Intravenous Induction Agents Research Articles

The sitting position in neurosurgery — Unresolved hemodynamic consequences!

ONTROVERSY continues to surround use of the sitting position for neurosurgical procedures. 1–3 The seated position, while presenting a number of challenges for the anesthesiologist, offers many surgical advantages for patients undergoing posterior fossa and cervical spine procedures. Specifically, the upright position improves operator orientation and surgical access to midline lesions in many posterior fossa cases. Gravitational drainage of venous blood from the surgical field and lowering of intracranial pressure increases technical ease and allows more rapid access to bleeding points. 4 An unobstructed view of the face allows motor responses to cranial nerve stimulation to be directly observed in the sitting position, and access to the anterior chest wall is facilitated in the event of cardiovascular collapse. Despite the many advantages offered from the surgical perspective, the sitting position presents unique physiological challenges for the anesthesiologist with the potential for serious complications. 1,5 Venous air embolism, with or without paradoxical air embolism, is a major concern in relation to the use of this position. 2,6 Hemodynamic instability with hypotension and potential compromise of cerebral and myocardial perfusion may occur. Reduction of inhaled volatile anesthetic agent and decreasing depth of anesthesia may predispose the seated patient to the risk of intraoperative awareness. Peripheral neuropathy 1 tension pneumocephalus, 7 and quadriplegia 1,2 are additional reported associated complications. The hemodynamic effects of anesthesia in the sitting position may be influenced by choice of ventilatory technique. Spontaneous ventilation with a volatile anesthetic agent in nitrous oxide/oxygen was popular in the 1960’s to provide signs of surgical encroachment on vital medullary and pontine structures. 8 The problems of cardiovascular instability and arterial hypotension associated with the upright position may be aggravated by the depressant effects of intravenous induction and volatile agents on myocardial contractility during general anesthesia and changes in venous return following intermittent positive pressure ventilation. 9 The volume of blood accumulating in the venous system may be influenced by patient factors - body mass index, intravascular volume status, pre-existing hypertension and mode of ventilation. As much as 1500 mL may be sequestered in the venous system of the lower limbs due to the effect of gravity 10 and increased diffusion through the capillary walls and venous dilatation associated with the use of volatile anesthetic agents. 11 Indicator dilution technique studies have confirmed a 14% redistribution of blood volume from the intra- to the extrathoracic compartment in anesthetized patients after a change from the supine to the sitting position. 12 Concomitant changes in arterial pressure and stroke volume index were thus attributed to alterations in cardiac preload. A number of techniques have been advocated to attenuate the hemodynamic effects of patient placement in the sitting position. Colloid preloading (10 mL·kg –1 ) 30 min before starting general anesthesia was reported to prevent decreases in systolic and central venous pressures during sitting patient positioning without adverse effects. 13 Compensatory mechanisms, perhaps mediated by the renin-angiotensin-aldosterone system or the sympathetic nervous system, may be operative in the awake or anesthetized state to attenuate adverse hemodynamic changes associated with the sitting position. Wrapping of the legs, application of anti-gravity suits and positioning of the knees at right heart level may all have potential benefits.

The Effects of Propofol on the Contraction in the Rat Uterine Smooth Muscle

Background: Propofol is an alternative to thiopental as an intravenous induction agent for cesarean section. It is also used as a sedative for supplementation of regional blockade during cesarean section. It has been reported that propofol relaxes not only vascular smooth muscle but also other smooth muscles. The aim of this study was to investigate the effect of propofol on rat uterine smooth muscle in an isolated preparation in the rat. Methods: Uterine smooth muscle tissues were obtained from rats (n = 21). The muscle strips were suspended in tissue baths and isometric tension was recorded. After spontaneous or oxytocin induced activity had been accomplished in the buffer solution as a control, propofol (1 to 20μg/ml) in fat emulsion was applied cumulatively to the bath and the effects were continuously recorded. Results: In vitro, propofol induced a dose-dependent inhibition of spontaneous as well as oxytocin induced myometrial contractile activity. Propofol concentration of 1μg/ml had no significant effects on the resting tension, active tention, and frequency of contraction developed by spontaneous and oxytocin induced uterine contractility. However, Complete muscular relaxations on spontaneous and oxytocin induced contractility were obtained at a concentration of 10μg/ml and 20μg/ml, respectively. Conclusions: Propofol inhibits spontaneous and oxytocin-induced uterine smooth muscle contractions in dose dependent pattern. (Korean J Anesthesiol 2007; 52: 72～76)

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.

