Intravenous Anaesthetic Induction Agents Research Articles

Effect of priming in preventing myoclonic movements after intravenous induction with etomidate in adult patients undergoing cardiac surgery: a randomised controlled interventional study

Etomidate is a hypnotic drug used as an intravenous anaesthetic induction agent. Etomidate causes myoclonic movements in 50-80% patients after induction which makes it less desirable for induction. Aim: Present study was to determine the effect of priming in preventing myoclonic movements after intravenous injection with etomidate in adult patients undergoing cardiac surgery. Materials and Methods: 108 patients ASA grade III scheduled for elective cardiac surgery were allocated randomly in two groups- Group A (n=54): Patients received induction dose of 0.3mg/kg I.V. etomidate, Group B (n=54): Patients received a priming dose of 0.03mg/kg etomidate I.V. followed after 1 minute by induction dose of 0.3 mg/kg I.V. etomidate over 20 seconds. 3 minutes after the start of induction with etomidate, patients in both groups were given injection fentanyl 4mcg/kg followed by injection Rocuronium (1mg/kg bodyweight) to facilitate tracheal intubation. The occurrence and intensity of myoclonus were observed for 3 min from the start of injection of the induction dose and graded clinically by a blinded observer as: 0=no myoclonus, 1=mild myoclonus, 2=moderate myoclonus and 3=severe myoclonus. Result: The average dose of etomidate used during induction and demographic variables were similar in both the groups. The incidence of myoclonus in priming Group (27/54 [50%] was significantly lower than in control Group (45/54 [83.33%].Myoclonus of moderate or severe grade occurred in significantly more patients in control Group (68.3%) than in priming Group (36.5%).Conclusion: Pre-treatment with etomidate (0.03 mg/kg), given 60 seconds before induction of anaesthesia is more effective in reducing the incidence of etomidate-induced myoclonus without related side-effects.

English

BACKGROUND Propofol is an appropriate intravenous anaesthetic induction agent for rapid induction and suppression of airway reflexes and is widely used for laryngeal mask airway insertion. Sevoflurane is a halogenated, non-pungent and non-explosive liquid anaesthetic agent with low blood gas solubility administered by inhalation for use in induction and maintenance of general anaesthesia. We wanted to compare the characteristics of sevoflurane and propofol for the induction of anaesthesia and laryngeal mask airway (LMA) insertion. METHODS We conducted a randomized control study among 70 patients (n=35 in each group) undergoing elective surgery. Patients were anaesthetised with either vital capacity breaths of 8% sevoflurane with 50% N2O and O2 or IV propofol, with loss of eyelash reflex considered as the end point of induction. RESULTS Both the drugs produced almost similar rapid loss of consciousness (propofol-45.29 ± 11.98 sec, sevoflurane-51.03±14.68 sec). The LMA was inserted more rapidly in propofol group (20.43±9.460 sec) than in the sevoflurane group (34.37 ± 17.338 sec), p=0.018. The score for jaw opening was better in the propofol group (2.94 ± 0.236) than in the sevoflurane group (2.66 ± 0.482), p=0.000. The ease of LMA insertion score was better in the propofol group (2.91 ± 0.284) than in the sevoflurane group (2.66 ± 0.482), p=0.008. Both groups had stable haemodynamic parameters. CONCLUSIONS Propofol was more favourable than sevoflurane for laryngeal mask airway insertion due to better jaw relaxation and less insertion time. However, sevoflurane is an alternative to propofol as an induction agent for laryngeal mask airway insertion. KEY WORDS Propofol, Sevoflurane, Laryngeal Mask Airway.

