Inhalational Anesthetic Agents Research Articles

A Randomized Crossover Comparison of the Effects of Propofol and Sevoflurane on Cerebral Hemodynamics during Carotid Endarterectomy

Intravenous and inhalational anesthetic agents have differing effects on cerebral hemodynamics: Sevoflurane causes some vasodilation, whereas propofol does not. The authors hypothesized that these differences affect internal carotid artery pressure (ICAP) and the apparent zero flow pressure (critical closing pressure) during carotid endarterectomy. Vasodilation is expected to increase blood flow, reduce ICAP, and reduce apparent zero flow pressure. In a randomized crossover study, the gradient between systemic arterial pressure and ICAP during carotid clamping was measured while changing between sevoflurane and propofol in 32 patients. Middle cerebral artery blood velocity, recorded by transcranial Doppler, and ICAP waveforms were analyzed to determine the apparent zero flow pressure. ICAP increased when changing from sevoflurane to propofol, causing the mean gradient between arterial pressure and ICAP to decrease by 10 mmHg (95% confidence interval, 6-14 mmHg; P<0.0001). Changing from propofol to sevoflurane had the opposite effect: The pressure gradient increased by 5 mmHg (95% confidence interval, 2-7 mmHg; P=0.002). Ipsilateral middle cerebral artery blood velocity decreased when changing from sevoflurane to propofol. Cerebral steal was detected in one patient after changing from propofol to sevoflurane. The apparent zero flow pressure (mean+/-SD) was 22+/-10 mmHg with sevoflurane and 30+/-14 mmHg with propofol (P<0.01). There was incomplete drug crossover due to the limited duration of carotid clamping. Compared with sevoflurane, ipsilateral ICAP and apparent zero flow pressure are both higher with propofol. Vasodilatation associated with sevoflurane can cause cerebral steal.

Takotsubo Cardiomyopathy after General Anesthesia for Eye Surgery

Takotsubo Cardiomyopathy after General Anesthesia for Eye Surgery

UK drug analysis prints and anaesthetic adverse drug reactions

Anaesthetic drugs were selected from the Medicines and Healthcare products Regulatory Agency Drug Analysis Prints in order to determine the number and types of reported reactions and associated mortality. The chosen drug groups were the intravenous induction agents, the neuromuscular blocking drugs and neostigmine, the inhalational anaesthetic agents and nitrous oxide, local anaesthetic agents and a selection of analgesics agents, naloxone and midazolam and its antagonist flumazenil. From each drug file, the number and type of reactions were analysed. Mortality was calculated as a percentage of the number of deaths against patient reports. A total of 11,199 reactions were analysed from 6603 patients of whom 620 (9%) died. Few drug records reported reactions from multiple constituent formulations. The majority of reactions were not allergic. The highest mortality was in the inhalational anaesthetic group. Although the greatest number of fatal events was associated with halothane, this drug is no longer used. Nevertheless the percentage remains high because cardiovascular mortality is still being reported. Local anaesthetic use was associated with the smallest percentage mortality (3%). The highest reported number of reactions was associated with the intravenous induction agents and idiosyncratic neurological and peripheral vascular reactions were linked with the use of etomidate. The reporting of allergic reactions was low. The data demonstrate that induction of anaesthesia presents the highest risk of adverse drug reaction; there is also mortality from newer drugs for example, desflurane, remifentanil as well as from drugs for which there is no alternative, for example, suxamethonium.

Clinical uses of dexmedetomidine in pediatric anesthesiology and critical care

Dexmedetomidine (Precedex®) is an α2-adrenergic agonist which is currently FDA-approved for the short-term (less than 24 hours) sedation of adult ICU patients. Its clinical effects include sedation, anxiolysis, analgesia, a decrease of the minimum alveolar concentration of inhalational anesthetic agents, blunting of the sympathetic nervous response to surgery, and lowering of heart rate and blood pressure. These beneficial physiologic effects combined with its relatively low incidence of adverse hemodynamic and respiratory effects have led to its use in the pediatric-aged patient in various applications including sedation during mechanical ventilation, prevention of emergence agitation following general anesthesia with sevoflurane or desflurane, provision of procedural-sedation, and to prevent withdrawal following the prolonged use of opioids and benzodiazepines. The following article reviews the reports of the use of dexmedetomidine in pediatric patients including dosing regimens and adverse effects. Its potential applications in the practice of pediatric anesthesiology and critical care are explored.

