Efeitos adversos da morfina, metadona e tramadol no pós-operatório de cães submetidos à cirurgia da coluna vertebral: 180 casos (2011-2016) / Adverse effects of morphine, methadone and tramadol in the postoperative period of dogs undergone vertebral surgery: 180 cases (2011-2016)

A dor pós-operatória em cães que são submetidos a cirurgias da coluna vertebral é considerada severa e seu manejo inadequado pode influenciar no tempo de recuperação do paciente, na qualidade de vida e no resultado cirúrgico. Dentre os analgésicos indicados para uso no pós-operatório dessas cirurgias tem-se os opioides, que podem apresentar inúmeros efeitos adversos que requerem atenção. Devido à escassez de estudos clínicos acerca desse assunto em se tratando do pós-operatório de cães, objetivou-se com o presente estudo retrospectivo apresentar os efeitos adversos da morfina, metadona e tramadol utilizados no pós-operatório de cirurgias da coluna vertebral. Foram revisadas e avaliadas as fichas de 180 cães e anotadas as alterações observadas no pós-operatório e decorrentes do uso de opioides. Os principais efeitos adversos observados foram anorexia, hiporexia, vômito, salivação, vocalização, bradicardia, hipotermia, ofegação e sedação. Também foi observada persistência da dor em alguns cães mesmo com o uso de analgésicos. Houve diferença na ocorrência de anorexia nos cães tratados com morfina e nos tratados com metadona em relação aos tratados com tramadol. Ocorreu diferença também entre a observação de dor dos grupos morfina e tramadol. A associação de dipirona com morfina e com metadona não revelou diferença com relação à ocorrência de efeitos adversos, bem como a variação de doses. Conclui-se que a morfina, a metadona e o tramadol apresentam efeitos adversos quando empregados para tratamento da dor pós-operatória em cães submetidos à cirurgia da coluna vertebral; a anorexia, a hiporexia e o vômito foram os efeitos adversos frequentes com o uso de morfina e de metadona e, mesmo que o tramadol apresente menor ocorrência desses efeitos, seu uso, na dose estudada, pode não ser vantajoso quando se leva em consideração o grau de dor para cirurgias da coluna vertebral.(AU)

Postoperative pain in dogs undergone vertebral surgery is classified as severe and it's important an adequate approach to it, because it can influence recovery time, quality of life and surgery outcome. Opioids are indicated for postoperative pain treatment in these surgeries. Opioids may have adverse effects that may require attention. There are few clinical studies that present the adverse effects of these analgesics in canine postoperative period. The aim of this retrospective study was to present the adverse effects of morphine, methadone and tramadol in canine vertebral surgery postoperative period. There were revised the postoperative records of 180 dogs and the changes resulted from the opioids use were noted. The adverse effects observed were anorexia, hyporexia, vomiting, vocalization, bradycardia, hypothermia, panting, sedation. Pain was also observed in some dogs. A significant difference was found in anorexia between dogs treated with morphine and tramadol and methadone and tramadol. Significant difference was also found in pain between dogs treated with morphine and tramadol. The association of metamizole and morphine or metamizole and methadone was not different in relation to the adverse effects. There was also no difference with the dosage variation and the adverse effects. In conclusion, morphine, methadone and tramadol have adverse effects when used for pain control in the postoperative period of dogs submitted to vertebral surgery. Anorexia, hypophagia and emesis were frequent the adverse effects observed with morphine and methadone and, despite tramadol presented less adverse effects, its use may be not beneficial in the studied doses when we consider the degree of pain, however more controlled studies with clinical situation are needed to confirm this.(AU)

QT interval prolongation associated with azithromycin/methadone combination / Prolongación del intervalo QT asociada con combinación de azitromicina/metadona

This report documents the occurrence of QT prolongation in a 57-year old man, on methadone replacement therapy, treated with azithromycin for community acquired pneumonia. This case highlights a hitherto unknown drug interaction. In light of ever-increasing use of azithromycin, it is imperative that azithromycin be used with caution in patients who are already on drugs that are known to cause QT prolongation or that cause torsades de pointes.