Comparison of efficacy of ketamine and dexmedetomidine for prevention of pain due to propofol injection

Background: Propofol is a popular intravenous anesthetic induction agent which produces a smooth, rapid induction with rapid clearance and recovery but Pain on injection with Propofol is a common problem and can be very distressing to the patient. Ketamine is a phencyclidine derivative routinely used as an inducing agent and Dexmedetomidine Hydrochloride, an imidazole compound is the alpha 2 agonist. The present study was undertaken to compare the efficacy of Ketamine (0.5 mg/kg) and Dexmedetomidine (0.5 mcg/kg) in preventing the incidence and reducing the severity of pain on Propofol injection.Method: 150 patients, ASA I&II, 18-60 year old undergoing elective surgical procedure under general anaesthesia (GA) were randomly assigned into 3 equal groups. Group C, Group K and Group D. In Group C 10 ml Normal Saline, In Group K Ketamine 0.5 mg/kg diluted to 10 ml with normal saline and in Group D Dexmedetomidine 0.5 mcg/kg diluted to 10 ml with normal saline was infused over 10 minutes before injecting Propofol. All study medications were prepared in a 10ML syringe that was covered with black tape by an anaesthesiologist who was not involved in the study. HR,BP,SPO2and Pain Scores were noted at baseline, after premedication, while injecting study drugs at 3, 5 and 10 minutes and while injecting Propofol at the beginning, after half Propofol was injected, after complete Propofol was injected and at 1,3 and 5 minutes after completing the Propofol. Incidence and severity of pain and involuntary movements, verbal communication by the patient was watched constantly. Injection pain was graded using a 4-point scale. The pain score was evaluated as ‘0’ when there was no discomfort in the injection area (no pain), ‘1’ when the patient simply answered

Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain

Background: Propofol injection pain is one of the significant drawbacks to its use as an intravenous (IV) anesthetic induction agent so this study has been undertaken to compare the efficacy of IV acetaminophen and lidocaine on propofol injection pain. Materials and Methods: After obtaining Institutional Ethical Committee approval, ninety adult patients of ages 18–60 years of both sexes and American Society of Anaesthesiologist I and II who underwent elective surgery from September 2013 to September 2015 in the Tertiary Care Hospital, Imphal, were randomly allocated to one of the three groups to receive 10 ml saline (Group 1), 40 mg lidocaine (loxicard) in 10 ml saline (Group 2) and acetaminophen 100 mg (10 ml) (Group 3) to compare the pain efficacy during propofol injection into the large dorsal vein on the left hand. Pain was assessed with a verbal rating scale. Results: It was observed that the number of patients experiencing pain was 20 (66.67%), i.e., mild: moderate: severe - 11 (36.67%): 6 (20%): 3 (10%) in Group 1, in Group 2 the incidence was 2 (6.67%) i.e., mild: moderate: severe - 2 (6.67%): 0: 0, and in Group 3 it was 6 (20%) i.e., mild: moderate: severe - 5 (16.67%): 1 (3.33%): 0, respectively (P < 0.001). Conclusion: IV acetaminophen and lidocaine could significantly reduce pain during propofol injection with a significant P< 0.001.

