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1.  Effects of etomidate on complications related to intubation and on mortality in septic shock patients treated with hydrocortisone: a propensity score analysis 
Critical Care  2012;16(6):R224.
Introduction
Endotracheal intubation in the ICU is associated with a high incidence of complications. Etomidate use is debated in septic shock because it increases the risk of critical illness-related corticosteroid insufficiency, which may impact outcome. We hypothesized that hydrocortisone, administered in all septic shock cases in our ICU, may counteract some negative effects of etomidate.
The aim of our study was to compare septic shock patients who received etomidate versus another induction drug both for short-term safety and for long-term outcomes.
Methods
A single-center observational study was carried out in septic shock patients, treated with hydrocortisone and intubated within the first 48 hours of septic shock. Co-primary end points were life-threatening complications incidence occurring within the first hour after intubation and mortality during the ICU stay. Statistical analyses included unmatched and matched cohorts using a propensity score analysis. P < 0.05 was considered significant.
Results
Sixty patients in the etomidate cohort and 42 patients in the non-etomidate cohort were included. Critical illness-related corticosteroid insufficiency was 79% in the etomidate cohort and 52% in the non-etomidate cohort (P = 0.01). After intubation, life-threatening complications occurred in 36% of the patients whatever the cohort. After adjustment with propensity score analysis, etomidate was a protective factor for death in the ICU both in unmatched (hazard ratio, 0.33 (0.15 to 0.75); P < 0.01)) and matched cohorts (hazard ratio, 0.33 (0.112 to 0.988); P = 0.04).
Conclusion
In septic shock patients treated with hydrocortisone, etomidate did not decrease life-threatening complications following intubation, but when associated with hydrocortisone it also did not impair outcome.
doi:10.1186/cc11871
PMCID: PMC3672604  PMID: 23171852
2.  Effects of Etomidate on Adrenal Suppression: A Review of Intubated Septic Patients 
Hospital Pharmacy  2014;49(2):177-183.
Abstract
Background:
Etomidate is a commonly used sedative during rapid sequence intubation (RSI). Septic patients are at an increased risk of independently developing adrenal suppression, which has been associated with increased mortality in some studies. Since etomidate affects cortisol production, its use in septic patients is controversial. However, data are still lacking to prove that etomidate should be avoided in this patient population.
Objectives:
The objective was to review patients diagnosed with sepsis who received etomidate during RSI. Our hypothesis is that patients who receive etomidate will experience clinically significant hypotension within the first 24 hours of intubation.
Methods:
A retrospective cohort study was conducted on patients intubated in the emergency department (ED) and medical/surgical floors at our institution from 2004 to 2010. Once patients with a diagnosis of sepsis were identified, it was determined whether the patients received etomidate or a different sedative during intubation. The primary endpoint was clinically significant hypotension: systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg.
Results:
One hundred fifty-seven patients, 110 etomidate and 47 non-etomidate, were included in the final analysis. Hypotension was seen in 79 (71.8%) patients who received etomidate and in 14 (29.8%) patients who received another sedative (P ≤ .001). There were no statistically significant differences in secondary objectives.
Conclusion:
Etomidate use for induction of anesthesia during RSI was associated with clinically significant hypotension when compared to other sedatives. The hypotension was transient and did not translate into statistically significant differences in the secondary clinical endpoints.
doi:10.1310/hpj4902-177
PMCID: PMC3940683  PMID: 24623871
adrenal suppression; etomidate; intubation; rapid sequence intubation; sepsis
3.  The Effect of Single-Bolus Etomidate on Septic Patient Mortality: A Retrospective Review 
Background
Because of its many desirable properties, etomidate is widely used as an induction agent for endotracheal intubation. However, some have recently called into question the safety of etomidate for even single-bolus use due to its known effects on adrenal suppression.
Objectives
We sought to compare the in-hospital mortality between septic patients given etomidate and those given alternative induction agents for intubation.
Methods
We performed a retrospective chart review of intubated septic patients treated in our hospital. We collected data from patients over the age of 18 with sepsis who were intubated in the pre-hospital setting, in our emergency department, or on the wards of our hospital, and calculated the in-hospital mortality of each group.
Results
We identified 181 patients with sepsis who were intubated over the study period; 135 received etomidate and 46 received alternative agents or no induction agent. Baseline characteristics, vital signs, and laboratory values were similar between the two groups. Of the 46 patients receiving alternative agents or no agent, 18 died, yielding an unadjusted mortality of 39.1% (95% CI 25.5% to 54.6%), while of the 135 patients receiving etomidate, 63 died, for an unadjusted mortality of 46.7% (95% CI 38.1% to 55.4%), P=0.38.
