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.

Maintenance of equine anaesthesia over the last 50 years: Controlled inhalation of volatile anaesthetics and pulmonary ventilation.

In the first edition of this journal, Barbara Weaver wrote a review titled 'Equine Anaesthesia', stating that, at that time, it was quickly becoming accepted practice that many horses were being anaesthetised 'by essentially similar procedures, i.e. premedication, induction and then maintenance by controlled inhalation'. To celebrate the 50th anniversary of the first edition of this journal, this review covers the development of understanding and practice of inhalational anaesthesia and controlled ventilation in horses over the last 50 years. We review how the perceived benefits of halothane led to its widespread use, but subsequently better understanding of halothane's effects led to changes in equine anaesthetic practice and the utilisation of different inhalation agents (e.g. isoflurane and sevoflurane). We discuss how more recently, better understanding of the effects of the 'newer' inhalation agents' effects has led to yet more changes in equine anaesthetic practice, and while, further new inhalation agents are unlikely to appear in the near future, further enhancements to anaesthetic practice may still lead to improved outcomes. We review advances in our understanding of the anatomy and pathophysiology of the equine lung as well of the effects of anaesthesia on lung function and how these predispose to some of the common problems of gas exchange and ventilation during anaesthesia. We identify the aims of optimal mechanical ventilation for anaesthetic management and whether the various methods of ventilatory support during equine anaesthesia achieve them. We also highlight that further developments in equipment and optimal ventilator modes are likely in the near future.

The Anesthesia Workstation: Quo Vadis?

Ensuring adequate ventilation and oxygenation and delivering inhaled anesthetic agent to the patient remain core responsibilities of the anesthesia provider during general anesthesia. Because of the emphasis placed on physiology, pharmacology, clinical sciences, and administrative duties, the stellar anesthesia workstation technology may be underutilized by the anesthesia community. Target-controlled O2 and agent delivery and automated end-expired CO2 control have entered the clinical arena, with only cost, luddism, and administrative hurdles preventing their more widespread use. This narrative review will explain technological aspects of existing and recently introduced anesthesia workstations. Concepts rather than particular anesthesia machines will be addressed, but examples will mostly pertain to the more recently introduced workstations. The anesthesia workstation consists of a ventilator, a carrier gas and agent delivery system, a scavenging system, and monitors. Mainly, the circle breathing circuit configuration, ventilator, and carrier gas and agent delivery technology are discussed. Occasionally, technical details are provided to give the reader a taste of the modern technology.

Effects of Dexmedetomidine-Isoflurane versus Isoflurane Anesthesia on Brain Injury After Cardiac Valve Replacement Surgery.

OBJECTIVES: To compare dexmedetomidine combined with isoflurane versus isoflurane anesthesia on brain injury after cardiac surgery. DESIGN: A prospective, randomized, single-blind study. SETTING: University hospital. PARTICIPANTS: Adult patients undergoing elective valve replacement surgery. INTERVENTIONS: Ninety-seven patients scheduled for valve replacement surgery were randomly divided into 2 groups: dexmedetomidine and isoflurane (Dex-Iso, n = 50) and isoflurane alone (Iso, n = 47). Dexemedetomidine was infused at 0.6 µg/kg as a bolus, followed with 0.2 µg/kg/h until the end of surgery. MEASUREMENTS AND MAIN RESULTS: Jugular blood samples were drawn for analysis of matrix metalloproteinase-9 (MMP-9) and glial fibrillary acidic protein (GFAP) levels on time points of: T1 (before induction); T2 (5 minutes after cardiopulmonary bypass [CPB] onset); T3 (after CPB off); T4 (the first day after operation); T5 (the second day after operation). Plasma lactate levels in arterial and jugular venous blood also were quantified. The difference between arterial and jugular bulb venous blood lactate levels (AVDL) was calculated. An antisaccadic eye movement (ASEM) test was carried out on the day before the operation and the seventh day postoperatively. In both groups, serum MMP-9 and GFAP concentrations increased after CPB, with the peak values occurring after CPB. At time point T5, MMP-9 and GFAP levels were close to those at T1. MMP-9 concentrations in the Dex-Iso group were lower than the Iso group at T3 and T4. GFAP concentrations in the Dex-Iso group were lower at T3 but were higher than the Iso group at T2. No significant differences were found in AVDL between the 2 groups perioperatively except at T2. The ASEM scores decreased significantly postoperatively. There was no significant difference in the ASEM scores between the 2 treatment groups before and after the operation. CONCLUSIONS: The use of dexmedetomidine decreased the biochemical markers of brain injury but did not improve the neuropsychological test result after cardiac surgery.