Abstract PR447

Background & Objectives: The hemodynamic response to laryngoscopy and intubation is associated with reflex sympathetic response resulting in undesirable increase in heart rate and blood pressure.1 Several techniques have been proposed to attenuate these sympathetic responses. Etomidate is an intravenous anesthetic induction agent remarkable for its minimal cardiovascular effects and rapid onset of action.2 Sevoflurane is relatively cardiostable inhaled anesthetic3 that is pleasant smelling and relatively non irritating to the airways.4 The objective of the study was to compare the effects of Etomidate, a cardiostable intravenous anesthetic induction agent with Sevoflurane, a relatively cardiostable inhaled anesthetic in attenuating the hemodynamic response to laryngoscopy and intubation. Materials & Methods: After obtaining approval from hospital ethics committee and informed consent from the patients, 66 ASA I and II status normotensive patients (n=33 in each group), aged 18 to 60 years scheduled for elective surgical procedures were allocated randomly into 2 groups to receive 4 % sevoflurane / 100% oxygen (S GROUP) or etomidate 0.4mg/kg for induction (E GROUP). 2 micrograms/kg of fentanyl was administered prior to induction and vecuronium for muscle relaxation. Hemodynamic parameters were recorded before induction, post induction, immediately after intubation and 1, 2, 3, 5 minutes from onset of laryngoscopy. Statistical analysis was carried out using Z test for proportions, independent sample t-test and paired t test (two sided). Statistical level of significance was set at P value < 0.05. Results: Demographic profiles of two groups were comparable. Maximum pressor response was observed immediately after intubation. The rise in heart rate, systolic, diastolic and mean arterial blood pressure was statistically significant in etomidate group than in sevoflurane group. The hemodynamic response to laryngoscopy and intubation was effectively decreased by sevoflurane -fentanyl induction and was highly significant on comparison(P<0.001)Conclusion: Sevoflurane inhalational induction is rapidly gaining popularity due to its smooth induction characteristics devoid of airway complications. Sevoflurane induction can be a better alternative to etomidate in attenuating hemodynamic responses to laryngoscopy and intubation in high risk patients with hypertension and coronary artery diseases.

Effectiveness of Midazolam in the Prevention of Etomidate Induced Myoclonus

Introduction: Etomidate, the imidazole derivative, is an intravenous anaesthetic induction agent, having stable hemodynamic profile, minimal respiratory side effects and histamine release. It is extremely useful in hemodynamically compromised patients. But the most common problem associated with its induction is myoclonus. Objective: To determine the effect of pretreatment with midazolam on the frequency of myoclonus after etomidate induction. Methods: Two hundred and fifty patients fulfilling the inclusion and exclusion criteria, scheduled for elective surgical procedures, were included. After all monitoring and intravenous access, the patients were given intravenous midazolam 0.05 mg/kg and after ninety seconds anesthesia induction was done with etomidate, and the myoclonic movements were noted for a minute after etomidate injection. The movement were recorded and graded on a scale of 0 to 3. Results: Myoclonus was developed in 15.45% (38/246) cases while in 84.55% (208/246) patients abnormal muscle movements was not observed after etomidate injection. Mild myoclonus (grade 1) was observed in 23 (9.3%) cases, moderate myoclonus (grade 2) in 11 (4.5%) and severe (grade 3) in 4 (1.6%) cases. Summary: The incidence of myoclonus was lowered significantly (15.45%) after 0.05mg/kg midazolam pretreatment.

Priming with atracurium efficiently suppresses etomidate-induced myoclonus

IntroductionEtomidate is a hypnotic drug widely used as an intravenous anesthetic induction agent. The incidence of etomidate-induced myoclonus has been reported as much as 50–80% after induction making it an undesirable drug for induction. ObjectiveOur aim is to use a priming dose of atracurium to suppress etomidate-induced myoclonus during induction of anesthesia. MethodsIn a double-blinded clinical trial 80 patients were randomly given either atracurium (20% of ED95 × kg) or saline as a priming agent. Then, induction of anesthesia was performed using 0.4 mg/kg etomidate. Age, weight, body mass index, bispectral index (BIS) monitor, and duration and grade of myoclonus were recorded. ResultsThe demographic characteristics, age, body mass index, BIS score, and weight were not significantly different between the atracurium (ATRA) priming group and control groups. The binomial regression model showed that BMI was an independent predictor variable for myoclonus (OR: 2.1, CI 95%: 1.7–7.5, p = 0.032). In this model, adjusted odds ratios (OR) of myoclonus (multivariate logistic regression analysis) in the control group was 6.6 (95% CI: 1.5–9.7, p = 0.013). ConclusionLow-dose atracurium priming could effectively suppress etomidate-induced myoclonus.