Drugs and the liver

The liver and its diseases can affect drug metabolism and drugs can modify liver function. Ethanol produces dose dependent liver damage and is the most common cause of cirrhosis. Aspirin has been associated with Reye's syndrome in children, which involves fatty degeneration of the viscera and liver failure. Most inhalational anaesthetic agents have been associated with postoperative liver dysfunction but much of the literatures concerns halothane. Halothane-associated hepatitis has been attributed to a direct effect of halothane or a metabolite on liver cells, while fulminating hepatic failure has been attributed to an immune reaction following repeat halothane exposure.

Professor Joseph Warren Horton (1889–1967): Biological Engineer

Joseph Warren Horton graduated with a degree in electrical engineering from the Massachusetts Institute of Technology (MIT) in 1914. He became involved in the early development of electrical measurement devices, televised image transmission, and the detection of underwater sound transmission. In the mid-1930s he was appointed the first leader of the newly created Department of Biological Engineering at MIT and in this position he made major contributions to the application of physics to human physiology, in particular by increasing the safety of explosive inhalational anaesthetic agents.

Microelectrode studies of isoflurane and oxygen vapour mixtures in dimethyl sulfoxide

The electrochemical reduction of the inhalation anaesthetic agent isoflurane was investigated at a commercially available Au microelectrode (5 μm) in DMSO solvent, individually, and also as a component of a simple vapour mixture with oxygen using both traditional voltammetric and potential step chronoamperometric techniques. In a binary gas mixture with oxygen, isoflurane is shown to react with the superoxide anion radical, formed from the electro-reduction of oxygen complicating their simultaneous detection. The observed cross-interference reaction is shown to be dependent of the electrode size and the concentration of the anaesthetic agent, isoflurane. Under steady-state conditions, and using small diameter microelectrodes (5 μm) and low isoflurane concentration ([ISO] <0.2% v/v), the superoxide/isoflurane reaction is shown to approach a one-electron process, where the coupled homogeneous reaction kinetics are almost “out-run”. The use of potential step chronoamperometric techniques however, is shown to significantly reduce the deleterious cross-interference reaction between superoxide and isoflurane. In essence, this work provides scope for the development of a rapid, accurate and inexpensive electrochemical gas sensor for measuring anaesthetic vapour mixture under clinically relevant conditions.

Effects of isoflurane and sevoflurane on the survival of skin flaps in rats

The effects of inhalational anaesthetic agents on survival of flaps are not well known. We investigated the effect of isoflurane and sevoflurane anaesthesia on survival of flaps using a caudally-based McFarlane skin flap in 20 male Wistar rats. Sevoflurane 1 minimum alveolar concentration (MAC) and isoflurane (1 MAC) in oxygen mixture was given to the animals. A 4 x10 cm caudally-based standard McFarlane flap was raised. There were no differences in any haemodynamic values or blood gases between the sevoflurane group and the isoflurane group. Skin flaps were assessed on the seventh day. The isoflurane group had a significantly smaller area of skin flap necrosis and an increased area of flap surviving than the sevoflurane group. We conclude that survival is significantly improved when isoflurane is used as the inhalational anaesthetic rather than sevoflurane.

Pharmacological and pathological modulation of cerebral physiology

Cerebrovascular physiology is modulated by anaesthetic agents and other drugs commonly used in the perioperative period, and may be substantially modified by common disease processes. The effect of any given intervention depends on baseline physiology, other interventions that are applied at the same time, and the duration for which interventions are used. In general, the intravenous anaesthetic agents tend to cause dose-related reductions in cerebral metabolism, and through flow metabolism coupling, proportionate reductions in cerebral blood flow and cerebral blood volume (and hence intracranial pressure). While intravenous anaesthetics can reduce cerebral activity to an isoelectric electroencephalogram, the opioids and benzodiazepines cannot achieve this. The inhalational anaesthetic agents produce similar effects to the intravenous agents at low dose levels, but at higher MAC values their intrinsic vasodilatory effects become prominent with resultant increases in cerebral blood flow and intracranial pressure. Nitrous oxide is an extremely potent vasodilator, the effects of which are not reversed by hyperventilation. There is much recent interest in xenon, which may have specific neuroprotective properties. Cerebral ischaemia, subarachnoid haemorrhage and head injury all impair cerebral autoregulatory responses and may alter responses to anaesthetic agents. The article outlines a rational approach to management of cerebrovascular physiology in the perioperative period.

Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane.

