Propofol V/S Thiopental Essay, Research Paper
Abstract
Neuromuscular blocking agents are an essential aspect of attaining adequate muscle relaxation in patients prior to attempting endotracheal intubation. Succinylcholine is one these agents used, most commonly when attempting a rapid sequence induction. Succinylcholine administration is associated with muscle fasciculations and subsequent myalgias postoperatively. A nondepolarizing neuromuscular agent is commonly administered to reduce the occurance of fasciculations and myalgias. Additionally, the induction agent Propofol, has been associated with further reducing fasciculations and myalgias. Propofol and Pentothol are commonly used anesthetic agents and are generally interchangable and equally efficacous.
Studies have elluded to the ability of Propofol to reduce theses occurances, but it has not been demonstrated in all areas. This study hypothesis that when a standard dose of nondepolarizing agent is given in conjuction with Propofol the occurances of fasciculations and myalgias will be reduced more effectively than with Pentothol.
An all male population has been selected to reduce confounding results that may be attained when female subjects are studied, as females are generally accepted to have greater levels of postoperative myalgia. Routine induction will proceed with the patient receiving standard doses of Fentanyl, Versed and a defasciculating dose of Rocuronium, calculated at 10% of the induction dose. Group A will receive 1.5 mg/kg to 2 mg/kg of Propofol and Group B will receive 3 mg/kg to 5 mg/kg of Pentothol. Patients will be graded on occurances of fasciculations on a scale of 0 (none) to 3 (severe). Patients will be contacted at 24 hours postop to ascertain a self report of perceived muscle myalgia, and will be reported on a scale of 0 (none) to 10 (severe).
The results of this study will be expected to demonstrate that the administration of Propofol will significantly reduce the incidence of fasciculations and myalgia over the adminstration of Pentothol.
Conculusions should demonstrate that administrating Propofol when attempting a rapid sequence induction with Succinylcholine will decrease patients fasciculations and perception of postoperative myalgias.
Introduction
Neuromuscular blocking agents are an essential aspect of attaining muscle relaxation in patients prior to attempting endotracheal intubation. They provide vocal cord paralysis which facilitates ease in intubating the trachea. A multitude of agents are available to assist in this procedure. Neuromuscular blocking agents are used for intubation based on the patients needs for length and onset of paralysis.
Commonly, patients present with various pathologies that demand the trachea be intubated with a Rapid Sequence Induction. The administration of Succinylcholine is considered the gold standard in the Rapid Sequence Induction. It attains proper muscle relaxation for intubating rapidly, and its short length of duration and allows the patient to spontaneously breath again, in minutes, if intubation was unsuccessful.
Succinylcholine in induction doses is responsible for patients experiencing muscle fasciculation’s. Fasciculation is the involuntary contraction or twitching of muscle fibers, frequently visible under the skin. They are the result of antidromically conducted axonal depolarization’s initiated by Succinylcholine binding on prejunctional nicotinic cholinergic receptors (Harvey, etal.., 1998). The reduction of fasciculation’s attributed to the pretreatment of non-depolarizing muscle relaxants are the result of competitive antagonism for postjunctional nicotinic cholinergic receptors. Fasciculation’s are not always visually noticeable, but their occurrence, visible or not, are highly attributable to patients suffering from postoperative myalgia.
Myalgia is characterized by general muscular discomfort or malaise that may also be acutely painful. Myalgia is due to the same physiological mechanisms that are attributed to muscular fasciculations. It is common place to “pretreat” patients with a non-depolarizing neuromuscular paralytic to reduce the occurrence of fasciculations with hopes that a subsequent reduction of postoperative myalgias will be reduced as well.
Significance to Nursing
The act of administering a pretreatment is termed a defasciculating dose. However, quite often the pretreatment is insufficient in effectively reducing the occurrence of fasciculation’s and myalgias. The administration of succinylcholine is credited with an incidence of myalgias near 75% without any pretreatments. The administration of rocuronium is credited with reducing the incidence by 60%. However, the administration of any non-depolarizing muscle relaxants to reduce postoperative myalgia remains controversial.
