The Safety of a New Amide Local Anesthetic - Article Example

 The Safety of a New Amide Local Anesthetic Abstract Using local anesthesia is a common dental daily practice; in addition, effective control of pain during performing a dental procedure is a key to a successful patient management. Malamed et al (2001) looked at the safety of articaine hydrochloride 4% with epinephrine 1:100.000 compared to lidocaine 2% with 1:100.000 epinephrine. They conducted three-single dose, randomized, double-blind, active controlled multicenter studies including 1325 participants, and inferred articaine is safe for dental clinical practice. However, they advised caution with hepatic, cardiovascular patients, and children below 4 years. The work aims at providing a critical review to this article. Introduction Applying existing best evidence to clinical practice has become an essential concept of the medical profession. This mandates critically reading research articles and developing the aptitude to explore research results in an autonomous and unbiased way. Critical reading helps to develop an insight, which promotes transferring best evidence into clinical practice (Shankar and Subish, 2007). A critical article review follows a structured framework that incites questions leading to better assessment of the value of a research paper. The primary aim of this framework is to question each section of the paper to achieve better interpretation of the content (Branson, 2004). This work aims at critically reviewing the article (Articaine hydrochloride: a study of the safety of a new amide local anesthetic) by Malamed et al (2001), following the structured framework described by Branson (2004). Article Summary Malamed et al (2001) designed three-single dose, randomized, double-blind, active controlled multicenter studies aiming to explore the safety and efficacy of articaine hydrochloride 4% (with 1:100000 epinephrine) compared to lidocaine 2% (with 1:100.000 epinephrine. They conducted their study on 1325 patients (882 received articaine, and 443 patients received lidocaine). Their results showed that articaine hydrochloride was both safe and effective as a local anesthetic to use in clinical dentistry setting. Article critical review Article title Research articles’ titles are either descriptive stating the focus of research or decisive stating the authors’ conclusion. In either case, the title should be clear telling the article’s hypothesis and methods. It should also contain enough key words to make search in databases easy (American Psychological Association, APA, 2001, pp. 3-30). The title of this article fulfills these conditions. Authors The authors’ institutional affiliations are relevant to the subject of the paper as it adds to the paper credibility (Dawson, 2002). This article’s authors are eminent dental practitioners and clinical researchers; besides, the senior author has a textbook dealing with local anesthesia (Malamed, 2004). Introduction and research problem statement The purpose of the introduction section is to underline the theoretical framework and the need to study a subject. Therefore a critical reader should spot three constituents, which are a description of the topic, research problem statement, and a review of the background literature. The research problem is the part that attracts the reader’s attention to the scope, impact and the status of the problem studied (Fawcett and Garity 2009). Further, the standard of best evidence attainment compels randomization of patients to evaluate alternative treatments or comparing known treatment strategies to newly developing ones. Apart from ethical issues, getting a balanced state of what is established, and what a new study suggests or the uncertainty level in results links strongly to the quality of study design (Oricha and Yauri, 2003). The authors focused on the history of articaine as a local anesthetic and did not provide a convincing research problem statement. Since the authors did not explain the theory behind the study design selected, which is a point of weakness, filling this gap mandates a discussion on the selected study design. Study design and theoretical framework The need of randomized studies in medical research is to determine the effects of a health care interference (diagnostic or therapeutic) effect when they are not completely obvious from observational studies (Smith, 2003). Randomized controlled studies are studies where patients (participants) are grouped arbitrarily, that are at random to receive one of several interventions. Random distribution reflects that participants’ allocation to one of the study groups by chance alone, which is not determined or influenced by investigators, the clinicians, or the study participants’ choice. The objective of these studies is to measure and compare different effects (outcomes) either present or absent after the participants receive the interventions. Since the outcomes are measured, these studies are quantitative; in addition, because these studies are used to compare intervention, they are comparative in nature (Altman, 2006). It is assumed that random distribution of participants, the participants’ traits are likely to be similar (baseline, or group balancing), although not always achieved, yet randomization in useful to isolate and quantify the study variables (interventions). In addition, it is useful to reduce the effect of individuals’ factors that might influence the outcome (confounding factors) (Kassirer, 2004). Blinding a randomized controlled study Based on the previous discussion, the four limbs of a randomised controlled study are the participants, investigators and data collectors-analysts and those who assess the study outcome (assessors). In double-blinded studies, participants, investigators and assessors are unaware of the intervention throughout the study course (Schulz and Grimes, 2002). Blinding of randomised studies reduces the inconsistency of outcome assessment; besides, conformity and retention of the study’s participants, further, it reduces the bias resulting from added care or treatment (Devereaux et al, 2001). Parallel group studies A parallel group design is the most common design for clinical trials, whereby subjects are allocated to receive one of several treatments (or treatment regimens). All subjects are independently allocated to one of the treatment groups. No subjects receive more than one of the treatments; in addition there is genuine uncertainty as to which of the options is best for the patient. In this design once eligibility was confirmed and consent obtained, randomization immediately followed and treatment starts. Such a trial is termed a two-treatment parallel group design. This is the most common design for comparative clinical trials (Machin et al, 2006). Figure 1 (adapted from Ang et al, 2001) shows a schematic representation of a two-treatment parallel group study. Figure 1: The question of