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The Knowledge of Eye Physicians on Local Anesthetic Toxicity and Intravenous Lipid Treatment: Questionnaire Study.

Introduction

Local anesthetics enable surgical procedures to be performed without requiring general anesthesia, but can result in a number of complications related both to the patient being awake and to administration errors. One of these complications is local anesthesia toxicity syndrome (LATS). Although rare, it can result in death if not treated early. LATS in the central nervous system (CNS) may initially manifest with non-specific findings such as a metallic taste in the mouth, perioral numbness, tinnitus, general malaise, slurred speech, and diplopia. However, these early signs are not always present; symptoms may begin with CNS excitation (agitation, confusion, convulsions) and progress if not treated to findings of depression (mental depression, coma, apnea). Cardiovascular system (CVS) findings may occur simultaneously with CNS signs or appear later, and can include hyperdynamic findings such as hypertension and tachyarrhythmia as well as signs of cardiac depression such as hypotension, bradyarrhythmia, conduction block, and asystole. (1)

The first guideline to facilitate the early recognition and treatment of LATS was published by the Association of Anaesthetists of Great Britain and Ireland in 2007 and was revised in 2010. (2) The common theme emphasized both in this guideline and later by the American Regional Anesthesia Society in 2010 and 2012 and the American Academy of Clinical Toxicologists in 2015 is the use of 20% intravenous lipid emulsion (IVLE) in combination with supportive therapy for the treatment of LATS. (3,4,5) In particular, it is known that cardiac arrest in LATS is resistant to standard resuscitation methods, and that IVLE therapy is critical as an initial therapy. (6) Although the mechanism of action is not fully known, lipids have been shown to exert a scavenging effect by binding local anesthetics in the circulation, and a direct inotropic effect by improving mitochondrial function of cardiac cells and increasing calcium uptake. (1) They have also been shown to provide significant symptomatic improvement in patients at various LATS stages with and without cardiac arrest. (7,8,9)

The majority of ophthalmic procedures (e.g., eyelid, cataract, strabismus, keratoplasty, and vitreoretinal surgeries) are performed under local anesthesia. (10) LATS can be recognized early and controlled in most cases with proper operating room monitorization and support from an anesthesia team. However, the true problem lies in the fact that most of these procedures are conducted in local operating rooms remote from well-equipped surgical theaters, without adequate monitoring or anesthesiologists in attendance. Therefore, it is important for ophthalmologists who frequently use local anesthesia to be aware of the early and late symptoms of LATS and to implement appropriate treatment options promptly when necessary.

In our literature review, we found studies applying similar surveys in all branches using local anesthetics, but there were no studies conducted exclusively among ophthalmologists. Considering the widespread use of local anesthesia in ophthalmology practice, the aim of this study was to increase awareness of this issue by evaluating the knowledge of ophthalmologists at all stages of training regarding local anesthetic toxicity and intravenous lipid emulsion used in its treatment.

Materials and Methods

The study was approved by the Sutcu Imam University Faculty of Medicine Clinical Research Ethics Committee (2017/02-02). The purpose and nature of the study were explained to all physicians and verbal consent was obtained from all participants prior to the study. A total of 104 ophthalmologists employed in different positions at different hospitals were asked to respond to a questionnaire consisting of 14 items concerning demographic information, their local anesthetic use, toxicity, and treatment methods. The questionnaire was applied in person when possible; otherwise, responses were collected by telephone or e-mail. The questionnaire was adapted from questions used in previous studies by Basaranoglu et al. (11) and Karasu et al. (12)

Statistical Analysis

Statistical analyses were done using IBM SPSS for Windows, version 22.0 (IBM Corporation, Armonk, New York, USA). Numerical variables are expressed as mean [+ or -] standard deviation, categorical variables as number and percentage. P<0.05 was accepted as the level of significance.