Postoperative myalgias are discomforting to the patient and often hinder the patients efforts to increase mobility, contribute to general malaise, and can result in increased pain relief needs. Nurse Anesthetists are often responsible to providing as much as 100% of the anesthetic medications depending on practice guidelines that vary from one institution to the next. Reducing postoperative pain through proactive measures is an outcome that is taken into the anesthetic plan. Therefore, measures that may be undertaken to reduce Succinylcholine induced fasciculation and subsequent myalgias are warranted.
Specific Aims
Several articles reviewed report various and often contradictory results regarding the most effacious method of pretreatment in preventing myalgia’s. It is commonly recommended that when pretreating patients with non-depolarizing muscle relaxants, 10% of the intubating dose offers some protective benefits without compromising the patients efforts to breathe spontaneously. Rocuronium is stated to be best defasiculating drug when administration of succinylcholine is within 1-4 minutes. Curare is stated best in reducing myalgias if a full 5 minutes are allowed between its administration and the administration of succinylcholine. However allowing for a full 5 minutes for the therapeutic effects of curare is not always plausible in the dynamic setting of the operating room. It is for reasons of time management that rocuronium is selected for this study.
Propofol has been credited with further reducing postoperative myalgias when used as the induction agent as opposed to pentothal It has been theorized that succinylcholine induced myalgias are partly attributable to the production of free radicals. Propofol has antioxidant properties and may for these reasons have advantages over other induction agents, i.e.. Pentothal Propofol and Pentothal are the most commonly used agents for induction. The goal of this study is to determine if a combination of rocuronium and Propofol is more efficaous than the combination of Rocuronium and Pentothol at reducing the incidence of postopertive myalgias
Review of Literature
This chapter presents a review of the literature pertaining to the practice of reducing succinylcholine induced postoperative myalgias, the technique of defasciculating dose and the efficacy of various drug agents employed. The literature on defasciculating doses focused on ascertaining which drug is most conducive in the operating room setting and also is most efficacious in reducing the occurrence fasciculation’s and myalgias. The review also considers which hypnotic drug used for anesthetic induction’s further reduce the incidence of postoperative myalgias. The information reviewed concerning hypnotic induction drugs focused on Propofol and pentothol. Pretreatment: (defasciculation dose) The intravenous administration of a dose that is 10% of the intubating dose of a nondepolarizing muscle relaxant prior to administering Succinylcholine. This paper uses specific technical terms that are defined as follows:
Induction is the administration of barbiturates, benzodiazepines, opioids, or other hypnotic medication in combination to produce surgical anesthesia. Usually followed by the administration of a muscle relaxant. A bolus is the single intravenous administration of a substantial volume of a dose of medication, in this study, Propofol, thiopental, and succinylcholine.
Framework
Fasciculations are the result of antidromically conducted axonal depolarization’s initiated by Succinylcholine binding on prejunctional nicotinic cholinergic receptors (Harvey, etal.., 1998). The reduction of fasciculation’s attributed to the pretreatment of non-depolarizing muscle relaxants are the result of competitive antagonism for postjunctional nicotinic cholinergic receptors.
The theory behind the defasciculation dose is that a small dose of a neuromuscular paralytic will partially occupy the post-junctional receptor in the neuromuscular junction, reducing the available receptor sites in the neuromuscular junction and diminishing the intensity of succinylcholine induced fasciculations.