Conclusion
We found a non-statistically significant 7.6% absolute increase in mortality in patients given etomidate in our small-sized study population.
PMCID: PMC2672284  PMID: 19561744
4.  Etomidate as an Induction Agent in Septic Patients: Red Flags or False Alarms? 
Despite its widespread use in North America and many other parts of the world, the safety of etomidate as an induction agent for rapid sequence intubation in septic patients is still debated. In this article, we evaluate the current literature on etomidate, review its clinical history, and discuss the controversy regarding its use, especially in sepsis. We address eight questions: (i) When did concern over the safety of etomidate first arise? (ii) What is the mechanism by which etomidate is thought to affect the adrenal axis? (iii) How has adrenal insufficiency in relation to etomidate use been defined or identified in the literature? (iv) What is the evidence that single dose etomidate is associated with subsequent adrenal-cortisol dysfunction? (v) What is the clinical significance of adrenal insufficiency or dysfunction associated with single dose etomidate, and where are the data that support or refute the contention that single-dose etomidate is associated with increased mortality or important post emergency department (ED) clinical outcomes? (vi) How should etomidate’s effects in septic patients best be measured? (vii) What are alternative induction agents and what are the advantages and disadvantages of these agents relative to etomidate? (viii) What future work is needed to further clarify the characteristics of etomidate as it is currently used in patients with sepsis? We conclude that the observational nature of almost all available data suggesting adverse outcomes from etomidate does not support abandoning its use for rapid sequence induction. However, because we see a need to balance theoretical harms and benefits in the presence of data supporting the non-inferiority of alternative agents without similar theoretical risks associated with them, we suggest that the burden of proof to support continued widespread use may rest with the proponents of etomidate. We further suggest that practitioners become familiar with the use of more than one agent while awaiting further definitive data.
PMCID: PMC2908652  PMID: 20823967
5.  Does Etomidate Increase Vasopressor Requirements in Patients Needing Mechanical Ventilation? 
Background:
Single-dose etomidate is used as an induction agent for rapid-sequence intubation and is associated with transient adrenal insufficiency. There is ongoing debate as to the clinical consequences of this transient adrenal insufficiency for critically ill patients.
Objective:
To determine if the use of etomidate is associated with higher requirements for a vasopressor, relative to other induction agents, at a single time point (24 h after administration of the induction agent) in patients needing mechanical ventilation.
Methods:
In this retrospective observational study utilizing electronic health records, a convenience sample of 50 patients who had undergone intubation in the emergency department with etomidate were matched (1:1) with patients who had received other induction agents. Matching was based on primary admitting diagnosis relating to the cause of shock, APACHE II (Acute Physiology and Chronic Health Evaluation II) score, age, and sex. All patients were subsequently admitted to critical care areas for management. As a surrogate marker of hemodynamic instability, the vasopressor dose was recorded 24 h after intubation. Vasopressor doses were converted to norepinephrine equivalents for comparison.
Results:
The mean dose of vasopressors, in norepinephrine equivalents, was 4 μg/min−1 for patients receiving etomidate and 3 μg/min−1 for the control group (mean difference 0.7 μg min−1, 95% confidence interval [CI] −1.9 to 3.2 μg min−1, p = 0.61). Twelve of the patients in the etomidate group and 16 of those in the control group required the use of vasopressors at 24 h following intubation (odds ratio 2.3, 95% CI 0.53 to 13.99, p = 0.34).
Conclusions:
Single-dose etomidate does not adversely affect hemodynamic stability, as measured by the dose of vasopressors required at 24 h after administration.
PMCID: PMC3420849  PMID: 22919104
etomidate; adrenal insufficiency; vasopressors; critical care; mechanical ventilation; étomidate; insuffisance surrénalienne; vasopresseurs; soins intensifs; ventilation artificielle
6.  The incidence of relative adrenal insufficiency in patients with septic shock after the administration of etomidate 
Critical Care  2006;10(4):R105.
Introduction
Etomidate blocks adrenocortical synthesis when it is administered intravenously as a continuous infusion or a single bolus. The influence of etomidate administration on the incidence of relative adrenal insufficiency in patients with septic shock has not been formally investigated. The objective of this study was to determine the incidence of relative adrenal insufficiency in patients with septic shock after etomidate administration compared with patients with septic shock who did not receive etomidate.
Methods
In this retrospective study, 152 adults with septic shock who had a consyntropin stimulation test between March 2002 and August 2003 in a tertiary medical center were included. Relative adrenal insufficiency was defined as a rise in serum cortisol ≤ 9 μg/dl after the administration of 250 μg of consyntropin. Patients were divided into those who did and those who did not receive etomidate before the stimulation test. The proportion of patients with relative adrenal insufficiency in these two groups was compared using Fischer's exact test. A P of value < 0.05 was considered statistically significant.