Este reporte documenta la ocurrencia de la prolongación del intervalo QT en un hombre de 57 años, en la terapia de reemplazo con metadona, tratado con azitromicina por pulmonía adquirida en la comunidad. Este caso destaca una interacción de medicamentos desconocida hasta ahora. En vista del uso cada vez mayor de la azitromicina, resulta absolutamente necesario usarla con precaución en pacientes que ya están bajo tratamiento con medicamentos de los cuales se sabe que causan prolongación del intervalo QT o que causan torsades de pointes.

effects of gabapentin on methadone based addiction treatment: a randomized controlled trial

Gabapentin is a potentially useful drug in alleviating the hyperexcitatory painful states in the control of opiate dependence in acute detoxification and the stabilization phase. This study aim was to evaluate the effectiveness of gabapentin adds-on methadone therapy on lowering the methadone. This randomized double blind controlled clinical trial conducted at an outpatient rehabilitation clinic. Sixty patients using opium, opium extract and heroin were randomly assigned to two groups [34 in treatment group and 26 in control group]; one group was prescribed combination of methadone [40-120 mg] and gabapentin [300 mg] as group A, and the other group was given methadone [40-120] and placebo as group B. The subjects were followed up for three weeks after intervention. There were 60 outpatients including 51 males with the mean age of 40.9 +/- 9.2. Daily dose and cumulative dose of methadone during the treatment was found to be significantly higher in group B [73.8 +/- 19.5 mg daily vs. 58.9 +/- 11 mg daily and cumulatively 1550.7 +/- 409.7 mg vs. 238.3 +/- 238.2 mg, p= 0.001]. When the patients were stratified based on the kind of abused drug, the methadone dose was seen to be significantly reduced in the opium addicted patients in the group A. Group A showed more withdrawal symptoms whereas the most common complain of group B was sedation particularly during the first three days. The results showed that gabapentin is an effective adds-on therapy when is added to methadone. This drug leads to relief of withdrawal symptoms and lower methadone consumption

Efeitos da metadona ou do neostigmine, associados à lidocaína administrados pela via epidural em cães / Effects of methadone or neostigmine in combination with lidocaine for epidural anesthesia in dogs

Seis cães adultos, de raças e sexos variados, com peso de 13,3±3,4kg (média±DP), foram utilizados no estudo. Os animais foram tranqüilizados com acepromazina (0,1mg/kg, IV) e, após 30 minutos, foram aleatoriamente submetidos à anestesia epidural com um dos seguintes tratamentos: lidocaína 2 por cento 0,25ml/kg (controle); neostigmine 0,01mg/kg+lidocaína (NEO); metadona 0,3mg/kg+lidocaína (MET). Todos os animais foram submetidos aos três tratamentos com intervalo mínimo de uma semana. Foram mensuradas as freqüências cardíaca (FC) e respiratória (FR), a pressão arterial sistólica (PAS), o tempo para a perda do reflexo interdigital, a duração e a altura do bloqueio sensitivo, durante um período de 90 minutos. Não houve diferença significativa entre os tratamentos nos valores de FC, PAS e FR, bem como na duração do bloqueio sensitivo e no tempo para a perda do reflexo interdigital. No grupo MET, houve diminuição de FC dos 30 aos 90 minutos em relação ao valor basal. Bloqueio sensitivo mais cranial também foi observado em MET. A associação de neostigmine ou metadona não prolongou o período hábil de anestesia epidural produzido pela lidocaína em cães. A metadona, mas não o neostigmine, parece estender mais cranialmente o bloqueio epidural pela lidocaína.

