Propofol vs thiopental Essay

This essay has a total of 5220 words and 36 pages.

Propofol vs thiopental





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.

The occurrence of myalgia's vary within different groups of patients and it has generally
understood that it occurs more frequently in women, for reasons yet not fully understood.
Propofol has been shown in some studies to reduce the incidence of muscle fasciculations
and postoperative myalgias, to a greater degree than with pretreatment alone. However,
Smith et al.. (1993) concluded that Propofol did not significantly reduce the incidence of
postoperative myalgia, however, the selection of an all female group may be a confounding
factor in the results. The results of the studies in women effectively demonstrate a
decreased occurrence of myalgias with the use of Propofol prior to succinylcholine. It
could perhaps be concluded that the incidence would be further reduced in men and is the
basis for selecting an all male group and controlling for this potential confounding
factor.



Method

Research Question
This study seeks to determine the incidence and severity of fasciculations and myalgias
associated with the administration of Succinylcholine. Is there an association between
incidence and severity of fasciculation's and myalgias and does the administration of
Propofol or Pentothol reduce the occurance after rapid sequence inductions?

Design
This study design will be quasi-experimental in nature and will be a prospective, randomized, single-blinded design.

Population & Sample
The convenience sample will be obtained by reviewing the surgical schedule for the next
day and selecting candidates that prospectively meet the criteria for inclusion. The
study is open only to males with no restriction on ethnicity. ASA is the American Society
of Anesthesiology risk categories that rates patients as healthy, ASA 1, to moribund, ASA
5. Inclusion criteria includes: Age 35 years and older, preoperative ASA classification
of 1 through 3, Surgical procedure which requires general surgery with rapid sequence
induction.

Exclusion criteria include: known hypersensitivity to Pentathol, Propofol or
Succinylcholine; personal or familial history of malignant hyperthermia; patients
undergoing emergency surgery, surgery of the neck and shoulder area, or laproscopic
surgery of the abdomen; body weight deviations greater than 25% from ideal; known
neuromuscular disorder; preexisting neck or shoulder discomfort: failure, inability or
unwillingness to give informed consent. Patients that are unable to receive either
Pentothol or Propofol in each case will not be included in the study.

Setting
The experimental study will be conducted at the Minneapolis Veterans Administration
Medical Center. The treatment will be administered in the operating room. The subjects
will be monitored using routine methods for ECG, blood pressure, oxygen saturation,
temperature, muscle paralysis and end tidal carbon dioxide.

Measurements
Fasciculations
Fasciculations are the involuntary muscle activity observed after the administration of
Succinylcholine. The rating of Muscle fasciculatio's tool used will be a standardized
numeric scale ranging from 0 through 3. Fasciculation's will be observed by the
anesthesia personnel administering the anesthetic. Criteria used to describe
fasciculation's will be described as: nil (0); fine tremors of the face and neck (1);
moderate fasciculation's affecting the neck and limbs (2); severe vigorous, widespread
fasciculation's (3). These conditions are ranked according to criteria similar to that
used by Demers-Pelletier, etal.. (1997). No validity are given by raters for this
measurement. However, a high level of rater reliability will be attained since the
primary investigator will be present to observe each case.

The occurance of fasciculation's will be monitored by the investigator by assessing for
muscle tremors and contractions immediately following the administration of
Succinylcholine until three minutes post administration. Succinylcholine is known to have
a rapid onset, generally occurring at the 60 to 90 second mark. The observations will be
rated and recorded on the standardized assessment tool.

Myalgia
Myalgia is the presence of muscle discomfort. May range from slight aching to pain that
limits activities. In this study, the pain experienced purportedly caused by the
administration of Succinylcholine. The rating of postoperative myalgia will be a
subjective measure reported by the patient instructed in the scale measurement. The
rating will be a standardized numeric scale ranging from 0 through 10. Patients will be
contacted at 24 hours postoperatively and asked to rate their myalgia. Patients reporting
no myalgia will rate a 0, increasing in intensity to 10. The neck and shoulders commonly
exhibit symptoms of Succinylcholine induced muscle myalgia, and will be the area assessed
for myalgia. Rater reliability will be attained since the primary investigator will
contact and record the results in each case.

Design
Subjects will be randomized into two treatment groups using the last digit of their social
security number (SSN). Subjects will be assigned to Group A if their SSN ends with zero
through four. Subjects will be assigned to Group B is their SSN ends with five through
nine. Both groups will receive a defaciculating dose of Rocuronium, being 10% of the
induction dose, followed three minutes later by induction. Group A will begin induction
by receiving 1.5 mg/kg to 2 mg/kg of Propofol, followed within 3 minutes by the
administration of 1.5 mg/kg of Succinylcholine. Group B will begin induction by receiving
3 mg/kg to 5 mg/kg of Pentathol, followed within 3 minutes by receiving 1.5 mg/kg to 2
mg/kg of Succinylcholine.

The CRNA performing the anesthetic will conduct drug preparation after determining the
group to which a given subject was assigned.



Proceedure
Subjects will be greeted in the operating room holding area. The investigator and the
case CRNA will conduct the standard anesthetic preoperative interview. Criteria for
exclusion will be addressed with the case CRNA, and the case anesthesiologist at that
time. Patients will be informed of the study and consent will be attained if subjects
agree to participate. An intravenous catheter will be placed in either arm.

Once consent has been attained, the subjects will be transported to the operating room.
The standard monitoring devices will be placed on the subject. All subjects will
routinely be medicated with 2mg of Midazolam and 3-5 CC of Fentanyl for sedation and
amnesia prior to the administration of the defasciculating dose of Rocuronium. The usual
induction will begin with preoxygenation, consisting of placing mask over the mouth and
nose and applying 8-12 L/minute flow to the patient. All medications will be administered
via the intravenous line as per usual routine.

Pretreatment is the intravenous administration of 10% of the calculated intubating dose
of Rocuronium three minutes prior to administering Succinylcholine. Once the investigator
and case anesthesia personnel are prepared for induction, a pretreatment is calculated as
10% of the intubating dose of Rocuronium and will be administered as the defasciculation
dose. Patients are monitored at this time for any changes in breathing or muscle
weakness. At the three minute mark, Group A will receive a bolus dose (1.5 mg/kg to 2
mg/kg) of Propofol, and Group B will receive a bolus dose of Pentathol (3mg/kg).
Induction will proceed within 3 minutes with the administration of a bolus dose of
Succinylcholine (1.5 mg/kg).

The usual rationale for utilizing either Pentathol or Propofol is based on the patients
ability to hemodynamically withstand the depressant effects of these two agents. The
Continues for 18 more pages >>




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