Comparison of two analgesia protocols for the treatment of pediatric orthopedic emergencies

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1 ORIGINAL ARTICLE Barcelos A et al. Comarison of two analgesia rotocols for the treatment of ediatric orthoedic emergencies Andrea Barcelos 1, Pedro Celiny Ramos Garcia 2 *, Janete L. Portela 3, Jefferson P. Piva 4, João Pedro Tedesco Garcia 5, João Carlos B. Santana 6 1 MSc in Pediatrics, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS). Emergency Room Pediatrician at the Hosital Universitário de Santa Maria, RS, Brazil 2 PhD in Medicine/Pediatrics, Universidade de São Paulo (USP). Titular Professor of the Medical School Pediatrics at PUCRS. Head of the Pediatrics Service and Intensive Care and Emergency Service at Hosital São Lucas, PUCRS, Porto Alegre, RS, Brazil 3 MSc in Child Health, PUCRS. Emergency Room Nurse at Hosital Universitário de Santa Maria, RS, Brazil. 4 PhD in Medicine/Pediatrics, Head of the Intensive Care and Emergency Service at Hosital de Clínicas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil 5 3 rd Year Resident Physician in the Otorhinolaryngology Service and Head and Neck Surgery at Hosital São Lucas, PUCRS, Porto Alegre, Brazil 6 PhD in Medicine/Pediatrics, UFRGS. Professor of the Medical School Pediatrics Deartment, UFRGS. Pediatrician of the Pediatrics Ward at Hosital São Lucas, PUCRS, Porto Alegre, RS, Brazil Summary Study conducted at Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil Article received: 6/24/2014 Acceted for ublication: 6/25/2014 *Corresondence: Address: Rua Curuaiti, 62 Porto Alegre, RS Brazil Postal code: celiny@terra.com.br htt://dx.doi.org/ / Financial suort: Pedro Celiny Ramos Garcia holds a roductivity scholarshi in 1D Research from the CNPQ Objectives: to comare the efficacy of two analgesia rotocols (ketamine versus morhine) associated with midazolam for the reduction of dislocations or closed fractures in children. Methods: randomized clinical trial comaring morhine (0.1mg/kg; max 5mg) and ketamine (2.0mg/kg, max 70mg) associated with midazolam (0.2mg/kg; max 10mg) in the reduction of dislocations or closed fractures in children treated at the ediatrics emergency room (October 2010 and Setember 2011). The grous were comared in terms of the times to erform the rocedures, analgesia, arent satisfaction and orthoedic team. Results: 13 atients were allocated to ketamine and 12 to morhine, without differences in relation to age, weight, gender, tye of injury, and ain scale before the intervention. There was no failure in any of the grous, no differences in time to start the intervention and overall rocedure time. The average hosital stay time was similar (ketamine = h versus morhine = hs; =0.447). The median ain (faces ain scale) scores after the rocedure was 2 in both grous. Amnesia was noted in 92.3% (ketamine) and 83.3% (morhine) (=0.904). Parents said they were very satisfied in relation to the analgesic intervention (84.6% in the ketamine grou and 66.6% in the morhine grou; =0.296). The satisfaction of the orthoedist regarding the intervention was 92.3% in the ketamine grou and 75% in the morhine grou (=0.222). Conclusion: by roducing results similar to morhine, ketamine can be considered as an excellent otion in ain management and hels in the reduction of dislocations and closed fractures in ediatric emergency rooms. Keywords: fractures, bones, clinical rotocols, ediatrics, analgesia. Introduction Traumatic injuries in childhood, esecially dislocations and fractures are one of the main reasons for services in ediatric emergency units (PEU). Several studies have demonstrated that analgesia and sedation for reducing dislocations or closed fractures are conducted in an imroer manner in ediatric emergency services. The ideal drug for sedation and analgesia used in these rocedures should have a fast onset, be safe and easy to administer, in addition to causing amnesia and muscle relaxation. 1-8 In ediatric emergency services, analgesia and sedation for the reduction of fractures and dislocations is often the resonsibility of the emergency ediatrician. There are a wide variety of ainkillers and sedatives to rovide favorable conditions for carrying out the rocedure safely. For this urose, the ediatrician should know the main harmacological characteristics, exected actions, adverse effects and, if necessary, how to antagonize them Oioids (morhine, fentanyl) are widely used due to their established efficacy and immediate availability. 2-5,10, R rev Assoc Med Bras 2015; 61(4):