Six mature mongrel dogs of both genders, weighing 13.3±3.4kg (mean±SD) were used in the present research. Thirty minutes after premedication with intravenous acepromazine (0.1mg/kg, IV), dogs were randomly assigned to receive epidural administration of one of following three treatments: 2 percent lidocaine 0.25ml/kg (control), or neostigmine 0.01mg/kg plus lidocaine (NEO), or methadone 0.3mg/kg plus lidocaine (MET). All dogs received all treatments in a cross-over design with at least one-week interval. Heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), time to loss of pedal withdrawal reflex, duration of epidural anesthesia, and cranial spread of epidural anesthesia were evaluated for 90 minutes. No differences among treatments in HR, RR, SAP, duration of anesthesia, and time to loss of pedal withdrawal reflex were found. In MET, HR decreased from 30 to 90 minutes compared to baseline and there was a higher cranial spread of epidural anesthesia than in controls and NEO animals. Neostigmine or methadone did not prolong epidural anesthesia with lidocaine in dogs. Methadone, but not neostigmine, appeared to result in more cranial spread of epidural anesthesia with lidocaine.

Neonatal abstinence syndrome.

OBJECTIVE: To study the substance misuse in pregnant mothers and its impact on their newborns. METHODS: Case note review of the study population was undertaken. Infants of mothers who had taken substance of misuse were monitored regularly using Finnegan's score and treatment initiated based on a pre-existing protocol. The parameters that were studied included maternal drug habits, antenatal problems, and neonatal epidemiology with particular reference to growth, neonatal abstinence syndrome (NAS), its severity and management. RESULTS: Out of 32 neonates, 28 had developed neonatal withdrawal requiring treatment. The earliest presentation of NAS was at six hours and the average time of presentation of NAS was 26 hours. The dose of methadone taken by the mother related well with the likelihood of development of NAS. The most common symptoms noted at the time of diagnosis were irritable cry, increased tone, tachypnea, sleeplessness and tremor. CONCLUSION: Majority of neonates born to mothers on methadone exhibit neonatal abstinence syndrome and require pharmacological treatment. Neonates who had not exhibited symptoms of drug withdrawal within the first 3 days of life are unlikely to present with NAS requiring treatment.

Maternal and Neonatal Effects of Substance Abuse during Pregnancy: Our Ten-year Experience

PURPOSE: The aim of the study was to assess perinatal outcome of pregnancy burdened with maternal addiction in comparison with an unselected population from a European transition country. MATERIALS AND METHODS: Data on pregnancies complicated by illicit drug abuse (n = 85) managed during a 10-year period (1997-2007) at Split University Hospital were analyzed. Data on the type of drug, course of gestation and labor, and on perinatal outcome were considered. Data on all non-dependence pregnancies recorded during the study period were used as a control group. RESULTS: During the study period, there were 85 dependence-complicated pregnancies (0.2%). Use of heroin alone during pregnancy was recorded in 51 women (50%), methadone alone in 6 (7%), and a combination of heroin and methadone in 9 (11%). Premature delivery was significantly more common in the group of pregnant addicts (21% vs. 6%); 49% of pregnant addicts were carriers of hepatitis C virus (HCV) and 14% of hepatitis B virus (HBV). Neonatal abstinence syndrome developed in 61 infants (7%) born to addicted mothers. There were 4 cases (4.6%) of early neonatal death; 7 neonates had 5-minute Apgar score < or = 7 (8%); 29 neonates had low birth weight for age (33%); and 7 neonates had congenital anomalies (8%). The risk of various congenital anomalies was 3-fold in the group of children born to addicted mothers. CONCLUSION: Addiction pregnancies present a small but high-risk group according to perinatal outcome. Appropriate obstetric and neonatal care can reduce the rate of complications in these pregnancies and improve perinatal outcome.