Refractory status epilepticus (RSE) is defined as continued seizures after 2 or 3 antiepileptic drugs have failed. Several intravenous agents have been used for RSE; however, problems occur with their toxicity and/or effectiveness. To report our experience with inhalational anesthesia (IA) in patients who were refractory to other antiepileptic drugs. Retrospective review during a 4-year period of patients with RSE treated with isoflurane and/or desflurane. Efficacy of IA on therapy in terminating RSE. Seven patients (4 male) aged 17 to 71 years received 7 to 15 (mean, 10) antiepileptic drugs in addition to IAs. The IAs were initiated after 1 to 103 (mean, 19) days of RSE and were used for a mean +/- SD 11 +/- 8.9 days. All patients received isoflurane, and 1 patient in addition received desflurane anesthesia 21 days after the onset of RSE for a total of 19 days. Regardless of seizure type, isoflurane and desflurane consistently stopped epileptic discharges with adequate, sustained electroencephalographic burst suppression within minutes of initiating IA therapy. Four patients had good outcomes, 3 died (1 of acute hemorrhagic leukoencephalitis, 1 of bowel infarction, and 1 of toxic encephalopathy, who remained in a persistent vegetative state until death 5.5 months after the onset of seizures). Complications during IA therapy included hypotension (7/7), atelectasis (7/7), infections (5/7), paralytic ileus (3/7), and deep venous thrombosis (2/7). No patient developed renal or hepatic dysfunction. Isoflurane and desflurane adequately suppressed RSE in all cases. Complications were common, but mortality and long-term morbidity were related to the underlying disease and duration of RSE. Prolonged use of isoflurane and desflurane is well tolerated.

Sedation after spinal anesthesia in elderly patients: a preliminary observational study with the PSA-4000.

Neuraxial blockade is known to have a sedative effect, decreasing the need for inhalational and iv anesthetic agents. The purpose of the present study was to quantify the sedative effect of spinal anesthesia and to determine the time of maximum sedation. This is an observational study in which 20 unsedated patients were scheduled to undergo urologic and orthopedic surgeries under spinal anesthesia. Patients with pre-existing neurological conditions or receiving psychotropic medications were excluded from the study. All received 1.5 mL (11.25 mg) of hyperbaric bupivacaine 0.75% intrathecally. No sedative or narcotic was administered intravenously or intrathecally. The Patient State Analyzer, (PSA-4000) was used to monitor sedation along with Observer's Assessment of Alertness and Sedation (OAA/S) scores every five minutes. Differences in patient state index (PSI) and OAA/S scores are expressed as median and range and were evaluated by Wilcoxon's signed rank test for non-parametric data; P < 0.05 was considered significant. PSI, OAA/S and time at lowest score are expressed as median(range). PSI scores decreased from baseline 99 (96-99) to 78 (56-87) at 35(14.5-54) min into the spinal anesthetic (P < 0.05). OAA/S scores decreased from baseline 5 to 4 (range 3-5) at the time of the lowest PSI scores (P < 0.05). In this elderly patient population, spinal anesthesia induced changes in the processed electroencephalogram with reduction in PSI and OAA/S scores. The reduction in afferent input to the reticular activating system could possibly explain the sedation that has been observed and the reduction in the PSA scores.

Principles of anaesthetic vaporizers

Inhalational anaesthetic agents are used for induction and maintenance of general anaesthesia and form the mainstay of modern anaesthetic practice. Inhalational agents have been developed and refined to suit changing anaesthetic requirements. The ideal characteristics of an inhalational agent are: • quick onset and offset • low airway irritability • cardiovascular stability • low incidence of side-effects. Vaporizer design has been influenced by the physical properties of the different agents and techniques to ensure their safe and accurate delivery. Some definitions relevant to the principles of vaporizers are given in Figure 1.

Desflurane does not accelerate recovery from operations of short duration: a practice audit.

Desflurane, a newer inhalation anesthetic agent, has been promoted as a superior drug because patients will awaken sooner after anesthesia. This has only been proven in operations of long duration (i.e., more than one hour). We assessed our experience using desflurane in short out-patient surgery with a retrospective analysis of a single surgeon's elective laparoscopic cholecystectomy patients. With Institutional consent, we performed a retrospective comparison of the postoperative recovery of patients who received desflurane/air/oxygen to historical control patients who received isoflurane/N2O/oxygen. Patient preoperative characteristics were similar in the two groups. Duration of surgery and the time from the end of surgery to patient leaving the operating room for the desflurane and isoflurane/N2O groups were (in minutes) 42.7 +/- 13.5 and 9.6 +/- 4.6 vs 47.2 +/- 15.1 and 8.5 +/- 4.1 respectively (P = NS). Total Aldrete scores upon presentation to the postanesthesia care unit (PACU) were 8.1 +/- 1.4 and 7.9 +/- 1.8 for the two groups respectively (P = NS). The percentage of patients who arrived in the PACU with consciousness scores of 2, 1, 0 for the desflurane and isoflurane/N2O groups were 20.4, 75.5, and 4.1 vs 14.6, 73.2 and 12.2 respectively (P = NS). Mean length of stay in the PACU for the two groups was 160 +/- 111 and 156 +/- 114 min (P = NS). Our results show that in short procedures the use of desflurane does not necessarily result in faster patient recovery or discharge from the PACU.