active-controlled studies In a clinical trial, determining the control group remains a controversial question. In a parallel group study design, one group of patients will be subjected to the new treatment and there is a need for a comparison group. In case there is no effective therapy, a pure control or placebo tested group can be selected. In the clinical settings of the article critiqued, there are alternatives to articaine; in addition, a local anesthetic is needed for most, if not all, patients included in the study. Therefore, the authors selected a comparison group receiving an accepted therapy (active control group) and the study is an active-controlled study (Appel, 2006). Critical review of the methods section The methods section of a research article should include adequate description of the research instrument (s) used, how findings are measured and the variables measured. These relate to validity and reliability of results (Hittleman and Simon, 2006). A research instrument is the study tool used for assessment of variables or factors that need measuring; they can be self-administered questionnaires or a battery of psychological tests. Measurement is the assignment of numbers to represent the amount of attribute present (Beck and Dennis, 2003). In their article, Malamed et al (2001) described adequately sample stratification, exclusion criteria, and allocation ratio to receive either articaine or lidocaine. In addition, they described the instruments used for safety evaluation (vital signs, assessment of side effects during the treatment session); besides a telephone follow up survey at 24 hours and seven days after receiving treatment. However, they did not describe the instruments they used to determine efficacy of the anesthetic given. Critical review of the results section Parallel group studies are meant to be descriptive that aim to describe a phenomenon, an effect, or a response of a group (s) of patients. The analysis of data from such studies uses descriptive statistics rather than significance testing or inferential statistics describing design variables that contribute to the design of a study. However, some statistical work would be in place for these studies especially as unpaired comparisons between groups, and one way analysis of variance. One way analysis of variance is a parametric test to detect if the means of two of more different experimental groups are affected by a single factor. It also confirms that samples are drawn from normally distributed populations with equal variance (Day, 2007). The authors adequately described study participants demographic characteristics, drug volume, duration of the dental procedure, and adverse effects reported by patients whether related to the anesthetic used or not. However, they did not provide any results or comments of the efficacy of articaine compared to lidocaine probably because of absent evaluation instruments. Further, they did not provide any statistical analysis of their results. Critiquing the literature review The literature review is that part of research where the authors provide a theoretically framed comprehensive and detailed review of relevant literature to clarify the theoretical framework, and explain the importance of current research. It should provide a comprehensive appreciation of the research problem and a justification of the research questions (Chapin, 2004). It can be located in the introduction section, or under a separate heading. In discussion section it aims at comparing the current study results in agreement or otherwise to other similar studies (Chapin, 2004). Malamed et al (2001) explained the main characteristic of articaine hydrochloride among amide group local anesthetic is it contains a thiophene ring, which increases its lipid solubility. The authors did not explain the significance of this property, Haas and Lennon (1995) explained the higher the lipid solubility, the higher the potency of the local anesthetic and the better the diffusion through injection site. Therefore, increased lipid solubility links to greater ability to cross the lipid membranes of the epineurium of pain sensitive nerves (Haas and Lennon, 1995), a fact confirmed in later studies (Hawkins and Moore, 2002). The authors mentioned the route of excretion of articaine but did not clarify the duration of action, which is reported by the same authors in a previous study (Malamed et al, 2000) to have a mean value of 68.2 minutes with a standard deviation of 8.3 minutes. In the lights of this information, the authors did not explain what the procedure in patients was where the dental therapeutic intervention lasted for more than one hour. Recent studies however, showed longer mean duration of action of articaine up to 168.2 minutes (Rebolledo et al, 2007). In the discussion section, the authors compared their results to those of Haas and Lennon (1995), and Hidding and Khoury (1991) (after Malamed et al, 2001). However, they overlooked earlier studies that showed articaine as safe, but with no significant difference in efficacy, as lidocaine (Vahatalo, et al, 1993, Cowan, 1977, Ruprecht et al, 1991, all after Rebolledo et al, 2007). Strengths and weaknesses The main strengths of this study are selecting a research design that suites the descriptive nature of results and the large sample size and participants diversity in age, demographic characteristics and clinical status. However, the authors to produce any objective evidence of articaine efficacy as local anesthetic as they mentioned in the abstract and the introduction section. No statistical analysis done to provide objectivity to their safety results. In addition they provided an inconsistent literature review. Further, the authors did not correlate the participants’ demographics (ethnicity, age, gender, and weight) to the safety response or drug volume needed; neither did they correlate patients’ variables (procedure duration, and clinical setting) to adverse events or drug dose needed to produce effect. Conclusion Malamed et al (2001) provided a descriptive study on the safety of articaine hydrochloride 4% as a dental local anesthetic compared to lidocaine hydrochloride 2% both with epinephrine 1:100.000. The authors inferred the drug was well tolerated in the majority of patients, and is safe to use in dental clinical practice. However, using articaine is not recommended in patients with liver disease, significant cardiac functions impairment, and children below 4 years. References Altman, D.G (2006). Practical Statistics for Medical Research. 2nd. London: Chapman & Hall American Psychological Association (2001). Publication manual of the American Psychological Association (fourth edition). Washington, DC: American Psychological Association (APA). Ang, E.S, Lee, S-T, Gan, CS-G, et al (2001). 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Medical journals and pharmaceutical companies: uneasy bedfellows. BMJ, 326, 1202-1205. Read More