ABSTRACT
Background@#Chronic glucocorticoid exposure is associated with resistance to nondepolarizing neuromuscular blocking agents. Therefore, we hypothesized that sugammadex-induced recovery would occur more rapidly in subjects exposed to chronic dexamethasone compared to those who were not exposed. This study evaluated the sugammadex-induced recovery profile after neuromuscular blockade (NMB) in rats exposed to chronic dexamethasone. @*Methods@#Sprague–Dawley rats were allocated to three groups (dexamethasone, control, and pair-fed group) for the in vivo study. The mice received daily intraperitoneal dexamethasone injections (500 μg/kg) or 0.9% saline for 15 days. To achieve complete NMB, 3.5 mg/kg rocuronium was administered on the sixteenth day. The recovery time to a train-of-four ratio ≥ 0.9 was measured to evaluate the complete recovery following the sugammadex injection. @*Results@#Among the groups, no significant differences were observed in the recovery time to a train-of-four ratio ≥ 0.9 following sugammadex administration (P = 0.531). The time to the second twitch of the train-of-four recovery following rocuronium administration indicated that the duration of NMB was significantly shorter in Group D than that in Groups C and P (P = 0.001). @*Conclusions@#Chronic exposure to dexamethasone did not shorten the recovery time of sugammadex-induced NMB reversal. However, the findings of this study indicated that no adjustments to sugammadex dosage or route of administration is required, even in patients undergoing long-term steroid treatment.
ABSTRACT
Dantrolene sodium (DS) was first introduced as an oral antispasmodic drug. However, in 1975, DS was demonstrated to be effective for managing malignant hyperthermia (MH) and was adopted as the primary therapeutic drug after intravenous administration. However, it is difficult to administer DS intravenously to manage MH. MH is life-threatening, pharmacogenomically related, and induced by depolarizing neuromuscular blocking agents or inhalational anesthetics. All anesthesiologists should know the pharmacology of DS. DS suppresses Ca2+ release from ryanodine receptors (RyRs). RyRs are expressed in various tissues, although their distribution differs among subtypes. The anatomical and physiological functions of RyRs have also been demonstrated as effective therapeutic drugs for cardiac arrhythmias, Alzheimer’s disease, and other RyR-related diseases. Recently, a new formulation was introduced that enhanced the hydrophilicity of the lipophilic DS. The authors summarize the pharmacological properties of DS and comment on its indications, contraindications, adverse effects, and interactions with other drugs by reviewing reference articles.
ABSTRACT
Sugammadex is a specific antagonist of aminosteroidal neuromuscular blocking agents with 1:1 binding to guest molecules. Sugammadex can also bind to other drugs having a steroid component in its chemical structure. In this in vivo experiment, we investigated the differences in the recovery of rocuronium-induced neuromuscular blockade using sugammadex pre-exposed with two different concentrations of hydrocortisone. Methods: The sciatic nerves and tibialis anterior muscles of 30 adult Sprague–Dawley rats were prepared for the experiment. The sciatic nerves were stimulated using a train-of-four (TOF) pattern with indirect supramaximal stimulation at 20 s intervals. After 15 min of stabilization, a 250 μg loading dose and 125 μg booster doses of rocuronium were serially administered until > 95% depression of the first twitch tension of TOF stimulation (T1) was confirmed. The study drugs were prepared by mixing sugamadex with the same volume of three different stock solutions (0.9% normal saline, 10 mg/ml hydrocortisone, and 100 mg/ ml hydrocortisone). The recovery of rats from neuromuscular blockade was monitored by assessing T1 and the TOF ratio (TOFR) simultaneously until T1 was recovered to > 95% and TOFR to > 0.9. Results: In the group injected with sugammadex premixed with a high concentration of hydrocortisone, statistically significant intergroup differences were observed in the recovery progression of T1 and TOFR (P < 0.050). Conclusions: When sugammadex was pre-exposed to a high dose of hydrocortisone only, recovery from neuromuscular blockade was delayed. Delayed recovery from neuromuscular blockade is not always plausible when sugammadex is pre-exposed to steroidal drugs.
ABSTRACT
Tables and figures are commonly adopted methods for presenting specific data or statistical analysis results. Figures can be used to display characteristics and distributions of data, allowing for intuitive understanding through visualization and thus making it easier to interpret the statistical results. To maximize the positive aspects of figure presentation and increase the accuracy of the content, in this article, the authors will describe how to choose an appropriate figure type and the necessary components to include. Additionally, this article includes examples of figures that are commonly used in research and their essential components using virtual data.