2 Comarison of two analgesia rotocols for the treatment of ediatric orthoedic emergencies There is evidence demonstrating safer treatment regimens than the combination of benzodiazeines and an oiate. is a otent dissociative analgesic which in usual doses does not cause resiratory deression or hemodynamic instability. Due to its efficacy and limited adverse effects, it has become the drug of choice for many ediatric rocedures. However, there are few well-designed, controlled and randomized clinical trials that have tested ketamine secifically in orthoedic emergencies. 1,2,4-19 This study aims to comare the efficacy of two analgesia rotocols (ketamine versus morhine) associated with midazolam for the reduction of dislocations or closed fractures in children treated at a reference ediatric emergency unit (PEU). Methods The authors conducted a randomized clinical study comaring two analgesia rotocols in orthoedic emergencies in the ediatric emergency service of Hosital Universitário de Santa Maria (SEP-HUSM). The HUSM is a ublic general hosital linked to the Universidade Federal de Santa Maria (UFSM), Brazil. It is the largest ublic hosital in the state of Rio Grande do Sul, with 311 beds, and it is a regional reference center for 46 municialities. At the SEP-HUSM about 1,140 children aged from birth to 14 years are treated. Between October 2010 and Setember 2011, all atients admitted between Monday and Friday at the SEP- HUSM, aged 3 years to 14 years, with dislocation or closed fracture that required orthoedic reduction maneuvers were included in the study. The study excluded atients with: (a) class III or higher of the American Society of Anesthesiologists (ASA III or above) (b) fractures for more than 24 hours (c) allergies or (d) contraindication to any medication used in the study and (e) arent or guardians who did not consent to articiate in the study. Protocol Patients were selected consecutively and allocated randomly to receive analgesia with ketamine or morhine associated with midazolam. Randomization was conducted in blocks of ten (each manila enveloe contained 5 aers from the ketamine grou and 5 from the morhine grou). Immediately after admission, the nurse resonsible erformed the draw, informed the ediatrician on duty of the results and reared the medications according to the redefined doses. Sedation, analgesia and management of comlications were under the resonsibility of the emergency ediatrician and the reduction rocedure was erformed by the orthoedic hysician. To induce sedation, all atients received intravenous midazolam (0.2 mg/kg u to a maximum dose of 10 mg) without additional doses. According to the draw erformed by the nurse, one grou received morhine 0.1 mg/kg intravenously, followed by increments of 0.05 mg/kg (at the hysician s discretion) u to a maximum dose of 5mg. The other grou received ketamine 2 mg/kg intravenously u to a maximum dose of 70 mg, without additional doses. 16 All atients were monitored according to the sedation and analgesia routines, including measurements of vital signs at the beginning, every 5 minutes and at the end of the rocedure. The SEP-HUSM nurse was resonsible for the monitoring and follow-u of each atient during the rocedure, recording adverse events. The faces ain scale was used to classify ain. 6 To assess arental and orthoedist satisfaction after the rocedure, the authors used the 5 oint Likert scale (1: very leased to 5: very dissatisfied). 7 Assessments For comarison between both analgesia grous, the outcomes considered were time to start the intervention, duration of the rocedure, the total time of the rocedure, the child s cooeration, arental satisfaction and the satisfaction of the surgeon resonsible for rocedure. The grous were also comared in relation to the occurrence of adverse events related to the medication. The time to start the intervention was defined as the time in minutes between the administration of drugs until the orthoedic hysician considered that there was suitable sedation/analgesia. The duration of the rocedure was established as the time in minutes from the beginning of the rocedure until the slint or laster was laced. The total time (intervention and rocedure) was defined as the time in minutes between the administration