Results

A total of 104 ophthalmologists participated in the survey and all provided appropriate responses to all of the questions. The mean age of the participants was 35.71[+ or -]6.53 years; 25% were residents, 67.3% were specialists, and 7.7% were academic faculty members (Figure 1). There were more participants from state hospitals (65.4%) than from university and private hospitals. In terms of professional experience, participants practicing ophthalmology for 10 or more years comprised the largest subgroup, with 34.6%. Seventy-six percent of the participants used local anesthetics every day or more than twice a week, though 56.7% of them stated that they had not received any training in the use of local anesthetics during their education. There were no statistically significant differences in education received about local anesthetics based on the participants' education level or years of experience in ophthalmology (p = 0.419). Bupivacaine was the most preferred local anesthetic among the physicians (61%). Despite the known cardiotoxic effects of bupivacaine, 97.1% of the participants reported not using a test dose prior to local anesthetic administration. The demographic data and information regarding local anesthetic use of the surveyed physicians are shown in Table 1.
Fiure 1. Education level of the surveyed ophthalmologists

Academic Faculty:           7.7%
Specialist:                67.3%
Resident:                  25%

Note: Table made from pie chart.


The participants' responses concerning local anesthetic toxicity and its treatment are given in Table 2. Of all the participants, 62.5% had never encountered local anesthetic toxicity. Allergy (76%) and hypotension (68.3%) were associated with early findings of toxicity, while cardiac arrest (57.4%) and hepatotoxicity (56.4%) were given as late findings. When asked how toxicity could be prevented, 72.4% said monitorization and 58.2% said by administering appropriate doses. Regarding what treatment is necessary in the event of toxicity, 72.4% of the participants said symptomatic therapy, and 58.8% said cardiopulmonary resuscitation and antihistaminics. Sixty-five percent of the participants had never heard of 20% IVLE therapy in toxicity; 3.9% stated that they knew this treatment was used in toxicity, but only 0.96% of the participants reported previously using 20% IVLE in the treatment of toxicity.

Discussion

This survey study demonstrated that there is some general knowledge about local anesthesia and LATS among ophthalmologists. However, despite the frequent use of local anesthetic agents in this branch of medicine, the education practitioners receive about this topic is insufficient. In particular, our results indicate that the majority of ophthalmologists are also not adequately informed about the use of lipid emulsions, which have been shown to effectively treat toxicity and are advised to have on hand wherever local anesthesia is practiced.

The ability to perform most ocular surgeries under local anesthesia is a great advantage in terms of avoiding complications associated with general anesthesia in this patient group, who are usually older adults with comorbid conditions. Despite the recent development of topical eye drop anesthesia to reduce complication rates, most ophthalmologists prefer injection anesthesia because it provides faster and stronger anesthesia as well as a more comfortable surgery due to akinesia. (10) Despite all of these advantages, injection anesthesia methods such as peribulbar anesthesia, sub-Tenon's block, and especially retrobulbar anesthesia can also lead to several complications. (13,14,15) Allergic reactions to the local anesthetic agents, hypoglycemia, stroke, oculocardiac reflex, and the potentially fatal LATS are among these complications. (14) Although LATS occurs rarely, it may lead to fatal outcomes if early intervention is not provided due to lack of awareness or the appropriate therapy cannot be given. (1) The high preference for local anesthesia makes it imperative that ophthalmologists receive continuing education concerning local anesthetics and LATS. Although 76% of the participants reported using local anesthetics every day or more than twice a week, 56.7% had not received any training in the use of local anesthetics during their education.

The characteristics of the local anesthetic agent used are also important in the development of LATS. Because ophthalmic anesthesia is generally applied in small amounts, toxic overdose is very rare and the characteristics of the local anesthetic agent are more relevant. Bupivacaine is an agent with serious cardiotoxic potential and patients who go into cardiac arrest due to bupivacaine-induced LATS are known to be resistant to resuscitation. (1) Our questionnaire revealed that bupivacaine was most preferred by the participants, likely due to its longer duration of action compared to other agents, but hardly any of the physicians used test doses. Due to the lack of adequate training on local anesthetics, the cardiotoxic effects of bupivacaine were not well known, suggesting that its long-acting nature was the sole reason for its popularity.

Besides the characteristics of the local anesthetic used, two main mechanisms related to the means of administration have been implicated in the development of LATS in ocular surgeries. The first mechanism is that the drug is accidentally injected into the ophthalmic artery, resulting in retrograde spread to the internal carotid artery and then the brain. In the second mechanism, the dural sheath surrounding the optic nerve is accidentally punctured, resulting in spread of the drug to the brain via the subdural and subarachnoid space. These can occur due to not performing aspiration prior to intraarterial injections, and using a long needle or not ensuring the eye is in neutral position for intrameningeal injections. Therefore, in addition to appropriate monitoring, is it recommended that aspiration be done before every injection, that the eye be in neutral position during injection, that shorter needles be used, and that methods such as ultrasound be used to help determine the injection site when applying local anesthesia. (16) Regarding how to prevent LATS, the participants in our study gave more priority to monitorization and use of appropriate doses of local anesthetics rather than methods such as aspiration test and intermittent injection which indicate improper intra-arterial injection technique.