ABSTRACT
This article introduces a crossover design that is often used in clinical studies, with the advantage of comparing treatment effects within one study subject. In particular, the advantages and disadvantages of the two-period, two-sequence crossover design (2 × 2 or AB/BA crossover design), which is widely used in clinical practice, are identified, and the elements necessary for analysis are introduced. This article explains the carryover effect, period effect, sequence effect, and period-by-treatment interaction in a crossover design and examines the analysis commands of SAS along with example data. After confirming the carryover effect using a general linear model, the treatment effect is analyzed using a linear mixed effect model.
ABSTRACT
General medical journals such as the Korean Journal of Anesthesiology (KJA) receive numerous manuscripts every year. However, reviewers have noticed that the tables presented in various manuscripts have great diversity in their appearance, resulting in difficulties in the review and publication process. It might be due to the lack of clear written instructions regarding reporting of statistical results for authors. Therefore, the present article aims to briefly outline reporting methods for several table types, which are commonly used to present statistical results. We hope this article will serve as a guideline for reviewers as well as for authors, who wish to submit a manuscript to the KJA.
ABSTRACT
This article introduces a crossover design that is often used in clinical studies, with the advantage of comparing treatment effects within one study subject. In particular, the advantages and disadvantages of the two-period, two-sequence crossover design (2 × 2 or AB/BA crossover design), which is widely used in clinical practice, are identified, and the elements necessary for analysis are introduced. This article explains the carryover effect, period effect, sequence effect, and period-by-treatment interaction in a crossover design and examines the analysis commands of SAS along with example data. After confirming the carryover effect using a general linear model, the treatment effect is analyzed using a linear mixed effect model.
ABSTRACT
General medical journals such as the Korean Journal of Anesthesiology (KJA) receive numerous manuscripts every year. However, reviewers have noticed that the tables presented in various manuscripts have great diversity in their appearance, resulting in difficulties in the review and publication process. It might be due to the lack of clear written instructions regarding reporting of statistical results for authors. Therefore, the present article aims to briefly outline reporting methods for several table types, which are commonly used to present statistical results. We hope this article will serve as a guideline for reviewers as well as for authors, who wish to submit a manuscript to the KJA.
ABSTRACT
Background@#In this study, we used an ex-vivo model to investigate the recovery pattern of both the train-of-four (TOF) ratio and first twitch tension of TOF (T1), and determined their relationship during recovery from rocuronium-induced neuromuscular blockade at various concentrations of sugammadex. @*Methods@#Tissue specimens of the phrenic nerve-hemidiaphragm were obtained from 60 adult Sprague-Dawley rats. Each specimen was immersed in an organ bath filled with Krebs buffer solution and stimulated with the TOF pattern using indirect supramaximal stimulation at 20-second intervals. After a 30-minute stabilization period, rocuronium loading and booster doses were serially administered at 10-minute intervals in each sample until > 95% depression of T1 was confirmed. Specimens were randomly allocated to either the control group (washout) or to one of five sugammadex concentration groups (0.75, 1, 2, 4, or 8 times equimolar doses of rocuronium to produce >95% T1 depressions; SGX0.75, SGX1, SGX2, SGX4, and SGX8, respectively). Recovery from neuromuscular blockade was monitored using T1 and the TOF ratio simultaneously until the recovery of T1 to > 95% and the TOF ratio to > 0.9. @*Results@#Statistically significant intergroup differences were observed between the recovery patterns of T1 and the TOF ratio (TOFR, p<0.050), except between SGX2 and SGX4 groups. TOFR/T1 values were maintained at nearly 1 in the control, SGX0.75, and SGX1 groups; however, they were exponentially decayed in the SGX2, SGX4, and SGX8 groups. @*Conclusions@#Recovery of the TOF ratio may be influenced by the sugammadex dose, and a TOF ratio of 1.0 may be achieved before full T1 recovery if administration of sugammadex exceeds that of rocuronium.
ABSTRACT
Properly set sample size is one of the important factors for scientific and persuasive research. The sample size that can guarantee both clinically significant differences and adequate power in the phenomena of interest to the investigator, without causing excessive financial or medical considerations, will always be the object of concern. In this paper, we reviewed the essential factors for sample size calculation. We described the primary endpoints that are the main concern of the study and the basis for calculating sample size, the statistics used to analyze the primary endpoints, type I error and power, the effect size and the rationale. It also included a method of calculating the adjusted sample size considering the dropout rate inevitably occurring during the research. Finally, examples regarding sample size calculation that are appropriately and incorrectly described in the published papers are presented with explanations.