Breathing systems

The classification of apparatus used to deliver inhalational anaesthetic agents to a patient has undergone numerous revisions over the years. The classical terms, open, semi-open, semi-closed and closed, were applicable to the use of ether and are now outdated. Small changes in geometry and gas flow rates can lead to conversion from one type to another, causing confusion. The term breathing system is preferred to the old term breathing circuit, because gases do not flow in a circular path, with the exception of circle systems. A breathing system describes the components and its mode of operation. The terminology can be used generically (e.g. Mapleson A breathing system) or specifically (e.g. Magill breathing system). Breathing systems are customarily divided into three groups: • non-rebreathing systems • systems in which rebreathing is possible • systems using carbon dioxide absorption. By convention, rebreathing in an anaesthetic system refers to inhalation of some or all of the previously exhaled gases, including carbon dioxide and water. This is often considered to be a bad thing, but some rebreathing systems allow for the rebreathing of the alveolar dead space gas, which has already been warmed and humidified and contains no carbon dioxide, hardly an undesirable gas mixture.

Reduction of bispectral index value associated with clinically significant cerebral air embolism

Reduction of bispectral index value associated with clinically significant cerebral air embolism

Electrochemical reduction of the anaesthetic agent sevoflurane (fluoromethyl 2,2,2-trifluoro-1-[trifluoromethyl] ethyl ether) in the presence of oxygen and nitrous oxide

The electrochemical reduction of the inhalation anaesthetic agent sevoflurane was investigated at a variety of microelectrode substrates (Au, Ag and Cu) in dimethyl sulphoxide (DMSO) solvent, individually, and also as a component of a simple tertiary gas mixture with oxygen and nitrous oxide. In a gas mixture with oxygen, sevoflurane is shown to react with the superoxide anion radical, formed from the electro-reduction of oxygen complicating their simultaneous detection. However, the apparent timescale of reaction between the electrochemically produced superoxide and sevoflurane is shown to be dependent of the electrode size and the concentration of the anaesthetic agent, sevoflurane. Using microelectrodes with diameters ≤5 μm and low sevoflurane concentration ([SEVO]<0.2%, v/v), the reduction is shown to be a one-electron process, the superoxide/sevoflurane reaction kinetics are essentially “out run”. Using larger microelectrodes (diameters≥10 μm), or with higher concentrations of sevoflurane (0.5<[SEVO]<2.0%, v/v) the reduction current is augmented by the catalytic regeneration of oxygen, formed by the reaction between superoxide and sevoflurane. By contrast, in a tertiary gas mixture with nitrous oxide, sevoflurane reduction is shown to be unaffected by nitrous oxide or its reduction products. Unlike other anaesthetic agents, the reduction wave for sevoflurane no longer lies concomitant with the reduction wave of nitrous oxide. This work is a continuation of the development towards a rapid, accurate and inexpensive electrochemical gas sensor for the delivery of anaesthetic agents during surgery.

Comparisons of Myocardial Protective Effects of Sevoflurane at Different Concentrations against Ischemia in Isolated Rat Heart

Background: Sevoflurane, a newly developed halogenated inhalation anesthetic agent shows myocardial protective effects against global ischemia like other inhalation agents. We investigated differences between pharmacologic preconditioning effects at various concentrations of sevoflurane. Methods: Forty male Sprague-Dawley rats were subdivided into 4 groups (each n = 10). All groups underwent the same procedure (Langendorff preparation, 30 minutes ischemia and 60 minutes reperfusion) except for the concentrations of sevoflurane. The control group received no sevoflurane treatment. The sevo 1.6% group was given 1.6% sevoflurane before ischemia, the sevo 2.05% group was given 2.05% sevoflurane before ischemia, and the sevo 2.5% group was given 2.5% sevoflurane before ischemia. Hemodynamic parameters of all groups were recorded through a thin, saline-filled latex balloon and a transducer. Coronary flows were also measured. All hearts were stained by triphenyl tetrazolium to measure infarct size. Results: The sevoflurane administered groups showed higher left ventricular end systolic pressures and lower left ventricular end diastolic pressures than the control group after ischemia and reperfusion. The dP/ of the sevoflurane administration groups showed a more rapid recovery pattern after ischemia than the control. But no differences were found between the sevoflurane administered groups. Infarct sizes in the sevoflurane administered groups were smaller than those in the control group, and there were no significant differences between the sevoflurane administered groups. Conclusions: Sevoflurane (even below one MAC) administration before myocardial ischemia has a superb cardioprotective effects, i.e., rapid recovery of left ventricular fuctions, less stiffness development, and a reduced infarct size. There were no significant differences between the sevoflurane administered groups.