Propofol limits rat myocardial ischemia and reperfusion injury with an associated reduction in apoptotic cell death in vivo

Propofol, a rapidly acting, short duration, intravenous hypnotic anesthetic induction agent, is often used in clinical situations where myocardial ischemia/ reperfusion (I/R) injury is a threat. The aim of the present study was to evaluate the protective effect of propofol on myocardial I/R injury in rat due to apoptosis. Myocardial I/R injury were induced by occluding the left anterior descending (LAD) coronary artery for 25 min followed by either 2 h or 6 h reperfusion. Apoptosis was evaluated by Western blot analysis (Bcl-2, Bax expression), DNA strand breaks, TUNEL analysis and measuring myocardial caspase-3 activity. Propofol significantly reduced infarct size and improved I/R-induced myocardial contractile dysfunction by improving left ventricular diastolic pressure and positive and negative maximal values of the first derivative (+ d p/d t) of left ventricular pressure. Propofol increased Bcl-2/Bax expression ratio and decreased caspase-3 activity in I/R rat hearts, which resulted in reduction of myocardial apoptosis as evidenced by TUNEL analysis and DNA laddering experiments. In an in vitro study, propofol increased H9c2 cell viability against oxidative stress induced by glucose oxidase (GOX) in a dose-dependent manner. These data suggest propofol limits I/R injury with an associated reduction in apoptotic cell death in vivo.

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.

Effects of propofol and thiopentone on potassium- and carbachol-evoked [ 3H]noradrenaline release and increased [Ca 2+] i from SH-SY5Y human neuroblastoma cells

We have examined the effects of two intravenous anaesthetic induction agents, propofol and thiopentone, on K + and carbachol evoked [ 3H]noradrenaline release from a human neuroblastoma cell line, SH-SY5Y. In this model, we have previously demonstrated that K + evoked [ 3H]noradrenaline release was dependent on Ca 2+ entry and carbachol evoked release was extracellular Ca 2+-independent. Propofol inhibited K + (100 mM)-evoked ( IC 50 of 42 ± 11 μM), but not carbachol (1 mM)-evoked, [ 3H]noradrenaline release. Thiopentone inhibited both K +- and carbachol-evoked release with IC 50 values of 116 ± 15 μM and 169 ± 39 μM, respectively. These inhibitory effects were not due to changes in the release dynamics, as assessed using perfused cells. Furthermore, thiopentone inhibition of carbachol-evoked release was not due to muscarinic receptor antagonism. Both propofol and thiopentone caused noncompetitive inhibition of K +-stimulated Ca 2+ influx, with IC 50 values of 127 ± 7 μM and 121 ± 10 μM, respectively. These effects were not due to interaction with GABA A receptors, but suggest that both compounds block voltage-sensitive Ca 2+ channels. Thiopentone, but not propofol, inhibited carbachol-stimulated increased intracellular Ca 2+ concentrations in the presence and absence of extracellular Ca 2+. However, thiopentone had no effect on carbachol-stimulated inositol (1,4,5)-triphosphate formation, suggesting that thiopentone may directly inhibit Ca 2+ release from intracellular stores.

Immunomodulation: an important concept in modern anaesthesia.

This review summarises evidence for immunomodulatory effect of drugs administered peri-operatively. The clinical significance of the balance of pro- and anti-inflammatory cytokines may be seen in certain disease states, for example, meningococcal meningitis and Lyme arthritis. This balance may be altered peri-operatively. Traditionally, these changes are considered to be due to the stress response of surgery, the response to cardiopulmonary bypass, or endotoxaemia. This review presents in vitro evidence suggesting that drugs modulating this cytokine balance include non-steroidal anti-inflammatory agents, phosphodiesterase inhibitors and opioids, acting through effects on intracellular cyclic nucleotide messenger systems. An important consequence of the pro-inflammatory cytokine activity is increased adhesion of neutrophils. Aspects of this process may be inhibited by avoiding low blood flow states, by reducing adhesion molecule expression (for example by use of pentoxifylline), or by use of negatively charged anions such as heparin. Neutrophil activity is generally depressed by intravenous anaesthetic induction agents, but is enhanced by opioids. Natural killer cell activity, which is involved in immunity against tumour cells and virally infected cells is transiently depressed by volatile anaesthetic agents and opioids. In contrast catecholamines enhance natural killer cell activity. Whereas decrease in immunoglobulin levels occur peri-operatively, this is not thought to be as a result of drugs at clinically used concentrations but rather due to haemodilution.