Results
The mean age of the patients was 64 years, 59% of patients were male, 97% of patients were white and their hospital mortality rate was 57%. Thirty-eight patients (25%) received etomidate before the cosyntropin stimulation test, and the median (interquartile range) time interval between the administration of the drug and the test was 7 (4–10) hours. The incidence of relative adrenal insufficiency was 76% in the patients who received etomidate compared with 51% in the patients who did not (P = 0.0077).
Conclusion
The incidence of relative adrenal insufficiency in patients with septic shock is increased when the stimulation test is performed after the administration of etomidate.
doi:10.1186/cc4979
PMCID: PMC1751010  PMID: 16859529
7.  Etomidate Should be Used Carefully for Emergent Endotracheal Intubation in Patients with Septic Shock 
Journal of Korean Medical Science  2008;23(6):988-991.
Etomidate and midazolam are the most popular drugs among the induction agents for emergent endotracheal intubation. The purpose of this study was to compare the incidence of adrenal insufficiency and mortality between the septic shock patients who received etomidate (ETM group) and those who received midazolam (MDZ group). Between November 2004 and September 2006, 65 patients were analyzed in this study. The hospital mortality rate was 36% in the ETM group (n=25) and 50% in the MDZ group (n=40), which was not statistically significant (p=0.269). The incidence of relative adrenal insufficiency was significantly higher in the ETM group than in the MDZ group (84% and 48%, respectively; p=0.003). On multivariate analysis, the use of etomidate was the only significant factor affecting the incidence of relative adrenal insufficiency (odds radio, 5.59; 95% confidence interval, 1.61-19.4). In conclusion, we think that physicians who treat patients with septic shock should be aware that etomidate can cause adrenal insufficiency, and should start corticosteroids if etomidate is administered.
doi:10.3346/jkms.2008.23.6.988
PMCID: PMC2610664  PMID: 19119441
Etomidate; Midazolam; Intubation; Adrenal Insufficiency; Shock, Septic
8.  One single dose of etomidate negatively influences adrenocortical performance for at least 24 h in children with meningococcal sepsis 
Intensive Care Medicine  2007;34(1):163-168.
Objective
To investigate the effect of one single bolus of etomidate used for intubation on adrenal function in children with meningococcal sepsis.
Design
Retrospective study conducted between 1997 and 2004.
Setting
University-affiliated paediatric intensive care unit (PICU).
Patients and participants
Sixty children admitted to the PICU with meningococcal sepsis, not treated with steroids.
Interventions
Adrenal hormone concentrations were determined as soon as possible after PICU admission, and after 12 h and 24 h. To assess disease severity, PRISM score and selected laboratory parameters were determined.
Measurements and main results
On admission, before blood was drawn, 23 children had been intubated with etomidate, 8 without etomidate and 29 were not intubated. Children who were intubated had significantly higher disease severity parameters than those not intubated, whereas none of these parameters significantly differed between children intubated with or without etomidate. Children who received etomidate had significantly lower cortisol, higher ACTH and higher 11-deoxycortisol levels than those who did not receive etomidate. Arterial glucose levels were significantly lower in children who were intubated with etomidate than in non-intubated children. When children were intubated with etomidate, cortisol levels were 3.2 times lower for comparable 11-deoxycortisol levels. Eight children died, seven of whom had received etomidate. Within 24 h cortisol/ACTH and cortisol/11-deoxycortisol ratios increased significantly in children who received etomidate, but not in children who did not, resulting in comparable cortisol/ACTH ratios with still significantly lowered cortisol/11-deoxycortisol ratios 24 h after admission.
Conclusions
Our data imply that even one single bolus of etomidate negatively influences adrenal function for at least 24 h. It might therefore increase risk of death.
doi:10.1007/s00134-007-0836-3
PMCID: PMC2668631  PMID: 17710382
Adrenal insufficiency; Etomidate; Critical illness; Meningococcal disease; Child
9.  Etomidate for intubation of patients who have sepsis or septic shock - where do we go from here? 
Critical Care  2012;16(6):189.
Etomidate is an intravenous induction agent that is associated with hemodynamic stability during intubation. The agent is therefore attractive for use in critically ill patients who have a high risk of hemodynamic instability during this procedure. However, etomidate causes adrenal suppression, which itself has been associated with increased mortality in critically ill patients. The ongoing debate surrounding use of etomidate is thus centered on the immediate favorable hemodynamic profile versus the long-term risks of adrenal insufficiency, particularly in patients who have severe sepsis or septic shock.
doi:10.1186/cc11889
PMCID: PMC3672616  PMID: 23273139
10.  Prevention of etomidate-related myoclonus in anesthetic induction by pretreatment with magnesium 
BACKGROUND:
Etomidate frequently leads to myoclonic jerks during anesthetic induction. This study aimed to detect if pretreatment with magnesium decreases myoclonus incidence.