ABSTRACT
Background@#Methods of determining proper endotracheal tube (ETT) cuff pressure to prevent air leakage include the minimal occlusive volume (MOV) technique, which uses auscultation, and the spirometer technique, which directly measures inspiratory and expiratory breathing volumes. Spirometers may measure even small air leakage, therefore, the spirometer technique requires a higher cuff pressure than the MOV technique to completely seal the airway. This study aimed to evaluate the difference in cuff pressure between the two techniques used to seal the airway. @*Methods@#Thirty-five female patients were intubated using an ETT with a cuff, and cuff inflation was performed with both techniques at a 10-min interval in random order—the MOV technique and then the spirometer technique or vice versa. The cuff pressure was measured at each period. @*Results@#The cuff pressures were 16.7 ± 1.2 cm H2O and 18.7 ± 1.3 cm H2O for the MOV and spirometer techniques, respectively. The cuff pressure for the spirometer technique was 2 cm H2O higher than that for the MOV technique and this difference was statistically significant (95% confidence interval, 0.7–3.3; P = 0.003). Considering the upper end (3.3 cm H2O) of the 95% confidence interval and the size of one scale unit (2 cm H2O) of a manometer, the difference in cuff pressure was up to 4 cm H2O in practice. @*Conclusions@#Even though the air leakage sound disappears on auscultation, unlike the previous recommendation, the airway sealing would be completed only by increasing the cuff pressure by approximately 4 cm H2O.
ABSTRACT
As a follow-up to a previous article, this review provides several in-depth concepts regarding a survival analysis. Also, several codes for specific survival analysis are listed to enhance the understanding of such an analysis and to provide an applicable survival analysis method. A proportional hazard assumption is an important concept in survival analysis. Validation of this assumption is crucial for survival analysis. For this purpose, a graphical analysis method and a goodness-of-fit test are introduced along with detailed codes and examples. In the case of a violated proportional hazard assumption, the extended models of a Cox regression are required. Simplified concepts of a stratified Cox proportional hazard model and time-dependent Cox regression are also described. The source code for an actual analysis using an available statistical package with a detailed interpretation of the results can enable the realization of survival analysis with personal data. To enhance the statistical power of survival analysis, an evaluation of the basic assumptions and the interaction between variables and time is important. In doing so, survival analysis can provide reliable scientific results with a high level of confidence.
Subject(s)
Humans , Follow-Up Studies , Methods , Proportional Hazards Models , Statistics as Topic , Survival AnalysisABSTRACT
BACKGROUND: The facilitator effects of steroids on neuromuscular transmission may cause resistance to neuromuscular blocking agents. Additionally, steroids may hinder sugammadex reversal of neuromuscular blockade, but these findings remain controversial. Therefore, we explored the effect of dexamethasone and hydrocortisone on rocuronium-induced neuromuscular blockade and their inhibitory effect on sugammadex. METHODS: We explored the effects of steroids, dexamethasone and hydrocortisone, in vitro using a phrenic nerve-hemidiaphragm rat model. In the first phase, an effective dose of rocuronium was calculated, and in the second phase, following sugammadex administration, the recovery of the train-of-four (TOF) ratio and T1 was evaluated for 30 minutes, and the recovery index was calculated in dexamethasone 0, 0.5, 5, and 50 μg/ml, or hydrocortisone 0, 1, 10, or 100 μg/ml. RESULTS: No significant effect of steroids on the effective dose of rocuronium was observed. The TOF ratios at 30 minutes after sugammadex administration were decreased significantly only at high experimental concentrations of steroids: dexamethasone 50 μg/ml and hydrocortisone 100 μg/ml (P < 0.001 and P = 0.042, respectively). There were no statistical significances in other concentrations. No differences were observed in T1. Recovery index was significantly different only in 100 μg/ml of hydrocortisone (P = 0.03). CONCLUSIONS: Acute exposure to steroids did not resist the neuromuscular blockade caused by rocuronium. And inhibition of sugammadex reversal on rocuronium-induced neuromuscular blockade is unlikely at typical clinical doses of dexamethasone and also hydrocortisone. Conclusively, we can expect proper effects of rocuronium and sugammadex when dexamethasone or hydrocortisone is used during general anesthesia.
Subject(s)
Animals , Rats , Anesthesia, General , Dexamethasone , Hydrocortisone , In Vitro Techniques , Models, Animal , Neuromuscular Blockade , Neuromuscular Blocking Agents , Neuromuscular Monitoring , SteroidsABSTRACT
The Appendix of this article contained an error throughout in which an incorrect symbol was used for the assignment.