Defasciculating drugs
Harvey, Roland, Bailey, Tomlin and Williams (1998) conducted a study comparing d-Tubocurarine, Rocuronium and “mini dose” Succinylcholine in reducing Succinylcholine-induced fasciculation’s and myalgias. One hundred one patients were included in a randomized single blinded study randomized into 5 study groups. Groups were randomized according to the pretreatment given prior to receiving 1.5 mg/kg of succinylcholine. Group one was the control group, receiving normal saline, group two received 0.03 mg/kg of rocuronium, group three received 0.05 mg/kg of Rocuronium, group four received 0.05 mg/kg and group five received 0.03 mg/kg of succinylcholine. Pentothal 4-5 mg/kg was administered 3.5 minutes after the pretreatment and 1.5 mg/kg of Succinylcholine was subsequently administered after establishing an airway following pentothal induction. Fasciculations were graded from none or from 0-2, being mild moderate and severe, respectively. All participants were contacted on the day following surgery and myalgias were rated on a similar scale ranging from none to severe.
The results showed that fasciculations were absent in 5% or group one, 90% in group 2, 75% in group 3, 80% in group 4 and 30% of group 5. There was no difference in the severity of fasciculations of between the groups administered Rocuronium or d-Tubocurare. The difference in fasciculations between the control group and the “mini dose” Succinylcholine groups were similar. The occurrence of postoperative myalgias was 11.5% and was not significantly different across the groups. The results support that Rocuronium is as efficacious as d-Tubocurare in reducing fasciculation’s at equipotent doses, with on difference in the occurrence of myalgias.
Tsui, Reid, Gupta, Kearney, Mayson and Finucane conducted a study to determine if Rocuronium was superior to Atracurium in reducing fasciculations and postoperative myalgias. They conducted a prospective double-blind randomized study with 42 patients assigned to 3 pretreatment groups. Group one received normal saline, group two received 0.1 mg/kg of Atracurium and group three was pretreated with 0.1 mg/kg of Rocuronium. Standardized induction for all groups commenced with 1.5 mic/kg of fentanyl and 0.5 mg/kg of lidocaine, pretreatment was administered immediately after, followed 60 seconds later with 2.5 mg/kg of Propofol and 1.5 mg/kg of Succinylcholine at 90 seconds after pretreatment.
Fasciculations and myalgias were rated on four point scales by ranking them from none to severe. The incidence of fasciculations among the participants pretreated with Rocuronium was 21.4%, lower than Atracurium by 57.1%. The occurrence of fasciculation’s in the control group was 92.8%. The incidence of postoperative myalgias was 14.2% in the Rocuronium group, 85.7% in the atracurium group and 78,2% in the control group. The researchers used fishers exact test to conclude that rocuronium with Propofol reduced significantly the occurrence of fasciculations and myalgias.
Demers, Pelletier, Drolet, Girard and Donati (1997) conducted a study comparing d-Tubocurare and Rocuronium for preventing Succinylcholine induced fasciculations and postoperative myalgia. Seventy five women wee included into the study whom presented for short surgery. They were randomized in a double-blind fashion and placed into one of three study groups. Group SAL received normal saline, group ROC received 0.05 mg/kg of Rocuronium and group DTC received 0.05 mg/kg of D-tubocurare, all followed by the administration of 1.5 mg/kg of Succinylcholine. Fasciculation’s were assessed as nil, fine, moderate, and severe and rated by a blinded observer on a scale of 0-3, respectively. Patients were contacted at 24 and 48 hours postop and were asked to rate their myalgia on a scale of 0-10. Fasciculations were rated as more intense in the SAL group than in the ROC or the DTC groups with no significant difference between ROC or DTC groups. Patients rated postoperative myalgias as less intense only in the ROC group. They concluded that Rocuronium reduces fasciculation’s as well as d-tubocurare and is the more efficacious in reducing postoperative myalgia.