Anesthesia-Related Carbon Monoxide Exposure: Toxicity and Potential Therapy.

Exposure to carbon monoxide (CO) during general anesthesia can result from volatile anesthetic degradation by carbon dioxide absorbents and rebreathing of endogenously produced CO. Although adherence to the Anesthesia Patient Safety Foundation guidelines reduces the risk of CO poisoning, patients may still experience subtoxic CO exposure during low-flow anesthesia. The consequences of such exposures are relatively unknown. In contrast to the widely recognized toxicity of high CO concentrations, the biologic activity of low concentration CO has recently been shown to be cytoprotective. As such, low-dose CO is being explored as a novel treatment for a variety of different diseases. Here, we review the concept of anesthesia-related CO exposure, identify the sources of production, detail the mechanisms of overt CO toxicity, highlight the cellular effects of low-dose CO, and discuss the potential therapeutic role for CO as part of routine anesthetic management.

Inhaled anaesthetics and nitrous oxide: Complexities overlooked: things may not be what they seem.

This review re-examines existing pharmacokinetic and pharmacodynamic concepts of inhaled anaesthetics. After showing where uptake is hidden in the classic FA/FI curve, it is argued that target-controlled delivery of inhaled agents warrants a different interpretation of the factors affecting this curve (cardiac output, ventilation and blood/gas partition coefficient). Blood/gas partition coefficients of modern agents may be less important clinically than generally assumed. The partial pressure cascade from delivered to inspired to end-expired is re-examined to better understand the effect of rebreathing during low-flow anaesthesia, including the possibility of developing a hypoxic inspired mixture despite existing machine standards. Inhaled agents are easy to administer because they are transferred according to partial pressure gradients. In addition, the narrow dose-response curves for the three end points of general anaesthesia (loss of response to verbal command, immobility and autonomic reflex control) allow the clinical use of MACawake, MAC and MACBAR to determine depth of anaesthesia. Opioids differentially affect these clinical effects of inhaled agents. The effect of ventilation-perfusion relationships on gas uptake is discussed, and it is shown how moving beyond Riley's useful but simplistic model allows us to better understand both the concept and the magnitude of the second gas effect of nitrous oxide. It is argued that nitrous oxide remains a clinically useful drug. We hope to bring old (but ignored) and new (but potentially overlooked) information into the educational and clinical arenas to stimulate discussion among clinicians and researchers. We should not let technology pass by our all too engrained older concepts.

Nitrous oxide-induced slow and delta oscillations.

OBJECTIVES: Switching from maintenance of general anesthesia with an ether anesthetic to maintenance with high-dose (concentration >50% and total gas flow rate >4 liters per minute) nitrous oxide is a common practice used to facilitate emergence from general anesthesia. The transition from the ether anesthetic to nitrous oxide is associated with a switch in the putative mechanisms and sites of anesthetic action. We investigated whether there is an electroencephalogram (EEG) marker of this transition. METHODS: We retrospectively studied the ether anesthetic to nitrous oxide transition in 19 patients with EEG monitoring receiving general anesthesia using the ether anesthetic sevoflurane combined with oxygen and air. RESULTS: Following the transition to nitrous oxide, the alpha (8-12 Hz) oscillations associated with sevoflurane dissipated within 3-12 min (median 6 min) and were replaced by highly coherent large-amplitude slow-delta (0.1-4 Hz) oscillations that persisted for 2-12 min (median 3 min). CONCLUSIONS: Administration of high-dose nitrous oxide is associated with transient, large amplitude slow-delta oscillations. SIGNIFICANCE: We postulate that these slow-delta oscillations may result from nitrous oxide-induced blockade of major excitatory inputs (NMDA glutamate projections) from the brainstem (parabrachial nucleus and medial pontine reticular formation) to the thalamus and cortex. This EEG signature of high-dose nitrous oxide may offer new insights into brain states during general anesthesia.

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.

Effects of inhalational anaesthesia with low tidal volume ventilation on end-tidal sevoflurane and carbon dioxide concentrations: prospective randomized study / Efectos de la anestesia inhalatoria con baja concentración final de volumen corriente de sevoflurano y dióxido de carbono: estudio prospectivo aleatorizado