METHODS:
A hundred ASA (the American Society of Anesthesiologists) I-II patients were included and randomized into 2 groups. Three minutes before etomidate induction of anesthesia (by 0.3 mg/kg intravenous etomidate), Group M received 2.48 mmol (60 mg) intravenous magnesium sulphate and Group P received equal volume of intravenous saline. Myoclonus was evaluated as “present/absent”.
RESULTS:
The rate of myoclonus was significantly lower in Group M than in Group P (p < 0.01). Hemodynamic parameters revealed no significant difference between the two groups.
CONCLUSIONS:
Low dose magnesium pretreatment before etomidate induction of anesthesia significantly reduces unwanted myoclonic jerks and also protects the hemodynamic stability.
PMCID: PMC3430068  PMID: 22973352
Etomidate; Myoclonus; Magnesium Sulphate
11.  Effect of induction agent on vasopressor and steroid use, and outcome in patients with septic shock 
Critical Care  2007;11(3):R56.
Introduction
In seriously ill patients, etomidate gives cardiovascular stability at induction of anaesthesia, but there is concern over possible adrenal suppression. Etomidate could reduce steroid synthesis and increase the need for vasopressor and steroid therapy. The outcome could be worse than in patients given other induction agents.
Methods
We reviewed 159 septic shock patients admitted to our intensive care unit (ICU) over a 40-month period to study the association between induction agent and clinical outcome, including vasopressor, inotrope, and steroid therapy. From our records, we retrieved induction agent use; vasopressor administration at induction; vasopressor, inotrope, and steroid administration in the ICU; and hospital outcome.
Results
Hospital mortality was 65%. The numbers of patients given an induction agent were 74, etomidate; 25, propofol; 26, thiopental; 18, other agent; and 16, no agent. Vasopressor, inotrope, or steroid administration and outcome were not related to the induction agent chosen. Corticosteroid therapy given to patients who received etomidate did not affect outcome. Vasopressor therapy was required less frequently and in smaller doses when etomidate was used to induce anaesthesia. We found no evidence that either clinical outcome or therapy was affected when etomidate was used. Etomidate caused less cardiovascular depression than other induction agents in patients with septic shock.
Conclusion
Etomidate use for critically ill patients should consider all of these issues and not simply the possibility of adrenal suppression, which may not be important when steroid supplements are used.
doi:10.1186/cc5916
PMCID: PMC2206408  PMID: 17506873
12.  Appropriateness of Adrenocorticotropic Hormone Stimulation Test for Critically Ill Patients 
Background:
In earlier work, it was shown that patients with septic shock who also have adrenal insufficiency experience a benefit in terms of lower mortality rates with hydrocortisone supplementation. As such, the adrenocorticotropic hormone (ACTH) stimulation test has been used frequently to identify these patients. However, recent evidence has suggested that the identification and treatment of adrenal insufficiency in patients with septic shock does not reduce mortality. These results call into question the utility of the ACTH stimulation test in this patient population.
Objectives:
To determine the indications for ordering the ACTH stimulation test for critically ill patients at a tertiary care hospital and to classify the indications as either appropriate (e.g., primary adrenal insufficiency or medication-induced suppression of the hypothalamus–pituitary–adrenal axis) or inappropriate (e.g., patients with septic shock, prior etomidate exposure, or absence of steroid use).
Methods:
A retrospective analysis of health care records was conducted for all patients who had been admitted to the intensive care unit and who had undergone an ACTH stimulation test during 2007. For each patient, the indication for the test was identified and classified as appropriate or inappropriate.
Results:
A total of 35 ACTH stimulation tests were performed during the study period, of which 8 (23%) were classified as having an appropriate indication and 27 (77%) as having an inappropriate indication. Of the tests with an inappropriate indication, 15 (56%) were ordered for patients with septic shock. However, the number of ACTH tests ordered for this indication declined as the year progressed.
Conclusions:
The ACTH stimulation test was often used inappropriately for patients with septic shock. Over time, there appeared to be a trend away from use of this test in this patient population, perhaps reflecting increasing awareness of the lack of benefit.
PMCID: PMC2832565  PMID: 22478947
adrenocorticotropic hormone stimulation test; septic shock; adrenal insufficiency; épreuve de stimulation à l’adrénocorticotrophine synthétique; choc septique; insuffisance surrénalienne
13.  Midazolam is more likely to cause hypotension than etomidate in emergency department rapid sequence intubation 
Emergency Medicine Journal : EMJ  2004;21(6):700-702.