Entropy Responses to Endotracheal Intubation during Anesthetic Induction Using Thiopental or Propofol and Succinylcholine

Background: Thiopental and propofol are commonly used intravenous induction agents and entropy is a new method of assessing depth of anesthesia. In this study we evaluated the entropy responses to endotracheal intubation during anesthetic induction with thiopental or propofol. Methods: Forty ASA class I and II adult female patients undergoing elective surgeries were enrolled into this randomized, prospective study. At 1 minute after fentanyl 2/kg, thiopental 5 mg/kg (group T) or propofol 2 mg/kg (group P) was administered for induction. And endotracheal intubation was performed following succiny choline 1 mg/kg. From pre-induction till post- intubation 10 minutes, the entropy and hemodynamic variables were measured and compared. Results: The entropy following intubation increased significantly in both groups. But entropy changes in group T were greater than those in group P remained below 65. Conclusions: Our results using the entropy to monitor anesthetic depth during induction and intubation, suggest that thiopental 5 mg/kg is more likely to be associated with lighter planes of anesthesia and consequent risk of arousal reaction following endotracheal intubation than propofol 2 mg/kg.

Difficult Intubation due to Low Located and Right Deviated Thyroid Cartilage: A case report

We report a case of difficult intubation due to a low located thyroid cartilage and a left deviated glottis abnormality. A 35-year-old woman was scheduled to undergo a laminectomy and discectomy for a L4-5 disc herniation. After injecting intravenous induction agents and muscle relaxant, intubation was attempted with a direct laryngoscope. However, no vocal cords were seen and only the epiglottis was seen albeit only slightly. According to Cormack and Lehane`s grading, the patient was grade III. Although intubation was re-attempted after changing the anesthesiologist and device such as a light wand, the endotracheal tube could not be advanced below the epiglottis because of resistance. When patient was rechecked, her thyroid cartilage was located abnormally low and the thyromental distance was 14.5 cm. In addition, the preoperative chest X-ray revealed her airway to be deviated to the left. Intubation could be successfully performed after additional 100% oxygen mask ventilation. An otolaryngologic examination revealed that the glottic opening was deviated to the left, and ventricle of the larynx, which is normally not seen with a laryngocope was located to the center. It is believed that the reason for resistance of the advancing endotracheal tube was a centrally located ventricle of the larynx. (Korean J Anesthesiol 2006; 51: 742~5)

The Clinical Utility of Inhalational Anesthesia With Sevoflurane in Electroconvulsive Therapy

Anesthesia in electroconvulsive therapy (ECT) almost always is induced with intravenous agents, typically barbiturates, etomidate, or propofol. There are, however, circumstances in which an inhalational agent would be preferable for induction of general anesthesia. These uncommon clinical scenarios include severe needle stick phobia, agitation preventing insertion of an intravenous catheter, and poor tolerance of intravenous induction agents. Among the inhalational agents available, sevoflurane has several properties that make it the most desirable. In this case series, we describe several patients in our ECT practice in whom inhalational induction of general anesthesia with sevoflurane was deemed appropriate. In all patients, this method was well tolerated and offered distinct advantages compared with an intravenous induction agent. We conclude that ECT practitioners should keep this option in mind for select patients.