of the drugs and the end of the lacement of the slint or laster. The rocedure was considered successful if the atient did not need further reduction in the oerating room. In the case of multile reduction attemts only, the first attemt was included in the study. Demograhic data, medication doses, fasting time, time for the start of the intervention, rocedure duration and duration of hositalization were recorded. Before sedation and analgesia, and after the reduction rocedure, the atient was assessed by the nurse using the faces ain scale. At the end of the rocedure, a Likert scale was alied to assess arental and orthoedist satisfaction in relation to the rocedure. Before discharge, the child was questioned as to whether they remembered the rocedure Rev Assoc Med Bras 2015; 61(4):

3 Barcelos A et al. by answering yes or no. The recommended criteria for hosital discharge were stable and satisfactory cardiovascular function, atent airways and ease in waking u the atient, able to talk and sit unaided and with rotective reflexes intact. The study was aroved by the Research Ethics Committee at the UFSM (CAAE ), requiring arents or guardians to sign an informed consent form after being suitably informed in order to articiate in the study. Statistical analysis The categorical variables were exressed as ercentages and comared using the chi-square test or Fisher s exact test. Continuous variables with normal distribution, were exressed using the mean with standard deviation, and comared using the Student s t-test. Variables without a normal distribution were exressed as a median with the resective interquartile range (IQ 25%-75%) and comared using the Mann-Whitney U test. The data were transcribed into an Excel sreadsheet for Windows (Microsoft Office) and analyzed using SPSS software version Results During the study eriod, 79 atients attended the SEP- -HUSM due to an osteoarticular injury. Among these, 54 (68%) did not resent criteria for inclusion in the samle (three under the age of three years, 18 required surgical treatment, 10 had oen fractures and 23 were treated on weekends). 25 atients with a closed fracture or dislocation remained, who required intravenous sedation and analgesia to erform a closed reduction, with 13 atients allocated to ketamine and 12 to the morhine grou. There were no differences between the grous with resect to age, weight, gender, fasting time, tye of injury, vital signs on arrival to the emergency and ain scale before the intervention (Table 1). TABLE 1 General characteristics and vital signs of the two analgesia grous before the start of orthoedic reduction rocedures. Age (months) Median Weight (kg) Median 90.7± ( ) 27.5± ( ) 102.1± ( ) 30.4± ( ) a b Male N (%) 11 (57.9) 8 (42.1) c Fasting time (hours) 6 ( ) 6 ( ) b (Continue) TABLE 1 (Cont.) General characteristics and vital signs of the two analgesia grous before the start of orthoedic reduction rocedures. Tye of injury Fracture Dislocation c Heart rate (bm) 112.5± ± b Resiratory rate (mrm) Oxygen saturation (%) Diastolic blood ressure (mmhg) 25.8± ± a 99.0± ± b 69.0± ± b The averages are exressed with the resective standard deviation (DP), while the medians are accomanied by the resective ranges (minimum and maximum value) and absolute values (N) accomanied by the ercentage (%). a Continuous variables with normal distribution comared using Student s t-test. b Continuous variables without normal distribution comared using Mann-Whitney U test. c Categorical variables comared using chi-square or Fisher exact tests. Both rotocols were shown to be effective, with no treatment failures in either grou. The authors did not observe significant differences in the time to begin the intervention, or in the total rocedure time between the two grous (Table 2). However, the duration of the intervention was significantly lower in the morhine grou in relation to the ketamine grou (median of 3 versus 5 minutes; <0.027). TABLE 2 Comarison between analgesia grous in relation to the time to start the intervention, rocedure duration and total time (intervention and rocedure). Time to start intervention (min.) 3 ( ) 2.5 ( ) b Procedure duration time (min.) 5 ( ) 3 ( ) b Total time intervention and rocedure (min.) 10 ( ) 6 ( ) b b Medians and resective ranges (minimum and maximum value) comared using Mann- Whitney U test. Based on Table 3, it is clear that the average time of hositalization was similar between the two grous (ketamine = 10.8±5.2 hours versus morhine = 12.3±4.4 hours; =0.447). The median ain analyzed using the faces ain scale following the rocedure was 2 on both grous. Alying the delta test, no statistically significant difference was found in the resence of ain at the end of the rocedure. Most of the children did not remember erforming the roce- 364R rev Assoc Med Bras 2015; 61(4):