Objective. We investigated how ventilation with low tidal volumes affects the pharmacokinetics of sevoflurane uptake during the first minutes of inhaled anaesthesia. Methods. Forty-eight patients scheduled for lung resection were randomly assigned to three groups. Patients in group 1, 2 and 3 received 3% sevoflurane for 3 min via face mask and controlled ventilation with a tidal volume of 2.2, 8 and 12 ml kg−1, respectively (Phase 1). After tracheal intubation (Phase 2), 3% sevoflurane was supplied for 2 min using a tidal volume of 8 ml kg−1 (Phase 3). Results. End-tidal sevoflurane concentrations were significantly higher in group 1 at the end of phase 1 and lower at the end of phase 2 than in the other groups as follows: median of 2.5%, 2.2% and 2.3% in phase 1 for groups 1, 2 and 3, respectively (P < 0.001); and 1.7%, 2.1% and 2.0% in phase 2, respectively (P < 0.001). End-tidal carbon dioxide values in group 1 were significantly lower at the end of phase 1 and higher at the end of phase 2 than in the other groups as follows: median of 16.5, 31 and 29.5 mmHg in phase 1 for groups 1, 2 and 3, respectively (P < 0.001); and 46.2, 36 and 33.5 mmHg in phase 2, respectively (P < 0.001). Conclusion. When sevoflurane is administered with tidal volume approximating the airway dead space volume, end-tidal sevoflurane and end-tidal carbon dioxide may not correctly reflect the concentration of these gases in the alveoli, leading to misinterpretation of expired gas data (AU)

Objetivo. Investigamos cómo la ventilación controlada con volúmenes corrientes bajos afecta a la farmacocinética del sevoflurano durante los primeros minutos de anestesia inhalada. Métodos. Cuarenta y ocho pacientes programados para cirugía de resección pulmonar fueron distribuidos al azar en tres grupos. Los pacientes del grupo 1, 2 y 3 recibieron sevoflurano al 3% durante 3 minutos mediante ventilación controlada a través de mascarilla con un volumen corriente de 2,2, 8 y 12 ml kg−1, respectivamente (Fase 1). Después de la intubación traqueal (Fase 2), se administró sevoflurano al 3% durante 2 minutos usando un volumen corriente de 8 ml kg−1 (Fase 3). Resultados. las concentraciones finales de sevoflurano fueron significativamente superiores en el grupo 1 al final de la fase I e inferiores al final de la fase II con respecto a los otros grupos: mediana del 2,5%, 2,2% y 2,3% en la fase I para los grupos 1, 2 y 3, respectivamente (P < 0,001), y 1,7%, 2,1% y 2,0% en la fase II, respectivamente (P < 0,001). Los valores de dióxido de carbono en el grupo 1 fueron significativamente inferiores al final de la fase I y superiores al final de la fase II frente a los otros grupos: mediana de 16,5, 31 y 29,5 mmHg en la fase I para los grupos 1, 2 y 3, respectivamente (P < 0,001), y 46,2 36, y 33,5 mmHg en fase II, respectivamente (P < 0,001). Conclusión. Cuando el sevoflurano se administra mediante volúmenes corrientes cercanos al volumen de espacio muerto de la vía aérea, las concentraciones finales de sevoflurano y dióxido de carbono pueden no reflejar correctamente la concentración de estos gases en los alvéolos, lo que puede conducir a una interpretación incorrecta de los gases expirados (AU)

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Rapid sequence induction and intubation: current controversy.

The changing opinion regarding some of the traditional components of rapid sequence induction and intubation (RSII) creates wide practice variations that impede attempts to establish a standard RSII protocol. There is controversy regarding the choice of induction drug, the dose, and the method of administration. Whereas some prefer the traditional rapid injection of a predetermined dose, others use the titration to loss of consciousness technique. The timing of neuromuscular blocking drug (NMBD) administration is different in both techniques. Whereas the NMBD should immediately follow the induction drug in the traditional technique, it is only given after establishing loss of consciousness in the titration technique. The optimal dose of succinylcholine is controversial with advocates and opponents for both higher and lower doses than the currently recommended 1.0 to 1.5 mg/kg dose. Defasciculation before succinylcholine was traditionally recommended in RSII but is currently controversial. Although the priming technique was advocated to accelerate onset of nondepolarizing NMBDs, its use has decreased because of potential complications and the introduction of rocuronium. Avoidance of manual ventilation before tracheal intubation was traditionally recommended to avoid gastric insufflation, but its use is currently acceptable and even recommended by some to avoid hypoxemia and to "test" the ability to mask ventilate. Cricoid pressure remains the most heated controversy; some believe in its effectiveness in preventing pulmonary aspiration, whereas others believe it should be abandoned because of the lack of scientific evidence of benefit and possible complications. There is still controversy regarding the best position and whether the head-up, head-down, or supine position is the safest during induction of anesthesia in full-stomach patients. These controversial components need to be discussed, studied, and resolved before establishing a standard RSII protocol.

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