Our results indicated that a majority (62.5%) of the participants had never encountered LATS; they most commonly listed allergies and hypotension as early signs and cardiac arrest and hepatotoxicity as late signs. Although the findings of LATS are generally classified as early and late findings, the clinical presentation may not always follow this order. In most cases, CNS involvement first appears with nonspecific findings such as a metallic taste in the mouth, perioral numbness, tinnitus, lightheadedness, and slurred speech; however, it may manifest with convulsions and progress to coma and respiratory depression. CVS manifestations can exhibit a wide spectrum at every stage, ranging from signs of stimulation (hypertension, tachyarrhythmia) to depression (hypotension, bradyarrhythmia, cardiac arrest). (1) In ophthalmic anesthesia, more importance is given to onset time and the mechanisms by which toxicity occurs, rather than to the sequence of LATS findings. In particular, apnea or cardiac manifestations occur within seconds with intraarterial injections, while these findings appear more slowly with intrameningeal spread, over the course of minutes. (16) A large study of retrobulbar block including 6,000 patients showed that symptoms appeared after 2-40 min (mean 8 min) due to probable meningeal spread of local anesthetic to the CNS. (13) In contrast, Dettoraki et al. (17) reported a case receiving retrobulbar block for vitrectomy in which convulsions and contralateral hemiparesis occurred immediately after local anesthetic was administered due to intraarterial injection.

In addition to closely following patients receiving local anesthesia with appropriate monitoring and intravenous catheterization, guidelines released in recent years have emphasized the importance of airway control, 100% O2 ventilation, anticonvulsive therapy, and the use of 20% IVLE with resuscitation in case of cardiac arrest in patients who develop LATS. (2,4) When toxicity is suspected, it is recommended to initiate 20% IVLE with a bolus dose of 1.5 mL/kg and continue with infusion at 15 mL/kg/hr. If symptoms do not improve, two additional bolus doses can be administered and therapy continued to a maximum dose of 10 mL/kg. (1) Our literature search yielded no studies concerning intralipid therapy for patients with LATS associated with ophthalmic anesthesia, but rapid improvement of LATS symptoms has been demonstrated with 20% IVLE therapy in other surgical settings, both in patients with and without cardiac arrest. (7) In a study conducted by Basaranoglu et al. (11) among physicians who frequently use local anesthesia, it was found that 65.7% of physicians in all branches had never heard of this treatment in relation to LATS and 21.4% said they could not recall, whereas 70.4% of anesthetists were aware of lipid therapy. Similarly, a survey of residents from all branches conducted by Karasu et al. (12) revealed that 67.4% of the participants had never heard of this treatment. In addition, despite a high rate of training among anesthesiology residents (76.9%), some of the other clinical residents reported having had no training on this subject. This high rate among anesthesiologists may be attributable to the frequent use of peripheral and central blocks. Nevertheless, a study conducted among anesthetists in Denmark showed that although 65% were aware of the use of lipid therapy to treat LATS, only 8 (24%) anesthetists knew the treatment protocol and only 1 (3%) of the anesthetists had ever witnessed the use of lipid in the clinic. (18) In the present study, 20% IVLE therapy was generally unrecognized by ophthalmologists as a treatment for LATS. This may be explained by the fact that they had never heard of this treatment or, even if they had, were not adequately trained in this subject, or by the low frequency of LATS encounters.

Study Limitations

In this survey, we collected responses to the prepared questionnaire via face-to-face interviews with the ophthalmologists we were able to reach and via phone and e-mail for the others. Although we contacted as many physicians as we could within a certain time, the participation rate was not very high. For this reason, we think that conducting such surveys through established associations in the relevant field would yield higher participation rates.

Conclusion

LATS is rare but can be fatal if intervention is delayed. The inclusion of this subject in the compulsory curriculum would significantly increase awareness in ophthalmology practices, where local anesthesia is frequently used. In particular, the importance of 20% IVLE therapy in LATS treatment and the need for 20% lipid emulsion to be available to ophthalmologists wherever they apply local anesthesia should be emphasized.