Hypnotic drugs
McClymont (1994) investigated the incidence of postoperative myalgia in a comparison study between Propofol and Pentothal prior to the administration of succinylcholine. A total of 51 patients, presenting for laparoscopic gynecological surgery, were enrolled in this prospective, blinded, experimental study. The subjects were assigned into 2 study groups, group A received Propofol and group B received pentothal as their induction agent prior to the administration of succinylcholine. Both groups were given 1mg/kg of succinylcholine to facilitate the insertion of an endotracheal tube. A questionnaire was sent home with the participants to complete and return. Subjects were instructed on how to properly complete questionnaire as it contained a pain linear analogue scale. The results were analyzed with Student’s t-test and the nonparametric data were analyzed with a fisher’s exact test. The results concluded that Propofol effectively reduces the incidence of succinylcholine induced myalgias, when compared to pentothal The pentothal group experienced myalgias at a 63% incidence as opposed to 19% in the Propofol group.
A study conducted by Maddineni, Mirakhur and Cooper (1992) sought to correlate the incidence of postoperative myalgias and changes in creatine kinase following 1mg/kg of succinylcholine immediately or two minutes after anesthetic induction with Propofol, 2-3mg/kg, or pentothal 3-5mg/kg, in patients having dental or ophthalmic surgery. In 1992, Propofol was recently introduced and the researchers recognized a gap in knowledge concerning potential benefits or adversities when given prior to succinylcholine. The study was designed to assess the incidence of fasciculatio’s, myalgias and muscle damage, measured by creatine kinase levels. Eighty patients between ages, 16 and 65 were enrolled into the study, 40 patients into each Propofol and pentothal groups. Twenty patients in each group were further randomized into groups receiving succinylcholine immediately after and two minutes after the induction agents Propofol or pentothal Fasciculations were observed in nearly 90% of the participants, however, myalgias were reported at 46% incidence. The occurrence appeared to reduced when succinylcholine was administered immediately after the induction agent, however, no significant difference was noted. The researchers reported that their findings of the incidence of myalgias were comparable to previously studied control groups receiving no treatment. Propofol was not concluded to have any greater beneficial effects on postoperative succinylcholine induced myalgias.
Smith, Ding and White (1993) conducted a single-blind, randomized study to compare various pharmacological techniques in relation to succinylcholine induced myalgias. The study included 155 women undergoing laproscopic surgery and assigned to one of five study groups. Group one received pentothal, 4mg/kg, and succinylcholine, 1mg/kg, followed by enflurane and nitrous oxide inhalation agents. Group 2 only varied by receiving d-Tubocurare, 3mg, and succinylcholine 1.5mg/kg. Groups 3 and 4 only varied by receiving Propofol, 2mg/kg, instead of pentothal, and group 4 received a continuous infusion of Propofol. Group 5 received atracurium instead of succinylcholine. All groups were treated similar in the postoperative phase.
The incidence of myalgias were reduced in group two, and fasciculations were not observed when succinylcholine was not administered. Myalgias were measured by the presence of shoulder and/or neck pain. Shoulder pain was present in 81% of all patients, with no significant difference among the groups. Neck pain occurred less often in all groups and the incidence was even less in group 5. Propofol had no significant effect in reducing postoperative myalgias. The study concluded that laproscopic surgery has a high incidence of shoulder pain and was present in the absence of succinylcholine. The only significant finding was that the avoidance of succinylcholine resulted in less neck pain.
Gap
In summary, the research presented in this literature review will be utilized as the basis for design of this research proposal. The pretreatment or defasciculation doses of nondepolarizing neuromuscular muscle relaxants have been shown to significantly reduce the incidence of myalgias and fasciculation’s when administered from 90 seconds to 4 minutes prior to succinylcholine. The recommended dose of 10% of the intubating dose of Rocuronium, d-tubocurare, succinylcholine and atracurium have all shown to reduce these incidences. Rocuronium has been shown as efficacious in reducing the incidence of fasciculation’s and myalgias as d-tubocurare, and allows for the administration of succinylcholine in 90 seconds as opposed to 3-5 minutes for d-tubocurare. These results serve as the basis for selecting Rocuronium as the defasciculation agent.