Objective: To compare the haemodynamic effect of low dose midazolam and etomidate as induction agent in emergency department rapid sequence intubation.
Methods: A prospective observational study in two phases. In phase one, midazolam 2–4 mg was used as induction agent and in phase two, etomidate 0.2–0.3 mg/kg was used. The haemodynamic data were recorded before and after intubation for comparison. Changes in mean systolic blood pressure were analysed with SPSS software.
Results: A 10% decrease in mean systolic blood pressure was observed in the midazolam group (p = 0.001) while there was no significant change in the etomidate group. Some 19.5% of patients had hypotension after being given midazolam while only 3.6% with etomidate (p = 0.002). Patients older than 70 tended to have more hypotension episodes but the difference was not statistically significant.
Conclusions: Midazolam, even in low dose, was more likely than etomidate to cause significant hypotension when used as an induction agent for rapid sequence intubation. Etomidate is a better alternative.
doi:10.1136/emj.2002.004143
PMCID: PMC1726487  PMID: 15496697
14.  Comparison of anesthetics in electroconvulsive therapy: an effective treatment with the use of propofol, etomidate, and thiopental 
Objectives
Electroconvulsive therapy (ECT) is considered to be one of the most effective treatments in psychiatry. Currently, three medications for anesthesia are used routinely during ECT: propofol, etomidate, and thiopental. The objective of this study was to evaluate the effects of the anesthetics used in ECT on seizure threshold and duration, hemodynamics, recovery from ECT, and immediate side effects.
Methods
Our study is a retrospective cohort study, in which a comparison was made between three groups of patients who underwent ECT and were anesthetized with propofol, etomidate, or thiopental. The main effect compared was treatment dose and seizure duration. All patients were chosen as responders to ECT.
Results
Data were gathered about 91 patients (39 were anesthetized with thiopental, 29 with etomidate, and 23 with propofol). Patients in the thiopental group received a lower electrical dose compared to the propofol and etomidate group (mean of 459 mC compared to 807 mC and 701 mC, respectively, P<0.001). Motor seizure duration was longer in the thiopental group compared to propofol and etomidate (mean of 40 seconds compared to 21 seconds and 23 seconds, respectively, P=0.018). Seizure duration recorded by electroencephalography was similar in the thiopental and etomidate groups and lower in the propofol group (mean of 57 seconds in both groups compared to 45 seconds, respectively, P=0.038).
Conclusion
Patients who were anesthetized with thiopental received a lower electrical treatment dose without an unwanted decrease in seizure duration. Thiopental might be the anesthetic of choice when it is congruent with other medical considerations.
doi:10.2147/NDT.S58330
PMCID: PMC3934661  PMID: 24591833
anesthesia; ECT; seizure
15.  Etomidate, sepsis, and adrenal function: not as bad as we thought? 
Critical Care  2007;11(3):145.
The choice of induction agent for endotracheal intubation can have significant downstream effects, especially in critically ill patients. In a retrospective study, Ray and McKeown found that the choice of induction agent had no significant effect on use of vasoactive medications, corticosteroids, or mortality. Given the heated debate regarding corticosteroids in septic shock and the role that etomidate may play in leading to adrenal insufficiency, enthusiasm for etomidate as an induction agent should be tempered by its possible, significant side effects in these critically ill patients.
doi:10.1186/cc5939
PMCID: PMC2206428  PMID: 17610749
16.  Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial 
Background
Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock.
Methods
We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality.
Results
The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98–2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92–1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04–6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08–8.36, p = 0.02).
Interpretation
Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.)
doi:10.1503/cmaj.090707
PMCID: PMC3001503  PMID: 21059778
17.  Pro/con debate: Is etomidate safe in hemodynamically unstable critically ill patients? 
Critical Care  2012;16(4):227.
Etomidate is an induction agent known for its smooth intubating conditions and cardiovascular stability. Studies, however, have shown that a single dose of etomidate can result in a prolonged adrenal insufficiency. The impact of this in patients with sepsis has been a matter for debate. This review presents a pro/con case for using etomidate in hemodynamically unstable critically ill patients and provides guidance for alternative induction techniques and when the use of etomidate might be justified despite these concerns.
doi:10.1186/cc11242
PMCID: PMC3580672  PMID: 22809235
18.  Clinical study of etomidate emulsion combined with remifentanil in general anesthesia 
Background
The aim of this study was to investigate and evaluate the safety, recovery time, and side effects of general anesthesia with different doses of etomidate emulsion combined with remifentanil.