4 Comarison of two analgesia rotocols for the treatment of ediatric orthoedic emergencies dure in both tyes of analgesia (ketamine = 92.3% versus morhine = 83.3%; =0.904). Adverse effects related to use of the drugs were similar in both grous. No atient suffered anea, laryngosasm, tachycardia, or hyotension, neither was the use of antagonists (flumazenil or naloxone) required. TABLE 3 Comarison between the two grous of analgesia in relation to ain scale, satisfaction of arents and orthoedist, amnesia in relation to the rocedure, adverse reactions to the analgesic and hosital stay. Hositalization time (hours) 10.8± ± a Pain scale (after rocedure) 2 ( ) 2 ( ) b Pain delta (after rocedure) 4 ( ) 4 ( ) b Amnesia of the rocedure (yes) % 12 (92.3) 10 (83.3) c Vomiting (yes) % 1 (7.7) 3 (25.0) c Agitation/hallucination (yes) % 2 (15.4) 4 (33.3) c Fall in oxygen saturation (yes) % Parental satisfaction (very satisfied) % Orthoedist satisfaction (very satisfied) % 1 (7.7) 3 (25.0) c 11 (84.6) 8 (66.6) c 12 (92.3) 9 (75) c Key to tables: The measurements are exressed with the resective standard deviation ( SD) while the medians are resent with their resective ranges (minimum and maximum value) and absolute values (N) accomanied by the ercentage (%). a Continuous variables with normal distribution comared using Student s t-test. b Continuous variables without normal distribution comared using Mann-Whitney U test. c Categorical variables comared using chi-square or Fisher exact tests. Parents said they were very satisfied in relation to the analgesic intervention in 84.6% of atients that used ketamine, and in 66.6% that used morhine (=0.296). In the same manner, the maximum satisfaction of the orthoedist regarding the intervention was 92.3% in the ketamine grou and 75% in the morhine grou (=0.222). Discussion Sedoanalgesia is an essential rocedure for closed orthoedic reduction at PEUs. The resent study demonstrated that analgesia with ketamine for closed reduction of fractures and dislocations showed similar clinical results to those obtained with morhine. Both arents and orthoedic teams exressed satisfaction with both medications. Therefore, by adoting morhine by default in this tye of rocedure, it may be concluded that ketamine had the same degree of effectiveness, alongside its known safety and low incidence of side effects. Sedation and analgesia in PEUs should be directed according to the effectiveness, safety and cost, and should be erformed by hysicians exerienced in airway management and treatment of cardio-resiratory comlications, familiar with the harmacodynamics and harmacokinetics of the drugs used. 1,8,9,17,19-21 Sedation and analgesia in these situations should be erformed in a service that has suort from nursing staff for the monitoring of vital signs and continuous clinical observation of the atient, in addition to aroriate equiment for airway management and cardioulmonary resuscitation, esecially heart monitors and/or continuous ulse oximetry. 8,22,23 In this study, both analgesia rotocols had favorable outcomes, notably in terms of ain control, start time of the intervention by the orthoedist, the total rocedure time, success in reducing the fracture and the occurrence of amnesia, in agreement with other studies. 1,2,4-7,12-17,23,24 The rocedure duration time in the morhine grou was slightly lower than in the ketamine grou, a result also found in a similar study. 9,10 The sedation and analgesia schemes most commonly used in PEU involve the association of an oioid (morhine or fentanyl) with midazolam or the administration of ketamine with or without midazolam remains the most widely used drug in severe and chronic ain, however, fentanyl has been emloyed in more time-consuming rocedures due to its faster start and eak of action and more rolonged effect. is a dissociative agent, blocking oioid recetors, which raidly induces sedation, rofound analgesia, immobility and catalegia, reserving sontaneous resiration. 