Postoperative shivering in children and causative factors

The aim of this study is to investigate the incidence of shivering in children and to reveal the causative factors as well as any possible clinical implications. This study was conducted on 1507 children who underwent surgery under general anesthesia. The patients were admitted to the postanesthesia care unit after the operation and their body temperatures measured from the tympanic membrane. The type of operation, operative time, method of anesthesia induction, age, and number of cases in which caudal block had been used were recorded. Of the 1507 children, 53 (3.5%) experienced shivering. The use of intravenous induction agents, age older than 6 years, and prolonged duration of surgery were associated with shivering. The type of the operation and gender had no effect. The frequency of shivering was lower in children who underwent caudal block with a statistical significance (P < 0.05). The overall incidence of shivering in children is low (3.5%). Use of intravenous induction agents, age older than 6 years, and prolonged duration of surgery were associated with shivering; prophylaxis is not necessary in children, treatment is given only when shivering occurs.

Effects of Etomidate, Thiopental Sodium and Propofol on Intraocular Pressure Associated with Tracheal Intubation

Background: During ophthalmologic surgery, various intravenous anesthetic induction agents are used to prevent an intraocular pressure (IOP) increase. This study was designed to compare the effects of etomidate on IOP with those of thiopental sodium and propofol in patients receiving vecronium bromide, and in whom tracheal intubation was performed. Methods: Forty-five patients undergoing elective surgery were ramdomized to receive etomidate 0.3 mg/kg (E group, n = 15), thiopental sodium 5 mg/kg (T group, n = 15) or propofol 2.5 mg/kg (P group, n = 15). IOP, systolic arterial pressure (SAP) and heart rate (HR) were measured before induction (B), after the adminstration of the induction agents (), before intubation () and at 1, 2 and 3 mins after intubation (, and ). Results: The IOP after and in the E , T and P groups were significantly lower than in group B (P ＜ 0.05). The IOP at , and in the E, T and P groups were not found to be significantly different from group B. The IOP, SAP and HR at , , and in the E, T and P groups were significantly higher than at and (P ＜ 0.05). No significant differences were observed between the groups in term of IOP. The SAP and HR at , and in the P group were significantly lower than in the other two groups (P ＜ 0.05). Conclusions: We concluded that etomidate, thiopental sodium and propofol may be useful induction agents for general anesthesia in ophthalmologic surgery but that they do not prevent IOP elevation during endotracheal intubation.

Intravenous induction agents

This article introduces the pharmacology of the intravenous induction agents (IAA) in current use. The properties of the ideal IAA are listed and the basic pharmacokinetics during the induction and recovery of a bolus dose of IAA are discussed. Diagrams showing the distribution and elimination of the IAA complement the text. The barbiturates as a group are explored with particular emphasis on the thio-barbiturate, thiopental, which is retained as the gold standard for comparison purposes. The other IAAs covered are the sterically hindered alkyl phenol, propofol, the carboxylated imidazole, etomidate and the phencyclidine derivative, ketamine. Each agent is described giving its physical properties and notes about its use. The pharmacodynamics of IAAs are covered comparing and contrasting the action of the drugs on the various systems of the body. The safety of the IAAs is recorded. A table shows some of the pharmacological properties of the four drugs to enable the reader to compare them.

Lactic Acidosis during Propofol–Remifentanil Anesthesia in an Adult

Lactic Acidosis during Propofol–Remifentanil Anesthesia in an Adult

Effects of Intravenous Induction Drugs on Intubation Conditions Using Rocuronium for Rapid Sequence Induction

Background: We assessed the effect of intravenous induction agents on intubation conditions and hemodynamic changes when using rocuronium 0.7 mg/kg for rapid sequence induction. Methods: Sixty ASA class I or II patients undergoing elective surgery were divided into a thiopental group (5 mg/kg, n = 20), a propofol group (2 mg/kg, n = 20) and an etomidate group (0.2 mg/kg, n = 20). Anesthesia was induced with intravenous induction agents. After loss of consciousness, rocuronium 0.7 mg/kg was injected. Intubation was attempted at 60 seconds after rocuronium administration. Arterial blood pressure and heart rate were measured before induction, immediately after intubation, and 1, 3, 5, and 10 minutes after intubation. Intubation conditions were assessed by jaw relaxation, vocal cord movement, response to tracheal intubation, and were evaluated as excellent, good, fair, and poor. Results: Excellent intubation conditions were obtained 55% (n = 11) in the thiopental group, 60% (n = 12) in the propofol group, and 45% (n = 9) in the etomidate group. Systolic and diastolic arterial blood pressures were elevated after intubation in all three groups. But these changes were minimal in the propofol group. Conclusions: Intubation conditions were not significantly different after the intravenous injection of thiopental 5 mg/kg, propofol 2mg/kg, or etomidate 0.2 mg/kg when using rocuronium 0.7 mg/kg for rapid sequence induction.