Methods
One hundred ten patients of American Society of Anesthesiologists class 1 or 2 who underwent gynecological general anesthesia with a 1–3-hour operation time were randomly divided into the following groups: etomidate emulsion group 1 ([E1] n = 30); etomidate emulsion group 2 ([E2] n = 30); etomidate emulsion group 3 ([E3] n = 20); and propofol group ([P group] n = 30). For induction of anesthesia, 0.3 mg/kg etomidate emulsion, and the continuous remifentanil infusion also to induce anesthesia (0.1~0.3 μg · kg−1 · min−1), was applied in all cases. Afterwards, continuous infusion of etomidate emulsion and remifentanil, respectively (E1: 10 μg · kg−1 · min−1 and 0.1 μg · kg−1 · min−1; E2: 15 μg · kg−1 · min−1 and 0.2 μg · kg−1 · min−1; E3: 20 μg · kg−1 · min−1 and 0.2 μg · kg−1 · min−1), and propofol (P group: 6~10 mg · kg−1 · h−1) were administered. Changes in blood flow kinetics and adverse reactions were noted and compared between the four groups.
Results
Both arterial blood pressure (BP) and heart rate (HR) decreased after induction of anesthesia (P < 0.05). Systolic (SBP) and diastolic (DBP) BP changed only slightly, and HRs were slightly infected in E1, E2, and E3. SBP, DBP, and HR during the operation all decreased significantly in P group (P < 0.05). Muscle tremor at the time of induction occurred in 13 cases (11.8%). Following etomidate emulsion anesthesia maintenance, postoperative agitation occurred in seven cases (8.75%), lethargy in 20 cases (25%), and vomiting in 19 cases (23.75%). No adverse reactions were found in P group.
Conclusion
Continuous infusion of etomidate emulsion at 10 μg · kg−1 · minute−1 combined with remifentanil during anesthesia has the advantages of hemodynamic stability, quick wake-up, and few adverse reactions. Increasing the dose of etomidate emulsion increases the incidence of adverse reactions.
doi:10.2147/DDDT.S45979
PMCID: PMC3753064  PMID: 23990706
etomidate emulsion; remifentanil; general anesthesia
19.  Intra-abdominal pressure and abdominal perfusion pressure in cirrhotic patients with septic shock 
Annals of Intensive Care  2012;2(Suppl 1):S4.
Background
The importance of intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) in cirrhotic patients with septic shock is not well studied. We evaluated the relationship between IAP and APP and outcomes of cirrhotic septic patients, and assessed the ability of these measures compared to other common resuscitative endpoints to differentiate survivors from nonsurvivors.
Methods
This study was a post hoc analysis of a randomized double-blind placebo-controlled trial in which mean arterial pressure (MAP), central venous oxygen saturation (ScvO2) and IAP were measured every 6 h in 61 cirrhotic septic patients admitted to the intensive care unit. APP was calculated as MAP - IAP. Intra-abdominal hypertension (IAH) was defined as mean IAP ≥ 12 mmHg, and abdominal hypoperfusion as mean APP < 60 mmHg. Measured outcomes included ICU and hospital mortality, need for renal replacement therapy (RRT) and ventilator- and vasopressor-free days.
Results
IAH prevalence on the first ICU day was 82%, and incidence in the first 7 days was 97%. Compared to patients with normal IAP, IAH patients had significantly higher ICU mortality (74.0% vs. 27.3%, p = 0.005), required more RRT (78.0% vs. 45.5%, p = 0.06) and had lower ventilator- and vasopressor-free days. On a multivariate logistic regression analysis, IAH was an independent predictor of both ICU mortality (odds ratio (OR), 12.20; 95% confidence interval (CI), 1.92 to 77.31, p = 0.008) and need for RRT (OR, 6.78; 95% CI, 1.29 to 35.70, p = 0.02). Using receiver operating characteristic curves, IAP (area under the curve (AUC) = 0.74, p = 0.004), APP (AUC = 0.71, p = 0.01), Acute Physiology and Chronic Health Evaluation II score (AUC = 0.71, p = 0.02), but not MAP, differentiated survivors from nonsurvivors.
Conclusions
IAH is highly prevalent in cirrhotic patients with septic shock and is associated with increased ICU morbidity and mortality.
doi:10.1186/2110-5820-2-S1-S4
PMCID: PMC3390301  PMID: 22873420
liver cirrhosis; sepsis; compartment syndrome; septic shock; ascites; mortality.
20.  Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial 
Critical Care  2007;11(1):R21.
Introduction
Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock. The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered. Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach.
Methods
In this prospective randomized study, we compared the blood glucose profiles, insulin requirements, amount of nursing workload needed, and shock reversal in 48 septic shock patients who received hydrocortisone treatment either by bolus or by continuous infusion with equivalent dose (200 mg/day). Duration of hydrocortisone treatment was five days.