Concepts in the prevention and management of malignant hyperthermia

Malignant hyperthermia (MH) is a potentially life-threatening hypermetabolic condition that is triggered in susceptible individuals by several inhalation anesthetic agents and/or succinylcholine. The triggering agents reduce the uptake of calcium from the sarcoplasmic reticulum of skeletal muscle in susceptible patients. The increased cytoplasmic calcium sustains uncontrolled contraction in the skeletal muscles, resulting in the symptoms of MH. 1 Jurkat-Rott K. McCarthy T. Lehmann-Horn F. Genetics and pathogenesis of malignant hyperthermia. Muscle Nerve. 2000; 23: 4 Crossref PubMed Scopus (271) Google Scholar MH is inherited as an autosomal dominant disorder, and most susceptible individuals are asymptomatic until they are exposed to a triggering agent. When exposed to a triggering agent, tachycardia, hypercapnia, tachypnea, hyperthermia, hypermetabolism, acidemia, cardiac dysrhythmias, hypercalcemia, hyperkalemia, elevated creatinine kinase (CK) and transaminases, skin mottling, and muscle rigidity may become evident. If untreated, mortality approaches 70%. 2 Rosenberg H. Fletcher J.E. An update on the malignant hyperthermia syndrome. Ann Acad Med Singapore. 1994; 23: 84 PubMed Google Scholar

Successful implementation of a protocol for photorefractive keratectomy in children requiring anesthesia

Purpose To describe a protocol for treating children with photorefractive keratectomy (PRK) under general anesthesia and to review intraoperative and postoperative complications. Setting Institutional academic practice. Methods Nine patients between 3 years and 9 years of age were treated with PRK under general anesthesia for anisometropia with unilateral high myopia or high hyperopia and amblyopia of the affected eye. Induction of anesthesia and the surgical procedure were carried out in separate rooms. The laser beam was centered on the entrance pupil, and eye position was monitored throughout the procedure. Specific precautions were taken before and during the procedure to prevent unwanted effects of inhalational anesthetic agents on laser performance. Results All children did well, with no anesthesia-related or treatment-related complications. Conclusions Our protocol for PRK under general anesthesia was effective and efficient in children who were unable to cooperate for the procedure using local anesthesia. It can be adapted for laser in situ keratomileusis and other refractive surgical procedures in children and uncooperative adults.

Electrochemical studies of the anaesthetic agent isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether) in binary gas mixtures with oxygen and nitrous oxide

The electrochemical reduction of the inhalation anaesthetic agent isoflurane was investigated at a variety of microelectrode substrates (Au, Ag and Cu) in DMSO solvent, individually, and also as a component of a simple binary gas mixture with oxygen or nitrous oxide. In a binary gas mixture with oxygen, isoflurane is shown to react with the superoxide anion radical, formed from the electro-reduction of oxygen complicating their simultaneous detection. However, the electro-reduction of oxygen is shown to be dependent of the electrode size and the concentration of the anaesthetic agent, isoflurane. Using microelectrodes with diameters ≤5 μm and low isoflurane concentration ([ISO]<0.2% (v/v)), the reduction is shown to be a one-electron process, since the homogeneous reaction kinetics are essentially “out-run”. Using larger microelectrodes (diameters≥10 μm), or with higher concentrations of isoflurane, (0.5>[ISO]<2.0% (v/v)) the reduction current is augmented by the catalytic regeneration of oxygen, formed by the reaction between superoxide and isoflurane. By contrast, in a binary gas mixture with nitrous oxide, isoflurane reduction is shown to be unaffected by nitrous oxide or it is reduction products. The reduction waves for isoflurane and nitrous oxide are concomitant which complicates their simultaneous detection somewhat. In essence, this work provides scope for the development of a rapid, accurate and inexpensive electrochemical gas sensor for measuring the concentration of anaesthetic agents during surgery.