Ethics

Ethics Committee Approval: Kahramanmaras Sutcu Imam University Faculty of Medicine Clinical Research Ethics Committee (2017/02-02).

Peer-review: Externally peer-reviewed.

Authorship Contributions

Concept: Aykut Urfalioglu, Selma Urfalioglu, Gozen Oksuz, Design: Aykut Urfalioglu, Selma Urfalioglu, Gozen Oksuz, Data Collection or Processing: Aykut Urfalioglu, Selma Urfalioglu, Analysis or Interpretation: Aykut Urfalioglu, Selma Urfalioglu, Gozen Oksuz, Literature Search: Aykut Urfalioglu, Selma Urfalioglu, Gozen Oksuz, Writing: Aykut Urfalioglu.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

References

(1.) El-Boghdadly K, Chin KJ. Local anesthetic systemic toxicity: Continuing Professional development. Can J Anesth. 2016;63:330-349.

(2.) The Association of Anaesthetist of Great Britain and Ireland. AAGBI Safety Guideline: Management of Severe Local Anaesthetic Toxicity 2010; Available from URL: http://www.aagbi.org/sites/default/files/la_toxicity_2010_pdf.

(3.) Neal JM, Bernards CM, Butterworth JF, Di Gregorio G, Drasner K, Hejtmanek MR, Mulroy MF, Rosenquist RW, Weinberg GL. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010;35:152-161.

(4.) Neal JM, Mulroy MF, Weinberg GL; American Society of Regional Anesthesia and Pain Medicine. American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic toxicity: 2012 version. Reg Anesth Pain Med. 2012;37:16-18.

(5.) Gosselin S, Morris M, Miller-Nesbitt A, Hoffman RS, Hayes BD, Turgeon AF, Gilfix BM, Grunbaum AM, Bania TC, Thomas SH, Morais JA, Graudins A, Bailey B, Megarbane B, Calello DP, Levine M, Stellpflug SJ, Hoegberg LC, Chuang R, Stork C, Bhalla A, Rollins CJ, Lavergne V; AACT Lipid Emulsion Therapy workgroup. Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol (Phila). 2015;53:557-564.

(6.) Ciechanowicz SJ, Patil VK; Association of Anaesthetists of Great Britain and Ireland. Intravenous lipid emulsion-rescued at LAST. Br Dent J. 2012;212:237-241.

(7.) Fettiplace MR, Weinberg G. Past, Present, and Future of Lipid Resuscitation Therapy. JPEN J Parenter Enteral Nutr. 2015;39(1 Suppl):72-83.

(8.) Rosenblatt MA, Abel M, Fischer GW Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105:217-218.

(9.) Suzer MA, Ozhan MO, Eskin MB, Atik B, Caparlar C. Lipid infuzyonu kullanilarak basariyla tedavi edilen bir lokal anestezik toksisitesi. J Turk Anaest Int Care. 2011;39:159-163.

(10.) Yasar T, Caglar C. Local injection anesthesias in ophthalmic surgery Review. Turk J Ophthalmol. 2009;39:496-505.

(11.) Basaranoglu G, Teker MG, Saidoglu L, Muhammedoglu N, Ozdemir H. Lokal anestezik kullanan hekimlerin toksisite ve intralipid tedavisi hakkinda bilgileri. J Turk Anaest Int Care. 2010;38:262267.

(12.) Karasu D, Yilmaz C, Ozgunay SE, Dayioglu M, Baytar C, Korfali G. Knowledge of the research assistants regarding local anaesthetics and toxicity. Turk J Anaesthesiol Reanim. 2016;44:201-205.

(13.) Nicoll JM, Acharya PA, Ahlen K, Baguneid S, Edge KR. Central nervous system complications after 6000 retrobulbar blocks. Anesth Analg. 1987;66:1298-1302.

(14.) Bensghir M, Badou N, Houba A, Balkhi H, Haimeur C, Azendour H. Convulsions during cataract surgery under peribulbar anesthesia: a case report. J Med Case Rep. 2014;8:218.

(15.) Quantock CL, Goswami T. Death potentially secondary to sub-Tenon's block. Anaesthesia. 2007;62:175-177.