Results
The mean blood glucose levels were similar in the two groups, but the number of hyperglycemic episodes was significantly higher in those patients who received bolus therapy (15.7 ± 8.5 versus 10.5 ± 8.6 episodes per patient, p = 0.039). Also, more changes in insulin infusion rate were needed to maintain strict normoglycemia in the bolus group (4.7 ± 2.2 versus 3.4 ± 1.9 adjustments per patient per day, p = 0.038). Hypoglycemic episodes were rare in both groups. No difference was seen in shock reversal.
Conclusion
Strict normoglycemia is more easily achieved if the hydrocortisone therapy is given to septic shock patients by continuous infusion. This approach also reduces nursing workload needed to maintain tight blood glucose control.
Trial Registration Number
ISRCTN98820688
doi:10.1186/cc5696
PMCID: PMC2151907  PMID: 17306016
21.  Hemodynamic Stability during Induction of Anesthesia in ElderlyPatients: Propofol + Ketamine versus Propofol + Etomidate 
Introduction: Various methods have been recommended to prevent hemodynamic instability caused by propofol induction. Current study evaluates hemodynamic effects of ketamine and propofol in comparison to etomidate and propofol during anesthesia induction.
Methods: Sixty-two patients over 50 years old undergoing elective surgeries were randomly assigned to ketamine + propofol (ketofol) (n=30) and etomidate + propofol (etofol) (n=32) groups. Patients in ketofol group were induced with ketamine 0.75 mg/kg and propofol 1 mg/kg. In etofol group, induction was performed with etomidate 0.2 mg/kg and propofol 1 mg/kg. Hemodynamic states before and after induction, first, third and sixth minutes after intubation were measured and compared between groups.
Results: There was no difference between groups in systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP), heart rate (HR) and blood oxygen saturation (SaO2). There was significant decrease in SAP, DAP and MAP after induction and 6 minutes after intubation and in HR after induction than values before induction. There was significant increase in SaO2 in all evaluated periods than before induction in etofol group; however, the difference in ketofol group was not significant.
Conclusion: Both methods of induction -ketamine + propofol and etomidate + propofol- are effective in maintaining hemodynamic stability and preventing hemodynamic changes due to propofol administration.
doi:10.5681/jcvtr.2013.011
PMCID: PMC3825382  PMID: 24251011
Ketamine; Etomidate; Intubation; Hemodynamic
22.  Steroidogenesis in the adrenal dysfunction of critical illness: impact of etomidate 
Critical Care  2012;16(4):R121.
Introduction
This study was aimed at characterizing basal and adrenocorticotropic hormone (ACTH)-induced steroidogenesis in sepsis and nonsepsis patients with a suspicion of critical illness-related corticosteroid insufficiency (CIRCI), taking the use of etomidate-inhibiting 11β-hydroxylase into account.
Method
This was a prospective study in a mixed surgical/medical intensive care unit (ICU) of a university hospital. The patients were 62 critically ill patients with a clinical suspicion of CIRCI. The patients underwent a 250-μg ACTH test (n = 67). ACTH, adrenal steroids, substrates, and precursors (modified tandem mass spectrometry) also were measured. Clinical characteristics including use of etomidate to facilitate intubation (n = 14 within 72 hours of ACTH testing) were recorded.
Results
At the time of ACTH testing, patients had septic (n = 43) or nonseptic critical illness (n = 24). Baseline cortisol directly related to sepsis and endogenous ACTH, independent of etomidate use. Etomidate was associated with a lower baseline cortisol and cortisol/11β-deoxycortisol ratio as well as higher 11β-deoxycortisol, reflecting greater 11β-hydroxylase inhibition in nonsepsis than in sepsis. Cortisol increases < 250 mM in exogenous ACTH were associated with relatively low baseline (HDL-) cholesterol, and high endogenous ACTH with low cortisol/ACTH ratio, independent of etomidate. Although cortisol increases with exogenous ACTH, levels were lower in sepsis than in nonsepsis patients, and etomidate was associated with diminished increases in cortisol with exogenous ACTH, so that its use increased, albeit nonsignificantly, low cortisol increases to exogenous ACTH from 38% to 57%, in both conditions.
Conclusions
A single dose of etomidate may attenuate stimulated more than basal cortisol synthesis. However, it may only partly contribute, particularly in the stressed sepsis patient, to the adrenal dysfunction of CIRCI, in addition to substrate deficiency.
doi:10.1186/cc11415
PMCID: PMC3580698  PMID: 22781364
23.  Cardiac effects of induction agents in the septic rat heart 
Critical Care  2009;13(5):R144.