ABSTRACT
Randomized controlled trial is widely accepted as the best design for evaluating the efficacy of a new treatment because of the advantages of randomization (random allocation). Randomization eliminates accidental bias, including selection bias, and provides a base for allowing the use of probability theory. Despite its importance, randomization has not been properly understood. This article introduces the different randomization methods with examples: simple randomization; block randomization; adaptive randomization, including minimization; and response-adaptive randomization. Ethics related to randomization are also discussed. The study is helpful in understanding the basic concepts of randomization and how to use R software.
Subject(s)
Bias , Ethics , Probability Theory , Random Allocation , Selection BiasABSTRACT
In a large number of randomized controlled trials, researchers provide P values for demographic data, which are commonly reported in table 1 of the article for the purpose of emphasizing the lack of differences between or among groups. As such, the authors intend to demonstrate that statistically insignificant P values in the demographic data confirm that group randomization was adequately performed. However, statistically insignificant P values do not necessarily reflect successful randomization. It is more important to rigorously establish a plan for statistical analysis during the design and planning stage of the study, and to consider whether any of the variables included in the demographic data could potentially affect the research results. If a researcher rigorously designed and planned a study, and performed it accordingly, the conclusions drawn from the results would not be influenced by P values, regardless of whether they were significant. In contrasts, imbalanced variables could affect the results after variance controlling, even though whole study process are well planned and executed. In this situation, the researcher can provide results with both the initial method and a second stage of analysis including such variables. Otherwise, for brief conclusions, it would be pointless to report P values in a table simply listing baseline data of the participants.
Subject(s)
Bias , Methods , Random AllocationABSTRACT
As a follow-up to a previous article, this review provides several in-depth concepts regarding a survival analysis. Also, several codes for specific survival analysis are listed to enhance the understanding of such an analysis and to provide an applicable survival analysis method. A proportional hazard assumption is an important concept in survival analysis. Validation of this assumption is crucial for survival analysis. For this purpose, a graphical analysis method and a goodness-of-fit test are introduced along with detailed codes and examples. In the case of a violated proportional hazard assumption, the extended models of a Cox regression are required. Simplified concepts of a stratified Cox proportional hazard model and time-dependent Cox regression are also described. The source code for an actual analysis using an available statistical package with a detailed interpretation of the results can enable the realization of survival analysis with personal data. To enhance the statistical power of survival analysis, an evaluation of the basic assumptions and the interaction between variables and time is important. In doing so, survival analysis can provide reliable scientific results with a high level of confidence.
ABSTRACT
Randomized controlled trial is widely accepted as the best design for evaluating the efficacy of a new treatment because of the advantages of randomization (random allocation). Randomization eliminates accidental bias, including selection bias, and provides a base for allowing the use of probability theory. Despite its importance, randomization has not been properly understood. This article introduces the different randomization methods with examples: simple randomization; block randomization; adaptive randomization, including minimization; and response-adaptive randomization. Ethics related to randomization are also discussed. The study is helpful in understanding the basic concepts of randomization and how to use R software.
ABSTRACT
BACKGROUND@#The facilitator effects of steroids on neuromuscular transmission may cause resistance to neuromuscular blocking agents. Additionally, steroids may hinder sugammadex reversal of neuromuscular blockade, but these findings remain controversial. Therefore, we explored the effect of dexamethasone and hydrocortisone on rocuronium-induced neuromuscular blockade and their inhibitory effect on sugammadex.@*METHODS@#We explored the effects of steroids, dexamethasone and hydrocortisone, in vitro using a phrenic nerve-hemidiaphragm rat model. In the first phase, an effective dose of rocuronium was calculated, and in the second phase, following sugammadex administration, the recovery of the train-of-four (TOF) ratio and T1 was evaluated for 30 minutes, and the recovery index was calculated in dexamethasone 0, 0.5, 5, and 50 μg/ml, or hydrocortisone 0, 1, 10, or 100 μg/ml.@*RESULTS@#No significant effect of steroids on the effective dose of rocuronium was observed. The TOF ratios at 30 minutes after sugammadex administration were decreased significantly only at high experimental concentrations of steroids: dexamethasone 50 μg/ml and hydrocortisone 100 μg/ml (P < 0.001 and P = 0.042, respectively). There were no statistical significances in other concentrations. No differences were observed in T1. Recovery index was significantly different only in 100 μg/ml of hydrocortisone (P = 0.03).@*CONCLUSIONS@#Acute exposure to steroids did not resist the neuromuscular blockade caused by rocuronium. And inhibition of sugammadex reversal on rocuronium-induced neuromuscular blockade is unlikely at typical clinical doses of dexamethasone and also hydrocortisone. Conclusively, we can expect proper effects of rocuronium and sugammadex when dexamethasone or hydrocortisone is used during general anesthesia.
ABSTRACT
The Appendix of this article contained an error throughout in which an incorrect symbol was used for the assignment.