Malignant hyperthermia.

Malignant Hyperthermia (MH) has been a recognized complication of general anesthesia after the first case reports in the 1940's. Since then a great deal has been discovered about the genetics, pathophysiology and treatment of this once fatal syndrome. MH is the only clinical entity specifically related to and caused by anesthetic agents. MH once triggered during anesthesia results in a profound hyper metabolic state with rise in the core temperature, increased carbon dioxide production and oxygen consumption. Death will ensue if specific treatment is not started. The incidence of fulminant MH ranges from 1:62,000 to 1: 84,000 of general anesthesia cases if succinylcholine and inhalation agents are used. Massseter muscle spasm on induction of anesthesia, with an incidence of between 1:16,000 and 1:4,000, may be a predromal indication of the development of MH. Anesthetic agents, which may trigger MH in susceptible individuals, are the depolarizing muscle relaxant, succinyl choline and all the volatile anesthetic gasses. Nitrous oxide, intravenous induction agents, benzodiazepines, opioids, and the non-depolarizing relaxants do not trigger MH. MH susceptibility is associated with certain disorders, such as Duchene muscular dystrophy, and triggering agent should not be used in these patients. Inheritance is an autosomal dominant trait with variable penetrance. The pathogenesis of MH involves the loss of control of intracellular calcium ions in skeletal muscle with resultant protracted spasm and hyper metabolism. Clinically this will progress to hypercarbia, hypoxia, hyperthermia, hyperkalemia and death will result if specific treatment is not started. Management involves immediate discontinuation of the triggering anesthetics, hyperventilation with 100% oxygen and most importantly the definitive treatment with intravenous dantrolene.The importance of instigating the use of dantrolene in cases of MH cannot be overemphasized. MH is now treatable when once it would be fatal before the availability of dantrolene. Unless of an emergent nature, surgery should be canceled following the acute phase of MH. The patient should be admitted to intensive care for at least 24 hours and dantrolene continued as recurrence has been described. It is imperative that the patient and their family are counseled, Medalert bracelets provided and registration with the Malignant Hyperthermia Association of the United States (MHAUS), encouraged. The caffeine/halothane testing of muscle biopsies is currently the most definitive test for malignant hyperthermia susceptibility. The routine use in suspected cases or the immediate family of known cases remains a matter of contention.

Intravenous Induction Agents: Opioids

Intravenous Induction Agents: Opioids

The Comparison of Characteristics in Emergence between Inhalational Anesthesia Using Isoflurane and Total Intravenous Anesthesia Using Propofol and Ketamine

