key: cord-0254554-o73474jj authors: Munasinghe, B. M.; Arambepola, A.; Subramaniam, N.; Srisothinathan, N.; Gunathilake, K. U. I. S.; Arachchi, R. D. N.; Karunathilake, S. K.; Jayamanne, B. D. W. title: Study of knowledge and practices of local anaesthetic systemic toxicity among Doctors in Sri Lanka date: 2021-04-20 journal: nan DOI: 10.1101/2021.04.19.21255661 sha: 9a00b91d555e1d31c9efea4fb1734b560089bc3d doc_id: 254554 cord_uid: o73474jj Background Local anaesthetic systemic toxicity (LAST) could be potentially life threatening. This study focused on describing the knowledge and practices of use of local anaesthetics (LA) among the doctors in Sri Lanka and the ability to detect and manage an event of LAST. Materials and methods A descriptive cross-sectional study was conducted among doctors in Sri Lanka using an online self-administered questionnaire based on AAGBI guidelines (2010). Descriptive statistics were analyzed by cross-tabulations and presented as numbers and percentages using IBM-SPSS 25. Results The response rate was 60% out of 600. Majority were males (58%) while 45% of the respondents were anesthetists. Ultrasound was used by 47.4% during LA. The majority considered total body weight for dose calculations. Around 50% of respondents identified bupivacaine as the most cardiotoxic. The majority utilized some form of monitoring and were knowledgeable on identification, prevention and initial management of LAST. Approximately 45% identified Intralipid (ILE) as the definitive treatment of LAST, out of which, 66.8% knew the correct dose and 77.2% and 26.5%, the availability and location of storage, respectively. Conclusion The basic knowledge on LAST was satisfactory among the respondents. A statistically significant difference on knowledge on maximum safe doses of LA, ILE in established LAST, its dosage and the availability was identified between anaesthetic and non-anaesthetic doctors and post graduate trainees and the rest of the doctors. Overall, significant lapses were noted with regard to the use of total body weight for dose calculations, use of ultrasound during LA administration and dosage, availability and storage of the definitive therapy, ILE, suggesting updates in these key areas. Local anaesthetic systemic toxicity (LAST) is rare, underdiagnosed and underreported [1] , but could result in serious morbidity and mortality [2] . Existing literature emphasizes the importance of knowledge on LAST [3] . Knowledge and practices in recognizing, preventing and treating LAST is essential in minimizing and ultimately managing an event of LAST. We reviewed the literature on factors contributing to LAST and management protocols and studied the knowledge and practices among the doctors in our study population regarding identifying, preventing and managing LAST. The study was conducted as a descriptive cross-sectional study among middle and intermediate-grade doctors in Sri Lanka. Considering 20,000 practicing doctors' population were eligible for our study [4] and level of awareness on LAST in a regional study among doctors [5] being around 30% (outcome factor of 30% selected), at 7.5% confidence limit and 95% confidence interval with a design effect (2.0) for cluster sampling, a sample size of 285 was calculated. Following attrition for 20% for non-responders, the minimum sample size required was 342. A self-administered questionnaire(SAQ) was prepared following review of literature and the Association of Anaesthetists of Great Britain and Ireland (AAGBI) guideline . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 20, 2021. ; https://doi.org/10.1101/2021.04. 19 .21255661 doi: medRxiv preprint on LAST (2010). Face and content validity and appropriateness to culture were assessed and certified by an expert panel. A single-stage cluster sampling method was utilized. Hospitals were chosen randomly. Following establishing remote verified individual communications (via email or social media (WhatsApp/Viber/ Facebook) the questionnaire was distributed. The questionnaire was accessible to the participants only after the consent. The responses were stored in password-protected online cloud. The analysis of data was done with IBM SPSS (version 25) by applying relevant statistical tests accordingly. P < 0.05 was considered as statistically significant. Ethical approval was obtained from the Ethical review committee of the Sri Lanka Medical Association. (ERC/20/023) Out of 600 participants, 360 responded (response rate -60%) where 58.3 % were males (210). Median age was 32 years (Q1=29.7, Q3=34.4, IQR=4.7). Majority of respondents were experienced as doctors for 2 to 5 years ( is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 20, 2021 Practices of use of three local anaesthetic agents (LA) The frequency and route of usage of the three LA; lignocaine, bupivacaine and prilocaine were studied. Plain Lignocaine was the most commonly used and Prilocaine was the least commonly used. (Table 03) . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 20, 2021 is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 20, 2021. With regard to monitoring during LA, the preferred mode was found to be the pulse oximetry. This was utilized by 234 (65%, 95% CI 59.9-70). Out of the participants, 33.3% (120) (95% CI 28.3-38.3), were utilizing all (Pulse oximetry, ECG, Non-invasive blood pressure). Around 14.2% (51) used at least pulseoximetry while 6.1% (22) opted for non-invasive blood pressure monitoring and 3.3% (12) ECG only. Table 5 ). . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 20, 2021. Local anaesthetic agents are used frequently in most subspecialties of medicine [6] . The growing interest in regional nerve blocks, enhanced recovery after surgery (ERAS) protocols and multimodal analgesic regimens, have led to an increase in the usage of LA [7] . Global increase in aging population may further increase the potential of LAST in the future [8] . The incidence of LAST is about 0.87 per 1000 peripheral nerve blocks [9] Epidural blocks are commonly associated with LAST, followed by axillary and interscalene blocks [10] . Most cases reported are related to bupivacaine, attributed to its increased cardiotoxicity. Serious LAST can be as common as epidural haematomas and peripheral nerve injury [11] . LAST could occur after continuous infusions as well as single injections of LA [1] Interestingly, a case series revealed that around 20% cases of LAST has been occurring outside the conventional hospital setting where 50% involved were non-anaesthetists and 20% of events were following simple infiltration [11] . About 60% of LAST presents with a typical picture comprising of central neurological (CNS) and cardiovascular (CVS) symptoms. Seizures, agitation and loss of consciousness are common CNS symptoms . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255661 doi: medRxiv preprint while dysarthria, perioral numbness, confusion, obtundation and dizziness are rare. CNS symptoms typically precede CVS symptoms [10] which include both tachy and bradyarrhythmias resulting in reduced cardiac output [12] . This results in a vicious cycle of reduced coronary perfusion which can ultimately result in cardiac arrest [8] . However, 40% of patients can present atypically where symptoms can either delay or CVS symptoms can occur without CNS manifestations [11] . Our study demonstrated that, out of the basic monitoring of ECG, non-invasive blood pressure and peripheral oxygen saturation, around one-quarter (24%) did not establish any monitoring during LA administration and one-third (33.3%) were opting for all three parameters. Monitoring electrocardiography (ECG), pulse oximetry and blood pressure are important in detecting LAST early [3] . Further, monitoring should be continued for some time for recurrent [1] and late-onset toxicity, especially in cases of continuous infusions [13] . The pulse oximetry was preferred in this study by many probably due to the ease of use. The study revealed a higher percentage (25%) of participants stating giving a test dose. In contrast, a recent cross-sectional study among emergency physicians in Turkey [14] , demonstrated a relatively lesser proportion (5%) during their analysis. A different study conducted among the ophthalmologists in Turkey revealed that around 97.1% of the participants were not using a test dose [15] . Some authors suggest the use of a test dose particularly during nerve blockade whenever critical LA volumes are used or for normal volumes in patients with co-morbidities, in view of minimizing LAST [16] . Safe dose of LA is dependent on multiple factors including the agent, the type of block, age of the patient, body weight, comorbidities and physiological variations such as pregnancy [3, 8, 13, 17] . Though there is no clear evidence of exact safe doses of the different agents, maximum safe doses found in literature [18] are shown in Table 6 . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 20, 2021 [13] , while lean body weight is preferred by others [19] . Total body weight can overestimate total dose in obese and pregnant patients, therefore ideal or lean body weight is more appropriate [13] . Among our respondents, only about 27% were using ideal or lean body weight, with no significant association with experience, PG training and between anaesthetists and non-anaesthetists. The proportion, who considered comorbidities, were also just under 50%. The patients with liver, renal, cardiac and central nervous system diseases are at a higher risk of LAST thus doses should be titrated accordingly [11] . The respondents of this study were commonly using lignocaine and bupivacaine for subcutaneous infiltration and regional blocks. Prilocaine was the least used LA. Considering the ubiquitous use of rest of LA, a significant lapse of knowledge was noteworthy with regard to maximum safe doses. The relatively infrequent use and unavailability (specially the parenteral preparations) of prilocaine in Sri Lanka probably explain the significantly less (around 10%) knowledge on its safe dose. Just under half . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255661 doi: medRxiv preprint identified bupivacaine as the most cardiotoxic. Seven respondents (Paediatrics) considered intravenous use of bupivacaine which could be catastrophic and should be avoided at all times. Airway management, oxygenation, ventilation and control of seizures are essential components of supportive management in established LAST [3, 8] . Intravenous 20% lipid emulsion (ILE) given as a 1.5ml/kg bolus, followed by an infusion of 15ml/kg/hr is used as specific management. The patient is reassessed at 5-minute intervals and bolus dose is repeated up to 3 times and the infusion rate doubled if toxic features are not resolved [20] . ILE cannot be substituted by propofol [3] . ILE and management protocols should be kept readily available in facilities where local anaesthesia is practiced [1, 8] . On steps to minimize LAST, vital parameter monitoring, aspiration before injection and use of ultrasound were considered by most. Addition of adrenaline to LA was the least preferred. The physiological response to adrenaline (increments of heart rate by around 10 beats/min and blood pressure by 10-15mmHg) [21] could be an important marker of intravascular injection, particularly as there is a false negative rate of around 2%. [11] Tachycardia and hypertension, generally considered as cardiovascular prodromal signs were chosen by less number of respondents. Given that the typical pattern of toxicity with preceding neurological features may not be seen among 40% and as the patients could present with cardiovascular collapse [10] , the detection of the former could be decisive. With respect to neurological prodromal symptoms, metallic taste, visual or auditory disturbances were considered by relatively less number of respondents (60%). Overall, a comparative lack of knowledge on the prodromal features of LAST was evident. Safe administration of LA guided by ultrasonography will further prevent or minimize LAST. Even though, the majority in our study considered ultrasound in minimizing LAST, its practical use was far less. This could be explained by the preference, access to ultrasound and routes of LA administered. For instance, nearly 90% who utilized ultrasound 'Always' or 'Frequently' were anaesthetists, who perform more regional nerve blocks and access to ultrasound is greater. Use of ultrasound during administration of LA is known to reduce LAST [1] , with evidence of 65% reduction compared to nerve stimulation alone [9] . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 20, 2021 The basic management of an established LAST was known by a significantly high number of respondents with majority opting for intravenous fluids and Oxygen. The relatively less proportion (60%) recognized prolonged cardiopulmonary resuscitation (when indicated) where only 13.5% recognized cardiopulmonary bypass as a treatment option. Being an advanced therapy and mostly encountered and taught in the academic scope of postgraduate trainees are most probable reasons for this observation. The most important aspect of LAST, the definitive therapy with the use of ILE was relatively less known. Some respondents chose propofol but it should be remembered that ILE is not to be substituted by propofol due to relatively low lipid content, potential cardiovascular compromise and the need of larger volumes [22] . Moreover, the knowledge on the correct dose, availability and the location of storage followed the same pattern. Numerous surveys assessing ILE therapy are found in the literature. A study by Edwards et al at demonstrated an overall deficit in knowledge on LAST (including ILE therapy) in a Maternity unit in a UK Hospital. However, teaching programmes led to a significant improvement in knowledge [23] . A Danish study in 2011, conducted among anaesthetists, revealed that around 50% knew about lipid therapy but were not aware how to acquire ILE and that it was not available at places where LA was administered [24] . In a cross-sectional study in Turkey, 42% of the Emergency physicians, correctly identified ILE dosage [14] . A prospective study among junior surgeons and anaesthetists in the UK suggested a significantly lack of knowledge on ILE among the former group (7.3% vs 100%) [25] . The AAGBI, American Society of Regional Anaesthesia and Pain Medicine and American Heart Association [26] , all have endorsed the use of ILE during established LAST. In this modern era of mobile applications and widespread availability of the internet, dosages of most of the drugs could be easily acquired and the dose of ILE in particular, is available in flow charts in most tertiary care centers. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255661 doi: medRxiv preprint Nonetheless, LAST being an emergency where minutes count, quick access to ILE will undoubtedly be decisive. The subgroup analysis in this study revealed significant statistical differences in knowledge on maximum safe doses of LA, cardiotoxicity of bupivacaine, prodromal cardiovascular features of LAST and addition of adrenaline and performance of a test dose between postgraduate trainees vs non-postgraduate doctors, Anesthetic vs non-anaesthetic doctors and experienced (>10 years) vs less experienced doctors. With regard to the ILE therapy, the correct drug, dosage, availability and location of storage was known with significant statistical significance by anaesthetists and post graduate trainees. The familiarity, increased frequency of LA use, ILE mainly stored in operating theatres and continuous medical education on this aspect among these categories could possibly explain this observation. The response rate was relatively low for the study. Out of the respondents, almost 50% were anaesthetists. The other subspecialties where LA use is common, in higher concentrations and volumes, such as general surgery, Ophthalmology, Gynaecology and Obstetrics, Orthopaedics and dentistry, the response rate was relatively insufficient. Fields where topical LA is used in higher doses (Respiratory medicine for bronchoscopic procedures for instance), the same pattern was noticed. Even though the frequency of use was assessed, the volumes of LA, were not evaluated. The correct answers were provided following the submission of the questionnaire, although, the reduced response rate of the initial study and the prevailing pandemic (COVID-19) prompted the authors not to proceed with reassessment of knowledge which could have been informative. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255661 doi: medRxiv preprint The basic knowledge on LAST was satisfactory among the respondents. Significant lapses were identified with regard to use of total body weight for dose calculations, use of ultrasound during LA administration and dosage and importantly availability and storage of the definitive therapy, ILE. The authors suggest the following:  Education programmes on LAST to be conducted specially for the non-anaesthetic doctors who frequently use LA.  A brief presentation on LAST during academic sessions on regional nerve blocks/ Inclusion of a segment on LAST to the curriculum of the non-anaesthetic post-graduate trainees. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.21255661 doi: medRxiv preprint ESRA19-0705 Systemic local anaesthetic toxicity: last and beyond Local anesthetic systemic toxicity: A narrative literature review and clinical update on prevention, diagnosis, and management. 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