Ketamine inhibits K+ evoked [3H] noradrenaline release from SH-SY5Y cells by reducing calcium influx.

The non competitive NMDA receptor antagonist ketamine is used as an intravenous anaesthetic induction agent [ I ] Whilst a general reduction in excitatory neurotransmission (via NMDA receptor inhibition) may produce anaesthesia a role for direct Ca” channel blockade cannot be excluded. We have reviously reported that ketamine selectively inhibits K’ evoked [-Hlnoradrenaline release from SH-SY5Y cells with an IC,, of 170pM [2]. As K’ evoked release is entirely extracellular Ca” dependent [3] our data infer that ketamine inhibits Ca2’ influx through voltage sensitive Ca” channels in these cells In this study we have examined the effects of ketamine on K’ stimulated increases in [CaZL], in fura-2 loaded cells P

2 Upper airway reflexes

The maintenance of a clear unobstructed upper airway and the rapid return of normal laryngeal reflexes after the end of general anaesthesia form two of the most fundamental principles of modern anaesthetic practice. Upper airway reflexes are of considerable importance to clinical anaesthetists. The sensitivity of the upper airway reflexes are important during induction of anaesthesia, when heightened upper airway reflexes may lead to the development of life threatening laryngospasm. Following anaesthesia the larynx plays a primary role in protecting the lungs from aspiration of foreign material. The irritant nature of inhalation anaesthetic agents varies, with halothane being one of the least irritant. Newer agents including isoflurane and desflurane have been found to be associated with a much higher incidence of airway irritation. The intravenous anaesthetic induction agents thiopentone and propofol seem to have different actions on the sensitivity of upper airway reflexes during induction of anaesthesia, the upper airway appearing to be less irritable following propofol. Laryngospasm is a common and potentially dangerous complication of general anaesthesia, the incidence is higher in young children particularly between the ages of 1 and 3 months. Upper respiratory tract infection increases the incidence of laryngospasm. This is thought to be due to the viral infection causing shedding of epithelial cells, leading to increased exposure of intraepithelial sensory receptors to inhaled irritants. Histologically, sensory nerve fibres are found in almost all areas of the laryngeal mucosa. A particularly high density of sensory free nerve endings are found in the posterior supraglottis. Stimulation of irritant receptors in the upper respiratory tract causes a reflex motor response, afferent signals travel in the vagus nerve and project centrally to the caudal and posterior parts of the nucleus tractus solitarius. The efferent response results in vocal cord closure, changes in respiratory rhythm and coughing, which together act to protect the lower airway from foreign material.

