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.

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 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).

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.

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.

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.

Inhalation anaesthesia: from diethyl ether to xenon.

Modern anaesthesia is said to have began with the successful demonstration of ether anaesthesia by William Morton in October 1846, even though anaesthesia with nitrous oxide had been used in dentistry 2 years before. Anaesthesia with ether, nitrous oxide and chloroform (introduced in 1847) rapidly became commonplace for surgery. Of these, only nitrous oxide remains in use today. All modern volatile anaesthetics, with the exception of halothane (a fluorinated alkane), are halogenated methyl ethyl ethers. Methyl ethyl ethers are more potent, stable and better anaesthetics than diethyl ethers. They all cause myocardial depression, most markedly halothane, while isoflurane and sevoflurane cause minimal cardiovascular depression. The halogenated ethers also depress the normal respiratory response to carbon dioxide and to hypoxia. Other adverse effects include hepatic and renal damage. Hepatitis occurs most frequently with halothane, although rare cases have been reported with the other agents. Liver damage is not caused by the anaesthetics themselves, but by reactive metabolites. Type I hepatitis occurs fairly commonly and takes the form of a minor disturbance of liver enzymes, which usually resolves without treatment. Type II, thought to be immune-mediated, is rare, unpredictable and results in a severe fulminant hepatitis with a high mortality. Renal damage is rare, and was most often associated with methoxyflurane because of excessive plasma fluoride concentrations resulting from its metabolism. Methoxyflurane was withdrawn from the market because of the high incidence of nephrotoxicity. Among the contemporary anaesthetics, the highest fluoride concentrations have been reported with sevoflurane, but there are no reports of renal dysfunction associated with its use. Recently there has been a renewed interest in xenon, one of the noble gases. Xenon has many of the properties of an ideal anaesthetic. The major factor limiting its more widespread is the high cost, about 2,000 times the cost of nitrous oxide.

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.

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.

One-lung anesthesia update.

One-lung ventilation is used during a variety of cardiac, thoracic, and major vascular procedures. Endobronchial tubes, bronchial blockers, and occasionally, single-lumen tubes are used to isolate the lungs. Patients with difficult airways and pediatric patients provide special challenges for lung isolation. Finally, intraoperative hypoxia and hypercarbia in patients with intrinsic lung disease frequently complicate one-lung anesthesia. The concepts and controversies in lung isolation techniques are discussed.

Neuro anaesthesia--a review of the basic principles and current practices.

The changes in intracranial pressure which occur following a change in one of the constituent volumes within the skull are governed by the Monro-Kellie doctrine, stated in the late 18th century and describes how an increase in one of the constituent volumes must be reflected by a reciprocal decrease in another volume to avoid any change in pressure and that if this does not occur, there is a rapid rise in intracranial pressure. Cerebral blood flow is affected by many physiological and pharmacological factors, and is relevant as a change in cerebral blood flow results in a similar alteration in cerebral arterial volume which will affect intracranial dynamics. Another important concept to be understood is cerebral perfusion pressure, how it is related to intracranial and arterial pressures and its relevance during the conduct of any neuroanaesthetic. Both carbon dioxide and the volatile agents are potent vasodilating agents and will cause a catastrophic rise in intracranial pressure and fall in cerebral perfusion pressure if hypercapnia develops in the presence of more than one MAC of a volatile agent. The volatile agents are reviewed and it is stressed that while isoflurane may have advantages over the older volatile agents it is not without complication and nitrous oxide which has always been regarded as an innocuous agent may also have some significant intracranial affects. The use of propofol, as an infusion and the neuromuscular blocking agents and narcotics are described. Recently the use of induced hypotension during clipping of cerebral aneurysms has been questioned and this view and the treatment of vasospasm is discussed in some detail.(ABSTRACT TRUNCATED AT 250 WORDS)

New advances in anesthesia.

Pharmacologic advances in anesthesia over the last decade have focused on drug safety, shorter durations of action, reversibility, and ease of administration. This is reflective of major changes in the focus of patient care from inpatient to outpatient settings as well as from available risk management data that support the investigation of these new drugs. The pharmacologic advances discussed included those drugs in current practice as well as experimental drugs yet to be released for general clinical use. Inhaled agents, such as isoflurane and perhaps the experimental agent, desflurane, will maintain or achieve their popularity because of the relative ease of administration and wide margins of safety. Propofol, the most recent intravenous anesthetic available for clinical use, has already gained wide acceptance because of its dual function as an induction and maintenance agent and its appropriateness for use in the ambulatory surgical population. The role of midazolam in anesthesia practice has increased to such an extent that it has largely supplanted the use of diazepam (Valium). The introduction of the antagonist, flumazenil, will undoubtedly enhance the safety and efficacy of midazolam as well as broaden its applicability of use across various patient populations. Several of the newer synthetic narcotics, such as alfentanil and sufentanil, have replaced other narcotics formerly used in anesthesia practice, such as meperidine and morphine, primarily because of their short action and lack of significant side effects. The use of muscle relaxants as a critical component of anesthetic management has led to the development of a number of new drugs in this classification. Pharmacologic management of patients under anesthesia will at some future date likely include the administration of alpha 2 agonists. Administration of these drugs can reduce anesthetic requirements of traditional agents by as much as 50%. As research continues, new drugs will be incorporated into the practice of anesthesia, ones that will promote rapid uptake, low toxicity, intense analgesia, easy reversibility, shorter durations, and fewer side effects. One measure of success relative to pharmacologic development in anesthesia is the recent and dramatic decreases in patient morbidity and mortality figures over the last decade. This attests to the rapid growth and development of not only improved patient monitoring systems but also newly improved "agents of sleep."

Xenon: anesthesia for the 21st century.

Xenon is a naturally occurring, gaseous element that comprises 0.000008% of air, or 0.05 parts per million. It was discovered by Ramsey and Travers in 1898. Xenon is found on the Periodic Table in group 0, which is the group commonly referred to as the noble or inert gases. It is obtained by fractionally distilling liquefied air. Xenon has been studied sporadically within the discipline of anesthesia as a replacement for nitrous oxide. Because it is a naturally occurring element, xenon is not a pollutant. It is not an occupationally hazardous gas. It is neither teratogenic nor fetotoxic, as is nitrous oxide; it does not contribute to the depletion of stratospheric ozone, as do chlorofluorocarbons and nitrous oxide. Xenon does not contribute to global warming and the greenhouse effect, as does nitrous oxide. Xenon provides excellent anesthesia and analgesia at its minimum alveolar concentration, 71%, as well as excellent analgesia at "subanesthetic" concentrations. Xenon also provides excellent cardiovascular and hemodynamic stability and offers both rapid induction and emergence. Because of the relatively high cost of xenon, a low-flow, closed-system technique is needed to be most cost effective.