Background: Total intravenous anesthesia (TIVA) is one of the anesthetic techniques that needs no inhalational agent but only an intravenous agent for induction and maintenance of anesthesia. Among drugs used in TIVA, propofol is the most popular agent. Rapid emergence and antiemetic characteristics of propofol are well known advantages but a dose dependent cardiovascular depressant effect is one of the disadvantages of this drug. Otherwise, ketamine, a dissociative agent, has been restricted in its use because of bad dreams, delirium and delayed emergence even though it has profound analgesic characteristics. However, ketamine has a stimulatory effect on the cardiovascular system, so it can raise blood pressure and pulse rate and in the case of TIVA, these properties can be advantageous when used with propofol. This study was aimed to decide whether TIVA using propofol and ketamine would have more stable vital signs during anesthesia and more rapid and smoother emergence in comparison with inhalational anesthesia using isoflurane. Methods: Thirty two patients scheduled for elective general anesthesia were randomly allocated into two groups; I (inhalational anesthesia using isoflurane) group and PK (TIVA using propofol and ketamine) group. I group was controlled with isoflurane 1-1.5 vol% and the PK group was controlled with propofol 3-12 mg/kg/hr and ketamine 0.5-1.0 mg/kg/hr. Arriving at the recovery room, a single observer recorded the time to spontaneous movement, responses to painful pinch and verbal command, and orientation to age, name, place, date and time. At 5, 10, and 30 minutes after anesthesia, a PARS (postanesthesia recovery score), count-down test, and VAS (visual analogue scale) were checked. Postoperative events were checked in the recovery room and 24 hours lator. Results: There was no significant difference in demographic data or characteristics of operation. Compared with the I group, the PK group had significantly rapid orientation responses on place, date and time. Restoration in the count-down test was more rapid in the PK group after 10 minutes in the recovery room. The VAS was lower in the PK group after 30 minutes in the recovery room.

Effects of Etomidate, Propofol and Thiopental Sodium on Intraocular Pressure during the Induction of Anesthesia

Background: During ophthalmologic surgery, a variety of anesthetic induction techniques are used in an attempt to prevent the rise of intraocular pressure (IOP). This study compared the effects of etomidate, a new intravenous anesthetic agent, on the changes in IOP with those of thiopental sodium and propofol. Methods: Forty-five patients were randomly allocated and divided into three groups to be injected intravenously with etomidate 0.2 0.3 mg/kg (E-group, n = 15), propofol 2 3 mg/kg (P-group, n = 15) or thiopental sodium 4 - 5 mg/kg (T-group, n = 15). Systolic arterial pressure (SAP), heart rate (HR) and intraocular pressure (IOP) were measured at 1, 2 and 3 minutes after the administration of the induction agents. During the induction of anesthesia, the incidence of IV injection pain, myoclonus, hiccup and a decrease in SAP of more than 30% were investigated. Results: At 1, 2 and 3 min following the induction of anesthesia, the SAP in the P-Group decreased significantly more than that in the other two groups (P < 0.05). After the induction, heart rate in the T-Group increased significantly more than that in the other two groups (P < 0.05). The three intravenous agents induced a significant decrease in IOP after an injection (P < 0.05). Comparing the three groups, the IOP in the E- and P-Group decreased significantly more than that in the T-Group (P < 0.05). Conelusions: Etomidate may be used as a choice of intravenous induction agent to reduce intraocular pressure in ophthalmologic operations especially in an emergency situation, geriatric and hypovolemic patients.

Anaesthetic methods for carotid surgery

The pathophysiology and consequences of occlusive atherosclerotic disease of carotid arteries are discussed. Careful preoperative assessment of a patient scheduled for carotid surgery is needed owing to coexisting medical problems. The premedication with a benzodiazepine is recommended. A variety of anaesthetic technique are used to anaesthetize patients undergoing carotid endarterectomy. There is no evidence that one particular technique is superior to another. All intravenous induction agents, except ketamin, reduce CMRO, and may be cerebroprotective, but their effects on rCBF are very different. Isoflurane in a concentration of less than 1 MAC supplemented with opioids or total intravenous anaesthesia with propofol, or midazolam in combination with synthetic opioids have proved to be acceptable methods for carotid endarterectomy. Loco-regional anaesthesia (cervical plexus or epidural block) gives a chance for continuous neurological assessment. Intraoperative monitoring should include the routine monitors of cardiovascular, respiratory and metabolic function employed during general or loco-regional anaesthetics. Additional monitoring techniques (EEG, SSEP, rCBF internal carotid stump pressure, JSO 2 or cerebral oximetry) may be valuable. In the postoperative period the high-risk patient should, ideally, be transferred to a high-dependency unit and can be observed for postoperative complication.

Computer simulation of intracranial pressure changes during induction of anesthesia: comparison of thiopental, propofol, and etomidate.