Effect of Infusion Rate on Thiopental Dose-Response Relationships

The rate of administration of an intravenous anesthetic induction agent is an important variable determining the total dose required to reach a given endpoint, such as loss of consciousness (LOC). The influence of infusion rate on the dose-response relationship has not been described rigorously. In this study we characterized the effect of different thiopental infusion rates on the times and doses required to reach a clinical (induction) endpoint. Fifty-six healthy, non-premedicated men, aged 19-59 yr, were randomly assigned to receive one of seven different thiopental infusion rates (40, 60, 75, 150, 300, 600, and 1,200 mg/min). The infusion was continued until the patient dropped a held object, indicating LOC. The infusion rates were selected using a simulation which predicted the relationship between the rate of administration and cumulative dose administered at the time of LOC. Average population pharmacokinetic parameters from a three-compartment thiopental model were combined with an effect-site rate constant for thiopental equilibration of 0.58 min-1 and a median effect-site concentration of 13.8 mg/l from previously published pharmacokinetic and pharmacodynamic models for thiopental. This derived model was used to predict the total amount of thiopental required, at each infusion rate, to produce LOC. The observed median effective doses for infusion rates of 40-150 mg/min were similar and ranged from 296 to 318 mg. Dose requirements increased significantly with increasing infusion rates greater than 150 mg/min; median effective doses for infusion rates of 300, 600, and 1,200 mg/min were significantly different from each other (436, 555, and 711 mg, respectively). The original simulation underestimated the observed thiopental doses at all but the lowest infusion rate. A new simulation was performed using a recently developed combined pharmacokinetic-pharmacodynamic model. This model incorporated a four-compartment thiopental pharmacokinetic model with quantal dose-response data to derive an effect-site rate constant for thiopental equilibration of 0.29 min-1 and a median effect-site concentration for LOC of 11.3 mg/l. The median thiopental doses predicted by this new simulation under the extreme conditions of a 30-fold range of infusion rates were within 13% of the observed doses. In this study we quantified the relationship between the rate of thiopental administration and the resultant cumulative thiopental dose necessary to produce LOC. This study validated a novel pharmacokinetic-pharmacodynamic model based on a four-compartment pharmacokinetic model and infusion quantal dose-response data. Finally, we demonstrated that thiopental dose-response relationships are dependent on drug administration rate, and found that the ability to predict this dependence accurately is influenced by the pharmacokinetics, pharmacodynamics, and median effect-site concentration used to simulate the dose-response relationships.

Etomidate: a new intravenous anesthetic induction agent.

Currently available anesthetic induction agents provide adequate hypnosis but are not ideal, particularly in the high risk patient (ASA class III-V), because most cause myocardial and/or respiratory depression and some have other important side effects. Etomidate was recently marketed as an intravenous anesthetic induction agent. It is a non-barbiturate hypnotic without analgesic properties that has less cardiovascular and respiratory depressant actions than sodium thiopental, even in patients with minimal cardiovascular reserve. Laboratory studies indicate that etomidate is approximately 25 times more potent and has a therapeutic index six times greater than sodium thiopental. In contrast to most other induction agents, etomidate does not cause histamine release. Furthermore, tolerance does not occur with repeated administration. Etomidate's rapid distribution half life (t 1/2 alpha = 2.81 +/- 1.64 min), short elimination half life 1/2 beta = 3.88 +/- 1.11 hr) and rapid clearance (954 +/- 178 ml/min) explain its rapid onset and short duration of action. The compound produces electroencephalographic changes and effects on cerebral blood flow, metabolism and intracranial pressure that are similar to sodium thiopental, suggesting that it may have a place in neurosurgery and as a "brain protective" agent in patients at risk of a brain hypoxic insult. Etomidate did not affect hepatorenal and hematologic function after repeated injections in animal toxicology studies, but few investigations addressing its effects on hepatic, renal, and neuromuscular function in man have been accomplished. The most noticeable side effects of etomidate include myoclonia, pain on injection and postoperative nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Midazolam for the intravenous induction of anaesthesia in children.

Midazolam was compared with thiopentone as an intravenous anaesthetic induction agent in children between four and twelve years of age undergoing elective minor surgical procedures. Successful induction of anaesthesia was achieved in both groups of patients. With midazolam induction time was longer than with thiopentone, but the difference was not statistically significant. The incidence of apnoea was greater with thiopentone, but not significantly so. It is concluded that midazolam is effective and safe, and could prove a reasonable alternative to thiopentone as an intravenous induction agent in children undergoing elective minor operations.

Skin depigmentation associated with intravenous anaesthetic induction agents

A case of skin depigmentation associated with intravenous anaesthetic induction agents is described. The differential diagnosis is briefly discussed.

Adverse reactions to intravenous anaesthetic induction agents.

Adverse reactions to intravenous anaesthetic induction agents.