOME MEASURES: Differences in numbers of NPOBCs between two anaesthesia techniques, and NPOBC analysis by subscales. RESULTS: The prevalence of at least one NPOBC after surgery ranged from a maximum of 80% [95% confidence interval (CI) 71 to 90%] on POD 1 to a minimum of 43% (95% CI 31 to 56%) 6 months after surgery. Absolute risk reduction for at least one NPOBC in the TIVA group compared with the S group increased from 0.24 on POD 1 to 0.55 6 months after surgery. The number of NPOBCs was also lower in the TIVA group [median 5, interquartile range (IQR) 2 to 10] than in the S group (median 22, IQR 10 to 32) (P < 0.001). The overall number of NPOBCs within PHBQ subscales was significantly lower in the TIVA group than in the S group. The largest difference in the number of NPOBCs between groups was observed for the separation anxiety subscale (mean 5, 95% CI 1 to 9; P < 0.001) followed by the general anxiety subscale (mean 4, 95% CI 3 to 5; P < 0.001) and apathy/withdrawal subscale (mean 3, 95% CI 1 to 5; P < 0.001). CONCLUSION: The prevalence of NPOBC after elective adenotonsillectomy in 6 to 12-year-old children was very high (80%). The choice of anaesthetic technique for adenotonsillectomy in children influenced the incidence and type of NPOBC. Sevoflurane/nitrous oxide anaesthesia was associated with more frequent and prolonged NPOBCs than TIVA, especially in the separation anxiety, general anxiety and withdrawal/apathy subscales.

Total intravenous anesthesia for aortic aneurysm replacement surgery in a patient with limb-girdle dystrophy / Anestesia total intravenosa para sustitución de aorta ascendente por aneurisma en paciente con distrofia muscular de cinturas

We report the anesthetic management with total intravenous anesthesia of a 61-year-old male diagnosed with limb-girdle muscular dystrophy admitted for replacement of ascending aorta due to an aortic aneurysm. Limb-girdle muscular dystrophy belongs to a genetically heterogeneous group of muscular dystrophies involving shoulder and hip girdles. Although the risk of malignant hyperthermia does not seem to be increased in these patients compared with the general population, the exposure to inhaled anesthetics and succinylcholine should probably be avoided because these patients have a predisposition to hyperkalemia and rhabdomyolysis. We chose to use total intravenous anesthesia with propofol, remifentanil and muscle relaxants to reduce oxygen consumption, and later to reduce the doses of propofol and remifentanil. The combination of a carefully planned anesthetic strategy, anesthetic depth, and neuromuscular blockade monitoring is explained (AU)

Presentamos el tratamiento anestésico con anestesia total intravenosa de un varón de 61 años diagnosticado de distrofia muscular de cinturas para sustitución de aorta ascendente por aneurisma aórtico. La distrofia muscular de cinturas es un grupo genéticamente heterogéneo de distrofias musculares que afecta predominantemente la cintura escapular y pélvica. Aunque el riesgo de hipertermia maligna no parece estar aumentado en estos pacientes en comparación con la población general, la exposición a anestésicos inhalatorios y succinilcolina probablemente deba evitarse ya que existe una predisposición a la hiperpotasemia y rabdomiólisis. Utilizamos anestesia intravenosa total con propofol y remifentanilo, además de bloqueanttes musculares durante el procedimiento quirúrgico, para reducir el consumo de oxígeno y minimizar las dosis de propofol y remifentanilo. La combinación de una estrategia anestésica cuidadosa, monitorización de bloqueo neuromuscular y profundidad anestésica se describen a continuación (AU)

Anestesia regional intravenosa con anestésicos locales de larga duración. Actualización / Intravenous regional anesthesia with long-acting local anesthetics. An update

La anestesia regional intravenosa es una técnica ampliamente utilizada en intervenciones quirúrgicas de poca duración, especialmente en las extremidades superiores, y menos frecuentemente en las inferiores. Su primera aparición data de principios del siglo xx, cuando Bier inyectó procaína como anestésico local. La ejecución de esta técnica como anestesia quirúrgica no ha cambiado mucho desde entonces, si bien diversos fármacos, particularmente anestésicos locales de larga duración como ropivacaína y levobupivacaína en bajas concentraciones, han sido introducidos en la práctica clínica. Además, fármacos como opioides, bloqueantes neuromusculares, paracetamol, neostigmina, magnesio, ketamina, keterolaco y clonidina han sido investigados como complementarios a los anestésicos locales, y parecen aportar beneficios en cuanto al inicio de la anestesia y una más larga duración de la analgesia perioperatoria. Este artículo de revisión intenta dar una visión global de los conocimientos actuales en anestésicos locales de larga duración para anestesia regional intravenosa (AU)

Intravenous regional anesthesia is a widely used technique for brief surgical interventions, primarily on the upper limbs and less frequently, on the lower limbs. It began being used at the beginning of the 20th century, when Bier injected procaine as a local anesthetic. The technique to accomplish anesthesia has not changed much since then, although different drugs, particularly long-acting local anesthetics, such as ropivacaine and levobupivacaine in low concentrations, were introduced. Additionally, drugs like opioids, muscle relaxants, paracetamol, neostigmine, magnesium, ketamine, clonidine, and ketorolac, have all been investigated as adjuncts to intravenous regional anesthesia, and were found to be fairly useful in terms of an increased onset of operative anesthesia and longer lasting perioperative analgesia. The present article provides an overview of current knowledge with emphasis on long-acting local anesthetic drugs (AU)

[Intravenous regional anesthesia with long-acting local anesthetics. An update]. / Anestesia regional intravenosa con anestésicos locales de larga duración. Actualización.