16 Havel et al. monitored 89 children who received two different analgesia schemes for fracture reduction (midazolam/morhine vs. roofol/morhine) and found that both grous had similar efficiencies and insignificant adverse events. 24 Godambe et al. analyzed analgesia used on 113 children undergoing orthoedic rocedures and found that both rotocols (ketamine/midazolam vs. roofol/fentanyl) had similar results for the relief of ain and anxiety, although the roofol/fentanyl grou resented a shorter rocedure time. 2 In this study, the resence of hyoxemia was an unusual finding and there was significant difference between the grous who used ketamine or morhine. However, hyoxia is one of the adverse effects associated with the use of oioids cited most in the literature. 2, 5,10 Kennedy et al. observed that the grou of atients using analgesia with fentanyl/midazolam had more hyoxemia (25% vs. 6%; <0.001), requiring resiratory stimulation (12% vs. 1%; <0.01) and oxygen theray (20% vs. 10%; <0.05) than Rev Assoc Med Bras 2015; 61(4):

5 Barcelos A et al. those who received ketamine/midazolamm. 5 administered by intravenous or intramuscular routes, even as a single drug, has been indicated as a safe and effective alternative for raid analgesia. 6,10,27,28 In a systematic review of randomized trials of analgesia and sedation for reduction of fractures in children at a PEU, ketamine/ midazolam roved to be more effective as an analgesic and had fewer adverse effects than combinations of fentanyl/midazolam or roofol/midazolam. 1,2,4,5,15,25 When the level of satisfaction of arents and orthoedists were analyzed with analgesia for the orthoedic rocedure, it was found that levels were quite high. Satisfaction was similar regardless of analgesic used, whether morhine or ketamine, a fact also described in other studies. 2,29 Conclusion Considering ain control, shorter start time of the intervention by the orthoedist, lower total rocedure time, success in reduction of the fracture, the resence of amnesia and low incidence of adverse effects, esecially resiratory disorders, ketamine was shown to be a safe and effective analgesic for use in orthoedic emergencies. As these results were equivalent to those found in the grou using morhine, a widely used analgesic, ketamine can be considered as an excellent otion in ain management, and hels in the reduction of dislocations and closed fractures in ediatric emergency rooms. Resumo Comaração de dois rotocolos de analgesia ara tratamento de emergências ortoédicas ediátricas Objetivo: comarar a eficácia de dois rotocolos de analgesia (cetamina versus morfina) associados ao midazolam ara a redução de luxações ou fraturas fechadas em crianças. Métodos: ensaio clínico randomizado comarando morfina (0,1 mg/kg; máx. 5 mg) e cetamina (2,0 mg/kg; máx. 70 mg) associados a midazolam (0,2 mg/kg; máx. 10 mg) na redução de luxações ou fraturas fechadas em crianças atendidas em emergência ediátrica, no eríodo de outubro de 2010 a setembro de Os gruos foram comarados segundo os seguintes indicadores: temo ara realizar os rocedimentos, analgesia, satisfação de ais e da equie ortoédica. Resultados: treze acientes foram alocados ara cetamina e 12 ara morfina, sem diferenças em relação a idade, eso, gênero, tio de lesão e escala da dor antes da intervenção. Não houve falha em nenhum dos gruos, sem diferenças no temo ara iniciar a intervenção e no temo total de rocedimento. O temo médio de hositalização foi similar (cetamina=10,8±5,1 h versus morfina=12,3±4,4 h; =0,447). A mediana de dor (escala de faces da dor) aós o rocedimento foi de 2 em ambos os gruos. Amnésia foi observada em 92,3% (cetamina) e 83,3% (morfina) (=0,904). Os ais declararam estar muito satisfeitos em relação à intervenção analgésica (84,6% no gruo cetamina e 66,6% no gruo morfina; =0,296). A satisfação do ortoedista em relação à intervenção foi de 92,3% no gruo cetamina e 75% no gruo da morfina (=0,222). Conclusão: a cetamina, ao aresentar resultados semelhantes à morfina, ode ser considerada uma excelente oção no manejo da dor e no auxílio da redução de luxações e fraturas fechadas em salas de emergência ediátrica. Palavras-chave: fraturas ósseas, rotocolos clínicos, ediatria, analgesia. References 1. Migita RT, Klein EJ, Garrison MM. Sedation and analgesia for ediatric fracture reduction in the emergency deartment: a systematic review. 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