(16.) Carneiro HM, Oliviera B, Avila MP, Alves Neto O. Brainstem anesthesia after extraconal retrobulbar block. Can it be avoided? Case Report. Rev Bras Anestesiol. 2007;57:391-400.

(17.) Dettoraki M, Dimitropoulou C, Nomikarios N, Moschos MM, Brouzas D. Generalized seizures and transient contralateral hemiparesis following retrobulbar anesthesia: a case report. BMC Anesthesiol. 2015;15:108.

(18.) Jensen-Gadegaard P, Skjcentsnnemand M, Damgaard-Jensen J, Gottschau B. Limited knowledge of lipid rescue therapy in local anaesthetic systemic toxicity. Dan Med Bul. 2011;58:4226.

Aykut Urfalioglu (*), Selma Urfalioglu (**), Gozen Oksuz (*)

(*) Sutgu Imam University Faculty of Medicine, Department of Anesthesiology and Reanimation, Kahramanmaras, Turkey

(**) Necip Fazil State Hospital, Opthalmology Clinic, Kahramanmaras, Turkey

Address for Correspondence: Aykut Urfalioglu MD, Sut[xi]u Imam University Faculty of Medicine, Department of Anesthesiology and Reanimation, Kahramanmaras, Turkey

Phone: +90 344 216 23 13 E-mail: aykutmd1903@gmail.com ORC[PI]MD: orcid.org/0000-0002-0657-7578

Received: 08.03.2017 Accepted: 19.04.2017

DOI: 10.4274/tjo.79446
Table 1. Demographic data of the survey participants and their
responses regarding local anesthetic use

                                            Mean [+ or -] Standard
                                            deviation or %

Age (years)                                       35.71[+ or -]6.53
Place of employment
State hospital                                    65.4
University hospital                               22.1
Private hospital                                  12.5
Professional experience (years)
0-2                                               17.3
2-4                                               19.2
4-6                                               12.5
6-10                                              16.3
10>                                               34.6
Most preferred local anesthetic
Bupivacaine                                       61
Lidocaine                                         28
Prilocaine                                        11
Frequency of local anesthetic use
Every day                                         40.4
>Twice/week                                       35.6
Once a week                                       17.3
Once a month                                       3.8
3-4 times a year                                   2.9
Use test dose?
Yes                                                2.9
No                                                97.1
Received training on local anesthetics?
Yes                                               28.8
No                                                56.7
Cannot recall                                     14.4

Table 2. The participants' responses concerning local anesthetic
toxicity and its treatment

                                                                  %

Have you ever encountered local anesthetic toxicity?
Yes                                                              29.9
No                                                               62.5
I am not aware of it                                              7.7
I cannot recall                                                   2.9
What are the early signs of toxicity?
Allergy                                                          76
Hypotension                                                      68.3
Anaphylaxis                                                      56.7
Arrhythmia                                                       52.9
Metallic taste in mouth                                          28.8
Tinnitus                                                         19.2
Other                                                             1.9
What are the late signs of toxicity?
Cardiac arrest                                                   57.4
Hepatotoxicity                                                   56.4
Loss of consciousness                                            45.5
Ischemia                                                         26.7
Infection                                                         9.9
Other                                                             4
How is toxicity treated?
Symptomatic                                                      74.5
Cardiopulmonary resuscitation                                    58.8
Antihistaminic                                                   58.8
Methylene blue                                                   13.7
20% lipid emulsion                                               12.7
What precautions do you take to prevent toxicity?
Monitorization                                                  272.49
Using appropriate doses                                          58.2
Test dose with adrenaline                                        18.4
Test dose with adrenaline                                         7.3
Aspiration                                                        6.1
What do you know about the use of lipids
in the treatment of toxicity?
Never heard of it                                                65
I've heard of it, but I can't recall                             31.1
I've read a scientific article on this subject                    2.9
I know when and how it is used                                    2.1
Have you ever used lipid therapy to treat toxicity?
I have never encountered toxicity                                82.7
I used a different treatment when faced with                     16.3
toxicity
I have used lipid therapy to treat toxicity                       0.96
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Title Annotation:Original Article
Author:Urfalioglu, Aykut; Urfalioglu, Selma; Oksuz, Gozen
Publication:Turkish Journal of Ophthalmology
Article Type:Report
Date:Nov 1, 2017
Words:3444
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