Intravenous regional anesthesia is a widely used technique for brief surgical interventions, primarily on the upper limbs and less frequently, on the lower limbs. It began being used at the beginning of the 20th century, when Bier injected procaine as a local anesthetic. The technique to accomplish anesthesia has not changed much since then, although different drugs, particularly long-acting local anesthetics, such as ropivacaine and levobupivacaine in low concentrations, were introduced. Additionally, drugs like opioids, muscle relaxants, paracetamol, neostigmine, magnesium, ketamine, clonidine, and ketorolac, have all been investigated as adjuncts to intravenous regional anesthesia, and were found to be fairly useful in terms of an increased onset of operative anesthesia and longer lasting perioperative analgesia. The present article provides an overview of current knowledge with emphasis on long-acting local anesthetic drugs.

[Update on propofol TCI in children]. / Nouvelles avancées en AIVOC pédiatrique au propofol.

For several years, total intravenous anaesthesia (TIVA) has demonstrated many advantages that allow considering propofol anaesthesia as an interesting alternative in pediatric anaesthesia. TCI in children requires calculation and validation of pharmacokinetic (PK) models specifically adapted to the paediatric population. Several PK models based on a 3-compartement approach have been proposed in children: all these models, which integrate only weight as covariable, show increased distribution volumes with a wide interindividual variability. The particular importance to include physiological covariables, as age and lean body mass, to describe metabolic processes during growth and maturation in pediatric PKPD models is in agreement with recent allometric scaling works in children. However, as pharmacodynamic (PD) parameters are still debated in children, there is up to now, no PKPD model currently available for paediatric anaesthesia. Schnider et al.'s model, a model described in adults that includes numerous covariables, may be adapted and more efficient than the classical paediatric models to describe propofol-PKPD relationship in children over 5years. Whatever the model, a pharmacodynamic feedback such as the bispectral index may be useful to counteract interindividual variability in the paediatric population.

Descripción de un paciente sometido a radiofrecuencia hepática percutánea / No disponible

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New drugs and technologies, intravenous anaesthesia is on the move (again).

Although well established in clinical practice, both propofol and midazolam have limitations. New hypnotics with different and potentially superior pharmacokinetics and pharmacodynamics are under development. These include the benzodiazepine receptor agonists CNS7056 and JM-1232 (-), the etomidate-based methoxycarbonyl-etomidate and carboetomidate, the propofol-related structures PF0713 and fospropofol, and THRX-918661/AZD3043. The basic pharmacology and the initial anaesthesia studies for each of these agents are reviewed. Several of the agents (CNS7056, THRX-918661/AZD3043, and fospropofol) have reached the stage of clinical trials. To be successful, novel compounds need to establish clear clinical advantages over existing agents and where possible the new agents are discussed in this context. Computer-controlled drug administration offers the ability to automatically implement infusion schemes too complex for manual use and the possibility of linking patient monitoring to administration to enhance patient safety.

World SIVA: the pediatric initiative.

Total intravenous anesthesia and targeted controlled infusions are emerging and developing techniques that can have a broad range of important clinical applications in future pediatric care.

TIVA, TCI, and pediatrics: where are we and where are we going?

The current role of TIVA in children is limited because of hardware limitations, and pharmacokinetic and monitoring issues. Nonetheless, the role of TIVA in children has been increasing in the past decade, in part because of surgical and medical indications. If TIVA is to become more widely used, it must be easy and simple to set up, without serious drawbacks and without added risks. Currently, many drugs destined for use with TIVA in children are off-label, and their pharmacology is poorly understood. Such off-label designations must be resolved if TIVA is to become more widely used. At the same time, many institutions have a limited number of infusion pumps, which creates a serious bottleneck and restriction on the use of TIVA.. If a true TIVA technique is used, i.v. access must be established before induction of anesthesia, which will require a means to establish i.v. access painlessly, e.g., using a topical local anesthetic. This is not a common practice in a number of jurisdictions but must be introduced if TIVA is to expand in its scope in children. Currently, I believe that we deliver a 'partial' TIVA technique in which TIVA occasionally follows an inhalational induction but in the future when the current obstacles have been resolved, I believe that we will be able practice a true TIVA technique ubiquitously in children.