We have developed a computer model of cerebrovascular hemodynamics that interacts with a pharmacokinetic drug model. We used this model to examine the effects of various stimuli occurring during anesthesia on cerebral blood flow (CBF) and intracranial pressure (ICP). The model is a seven-compartment constant-volume system. A series of resistances and compliances relate blood and cerebrovascular fluid fluxes to pressure gradients between compartments. Variable arterial-arteriolar resistance (Ra-ar) and arteriolar-capillary resistance (Rar-c) simulate autoregulation and drug effects, respectively. Rar-c is also used to account for the effect of CO2 on the cerebral circulation. A three-compartment pharmacokinetic model predicts concentration-time profiles of intravenous induction agents. The effect-site compartment is included to account for disequilibrium between drug plasma and biophase concentrations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible personal computer. Using the model, we have predicted ICP responses during induction of anesthesia for a simulated patient with normal as well as elevated ICP. Simulation shows that the induction dose of intravenous anesthetic reduces ICP up to 30% (propofol > thiopental > etomidate). The duration of this effect is limited to less than 5 minutes by rapid drug redistribution and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial ICP. ICP elevation is more pronounced in a nonautoregulated cerebral circulation. Simulation results are in good agreement with the available experimental data. The presented model allows comparison of various drug administration schedules to control ICP.

Anaesthesia for assisted conception

Anaesthesia for assisted conception

The effect of propofol on isolated human pregnant uterine muscle.

Propofol is an alternative to thiopental as an intravenous induction agent for cesarean section. Because it has relaxant effects on vascular and other smooth muscles, the authors set out to determine whether propofol has any effect on pregnant human uterine smooth muscle in an isolated preparation. Myometrial specimens were excised from 10 parturients undergoing elective cesarean section. The muscle strips were suspended in tissue baths and isometric tension was recorded. After establishment of rhythmic contractions in the buffer solution as a control, propofol (0.5 to 10 microg/ml) in fat emulsion was applied cumulatively to the bath. The effect of the fat emulsion at equivalent concentrations was also examined. Propofol concentrations of 2.7 x 10(-6) M (0.5 microg/ml) and 1.1 x 10(-5) M (2 microg/ml) had no significant effect on the active tension developed by muscle contraction. However, propofol at concentration of 5.5 x 10(-5) M (10 microg/ml) reduced the active tension by 45% (P < 0.02) compared with the control value. The fat emulsion had no effects on the active tension. These results imply that the decline in the active tension of muscle contraction was most likely caused by propofol and not by the fat emulsion. However, the propofol concentrations needed to produce a significant reduction in the uterine muscle tension appear to be much greater than the free propofol concentrations reported by others during cesarean section.

Etomidate inhibits [ 3H]noradrenaline release from SH-SY5Y human neuroblastoma cells

We have examined the effects of the intravenous anaesthetic induction agent etomidate on K + and carbachol evoked [ 3H]noradrenaline ([ 3H]NA) release and the associated increase in [Ca 2+] i in SH-SY5Y human neuroblastoma cells in a attempt to study potential anaesthetic target site(s). Preincubation with etomidate produced a dose-dependent inhibition of both K + and carbachol evoked [ 3H]NA release with estimated IC 50 values of 88 and 69 μM, respectively. Only K + stimulated increase in [Ca 2+] i was inhibited by etomidate preincubation with an IC 50 of 146 μM. Acute addition of etomidate after K + challenge also inhibited the increase in [Ca 2+] i with an IC 50 of 99 μM. In addition etomidate displaced the binding of [ 3H]PN200-110 to L-type voltage sensitive Ca 2+ channels with a K i of 48 μM. As K + but not carbachol evoked [ 3H]NA release is extracellular Ca 2+ dependent and was inhibited by etomidate these data coupled with the PN200-110 displacement studies suggest that etomidate may interact with L-type voltage sensitive Ca 2+ channels. The inhibition of carbachol evoked release without affecting the associated increase in [Ca 2+] i suggests that etomidate may exert additional effects at either the muscarinic receptor or the secretory machinery in these cells.