Introduction
The current debate about the side effects of induction agents, e.g. possible adrenal suppression through etomidate, emphasizes the relevance of choosing the correct induction agent in septic patients. However, cardiovascular depression is still the most prominent adverse effect of these agents, and might be especially hazardous in septic patients presenting with a biventricular cardiac dysfunction - or so-called septic cardiomyopathy. Therefore, we tested the dose-response direct cardiac effects of clinically available induction agents in an isolated septic rat heart model.
Methods
A polymicrobial sepsis was induced via cecal ligation and single puncture. Hearts (n = 50) were isolated and randomly assigned to five groups, each receiving etomidate, s(+)-ketamine, midazolam, propofol, or methohexitone at concentrations of 1 × 10-8 to 1 × 10-4 M. Left ventricular pressure, contractility and lusitropy, and coronary flow were measured. Cardiac work, myocardial oxygen delivery, oxygen consumption, and percentage of oxygen extraction were calculated.
Results
All of the induction agents tested showed a dose-dependent depression of cardiac work. Maximal cardiac work dysfunction occurred in the rank order of s(+)-ketamine (-6%)
Conclusions
Overall, this study demonstrates that these tested drugs indeed have differential direct cardiac effects in the isolated septic heart. Propofol showed the most pronounced adverse direct cardiac effects. In contrast, S(+)ketamine showed cardiovascular stability over a wide range of concentrations, and might therefore be a beneficial alternative to etomidate.
doi:10.1186/cc8038
PMCID: PMC2784361  PMID: 19737388
Background:
Etomidate and Propofol are common anesthetic agents. Previous studies say that Etomidate can be used in patients with limited hemodynamic reserve and Propofol can lead to more hemodynamic instabilities. This study was performed to explore the cardiovascular response during the induction of anesthesia with Etomidate or for comparison, Propofol in elective orthopedic surgeries.
Materials and Methods:
This study was a double-blinded randomized clinical trial study including patients 18-45 years of age that were admitted for elective orthopedic surgeries in 2012. 25consenting, ASA I (American Society of Anaesthesiologists), patients were evaluated randomly in two groups, and their cardiovascular responses including: systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and O2 saturation (O2 sat) were measured before the laryngoscopy, during the anesthesia induction with Etomidate (0.3 mg/kg) in group A and propfol (2-2.5 mg/kg) in group B and at 1, 3, 5,10 min after the induction.
Results:
There were no statistical differences between both groups regarding gender, age, body mass index, and laryngoscopic grade of patients (P > 0.05). Changes of SBP in the group B was significantly higher (P = 0.019). Furthermore, changes of the DBP was significantly higher in the group B (P = 0.001). The changes of MAP was higher in group B (P = 0.008). Hypotension happened in 26.1% of group B and 8% of group A (P = 0.09). There were no significant differences among groups A and B in terms of HR (P = 0.47) and O2 sat (P = 0.21), tachycardia (P = 0.6), bradycardia (P = 0.66) and hypertension (P = 0.95).
Conclusion:
Since, patients receiving Etomidate have more stable hemodynamic condition, if there would be no contraindications, it could be preferred over Propofol for general anesthesia.
PMCID: PMC3897071  PMID: 24497858
Cardiovascular response; etomidate; hemodynamic changes; laryngoscopy; propofol
Introduction:
Presence of a sore throat after surgery is a common side effect of general anesthesia with intratracheal intubation and can cause discomfort for the patient and prolong the recovery process. In this study we compared the effect of dexamethasone before and after intubation on the incidence of sore throat after tympanoplasty surgery.
Materials and Methods:
In a double-blind, randomized clinical trial, 70 patients aged 30–60 years with American Society of Anesthesiologists (ASA) physical status I or II who were candidates for tympanoplasty under anesthetic conditions were studied in two separate groups. The first group received intravenous (IV) dexamethasone (8 mg) 30 mins prior to intubation while the second group received the same dose of dexamethasone 30 mins after intubation. The incidence and severity of the sore throat in both groups were then evaluated.
Results:
There was no significant difference between two groups in intensity of sore throat (62.9% vs. 57.1%), cough (65.7% vs. 62.9%), or hoarseness (62.9% vs. 65.7%) within 24 h after surgery. Detection of blood in oral secretions or on the tracheal tube was the same in both groups (5.7%). The incidence of coughs during the extubation was 0% in first group and 11.4% in second group.
Conclusion:
According to the results of this research there was no significant difference in incidence and intensity of sore throat in patients receiving dexamethasone before or after intubation. Further, no significant difference in intensity of coughs or hoarseness was observed.
PMCID: PMC3989873  PMID: 24744997
Dexamethasone; Intubation; Sore throat

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