Efeitos sedativo e cardiorrespiratório da administração da metadona, isoladamente ou em associação à acepromazina ou xilazina, em gatos / Sedative and cardiorespiratory effects of methadone, alone or in combination with acepromazine or xylazine, in cats

Seis felinos com peso médio de 3,3±0,3 kg foram aleatoriamente submetidos a 6 tratamentos, com intervalo mínimo de 1 semana. Os animais receberam a administração intramuscular de solução fisiológica (controle), metadona (0,3 mg/kg), acepromazina (0,1 mg/kg), xilazina (1,0 mg/kg), acepromazina (0,05 mg/kg) + metadona (0,3 mg/kg) ou xilazina (0,5 mg/kg) + metadona (0,3 mg/kg). As freqüências cardíaca (FC) e respiratória (FR), a pressão arterial sistólica (PAS), a temperatura retal, o grau de sedação e o reflexo interdigital foram avaliados antes (basal) e após a administração dos tratamentos em intervalos específicos por 90 minutos. Nos animais tratados com xilazina ou xilazina/metadona, houve diminuição em FR, FC e na temperatura retal. Nos mesmos tratamentos, 1/6 e 2/6 animais não apresentaram reflexo interdigital em pelo menos um dos momentos avaliados. Nos animais que receberam a administração de 0,1 mg/kg de acepromazina, houve diminuição em PAS. Os escores de sedação foram mais elevados nos animais que receberam a administração de xilazina ou xilazina associada à metadona. A administração da metadona isolada ou associada à acepromazina resultou em sedação considerada insatisfatória e sinais de excitação em alguns animais. O uso da metadona isolado ou em associação à acepromazina foi considerado ineficaz quando se objetiva sedação moderada à intensa. A associação da metadona à xilazina produz sedação moderada à intensa, sendo esse efeito semelhante àquele observado após a administração da xilazina isoladamente em dose mais elevada.

Six cats weighting 3.3±0.3 kg were randomly allocated to 6 treatments, with at least one-week intervals. The cats received intramuscular administration of physiological saline (control), methadone (0.3 mg/kg), acepromazine (0,1 mg/kg), xylazine (1.0 mg/kg), acepromazine (0.05 mg/kg) plus methadone (0.3 mg/kg) or xylazine (0.5 mg/kg) plus methadone (0.3 mg/kg). Heart rate (HR), respiratory rate (RR), indirect systolic arterial pressure (SAP), rectal temperature, sedation score and pedal withdrawal reflex were evaluated before (baseline) and at selected intervals after treatment administration for 90 minutes. Respiratory rate, HR and rectal temperature decreased in cats given xylazine or xylazine plus methadone. In 1 out of 6 cats given xylazine and 2 out of 6 cats given xylazine/methadone, pedal withdrawal reflex was absent. In cats given 0.1 mg/kg of acepromazine, SAP decreased compared to baseline. Sedation scores were greater in cats given xylazine or xylazine plus methadone. Methadone alone or in combination with acepromazine did not produce a satisfactory degree of sedation and resulted in signs of excitement in some of the cats. Methadone alone or combination with acepromazine was not considered an effective protocol when moderate to deep sedation is required in cats. Methadone in combination with xylazine produces moderate to deep sedation, being this effect comparable to that achieved with a higher dose of xylazine alone.

Un caso de prolongación del intervalo QT asociado a consumo de metadona / QT interval prolongation associated with methadone consumption: report of a case

La farmacodependencia es una epidemia de nuestro tiempo, con graves consecuencias sanitarias y económicas, tanto para la sociedad como para el individuo. A continuación presentamos el caso clínico de un hombre de 37 años con antecedentes de abuso de drogas (cocaína, antidepresivos, benzodiacepinas y heroína), en tratamiento con metadona, y que es hallado en su hogar en coma. Tras presentar síndrome de deprivación se reinició metadona, a partir del tercer día de evolución presenta bradicardia sinusal progresiva, con prolongación del intervalo QT hasta 0,64 segundos y un episodio de fibrilación ventricular (FV), que responde a desfibrilación con 200 J. Se sospecha rol etiológico de la metadona y se inicia su descenso gradual. Se observa en los días sucesivos la progresiva y definitiva normalización del ritmo y duración del intervalo QT (Figura 1, 2, 3). Consideramos que la medición rutinaria del intervalo QT corregido parece justificada en presencia de factores de riesgo y cuando se está prescribiendo fármacos con conocido efecto sobre él.